FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bushinsky, DA Williams, GH Pitt, B Weir, MR Freeman, MW Garza, D Stasiv, Y Li, E Berman, L Bakris, GL AF Bushinsky, David A. Williams, Gordon H. Pitt, Bertram Weir, Matthew R. Freeman, Mason W. Garza, Dahlia Stasiv, Yuri Li, Elizabeth Berman, Lance Bakris, George L. TI Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; hyperkalemia; potassium binder; renin-angiotensin-aldosterone system inhibitor ID SODIUM POLYSTYRENE SULFONATE; ANGIOTENSIN-ALDOSTERONE SYSTEM; INTESTINAL NECROSIS; HEART-FAILURE; MANAGEMENT; RESONIUM; THERAPY; PREVENTION; INHIBITORS; SORBITOL AB Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin-angiotensin-aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD and hyperkalemia on RAASi. Here, patiromer's onset of action was determined in patients with CKD and hyperkalemia taking at least one RAASi. After a 3-day potassium-and sodium-restricted diet in an inpatient research unit, those with sustained hyperkalemia (serum potassium 5.5 -under 6.5 mEq/l) received patiromer 8.4 g/dose with morning and evening meals for a total of four doses. Serum potassium was assessed at baseline (0 h), 4 h postdose, then every 2-4 h to 48 h, at 58 h, and during outpatient follow-up. Mean baseline serum potassium was 5.93 mEq/l and was significantly reduced by 7 h after the first dose and at all subsequent times through 48 h. Significantly, mean serum potassium under 5.5 mEq/l was achieved within 20 h. At 48 h (14 h after last dose), there was a significant mean reduction of 0.75mEq/l. Serum potassium did not increase before the next dose or for 24 h after the last dose. Patiromer was well tolerated, without serious adverse events and no withdrawals. The most common gastrointestinal adverse event was mild constipation in two patients. No hypokalemia (serum potassium under 3.5 mEq/l) was observed. Thus, patiromer induced an early and sustained reduction in serum potassium and was well tolerated in patients with CKD and sustained hyperkalemia on RAASis. C1 [Bushinsky, David A.] Univ Rochester, Sch Med, Div Nephrol, Rochester, NY 14642 USA. [Williams, Gordon H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Endocrinol, Boston, MA 02115 USA. [Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Weir, Matthew R.] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA. [Freeman, Mason W.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. [Garza, Dahlia; Stasiv, Yuri; Berman, Lance] Relypsa, Redwood City, CA USA. [Li, Elizabeth] PharmaStat, Newark, CA USA. [Bakris, George L.] Univ Chicago Med, Comprehens Hypertens Ctr, Chicago, IL USA. RP Bushinsky, DA (reprint author), Univ Rochester, Med Ctr, Div Nephrol, 601 Elmwood Ave,Box 675, Rochester, NY 14642 USA. EM david_bushinsky@urmc.rochester.edu FU Relypsa; Relypsa, Inc. FX The authors had full access to the data. The first author wrote the first draft of the introduction and discussion. A medical writer (Wendy Gattis Stough, PharmD), funded by Relypsa, prepared the first draft of the methods and results sections under the supervision of the first author, and Jennifer Tyson (AlphaBioCom), funded by Relypsa, provided additional editorial support. All authors reviewed and revised the manuscript and made the decision to submit the manuscript for publication. This study was conducted by five principal investigators at one site in Bulgaria and four sites in Georgia. The results of the study were previously presented as a poster at the 2014 American Nephrology Society's Kidney Week. This study was funded by Relypsa, Inc. Clinical trial registration: EudraCT # 2013-000481-10. NR 32 TC 19 Z9 20 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2015 VL 88 IS 6 BP 1427 EP 1433 DI 10.1038/ki.2015.270 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CY4RG UT WOS:000366395300029 ER PT J AU Ghobrial, IM Redd, R Armand, P Banwait, R Boswell, E Chuma, S Huynh, D Sacco, A Roccaro, AM Perilla-Glen, A Noonan, K MacNabb, M Leblebjian, H Warren, D Henrick, P Castillo, JJ Richardson, PG Matous, J Weller, E Treon, SP AF Ghobrial, I. M. Redd, R. Armand, P. Banwait, R. Boswell, E. Chuma, S. Huynh, D. Sacco, A. Roccaro, A. M. Perilla-Glen, A. Noonan, K. MacNabb, M. Leblebjian, H. Warren, D. Henrick, P. Castillo, J. J. Richardson, P. G. Matous, J. Weller, E. Treon, S. P. TI Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia SO LEUKEMIA LA English DT Article ID II TRIAL; INHIBITOR EVEROLIMUS; LYMPHOPLASMACYTIC LYMPHOMA; INTERNATIONAL WORKSHOP; MAMMALIAN TARGET; MYD88 L265P; RAPAMYCIN; THERAPY; RECOMMENDATIONS; MANAGEMENT AB We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1-16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76-96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38-67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12-not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM. C1 [Ghobrial, I. M.; Armand, P.; Banwait, R.; Boswell, E.; Chuma, S.; Huynh, D.; Sacco, A.; Roccaro, A. M.; Perilla-Glen, A.; Noonan, K.; MacNabb, M.; Leblebjian, H.; Warren, D.; Henrick, P.; Castillo, J. J.; Richardson, P. G.; Treon, S. P.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Redd, R.; Weller, E.] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Matous, J.] Colorado Blood Canc Inst, Denver, CO USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM Irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128; Castillo, Jorge/0000-0001-9490-7532 FU Novartis Inc. [1R01FD003743]; Millenium/Takeda Inc.; International Waldenstrom Macroglobulinemia Foundation (IWMF) FX Supported in part by 1R01FD003743, Novartis Inc., Millenium/Takeda Inc. and the International Waldenstrom Macroglobulinemia Foundation (IWMF). NR 37 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD DEC PY 2015 VL 29 IS 12 BP 2338 EP 2346 DI 10.1038/leu.2015.164 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA CY4QS UT WOS:000366393900008 PM 26139427 ER PT J AU Peng, X Dong, M Ma, L Jia, XE Mao, J Jin, C Chen, Y Gao, L Liu, X Ma, K Wang, L Du, T Jin, Y Huang, Q Li, K Zon, LI Liu, T Deng, M Zhou, Y Xi, X Zhou, Y Chen, S AF Peng, X. Dong, M. Ma, L. Jia, X-E Mao, J. Jin, C. Chen, Y. Gao, L. Liu, X. Ma, K. Wang, L. Du, T. Jin, Y. Huang, Q. Li, K. Zon, L. I. Liu, T. Deng, M. Zhou, Y. Xi, X. Zhou, Y. Chen, S. TI A point mutation of zebrafish c-cbl gene in the ring finger domain produces a phenotype mimicking human myeloproliferative disease SO LEUKEMIA LA English DT Article ID JUVENILE MYELOMONOCYTIC LEUKEMIA; HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; KINASE INHIBITOR PKC412; GAIN-OF-FUNCTION; UNIPARENTAL DISOMY; DANIO-RERIO; EXON 8; NEOPLASMS; FLT3 AB Controlled self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs) are critical for vertebrate development and survival. These processes are tightly regulated by the transcription factors, signaling molecules and epigenetic factors. Impaired regulations of their function could result in hematological malignancies. Using a large-scale zebrafish N-ethyl-N-nitrosourea mutagenesis screening, we identified a line named LDD731, which presented significantly increased HSPCs in hematopoietic organs. Further analysis revealed that the cells of erythroid/myeloid lineages in definitive hematopoiesis were increased while the primitive hematopoiesis was not affected. The homozygous mutation was lethal with a median survival time around 14-15 days post fertilization. The causal mutation was located by positional cloning in the c-cbl gene, the human ortholog of which, c-CBL, is found frequently mutated in myeloproliferative neoplasms (MPN) or acute leukemia. Sequence analysis showed the mutation in LDD731 caused a histidine-to-tyrosine substitution of the amino acid codon 382 within the RING finger domain of c-Cbl. Moreover, the myeloproliferative phenotype in zebrafish seemed dependent on the Flt3 (fms-like tyrosine kinase 3) signaling, consistent with that observed in both mice and humans. Our study may shed new light on the pathogenesis of MPN and provide a useful in vivo vertebrate model of this syndrome for screening drugs. C1 [Peng, X.; Ma, L.; Mao, J.; Chen, Y.; Liu, X.; Du, T.; Jin, Y.; Huang, Q.; Li, K.; Liu, T.; Xi, X.; Chen, S.] Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, Shanghai Inst Hematol,State Key Lab Med Genom, Shanghai 200025, Peoples R China. [Peng, X.; Ma, L.; Mao, J.; Chen, Y.; Liu, X.; Du, T.; Jin, Y.; Huang, Q.; Li, K.; Xi, X.] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Syst Biomed, Shanghai 200025, Peoples R China. [Jia, X-E; Jin, C.; Gao, L.; Ma, K.; Wang, L.; Liu, T.; Deng, M.; Zhou, Y.] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai, Peoples R China. [Dong, M.; Jia, X-E; Jin, C.; Gao, L.; Ma, K.; Wang, L.; Liu, T.; Deng, M.; Zhou, Y.] Chinese Acad Sci, Grad Univ, Shanghai, Peoples R China. [Dong, M.; Jia, X-E; Jin, C.; Gao, L.; Ma, K.; Wang, L.; Liu, T.; Deng, M.; Zhou, Y.] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China. [Ma, L.] Shanghai Jiao Tong Univ, Key Lab Syst Biomed, Minist Educ, Shanghai Ctr Syst Biomed, Shanghai 200025, Peoples R China. [Zon, L. I.; Zhou, Y.] Childrens Hosp, Stem Cell Program, Hematol Oncol Program, Boston, MA 02115 USA. [Zon, L. I.; Zhou, Y.] Harvard Univ, Sch Med, Dana Faber Canc Inst, Boston, MA USA. [Zon, L. I.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Chen, S (reprint author), Shanghai Jiao Tong Univ, Sch Med, Collaborat Innovat Ctr Syst Biomed, Shanghai Inst Hematol,State Key Lab Med Genom,Rui, 197 Rui Jin Rd 2, Shanghai 200025, Peoples R China. EM mdeng@sibs.ac.cn; zhouyong@sibs.ac.cn; yzhou@enders.tch.harvard.edu; sjchen@stn.sh.cn FU Chinese National Key Basic Research Project [2013CB966800, 2011CB964803]; Ministry of Health [201202003]; Mega-projects of Science Research for the 12th Five-Year Plan [2013ZX09303302]; National Natural Science Foundation of China [81123005] FX We thank Profs Zhu Chen for carefully revising the paper and guiding the work and Qiang Li critical reading of the manuscript, all members of the Laboratory of Development and Disease (LDD) for their technical assistance and helpful discussions, and for Drs Anskar Leung and Bai-Liang He for sharing the flt3 morpholino. This work was supported in part by Chinese National Key Basic Research Project (2013CB966800, 2011CB964803), Special Grant of Ministry of Health (201202003), Mega-projects of Science Research for the 12th Five-Year Plan (2013ZX09303302) and the National Natural Science Foundation of China (81123005). NR 60 TC 2 Z9 3 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD DEC PY 2015 VL 29 IS 12 BP 2355 EP 2365 DI 10.1038/leu.2015.154 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CY4QS UT WOS:000366393900010 PM 26104663 ER PT J AU Kenderian, SS Rosado, FG Sykes, DB Hoyer, JD Lacy, MQ AF Kenderian, S. S. Rosado, F. G. Sykes, D. B. Hoyer, J. D. Lacy, M. Q. TI Long-term complete clinical and hematological responses of the TEMPI syndrome after autologous stem cell transplantation SO LEUKEMIA LA English DT Letter ID BORTEZOMIB; OUTCOMES; MYELOMA C1 [Kenderian, S. S.; Lacy, M. Q.] Mayo Clin, Div Hematol, Dept Internal Med, Rochester, MN 55905 USA. [Rosado, F. G.; Hoyer, J. D.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Sykes, D. B.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Kenderian, SS (reprint author), Mayo Clin, Div Hematol, Dept Internal Med, Rochester, MN 55905 USA. EM Lacy.martha@mayo.edu OI Kenderian, Saad/0000-0003-2767-3830 NR 11 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD DEC PY 2015 VL 29 IS 12 BP 2414 EP 2416 DI 10.1038/leu.2015.298 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA CY4QS UT WOS:000366393900021 PM 26500143 ER PT J AU Jafarnejad, M Woodruff, MC Zawieja, DC Carroll, MC Moore, JE AF Jafarnejad, Mohammad Woodruff, Matthew C. Zawieja, David C. Carroll, Michael C. Moore, J. E., Jr. TI Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; SHEAR-STRESS; PROTEIN-CONCENTRATION; B-CELLS; HYDRAULIC CONDUCTIVITY; SUBCAPSULAR SINUS; DENDRITIC CELLS; POPLITEAL NODE; RAT; PRESSURE C1 [Jafarnejad, Mohammad; Moore, J. E., Jr.] Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, London SW7 2AZ, England. [Woodruff, Matthew C.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Zawieja, David C.] Texas A&M Hlth Sci Ctr, Dept Med Physiol, Temple, TX USA. [Carroll, Michael C.] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. RP Moore, JE (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, South Kensington Campus,Royal Sch Mines Bldg, London SW7 2AZ, England. EM james.moore.jr@imperial.ac.uk FU NIH [R01 HL094269, HL096552, HL070308, AI039246-19, U01 HL123420-01]; Royal Society; Royal Academy of Engineering; Sir Leon Bagrit Trust FX The authors would like to acknowledge NIH Grant Nos. R01 HL094269, HL096552, HL070308, AI039246-19 and U01 HL123420-01 for funding this project. Moore wishes to acknowledge the support of The Royal Society, The Royal Academy of Engineering, and The Sir Leon Bagrit Trust. NR 70 TC 4 Z9 4 U1 2 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 EI 1557-8585 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PD DEC 1 PY 2015 VL 13 IS 4 BP 234 EP 247 PG 14 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA CY9IB UT WOS:000366719500002 PM 26683026 ER PT J AU Sharabi, K Tavares, CDJ Rines, AK Puigserver, P AF Sharabi, Kfir Tavares, Clint D. J. Rines, Amy K. Puigserver, Pere TI Molecular pathophysiology of hepatic glucose production SO MOLECULAR ASPECTS OF MEDICINE LA English DT Review DE liver; glucose; gluconeogenesis; insulin; glucagon ID DEPENDENT DIABETES-MELLITUS; CREB COACTIVATOR TORC2; FREE FATTY-ACID; INSULIN-RESISTANCE; PHOSPHOENOLPYRUVATE CARBOXYKINASE; FRUCTOSE 2,6-BISPHOSPHATE; PERIPHERAL INSULIN; IN-VIVO; POSTPRANDIAL HYPERGLYCEMIA; GLUCOCORTICOID-RECEPTOR AB Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays amajor role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Sharabi, Kfir; Tavares, Clint D. J.; Rines, Amy K.; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol,Dept Canc Biol, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave CLSB 11144, Boston, MA 02215 USA. EM pere_puigserver@dfci.harvard.edu FU NIH [R24 DK080261-06, RO1 DK081418, RO1 DK089883, RO1 DK069966]; American Diabetes Association; American Heart Association Postdoctoral Fellowship; NIDDK [F32DK102293-01] FX This work was supported by NIH grants (R24 DK080261-06, RO1 DK081418, RO1 DK089883, RO1 DK069966) and American Diabetes Association grant to P.P. K.S is supported by the American Heart Association Postdoctoral Fellowship. A.K.R is supported by NIDDK grant F32DK102293-01. NR 114 TC 13 Z9 14 U1 4 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0098-2997 EI 1872-9452 J9 MOL ASPECTS MED JI Mol. Asp. Med. PD DEC PY 2015 VL 46 BP 21 EP 33 DI 10.1016/j.mam.2015.09.003 PG 13 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA CY6QP UT WOS:000366534200005 PM 26549348 ER PT J AU Kaittanis, C Shaffer, TM Bolaender, A Appelbaum, Z Appelbaum, J Chiosis, G Grimm, J AF Kaittanis, Charalambos Shaffer, Travis M. Bolaender, Alexander Appelbaum, Zachary Appelbaum, Jeremy Chiosis, Gabriela Grimm, Jan TI Multifunctional MRI/PET Nanobeacons Derived from the in Situ Self-Assembly of Translational Polymers and Clinical Cargo through Coalescent Intermolecular Forces SO NANO LETTERS LA English DT Article DE Lymph node resection; Cerenkov-guided surgery; combination therapy ID CANCER-THERAPY; BREAST-CANCER; LYMPH-NODES; NANOPARTICLES; DELIVERY; TUMORS; LYMPHANGIOGENESIS; CHEMOTHERAPY; NETWORKS; EFFICACY AB Novel multifunctional platforms are needed for oncology in order to assist physicians during surgery and chemotherapy. In the present study, we show that polymeric nanobeacons, consisting of the glucose-based polymer dextran, can be used to guide surgery and improve drug delivery. For imaging, the nanobeacons stably retained the positron emitter 89-zirconium and the MRI contrast agent gadolinium, without the need of a chelator. In addition to using them for PET imaging, the Zr-89-nanobeacons guided the surgical resection of sentinel lymph nodes, utilizing their inherent Cerenkov luminescence. Through weak electrostatic interactions, the nanoparticles carried combinations of chemotherapeutics for the simultaneous inhibition of oncogenic pathways, resulting in enhanced tumor regression. The nanobeacons also allowed monitoring of drug release via MRI, through the quenching of the gadolinium signal by the coloaded drug, making them a new multifunctional theranostic nanotechnology platform for the clinic. C1 [Kaittanis, Charalambos; Shaffer, Travis M.; Bolaender, Alexander; Appelbaum, Zachary; Appelbaum, Jeremy; Chiosis, Gabriela; Grimm, Jan] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, New York, NY 10065 USA. [Grimm, Jan] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Kaittanis, Charalambos] Massachusetts Gen Hosp, Dept Radiol, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Shaffer, Travis M.] CUNY Hunter Coll, Dept Chem, New York, NY 10065 USA. [Shaffer, Travis M.] CUNY, Grad Ctr, New York, NY 10065 USA. [Grimm, Jan] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA. [Grimm, Jan] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA. RP Grimm, J (reprint author), Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, 1275 York Ave, New York, NY 10065 USA. EM grimmj@mskcc.org FU Prostate Cancer Foundation; Alex's Lemonade Stand Foundation; Starr Cancer Consortium [I4-A427]; NIH [1R01CA183953-01A1, R01EB014944, 1 S10 OD016207-01]; National Science Foundation [DGS 0965983]; Department of Defense Prostate Cancer Research Program of the Congressionally Directed Medical Research Programs [W81XWH-12-1-0509]; MSKCC NIH Core Grant [P30-CA008748]; MSKCC's Experimental Therapeutics Center; Commonwealth Foundation for Cancer Research; Center for Experimental Therapeutics of Memorial Sloan Kettering Cancer Center; Center of Molecular Imaging and Nanotechnology FX This study was supported by the Prostate Cancer Foundation (to C.K.), Alex's Lemonade Stand Foundation (to C.K.), and Starr Cancer Consortium (I4-A427 to J.G.). This research was also partially supported by Mr. William H. and Mrs. Alice Goodwin, the Commonwealth Foundation for Cancer Research, the Center for Experimental Therapeutics of Memorial Sloan Kettering Cancer Center, the Center of Molecular Imaging and Nanotechnology and the NIH funds 1R01CA183953-01A1 and R01EB014944 (all to J.G.). T.M.S. is funded by a National Science Foundation Integrative Graduate Education and Research Traineeship (DGS 0965983 at Hunter College). This study was supported by the Department of Defense Prostate Cancer Research Program of the Congressionally Directed Medical Research Programs under Award No. W81XWH-12-1-0509 to J.G. (opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the funding agency). The authors thank the staff of the MSKCC animal MM core for providing expert technical assistance. Technical services provided by the MSKCC Small Animal Imaging Core Facility were supported in part by the MSKCC NIH Core Grant (P30-CA008748) and NIH Shared Instrumentation Grant 1 S10 OD016207-01, which provided funding support for the purchase of the Inveon PET/CT. Funding for the AMF was provided by a Core Support Grant of MSKCC's Experimental Therapeutics Center (to J.G. as Co-PI). NR 37 TC 4 Z9 4 U1 14 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 EI 1530-6992 J9 NANO LETT JI Nano Lett. PD DEC PY 2015 VL 15 IS 12 BP 8032 EP 8043 DI 10.1021/acs.nanolett.5b03370 PG 12 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CY3WC UT WOS:000366339600038 PM 26540670 ER PT J AU Bui, E Anderson, E Goetter, E Campbell, A Barrett, LF Simon, N AF Bui, Eric Anderson, Eric Goetter, Elizabeth Campbell, Allison Barrett, Lisa Feldman Simon, Naomi TI Heightened Sensitivity to Emotional Expressions in Generalized Anxiety Disorder Compared to Social Anxiety Disorder and Controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Emotion Perception; social anxiety; generalized anxiety disorder C1 [Bui, Eric; Anderson, Eric; Goetter, Elizabeth; Campbell, Allison; Barrett, Lisa Feldman; Simon, Naomi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W12 BP S450 EP S450 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700740 ER PT J AU Camprodon, J Zimmerman, J Ellard, K Chau, P Kaur, N Makris, N Fava, M Dougherty, D AF Camprodon, Joan Zimmerman, Jared Ellard, Kristen Chau, Peggy Kaur, Navneet Makris, Nikos Fava, Maurizio Dougherty, Darin TI Electroconvulsive Therapy (ECT) Modulation of Reward Processing and Circuit Dynamics in Depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE electroconvulsive therapy; reward neural circuitry; Depression; Resting State Functional Connectivity; new targets C1 [Camprodon, Joan; Zimmerman, Jared; Ellard, Kristen; Chau, Peggy; Kaur, Navneet; Makris, Nikos; Fava, Maurizio; Dougherty, Darin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W90 BP S499 EP S500 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700816 ER PT J AU Cohen, L Viguera, A Freeman, M Sosinsky, A Moustafa, D Hernandez-Diaz, S AF Cohen, Lee Viguera, Adele Freeman, Marlene Sosinsky, Alexandra Moustafa, Danna Hernandez-Diaz, Sonia TI The National Pregnancy Registry for Atypical Antipsychotics: Effects of Fetal Exposure on Risk for Major Malformations SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Atypical antipsychotics; Women's Mental Health; pregnancy C1 [Cohen, Lee; Viguera, Adele; Freeman, Marlene; Sosinsky, Alexandra; Moustafa, Danna; Hernandez-Diaz, Sonia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T79 BP S321 EP S322 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700548 ER PT J AU Deckersbach, T Franklin, R Peters, A Stange, J Peckham, A Arulpragasam, A Sylvia, L Nierenberg, A Dougherty, D AF Deckersbach, Thilo Franklin, Rachel Peters, Amy Stange, Jonathan Peckham, Andrew Arulpragasam, Amanda Sylvia, Louisa Nierenberg, Andrew Dougherty, Darin TI Neural Predictors of Treatment Response to Psychotherapy for Depression in Bipolar Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Bipolar Disorder; fMRI; Depression C1 [Deckersbach, Thilo; Franklin, Rachel; Peters, Amy; Stange, Jonathan; Peckham, Andrew; Arulpragasam, Amanda; Sylvia, Louisa; Nierenberg, Andrew; Dougherty, Darin] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M91 BP S164 EP S165 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700299 ER PT J AU DeLisi, LE Homann, O Misura, K Nelson, P McDonough, S AF DeLisi, Lynn E. Homann, Oliver Misura, Kira Nelson, Paul McDonough, Stefan TI DNA Sequencing in Multiplex Families with Schizophrenia and Affective Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE DNA sequencing; Multiplex families; schizophrenia; bipolar disorder; missence mutations C1 [DeLisi, Lynn E.; Homann, Oliver; Misura, Kira; Nelson, Paul; McDonough, Stefan] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T163 BP S376 EP S377 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700630 ER PT J AU Ellard, K Zimmerman, J Zorowitz, S Roffman, J Van Dijk, K Dougherty, D Deckersbach, T Camprodon, J AF Ellard, Kristen Zimmerman, Jared Zorowitz, Samuel Roffman, Joshua Van Dijk, Koene Dougherty, Darin Deckersbach, Thilo Camprodon, Joan TI Resting-State Functional Connectivity of Anterior Insula Differentiates Bipolar and Unipolar Depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE mood disorders; Insula Connectivity; Resting State Functional Connectivity C1 [Ellard, Kristen; Zimmerman, Jared; Zorowitz, Samuel; Roffman, Joshua; Van Dijk, Koene; Dougherty, Darin; Deckersbach, Thilo; Camprodon, Joan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Van Dijk, Koene/G-3317-2012 OI Van Dijk, Koene/0000-0001-6137-4282 NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W85 BP S496 EP S497 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700811 ER PT J AU Garza, J Gjeluci, K Leussis, M Deniri, J Petryshen, T AF Garza, Jacob Gjeluci, Klaudio Leussis, Melanie Deniri, Jennifer Petryshen, Tracey TI Ankyrin-3 Bipolar Disorder GWAS Gene Regulates Activity of Dentate Gyrus Granule Neurons and Adult Hippocampal Neurogenesis SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE ankyrin-3; adult neurogenesis; impulsivity; c-Fos C1 [Garza, Jacob; Gjeluci, Klaudio; Leussis, Melanie; Deniri, Jennifer; Petryshen, Tracey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M99 BP S169 EP S170 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700307 ER PT J AU Geller, DA McGuire, JF Orr, SP Small, BJ Gomez, AF Murphy, T Wilhelm, S Pine, D Storch, EA AF Geller, Daniel A. McGuire, Joseph F. Orr, Scott P. Small, Brent J. Gomez, Angelina F. Murphy, Tanya Wilhelm, Sabine Pine, Daniel Storch, Eric A. TI Fear Conditioning and Extinction in Pediatric Obsessive Compulsive Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE OCD; Fear extinction; Fear conditioning; pediatric; CBT C1 [Geller, Daniel A.; McGuire, Joseph F.; Orr, Scott P.; Small, Brent J.; Gomez, Angelina F.; Murphy, Tanya; Wilhelm, Sabine; Pine, Daniel; Storch, Eric A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T22 BP S285 EP S286 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700493 ER PT J AU Gjeluci, K Garza, J Meyer, F Eijsink, V Martens, G Poelmans, G Petryshen, T AF Gjeluci, Klaudio Garza, Jacob Meyer, Francisca Eijsink, Vivian Martens, Gerard Poelmans, Geert Petryshen, Tracey TI The Ankyrin 3 Bipolar Disorder Risk Gene Regulates Neuronal Cytoskeleton Dynamics SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE genetic mouse model; RNA Sequencing; Hippocampus; cytoskeleton C1 [Gjeluci, Klaudio; Garza, Jacob; Meyer, Francisca; Eijsink, Vivian; Martens, Gerard; Poelmans, Geert; Petryshen, Tracey] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T57 BP S307 EP S308 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700526 ER PT J AU Hoeppner, S Schoenfeld, D Cather, C Pachas, G Evins, AE AF Hoeppner, Susanne Schoenfeld, David Cather, Corinne Pachas, Gladys Evins, Anne Eden TI Effects of Maintenance Varenicline on Relapse in Those With and Without Schizophrenia Spectrum and Bipolar Disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE schizophrenia; nicotine; varenicline; maintenance treatment; relapse C1 [Hoeppner, Susanne; Schoenfeld, David; Cather, Corinne; Pachas, Gladys; Evins, Anne Eden] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M235 BP S254 EP S254 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700443 ER PT J AU Ionescu, D Baer, L Shelton, R Papakostas, G AF Ionescu, Dawn Baer, Lee Shelton, Richard Papakostas, George TI Ziprasidone vs. Placebo Augmentation of Escitalopram for Patients with vs. Without Anxious Depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Treatment Resistant Depression; Psychiatric Comorbidity; ziprasidone; mood and anxiety disorders C1 [Ionescu, Dawn; Baer, Lee; Shelton, Richard; Papakostas, George] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M103 BP S172 EP S173 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700311 ER PT J AU Joffe, H Crawford, S Freeman, M Athappilly, G Wolfe, D Kim, S Galvan, T Camuso, J Freid, C Cohen, L Hall, J AF Joffe, Hadine Crawford, Sybil Freeman, Marlene Athappilly, Geena Wolfe, David Kim, Semmie Galvan, Thania Camuso, Julia Freid, Cathryn Cohen, Lee Hall, Janet TI Influence of Reproductive Hormones and Nighttime Hot Flashes on Mood in Depressed Perimenopausal Women Reporting Stressful Life Events SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Depression; Estradiol; Progesterone; Perimenopause; Hot Flashes C1 [Joffe, Hadine; Crawford, Sybil; Freeman, Marlene; Athappilly, Geena; Wolfe, David; Kim, Semmie; Galvan, Thania; Camuso, Julia; Freid, Cathryn; Cohen, Lee; Hall, Janet] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M113 BP S179 EP S180 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700321 ER PT J AU Kucyi, A Hove, M Esterman, M Biederman, J Valera, E AF Kucyi, Aaron Hove, Michael Esterman, Michael Biederman, Joseph Valera, Eve TI Brain Dynamics of Ongoing Attentional Fluctuations in ADHD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE ADHD; behavioral variability; fMRI C1 [Kucyi, Aaron; Hove, Michael; Esterman, Michael; Biederman, Joseph; Valera, Eve] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W26 BP S458 EP S459 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700754 ER PT J AU Liu, HS Wang, DH Buckner, R AF Liu, Hesheng Wang, Danhong Buckner, Randy TI Mapping Functional Connectivity Networks in the Individual SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Resting State Functional Connectivity; obsessive-compulsive disorder; fMRI; individual differences C1 [Liu, Hesheng; Wang, Danhong; Buckner, Randy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T125 BP S352 EP S353 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700593 ER PT J AU Liu, HS AF Liu, Hesheng TI Mapping Functional Connectivity Networks in the Individual SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 [Liu, Hesheng] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA 56.3 BP S99 EP S99 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700197 ER PT J AU Marin, MF Weddington, J Zsido, R Song, HJ Lasko, N Milad, M AF Marin, Marie-France Weddington, Javier Zsido, Rachel Song, Huijing Lasko, Natasha Milad, Mohammed TI Skin Conductance Responses and Neuroimaging Correlates of Fear Conditioning and Fear Renewal in Healthy Controls and Traumatized Individuals With and Without Post-Traumatic Stress Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Trauma exposure; PTSD; fMRI; Conditioned responses; Unconditioned responses C1 [Marin, Marie-France; Weddington, Javier; Zsido, Rachel; Song, Huijing; Lasko, Natasha; Milad, Mohammed] Harvard Univ, Med Sch, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W120 BP S517 EP S518 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700844 ER PT J AU Milad, M AF Milad, Mohammed TI Fear Network Reactivity and Communication in Response to Conditioned Threat Across Anxiety Disorders and PTSD SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 [Milad, Mohammed] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA 6.2 BP S11 EP S11 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700023 ER PT J AU Mischoulon, D AF Mischoulon, David TI Depression, Inflammation, and Omega-3 Fatty Acids SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 [Mischoulon, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA 27.2 BP S46 EP S46 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700091 ER PT J AU Oribe, N Hirano, Y Kanba, S Onitsuka, T Seidman, L Mesholam-Gately, R Woodberry, K Wojcik, J Shenton, M Goldstein, J Niznikiewicz, M McCarley, R Spencer, K AF Oribe, Naoya Hirano, Yoji Kanba, Shigenobu Onitsuka, Toshiaki Seidman, Larry Mesholam-Gately, Raquelle Woodberry, Kristen Wojcik, Joanne Shenton, Martha Goldstein, Jill Niznikiewicz, Margaret McCarley, Robert Spencer, Kevin TI Progressive Reduction of Auditory Evoked Gamma in First Episode Schizophrenia but Not Clinical High Risk Individuals SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE gamma oscillation; first-episode schizophrenia; clinical high risk; EEG C1 [Oribe, Naoya; Hirano, Yoji; Kanba, Shigenobu; Onitsuka, Toshiaki; Seidman, Larry; Mesholam-Gately, Raquelle; Woodberry, Kristen; Wojcik, Joanne; Shenton, Martha; Goldstein, Jill; Niznikiewicz, Margaret; McCarley, Robert; Spencer, Kevin] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T155 BP S371 EP S371 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700622 ER PT J AU Ozburn, A AF Ozburn, Angela TI Effects of Chronic Alcohol Drinking on Circadian Gene Expression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Alcohol; circadian; gene expression; genetic mouse model C1 [Ozburn, Angela] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W239 BP S596 EP S597 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700963 ER PT J AU Papakostas, G Fava, M Mischoulon, D Shelton, R AF Papakostas, George Fava, Maurizio Mischoulon, David Shelton, Richard TI Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Safety and Tolerability SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE augmentation; Treatment Resistant Depression; Atypical antipsychotics C1 [Papakostas, George; Fava, Maurizio; Mischoulon, David; Shelton, Richard] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M65 BP S146 EP S147 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700273 ER PT J AU Roffman, J Tanner, A Eryilmaz, H Silverstein, N Ho, NF Nitenson, A Greve, D Buckner, R Manoach, D Rosen, B Abi-Dargham, A Hooker, J Catana, C AF Roffman, Joshua Tanner, Alexandra Eryilmaz, Hamdi Silverstein, Noah Ho, New Fei Nitenson, Adam Greve, Douglas Buckner, Randy Manoach, Dara Rosen, Bruce Abi-Dargham, Anissa Hooker, Jacob Catana, Ciprian TI Cortical D1 Tone Predicts Network Dynamics of Working Memory: A Simultaneous PET-fMRI Investigation SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Dopamine; PET; fMRI Functional Connectivity; working memory; default network C1 [Roffman, Joshua; Tanner, Alexandra; Eryilmaz, Hamdi; Silverstein, Noah; Ho, New Fei; Nitenson, Adam; Greve, Douglas; Buckner, Randy; Manoach, Dara; Rosen, Bruce; Abi-Dargham, Anissa; Hooker, Jacob; Catana, Ciprian] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T180 BP S388 EP S388 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700647 ER PT J AU Sahay, A AF Sahay, Amar TI Tuning Lineage Homeostasis to Rejuvenate Memory Circuits and Constrain Fear Generalization in Adulthood and Aging SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 [Sahay, Amar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA 10.1 BP S15 EP S15 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700032 ER PT J AU Schuster, R Hoeppner, S Gilman, J Evins, AE AF Schuster, Randi Hoeppner, Susanne Gilman, Jodi Evins, Anne Eden TI Deficient Encoding Leads to Reduced Delayed Recall among Young Adult Marijuana Users SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE cannabis use; Memory and Learning; Adolescence; neuropsychology C1 [Schuster, Randi; Hoeppner, Susanne; Gilman, Jodi; Evins, Anne Eden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA T260 BP S440 EP S441 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700726 ER PT J AU Schwartz, C Kunwar, P Greve, D Block, S Franklin, R Viner, J Moran, L AF Schwartz, Carl Kunwar, Pratap Greve, Douglas Block, Stefanie Franklin, Rachel Viner, Jane Moran, Lyndsey TI High-Reactive Infant Behavior Predicts Reduced Amygdala Volume in Young Adults SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Brain development; infant; Amygdala; individual differences; behavioral inhibition C1 [Schwartz, Carl; Kunwar, Pratap; Greve, Douglas; Block, Stefanie; Franklin, Rachel; Viner, Jane; Moran, Lyndsey] Harvard Univ, Med Schol, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W25 BP S458 EP S458 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700753 ER PT J AU Tregellas, J Wylie, K Smucny, J Olincy, A Legget, K AF Tregellas, Jason Wylie, Korey Smucny, Jason Olincy, Ann Legget, Kristina TI Altered Insula Between-Network Connectivity in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE schizophrenia; Insula; functional connectivity C1 [Tregellas, Jason; Wylie, Korey; Smucny, Jason; Olincy, Ann; Legget, Kristina] Univ Colorado, Denver VA Med Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W179 BP S558 EP S558 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700903 ER PT J AU Van de Bittner, G Riley, M Cao, LX Ehses, J Herrick, S Ricq, E Smith, J Wang, CN Schroeder, F Albers, M Hooker, J AF Van de Bittner, Genevieve Riley, Misha Cao, Luxiang Ehses, Janina Herrick, Scott Ricq, Emily Smith, Jaclyn Wang, Changning Schroeder, Frederick Albers, Mark Hooker, Jacob TI [11C]Neuroflux: In Vivo Measurement of Neuron Population Flux SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE PET Imaging; Neurodevelopment; Aging; Neurodegenerative Disease; Radiotracer C1 [Van de Bittner, Genevieve; Riley, Misha; Cao, Luxiang; Ehses, Janina; Herrick, Scott; Ricq, Emily; Smith, Jaclyn; Wang, Changning; Schroeder, Frederick; Albers, Mark; Hooker, Jacob] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M146 BP S198 EP S199 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700354 ER PT J AU Vervliet, B Marin, MF Song, D Milad, M AF Vervliet, Bram Marin, Marie-France Song, David Milad, Mohammed TI From Relief to Safety: Omission-Induced Activation of the Nucleus Accumbens in Fear Conditioning and Extinction SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Fear conditioning; fear extinction; reward prediction error; Nucleus Accumbens C1 [Vervliet, Bram; Marin, Marie-France; Song, David; Milad, Mohammed] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W13 BP S451 EP S451 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700741 ER PT J AU Vervliet, B AF Vervliet, Bram TI Aversive Learning and Generalization Predict Sub-Clinical Anxiety Symptoms Six Months Later SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol C1 [Vervliet, Bram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA 41.3 BP S72 EP S72 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700143 ER PT J AU Widge, A Zorowitz, S Link, K Tang, W Deckersbach, T Miller, E Dougherty, D AF Widge, Alik Zorowitz, Samuel Link, Katherine Tang, Wei Deckersbach, Thilo Miller, Earl Dougherty, Darin TI Behavioral and Neural Biomarkers of Improved Top-Down Control during Ventral Capsule/Ventral Striatum Deep Brain Stimulation in Major Depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE deep brain stimulation; executive function; Brain Based Markers for Depression; cognitive control C1 [Widge, Alik; Zorowitz, Samuel; Link, Katherine; Tang, Wei; Deckersbach, Thilo; Miller, Earl; Dougherty, Darin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA M90 BP S164 EP S164 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700298 ER PT J AU Zsido, R Cagliero, D Song, HJ Milad, M Marin, MF AF Zsido, Rachel Cagliero, Diana Song, Huijing Milad, Mohammed Marin, Marie-France TI Sex Differences in Fear Conditioning and Extinction in Trauma-Exposed Individuals With and Without Post-Traumatic Stress Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology (ACNP) CY DEC 06-10, 2015 CL Hollywood, FL SP Amer Coll Neuropsychopharmacol DE Extinction memory recall; Trauma exposure; Sex differences; fMRI; Skin conductance response C1 [Zsido, Rachel; Cagliero, Diana; Song, Huijing; Milad, Mohammed; Marin, Marie-France] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 SU 1 MA W118 BP S516 EP S516 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY7OI UT WOS:000366597700842 ER PT J AU Bianchi, DW Chudova, D Sehnert, AJ Bhatt, S Murray, K Prosen, TL Garber, JE Wilkins-Haug, L Vora, NL Warsof, S Goldberg, J Ziainia, T Halks-Miller, M AF Bianchi, Diana W. Chudova, Darya Sehnert, Amy J. Bhatt, Sucheta Murray, Kathryn Prosen, Tracy L. Garber, Judy E. Wilkins-Haug, Louise Vora, Neeta L. Warsof, Stephen Goldberg, James Ziainia, Tina Halks-Miller, Meredith TI Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Bianchi, Diana W.] Tufts Med Ctr, Mother Infant Res Inst, Boston, MA 02111 USA. [Chudova, Darya; Sehnert, Amy J.; Bhatt, Sucheta; Halks-Miller, Meredith] Illumina, Redwood City, CA USA. [Murray, Kathryn] Ctr Genet & Maternal Fetal Med, Springfield, OR USA. [Prosen, Tracy L.] Univ Minnesota, Dept Obstet & Gynecol, Div Maternal Fetal Med, Minneapolis, MN 55455 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wilkins-Haug, Louise] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med & Reprod Genet, Boston, MA 02115 USA. [Vora, Neeta L.] Univ N Carolina, Chapel Hill, NC USA. [Warsof, Stephen] Eastern Virginia Med Sch, Dept Obstet & Gynecol, Div Maternal Fetal Med, Norfolk, VA 23501 USA. [Goldberg, James] San Francisco Perinatal Associates, San Francisco, CA USA. [Ziainia, Tina] Sharp Rees Stealy Med Grp, San Diego, CA USA. RP Bianchi, DW (reprint author), Tufts Med Ctr, Mother Infant Res Inst, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD DEC PY 2015 VL 70 IS 12 BP 744 EP 746 DI 10.1097/01.ogx.0000473791.14913.b7 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CY3RQ UT WOS:000366327900008 ER PT J AU Day, FR Ruth, KS Thompson, DJ Lunetta, KL Pervjakova, N Chasman, DI Stolk, L Finucane, HK Sulem, P Bulik-Sullivan, B Esko, T Johnson, AD Elks, CE Franceschini, N He, C Altmaier, E Brody, JA Franke, LL Huffman, JE Keller, MF McArdle, PF Nutile, T Porcu, E Robino, A Rose, LM Schick, UM Smith, JA Teumer, A Traglia, M Vuckovic, D Yao, J Zhao, W Albrecht, E Amin, N Corre, T Hottenga, JJ Mangino, M Smith, AV Tanaka, T Abecasis, GR Andrulis, IL Anton-Culver, H Antoniou, AC Arndt, V Arnold, AM Barbieri, C Beckmann, MW Beeghly-Fadiel, A Benitez, J Bernstein, L Bielinski, SJ Blomqvist, C Boerwinkle, E Bogdanova, NV Bojesen, SE Bolla, MK Borresen-Dale, AL Boutin, TS Brauch, H Brenner, H Bruning, T Burwinkel, B Campbell, A Campbell, H Chanock, SJ Chapman, JR Chen, YDI Chenevix-Trench, G Couch, FJ Coviello, AD Cox, A Czene, K Darabi, H De Vivo, I Demerath, EW Dennis, J Devilee, P Dork, T dos-Santos-Silva, I Dunning, AM Eicher, JD Fasching, PA Faul, JD Figueroa, J Flesch-Janys, D Gandin, I Garcia, ME Garcia-Closas, M Giles, GG Girotto, GG Goldberg, MS Gonzalez-Neira, A Goodarzi, MO Grove, ML Gudbjartsson, DF Guenel, P Guo, XQ Haiman, CA Hall, P Hamann, U Henderson, BE Hocking, LJ Hofman, A Homuth, G Hooning, MJ Hopper, JL Hu, FB Huang, JY Humphreys, K Hunter, DJ Jakubowska, A Jones, SE Kabisch, M Karasik, D Knight, JA Kolcic, I Kooperberg, C Kosma, VM Kriebel, J Kristensen, V Lambrechts, D Langenberg, C Li, JM Li, X Lindstrom, S Liu, YM Luan, JA Lubinski, J Magi, R Mannermaa, A Manz, J Margolin, S Marten, J Martin, NG Masciullo, C Meindl, A Michailidou, K Mihailov, E Milani, L Milne, RL Muller-Nurasyid, M Nalls, M Neale, BM Nevanlinna, H Neven, P Newman, AB Nordestgaard, BG Olson, JE Padmanabhan, S Peterlongo, P Peters, U Petersmann, A Peto, J Pharoah, PDP Pirastu, NN Pirie, A Pistis, G Polasek, O Porteous, D Psaty, BM Pylkas, K Radice, P Raffel, LJ Rivadeneira, F Rudan, I Rudolph, A Ruggiero, D Sala, CF Sanna, S Sawyer, EJ Schlessinger, D Schmidt, MK Schmidt, F Schmutzler, RK Schoemaker, MJ Scott, RA Seynaeve, CM Simard, J Sorice, R Southey, MC Stockl, D Strauch, K Swerdlow, A Taylor, KD Thorsteinsdottir, U Toland, AE Tomlinson, I Truong, T Tryggvadottir, L Turner, ST Vozzi, D Wang, Q Wellons, M Willemsen, G Wilson, JF Winqvist, R Wolffenbuttel, BBHR Wright, AF Yannoukakos, D Zemunik, T Zheng, W Zygmunt, M Bergmann, S Boomsma, DI Buring, JE Ferrucci, L Montgomery, GW Gudnason, V Spector, TD van Duijn, CM Alizadeh, BZ Ciullo, M Crisponi, L Easton, DF Gasparini, PP Gieger, C Harris, TB Hayward, C Kardia, SLR Kraft, P McKnight, B Metspalu, A Morrison, AC Reiner, AP Ridker, PM Rotter, JI Toniolo, D Uitterlinden, AG Ulivi, S Volzke, H Wareham, NJ Weir, DR Yerges-Armstrong, LM Price, AL Stefansson, K Visser, JA Ong, KK Chang-Claude, J Murabito, JM Perry, JRB Murray, A AF Day, Felix R. Ruth, Katherine S. Thompson, Deborah J. Lunetta, Kathryn L. Pervjakova, Natalia Chasman, Daniel I. Stolk, Lisette Finucane, Hilary K. Sulem, Patrick Bulik-Sullivan, Brendan Esko, Tonu Johnson, Andrew D. Elks, Cathy E. Franceschini, Nora He, Chunyan Altmaier, Elisabeth Brody, Jennifer A. Franke, Lude L. Huffman, Jennifer E. Keller, Margaux F. McArdle, Patrick F. Nutile, Teresa Porcu, Eleonora Robino, Antonietta Rose, Lynda M. Schick, Ursula M. Smith, Jennifer A. Teumer, Alexander Traglia, Michela Vuckovic, Dragana Yao, Jie Zhao, Wei Albrecht, Eva Amin, Najaf Corre, Tanguy Hottenga, Jouke-Jan Mangino, Massimo Smith, Albert V. Tanaka, Toshiko Abecasis, Goncalo R. Andrulis, Irene L. Anton-Culver, Hoda Antoniou, Antonis C. Arndt, Volker Arnold, Alice M. Barbieri, Caterina Beckmann, Matthias W. Beeghly-Fadiel, Alicia Benitez, Javier Bernstein, Leslie Bielinski, Suzette J. Blomqvist, Carl Boerwinkle, Eric Bogdanova, Natalia V. Bojesen, Stig E. Bolla, Manjeet K. Borresen-Dale, Anne-Lise Boutin, Thibaud S. Brauch, Hiltrud Brenner, Hermann Bruening, Thomas Burwinkel, Barbara Campbell, Archie Campbell, Harry Chanock, Stephen J. Chapman, J. Ross Chen, Yii-Der Ida Chenevix-Trench, Georgia Couch, Fergus J. Coviello, Andrea D. Cox, Angela Czene, Kamila Darabi, Hatef De Vivo, Immaculata Demerath, Ellen W. Dennis, Joe Devilee, Peter Doerk, Thilo dos-Santos-Silva, Isabel Dunning, Alison M. Eicher, John D. Fasching, Peter A. Faul, Jessica D. Figueroa, Jonine Flesch-Janys, Dieter Gandin, Ilaria Garcia, Melissa E. Garcia-Closas, Montserrat Giles, Graham G. Girotto, Giorgia G. Goldberg, Mark S. Gonzalez-Neira, Anna Goodarzi, Mark O. Grove, Megan L. Gudbjartsson, Daniel F. Guenel, Pascal Guo, Xiuqing Haiman, Christopher A. Hall, Per Hamann, Ute Henderson, Brian E. Hocking, Lynne J. Hofman, Albert Homuth, Georg Hooning, Maartje J. Hopper, John L. Hu, Frank B. Huang, Jinyan Humphreys, Keith Hunter, David J. Jakubowska, Anna Jones, Samuel E. Kabisch, Maria Karasik, David Knight, Julia A. Kolcic, Ivana Kooperberg, Charles Kosma, Veli-Matti Kriebel, Jennifer Kristensen, Vessela Lambrechts, Diether Langenberg, Claudia Li, Jingmei Li, Xin Lindstroem, Sara Liu, Yongmei Luan, Jian'an Lubinski, Jan Maegi, Reedik Mannermaa, Arto Manz, Judith Margolin, Sara Marten, Jonathan Martin, Nicholas G. Masciullo, Corrado Meindl, Alfons Michailidou, Kyriaki Mihailov, Evelin Milani, Lili Milne, Roger L. Mueller-Nurasyid, Martina Nalls, Michael Neale, Benjamin M. Nevanlinna, Heli Neven, Patrick Newman, Anne B. Nordestgaard, Borge G. Olson, Janet E. Padmanabhan, Sandosh Peterlongo, Paolo Peters, Ulrike Petersmann, Astrid Peto, Julian Pharoah, Paul D. P. Pirastu, Nicola N. Pirie, Ailith Pistis, Giorgio Polasek, Ozren Porteous, David Psaty, Bruce M. Pylkaes, Katri Radice, Paolo Raffel, Leslie J. Rivadeneira, Fernando Rudan, Igor Rudolph, Anja Ruggiero, Daniela Sala, Cinzia F. Sanna, Serena Sawyer, Elinor J. Schlessinger, David Schmidt, Marjanka K. Schmidt, Frank Schmutzler, Rita K. Schoemaker, Minouk J. Scott, Robert A. Seynaeve, Caroline M. Simard, Jacques Sorice, Rossella Southey, Melissa C. Stoeckl, Doris Strauch, Konstantin Swerdlow, Anthony Taylor, Kent D. Thorsteinsdottir, Unnur Toland, Amanda E. Tomlinson, Ian Truong, Therese Tryggvadottir, Laufey Turner, Stephen T. Vozzi, Diego Wang, Qin Wellons, Melissa Willemsen, Gonneke Wilson, James F. Winqvist, Robert Wolffenbuttel, Bruce B. H. R. Wright, Alan F. Yannoukakos, Drakoulis Zemunik, Tatijana Zheng, Wei Zygmunt, Marek Bergmann, Sven Boomsma, Dorret I. Buring, Julie E. Ferrucci, Luigi Montgomery, Grant W. Gudnason, Vilmundur Spector, Tim D. van Duijn, Cornelia M. Alizadeh, Behrooz Z. Ciullo, Marina Crisponi, Laura Easton, Douglas F. Gasparini, Paolo P. Gieger, Christian Harris, Tamara B. Hayward, Caroline Kardia, Sharon L. R. Kraft, Peter McKnight, Barbara Metspalu, Andres Morrison, Alanna C. Reiner, Alex P. Ridker, Paul M. Rotter, Jerome I. Toniolo, Daniela Uitterlinden, Andre G. Ulivi, Sheila Voelzke, Henry Wareham, Nicholas J. Weir, David R. Yerges-Armstrong, Laura M. Price, Alkes L. Stefansson, Kari Visser, Jenny A. Ong, Ken K. Chang-Claude, Jenny Murabito, Joanne M. Perry, John R. B. Murray, Anna CA PRACTICAL Consortium kConFab Investigators AOCS Investigators Generation Scotland EPIC-Interact Consortium LifeLines Cohort Study TI Large-Scale Genomic Analyses Link Reproductive Aging to Hypothalamic Signaling, Breast Cancer Susceptibility, and BRCA1-Mediated DNA Repair EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Day, Felix R.; Elks, Cathy E.; Langenberg, Claudia; Luan, Jian'an; Scott, Robert A.; Wareham, Nicholas J.; Ong, Ken K.; Perry, John R. B.] Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Ruth, Katherine S.; Jones, Samuel E.; Murray, Anna] Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England. [Thompson, Deborah J.; Antoniou, Antonis C.; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Pharoah, Paul D. P.; Pirie, Ailith; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lunetta, Kathryn L.; Johnson, Andrew D.; Huffman, Jennifer E.; Eicher, John D.; Murabito, Joanne M.] NHLBI, Framingham, MA USA. [Lunetta, Kathryn L.; Johnson, Andrew D.; Huffman, Jennifer E.; Eicher, John D.; Murabito, Joanne M.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Pervjakova, Natalia; Esko, Tonu; Maegi, Reedik; Mihailov, Evelin; Milani, Lili; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Pervjakova, Natalia] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Chasman, Daniel I.; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Chasman, Daniel I.; Karasik, David; Buring, Julie E.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging & Natl Genom In, Leiden, Netherlands. [Finucane, Hilary K.; De Vivo, Immaculata; Hu, Frank B.; Hunter, David J.; Li, Xin; Lindstroem, Sara; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Finucane, Hilary K.] MA Inst Technol, Dept Math, Cambridge, MA USA. [Sulem, Patrick; Gudbjartsson, Daniel F.; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet Amgen Inc, Reykjavik, Iceland. [Bulik-Sullivan, Brendan; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Bulik-Sullivan, Brendan; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bulik-Sullivan, Brendan; Neale, Benjamin M.] Broad Inst, Med & Populat Genet, Cambridge, MA USA. [Esko, Tonu] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Esko, Tonu; Hunter, David J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [He, Chunyan] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA. [He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Altmaier, Elisabeth; Kriebel, Jennifer; Manz, Judith; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Neuherberg, Germany. [Altmaier, Elisabeth; Albrecht, Eva; Mueller-Nurasyid, Martina; Strauch, Konstantin; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Altmaier, Elisabeth; Kriebel, Jennifer; Manz, Judith; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Franke, Lude L.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Huffman, Jennifer E.; Boutin, Thibaud S.; Marten, Jonathan; Wilson, James F.; Wright, Alan F.; Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Keller, Margaux F.] Merck Pharmaceut, Boston, MA USA. [McArdle, Patrick F.; Yerges-Armstrong, Laura M.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized Med, Baltimore, MD 21201 USA. [Nutile, Teresa; Ruggiero, Daniela; Sorice, Rossella; Ciullo, Marina] Inst Genet & Biophys, Natl Res Council, Naples, Italy. [Porcu, Eleonora; Pistis, Giorgio; Sanna, Serena; Crisponi, Laura] Inst Genet & Biomed Res, Natl Res Council, Cagliari, Italy. [Porcu, Eleonora; Pistis, Giorgio] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. [Porcu, Eleonora; Abecasis, Goncalo R.; Pistis, Giorgio] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Robino, Antonietta; Vuckovic, Dragana; Barbieri, Caterina; Gandin, Ilaria; Pirastu, Nicola N.; Vozzi, Diego; Gasparini, Paolo P.; Ulivi, Sheila] Hospitalisat & Hlth Care BurloGarofolo, Inst Maternal & Child Hlth, Sci Inst Res, Trieste, Italy. [Schick, Ursula M.; Kooperberg, Charles; Peters, Ulrike; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Smith, Jennifer A.; Zhao, Wei; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Teumer, Alexander; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Traglia, Michela; Barbieri, Caterina; Masciullo, Corrado; Sala, Cinzia F.; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Vuckovic, Dragana; Gandin, Ilaria; Girotto, Giorgia G.; Pirastu, Nicola N.; Gasparini, Paolo P.] Univ Trieste, Dept Clin Med Sci Surg & Hlth, Trieste, Italy. [Yao, Jie; Chen, Yii-Der Ida; Guo, Xiuqing; Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Amin, Najaf; Hofman, Albert; Rivadeneira, Fernando; van Duijn, Cornelia M.; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Corre, Tanguy; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland. [Corre, Tanguy; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland. 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[Guenel, Pascal; Truong, Therese] Univ Paris Sud, UMRS 1018, Villejuif, France. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hamann, Ute; Kabisch, Maria] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany. [Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland. [Homuth, Georg; Schmidt, Frank] Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Hooning, Maartje J.; Seynaeve, Caroline M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Huang, Jinyan] Shanghai Jiao Tong Univ, RuiJin Hosp, Shanghai Inst Hematol, Sch Med,State Key Lab Med Genom, Shanghai 200030, Peoples R China. [Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Karasik, David] Hebrew Senior Life Inst Aging Res, Boston, MA USA. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Kolcic, Ivana; Polasek, Ozren; Zemunik, Tatijana] Univ Split, Fac Med, Split, Croatia. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Kuopio, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland. [Kriebel, Jennifer; Stoeckl, Doris] German Ctr Diabet Res, Neuherberg, Germany. [Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA. [Margolin, Sara] Karolinska Inst, Dept Oncology Pathol, Stockholm, Sweden. [Martin, Nicholas G.; Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Meindl, Alfons] Tech Univ Munich, Div Obstet & Gynecol, D-80290 Munich, Germany. [Mueller-Nurasyid, Martina] Ludwig Maximilians Univ Munchen, Dept Med, Munich, Germany. [Mueller-Nurasyid, Martina] German Ctr Cardiovascular Res DZHK, Partner site Munich Heart Alliance, Munich, Germany. [Nalls, Michael] Natl Inst Aging, Neurogenet Lab, Bethesda, MD USA. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Neven, Patrick] Univ Hosp Leuven, Dept Oncol, Leuven, Belgium. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [Padmanabhan, Sandosh] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci,Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol IFOM, Milan, Italy. [Petersmann, Astrid] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Psaty, Bruce M.; Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Pylkaes, Katri; Winqvist, Robert] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland. [Pylkaes, Katri; Winqvist, Robert] Ctr NordLab, Northen Finland Lab, Lab Canc Genet & Tumor Biol, Oulu, Finland. [Radice, Paolo] Fdn IRCCS, Ist Nazionaledci Tumori, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy. [Raffel, Leslie J.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Raffel, Leslie J.] Cedars Sinai Med Ctr, UCLA Clin & Translat Sci Inst, Los Angeles, CA 90048 USA. [Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Sawyer, Elinor J.] Guys Hosp, Kings Coll London, Res Oncol, London SE1 9RT, England. [Schlessinger, David] Natl Inst Aging, Intramural Res Program, Baltimore, MD USA. [Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Schmutzler, Rita K.] Univ Hosp Cologne, Div Mol Gyneco Oncol, Dept Gynecol & Obstet, Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany. [Simard, Jacques] Univ Laval, Ctr Hosp Univ, Quebec Res Ctr, Quebec City, PQ, Canada. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Strauch, Konstantin] Univ Munich, Inst Med Informat Biometry & Epidemiol, Genet Epidemiol, Munich, Germany. [Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Toland, Amanda E.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Tomlinson, Ian] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England. [Tryggvadottir, Laufey] Iceland Canc Registry, Reykjavik, Iceland. [Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA. [Wellons, Melissa] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Wolffenbuttel, Bruce B. H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Wolffenbuttel, Bruce B. H. R.] Univ Groningen, Univ Med Ctr Groningen, Life Lines Cohort Study & Biobank, Groningen, Netherlands. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Inst Radioisotopes & Radiodiagnost Prod, Mol Diagnost Lab, Athens, Greece. [Zygmunt, Marek] Univ Med Greifswald, Dept Obstet & Gynecol, Greifswald, Germany. [Alizadeh, Behrooz Z.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Day, FR (reprint author), Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England. RI Knight, Julia/A-6843-2012; Li, Jingmei/I-2904-2012; Bielinski, Suzette/A-2238-2009; Bruning, Thomas/G-8120-2015; Franke, Lude/P-7036-2016; Brenner, Hermann/B-4627-2017; Polasek, Ozren/B-6002-2011; Kolcic, Ivana/E-2713-2017 OI Li, Jingmei/0000-0001-8587-7511; Bielinski, Suzette/0000-0002-2905-5430; Bruning, Thomas/0000-0001-9560-5464; Franke, Lude/0000-0002-5159-8802; Brenner, Hermann/0000-0002-6129-1572; Polasek, Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052 FU Cancer Research UK [16561] NR 0 TC 0 Z9 0 U1 4 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7828 EI 1533-9866 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD DEC PY 2015 VL 70 IS 12 BP 758 EP 762 DI 10.1097/01.ogx.0000473766.71624.99 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CY3RQ UT WOS:000366327900016 ER PT J AU Cifter, G Chin, J Cifter, F Altundal, Y Sinha, N Sajo, E Ngwa, W AF Cifter, G. Chin, J. Cifter, F. Altundal, Y. Sinha, N. Sajo, E. Ngwa, W. TI Targeted radiotherapy enhancement during electronic brachytherapy of accelerated partial breast irradiation (APBI) using controlled release of gold nanoparticles SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Article DE APBI; Dose enhancement; Gold; Nanoparticles; 50 kVp; Xoft electronic brachytherapy ID RADIATION-THERAPY; CELLULAR UPTAKE; CANCER; MASTECTOMY; TOXICITY; SURVIVAL; TRIAL AB Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy. (C) 2015 Published by Elsevier Ltd on behalf of Associazione Italiana di Fisica Medica. C1 [Cifter, G.; Chin, J.; Altundal, Y.; Sajo, E.; Ngwa, W.] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA 01854 USA. [Cifter, G.; Cifter, F.; Ngwa, W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. [Sinha, N.] Wentworth Inst Technol, Dept Sci, Boston, MA 02115 USA. RP Cifter, G (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol,Dana Farber Canc Inst, 450 Brookline Ave,Jimmy Fund Bldg, Boston, MA 02215 USA. EM gizemcifter@gmail.com FU NIH/NCI [1 K01 CA172478-01] FX The authors acknowledge funding support from NIH/NCI 1 K01 CA172478-01 NR 24 TC 7 Z9 7 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 EI 1724-191X J9 PHYS MEDICA JI Phys. Medica PD DEC PY 2015 VL 31 IS 8 BP 1070 EP 1074 DI 10.1016/j.ejmp.2015.07.138 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CY8LR UT WOS:000366660400030 PM 26404139 ER PT J AU Sitek, A Celler, AM AF Sitek, Arkadiusz Celler, Anna M. TI Limitations of Poisson statistics in describing radioactive decay SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS LA English DT Article DE Radioactive decay; Statistics; Poisson distribution ID DENSITY-FUNCTION AB Objectives: The assumption that nuclear decays are governed by Poisson statistics is an approximation. This approximation becomes unjustified when data acquisition times longer than or even comparable with the half-lives of the radioisotope in the sample are considered. In this work, the limits of the Poisson-statistics approximation are investigated. Methods: The formalism for the statistics of radioactive decay based on binomial distribution is derived. The theoretical factor describing the deviation of variance of the number of decays predicated by the Poisson distribution from the true variance is defined and investigated for several commonly used radiotracers such as F-18, O-15, Rb-82, N-13, Tc-99m, I-123, and Tl-201. Results: The variance of the number of decays estimated using the Poisson distribution is significantly different than the true variance for a 5-minute observation time of C-11, O-15, N-13, and Rb-82. Conclusions: Durations of nuclear medicine studies often are relatively long; they may be even a few times longer than the half-lives of some short-lived radiotracers. Our study shows that in such situations the Poisson statistics is unsuitable and should not be applied to describe the statistics of the number of decays in radioactive samples. However, the above statement does not directly apply to counting statistics at the level of event detection. Low sensitivities of detectors which are used in imaging studies make the Poisson approximation near perfect. (C) 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. C1 [Sitek, Arkadiusz] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Dept Radiol, Boston, MA 01721 USA. [Sitek, Arkadiusz] Harvard Univ, Sch Med, Boston, MA 01721 USA. [Celler, Anna M.] Univ British Columbia, Med Imaging Res Grp, Dept Radiol, Vancouver, BC V5Z 1L8, Canada. [Celler, Anna M.] Vancouver Coastal Hlth Res Inst, Vancouver, BC V5Z 1L8, Canada. RP Sitek, A (reprint author), Philips Res North Amer, 2 Canal Pk, Cambridge, MA 02141 USA. EM arkadiusz.sitek@philips.com OI Sitek, Arkadiusz/0000-0002-0677-4002 NR 13 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1120-1797 EI 1724-191X J9 PHYS MEDICA JI Phys. Medica PD DEC PY 2015 VL 31 IS 8 BP 1105 EP 1107 DI 10.1016/j.ejmp.2015.08.015 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CY8LR UT WOS:000366660400036 PM 26508015 ER PT J AU Hennessy, S Kurichi, JE Pan, Q Streim, JE Bogner, HR Xie, DW Stineman, MG AF Hennessy, Sean Kurichi, Jibby E. Pan, Qiang Streim, Joel E. Bogner, Hillary R. Xie, Dawei Stineman, Margaret G. TI Disability Stage is an Independent Risk Factor for Mortality in Medicare Beneficiaries Aged 65 Years and Older SO PM&R LA English DT Article ID COMMUNITY-DWELLING PERSONS; ACTIVITY LIMITATION; ELDERLY-PEOPLE; HOME ACCESSIBILITY; FUNCTIONAL STATUS; HEALTH-CARE; CASE-MIX; LIFE; POPULATION; HOSPITALIZATION AB Background: Stages of activity limitation based on activities of daily living (ADLs) and instrumental activities of daily living (IADLs) have been found to predict mortality in persons aged 70 years and older but have not been examined in Medicare beneficiaries aged 65 years and older using data that are routinely collected. Objective: To examine the association between functional stages based on items of ADLs and IADLs with 3-year mortality in Medicare beneficiaries aged 65 years and older, accounting for baseline sociodemographics, health status, smoking, subjective health, and psychological well-being. Design: A cohort study using the Medicare Current Beneficiary Survey (MCBS) and associated health care utilization data. Setting: Community administered survey. Participants: The study included 9698 Medicare beneficiaries aged 65 years and older who participated in the MCBS in 2005-2007. Main Outcome Measures: Death within 3 years of cohort entry. Results: The overall mortality rate was 3.6 per 100 person years, and 3-year cumulative mortality was 10.3%. Unadjusted 3-year mortality was monotonically associated with both ADL stage and IADL stage. Adjusted 3-year mortality was associated with ADL and IADL stages, except that in some models the hazard ratio for stage III (which includes persons with atypical activity limitation patterns) was numerically lower than that for stage II. Conclusion: We found nearly monotonic relationships between ADL and IADL stage and adjusted 3-year mortality. These findings could aid in the development of population health approaches and metrics for evaluating the success of alternative economic, social, or health policies on the longevity of older adults with activity limitations. C1 [Hennessy, Sean; Kurichi, Jibby E.; Pan, Qiang; Xie, Dawei] Univ Penn, Perelman Sch Med, Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Hennessy, Sean] Univ Penn, Ctr Pharmacoepidemiol Res & Training, Philadelphia, PA 19104 USA. [Streim, Joel E.] Univ Penn, Perelman Sch Med, Geriatr Psychiat Sect, Dept Psychiat, Philadelphia, PA 19104 USA. [Streim, Joel E.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Bogner, Hillary R.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Stineman, Margaret G.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. RP Hennessy, S (reprint author), Univ Penn, Perelman Sch Med, Clin Epidemiol & Biostat, 803 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM hennessy@upenn.edu FU National Institutes of Health [R01AG040105, R01HD074756, R01AG025152, R01DK102694] FX This research was supported by the National Institutes of Health (R01AG040105, R01HD074756, R01AG025152, and R01DK102694). Neither the National Institutes of Health nor the Centers for Medicare and Medicaid Services (which provided the data) played a role in the design or conduct of the study, in the analysis or interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 27 TC 6 Z9 6 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD DEC PY 2015 VL 7 IS 12 BP 1215 EP 1225 DI 10.1016/j.pmrj.2015.05.014 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CZ1FP UT WOS:000366851600003 PM 26003869 ER PT J AU Suri, P Fry, AL Gellhorn, AC AF Suri, Pradeep Fry, Adrielle L. Gellhorn, Alfred C. TI Do Muscle Characteristics on Lumbar Spine Magnetic Resonance Imaging or Computed Tomography Predict Future Low Back Pain, Physical Function, or Performance? A Systematic Review SO PM&R LA English DT Review ID CROSS-SECTIONAL AREA; PSYCHOPHYSICAL LIFTING STRENGTH; OLDER-ADULTS; PARASPINAL MUSCLES; MULTIFIDUS; ENDURANCE; SIZE; ASSOCIATION; IMPROVEMENT; DISABILITY AB Objective: To determine whether lumbar muscle characteristics on magnetic resonance imaging (MRI) or computed tomography (CT) can inform clinicians as to the course of future low back pain (LBP), functional limitations, or physical performance, in adults with or without LBP. Type: Systematic review. Literature Review: We searched PubMed, Embase, and CINAHL through October 2014 for articles published in English in which authors assessed lumbar muscle characteristics on conventional MRI/CT as predictors of future LBP, functional limitations, or physical performance in adults. Studies with only postsurgical subjects were excluded. Our search identified 3554 articles, of which 6 observational cohort studies were included in the final review. Methodology: We used the Newcastle Ottawa Scale to evaluate potential bias. Data were extracted on study design, study population, sample size, participant characteristics, details of MRI/CT assessments, interventions, study outcomes, analysis methods, and study results. Because of heterogeneity between studies, we conducted a qualitative evidence synthesis. Synthesis: Among high-quality studies, there was limited evidence that, for individuals with or without LBP, greater MRI-detected multifidus cross-sectional area at L5-S1 predicted greater LBP intensity at 1-year follow-up, lesser erector spinae fat infiltration (FI) at L5-S1 predicted greater LBP intensity at 15-year follow-up, and greater erector spinae side-to-side FI asymmetry at L3-L4 predicted lower LBP frequency at 15-year follow-up; however, there was also limited evidence that all other MRI-detected paraspinal muscle characteristics examined were not predictive of LBP incidence, prevalence, frequency, or intensity at follow-up durations ranging from 1 to 15 years. There was limited evidence that greater CT-detected trunk muscle FI predicted worse physical performance in older adults at 3-year follow-up, but that trunk muscle cross-sectional area did not. Conclusion: Few lumbar muscle characteristics have limited evidence for an association with future LBP and physical performance outcomes, and the vast majority have limited evidence for having no association with such outcomes. C1 [Suri, Pradeep] VA Puget Sound Healthcare Syst, Div Rehabil Care Serv, ERIC, Seattle, WA 98108 USA. [Suri, Pradeep; Fry, Adrielle L.; Gellhorn, Alfred C.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Gellhorn, Alfred C.] Weill Cornell Med Coll, Div Rehabil Med, New York, NY USA. RP Suri, P (reprint author), VA Puget Sound Healthcare Syst, Div Rehabil Care Serv, ERIC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM pradeep.suri@va.gov FU VA Puget Sound Health Care System FX Dr. Suri's participation is this study was funded by VA Puget Sound Health Care System. The authors report no financial arrangements that may represent a possible conflict of interest with the work presented. A portion of this research was submitted as an abstract to the American Association of Academic Physiatrists Annual Meeting 2015, in San Antonio, TX. NR 36 TC 4 Z9 4 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD DEC PY 2015 VL 7 IS 12 BP 1269 EP 1281 DI 10.1016/j.pmrj.2015.04.016 PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CZ1FP UT WOS:000366851600009 PM 25952771 ER PT J AU Lee, LO Aldwin, CM Kubzansky, LD Chen, E Mroczek, DK Wang, JM Spiro, A AF Lee, Lewina O. Aldwin, Carolyn M. Kubzansky, Laura D. Chen, Edith Mroczek, Daniel K. Wang, Joyce M. Spiro, Avron, III TI Do Cherished Children Age Successfully? Longitudinal Findings From the Veterans Affairs Normative Aging Study SO PSYCHOLOGY AND AGING LA English DT Article DE early adversity; hedonic well-being; eudaimonic well-being; successful aging; latent class analysis ID ADVERSE CHILDHOOD EXPERIENCES; PERCEIVED SOCIAL SUPPORT; WELL-BEING SCALES; RETROSPECTIVE REPORTS; MENTAL-HEALTH; LIFE-COURSE; OLD-AGE; SUPPRESSOR VARIABLES; SOCIOECONOMIC-STATUS; STRUCTURAL MODELS AB Although early adversity has been linked to worse mental and physical health in adulthood, few studies have investigated the pathways through which positive and negative dimensions of early experiences can jointly influence psychological well-being in later life. This study examined: (a) profiles of early experiences across multiple domains, (b) the relations of these profiles to hedonic and eudaimonic well-being in later life, and (c) whether midlife social support mediated these relations. We first conducted latent class analysis of early experiences using data from 1,076 men in the VA Normative Aging Study who completed the Childhood Experiences Scale (age: M = 69, SD = 7). Analyses yielded 3 profiles of early experiences, labeled as cherished (strong support and some losses), harshly disciplined (harsh parental discipline, low positive reinforcement, and nonnormative stressors), and ordinary (few stressors and low parental attention). Next, we applied structural equation modeling to data on a subset of this sample assessed 7 years later on hedonic and eudaimonic well-being (n = 496; age: M = 76, SD = 7). In general, the cherished group reported stronger qualitative social support in midlife than the harshly disciplined and ordinary groups, which in turn was related to greater hedonic (life satisfaction, positive affect) and eudaimonic (competence, positive relations with others) well-being in later life. The cherished group also reported higher autonomy than the ordinary group, but this association was independent of midlife social support. Our findings suggest that experiencing adversity in the context of a nurturing early environment can promote successful aging through the maintenance of supportive relationships in midlife. C1 [Lee, Lewina O.; Wang, Joyce M.; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Lee, Lewina O.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Lee, Lewina O.] Boston Healthcare Syst, Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder NCPTSD, Boston, MA USA. [Aldwin, Carolyn M.] Oregon State Univ, Coll Publ Hlth & Human Sci, Sch Social & Behav Hlth Sci, Human Dev & Family Sci, Corvallis, OR 97331 USA. [Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Cambridge, MA 02138 USA. [Chen, Edith; Mroczek, Daniel K.] Northwestern Univ, Dept Psychol, Evanston, IL USA. [Chen, Edith] Northwestern Univ, Inst Policy Res, Chicago, IL 60611 USA. [Mroczek, Daniel K.] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Wang, Joyce M.] Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Med, Dept Hlth Policy & Hlth Serv Res, Goldman Sch Dent Med, Boston, MA 02118 USA. [Spiro, Avron, III] Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Spiro, Avron, III] Boston Healthcare Syst, Dept Vet Affairs, NC PTSD, Boston, MA USA. RP Lee, LO (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 151-C, Boston, MA 02446 USA. EM lewina@bu.edu FU National Institutes of Health [R01-AG032037, R01-AG018436]; Clinical Science Research and Development Service, U. S. Department of Veterans Affairs; BU/VA Boston CTSI Pilot Grant; VA Cooperative Studies Program/Epidemiological Research Centers FX This study was supported by National Institutes of Health grants R01-AG032037, R01-AG018436, a Senior Research Career Scientist Award from the Clinical Science Research and Development Service, U. S. Department of Veterans Affairs to Avron Spiro, and a BU/VA Boston CTSI Pilot Grant to Lewina O. Lee. The VA Normative Aging Study is a research component of MAVERIC and is supported by the VA Cooperative Studies Program/Epidemiological Research Centers. The views expressed in this article are those of the authors and do not necessarily represent the views of the U. S. Department of Veterans Affairs or other support institutions. NR 112 TC 0 Z9 0 U1 5 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 EI 1939-1498 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 2015 VL 30 IS 4 BP 894 EP 910 DI 10.1037/pag0000050 PG 17 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA CZ0TY UT WOS:000366820100015 PM 26436456 ER PT J AU Li, XB Black, M Xia, SG Zhan, CY Bertisch, HC Branch, CA DeLisi, LE AF Li, Xiaobo Black, Margaret Xia, Shugao Zhan, Chenyang Bertisch, Hilary C. Branch, Craig A. DeLisi, Lynn E. TI Subcortical structure alterations impact language processing in individuals with schizophrenia and those at high genetic risk SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Structural MRI; Schizophrenia; Genetic high-risk; Subcortical structures; Language processing ID SCHIZOAFFECTIVE DISORDER; BIPOLAR DISORDER; PATHWAYS; AMYGDALA; FMRI AB Objective: Cortical structural and functional anomalies have been found to associate with language impairments in both schizophrenia patients and genetic high risk individuals for developing schizophrenia. However, subcortical structures that contribute to language processing haven't been well studied in this population, and thus became the main objective of this study. Method: We examined structural MRI data from 20 patients with schizophrenia, 21 individuals at genetic high risk, and 48 controls. Surface shape and volume differences of 6 subcortical structures that are involved in language processing, including nuclei pallidum, putamen, caudate, amygdala, thalamus, and hippocampus from both hemispheres, were compared between groups. Performance scores of language-associated cognitive tests were obtained to identify relationships of subcortical structures to language-related behaviors. Results: Significantly reduced volumes of both the left and right side caudate nuclei, thalami and right side amygdala were shown in patients when compared with controls. Very interestingly, the high risk group demonstrated significantly increased correlations between volumes of left side pallidum nucleus and bilateral thalami and language-related cognitive test scores when compared to controls. Conclusions: This study furthers our understanding of subcortical structural alterations in schizophrenia and high risk individuals, and suggests the contribution of subcortical structures to the language impairments that may serve as an early sign for impending development of schizophrenia. (C) 2015 Elsevier B.V. All rights reserved. C1 [Li, Xiaobo] New Jersey Inst Technol, Dept Biomed Engn, Newark, NJ 07102 USA. [Li, Xiaobo; Black, Margaret; Xia, Shugao; Zhan, Chenyang; Branch, Craig A.] Gruss Magnet Resonance Res Ctr, Bronx, NY USA. [Li, Xiaobo; Branch, Craig A.] Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. [Bertisch, Hilary C.; DeLisi, Lynn E.] NYU, Sch Med, New York, NY 10003 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. RP Li, XB (reprint author), New Jersey Inst Technol, Dept Biomed Engn, Newark, NJ 07102 USA. EM xli.aecom@gmail.com FU NIMH [R21 MH071720] FX This project was partially supported by a grant from NIMH, R21 MH071720. NR 39 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 76 EP 82 DI 10.1016/j.schres.2015.08.001 PG 7 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600011 PM 26386898 ER PT J AU Rodriguez-Jimenez, R Dompablo, M Bagney, A Santabarbara, J Aparicio, AI Torio, I Moreno-Ortega, M Lopez-Anton, R Lobo, A Kern, RS Green, MF Jimenez-Arriero, MA Santos, JL Nuechterlein, KH Palomo, T AF Rodriguez-Jimenez, R. Dompablo, M. Bagney, A. Santabarbara, J. Aparicio, A. I. Torio, I. Moreno-Ortega, M. Lopez-Anton, R. Lobo, A. Kern, R. S. Green, M. F. Jimenez-Arriero, M. A. Santos, J. L. Nuechterlein, K. H. Palomo, T. TI The MCCB impairment profile in a Spanish sample of patients with schizophrenia: Effects of diagnosis, age, and gender on cognitive functioning SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Cognition; MATRICS; MCCB; Age; Gender ID 1ST-EPISODE SCHIZOPHRENIA; BATTERY; STANDARDIZATION; INDIVIDUALS; PERFORMANCE; DEFICIT AB The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293 schizophrenia outpatients and 210 community residents in Spain. Our first objective was to identify the age-and gender-corrected MCCB cognitive profile of patients with schizophrenia. The profile of schizophrenia patients showed deficits when compared to controls across the seven MCCB domains. Reasoning and Problem Solving and Social Cognition were the least impaired, while Visual Learning and Verbal Learning showed the greatest deficits. Our second objective was to study the effects on cognitive functioning of age and gender, in addition to diagnosis. Diagnosis was found to have the greatest effect on cognition (Cohen's d > 0.8 for all MCCB domains); age and gender also had effects on cognitive functioning, although to a lesser degree (with age usually having slightly larger effects than gender). The effects of age were apparent in all domains (with better performance in younger subjects), except for Social Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning and Problem Solving (better performance in males), and Social Cognition (better performance in females). No interaction effects were found between diagnosis and age, or between diagnosis and gender. This lack of interactions suggests that age and gender effects are not different in patients and controls. (C) 2015 Elsevier B.V. All rights reserved. C1 [Rodriguez-Jimenez, R.; Dompablo, M.; Bagney, A.; Torio, I.; Moreno-Ortega, M.; Jimenez-Arriero, M. A.; Palomo, T.] Inst Invest Hosp 12 Octubre I 12, Dept Psychiat, Madrid 28041, Spain. [Rodriguez-Jimenez, R.; Dompablo, M.; Bagney, A.; Santabarbara, J.; Moreno-Ortega, M.; Lopez-Anton, R.; Lobo, A.; Jimenez-Arriero, M. A.; Palomo, T.] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain. [Rodriguez-Jimenez, R.; Jimenez-Arriero, M. A.; Palomo, T.] Univ Complutense Madrid, Dept Psychiat, E-28040 Madrid, Spain. [Santabarbara, J.] Univ Zaragoza, Dept Prevent Med & Publ Hlth, E-50009 Zaragoza, Spain. [Aparicio, A. I.; Santos, J. L.] Hosp Virgen La Luz, Dept Psychiat, Cuenca, Spain. [Lopez-Anton, R.] Univ Zaragoza, Dept Psychol & Sociol, E-50009 Zaragoza, Spain. [Lobo, A.] Univ Zaragoza, Dept Psychiat, IIS Aragon, E-50009 Zaragoza, Spain. [Kern, R. S.; Green, M. F.; Nuechterlein, K. H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Kern, R. S.; Green, M. F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Nuechterlein, K. H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Rodriguez-Jimenez, R (reprint author), Inst Invest Hosp 12 Octubre I 12, Dept Psychiat, Avda Cordoba S-N, Madrid 28041, Spain. EM roberto.rodriguez.jimenez@gmail.com FU Fondo de Investigaciones Sanitarias, FIS [PI080514]; Madrid's Regional Government [S2010/BMD-2422 AGES]; European Union Structural Funds; Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM) of the Instituto de Salud Carlos III FX This research was supported in part by grant PI080514 (Fondo de Investigaciones Sanitarias, FIS), by Madrid's Regional Government (S2010/BMD-2422 AGES) and European Union Structural Funds, and by the Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM) of the Instituto de Salud Carlos III. NR 30 TC 0 Z9 0 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 116 EP 120 DI 10.1016/j.schres.2015.09.013 PG 5 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600017 PM 26416441 ER PT J AU Perkins, DO Jeffries, CD Cornblatt, BA Woods, SW Addington, J Bearden, CE Cadenhead, KS Cannon, TD Heinssen, R Mathalon, DH Seidman, LJ Tsuang, MT Walker, EF McGlashan, TH AF Perkins, Diana O. Jeffries, Clark D. Cornblatt, Barbara A. Woods, Scott W. Addington, Jean Bearden, Carrie E. Cadenhead, Kristin S. Cannon, Tyrone D. Heinssen, Robert Mathalon, Daniel H. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. McGlashan, Thomas H. TI Severity of thought disorder predicts psychosis in persons at clinical high-risk SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Psychosis; High-risk; Risk prediction; Symptom severity; Schizophrenia; Survival ID ULTRA-HIGH-RISK; INTERRATER RELIABILITY; PRODROMAL SYNDROMES; FOLLOW-UP; VALIDITY; POPULATION; SCHIZOPHRENIA; VALIDATION; DIAGNOSIS; PSYCHOPATHOLOGY AB Background: Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction. Methods: Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n=296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n=592) served as an independent test set. Results: We derived 2-Item and 4-Item subscales. Both included unusual thought content and suspiciousness; the latter added reduced ideational richness and difficulties with focus/concentration. The Concordance Index (C-Index), a measure of discrimination, was similar for each subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI=[0.64, 0.77], Cohort-1: 0.74, 95% CI=[0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI=[0.3, 0.76], Cohort-1: 0.72, 95% CI=[0.66-0.79]). The 4-Item performed better than the 2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects (p-value=1.3E-55). Subscale calibration between cohorts was proportional (higher scores/lower survival), but absolute conversion risk predicted from Cohort-1 was higher than that observed in Cohort-2, reflecting the cohorts' differences in 2-year conversion rates (Cohort-2: 0.16, 95% CI=[0.13, 0.19]; Cohort-1: 0.30, 95% CI=[0.24, 0.36]). Conclusion: Severity of unusual thought content, suspiciousness, reduced ideational richness, and difficulty with focus/concentration informed psychosis risk prediction. Scales based on these symptoms may have utility in research and, assuming further validation, eventual clinical applications. (C) 2015 Elsevier B.V. All rights reserved. C1 [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA. [Jeffries, Clark D.] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Woods, Scott W.; Cannon, Tyrone D.; McGlashan, Thomas H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cadenhead, Kristin S.; Tsuang, Ming T.] UCSD, Dept Psychiat, San Diego, CA USA. [Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Heinssen, Robert] NIMH, Rockville, MD USA. [Mathalon, Daniel H.] UCSF, Dept Psychiat, San Francisco, CA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Perkins, DO (reprint author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA. EM Diana_Perkins@unc.edu FU National Institutes of Health FX This project was a cooperative agreement between the investigator sites and the National Institutes of Health. NR 53 TC 2 Z9 2 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 169 EP 177 DI 10.1016/j.schres.2015.09.008 PG 9 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600026 PM 26441004 ER PT J AU Schlosser, DA Campellone, TR Biagianti, B Delucchi, KL Gard, DE Fulford, D Stuart, BK Fisher, M Loewy, RL Vinogradov, S AF Schlosser, Danielle A. Campellone, Timothy R. Biagianti, Bruno Delucchi, Kevin L. Gard, David E. Fulford, Daniel Stuart, Barbara K. Fisher, Melissa Loewy, Rachel L. Vinogradov, Sophia TI Modeling the role of negative symptoms in determining social functioning in individuals at clinical high risk of psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Motivation; Social functioning; Prodromal; Psychosis; Experiential negative symptoms; Expressive negative symptoms ID ULTRA-HIGH RISK; MOTIVATIONAL DEFICITS; SCHIZOPHRENIA; NEUROCOGNITION; DIMENSIONS; PREDICTION; INTERVIEW; PRODROME; OUTCOMES; IMPACT AB A priority for improving outcome in individuals at clinical high risk (CHR) is enhancing our understanding of predictors of psychosis as well as psychosocial functioning. Social functioning, in particular, is a unique indicator of risk as well as an important outcome in itself. Negative symptoms are a significant determinant of social functioning in CHR individuals; yet, it is unclear which specific negative symptoms drive functional outcomeand how these symptoms function relative to other predictors, such as neurocognition and mood/anxiety symptoms. In a sample of 85 CHR individuals, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential vs expressive symptoms) would be replicated in a CHR sample; and tested the degree to which specific negative symptoms predict social functioning, relative to neurocognition and mood/anxiety symptoms, which are known to predict functioning. The two-factor negative symptom solution was replicated in this CHR sample. Negative symptom severity was found to be uniquely predictive of social functioning, above and beyond depression/anxiety and neurocognition. Experiential symptoms were more strongly associated with social functioning, relative to expression symptoms. In addition, experiential symptoms mediated the relationship between expressive negative symptoms and social functioning. These results suggest that experiences of motivational impairment are more important in determining social functioning, relative to affective flattening and alogia, in CHR individuals, thereby informing the development of more precise therapeutic targets. Developing novel interventions that stimulate goal-directed behavior and reinforce rewarding experiences in social contexts are recommended. (C) 2015 Elsevier B.V. All rights reserved. C1 [Schlosser, Danielle A.; Campellone, Timothy R.; Biagianti, Bruno; Delucchi, Kevin L.; Stuart, Barbara K.; Fisher, Melissa; Loewy, Rachel L.; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Campellone, Timothy R.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Gard, David E.] San Francisco State Univ, San Francisco, CA USA. [Fulford, Daniel] Boston Univ, Boston, MA 02215 USA. [Fisher, Melissa; Vinogradov, Sophia] San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Schlosser, DA (reprint author), 401 Parnassus Ave, San Francisco, CA 94134 USA. EM Danielle.schlosser@ucsf.edu OI Gard, David/0000-0002-0446-4000 FU NIMH [K23 MH097795-01, R34 MH100399, R01 01MH081051] FX This research was supported by the following funding sources: NIMH K23 MH097795-01 (Schlosser); NIMH R34 MH100399 (Schlosser/Vinogradov); and NIMH R01 01MH081051 (Vinogradov). The funding sources had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 33 TC 3 Z9 3 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 204 EP 208 DI 10.1016/j.schres.2015.10.036 PG 5 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600031 PM 26530628 ER PT J AU Gonzalez-Heydrich, J Enlow, MB D'Angelo, E Seidman, LJ Gumlak, S Kim, A Woodberry, KA Rober, A Tembulkar, S Graber, K O'Donnell, K Hamoda, HM Kimball, K Rotenberg, A Oberman, LM Pascual-Leone, A Keshavan, MS Duffy, FH AF Gonzalez-Heydrich, Joseph Enlow, Michelle Bosquet D'Angelo, Eugene Seidman, Larry J. Gumlak, Sarah Kim, April Woodberry, Kristen A. Rober, Ashley Tembulkar, Sahil Graber, Kelsey O'Donnell, Kyle Hamoda, Hesham M. Kimball, Kara Rotenberg, Alexander Oberman, Lindsay M. Pascual-Leone, Alvaro Keshavan, Matcheri S. Duffy, Frank H. TI Early auditory processing evoked potentials (N100) show a continuum of blunting from clinical high risk to psychosis in a pediatric sample SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Psychosis; Clinical high risk; N100; Early onset; Superior temporal cortex ID 1ST EPISODE SCHIZOPHRENIA; 1ST-EPISODE SCHIZOPHRENIA; P300 TOPOGRAPHY; INDIVIDUALS; NEUROCOGNITION; PERSPECTIVE; TRANSITION; RELATIVES; COMPONENT; SYMPTOMS AB Background: The N100 is a negative deflection in the surface EEG approximately 100ms after an auditory signal. It has been shown to be reduced in individuals with schizophrenia and those at clinical high risk (CHR). N100 blunting may index neural network dysfunction underlying psychotic symptoms. This phenomenon has received little attention in pediatric populations. Method: This cross-sectional study compared the N100 response measured via the average EEG response at the left medial frontal position FC1 to 150 sinusoidal tones in participants ages 5 to 17 years with a CHR syndrome (n=29), a psychotic disorder (n=22), or healthy controls (n=17). Results: Linear regression analyses that considered potential covariates (age, gender, handedness, family mental health history, medication usage) revealed decreasing N100 amplitude with increasing severity of psychotic symptomatology from healthy to CHR to psychotic level. Conclusions: Longitudinal assessment of the N100 in CHR children who do and do not develop psychosis will inform whether it predicts transition to psychosis and if its response to treatment predicts symptom change. (C) 2015 Elsevier B.V. All rights reserved. C1 [Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene; Gumlak, Sarah; Kim, April; Rober, Ashley; Tembulkar, Sahil; Graber, Kelsey; O'Donnell, Kyle; Hamoda, Hesham M.; Kimball, Kara; Rotenberg, Alexander; Duffy, Frank H.] Boston Childrens Hosp, Boston, MA 02115 USA. [Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene; Seidman, Larry J.; Woodberry, Kristen A.; Hamoda, Hesham M.; Keshavan, Matcheri S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Woodberry, Kristen A.; Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Commonwealth Res Ctr, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rotenberg, Alexander; Pascual-Leone, Alvaro; Duffy, Frank H.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Oberman, Lindsay M.] EP Bradley Hosp, East Providence, RI 02915 USA. [Oberman, Lindsay M.] Brown Univ, Warren Alpert Med Sch, Neuroplast & Autism Spectrum Disorder Program, East Providence, RI 02915 USA. [Oberman, Lindsay M.] Dept Psychiat & Human Behav, East Providence, RI 02915 USA. [Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Div Cognit Neurol, Boston, MA 02115 USA. [Pascual-Leone, Alvaro] Berenson Allen Ctr, Boston, MA 02115 USA. RP Gonzalez-Heydrich, J (reprint author), Boston Childrens Hosp, Dept Psychiat, 300 Longwood Ave, Boston, MA 02115 USA. EM Joseph.Gonzalez-Heydrich@childrens.harvard.edu OI Bosquet Enlow, Michelle/0000-0003-2598-3894 FU Tommy Fuss Fund; National Institute of Mental Health [1R01MH100186]; Simons Foundation; Nancy Lurie Marks Family Foundation; Faculty Development Fellowship from Boston Children's Hospital; Program for Behavioral Science in the Department of Psychiatry at Boston Children's Hospital; NAPLS-2 grant [U01 MH08198-06A1] FX This work was supported by the Tommy Fuss Fund (Joseph Gonzalez-Heydrich, Michelle Bosquet Enlow, Eugene D'Angelo, Sarah Gumlak, April Kim, Ashley Rober, Sahil Tembulkar, Kelsey Graber, Kyle O'Donnell, Kara Kimball, Frank H. Duffy). During preparation of this manuscript, the authors were supported by the National Institute of Mental Health (1R01MH100186, Lindsay Oberman), the Simons Foundation (Lindsay Oberman), the Nancy Lurie Marks Family Foundation (Lindsay Oberman), a Faculty Development Fellowship from Boston Children's Hospital (Hesham M. Hamoda), and the Program for Behavioral Science in the Department of Psychiatry at Boston Children's Hospital (Michelle Bosquet Enlow). Some participants were referred by the NAPLS-2 grant (U01 MH08198-06A1, Larry J. Seidman, Kristen A. Woodberry). None of the funding agencies had any role in the study design, the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not represent the official views of any funding entity. NR 47 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 340 EP 345 DI 10.1016/j.schres.2015.10.037 PG 6 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600052 PM 26549629 ER PT J AU Tregellas, JR Smucny, J Legget, KT Stevens, KE AF Tregellas, Jason R. Smucny, Jason Legget, Kristina T. Stevens, Karen E. TI Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Gating; Ketogenic diet; Hippocampus; P50; Schizophrenia ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CEREBRAL-BLOOD-FLOW; NEUROPHYSIOLOGICAL EVIDENCE; HIPPOCAMPAL-FORMATION; SCHIZOPHRENIA; DYSFUNCTION; EPILEPSY; HYPERACTIVITY; INHIBITION; MECHANISMS AB Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia. Published by Elsevier B.V. C1 [Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Tregellas, Jason R.; Smucny, Jason; Legget, Kristina T.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Tregellas, Jason R.; Smucny, Jason; Legget, Kristina T.; Stevens, Karen E.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Tregellas, JR (reprint author), Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO 80045 USA. EM Jason.Tregellas@ucdenver.edu OI Smucny, Jason/0000-0001-5656-7987; Legget, Kristina/0000-0002-2948-506X FU VA Biomedical Laboratory and Clinical Science Research and Development Service; Brain and Behavior Research Foundation; NIH [DK-089095, DK-103691, MH-102224, MH-102879] FX This work was supported by the VA Biomedical Laboratory and Clinical Science Research and Development Service (grant to Dr. Tregellas), the Brain and Behavior Research Foundation (grant to Dr. Tregellas), NIH grants DK-089095, DK-103691 and MH-102224 (grants to Dr. Tregellas), and NIH fellowship MH-102879 (grant to Mr. Smucny). NR 45 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 351 EP 354 DI 10.1016/j.schres.2015.09.022 PG 4 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600054 PM 26453015 ER PT J AU Liu, JY Julnes, PS Chen, JY Ehrlich, S Walton, E Calhoun, VD AF Liu, Jingyu Julnes, Peter Siyahhan Chen, Jiayu Ehrlich, Stefan Walton, Esther Calhoun, Vince D. TI The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE DNA methylation; Brain volume; Schizophrenia; Multivariate association; Cerebellum ID NEUROLOGICAL SOFT SIGNS; GRAY-MATTER VOLUME; 1ST-EPISODE AFFECTIVE PSYCHOSIS; MONOZYGOTIC TWINS DISCORDANT; AUDITORY HALLUCINATIONS; NEURONAL EXCITABILITY; INSULIN-SECRETION; ENTORHINAL CORTEX; BIPOLAR DISORDER; NERVOUS-SYSTEM AB Both methylation and brain volume patterns hold important biological information for the development and prognosis of schizophrenia (SZ). A combined study to probe the association between them provides a new perspective to understanding SZ. Genomic methylation of peripheral blood and regional brain volumes derived from magnetic resonance imaging were analyzed using parallel independent component analyses in this study. Nine methylation components and five brain volumetric components were extracted for 94 SZ patients and 106 healthy controls. After controlling for age, sex, race, and substance use, a component comprised primarily of bilateral cerebellar volumes was significantly correlated to a methylation component from 14 CpG sites in 13 genes. Both patients and healthy controls demonstrated similar associations, but patients had significantly smaller cerebellar volumes and dysmethylation in the associated epigenetic component compared to controls. The 13 genes are enriched in cellular growth and proliferation with some genes involved in neuronal growth and cerebellum development (GATA4, ADRA1D, EPHA3, and KCNK10), and these genes are prominently associated with neurological and psychological disorders. Such findings suggest that the methylation pattern of the genes coding for cellular growth may influence the cerebellar development through regulating gene expression, and the alteration in the methylation of these genes in SZ patients may contribute to the cerebellar volume reduction observed in patients. (C) 2015 Elsevier B.V. All rights reserved. C1 [Liu, Jingyu; Julnes, Peter Siyahhan; Chen, Jiayu; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87106 USA. [Liu, Jingyu; Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Ehrlich, Stefan; Walton, Esther] TU Dresden, Dept Child & Adolescent Psychiat, Fac Med, Dev Neurosci Sect, Dresden, Germany. [Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Liu, JY (reprint author), Mind Res Network, 1101 Yale Blvd NE, Albuquerque, NM 87106 USA. EM jliu@mrn.org OI Walton, Esther/0000-0002-0935-2200; Liu, Jingyu/0000-0002-1724-7523 FU National Institutes of Health (USA) Center of Biomedical Research Excellence [P20GM103472] FX This work was funded by the National Institutes of Health (USA) Center of Biomedical Research Excellence grant P20GM103472 to VC. We would like to thank the MCIC group for providing the data. NR 56 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2015 VL 169 IS 1-3 BP 447 EP 452 DI 10.1016/j.schres.2015.08.035 PG 6 WC Psychiatry SC Psychiatry GA CY5PC UT WOS:000366458600069 PM 26381449 ER PT J AU Block, KI Gyllenhaal, C Lowe, L Amedei, A Amin, ARMR Amin, A Aquilano, K Arbiser, J Arreola, A Arzumanyan, A Ashraf, SS Azmi, AS Benencia, F Bhakta, D Bilsland, A Bishayeen, A Blain, SW Block, PB Boosani, CS Carey, TE Carnero, A Carotenuto, M Casey, SC Chakrabarti, M Chaturvedi, R Chen, GZ Chenx, H Chen, S Chen, YC Choi, BK Ciriolo, MR Coley, HM Collins, AR Connell, M Crawford, S Curran, CS Dabrosin, C Damia, G Dasgupta, S DeBerardinis, RJ Decker, WK Dhawan, P Diehl, AME Dong, JT Dou, QP Drew, JE Elkord, E El-Rayes, B Feitelson, MA Felsher, DW Ferguson, LR Fimognari, C Firestone, GL Frezza, C Fujii, H Fuster, MM Generali, D Georgakilas, AG Gieseler, F Gilbertson, M Green, MF Grue, B Guha, G Halicka, D Helferich, WG Heneberg, P Hentosh, P Hirschey, MD Hofseth, LJ Holcombe, RF Honoki, K Hsu, HY Huang, GS Jensen, LD Jiang, WG Jones, LW Karpowicz, PA Keith, WN Kerkar, SP Khan, GN Khatami, M Ko, YH Kucuk, O Kulathinal, RJ Kumar, NB Kwon, BS Le, A Lea, MA Lee, HY Lichtor, T Lin, LT Locasale, JW Lokeshwar, BL Longo, VD Lyssiotis, CA MacKenzie, KL Malhotra, M Marino, M Martinez-Chantar, ML Matheu, A Maxwell, C McDonnell, E Meeker, AK Mehrmohamadi, M Mehta, K Michelotti, GA Mohammad, RM Mohammed, SI Morre, DJ Muqbil, I Muralidhar, V Murphy, MP Nagaraju, GP Nahta, R Niccolai, E Nowsheen, S Panis, C Pantano, F Parslow, VR Pawelec, G Pedersen, PL Poore, B Poudyal, D Prakash, S Prince, M Raffaghello, L Rathmell, JC Rathmell, WK Ray, SK Reichrath, J Rezazadeh, S Ribatti, D Ricciardiello, L Robey, RB Rodier, F Rupasinghe, HPV Russo, GL Ryan, EP Samadi, AK Sanchez-Garcia, I Sanders, AJ Santini, D Sarkar, M Sasada, T Saxena, NK Shackelford, RE Kumara, HMCS Sharma, D Shin, DM Sidransky, D Siegelin, MD Signori, E Singh, N Sivanand, S Sliva, D Smythe, C Spagnuolo, C Stafforini, DM Stagg, J Subbarayan, PR Sundin, T Talib, WH Thompson, SK Tran, PT Ungefroren, H Vander Heiden, MG Venkateswaran, V Vinay, DS Vlachostergios, PJ Wang, ZW Wellendx, KE Whelan, RL Yang, ES Yang, HJ Yang, XJ Yaswen, P Yedjou, C Yin, X Zhu, JY Zollo, M AF Block, Keith I. Gyllenhaal, Charlotte Lowe, Leroy Amedei, Amedeo Amin, A. R. M. Ruhul Amin, Amr Aquilano, Katia Arbiser, Jack Arreola, Alexandra Arzumanyan, Alla Ashraf, S. Salman Azmi, Asfar S. Benencia, Fabian Bhakta, Dipita Bilsland, Alan Bishayeen, Anupam Blain, Stacy W. Block, Penny B. Boosani, Chandra S. Carey, Thomas E. Carnero, Amancio Carotenuto, Marianeve Casey, Stephanie C. Chakrabarti, Mrinmay Chaturvedi, Rupesh Chen, Georgia Zhuo Chenx, Helen Chen, Sophie Chen, Yi Charlie Choi, Beom K. Ciriolo, Maria Rosa Coley, Helen M. Collins, Andrew R. Connell, Marisa Crawford, Sarah Curran, Colleen S. Dabrosin, Charlotta Damia, Giovanna Dasgupta, Santanu DeBerardinis, Ralph J. Decker, William K. Dhawan, Punita Diehl, Anna Mae E. Dong, Jin-Tang Dou, Q. Ping Drew, Janice E. Elkord, Eyad El-Rayes, Bassel Feitelson, Mark A. Felsher, Dean W. Ferguson, Lynnette R. Fimognari, Carmela Firestone, Gary L. Frezza, Christian Fujii, Hiromasa Fuster, Mark M. Generali, Daniele Georgakilas, Alexandros G. Gieseler, Frank Gilbertson, Michael Green, Michelle F. Grue, Brendan Guha, Gunjan Halicka, Dorota Helferich, William G. Heneberg, Petr Hentosh, Patricia Hirschey, Matthew D. Hofseth, Lorne J. Holcombe, Randall F. Honoki, Kanya Hsu, Hsue-Yin Huang, Gloria S. Jensen, Lasse D. Jiang, Wen G. Jones, Lee W. Karpowicz, Phillip A. Keith, W. Nicol Kerkar, Sid P. Khan, Gazala N. Khatami, Mahin Ko, Young H. Kucuk, Omer Kulathinal, Rob J. Kumar, Nagi B. Kwon, Byoung S. Le, Anne Lea, Michael A. Lee, Ho-Young Lichtor, Terry Lin, Liang-Tzung Locasale, Jason W. Lokeshwar, Bal L. Longo, Valter D. Lyssiotis, Costas A. MacKenzie, Karen L. Malhotra, Meenakshi Marino, Maria Martinez-Chantar, Maria L. Matheu, Ander Maxwell, Christopher McDonnell, Eoin Meeker, Alan K. Mehrmohamadi, Mahya Mehta, Kapil Michelotti, Gregory A. Mohammad, Ramzi M. Mohammed, Sulma I. Morre, D. James Muqbil, Irfana Muralidhar, Vinayak Murphy, Michael P. Nagaraju, Ganji Purnachandra Nahta, Rita Niccolai, Elena Nowsheen, Somaira Panis, Carolina Pantano, Francesco Parslow, Virginia R. Pawelec, Graham Pedersen, Peter L. Poore, Brad Poudyal, Deepak Prakash, Satya Prince, Mark Raffaghello, Lizzia Rathmell, Jeffrey C. Rathmell, W. Kimryn Ray, Swapan K. Reichrath, Joerg Rezazadeh, Sarallah Ribatti, Domenico Ricciardiello, Luigi Robey, R. Brooks Rodier, Francis Rupasinghe, H. P. Vasantha Russo, Gian Luigi Ryan, Elizabeth P. Samadi, Abbas K. Sanchez-Garcia, Isidro Sanders, Andrew J. Santini, Daniele Sarkar, Malancha Sasada, Tetsuro Saxena, Neeraj K. Shackelford, Rodney E. Kumara, H. M. C. Shantha Sharma, Dipali Shin, Dong M. Sidransky, David Siegelin, Markus David Signori, Emanuela Singh, Neetu Sivanand, Sharanya Sliva, Daniel Smythe, Carl Spagnuolo, Carmela Stafforini, Diana M. Stagg, John Subbarayan, Pochi R. Sundin, Tabetha Talib, Wamidh H. Thompson, Sarah K. Tran, Phuoc T. Ungefroren, Hendrik Vander Heiden, Matthew G. Venkateswaran, Vasundara Vinay, Dass S. Vlachostergios, Panagiotis J. Wang, Zongwei Wellendx, Kathryn E. Whelan, Richard L. Yang, Eddy S. Yang, Huanjie Yang, Xujuan Yaswen, Paul Yedjou, Clement Yin, Xin Zhu, Jiyue Zollo, Massimo TI Designing a broad-spectrum integrative approach for cancer prevention and treatment SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Multi-targeted; Cancer hallmarks; Phytochemicals; Targeted therapy; Integrative medicine ID RANDOMIZED CONTROLLED-TRIALS; TEA POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE; BOTANICAL DIETARY-SUPPLEMENTS; TRADITIONAL CHINESE MEDICINE; CONTROLLED CLINICAL-TRIAL; METASTATIC BREAST-CANCER; ENDOTHELIAL-CELL-GROWTH; III COLON-CANCER; PHASE-I TRIAL; LOW-FAT DIETS AB Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd. C1 [Block, Keith I.; Gyllenhaal, Charlotte; Block, Penny B.] Block Ctr Integrat Canc Treatment, Skokie, IL 60077 USA. [Lowe, Leroy] Getting Know Canc, Truro, NS, Canada. [Amedei, Amedeo] Univ Florence, Dept Expt & Clin Med, Florence, Italy. [Amin, Amr] Univ Florence, Dept Expt & Clin Med, Florence, Italy. [Aquilano, Katia; Ciriolo, Maria Rosa] United Arab Emirates Univ, Coll Sci, Dept Biol, Al Ain, U Arab Emirates. [Arreola, Alexandra; Rathmell, W. Kimryn] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Arzumanyan, Alla; Feitelson, Mark A.; Kulathinal, Rob J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Ashraf, S. Salman] Temple Univ, Dept Biol, Philadelphia, PA 19122 USA. [Azmi, Asfar S.; Dou, Q. Ping; Mohammad, Ramzi M.; Muqbil, Irfana] United Arab Emirates Univ, Coll Sci, Dept Chem, Al Ain, U Arab Emirates. [Benencia, Fabian] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Bhakta, Dipita; Guha, Gunjan] Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. [Bilsland, Alan; Keith, W. Nicol] SASTRA Univ, Sch Chem & Bio Technol, Thanjavur, Tamil Nadu, India. [Bishayeen, Anupam] Univ Glasgow, Glasgow, Lanark, Scotland. [Blain, Stacy W.] Larkin Hlth Sci Inst, Coll Pharm, Dept Pharmaceut Sci, Miami, FL USA. [Boosani, Chandra S.] Suny Downstate Med Ctr, Dept Pediat, Brooklyn, NY USA. [Carey, Thomas E.] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. [Carnero, Amancio] Univ Michigan, Head & Neck Canc Biol Lab, Ann Arbor, MI USA. [Carotenuto, Marianeve; Zollo, Massimo] CSIC, Inst Biomed Sevilla, Seville, Spain. [Carotenuto, Marianeve; Zollo, Massimo] Ctr Ingn Genet & Biotecnol Avanzate, Naples, Italy. [Casey, Stephanie C.; Felsher, Dean W.] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, I-80131 Naples, Italy. [Chakrabarti, Mrinmay; Ray, Swapan K.] Stanford Univ, Div Oncol, Dept Pathol & Med, Stanford, CA 94305 USA. [Chaturvedi, Rupesh] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA. [Chenx, Helen; Connell, Marisa; Maxwell, Christopher] Jawaharlal Nehru Univ, Sch Biotechnol, New Delhi 110067, India. [Chen, Sophie] Univ British Columbia, Dept Pediat, Michael Cuccione Childhood Canc Res Program, Child & Family Res Inst, Vancouver, BC V6T 1W5, Canada. [Chen, Yi Charlie] Ovarian & Prostate Canc Res Lab, Guildford, Surrey, England. [Chen, Yi Charlie] Alderson Broaddus Univ, Dept Biol, Philadelphia, PA USA. [Gyllenhaal, Charlotte; Choi, Beom K.; Kwon, Byoung S.] Natl Canc Ctr, Div Canc Biol, Canc Immunol Branch, Goyang, Gyeonggi, South Korea. [Coley, Helen M.] Univ Surrey, Fac Hlth & Med Sci, Guildford GU2 5XH, Surrey, England. [Collins, Andrew R.] Univ Oslo, Fac Med, Dept Nutr, Oslo 3, Norway. [Crawford, Sarah] So Connecticut State Univ, Canc Biol Res Lab, New Haven, CT 06515 USA. [Curran, Colleen S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Dabrosin, Charlotta] Linkoping Univ, Dept Oncol, Linkoping, Sweden. [Dabrosin, Charlotta] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Damia, Giovanna] Ist Ric Farmacol Mario Negri, Ist Ricovero Cura Carattere Sci, Dept Oncol, Milan, Italy. [Dasgupta, Santanu] Univ Texas Hlth Sci Ctr Tyler, Dept Cellular & Mol Biol, Tyler, TX USA. [Vinay, Dass S.] Tulane Univ, Hlth Sci Ctr, Dept Med, Sect Clin Immunol Allergy & Rheumatol, New Orleans, LA USA. [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA. [Decker, William K.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Dhawan, Punita] Vanderbilt Univ, Sch Med, Div Surg Oncol, Dept Surg & Canc Biol, Nashville, TN 37212 USA. [Diehl, Anna Mae E.; Michelotti, Gregory A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Drew, Janice E.] Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen, Scotland. [Elkord, Eyad] United Arab Emirates Univ, Coll Med & Hlth Sci, Al Ain, U Arab Emirates. [El-Rayes, Bassel; Nagaraju, Ganji Purnachandra] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Ferguson, Lynnette R.; Parslow, Virginia R.] Univ Auckland, Discipline Nutr, Auckland 1, New Zealand. [Fimognari, Carmela] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1, New Zealand. [Firestone, Gary L.] Univ Bologna, Dipartimento Sci Qualita Vita Alma Mater Studioru, Rimini, Italy. [Frezza, Christian] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Fujii, Hiromasa] Univ Cambridge, Hutchison MRC Res Ctr, Med Res Council Canc Unit, Cambridge, England. [Fuster, Mark M.; Yin, Xin] Nara Med Univ, Dept Orthoped Surg, Kashihara, Nara 634, Japan. [Generali, Daniele] Univ Calif San Diego, Med & Res Serv, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA. [Generali, Daniele] Univ Calif San Diego, San Diego, CA 92103 USA. [Georgakilas, Alexandros G.] Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy. [Gieseler, Frank; Ungefroren, Hendrik] Azienda Osped Ist Ospitalieri Cremona, Mol Therapy & Pharrnacogen Unit, Cremona, Italy. [Gilbertson, Michael] Natl Tech Univ Athens, Sch Appl Math & Phys Sci, Dept Phys, Athens, Greece. [Green, Michelle F.; Hirschey, Matthew D.; McDonnell, Eoin; Rathmell, Jeffrey C.] Univ Hosp Schleswig Holstein, Dept Med 1, Lubeck, Germany. [Grue, Brendan] Getting Know Canc, Guelph, ON, Canada. [Halicka, Dorota] Duke Univ, Med Ctr, Duke Mol Physiol Inst, Durham, NC USA. [Helferich, William G.; Yang, Xujuan] Dalhousie Univ, Dept Environm Sci Microbiol & Immunol, Halifax, NS, Canada. [Heneberg, Petr] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Hentosh, Patricia] Univ Illinois, Champaign, IL 61820 USA. [Hofseth, Lorne J.; Poudyal, Deepak] Charles Univ Prague, Fac Med 3, Prague, Czech Republic. [Holcombe, Randall F.] Old Domin Univ, Sch Med Lab & Radiat Sci, Norfolk, VA USA. [Hsu, Hsue-Yin] Univ S Carolina, Coll Pharm, Columbia, SC 29208 USA. [Huang, Gloria S.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Jensen, Lasse D.] Tzu Chi Univ, Dept Life Sci, Hualien, Taiwan. [Jensen, Lasse D.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Jensen, Lasse D.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Jensen, Lasse D.] Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden. [Jensen, Lasse D.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Jiang, Wen G.; Sanders, Andrew J.] Cardiff Univ, Sch Med, Heath Pk, Cardiff, Wales. [Jones, Lee W.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Karpowicz, Phillip A.] Univ Windsor, Windsor, ON N9B 3P4, Canada. 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[Pawelec, Graham] Univ Tubingen, Med Res Ctr, Tubingen, Germany. [Pedersen, Peter L.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Biol Chem & Oncol Member Large, Baltimore, MD USA. [Prince, Mark] Univ Michigan, Sch Med, Dept Otolaryngol Head & Neck, Ann Arbor, MI USA. [Raffaghello, Lizzia] Ist Giannina Gaslini, Lab Oncol, I-16148 Genoa, Italy. [Reichrath, Joerg] Saarland Univ Hosp, Clin Dermatol Venerol & Allergol, Ctr Clin & Expt Photodermatol, Homburg, Germany. [Rezazadeh, Sarallah] Univ Rochester, Dept Biol, Rochester, NY 14627 USA. [Ribatti, Domenico] Univ Bari, Sch Med, Dept Basic Med Sci Neurosci & Sensory Organs, Bari, Italy. [Ricciardiello, Luigi] Natl Canc Inst Giovanni Paolo II, Bari, Italy. [Robey, R. Brooks] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy. [Robey, R. Brooks] White River Junct Vet Affairs Med Ctr, White River Jct, VT USA. [Rodier, Francis] Geisel Sch Med Dartmouth, Hanover, NH USA. 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[Stafforini, Diana M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Stagg, John] Univ Utah, Dept Internal Med, Salt Lake City, UT USA. [Subbarayan, Pochi R.] Univ Montreal, Ctr Rech Ctr Hosp, Faculte Pharmacie, Inst Canc Montreal, Montreal, PQ, Canada. [Sundin, Tabetha] Univ Miami, Sch Med, Dept Med, Miami, FL USA. [Talib, Wamidh H.] Sentara Healthcare, Dept Mol Diagnost, Norfolk, VA USA. [Thompson, Sarah K.] Appl Sci Univ, Dept Clin Pharm & Therapeut, Amman, Jordan. [Tran, Phuoc T.] Royal Adelaide Hosp, Dept Surg, Adelaide, SA 5000, Australia. [Venkateswaran, Vasundara] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Vlachostergios, Panagiotis J.] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD USA. [Wang, Zongwei] Johns Hopkins Univ, Dept Mol Radiat Sci Oncol & Urol, Baltimore, MD USA. [Venkateswaran, Vasundara] Univ Toronto, Dept Surg, Div Urol, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. 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EM drblock@blockmedical.com; Leroy.lowe@gettingtoknowcancer.org RI Bhakta-Guha, Dipita/E-8076-2012; IBIS, CANCER/P-3323-2015; Keith, Nicol/D-3325-2009; Zollo, Massimo/K-5857-2016; niccolai, elena/K-6091-2016; Ciriolo, Maria /K-6572-2016; AQUILANO, KATIA/K-8888-2016; Jiang, Wen/B-1293-2010; Ganji, Purna chandra N/D-4193-2011; Robey, R. Brooks/J-7099-2013; Karpowicz, Phillip/C-3334-2016; Heneberg, Petr/C-1881-2012; Mackenzie, Karen/F-1310-2011 OI Pantano, Francesco/0000-0002-2894-9686; Raffaghello, Lizzia/0000-0003-2357-0607; Bhakta-Guha, Dipita/0000-0002-7144-3947; Gieseler, Frank/0000-0001-6409-3822; RICCIARDIELLO, LUIGI/0000-0003-2568-6208; SANCHEZ-GARCIA, ISIDRO/0000-0001-6989-9905; Elkord, Eyad/0000-0002-3868-0318; Locasale, Jason/0000-0002-7766-3502; Keith, Nicol/0000-0001-7862-3580; Zollo, Massimo/0000-0002-0970-7243; niccolai, elena/0000-0002-9205-8079; AQUILANO, KATIA/0000-0002-5905-9870; Jiang, Wen/0000-0002-3283-1111; Ganji, Purna chandra N/0000-0002-4989-5234; Robey, R. Brooks/0000-0001-5059-3965; signori, emanuela/0000-0003-0286-7401; Heneberg, Petr/0000-0002-0703-951X; FU Terry Fox Foundation Grant [TF-13-20]; UAEU Program for Advanced Research (UPAR) [31S118]; NIH [AR47901, R21CA188818, R15 CA137499-01, F32CA177139, P20RR016477, P20GM103434, R01CA170378, U54CA149145, U54CA143907, R01-HL107652, R01CA166348, R01GM071725, R01 CA109335-04A1, 109511R01CA151304CA168997 A11106131R03CA1711326 1P01AT003961RO1 CA100816P01AG034906 R01AG020642P01AG034906-01A1R01HL108006]; NIH NRSA Grant [F31CA154080]; NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer [AI076535]; Sky Foundation Inc. Michigan; University of Glasgow; Beatson Oncology Centre Fund; Spanish Ministry of Economy and Competitivity, ISCIII [PI12/00137, RTICC: RD12/0036/0028]; FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion [CTS-6844, CTS-1848]; Consejeria de Salud of the Junta de Andalucia [PI-0135-2010, PI-0306-2012]; ISCIII [PIE13/0004]; FEDER funds; United Soybean Board; NIH NCCAM Grant [K01AT007324]; NIH NCI Grant [R33 CA161873-02]; Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Ovarian and Prostate Cancer Research Trust, UK; West Virginia Higher Education Policy Commission/Division of Science Research; National Institutes of Health; Italian Association for Cancer Research (AIRC) [IG10636, 15403]; GRACE Charity, UK; Breast Cancer Campaign, UK; Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Connecticut State University; Swedish Research Council; Swedish Research Society; University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; CPRIT; Cancer Prevention and Research Institute of Texas; NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA); Gilead and Shire Pharmaceuticals; NIH/NCI [1R01CA20009, 5R01CAl27258-05, R21CA184788, NIH P30 CA22453, NCI RO1 28704]; Scottish Government's Rural and Environment Science and Analytical Services Division; National Research Foundation; United Arab Emirates University; Terry Fox Foundation; Novartis Pharmaceutical; Aveo Pharmaceutical; Roche; Bristol Myers Squibb; Bayer Pharmaceutical; Pfizer; Kyowa Kirin; NIH/NIAID Grant [A1076535]; Auckland Cancer Society; Cancer Society of New Zealand; NIH Public Service Grant from the National Cancer Institute [CA164095]; Medical Research Council CCU-Program Grant on cancer metabolism; EU Marie Curie Reintegration Grant [MC-CIG-303514]; Greek National funds through the Operational Program 'Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES [MIS 379346]; COST Action CM1201 `Biomimetic Radical Chemistry'; Duke University Molecular Cancer Biology T32 Training Grant; National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Charles University in Prague projects [UNCE 204015, PRVOUK P31/2012]; Czech Science Foundation projects [15-03834Y, P301/12/1686]; Czech Health Research Council AZV project [15-32432A]; Internal Grant Agency of the Ministry of Health of the Czech Republic project [NT13663-3/2012]; National Institute of Aging [P30AG028716-01]; NIH/NCI training grants to Duke University [T32-CA059365-19, 5T32-CA059365]; Ministry of Education, Culture, Sports, Science and Technology, Japan [24590493]; Ministry of Health and Welfare [CCMP101-RD-031, CCMP102-RD-112]; Tzu-Chi University of Taiwan [61040055-10]; Svenska Sallskapet for Medicinsk Forskning; Cancer Research Wales; Albert Hung Foundation; Fong Family Foundation; Welsh Government A4B scheme; NIH NCI; University of Glasgow, Beatson Oncology Centre Fund, CRUK [C301/A14762]; NIH Intramural Research Program; National Science Foundation; American Cancer Society; National Cancer Center [NCC-1310430-2]; National Research Foundation [NRF-2005-0093837]; Sol Goldman Pancreatic Cancer Research Fund Grant [80028595]; Lustgarten Fund Grant [90049125, NIHR21CA169757]; Alma Toorock Memorial for Cancer Research; National Research Foundation of Korea (NRF); Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea [2011-0017639, 2011-0030001]; Ministry of Education of Taiwan [TMUTOP103005-4]; International Life Sciences Institute; United States' Public Health Services Grants [NIH R01CA156776]; VA-BLR&D Merit Review Grant [5101-BX001517-02]; V Foundation; Pancreatic Cancer Action Network; Damon Runyon Cancer Research Foundation; Children's Cancer Institute Australia; University Roma Tre; Italian Association for Cancer Research (AIRC-Grant) [IG15221]; Carlos III Health Institute; Feder funds [AM: CP10/00539, PI13/02277]; Basque Foundation for Science (IKERBASQUE); Marie Curie CIG Grant [2012/712404]; Canadian Institutes of Health Research; Avon Foundation for Women [OBC-134038]; Canadian Institutes of Health [MSH-136647, MOP 64308]; Bayer Healthcare System G4T (Grants4Targets); NIH NIDDK; NIH NIAAA; Shire Pharmaceuticals; Harvard-MIT Health Sciences and Technology Research Assistantship Award; Italian Ministry of University; University of Italy; Auckland Cancer Society Research Centre (ACSRC); German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) [16SV5536K]; European Commission [FP7 259679 "IDEAL"]; Cinque per Mille dell'IRPEF-Finanziamento della Ricerca Sanitaria; European Union Seventh Framework Programme (FP7) [278570]; AIRC [10216, 13837]; European Community's Seventh Framework Program FP7 [311876]; Canadian Institute for Health Research [MOP114962, MOP125857]; Fonds de Recherche Quebec Sante [22624]; Terry Fox Research Institute [1030]; FEDER; MICINN [SAF2012-32810]; Junta de Castilla y Leon [BIO/SA06/13]; ARIMMORA project [FP7-ENV-2011]; European Union; NIH NIDDK [K01DK077137, R03DK089130]; NIH NCI grants [R01CA131294, R21 CA155686]; Avon Foundation; Breast Cancer Research Foundation Grant [90047965]; National Institute of Health, NINDS Grant [K08NS083732]; AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research [13-20-23-SIEG]; Department of Science and Technology, New Delhi, India [SR/FT/LS-063/2008]; Yorkshire Cancer Research; Wellcome Trust, UK; Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region; National Cancer Institute [5P01CA073992]; IDEA Award from the Department of Defense [W81XWH-12-1-0515]; Huntsman Cancer Foundation; University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant [CTSI-2013-P03]; SEEDS You Choose Awards; DoD [W81XVVH-11-1-0272, W81XWH-13-1-0182]; Kimmel Translational Science Award [SKF-13-021]; ACS Scholar award [122688-RSG-12-196-01-TBG]; National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts; American Diabetes Association; Elsa U. Pardee Foundation; Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin [2012RFLX5011]; United States National Institutes of Health [ES019458]; California Breast Cancer Research Program [17UB-8708]; National Institutes of Health through the RCMI-Center for Environmental Health [G1200MD007581]; NIH/National Heart, Lung, and Blood Institute Training Grant [T32HL098062]; European FP7-TuMIC [HEALTH-F2-2008-201662]; Italian Association for Cancer research (AIRC) Grant IG [11963]; Regione Campania L.R:N.5; European National Funds [PON01-02388/1 2007-2013] FX Amr Amin was funded by Terry Fox Foundation Grant # TF-13-20 and UAEU Program for Advanced Research (UPAR) #31S118; Jack Arbiser was funded by NIH AR47901; Alexandra Arreola was funded by NIH NRSA Grant F31CA154080; Alla Arzumanyan was funded by NIH (NIAID) R01: Combination therapies for chronic HBV, liver disease, and cancer (AI076535); Work in the lab of Asfar S. Azmi is supported by NIH R21CA188818 as well as from Sky Foundation Inc. Michigan; Fabian Benencia was supported by NIH Grant R15 CA137499-01; Alan Bilsland was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www. cancerresearchuk.org) Grant C301/A14762; Amancio Carnero was supported by grants from the Spanish Ministry of Economy and Competitivity, ISCIII (Fis: PI12/00137, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-6844 and CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0135-2010 and PI-0306-2012). His work on this project has also been made possible thanks to the Grant PIE13/0004 co-funded by the ISCIII and FEDER funds; Stephanie C. Casey was supported by NIH Grant F32CA177139; Mrinmay Chakrabarti was supported by the United Soybean Board; Rupesh Chaturvedi was supported by an NIH NCCAM Grant (K01AT007324); Georgia Zhuo Chen was supported by an NIH NCI Grant (R33 CA161873-02); Helen Chen acknowledges financial support from the Michael Cuccione Childhood Cancer Foundation Graduate Studentship; Sophie Chen acknowledges financial support from the Ovarian and Prostate Cancer Research Trust, UK; Yi Charlie Chen acknowledges financial support from the West Virginia Higher Education Policy Commission/Division of Science Research, his research was also supported by NIH grants (P20RR016477 and P20GM103434) from the National Institutes of Health awarded to the West Virginia IDeA Network of Biomedical Research Excellence; Maria Rosa Ciriolo was partially supported by the Italian Association for Cancer Research (AIRC) Grants #IG10636 and #15403; Helen M. Coley acknowledges financial support from the GRACE Charity, UK and the Breast Cancer Campaign, UK; Marisa Connell was supported by a Michael Cuccione Childhood Cancer Foundation Postdoctoral Fellowship; Sarah Crawford was supported by a research grant from Connecticut State University; Charlotta Dabrosin acknowledges financial support from the Swedish Research Council and the Swedish Research Society; Giovanna Damia gratefully acknowledges the generous contributions of The Italian Association for Cancer Research (IG14536 to G.D.); Santanu Dasgupta gratefully acknowledges the support of the University of Texas Health Science Centre at Tyler, Elsa U. Pardee Foundation; William K. Decker was supported in part by CPRIT, the Cancer Prevention and Research Institute of Texas; Anna Mae E. Diehl was supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the NIH National Institute on Alcohol Abuse and Alcoholism (NIAAA), Gilead and Shire Pharmaceuticals; Q. Ping Dou was partially supported by NIH/NCI (1R01CA20009, 5R01CAl27258-05 and R21CA184788), and NIH P30 CA22453 (to Karmanos Cancer Institute); Janice E.; Drew was supported by the Scottish Government's Rural and Environment Science and Analytical Services Division; Eyad Elkord thanks the National Research Foundation, United Arab Emirates University and the Terry Fox Foundation for supporting research projects in his lab; Bassel El-Rayes was supported by Novartis Pharmaceutical, Aveo Pharmaceutical, Roche, Bristol Myers Squibb, Bayer Pharmaceutical, Pfizer, and Kyowa Kirin; Mark A. Feitelson was supported by NIH/NIAID Grant A1076535; Dean W. Felsher was supported by NIH grants (R01CA170378, U54CA149145, and U54CA143907); Lynnette R Ferguson was financially supported by the Auckland Cancer Society and the Cancer Society of New Zealand; Gary L. Firestone was supported by NIH Public Service Grant CA164095 awarded from the National Cancer Institute; Christian Frezza "would like to acknowledge funding from a Medical Research Council CCU-Program Grant on cancer metabolism, and a unique applicant AICR project grant"; Mark M. Fuster was supported by NIH Grant R01-HL107652; Alexandros G. Georgakilas was supported by an EU Marie Curie Reintegration Grant MC-CIG-303514, Greek National funds through the Operational Program 'Educational and Lifelong Learning of the National Strategic Reference Framework (NSRF)-Research Funding Program THALES (Grant number MIS 379346) and COST Action CM1201 `Biomimetic Radical Chemistry'; Michelle F. Green was supported by a Duke University Molecular Cancer Biology T32 Training Grant; Brendan Grue was supported by a National Sciences Engineering and Research Council Undergraduate Student Research Award in Canada; Dorota Halicka was supported by by NIH NCI grant NCI RO1 28704; Petr Heneberg was supported by the Charles University in Prague projects UNCE 204015 and PRVOUK P31/2012, by the Czech Science Foundation projects 15-03834Y and P301/12/1686, by the Czech Health Research Council AZV project 15-32432A, and by the Internal Grant Agency of the Ministry of Health of the Czech Republic project NT13663-3/2012; Matthew D. Hirschey wishes to acknowledge Duke University Institutional Support, the Duke Pepper Older Americans Independence Center (OAIC) Program in Aging Research supported by the National Institute of Aging (P30AG028716-01) and NIH/NCI training grants to Duke University (T32-CA059365-19 and 5T32-CA059365); Lorne J. Hofseth was supported by NIH grants (1R01CA151304,1R03CA1711326, and 1P01AT003961); Kanya Honoki was supported in part by the grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (No. 24590493); Hsue-Yin Hsu was supported in part by grants from the Ministry of Health and Welfare (CCMP101-RD-031 and CCMP102-RD-112) and Tzu-Chi University (61040055-10) of Taiwan; Lasse D. Jensen was supported by Svenska Sallskapet for Medicinsk Forskning, Gosta Fraenkels Stiftelse, Ak.e Wibergs Stiftelse, kopings Universitet and the Karolinska Institute, Sweden; Wen G. Jiang wishes to ackOllie och Elof Ericssons Stiftelse, Linnowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Lee W. Jones was supported in part by grants from the NIH NCI; W Nicol Keith was supported by the University of Glasgow, Beatson Oncology Centre Fund, CRUK (www. cancerresearchuk.org) Grant C301/A14762; Sid P. Kerkar was supported by the NIH Intramural Research Program; Rob J. Kulathinal was supported by the National Science Foundation, and the American Cancer Society; Byoung S.; Kwon was supported in part by National Cancer Center (NCC-1310430-2) and National Research Foundation (NRF-2005-0093837); Anne Le was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, a Lustgarten Fund Grant 90049125 and Grant NIHR21CA169757 (to Anne Le); Michael A. Lea was funded by the The Alma Toorock Memorial for Cancer Research; Ho-Young Lee This work was supported by grants from the National Research Foundation of Korea (NRF), the Ministry of Science, ICT & Future Planning (MSIP), Republic of Korea (Nos. 2011-0017639 and 2011-0030001) and by a NIH Grant RO1 CA100816; Liang-Tzung Lin was supported in part by a grant from the Ministry of Education of Taiwan (TMUTOP103005-4); Jason W. Locasale acknowledges support from NIH awards (CA168997 and A1110613) and the International Life Sciences Institute; Bal L. Lokeshwar was supported in part by United States' Public Health Services Grants: NIH R01CA156776 and VA-BLR&D Merit Review Grant No. 5101-BX001517-02; Valter D. Longo acknowleages support from NIH awards (P01AG034906 and R01AG020642) and from the V Foundation; Costas A. Lyssiotis was funded in part by the Pancreatic Cancer Action Network as a Pathway to Leadership Fellow and through a Dale F. Frey Breakthrough award from the Damon Runyon Cancer Research Foundation; Karen L. MacKenzie wishes to acknowledge the support from the Children's Cancer Institute Australia (affiliated with the University of New South Wales, Australia and the Sydney Children's Hospital Network); Maria Marino was supported by grant from University Roma Tre to M.M. (CLA 2013) and by the Italian Association for Cancer Research (AIRC-Grant #IG15221); Ander Matheu is funded by Carlos III Health Institute and Feder funds (AM: CP10/00539, PI13/02277), Basque Foundation for Science (IKERBASQUE) and Marie Curie CIG Grant (AM: 2012/712404); Christopher Maxwell was supported by funding from the Canadian Institutes of Health Research, in partnership with the Avon Foundation for Women (OBC-134038) and the Canadian Institutes of Health Research New Investigator Salary Award (MSH-136647); Eoin McDonnell received Duke University Institutional Support; Kapil Mehta was supported by Bayer Healthcare System G4T (Grants4Targets); Gregory A. Michelotti received support from NIH NIDDK, NIH NIAAA, and Shire Pharmaceuticals; Vinayak Muralidhar was supported by the Harvard-MIT Health Sciences and Technology Research Assistantship Award; Elena Niccolai was supported by the Italian Ministry of University and the University of Italy; Virginia R. Parslow gratefully acknowledges the financial support of the Auckland Cancer Society Research Centre (ACSRC); Graham Pawelec was supported by the German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF) Grant number 16SV5536K, and by the European Commission (FP7 259679 "IDEAL"); Peter L. Pedersen was supported by NIH Grant CA-10951; Brad Poore was supported by Sol Goldman Pancreatic Cancer Research Fund Grant 80028595, the Lustgarten Fund Grant 90049125, and Grant NIHR21CA169757 (to Anne Le); Satya Prakash was supported by a Canadian Institutes of Health Research Grant (MOP 64308); Lizzia Raffaghello was supported by an NIH Grant (P01AG034906-01A1) and Cinque per Mille dell'IRPEF-Finanziamento della Ricerca Sanitaria; Jeffrey C. Rathmell was supported by an NIH Grant (R01HL108006); Swapan K.; Ray was supported by the United Soybean Board; Domenico Ribatti received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant agreement no 278570; Luigi Ricciardiello was supported by the AIRC Investigator Grants 10216 and 13837, and the European Community's Seventh Framework Program FP7/2007-2013 under Grant agreement 311876; Francis Rodier acknowledges the support of the Canadian Institute for Health Research (FR: MOP114962, MOP125857), Fonds de Recherche Quebec Sante (FR: 22624), and the Terry Fox Research Institute (FR: 1030); Gian Luigi Russo contributed to this effort while participating in the Fulbright Research Scholar Program 2013-14; Isidro Sanchez-Garcia is partially supported by FEDER and by MICINN (SAF2012-32810), by NIH Grant (R01 CA109335-04A1), by Junta de Castilla y Leon (BIO/SA06/13) and by the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program). Isidro SanchezGarcia's lab is also a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program; Andrew J. Sanders wishes to acknowledge the support by Cancer Research Wales, the Albert Hung Foundation, the Fong Family Foundation, and Welsh Government A4B scheme; Neeraj K. Saxena was supported by grant funding from NIH NIDDK (K01DK077137, R03DK089130); Dipali Sharma was partially funded by NIH NCI grants (R01CA131294, R21 CA155686), the Avon Foundation and a Breast Cancer Research Foundation Grant (90047965); Markus David Siegelin received funding from National Institute of Health, NINDS Grant K08NS083732, and the 2013 AACR-National Brain Tumor Society Career Development Award for Translational Brain Tumor Research, Grant Number 13-20-23-SIEG; Neetu Singh was supported by funds from the Department of Science and Technology (SR/FT/LS-063/2008), New Delhi, India; Carl Smythe was supported by Yorkshire Cancer Research and The Wellcome Trust, UK; Carmela Spagnuolo was supported by funding from Project C.I.S.I.A., act n. 191/2009 from the Italian Ministry of Economy and Finance Project CAMPUS-QUARC, within program FESR Campania Region 2007/2013, objectives 2.1, 2.2; Diana M. Stafforini was supported by grants from the National Cancer Institute (5P01CA073992), IDEA Award W81XWH-12-1-0515 from the Department of Defense, and by the Huntsman Cancer Foundation; John Stagg was supported by the Canadian Institutes of Health Research; Pochi R. Subbarayan was supported by the University of Miami Clinical and Translational Science Institute (CTSI) Pilot Research Grant (CTSI-2013-P03) and SEEDS You Choose Awards; Phuoc T. Tran was funded by the DoD (W81XVVH-11-1-0272 and W81XWH-13-1-0182), a Kimmel Translational Science Award (SKF-13-021), an ACS Scholar award (122688-RSG-12-196-01-TBG) and the NIH (R01CA166348); Kathryn E. Wellen receives funding from the National Cancer Institute, Pancreatic Cancer Action Network, Pew Charitable Trusts, American Diabetes Association, and Elsa U.; Pardee Foundation; Huanjie Yang was partially supported by the Scientific Research Foundation for the Returned Oversea Scholars, State Education Ministry and Scientific and Technological Innovation Project, Harbin (2012RFLX5011); Paul Yaswen was supported by funding from the United States National Institutes of Health (ES019458) and the California Breast Cancer Research Program (17UB-8708); Clement Yedjou was supported by a grant from the National Institutes of Health (Grant # G1200MD007581), through the RCMI-Center for Environmental Health; Xin Yin was supported by NIH/National Heart, Lung, and Blood Institute Training Grant T32HL098062.; Jiyue Zhu was supported by NIH Grant R01GM071725; Massimo Zollo was supported by the European FP7-TuMIC HEALTH-F2-2008-201662, the Italian Association for Cancer research (AIRC) Grant IG # 11963 and the Regione Campania L.R:N.5, the European National Funds PON01-02388/1 2007-2013. NR 261 TC 31 Z9 31 U1 7 U2 31 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2015 VL 35 SU S BP S276 EP S304 DI 10.1016/j.semcancer.2015.09.007 PG 29 WC Oncology SC Oncology GA CY7WG UT WOS:000366619400013 PM 26590477 ER PT J AU Hirschey, MD DeBerardinis, RJ Diehl, AME Drew, JE Frezza, C Green, MF Jones, LW Ko, YH Le, A Lea, MA Locasale, JW Longo, VD Lyssiotis, CA McDonnell, E Mehrmohamadi, M Michelotti, G Muralidhar, V Murphy, MP Pedersen, PL Poore, B Raffaghello, L Rathmell, JC Sivanand, S Vander Heiden, MG Wellen, KE AF Hirschey, Matthew D. DeBerardinis, Ralph J. Diehl, Anna Mae E. Drew, Janice E. Frezza, Christian Green, Michelle F. Jones, Lee W. Ko, Young H. Le, Anne Lea, Michael A. Locasale, Jason W. Longo, Valter D. Lyssiotis, Costas A. McDonnell, Eoin Mehrmohamadi, Mahya Michelotti, Gregory Muralidhar, Vinayak Murphy, Michael P. Pedersen, Peter L. Poore, Brad Raffaghello, Lizzia Rathmell, Jeffrey C. Sivanand, Sharanya Vander Heiden, Matthew G. Wellen, Kathryn E. CA Target Validation Team TI Dysregulated metabolism contributes to oncogenesis SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Cancer metabolism; Mitochondria; Warburg; Host metabolism; Cancer therapy ID BREAST-CANCER SURVIVORS; PYRUVATE-KINASE M2; N-ACETYLGLUCOSAMINE TRANSFERASE; LIFE-SPAN EXTENSION; MAGNETIC-RESONANCE-SPECTROSCOPY; MODIFICATIONS PREDICT PROGNOSIS; GLOBAL HISTONE MODIFICATIONS; RANDOMIZED CONTROLLED-TRIAL; SMALL-MOLECULE INHIBITION; CORONARY-ARTERY-DISEASE AB Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. (C) 2015 Elsevier Ltd. C1 [Hirschey, Matthew D.; Diehl, Anna Mae E.; Michelotti, Gregory] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Hirschey, Matthew D.; McDonnell, Eoin; Rathmell, Jeffrey C.] Duke Univ, Med Ctr, Duke Mol Physiol Inst, Durham, NC 27701 USA. [Hirschey, Matthew D.; Locasale, Jason W.; Rathmell, Jeffrey C.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA. [Drew, Janice E.] Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen, Scotland. [Frezza, Christian] Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge, England. [Jones, Lee W.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Ko, Young H.] Univ Maryland BioPk, KoDiscovery, Baltimore, MD 20201 USA. [Le, Anne] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA. [Lea, Michael A.] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07103 USA. [Locasale, Jason W.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14850 USA. [Locasale, Jason W.] Cornell Univ, Field Genet Gen & Dev, Ithaca, NY 14850 USA. [Longo, Valter D.] Univ So Calif, Andrus Gerontol Ctr, Div Biogerontol, Los Angeles, CA 90089 USA. [Lyssiotis, Costas A.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Lyssiotis, Costas A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Muralidhar, Vinayak; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Muralidhar, Vinayak; Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [Murphy, Michael P.] Wellcome Trust MRC Bldg, MRC Mitochondrial Biol Unit, Cambridge, England. [Pedersen, Peter L.] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21205 USA. [Pedersen, Peter L.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. [Raffaghello, Lizzia] Ist Giannina Gaslini, Lab Oncol, I-16148 Genoa, Italy. [Sivanand, Sharanya; Wellen, Kathryn E.] Univ Penn, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hirschey, MD (reprint author), Duke Mol Physiol Inst, 300 N Duke St, Durham, NC 27701 USA. EM matthew.hirschey@duke.edu RI Keith, Nicol/D-3325-2009; niccolai, elena/K-6091-2016; OI Keith, Nicol/0000-0001-7862-3580; niccolai, elena/0000-0002-9205-8079; Raffaghello, Lizzia/0000-0003-2357-0607; Locasale, Jason/0000-0002-7766-3502 FU Medical Research Council [MC_UP_1101/3, MC_U105663142, MC_UU_12022/6]; NCI NIH HHS [T32 CA059365]; NIA NIH HHS [R01 AG045351] NR 329 TC 19 Z9 20 U1 6 U2 19 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2015 VL 35 SU S BP S129 EP S150 DI 10.1016/j.semcancer.2015.10.002 PG 22 WC Oncology SC Oncology GA CY7WG UT WOS:000366619400007 PM 26454069 ER PT J AU Wang, ZW Dabrosin, C Yin, X Fuster, MM Arreola, A Rathmell, WK Generali, D Nagaraju, GP El-Rayes, B Ribatti, D Chen, YC Honoki, K Fujii, H Georgakilas, AG Nowsheen, S Amedei, A Niccolai, E Amin, A Ashraf, SS Helferich, B Yang, XJ Guha, G Bhakta, D Ciriolo, MR Aquilano, K Chen, S Halicka, D Mohammed, SI Azmi, AS Bilsland, A Keith, WN Jensen, LD AF Wang, Zongwei Dabrosin, Charlotta Yin, Xin Fuster, Mark M. Arreola, Alexandra Rathmell, W. Kimryn Generali, Daniele Nagaraju, Ganji P. El-Rayes, Bassel Ribatti, Domenico Chen, Yi Charlie Honoki, Kanya Fujii, Hiromasa Georgakilas, Alexandros G. Nowsheen, Somaira Amedei, Amedeo Niccolai, Elena Amin, Amr Ashraf, S. Salman Helferich, Bill Yang, Xujuan Guha, Gunjan Bhakta, Dipita Ciriolo, Maria Rosa Aquilano, Katia Chen, Sophie Halicka, Dorota Mohammed, Sulma I. Azmi, Asfar S. Bilsland, Alan Keith, W. Nicol Jensen, Lasse D. TI Broad targeting of angiogenesis for cancer prevention and therapy SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Angiogenesis; Cancer; Phytochemicals; Treatment; Anti-angiogenic ID CELL-CYCLE ARREST; HUMAN BREAST-CANCER; ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; INTERSTITIAL FLUID PRESSURE; INHIBITS TUMOR-GROWTH; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; LYMPH-NODE METASTASIS; LEWIS LUNG-CARCINOMA; RETINOBLASTOMA (PRB)-E2F/DP PATHWAY AB Deregulation of angiogenesis - the growth of new blood vessels from an existing vasculature is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development. Unfortunately the clinically approved anti-angiogenic drugs in use today are only effective in a subset of the patients, and many who initially respond develop resistance overtime. Also, some of the anti-angiogenic drugs are toxic and it would be of great importance to identify alternative compounds, which could overcome these drawbacks and limitations of the currently available therapy. Finding "the most important target" may, however, prove a very challenging approach as the tumor environment is highly diverse, consisting of many different cell types, all of which may contribute to tumor angiogenesis. Furthermore, the tumor cells themselves are genetically unstable, leading to a progressive increase in the number of different angiogenic factors produced as the cancer progresses to advanced stages. As an alternative approach to targeted therapy, options to broadly interfere with angiogenic signals by a mixture of nontoxic natural compound with pleiotropic actions were viewed by this team as an opportunity to develop a complementary anti-angiogenesis treatment option. As a part of the "Halifax Project" within the "Getting to know cancer" framework, we have here, based on a thorough review of the literature, identified 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. (C) 2015 The Authors. Published by Elsevier Ltd. C1 [Wang, Zongwei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Dabrosin, Charlotta] Linkoping Univ, Dept Oncol, SE-58185 Linkoping, Sweden. [Dabrosin, Charlotta] Linkoping Univ, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden. [Yin, Xin; Fuster, Mark M.] Vet Affairs San Diego Healthcare Syst, Med & Res Serv, San Diego, CA USA. [Yin, Xin; Fuster, Mark M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Arreola, Alexandra; Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Generali, Daniele] AO Isituti Ospitalieri Cremona, Mol Therapy & Pharmacogen Unit, Cremona, Italy. [Nagaraju, Ganji P.; El-Rayes, Bassel] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Ribatti, Domenico] Univ Bari, Sch Med, Dept Basic Med Sci Neurosci & Sensory Organs, Bari, Italy. [Ribatti, Domenico] Natl Canc Inst Giovanni Paolo II, Bari, Italy. [Chen, Yi Charlie] Alderson Broaddus Univ, Dept Biol, Philippi, WV USA. [Honoki, Kanya; Fujii, Hiromasa] Nara Med Univ, Dept Orthoped Surg Arthroplasty & Regenerat Med, Nara, Japan. [Georgakilas, Alexandros G.] Natl Tech Univ Athens, Dept Phys, Sch Appl Math & Phys Sci, GR-15773 Athens, Greece. [Nowsheen, Somaira] Mayo Clin, Coll Med, Mayo Grad Sch, Rochester, MN USA. [Amedei, Amedeo; Niccolai, Elena] Univ Florence, Dept Expt & Clin Med, Florence, Italy. [Amin, Amr] United Arab Emirates Univ, Coll Sci, Dept Biol, Al Ain, U Arab Emirates. [Amin, Amr] Cairo Univ, Fac Sci, Cairo, Egypt. [Ashraf, S. Salman] United Arab Emirates Univ, Coll Sci, Dept Chem, Al Ain, U Arab Emirates. [Helferich, Bill; Yang, Xujuan] Univ Illinois, Urbana, IL USA. [Guha, Gunjan; Bhakta, Dipita] SASTRA Univ, Sch Chem & Bio Technol, Thanjavur, India. [Ciriolo, Maria Rosa; Aquilano, Katia] Univ Roma Tor Vergata, Dept Biol, Rome, Italy. [Chen, Sophie] Ovarian & Prostate Canc Res Trust Lab, Surrey, England. [Halicka, Dorota] New York Med Coll, New York, NY USA. [Mohammed, Sulma I.] Purdue Univ, Ctr Canc Res, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [Azmi, Asfar S.] Wayne State Univ, Sch Med, Detroit, MI USA. [Bilsland, Alan; Keith, W. Nicol] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland. [Jensen, Lasse D.] Linkoping Univ, Dept Med & Hlth Sci, SE-58185 Linkoping, Sweden. [Jensen, Lasse D.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. RP Jensen, LD (reprint author), Linkoping Univ, Dept Med & Hlth Sci, Farmakologen Ingang 68 Pl 08, SE-58185 Linkoping, Sweden. EM zwang0@partners.org; lasse.jensen@liu.se RI Keith, Nicol/D-3325-2009; niccolai, elena/K-6091-2016; Ciriolo, Maria /K-6572-2016; AQUILANO, KATIA/K-8888-2016; Ganji, Purna chandra N/D-4193-2011; Bhakta-Guha, Dipita/E-8076-2012 OI Keith, Nicol/0000-0001-7862-3580; niccolai, elena/0000-0002-9205-8079; AQUILANO, KATIA/0000-0002-5905-9870; Ganji, Purna chandra N/0000-0002-4989-5234; Bilsland, Alan/0000-0003-0957-3908; Wang, Zongwei/0000-0002-1215-2912; Bhakta-Guha, Dipita/0000-0002-7144-3947 FU Swedish Society for Medical Research; Goesta Fraenkel Foundation; Ake Wiberg's Foundation; Ollie och Elof Ericsson's Foundation; Karolinska Institute; Linkoping University; University of Glasgow; Beatson Oncology Center Fund; Cancer Research UK grant [C301/A14762]; NIH NRSA grant [F31CA154080]; EU grant [MC-CIG-303514]; National Strategic Reference Framework grant [MIS-379346]; COST action [CM1201]; University of Florence; Italian Ministry of Research; Terry Fox Foundation; UAEU Program for Advanced Research; West Virginia Experimental Program; NIH [5P20RR016477, 8P20GM104434]; Swedish Research Council; Swedish Research Society; EU [278570]; University of Italy; Japanese Ministry of Science grant [24590493]; Galaxo Smith Kline; AIRC; NIH/NHLBI grant [R01HL107652, T32HL098062]; Eisai Healthcare Investigator grant; Ovarian and Prostate Cancer Research Trust FX We would like to thank Mr. Leroy Lowe for his vision and initiative in the GettingToKnowCancer organization. Dr. Jensen was funded by the Swedish Society for Medical Research, the Goesta Fraenkel Foundation, Ake Wiberg's Foundation, Ollie och Elof Ericsson's Foundation, the Karolinska Institute and Linkoping University. Drs Keith and Bilsland were funded by the University of Glasgow, Beatson Oncology Center Fund and Cancer Research UK grant C301/A14762. Dr. Arreola was funded by NIH NRSA grant F31CA154080. Dr. Georgakilas was funded by EU grant MC-CIG-303514, the National Strategic Reference Framework grant MIS-379346 and COST action CM1201. Dr. Amedei was funded by the University of Florence and the Italian Ministry of Research. Dr. Amin was partially funded by the Terry Fox Foundation, 2013 and the UAEU Program for Advanced Research 2013. Dr. Yi Charlie Chen was funded by the West Virginia Experimental Program to Stimulate Competitive Research and NIH grants 5P20RR016477 and 8P20GM104434. Dr. Dabrosin was funded by the Swedish Research Council and the Swedish Research Society. Dr. Generali was funded by the EU Seventh Framework Program grant 278570. Dr. Halicka was funded by the NIH. Dr. Niccolai was funded by the Italian Ministry of Research and the University of Italy. Dr. Honoki was funded by the Japanese Ministry of Science grant 24590493. Dr. Rathmell was funded by Galaxo Smith Kline for an investigator-initiated clinical trial. Dr. Ciriolo was funded by the AIRC. Dr. Fuster was funded by the NIH/NHLBI grant R01HL107652 and an Eisai Healthcare Investigator grant. Dr. Sophie Chen was funded by the Ovarian and Prostate Cancer Research Trust. Dr. Yin was funded by NIH/NHLBI grant T32HL098062. NR 465 TC 39 Z9 45 U1 14 U2 46 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2015 VL 35 SU S BP S224 EP S243 DI 10.1016/j.semcancer.2015.01.001 PG 20 WC Oncology SC Oncology GA CY7WG UT WOS:000366619400011 PM 25600295 ER PT J AU Calhoun, AW Pian-Smith, MCM Truog, RD Gaba, DM Meyer, EC AF Calhoun, Aaron William Pian-Smith, May C. M. Truog, Robert D. Gaba, David M. Meyer, Elaine C. TI The Importance of Deception in Simulation A Response SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Letter ID ISSUES C1 [Calhoun, Aaron William] Univ Louisville, Div Pediat Crit Care Med, Louisville, KY 40292 USA. [Pian-Smith, May C. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. [Truog, Robert D.] Harvard Univ, Sch Med,Div Med Eth, Inst Professionalism & Eth Practice,Dept Social M, Dept Anesthesiol Perioperat & Pain Med,Boston Chi, Boston, MA USA. [Gaba, David M.] Stanford Univ, Ctr Immers & Simulation Based Learning, Sch Med, Palo Alto, CA 94304 USA. [Gaba, David M.] VA Palo Alto HCS, Simulat Ctr, Palo Alto, CA USA. [Meyer, Elaine C.] Harvard Univ, Sch Med, Dept Psychiat, Inst Professionalism & Eth Practice,Boston Childr, Boston, MA 02115 USA. RP Calhoun, AW (reprint author), Univ Louisville, Div Pediat Crit Care Med, Louisville, KY 40292 USA. EM aaron.calhoun@louisville.edu NR 10 TC 0 Z9 0 U1 13 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD DEC PY 2015 VL 10 IS 6 BP 387 EP 390 DI 10.1097/SIH.0000000000000127 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY7OK UT WOS:000366597900011 ER PT J AU Yetisen, AK Davis, J Coskun, AF Church, GM Yun, SH AF Yetisen, Ali K. Davis, Joe Coskun, Ahmet F. Church, George M. Yun, Seok Hyun TI Bioart SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID GENETIC ART; BACTERIA; CULTURES; ARCHAEA; CELLS AB Bioart is a creative practice that adapts scientific methods and draws inspiration from the philosophical, societal, and environmental implications of recombinant genetics, molecular biology, and biotechnology. Some bioartists foster interdisciplinary relationships that blur distinctions between art and science. Others emphasize critical responses to emerging trends in the life sciences. Since bioart can be combined with realistic views of scientific developments, it may help inform the public about science. Artistic responses to biotechnology also integrate cultural commentary resembling political activism. Art is not only about 'responses', however. Bioart can also initiate new science and engineering concepts, foster openness to collaboration and increasing scientific literacy, and help to form the basis of artists' future relationships with the communities of biology and the life sciences. C1 [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Davis, Joe] MIT, Dept Biol, Cambridge, MA 02139 USA. [Davis, Joe; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Coskun, Ahmet F.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. [Yun, Seok Hyun] Harvard MIT Div Hlth Sci & Technol, MIT, Cambridge, MA 02139 USA. RP Yetisen, AK (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St, Cambridge, MA 02139 USA. EM ayetisen@mgh.harvard.edu; syun@mgh.harvard.edu NR 63 TC 4 Z9 4 U1 3 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD DEC PY 2015 VL 33 IS 12 BP 724 EP 734 DI 10.1016/j.tibtech.2015.09.011 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CZ0AV UT WOS:000366768400003 PM 26617334 ER PT J AU Friedman, GN Grannan, BL Nahed, BV Codd, PJ AF Friedman, Gabriel N. Grannan, Benjamin L. Nahed, Brian V. Codd, Patrick J. TI Initial Experience with High-Definition Camera-On-a-Chip Flexible Endoscopy for Intraventricular Neurosurgery SO WORLD NEUROSURGERY LA English DT Article DE Biopsy; Endoscopy; Flexible scope; High-definition; Third ventriculostomy ID CHOROID-PLEXUS CAUTERIZATION; 3RD VENTRICULOSTOMY; NEUROENDOSCOPY; TUMORS; HYDROCEPHALUS; MANAGEMENT AB OBJECTIVE: The usefulness of existing neuroendoscopes has been limited by either decreased range of motion or suboptimal image resolution. The flexible high-definition chip-camera endoscope has emerged as a potential solution to the shortcomings of available instruments by combining superior flexibility and image quality in order to better operate within spatially constrained intraventricular operations. CASE DESCRIPTION: Here we describe a 36-year-old woman who presented with hydrocephalus caused by an obstructive mass arising from the tectum. A high-definition camera-on-a-chip flexible neuroendoscope was used to sample the tectal mass after a traditional neuroendoscope was used to perform a third ventriculostomy. CONCLUSIONS: As demonstrated by this initial experience, the use of high-definition camera-on-a-chip flexible endoscopy may provide enhanced intraoperative visualization and application for intraventricular neurosurgery. C1 [Friedman, Gabriel N.; Grannan, Benjamin L.; Nahed, Brian V.; Codd, Patrick J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Friedman, Gabriel N.; Grannan, Benjamin L.; Nahed, Brian V.; Codd, Patrick J.] Harvard Univ, Sch Med, Boston, MA USA. RP Codd, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. EM patrick.codd@duke.edu NR 24 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD DEC PY 2015 VL 84 IS 6 BP 2053 EP 2058 DI 10.1016/j.wneu.2015.07.056 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CY3CQ UT WOS:000366286300092 PM 26255242 ER PT J AU Borus, JF Alexander, EK Bierer, BE Bringhurst, FR Clark, C Klanica, KE Stewart, EC Friedman, LS AF Borus, Jonathan F. Alexander, Erik K. Bierer, Barbara E. Bringhurst, F. Richard Clark, Christopher Klanica, Kaley E. Stewart, Erin C. Friedman, Lawrence S. TI The Education Review Board: A Mechanism for Managing Potential Conflicts of Interest in Medical Education SO ACADEMIC MEDICINE LA English DT Article AB Concerns about the influence of industry support on medical education, research, and patient care have increased in both medical and political circles. Some academic medical centers, questioning whether industry support of medical education could be appropriate and not a conflict of interest, banned such support. In 2009, a Partners HealthCare System commission concluded that interactions with industry remained important to Partners' charitable academic mission and made recommendations to transparently manage such relationships. An Education Review Board (ERB) was created to oversee and manage all industry support of Partners educational activities. Using a case review method, the ERB developed guidelines to implement the commission's recommendations. A multi-funder rule was established that prohibits industry support from only one company for any Partners educational activity. Within that framework, the ERB established guidelines on industry support of educational conferences, clinical fellowships, and trainees' expenses for attending external educational programs; gifts of textbooks and other educational materials; promotional opportunities associated with Partners educational activities; Partners educational activities under contract with an industry entity; and industry-run programs using Partners resources. Although many changes have resulted from the implementation of the ERB guidelines, the number of industry grants for Partners educational activities has remained relatively stable, and funding for these activities declined only moderately during the first three full calendar years (2011-2013) of ERB oversight. The ERB continually educates both the Partners community and industry about the rationale for its guidelines and its openness to their refinement in response to changes in the external environment. C1 [Borus, Jonathan F.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Borus, Jonathan F.; Alexander, Erik K.; Bierer, Barbara E.; Bringhurst, F. Richard] Harvard Univ, Sch Med, Boston, MA USA. [Alexander, Erik K.; Bierer, Barbara E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bringhurst, F. Richard] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Clark, Christopher; Klanica, Kaley E.; Stewart, Erin C.] Partners HealthCare, Off Interact Ind, Boston, MA USA. [Clark, Christopher] Partners HealthCare, Off Gen Counsel, Boston, MA USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA USA. [Friedman, Lawrence S.] Harvard Univ, Sch Med, Med, Boston, MA USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Borus, JF (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jborus@partners.org NR 13 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD DEC PY 2015 VL 90 IS 12 BP 1611 EP 1617 DI 10.1097/ACM.0000000000000788 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA CX3FB UT WOS:000365580300017 PM 26083402 ER PT J AU Huang, WL Ojo, KK Zhang, ZS Rivas, K Vidadala, RSR Scheele, S DeRocher, AE Choi, R Hulverson, MA Barrett, LK Bruzual, I Siddaramaiah, LK Kerchner, KM Kurnick, MD Freiberg, GM Kempf, D Hol, WGJ Merritt, EA Neckermann, G de Hostos, EL Isoherranen, N Maly, DJ Parsons, M Doggett, JS Van Voorhis, WC Fang, EK AF Huang, Wenlin Ojo, Kayode K. Zhang, Zhongsheng Rivas, Kasey Vidadala, Rama Subba Rao Scheele, Suzanne DeRocher, Amy E. Choi, Ryan Hulverson, Matthew A. Barrett, Lynn K. Bruzual, Igor Siddaramaiah, Latha Kallur Kerchner, Keshia M. Kurnick, Matthew D. Freiberg, Gail M. Kempf, Dale Hol, Wim G. J. Merritt, Ethan A. Neckermann, Georg de Hostos, Eugenio L. Isoherranen, Nina Maly, Dustin J. Parsons, Marilyn Doggett, J. Stone Van Voorhis, Wesley C. Fang, Erkang TI SAR Studies of 5-Aminopyrazole-4-carboxamide Analogues as Potent and Selective Inhibitors of Toxoplasma gondii CDPK1 SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Toxoplasma gondii; calcium-dependent protein kinase-1; enzyme inhibitor; structure-activity relationship studies ID PROTEIN-KINASE 1; CRYPTOSPORIDIUM-PARVUM; HOST-CELLS; T. GONDII; C. PARVUM; CALCIUM; INVASION; TARGET AB We previously discovered compounds based on a 5-aminopyrazole-4-carboxamide scaffold to be potent and selective inhibitors of CDPK1 from T. gondii. The current work, through structure-activity relationship studies, led to the discovery of compounds (34 and 35) with improved characteristics over the starting inhibitor 1 in terms of solubility, plasma exposure after oral administration in mice, or efficacy on parasite growth inhibition. Compounds 34 and 35 were further demonstrated to be more effective than 1 in a mouse infection model and markedly reduced the amount of T. gondii in the brain, spleen, and peritoneal fluid, and 35 given at 20 mg/kg eliminated T. gondii from the peritoneal fluid. C1 [Huang, Wenlin; Zhang, Zhongsheng; Siddaramaiah, Latha Kallur; Kerchner, Keshia M.; Hol, Wim G. J.; Merritt, Ethan A.; Fang, Erkang] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Ojo, Kayode K.; Rivas, Kasey; Choi, Ryan; Van Voorhis, Wesley C.] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98109 USA. [Ojo, Kayode K.; Rivas, Kasey; Choi, Ryan; Van Voorhis, Wesley C.] Univ Washington, Dept Med, Ctr Emerging & Reemerging Infect Dis, Seattle, WA 98109 USA. [Vidadala, Rama Subba Rao; Maly, Dustin J.] Univ Washington, Dept Chem, Seattle, WA 98195 USA. [Scheele, Suzanne; DeRocher, Amy E.; Parsons, Marilyn] Ctr Infect Dis Res, Seattle, WA 98109 USA. [Bruzual, Igor] Portland VA Med Ctr, Portland, OR 97239 USA. [Kurnick, Matthew D.; Freiberg, Gail M.; Kempf, Dale] AbbVie, N Chicago, IL 60064 USA. [Neckermann, Georg; de Hostos, Eugenio L.] PATH, San Francisco, CA 94102 USA. [Isoherranen, Nina] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Parsons, Marilyn; Van Voorhis, Wesley C.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. RP Fang, EK (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA. EM wesley@uw.edu; erkang@uw.edu OI Parsons, Marilyn/0000-0003-3994-8096 FU National Institute of Allergy and Infectious Diseases; National Institute of Child Health and Human Development of the National Institutes of Health [R01AI089441, R01AI111341, R01HD080670]; United States Department of Agriculture [2014-06183]; United States Department of Veterans Affairs Biomedical Laboratory Research and Development [BX002440]; U.S. Department of Energy Office of Basic Energy Sciences [DE-AC02-76SF00515]; National Institutes of Health [P41GM103393] FX Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases and National Institute of Child Health and Human Development of the National Institutes of Health under award numbers R01AI089441, R01AI111341, and R01HD080670. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported in part by Award #2014-06183 from the United States Department of Agriculture and by Career Development Award #BX002440 from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development. Crystallography performed in support of the work benefitted from remote access to resources at the Stanford Synchrotron Radiation Lightsource supported by the U.S. Department of Energy Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515 and by the National Institutes of Health (P41GM103393). NR 22 TC 8 Z9 9 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD DEC PY 2015 VL 6 IS 12 BP 1184 EP 1189 DI 10.1021/acsmedchemlett.5b00319 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CY3XO UT WOS:000366343400003 PM 26693272 ER PT J AU Shen, T Baker, K AF Shen, Tao Baker, Keith TI Venous return and clinical hemodynamics: how the body works during acute hemorrhage SO ADVANCES IN PHYSIOLOGY EDUCATION LA English DT Article DE hemorrhage; venous return; circulation; Guyton ID SYSTEMIC VASCULAR COMPLIANCE; INTENSIVE-CARE-UNIT; CARDIAC-OUTPUT; VOLUME RELATIONSHIPS; UNSTRESSED VOLUME; FILLING PRESSURE; CAPACITY; CURVES; REFLEX; HEART AB Venous return is a major determinant of cardiac output. Adjustments within the venous system are critical for maintaining venous pressure during loss in circulating volume. This article reviews two factors that are thought to enable the venous system to compensate during acute hemorrhage: 1) changes in venous elastance and 2) mobilization of unstressed blood volume into stressed blood volume. We show that mobilization of unstressed blood volume is the predominant and more effective mechanism in preserving venous pressure. Preservation of mean circulatory filling pressure helps sustain venous return and thus cardiac output during significant hemorrhage. C1 [Shen, Tao] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shen, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Gray Bigelow 444,55 Fruit St, Boston, MA 02114 USA. EM tshen2@partners.org NR 30 TC 0 Z9 0 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1043-4046 EI 1522-1229 J9 ADV PHYSIOL EDUC JI Adv. Physiol. Educ. PD DEC 1 PY 2015 VL 39 IS 4 BP 267 EP 271 DI 10.1152/advan.00050.2015 PG 5 WC Education, Scientific Disciplines; Physiology SC Education & Educational Research; Physiology GA CY1AI UT WOS:000366138100004 PM 26628647 ER PT J AU Haran, JP Wu, G Bucci, V Fischer, A Boyer, EW Hibberd, PL AF Haran, John P. Wu, Gregory Bucci, Vanni Fischer, Andrew Boyer, Edward W. Hibberd, Patricia L. TI Treatment of bacterial skin infections in ED observation units: factors influencing prescribing practice SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID CLOSTRIDIUM-DIFFICILE INFECTION; SOFT-TISSUE INFECTIONS; ANTIBIOTIC-ASSOCIATED DIARRHEA; SEX-DIFFERENCES; MEDICAL-CARE; DISPARITIES; DIAGNOSIS; SEPSIS; RISK AB Objective: The Infectious Disease Society of America (IDSA) publishes evidence-based guidelines for the treatment of skin and soft tissue infections. How closely physicians follow these guidelines is unknown, particularly in the emergency department observation unit (EDOU) where increasing numbers of patients are treatment for these infections. Our objectives were to describe (1) the antibiotic treatment patterns EDOU patients, (2) physicians' adherence to the IDSA guidelines, and (3) factors that influence physician's prescribing practices. Methods: This prospective cohort enrolled adult patients discharged froman EDOU at an academic medical center after treatment for a skin or soft tissue infection. Information was collected from chart review and patient interview pertaining to the patient's sociodemographic characteristics, presenting illness, and antibiotic treatment regimens. Treatment regimens were compared with national guidelines. Results: The study included 193 patients of which only 43% were treated according to IDSA guidelines, 42% were overtreated, and 15% were undertreated. Women were more likely to be undertreated (relative risk, 1.58; 95% confidence interval, 1.21-2.06), whereas patients 50 years and older were at risk for overtreatment (relative risk, 1.44; 95% confidence interval, 1.03-2.02). Women also received shorter courses of antibiotic therapy with an average of 9.6 days of treatment compared with 10.6 days for men. Conclusions: Physician antibiotic prescribing practices demonstrated poor adherence to IDSA guidelines and were influenced by the patient's age and sex. Standardized antibiotic protocols for treatment of skin and soft tissue infections to IDSA guidelines in the EDOU would minimize physician bias. (C) 2015 Elsevier Inc. All rights reserved. C1 [Haran, John P.; Wu, Gregory; Fischer, Andrew; Boyer, Edward W.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Bucci, Vanni] Univ Massachusetts Dartmouth, Dept Biol, N Dartmouth, MA USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA. RP Haran, JP (reprint author), 55 Lake Ave North, Worcester, MA 01655 USA. EM john.haran@umassmed.edu FU Department of Emergency Medicine; National Institutes of Health [1R15AI112985-01A1, 5K24AT003683-09] FX This study was designed and carried out at the University of Massachusetts Medical School and was supported by an intradepartmental grant through the Department of Emergency Medicine. VB is supported by an National Institutes of Health award 1R15AI112985-01A1 and PLH by 5K24AT003683-09. NR 30 TC 1 Z9 1 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD DEC PY 2015 VL 33 IS 12 BP 1780 EP 1785 DI 10.1016/j.ajem.2015.08.035 PG 6 WC Emergency Medicine SC Emergency Medicine GA CY1IC UT WOS:000366158900012 PM 26381681 ER PT J AU Brumfield, E Bernard, KRL Kabrhel, C AF Brumfield, Emily Bernard, Kenneth R. L. Kabrhel, Christopher TI Life-threatening flecainide overdose treated with intralipid and extracorporeal membrane oxygenation SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID RESUSCITATION; INTOXICATION; INFUSION; EMULSION; SUPPORT AB Flecainide is a Class Ic antiarrythmic agent associated with adverse events due to its pro-arrythmic effects. We report the case of a 33-year-old female presenting in cardiac arrest after a flecainide overdose treated with intravenous fat emulsion (IFE), sodium bicarbonate (NaHCO3), and extracorporeal membrane oxygenation (ECMO). This case reviews the pathophysiology and management of flecainide toxicity including novel strategies of IFE and ECMO. C1 [Brumfield, Emily; Bernard, Kenneth R. L.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Kabrhel, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Brumfield, E (reprint author), Brigham & Womens Hosp, 75 Francis St,Neville House, Boston, MA 02115 USA. EM ebrumfield@partners.org; kbernard@partners.org; ckabrhel@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 NR 14 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD DEC PY 2015 VL 33 IS 12 AR 1840.e3 DI 10.1016/j.ajem.2015.04.012 PG 3 WC Emergency Medicine SC Emergency Medicine GA CY1IC UT WOS:000366158900036 PM 25921969 ER PT J AU Molina, RL Easter, SR Venkatesh, KK Cantonwine, DE Kaimal, AJ Tuomala, RE Riley, LE AF Molina, Rose L. Easter, Sarah Rae Venkatesh, Kartik K. Cantonwine, David E. Kaimal, Anjali J. Tuomala, Ruth E. Riley, Laura E. TI Defining Physiological Predictors of Peripartum Maternal Bacteremia SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Scientific Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 02-07, 2015 CL San Diego, CA SP Soc Maternal Fetal Med DE bacteremia; infection; peripartum; sepsis; vital signs ID SEVERE SEPSIS; PREGNANCY; MORBIDITY; MORTALITY; RISK AB Objective This study aims to examine physiological and laboratory parameters associated with peripartum maternal bacteremia. Study Design This case control study matched 115 cases (women with fever and bacteremia during the peripartum period) to 285 controls (defined as the next two febrile women with negative blood cultures at the same institution) from two academic medical centers from 2009 to 2013. Conditional logistic regression models were used to evaluate the association of physiological and laboratory parameters with maternal bacteremia at the time of initial and maximum fever. Results At the time of initial fever, temperature > 103 degrees F (adjusted odds ratio [aOR]: 5.58, 95% confidence interval [CI]: 2.05-15.19) and respiratory rate (RR) > 20 respirations per minute (aOR: 5.27, 95% CI: 2.32-11.96) were associated with bacteremia. At the time of maximum fever, temperature (> 102 degrees F, aOR: 3.37, 95% CI: 1.61-7.06; > 103 degrees F, aOR: 7.96, 95% CI: 3.56-17.82), heart rate > 110 beats per minute (aOR: 2.20, 95% CI: 1.21-3.99), and RR > 20 (aOR: 3.65, 95% CI: 1.65-8.08) were associated with bacteremia. Bandemia > 10% (aOR: 2.44, 95% CI: 1.07-5.54) was associated with bacteremia. Conclusion Physiological and laboratory parameters associated with maternal bacteremia differed from those reported with sepsis in the adult critical care population. Further studies of objective markers are needed to improve detection and treatment of peripartum bacteremia. C1 [Molina, Rose L.; Easter, Sarah Rae; Venkatesh, Kartik K.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02120 USA. [Molina, Rose L.; Easter, Sarah Rae; Venkatesh, Kartik K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cantonwine, David E.; Tuomala, Ruth E.] Brigham & Womens Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Kaimal, Anjali J.; Riley, Laura E.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Molina, RL (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1620 Tremont St,OBC3, Boston, MA 02120 USA. EM rlmolina@partners.org OI Easter, Sarah Rae/0000-0002-0150-3537 NR 15 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 EI 1098-8785 J9 AM J PERINAT JI Am. J. Perinatol. PD DEC PY 2015 VL 32 IS 14 BP 1342 EP 1350 DI 10.1055/s-0035-1565995 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CY2GG UT WOS:000366226200010 PM 26489062 ER PT J AU Levy, BD Noel, PJ Freemer, MM Cloutier, MM Georas, SN Jarjour, NN Ober, C Woodruff, P Barnes, KC Bender, BG Camargo, CA Chupp, GL Denlinger, LC Fahy, JV Fitzpatrick, AM Fuhlbrigge, A Gaston, BM Hartert, TV Kolls, JK Lynch, SV Moore, WC Morgan, WJ Nadeau, KC Ownby, DR Solway, J Szefler, SJ Wenzel, SE Wright, RJ Smith, RA Erzurum, SC AF Levy, Bruce D. Noel, Patricia J. Freemer, Michelle M. Cloutier, Michelle M. Georas, Steve N. Jarjour, Nizar N. Ober, Carole Woodruff, PrescottG. Barnes, Kathleen C. Bender, Bruce G. Camargo, Carlos A., Jr. Chupp, Geoff L. Denlinger, Loren C. Fahy, John V. Fitzpatrick, Anne M. Fuhlbrigge, Anne Gaston, Ben M. Hartert, Tina V. Kolls, Jay K. Lynch, Susan V. Moore, Wendy C. Morgan, Wayne J. Nadeau, Kari C. Ownby, Dennis R. Solway, Julian Szefler, Stanley J. Wenzel, Sally E. Wright, Rosalind J. Smith, Robert A. Erzurum, Serpil C. TI Future Research Directions in Asthma An NHLBI Working Group Report SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE asthma; prevention; phenotype; disease modification; implementation ID INNATE LYMPHOID-CELLS; CLUSTER-ANALYSIS; RESEARCH-PROGRAM; SYSTEMS BIOLOGY; PHENOTYPES; LUNG; INFLAMMATION; DISEASES; ADHERENCE; WORKSHOP AB Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma. C1 [Levy, Bruce D.; Fuhlbrigge, Anne] Brigham & Womens Hosp, Boston, MA 02115 USA. [Noel, Patricia J.; Freemer, Michelle M.; Smith, Robert A.] NHLBI, Bethesda, MD 20892 USA. [Cloutier, Michelle M.] Univ Connecticut, Ctr Hlth, Hartford, CT 06112 USA. [Georas, Steve N.] Univ Rochester, Rochester, NY USA. [Jarjour, Nizar N.; Denlinger, Loren C.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Ober, Carole; Solway, Julian] Univ Chicago, Chicago, IL 60637 USA. [Woodruff, PrescottG.; Lynch, Susan V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, Kathleen C.] Johns Hopkins Univ, Baltimore, MD USA. [Bender, Bruce G.] Natl Jewish Hlth, Denver, CO USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chupp, Geoff L.] Yale Univ, Sch Med, New Haven, CT USA. [Fitzpatrick, Anne M.] Emory Univ, Sch Med, Atlanta, GA USA. [Gaston, Ben M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Hartert, Tina V.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Kolls, Jay K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Moore, Wendy C.] Wake Forest Sch Med, Winston Salem, NC USA. [Morgan, Wayne J.] Univ Arizona, Tucson, AZ USA. [Nadeau, Kari C.] Stanford Sch Med, Stanford, CA USA. [Ownby, Dennis R.] Georgia Regents Univ, Augusta, GA USA. [Szefler, Stanley J.] Childrens Hosp Colorado, Denver, CO USA. [Szefler, Stanley J.] Univ Colorado, Sch Med, Denver, CO USA. [Wright, Rosalind J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Erzurum, Serpil C.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. RP Noel, PJ (reprint author), NHLBI, Div Lung Dis, Bldg 10, Bethesda, MD 20892 USA. EM noelp@nih.gov RI Morgan, Grace/C-8098-2013 OI Morgan, Grace/0000-0002-5467-0507 FU NHLBI, National Institutes of Health FX Supported by the NHLBI, National Institutes of Health. NR 40 TC 7 Z9 7 U1 0 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2015 VL 192 IS 11 BP 1366 EP 1372 DI 10.1164/rccm.201505-0963WS PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CX6RU UT WOS:000365829900017 PM 26305520 ER PT J AU Weiss, A Parina, RP Tang, JA Brumund, KT Chang, DC Bouvet, M AF Weiss, Anna Parina, Ralitza P. Tang, Jessica A. Brumund, Kevin T. Chang, David C. Bouvet, Michael TI Outcomes of thyroidectomy from a large California state database SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Southwestern-Surgical-Congress CY APR 26, 2015 CL Monterey, CA SP SW Surg Congress DE Outcomes after thyroidectomy; Thyroid surgery; Outcomes research; Thyroid; Outcomes; Complications ID RECURRENT LARYNGEAL NERVE; UNDERGO PARATHYROID AUTOTRANSPLANTATION; NATIONWIDE INPATIENT SAMPLE; POSTOPERATIVE HYPOCALCEMIA; SURGEON VOLUME; COMPLICATIONS; HEMATOMA; RISK AB BACKGROUND: Thyroidectomy is an operation with infrequent but potentially significant complications. This study aimed to determine risk factors for complication after thyroidectomy in California. METHODS: The California Office of Statewide Health Planning and Development database was retrospectively analyzed from 1995 to 2010. Main outcome measures were complications including death. Logistic regression identified risk factors for complications. RESULTS: There were 106,773 patients; 61% were women and 44% Caucasian; 16,287 (15%) thyroidectomies were performed at high-volume centers. Complication rates included voice change (.5%), vocal cord dysfunction (1.1%), hypocalcemia (4.5%), tracheostomy (1.62%), hematoma (1.75%), and death (.3%). There was significantly increased risk of complications for patients older than 65 compared with those younger than 40 years (odds ratio, 2.0; 95% confidence interval, 1.8 to 2.3; P < .01). High-volume hospitals were protective against complication (odds ratio, .8; 95% confidence interval, .6 to.97; P = .026). CONCLUSIONS: Older age was a significant risk factor for complication after thyroidectomy. Highvolume hospitals had lower risk. This information is useful in counseling patients about the risks of thyroid surgery. (C) 2015 Elsevier Inc. All rights reserved. C1 [Weiss, Anna; Parina, Ralitza P.; Tang, Jessica A.; Brumund, Kevin T.; Bouvet, Michael] Univ Calif San Diego, Dept Surg, La Jolla, CA 92093 USA. [Chang, David C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Bouvet, M (reprint author), Univ Calif San Diego, Dept Surg, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM mbouvet@ucsd.edu NR 21 TC 4 Z9 4 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2015 VL 210 IS 6 BP 1170 EP 1176 DI 10.1016/j.amjsurg.2015.08.011 PG 7 WC Surgery SC Surgery GA CY1OZ UT WOS:000366178300058 PM 26482517 ER PT J AU Bullman, T Hoffmire, C Schneiderman, A Bossarte, R AF Bullman, Tim Hoffmire, Claire Schneiderman, Aaron Bossarte, Robert TI Time dependent gender differences in suicide risk among Operation Enduring Freedom and Operation Iraqi Freedom veterans SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material DE Veterans; Suicide; Gender C1 [Bullman, Tim; Schneiderman, Aaron; Bossarte, Robert] US Dept Vet Affairs, Off Publ Hlth, Program Epidemiol, Washington, DC 20420 USA. [Hoffmire, Claire] US Dept Vet Affairs, Rocky Mt MIRECC Suicide Prevent, Denver, CO USA. RP Bullman, T (reprint author), US Dept Vet Affairs, Off Publ Hlth, Program Epidemiol, 810 Vermont Ave, Washington, DC 20420 USA. EM tim.bullman@va.gov NR 7 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD DEC PY 2015 VL 25 IS 12 BP 964 EP 965 DI 10.1016/j.annepidem.2015.09.008 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CY5IK UT WOS:000366441100015 PM 26493115 ER PT J AU Everson, GT Towner, WJ Davis, MN Wyles, DL Nahass, RG Thuluvath, PJ Etzkorn, K Hinestrosa, F Tong, M Rabinovitz, M McNally, J Brainard, DM Han, LL Doehle, B McHutchison, JG Morgan, T Chung, RT Tran, TT AF Everson, Gregory T. Towner, William J. Davis, Mitchell N. Wyles, David L. Nahass, Ronald G. Thuluvath, Paul J. Etzkorn, Kyle Hinestrosa, Federico Tong, Myron Rabinovitz, Mordechai McNally, John Brainard, Diana M. Han, Lingling Doehle, Brian McHutchison, John G. Morgan, Timothy Chung, Raymond T. Tran, Tram T. TI Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NATURAL-HISTORY; EPIDEMIOLOGY AB Background: Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. Objective: To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. Design: Randomized, phase 2, open-label study. (ClinicalTrials.gov:NCT01858766) Setting: 48 U.S. sites. Patients: 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. Measurements: Sustained virologic response at 12 weeks (SVR12). Results: In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. Limitation: The study was open-label, no inferential statistics were planned, and sample sizes were small. Conclusion: Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. C1 [Everson, Gregory T.] Univ Colorado Denver, Sch Med, Hepatol, Aurora, CO 80045 USA. [Towner, William J.] Kaiser Permanente, Los Angeles, CA 90027 USA. [Tran, Tram T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Davis, Mitchell N.] South Florida Ctr Gastroenterol, Digest CARE, Wellington, FL 33414 USA. [Wyles, David L.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Nahass, Ronald G.] ID CARE, Hillsborough, NJ 08844 USA. [Thuluvath, Paul J.] Mercy Med Ctr, Baltimore, MD 21202 USA. [Etzkorn, Kyle] Borland Groover Clin, Jacksonville, FL 32256 USA. [Hinestrosa, Federico] Orlando Immunol Ctr, Orlando, FL 32803 USA. [Tong, Myron] Huntington Med Res Inst, Pasadena, CA 91105 USA. [Rabinovitz, Mordechai] Univ Pittsburgh, Pittsburgh, PA 15217 USA. [McNally, John; Brainard, Diana M.; Han, Lingling; Doehle, Brian; McHutchison, John G.] Gilead Sci Inc, Foster City, CA 94404 USA. [Morgan, Timothy] VA Long Beach Healthcare Syst, Long Beach, CA 90822 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Everson, GT (reprint author), Univ Colorado Denver, Sch Med, Hepatol, 1635 Aurora Court,B-154, Aurora, CO 80045 USA. EM greg.everson@ucdenver.edu FU Gilead Sciences FX Gilead Sciences. NR 18 TC 20 Z9 20 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 2015 VL 163 IS 11 BP 818 EP + DI 10.7326/M15-1000 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CX7FB UT WOS:000365866500005 PM 26551051 ER PT J AU Della-Torre, E Feeney, E Deshpande, V Mattoo, H Mahajan, V Kulikova, M Wallace, ZS Carruthers, M Chung, RT Pillai, S Stone, JH AF Della-Torre, Emanuel Feeney, Eoin Deshpande, Vikram Mattoo, Hamid Mahajan, Vinay Kulikova, Maria Wallace, Zachary S. Carruthers, Mollie Chung, Raymond T. Pillai, Shiv Stone, John H. TI B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID LIVER FIBROSIS; SYSTEMIC-SCLEROSIS; HEPATITIS-C; RITUXIMAB; MECHANISMS; EXPRESSION; FIBROBLASTS; IGG4 AB Objectives Fibrosis is a predominant feature of IgG4-related disease (IgG4-RD). B-cell depletion induces a prompt clinical and immunological response in patients with IgG4-RD, but the effects of this intervention on fibrosis in IgG4-RD are unknown. We used the enhanced liver fibrosis (ELF) score to address the impact of rituximab on fibroblast activation. The ELF score is an algorithm based on serum concentrations of procollagen-III aminoterminal propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid. Methods Ten patients with active, untreated IgG4-RD were enrolled. ELF scores were measured and correlated with the IgG4-RD Responder Index, serum IgG4, circulating plasmablasts and imaging studies. Through immunohistochemical stains for CD3, CD20, IgG4 and a-smooth muscle actin, we assessed the extent of the lymphoplasmacytic infiltration and the degree of fibroblast activation in one patient with tissue biopsies before and after rituximab. Results The ELF score was increased in patients with IgG4-RD compared with healthy controls (8.3 +/- 1.4 vs 6.2 +/- 0.9; p=0.002) and correlated with the number of organs involved (R-2=0.41; p=0.04). Rituximab induced significant reductions in the ELF score, the number of circulating plasmablasts and the IgG4-RD Responder Index (p<0.05 for all three parameters). Rituximab reduced both the lymphoplasmacytic infiltrate and myofibroblast activation. IgG4-RD relapse coincided with recurrent increases in the ELF score, indicating reactivation of collagen deposition. Conclusions The ELF score may be a clinically useful indicator of active fibrosis and the extent of disease in IgG4-RD. B-cell depletion has the potential to halt continued collagen deposition by attenuating the secretory phenotype of myofibroblasts in IgG4-RD lesions. C1 [Della-Torre, Emanuel; Mattoo, Hamid; Mahajan, Vinay; Kulikova, Maria; Pillai, Shiv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Della-Torre, Emanuel] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Unit Med & Clin Immunol, Milan, Italy. [Feeney, Eoin; Chung, Raymond T.] Massachusetts Gen Hosp, Ctr Liver, Boston, MA 02114 USA. [Feeney, Eoin; Chung, Raymond T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wallace, Zachary S.; Carruthers, Mollie; Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM jhstone@mgh.harvard.edu OI Della Torre, Emanuel/0000-0002-9192-4270 FU National Institutes of Health [AI 064930, AI 076505]; Autoimmunity Center of Excellence in IgG4-RD - National Institute of Allergy and Infectious Diseases FX This work was funded in part by grants AI 064930 and AI 076505 from the National Institutes of Health and by the Autoimmunity Center of Excellence in IgG4-RD, funded by the National Institute of Allergy and Infectious Diseases. NR 35 TC 11 Z9 16 U1 1 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 2015 VL 74 IS 12 BP 2236 EP 2243 DI 10.1136/annrheumdis-2014-205799 PG 8 WC Rheumatology SC Rheumatology GA CX6YA UT WOS:000365846400027 PM 25143523 ER PT J AU Shahian, DM AF Shahian, David M. TI 50TH ANNIVERSARY LANDMARK COMMENTARY ON EDWARDS FH, CLARK RE, SCHWARTZ M. CORONARY ARTERY BYPASS GRAFTING: THE SOCIETY OF THORACIC SURGEONS NATIONAL DATABASE EXPERIENCE. ANN THORAC SURG 1994;57:12-9 SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID MODEL C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, Bulfinch 2,55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 1990 EP 1991 DI 10.1016/j.athoracsur.2015.10.057 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700011 PM 26652510 ER PT J AU Jacobs, JP Shahian, DM Prager, RL Edwards, FH McDonald, D Han, JM D'Agostino, RS Jacobs, ML Kozower, BD Badhwar, V Thourani, VH Gaissert, HA Fernandez, FG Wright, C Fann, JI Paone, G Sanchez, JA Cleveland, JC Brennan, JM Dokholyan, RS O'Brien, SM Peterson, ED Grover, FL Patterson, GA AF Jacobs, Jeffrey P. Shahian, David M. Prager, Richard L. Edwards, Fred H. McDonald, Donna Han, Jane M. D'Agostino, Richard S. Jacobs, Marshall L. Kozower, Benjamin D. Badhwar, Vinay Thourani, Vinod H. Gaissert, Henning A. Fernandez, Felix G. Wright, Cam Fann, James I. Paone, Gaetano Sanchez, Juan A. Cleveland, Joseph C., Jr. Brennan, J. Matthew Dokholyan, Rachel S. O'Brien, Sean M. Peterson, Eric D. Grover, Frederick L. Patterson, G. Alexander TI Introduction to the STS National Database Series: Outcomes Analysis, Quality Improvement, and Patient Safety SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID SURGERY DATABASE; MAJOR MORBIDITY; MORTALITY; SOCIETY; PREDICTORS; CANCER AB The Society of Thoracic Surgeons (STS) National Database is the foundation for most of the Society's quality, research, and patient safety activities. Beginning in January 2016 and repeating each year, The Annals of Thoracic Surgery will publish a monthly Database series of scholarly articles on outcomes analysis, quality improvement, and patient safety. Six articles will be directly derived from the STS National Database and will be published every other month: three articles on outcomes and quality (one each from the STS Adult Cardiac Surgery Database, the STS Congenital Heart Surgery Database, and the STS General Thoracic Surgery Database), and three articles on research (one from each of these three specialty databases). These six articles will alternate with five additional articles on topics related to patient safety. The final article, to be published in December, will provide a summary of the prior 11 manuscripts. This series will allow STS and its Workforces on National Databases, Research Development, and Patient Safety to convey timely information aimed at improving the quality and safety of cardiothoracic surgery. (C) 2015 by The Society of Thoracic Surgeons C1 [Jacobs, Jeffrey P.; Jacobs, Marshall L.; Sanchez, Juan A.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, Dept Surg, Div Cardiovasc Surg, St Petersburg, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Florida Hosp Children, St Petersburg, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, Dept Surg, Div Cardiovasc Surg, Tampa, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Florida Hosp Children, Tampa, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, Dept Surg, Div Cardiovasc Surg, Orlando, FL USA. [Jacobs, Jeffrey P.; Jacobs, Marshall L.] Florida Hosp Children, Orlando, FL USA. [Shahian, David M.; Gaissert, Henning A.; Wright, Cam] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Prager, Richard L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Edwards, Fred H.] Univ Florida, Coll Med, Jacksonville, FL USA. [McDonald, Donna; Han, Jane M.] Soc Thorac Surg, Chicago, IL USA. [D'Agostino, Richard S.] Lahey Hosp & Med Ctr, Burlington, MA USA. [Kozower, Benjamin D.] Univ Virginia, Charlottesville, VA USA. [Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Thourani, Vinod H.; Fernandez, Felix G.] Emory Univ, Atlanta, GA 30322 USA. [Fann, James I.] Stanford Univ, Stanford, CA 94305 USA. [Paone, Gaetano] Henry Ford Hosp, Detroit, MI 48202 USA. [Cleveland, Joseph C., Jr.; Grover, Frederick L.] Univ Colorado, Sch Med, Aurora, CO USA. [Brennan, J. Matthew; Dokholyan, Rachel S.; O'Brien, Sean M.; Peterson, Eric D.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Patterson, G. Alexander] Washington Univ, Sch Med, St Louis, MO USA. RP Jacobs, JP (reprint author), John Hopkins All Childrens Heart Inst, Div Cardiovasc Surg, 601 Fifth St S, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com NR 9 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 1992 EP 2000 DI 10.1016/j.athoracsur.2015.10.060 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700012 PM 26525868 ER PT J AU MacGillivray, TE AF MacGillivray, Thomas E. TI Scholarship in Education: The Clarion Call SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material AB I vividly remember the orientation session for my surgical internship. One of my eager cointerns bravely asked our sage but salty program director to explain the surgical residency curriculum. The program director pondered for a moment and responded, "Your training starts on July 1st Year One and finishes on June 30th five years from now. Everything that happens between now and then is your curriculum." C1 [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox 650, Boston, MA 02114 USA. EM tmacgillivray@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 2001 EP 2002 DI 10.1016/j.athoracsur.2015.10.058 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700013 PM 26652511 ER PT J AU Heng, E Stone, JR Kim, JB Lee, H MacGillivray, TE Sundt, TM AF Heng, Elbert Stone, James R. Kim, Joon Bum Lee, Hang MacGillivray, Thomas E. Sundt, Thoralf M. TI Comparative Histology of Aortic Dilatation Associated With Bileaflet Versus Trileaflet Aortic Valves SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 05-08, 2014 CL Tucson, AZ SP So Thorac Surg Assoc ID DILATED ASCENDING AORTA; THORACIC AORTA; RISK-FACTORS; REPLACEMENT; DISSECTION; DISEASE; MANAGEMENT; ANEURYSM; GUIDELINES; STENOSIS AB Background. A more aggressive posture toward resection of the dilated aorta has been advocated when associated with bicuspid aortic valve (BAV), based on the notion that aortic material properties are weaker in this setting despite scant data to support or refute this position. The hypothesis that histologic abnormality reflects aortic wall strength was tested by comparing aortas from patients with BAV and trileaflet aortic valve. Methods. Resected aortas associated with BAV (n = 60) and trileaflet aortic valve (n = 24) were compared with normal diameter aortas from patients undergoing cardiac transplantation (n = 16) by five histologic criteria: elastic fiber loss (graded 0-4), smooth muscle cell loss (graded 0-4), medial proteoglycan accumulation (graded 0-3), medial fibrosis (graded 0-3), and atherosclerosis (graded 0-3). Patients with known connective tissue disorders, systemic inflammatory conditions, dissection, or prior heart surgery were excluded. Results. Patients with BAV were a decade younger and more often had functional stenosis. The extent of elastic fiber loss, smooth muscle cell loss, medial fibrosis, and atherosclerosis was more severe in trileaflet aortic valve than BAV when considered across all diameters and when stratified to those between 4 and 5 cm. Conclusions. More severe histologic abnormalities associated with trileaflet aortic valve compared with BAV, especially when stratified by diameter, do not support a more aggressive approach to surgical intervention for dilatation associated with BAV. Indeed, if based on histologic diagnosis alone, our findings are suggestive that the converse might be true. Additionally, the lack of correlation between aortic diameter and histologic abnormality in the setting of BAV highlights the inadequacy of diameter alone as a criterion for aortic resection. (C) 2015 by The Society of Thoracic Surgeons C1 Brown Univ, Sch Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Dept Pathol, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Thorac & Cardiovasc Surg, Seoul, South Korea. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 01224 USA. EM tsundt@mgh.harvard.edu OI Kim, Joon Bum/0000-0001-5801-2395 NR 31 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 2095 EP 2101 DI 10.1016/j.athoracsur.2015.05.105 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700028 PM 26338050 ER PT J AU Marsteller, JA Wen, M Hsu, YJ Bauer, LC Schwann, NM Young, CJ Sanchez, JA Errett, NA Gurses, AP Thompson, DA Wahr, JA Martinez, EA AF Marsteller, Jill A. Wen, Mei Hsu, Yea-Jen Bauer, Laura C. Schwann, Nanette M. Young, Christopher J. Sanchez, Juan A. Errett, Nicole A. Gurses, Ayse P. Thompson, David A. Wahr, Joyce A. Martinez, Elizabeth A. TI y Safety Culture in Cardiac Surgical Teams: Data From Five Programs and National Surgical Comparison SO ANNALS OF THORACIC SURGERY LA English DT Article ID HEALTH-CARE; CLIMATE; BEHAVIOR; ERRORS; NURSES; BLAME AB Background. Little is known about safety culture in the area of cardiac surgery as compared with other types of surgery. The unique features of cardiac surgical teams may result in different perceptions of patient safety and patient safety culture. Methods. We measured and described safety culture in five cardiovascular surgical centers using the Hospital Survey on Patient Safety Culture, and compared the data with the Agency for Healthcare Research and Quality (AHRQ) 2010 comparative database in surgery and anesthesiology (all types). We reported mean scores, standard deviations, and percent positive responses for the two single-item measures and 12 patient safety climate dimensions in the Hospital Survey on Patient Safety Culture. Results. In the five cardiac surgical programs, the dimension of teamwork within hospital units had the highest positive score (74% positive responses), and the dimension of nonpunitive response to error had the lowest score (38% positive responses). Surgeons and support staff perceived better safety climate than nurses, perfusionists, and anesthesia practitioners. The cardiac surgery cohort reported more positive safety climate than the AHRQ all-type surgery cohort in four dimensions but lower frequency of reporting mistakes. The cardiac anesthesiology cohort scored lower on two dimensions compared with the AHRQ all-type anesthesiology cohort. Conclusions. This study identifies patient safety areas for improvement in cardiac surgical teams in comparison with all-type surgical teams. We also found that different professional disciplines in cardiac surgical teams perceive patient safety differently. (C) 2015 by The Society of Thoracic Surgeons C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Sch Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD USA. Western Illinois Univ, Coll Educ & Human Serv, Dept Hlth Sci, Macomb, IL 61455 USA. Univ S Florida, Morsani Coll Med, Dept Anesthesiol, Lehigh Valley Hlth Network, Tampa, FL USA. Univ Missouri, Kansas City, MO 64110 USA. Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. Soc Cardiovasc Anesthesiologists Fdn, Richmond, VA USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Marsteller, JA (reprint author), 624 N Broadway, Baltimore, MD 21205 USA. EM jmarste2@jhu.edu FU Society of Cardiovascular Anaesthesiologists Foundation FX This research was supported by the Society of Cardiovascular Anaesthesiologists Foundation. The authors acknowledge Baystate Medical Center, Massachusetts; Medical University of South Carolina, South Carolina; New York University Medical Center, New York; Lehigh Valley Health Network, Pennsylvania; and St. Johns Medical Center, Missouri, for their participation in and devotion to the study. NR 28 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 2182 EP 2189 DI 10.1016/j.athoracsur.2015.05.109 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700039 PM 26330011 ER PT J AU Pantoja, JL Zhang, ZH Tartibi, M Sun, K Macmillan, W Guccione, JM Ge, L Ratcliffe, MB AF Pantoja, Joe Luis Zhang, Zhihong Tartibi, Mehrzad Sun, Kay Macmillan, Warrick Guccione, Julius M. Ge, Liang Ratcliffe, Mark B. TI Residual Stress Impairs Pump Function After Surgical Ventricular Remodeling: A Finite Element Analysis SO ANNALS OF THORACIC SURGERY LA English DT Article ID REDUCTION SURGERY; MODEL; ANEURYSM; RESTORATION; MECHANICS; MYOCARDIUM; MUSCLE AB Background. Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. Methods. Previously described finite element models of the LV based on magnetic resonance imaging data obtained in 5 sheep 16 weeks after anteroapical myocardial infarction were used. Simulated polyethylene terephthalate fiber (Dacron) patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated, and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. Results. VIRTUAL-DOR was associated with significant RS that was tensile (2.89 +/- 1.31 kPa) in the remote myocardium and compressive (234.15 +/- 65.53 kPa) in the border zone. VIRTUAL-DOR+RS (compared with VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS, with the greatest change in the border zone (43.5-fold and 7.1-fold, respectively; p < 0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%; p = 0.0606, and 10.6%; p = 0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. Conclusions. Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the border zone and associated with reductions in FS and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function. (C) 2015 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@va.gov FU NIH grant [R01-HL-63348] FX This study was supported by NIH grant R01-HL-63348 (Dr Ratcliffe). This support is gratefully acknowledged. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 2198 EP 2205 DI 10.1016/j.athoracsur.2015.05.119 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700041 PM 26341601 ER PT J AU Luthra, S Leiva-Juarez, MM Taggart, DP AF Luthra, Suvitesh Leiva-Juarez, Miguel M. Taggart, David P. TI Systematic Review of Therapies for Stable Coronary Artery Disease in Diabetic Patients SO ANNALS OF THORACIC SURGERY LA English DT Review ID BARI 2D TRIAL; REVASCULARIZATION INVESTIGATION BARI; SIROLIMUS-ELUTING STENT; BYPASS-SURGERY; MULTIVESSEL DISEASE; RANDOMIZED-TRIAL; CLINICAL-TRIALS; MEDICAL THERAPY; GLUCOSE CONTROL; TASK-FORCE AB Diabetes mellitus is a significant risk modifier for stable coronary artery disease, causing patients to have more extensive and diffuse lesions. Opposing treatment strategies remain a matter of debate. A multiple database search was conducted and outcomes, lesion, and patient characteristics were compared. Overall mortality, cardiac death, major adverse cardiovascular and cerebrovascular events, and need for revascularization were higher with percutaneous coronary intervention than with coronary artery bypass graft surgery. Multivessel disease and high Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) scores were associated with better outcomes for coronary artery bypass graft surgery. (C) 2015 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Div Cardiac Surg, Corrigan Minehan Heart Ctr, Boston, MA 02114 USA. John Radcliffe Hosp, Oxford Heart Ctr, Oxford OX3 9DU, England. RP Luthra, S (reprint author), New Cross Hosp, Div Cardiac Surg, RWH, Wolverhampton WV10 0QP, W Midlands, England. EM suviteshluthra@yahoo.com NR 50 TC 4 Z9 4 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2015 VL 100 IS 6 BP 2383 EP 2397 DI 10.1016/j.athoracsur.2015.07.005 PG 15 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6QD UT WOS:000365824700082 PM 26530540 ER PT J AU Pulli, B Ali, M Iwamoto, Y Zeller, MWG Schob, S Linnoila, JJ Chen, JW AF Pulli, Benjamin Ali, Muhammad Iwamoto, Yoshiko Zeller, Matthias W. G. Schob, Stefan Linnoila, Jenny J. Chen, John W. TI Myeloperoxidase-Hepatocyte-Stellate Cell Cross Talk Promotes Hepatocyte Injury and Fibrosis in Experimental Nonalcoholic Steatohepatitis SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID FATTY LIVER-DISEASE; MITOCHONDRIAL PERMEABILITY TRANSITION; N-TERMINAL KINASE; HEPATIC-FIBROSIS; OXIDATIVE STRESS; NATURAL-HISTORY; REACTIVE OXYGEN; OXIDANT STRESS; TGF-BETA; RAT AB Aims: Myeloperoxidase (MPO), a highly oxidative enzyme secreted by leukocytes has been implicated in human and experimental nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain unknown. In this study, we investigated how MPO contributes to progression from steatosis to NASH. Results: In C57Bl/6J mice fed a diet deficient in methionine and choline to induce NASH, neutrophils and to a lesser extent inflammatory monocytes are markedly increased compared with sham mice and secrete abundant amounts of MPO. Through generation of HOCl, MPO directly causes hepatocyte death in vivo. In vitro experiments demonstrate mitochondrial permeability transition pore induction via activation of SAPK/JNK and PARP. MPO also contributes to activation of hepatic stellate cells (HSCs), the most important source of collagen in the liver. In vitro MPO-activated HSCs have an activation signature (MAPK and PI3K-AKT phosphorylation) and upregulate COL1A1, -SMA, and CXCL1. MPO-derived oxidative stress also activates transforming growth factor (TGF-) in vitro, and TGF- signaling inhibition with SB-431542 decreased steatosis and fibrosis in vivo. Conversely, congenital absence of MPO results in reduced hepatocyte injury, decreased levels of TGF-, fewer activated HSCs, and less severe fibrosis in vivo. Innovation and Conclusion: Cumulatively, these findings demonstrate important cross talk between inflammatory myeloid cells, hepatocytes, and HSCs via MPO and establish MPO as part of a proapoptotic and profibrotic pathway of progression in NASH, as well as a potential therapeutic target to ameliorate this disease. Antioxid. Redox Signal. 23, 1255-1269. C1 [Pulli, Benjamin; Ali, Muhammad; Iwamoto, Yoshiko; Zeller, Matthias W. G.; Schob, Stefan; Linnoila, Jenny J.; Chen, John W.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Pulli, Benjamin; Ali, Muhammad; Iwamoto, Yoshiko; Zeller, Matthias W. G.; Schob, Stefan; Linnoila, Jenny J.; Chen, John W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pulli, Benjamin; Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chen, JW (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM jwchen@mgh.harvard.edu FU Ernst Schering Foundation in Berlin, Germany; National Natural Science Foundation, Beijing, China; NIH [R01-NS070835, R01-NS072167] FX B.P. has received a fellowship from the Ernst Schering Foundation in Berlin, Germany, and a grant from the National Natural Science Foundation, Beijing, China. This study was supported, in part, by the NIH (R01-NS070835 and R01-NS072167 to J.W.C.). NR 56 TC 2 Z9 2 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC 1 PY 2015 VL 23 IS 16 BP 1255 EP 1269 DI 10.1089/ars.2014.6108 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CY3ST UT WOS:000366330900001 PM 26058518 ER PT J AU Nierenberg, AA Hearing, CM Mathias, IS Young, LT Sylvia, LG AF Nierenberg, Andrew A. Hearing, Casey M. Mathias, Isadora Sande Young, L. Trevor Sylvia, Louisa G. TI Getting to wellness: The potential of the athletic model of marginal gains for the treatment of bipolar disorder SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Review DE Bipolar disorder; marginal gains; supplements; behavioral change ID LIFE EVENTS; ADHERENCE; THERAPY; SLEEP; RHYTHMS; MOOD AB Objective: People with bipolar disorder frequently have persistent symptoms, continued problems functioning and comorbid medical conditions. We propose applying the athletic coaching concept of marginal gains to help patients address these challenges to achieve wellness. Method: We review the concept of marginal gains and potential interventions to improve long-term outcomes for bipolar patients. Results: Evidence exists to help bipolar patients with diet and exercise, gradual behavioral change, mobile applications and peer support. Conclusion: Marginal gains, small and doable improvements across a broad range of areas, have great potential to improve the lives of people with bipolar disorder. C1 [Nierenberg, Andrew A.; Hearing, Casey M.; Sylvia, Louisa G.] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Sylvia, Louisa G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Mathias, Isadora Sande] Univ Fed Bahia UFBA, Fac Med, CAPES Brasil Sponsorship, Salvador, BA, Brazil. [Young, L. Trevor] Univ Toronto, Dept Psychiat, CAMH, Toronto, ON, Canada. RP Sylvia, LG (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM lsylvia2@partners.org NR 47 TC 1 Z9 1 U1 3 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD DEC PY 2015 VL 49 IS 12 SI SI BP 1207 EP 1214 DI 10.1177/0004867415607364 PG 8 WC Psychiatry SC Psychiatry GA CY1VK UT WOS:000366195900005 PM 26460331 ER PT J AU Dehaes, M Cheng, HH Buckley, EM Lin, PY Ferradal, SL Williams, K Vyas, R Hagan, K Wigmore, D McDavitt, E Soul, JS Franceschini, MA Newburger, JW Grant, PE AF Dehaes, Mathieu Cheng, Henry H. Buckley, Erin M. Lin, Pei-Yi Ferradal, Silvina L. Williams, Kathryn Vyas, Rutvi Hagan, Katherine Wigmore, Daniel McDavitt, Erica Soul, Janet S. Franceschini, Maria Angela Newburger, Jane W. Grant, P. Ellen TI Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID CONGENITAL HEART-DISEASE; NEAR-INFRARED SPECTROSCOPY; HYPOTHERMIC CARDIOPULMONARY BYPASS; RESONANCE-IMAGING ABNORMALITIES; POSITRON EMISSION TOMOGRAPHY; INFANT CARDIAC-SURGERY; WHITE-MATTER INJURY; BRAIN-INJURY; BLOOD-FLOW; CIRCULATORY ARREST AB Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi), cerebral oxygen metabolism (CMRO2i) and SO2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO2i and CBFi, which returned to baseline when stable. However, SO2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO2 alone. (C) 2015 Optical Society of America C1 [Dehaes, Mathieu; Ferradal, Silvina L.; Vyas, Rutvi; Hagan, Katherine; Grant, P. Ellen] Boston Childrens Hosp, Div Newborn Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. [Dehaes, Mathieu; Cheng, Henry H.; Ferradal, Silvina L.; Williams, Kathryn; Vyas, Rutvi; Hagan, Katherine; Wigmore, Daniel; McDavitt, Erica; Franceschini, Maria Angela; Newburger, Jane W.; Grant, P. Ellen] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cheng, Henry H.; Williams, Kathryn; Wigmore, Daniel; McDavitt, Erica; Newburger, Jane W.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Buckley, Erin M.; Lin, Pei-Yi; Franceschini, Maria Angela] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Buckley, Erin M.; Franceschini, Maria Angela] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Soul, Janet S.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Dehaes, M (reprint author), Boston Childrens Hosp, Div Newborn Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. EM mathieu.dehaes@umontreal.ca; ellen.grant@childens.harvard.edu FU NIBIB NIH HHS [R01 EB017337]; NICHD NIH HHS [R01 HD042908, R01 HD076258, R21 HD072505] NR 69 TC 6 Z9 6 U1 3 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2015 VL 6 IS 12 BP 4749 EP 4767 DI 10.1364/BOE.6.004749 PG 19 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CY0UT UT WOS:000366122800010 PM 26713191 ER PT J AU Yaseen, MA Srinivasan, VJ Gorczynska, I Fujimoto, JG Boas, DA Sakadzic, S AF Yaseen, Mohammad A. Srinivasan, Vivek J. Gorczynska, Iwona Fujimoto, James G. Boas, David A. Sakadzic, Sava TI Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID BLOOD-FLOW; COHERENCE TOMOGRAPHY; FUNCTIONAL ACTIVATION; MULTIPHOTON MICROSCOPY; 2-PHOTON MICROSCOPY; TISSUE OXYGENATION; INTRACELLULAR NADH; PARTIAL-PRESSURE; FLUORESCENCE; VESSELS AB Improving our understanding of brain function requires novel tools to observe multiple physiological parameters with high resolution in vivo. We have developed a multimodal imaging system for investigating multiple facets of cerebral blood flow and metabolism in small animals. The system was custom designed and features multiple optical imaging capabilities, including 2-photon and confocal lifetime microscopy, optical coherence tomography, laser speckle imaging, and optical intrinsic signal imaging. Here, we provide details of the system's design and present in vivo observations of multiple metrics of cerebral oxygen delivery and energy metabolism, including oxygen partial pressure, microvascular blood flow, and NADH autofluorescence. (C) 2015 Optical Society of America C1 [Yaseen, Mohammad A.; Srinivasan, Vivek J.; Boas, David A.; Sakadzic, Sava] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,MGH MIT HMS Athinuola A Martinos Ctr, Charlestown, MA USA. [Gorczynska, Iwona; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Gorczynska, Iwona; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Yaseen, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,MGH MIT HMS Athinuola A Martinos Ctr, Charlestown, MA USA. EM mayaseen@nmr.mgh.harvard.edu RI Gorczynska, Iwona/P-9367-2015 OI Gorczynska, Iwona/0000-0002-6120-8791 FU National Institutes of Health (NIH) [K99AG042026, R00NS067050, P50-NS010828, R01-NS057476, R01-EB000790, R24NS092986, R01NS091230, R01EB018464]; American Heart Association (AHA) [11SDG7600037] FX This work is supported by the National Institutes of Health (NIH) (K99AG042026, R00NS067050, P50-NS010828, R01-NS057476, R01-EB000790, R24NS092986, R01NS091230, R01EB018464) and the American Heart Association (AHA) (11SDG7600037). The authors wish to thank Drs. Anna Devor and Louis Gagnon for their help with data acquisition, processing, and interpretation. We also thank Svetlana Ruvinskaya, Dr. Weicheng Wu, and Dr. Buyin Fu for their extensive efforts with animal preparation, and we extend our deepest thanks to Drs. Cenk Ayata and Fumiaki Oka for their guidance with the dMCAO model. NR 43 TC 4 Z9 4 U1 1 U2 15 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD DEC 1 PY 2015 VL 6 IS 12 BP 4994 EP 5007 DI 10.1364/BOE.6.004994 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CY0UT UT WOS:000366122800031 PM 26713212 ER PT J AU Yu, M O'Leary, RM Kaz, AM Morris, SM Carter, KT Chak, A Chandar, A Willis, JE Moinova, HR Markowitz, SD Brenner, DE Anandabapasathy, S Westerhoff, M Wong, CJ Shaheen, NJ Chen, YW Barnholtz-Sloan, JS Grady, WM AF Yu, Ming O'Leary, Rachele M. Kaz, Andrew M. Morris, Shelli M. Carter, Kelly T. Chak, Amitabh Chandar, Apoorva Willis, Joseph E. Moinova, Helen R. Markowitz, Sanford D. Brenner, Dean E. Anandabapasathy, Sharmila Westerhoff, Maria Wong, Chao-Jen Shaheen, Nicholas J. Chen, Yanwen Barnholtz-Sloan, Jill S. Grady, William M. TI Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DNA METHYLATION; ADENOCARCINOMA INCIDENCE; GASTROESOPHAGEAL REFLUX; COLORECTAL-CANCER; RISK; SURVEILLANCE; PROGRESSION; SIGNATURES; MORTALITY; SYMPTOMS AB Background: Barrett's esophagus (BE) is a preneoplastic condition in which normal esophageal squamous epithelium (SQ) is replaced by specialized intestinal metaplasia. It is the presumed precursor for esophageal adenocarcinoma (EAC) as well as the strongest risk factor for this cancer. Unfortunately, many patients with BE go undiagnosed under the current BE screening guidelines. The development of noninvasive and accurate BE detection assays could potentially identify many of these undiagnosed BE patients. Methods: DNA methylation is a common epigenetic alteration in BE. Therefore, we conducted a genome-wide methylation screen to identify potential BE biomarkers. Samples from SQ (N = 12), stomach (N = 28), and BE (N = 29) were analyzed and methylation levels at over 485,000 CpG sites were compared. Pyrosequencing assays were used to validate the results and MethyLight assays were developed to detect the methylated alleles in endoscopic brushings. Results: We discovered two genes, B3GAT2 and ZNF793, that are aberrantly methylated in BE. Clinical validation studies confirmed B3GAT2 and ZNF793 methylation levels were significantly higher in BE samples (median = 32.5% and 33.1%, respectively) than in control tissues (median = 2.29% and 2.52%, respectively; P < 0.0001 for both genes). Furthermore, gene-specific MethyLight assays could accurately detect BE (P < 0.0001 for both) in endoscopic brushing samples. Conclusion: B3GAT2 and ZNF793 are hypermethylated in BE, and the methylation status of these genes can be used to detect BE in tissue samples. Impact: These findings support the development of methylated B3GAT2 and ZNF793 as biomarkers for noninvasive assays for the detection of BE. (C)2015 AACR. C1 [Yu, Ming; O'Leary, Rachele M.; Morris, Shelli M.; Carter, Kelly T.; Wong, Chao-Jen; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Chak, Amitabh; Chandar, Apoorva] Univ Hosp Case Med Ctr, Div Gastroenterol, Cleveland, OH USA. [Chak, Amitabh; Chandar, Apoorva] Univ Hosp Case Med Ctr, Div Oncol, Cleveland, OH USA. [Willis, Joseph E.] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH USA. [Moinova, Helen R.; Markowitz, Sanford D.] Univ Hosp Case Med Ctr, Dept Med, Cleveland, OH USA. [Markowitz, Sanford D.; Chen, Yanwen; Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA. [Brenner, Dean E.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Anandabapasathy, Sharmila] Baylor Coll Med, Dept Med & Gastroenterol, Houston, TX 77030 USA. [Westerhoff, Maria] Univ Washington, Sch Med, Dept Anat Pathol, Seattle, WA USA. [Shaheen, Nicholas J.] Univ North Carolina Hosp, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA. EM wgrady@fredhutch.org FU NIH [UO1 CA152756, 5P30CA015704, U01CA086402, U01CA182940, U54CA163060, P50CA150964, U01CA86400, T32DK007742] FX These studies were supported by funding from the NIH: UO1 CA152756, 5P30CA015704, U01CA086402, and U01CA182940 to W.M. Grady; U54CA163060 to A. Chak, W.M. Grady, S.D. Markowitz, and J.E. Willis; P50CA150964 to S.D. Markowitz, A. Chak, and J.E. Willis; U01CA86400 to D.E. Brenner; and T32DK007742 to M. Yu. NR 29 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2015 VL 24 IS 12 BP 1890 EP 1897 DI 10.1158/1055-9965.EPI-15-0370 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CY0XB UT WOS:000366129100011 PM 26545406 ER PT J AU Palchaudhuri, R Lambrecht, MJ Botham, RC Partlow, KC van Ham, TJ Putt, KS Nguyen, LT Kim, SH Peterson, RT Fan, TM Hergenrother, PJ AF Palchaudhuri, Rahul Lambrecht, Michael J. Botham, Rachel C. Partlow, Kathryn C. van Ham, Tjakko J. Putt, Karson S. Nguyen, Laurie T. Kim, Seok-Ho Peterson, Randall T. Fan, Timothy M. Hergenrother, Paul J. TI A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed SO CELL REPORTS LA English DT Article ID CYTOCHROME-C RELEASE; CASPASE ACTIVATION; MITOCHONDRIA; CELLS; INHIBITOR; DYNAMICS; CLEAVAGE; DEATH; ASSAY; P53 AB Apoptosis is generally believed to be a process that requires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals that Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the critical roles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III, and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility for studying apoptosis in vivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery. C1 [Palchaudhuri, Rahul; Lambrecht, Michael J.; Botham, Rachel C.; Partlow, Kathryn C.; Kim, Seok-Ho; Hergenrother, Paul J.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [van Ham, Tjakko J.; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [van Ham, Tjakko J.; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Charlestown, MA 02129 USA. [van Ham, Tjakko J.; Peterson, Randall T.] Broad Inst, Cambridge, MA 02142 USA. [Putt, Karson S.; Nguyen, Laurie T.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. [Fan, Timothy M.] Univ Illinois, Dept Vet Clin Med, Urbana, IL 61802 USA. RP Hergenrother, PJ (reprint author), Univ Illinois, Dept Chem, Urbana, IL 61801 USA. EM hergenro@illinois.edu OI van Ham, Tjakko/0000-0002-2175-8713 FU NIH Chemistry-Biology Interface Training Grant [NRSA 1-T32-GM070421]; University of Illinois; National Institutes of Health [R01-CA120439, NS079201]; Charles and Ann Sanders MGH Scholar Award FX We would like to thank the University of Illinois at Urbana-Champaign flow cytometry core facility, the W.M. Keck Center for comparative and functional genomics systems biology core, the Roy J. Carver Biotechnology Center for LC/MS analysis, and the electron microscopy facility at the college of veterinary medicine. R.C.B. is a National Science Foundation predoctoral fellow and a Robert C. and Carolyn J. Springborn graduate fellow. M.J.L. and R.C.B. are members of the NIH Chemistry-Biology Interface Training Grant (NRSA 1-T32-GM070421). This work was supported by the University of Illinois, the National Institutes of Health (R01-CA120439 to P.J.H.) and (NS079201 to R.T.P.) and the Charles and Ann Sanders MGH Scholar Award (to R.T.P.). NR 44 TC 2 Z9 2 U1 3 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD DEC 1 PY 2015 VL 13 IS 9 BP 2027 EP 2036 DI 10.1016/j.celrep.2015.10.042 PG 10 WC Cell Biology SC Cell Biology GA CX9SY UT WOS:000366047000026 PM 26655912 ER PT J AU Stewart, IJ Sosnov, JA Howard, JT Orman, JA Fang, R Morrow, BD Zonies, DH Bollinger, M Tuman, C Freedman, BA Chung, KK AF Stewart, Ian J. Sosnov, Jonathan A. Howard, Jeffrey T. Orman, Jean A. Fang, Raymond Morrow, Benjamin D. Zonies, David H. Bollinger, Mary Tuman, Caroline Freedman, Brett A. Chung, Kevin K. TI Retrospective Analysis of Long-Term Outcomes After Combat Injury A Hidden Cost of War SO CIRCULATION LA English DT Article DE coronary disease; diabetes mellitus; hypertension; kidney; mortality ID POSTTRAUMATIC-STRESS-DISORDER; CHRONIC KIDNEY-DISEASE; VA HEALTH-CARE; MILITARY SERVICE; COMPETING RISK; PREVALENCE; SEVERITY; SYSTEM; AKI; HYPERTENSION AB Background During the conflicts in Iraq and Afghanistan, 52087 service members have been wounded in combat. The long-term sequelae of these injuries have not been carefully examined. We sought to determine the relation between markers of injury severity and the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. Methods and Results Retrospective cohort study of critically injured US military personnel wounded in Iraq or Afghanistan from February 1, 2002 to February 1, 2011. Patients were then followed until January 18, 2013. Chronic disease outcomes were assessed by International Classification of Diseases, 9th edition codes and causes of death were confirmed by autopsy. From 6011 admissions, records were excluded because of missing data or if they were for an individual's second admission. Patients with a disease diagnosis of interest before the injury date were also excluded, yielding a cohort of 3846 subjects for analysis. After adjustment for other factors, each 5-point increment in the injury severity score was associated with a 6%, 13%, 13%, and 15% increase in incidence rates of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease, respectively. Acute kidney injury was associated with a 66% increase in rates of hypertension and nearly 5-fold increase in rates of chronic kidney disease. Conclusions In Iraq and Afghanistan veterans, the severity of combat injury was associated with the subsequent development of hypertension, coronary artery disease, diabetes mellitus, and chronic kidney disease. C1 [Stewart, Ian J.] David Grant Med Ctr, Travis Afb, CA 94535 USA. [Stewart, Ian J.; Sosnov, Jonathan A.; Morrow, Benjamin D.; Chung, Kevin K.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Sosnov, Jonathan A.; Morrow, Benjamin D.] San Antonio Mil Med Ctr, San Antonio, TX USA. [Howard, Jeffrey T.; Orman, Jean A.; Chung, Kevin K.] US Army Inst Surg Res, San Antonio, TX USA. [Fang, Raymond] US Air Force Ctr Sustainment Trauma & Readiness S, Baltimore, MD USA. [Zonies, David H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bollinger, Mary] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Tuman, Caroline; Freedman, Brett A.] Landstuhl Reg Med Ctr, Landstuhl, Germany. RP Stewart, IJ (reprint author), David Grant Med Ctr, Clin Invest Facil, 101 Bodin Circle, Travis Afb, CA 94535 USA. EM ian.stewart@us.af.mil FU Oak Ridge Institute of Science and Education FX This study was funded in part by a postdoctoral fellowship provided by the Oak Ridge Institute of Science and Education. NR 39 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 1 PY 2015 VL 132 IS 22 BP 2126 EP 2133 DI 10.1161/CIRCULATIONAHA.115.016950 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CY1SE UT WOS:000366187100005 PM 26621637 ER PT J AU Estes, NAM Kovacs, RJ Baggish, AL Myerburg, RJ AF Estes, N. A. Mark, III Kovacs, Richard J. Baggish, Aaron L. Myerburg, Robert J. CA Amer Heart Assoc Amer Coll Cardiology TI Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 11: Drugs and Performance-Enhancing Substances A Scientific Statement From the American Heart Association and American College of Cardiology SO CIRCULATION LA English DT Article DE AHA Scientific Statements; athletes; cardiovascular abnormalities; drugs; performance-enhancing substances ID SPORTS C1 [Estes, N. A. Mark, III] Tufts Univ, Medford, MA 02155 USA. [Baggish, Aaron L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Kovacs, Richard J.] Indiana Univ, Bloomington, IN 47405 USA. [Myerburg, Robert J.] Univ Miami, Coral Gables, FL 33124 USA. RP Estes, NAM (reprint author), Tufts Univ, Medford, MA 02155 USA. NR 9 TC 1 Z9 1 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 1 PY 2015 VL 132 IS 22 BP E330 EP E333 DI 10.1161/CIR.0000000000000247 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CY1SA UT WOS:000366186700013 PM 26621651 ER PT J AU Levine, BD Baggish, AL Kovacs, RJ Link, MS Maron, MS Mitchell, JH AF Levine, Benjamin D. Baggish, Aaron L. Kovacs, Richard J. Link, Mark S. Maron, Martin S. Mitchell, Jere H. CA Council Clinical Cardiology Council Cardiovasc Dis Young Council Cardiovasc & Stroke Nursin Council Functional Genomics & Tran Amer Coll Cardiology TI Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 1: Classification of Sports: Dynamic, Static, and Impact A Scientific Statement From the American Heart Association and American College of Cardiology SO CIRCULATION LA English DT Article DE AHA Scientific Statements; athletes; blood pressure; cardiac output; cardiovascular abnormalities; classification; oxygen saturation; sport ID ARTERIAL BLOOD-PRESSURE; NEURAL-CONTROL; EXERCISE; ALTITUDE; CIRCULATION; PERFORMANCE C1 [Levine, Benjamin D.; Mitchell, Jere H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Levine, Benjamin D.] Texas Hlth Presbyterian Hosp Dallas, Inst Exercise & Environm Med, Dallas, TX USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kovacs, Richard J.] Indiana Univ, Bloomington, IN 47405 USA. [Link, Mark S.] Tufts Univ, Dallas, TX USA. [Maron, Martin S.] Tufts Med Ctr, Dallas, TX USA. RP Levine, BD (reprint author), Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 1 PY 2015 VL 132 IS 22 BP E262 EP E266 DI 10.1161/CIR.0000000000000237 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CY1SA UT WOS:000366186700003 PM 26621643 ER PT J AU Maron, BJ Levine, BD Washington, RL Baggish, AL Kovacs, RJ Maron, MS AF Maron, Barry J. Levine, Benjamin D. Washington, Reginald L. Baggish, Aaron L. Kovacs, Richard J. Maron, Martin S. CA Council Clinical Cardiology Council Cardiovasc Dis Young Council Cardiovasc & Stroke Nursin Council Functional Genomics & Tran Amer Coll Cardiology TI Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes A Scientific Statement From the American Heart Association and American College of Cardiology SO CIRCULATION LA English DT Article DE AHA Scientific Statements; athletes; cardiovascular abnormalities; competitive athletes; preparticipation screening; sudden death ID SUDDEN CARDIAC DEATH; HYPERTROPHIC CARDIOMYOPATHY; EUROPEAN-SOCIETY; ELECTROCARDIOGRAPHIC PATTERNS; UNITED-STATES; YOUNG; ECG; SPORTS; POPULATION; PREVALENCE C1 [Maron, Barry J.] Minneapolis Heart Inst Fdn, Minneapolis, MN 55455 USA. [Baggish, Aaron L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Kovacs, Richard J.] Indiana Univ, Bloomington, IN 47405 USA. [Levine, Benjamin D.] Univ Texas Southwestern Med Ctr, Dallas, TX USA. [Maron, Martin S.] Tufts Med Ctr, Dallas, TX USA. [Washington, Reginald L.] Rocky Mt Hosp Children, Dallas, TX USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Minneapolis, MN 55455 USA. NR 39 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 1 PY 2015 VL 132 IS 22 BP E267 EP E272 DI 10.1161/CIR.0000000000000238 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CY1SA UT WOS:000366186700004 PM 26527714 ER PT J AU Scirica, BM Morrow, DA AF Scirica, Benjamin M. Morrow, David A. TI In Search of the 1-Hour Rule-Out for Acute Myocardial Infarction SO CLINICAL CHEMISTRY LA English DT Editorial Material ID EMERGENCY-DEPARTMENT PATIENTS; ACUTE CORONARY SYNDROME; EARLY-DIAGNOSIS; TROPONIN-I; COPEPTIN C1 [Scirica, Benjamin M.; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 15 TC 1 Z9 1 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2015 VL 61 IS 12 BP 1427 EP 1429 DI 10.1373/clinchem.2015.247536 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CY0BT UT WOS:000366071900001 PM 26503967 ER PT J AU Leehey, DJ Zhang, JH Emanuele, NV Whaley-Connell, A Palevsky, PM Reilly, RF Guarino, P Fried, LF AF Leehey, David J. Zhang, Jane H. Emanuele, Nicholas V. Whaley-Connell, Adam Palevsky, Paul M. Reilly, Robert F. Guarino, Peter Fried, Linda F. CA VA NEPHRON-D Study Grp TI BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BLOOD-PRESSURE CONTROL; RANDOMIZED CONTROLLED-TRIAL; ANTIHYPERTENSIVE TREATMENT; HYPERTENSION; PROGRESSION; ALBUMINURIA; INHIBITION; MANAGEMENT AB Background and objectives Proteinuric diabetic kidney disease frequently progresses to ESRD. Control of BP delays progression, but the optimal BP to improve outcomes remains unclear. The objective of this analysis was to evaluate the relationship between BP and renal outcomes in proteinuric diabetic kidney disease. Design, setting, participants, & measurements BP data from all 1448 randomized participants in the Veterans Affairs Nephropathy in Diabetes Trial were included in a post hoc analysis. The associations of mean on treatment BP with the primary end point (decline in eGFR, ESRD, or death), renal end point (decline in eGFR or ESRD), rate of eGFR decline, and mortality were measured. Results The median (25th, 75th percentile) follow-up time was 2.2 (1.2, 3.0) years. There were 284 primary end points. In univariate analyses, both mean systolic and mean diastolic BPs were strongly associated (P<0.001) with the primary end point. After multivariate adjustment, the hazard of developing the primary end point became progressively higher as mean systolic BID rose from <120 to >= 150 mmHg (P=0.02), with a significantly higher hazard ratio for 140-149 versus 120-129 mmHg (1.51 [1.06, 2.15]; P=0.02). There was also a significant association of mean diastolic BP with the hazard of developing the primary end point (P<0.01), with a significantly higher hazard ratio when mean diastolic BP was 80-89 versus 70-79 mmHg (1.54 [1.05, 2.25]; P=0.03); there was also a strong trend when mean diastolic BP was <60 mmHg. Associations between BP and both renal end point and rate of eGFR decline were similar to those with the primary end point. No association of BP with mortality was observed, possibly because of the limited number of mortality events. Conclusions In patients with proteinuric diabetic kidney disease, mean systolic BP >= 140 mmHg and mean diastolic BP mmHg were associated with worse renal outcomes. C1 [Leehey, David J.; Emanuele, Nicholas V.] Vet Affairs Hosp, Dept Med, Hines, IL USA. [Leehey, David J.; Emanuele, Nicholas V.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Zhang, Jane H.; Guarino, Peter] Vet Affairs Connecticut Healthcare Syst, Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. [Whaley-Connell, Adam] Harry S Truman Mem Vet Affairs Hosp, Dept Med, Columbia, MO USA. [Whaley-Connell, Adam] Univ Missouri, Sch Med, Columbia, MO USA. [Palevsky, Paul M.; Fried, Linda F.] Dept Med Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Palevsky, Paul M.; Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Palevsky, Paul M.; Reilly, Robert F.; Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. [Reilly, Robert F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Leehey, DJ (reprint author), Hines Vet Affairs Hosp 111L, Hines, IL 60141 USA. EM david.leehey@va.gov OI Palevsky, Paul/0000-0002-7334-5400; Whaley-Connell, Adam/0000-0001-8955-5560 FU Cooperative Studies Program of Department of Veterans Affairs Office of Research and Development FX This study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development. NR 32 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD DEC PY 2015 VL 10 IS 12 BP 2159 EP 2169 DI 10.2215/CJN.02850315 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA CX9EF UT WOS:000366007100010 PM 26482258 ER PT J AU Hoexter, MQ Diniz, JB Lopes, AC Batistuzzo, MC Shavitt, RG Dougherty, DD Duran, FLS Bressan, RA Busatto, GF Miguel, EC Sato, JR AF Hoexter, Marcelo Q. Diniz, Juliana B. Lopes, Antonio C. Batistuzzo, Marcelo C. Shavitt, Roseli G. Dougherty, Darin D. Duran, Fabio L. S. Bressan, Rodrigo A. Busatto, Geraldo F. Miguel, Euripides C. Sato, Joao R. TI ORBITOFRONTAL THICKNESS AS A MEASURE FOR TREATMENT RESPONSE PREDICTION IN OBSESSIVE-COMPULSIVE DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE neuroimaging; magnetic resonance imaging; treatment outcome; decision support techniques; logistic models ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CLINICAL-TRIAL; TRANSCRANIAL MAGNETIC STIMULATION; SEROTONIN REUPTAKE INHIBITORS; GAMMA VENTRAL CAPSULOTOMY; DEEP BRAIN-STIMULATION; HUMAN CEREBRAL-CORTEX; EARLY IMPROVEMENT; FOLLOW-UP; FLUOXETINE AB BackgroundEarly prediction of treatment response could reduce exposure to ineffective treatments and optimize the use of medical resources. Neuroimaging techniques have been used to identify biomarkers that are predictive of outcomes. The aims of this study were to investigate orbitofrontal cortex (OFC) thickness as a potential morphometric biomarker to discriminate outcomes in obsessive-compulsive disorder (OCD) and then to reexamine this biomarker in an independent cohort MethodsUsing a logistic regression model based on the mean baseline thickness of subregions of the OFC, we estimated the probability of treatment response in 29 treatment-naive OCD patients who participated in a clinical trial. That algorithm was then tested in an independent cohort of 12 patients with a confirmed diagnosis of refractory OCD ResultsAmong the treatment-naive OCD patients, measures of OFC thickness statistically significantly differentiated responders (n = 13) and nonresponders (n = 16), with an overall classification accuracy of approximate to 80%, a sensitivity of 77% (10/13), and a specificity of 81% (13/16). Of the refractory OCD patients in the second independent cohort, 67% were correctly classified as nonresponders. The most discriminative measures in the initial cohort of treatment-naive patients were the thicknesses of the left and right medial OFC (P = .009 and P = .028, respectively) ConclusionsWe found OFC thickness to be a strong predictor of treatment response in treatment-naive OCD patients. Although there are not yet any brain imaging biomarkers with clinical utility, our results highlight the potential of these measures as tools for predicting treatment outcomes in OCD. C1 [Hoexter, Marcelo Q.; Diniz, Juliana B.; Lopes, Antonio C.; Batistuzzo, Marcelo C.; Shavitt, Roseli G.; Duran, Fabio L. S.; Busatto, Geraldo F.; Miguel, Euripides C.] Univ Sao Paulo, Sch Med, Dept Psychiat, Inst Psychiat, BR-05403010 Sao Paulo, SP, Brazil. [Hoexter, Marcelo Q.; Bressan, Rodrigo A.] Univ Fed Sao Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci, Sao Paulo, Brazil. [Hoexter, Marcelo Q.; Dougherty, Darin D.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sato, Joao R.] Fed Univ ABC, Ctr Math Computat & Cognit, Santo Andre, Brazil. RP Hoexter, MQ (reprint author), Univ Sao Paulo, Sch Med, Dept Psychiat, Inst Psychiat, Rua Ovidio Pires Campos 785,3 Andar Ala Norte, BR-05403010 Sao Paulo, SP, Brazil. EM mqhoexter@gmail.com RI Busatto, Geraldo/D-4431-2009; Duran, Fabio/L-1371-2013; Hoexter, Marcelo/D-7620-2013; Batistuzzo, Marcelo/H-7790-2015; OI Duran, Fabio/0000-0002-7603-6152; Hoexter, Marcelo/0000-0002-9302-4380; Bressan, Rodrigo/0000-0002-0868-4449 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo Research Foundation) [2011/21357-9, 2013/16864-4, 2013/10498-6, 2013/00506-1] FX Contract grant sponsor: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo Research Foundation); Contract grant numbers: 2011/21357-9 (to Dr. Miguel), 2013/16864-4 (to Dr. Hoexter), 2013/10498-6 and 2013/00506-1 (to Dr. Sato). NR 42 TC 2 Z9 2 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD DEC PY 2015 VL 32 IS 12 BP 900 EP 908 DI 10.1002/da.22380 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA CY4VK UT WOS:000366406700004 PM 26032588 ER PT J AU Zeitler, P Hirst, K Copeland, KC El Ghormli, L Katz, LL Levitsky, LL Linder, B McGuigan, P White, NH Wilfley, D AF Zeitler, Phil Hirst, Kathryn Copeland, Kenneth C. El Ghormli, Laure Katz, Lorraine Levitt Levitsky, Lynne L. Linder, Barbara McGuigan, Paul White, Neil H. Wilfley, Denise CA TODAY Study Grp TI HbA(1c) After a Short Period of Monotherapy With Metformin Identifies Durable Glycemic Control Among Adolescents With Type 2 Diabetes SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; GLUCOSE CONTROL; YOUTH; COMPLICATIONS; OUTCOMES; INSULIN; CURVE AB OBJECTIVETo determine whether clinically accessible parameters early in the course of youth-onset type 2 diabetes predict likelihood of durable control on oral therapy.RESEARCH DESIGN AND METHODSTODAY was a randomized clinical trial of adolescents with type 2 diabetes. Two groups, including participants from all three treatments, were defined for analysis: 1) those who remained in glycemic control for at least 48 months of follow-up and 2) those who lost glycemic control before 48 months. Outcome group was analyzed in univariate and multivariate models as a function of baseline characteristics (age, sex, race/ethnicity, socioeconomic status, BMI, waist circumference, Tanner stage, disease duration, depressive symptoms) and biochemical measures (HbA(1c), C-peptide, lean and fat body mass, insulin inverse, insulinogenic index). Receiver operating characteristic curves were used to analyze HbA(1c) cut points.RESULTSIn multivariate models including factors significant in univariate analysis, only HbA(1c) and insulinogenic index at randomization remained significant (P < 0.0001 and P = 0.0002, respectively). An HbA(1c) cutoff of 6.3% (45 mmol/mol) (positive likelihood ratio [PLR] 3.7) was identified that optimally distinguished the groups; sex-specific cutoffs were 6.3% (45 mmol/mol) for females (PLR 4.4) and 5.6% (38 mmol/mol) for males (PLR 2.1).CONCLUSIONSIdentifying youth with type 2 diabetes at risk for rapid loss of glycemic control would allow more targeted therapy. HbA(1c) is a clinically accessible measure to identify high risk for loss of glycemic control on oral therapy. Adolescents with type 2 diabetes unable to attain a non-diabetes range HbA(1c) on metformin are at increased risk for rapid loss of glycemic control. C1 [Zeitler, Phil] Univ Colorado, Sch Med, Dept Pediat, Endocrinol Sect, Aurora, CO USA. [Hirst, Kathryn; El Ghormli, Laure] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Copeland, Kenneth C.] Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA. [Katz, Lorraine Levitt] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Levitsky, Lynne L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Linder, Barbara] Natl Inst Diabet & Digest & Kidney Dis, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. [McGuigan, Paul] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [White, Neil H.; Wilfley, Denise] Washington Univ, Sch Med, St Louis, MO USA. RP Hirst, K (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. EM khirst@bsc.gwu.edu OI Zeitler, Philip/0000-0001-5756-7858 FU NIDDK; National Institutes of Health Office of the Director [U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research Resources (NCRR) General Clinical Research Centers Program [M01-RR00036, M01-RR00043-45, M01-RR00069, M01-RR00084, M01-RR01066, M01-RR00125, M01-RR14467]; NCRR Clinical and Translational Science Awards [UL1-RR024134, UL1-RR024139, UL1-RR024153, UL1-RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780] FX This work was completed with funding from NIDDK and the National Institutes of Health Office of the Director through grants U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254; from the National Center for Research Resources (NCRR) General Clinical Research Centers Program through grants M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Children's Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and from the NCRR Clinical and Translational Science Awards through grants UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children's Hospital of Pittsburgh), UL1-RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University in St. Louis), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver). The NIDDK project office was involved in all aspects of the study, including design and conduct; collection, management, analysis, and interpretation of data; review and approval of the manuscript; and decision to submit the manuscript for publication. NR 25 TC 2 Z9 2 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2015 VL 38 IS 12 BP 2285 EP 2292 DI 10.2337/dc15-0848 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CY0TK UT WOS:000366118800028 PM 26537182 ER PT J AU Boyko, EJ AF Boyko, Edward J. TI Do We Know What Homeostatis Model Assessment Measures? If Not, Does It Matter? Diabetes Care 2007;30:2725-2728 SO DIABETES CARE LA English DT Letter C1 [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle, WA 98493 USA. RP Boyko, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98493 USA. EM eboyko@uw.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2015 VL 38 IS 12 BP E214 EP E214 DI 10.2337/dci15-0021 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CY0TK UT WOS:000366118800011 PM 26604290 ER PT J AU Tereshchenko, LG Cheng, A Park, J Wold, N Meyer, TE Gold, MR Mittal, S Singh, J Stein, KM Ellenbogen, KA AF Tereshchenko, Larisa G. Cheng, Alan Park, Jason Wold, Nicholas Meyer, Timothy E. Gold, Michael R. Mittal, Suneet Singh, Jagmeet Stein, Kenneth M. Ellenbogen, Kenneth A. CA SMART-AV Trial Investigators TI Novel measure of electrical dyssynchrony predicts response in cardiac resynchronization therapy: Results from the SMART-AV Trial SO HEART RHYTHM LA English DT Article DE Cardiac resynchronization therapy; Heart failure; Remodeling; SAI QRST ID BUNDLE-BRANCH BLOCK; HEART-FAILURE; QRS DURATION; MORPHOLOGY; REPOLARIZATION; REDUCTION; MORBIDITY; MORTALITY; OUTCOMES; REVERSE AB BACKGROUND Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in selected heart failure patients. However, not all patients respond to CRT. OBJECTIVE We hypothesized that a novel measure of electrical dyssynchrony, sum absolute QRST integral (SAI QRST), predicts CRT response independent of QRS duration and morphology. METHODS We retrospectively analyzed baseline 121ead electrocardiograms of SmartDelay Determined AV Optimization: A comparison to other AV delay methods used in cardiac resynchronization therapy (SMART-AV) trial study participants (N = 234; mean age 67 years; 163 (70%) men; 140 (60%) ischemic cardiomyopathy; mean left ventricular ejection fraction 25%; mean QRS duration 152 ms; 179 (77%) had left bundle branch block). Baseline pre-implant electrocardiograms were digitized, transformed into orthogonal XYZ, and analyzed automatically by customized MATLAB software. SAI QRST was measured as an averaged arithmetic sum of absolute areas under the QRST curve. Patients were followed prospectively 6 months after CRT-defibrillator implantation. Patients with a decrease in left ventricular end-systolic volume >15 mL after 6 months of CRT were considered responders. The logistic regression model was adjusted for age, sex, bundle branch block morphology, left ventricular ejection fraction, cardiomyopathy type, and (IRS duration. RESULTS Patients with the high mean SAI QRST (third tertile) had 2.5 times greater odds of response than those with the low mean SAI QRST (first tertile: odds ratio [OR] 2.5; 95% confidence interval [CI] 1.3-5.0; P =.010) and 1.9 times greater than the lower 2 tertiles combined (OR 1.9; 950/0 CI 1.1-3.5; P =.03). Adjustment for renal function (OR 2.33; 950/0 CI 1.32-4.11; P =.003) and left ventricular lead position in right anterior oblique and left anterior oblique views (OR 1.7; 950/0 CI 0.9-3.2; P =.087) did not attenuate association of SAI QRST with outcome. CONCLUSION High SAI QRST independently predicts CRT response in the SMART-AV study. C1 [Tereshchenko, Larisa G.; Cheng, Alan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Tereshchenko, Larisa G.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Park, Jason] Johns Hopkins Univ, Whiting Sch Engn, Baltimore, MD USA. [Wold, Nicholas; Meyer, Timothy E.; Stein, Kenneth M.] Boston Sci, St Paul, MN USA. [Gold, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mittal, Suneet] Valley Hosp, Ridgewood, NJ USA. [Singh, Jagmeet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. RP Tereshchenko, LG (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3181 SW Sam Jackson Pk Rd,UHN62, Portland, OR 97239 USA. EM tereshch@ohsu.edu OI Tereshchenko, Larisa/0000-0002-6976-1313 FU Boston Scientific; National Institutes of Health [1R01HL118277] FX The SMART AV study was sponsored by Boston Scientific. This research was supported in part by the National Institutes of Health (grant no. 1R01HL118277, to Dr Tereshchenko). NR 32 TC 3 Z9 3 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2015 VL 12 IS 12 BP 2402 EP 2410 DI 10.1016/j.hrthm.2015.08.009 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY0SL UT WOS:000366116200009 PM 26272523 ER PT J AU Bento, ASA Bacic, D Carneiro, JS Nearing, BD Fuller, H Justo, FA Rajamani, S Belardinelli, L Verrier, RL AF Bento, Afonso S. Alves Bacic, Danilo Carneiro, Juliana Saran Nearing, Bruce D. Fuller, Henrique Justo, Fernanda A. Rajamani, Sridharan Belardinelli, Luiz Verrier, Richard L. TI Selective late I-Na inhibition by GS-458967 exerts parallel suppression of catecholamine-induced hemodynamically significant ventricular tachycardia and T-wave alternans in an intact porcine model SO HEART RHYTHM LA English DT Article DE Late I-Na inhibition; Ventricular tachycardia; T-wave alternans; Catecholamines; Sodium ID LATE SODIUM CURRENT; CARDIAC-ARRHYTHMIAS; FIBRILLATION; HETEROGENEITY AB BACKGROUND Catecholamines can elicit early and delayed afterdepolarizations (EADs and DADs), resulting in ventricular tachyarrhythmias. OBJECTIVE As inhibition of the cardiac late sodium current (I-Na) suppresses EADs and DADs, we examined whether GS-458967 (GS-967), a potent inhibitor of this current that is devoid of beta-adrenergic blocking action, can prevent epinephrine-induced ventricular tachycardia (VT) induction in an intact porcine model. METHODS In 12 dosed-chest anesthetized pigs, spontaneous VT was induced by epinephrine administration (2.0 mu g/kg, intravenous, bolus over 1 minute). Effects of GS-967 (0.4 mg/kg, intravenous, infused over 30 minutes) on VT incidence, 1-wave alternans (TWA) level, and hemodynamic and electrophysiologic parameters before and after epinephrine were analyzed (N = 6). Effects of vehicle control were investigated in 6 animals. TWA was measured using the Modified Moving Average method. RESULTS Epinephrine elicited spontaneous hemodynamically significant nonsustained VT in all 6 pigs and increased TWA by 28-fold compared to baseline (P < .001). GS-967 reduced mean 3- to 7-beat VT incidence by 55% (from 9.5 +/- 2.72 to 4.3 +/- 0.76 beats/min, P = .020) and >= 8-beat VT incidence by 56% (from 1.6 +/- 0.47 to 0.7 +/- 0.42 beats/2 min, P = .033) and eliminated the VT-associated hypotension, with no changes in chronotropic and minimal attenuation of the inotropic responses to epinephrine. Concurrently, GS-967 at 30, 60, and 90 minutes reduced the magnitude of the epinephrine-induced surge in TWA by 56% (from 140 +/- 13.2 to 62 +/- 12.1 mu V, P < .01), 62% (to 53 +/- 8.3 mu V, P < .01), and 51% (to 69 +/- 14.0 0, P < .01) (means +/- SEM), respectively. CONCLUSION Selective cardiac late I-Na inhibition with GS-967 confers significant protection against catecholamine-induced VT and TWA. C1 [Bento, Afonso S. Alves; Bacic, Danilo; Carneiro, Juliana Saran; Nearing, Bruce D.; Fuller, Henrique; Justo, Fernanda A.; Verrier, Richard L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bento, Afonso S. Alves; Bacic, Danilo; Carneiro, Juliana Saran; Fuller, Henrique; Justo, Fernanda A.] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. [Nearing, Bruce D.; Verrier, Richard L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Rajamani, Sridharan; Belardinelli, Luiz] Gilead Sci Inc, Foster City, CA 94404 USA. [Rajamani, Sridharan; Belardinelli, Luiz] Gilead Sci Inc, Fremont, CA USA. RP Verrier, RL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,Harvard Thorndike Electrophysi, 99 Brookline Ave,RN-301, Boston, MA 02215 USA. EM rverrier@bidmc.harvard.edu FU Gilead Sciences; "Science without Borders" (CAPES of the Brazilian Federal Government), Banco Santander Brasil; Harvard University's David Rockefeller Center for Latin American Studies FX This study was funded by a grant from Gilead Sciences to Beth Israel Deaconess Medical Center (Dr Verrier, P.I.). Messrs Bento, Bacic, and Fuller and Mesdames Carneiro and Justo received support from "Science without Borders" (CAPES of the Brazilian Federal Government), Banco Santander Brasil, Dr Miguel Srougi, and Harvard University's David Rockefeller Center for Latin American Studies. Drs Rajamani and Belardinelli are employees of Gilead Sciences, the company that supported this study. Drs Verrier and Nearing have received royalties from Georgetown University and Beth Israel Deaconess Medical Center for intellectual property on the Modified Moving Average method for T-wave alternans analysis, which was used in this study. NR 20 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2015 VL 12 IS 12 BP 2508 EP 2514 DI 10.1016/j.hrthm.2015.07.025 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY0SL UT WOS:000366116200023 ER PT J AU Puram, SV Rocco, JW AF Puram, Sidharth V. Rocco, James W. TI Molecular Aspects of Head and Neck Cancer Therapy SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Head and neck cancer; Squamous cell carcinoma; Molecular biology; Targeted therapy; Synthetic lethality; Genomic sequencing; Intratumor heterogeneity ID SQUAMOUS-CELL CARCINOMA; INTRATUMOR GENETIC-HETEROGENEITY; HISTONE DEACETYLASE INHIBITORS; ADVANCED OROPHARYNGEAL CANCER; SYNTHETIC LETHAL INTERACTIONS; PAPILLOMAVIRUS-RELATED HEAD; RAS ONCOGENE MUTATION; COPY NUMBER; GENOMIC INSTABILITY; SIGNALING PATHWAY AB In spite of a rapidly expanding understanding of head and neck tumor biology and optimization of radiation, chemotherapy, and surgical treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer-related morbidity and mortality. Although our biologic understanding of these tumors had largely been limited to pathways driving proliferation, survival, and differentiation, the identification of HPV as a major driver of HNSCC and genomic sequencing analyses has dramatically influenced our understanding of tumor biology and approach to therapy. Here, we summarize molecular aspects of HNSCC biology and identify promising areas for potential diagnostic and therapeutic agents. C1 [Puram, Sidharth V.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Puram, Sidharth V.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Rocco, James W.] Ohio State Univ, Dept Otolaryngol Head & Neck Surg, Wexner Med Ctr, James Canc Hosp,Solove Res Inst, Columbus, OH 43210 USA. RP Rocco, JW (reprint author), Ohio State Univ, Dept Otolaryngol Head & Neck Surg, Wexner Med Ctr, James Canc Hosp,Solove Res Inst, 320 West 10th Ave, Columbus, OH 43210 USA. EM james.rocco@osumc.edu FU NIDCR NIH HHS [R01 DE022087] NR 102 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2015 VL 29 IS 6 BP 971 EP + DI 10.1016/j.hoc.2015.07.003 PG 23 WC Oncology; Hematology SC Oncology; Hematology GA CX9YT UT WOS:000366063400002 PM 26568543 ER PT J AU Chau, NG Haddad, RI AF Chau, Nicole G. Haddad, Robert I. TI Sequential and Concurrent Chemoradiation State of the Art SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Head and neck cancer; Chemoradiation; Induction chemotherapy; Sequential therapy; Treatment ID SQUAMOUS-CELL CARCINOMA; PHASE-III TRIAL; LOCALLY ADVANCED HEAD; INDUCTION CHEMOTHERAPY; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; NAB-PACLITAXEL; OROPHARYNGEAL CANCER; LARYNX PRESERVATION; UNRESECTABLE HEAD AB Most patients diagnosed with head and neck cancer have locally advanced disease. Sequential and concurrent chemoradiation are standard, nonsurgical, curative-intent treatment options. Controversy remains regarding the superiority of one approach to another. Definitive management strategies are evolving with increasing efforts to pursue deintensification of therapy for low-risk patients, and to pursue therapeutic intensification for high-risk patients. Both sequential therapy and concurrent chemoradiation play important roles in shaping treatment paradigms because both approaches may be used to investigate deintensification or intensification strategies. This article examines the latest evidence and state-of-the-art approaches, highlighting ongoing controversies and future directions. C1 [Chau, Nicole G.; Haddad, Robert I.] Harvard Univ, Dana Farber Canc Inst, Ctr Head & Neck Oncol, Sch Med, Boston, MA 02115 USA. [Chau, Nicole G.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chau, Nicole G.; Haddad, Robert I.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Haddad, RI (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Robert_haddad@dfci.harvard.edu NR 32 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2015 VL 29 IS 6 BP 1061 EP + DI 10.1016/j.hoc.2015.07.005 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA CX9YT UT WOS:000366063400007 PM 26568548 ER PT J AU Margalit, DN Schoenfeld, JD Tishler, RB AF Margalit, Danielle N. Schoenfeld, Jonathon D. Tishler, Roy B. TI Radiation Oncology-New Approaches in Squamous Cell Cancer of the Head and Neck SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Squamous cancer; Head and neck; Intensity modulated radiation therapy; Radiation planning; Adaptive replanning; Image guided ID INTENSITY-MODULATED RADIOTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; LOCALLY ADVANCED HEAD; PROTON-BEAM THERAPY; QUALITY-OF-LIFE; OROPHARYNGEAL CANCER; NASOPHARYNGEAL CARCINOMA; TUMOR VOLUME; DEFORMABLE REGISTRATION; CONFORMAL RADIOTHERAPY AB The many advances in radiotherapy for squamous cell cancer of the head and neck described in this article will have significant effects on the ultimate outcomes of patients who receive this treatment. The technological and clinical advances should allow one to maintain or improve disease control, while moderating the toxicity associated with head and neck radiation therapy. C1 [Margalit, Danielle N.; Schoenfeld, Jonathon D.; Tishler, Roy B.] Harvard Univ, Dept Radiat Oncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tishler, RB (reprint author), Harvard Univ, Dept Radiat Oncol, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM roy_tishler@dfci.harvard.edu NR 81 TC 0 Z9 0 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 2015 VL 29 IS 6 BP 1093 EP + DI 10.1016/j.hoc.2015.07.008 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA CX9YT UT WOS:000366063400009 PM 26568550 ER PT J AU Wachinger, C Fritscher, K Sharp, G Golland, P AF Wachinger, Christian Fritscher, Karl Sharp, Greg Golland, Polina TI Contour-Driven Atlas-Based Segmentation SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Atlas; Gaussian process; image segmentation; left atrium; parotid glands; patch; spectral clustering ID BRAIN MRI SEGMENTATION; IMAGE SEGMENTATION; LABEL FUSION; REGISTRATION; MODEL; CUTS AB We propose new methods for automatic segmentation of images based on an atlas of manually labeled scans and contours in the image. First, we introduce a Bayesian framework for creating initial label maps from manually annotated training images. Within this framework, we model various registration- and patch-based segmentation techniques by changing the deformation field prior. Second, we perform contour-driven regression on the created label maps to refine the segmentation. Image contours and image parcellations give rise to non-stationary kernel functions that model the relationship between image locations. Setting the kernel to the covariance function in a Gaussian process establishes a distribution over label maps supported by image structures. Maximum a posteriori estimation of the distribution over label maps conditioned on the outcome of the atlas-based segmentation yields the refined segmentation. We evaluate the segmentation in two clinical applications: the segmentation of parotid glands in head and neck CT scans and the segmentation of the left atrium in cardiac MR angiography images. C1 [Wachinger, Christian; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Wachinger, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Fritscher, Karl; Sharp, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Wachinger, C (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. EM wachinger@csail.mit.edu FU Humboldt foundation; National Alliance for Medical Image Computing (NIH NIBIB NAMIC) [U54-EB005149]; NeuroImaging Analysis Center (NIH NIBIB NAC) [P41-EB-015902]; Wistron Corporation FX This work was supported in part by the Humboldt foundation, the National Alliance for Medical Image Computing (NIH NIBIB NAMIC U54-EB005149), the NeuroImaging Analysis Center (NIH NIBIB NAC P41-EB-015902), and the Wistron Corporation. NR 59 TC 1 Z9 1 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2015 VL 34 IS 12 BP 2492 EP 2505 DI 10.1109/TMI.2015.2442753 PG 14 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CY0OD UT WOS:000366104500007 PM 26068202 ER PT J AU Luegmair, G Mehta, DD Kobler, JB Dollinger, M AF Luegmair, Georg Mehta, Daryush D. Kobler, James B. Doellinger, Michael TI Three-Dimensional Optical Reconstruction of Vocal Fold Kinematics Using High-Speed Video With a Laser Projection System SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Distance measurement; image segmentation; stereo vision; surface reconstruction; vocal folds ID VOICE PRODUCTION MECHANISMS; MEDIAL SURFACE DYNAMICS; IN-VIVO; VIDEOENDOSCOPY; VIBRATIONS; PHONATION AB Vocal fold kinematics and its interaction with aerodynamic characteristics play a primary role in acoustic sound production of the human voice. Investigating the temporal details of these kinematics using high-speed videoendoscopic imaging techniques has proven challenging in part due to the limitations of quantifying complex vocal fold vibratory behavior using only two spatial dimensions. Thus, we propose an optical method of reconstructing the superior vocal fold surface in three spatial dimensions using a high-speed video camera and laser projection system. Using stereo-triangulation principles, we extend the camera-laser projector method and present an efficient image processing work-flow to generate the three-dimensional vocal fold surfaces during phonation captured at 4000 frames per second. Initial results are provided for airflow-driven vibration of an ex vivo vocal fold model in which at least 75% of visible laser points contributed to the reconstructed surface. The method captures the vertical motion of the vocal folds at a high accuracy to allow for the computation of three-dimensional mucosal wave features such as vibratory amplitude, velocity, and asymmetry. C1 [Luegmair, Georg] Univ Calif Los Angeles, Speech Prod Lab, Los Angeles, CA 90095 USA. [Mehta, Daryush D.; Kobler, James B.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Mehta, Daryush D.; Kobler, James B.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Mehta, Daryush D.] MGH Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02129 USA. [Doellinger, Michael] Univ Hosp, Dept Phoniatr & Pedaudiol, D-91054 Erlangen, Germany. RP Luegmair, G (reprint author), Univ Calif Los Angeles, Speech Prod Lab, Los Angeles, CA 90095 USA. EM georg.luegmair@gmail.com; mehta.daryush@mgh.harvard.edu; james.kobler@mgh.harvard.edu FU Deutsche Krebshilfe e.V. [111332]; American Speech-Language-Hearing Foundation Speech Science; NIH National Institute on Deafness and Other Communication Disorders [R01 DC007640]; Voice Health Institute FX Dollinger's contribution was supported by Deutsche Krebshilfe e.V. Grant 111332. Research supported by an American Speech-Language-Hearing Foundation Speech Science Grant, by the NIH National Institute on Deafness and Other Communication Disorders (R01 DC007640), and by the Voice Health Institute. The paper's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 33 TC 4 Z9 4 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 EI 1558-254X J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD DEC PY 2015 VL 34 IS 12 BP 2572 EP 2582 DI 10.1109/TMI.2015.2445921 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA CY0OD UT WOS:000366104500013 PM 26087485 ER PT J AU Chen, LF Vander, MW Hofmann, DA Reisinger, HS AF Chen, Luke F. Vander, Mark W. Hofmann, David A. Reisinger, Heather Schacht TI The Hawthorne Effect in Infection Prevention and Epidemiology SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Review ID HAND HYGIENE COMPLIANCE; URINARY CATHETER USE; REACTIVITY; FEEDBACK; SYSTEM AB The Hawthorne Effect is a prevalent observer effect that causes behavioral changes among participants of epidemiological studies or infection control interventions. The purpose of the review is to describe the origins of the Hawthorne Effect, to understand the term in relation to current scientific literature, to describe characteristics of the Hawthorne effect, and to discuss methods to quantify and overcome limitations associated with the Hawthorne Effect. Infect. Control Hosp. Epidemiol. 2015;36(12):1444-1450 C1 [Chen, Luke F.] Duke Univ, Program Infect Prevent & Epidemiol, Med Ctr, Durham, NC USA. [Chen, Luke F.] Duke Univ, Duke Infect Control Outreach Network, Med Ctr, Durham, NC USA. [Chen, Luke F.] Duke Univ, CDC Prevent Epictr Program, Durham, NC USA. [Vander, Mark W.; Reisinger, Heather Schacht] Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Vander, Mark W.; Reisinger, Heather Schacht] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Vander, Mark W.] Univ Iowa, Dept Psychol, Coll Liberal Arts & Sci, Iowa City, IA 52242 USA. [Hofmann, David A.] Univ N Carolina, Kenan Flagler Business Sch, Dept Org Behav & Strategy, Chapel Hill, NC USA. [Reisinger, Heather Schacht] US Dept Vet Affairs, Natl Ctr Occupat Hlth & Infect Control COHIC, Gainesville, FL USA. RP Chen, LF (reprint author), Duke Univ, Durham, NC USA. EM luke.chen@duke.edu NR 56 TC 4 Z9 4 U1 1 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2015 VL 36 IS 12 BP 1444 EP 1450 DI 10.1017/ice.2015.216 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CY0UV UT WOS:000366123000011 PM 26383964 ER PT J AU Martin, H Hermos, C Barysauskas, CM Bradbury, S Sullivan, S Ellison, RT AF Martin, Hannah Hermos, Christina Barysauskas, Constance M. Bradbury, Susan Sullivan, Susan Ellison, Richard T., III TI Accidental Needlestick Exposures linked to the Administration of Local Anesthesia by Healthcare Workers SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID INJURIES C1 [Martin, Hannah; Hermos, Christina; Ellison, Richard T., III] Univ Massachusetts, Sch Med, Worcester, MA USA. [Hermos, Christina] UMass Mem Childrens Med Ctr, Dept Pediat, Div Infect Dis, Worcester, MA USA. [Barysauskas, Constance M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Bradbury, Susan] UMass Mem Med Ctr, Dept Infect Control, Worcester, MA USA. [Sullivan, Susan] UMass Mem Med Ctr, Dept Employee Hlth Serv, Worcester, MA USA. [Ellison, Richard T., III] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA USA. RP Martin, H (reprint author), 14 Trumbull St, New Haven, CT 06511 USA. EM hcmartin11@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2015 VL 36 IS 12 BP 1487 EP 1488 DI 10.1017/ice.2015.229 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CY0UV UT WOS:000366123000029 PM 26449423 ER PT J AU Peters, RM Claessen, FMAP Doornberg, JN Kolovich, GP Diercks, RL van den Bekerom, MPJ AF Peters, Rinne M. Claessen, Femke M. A. P. Doornberg, Job N. Kolovich, Gregory P. Diercks, Ron L. van den Bekerom, Michel P. J. TI Union rate after operative treatment of humeral shaft nonunion - A systematic review SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Review DE Nonunion; Humeral shaft; Treatment; Union rate ID BONE-GRAFT; INTERNAL-FIXATION; COMPRESSION PLATE; DIAPHYSEAL FRACTURES; SURGICAL-TREATMENT; EXTERNAL FIXATOR; ASEPTIC NONUNION; FAILURE; NAILS; EXPERIENCE AB Introduction: Humeral shaft nonunions can lead to morbidity from subsequent operations, complications and impaired function. Currently there is no evidenced-based consensus for treatment of humeral shaft nonunions. Aim: We aimed to summarize and analyze union rates and complications after operative treatment for humeral shaft nonunion. Methods: Studies investigating operative treatment strategies for humeral shaft nonunion were identified by searching: EMBASE, MEDLINE, Ovid SP, Web of Science, Cochrane Central, PubMed and Google Scolar up to October 24, 2014. Studies were eligible if: (1) outcome of operative treatment for humeral shaft nonunion was reported; (2) at least ten adult patients with humeral shaft nonunion included; (3) full text article available; (4) written in English, German or Dutch; and (5) nonunion was defined as no bone-bridging between the fracture ends after 6 months. Results: Thirty-six studies were included. A union rate of 98% was found in patients (n = 672) who underwent plate fixation with autologous bone grafting (ABG), 95% in plate fixation without ABG (n = 19), 88% in intramedullary nailing with ABG (n = 164), 66% in intramedullary nailing without ABG (n = 78), 92% in bone strut fixation (n = 91) and 98% in external fixation (n = 152). A total complication rate of 12% was found in patients treated with plate fixation combined with ABG, 15% in intramedullary nail with ABG and 8% intramedullary nailing without ABG, 20% in bone strut fixation and 22% in external fixation. Conclusion: Plate fixation with ABG was recommended for humeral shaft nonunion, since the union rate is highest and the complication rate is relatively low. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Peters, Rinne M.; Diercks, Ron L.] Univ Groningen, Univ Med Ctr Groningen, Dept Orthopaed Surg, NL-9713 GZ Groningen, Netherlands. [Claessen, Femke M. A. P.; Kolovich, Gregory P.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Doornberg, Job N.] Univ Amsterdam, Orthopaed Residency Program PGY 5, Orthotrauma Res Ctr, Amsterdam, Netherlands. [van den Bekerom, Michel P. J.] Onze Lieve Vrouw Hosp, Shoulder & Elbow Unit, Amsterdam, Netherlands. RP Peters, RM (reprint author), Tuinderslaan 2, NL-7887 VA Erica, Netherlands. EM rinnepeters27@hotmail.com OI Peters, Rinne/0000-0002-1484-4226 NR 48 TC 3 Z9 4 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD DEC PY 2015 VL 46 IS 12 BP 2314 EP 2324 DI 10.1016/j.injury.2015.09.041 PG 11 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CX9IW UT WOS:000366020000003 PM 26499226 ER PT J AU Stanford, FC Kyle, TK AF Stanford, F. C. Kyle, T. K. TI Why food policy and obesity policy are not synonymous: the need to establish clear obesity policy in the United States SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Editorial Material ID ENERGY-BALANCE; PREVENTION; CHILDHOOD; EPIDEMIC; SCIENCE C1 [Stanford, F. C.] Massachusetts Gen Hosp, Dept Med, MGH Weight Ctr, Div Gastroenterol, Boston, MA 02114 USA. [Stanford, F. C.] Mongan Inst Hlth Policy, Dept Pediat, Boston, MA USA. [Stanford, F. C.] Harvard Univ, Sch Med, Boston, MA USA. [Kyle, T. K.] ConscienHlth, Pittsburgh, PA USA. [Kyle, T. K.] Obes Act Coalit, Tampa, FL USA. RP Stanford, FC (reprint author), Massachusetts Gen Hosp, Dept Med, MGH Weight Ctr, Div Gastroenterol, Boston, MA 02114 USA. EM fstanford@mgh.harvard.edu OI Stanford, Fatima/0000-0003-4616-533X NR 18 TC 2 Z9 2 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2015 VL 39 IS 12 BP 1667 EP 1668 DI 10.1038/ijo.2015.191 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CY0RT UT WOS:000366114100001 PM 26643152 ER PT J AU Iverson, GL Silverberg, ND Mannix, R Maxwell, BA Atkins, JE Zafonte, R Berkner, PD AF Iverson, Grant L. Silverberg, Noah D. Mannix, Rebekah Maxwell, Bruce A. Atkins, Joseph E. Zafonte, Ross Berkner, Paul D. TI Factors Associated With Concussion-like Symptom Reporting in High School Athletes SO JAMA PEDIATRICS LA English DT Article ID SPORT-RELATED CONCUSSION; BASE-LINE VALUES; NEUROCOGNITIVE PERFORMANCE; SEX-DIFFERENCES; MANAGEMENT; RECOVERY; INJURY; CONSEQUENCES; METAANALYSIS; ADOLESCENTS AB IMPORTANCE Every state in the United States has passed legislation for sport-related concussion, making this health issue important for physicians and other health care professionals. Safely returning athletes to sport after concussion relies on accurately determining when their symptoms resolve. OBJECTIVE To evaluate baseline concussion-like symptom reporting in uninjured adolescent student athletes. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional, observational study, we studied 31 958 high school athletes from Maine with no concussion in the past 6 months who completed a preseason baseline testing program between 2009 and 2013. RESULTS Symptom reporting was more common in girls than boys. Most students with preexisting conditions reported one or more symptoms (60%-82% of boys and 73%-97% of girls). Nineteen percent of boys and 28% of girls reported having a symptom burden resembling an International Classification of Diseases, 10th Revision (ICD-10) diagnosis of postconcussional syndrome (PCS). Students with preexisting conditions were even more likely to endorse a symptom burden that resembled PCS (21%-47% for boys and 33%-72% for girls). Prior treatment of a psychiatric condition was the strongest independent predictor for symptom reporting in boys, followed by a history of migraines. For girls, the strongest independent predictors were prior treatment of a psychiatric condition or substance abuse and attention-deficit/hyperactivity disorder. The weakest independent predictor of symptoms for both sexes was history of prior concussions. CONCLUSIONS AND RELEVANCE In the absence of a recent concussion, symptom reporting is related to sex and preexisting conditions. Consideration of sex and preexisting health conditions can help prevent misinterpretation of symptoms in student athletes who sustain a concussion. C1 [Iverson, Grant L.; Zafonte, Ross] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Massachusetts Gen Hosp, Children Sports Concuss Program, Boston, MA 02114 USA. [Iverson, Grant L.; Zafonte, Ross] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Silverberg, Noah D.] Univ British Columbia, Div Phys Med & Rehabil, Vancouver, BC V5Z 1M9, Canada. [Silverberg, Noah D.] GF Strong Rehab Ctr, Vancouver, BC, Canada. [Mannix, Rebekah] Boston Childrens Hosp, Div Emergency Med, Boston, MA USA. [Maxwell, Bruce A.] Colby Coll, Dept Comp Sci, Waterville, ME 04901 USA. [Atkins, Joseph E.] Colby Coll, Dept Psychol, Waterville, ME USA. [Berkner, Paul D.] Colby Coll, Hlth Serv, Waterville, ME 04901 USA. [Berkner, Paul D.] Colby Coll, Dept Biol, Waterville, ME 04901 USA. RP Iverson, GL (reprint author), Harvard Univ, Sch Med, Ctr Hlth & Rehabil, Dept Phys Med & Rehabil, 79-96 13th St Charlestown Navy Yard, Charlestown, MA 02129 USA. EM giverson@mgh.harvard.edu FU Goldfarb Center for Public Policy and Civic Engagement/Colby College; Bill and Joan Alfond Foundation; Harvard Integrated Program to Protect and Improve the Health of National Football League Players Association Members; Mooney-Reed Charitable Foundation FX This study was supported by the Goldfarb Center for Public Policy and Civic Engagement/Colby College, the Bill and Joan Alfond Foundation, the Harvard Integrated Program to Protect and Improve the Health of National Football League Players Association Members (Dr Zafonte), and the Mooney-Reed Charitable Foundation (Drs Iverson and Zafonte). NR 40 TC 11 Z9 11 U1 4 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD DEC PY 2015 VL 169 IS 12 BP 1132 EP 1140 DI 10.1001/jamapediatrics.2015.2374 PG 9 WC Pediatrics SC Pediatrics GA CY3UE UT WOS:000366334600017 PM 26457403 ER PT J AU Altan, A Shiozawa, A Bancroft, T Singh, JA AF Altan, Aylin Shiozawa, Aki Bancroft, Tim Singh, Jasvinder A. TI A Real-World Study of Switching From Allopurinol to Febuxostat in a Health Plan Database SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE comparative effectiveness; gout; medication switching; serum urate; urate-lowering therapy ID ADMINISTRATIVE CLAIMS ANALYSIS; EVIDENCE BASED RECOMMENDATIONS; OF-RHEUMATOLOGY GUIDELINES; SERUM URATE; GOUTY-ARTHRITIS; TASK-FORCE; HYPERURICEMIA; THERAPY; MANAGEMENT; PREVALENCE AB Objective The objective of this study was to assess the real-world comparative effectiveness of continuing on allopurinol versus switching to febuxostat. Methods In a retrospective claims data study of enrollees in health plans affiliated with Optum, we evaluated patients from February 1, 2009, to May 31, 2012, with a gout diagnosis, a pharmacy claim for allopurinol or febuxostat, and at least 1 serum uric acid (SUA) result available during the follow-up period. Univariate and multivariable-adjusted analyses (controlling for patient demographics and clinical factors) assessed the likelihood of SUA lowering and achievement of target SUA of less than 6.0 mg/dL or less than 5.0 mg/dL in allopurinol continuers versus febuxostat switchers. Results The final study population included 748 subjects who switched to febuxostat from allopurinol and 4795 continuing users of allopurinol. The most common doses of allopurinol were 300 mg/d or less in 95% of allopurinol continuers and 93% of febuxostat switchers (prior to switching); the most common dose of febuxostat was 40 mg/d, in 77% of febuxostat switchers (after switching). Compared with allopurinol continuers, febuxostat switchers had greater (1) mean preindex SUA, 8.0 mg/dL versus 6.6 mg/dL (P < 0.001); (2) likelihood of postindex SUA of less than 6.0 mg/dL, 62.2% versus 58.7% (P = 0.072); (3) likelihood of postindex SUA of less than 5.0 mg/dL, 38.9% versus 29.6% (P < 0.001); and (4) decrease in SUA, 1.8 (SD, 2.2)mg/dL versus 0.4 (SD, 1.7)mg/dL (P < 0.001). In multivariable-adjusted analyses, compared with allopurinol continuers, febuxostat switchers had significantly higher likelihood of achieving SUA of less than 6.0 mg/dL (40% higher) and SUA of less than 5.0 mg/dL (83% higher). Conclusions In this real-world setting, many patients with gout not surprisingly were not treated with maximum permitted doses of allopurinol. Patients switched to febuxostat were more likely to achieve target SUA levels than those who continued on generally stable doses of allopurinol. C1 [Altan, Aylin; Bancroft, Tim] Optum, Eden Prairie, MN USA. [Shiozawa, Aki] Takeda Pharmaceut Int Inc, Deerfield, IL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Sch Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com RI Shiozawa, Aki/O-2443-2014 OI Shiozawa, Aki/0000-0001-9757-6337 FU Takeda Pharmaceuticals International, Inc. FX This study was supported by Takeda Pharmaceuticals International, Inc. EPI-Q, Inc, provided medical writing assistance and editorial services for this manuscript and was compensated by Takeda Pharmaceuticals International, Inc. OptumInsight was hired by Takeda Pharmaceuticals International, Inc, to conduct analyses for this study. NR 23 TC 2 Z9 2 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD DEC PY 2015 VL 21 IS 8 BP 411 EP 418 DI 10.1097/RHU.0000000000000322 PG 8 WC Rheumatology SC Rheumatology GA CX5BK UT WOS:000365715400004 PM 26580304 ER PT J AU Badour, CL Hirsch, RL Zhang, JM Mandel, H Hamner, M Wang, ZW AF Badour, Christal L. Hirsch, R. Louis Zhang, Jingmei Mandel, Howard Hamner, Mark Wang, Zhewu TI Exploring the association between a cholecystokinin promoter polymorphism (rs1799923) and posttraumatic stress disorder in combat veterans SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Cholecystokinin; CCK; Posttraumatic Stress; PTSD; Anxiety ID PANIC DISORDER; DOPAMINE TRANSPORTER; HEALTHY-VOLUNTEERS; GENE POLYMORPHISMS; T POLYMORPHISM; PTSD SYMPTOMS; WAR VETERANS; B-RECEPTOR; DRD2 GENE; TETRAPEPTIDE AB Background: Cholecystokinin (CCK) is a neuropeptide that has been implicated in understanding the acquisition and extinction of fear. Research on CCK in anxiety has primarily focused on understanding panic attacks and panic disorder. Emerging data suggests that CCK may also hold promise in understanding the development and maintenance of posttraumatic stress disorder (PTSD). Method: The present study examined whether a single nucleotide polymorphism in the promoter region of the CCK gene (C > T; rs1799923) was associated with an increased prevalence of PTSD as well as with severity of PTSD symptoms among a sample of 457 combat veterans. Results: Results demonstrated that participants with either the heterozygous or homozygous T allele had an increased prevalence of PTSD relative to participants with the CC genotype (OR=2.17; 95% CI [1.37-3.43]). Limitations: The relatively small sample size precluded examination of racial/ethnic differences. Findings were also limited by the absence of a systematic assessment of comorbid anxiety psychopathology. Conclusions: These data offer preliminary evidence supporting an association between the rs1799923 polymorphism in the CCK gene and PTSD. Additional research is needed to better understand the nature of this relationship. Published by Elsevier Ltd. C1 [Badour, Christal L.; Hirsch, R. Louis; Zhang, Jingmei; Hamner, Mark; Wang, Zhewu] Med Univ S Carolina, Charleston, SC 29425 USA. [Hirsch, R. Louis; Mandel, Howard; Hamner, Mark; Wang, Zhewu] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Wang, ZW (reprint author), 67 President St,South Bldg,MSC 861, Charleston, SC 29425 USA. EM wanzh@musc.edu FU Ralph H. Johnson VA Medical Center; Clinical Sciences Program of the Department of Veterans Affairs [1I01CX000487-01A1]; National Institute of Mental Health [T32 MH018869] FX This work was supported by the Ralph H. Johnson VA Medical Center and the Clinical Sciences Program of the Department of Veterans Affairs (Merit Review grant # 1I01CX000487-01A1), as well as the National Institute of Mental Health (T32 MH018869; Dr. Christal Badour). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the National Institutes of Health, or the United States government. There are no conflicts of interest to disclose. NR 55 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD DEC PY 2015 VL 36 BP 78 EP 83 DI 10.1016/j.janxdis.2015.09.009 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CY2GK UT WOS:000366226600009 PM 26454231 ER PT J AU Cigrang, JA Rauch, SAM Mintz, J Brundige, A Avila, LL Bryan, CJ Goodie, JL Peterson, AL AF Cigrang, Jeffrey A. Rauch, Sheila A. M. Mintz, Jim Brundige, Antoinette Avila, Laura L. Bryan, Craig J. Goodie, Jeffrey L. Peterson, Alan L. CA STRONG STAR Consortium TI Treatment of active duty military with PTSD in primary care: A follow-up report SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Military; Primary care; Trauma; Treatment ID POSTTRAUMATIC-STRESS-DISORDER; PROLONGED EXPOSURE; DEPRESSION; VETERANS; RELIABILITY; VALIDITY; TRIAL AB First-line trauma-focused therapies offered in specialty mental health clinics do not reach many veterans and active duty service members with posttraumatic stress disorder (PTSD). Primary care is an ideal environment to expand access to mental health care. Several promising clinical case series reports of brief PTSD therapies adapted for primary care have shown positive results, but the long-term effectiveness with military members is unknown. The purpose of this study was to determine the long-term outcome of an open trial of a brief cognitive-behavioral primary care-delivered protocol developed specifically for deployment-related PTSD in a sample of 24 active duty military (15 men, 9 women). Measures of PTSD symptom severity showed statistically and clinically significant reductions from baseline to post-treatment that were maintained at the 6-month and 1-year follow-up assessments. Similar reductions were maintained in depressive symptoms and ratings of global mental health functioning. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Cigrang, Jeffrey A.] Wright State Univ, Dayton, OH 45402 USA. [Rauch, Sheila A. M.] Emory Univ, Sch Med, Atlanta, GA USA. [Rauch, Sheila A. M.] Atlanta VA Med Ctr, Atlanta, GA USA. [Mintz, Jim; Brundige, Antoinette; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Avila, Laura L.] San Antonio Mil Med Ctr, Joint Base San Antonio Ft Sam Houston, San Antonio, TX USA. [Bryan, Craig J.] Natl Ctr Vet Studies, Salt Lake City, UT USA. [Bryan, Craig J.] Univ Utah, Salt Lake City, UT USA. [Goodie, Jeffrey L.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Peterson, Alan L.] Univ Texas San Antonio, San Antonio, TX USA. RP Cigrang, JA (reprint author), Wright State Univ, Sch Profess Psychol, Ellis Human Dev Inst 221, 9N Edwin C Moses Blvd, Dayton, OH 45402 USA. EM jeffrey.cigrang@wright.edu; sheila.a.m.rauch@emory.edu; mintz@uthscsa.edu; brundige@uthscsa.edu; laura.l.avila.civ@mail.mil; craig.biyan@utah.edu; jeffrey.goodie@usuhs.edu; petersona3@uthscsa.edu RI Rauch, Sheila/K-4450-2015; OI Rauch, Sheila/0000-0001-9686-4011; Bryan, Craig/0000-0002-9714-0733 FU Department of Defense through the U.S. Army Medical Research and Materiel Command [W81XWH-08-02-0109]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development FX Funding for this work was made possible by the Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program award W81XWH-08-02-0109. Dr. Rauch's work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research and Development. NR 26 TC 3 Z9 3 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD DEC PY 2015 VL 36 BP 110 EP 114 DI 10.1016/j.janxdis.2015.10.003 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CY2GK UT WOS:000366226600014 PM 26519833 ER PT J AU Zumbrunn, T Varadarajan, KM Rubash, HE Malchau, H Li, GA Muratoglu, OK AF Zumbrunn, Thomas Varadarajan, Kartik Mangudi Rubash, Harry E. Malchau, Henrik Li, Guoan Muratoglu, Orhun K. TI Regaining Native Knee Kinematics Following Joint Arthroplasty: A Novel Biomimetic Design with ACL and PCL Preservation SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; ACL preservation; BCR implant design; biomimetic; kinematics; dynamic simulations ID IN-VIVO KINEMATICS; CRUCIATE LIGAMENTS; MOTION CHARACTERISTICS; OSTEOARTHRITIC KNEES; ORIENTATION; ROTATION; COMPLEX; BEARING; FLEXION AB Lack of ACL and non-anatomic articular surfaces in contemporary total knee implants result in kinematic abnormalities. We hypothesized that such abnormalities may be addressed with a biomimetic bi-cruciate retaining (BCR) design having anatomical articular surfaces. We used dynamic computer simulations to compare kinematics among the biomimetic BCR, a contemporary BCR and cruciate-retaining implant for activities of daily living. During simulated deep knee bend, chair-sit and walking, the biomimetic BCR implant showed activity dependent kinematics similar to healthy knees in vivo. Restoring native knee geometry together with ACL preservation provided these kinematic improvements over contemporary ACL-preserving and ACL-sacrificing implants. Further clinical studies are required to determine if such biomimetic implants can result in more normal feeling knees and improve quality of life for active patients. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zumbrunn, Thomas; Varadarajan, Kartik Mangudi; Rubash, Harry E.; Malchau, Henrik; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Technol Implementat Res Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. [Zumbrunn, Thomas] ETH, Dept Hlth Sci & Technol, Swiss Fed Inst Technol, Zurich, Switzerland. [Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. RP Zumbrunn, T (reprint author), Massachusetts Gen Hosp, Technol Implementat Res Ctr, 55 Fruit St,GRJ 1223, Boston, MA 02114 USA. NR 38 TC 1 Z9 1 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2015 VL 30 IS 12 BP 2143 EP 2148 DI 10.1016/j.arth.2015.06.017 PG 6 WC Orthopedics SC Orthopedics GA CY1JA UT WOS:000366161300019 PM 26195354 ER PT J AU Varadarajan, KMM Zumbrunn, T Rubash, HE Malchau, H Li, GA Muratoglu, OK AF Varadarajan, Kartik Mangudi M. Zumbrunn, Thomas Rubash, Harry E. Malchau, Henrik Li, Guoan Muratoglu, Orhun K. TI Cruciate Retaining Implant With Biomimetic Articular Surface to Reproduce Activity Dependent Kinematics of the Normal Knee SO JOURNAL OF ARTHROPLASTY LA English DT Article DE Total knee arthroplasty; cruciate retaining; implant design; knee kinematics; biomimetic; normal function ID MOLECULAR-WEIGHT POLYETHYLENE; OSTEOARTHRITIC KNEES; HIGH FLEXION; ARTHROPLASTY; JOINT; REPLACEMENT; MOVEMENT; ROTATION; COMPLEX; BEARING AB Alterations in normal knee kinematics following total knee arthroplasty (TKA) arise in part from the non-anatomic articular geometry of contemporary implants. In this study, the kinematics of a novel posterior cruciate-retaining (CR) implant with anatomic (biomimetic) articular surface, were compared to that of contemporary CR implants during various simulated activities. Across different simulated activities the biomimetic-CR mimicked normal kinematic patterns more closely than contemporary CR implants. In particular, during deep knee bend and chair-sit, the biomimetic-CR showed medial pivot motion, while other CR implants showed abnormal motion including lateral pivot or no pivot, and paradoxical anterior sliding. Further in vivo and clinical studies are needed to determine whether such biomimetic implants can truly help to achieve a more normal feeling knee and improved patient satisfaction. (C) 2015 Elsevier Inc. All rights reserved. C1 [Varadarajan, Kartik Mangudi M.; Zumbrunn, Thomas; Rubash, Harry E.; Malchau, Henrik; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Technol Implementat Res Ctr, Dept Orthopaed Surg, Boston, MA 02114 USA. [Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. RP Varadarajan, KMM (reprint author), Massachusetts Gen Hosp, Technol Implementat Res Ctr, 55 Fruit St,GRJ 1223, Boston, MA 02114 USA. FU MAKO Surgical Corp. FX This work was supported in part by research grant from MAKO Surgical Corp. NR 46 TC 2 Z9 2 U1 2 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2015 VL 30 IS 12 BP 2149 EP U424 DI 10.1016/j.arth.2015.06.018 PG 7 WC Orthopedics SC Orthopedics GA CY1JA UT WOS:000366161300020 PM 26154569 ER PT J AU Troelsen, A Greene, ME Ayers, DC Bragdon, CR Malchau, H AF Troelsen, Anders Greene, Meridith E. Ayers, David C. Bragdon, Charles R. Malchau, Henrik TI A Novel Method for Assessment of Polyethylene Liner Wear in Radiopaque Tantalum Acetabular Cups: Clinical Validation in Patients Enrolled in a Randomized Controlled Trial SO JOURNAL OF ARTHROPLASTY LA English DT Article DE radiostereometric analysis (RSA); polyethylene wear; novel method for wear measurement; total hip replacement; conventional polyethylene; highly cross-linked polyethylene ID TOTAL HIP-ARTHROPLASTY; CROSS-LINKED POLYETHYLENE; FEMORAL-HEAD PENETRATION; MOLECULAR-WEIGHT POLYETHYLENE; HAP-PAUL-AWARD; RADIOSTEREOMETRIC ANALYSIS; OSTEOLYSIS; REPLACEMENT; RECIPIENT; SURGERY AB Conventional radiostereometric analysis (RSA) for wear is not possible in patients with tantalum cups. We propose a novel method for wear analysis in tantalum cups. Wear was assessed by gold standard RSA and the novel method in total hip arthroplasty patients enrolled in a randomized controlled trial receiving either titanium or tantalum cups (n = 46). The novel method estimated the center of the head using a model based on identification of two proximal markers on the stem and knowledge of the stem head configuration. The novel method was able to demonstrate a pattern of wear that was similar to the gold standard in titanium cups. The novel method offered accurate assessment and is a viable solution for assessment of wear in studies with tantalum cups. (C) 2015 Elsevier Inc. All rights reserved, C1 [Troelsen, Anders; Greene, Meridith E.; Bragdon, Charles R.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthoped, Boston, MA 02114 USA. [Troelsen, Anders] Univ Copenhagen, Hvidovre Hosp, Dept Orthoped Surg, DK-2650 Hvidovre, Denmark. [Ayers, David C.] Univ Massachusetts, Sch Med, Dept Orthoped, Arthrit & Joint Replacement Ctr, Worcester, MA USA. RP Greene, ME (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD DEC PY 2015 VL 30 IS 12 BP 2354 EP 2359 DI 10.1016/j.arth.2015.06.050 PG 6 WC Orthopedics SC Orthopedics GA CY1JA UT WOS:000366161300062 PM 26216229 ER PT J AU Nagaraja, AK Bass, AJ AF Nagaraja, Ankur K. Bass, Adam J. TI Hitting the Target in BRAF-Mutant Colorectal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MEK INHIBITION; IMPROVED SURVIVAL; COLON-CANCER; MELANOMA; VEMURAFENIB; RESISTANCE; SORAFENIB; MUTATIONS; DABRAFENIB; ACTIVATION C1 [Nagaraja, Ankur K.; Bass, Adam J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bass, Adam J.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. RP Nagaraja, AK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 2 Z9 2 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2015 VL 33 IS 34 BP 3990 EP + DI 10.1200/JCO.2015.63.7793 PG 4 WC Oncology SC Oncology GA CX9JE UT WOS:000366021000005 PM 26460302 ER PT J AU Corcoran, RB Atreya, CE Falchook, GS Kwak, EL Ryan, DP Bendell, JC Hamid, O Messersmith, WA Daud, A Kurzrock, R Pierobon, M Sun, P Cunningham, E Little, S Orford, K Motwani, M Bai, YC Patel, K Venook, AP Kopetz, S AF Corcoran, Ryan B. Atreya, Chloe E. Falchook, Gerald S. Kwak, Eunice L. Ryan, David P. Bendell, Johanna C. Hamid, Omid Messersmith, Wells A. Daud, Adil Kurzrock, Razelle Pierobon, Mariaelena Sun, Peng Cunningham, Elizabeth Little, Shonda Orford, Keith Motwani, Monica Bai, Yuchen Patel, Kiran Venook, Alan P. Kopetz, Scott TI Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DOSE-ESCALATION TRIAL; MICROSATELLITE INSTABILITY; V600E MUTATION; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; IMPROVED SURVIVAL; COLON-CANCER; VEMURAFENIB; GENE; EGFR AB Purpose To evaluate dabrafenib, a selective BRAF inhibitor, combined with trametinib, a selective MEK inhibitor, in patients with BRAF V600-mutant metastatic colorectal cancer (mCRC). Patients and Methods A total of 43 patients with BRAF V600-mutant mCRC were treated with dabrafenib (150 mg twice daily) plus trametinib (2 mg daily), 17 of whom were enrolled onto a pharmacodynamic cohort undergoing mandatory biopsies before and during treatment. Archival tissues were analyzed for microsatellite instability, PTEN status, and 487-gene sequencing. Patient-derived xenografts were established from core biopsy samples. Results Of 43 patients, five (12%) achieved a partial response or better, including one (2%) complete response, with duration of response > 36 months; 24 patients (56%) achieved stable disease as best confirmed response. Ten patients (23%) remained in the study > 6 months. All nine evaluable during-treatment biopsies had reduced levels of phosphorylated ERK relative to pretreatment biopsies (average decrease standard deviation, 47% +/- 24%). Mutational analysis revealed that the patient achieving a complete response and two of three evaluable patients achieving a partial response had PIK3CA mutations. Neither PTEN loss nor microsatellite instability correlated with efficacy. Responses to dabrafenib plus trametinib were comparable in patient-derived xenograft-bearing mice and the biopsied lesions from each corresponding patient. Conclusion The combination of dabrafenib plus trametinib has activity in a subset of patients with BRAF V600-mutant mCRC. Mitogen-activated protein kinase signaling was inhibited in all patients evaluated, but to a lesser degree than observed in BRAF-mutant melanoma with dabrafenib alone. PIK3CA mutations were identified in responding patients and thus do not preclude response to this regimen. Additional studies targeting the mitogen-activated protein kinase pathway in this disease are warranted. (C) 2015 by American Society of Clinical Oncology C1 [Corcoran, Ryan B.; Kwak, Eunice L.; Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Corcoran, Ryan B.; Kwak, Eunice L.; Ryan, David P.] Harvard Univ, Sch Med, Boston, MA USA. [Atreya, Chloe E.; Daud, Adil; Venook, Alan P.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Falchook, Gerald S.] HealthONE, Sarah Cannon Res Inst, Denver, CO USA. [Messersmith, Wells A.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Messersmith, Wells A.] Univ Colorado, Aurora, CO USA. [Bendell, Johanna C.] Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA. [Kurzrock, Razelle; Kopetz, Scott] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pierobon, Mariaelena] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. [Sun, Peng; Cunningham, Elizabeth; Little, Shonda; Orford, Keith; Motwani, Monica; Bai, Yuchen] GlaxoSmithKline, Philadelphia, PA USA. [Patel, Kiran] Incyte, Wilmington, DE USA. RP Corcoran, RB (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th Floor, Boston, MA 02129 USA. EM rbcorcoran@partners.org FU GlaxoSmithKline; Damon Runyon Clinical Investigator Award; National Cancer Institute (NCI), National Institute of Health (NIH) [P50CA127003, K08CA166510]; NCI, NIH [K08CA175143]; NIH Clinical and Translational Science Award [UL1 RR024148]; NIH Cancer Center Support Grant [CA016672]; NCI [R01CA172670, R01CA184843] FX Supported by GlaxoSmithKline and in part by a Damon Runyon Clinical Investigator Award and Awards No. P50CA127003 and K08CA166510 from the National Cancer Institute (NCI), National Institute of Health (NIH; R.B.C.); by Award No. K08CA175143 from the NCI, NIH (C.E.A.); by NIH Clinical and Translational Science Award No. UL1 RR024148 and NIH Cancer Center Support Grant No. CA016672 to MD Anderson Cancer Center (G.F.); and by Awards No. R01CA172670 and R01CA184843 from the NCI (S.K.). NR 44 TC 51 Z9 51 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2015 VL 33 IS 34 BP 4023 EP + DI 10.1200/JCO.2015.63.2471 PG 11 WC Oncology SC Oncology GA CX9JE UT WOS:000366021000010 PM 26392102 ER PT J AU Lawson, DH Lee, S Zhao, FM Tarhini, AA Margolin, KA Ernstoff, MS Atkins, MB Cohen, GI Whiteside, TL Butterfield, LH Kirkwood, JM AF Lawson, David H. Lee, Sandra Zhao, Fengmin Tarhini, Ahmad A. Margolin, Kim A. Ernstoff, Marc S. Atkins, Michael B. Cohen, Gary I. Whiteside, Theresa L. Butterfield, Lisa H. Kirkwood, John M. TI Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE INTERFERON-ALPHA-2B; METASTATIC MELANOMA; ADJUVANT THERAPY; DENDRITIC CELLS; SARGRAMOSTIM; INTERGROUP AB Purpose We conducted a double-blind, placebo-controlled trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and peptide vaccination (PV) on relapse-free survival (RFS) and overall survival (OS) in patients with resected high-risk melanoma. Patients and Methods Patients with completely resected stage IV or high-risk stage III melanoma were grouped by human leukocyte antigen (HLA) -A2 status. HLA-A2-positive patients were randomly assigned to receive GM-CSF, PV, both, or placebo; HLA-A2-negative patients, GM-CSF or placebo. Treatment lasted for 1 year or until recurrence. Efficacy analyses were conducted in the intent-to-treat population. Results A total of 815 patients were enrolled. There were no significant improvements in OS (stratified log-rank P = .528; hazard ratio, 0.94; 95% repeated CI, 0.77 to 1.15) or RFS (P = .131; hazard ratio, 0.88; 95% CI, 0.74 to 1.04) in the patients assigned to GM-CSF (n = 408) versus those assigned to placebo (n = 407). The median OS times with GM-CSF versus placebo treatments were 69.6 months (95% CI, 53.4 to 83.5 months) versus 59.3 months (95% CI, 44.4 to 77.3 months); the 5-year OS probability rates were 52.3% (95% CI, 47.3% to 57.1%) versus 49.4% (95% CI, 44.3% to 54.3%), respectively. The median RFS times with GM-CSF versus placebo were 11.4 months (95% CI, 9.4 to 14.8 months) versus 8.8 months (95% CI, 7.5 to 11.2 months); the 5-year RFS probability rates were 31.2% (95% CI, 26.7% to 35.9%) versus 27.0% (95% CI, 22.7% to 31.5%), respectively. Exploratory analyses showed a trend toward improved OS in GM-CSF-treated patients with resected visceral metastases. When survival in HLA-A2-positive patients who received PV versus placebo was compared, RFS and OS were not significantly different. Treatment-related grade 3 or greater adverse events were similar between GM-CSF and placebo groups. Conclusion Neither adjuvant GM-CSF nor PV significantly improved RFS or OS in patients with high-risk resected melanoma. Exploratory analyses suggest that GM-CSF may be beneficial in patients with resected visceral metastases; this observation requires prospective validation. (C) 2015 by American Society of Clinical Oncology C1 [Lawson, David H.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Lee, Sandra; Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tarhini, Ahmad A.; Whiteside, Theresa L.; Butterfield, Lisa H.; Kirkwood, John M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Margolin, Kim A.] Seattle Canc Care Alliance, Seattle, WA USA. [Ernstoff, Marc S.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Cohen, Gary I.] Greater Baltimore Med Ctr, Baltimore, MD 21204 USA. RP Lawson, DH (reprint author), 1365C Clifton Rd, Atlanta, GA 30322 USA. EM dlawson@emory.edu FU Public Health Service [CA180802, CA180794, CA180864, CA180844, CA180854, CA18082, CA32102, CA180888, CA20319, CA31946, CA04326]; National Institutes of Health [P30CA047904]; National Cancer Institute, the National Institutes of Health; Department of Health and Human Services FX Supported in part by Public Health Service Grants No. CA180802, CA180794, CA180864, CA180844, CA180854, CA18082, CA32102, CA180888, CA20319, CA31946, and CA04326 (for coordination by the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, group co-chairs); by National Institutes of Health Grant No. P30CA047904 (through use of the Eastern Cooperative Oncology Group Central Immunology Laboratory [Frontier Science and Technology Research Foundation] at the University of Pittsburgh Cancer Institute Immunological Monitoring and Cellular Products Laboratory for this and correlative studies); and by the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. NR 18 TC 10 Z9 10 U1 1 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2015 VL 33 IS 34 BP 4066 EP + DI 10.1200/JCO.2015.62.0500 PG 13 WC Oncology SC Oncology GA CX9JE UT WOS:000366021000015 PM 26351350 ER PT J AU Kearney, LK Smith, CA Pomerantz, AS AF Kearney, Lisa K. Smith, Clifford A. Pomerantz, Andrew S. TI Capturing Psychologists' Work in Integrated Care: Measuring and Documenting Administrative Outcomes SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE Clinic administration; Access; Productivity; Integrated care ID BEHAVIORAL HEALTH-SERVICES; MENTAL-HEALTH; TREATMENT ENGAGEMENT; ADVANCED ACCESS; REFERRAL CARE; MANAGEMENT; SYSTEM AB With the expansion of integrated primary care and the increased focus on fiscal sustainability, it is critical for clinical managers of these innovative systems to have practical methods for measuring administrative outcomes. Administrative outcomes will assist leadership in the development of efficient, streamlined clinics to provide services to the primary care population. Additionally, administrative measures can be utilized to provide information to assist in guiding resource utilization and management decisions. Several administrative outcomes are suggested for integrated primary care managers to consider for application, including: clinic utilization measures, integrated care administrative measures, wait time and access metrics, and productivity monitors. Effective utilization of these measures can help office managers and clinic leadership not only to maximize patient care, but also to enhance essential business operations, which increase the long-term sustainability of integrated primary care programs. C1 [Kearney, Lisa K.] Vet Hlth Adm, VACO Off Mental Hlth Operat, Off Mental Hlth Operat, Dept Vet Affairs,VISN Mental Hlth Off Plaza Lecea, San Antonio, TX 78240 USA. [Smith, Clifford A.] Iron Mt VA Med Ctr, Iron Mountain, MI USA. [Pomerantz, Andrew S.] Mental Hlth Serv, Vet Hlth Adm, Dept Vet Affairs, Washington, DC USA. [Kearney, Lisa K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Smith, Clifford A.] Michigan State Univ, Dept Psychiat, E Lansing, MI 48824 USA. [Pomerantz, Andrew S.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. RP Kearney, LK (reprint author), Vet Hlth Adm, VACO Off Mental Hlth Operat, Off Mental Hlth Operat, Dept Vet Affairs,VISN Mental Hlth Off Plaza Lecea, 5441 Babcock Rd,Suite 300, San Antonio, TX 78240 USA. EM Lisa.Kearney3@va.gov; Clifford.Smith2@va.gov; Andrew.Pomerantz@va.gov NR 39 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 EI 1573-3572 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD DEC PY 2015 VL 22 IS 4 BP 232 EP 242 DI 10.1007/s10880-015-9442-7 PG 11 WC Psychology, Clinical SC Psychology GA CY4BI UT WOS:000366353200005 PM 26645090 ER PT J AU Gomes, BPFA Berber, VB Kokaras, AS Chen, T Paster, BJ AF Gomes, Brenda P. F. A. Berber, Vanessa B. Kokaras, Alexis S. Chen, Tsute Paster, Bruce J. TI Microbiomes of Endodontic-Periodontal Lesions before and after Chemomechanical Preparation SO JOURNAL OF ENDODONTICS LA English DT Article DE Bacteria; culture; endodontic-periodontal lesions; Human Oral Microbe Identification using Next Generation Sequencing; next-generation sequencing ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; INFECTED ROOT CANALS; ENTEROCOCCUS-FAECALIS; TEETH; BACTERIA; ENDOTOXINS; PREVALENCE; PATHOGENS; CULTURE AB Introduction: This study was conducted to evaluate the microbiomes of endodontic-periodontal lesions before and after chemomechanical preparation (CMP). Methods: Clinical samples were taken from 15 root canals (RCs) with necrotic pulp tissues and from their associated periodontal pockets (PPs) (n = 15) of teeth with endodontic-periodontal lesions before and after CMP. The Human Oral Microbe Identification using Next Generation Sequencing (NGS) protocol and viable culture were used to analyze samples from RCs and PPs. The Mann-Whitney U test and Benjamini-Hochberg corrections were performed to correlate the clinical and radiographic findings with microbial findings (P < .05). Results: Bacteria were detected in 100% of the samples in both sites (15/15) using NGS. Firmicutes was the most predominant phylum in both sites using both methods. The most frequently detected species in the RCs before and after CMP using NGS were Enterococcus faecalis, Parvimonas micra, Mogibacterium timidum, Filifactor alocis, and Fretibacterium fastidiosum. The species most frequently detected in the PPs before and after CMP using NGS were P. micra, E. faecalis, Streptococcus constellatus, Eubacterium brachy, Tannerella forsythia, and F. alocis. Associations were found between periapical lesions <= 2 mm and Desulfobulbus sp oral taxon 041 and with periodontal pockets >= 6mm and Dialister invisius and Peptostreptococcus stomatis (all P < .05, found in the RCs before CMP). Conclusions: It is concluded that the microbial community present in combined endodontic-periodontal lesions is complex and more diverse than previously reported. It is important to note that bacteria do survive in some root canals after CMP. Finally, the similarity between the microbiota of both sites, before and after CMP, suggests there may be a pathway of infection between the pulp and periodontium. C1 [Gomes, Brenda P. F. A.; Berber, Vanessa B.] State Univ Campinas UNICAMP, Piracicaba Dent Sch, Endodont Div, Dept Restorat Dent, BR-13414903 Piracicaba, SP, Brazil. [Gomes, Brenda P. F. A.; Kokaras, Alexis S.; Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Chen, Tsute] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. RP Gomes, BPFA (reprint author), State Univ Campinas UNICAMP, Piracicaba Dent Sch, Endodont Div, Av Limeira 901, BR-13414903 Piracicaba, SP, Brazil. EM bpgomes@fop.unicamp.br RI Gomes, Brenda/B-8024-2014 OI Gomes, Brenda/0000-0002-8449-0646 FU Brazilian agency FAPESP [14/01655-3]; Brazilian agency CNPq [308162/2014-5]; Brazilian agency CAPES; Brazilian agency FAEPEX FX Supported by the Brazilian agencies FAPESP (14/01655-3), CNPq (308162/2014-5), CAPES, and FAEPEX (2012/15). NR 35 TC 13 Z9 15 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 EI 1878-3554 J9 J ENDODONT JI J. Endod. PD DEC PY 2015 VL 41 IS 12 BP 1975 EP 1984 DI 10.1016/j.joen.2015.08.022 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CY1DF UT WOS:000366146200005 PM 26521147 ER PT J AU Puram, SV Herrmann, B Barker, FG Lee, DJ AF Puram, Sidharth V. Herrmann, Barbara Barker, Fred G., II Lee, Daniel J. TI Retrosigmoid Craniotomy for Auditory Brainstem Implantation in Adult Patients with Neurofibromatosis Type 2 SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE LA English DT Article DE auditory brainstem implant (ABI); neurofibromatosis type 2 (NF2); retrosigmoid craniotomy ID COCHLEAR IMPLANTATION; PERSPECTIVES; EXPERIENCE AB ObjectiveTo report our technique and experience using a retrosigmoid craniotomy approach for auditory brainstem implantation (ABI) placement in adult neurofibromatosis type 2 (NF2) patients. DesignRetrospective case series. SettingSingle-center study, Boston, Massachusetts, United States. ParticipantsAll NF2 patients who underwent evaluation at Massachusetts Eye and Ear Infirmary and surgery at Massachusetts General Hospital from 2009 to 2013 were reviewed. Six cases of retrosigmoid craniotomy for ABI surgery in five adult NF2 patients were identified. The clinical history, operative course, and outcomes in these patients were reviewed. Main Outcome MeasuresPostoperative complications and audiological outcomes. ResultsIndications for ABI surgery were profound hearing loss associated with growth or treatment of bilateral vestibular schwannomas. In all cases, a retrosigmoid craniotomy was performed for tumor resection and ABI placement without complication. Electrode placement was confirmed intraoperatively using electrical-evoked auditory brainstem responses. The ABI was activated in the awake patient 4 to 6 weeks postoperatively. Audiological testing was used to evaluate sound detection and speech perception with the ABI. There were no cases of cerebrospinal fluid leak. ConclusionRetrosigmoid craniotomy is a safe and effective means to provide access to the cochlear nucleus for ABI placement following tumor resection in the adult NF2 patient. Preliminary data indicate that this approach has few complications while offering benefits for hearing. The retrosigmoid craniotomy should be considered a reasonable alternative to the traditional translabyrinthine approach for placement of the ABI in deaf patients who are not candidates for the cochlear implant. C1 [Puram, Sidharth V.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Puram, Sidharth V.; Herrmann, Barbara; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Herrmann, Barbara] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. [Barker, Fred G., II] Harvard Univ, Dept Surg Neurosurg, Sch Med, Boston, MA 02115 USA. RP Lee, DJ (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Daniel_Lee@meei.harvard.edu NR 27 TC 0 Z9 0 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6331 EI 2193-634X J9 J NEUROL SURG PART B JI Journal of Neurol. Surg. Part B PD DEC PY 2015 VL 76 IS 6 BP 440 EP 450 DI 10.1055/s-0034-1544121 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CY2BI UT WOS:000366213400006 PM 27054058 ER PT J AU Eviston, TJ Croxson, GR Kennedy, PGE Hadlock, T Krishnan, AV AF Eviston, Timothy J. Croxson, Glen R. Kennedy, Peter G. E. Hadlock, Tessa Krishnan, Arun V. TI Bell's palsy: aetiology, clinical features and multidisciplinary care SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID HERPES-SIMPLEX-VIRUS; FACIAL PARALYSIS; SODIUM-CHANNELS; GRADING SYSTEM; PREDNISOLONE; MANAGEMENT; INJURY; DEGENERATION; MULTICENTER; LATENCY AB Bell's palsy is a common cranial neuropathy causing acute unilateral lower motor neuron facial paralysis. Immune, infective and ischaemic mechanisms are all potential contributors to the development of Bell's palsy, but the precise cause remains unclear. Advancements in the understanding of intra-axonal signal molecules and the molecular mechanisms underpinning Wallerian degeneration may further delineate its pathogenesis along with in vitro studies of virus-axon interactions. Recently published guidelines for the acute treatment of Bell's palsy advocate for steroid monotherapy, although controversy exists over whether combined corticosteroids and antivirals may possibly have a beneficial role in select cases of severe Bell's palsy. For those with longstanding sequaelae from incomplete recovery, aesthetic, functional (nasal patency, eye closure, speech and swallowing) and psychological considerations need to be addressed by the treating team. Increasingly, multidisciplinary collaboration between interested clinicians from a wide variety of subspecialties has proven effective. A patient centred approach utilising physiotherapy, targeted botulinum toxin injection and selective surgical intervention has reduced the burden of long-term disability in facial palsy. C1 [Eviston, Timothy J.; Krishnan, Arun V.] Univ NSW, Prince Wales Clin Sch, Sydney, NSW, Australia. [Croxson, Glen R.] Royal Prince Alfred Hosp, Dept Otolaryngol, Sydney, NSW, Australia. [Kennedy, Peter G. E.] Univ Glasgow, So Gen Hosp, Dept Neurol, Glasgow, Lanark, Scotland. [Hadlock, Tessa] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hadlock, Tessa] Harvard Univ, Sch Med, Boston, MA USA. RP Krishnan, AV (reprint author), Univ New S Wales, Prince Wales Clin Sch, Randwick, NSW 2031, Australia. EM Arun.Krishnan@unsw.edu.au NR 40 TC 5 Z9 5 U1 8 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD DEC PY 2015 VL 86 IS 12 BP 1356 EP 1361 DI 10.1136/jnnp-2014-309563 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA CX7CU UT WOS:000365859500013 PM 25857657 ER PT J AU LeBaron, VT Cooke, A Resmini, J Garinther, A Chow, V Quinones, R Noveroske, S Baccari, A Smith, PT Peteet, J Balboni, TA Balboni, MJ AF LeBaron, Virginia T. Cooke, Amanda Resmini, Jonathan Garinther, Alexander Chow, Vinca Quinones, Rebecca Noveroske, Sarah Baccari, Andrew Smith, Patrick T. Peteet, John Balboni, Tracy A. Balboni, Michael J. TI Clergy Views on a Good Versus a Poor Death: Ministry to the Terminally III SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CARE NEAR-DEATH; ADVANCED CANCER; MEDICAL-CARE; SPIRITUAL SUPPORT; MENTAL-HEALTH; END; ASSOCIATIONS; PREDICTORS; PROVISION AB Background: Clergy are often important sources of guidance for patients and family members making medical decisions at the end-of-life (EOL). Previous research revealed spiritual support by religious communities led to more aggressive care at the EOL, particularly among minority patients. Understanding this phenomenon is important to help address disparities in EOL care. Objective: The study objective was to explore and describe clergy perspectives regarding good versus poor death within the participant's spiritual tradition. Methods: This was a qualitative, descriptive study. Community clergy from various spiritual backgrounds, geographical locations within the United States, and races/ethnicities were recruited. Participants included 35 clergy who participated in one-on-one interviews (N=14) and two focus groups (N=21). Semistructured interviews explored clergy viewpoints on factors related to a good death. Principles of grounded theory were used to identify a final set of themes and subthemes. Results: A good death was characterized by wholeness and certainty and emphasized being in relationship with God. Conversely, a poor death was characterized by separation, doubt, and isolation. Clergy identified four primary determinants of good versus poor death: dignity, preparedness, physical suffering, and community. Participants expressed appreciation for contextual factors that affect the death experience; some described a middle death, or one that integrates both positive and negative elements. Location of death was not viewed as a significant contributing factor. Conclusions: Understanding clergy perspectives regarding quality of death can provide important insights to help improve EOL care, particularly for patients highly engaged with faith communities. These findings can inform initiatives to foster productive relationships between clergy, clinicians, and congregants and reduce health disparities. C1 [LeBaron, Virginia T.] Univ Virginia, Sch Nursing, Charlottesville, VA 22903 USA. [Quinones, Rebecca; Noveroske, Sarah; Peteet, John; Balboni, Tracy A.; Balboni, Michael J.] Dana Farber Canc Inst, Harvard Canc Ctr, Boston, MA 02115 USA. [Cooke, Amanda] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Resmini, Jonathan] Boston Univ, Sch Theol, Boston, MA 02215 USA. [Garinther, Alexander] Boston Coll, Boston, MA USA. [Chow, Vinca] Brigham & Womens Hosp, Boston, MA 02115 USA. [Baccari, Andrew] Harvard Univ, Sch Divin, Boston, MA 02115 USA. [Smith, Patrick T.] Gordon Conwell Theol Seminary, Boston, MA USA. RP LeBaron, VT (reprint author), Univ Virginia, Sch Nursing, McLead Hall,202 Jeanette Lancaster Way, Charlottesville, VA 22903 USA. EM vlebaron@virginia.edu FU NCI NIH HHS [U54 CA156732]; PHS HHS [CAI56732] NR 26 TC 2 Z9 2 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC 1 PY 2015 VL 18 IS 12 BP 1000 EP 1007 DI 10.1089/jpm.2015.0176 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CY2VJ UT WOS:000366266000004 PM 26317801 ER PT J AU Palakshappa, D Carter, LP El Saleeby, CM AF Palakshappa, Deepak Carter, Lindsay P. El Saleeby, Chadi M. TI Discrepancies in After-Hours Communication Attitudes between Pediatric Residents and Supervising Physicians SO JOURNAL OF PEDIATRICS LA English DT Article ID UNSUPERVISED TASKS; ENTRUST RESIDENTS; AUTONOMY; COMPETENCE; ATTENDINGS; EDUCATION; DECIDE; NIGHT; WORK; CALL AB Objective To examine differences in expectations when a resident should contact a supervising physician in several hospital-based, after-hours clinical circumstances. Study design We developed 34 scenarios collectively considered the most common or serious issues encountered by on-call residents, and incorporated them into a survey of pediatric residents, fellows, and attendings. For each scenario, participants were asked whether the resident should talk to the attending/fellow immediately or delay communication until the next day. ORs comparing attendings/fellows and residents were calculated, and subgroup analyses were performed examining differences among the study populations. Results A total of 112 participants completed the survey (91% response rate). In 17 of the 34 scenarios (50%), more attendings/fellows than residents asked for immediate communication (OR >1; P<.05). Most discrepant scenarios were in uncertain areas in which residents may feel comfortable managing the issue without supervisory input or, alternatively, fail to recognize an evolving matter or a deteriorating clinical status. In subgroup analyses, residents were homogeneous in their responses; however, responses of fellows and junior faculty differed from those of senior faculty in 7 of the 34 scenarios, with senior attendings more likely desiring immediate communication. Conclusion We found differences in expectations of when a pediatric resident should contact a supervising physician after hours not only between residents and attendings/fellows, but among attendings themselves. These differences could lead to medical errors, miscommunication, and inconsistent supervision for overnight residents. C1 [Palakshappa, Deepak; Carter, Lindsay P.; El Saleeby, Chadi M.] Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Med Serv, Boston, MA USA. [Carter, Lindsay P.; El Saleeby, Chadi M.] Harvard Univ, Sch Med, Div Pediat Hosp Med, MassGen Hosp Children, Boston, MA USA. [El Saleeby, Chadi M.] Harvard Univ, Sch Med, Dept Pediat, Div Pediat Infect Dis,MassGen Hosp Children, Boston, MA 02115 USA. RP Palakshappa, D (reprint author), Childrens Hosp Philadelphia, Dept Pediat, CHOP North 1494,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM PalakshappaD@email.chop.edu OI Palakshappa, Deepak/0000-0003-1467-4965 FU National Research Service Award [HRSA T32 HP10026-11] FX D.P. is supported by a National Research Service Award (HRSA T32 HP10026-11). The authors declare no conflicts of interest. NR 26 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 2015 VL 167 IS 6 BP 1429 EP + DI 10.1016/j.jpeds.2015.08.052 PG 9 WC Pediatrics SC Pediatrics GA CY1CI UT WOS:000366143900047 PM 26411863 ER PT J AU Kang, EH Lee, JT Lee, HJ Lee, JY Chang, SH Cho, HJ Choi, BY Ha, YJ Park, KU Song, YW Van Dyke, TE Lee, YJ AF Kang, Eun Ha Lee, Jung Tae Lee, Hyo-Jung Lee, Joo Youn Chang, Sung Hae Cho, Hyon Joung Choi, Byoong Yong Ha, You-Jung Park, Kyoung Un Song, Yeong Wook Van Dyke, Thomas E. Lee, Yun Jong TI Chronic Periodontitis Is Associated With Spinal Dysmobility in Patients With Ankylosing Spondylitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Chronic periodontitis; Porphyromonas gingivalis; range of motion; articular; spine; spondylitis; ankylosing ID NECROSIS-FACTOR-ALPHA; BONE MORPHOGENETIC PROTEINS; PORPHYROMONAS-GINGIVALIS; RHEUMATOID-ARTHRITIS; ORAL PATHOGEN; TNF-ALPHA; DISEASE; THERAPY; INFLAMMATION; PARAMETERS AB Background: Although microbes have been suggested to play a role in the pathogenesis of ankylosing spondylitis (AS), several studies present contradictory results regarding the association between AS and chronic periodontitis (CP). Methods: Clinical, laboratory, and medication data were collected from 84 patients with AS and 84 age-and sex-matched controls. Periodontal measurements, including probing depths (PDs), clinical attachment loss (AL), serum anti-Porphyromonas gingivalis titers, and the detection of P. gingivalis DNA in gingival crevicular fluid, were recorded. All participants with periodontitis with PD >= 4 to < 7 mm received scaling and root planing and were re-evaluated at 12 weeks; those still exhibiting periodontitis with PD of >= 4 to < 7 mm at 12 weeks were followed at 24 weeks. Results: The prevalence of moderate-to-severe CP was not different between patients with AS and controls (70.2% versus 66.6%). The P. gingivalis detection rate was not different between patients with AS and controls or between patients with AS receiving and not receiving anti-tumor necrosis factor (TNF)-alpha agents. However, CP was positively associated with impaired spinal mobility of patients with AS in multivariate analyses. After periodontal treatment, PD and AL levels were improved in both groups, but the change was significantly greater in patients with AS than in controls. Patients with AS receiving anti-TNF-alpha agents exhibited a greater improvement in PD and AL than those who did not. Conclusions: Although AS was not associated with the presence of CP, CP was associated positively with the severity of spinal dysmobility in Korean patients with AS. These results suggest that periodontitis can have a negative effect on axial movement in AS. C1 [Kang, Eun Ha; Cho, Hyon Joung; Ha, You-Jung; Lee, Yun Jong] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Div Rheumatol, Songnam, South Korea. [Lee, Jung Tae; Lee, Hyo-Jung] Seoul Natl Univ, Bundang Hosp, Sect Dent, Dept Periodontol, Seoul 151, South Korea. [Lee, Joo Youn; Song, Yeong Wook] Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. [Chang, Sung Hae] Soonchunhyang Univ, Cheonan Hosp, Dept Internal Med, Cheonan, South Korea. [Choi, Byoong Yong] Seoul Med Ctr Publ Corp, Dept Internal Med, Seoul, South Korea. [Park, Kyoung Un] Seoul Natl Univ, Bundang Hosp, Dept Lab Med, Seoul 151, South Korea. [Song, Yeong Wook; Lee, Yun Jong] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. RP Lee, YJ (reprint author), Seoul Natl Univ, Bundang Hosp, Dept Internal Med, 82 Gumi Ro 173 Beon Gil, Songnam 463707, Gyeonggi Do, South Korea. EM yn35@snu.ac.kr FU Abbott Investigator-Initiated Research Program Grant [IMM-12-0004]; National Institute of Dental and Craniofacial Research Grant [DE15566] FX The authors thank Prof. Soyeon Ahn, Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea, for statistical assistance. This study was supported by Abbott Investigator-Initiated Research Program Grant IMM-12-0004 (YJL) and National Institute of Dental and Craniofacial Research Grant DE15566 (TEVD). This trial is registered at ClinicalTrials.gov as NCT01750528. EHK and JTL equally contributed to this work. The authors report no conflicts of interest related to this study. NR 55 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD DEC PY 2015 VL 86 IS 12 BP 1303 EP 1313 DI 10.1902/jop.2015.150202 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CX9RX UT WOS:000366044100001 PM 26291296 ER PT J AU Petkovic, J Epstein, J Buchbinder, R Welch, V Rader, T Lyddiatt, A Clerehan, R Christensen, R Boonen, A Goel, N Maxwell, LJ Toupin-April, K De Wit, M Barton, J Flurey, C Jull, J Barnabe, C Sreih, AG Campbell, W Pohl, C Duruoz, MT Singh, JA Tugwell, PS Guillemin, F AF Petkovic, Jennifer Epstein, Jonathan Buchbinder, Rachelle Welch, Vivian Rader, Tamara Lyddiatt, Anne Clerehan, Rosemary Christensen, Robin Boonen, Annelies Goel, Niti Maxwell, Lara J. Toupin-April, Karine De Wit, Maarten Barton, Jennifer Flurey, Caroline Jull, Janet Barnabe, Cheryl Sreih, Antoine G. Campbell, Willemina Pohl, Christoph Duruoz, Mehmet Tuncay Singh, Jasvinder A. Tugwell, Peter S. Guillemin, Francis TI Toward Ensuring Health Equity: Readability and Cultural Equivalence of OMERACT Patient-reported Outcome Measures SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE HEALTH EQUITY; MUSCULOSKELETAL CONDITIONS; RHEUMATOLOGY; LITERACY; CULTURAL ADAPTATION ID QUALITY-OF-LIFE; LITERACY LEVELS; ADAPTATION; TRANSLATION; INSTRUMENTS; GUIDELINES; PEOPLE AB Objective. The goal of the Outcome Measures in Rheumatology (OMERACT) 12 (2014) equity working group was to determine whether and how comprehensibility of patient-reported outcome measures (PROM) should be assessed, to ensure suitability for people with low literacy and differing cultures. Methods. The English, Dutch, French, and Turkish Health Assessment Questionnaires and English and French Osteoarthritis Knee and Hip Quality of Life questionnaires were evaluated by applying 3 readability formulas: Flesch Reading Ease, Flesch-Kincaid grade level, and Simple Measure of Gobbledygook; and a new tool, the Evaluative Linguistic Framework for Questionnaires, developed to assess text quality of questionnaires. We also considered a study assessing cross-cultural adaptation with/without back-translation and/or expert committee. The results of this preconference work were presented to the equity working group participants to gain their perspectives on the importance of comprehensibility and cross-cultural adaptation for PROM. Results. Thirty-one OMERACT delegates attended the equity session. Twenty-six participants agreed that PROM should be assessed for comprehensibility and for use of suitable methods (4 abstained, 1 no). Twenty-two participants agreed that cultural equivalency of PROM should be assessed and suitable methods used (7 abstained, 2 no). Special interest group participants identified challenges with cross-cultural adaptation including resources required, and suggested patient involvement for improving translation and adaptation. Conclusion. Future work will include consensus exercises on what methods are required to ensure PROM are appropriate for people with low literacy and different cultures. C1 [Petkovic, Jennifer; Maxwell, Lara J.] Univ Ottawa, Ctr Global Hlth, Ottawa, ON K1N 5C8, Canada. [Epstein, Jonathan; Guillemin, Francis] Univ Lorraine, EA Apemac 4360, Nancy, France. [Buchbinder, Rachelle] Cabrini Inst, Melbourne, Vic, Australia. [Buchbinder, Rachelle] Monash Univ, Melbourne, Vic 3004, Australia. [Welch, Vivian] Univ Ottawa, Bruyere Res Inst, Ottawa, ON, Canada. [Rader, Tamara] Univ Ottawa, Inst Populat Hlth, Ottawa, ON, Canada. [Clerehan, Rosemary] Monash Univ, Fac Med Nursing & Hlth Sci, Clayton, Vic 3800, Australia. [Christensen, Robin] Copenhagen Univ Hosp, Musculoskeletal Stat Unit, Parker Inst, Dept Rheumatol, Bispebjerg, Denmark. [Christensen, Robin] Copenhagen Univ Hosp, Musculoskeletal Stat Unit, Parker Inst, Dept Rheumatol, Frederiksberg, Denmark. Maastricht Univ, Dept Internal Med, Div Rheumatol, Med Ctr, NL-6200 MD Maastricht, Netherlands. [Boonen, Annelies] Maastricht Univ, Caphri Res Inst, Rheumatol, NL-6200 MD Maastricht, Netherlands. [Goel, Niti] Quintiles Inc, Durham, NC USA. [Goel, Niti] Duke Univ, Sch Med, Dept Med, Div Rheumatol, Durham, NC 27706 USA. [Toupin-April, Karine] Univ Ottawa, Dept Pediat, Childrens Hosp, Eastern Ontario Res Inst, Ottawa, ON K1N 6N5, Canada. [De Wit, Maarten] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Barton, Jennifer] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Flurey, Caroline] Univ W England, Fac Hlth & Appl Sci, Bristol BS16 1QY, Avon, England. [Barnabe, Cheryl] Univ Calgary, Dept Med & Community Hlth Sci, Cumming Sch Med, Calgary, AB, Canada. [Pohl, Christoph] Charite, Dept Internal Med Rheumatol Clin Immunol Osteol P, Schlosspark Klin, Teaching Hosp, D-13353 Berlin, Germany. [Duruoz, Mehmet Tuncay] Univ Marmara, Fac Med, Dept Phys & Rehabil Med, Rheumatol Clin, Istanbul, Turkey. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Sreih, Antoine G.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Campbell, Willemina] Toronto Western Hosp, UHN, Toronto, ON M5T 2S8, Canada. RP Petkovic, J (reprint author), Univ Ottawa, Ctr Global Hlth, 43 Bruyere St,Annex E,Room 302, Ottawa, ON K1N 5C8, Canada. EM jennifer.petkovic@uottawa.ca OI Petkovic, Jennifer/0000-0002-5824-584X; Tugwell, Peter/0000-0001-5062-0556 FU La Mission Recherche de la Direction de la recherche, des etudes, de l'evaluation et des statistiques; Australian National Health and Medical Research Council Practitioner Fellowship; Arthritis Research UK Fellowship; Canadian Rheumatology Association; Arthritis Society Clinician Investigator Award; Oak Foundation; Agency for Health Quality and Research Center for Education and Research on Therapeutics [U19 HS021110]; US National Institute of Arthritis, Musculoskeletal and Skin Diseases [P50 AR060772, U34 AR062891]; National Institute on Aging [U01 AG018947]; National Cancer Institute [U10 CA149950]; Patient Centered Outcomes Research Institute [CE-1304-6631] FX As an OMERACT Fellow, J. Epstein received a bursary from the European League Against Rheumatism and support from OMERACT to attend the meeting; F. Guillemin was supported by La Mission Recherche de la Direction de la recherche, des etudes, de l'evaluation et des statistiques as part of financial support provided to Institut de Recherche en Sante Publique, in the domain of handicap and loss of autonomy; R. Buchbinder is supported in part by an Australian National Health and Medical Research Council Practitioner Fellowship; conference attendance for A. Lyddiatt was made possible by The Arthritis Society, Canada; J. Barton received support from the American College of Rheumatology, Rheumatology Research Foundation, to attend the meeting; C. Flurey is funded by an Arthritis Research UK Fellowship and received support from OMERACT to attend the meeting; C. Barnabe receives salary support from the Canadian Rheumatology Association and The Arthritis Society Clinician Investigator Award, and is a Canadian Institutes of Health Research New Investigator; (Community-Based Primary Health Care); R. Christensen is supported by grants from the Oak Foundation; J. A. Singh is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics U19 HS021110, US National Institute of Arthritis, Musculoskeletal and Skin Diseases P50 AR060772 and U34 AR062891, National Institute on Aging U01 AG018947, National Cancer Institute U10 CA149950, the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute. NR 33 TC 2 Z9 2 U1 1 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2015 VL 42 IS 12 BP 2448 EP 2459 DI 10.3899/jrheum.141168 PG 12 WC Rheumatology SC Rheumatology GA CX7VB UT WOS:000365909900034 PM 26077410 ER PT J AU Grainger, R Dalbeth, N Keen, H Durcan, L Edwards, NL Perez-Ruiz, F Diaz-Torne, C Singh, JA Khanna, D Simon, LS Taylor, WJ AF Grainger, Rebecca Dalbeth, Nicola Keen, Helen Durcan, Laura Edwards, N. Lawrence Perez-Ruiz, Fernando Diaz-Torne, Cesar Singh, Jasvinder A. Khanna, Dinesh Simon, Lee S. Taylor, William J. TI Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; OUTCOME MEASURES; MEDICAL IMAGING; OMERACT ID RHEUMATOID-ARTHRITIS; CLINICAL-PRACTICE; TOPHACEOUS GOUT; HYPERURICEMIA; TRIALS AB Objective. The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0. Methods. During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented. Results. The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage. Conclusion. The working group prioritized gaps in the data and identified a research agenda. C1 Univ Otago Wellington, Dept Med, Wellington, New Zealand. Univ Auckland, Dept Med, Auckland 1, New Zealand. Mater Misericordiae Univ Hosp, Dublin, Ireland. Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. Univ Florida, Dept Med, Gainesville, FL USA. Hosp Univ Cruces, Div Rheumatol, Vizcaya, Spain. BioCruces Hlth Res Inst, Vizcaya, Spain. Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Div Rheumatol, E-08193 Barcelona, Spain. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Michigan, Dept Med, Div Rheumatol, Ann Arbor, MI 48109 USA. SDG LLC, Cambridge, MA USA. RP Taylor, WJ (reprint author), Univ Otago Wellington, Rehabil Teaching & Res Unit, 23a Mein St,POB 7343, Wellington 6242, New Zealand. EM william.taylor@otago.ac.nz OI Perez-Ruiz, Fernando/0000-0002-5268-1894 FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; US National Institute of Arthritis, Musculoskeletal and Skin Diseases [P50 AR060772, U34 AR062891]; US National Institute on Aging [U01 AG018947]; US National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute [CE-1304-6631] FX JAS is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110, US National Institute of Arthritis, Musculoskeletal and Skin Diseases P50 AR060772 and U34 AR062891, US National Institute on Aging U01 AG018947; US National Cancer Institute (NCI) U10 CA149950; the resources and use of facilities at the VA Medical Center at Birmingham, Alabama; and research CE-1304-6631 from the Patient Centered Outcomes Research Institute. NR 24 TC 7 Z9 7 U1 2 U2 10 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2015 VL 42 IS 12 BP 2460 EP 2464 DI 10.3899/jrheum.141164 PG 5 WC Rheumatology SC Rheumatology GA CX7VB UT WOS:000365909900035 PM 25641895 ER PT J AU Singh, JA Dohm, M Sprowson, AP Wall, PD Richards, BL Gossec, L Hawker, GA Riddle, DL Buchbinder, R AF Singh, Jasvinder A. Dohm, Michael Sprowson, Andrew P. Wall, Peter D. Richards, Bethan L. Gossec, Laure Hawker, Gillian A. Riddle, Daniel L. Buchbinder, Rachelle TI Outcome Domains and Measures in Total Joint Replacement Clinical Trials: Can We Harmonize Them? An OMERACT Collaborative Initiative SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ARTHROPLASTY; TOTAL JOINT REPLACEMENT; OUTCOME MEASURES; DOMAINS; HARMONIZATION; CONSENSUS ID KNEE ARTHROPLASTY REGISTER; FILTER IMPLICATIONS; UNITED-STATES; TOTAL HIP; MEASUREMENT SETS; PREVALENCE; CONSENSUS; SURGERY; VOLUME AB Objective. To develop a plan for harmonizing outcomes for people undergoing total joint replacement (TJR), to achieve consensus regarding TJR outcome research. Methods. The TJR working group met during the 2014 Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary. Multiple conference calls preceded the face-to-face meeting. Brief presentations were made during a 1.5-h meeting, which included an overview of published systematic reviews of TJR trials and the results of a recent systematic review of TJR clinical trial outcome domains and measures. This was followed by discussion of potential core set areas/domains for TJR clinical trials (as per OMERACT Filter 2.0) as well as the challenges associated with the measurement of these domains. Results. Working group participants discussed which TJR clinical trial outcome domains/areas map to the inner versus outer core for core domain set. Several challenges were identified with TJR outcomes including how to best measure function after TJR, elucidating the source of the pre- and post-TJR joint pain being measured, joint-specific versus generic quality of life instruments and the importance of patient satisfaction and revision surgery as outcomes. A preliminary core domain set for TJR clinical trials was proposed and included pain, function, patient satisfaction, revision, adverse events, and death. This core domain set will be further vetted with a broader audience. Conclusion. An international effort with active collaboration with the orthopedic community to standardize key outcome domains and measures is under way with the TJR working group. This effort will be further developed with new collaborations. C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. Univ Arizona, Tucson, AZ USA. [Wall, Peter D.] Univ Warwick, Warwick Clin Trials Unit, Coventry CV4 7AL, W Midlands, England. [Richards, Bethan L.] Royal Prince Alfred Hosp, Inst Rheumatol & Orthoped, Sydney, NSW, Australia. [Richards, Bethan L.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. Univ Paris 06, Sorbonne Univ, Inst Pierre Louis Epidemiol & Sante Publ, Paris, France. Grp Hosp Pitie Salpetriere, AP HP, Dept Rheumatol, F-75634 Paris, France. Univ Toronto, Dept Med, Toronto, ON, Canada. [Hawker, Gillian A.] Univ Toronto, Womens Coll Hosp, Toronto, ON, Canada. Virginia Commonwealth Univ, Richmond, VA USA. Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Buchbinder, Rachelle] Cabrini Hosp, Monash Dept Clin Epidemiol, Melbourne, Australia. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com RI Wall, Peter/O-6408-2016 OI Wall, Peter/0000-0003-3149-3373 FU US Agency for Health Quality and Research Center for Education and Research on Therapeutics; National Institute of Arthritis; Musculoskeletal and Skin Diseases [P50]; National Institute of Aging [U01]; National Cancer Institute; Patient Centered Outcomes Research [CE-1304-6631]; Takeda; Savient; Regeneron; Allergan FX JAS is supported by grants from the US Agency for Health Quality and Research Center for Education and Research on Therapeutics, National Institute of Arthritis, Musculoskeletal and Skin Diseases P50, National Institute of Aging U01, National Cancer Institute, the resources and the use of facilities at the Veterans Affair (VA) Medical Center at Birmingham, Alabama, and research contract CE-1304-6631 from the Patient Centered Outcomes Research. JAS has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Regeneron, and Allergan. JAS is a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; the VA Rheumatology Field Advisory Committee; and the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. NR 41 TC 3 Z9 3 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2015 VL 42 IS 12 BP 2496 EP 2502 DI 10.3899/jrheum.141201 PG 7 WC Rheumatology SC Rheumatology GA CX7VB UT WOS:000365909900042 PM 25834208 ER PT J AU Hoffmann, U Akers, SR Brown, RKJ Cummings, KW Cury, RC Greenberg, SB Ho, VB Hsu, JY Min, JK Panchal, KK Stillman, AE Woodard, PK Jacobs, JE AF Hoffmann, Udo Akers, Scott R. Brown, Richard K. J. Cummings, Kristopher W. Cury, Ricardo C. Greenberg, S. Bruce Ho, Vincent B. Hsu, Joe Y. Min, James K. Panchal, Kalpesh K. Stillman, Arthur E. Woodard, Pamela K. Jacobs, Jill E. TI ACR Appropriateness Criteria Acute Nonspecific Chest Pain-Low Probability of Coronary Artery Disease SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article ID EMERGENCY-DEPARTMENT PATIENTS; CARDIAC COMPUTED-TOMOGRAPHY; ACUTE PULMONARY-EMBOLISM; CARDIOVASCULAR MAGNETIC-RESONANCE; ELEVATION MYOCARDIAL-INFARCTION; TRIPLE RULE-OUT; CT ANGIOGRAPHY; HEART-ASSOCIATION; AMERICAN-COLLEGE; DIAGNOSTIC YIELD AB Primary imaging options in patients at low risk fur coronary artery disease (CAD) who present with undifferentiated chest pain and without signs of ischemia are functional testing with exercise or pharmacologic stress-based electrocardiography, echocardiography, or myocardial perfusion imaging to exclude myocardial ischernia after rule-out of myocardial infarction and early cardiac CT because of its high negative predictive value to exclude CAD. Although possible, is not conclusive whether triple-rule-out CT (CAD, pulmonary embolism, and aortic dissection) might improve the efficiency of patient management: More advanced noninvasive tests such as cardiac MRI and invasive imaging with transesophageal echocardiography or coronary angiography are rarely indicated. With increased likelihood of noncardiac causes, a number of diagnostic tests, among them ultrasound of the abdomen, MR angiogtaphy of the aorta with or without contrast, x-ray rib views, x-ray barium swallow, and upper gastrointestinal series, can also be appropriate. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. This recommendation is based on excellent evidence, including several randomized comparative effectiveness trials and blinded observational cohort studies. Copyright (C) 2015 American College of Radiology C1 [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Akers, Scott R.] VA Med Ctr, Philadelphia, PA USA. [Brown, Richard K. J.] Univ Hosp, Ann Arbor, MI USA. [Cummings, Kristopher W.; Woodard, Pamela K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Cury, Ricardo C.] Miami Cardiac & Vasc Inst, Miami, FL USA. [Cury, Ricardo C.] Baptist Hlth South Florida, Miami, FL USA. [Greenberg, S. Bruce] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Ho, Vincent B.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Hsu, Joe Y.] Diagnost Imaging, Los Angeles, CA USA. [Min, James K.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Min, James K.] Amer Coll Cardiol, Los Angeles, CA USA. [Panchal, Kalpesh K.] Univ Cincinnati Hosp, Cincinnati, OH USA. [Stillman, Arthur E.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Jacobs, Jill E.] NYU, Med Ctr, New York, NY 10016 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 57 TC 4 Z9 4 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2015 VL 12 IS 12 BP 1266 EP 1271 DI 10.1016/j.jacr.2015.09.004 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CY2HU UT WOS:000366230200010 PM 26653833 ER PT J AU Boland, GW Duszak, R AF Boland, Giles W. Duszak, Richard, Jr. TI Structured Reporting and Communication SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Sch Med, Dept Radiol, Atlanta, GA USA. RP Boland, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2015 VL 12 IS 12 BP 1286 EP 1288 DI 10.1016/j.jacr.2015.08.001 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CY2HU UT WOS:000366230200013 PM 26421851 ER PT J AU Clark, TJ Flood, TF Maximin, ST Sachs, PB AF Clark, Toshimasa J. Flood, Thomas F. Maximin, Suresh T. Sachs, Peter B. TI Lung CT Screening Reporting and Data System Speed and Accuracy Are Increased With the Use of a Semiautomated Computer Application SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Lung-RADS; decision support; lung cancer screening ID IMAGING 3.0; CANCER; NODULES AB Purpose: The Lung CT Screening Reporting and Data System (LungRADS(TM)) is an algorithm that can be used to classify lung nodules in patients with significant smoking histories. It is published in table format but can be implemented as a computer program. The aim of this, study was to assess the efficiency and accuracy of the use of a computer program versus the table in categorizing lung nodules. Methods: The Lung-RADS algorithm was implemented as a computer program. Through the use of a survey tool, respondents were asked to categorize 13 simulated lung nodules using the computer program and the Lung-RADS table as published. Data were gathered regarding time to completion, accuracy of each nodule's categorization, users' subjective categorization confidence, and users' perceived efficiency using-each method. Results: The use of a computer program to categorize lung nodules resulted in significantly increased interpretation speed (80.8 +/- 37.7 vs 156 105 seconds, P < .0001), lung nodule classification accuracy (99.6% vs 76.5%, P < .0001), and perceived confidence and efficiency compared with the use of the table. There were no significant differences in accuracy when comparing thoracic radiologists with the remainder of the group. Conclusions: Radiologists were both more efficient and more accurate in lung nodule categorization when using computerized decision support tools. The authors propose that other institutions use computerized implementations of Lung-RADS in the interests of both efficiency and patient outcomes through proper management. Furthermore, they suggest the ACR design future iterations of the Lung-RADS algorithm with computerized decision support in mind. Copyright (C) 2015 American College of Radiology C1 [Clark, Toshimasa J.; Flood, Thomas F.; Sachs, Peter B.] Univ Colorado Denver, Aurora, CO 80045 USA. [Maximin, Suresh T.] Univ Washington, Seattle, WA 98195 USA. [Maximin, Suresh T.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Clark, TJ (reprint author), Univ Colorado Denver, 12401 E 17th Ave,Mail Stop L-954, Aurora, CO 80045 USA. EM toshimasa.clark@ucdenver.edu NR 9 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2015 VL 12 IS 12 BP 1301 EP 1306 DI 10.1016/j.jacr.2015.07.015 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CY2HU UT WOS:000366230200018 PM 26507823 ER PT J AU Paganetti, H Zietman, A AF Paganetti, Harald Zietman, Anthony TI Why Is Proton Beam Therapy So Controversial? SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Paganetti, Harald; Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Fruit St, Boston, MA 02114 USA. EM azietman@partners.org OI Paganetti, Harald/0000-0002-6257-2413 NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD DEC PY 2015 VL 12 IS 12 BP 1318 EP 1319 DI 10.1016/j.jacr.2015.09.019 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CY2HU UT WOS:000366230200022 PM 26653836 ER PT J AU Valentine, SE Elsesser, S Grasso, C Safren, SA Bradford, JB Mereish, E O'Cleirigh, C AF Valentine, Sarah E. Elsesser, Steven Grasso, Chris Safren, Steven A. Bradford, Judith B. Mereish, Ethan O'Cleirigh, Conall TI The Predictive Syndemic Effect of Multiple Psychosocial Problems on Health Care Costs and Utilization among Sexual Minority Women SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Lesbian; Bisexual; Mental health; Health care costs; Health care utilization; Sexual minority ID MENTAL-HEALTH; BISEXUAL WOMEN; LESBIAN WOMEN; PUBLIC-HEALTH; UNITED-STATES; ALCOHOL-USE; RISK; BEHAVIORS; GAY; HIV AB Previous studies documenting sexual minority women's disproportionate risk for a range of medical, mental health, and substance use disorders have not provided a predictive framework for understanding their interrelations and outcomes. The present study aimed to address this gap by testing the syndemic effect of co-occurring psychosocial problems on 7-year health care costs and utilization among sexual minority women. The sample was comprised of sexual minority women (N = 341) who were seen at an urban LGBT-affirmative community health center. Medical and mental health care utilization and cost data were extracted from electronic medical records. Demographically adjusted regression models revealed that co-occurring psychosocial problems (i.e., childhood sexual abuse, partner violence, substance use, and mental health distress [history of suicide attempt]) were all strongly interrelated. The presence of these indicators had a syndemic (additive) effect on medical costs and utilization and mental health utilization over 7-year follow-up, but no effect on 7-year mental health costs. These results suggest that the presence and additive effect of these syndemic conditions may, in part, explain increased medical costs and utilization (and higher medical morbidity) among sexual minority women. C1 [Valentine, Sarah E.; Safren, Steven A.; O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Valentine, Sarah E.; Safren, Steven A.; O'Cleirigh, Conall] Harvard Univ, Sch Med, Boston, MA USA. [Elsesser, Steven; Grasso, Chris; Safren, Steven A.; Bradford, Judith B.; O'Cleirigh, Conall] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mereish, Ethan] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA. RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM cocleirigh@mgh.harvard.edu FU National Institute of Mental Health [R01 MH095624] FX Dr. Conall O'Cleirigh's time on this manuscript was supported in part by a National Institute of Mental Health grant R01 MH095624 (PI: O'Cleirigh). NR 44 TC 1 Z9 1 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 EI 1468-2869 J9 J URBAN HEALTH JI J. Urban Health PD DEC PY 2015 VL 92 IS 6 BP 1092 EP 1104 DI 10.1007/s11524-015-9989-5 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CY4AR UT WOS:000366351500008 PM 26438415 ER PT J AU Sheth, RA Patel, MS Koottappillil, B Shah, JA Oklu, R Mueller, P Vagefi, PA Ganguli, S AF Sheth, Rahul A. Patel, Madhukar S. Koottappillil, Brian Shah, Jigesh A. Oklu, Rahmi Mueller, Peter Vagefi, Parsia A. Ganguli, Suvranu TI Role of Locoregional Therapy and Predictors for Dropout in Patients with Hepatocellular Carcinoma Listed for Liver Transplantation SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ORGAN ALLOCATION POLICY; RADIOFREQUENCY ABLATION; TRANSARTERIAL CHEMOEMBOLIZATION; CIRRHOTIC-PATIENTS; BRIDGE THERAPY; WAITING-LIST; EFFICACY; CANDIDATES; PROGNOSIS AB Purpose: To identify factors associated with removal from the liver transplantation waitlist because of death, deterioration of condition, or exceeding Milan criteria in patients with hepatocellular carcinoma (HCC), with emphasis on the role of locoregional therapy (LRT), defined as percutaneous thermal ablation and drug-eluting embolic chemoembolization, as bridge therapy. Materials and Methods: All patients listed for liver transplant at a single institution with exception points for HCC during 2004-2012 were evaluated. The most common cause of cirrhosis was hepatitis C (68%; 121/177). Seventy-one percent (125/177) of patients underwent liver transplantation, and 83% (147/177) underwent at least 1 LRT procedure. Of the 52 patients who did not undergo liver transplantation, 31 (60%) of livers were removed because of progression of HCC. Results: The likelihood of transplant was higher for patients who received LRT (odds ratio [OR], 2.9; confidence interval [Cl], 2.2-7.2) and lower for patients with multifocal tumors (OR, 0.25; CI, 0.12-0.52) and with larger tumors (OR, 0.94; CI, 0.90- 0.98). Time on the waitlist (OR, 0.99; CI, 0.99-1.0) was not found to correlate with removal. LRT increased the likelihood of liver transplantation, specifically for patients with prolonged wait times. Patients who demonstrated complete response (CR) to LRT on the first follow-up imaging study were more likely to undergo liver transplantation. Conclusions: LRT increased the likelihood of a patient with HCC achieving liver transplant, particularly in patients facing prolonged waiting times. CR after LRT significantly increased the likelihood of liver transplantation. C1 [Sheth, Rahul A.; Koottappillil, Brian; Oklu, Rahmi; Mueller, Peter; Ganguli, Suvranu] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, Boston, MA 02114 USA. [Patel, Madhukar S.; Shah, Jigesh A.; Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Transplant Surg, Boston, MA 02114 USA. RP Sheth, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. EM rsheth@partners.org NR 20 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2015 VL 26 IS 12 BP 1761 EP 1768 DI 10.1016/j.jvir.2015.08.015 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CY2HX UT WOS:000366230500002 PM 26419427 ER PT J AU Oklu, R Haas, D Kaplan, RS Brinegar, KN Bassoff, N Harvey, HB Brink, JA Prabhakar, AM AF Oklu, Rahmi Haas, Derek Kaplan, Robert S. Brinegar, Katelyn N. Bassoff, Nicole Harvey, H. Benjamin Brink, James A. Prabhakar, Anand M. TI Time-Driven Activity-Based Costing in IR SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID HEALTH-CARE; IMPROVEMENT; STEP C1 [Oklu, Rahmi; Brinegar, Katelyn N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Intervent Radiol, Boston, MA USA. [Harvey, H. Benjamin; Brink, James A.; Prabhakar, Anand M.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Haas, Derek; Kaplan, Robert S.; Bassoff, Nicole] Harvard Univ, Sch Business, Boston, MA 02163 USA. [Oklu, Rahmi] Harvard Univ, Sch Med, Brigham & Womens Hosp, Biomat Innovat Res Ctr,Dept Med, Cambridge, MA 02138 USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, 55 Fruit St,GRB 290A, Boston, MA 02114 USA. EM roklu@mgh.harvard.edu NR 17 TC 1 Z9 1 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD DEC PY 2015 VL 26 IS 12 BP 1827 EP 1831 DI 10.1016/j.jvir.2015.07.007 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CY2HX UT WOS:000366230500012 PM 26596176 ER PT J AU Richardson, PG Jagannath, S Moreau, P Jakubowiak, AJ Raab, MS Facon, T Vij, R White, D Reece, DE Benboubker, L Zonder, J Tsao, LC Anderson, KC Bleickardt, E Singhal, AK Lonial, S AF Richardson, Paul G. Jagannath, Sundar Moreau, Philippe Jakubowiak, Andrzej J. Raab, Marc S. Facon, Thierry Vij, Ravi White, Darrell Reece, Donna E. Benboubker, Lotfi Zonder, Jeffrey Tsao, L. Claire Anderson, Kenneth C. Bleickardt, Eric Singhal, Anil K. Lonial, Sagar CA 1703 Study Investigators TI Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study SO LANCET HAEMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; MONOCLONAL-ANTIBODY; PLUS DEXAMETHASONE; MAINTENANCE THERAPY; SERUM-PROTEIN; ELECTROPHORESIS; INTERFERENCE; CYTOTOXICITY; MULTICENTER; DARATUMUMAB AB Background Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b-2 study, 82% of patients with relapsed multiple myeloma who were given elotuzumab plus lenalidomide and dexamethasone achieved an overall response. Here we report the final phase 2 results. Methods We did this randomised, multicentre, open-label, dose-escalation study (1703) at 17 hospitals in the USA, Canada, France, and Germany. Patients aged at least 18 years with confirmed, relapsed multiple myeloma, Eastern Cooperative Oncology Group performance status 0-2, and one to three previous therapies but no previous lenalidomide were eligible for phase 2. We randomly assigned patients (1:1) to either 10 mg/kg or 20 mg/kg intravenous elotuzumab plus oral lenalidomide (25 mg) and dexamethasone (40 mg). We stratified patients on the basis of the number of previous therapies (one versus two or three), and status of previous treatment with immunomodulatory drugs (yes or no), and used permuted block randomisation with a block size of four. Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred (elotuzumab was given on days 1, 8, 15, and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles; lenalidomide was given on days 1-21 and dexamethasone once per week). The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria. Primary analyses were done in the intentionto- treat population, and safety was analysed in all patients who received at least one dose of study drugs. This study is registered with ClinicalTrials. gov, number NCT00742560. Findings Between Jan 4, 2010, and Dec 21, 2010, we recruited and randomly assigned 73 patients to elotuzumab (36 to 10 mg/kg, 37 to 20 mg/kg). At data cutoff (Jan 16, 2014), 13 patients remained on treatment (six on 10 mg/kg, seven on 20 mg/kg). 61 (84%) patients achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg). The most common treatment-emergent adverse events of any grade were diarrhoea (48 [66%]), muscle spasms (45 [62%]), and fatigue (41 [56%]). 57 (78%) patients had grade 3-4 events, the most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). Three deaths occurred, none related to the study drugs. Interpretation Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only. Phase 3 trials are in progress. C1 [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Richardson, Paul G.; Jagannath, Sundar; Jakubowiak, Andrzej J.; Vij, Ravi; Zonder, Jeffrey; Anderson, Kenneth C.; Lonial, Sagar] Multiple Myeloma Res Consortium, Norwalk, CT USA. [Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA. [Moreau, Philippe] Univ Hosp, Nantes, France. [Jakubowiak, Andrzej J.] Univ Chicago, Chicago, IL 60637 USA. [Raab, Marc S.] Univ Klinikum Heidelberg, Heidelberg, Germany. [Facon, Thierry] Hop Claude Huriez, Lille, France. [Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA. [White, Darrell] Dalhousie Univ, Halifax, NS, Canada. [White, Darrell] QE Hlth Sci Ctr, Halifax, NS, Canada. [Reece, Donna E.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Benboubker, Lotfi] Hop Bretonneau, CHU Tours, Tours, France. [Zonder, Jeffrey] Karmanos Canc Inst, Detroit, MI USA. [Tsao, L. Claire; Singhal, Anil K.] AbbVie Biotherapeut, Redwood City, CA USA. [Bleickardt, Eric] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Lonial, Sagar] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; FU Bristol-Myers Squibb; AbbVie Biotherapeutics (Redwood City, CA, USA). FX This study was funded by Bristol-Myers Squibb in collaboration with AbbVie Biotherapeutics (Redwood City, CA, USA). We thank all the patients, their families, and the investigators who are participating in this study. Analysis production and validation were done by Pingping Xia and Qin Pan, respectively, at AbbVie Biotherapeutics. Medical writing support and editorial assistance was provided by Kate Rees and Carol Cooper, respectively, at Caudex (Oxford, UK) and funded by Bristol-Myers Squibb. The support was given under the direction of, and with input from, the authors at all stages. NR 40 TC 30 Z9 30 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2352-3026 J9 LANCET HAEMATOL JI Lancet Haematol. PD DEC PY 2015 VL 2 IS 12 BP E516 EP E527 DI 10.1016/S2352-3026(15)00197-0 PG 12 WC Hematology SC Hematology GA CX9OB UT WOS:000366033900010 PM 26686406 ER PT J AU Kyle, RA Steensma, DP Shampo, MA AF Kyle, Robert A. Steensma, David P. Shampo, Marc A. TI Friedrich August Johannes Loffler (Loeffler), German Bacteriologist SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Kyle, Robert A.; Shampo, Marc A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Steensma, David P.] Boston Med Sch, Boston, MA USA. RP Kyle, RA (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM Kyle.robert@mayo.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 2015 VL 90 IS 12 BP E135 EP E135 DI 10.1016/j.mayocp.2015.07.032 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CX9TC UT WOS:000366047500002 PM 26653308 ER PT J AU Mack, JW Chen, K Boscoe, FP Gesten, FC Roohan, PJ Schymura, MJ Schrag, D AF Mack, Jennifer W. Chen, Kun Boscoe, Francis P. Gesten, Foster C. Roohan, Patrick J. Schymura, Maria J. Schrag, Deborah TI High Intensity of End-of-Life Care Among Adolescent and Young Adult Cancer Patients in the New York State Medicaid Program SO MEDICAL CARE LA English DT Article DE cancer; end of life; Medicaid; adolescent; young adult; hospice ID PALLIATIVE CARE; TREATMENT PREFERENCES; ONCOLOGIST ALLIANCE; ETHNIC-DIFFERENCES; COLORECTAL-CANCER; HOSPICE CARE; QUALITY; HEALTH; AGGRESSIVENESS; ASSOCIATIONS AB Background:Little is known about the care that adolescent and young adult (AYA) cancer patients receive at the end of life (EOL).Objective:To evaluate use of intensive measures and hospice and location of death of AYA cancer patients insured by Medicaid in New York State.Design:Using linked patient-level data from the New York State Cancer Registry and state Medicaid program, we identified 705 Medicaid patients who were diagnosed with cancer between the ages of 15 and 29 in the years 2004-2011, who subsequently died, and who were continuously enrolled in Medicaid in the last 60 days of life. We evaluated use of intensive EOL measures (chemotherapy within 14 d of death; intensive care unit care, >1 emergency room visit, and hospitalizations in the last 30 d of life), hospice use, and location of death (inpatient hospice, long-term care facility, acute care facility, home with hospice, home without hospice).Results:75% of AYA Medicaid decedents used at least 1 aspect of intensive EOL care. 38% received chemotherapy in the last 2 weeks of life; 21% received intensive care unit care, 44% had >1 emergency room visit, and 64% were hospitalized in the last month of life. Only 23% used hospice. 65% of patients died in acute care settings, including the inpatient hospital or emergency room.Conclusions:Given the high rates of intensive measures and low utilization of hospice at the EOL among AYA Medicaid enrollees, opportunities to maximize the quality of EOL care in this high-risk group should be prioritized. C1 [Mack, Jennifer W.] Dept Pediat Oncol, Boston, MA USA. [Mack, Jennifer W.; Chen, Kun; Schrag, Deborah] Dana Farber Canc Inst, Div Populat Sci, Ctr Outcomes & Policy Res, Boston, MA 02215 USA. [Mack, Jennifer W.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Boscoe, Francis P.; Schymura, Maria J.] New York State Dept Hlth, State Canc Registry, Albany, NY 12201 USA. [Gesten, Foster C.; Roohan, Patrick J.] New York State Dept Hlth, Off Qual & Patient Safety, Albany, NY USA. [Schrag, Deborah] Dana Farber Canc Inst, Med Oncol, Boston, MA 02215 USA. RP Mack, JW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_mack@dfci.harvard.edu FU National Cancer Institute [R01CA131847]; Young Adult Program at the Dana-Farber Cancer Institute; Association of Schools of Public Health/Centers for Disease Control and Prevention [S3888] FX Supported by the National Cancer Institute (R01CA131847 to D.S.). Additional project support was obtained from the Young Adult Program at the Dana-Farber Cancer Institute (to J.W.M.) and the Association of Schools of Public Health/Centers for Disease Control and Prevention Cooperative Agreement S3888 (Augmenting New York Cancer Registry Data to Assess Breast and Colorectal Cancer Care to M.J.S.). NR 35 TC 1 Z9 1 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2015 VL 53 IS 12 BP 1018 EP 1026 DI 10.1097/MLR.0000000000000437 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CX3RI UT WOS:000365616400004 PM 26492211 ER PT J AU Mitra, M Clements, KM Zhang, JY Iezzoni, LI Smeltzer, SC Long-Bellil, LM AF Mitra, Monika Clements, Karen M. Zhang, Jianying Iezzoni, Lisa I. Smeltzer, Suzanne C. Long-Bellil, Linda M. TI Maternal Characteristics, Pregnancy Complications, and Adverse Birth Outcomes Among Women With Disabilities SO MEDICAL CARE LA English DT Article DE prenatal care; pregnancy complications; women with disabilities; birth outcomes; disability ID CHRONIC PHYSICAL-DISABILITIES; INTELLECTUAL DISABILITY; HEALTH-CARE; US WOMEN; EXPERIENCES; MOTHERS; RISK; PREVALENCE; STRESS; LABOR AB Objectives:The objective of this study is to describe the maternal characteristics, pregnancy complications, and birth outcomes among a representative sample of Rhode Island women with disabilities who recently gave birth.Methods:Data from the 2002-2011 Rhode Island Pregnancy Risk Assessment Monitoring System survey were analyzed.Results:Approximately 7% of women in Rhode Island reported a disability. Women with disabilities reported significant disparities in their health care utilization, health behaviors, and health status before and during pregnancy and during the postpartum period. Compared with nondisabled women, they were significantly more likely to report stressful life events and medical complications during their most recent pregnancy, were less likely to receive prenatal care in the first trimester, and more likely to have preterm births (13.4%; 95% CI, 11.6-15.6 compared with 8.9%; 95% CI, 8.5-9.3 for women without disabilities) and low-birth-weight babies (10.3%; 95% CI, 9.4-11.2 compared with 6.8%; 95% CI, 6.8-6.9). There was no difference in the rates of cesarean section between women with and without disabilities.Conclusions:These findings support the need for clinicians providing care to pregnant women with disabilities to be aware of the increased risk for medical problems during pregnancy and factors that increase the risk for poor infant outcomes. C1 [Mitra, Monika; Clements, Karen M.; Zhang, Jianying; Long-Bellil, Linda M.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Shrewsbury, MA 01545 USA. [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Smeltzer, Suzanne C.] Villanova Univ, Coll Nursing, Ctr Nursing Res, Villanova, PA 19085 USA. RP Mitra, M (reprint author), Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, 333 South St, Shrewsbury, MA 01545 USA. EM monika.mitra@umassmed.edu FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health & Human Development [R01HD074581] FX Supported by a grant from the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health & Human Development. Award number: R01HD074581. NR 38 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD DEC PY 2015 VL 53 IS 12 BP 1027 EP 1032 DI 10.1097/MLR.0000000000000427 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CX3RI UT WOS:000365616400005 PM 26492209 ER PT J AU Whittaker, SR Cowley, GS Wagner, S Luo, F Root, DE Garraway, LA AF Whittaker, Steven R. Cowley, Glenn S. Wagner, Steve Luo, Flora Root, David E. Garraway, Levi A. TI Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MAPK PATHWAY; BRAF(V600E) INHIBITION; ACQUIRED-RESISTANCE; FEEDBACK INHIBITION; MUTANT MELANOMA; CANCER-CELLS; BRAF; KINASE; ACTIVATION; DISCOVERY AB RAF and MEK inhibitors are effective in BRAF-mutant melanoma but not in BRAF-mutant colorectal cancer. To gain additional insights into this difference, we performed a genome-scale pooled shRNA enhancer screen in a BRAF-mutant, RAF inhibitor-resistant colorectal cancer cell line exposed to the selective RAF inhibitor PLX4720. We identified multiple genes along the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) signaling axis that, when suppressed, either genetically or pharmacologically, sensitized cells to the selective RAF inhibitor through sustained inhibition of MAPK signaling. Strikingly, CRAF was a key mediator of resistance that could be overcome by the use of pan-RAF inhibitors in combination with a MEK inhibitor. Furthermore, the combination of pan-RAF and MEK inhibitors displayed strong synergy in melanoma and colorectal cancer cell lines with RAS-activating events such as RTK activation, KRAS mutation, or NF1 loss-of-function mutations. Combinations of selective RAF inhibitors, such as PLX4720 or dabrafenib, with MEK inhibitors did not incur such profound synergy, suggesting that inhibition of CRAF by pan-RAF inhibitors plays a key role in determining cellular response. Importantly, in contrast to the modest activity seen with single-agent treatment, dual pan-RAF and MEK inhibition results in the induction of apoptosis, greatly enhancing efficacy. Notably, combined pan-RAF and MEK inhibition can overcome intrinsic and acquired resistance to single-agent RAF/MEK inhibition, supporting dual pan-RAF and MEK inhibition as a novel therapeutic strategy for BRAF- and KRAS-mutant cancers. (C)2015 AACR. C1 [Whittaker, Steven R.; Luo, Flora; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Whittaker, Steven R.; Cowley, Glenn S.; Luo, Flora; Root, David E.; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. [Whittaker, Steven R.; Wagner, Steve] Inst Canc Res, Div Canc Therapeut, London SW3 6JB, England. [Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Garraway, Levi A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,D1542, Boston, MA 02215 USA. EM levi_garraway@dfci.harvard.edu FU National Cancer Institute [5P50CA127003-05]; STARR Cancer Consortium [I4-A448]; NIH New Innovator Award [DP2OD002750]; Melanoma Research Alliance FX This study was supported by grants to L.A. Garraway from the National Cancer Institute (5P50CA127003-05) STARR Cancer Consortium (I4-A448), the NIH New Innovator Award (DP2OD002750), and the Melanoma Research Alliance. NR 54 TC 9 Z9 10 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2015 VL 14 IS 12 BP 2700 EP 2711 DI 10.1158/1535-7163.MCT-15-0136-T PG 12 WC Oncology SC Oncology GA CX9VZ UT WOS:000366055100003 PM 26351322 ER PT J AU Parrish, KE Cen, L Murray, J Calligaris, D Kizilbash, S Mittapalli, RK Carlson, BL Schroeder, MA Sludden, J Boddy, AV Agar, NYR Curtin, NJ Elmquist, WF Sarkaria, JN AF Parrish, Karen E. Cen, Ling Murray, James Calligaris, David Kizilbash, Sani Mittapalli, Rajendar K. Carlson, Brett L. Schroeder, Mark A. Sludden, Julieann Boddy, Alan V. Agar, Nathalie Y. R. Curtin, Nicola J. Elmquist, William F. Sarkaria, Jann N. TI Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; BLOOD-BRAIN-BARRIER; RESISTANCE PROTEIN ABCG2; P-GLYCOPROTEIN ABCB1; BREAST-CANCER; TEMOZOLOMIDE RESISTANCE; METASTATIC MELANOMA; ACTIVE EFFLUX; TUMOR BARRIER; SOLID TUMORS AB PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patientderived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts. In contrast, the addition of rucaparib had no impact on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin-Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1, cell accumulation studies demonstrated that rucaparib is transported by both transporters. Consistent with the influence of these efflux pumps on central nervous system drug distribution, Mdr1a/b(-/-) Bcrp1(-/-) knockout mice had a significantly higher brain to plasma ratio for rucaparib (1.61 +/- 0.25) than wild-type mice (0.11 +/- 0.08). A pharmacokinetic and pharmacodynamic evaluation after a single dose confirmed limited accumulation of rucaparib in the brain is associated with substantial residual PARP enzymatic activity. Similarly, matrix-assisted laser desorption/ionization mass spectrometric imaging demonstrated significantly enhanced accumulation of drug in flank tumor compared with normal brain or orthotopic tumors. Collectively, these results suggest that limited drug delivery into brain tumors may significantly limit the efficacy of rucaparib combined with temozolomide in GBM. (C)2015 AACR. C1 [Parrish, Karen E.; Mittapalli, Rajendar K.; Elmquist, William F.; Sarkaria, Jann N.] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. [Cen, Ling; Carlson, Brett L.; Schroeder, Mark A.] Mayo Clin, Dept Radiat Oncol, Rochester, MN 55905 USA. [Murray, James; Sludden, Julieann; Boddy, Alan V.; Curtin, Nicola J.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Calligaris, David; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dept Neurosurg, Brigham & Womens Hosp, Boston, MA USA. [Kizilbash, Sani] Mayo Clin, Dept Med Oncol, Rochester, MN 55905 USA. [Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Sarkaria, JN (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM sarkaria.jann@mayo.edu OI Boddy, Alan/0000-0002-8920-9286 FU Mayo Foundation; NIH [CA141121, CA127716, CA138437, NS077921]; Brain Tumor Funders Consortium; National Institute of Health [1DP2OD007383-01]; Dana-Farber PLGA Foundation; Daniel E. Ponton fund for the Neurosciences; American Foundation for Pharmaceutical Education FX This work was supported in part by grants to J.N. Sarkaria from the Mayo Foundation, the NIH (CA141121 and CA127716) and the Brain Tumor Funders Consortium. This work was also supported in part by grants to W.F. Elmquist from the NIH (CA138437) and to both J.N. Sarkaria and W.F. Elmquist from the NIH (NS077921). N.Y.R. Agar was funded by the National Institute of Health Director's New Innovator Award (1DP2OD007383-01), Dana-Farber PLGA Foundation, and Daniel E. Ponton fund for the Neurosciences. K.E. Parrish was supported by the Ronald J. Sawchuk, Edward G. Rippie and American Foundation for Pharmaceutical Education Pre-Doctoral Fellowships. NR 50 TC 3 Z9 3 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2015 VL 14 IS 12 BP 2735 EP 2743 DI 10.1158/1535-7163.MCT-15-0553 PG 9 WC Oncology SC Oncology GA CX9VZ UT WOS:000366055100006 PM 26438157 ER PT J AU DiCarlo, JE Chavez, A Dietz, SL Esvelt, KM Church, GM AF DiCarlo, James E. Chavez, Alejandro Dietz, Sven L. Esvelt, Kevin M. Church, George M. TI Safeguarding CRISPR-Cas9 gene drives in yeast SO NATURE BIOTECHNOLOGY LA English DT Article ID DROSOPHILA; SYSTEM; CAS9; DNA; GENERATION; MUTATIONS; GERMLINE; REPAIR; TOOLS AB RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the prospect of unanticipated ecological change, demands caution. We report the efficacy of CRISPR-Cas9 gene drive systems in wild and laboratory strains of the yeast Saccharomyces cerevisiae. Furthermore, we address concerns surrounding accidental genome editing by developing and validating methods of molecular confinement that minimize the risk of unwanted genome editing. We also present a drive system capable of overwriting the changes introduced by an earlier gene drive. These molecular safeguards should enable the development of safe CRISPR gene drives for diverse organisms. C1 [DiCarlo, James E.; Chavez, Alejandro; Dietz, Sven L.; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [DiCarlo, James E.; Chavez, Alejandro; Dietz, Sven L.; Esvelt, Kevin M.; Church, George M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [DiCarlo, James E.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Chavez, Alejandro; Dietz, Sven L.; Esvelt, Kevin M.; Church, George M.] Wyss Inst Biol Inspired Engn, Boston, MA USA. [Chavez, Alejandro] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dietz, Sven L.] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland. RP Esvelt, KM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM kevin.esvelt@wyss.harvard.edu; gmc@harvard.edu OI Esvelt, Kevin/0000-0001-8797-3945 FU Department of Energy (DOE) [DE-FG02-02ER63445]; National Science Foundation (NSF) [SynBERC SA5283-11210, MCB-1330914]; National Cancer Institute (NCI) [5T32CA009216-34]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [1K99DK102669-01]; Wyss Institute for Biologically Inspired Engineering (Technology Development Fellowship) FX We are very grateful to S. Doris, D. Spatt and F. Winston for their incredible patience, generosity and expertise in tetrad dissection. We also thank F. Winston for providing us with SK1 strains and members of the Church laboratory for insightful discussions. This work was supported by grants from the Department of Energy (DOE) (DE-FG02-02ER63445 to G.M.C.), National Science Foundation (NSF) (SynBERC SA5283-11210 and MCB-1330914 to G.M.C.), National Cancer Institute (NCI) (5T32CA009216-34 to A.C.), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (1K99DK102669-01 to K.M.E.) and the Wyss Institute for Biologically Inspired Engineering (Technology Development Fellowship to K.M.E.). NR 31 TC 19 Z9 21 U1 32 U2 92 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2015 VL 33 IS 12 BP 1250 EP + DI 10.1038/nbt.3412 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CY4OO UT WOS:000366387700016 PM 26571100 ER PT J AU Kleinstiver, BP Prew, MS Tsai, SQ Nguyen, NT Topkar, VV Zheng, ZL Joung, JK AF Kleinstiver, Benjamin P. Prew, Michelle S. Tsai, Shengdar Q. Nguyen, Nhu T. Topkar, Ved V. Zheng, Zongli Joung, J. Keith TI Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition SO NATURE BIOTECHNOLOGY LA English DT Article ID CAS SYSTEMS; STREPTOCOCCUS-THERMOPHILUS; CRYSTAL-STRUCTURE; GUIDE RNA; DUAL-RNA; DNA; ENDONUCLEASE; NUCLEASES; MUTAGENESIS; DIVERSITY AB CRISPR-Cas9 nucleases target specific DNA sequences using a guide RNA but also require recognition of a protospacer adjacent motif (PAM) by the Cas9 protein. Although longer PAMs can potentially improve the specificity of genome editing, they limit the range of sequences that Cas9 orthologs can target. One potential strategy to relieve this restriction is to relax the PAM recognition specificity of Cas9. Here we used molecular evolution to modify the NNGRRT PAM of Staphylococcus aureus Cas9 (SaCas9). One variant we identified, referred to as KKH SaCas9, showed robust genome editing activities at endogenous human target sites with NNNRRT PAMs, thereby increasing SaCas9 targeting range by two-to fourfold. Using GUIDE-seq, we show that wild-type and KKH SaCas9 induce comparable numbers of off-target effects in human cells. Our strategy for evolving PAM specificity does not require structural information and therefore should be applicable to a wide range of Cas9 orthologs. C1 [Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Topkar, Ved V.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Topkar, Ved V.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Topkar, Ved V.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Kleinstiver, Benjamin P.; Tsai, Shengdar Q.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zheng, Zongli] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Hong Kong, Peoples R China. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM bkleinstiver@mgh.harvard.edu; jjoung@mgh.harvard.edu RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 FU US National Institutes of Health (NIH) [DP1 GM105378]; NIH [R01 GM107427]; Jim and Ann Orr Research Scholar Award; Natural Sciences and Engineering Research Council of Canada FX We thank D. Edgell (University of Western Ontario) for providing the bacterial strain and precursor plasmids related to the bacterial selections, T. Cathomen (Freiburg) for providing the U2OS cells, and J. Angstman for comments on the manuscript. This work was supported by a US National Institutes of Health (NIH) Director's Pioneer Award (DP1 GM105378) and NIH R01 GM107427 to J.K.J., the Jim and Ann Orr Research Scholar Award (to J.K.J.), and a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship (to B.P.K.). New reagents described in this work will be deposited with the nonprofit plasmid distribution service Addgene (http://www.addgene.org/crispr-cas). NR 33 TC 56 Z9 59 U1 20 U2 49 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD DEC PY 2015 VL 33 IS 12 BP 1293 EP + DI 10.1038/nbt.3404 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CY4OO UT WOS:000366387700022 PM 26524662 ER PT J AU Loh, PR Bhatia, G Gusev, A Finucane, HK Bulik-Sullivan, BK Pollack, SJ de Candia, TR Lee, SH Wray, NR Kendler, KS O'Donovan, MC Neale, BM Patterson, N Price, AL AF Loh, Po-Ru Bhatia, Gaurav Gusev, Alexander Finucane, Hilary K. Bulik-Sullivan, Brendan K. Pollack, Samuela J. de Candia, Teresa R. Lee, Sang Hong Wray, Naomi R. Kendler, Kenneth S. O'Donovan, Michael C. Neale, Benjamin M. Patterson, Nick Price, Alkes L. CA Psychiat Genomics Consortium TI Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; PARTITIONING HERITABILITY; COMMON SNPS; HUMAN HEIGHT; RISK LOCI; SUSCEPTIBILITY; METAANALYSIS; INFERENCE; TRAITS; INFORMATION AB Heritability analyses of genome-wide association study (GWAS) cohorts have yielded important insights into complex disease architecture, and increasing sample sizes hold the promise of further discoveries. Here we analyze the genetic architectures of schizophrenia in 49,806 samples from the PGC and nine complex diseases in 54,734 samples from the GERA cohort. For schizophrenia, we infer an overwhelmingly polygenic disease architecture in which >= 71% of 1-Mb genomic regions harbor >= 1 variant influencing schizophrenia risk. We also observe significant enrichment of heritability in GC-rich regions and in higher-frequency SNPs for both schizophrenia and GERA diseases. In bivariate analyses, we observe significant genetic correlations (ranging from 0.18 to 0.85) for several pairs of GERA diseases; genetic correlations were on average 1.3 tunes stronger than the correlations of overall disease liabilities. To accomplish these analyses, we developed a fast algorithm for multicomponent, multi-trait variance-components analysis that overcomes prior computational barriers that made such analyses intractable at this scale. C1 [Loh, Po-Ru; Bhatia, Gaurav; Gusev, Alexander; Pollack, Samuela J.; Price, Alkes L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02163 USA. [Loh, Po-Ru; Bhatia, Gaurav; Gusev, Alexander; Bulik-Sullivan, Brendan K.; Pollack, Samuela J.; Neale, Benjamin M.; Patterson, Nick; Price, Alkes L.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Finucane, Hilary K.] MIT, Dept Math, Cambridge, MA 02139 USA. [Bulik-Sullivan, Brendan K.; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Pollack, Samuela J.; Price, Alkes L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [de Candia, Teresa R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Lee, Sang Hong; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Lee, Sang Hong] Univ New England, Sch Environm & Rural Sci, Armidale, NSW, Australia. [Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat & Human Genet, Richmond, VA USA. [O'Donovan, Michael C.] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Ctr Neuropsychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales. RP Loh, PR (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02163 USA. EM loh@hsph.harvard.edu; aprice@hsph.harvard.edu RI Hansen, Thomas Folkmann/O-5965-2014; Hammer, Christian/C-5827-2014; Pantelis, Christos/H-7722-2014; Melle, Ingrid /B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lee, Sang Hong/A-2569-2011; Webb, Bradley/B-1459-2009; Wray, Naomi/C-8639-2015; OI O'Neill, Francis Anthony/0000-0002-7531-7657; Adolfsson, Rolf/0000-0001-9785-8473; Nothen, Markus/0000-0002-8770-2464; Domenici, Enrico/0000-0001-7436-6919; Visscher, Peter/0000-0002-2143-8760; Knight, Joanne/0000-0002-7148-1660; Hansen, Thomas Folkmann/0000-0001-6703-7762; Hammer, Christian/0000-0003-4548-7548; Walters, James/0000-0002-6980-4053; Pantelis, Christos/0000-0002-9565-0238; Melle, Ingrid /0000-0002-9783-548X; Ruderfer, Douglas/0000-0002-2365-386X; Lee, Sang Hong/0000-0001-9701-2718; Webb, Bradley/0000-0002-0576-5366; Wray, Naomi/0000-0001-7421-3357; Gusev, Alexander/0000-0002-7980-4620; Bruggeman, Richard/0000-0002-3238-8471 FU US National Institutes of Health [R01 HG006399, R01 MH101244]; US National Institutes of Health fellowship [F32 HG007805]; Fannie and John Hertz Foundation; Netherlands Scientific Organization [NWO 480-05-003]; US National Center for Research Resources [1S10RR028832-01] FX We are grateful to K. Galinsky, T. Hayeck, P. Palamara, J. Listgarten, V. Anttila, S. Sunyaev, D. Howrigan, R. Walters, P. Sullivan, M. Keller, M. Goddard, P. Visscher, J. Yang, S. Ripke, D. Golan and S. Rosset for helpful discussions. This research was supported by US National Institutes of Health grants R01 HG006399 and R01 MH101244 and US National Institutes of Health fellowship F32 HG007805. H.K.F. was supported by the Fannie and John Hertz Foundation. Members of the Schizophrenia Working Group of the Psychiatric Genomics Consortium are listed in the Supplementary Note. Statistical analyses of PGC2 data were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org/) hosted by SURFsara and financially supported by the Netherlands Scientific Organization (NWO 480-05-003, principal investigator D. Posthuma) along with a supplement from the Dutch Brain Foundation and VU University Amsterdam. Analyses of GERA data were conducted on the Orchestra High-Performance Compute Cluster at Harvard Medical School, which is partially supported by US National Center for Research Resources grant 1S10RR028832-01. NR 64 TC 22 Z9 23 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2015 VL 47 IS 12 BP 1385 EP + DI 10.1038/ng.3431 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CX6LT UT WOS:000365813200007 PM 26523775 ER PT J AU Valentijn, LJ Koster, J Zwijnenburg, DA Hasselt, NE van Sluis, P Volckmann, R van Noesel, MM George, RE Tytgat, GAM Molenaar, JJ Versteeg, R AF Valentijn, Linda J. Koster, Jan Zwijnenburg, Danny A. Hasselt, Nancy E. van Sluis, Peter Volckmann, Richard van Noesel, Max M. George, Rani E. Tytgat, Godelieve A. M. Molenaar, Jan J. Versteeg, Rogier TI TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors SO NATURE GENETICS LA English DT Article ID PROMOTER MUTATIONS; HTERT GENE; TRANSCRIPTION; LANDSCAPE; MELANOMA; CANCER AB Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up-and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis. C1 [Valentijn, Linda J.; Koster, Jan; Zwijnenburg, Danny A.; Hasselt, Nancy E.; van Sluis, Peter; Volckmann, Richard; Molenaar, Jan J.; Versteeg, Rogier] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands. [van Noesel, Max M.; Tytgat, Godelieve A. M.] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands. [George, Rani E.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. [George, Rani E.] Boston Childrens Hosp, Boston, MA USA. [George, Rani E.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Tytgat, Godelieve A. M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat Oncol, NL-1105 AZ Amsterdam, Netherlands. RP Versteeg, R (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Oncogen, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM r.versteeg@amc.uva.nl FU Villa Joep Foundation; Children Cancer-Free Foundation; KWF/Netherlands Cancer Foundation; European Union European Research Council (ERC) Advanced grant FX This study was supported by grants from the Villa Joep Foundation, the Children Cancer-Free Foundation (KIKA) and the KWF/Netherlands Cancer Foundation and by a European Union European Research Council (ERC) Advanced grant to R. Versteeg. NR 16 TC 18 Z9 18 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2015 VL 47 IS 12 BP 1411 EP + DI 10.1038/ng.3438 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA CX6LT UT WOS:000365813200012 PM 26523776 ER PT J AU Gaulton, KJ Ferreira, T Lee, Y Raimondo, A Maegi, R Reschen, ME Mahajan, A Locke, A Rayner, NW Robertson, N Scott, RA Prokopenko, I Scott, LJ Green, T Sparso, T Thuillier, D Yengo, L Grallert, H Wahl, S Franberg, M Strawbridge, RJ Kestler, H Chheda, H Eisele, L Gustafsson, S Steinthorsdottir, V Thorleifsson, G Qi, L Karssen, LC van Leeuwen, EM Willems, SM Li, M Chen, H Fuchsberger, C Kwan, P Ma, C Linderman, M Lu, YC Thomsen, SK Rundle, JK Beer, NL van de Bunt, M Chalisey, A Kang, HM Voight, BF Abecasis, GR Almgren, P Baldassarre, D Balkau, B Benediktsson, R Bluher, M Boeing, H Bonnycastle, LL Bottinger, EP Burtt, NP Carey, J Charpentier, G Chines, PS Cornelis, MC Couper, DJ Crenshaw, AT van Dam, RM Doney, ASF Dorkhan, M Edkins, S Eriksson, JG Esko, T Eury, E Fadista, J Flannick, J Fontanillas, P Fox, C Franks, PW Gertow, K Gieger, C Gigante, B Gottesman, O Grant, GB Grarup, N Groves, CJ Hassinen, M Have, CT Herder, C Holmen, OL Hreidarsson, AB Humphries, SE Hunter, DJ Jackson, AU Jonsson, A Jorgensen, ME Jorgensen, T Kao, WHL Kerrison, ND Kinnunen, L Klopp, N Kong, A Kovacs, P Kraft, P Kravic, J Langford, C Leander, K Liang, L Lichtner, P Lindgren, CM Lindholm, E Linneberg, A Liu, CT Lobbens, S Luan, J Lyssenko, V Mannisto, S McLeod, O Meyer, J Mihailov, E Mirza, G Muhleisen, TW Muller-Nurasyid, M Navarro, C Nothen, MM Oskolkov, NN Owen, KR Palli, D Pechlivanis, S Peltonen, L Perry, JRB Platou, CGP Roden, M Ruderfer, D Rybin, D van der Schouw, YT Sennblad, B Sigurdsson, G Stancakova, A Steinbach, G Storm, P Strauch, K Stringham, HM Sun, Q Thorand, B Tikkanen, E Tonjes, A Trakalo, J Tremoli, E Tuomi, T Wennauer, R Wiltshire, S Wood, AR Zeggini, E Dunham, I Birney, E Pasquali, L Ferrer, J Loos, RJF Dupuis, J Florez, JC Boerwinkle, E Pankow, JS van Duijn, C Sijbrands, E Meigs, JB Hu, FB Thorsteinsdottir, U Stefansson, K Lakka, TA Rauramaa, R Stumvoll, M Pedersen, NL Lind, L Keinanen-Kiukaanniemi, SM Korpi-Hyovalti, E Saaristo, TE Saltevo, J Kuusisto, J Laakso, M Metspalu, A Erbel, R Jocke, KH Moebus, S Ripatti, S Salomaa, V Ingelsson, E Boehm, BO Bergman, RN Collins, FS Mohlke, KL Koistinen, H Tuomilehto, J Hveem, K Njolstad, I Deloukas, P Donnelly, PJ Frayling, TM Hattersley, AT de Faire, U Hamsten, A Illig, T Peters, A Cauchi, S Sladek, R Froguel, P Hansen, T Pedersen, O Morris, AD Palmer, CNA Kathiresan, S Melander, O Nilsson, PM Groop, LC Barroso, I Langenberg, C Wareham, NJ O'Callaghan, CA Gloyn, AL Altshuler, D Boehnke, M Teslovich, TM McCarthy, MI Morris, AP AF Gaulton, Kyle J. Ferreira, Teresa Lee, Yeji Raimondo, Anne Maegi, Reedik Reschen, Michael E. Mahajan, Anubha Locke, Adam Rayner, N. William Robertson, Neil Scott, Robert A. Prokopenko, Inga Scott, Laura J. Green, Todd Sparso, Thomas Thuillier, Dorothee Yengo, Loic Grallert, Harald Wahl, Simone Franberg, Mattias Strawbridge, Rona J. Kestler, Hans Chheda, Himanshu Eisele, Lewin Gustafsson, Stefan Steinthorsdottir, Valgerdur Thorleifsson, Gudmar Qi, Lu Karssen, Lennart C. van Leeuwen, Elisabeth M. Willems, Sara M. Li, Man Chen, Han Fuchsberger, Christian Kwan, Phoenix Ma, Clement Linderman, Michael Lu, Yingchang Thomsen, Soren K. Rundle, Jana K. Beer, Nicola L. van de Bunt, Martijn Chalisey, Anil Kang, Hyun Min Voight, Benjamin F. Abecasis, Goncalo R. Almgren, Peter Baldassarre, Damiano Balkau, Beverley Benediktsson, Rafn Blueher, Matthias Boeing, Heiner Bonnycastle, Lori L. Bottinger, Erwin P. Burtt, Noel P. Carey, Jason Charpentier, Guillaume Chines, Peter S. Cornelis, Marilyn C. Couper, David J. Crenshaw, Andrew T. van Dam, Rob M. Doney, Alex S. F. Dorkhan, Mozhgan Edkins, Sarah Eriksson, Johan G. Esko, Tonu Eury, Elodie Fadista, Joao Flannick, Jason Fontanillas, Pierre Fox, Caroline Franks, Paul W. Gertow, Karl Gieger, Christian Gigante, Bruna Gottesman, Omri Grant, George B. Grarup, Niels Groves, Christopher J. Hassinen, Maija Have, Christian T. Herder, Christian Holmen, Oddgeir L. Hreidarsson, Astradur B. Humphries, Steve E. Hunter, David J. Jackson, Anne U. Jonsson, Anna Jorgensen, Marit E. Jorgensen, Torben Kao, Wen-Hong L. Kerrison, Nicola D. Kinnunen, Leena Klopp, Norman Kong, Augustine Kovacs, Peter Kraft, Peter Kravic, Jasmina Langford, Cordelia Leander, Karin Liang, Liming Lichtner, Peter Lindgren, Cecilia M. Lindholm, Eero Linneberg, Allan Liu, Ching-Ti Lobbens, Stephane Luan, Jian'an Lyssenko, Valeriya Mannisto, Satu McLeod, Olga Meyer, Julia Mihailov, Evelin Mirza, Ghazala Muehleisen, Thomas W. Mueller-Nurasyid, Martina Navarro, Carmen Noethen, Markus M. Oskolkov, Nikolay N. Owen, Katharine R. Palli, Domenico Pechlivanis, Sonali Peltonen, Leena Perry, John R. B. Platou, Carl G. P. Roden, Michael Ruderfer, Douglas Rybin, Denis van der Schouw, Yvonne T. Sennblad, Bengt Sigurdsson, Gunnar Stancakova, Alena Steinbach, Gerald Storm, Petter Strauch, Konstantin Stringham, Heather M. Sun, Qi Thorand, Barbara Tikkanen, Emmi Tonjes, Anke Trakalo, Joseph Tremoli, Elena Tuomi, Tiinamaija Wennauer, Roman Wiltshire, Steven Wood, Andrew R. Zeggini, Eleftheria Dunham, Ian Birney, Ewan Pasquali, Lorenzo Ferrer, Jorge Loos, Ruth J. F. Dupuis, Josee Florez, Jose C. Boerwinkle, Eric Pankow, James S. van Duijn, Cornelia Sijbrands, Eric Meigs, James B. Hu, Frank B. Thorsteinsdottir, Unnur Stefansson, Kari Lakka, Timo A. Rauramaa, Rainer Stumvoll, Michael Pedersen, Nancy L. Lind, Lars Keinanen-Kiukaanniemi, Sirkka M. Korpi-Hyovalti, Eeva Saaristo, Timo E. Saltevo, Juha Kuusisto, Johanna Laakso, Markku Metspalu, Andres Erbel, Raimund Joecke, Karl-Heinz Moebus, Susanne Ripatti, Samuli Salomaa, Veikko Ingelsson, Erik Boehm, Bernhard O. Bergman, Richard N. Collins, Francis S. Mohlke, Karen L. Koistinen, Heikki Tuomilehto, Jaakko Hveem, Kristian Njolstad, Inger Deloukas, Panagiotis Donnelly, Peter J. Frayling, Timothy M. Hattersley, Andrew T. de Faire, Ulf Hamsten, Anders Illig, Thomas Peters, Annette Cauchi, Stephane Sladek, Rob Froguel, Philippe Hansen, Torben Pedersen, Oluf Morris, Andrew D. Palmer, Collin N. A. Kathiresan, Sekar Melander, Olle Nilsson, Peter M. Groop, Leif C. Barroso, Ines Langenberg, Claudia Wareham, Nicholas J. O'Callaghan, Christopher A. Gloyn, Anna L. Altshuler, David Boehnke, Michael Teslovich, Tanya M. McCarthy, Mark I. Morris, Andrew P. CA DIAbet Genetics Replication Meta-A TI Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci SO NATURE GENETICS LA English DT Article ID LARGE-SCALE ASSOCIATION; HUMAN PANCREATIC-ISLETS; WIDE ASSOCIATION; BETA-CELL; TRANSCRIPTION FACTORS; GLUCOSE-HOMEOSTASIS; GENOTYPE IMPUTATION; INSULIN-SECRETION; COMMON VARIANTS; GLYCEMIC TRAITS AB We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease. C1 [Gaulton, Kyle J.; Ferreira, Teresa; Mahajan, Anubha; Rayner, N. William; Robertson, Neil; Beer, Nicola L.; van de Bunt, Martijn; Lindgren, Cecilia M.; Steinbach, Gerald; Trakalo, Joseph; Wiltshire, Steven; Ingelsson, Erik; Donnelly, Peter J.; Gloyn, Anna L.; McCarthy, Mark I.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Gaulton, Kyle J.; Tikkanen, Emmi; Ripatti, Samuli] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Lee, Yeji; Locke, Adam; Scott, Laura J.; Fuchsberger, Christian; Kwan, Phoenix; Ma, Clement; Kang, Hyun Min; Abecasis, Goncalo R.; Jackson, Anne U.; Stringham, Heather M.; Tuomi, Tiinamaija; Boehnke, Michael; Teslovich, Tanya M.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Raimondo, Anne; Rayner, N. William; Robertson, Neil; Thomsen, Soren K.; Rundle, Jana K.; Beer, Nicola L.; van de Bunt, Martijn; Groves, Christopher J.; Owen, Katharine R.; Tuomi, Tiinamaija; Collins, Francis S.; Gloyn, Anna L.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Maegi, Reedik; Esko, Tonu; Mihailov, Evelin; Wennauer, Roman; Sijbrands, Eric; Metspalu, Andres; Koistinen, Heikki; Morris, Andrew P.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Reschen, Michael E.; Chalisey, Anil; Wood, Andrew R.; Frayling, Timothy M.; O'Callaghan, Christopher A.] Univ Oxford, Nuffield Dept Med, Ctr Cellular & Mol Physiol, Oxford, England. [Rayner, N. William; Edkins, Sarah; Langford, Cordelia; Peltonen, Leena; Zeggini, Eleftheria; Dunham, Ian; Birney, Ewan; Ripatti, Samuli; Deloukas, Panagiotis; Barroso, Ines] Wellcome Trust Sanger Inst, Hinxton, England. [Scott, Robert A.; Willems, Sara M.; Kerrison, Nicola D.; Luan, Jian'an; Perry, John R. B.; Pasquali, Lorenzo; Loos, Ruth J. F.; Langenberg, Claudia; Wareham, Nicholas J.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England. 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[Pasquali, Lorenzo] Germans Trias & Pujol Univ Hosp & Res Inst, Div Endocrinol, Badalona, Spain. [Pasquali, Lorenzo] Josep Carreras Leukaemia Res Inst, Badalona, Spain. [Pasquali, Lorenzo] CIBERDEM, Barcelona, Spain. [Ferrer, Jorge] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Ferrer, Jorge] Inst Invest Biomed August Pi & Sunyer, Ctr Esther Koplowitz, Barcelona, Spain. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.; Kathiresan, Sekar; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.; Altshuler, David] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [van Duijn, Cornelia] Netherlands Consortium Hlth Ageing, Netherlands Genom Initiat, Rotterdam, Netherlands. [van Duijn, Cornelia] Ctr Med Syst Biol, Rotterdam, Netherlands. [Meigs, James B.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Lakka, Timo A.; Joecke, Karl-Heinz] Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland. [Lakka, Timo A.; Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Lind, Lars] Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden. [Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland. [Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland. [Korpi-Hyovalti, Eeva] South Ostrobothnia Cent Hosp, Seinajoki, Finland. [Saaristo, Timo E.] Finnish Diabet Assoc, Tampere, Finland. [Saaristo, Timo E.] Pirkanmaa Dist Hosp, Tampere, Finland. [Saltevo, Juha] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland. [Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Erbel, Raimund] Univ Duisdurg Essen, Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, Essen, Germany. [Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Boehm, Bernhard O.] Univ Med Ctr Ulm, Dept Internal Med, Div Endocrinol & Diabet, Ulm, Germany. [Boehm, Bernhard O.] Univ London Imperial Coll Sci Technol & Med, Lee Kong Chian Sch Med, London SW7 2AZ, England. [Boehm, Bernhard O.] Nanyang Technol Univ, Singapore 639798, Singapore. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Koistinen, Heikki] Univ Helsinki, Cent Hosp, Dept Med, Div Endocrinol, Helsinki, Finland. [Koistinen, Heikki] Minerva Fdn, Helsinki, Finland. [Tuomilehto, Jaakko] Hosp Univ La Paz, Inst Invest Sanitaria, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia. [Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Deloukas, Panagiotis] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Donnelly, Peter J.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Hattersley, Andrew T.] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England. [Sladek, Rob] Ctr Hosp Univ Montreal, Ctr Rech, Montreal Diabet Res Ctr, Montreal, PQ, Canada. [Sladek, Rob] McGill Univ, Montreal, PQ, Canada. [Sladek, Rob] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Morris, Andrew D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Cambridge, England. [Barroso, Ines] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Morris, Andrew P.] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool L69 3BX, Merseyside, England. RP Gaulton, KJ (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM kgaulton@gmail.com; mark.mccarthy@drl.ox.ac.uk; apmorris@liverpool.ac.uk RI Leander, Karin/C-7261-2017; Yengo, Loic/D-2692-2017; Johnson, Andrew/G-6520-2013; Ferrer, Jorge/A-3176-2012; Deloukas, Panos/B-2922-2013; Thorand, Barbara/B-5349-2014; Peters, Annette/A-6117-2011; Grallert, Harald/B-3424-2013; Veglia, Fabrizio/K-1958-2016; kinnunen, leena/B-7059-2012; Palmer, Colin/C-7053-2008; Study, GoDARTS/K-9448-2016; Grarup, Niels/K-2807-2015; van der Schouw, Yvonne/F-8327-2014; Ruderfer, Douglas/M-5795-2016 OI Nothen, Markus/0000-0002-8770-2464; Chen, Han/0000-0002-9510-4923; Tuomi, Tiinamaija/0000-0002-8306-6202; Have, Christian Theil/0000-0002-8634-4781; Jorgensen, Torben/0000-0001-9453-2830; Eriksson, Johan/0000-0002-2516-2060; Pankow, James/0000-0001-7076-483X; Karssen, Lennart C./0000-0002-1959-342X; Hattersley, Andrew/0000-0001-5620-473X; Linneberg, Allan/0000-0002-0994-0184; Peters, Annette/0000-0001-6645-0985; Gieger, Christian/0000-0001-6986-9554; PALLI, Domenico/0000-0002-5558-2437; van de Bunt, Martijn/0000-0002-6744-6125; Mannisto, Satu/0000-0002-8668-3046; Lakka, Timo/0000-0002-9199-2871; Gigante, Bruna/0000-0003-4508-7990; Koistinen, Heikki/0000-0001-7870-070X; Dunham, Ian/0000-0003-2525-5598; Birney, Ewan/0000-0001-8314-8497; Thomsen, Soren Krogsgaard/0000-0001-8894-2868; Forouhi, Nita/0000-0002-5041-248X; Leander, Karin/0000-0002-1404-9222; Yengo, Loic/0000-0002-4272-9305; Pasquali, Lorenzo/0000-0003-2423-1826; Rybin, Denis/0000-0002-3657-4829; Gaulton, Kyle/0000-0003-1318-7161; Sijbrands, Eric/0000-0001-8857-7389; TREMOLI, ELENA/0000-0002-0929-6106; Magi, Reedik/0000-0002-2964-6011; Fuchsberger, Christian/0000-0002-5918-8947; Humphries, Stephen E/0000-0002-8221-6547; Locke, Adam/0000-0001-6227-198X; Deloukas, Panos/0000-0001-9251-070X; Thorand, Barbara/0000-0002-8416-6440; Veglia, Fabrizio/0000-0002-9378-8874; kinnunen, leena/0000-0001-8739-4812; Palmer, Colin/0000-0002-6415-6560; Grarup, Niels/0000-0001-5526-1070; van der Schouw, Yvonne/0000-0002-4605-435X; Ruderfer, Douglas/0000-0002-2365-386X FU Academy of Finland [77299, 102318, 10493, 118065, 123885, 124243, 129293, 129680, 136895, 139635, 211119, 213506, 251217, 263836]; Agence National de la Recherche; Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques; Association Diabeete Risque Vasculaire; Association Francaise des Diabetiques; Association of Danish Pharmacies; Augustinus Foundation; Becket Foundation; British Diabetes Association (BDA) Research; British Heart Foundation; Central Norway Health Authority; Central Finland Hospital District; Center for Inherited Disease Research (CIDR); City of Kuopio; City of Leutkirch; Copenhagen County; Danish Centre for Evaluation and Health Technology Assessment; Danish Council for Independent Research; Danish Heart Foundation; Danish Research Councils; Deutsche Forschungsgemeinschaft [ER 155/6-2]; Diabetes Research Foundation; Diabetes UK; Doris Duke Charitable Foundation; Erasmus Medical Center; Erasmus University; Estonian government [SF0180142s08]; European Commission [ENGAGE HEALTH-F4-2007-201413, FP7-201413, FP7-245536, EXGENESIS LSHM-CT-2004-005272, FP6 LSHM_CT_2006_037197, LSHM-CT-2007-037273, C-Public Health 2004310]; European Regional Development Fund; Federal Ministry of Education and Research, Germany [FKZ 01GI1128, FKZ 01EO1001]; Federal Ministry of Health, Germany; Finnish Diabetes Association; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Medical Society; Folkhalsan Research Foundation; Foundation for Life and Health in Finland; Foundation for Old Servants; Fredrick och Ingrid Thuring Foundation; French region of Nord-Pas-de-Calais (Contrat de Projets Etat-Region); German Center for Diabetes Research; German Research Council [GRK1041]; German National Genome Research Network; Groupe d'Etude des Maladies Metaboliques et Systemiques; Health Care Centers in Vasa, Narpes and Korsholm, Finland; Health Foundation; Heinz Nixdorf Foundation; Helmholtz Zentrum Munchen; Helsinki University Central Hospital Research Foundation; Hospital District of Southwest Finland; Ib Henriksens Foundation; IngaBritt and Arne Lundberg's Research Foundation [359]; Karolinska Institutet; Knut and Alice Wallenberg Foundation [KAW 2009.0243]; Kuopio University Hospital; Lundbeck Foundation; Magnus Bergvall Foundation; Medical Faculty of University Duisburg-Essen; Medical Research Council, UK [G0000649, G0601261]; Ministry for Health, Welfare and Sports, the Netherlands; Ministry of Education and Culture, Finland [722, 627]; Ministry of Education, Culture and Science, the Netherlands; Ministry of Health and Prevention, Denmark; Ministry of Social Affairs and Health, Finland; Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia, Germany; Munich Center of Health Sciences; Municipal Health Care Center and Hospital in Jakobstad, Finland; municipality of Rotterdam, the Netherlands; Narpes Health Care Foundation; National Health Screening Service of Norway; National Heart, Lung, and Blood Institute, USA [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, N01HC25195, N02HL64278, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute, USA [U01HG004402, N01HG65403]; National Institute for Diabetes and Digestive and Kidney Diseases, USA [R01DK078616, U01DK085526, K24DK080140, R01DK073490]; National Institute for Health and Welfare, Finland; National Institutes of Health, USA [HHSN268200625226C, UL1RR025005, R01DK062370, R01DK072193, 1Z01HG000024, AG028555, AG08724, AG04563, AG10175, AG08861, U01HG004399, DK58845, CA055075, DK085545, DK098032]; Netherlands Genomics Initiative; Netherlands Organisation for Health Research and Development; Netherlands Organisation of Scientific Research NOW Investments [175.010.2005.011, 911-03-012, 050-060-810]; Nord-Trondelag County Council; Nordic Center of Excellence in Disease Genetics; Norwegian Institute of Public Health; Norwegian Research Council; Novo Nordisk Foundation; Ollquist Foundation; Oxford National Institute for Health Research (NIHR) Biomedical Research Centre; Paavo Nurmi Foundation; Paivikki and Sakari Sohlberg Foundation; Perklen Foundation; Pirkanmaa Hospital District, Finland; Programme Hospitalier de Recherche Clinique; Programme National de Recherche sur la Diabete; Research Institute for Diseases in the Elderly [014-93-015]; Robert Dawson Evans Endowment, Department of Medicine, Boston University School of Medicine and Boston Medical Center; Royal Swedish Academy of Sciences; Sarstedt, Germany; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Slottery Machine Association, Finland; Social Insurance Institution of Finland; South OstroBothnia Hospital District; state of Baden-Wurttemberg, Germany; Stockholm County Council [560183]; Swedish Cultural Foundation, Finland; Swedish Diabetes Foundation; Swedish e-science Research Center; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Research Council [SFO EXODIAB 2009-1039, 521-2010-3490, 521-2007-4037, 521-2008-2974, ANDIS 825-2010-5983, LUDC 349-2008-6589, 8691]; Swedish Society of Medicine; Tore Nilsson Foundation; Torsten and Ragnar Soderbergs Stiftelser [MT33/09]; University Hospital Essen; University of Tromso; University College London NIHR Biomedical Research Centre; UK NIHR Cambridge Biomedical Research Centre; Uppsala University; Uppsala University Hospital; Vaasa Hospital District; Velux Foundation; Wellcome Trust [GR072960, 076113, 083948, 090367, 090532, 083270, 086596, 098017, 095101, 098051, 098381] FX Funding for the research undertaken in this study has been received from the Academy of Finland (including grants 77299, 102318, 10493, 118065, 123885, 124243, 129293, 129680, 136895, 139635, 211119, 213506, 251217 and 263836); Agence National de la Recherche; Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques; Association Diabeete Risque Vasculaire; Association Francaise des Diabetiques; the Association of Danish Pharmacies; the Augustinus Foundation; the Becket Foundation; the British Diabetes Association (BDA) Research; the British Heart Foundation; the Central Norway Health Authority; the Central Finland Hospital District; the Center for Inherited Disease Research (CIDR); the City of Kuopio; the City of Leutkirch; Copenhagen County; the Danish Centre for Evaluation and Health Technology Assessment; the Danish Council for Independent Research; the Danish Heart Foundation; the Danish Research Councils; Deutsche Forschungsgemeinschaft (including project ER 155/6-2); the Diabetes Research Foundation; Diabetes UK; the Doris Duke Charitable Foundation; Erasmus Medical Center; Erasmus University; the Estonian government (SF0180142s08); the European Commission (including ENGAGE HEALTH-F4-2007-201413, FP7-201413, FP7-245536, EXGENESIS LSHM-CT-2004-005272, FP6 LSHM_CT_2006_037197, LSHM-CT-2007-037273, Directorate C-Public Health 2004310, DG XII); the European Regional Development Fund; the Federal Ministry of Education and Research, Germany (including FKZ 01GI1128 and FKZ 01EO1001); the Federal Ministry of Health, Germany; the Finnish Diabetes Association; the Finnish Diabetes Research Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Medical Society; the Folkhalsan Research Foundation; the Foundation for Life and Health in Finland; the Foundation for Old Servants; the Fredrick och Ingrid Thuring Foundation; the French region of Nord-Pas-de-Calais (Contrat de Projets Etat-Region); the German Center for Diabetes Research; the German Research Council (including grant GRK1041); the German National Genome Research Network; Groupe d'Etude des Maladies Metaboliques et Systemiques; the Health Care Centers in Vasa, Narpes and Korsholm, Finland; the Health Foundation; the Heinz Nixdorf Foundation; Helmholtz Zentrum Munchen; the Helsinki University Central Hospital Research Foundation; the Hospital District of Southwest Finland; the Ib Henriksens Foundation; IngaBritt and Arne Lundberg's Research Foundation (including grant 359); Karolinska Institutet; the Knut and Alice Wallenberg Foundation (including grant KAW 2009.; 0243); Kuopio University Hospital; the Lundbeck Foundation; the Magnus Bergvall Foundation; the Medical Faculty of University Duisburg-Essen; the Medical Research Council, UK (including grants G0000649 and G0601261); the Ministry for Health, Welfare and Sports, the Netherlands; the Ministry of Education and Culture, Finland (including grants 722 and 627; 2004-2011); the Ministry of Education, Culture and Science, the Netherlands; the Ministry of Health and Prevention, Denmark; the Ministry of Social Affairs and Health, Finland; the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia, Germany; the Munich Center of Health Sciences; the Municipal Health Care Center and Hospital in Jakobstad, Finland; the municipality of Rotterdam, the Netherlands; the Narpes Health Care Foundation; the National Health Screening Service of Norway; the National Heart, Lung, and Blood Institute, USA (including grant numbers/contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, N01HC25195, N02HL64278, R01HL087641, R01HL59367 and R01HL086694); the National Human Genome Research Institute, USA (including grant numbers/contracts U01HG004402 and N01HG65403); the National Institute for Diabetes and Digestive and Kidney Diseases, USA (including grants R01DK078616, U01DK085526, K24DK080140 and R01DK073490); the National Institute for Health and Welfare, Finland; the National Institutes of Health, USA (including grant numbers/contracts HHSN268200625226C, UL1RR025005, R01DK062370, R01DK072193, 1Z01HG000024, AG028555, AG08724, AG04563, AG10175, AG08861, U01HG004399, DK58845, CA055075, DK085545 and DK098032); the Netherlands Genomics Initiative; the Netherlands Organisation for Health Research and Development; the Netherlands Organisation of Scientific Research NOW Investments (including grants 175.010.2005.; 011, 911-03-012 and 050-060-810); the Nord-Trondelag County Council; the Nordic Center of Excellence in Disease Genetics; the Norwegian Institute of Public Health; the Norwegian Research Council; the Novo Nordisk Foundation; the Ollquist Foundation; the Oxford National Institute for Health Research (NIHR) Biomedical Research Centre; the Paavo Nurmi Foundation; the Paivikki and Sakari Sohlberg Foundation; the Perklen Foundation; the Pirkanmaa Hospital District, Finland; Programme Hospitalier de Recherche Clinique; Programme National de Recherche sur la Diabete; the Research Institute for Diseases in the Elderly (including grant 014-93-015); the Robert Dawson Evans Endowment, Department of Medicine, Boston University School of Medicine and Boston Medical Center; the Royal Swedish Academy of Sciences; Sarstedt, Germany; the Signe and Ane Gyllenberg Foundation; the Sigrid Juselius Foundation; the Slottery Machine Association, Finland; the Social Insurance Institution of Finland; the South OstroBothnia Hospital District; the state of Baden-Wurttemberg, Germany; the Stockholm County Council (including grant 560183); the Swedish Cultural Foundation, Finland; the Swedish Diabetes Foundation; the Swedish e-science Research Center; the Swedish Foundation for Strategic Research; the Swedish Heart-Lung Foundation; the Swedish Research Council (including grants SFO EXODIAB 2009-1039, 521-2010-3490, 521-2007-4037, 521-2008-2974, ANDIS 825-2010-5983, LUDC 349-2008-6589 and 8691); the Swedish Society of Medicine; the Tore Nilsson Foundation; the Torsten and Ragnar Soderbergs Stiftelser (including grant MT33/09); University Hospital Essen; University of Tromso; the University College London NIHR Biomedical Research Centre; the UK NIHR Cambridge Biomedical Research Centre; Uppsala University; Uppsala University Hospital; the Vaasa Hospital District; the Velux Foundation; and the Wellcome Trust (including the Biomedical Collections Grant GR072960 and grants 076113, 083948, 090367, 090532, 083270, 086596, 098017, 095101, 098051 and 098381). We are grateful to R. Scharfmann (INSERM U1016, Cochin Institute Paris) for the gift of EndoC beta H1 cells and for providing technical support with their maintenance. We thank P. Johnson and the Oxford NIHR Biomedical Research Centre-funded Islet Isolation facility for providing human islets for this study. Detailed acknowledgments are provided in the Supplementary Note. NR 75 TC 47 Z9 47 U1 6 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2015 VL 47 IS 12 BP 1415 EP + DI 10.1038/ng.3437 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA CX6LT UT WOS:000365813200013 PM 26551672 ER PT J AU Moon, DH Segal, M Boyraz, B Guinan, E Hofmann, I Cahan, P Tai, AK Agarwal, S AF Moon, Diane H. Segal, Matthew Boyraz, Baris Guinan, Eva Hofmann, Inga Cahan, Patrick Tai, Albert K. Agarwal, Suneet TI Poly(A)-specific ribonuclease (PARN) mediates 3 '-end maturation of the telomerase RNA component SO NATURE GENETICS LA English DT Article ID LINKED DYSKERATOSIS-CONGENITA; PULMONARY-FIBROSIS; MESSENGER-RNA; MUTATIONS; LENGTH; TERC; CANCER; CELLS; GENE; DEADENYLATION AB Mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita(1,2), but how PARN deficiency impairs telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem cells (iPSCs) from patients with dyskeratosis congenita with PARN mutations, we show that PARN is required for the 3'-end maturation of the telomerase RNA component (TERC). Patient-derived cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3' termini shows that PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results demonstrate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to telomere diseases. C1 [Moon, Diane H.; Segal, Matthew; Boyraz, Baris; Hofmann, Inga; Cahan, Patrick; Agarwal, Suneet] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Moon, Diane H.; Segal, Matthew; Boyraz, Baris; Agarwal, Suneet] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Moon, Diane H.; Segal, Matthew; Boyraz, Baris; Hofmann, Inga; Agarwal, Suneet] Harvard Stem Cell Inst, Boston, MA USA. [Moon, Diane H.; Segal, Matthew; Boyraz, Baris; Hofmann, Inga; Agarwal, Suneet] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Boyraz, Baris] Hacettepe Univ, Inst Canc, Dept Basic Oncol, Ankara, Turkey. [Guinan, Eva] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Tai, Albert K.] Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, Boston, MA 02111 USA. RP Agarwal, S (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM suneet.agarwal@childrens.harvard.edu RI Bayram, Cem/D-7403-2013 OI Bayram, Cem/0000-0001-8717-4668 FU Translational Research Program; Stem Cell Program, Boston Children's Hospital; Manton Center for Orphan Disease Research; Scientific and Technological Research Council of Turkey FX We thank the patients and their families for participation in the research; B.A. Croker, G.Q. Daley and L.I. Zon for comments on the manuscript; and K.E. Gagne for technical assistance. The work was funded in part by the Translational Research Program and the Stem Cell Program, Boston Children's Hospital (S.A.); the Manton Center for Orphan Disease Research (D.H.M.); and the Scientific and Technological Research Council of Turkey (B.B.). NR 54 TC 11 Z9 11 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 2015 VL 47 IS 12 BP 1482 EP + DI 10.1038/ng.3423 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CX6LT UT WOS:000365813200022 PM 26482878 ER PT J AU Begley, MJ Yun, CH Gewinner, CA Asara, JM Johnson, JL Coyle, AJ Eck, MJ Apostolou, I Cantley, LC AF Begley, Michael J. Yun, Cai-hong Gewinner, Christina A. Asara, John M. Johnson, Jared L. Coyle, Anthony J. Eck, Michael J. Apostolou, Irina Cantley, Lewis C. TI EGF-receptor specificity for phosphotyrosine-primed substrates provides signal integration with Src SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; C-SRC; TYROSINE KINASE; SH2 DOMAIN; PHOSPHORYLATION SITES; PROTEIN-KINASES; FAMILY KINASES; ACTIVATION; MECHANISM AB Aberrant activation of the EGF receptor (EGFR) contributes to many human cancers by activating the Ras-MAPK pathway and other pathways. EGFR signaling is augmented by Src-family kinases, but the mechanism is poorly understood. Here, we show that human EGFR preferentially phosphorylates peptide substrates that are primed by a prior phosphorylation. Using peptides based on the sequence of the adaptor protein Shc1, we show that Src mediates the priming phosphorylation, thus promoting subsequent phosphorylation by EGFR. Importantly, the doubly phosphorylated Shcl peptide binds more tightly than singly phosphorylated peptide to the Ras activator Grb2; this binding is a key step in activating the Ras-MAPK pathway. Finally, a crystal structure of EGFR in complex with a primed Shcl peptide reveals the structural basis for EGFR substrate specificity. These results provide a molecular explanation for the integration of Src and EGFR signaling with downstream effectors such as Ras. C1 [Begley, Michael J.; Gewinner, Christina A.; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Begley, Michael J.; Coyle, Anthony J.; Apostolou, Irina] Pfizer, Ctr Therapeut Innovat, Boston, MA USA. [Yun, Cai-hong; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yun, Cai-hong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Johnson, Jared L.; Cantley, Lewis C.] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. EM lcantley@med.cornell.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU US National Institutes of Health [2P01CA120964, S10OD010612] FX We thank S. Breitkopf and M. Yuan for help with MS experiments and Y. Zheng for help with HPLC experiments. We thank B. Murray for critical reading of the manuscript. This work was partially supported by US National Institutes of Health grants 2P01CA120964 (J.M.A.) and S10OD010612 (J.M.A.). NR 49 TC 4 Z9 5 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD DEC PY 2015 VL 22 IS 12 BP 983 EP 990 DI 10.1038/nsmb.3117 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA CY1FP UT WOS:000366152400011 PM 26551075 ER PT J AU Korshunov, A Jakobiec, FA Eberhart, CG Hovestadt, V Capper, D Jones, DTW Sturm, D Stagner, AM Edward, DP Eagle, RC Proia, AD Koch, A Ryzhova, M Ektova, A Schuller, U Zheludkova, O Lichter, P von Deimling, A Pfister, SM Kool, M AF Korshunov, Andrey Jakobiec, Frederick A. Eberhart, Charles G. Hovestadt, Volker Capper, David Jones, David T. W. Sturm, Dominik Stagner, Anna M. Edward, Deepak P. Eagle, Ralph C. Proia, Alan D. Koch, Arend Ryzhova, Marina Ektova, Anastasia Schueller, Ulrich Zheludkova, Olga Lichter, Peter von Deimling, Andreas Pfister, Stefan M. Kool, Marcel TI Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities SO NEUROPATHOLOGY LA English DT Article DE brain; chromosomal aberrations; epigenetic; eye; medulloepithelioma ID ABUNDANT NEUROPIL; TRUE ROSETTES; BRAIN-TUMORS; AMPLIFICATION; C19MC; EXPRESSION; COMPRISE AB Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR. C1 [Korshunov, Andrey; Capper, David; von Deimling, Andreas] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany. [Korshunov, Andrey; Capper, David; von Deimling, Andreas] Univ Heidelberg Hosp, Dept Neuropathol, Heidelberg, Germany. [Korshunov, Andrey; Capper, David; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M.] Core Ctr Heidelberg, German Canc Consortium DKTK, Heidelberg, Germany. [Jakobiec, Frederick A.; Stagner, Anna M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Eberhart, Charles G.; Edward, Deepak P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Eberhart, Charles G.; Edward, Deepak P.] King Khalid Eye Specialist Hosp, Riyadh 11462, Saudi Arabia. [Hovestadt, Volker; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany. [Jones, David T. W.; Sturm, Dominik; Pfister, Stefan M.; Kool, Marcel] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany. [Sturm, Dominik; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany. [Eagle, Ralph C.] Thomas Jefferson Univ, Wills Eye Hosp, Philadelphia, PA 19107 USA. [Proia, Alan D.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. [Koch, Arend] Charite, Inst Neuropathol, D-13353 Berlin, Germany. [Ryzhova, Marina] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow, Russia. [Ektova, Anastasia] Russian Childrens Clin Hosp, Dept Pathol, Moscow, Russia. [Schueller, Ulrich] Univ Munich, Ctr Neuropathol, Munich, Germany. [Zheludkova, Olga] Russian Sci Ctr Radiol, Dept Neurooncol, Moscow, Russia. RP Korshunov, A (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM andrey.korshunov@med.uni-heidelberg.de RI von Deimling, Andreas/F-7774-2013; Pfister, Stefan/F-6860-2013; Capper, David/I-8500-2014; OI von Deimling, Andreas/0000-0002-5863-540X; Pfister, Stefan/0000-0002-5447-5322; Sturm, Dominik/0000-0003-0250-1696; Hovestadt, Volker/0000-0002-3480-6649 FU German Cancer Research Center (DKFZ) - Heidelberg Center for Personalized Oncology (HIPO) Personalized Oncology Programm (POP) FX For technical support we thank Irina Lei beta, Andrea Wittmann and Kerstin Lindenberg. For technical expertise we thank Mattihias Schick, Roger Fisher and Melanie Bewerunge-Hudler from the DKFZ Genomic and Proteomic Core Facility. This work was principally supported from the German Cancer Research Center (DKFZ) - Heidelberg Center for Personalized Oncology (HIPO) Personalized Oncology Programm (POP). NR 22 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0919-6544 EI 1440-1789 J9 NEUROPATHOLOGY JI Neuropathology PD DEC PY 2015 VL 35 IS 6 BP 538 EP 544 DI 10.1111/neup.12227 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CY1AF UT WOS:000366137700005 PM 26183384 ER PT J AU Kautza, B Gomez, H Escobar, D Corey, C Ataya, B Luciano, J Botero, AM Gordon, L Brumfield, J Martinez, S Holder, A Ogundele, O Pinsky, M Shiva, S Zuckerbraun, BS AF Kautza, Benjamin Gomez, Hernando Escobar, Daniel Corey, Catherine Ataya, Bilal Luciano, Jason Botero, Ana Maria Gordon, Lisa Brumfield, John Martinez, Silvia Holder, Andre Ogundele, Olufunmilayo Pinsky, Michael Shiva, Sruti Zuckerbraun, Brian S. TI Inhaled, nebulized sodium nitrite protects in murine and porcine experimental models of hemorrhagic shock and resuscitation by limiting mitochondrial injury SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Nitrite; Mitochondria; Hemorrhage; Shock; Respiration ID VIVO ISCHEMIA-REPERFUSION; MICROVASCULAR INFLAMMATION; DIETARY NITRATE; COMPLEX I; KINASE-A; OXIDE; ACTIVATION; THERAPY; LIVER; ISCHEMIA/REPERFUSION AB Objective: The cellular injury that occurs in the setting of hemorrhagic shock and resuscitation (HS/R) affects all tissue types and can drive altered inflammatory responses. Resuscitative adjuncts hold the promise of decreasing such injury. Here we test the hypothesis that sodium nitrite (NaNO2), delivered as a nebulized solution via an inhalational route, protects against injury and inflammation from HS/R. Methods: Mice underwent HS/R to a mean arterial pressure (MAP) of 20 or 25 mmHg. Mice were resuscitated with Lactated Ringers after 90-120 min of hypotension. Mice were randomized to receive nebulized NaNO2 via a flow through chamber (30 mg in 5 mL PBS). Pigs (30-35 kg) were anesthetized and bled to a MAP of 30-40 mmHg for 90 min, randomized to receive NaNO2 (11 mg in 2.5 mL PBS) nebulized into the ventilator circuit starting 60 min into the hypotensive period, followed by initial resuscitation with Hextend. Pigs had ongoing resuscitation and support for up to four hours. Hemodynamic data were collected continuously. Results: NaNO2 limited organ injury and inflammation in murine hemorrhagic shock. A nitrate/nitrite depleted diet exacerbated organ injury, as well as mortality, and inhaled NaNO2 significantly reversed this effect. Furthermore, NaNO2 limited mitochondrial oxidant injury. In porcine HS/R, NaNO2 had no significant influence on shock induced hemodynamics. NaNO2 limited hypoxia/reoxia or HS/R-induced mitochondrial injury and promoted mitochondrial fusion. Conclusion: NaNO2 may be a useful adjunct to shock resuscitation based on its limitation of mitochondrial injury. Published by Elsevier Inc. C1 [Corey, Catherine; Shiva, Sruti; Zuckerbraun, Brian S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), F1267 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM sss43@pitt.edu; zuckerbraunbs@upmc.edu FU National Institutes of Health [R01GM082830, UM1 HL120877-01, 1K12HL109068-02]; Veterans Affairs Merit Award [1I01BX000566]; Department of Defense [DM102439]; Hemophilia Center of Western Pennsylvania; UPMC Center for Military Medicine Research; Center for Metabolism and Mitochondrial Medicine FX This work is supported by National Institutes of Health grants R01GM082830 (BSZ), UM1 HL120877-01 (BSZ), 1K12HL109068-02 (HG), Veterans Affairs Merit Award 1I01BX000566 (BSZ), Department of Defense DM102439 (BSZ), Hemophilia Center of Western Pennsylvania (SS) and UPMC Center for Military Medicine Research (SS), Center for Metabolism and Mitochondrial Medicine (SS). NR 48 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 EI 1089-8611 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD DEC 1 PY 2015 VL 51 BP 7 EP 18 DI 10.1016/j.niox.2015.09.006 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CX9ZK UT WOS:000366065100002 PM 26410351 ER PT J AU Uribe-Patarroyo, N Bouma, BE AF Uribe-Patarroyo, Nestor Bouma, Brett E. TI Rotational distortion correction in endoscopic optical coherence tomography based on speckle decorrelation SO OPTICS LETTERS LA English DT Article ID OCT; REGISTRATION; ESOPHAGUS; SEQUENCES; CATHETER; IVUS AB We present a new technique for the correction of nonuniform rotation distortion in catheter-based optical coherence tomography (OCT), based on the statistics of speckle between A-lines using intensity-based dynamic light scattering. This technique does not rely on tissue features and can be performed on single frames of data, thereby enabling real-time image correction. We demonstrate its suitability in a gastrointestinal (GI) balloon-catheter OCT system, determining the actual rotational speed with high temporal resolution, and present corrected cross-sectional and en face views showing significant enhancement of image quality. (C) 2015 Optical Society of America C1 [Uribe-Patarroyo, Nestor; Bouma, Brett E.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Uribe-Patarroyo, Nestor; Bouma, Brett E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bouma, Brett E.] Harvard Program Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Uribe-Patarroyo, N (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM uribepatarroyo.nestor@mgh.harvard.edu FU National Institutes of Health (NIH) [P41 EB015903]; Terumo Corporation FX National Institutes of Health (NIH) (P41 EB015903); Terumo Corporation. NR 16 TC 1 Z9 1 U1 2 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD DEC 1 PY 2015 VL 40 IS 23 BP 5518 EP 5521 DI 10.1364/OL.40.005518 PG 4 WC Optics SC Optics GA CY0YY UT WOS:000366134100026 PM 26625040 ER PT J AU Puram, SV Lee, DJ AF Puram, Sidharth V. Lee, Daniel J. TI Pediatric Auditory Brainstem Implant Surgery SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Auditory brainstem implant (ABI); Pediatric; Congenital hearing loss; Cochlear nerve hypoplasia or aplasia; Cochlear hypoplasia or aplasia; Retrosigmoid craniotomy ID INFRARED NEURAL STIMULATION; INNER-EAR MALFORMATIONS; NEUROFIBROMATOSIS TYPE-2; COCHLEAR IMPLANTATION; OPTOGENETIC STIMULATION; NERVE DEFICIENCY; CHILDREN; HEARING; OUTCOMES; PERFORMANCE AB Auditory brainstem implants (ABIs) provide auditory perception in patients with profound hearing loss who are not candidates for the cochlear implant (Cl) because of anatomic constraints or failed CI surgery. Herein, the authors discuss (1) preoperative evaluation of pediatric ABI candidates, (2) surgical approaches, and (3) contemporary ABI devices and their use in the pediatric population. The authors also review the surgical and audiologic outcomes following pediatric ABI surgery. The authors' institutional experience and the nearly 200 cases performed in Europe and the United States indicate that ABI surgery in children can be safe and effective. C1 [Puram, Sidharth V.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Puram, Sidharth V.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Daniel_lee@meei.harvard.edu NR 56 TC 1 Z9 1 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD DEC PY 2015 VL 48 IS 6 BP 1117 EP + DI 10.1016/j.otc.2015.07.013 PG 33 WC Otorhinolaryngology SC Otorhinolaryngology GA CY2FO UT WOS:000366224400017 PM 26553310 ER PT J AU O'Brien, JL Haaga, DAF AF O'Brien, Jennifer L. Haaga, David A. F. TI Empathic Accuracy and Compassion Fatigue Among Therapist Trainees SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE empathy; empathic accuracy; therapist training; compassion fatigue ID DEPRESSION; TRAUMA; CLINICIAN AB Psychotherapists are in the challenging position of needing to (a) listen to traumatic self-disclosures well enough to form empathically accurate responses to clients and (b) keep such self-disclosures and their own emotional reactions to them private, without (c) becoming burned out or suffering excessively from compassion fatigue. To shed light on these phenomena, we compared trait empathy as well as empathic accuracy and compassion fatigue in response to a standard videotaped trauma self-disclosure among advanced (fourth-/fifth-year graduate students, n = 18) and novice (first-year graduate students, n = 18) therapist trainees and age-and gender-matched nontherapists (n = 36). As expected, therapist trainees reported substantially (d = .77) less compassion fatigue than did nontherapists, and the trainees were substantially (d = .81) more accurate on a multiple-choice empathic accuracy test. However, therapist trainees did not differ from nontherapists in trait empathy or on a free-response measure of empathic accuracy. Advanced trainees did not differ from novice trainees on any measure. These results tentatively suggest that therapist trainee resilience in managing the stress of receiving traumatic self-disclosure stems more from selection, than retention or training/experience effects. Further research is needed to examine if these conclusions would hold up with interactive discussions rather than standard videotaped disclosures, or a wider range of therapist training and experience. A central implication of such an inquiry would be to determine the utility of promoting therapist resilience in clinical training programs. C1 [O'Brien, Jennifer L.] VA Boston Healthcare Syst, Clin Psychol, Jamaica Plain, MA 02130 USA. [Haaga, David A. F.] Amer Univ, Psychol, Washington, DC 20016 USA. RP O'Brien, JL (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM obrjennifer@gmail.com NR 27 TC 0 Z9 0 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2015 VL 46 IS 6 BP 414 EP 420 DI 10.1037/pro0000037 PG 7 WC Psychology, Multidisciplinary SC Psychology GA CY3MQ UT WOS:000366314300005 ER PT J AU Kuhn, E Crowley, JJ Hoffman, JE Eftekhari, A Ramsey, KM Owen, JE Reger, GM Ruzek, JI AF Kuhn, Eric Crowley, Jill J. Hoffman, Julia E. Eftekhari, Afsoon Ramsey, Kelly M. Owen, Jason E. Reger, Greg M. Ruzek, Josef I. TI Clinician Characteristics and Perceptions Related to Use of the PE (Prolonged Exposure) Coach Mobile App SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE posttraumatic stress disorder; mobile phone intervention; prolonged exposure therapy; diffusion of innovations; mobile apps ID DISORDER; MHEALTH; THERAPY; CARE AB Using smartphones in the provision of evidence-based psychotherapy holds tremendous potential for enhancing care. Mental health clinicians' perceptions of smartphone-delivered interventions will affect their decision to adopt these promising innovations. As a follow-up to our early study (Kuhn et al., 2014), here we investigated mental health clinicians' (N = 271) use of a patient-facing smartphone app for prolonged exposure (PE) therapy for posttraumatic stress disorder, called PE Coach. A Web-based survey assessed clinicians' perceptions of the app using diffusion of innovations constructs. Half of the sample practicing PE in the past year reported using PE Coach, with 93.6% intending to continue using it. For clinicians who did not use PE Coach, 77.6% intended to use it in the future. Perceptions of PE Coach were generally favorable regarding its relative advantage over current practices, compatibility with clinicians' values and needs, complexity, trialability, and observability. Younger clinicians (<40 years) had more favorable perceptions of the app's perceived complexity than did older clinicians (>= 40 years). Clinicians owning smartphones, relative to those not, had more favorable perceptions of compatibility, complexity, and trialability. PE Coach users, relative to nonusers, had more favorable perceptions across all constructs, except trialability. Finally, after controlling for number of PE patients seen in the past year, clinician age and perceived complexity of the app significantly predicted use of PE Coach. These findings suggest that clinicians are using PE Coach and have favorable perceptions of it, but enhanced dissemination efforts may be needed to increase adoption for certain clinician groups. C1 [Kuhn, Eric; Crowley, Jill J.; Hoffman, Julia E.; Eftekhari, Afsoon; Ramsey, Kelly M.; Owen, Jason E.; Ruzek, Josef I.] VA Natl Ctr PTSD, Disseminat & Training Div, Menlo Pk, CA 94025 USA. [Reger, Greg M.] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA USA. [Reger, Greg M.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA. RP Kuhn, E (reprint author), VA Natl Ctr PTSD, Disseminat & Training Div, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM eric.kuhn@va.gov RI Emchi, Karma/Q-1952-2016 NR 21 TC 3 Z9 3 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 EI 1939-1323 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2015 VL 46 IS 6 BP 437 EP 443 DI 10.1037/pro0000051 PG 7 WC Psychology, Multidisciplinary SC Psychology GA CY3MQ UT WOS:000366314300008 ER PT J AU Chang, YP Liu, WC Tseng, MC Chu, YH AF Chang, Yi-Pin Liu, Wei-Chun Tseng, Ming-Chung Chu, Yen-Ho TI Ionic liquids tailored for reaction-based gas sensing on quartz crystal microbalance SO REVIEWS IN ANALYTICAL CHEMISTRY LA English DT Article DE chemoselective gas sensing; ionic liquid; label-free detection; quartz crystal microbalance; volatile organic compound ID VOLATILE ORGANIC-COMPOUNDS; FIELD-EFFECT TRANSISTORS; MASS-SPECTROMETRY; OLFACTORY SYSTEM; SENSORS; SURFACE; PHASE; FILMS; OXIDE; VOCS AB Gas sensing technologies are of importance for a variety of industrial, environmental, medical, and even military applications. Many gases, such as man-made or naturally occurring volatile organic compounds (VOCs), can adversely affect human health or cause harm to the environment. Recent advances in "designer solvents" and sensor technologies have facilitated the development of ultrasensitive gas sensing ionic liquids (SILs) based on quartz crystal microbalance (QCM) that can real-time detect and discriminate VOCs. Based on specific chemical reactions at room temperature, thin-coated functionalized ionic liquids on quartz chips are able to capture VOCs chemoselectively with a single-digit parts-per-billion detection limit. The amalgamation of tailor-made functional SILs and QCM results in a new class of qualitative and semiquantitative gas sensing device, which represents a prototype of electronic nose. This review vignettes some conventional gas sensing approaches and collates latest research results in the exploration of SIL-on-QCM chips and gives an account of the state-of-the-art gas sensing technology. C1 [Tseng, Ming-Chung; Chu, Yen-Ho] Natl Chung Cheng Univ, Dept Chem & Biochem, Chiayi 62102, Taiwan. [Chang, Yi-Pin] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Liu, Wei-Chun] Taiwan Sugar Res Inst, Bioproc Engn Div, Tainan 70176, Taiwan. RP Chu, YH (reprint author), Natl Chung Cheng Univ, Dept Chem & Biochem, 168 Univ Rd, Chiayi 62102, Taiwan. EM cheyhc@ccu.edu.tw FU Ministry of Science and Technology of Taiwan, ROC [MOST 103-2113-M-194-002-MY3, NSC 100-2113-M-194-002-MY3, MOST 103-2811-M-194-014]; ANT Technology (Taipei, Taiwan) FX We gratefully acknowledge the grants from the Ministry of Science and Technology of Taiwan, ROC (MOST 103-2113-M-194-002-MY3, NSC 100-2113-M-194-002-MY3, and MOST 103-2811-M-194-014) and in part from ANT Technology (Taipei, Taiwan). NR 35 TC 3 Z9 3 U1 11 U2 30 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0793-0135 EI 2191-0189 J9 REV ANAL CHEM JI Rev. Anal. Chem. PD DEC PY 2015 VL 34 IS 3-4 BP 77 EP 86 DI 10.1515/revac-2015-0009 PG 10 WC Chemistry, Analytical SC Chemistry GA CY6NF UT WOS:000366525300002 ER PT J AU Chittle, MD Rao, SK Jaff, MR Patel, VI Gallen, KM Avadhani, R Ferris, TG Wasfy, JH AF Chittle, Melissa D. Rao, Sandhya K. Jaff, Michael R. Patel, Virendra I. Gallen, Kathleen M. Avadhani, Radhika Ferris, Timothy G. Wasfy, Jason H. TI Asynchronous vascular consultation via electronic methods: A feasibility pilot SO VASCULAR MEDICINE LA English DT Article DE Accountable Care Organization (ACO); asynchronous consult; care delivery; chronic disease management; e-consult; vascular care ID GLOBAL BURDEN; SYSTEMATIC ANALYSIS; DISEASE; PREVENTION; DEATHS; GAINS; CARE AB Management of chronic disease often requires multidisciplinary clinical efforts and specialist care. With the emergence of Accountable Care Organizations (ACOs), health care systems are incentivized to evaluate methods of information exchange between generalists and specialists in order to provide value while preserving quality. Our objective was to evaluate patient and referring provider satisfaction and outcomes of asynchronous electronic consultations in vascular care in a large tertiary academic medical center. Referring providers were offered a vascular 'e-consult' option through an electronic referral management system. We conducted chart review to understand the downstream effects and surveyed patients and referring providers to assess satisfaction. From 24 March 2014 to 1 March 2015, 54 e-consults were completed. Additional testing and recommendations were made in 49/54 (90.7%) e-consults, including lower-extremity venous duplex ultrasonography with reflux testing, duplex ultrasonography of the carotid artery, computed tomography, magnetic resonance imaging, non-invasive physiology arterial studies, laboratory tests, medications, compression stockings, and sequential lymphedema compression therapy. Referring providers were compliant with recommendations in 40/49 (81.6%) of e-consults. A total of 17/54 (31.5%) patients were surveyed with a median patient satisfaction score of 13.7/15 (91.3%) (SD +/- 6.4). The program was associated with high referring provider satisfaction, with 87.0% finding the e-consult very helpful and 80.0% stating it averted the need for a traditional visit. Our experience suggests that e-consults are an effective way to provide vascular care in some patients and are associated with high patient and provider satisfaction. E-consults may therefore be an efficient method of care delivery for vascular patients within an ACO. C1 [Chittle, Melissa D.] Massachusetts Gen Hosp, Div Intervent Radiol, Dept Radiol, Boston, MA 02113 USA. [Rao, Sandhya K.; Avadhani, Radhika; Ferris, Timothy G.; Wasfy, Jason H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Phys Org, Boston, MA USA. [Rao, Sandhya K.; Ferris, Timothy G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Jaff, Michael R.; Gallen, Kathleen M.] Massachusetts Gen Hosp, Paul & Phyllis Fireman Vasc Ctr, Boston, MA 02114 USA. [Patel, Virendra I.; Gallen, Kathleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovas Surg,Paul & Phyllis Fireman Va, Boston, MA USA. [Wasfy, Jason H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. RP Chittle, MD (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, Dept Radiol, 55 Fruit St,Blake 290, Boston, MA 02113 USA. EM mchittle@mgh.harvard.edu NR 20 TC 1 Z9 1 U1 4 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X EI 1477-0377 J9 VASC MED JI Vasc. Med. PD DEC PY 2015 VL 20 IS 6 BP 551 EP 556 DI 10.1177/1358863X15601734 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CY0JV UT WOS:000366093300007 PM 26385414 ER PT J AU Alberti, MO Jones, JJ Miglietta, R Ding, HT Bakshi, RK Edmonds, TG Kappes, JC Ochsenbauer, C AF Alberti, Michael O. Jones, Jennifer J. Miglietta, Riccardo Ding, Haitao Bakshi, Rakesh K. Edmonds, Tara G. Kappes, John C. Ochsenbauer, Christina TI Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; DEPENDENT CELLULAR CYTOTOXICITY; BROADLY NEUTRALIZING ANTIBODIES; INFECTIOUS MOLECULAR CLONES; T-LYMPHOCYTES; IN-VIVO; TRANSLATION INITIATION; VIRAL INFECTIVITY; DOWN-REGULATION AB We previously developed replication-competent reporter HIV-1 (referred to herein as LucR.T2A reporter viruses), utilizing a ribosome skipping T2A peptide strategy to link Renilla luciferase (LucR) with Nef expression. The demonstrated utility for HIV-1 vaccine and transmission study applications included measurement of neutralizing antibody (NAb) activity in vaccine sera, improved cell-mediated virus inhibition assays, such as T cell-mediated virus inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC) assays, and humanized mouse models. Herein, we extend our prior work and introduce reporter virus technology for applications that require fully functional Nef. We demonstrate that in CD4(+) T cells productively infected with LucR.T2A reporter viruses, T2A peptide-driven Nef expression and function, such as down-regulation of surface CD4 and MHC-I, were impaired. We overcame this limitation of LucR.T2A reporter viruses and achieved physiological Nef expression and function by engineering novel LucR reporter HIV-1 comprising 11 different internal ribosome entry site (IRES) elements chosen for size and relative activity. A range of Nef expression was observed in 293T cells transfected with the different LucR.IRES reporter virus constructs. Iteratively, we identified IRES reporter genomes that expressed Nef closest to physiological levels and produced virus with infectivity, titers, and replication kinetics similar to nonreporter viruses. Our results demonstrated that LucR reporter activity was stable over multiple replication cycles in peripheral blood mononuclear cells (PBMCs). Furthermore, we analyzed Nef functionality, i.e., down-modulation of MHC-I and CD4, following infection of T cell lines and PBMCs. Unlike LucR.T2A reporter virus, one of the redesigned LucR.IRES reporter viruses [containing the modified encephalomyocarditis virus (EMCV) 6ATR IRES element, 6ATRi] demonstrated Nef expression and function similar to parental nonreporter virus. In a previously validated (nef-independent) T cell-based NAb neutralization assay, LucR.6ATRi reporter virus performed indistinguishably from LucR.T2A reporter virus. In summary, reporter viruses comprising the 6ATRi element promise to augment HIV-1 vaccine and transmission research approaches requiring a sensitive reporter readout combined with wild-type Nef function. C1 [Alberti, Michael O.; Jones, Jennifer J.; Miglietta, Riccardo; Ding, Haitao; Bakshi, Rakesh K.; Edmonds, Tara G.; Kappes, John C.; Ochsenbauer, Christina] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Kappes, John C.; Ochsenbauer, Christina] Univ Alabama Birmingham, Ctr AIDS Res, Birmingham, AL 35294 USA. [Kappes, John C.; Ochsenbauer, Christina] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. RP Ochsenbauer, C (reprint author), Univ Alabama Birmingham, Dept Med, LHRB 619,701 19th St South, Birmingham, AL 35294 USA. EM ochsenba@uab.edu OI Alberti, Michael/0000-0003-4269-4701 FU Comprehensive Antibody Vaccine Immune Monitoring Consortium (CA-VIMC) [1032144]; Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID) [NIH U01-AI-067854]; Bill & Melinda Gates Foundation; Flow Cytometry cores of the UAB Center for AIDS Research (CFAR) [P30-AI-27767]; facilities of the Virology, Genetic Sequencing FX This work was supported by a subcontract to C.O. from the Comprehensive Antibody Vaccine Immune Monitoring Consortium (CA-VIMC) (grant #1032144), which is part of the Collaboration for AIDS Vaccine Discovery (CAVD)/CA-VIMC, funded by the Bill & Melinda Gates Foundation; a subcontract to J.C.K. from the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID), NIH U01-AI-067854; and facilities of the Virology, Genetic Sequencing, and Flow Cytometry cores of the UAB Center for AIDS Research (CFAR), P30-AI-27767. We would also like to acknowledge Dr. Marla Hertz and Dr. Sunnie Thompson for very helpful discussions and the generous provision of IRES reagents; Dr. James Hoxie for insightful discussion and anti-Nef antibodies; Dr. Alok Mulky and Dr. Qun Dai for technical expertise and useful discussions; and Dr. David Montefiori for his support and discussion. NR 85 TC 0 Z9 0 U1 3 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC 1 PY 2015 VL 31 IS 12 BP 1278 EP 1296 DI 10.1089/aid.2015.0074 PG 19 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA CX3EH UT WOS:000365578100015 PM 26101895 ER PT J AU Kleinman, RE AF Kleinman, Ronald E. TI Aspartic acid, phenylalanine, and early menarche SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID ARTIFICIAL SWEETENERS; GLUCOSE; HUMANS C1 [Kleinman, Ronald E.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kleinman, RE (reprint author), Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM rkleinman@partners.org NR 9 TC 0 Z9 0 U1 1 U2 5 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2015 VL 102 IS 6 BP 1617 EP 1618 DI 10.3945/ajcn.115.120857 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CX5BY UT WOS:000365717300041 PM 26628574 ER PT J AU Dabaja, BS Advani, R Hodgson, DC Dhakal, S Flowers, CR Ha, CS Hoppe, BS Mendenhall, NP Metzger, ML Plastaras, JP Roberts, KB Shapiro, R Smith, SM Terezakis, SA Winkfield, KM Younes, A Constine, LS AF Dabaja, Bouthaina S. Advani, Ranjana Hodgson, David C. Dhakal, Sughosh Flowers, Christopher R. Ha, Chul S. Hoppe, Bradford S. Mendenhall, Nancy P. Metzger, Monika L. Plastaras, John P. Roberts, Kenneth B. Shapiro, Ronald Smith, Sonali M. Terezakis, Stephanie A. Winkfield, Karen M. Younes, Anas Constine, Louis S. TI ACR Appropriateness Criteria (R) Diffuse Large B-Cell Lymphoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE lymphoma; radiation; appropriateness criteria; large B-cell lymphoma; non-Hodgkin's lymphoma ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; CHOP-LIKE CHEMOTHERAPY; LOCALIZED AGGRESSIVE LYMPHOMA; RANDOMIZED CONTROLLED-TRIAL; COOPERATIVE-ONCOLOGY-GROUP; DOSE-ADJUSTED EPOCH; ELDERLY-PATIENTS; YOUNG-PATIENTS AB The management of diffuse large B-cell lymphoma depends on the initial diagnosis including molecular and immunophenotypic characteristics, Ann Arbor staging, and International Prognostic Index (IPI score). Treatment approaches with different chemotherapy regimens used is discussed in detail. The role of radiation as a consolidation is discussed including: (1) the prerituximab randomized trials that challenged the role of radiation, (2) recent prospective studies (UNFOLDER/RICOVER-60), and (3) retrospective studies; the last 2 showed a potential benefit of radiation both for early and advanced stage. The document also discusses the role of positron emission tomography/computed tomography for predicting outcome and potentially guiding therapy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Dabaja, Bouthaina S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Advani, Ranjana] Stanford Canc Ctr, Amer Soc Clin Oncol, Stanford, CA USA. [Hodgson, David C.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Dhakal, Sughosh; Constine, Louis S.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Younes, Anas] Mem Sloan Kettering Canc Ctr, Amer Soc Clin Oncol, New York, NY 10021 USA. [Flowers, Christopher R.] Emory Univ, Amer Soc Clin Oncol, Atlanta, GA 30322 USA. [Ha, Chul S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hoppe, Bradford S.] Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. [Mendenhall, Nancy P.] Univ Florida, Gainesville, FL USA. [Metzger, Monika L.] St Jude Childrens Res Hosp, Amer Soc Clin Oncol, Memphis, TN 38105 USA. [Plastaras, John P.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Roberts, Kenneth B.] Yale Univ, Sch Med, New Haven, CT USA. [Shapiro, Ronald] Indiana Univ, Sch Med, Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Smith, Sonali M.] Univ Chicago, Amer Soc Hematol, Chicago, IL 60637 USA. [Terezakis, Stephanie A.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dabaja, BS (reprint author), Dept Radiat Oncol, 1515 Holcombe Blvd Unit 97, Houston, TX 77030 USA. EM bdabaja@mdanderson.org RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 FU Novartis; Johnson Johnson; Seattle Genetics; Merck; Genentech; Infinity; Gilead FX C.R.F.: provides consulting for the Prescription Solutions Pharmacy and Therapeutics division. Consultation involves advice on FDA Regulated drugs only. None of the consultation overlaps with existing or planned ACR guidelines. A.Y.: Honorarium from: Novartis, Seattle Genetics, Millenium, Clegene, Curis, Sanofi, Pharmacyclics, and Incyte. Research Support from: Novartis, Johnson & Johnson, Seattle Genetics, Merck, Genentech, Infinity, and Gilead. The remaining authors declare no conflicts of interest. NR 90 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2015 VL 38 IS 6 BP 610 EP 620 DI 10.1097/COC.0000000000000215 PG 11 WC Oncology SC Oncology GA CX5BM UT WOS:000365715700013 PM 26583344 ER PT J AU Deipolyi, AR Zhu, AX Oklu, R AF Deipolyi, Amy R. Zhu, Andrew X. Oklu, Rahmi TI Intratumoral Vascular Shunting Biomarker of Clinical Outcome and Source of Circulating Tumor Cells? SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE shunting; radioembolization; SIRT; angiogenesis; angiography ID INTERNAL RADIATION-THERAPY; HEPATOCELLULAR-CARCINOMA; LIVER METASTASES; INTERVENTIONAL ONCOLOGY; COLORECTAL-CANCER; RADIOEMBOLIZATION; MICROSPHERES; ANGIOGENESIS; MALIGNANCIES; BRACHYTHERAPY AB Predicting which patients will benefit from radioembolization remains a challenge, as reliable prognostic indicators are not defined. Abnormal tumor vascular anatomy could not only impact the ability of cancer therapies to penetrate tumors, but may also contribute to a lesion's metastatic potential. Specifically, intratumoral vascular shunts could allow circulating tumor cells to initiate metastases by allowing them to gain access to distant sites in the body, bypassing capillary beds. Here, we describe how tumoral angiogenesis occurs and how intratumoral vascular shunts may form. C1 [Deipolyi, Amy R.; Oklu, Rahmi] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Deipolyi, Amy R.; Zhu, Andrew X.; Oklu, Rahmi] Harvard Univ, Sch Med, Boston, MA USA. RP Oklu, R (reprint author), Massachusetts Gen Hosp, Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA. EM roklu@mgh.harvard.edu OI Deipolyi, Amy/0000-0003-3144-386X FU NIH [RO3 CA172738]; Department of Radiology, Massachusetts General Hospital FX Supported by NIH grant RO3 CA172738 (R.O.) and the Department of Radiology (R.O.), Massachusetts General Hospital. NR 35 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2015 VL 38 IS 6 BP 621 EP 626 DI 10.1097/COC.0000000000000145 PG 6 WC Oncology SC Oncology GA CX5BM UT WOS:000365715700014 PM 25333732 ER PT J AU Scahill, L McCracken, JT King, BH Rockhill, C Shah, B Politte, L Sanders, R Minjarez, M Cowen, J Mullett, J Page, C Ward, D Deng, YH Loo, S Dziura, J McDougle, CJ AF Scahill, Lawrence McCracken, James T. King, Bryan H. Rockhill, Carol Shah, Bhavik Politte, Laura Sanders, Roy Minjarez, Mendy Cowen, Jennifer Mullett, Jennifer Page, Chris Ward, Denise Deng, Yanhong Loo, Sandra Dziura, James McDougle, Christopher J. CA Res Units Pediat Psychopharmacolog TI Extended-Release Guanfacine for Hyperactivity in Children With Autism Spectrum Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; ABERRANT BEHAVIOR CHECKLIST; CLINICAL-TRIAL; YOUNG-PEOPLE; DOUBLE-BLIND; ADOLESCENTS; SYMPTOMS; PLACEBO; ADHD AB Objective: Hyperactivity, impulsiveness, and distractibility are common problems in children with autism spectrum disorder (ASD). Extended-release guanfacine is approved for children with attention deficit hyperactivity disorder but not well studied in ASD. Method: In a multisite, randomized clinical trial, extended-release guanfacine was compared with placebo in children with ASD accompanied by hyperactivity, impulsiveness, and distractibility. Results: Sixty-two subjects (boys, N=53; girls, N=9; mean age=8.5 years [SD=2.25]) were randomly assigned to guanfacine (N=30) or placebo (N=32) for 8 weeks. The guanfacine group showed a 43.6% decline in scores on the Aberrant Behavior Checklist-hyperactivity subscale (least squares mean from 34.2 to 19.3) compared with a 13.2% decrease in the placebo group (least squares mean from 34.2 to 29.7; effect size=1.67). The rate of positive response (much improved or very much improved on the Clinical Global Impression-Improvement scale) was 50% (15 of 30) for guanfacine compared with 9.4% (3 of 32) for placebo. A brief cognitive battery tapping working memory and motor planning showed no group differences before or after 8 weeks of treatment. The modal dose of guanfacine at week 8 was 3 mg/day (range: 1-4 mg/day), and the modal dose was 3 mg/day (range: 2-4 mg/day) for placebo. Four guanfacine-treated subjects (13.3%) and four placebo subjects (12.5%) exited the study before week 8. The most common adverse events included drowsiness, fatigue, and decreased appetite. There were no significant changes on ECG in either group. For subjects in the guanfacine group, blood pressure declined in the first 4 weeks, with return nearly to baseline by endpoint (week 8). Pulse rate showed a similar pattern but remained lower than baseline at endpoint. Conclusions: Extended-release guanfacine appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in children with ASD. C1 [Scahill, Lawrence] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Seattle Childrens Hosp, Dept Psychiat & Behav Sci, Seattle, WA USA. Massachusetts Gen Hosp, Lurie Ctr Autism, Dept Child & Adolescent Psychiat, Lexington, MA USA. Marcus Autism Ctr, Atlanta, GA USA. Yale Univ, Dept Biostat, New Haven, CT USA. Yale Univ, Dept Emergency Med, New Haven, CT USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Scahill, L (reprint author), Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. EM Lawrence.scahill@emory.edu FU NIMH [R01MH083707, RO1MH83739, RO1MH083747, R01MH86927]; Yale Clinical and Transitional Science Award from the NIH National Center for Research Resources [UL1 RR024139]; Atlanta Clinical and Translational Science Institute, Emory University; NIH National Center for Advancing Translational Sciences [UL1TR000454]; Roche; Seaside Therapeutics FX Supported by NIMH grants to Dr Scahill (R01MH083707), Dr. McDougle (RO1MH83739), Dr. McCracken (RO1MH083747), and Dr. King (R01MH86927); by a Yale Clinical and Transitional Science Award (UL1 RR024139) from the NIH National Center for Research Resources; and by Atlanta Clinical and Translational Science Institute, Emory University, which is supported by the NIH National Center for Advancing Translational Sciences under award UL1TR000454.; Dr. Scahill has served as a consultant for Bracket, Coronado, MedAdvante, Neuren, Roche, and Shire, and he has served on the speaker's bureau for the Tourette Syndrome Association. Dr. McCracken has served as a consultant for Dart Neuroscience and Roche; he has received research support from Roche; he has received study drug and matching placebo from Shire; and he has served on the speaker's bureau for the Tourette Syndrome Association. Dr. King has received research support from Roche and Seaside Therapeutics. All other authors report no financial relationships with commercial interests. NR 40 TC 7 Z9 7 U1 4 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2015 VL 172 IS 12 BP 1197 EP 1206 DI 10.1176/appi.ajp.2015.15010055 PG 10 WC Psychiatry SC Psychiatry GA CX6UJ UT WOS:000365836900007 PM 26315981 ER PT J AU Papakostas, GI Fava, M Baer, L Swee, MB Jaeger, A Bobo, WV Shelton, RC AF Papakostas, George I. Fava, Maurizio Baer, Lee Swee, Michaela B. Jaeger, Adrienne Bobo, William V. Shelton, Richard C. TI Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; ATYPICAL ANTIPSYCHOTICS; ADJUNCTIVE THERAPY; ANXIOUS DEPRESSION; CLINICAL-TRIALS; OPEN-LABEL; ARIPIPRAZOLE; ANTIDEPRESSANTS; METAANALYSIS; MULTICENTER AB Objective: The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. Method: This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academc medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures. Results: Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group. Conclusions: Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. C1 [Papakostas, George I.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Psychiat & Psychol, Rochester, MN 55905 USA. Univ Alabama Birmingham, Sch Med, Dept Psychiat & Behav Neurobiol, Birmingham, AL USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Clin Trials Network & Inst, Depress Clin & Res Program, Boston, MA 02114 USA. EM gpapakostas@partners.org FU NIMH [R01MH081235] FX Supported by the NIMH grant R01MH081235, Pfizer (which supplied blinded ziprasidone and placebo pills), and Forest Laboratories (which supplied escitalopram). NR 33 TC 9 Z9 9 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2015 VL 172 IS 12 BP 1251 EP 1258 DI 10.1176/appi.ajp.2015.14101251 PG 8 WC Psychiatry SC Psychiatry GA CX6UJ UT WOS:000365836900013 PM 26085041 ER PT J AU Kerr, DA Arora, KS Mahadevan, KK Hornick, JL Krane, JF Rivera, MN Ting, DT Deshpande, V Faquin, WC AF Kerr, Darcy A. Arora, Kshitij S. Mahadevan, Krishnan K. Hornick, Jason L. Krane, Jeffrey F. Rivera, Miguel N. Ting, David T. Deshpande, Vikram Faquin, William C. TI Performance of a Branch Chain RNA In Situ Hybridization Assay for the Detection of High-risk Human Papillomavirus in Head and Neck Squamous Cell Carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE human papillomavirus (HPV); head and neck cancer; squamous cell carcinoma; testing methods; p16; in situ hybridization (ISH) ID TONSILLAR CANCER; FAVORABLE PROGNOSIS; HPV; P16; EXPRESSION; GENOTYPES; EPIDEMIC; SPECIMEN; SURVIVAL; PRIMERS AB High-risk human papillomavirus (HR-HPV) is a major etiologic agent in a subset of head and neck squamous cell carcinomas (HNSCCs), and its recognition has prognostic and predictive implications. The availability of a sensitive and specific test to assess HR-HPV status is limited. We evaluate an RNA in situ hybridization (ISH) method using branch chain technology to detect HR-HPV and compare its results with DNA ISH, p16 immunohistochemistry, and polymerase chain reaction (PCR). Tissue sections from 54 patients were stained with a manual RNA ISH assay (ViewRNA), which detects 14 HR-HPV types, an automated DNA ISH assay, and p16 immunohistochemistry. Most cases (83%, n=45) were also tested on an automated platform for 14 HR-HPV types and 1 limited to HPV 16/18. PCR was performed in all cases and was successful in 93% (n=50). The RNA ISH assay produced results in 96% of the cases with strong signals and was easily interpreted. HR-HPV was detected in more cases (63%, n=34) by RNA ISH than by DNA ISH (39%, n=21). Compared with PCR, both ISH platforms were 94% specific. RNA ISH was more sensitive (91%) than DNA ISH (65%), and RNA ISH correlated more strongly with p16 immunostaining. HPV 16 represented 89% of HR-HPV detected. The cocktail HPV 16/18 platform was concordant with the pooled HR-HPV assay in all expected cases. The automated assay demonstrated high concordance (96%) with the manual version, showed decreased background, and should allow for easy implementation into the workflow of the diagnostic pathology laboratory. C1 [Kerr, Darcy A.; Rivera, Miguel N.; Deshpande, Vikram; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arora, Kshitij S.; Mahadevan, Krishnan K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ting, David T.] Massachusetts Gen Hosp, Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. [Hornick, Jason L.; Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kerr, Darcy A.; Hornick, Jason L.; Krane, Jeffrey F.; Rivera, Miguel N.; Ting, David T.; Deshpande, Vikram; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, MGH Pathol Serv, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@mgh.harvard.edu OI Ting, David/0000-0002-3261-2322 FU Affymetrix FX V.D., D.T.T., K.S.A., and M.N.R. have received research support from Affymetrix. For the remaining authors none were declared. NR 44 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2015 VL 39 IS 12 BP 1643 EP 1652 DI 10.1097/PAS.0000000000000516 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA CX3VI UT WOS:000365627200005 PM 26426378 ER PT J AU Ferry, JA Klepeis, V Sohani, AR Harris, NL Preffer, FI Stone, JH Grove, A Deshpande, V AF Ferry, Judith A. Klepeis, Veronica Sohani, Aliyah R. Harris, Nancy Lee Preffer, Frederic I. Stone, John H. Grove, Arthur Deshpande, Vikram TI IgG4-related Orbital Disease and Its Mimics in a Western Population SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE IgG4; orbit; ocular adnexa; lacrimal gland; dacryoadenitis; sclerosing inflammation ID CHRONIC SCLEROSING DACRYOADENITIS; IGG4-POSITIVE PLASMA-CELLS; LYMPHOPLASMACYTIC INFILTRATIVE DISORDER; OCULAR ADNEXAL LYMPHOMA; ROSAI-DORFMAN DISEASE; SYSTEMIC-DISEASE; CLINICOPATHOLOGICAL-ENTITY; CONSENSUS STATEMENT; MALT LYMPHOMA; IGG4 DISEASE AB Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). Fifteen patients had IgG4-related dacryoadenitis or orbital inflammation. These patients included 9 men and 6 women, aged 24 to 77 years (median, 64 y). Lesions involved orbital soft tissue (8 cases), lacrimal gland (6 cases), and canthus (1 case). In 1 case, focal in situ follicular neoplasia was seen in a background of IgG4-RD. In another case, a clonal IGH gene rearrangement was detected. Four patients with IgG4-RD had evidence of IgG4-RD in other anatomic sites. Five patients, 1 man and 4 women, aged 26 to 74 years (median 50 y) had orbital lesions (2 involving lacrimal gland, 3 involving soft tissue) suspicious for, but not diagnostic of, IgG4-RD. Of 16 patients with IgG4-RD or probable IgG4-RD with information available regarding the course of their disease, 11 patients experienced recurrent or persistent orbital disease. However, no patient developed lymphoma, and no patient died of complications of IgG4-RD. Eighteen patients had lesions not representing IgG4-RD. They included 6 male and 12 female individuals aged 6 to 77 years (median, 47 y). These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic inflammation and fibrosis involving lacrimal gland or soft tissue (12 cases), and others. Clinical and pathologic findings among our patients with IgG4-RD involving the orbit are similar to those previously described in Asian patients. Careful evaluation of histologic and immunophenotypic features and clinical correlation are required to distinguish orbital IgG4-RD from other sclerosing inflammatory lesions in the orbit. C1 [Ferry, Judith A.; Klepeis, Veronica; Sohani, Aliyah R.; Harris, Nancy Lee; Preffer, Frederic I.; Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,James Homer Wright Pathol, Boston, MA 02115 USA. [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol, Dept Internal Med, Boston, MA 02114 USA. [Grove, Arthur] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 51 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2015 VL 39 IS 12 BP 1688 EP 1700 DI 10.1097/PAS.0000000000000497 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA CX3VI UT WOS:000365627200011 PM 26379149 ER PT J AU Yamada, Y Nadazdin, O Boskovic, S Lee, S Zorn, E Smith, RN Colvin, RB Madsen, JC Cosimi, AB Kawai, T Benichou, G AF Yamada, Y. Nadazdin, O. Boskovic, S. Lee, S. Zorn, E. Smith, R. N. Colvin, R. B. Madsen, J. C. Cosimi, A. B. Kawai, T. Benichou, G. TI Repeated Injections of IL-2 Break Renal Allograft Tolerance Induced via Mixed Hematopoietic Chimerism in Monkeys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE animal models: nonhuman primate; basic (laboratory) research; science; bone marrow; hematopoietic stem cell transplantation; immunosuppression; immune modulation; tolerance: chimerism; tolerance: mechanisms; translational research; science; kidney (allograft) function; dysfunction; kidney transplantation; nephrology ID REGULATORY T-CELLS; HIGH-DOSE INTERLEUKIN-2; TRANSPLANTATION TOLERANCE; NONHUMAN-PRIMATES; ALLOGENEIC CHIMERISM; LYMPHOID NEOGENESIS; CYNOMOLGUS MONKEYS; IN-VIVO; REJECTION; MEMORY AB Tolerance of allografts achieved in mice via stable mixed hematopoietic chimerism relies essentially on continuous elimination of developing alloreactive T cells in the thymus (central deletion). Conversely, while only transient mixed chimerism is observed in nonhuman primates and patients, it is sufficient to ensure tolerance of kidney allografts. In this setting, it is likely that tolerance depends on peripheral regulatory mechanisms rather than thymic deletion. This implies that, in primates, upsetting the balance between inflammatory and regulatory alloimmunity could abolish tolerance and trigger the rejection of previously accepted renal allografts. In this study, six monkeys that were treated with a mixed chimerism protocol and had accepted a kidney allograft for periods of 1-10 years after withdrawal of immunosuppression received subcutaneous injections of IL-2 cytokine (0.6-3 x 10(6)IU/m(2)). This resulted in rapid rejection of previously tolerated renal transplants and was associated with an expansion and reactivation of alloreactive pro-inflammatory memory T cells in the host's lymphoid organs and in the graft. This phenomenon was prevented by anti-CD8 antibody treatment. Finally, this process was reversible in that cessation of IL-2 administration aborted the rejection process and restored normal kidney graft function. C1 [Yamada, Y.; Nadazdin, O.; Boskovic, S.; Lee, S.; Zorn, E.; Madsen, J. C.; Cosimi, A. B.; Kawai, T.; Benichou, G.] Harvard Univ, Sch Med, Dept Surg, Ctr Transplantat Sci, Boston, MA 02115 USA. [Smith, R. N.; Colvin, R. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Benichou, G (reprint author), Harvard Univ, Sch Med, Dept Surg, Ctr Transplantat Sci, Boston, MA 02115 USA. EM gbenichou@partners.org FU NIH [U19 AI102405, P01HL18646] FX This work was supported by grants from the NIH: U19 AI102405 and P01HL18646. NR 50 TC 9 Z9 10 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2015 VL 15 IS 12 BP 3055 EP 3066 DI 10.1111/ajt.13382 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA CX2NP UT WOS:000365534100007 PM 26190648 ER PT J AU Williams, WW Cherikh, WS Young, CJ Fan, PY Cheng, Y Distant, DA Bryan, CF AF Williams, W. W. Cherikh, W. S. Young, C. J. Fan, P. Y. Cheng, Y. Distant, D. A. Bryan, C. F. TI First Report on the OPTN National Variance: Allocation of A(2)/A(2)B Deceased Donor Kidneys to Blood Group B Increases Minority Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE health services and outcomes research; kidney transplantation; nephrology; Organ Procurement and Transplantation Network (OPTN); organ procurement and allocation; recipient selection; United Network for Organ Sharing (UNOS); waitlist management ID RENAL-TRANSPLANTATION; HEALTH DISPARITIES; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; A(2) KIDNEYS; DISEASE; ACCESS; CANDIDATES; RECIPIENTS AB In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, variance of practice to allow deceased donor, ABO blood group incompatible, A(2) antigen, kidney transplantation into blood group B recipients; outcomes of this cohort were compared to ABO compatible recipients. The goal of the variance was to increase the number of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti-A IgG titers (<1:8) were eligible to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A(2)/A(2)B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan-Meier graft survival rates for the B recipients of A(2)/A(2)B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparable to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p-value=0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in blood group A transplants. The data support the proposition that this allocation algorithm may provide a robust mechanism to increase access of blood group B minority candidates to kidney transplantation. C1 [Williams, W. W.] Massachusetts Gen Hosp, MGH Transplant Ctr, Boston, MA 02114 USA. [Williams, W. W.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Cherikh, W. S.; Cheng, Y.] United Network Organ Sharing, Richmond, VA USA. [Young, C. J.] Univ Alabama Birmingham, Birmingham, AL USA. [Fan, P. Y.] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Distant, D. A.] SUNY HSC, Brooklyn Univ Hosp, Brooklyn, NY USA. [Bryan, C. F.] Midwest Transplant Network, Westwood, KS USA. RP Williams, WW (reprint author), Massachusetts Gen Hosp, MGH Transplant Ctr, Boston, MA 02114 USA. EM wwwilliams@mgh.harvard.edu FU Health Resources and Services Administration (HRSA) [234-2005-370011C] FX This work was performed for the OPTN Minority Affairs Committee and was supported wholly or in part by Health Resources and Services Administration (HRSA) contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of HHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 22 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2015 VL 15 IS 12 BP 3134 EP 3142 DI 10.1111/ajt.13409 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA CX2NP UT WOS:000365534100013 PM 26372745 ER PT J AU Weidman, J Baker, K AF Weidman, Joseph Baker, Keith TI The Cognitive Science of Learning: Concepts and Strategies for the Educator and Learner SO ANESTHESIA AND ANALGESIA LA English DT Article ID IMPROVE METACOMPREHENSION ACCURACY; INTERNAL-MEDICINE RESIDENTS; LONG-TERM RETENTION; DELIBERATE PRACTICE; STUDENT PERFORMANCE; ANALOGICAL TRANSFER; SUPERIOR PERFORMANCE; EXPERT PERFORMANCE; RANDOMIZED-TRIAL; RETRIEVAL PRACTICE AB Education is the fundamental process used to develop and maintain the professional skills of physicians. Medical students, residents, and fellows are expected to learn considerable amounts of information as they progress toward board certification. Established practitioners must continue to learn in an effort to remain up-to-date in their clinical realm. Those responsible for educating these populations endeavor to teach in a manner that is effective, efficient, and durable. The study of learning and performance is a subdivision of the field of cognitive science that focuses on how people interpret and process information and how they eventually develop mastery. A deeper understanding of how individuals learn can empower both educators and learners to be more effective in their endeavors. In this article, we review a number of concepts found in the literature on learning and performance. We address both the theoretical principles and the practical applications of each concept. Cognitive load theory, constructivism, and analogical transfer are concepts particularly beneficial to educators. An understanding of goal orientation, metacognition, retrieval, spaced learning, and deliberate practice will primarily benefit the learner. When these concepts are understood and incorporated into education and study, the effectiveness of learning is significantly improved. C1 [Weidman, Joseph; Baker, Keith] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. RP Weidman, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM jweidman@partners.org NR 98 TC 2 Z9 2 U1 5 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2015 VL 121 IS 6 BP 1586 EP 1599 DI 10.1213/ANE.0000000000000890 PG 14 WC Anesthesiology SC Anesthesiology GA CX2BL UT WOS:000365499800002 PM 26579660 ER PT J AU Houle, TT AF Houle, Timothy T. TI An Innovative Analysis of Analgesic Consumption in the Postoperative Period SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Houle, Timothy T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Houle, TT (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM thoule1@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2015 VL 123 IS 6 BP 1227 EP 1228 DI 10.1097/ALN.0000000000000918 PG 2 WC Anesthesiology SC Anesthesiology GA CX1VL UT WOS:000365483600004 PM 26495979 ER PT J AU Haerter, F Simons, JCP Foerster, U Duarte, IM Diaz-Gil, D Ganapati, S Eikermann-Haerter, K Ayata, C Zhang, B Blobner, M Isaacs, L Eikermann, M AF Haerter, Friederike Simons, Jeroen Cedric Peter Foerster, Urs Duarte, Ingrid Moreno Diaz-Gil, Daniel Ganapati, Shweta Eikermann-Haerter, Katharina Ayata, Cenk Zhang, Ben Blobner, Manfred Isaacs, Lyle Eikermann, Matthias TI Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents SO ANESTHESIOLOGY LA English DT Article ID BLOCKADE; NEOSTIGMINE; ANTAGONISM; MUSCLE; ATRACURIUM; RATIO; HOST AB Background: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. Methods: The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine. Results:In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (K-a = 3.4 x 10(9) M-1 and K-a = 3.8 x 10(7) M-(1)). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate. Conclusions: Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats. C1 [Haerter, Friederike; Simons, Jeroen Cedric Peter; Duarte, Ingrid Moreno; Diaz-Gil, Daniel; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Haerter, Friederike; Simons, Jeroen Cedric Peter; Duarte, Ingrid Moreno; Diaz-Gil, Daniel; Eikermann-Haerter, Katharina; Ayata, Cenk; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Foerster, Urs; Blobner, Manfred] Tech Univ Munich, Klinikum Rechts Isar, Anesthesiol Clin, D-80290 Munich, Germany. [Ganapati, Shweta; Zhang, Ben; Isaacs, Lyle] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Eikermann-Haerter, Katharina; Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Eikermann, Matthias] Univ Duisburg Essen, Univ Hosp Essen, Dept Anesthesia & Crit Care Med, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM blobner@lrz.tum.de; lisaacs@umd.edu; meikermann@partners.org RI Isaacs, Lyle/B-4472-2009; Zhang, Ben/F-6580-2014 OI Isaacs, Lyle/0000-0002-4079-332X; FU Department of Anesthesia and Critical Care of the Massachusetts General Hospital (Boston, Massachusetss); National Institutes of Health (Bethesda, Maryland) [CA-168365] FX This study was supported by the Department of Anesthesia and Critical Care of the Massachusetts General Hospital (Boston, Massachusetss) and in part by the National Institutes of Health (Bethesda, Maryland; CA-168365). NR 33 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2015 VL 123 IS 6 BP 1337 EP 1349 DI 10.1097/ALN.0000000000000868 PG 13 WC Anesthesiology SC Anesthesiology GA CX1VL UT WOS:000365483600017 PM 26418697 ER PT J AU Cooper, Z Sayal, P Abbett, SK Neuman, MD Rickerson, EM Bader, AM AF Cooper, Zara Sayal, Puneet Abbett, Sarah K. Neuman, Mark D. Rickerson, Elizabeth M. Bader, Angela M. TI A Conceptual Framework for Appropriateness in Surgical Care Reviewing Past Approaches and Looking Ahead to Patient-centered Shared Decision Making SO ANESTHESIOLOGY LA English DT Article ID CAROTID-ENDARTERECTOMY; RISK; MEDICARE; DEFICITS; CRITERIA; OUTCOMES; SURGERY; FORMATS; COST C1 [Cooper, Zara; Bader, Angela M.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA USA. [Cooper, Zara] Brigham & Womens Hosp, Dept Surg, Boston, MA USA. [Cooper, Zara] Ariadne Labs, Boston, MA USA. [Sayal, Puneet] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Abbett, Sarah K.] St Francis Hosp & Med Ctr, Dept Obstet & Gynecol, Providence, RI USA. [Neuman, Mark D.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Rickerson, Elizabeth M.; Bader, Angela M.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Rickerson, Elizabeth M.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. RP Bader, AM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM abader@partners.org FU NIA NIH HHS [K08 AG043548] NR 22 TC 0 Z9 0 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 2015 VL 123 IS 6 BP 1450 EP 1454 DI 10.1097/ALN.0000000000000899 PG 5 WC Anesthesiology SC Anesthesiology GA CX1VL UT WOS:000365483600029 PM 26495980 ER PT J AU Hasegawa, K Calhoun, WJ Pei, YV Chasm, RM Youngquist, ST Bittner, JC Camargo, CA AF Hasegawa, Kohei Calhoun, William J. Pei, Y. Veronica Chasm, Rose M. Youngquist, Scott T. Bittner, Jane C. Camargo, Carlos A., Jr. TI Sex differences in hospital length of stay in children and adults hospitalized for asthma exacerbation SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID CARE; RISK C1 [Hasegawa, Kohei; Bittner, Jane C.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Calhoun, William J.] Univ Texas Med Branch, Dept Internal Med, Div Pulm Crit Care & Sleep Med, Galveston, TX 77555 USA. [Pei, Y. Veronica; Chasm, Rose M.] Univ Maryland, Med Ctr, Dept Emergency Med, Baltimore, MD 21201 USA. [Youngquist, Scott T.] Univ Utah, Med Ctr, Dept Emergency Med, Salt Lake City, UT USA. RP Hasegawa, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. EM khasegawa1@partners.org NR 9 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2015 VL 115 IS 6 BP 533 EP + PG 5 WC Allergy; Immunology SC Allergy; Immunology GA CX3PY UT WOS:000365612700020 PM 26481171 ER PT J AU Langdorf, MI Medak, AJ Hendey, GW Nishijima, DK Mower, WR Raja, AS Baumann, BM Anglin, DR Anderson, CL Lotfipour, S Reed, KE Zuabi, N Khan, NA Bithell, CA Rowther, AA Villar, J Rodriguez, RM AF Langdorf, Mark I. Medak, Anthony J. Hendey, Gregory W. Nishijima, Daniel K. Mower, William R. Raja, Ali S. Baumann, Brigitte M. Anglin, Deirdre R. Anderson, Craig L. Lotfipour, Shahram Reed, Karin E. Zuabi, Nadia Khan, Nooreen A. Bithell, Chelsey A. Rowther, Armaan A. Villar, Julian Rodriguez, Robert M. TI Prevalence and Clinical Import of Thoracic Injury Identified by Chest Computed Tomography but Not Chest Radiography in Blunt Trauma: Multicenter Prospective Cohort Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID X-RAY; CT; EFFICACY AB Study objective: Chest computed tomography (CT) diagnoses more injuries than chest radiography, so-called occult injuries. Wide availability of chest CT has driven substantial increase in emergency department use, although the incidence and clinical significance of chest CT findings have not been fully described. We determine the frequency, severity, and clinical import of occult injury, as determined by changes in management. These data will better inform clinical decisions, need for chest CT, and odds of intervention. Methods: Our sample included prospective data (2009 to 2013) on 5,912 patients at 10 Lever l' trauma center EDs with both chest radiography and chest CT at physician discretion. These patients were 40.6% of 14,553 enrolled in the parent study who had either chest radiography or chest CT. Occult injuries were pneumothorax, hemothorax, sternal or greater than 2 rib fractures, pulmonary contusion, thoracic spine or scapula fracture, and diaphragm or great vessel injury found on chest CT but not on preceding chest radiography. A priori, we categorized thoracic injuries as major (having invasive procedures), minor (observation or inpatient pain control >24 hours), or of no clinical significance. Primary outcome was prevalence and proportion of occult injury with major interventions of chest tube, mechanical ventilation, or surgery. Secondary outcome was minor interventions of admission rate or observation hours because of occult injury. Results: Two thousand forty-eight patients (34.6%) had chest injury on chest radiography or chest CT, whereas 1,454 of these patients (71.0%, 24.6% of all patients) had occult injury. Of these, in 954 patients (46.6% of injured, 16.1% of total), chest CT found injuries not observed on immediately preceding chest radiography. In 500 more patients (24.4% of injured patients, 8.5% of all patients), chest radiography found some injury, but chest CT found occult injury. Chest radiography found all injuries in only 29.0% of injured patients. Two hundred and two patients with occult injury (of 1,454, 13.9%) had major interventions, 343 of 1,454 (23.6%) had minor interventions, and 909 (62.5%) had no intervention. Patients with occult injury included 514 with pulmonary contusions (of 682 total, 75.4% occult), 405 with pneumothorax (of 597 total, 67.8% occult), 184 with hemothorax (of 230 total, 80.0% occult), those with greater than 2 rib fractures (n=672/1,120, 60.0% occult) or sternal fracture (n=269/281, 95.7% occult), 12 with great vessel injury (of 18 total, 66.7% occult), 5 with diaphragm injury (of 6, 83.3% occult), and 537 with multiple occult injuries. Interventions for patients with occult injury included mechanical ventilation for 31 of 514 patients with pulmonary contusion (6.0%), chesttube for 118 of 405 patients with pneumothorax (29.1%), and 75 of 184 patients with hemothorax (40.8%). Inpatient pain control or observation greater than 24 hours was conducted for 183 of 672 patients with rib fractures (27.2%) and 79 of 269 with sternal fractures (29.4%). Three of 12 (25%) patients with occult great vessel injuries had surgery. Repeated imaging was conducted for 50.6% of patients with occult injury (88.1% chest radiography, 11.9% chest CT, 7.5% both). For patients with occult injury, 90.9% (1,321/1,454) were admitted, with 9.1% observed in the ED for median 6.9 hours. Forty-four percent of observed patients were then admitted (4.0% of patients with occult injury). Conclusion: In a more seriously injured subset of patients with blunt trauma who had both chest radiography and chest CT, occult injuries were found by chest CT in 71% of those with thoracic injuries and one fourth of all those with blunt chest trauma. More than one third of occult injury had intervention (37.5%). Chest tubes composed 76.2% of occult injury major interventions, with observation or inpatient pain control greater than 24 hours in 32.4% of occult fractures. Only 1 in 20 patients with occult injury was discharged home from the ED. For these patients with blunt trauma, chest CT is useful to identify otherwise occult injuries. C1 [Langdorf, Mark I.; Anderson, Craig L.; Lotfipour, Shahram; Reed, Karin E.; Zuabi, Nadia; Khan, Nooreen A.; Bithell, Chelsey A.; Rowther, Armaan A.] Univ Calif Irvine, Dept Emergency Med, Orange, CA 92668 USA. [Medak, Anthony J.] Univ Calif San Diego, Dept Emergency Med, La Jolla, CA 92093 USA. [Hendey, Gregory W.] Univ Calif San Francisco, Dept Emergency Med, Fresno, CA USA. [Nishijima, Daniel K.] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA. [Mower, William R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA. [Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Baumann, Brigitte M.] Rowan Univ, Cooper Med Sch, Dept Emergency Med, Camden, NJ USA. [Anglin, Deirdre R.] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles, CA 90033 USA. [Villar, Julian; Rodriguez, Robert M.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA. RP Langdorf, MI (reprint author), Univ Calif Irvine, Dept Emergency Med, Orange, CA 92668 USA. EM mark.langdorf@uci.edu OI Hendey, Gregory/0000-0002-0170-8743 FU NCIPC CDC HHS [1 R01/CE001589-01] NR 22 TC 10 Z9 10 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD DEC PY 2015 VL 66 IS 6 BP 589 EP 600 DI 10.1016/j.annemergmed.2015.06.003 PG 12 WC Emergency Medicine SC Emergency Medicine GA CX6RG UT WOS:000365828500008 PM 26169926 ER PT J AU Ballard, DW Kim, AS Huang, J Park, DK Kene, MV Chettipally, UK Iskin, HR Hsu, J Vinson, DR Mark, DG Reed, ME AF Ballard, Dustin W. Kim, Anthony S. Huang, Jie Park, David K. Kene, Mamata V. Chettipally, Uli K. Iskin, Hilary R. Hsu, John Vinson, David R. Mark, Dustin G. Reed, Mary E. CA KP CREST Network Investigators TI Implementation of Computerized Physician Order Entry Is Associated With Increased Thrombolytic Administration for Emergency Department Patients With Acute Ischemic Stroke SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; ELECTRONIC HEALTH RECORDS; INTRAVENOUS THROMBOLYSIS; PERFORMANCE-MEASURES; UNITED-STATES; OUTCOMES; MORTALITY; CARE; OUTPATIENT; DISEASE AB Study objective: Electronic health record systems with computerized physician order entry and condition-specific order sets are intended to standardize patient management and minimize errors of omission. However, the effect of these systems on disease-specific process measures and patient outcomes is not well established. We seek to evaluate the effect of computerized physician order entry electronic health record implementation on process measures and short-term health outcomes for patients hospitalized with acute ischemic stroke. Methods: We conducted a quasi-experimental cohort study of patients hospitalized for acute ischemic stroke with concurrent controls that took advantage of the staggered implementation of a comprehensive computerized physician order entry electronic health record across 16 medical centers within an integrated health care delivery system from 2007 to 2012. The study population included all patients admitted to the hospital from the emergency department (ED) for acute ischemic stroke, with an initial neuroimaging study within 2.5 hours of ED arrival. We evaluated the association between the availability of a computerized physician order entry electronic health record and the rates of ED intravenous tissue plasminogen activator administration, hospital-acquired pneumonia, and inhospital and 90-day mortality, using doubly robust estimation models to adjust for demographics, comorbidities, secular trends, and concurrent primary stroke center certification status at each center. Results: Of 10,081 eligible patients, 6,686 (66.3%) were treated in centers after the computerized physician order entry electronic health record had been implemented. Computerized physician order entry was associated with significantly higher rates of intravenous tissue plasminogen activator administration (rate difference 3.4%; 95% confidence interval 0.8% to 6.0%) but not with significant rate differences in pneumonia or mortality. Conclusion: For patients hospitalized for acute ischemic stroke, computerized physician order entry use was associated with increased use of intravenous tissue plasminogen activator. C1 [Ballard, Dustin W.] Kaiser Permanente, San Rafael Med Ctr, San Rafael, CA 94903 USA. [Ballard, Dustin W.; Huang, Jie; Iskin, Hilary R.; Vinson, David R.; Reed, Mary E.] Kaiser Permanente, Div Res, Oakland, CA USA. [Kim, Anthony S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Park, David K.; Kene, Mamata V.] Kaiser Permanente, San Leandro Med Ctr, San Leandro, CA USA. [Chettipally, Uli K.] Kaiser Permanente, South San Francisco Med Ctr, San Francisco, CA USA. [Hsu, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy,Dept Hlth Care Policy, Boston, MA USA. [Vinson, David R.] Kaiser Permanente, Roseville Med Ctr, Roseville, CA USA. [Mark, Dustin G.] Kaiser Permanente, Oakland Med Ctr, Oakland, CA USA. RP Ballard, DW (reprint author), Kaiser Permanente, San Rafael Med Ctr, San Rafael, CA 94903 USA. EM dustin.ballard@kp.org FU Kaiser Foundation Research Institute Community Benefit Grant Program FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: This study was supported by a grant from the Kaiser Foundation Research Institute Community Benefit Grant Program. Dr. Ballard received travel support from the funding agency to present the preliminary results of this study at the plenary session of the Society for Academic Emergency Medicine annual meeting. NR 51 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD DEC PY 2015 VL 66 IS 6 BP 601 EP 610 DI 10.1016/j.annemergmed.2015.07.018 PG 10 WC Emergency Medicine SC Emergency Medicine GA CX6RG UT WOS:000365828500009 PM 26362574 ER PT J AU Wilcox, SR Kabrhel, C Channick, RN AF Wilcox, Susan R. Kabrhel, Christopher Channick, Richard N. TI Pulmonary Hypertension and Right Ventricular Failure in Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Review ID CONGESTIVE-HEART-FAILURE; CHEST COMPUTED-TOMOGRAPHY; SLEEP-APNEA SYNDROME; INTENSIVE-CARE-UNIT; ARTERIAL-HYPERTENSION; MANAGEMENT STRATEGIES; NATRIURETIC PEPTIDE; NONCARDIAC SURGERY; SEPTIC SHOCK; NITRIC-OXIDE AB Pulmonary hypertension is a hemodynamic condition, defined as a mean pulmonary artery pressure by right-sided heart catheterization of at least 25 mm Hg at rest. It is classified into 5 general groups based on the underlying cause, with left ventricular failure and chronic obstructive pulmonary disease being 2 of the most common causes in the United States. Although the specifics of the pathophysiology will vary with the cause, appreciating the risks of pulmonary hypertension and right ventricular failure is critical to appropriately evaluating and resuscitating pulmonary hypertension patients in the emergency department (ED). Patients may present to the ED with complaints related to pulmonary hypertension or unrelated ones, but this condition will affect all aspects of care. Exertional dyspnea is the most common symptom attributable to pulmonary hypertension, but the latter should be considered in any ED patient with unexplained dyspnea on exertion, syncope, or signs of right ventricular dysfunction. Patients with right ventricular failure are often volume overloaded, and careful volume management is imperative, especially in the setting of hypotension. Vasopressors and inotropes, rather than fluid boluses, are often required in shock to augment cardiac output and reduce the risk of exacerbating right ventricular ischemia. Intubation should be avoided if possible, although hypoxemia and hypercapnia may also worsen right-sided heart function. Emergency physicians should appreciate the role of pulmonary vasodilators in the treatment of pulmonary arterial hypertension and recognize that patients receiving these medications may rapidly develop right ventricular failure and even death without these therapies. Patients may require interventions not readily available in the ED, such as a pulmonary artery catheter, inhaled pulmonary vasodilators, and mechanical support with a right ventricular assist device or extracorporeal membrane oxygenation. Therefore, early consultation with a pulmonary hypertension specialist and transfer to a tertiary care center with invasive monitoring and mechanical support capabilities is advised. C1 [Wilcox, Susan R.; Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Channick, Richard N.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02114 USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM susanrwilcoxmd@gmail.com OI Kabrhel, Christopher/0000-0002-8699-7176 FU Massachusetts General Hospital; Actelion; Bayer; United Therapeutics FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This study was supported by Massachusetts General Hospital. Dr. Channick has been a consultant for and has received research grants from Actelion, Bayer, and United Therapeutics. NR 69 TC 1 Z9 1 U1 3 U2 26 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD DEC PY 2015 VL 66 IS 6 BP 619 EP 628 DI 10.1016/j.annemergmed.2015.07.525 PG 10 WC Emergency Medicine SC Emergency Medicine GA CX6RG UT WOS:000365828500013 PM 26342901 ER PT J AU Libby, P King, K AF Libby, Peter King, Kevin TI Biomarkers A Challenging Conundrum in Cardiovascular Disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE biological markers; clinical trial; laboratories; prognosis; risk assessment ID CORONARY-HEART-DISEASE; RISK; EVENTS; VALIDATION; PREVENTION; TROPONIN; WOMEN; PCSK9 AB The use of biomarkers has proven utility in cardiovascular medicine and holds great promise for future advances, but their application requires considerable rigor in thinking and methodology. Numerous confounding factors can cloud the clinical and investigative uses of biomarkers. Yet, the thoughtful and critical use of biomarkers can doubtless aid discovery of new pathogenic pathways, identify novel therapeutic targets, and provide a bridge between the laboratory and the clinic. Biomarkers can provide diagnostic and prognostic tools to the practitioner. The careful application of biomarkers can also help design and guide clinical trials required to establish the efficacy of novel interventions to improve patient outcomes. Point of care testing, technological advances, such as microfluidic and wearable devices, and the power of omics approaches all promise to elevate the potential contributions of biomarkers to discovery science, translation, clinical trials, and the practice of cardiovascular medicine. C1 [Libby, Peter; King, Kevin] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [King, Kevin] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu FU National Heart, Lung, and Blood Institute [1K99HL129168-01, R01 HL080472]; National Institutes of Health [U01 HL080731]; LaDue Fellowship from Harvard Medical School FX This work was funded by research support from the National Heart, Lung, and Blood Institute (1K99HL129168-01 to K. King and R01 HL080472 to P. Libby), the National Institutes of Health (U01 HL080731 to P. Libby), and the LaDue Fellowship from Harvard Medical School (to K. King). NR 32 TC 1 Z9 2 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2015 VL 35 IS 12 BP 2491 EP 2495 DI 10.1161/ATVBAHA.115.305233 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CX3JE UT WOS:000365594100003 PM 26543097 ER PT J AU Dodson, KH Echevarria, FD Li, DY Sappington, RM Edd, JF AF Dodson, Kirsten H. Echevarria, Franklin D. Li, Deyu Sappington, Rebecca M. Edd, Jon F. TI Retina-on-a-chip: a microfluidic platform for point access signaling studies SO BIOMEDICAL MICRODEVICES LA English DT Article DE Microfluidic tissue culture; Retina; Microenvironment ID CELL CULTURE ARRAY; MICROGLIAL CELLS; GANGLION-CELLS; LIPOPOLYSACCHARIDE; BRAIN; INTERLEUKIN-6; TRANSPORT; MEMBRANE; DESIGN; NEURODEGENERATION AB We report on a microfluidic platform for culture of whole organs or tissue slices with the capability of point access reagent delivery to probe the transport of signaling events. Whole mice retina were maintained for multiple days with negative pressure applied to tightly but gently bind the bottom of the retina to a thin poly-(dimethylsiloxane) membrane, through which twelve 100 mu m diameter through-holes served as fluidic access points. Staining with toluidine blue, transport of locally applied cholera toxin beta, and transient response to lipopolysaccharide in the retina demonstrated the capability of the microfluidic platform. The point access fluidic delivery capability could enable new assays in the study of various kinds of excised tissues, including retina. C1 [Dodson, Kirsten H.; Li, Deyu; Edd, Jon F.] Vanderbilt Univ, Dept Mech Engn, Nashville, TN 37235 USA. [Echevarria, Franklin D.; Sappington, Rebecca M.] Vanderbilt Univ, Sch Med, Vanderbilt Eye Inst, Dept Ophthalmol & Visual Sci, Nashville, TN 37212 USA. [Edd, Jon F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Edd, Jon F.] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. RP Li, DY (reprint author), Vanderbilt Univ, Dept Mech Engn, Nashville, TN 37235 USA. EM deyu.li@vanderbilt.edu; rebecca.m.sappington@vanderbilt.edu; jonedd2@gmail.com RI Li, Deyu/D-2938-2012; OI Li, Deyu/0000-0001-8364-0924; Sappington, Rebecca/0000-0002-3136-9631; Echevarria, Franklin/0000-0003-2833-1373 FU National Eye Institute [RO1EY020496-01, P30EY08126]; Research to Prevent Blindness, Inc.; National Science Foundation [0909667, 1445197] FX This material is based upon work supported by the following grants 1) National Eye Institute - RO1EY020496-01 (RMS) and P30EY08126 (Vanderbilt Vision Research Center), 2) Research to Prevent Blindness, Inc. - Unrestricted Grant (Vanderbilt Eye Institute) and Career Development Award (RMS), and 3) National Science Foundation Graduate Research Fellowship Program under Grant No. 0909667 and 1445197. NR 45 TC 2 Z9 2 U1 5 U2 18 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 EI 1572-8781 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD DEC PY 2015 VL 17 IS 6 DI 10.1007/s10544-015-0019-x PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA CX4XT UT WOS:000365704800013 PM 26559199 ER PT J AU Bateman, BT Gagne, JJ AF Bateman, B. T. Gagne, J. J. TI The Obstetric Comorbidity Index predicts severe maternal morbidity SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Editorial Material C1 [Bateman, B. T.; Gagne, J. J.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, B. T.; Gagne, J. J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bateman, B. T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 EI 1471-0528 J9 BJOG-INT J OBSTET GY JI BJOG PD DEC PY 2015 VL 122 IS 13 BP 1756 EP 1756 DI 10.1111/1471-0528.13297 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX1JJ UT WOS:000365452200006 PM 25639706 ER PT J AU Albiges, L De Velasco, G Gray, KP Carol, HA Caella, M Mickey, SS Fay, AP Mcdermott, DF Atkins, MB Heng, DY Signoretti, S Choueiri, TK AF Albiges, Laurence De Velasco, Guillermo Gray, Kathryn P. Carol, Hallie A. Caella, Marcella Mickey, Suzanne S. Fay, Andre P. Mcdermott, David F. Atkins, Michael B. Heng, Daniel Y. Signoretti, Sabina Choueiri, Toni K. TI The impact of MET expression on patient outcomes with metastatic renal cell carcinoma (mRCC) treated with VEGF-targeted therapy (TT) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL DE MET; mRCC; IHC; VEGF TI C1 [Albiges, Laurence; De Velasco, Guillermo; Gray, Kathryn P.; Carol, Hallie A.; Caella, Marcella; Mickey, Suzanne S.; Fay, Andre P.; Mcdermott, David F.; Signoretti, Sabina; Choueiri, Toni K.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Albiges, Laurence; De Velasco, Guillermo; Gray, Kathryn P.; Caella, Marcella; Mickey, Suzanne S.; Fay, Andre P.; Mcdermott, David F.; Atkins, Michael B.; Signoretti, Sabina] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Albiges, Laurence; De Velasco, Guillermo; Gray, Kathryn P.; Caella, Marcella; Mickey, Suzanne S.; Fay, Andre P.; Mcdermott, David F.; Heng, Daniel Y.; Signoretti, Sabina] Tom Baker Canc Clin, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 1 EP 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900003 ER PT J AU Choueiri, TK Michaelson, MD Posadas, EM Sonpavde, GP Mcdermott, DF Sean, BK Jivani, MA Adams, BJ Theuer, CP AF Choueiri, T. K. Michaelson, M. D. Posadas, E. M. Sonpavde, G. P. Mcdermott, D. F. Sean, B. K. Jivani, M. A. Adams, B. J. Theuer, C. P. TI A phase 1b dose-escalation study of TRC105 (anti-Endoglin Antibody) in combination with axitinib in patients with metastatic renal cell carcinoma (mRCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Posadas, E. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Sonpavde, G. P.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Mcdermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sean, B. K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Jivani, M. A.; Adams, B. J.; Theuer, C. P.] TRACON Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 4 EP 5 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900010 ER PT J AU Choueiri, TK Agarwal, N Ho, TH Pachynski, R Pal, S Ryan, CW Vaena, D Lara, P Lawler, W Posadas, E Sonpavde, GP Wang, P Gabrail, N Hammers, HJ Merchan, J Olencki, T Redman, B Sean, BK Adams, BJ Theuer, CP AF Choueiri, Toni K. Agarwal, Neeraj Ho, Thai H. Pachynski, Russell Pal, Sumanta Ryan, Christopher W. Vaena, Daniel Lara, Primo Lawler, William Posadas, Edwin Sonpavde, Guru P. Wang, Peng Gabrail, Nashat Hammers, Hans-Joerg Merchan, Jaime Olencki, Thomas Redman, Bruce Sean, Ben K. Adams, Bonne J. Theuer, Charles P. TI TRAXAR study: a randomized phase 2 trial of axitinib and TRC105 versus AXitinib alone in patients with advanced or metastatic renal cell carcinoma (mRCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Choueiri, Toni K.; Theuer, Charles P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Ho, Thai H.] Mayo Clin, Scottsdale, AZ USA. [Pachynski, Russell] Washington Univ, St Louis, MO USA. [Pal, Sumanta] City Hope Natl Med Ctr, Durante, CA USA. [Ryan, Christopher W.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Vaena, Daniel] Univ Iowa, Iowa City, IA USA. [Lara, Primo] Univ Calif Davis, Sacramento, CA 95817 USA. [Lawler, William] St Joseph Heritage Healthcare, Fullerton, CA USA. [Posadas, Edwin] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Sonpavde, Guru P.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Wang, Peng] Univ Kentucky, Lexington, KY USA. [Gabrail, Nashat] Gabrail Canc Ctr, Canton, OH USA. [Hammers, Hans-Joerg] Johns Hopkins Univ, Baltimore, MD USA. [Merchan, Jaime] Univ Miami, Miami, FL USA. [Olencki, Thomas] Ohio State Univ, Columbus, OH 43210 USA. [Redman, Bruce] Univ Michigan, Ann Arbor, MI 48109 USA. [Sean, Ben K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Adams, Bonne J.] TRACON Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 5 EP 6 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900012 ER PT J AU Choueiri, TK Plimack, ER Gupta, S Puzanov, I Mcdermott, DF Tarazi, J Keefe, S Rosbrook, B Atkins, MB AF Choueiri, Toni K. Plimack, Elizabeth R. Gupta, Shilpa Puzanov, Igor Mcdermott, David F. Tarazi, Jamal Keefe, Stephen Rosbrook, Brad Atkins, Michael B. TI Phase lb dose-finding study of axitinib plus pembrolizumab in treatment-naive patients with advanced renal cell carcinoma SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Gupta, Shilpa] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Mcdermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tarazi, Jamal; Rosbrook, Brad] Pfizer Oncol, San Diego, CA USA. [Keefe, Stephen] Merck Res Labs, N Wales, PA USA. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 5 EP 5 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900011 ER PT J AU Gill, D Agarwal, N Stenehjem, D Agarwa, FA Salama, M Merriman, J Freeman, GJ Choueiri, TK Signoretti, S AF Gill, David Agarwal, Neeraj Stenehjem, David Agarwa, Archana F. Salama, Mohamad Merriman, Joseph Freeman, Gordon J. Choueiri, Toni K. Signoretti, Sabina TI Correlation of tumor programmed death ligand-1 (PD-Ll) expression and response to treatment with high-dose interleukin-2 (HD IL-2) in metastatic clear cell renal cell carcinoma (mccRCC). SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Gill, David; Agarwal, Neeraj; Stenehjem, David; Agarwa, Archana F.; Merriman, Joseph] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Salama, Mohamad] Univ Utah, ARUP Labs, Dept Pathol, Salt Lake City, UT USA. [Freeman, Gordon J.; Choueiri, Toni K.; Signoretti, Sabina] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 8 EP 9 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900018 ER PT J AU Mahoney, KM Sun, H Liaols, X Hual, P Callea, M Greenfield, EA Hodils, FS Sharpe, AH Signoretti, S Rodig, SJ Freemanl, GJ AF Mahoney, Kathleen M. Sun, Heather Liaols, Xiaoyun Hual, Ping Callea, Marcella Greenfield, Edward A. Hodils, F. Stephen Sharpe, Arlene H. Signoretti, Sabina Rodig, Scott J. Freemanl, Gordon J. TI Different patterns of immunohistochemical staining of PD-Ll in tumors SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Mahoney, Kathleen M.; Greenfield, Edward A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mahoney, Kathleen M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02115 USA. [Sun, Heather; Callea, Marcella; Signoretti, Sabina; Rodig, Scott J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 16 EP 16 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900031 ER PT J AU Motzer, RJ Escudier, B Mcdermott, DF George, S Hammers, HJ Srinivas, S Tykodi, SS Sosman, JA Procopio, G Plimack, ER Castellano, D Gurney, H Donskov, F Bono, P Wagstaff, J Gauler, TC Ueda, T Xu, LA Waxman, IM Sharma, P AF Motzer, Robert J. Escudier, Bernard Mcdermott, David F. George, Saby Hammers, Hans J. Srinivas, Sandhya Tykodi, Scott S. Sosman, Jeffrey A. Procopio, Giuseppe Plimack, Elizabeth R. Castellano, Daniel Gurney, Howard Donskov, Frede Bono, Petri Wagstaff, John Gauler, Thomas C. Ueda, Takeshi Xu, Li-An Waxman, Ian M. Sharma, Padmanee CA Checkmate 025 Invest TI CheckMate 025: a randomized, open-label, phase Ill study of nivolumab versus everolimus in advanced renal cell carcinoma (RCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Escudier, Bernard] Inst Gustave Roussy, Villejuif, France. [Mcdermott, David F.] Dana Farber Harvard Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA USA. [George, Saby] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Hammers, Hans J.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Srinivas, Sandhya] Stanford Canc Inst, Stanford, CA USA. [Tykodi, Scott S.] Univ Washington, Seattle, WA 98195 USA. [Tykodi, Scott S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sosman, Jeffrey A.] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. [Procopio, Giuseppe] Fdn Ist Nazl Tumori, Milan, Italy. [Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Castellano, Daniel] Hosp Univ 12 De Octubre, Madrid, Spain. [Gurney, Howard] Westmead Hosp, Westmead, NSW, Australia. [Donskov, Frede] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Bono, Petri] Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Bono, Petri] Univ Helsinki, Helsinki, Finland. [Wagstaff, John] South West Wales Canc Inst, Swansea, W Glam, Wales. [Wagstaff, John] Swansea Univ, Coll Med, Swansea, W Glam, Wales. [Gauler, Thomas C.] Univ Duisburg Essen, Univ Hosp Essen, Essen, Germany. [Ueda, Takeshi] Chiba Canc Ctr, Chiba 2608717, Japan. [Xu, Li-An] Bristol Myers Squibb Co, Hopewell, NJ USA. [Waxman, Ian M.] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Sharma, Padmanee] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 17 EP 17 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900033 ER PT J AU Morales, JMR Wells, JC Donskov, F Bjarnason, GA Lee, JL Knox, JJ Beuselinck, B Vasihampayan, U Brugarolas, J Broom, R Koutsoukos, K Yuasa, T Srinivas, S Ernst, DS Pezaro, C Wood, LA Kollmannsberger, C Rini, BI Choueiri, TK Heng, DYC AF Morales, Jose Manuel Ruiz Wells, J. Connor Donskov, Frede Bjarnason, Georg A. Lee, Jae Lyun Knox, Jennifer J. Beuselinck, Benoit Vasihampayan, Ulka Brugarolas, James Broom, Reuben Koutsoukos, Konstantinos Yuasa, Takeshi Srinivas, Sandy Ernst, D. Scott Pezaro, Carmel Wood, Lori A. Kollmannsberger, Christian Rini, Brian I. Choueiri, Toni K. Heng, Daniel Y. C. TI First line sunitinib versus pazopanib in metastatic renal cell carcinoma: results from the international metastatic renal cell carcinoma database consortium SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Morales, Jose Manuel Ruiz] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Wells, J. Connor] Tom Baker Canc Clin, Calgary, AB, Canada. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Bjarnason, Georg A.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Lee, Jae Lyun] Univ Ulsan, Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea. [Knox, Jennifer J.] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Beuselinck, Benoit] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium. [Vasihampayan, Ulka] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Brugarolas, James] Univ Texas SW Med Ctr Dallas, Med Ctr, Dallas, TX 75390 USA. [Broom, Reuben] Auckland City Hosp, Auckland, New Zealand. [Koutsoukos, Konstantinos] Univ Athens, Dept Clin Therapeut, Athens, Greece. [Yuasa, Takeshi] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan. [Srinivas, Sandy] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Ernst, D. Scott] London Reg Canc Ctr, London, ON N6A 4L6, Canada. [Pezaro, Carmel] Royal Marsden NHS Fdn Trust, Inst Canc Res, Sutton, Surrey, England. [Wood, Lori A.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Kollmannsberger, Christian] BC Canc Agcy, Vancouver Canc Ctr, Vancouver, BC, Canada. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 20 EP 20 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900040 ER PT J AU Stukalina, I Wellsa, JC Donskovb, F Rinic, BI Leed, JL Bjarnasone, GA Beuselinckf, B Smoragiewicz, M Alvah, AS Srinivasi, S Woodi, L Saleemk, S Pal, SK Yuasam, T Broomn, RJ Kanesvaran, R Bamiasp, A Knoxq, JJ Henga, DYC Choueirir, TK AF Stukalina, Igor Wellsa, J. Connor Donskovb, Frede Rinic, Brian I. Leed, Jae-Lyun Bjarnasone, Georg A. Beuselinckf, Benoit Smoragiewicz, Martin Alvah, Ajjai Shivaram Srinivasi, Sandy Woodi, Lori Saleemk, Sadia Pal, Sumanta Kumar Yuasam, Takeshi Broomn, Reuben James Kanesvaran, Ravindran Bamiasp, Aristotelis Knoxq, Jennifer J. Henga, Daniel Y. C. Choueirir, Toni K. TI Third line therapy in metastatic renal cell carcinoma (mRCC): results from the international mRCC database consortium (IMDC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 14th International Kidney Cancer Symposium CY NOV 06-07, 2015 CL Miami, FL C1 [Stukalina, Igor; Pal, Sumanta Kumar] Tom Baker Canc Clin, Calgary, AB, Canada. [Wellsa, J. Connor] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Donskovb, Frede] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Rinic, Brian I.] Asan Med Ctr, Seoul, South Korea. [Leed, Jae-Lyun] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Bjarnasone, Georg A.] Univ Hosp Leuven, Leuven, Belgium. [Beuselinckf, Benoit] BC Canc Agcy, Vancouver, BC, Canada. [Smoragiewicz, Martin] Univ Michigan, Ann Arbor, MI 48109 USA. [Alvah, Ajjai Shivaram] Stanford Med Ctr, Stanford, CA USA. [Srinivasi, Sandy] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Woodi, Lori] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Saleemk, Sadia] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Yuasam, Takeshi] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo, Japan. [Broomn, Reuben James] Auckland City Hosp, Auckland, New Zealand. [Kanesvaran, Ravindran] Natl Canc Ctr Singapore, Singapore, Singapore. [Bamiasp, Aristotelis] Univ Athens, Athens 11528, Greece. [Knoxq, Jennifer J.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Henga, Daniel Y. C.; Choueirir, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2015 VL 116 SU 5 SI SI BP 21 EP 21 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA CY3CD UT WOS:000366284900042 ER PT J AU Mitsui, Y Chang, I Fukuhara, S Hiraki, M Arichi, N Yasumoto, H Hirata, H Yamamura, S Shahryari, V Deng, G Wong, DK Majid, S Shiina, H Dahiya, R Tanaka, Y AF Mitsui, Yozo Chang, Inik Fukuhara, Shinichiro Hiraki, Miho Arichi, Naoko Yasumoto, Hiroaki Hirata, Hiroshi Yamamura, Soichiro Shahryari, Varahram Deng, Guoren Wong, Darryn K. Majid, Shahana Shiina, Hiroaki Dahiya, Rajvir Tanaka, Yuichiro TI CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma SO BMC CANCER LA English DT Article DE Cytochrome 450 1B1; Renal cell carcinoma; Apoptosis; CDC20; DAPK1 ID SPINDLE ASSEMBLY CHECKPOINT; POOR-PROGNOSIS; PROTEIN-KINASE; CYTOCHROME-P450 1B1; KIDNEY CANCER; IN-VITRO; OVEREXPRESSION; METHYLATION; DEATH; CARCINOGENESIS AB Background: Cytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC. Methods: Expression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses. Results: First, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples. Conclusions: CYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC. C1 [Mitsui, Yozo; Hiraki, Miho; Arichi, Naoko; Yasumoto, Hiroaki; Shiina, Hiroaki] Shimane Univ, Fac Med, Dept Urol, Izumo, Shimane 6938501, Japan. [Mitsui, Yozo; Hirata, Hiroshi; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Wong, Darryn K.; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA. [Mitsui, Yozo; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Wong, Darryn K.; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Chang, Inik] Yonsei Univ, Coll Dens, Dept Oral Biol, Seoul 120749, South Korea. [Chang, Inik; Fukuhara, Shinichiro] Osaka Univ, Grad Sch Med, Dept Urol, Suita, Osaka 5650871, Japan. RP Mitsui, Y (reprint author), Shimane Univ, Fac Med, Dept Urol, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan. EM mitsui@med.shimane-u.ac.jp; Yuichiro.tanaka@ucsf.edu NR 44 TC 3 Z9 3 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD DEC 1 PY 2015 VL 15 AR 942 DI 10.1186/s12885-015-1951-0 PG 12 WC Oncology SC Oncology GA CX1YB UT WOS:000365490600002 PM 26626260 ER PT J AU Nicholas, CR Okonkwo, OC Bendlin, BB Oh, JM Asthana, S Rowley, HA Hermann, B Sager, MA Johnson, SC AF Nicholas, Christopher R. Okonkwo, Ozioma C. Bendlin, Barbara B. Oh, Jennifer M. Asthana, Sanjay Rowley, Howard A. Hermann, Bruce Sager, Mark A. Johnson, Sterling C. TI Posteromedial hyperactivation during episodic recognition among people with memory decline: findings from the WRAP study SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Alzheimer's; Preclinical; Cognition; Functional neuroimaging; Neuropsychological ID MILD COGNITIVE IMPAIRMENT; MIDDLE-AGED ADULTS; ALZHEIMERS-DISEASE; HIPPOCAMPAL ACTIVATION; BRAIN ACTIVATION; GENETIC RISK; OLDER-ADULTS; LIFE-SPAN; PATTERNS; INDIVIDUALS AB Episodic memory decline is one of the earliest preclinical symptoms of AD, and has been associated with an upregulation in the BOLD response in the prodromal stage (e.g. MCI) of AD. In a previous study, we observed upregulation in cognitively normal (CN) subjects with subclinical episodic memory decline compared to non-decliners. In light of this finding, we sought to determine if a separate cohort of Decliners will show increased brain activation compared to Stable subjects during episodic memory processing, and determine whether the BOLD effect was influenced by cerebral blood flow (CBF) or gray matter volume (GMV). Individuals were classified as a "Decliner" if scores on the Rey Auditory Verbal Learning Test (RAVLT) consistently fell a parts per thousand yenaEuro parts per thousand 1.5 SD below expected intra- or inter-individual levels. FMRI was used to compare activation during a facial recognition memory task in 90 Stable (age = 59.1) and 34 Decliner (age = 62.1, SD = 5.9) CN middle-aged adults and 10 MCI patients (age = 72.1, SD = 9.4). Arterial spin labeling and anatomical T1 MRI were used to measure resting CBF and GMV, respectively. Stables and Decliners performed similarly on the episodic recognition memory task and significantly better than MCI patients. Compared to Stables, Decliners showed increased BOLD signal in the left precuneus on the episodic memory task that was not explained by CBF or GMV, familial AD risk factors, or neuropsychological measures. These findings suggest that subtle changes in the BOLD signal reflecting altered neural function may be a relatively early phenomenon associated with memory decline. C1 [Nicholas, Christopher R.; Okonkwo, Ozioma C.; Asthana, Sanjay; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Nicholas, Christopher R.; Okonkwo, Ozioma C.; Bendlin, Barbara B.; Hermann, Bruce; Sager, Mark A.; Johnson, Sterling C.] Univ Wisconsin, Wisconsin Alzheimers Inst, Sch Med & Publ Hlth, Madison, WI USA. [Nicholas, Christopher R.; Okonkwo, Ozioma C.; Bendlin, Barbara B.; Oh, Jennifer M.; Asthana, Sanjay; Rowley, Howard A.; Sager, Mark A.; Johnson, Sterling C.] Univ Wisconsin, Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace,11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU NIA [R01 AG021155, R01 AG027161]; Veterans Administration Merit Review Grant [I01CX000165]; Veterans Administration Geriatrics Research and Clinical Center (GRECC) Advanced Fellowship in Geriatrics and Aging at the William S. Middleton Memorial Veterans Hospital, Madison, WI; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Veterans Administration FX This research was supported by NIA grants R01 AG021155 and R01 AG027161 (SCJ): by a Veterans Administration Merit Review Grant I01CX000165 (SCJ); and by a Veterans Administration Geriatrics Research and Clinical Center (GRECC) Advanced Fellowship in Geriatrics and Aging at the William S. Middleton Memorial Veterans Hospital, Madison, WI (CRN). Portions of this research were supported by the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, and from the Veterans Administration including facilities and resources at the GRECC, Madison, WI. NR 47 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2015 VL 9 IS 4 BP 690 EP 702 DI 10.1007/s11682-014-9322-z PG 13 WC Neuroimaging SC Neurosciences & Neurology GA CX5PX UT WOS:000365755500004 PM 25332108 ER PT J AU Schultz, SA Larson, J Oh, J Koscik, R Dowling, MN Gallagher, CL Carlsson, CM Rowley, HA Bendlin, BB Asthana, S Hermann, BP Johnson, SC Sager, M Larue, A Okonkwo, OC AF Schultz, Stephanie A. Larson, Jordan Oh, Jennifer Koscik, Rebecca Dowling, Maritza N. Gallagher, Catherine L. Carlsson, Cynthia M. Rowley, Howard A. Bendlin, Barbara B. Asthana, Sanjay Hermann, Bruce P. Johnson, Sterling C. Sager, Mark LaRue, Asenath Okonkwo, Ozioma C. TI Participation in cognitively-stimulating activities is associated with brain structure and cognitive function in preclinical Alzheimer's disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Preclinical Alzheimer's disease; Cognitive activity; Brain imaging; Cognition; AD prevention ID SURFACE-BASED ANALYSIS; LIFE-STYLE ACTIVITIES; MEMORY DECLINE; LEISURE ACTIVITIES; DEVELOP DEMENTIA; ADULTS; RISK; INDIVIDUALS; PERFORMANCE; IMPAIRMENT AB This study tested the hypothesis that frequent participation in cognitively-stimulating activities, specifically those related to playing games and puzzles, is beneficial to brain health and cognition among middle-aged adults at increased risk for Alzheimer's disease (AD). Three hundred twenty-nine cognitively normal, middle-aged adults (age range, 43.2-73.8 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention (WRAP) participated in this study. They reported their current engagement in cognitive activities using a modified version of the Cognitive Activity Scale (CAS), underwent a structural MRI scan, and completed a comprehensive cognitive battery. FreeSurfer was used to derive gray matter (GM) volumes from AD-related regions of interest (ROIs), and composite measures of episodic memory and executive function were obtained from the cognitive tests. Covariate-adjusted least squares analyses were used to examine the association between the Games item on the CAS (CAS-Games) and both GM volumes and cognitive composites. Higher scores on CAS-Games were associated with greater GM volumes in several ROIs including the hippocampus, posterior cingulate, anterior cingulate, and middle frontal gyrus. Similarly, CAS-Games scores were positively associated with scores on the Immediate Memory, Verbal Learning & Memory, and Speed & Flexibility domains. These findings were not modified by known risk factors for AD. In addition, the Total score on the CAS was not as sensitive as CAS-Games to the examined brain and cognitive measures. For some individuals, participation in cognitive activities pertinent to game playing may help prevent AD by preserving brain structures and cognitive functions vulnerable to AD pathophysiology. C1 [Schultz, Stephanie A.; Larson, Jordan; Oh, Jennifer; Gallagher, Catherine L.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Asthana, Sanjay; Johnson, Sterling C.; Okonkwo, Ozioma C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. [Schultz, Stephanie A.; Larson, Jordan; Oh, Jennifer; Dowling, Maritza N.; Carlsson, Cynthia M.; Rowley, Howard A.; Bendlin, Barbara B.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark; LaRue, Asenath; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53705 USA. [Koscik, Rebecca; Dowling, Maritza N.; Bendlin, Barbara B.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark; LaRue, Asenath; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53705 USA. [Dowling, Maritza N.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Rowley, Howard A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Radiol, Madison, WI 53705 USA. [Gallagher, Catherine L.; Hermann, Bruce P.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53705 USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Alzheimers Dis Res Ctr, Madison, WI 53792 USA. RP Okonkwo, OC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. EM ozioma@medicine.wisc.edu OI Schultz, Stephanie/0000-0001-8460-4415; Bendlin, Barbara/0000-0002-0580-9875 FU National Institute on Aging [K23 AG045957, R01 AG027161, R01 AG021155, P50 AG033514, P50 AG033514-S1]; Veterans Administration Merit Review Grant [I01CX000165]; Clinical and Translational Science Award [UL1RR025011]; Wisconsin Alumni Research Foundation; Helen Bader Foundation; Northwestern Mutual Foundation; Extendicare Foundation; Veterans Administration FX This work was supported by National Institute on Aging grants K23 AG045957 (OCO), R01 AG027161 (MAS), R01 AG021155 (SCJ), P50 AG033514 (SA), and P50 AG033514-S1 (OCO); by a Veterans Administration Merit Review Grant I01CX000165 (SCJ); and by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Wisconsin Alumni Research Foundation, the Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation; and from the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 38 TC 4 Z9 4 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2015 VL 9 IS 4 BP 729 EP 736 DI 10.1007/s11682-014-9329-5 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA CX5PX UT WOS:000365755500007 PM 25358750 ER PT J AU Leyland-Jones, B Gray, KP Abramovitz, M Bouzyk, M Young, B Long, B Kammler, R Dell'Orto, P Biasi, MO Thurlimann, B Harvey, V Neven, P Arnould, L Maibach, R Price, KN Coates, AS Goldhirsch, A Gelber, RD Pagani, O Viale, G Rae, JM Regan, MM AF Leyland-Jones, Brian Gray, Kathryn P. Abramovitz, Mark Bouzyk, Mark Young, Brandon Long, Bradley Kammler, Roswitha Dell'Orto, Patrizia Biasi, Maria Olivia Thuerlimann, Beat Harvey, Vernon Neven, Patrick Arnould, Laurent Maibach, Rudolf Price, Karen N. Coates, Alan S. Goldhirsch, Aron Gelber, Richard D. Pagani, Olivia Viale, Giuseppe Rae, James M. Regan, Meredith M. CA BIG 1-98 Collaborative Grp TI ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE ESR1; ESR2; Letrozole; Tamoxifen; Polymorphism ID ESTROGEN-RECEPTOR GENOTYPES; ALPHA GENE POLYMORPHISMS; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; MENOPAUSAL STATUS; LIPID-LEVELS; NATION SWAN; RISK; THERAPY; PVUII AB Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models. 3401 samples were successfully genotyped for five SNPs. ESR1 rs9340799(XbaI) (T > C) variants CC or TC were associated with reduced breast cancer risk (HR = 0.82,95 % CI = 0.67-1.0), and ESR1 rs2077647 (T > C) variants CC or TC was associated with reduced distant recurrence risk (HR = 0.69, 95 % CI = 0.53-0.90), both regardless of the treatments. No differential treatment effects (letrozole vs. tamoxifen) were observed for the association of outcome with any of the SNPs. Letrozole-treated patients with rs2077647 (T > C) variants CC and TC had a reduced risk of bone AE (HR = 0.75, 95 % CI = 0.58-0.98, P (interaction) = 0.08), whereas patients with rs4986938 (G > A) genotype variants AA and AG had an increased risk of bone AE (HR = 1.37, 95 % CI = 1.01-1.84, P (interaction) = 0.07). We observed that (1) rare ESR1 homozygous polymorphisms were associated with lower recurrence, and (2) ESR1 and ESR2 SNPs were associated with bone AEs in letrozole-treated patients. Genes that are involved in estrogen signaling and synthesis have the potential to affect both breast cancer recurrence and side effects, suggesting that individual treatment strategies can incorporate not only oncogenic drivers but also SNPs related to estrogen activity. C1 [Leyland-Jones, Brian; Young, Brandon] Avera Canc Inst, Sioux Falls, SD 57105 USA. [Gray, Kathryn P.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Int Breast Canc Study Grp Stat Ctr, Dana Farber Canc Inst,Dept Biostat & Computat Bio, Boston, MA 02215 USA. [Abramovitz, Mark] VM Inst Res, Montreal, PQ H4P 2R2, Canada. [Bouzyk, Mark] AKESOgen Inc, Norcross, GA 30071 USA. [Long, Bradley] Univ Chicago, Genom & Mol Pathol, Chicago, IL 60637 USA. [Kammler, Roswitha] Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland. [Kammler, Roswitha] Cent Pathol Off, CH-3008 Bern, Switzerland. [Dell'Orto, Patrizia] European Inst Oncol, Cent Pathol Off, Int Breast Canc Study Grp, Div Pathol & Lab Med, I-20146 Milan, Italy. [Biasi, Maria Olivia] European Inst Oncol, Div Pathol & Lab Med, I-20146 Milan, Italy. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, CH-9007 St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Thuerlimann, Beat; Harvey, Vernon; Coates, Alan S.; Goldhirsch, Aron; Pagani, Olivia] Int Breast Canc Study Grp, Bern, Switzerland. [Harvey, Vernon] Auckland City Hosp, Auckland 1344, New Zealand. [Harvey, Vernon] Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. [Neven, Patrick] KULeuven Univ Leuven, Univ Hosp Leuven, Multidisciplinary Breast Ctr, Dept Oncol, B-3000 Leuven, Belgium. [Arnould, Laurent] Inst Georges Francois Leclerc, F-21079 Dijon, France. [Maibach, Rudolf] Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02215 USA. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Program Breast Hlth Senol, I-20146 Milan, Italy. [Gelber, Richard D.] Harvard Univ, Frontier Sci & Technol Res Fdn, Int Breast Canc Study Grp Stat Ctr, TH Chan Sch Publ Hlth,Sch Med,Dana Farber Canc In, Boston, MA 02215 USA. [Pagani, Olivia] Osped Italiano, IOSI, CH-6962 Viganello, Switzerland. [Viale, Giuseppe] Univ Milan, European Inst Oncol, Int Breast Canc Study Grp Cent Pathol Off, Div Pathol & Lab Med, I-20146 Milan, Italy. [Rae, James M.] Univ Michigan, Ctr Comprehens Canc, Div Hematol Oncol, Ann Arbor, MI 48109 USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr,Dept Biostat &, Boston, MA 02215 USA. RP Leyland-Jones, B (reprint author), Avera Canc Inst, 1000 E 23rd St, Sioux Falls, SD 57105 USA. EM bleylandj@aol.com; pkruan@jimmy.harvard.edu; mark.abramovitz@gmail.com; mbouzyk@akesogen.com; brandon.young@avera.org; bradley.long@uchospitals.edu; rosita.kammler@ibcsg.org; patrizia.dellorto@ieo.it; olivia.biasi@ieo.it; vernonh@adhb.govt.nz; patrick.neven@uzleuven.be; larnould@dijon.fnclcc.fr; rudolf.maibach@ibcsg.org; price@jimmy.harvard.edu; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org; gelber@jimmy.harvard.edu; olivia.pagani@ibcsg.org; giuseppe.viale@ieo.it; jimmyrae@med.umich.edu; mregan@jimmy.harvard.edu FU Novartis; Susan G. Komen for Cure [KG080081]; Breast Cancer Research Foundation (BCRF) [N003173]; National Institutes of Health [1RO1GM099143]; IBCSG: United States National Cancer Institute [CA75362] FX The BIG 1-98 trial sponsor, Novartis, contracted with the IBCSG to design the BIG 1-98 trial; collect, analyze, and interpret the data; and report the results. This report presents a study based on collected tumor material (collection partially funded by Novartis) and genotyping (funded by a Promise Grant from the Susan G. Komen for the Cure). The translational research, including DNA extraction and genotyping, was funded by Susan G. Komen for the Cure Promise Grant (KG080081 to GV, OP, MMR), the Breast Cancer Research Foundation (BCRF) (N003173 to JMR), and the National Institutes of Health (1RO1GM099143 to JMR). The Breast International Group (BIG) 1-98 trial was funded by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Other support for the IBCSG: United States National Cancer Institute (CA75362 to MMR). The writing of this manuscript did not include representatives from Novartis or Susan G. Komen for the Cure. The BIG 1-98 Steering Committee reviewed the article, suggested changes, and is responsible for the decision to publish. NR 38 TC 3 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2015 VL 154 IS 3 BP 543 EP 555 DI 10.1007/s10549-015-3634-6 PG 13 WC Oncology SC Oncology GA CX4XY UT WOS:000365705400010 PM 26590813 ER PT J AU Berkey, CS Rosner, B Willett, WC Tamimi, RM Frazier, AL Colditz, GA AF Berkey, Catherine S. Rosner, Bernard Willett, Walter C. Tamimi, Rulla M. Frazier, A. Lindsay Colditz, Graham A. TI Prenatal factors and infant feeding in relation to risk of benign breast disease in young women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Birth weight; Maternal pre-pregnancy BMI; Gestational weight gain; Breast-fed; Soy formula; BBD ID BODY-MASS INDEX; CANCER RISK; BIRTH-WEIGHT; AMERICAN WOMEN; NURSES HEALTH; EARLY-LIFE; PREGNANCY; OBESITY; ADOLESCENTS; PREVENTION AB Benign breast disease (BBD) is a well-established risk factor for breast cancer, but little work has considered a girl's early life and her risk for BBD in adulthood. We investigated factors, from pre-conception through infant feeding practices, in relation to subsequent BBD risk in young women. The Growing Up Today Study (GUTS) includes 9032 females, born 1980-1987, who completed questionnaires annually from 1996 through 2001, then 2003, 2005, 2007, 2010, and 2013. In 1996, their mothers provided each participant's birth weight and length, gestational age, biological father's height, and infant feeding factors (e.g., breast-fed, type of formula). In 1999, their mothers reported maternal pre-pregnancy weight and weight gain during index pregnancy. Beginning in 2005, daughters (18 years+) reported whether they had ever been diagnosed with biopsy-confirmed BBD (n = 142 cases, through 2013). Logistic regression estimated associations between early life factors and biopsy-confirmed BBD. Girls whose mother's BMI prior to pregnancy was 20-25 kg/m(2) were at lower risk of BBD as young women (OR = 0.66, p = 0.04, vs. maternal pre-pregnancy BMI < 20). Girls whose mothers gained 20 + pounds (vs. < 20 pounds) during pregnancy were at lower risk (among full-term singleton births: OR = 0.48, p = 0.007, if mother gained 20-35 pounds). However, neither birth weight nor BMI at birth were associated with subsequent BBD risk. We found no evidence that infant feeding practices were linked to BBD. A healthy maternal BMI before pregnancy and sufficient weight gain during pregnancy may produce daughters at lower risk for BBD as young women. Further examination of these findings is needed. C1 [Berkey, Catherine S.; Rosner, Bernard; Tamimi, Rulla M.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Berkey, Catherine S.; Rosner, Bernard; Tamimi, Rulla M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. RP Berkey, CS (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM Catherine.Berkey@channing.harvard.edu FU Breast Cancer Research Foundation (NYC, NY); National Institutes of Health (Bethesda, MD) [DK046834]; American Institute for Cancer Research; American Cancer Society Clinical Research Professorship FX Supported by a Grant from The Breast Cancer Research Foundation (NYC, NY) and by DK046834 from the National Institutes of Health (Bethesda, MD). Dr. Frazier was supported by an award from the American Institute for Cancer Research. Dr. Colditz was supported, in part, by an American Cancer Society Clinical Research Professorship. The authors appreciate the ongoing, since 1996, dedication of our female GUTS participants and their mothers in NHSII. NR 38 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2015 VL 154 IS 3 BP 573 EP 582 DI 10.1007/s10549-015-3637-3 PG 10 WC Oncology SC Oncology GA CX4XY UT WOS:000365705400013 PM 26582399 ER PT J AU Braunstein, LZ Galland-Girodet, S Goldberg, S Warren, LEG Sadek, BT Shenouda, MN Abi-Raad, RF MacDonald, SM Taghian, AG AF Braunstein, Lior Z. Galland-Girodet, Sigolene Goldberg, Saveli Warren, Laura E. G. Sadek, Betro T. Shenouda, Mina N. Abi-Raad, Rita F. MacDonald, Shannon M. Taghian, Alphonse G. TI Long-term outcomes among breast cancer patients with extensive regional lymph node involvement: implications for locoregional management SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Mastectomy; Lumpectomy; Recurrence; Radiotherapy ID HIGH-DOSE CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; LOCAL RECURRENCE; CELL SUPPORT; MASTECTOMY; THERAPY; WOMEN; RADIOTHERAPY; IRRADIATION AB Extensive lymph node (LN) involvement portends significant risk for distant metastasis (DM) among breast cancer patients. As a result, local management may be of secondary import to systemic control in this population. We analyzed patients with a parts per thousand yen10 involved LNs (N3) to evaluate the feasibility of breast conserving therapy (BCT) vs modified radical mastectomy (MRM) in this high-risk cohort. Among 98 women with N3 disease 46 (46.9 %) underwent BCT and 52 (53.1 %) received MRM. Nearly all patients (92 %) received comprehensive radiotherapy (RT) including axillary and supraclavicular fields. The Kaplan-Meier method and Cox regression analyses were used to analyze time-to-event outcomes. Median follow-up was 76 months, with a 5-year DFS of 64.9 % and OS of 71.9 % among the cohort. Poorly differentiated (p = 0.007), ER-negative tumors (p = 0.015) had adverse DFS outcomes. Treatment groups did not differ with regard to 10-year DFS (45.4 % for MRM vs. 57.6 % for BCT; p = 0.31), or OS (61.4 vs. 63.7 %; p = 0.79). DM-free survival was 48.9 % following MRM and 60.6 % following BCT (p = 0.19). Patients with a parts per thousand yen10 involved LNs have similar outcomes following BCT or MRM, suggesting that RT may obviate the need for more-extensive surgery. While local control is comparably favorable regardless of surgical approach, systemic control remains a challenge in this population. C1 [Braunstein, Lior Z.; Warren, Laura E. G.] Harvard Radiat Oncol Program, Boston, MA USA. [Galland-Girodet, Sigolene; Goldberg, Saveli; Sadek, Betro T.; Shenouda, Mina N.; Abi-Raad, Rita F.; MacDonald, Shannon M.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM lbraunstein@partners.org; ataghian@mgh.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2015 VL 154 IS 3 BP 633 EP 639 DI 10.1007/s10549-015-3642-6 PG 7 WC Oncology SC Oncology GA CX4XY UT WOS:000365705400019 PM 26585579 ER PT J AU Chamie, K Williams, SB Hershman, DL Wright, JD Nguyen, PL Hu, JC AF Chamie, Karim Williams, Stephen B. Hershman, Dawn L. Wright, Jason D. Nguyen, Paul L. Hu, Jim C. TI Population-based assessment of determining predictors for quality of prostate cancer surveillance SO CANCER LA English DT Article DE prostate cancer; quality; surveillance; treatments; use ID ACTIVE SURVEILLANCE; UNITED-STATES; MANAGEMENT; BIOPSY; MEN; PROPHYLAXIS; VALIDATION AB BACKGROUNDDespite recent interest in the overdiagnosis and overtreatment of prostate cancer, the acceptance of expectant management for patients with indolent prostate cancer has remained slow. Moreover, the intensity of surveillance strategies remains to be elucidated. The objective of this study was to determine the population-based intensity of surveillance strategy among patients diagnosed with localized prostate cancer who undergo watchful waiting/active surveillance and those who receive active treatment. METHODSLinked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify men diagnosed with prostate cancer from 2004 to 2007 who were followed until December 31, 2009. Bivariate and multivariate regression analyses were used to quantify the use of prostate-specific antigen tests, office visits, and second prostate biopsies within 2 years of diagnosis. RESULTSCompared with patients who were receiving active treatment, those who were undergoing watchful waiting/active surveillance were less likely to receive prostate-specific antigen testing and to attend office visits within the 2 years after diagnosis (P<.01). Of the 3656 patients who were undergoing watchful waiting/active surveillance, only 166 (4.5%) were on active surveillance (according to the authors' a priori definition), although the number increased over the last 2 years of the study (hazard ratio, 2.18; 95% confidence interval, 1.28-3.71; P<.01). Limitations of the study included data limited to men aged 65 years or older and the lack of ability to discern between watchful waiting and active surveillance. CONCLUSIONSActive surveillance is underused, and there is uncertainty regarding the quality of surveillance for patients who undergo watchful waiting/active surveillance. Further research is needed into qualitatively describing the contributing factors that drive decision-making recommendations as well as improved surveillance measures for patients with prostate cancer. Cancer 2015;121:4150-4157. (c) 2015 American Cancer Society. Compared with patients who receive active treatment, those assigned to watchful waiting/active surveillance are less likely to undergo prostate-specific antigen testing or to attend office visits within the 2 years after diagnosis. In this study, of 3656 patients who are assigned to watchful waiting/active surveillance, only 166 (4.5%) are on active surveillance (according to the authors' a priori definition), although this number increased over the last 2 years of the study. C1 [Chamie, Karim] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Williams, Stephen B.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Hershman, Dawn L.] Columbia Univ, Coll Phys & Surg, Dept Med Oncol, New York, NY USA. [Hershman, Dawn L.; Wright, Jason D.] Columbia Univ, Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Hershman, Dawn L.] New York Presbyterian Hosp, New York, NY USA. [Wright, Jason D.] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY USA. [Wright, Jason D.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Wright, Jason D.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Wright, Jason D.] New York Presbyterian Hosp, New York, NY USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hu, Jim C.] Weill Cornell Med Coll, Dept Urol, New York, NY USA. RP Hu, JC (reprint author), Weill Cornell Med Coll, Dept Urol, Lefrak Ctr Robot Surg, 525 East 68th St,Starr Pavilion,Ninth Floor, New York, NY 10065 USA. EM jimhumd@gmail.com FU Department of Defense Prostate Cancer Physician Training Award [W81XWH-08-1-0283]; National Institutes of Health [L30 CA154326] FX This work is supported by a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283; presented to Dr. Hu) and by the National Institutes of Health Loan Repayment Program (L30 CA154326; presented to Dr. Chamie). NR 30 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2015 VL 121 IS 23 BP 4150 EP 4157 DI 10.1002/cncr.29574 PG 8 WC Oncology SC Oncology GA CX3TJ UT WOS:000365621900009 PM 26307939 ER PT J AU Nayak, L DeAngelis, LM Robins, HI Govindan, R Gadgeel, S Kelly, K Rigas, JR Peereboom, DM Rosenfeld, SS Muzikansky, A Zheng, M Urban, P Abrey, LE Omuro, A Wen, PY AF Nayak, Lakshmi DeAngelis, Lisa M. Robins, H. Ian Govindan, Ramaswamy Gadgeel, Shirish Kelly, Karen Rigas, James R. Peereboom, David M. Rosenfeld, Steven S. Muzikansky, Alona Zheng, Ming Urban, Patrick Abrey, Lauren E. Omuro, Antonio Wen, Patrick Y. TI Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer SO CANCER LA English DT Article DE brain metastases; chemotherapy; non-small cell lung cancer; patupilone; recurrent metastases ID TYROSINE KINASE INHIBITORS; PRIMARY PERITONEAL CANCER; II TRIAL; IN-VIVO; RADIATION-THERAPY; CLINICAL-TRIALS; DOSE-ESCALATION; TARGETED AGENTS; BREAST-CANCER; OPEN-LABEL AB BACKGROUNDTreatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. METHODSAdult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m(2) every 3 weeks. The primary endpoint of this multinomial 2-stage study combined early progression (EP; death or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w) to determine drug activity. RESULTSFifty patients with a median age of 60 years (range, 33-74 years) were enrolled; the majority were men (58%), and most had received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas under the concentration-time curve from time zero to 504 hours for cycles 1 and 3 of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution volume of 755 L/m(2). Grade 3/4 adverse events (AEs), regardless of their relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of 32 deaths were due to brain metastases. The median time to progression and the overall survival were 3.2 and 8.8 months, respectively. CONCLUSIONSThis is the first prospective study of chemotherapy for recurrent brain metastases from NSCLC. In this population, patupilone demonstrated activity in heavily treated patients. Cancer 2015;121:4165-4172. (c) 2015 American Cancer Society. This is the first prospective study of chemotherapy for recurrent brain metastases from non-small cell lung cancer. In this population, patupilone demonstrates activity in heavily treated patients. C1 [Nayak, Lakshmi; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [DeAngelis, Lisa M.; Abrey, Lauren E.; Omuro, Antonio] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Robins, H. Ian] Univ Wisconsin Hosp & Clin, Dept Human Oncol, Madison, WI 53792 USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Gadgeel, Shirish] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Kelly, Karen] Univ Calif Sacramento, Div Hematol & Oncol, Davis Comprehens Canc Ctr, Sacramento, CA USA. [Rigas, James R.] Norris Cotton Canc Ctr, Dartmouth Hitchcock Med Ctr, Lebanon, NH USA. [Peereboom, David M.] Cleveland Clin, Burkhardt Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Rosenfeld, Steven S.] Columbia Univ, Dept Neurol, Med Ctr New York Presbyterian, New York, NY USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Zheng, Ming; Urban, Patrick] Novartis Pharmaceut, E Hanover, NJ USA. RP Nayak, L (reprint author), Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM lakshmi_nayak@dfci.harvard.edu OI Omuro, Antonio/0000-0003-4299-3664 FU Novartis Pharmaceuticals Corporation; Novartis Pharmaceuticals FX This study was sponsored by Novartis Pharmaceuticals Corporation. Financial support for medical editorial assistance was also provided by Novartis Pharmaceuticals. NR 41 TC 3 Z9 4 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2015 VL 121 IS 23 BP 4165 EP 4172 DI 10.1002/cncr.29636 PG 8 WC Oncology SC Oncology GA CX3TJ UT WOS:000365621900011 PM 26308485 ER PT J AU Hillard, JR Graham, DY AF Hillard, James Randolph Graham, David Y. TI It is not all black and white: Future incidence of stomach cancer will be substantially higher than projected due to the effects of immigration and increasing Hispanic and Asian populations in the United States SO CANCER LA English DT Letter C1 [Hillard, James Randolph] Michigan State Univ, Coll Osteopath Med, Coll Human Med, Dept Psychiat, E Lansing, MI 48824 USA. [Graham, David Y.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Hillard, JR (reprint author), Michigan State Univ, Coll Osteopath Med, Coll Human Med, Dept Psychiat, E Lansing, MI 48824 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2015 VL 121 IS 23 BP 4266 EP 4267 DI 10.1002/cncr.29629 PG 2 WC Oncology SC Oncology GA CX3TJ UT WOS:000365621900023 PM 26280930 ER PT J AU Li, DK Chung, RT AF Li, Darrick K. Chung, Raymond T. TI Reply to direct-acting antiviral drugs and hepatitis C virus: A therapeutic revolution? SO CANCER LA English DT Letter ID COST-EFFECTIVENESS; UNITED-STATES; INFECTION; IMPACT C1 [Li, Darrick K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Ctr Liver, Boston, MA 02114 USA. RP Li, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU NIDDK NIH HHS [K24 DK078772] NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2015 VL 121 IS 23 BP 4269 EP 4270 DI 10.1002/cncr.29650 PG 2 WC Oncology SC Oncology GA CX3TJ UT WOS:000365621900026 PM 26287978 ER PT J AU Broekgaarden, M Weijer, R van Gulik, TM Hamblin, MR Heger, M AF Broekgaarden, Mans Weijer, Ruud van Gulik, Thomas M. Hamblin, Michael R. Heger, Michal TI Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Apoptosis signaling kinase 1; Heat shock factor 1; ER stress; Antioxidant response; Inflammatory response; Proteotoxic stress AB Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer therapies such as surgery, chemotherapy, and radiotherapy. PDT comprises the administration of a photosensitizer, its accumulation in tumor tissue, and subsequent irradiation of the photosensitizer-loaded tumor, leading to the localized photoproduction of reactive oxygen species (ROS). The resulting oxidative damage ultimately culminates in tumor cell death, vascular shutdown, induction of an antitumor immune response, and the consequent destruction of the tumor. However, the ROS produced by PDT also triggers a stress response that, as part of a cell survival mechanism, helps cancer cells to cope with the PDT-induced oxidative stress and cell damage. These survival pathways are mediated by the transcription factors activator protein 1 (AP-1), nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor 1 (HIF-1), nuclear factor kappa B (NF-kappa B), and those that mediate the proteotoxic stress response. The survival pathways are believed to render some types of cancer recalcitrant to PDT and alter the tumor microenvironment in favor of tumor survival. In this review, the molecular mechanisms are elucidated that occur post-PDT to mediate cancer cell survival, on the basis of which pharmacological interventions are proposed. Specifically, pharmaceutical inhibitors of the molecular regulators of each survival pathway are addressed. The ultimate aim is to facilitate the development of adjuvant intervention strategies to improve PDT efficacy in recalcitrant solid tumors. C1 [Broekgaarden, Mans; Weijer, Ruud; van Gulik, Thomas M.; Heger, Michal] Univ Amsterdam, Acad Med Ctr, Dept Expt Surg, NL-1105 AZ Amsterdam, Netherlands. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM m.heger@amc.uva.nl FU NIAID NIH HHS [R01 AI050875] NR 0 TC 14 Z9 14 U1 16 U2 53 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 EI 1573-7233 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2015 VL 34 IS 4 BP 643 EP 690 DI 10.1007/s10555-015-9588-7 PG 48 WC Oncology SC Oncology GA CX4YB UT WOS:000365705800008 PM 26516076 ER PT J AU Yeh, AC Ramaswamy, S AF Yeh, Albert C. Ramaswamy, Sridhar TI Mechanisms of Cancer Cell Dormancy-Another Hallmark of Cancer? SO CANCER RESEARCH LA English DT Review ID MAMMARY-CARCINOMA CELLS; CIRCULATING TUMOR-CELLS; BREAST-CANCER; MALIGNANT-MELANOMA; LATE RECURRENCE; BONE-MARROW; IN-VIVO; THERAPEUTIC TARGET; CUTANEOUS MELANOMA; METASTATIC GROWTH AB Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. (C) 2015 AACR. C1 [Yeh, Albert C.; Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Yeh, Albert C.; Ramaswamy, Sridhar] Harvard Univ, Sch Med, Boston, MA USA. [Ramaswamy, Sridhar] Broad Inst Harvard & MIT, Cambridge, MA USA. [Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA USA. [Ramaswamy, Sridhar] Harvard Ludwig Ctr Canc Res, Boston, MA USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St, Boston, MA 02114 USA. EM sridhar@mgh.harvard.edu FU National Cancer Institute [R01 CA185086]; Susan G. Komen for the Cure; Prostate Cancer Foundation; Stand Up to Cancer Innovative Research Grant, a program of the Entertainment Industry Foundation [SU2C-AACR-IRG0411]; Howard Hughes Medical Institute FX This work was supported by awards from the National Cancer Institute (R01 CA185086), Susan G. Komen for the Cure, and Prostate Cancer Foundation (S. Ramaswamy). S. Ramaswamy was supported by a Stand Up to Cancer Innovative Research Grant, a program of the Entertainment Industry Foundation (SU2C-AACR-IRG0411). S. Ramaswamy and A.C. Yeh were supported by awards from the Howard Hughes Medical Institute (Physician-Scientist Early Career Award, Medical Student Research Fellowship). NR 87 TC 13 Z9 13 U1 1 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2015 VL 75 IS 23 BP 5014 EP 5022 DI 10.1158/0008-5472.CAN-15-1370 PG 9 WC Oncology SC Oncology GA CX3ML UT WOS:000365603000003 PM 26354021 ER PT J AU Iafrate, AJ AF Iafrate, A. John TI CCR 20th Anniversary Commentary: Molecular Pathology of ALK-Rearranged Lung Tumors SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID EML4-ALK FUSION; CANCER; FEATURES; CRIZOTINIB; ADENOCARCINOMAS; EGFR AB The article by Rodig and colleagues, which was published in the August 15, 2009, issue of Clinical Cancer Research, helped detail the clinicopathologic profile of ALK-positive tumors and initiated the development of ALK diagnostics. Subsequent clinical trials utilized these findings, resulting in the approval of effective targeted therapies. The ALK story is a model for the development of therapies in the genomic era. (C) 2015 AACR. C1 [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM aiafrate@partners.org FU Blueprint Medicines FX A.J. Iafrate reports receiving a commercial research grant from Blueprint Medicines; has ownership interest (including patents) in ArcherDX; and is a consultant/advisory board member for Constellation Pharmaceuticals, Chugai Pharmaceutical, and Debiopharm. No other potential conflicts of interest were disclosed. NR 19 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2015 VL 21 IS 23 BP 5185 EP 5187 DI 10.1158/1078-0432.CCR-14-3130 PG 3 WC Oncology SC Oncology GA CX3MT UT WOS:000365603800001 PM 26626570 ER PT J AU Amaravadi, RK Hamilton, KE Ma, XH Piao, SF Del Portillo, A Nathanson, KL Carlino, MS Long, GV Puzanov, I Xu, XW Morrissette, JJD Tsai, KY Flaherty, KT Sosman, JA Goodman, GR McArthur, GA Rustgi, AK Metz, DC Schuchter, LM Chapman, PB Sepulveda, AR AF Amaravadi, Ravi K. Hamilton, Kathryn E. Ma, Xiaohong Piao, Shengfu Del Portillo, Armando Nathanson, Katherine L. Carlino, Matteo S. Long, Georgina V. Puzanov, Igor Xu, Xiaowei Morrissette, Jennifer J. D. Tsai, Kenneth Y. Flaherty, Keith T. Sosman, Jeffrey A. Goodman, Grant R. McArthur, Grant A. Rustgi, Anil K. Metz, David C. Schuchter, Lynn M. Chapman, Paul B. Sepulveda, Antonia R. TI Multiple Gastrointestinal Polyps in Patients Treated with BRAF Inhibitors SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC MELANOMA; MEK INHIBITION; RAS MUTATIONS; PROGRESSION; COLON; VEMURAFENIB; DABRAFENIB; ADENOMAS; SURVIVAL; CANCER AB Purpose: BRAF inhibitors (BRAFi) extend survival in BRAF-mutant melanoma but can promote the growth of Ras-mutant neoplasms. This study determined if gastrointestinal polyps found in BRAFi-treated patients harbored Ras mutations. Experimental Design: Colonic and gastric polyps were identified and resected from BRAFi-treated melanoma patients. Next-generation sequencing (NGS) was performed on polyps. The ability of BRAFi to promote polyp formation was functionally characterized in Apc Min(+/-) mice. MAPK and beta-catenin pathway activity was assessed by immunohistochemistry in mouse and human polyps. Results: Fourteen patients treated with BRAFi underwent endoscopy to assess for polyps. Seven out of 7 patients >40 years of age and treated for >2 years were found to have colonic tubular adenomas with 4 out of the 7 patients having 5 or more polyps. One patient presented with bleeding from hyperplastic gastric polyps that recurred 6 months after BRAFi rechallenge. NGS performed on polyps found no mutations in MAPK pathway genes, but found APC mutations in all tubular adenomas. A significant increase in the number of polyps was observed in BRAFi-treated compared with control-treated Apc Min(+/-) mice (20.8 +/- 9.2 vs 12.8 +/- 0.1; P = 0.016). No polyps were observed in BRAFi-treated wild-type mice. Conclusions: BRAFi may increase the risk of developing hyperplastic gastric polyps and colonic adenomatous polyps. Due to the risk of gastrointestinal bleeding and the possibility of malignant transformation, further studies are needed to determine whether or not endoscopic surveillance should be recommended for patients treated with BRAFi. (C) 2015 AACR. C1 [Amaravadi, Ravi K.; Hamilton, Kathryn E.; Ma, Xiaohong; Piao, Shengfu; Nathanson, Katherine L.; Rustgi, Anil K.; Metz, David C.; Schuchter, Lynn M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Amaravadi, Ravi K.; Nathanson, Katherine L.; Rustgi, Anil K.; Metz, David C.; Schuchter, Lynn M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Del Portillo, Armando; Sepulveda, Antonia R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Carlino, Matteo S.] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia. [Carlino, Matteo S.] Blacktown Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia. [Carlino, Matteo S.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Carlino, Matteo S.; Long, Georgina V.] Univ Sydney, Sydney, NSW 2006, Australia. [Puzanov, Igor; Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Xu, Xiaowei; Morrissette, Jennifer J. D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Tsai, Kenneth Y.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Goodman, Grant R.] Genentech Inc, San Francisco, CA 94080 USA. [McArthur, Grant A.] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. [McArthur, Grant A.] Univ Melbourne, Melbourne, Vic, Australia. [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Amaravadi, RK (reprint author), Univ Penn, 77 South Tower PCAM 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM ravi.amaravadi@uphs.upenn.edu FU Genentech FX Funding for this work was provided in part by Genentech through a sponsored research agreement with University of Pennsylvania (to R.K. Amaravadi). Additional resources used included the Molecular Pathology and Imaging, Molecular Biology and Gene Expression, and Transgenic and Chimeric Mouse Cores of the University of Pennsylvania Molecular Studies in Digestive and Liver Diseases Center (NIH/NIDDK P30 DK050306). DNA sequencing was performed using the Abramson Cancer Center Genomics Core services (P30 CA016520). NR 30 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2015 VL 21 IS 23 BP 5215 EP 5221 DI 10.1158/1078-0432.CCR-15-0469 PG 7 WC Oncology SC Oncology GA CX3MT UT WOS:000365603800007 PM 26202952 ER PT J AU Pandit-Taskar, N O'Donoghue, JA Durack, JC Lyashchenko, SK Cheal, SM Beylergil, V Lefkowitz, RA Carrasquillo, JA Martinez, DF Fung, AM Solomon, SB Gonen, M Heller, G Loda, M Nanus, DM Tagawa, ST Feldman, JL Osborne, JR Lewis, JS Reuter, VE Weber, WA Bander, NH Scher, HI Larson, SM Morris, MJ AF Pandit-Taskar, Neeta O'Donoghue, Joseph A. Durack, Jeremy C. Lyashchenko, Serge K. Cheal, Sarah M. Beylergil, Volkan Lefkowitz, Robert A. Carrasquillo, Jorge A. Martinez, Danny F. Fung, Alex Mak Solomon, Stephen B. Goenen, Mithat Heller, Glenn Loda, Massimo Nanus, David M. Tagawa, Scott T. Feldman, Jarett L. Osborne, Joseph R. Lewis, Jason S. Reuter, Victor E. Weber, Wolfgang A. Bander, Neil H. Scher, Howard I. Larson, Steven M. Morris, Michael J. TI A Phase I/II Study for Analytic Validation of Zr-89-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY J591; POSITRON-EMISSION-TOMOGRAPHY; MEMBRANE ANTIGEN-EXPRESSION; SOLID TUMORS; FDG-PET; THERAPY; C-11-ACETATE; LOCALIZATION; F-18-FDG; TRIAL AB Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of Zr-89-DFO-huJ591 (Zr-89-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of Zr-89-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. Results: Median standardized uptake value for Zr-89-J591-positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). Zr-89-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, Zr-89-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 Zr-89-J591-positive osseous sites and 14 of 16 Zr-89-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of Zr-89-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: Zr-89-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although Zr-89-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer. (C) 2015 AACR. C1 [Pandit-Taskar, Neeta; Durack, Jeremy C.; Cheal, Sarah M.; Beylergil, Volkan; Lefkowitz, Robert A.; Carrasquillo, Jorge A.; Fung, Alex Mak; Solomon, Stephen B.; Osborne, Joseph R.; Weber, Wolfgang A.; Larson, Steven M.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Pandit-Taskar, Neeta; Lefkowitz, Robert A.; Carrasquillo, Jorge A.; Solomon, Stephen B.; Osborne, Joseph R.; Lewis, Jason S.; Weber, Wolfgang A.; Larson, Steven M.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. [O'Donoghue, Joseph A.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10065 USA. [Lyashchenko, Serge K.; Cheal, Sarah M.; Lewis, Jason S.; Larson, Steven M.] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA. [Lyashchenko, Serge K.; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Radiochem & Mol Imaging Probe Core Facil, New York, NY 10065 USA. [Martinez, Danny F.; Feldman, Jarett L.; Scher, Howard I.; Morris, Michael J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Goenen, Mithat; Heller, Glenn] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10065 USA. [Loda, Massimo] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Brigham & Womens Hosp, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Boston, MA USA. [Nanus, David M.; Tagawa, Scott T.; Bander, Neil H.; Scher, Howard I.; Morris, Michael J.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Reuter, Victor E.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Bander, Neil H.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. RP Pandit-Taskar, N (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, Mol Imaging & Therapy Serv, 1275 York Ave,Box 77, New York, NY 10065 USA. EM pandit-n@mskcc.org OI O'Donoghue, Joseph A/0000-0002-2761-0015; Durack, Jeremy/0000-0002-0672-9586; Carrasquillo, Jorge/0000-0002-8513-5734 FU Starr Cancer Consortium; prostate cancer program of Memorial Sloan Kettering Cancer Center; Center for Targeted Radioimmunotherapy and Theranostics of the Ludwig Center for Cancer Immunotherapy; David H. Koch Foundation; NIH [P30CA008748]; Landy Research Fund; Hascoe Charitable Foundation FX This study was funded by Starr Cancer Consortium, the prostate cancer program of Memorial Sloan Kettering Cancer Center, the Center for Targeted Radioimmunotherapy and Theranostics of the Ludwig Center for Cancer Immunotherapy, and the David H. Koch Foundation. In addition, the Radiochemistry & Molecular Imaging Probes Core of MSK is supported in part by NIH P30CA008748, the Landy Research Fund, and Hascoe Charitable Foundation. NR 31 TC 22 Z9 23 U1 5 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2015 VL 21 IS 23 BP 5277 EP 5285 DI 10.1158/1078-0432.CCR-15-0552 PG 9 WC Oncology SC Oncology GA CX3MT UT WOS:000365603800013 PM 26175541 ER PT J AU Muralidhar, V Ziehr, DR Mahal, BA Chen, YW Nezolosky, MD Viswanathan, VB Choueiri, TK Sweeney, CJ Trinh, QD Nguyen, PL AF Muralidhar, Vinayak Ziehr, David R. Mahal, Brandon A. Chen, Yu-Wei Nezolosky, Michelle D. Viswanathan, Vidya B. Choueiri, Toni K. Sweeney, Christopher J. Quoc-Dien Trinh Nguyen, Paul L. TI Association Between Older Age and Increasing Gleason Score SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Age groups; Cancer screening; Gleason score; Prostate cancer; Prostate-specific antigen ID TASK-FORCE RECOMMENDATION; PROSTATE-CANCER MORTALITY; STAGE T1C; GRADE; DIAGNOSIS; IMPACT; DEDIFFERENTIATION; CARCINOMA; GUIDELINE; SURVIVAL AB There are few data about the risks versus benefits of screening older men for prostate cancer. Using a large national database, we found that older men diagnosed with prostate cancer have a higher probability of harboring high-risk or high-grade disease. These data could be used to help counsel healthy older men about the risks and benefits of prostate cancer screening. Introduction: In order to help inform the discussion about the risks versus benefits of prostate cancer screening among older men, we determined whether advanced age is associated with a higher probability of harboring high-grade or high-rik disease. Patients and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 383,039 men diagnosed with prostate cancer in 2004-2011. The percentage of patients diagnosed with low-, intermediate-, or high-risk disease or a Gleason score of 6, 7, or 8 to 10 was calculated by age range. As a secondary analysis, we examined whether this relationship was different in 2010-2011 versus 2007-2008 (before and after the 2009 publication of screening trials). Results: The probability of Gleason score 8 to 10 or high-risk disease increased significantly with increasing age. The percentage of Gleason score 8 to 10 disease among men ages 50 to 54, 70 to 74, and 80 to 84 years was 8.9%, 16.2%, and 28.5%, respectively, and the percentage of high-risk disease was 14.3%, 22.4%, and 38.7% (P<.001). There were similar relationships among men with stage T1c disease. In addition, older men experienced a significant increase in the relative probability of high-risk or high-grade disease from 2007-2008 to 2010-2011. Conclusion: In this large US-based cohort, older men had a much higher probability of high-grade or high-risk prostate cancer. Physicians and patients should take into account the higher risk of more aggressive or advanced disease in older men when discussing the risks and benefits of prostate-specific antigen screening with healthy older men with a substantial life expectancy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Ziehr, David R.; Mahal, Brandon A.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Yu-Wei] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA USA. [Nezolosky, Michelle D.; Viswanathan, Vidya B.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Nezolosky, Michelle D.; Viswanathan, Vidya B.; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02215 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Quoc-Dien Trinh] Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis Sr, Boston, MA 02215 USA. EM pnguyen@LROC.harvard.edu FU Health Sciences and Technology IDEA2 Program - Peter C. Farrell Fund; Prostate Cancer Foundation; Scott Forbes and Gina Ventre Fund FX This work was supported by grants from the Health Sciences and Technology IDEA2 Program supported by the Peter C. Farrell (1967) Fund, the Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, the Scott Forbes and Gina Ventre Fund, and a grant from an anonymous family foundation. NR 29 TC 1 Z9 1 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2015 VL 13 IS 6 BP 525 EP 530 DI 10.1016/j.clgc.2015.05.007 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CX3XV UT WOS:000365633700006 PM 26119229 ER PT J AU Carducci, MA Manola, J Nair, SG Liu, G Rousey, S Dutcher, JP Wilding, G AF Carducci, Michael A. Manola, Judith Nair, Suresh G. Liu, Glenn Rousey, Steven Dutcher, Janice P. Wilding, George TI Atrasentan in Patients With Advanced Renal Cell Carcinoma: A Phase 2 Trial of the ECOG-ACRIN Cancer Research Group (E6800) SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Bone metastases; Endothelin A receptor antagonist; Kidney cancer; Pain palliation; Progression-free survival ID REFRACTORY PROSTATE-CANCER; ENDOTHELIN-A RECEPTOR; III TRIAL; ZIBOTENTAN ZD4054; INTERFERON-ALPHA; DOUBLE-BLIND; PLACEBO; MEN; COMBINATION; EFFICACY AB The use of atrasentan, an endothelin receptor A antagonist, was studied in cohorts of patients with renal cell carcinoma (RCC) with and without prior immunotherapy and either measurable disease or bone metastases only in the pre-VEGF/TKI era. Although well tolerated, atrasentan did not yield 6-month progression-free rates supporting its use as first-line monotherapy in patients with advanced RCC. Background: Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era. Methods and Materials: Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. Results: From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months). Conclusion: Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC. (C) 2015 Elsevier Inc. All rights reserved. C1 [Carducci, Michael A.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Manola, Judith] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Nair, Suresh G.] Lehigh Valley Hosp Cedar Crest, Hematol Oncol Associates, Allentown, PA USA. [Liu, Glenn] Univ Wisconsin, Carbone Canc Ctr, Wisconsin Inst Med Res, Madison, WI USA. [Rousey, Steven] Metrominnesota CCOP, Edina, MN USA. [Dutcher, Janice P.] New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. [Wilding, George] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. RP Manola, J (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave,CLS 11003, Boston, MA 02115 USA. EM jmanola@jimmy.harvard.edu FU Public Health Service from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA180794, CA180820, CA180802, CA180799, CA189863, CA189859] FX This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD, and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and was supported in part by Public Health Service grants CA180794, CA180820, CA180802, CA180799, CA189863, and CA189859 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The investigational agent for the study was provided by Abbott Inc. This article's content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 32 TC 0 Z9 0 U1 1 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2015 VL 13 IS 6 BP 531 EP 539 DI 10.1016/clgc.2015.07.002 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CX3XV UT WOS:000365633700007 PM 26272427 ER PT J AU Braunstein, LZ Chen, MH Dosoretz, DE Salenius, SA Katin, MJ Nanda, A D'Amico, AV AF Braunstein, Lior Z. Chen, Ming-Hui Dosoretz, Daniel E. Salenius, Sharon A. Katin, Michael J. Nanda, Akash D'Amico, Anthony V. TI Whole Pelvis Versus Prostate-Only Radiotherapy With or Without Short-Course Androgen Deprivation Therapy and Mortality Risk SO CLINICAL GENITOURINARY CANCER LA English DT Article DE Hormonal therapy; Lymph nodes; Nodal irradiation; Pelvic radiation; Prostate cancer; Radiation therapy ID PHASE-III TRIAL; RADIATION-THERAPY; RANDOMIZED-TRIAL; SHORT-TERM; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; BREAST-CANCER; SUPPRESSION; NEOADJUVANT; SURVIVAL AB Whole-pelvis radiotherapy or a short-course (approximately 4 months) of androgen deprivation therapy yield an all-cause mortality benefit among patients with unfavorable-risk prostate cancer. However, the combination of these 2 treatments does not further improve mortality outcomes, suggesting a shared therapeutic mechanism. Background: The purpose of the study was to determine whether the extent of prostate radiotherapy (ie, whole-pelvic radiotherapy [WPRT] vs. prostate and seminal vesicle radiotherapy [PSVRT]) is associated with all-cause mortality (ACM) in men treated with or without androgen deprivation therapy (ADT). Patients and Methods: A multiple-institution cohort of 3709 prostate cancer patients was prospectively assembled from 1991 to 2006. The median age was 72 years and all patients had T1c-T3N0M0 adenocarcinoma of the prostate. Patients were treated with WPRT or PSVRT followed by a brachytherapy boost, with or without neoadjuvant ADT (median duration, 4.2 months). Seventy percent of patients had unfavorable-risk disease (Gleason score >= 7; prostate-specific antigen >= 10 ng/mL; or stage >= T2b). Cox regression was applied to determine whether the radiation treatment volume affected the risk of ACM. The interaction between radiation volume and ADT use was assessed. Results: After a median follow-up of 3.3 years, 561 deaths were observed. A decreased risk of ACM was noted with the use of WPRT versus PSVRT (adjusted hazard ratio [AHR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = .01), or with ADT use (AHR, 0.71; 95% CI, 0.58-0.90; P = .004). However, a combination of WPRT and ADT did not further improve ACM compared with either WPRT alone or PSVRT with ADT. Moreover, there was a significant interaction between the radiotherapeutic treatment volume and ADT (AHR, 1.61; 95% CI, 1.004-2.58; P = .048). Conclusion: Treatment with WPRT or short-course ADT is associated with a decreased risk of ACM, although a combination of the two does not yield greater benefit. This observation suggests a shared mechanism for this risk reduction, which we hypothesize to be via the treatment of micrometastatic disease within the pelvic lymph nodes. (C) 2015 Elsevier Inc. All rights reserved. C1 [Braunstein, Lior Z.] Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Dosoretz, Daniel E.; Salenius, Sharon A.; Katin, Michael J.] 21st Century Oncol, Ft Myers, FL USA. [Nanda, Akash] UF Hlth Canc Ctr, Orlando, FL USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Braunstein, LZ (reprint author), Harvard Radiat Oncol Program, 75 Francis St ASB-1 L2, Boston, MA 02115 USA. EM LBRAUNSTEIN@partners.org NR 28 TC 2 Z9 2 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 EI 1938-0682 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD DEC PY 2015 VL 13 IS 6 BP 555 EP 561 DI 10.1016/clgc.2015.04.010 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CX3XV UT WOS:000365633700010 PM 26003267 ER PT J AU Susarla, SM Grant, M Merbs, S Mahoney, N AF Susarla, Srinivas Murthy Grant, Michael Merbs, Shannath Mahoney, Nicholas TI Computer-Assisted Three-Dimensional Planning for Orbital Decompression (vol 8, pg 211, 2015) SO CRANIOMAXILLOFACIAL TRAUMA & RECONSTRUCTION LA English DT Correction C1 [Susarla, Srinivas Murthy; Grant, Michael] Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. [Grant, Michael; Merbs, Shannath; Mahoney, Nicholas] Johns Hopkins Univ Hosp, Dept Ophthalmol, Div Oculoplast Surg, Baltimore, MD 21287 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral Maxillofacial Surg, WACC230, Boston, MA 02114 USA. EM smsusarla@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1943-3875 EI 1943-3883 J9 CRANIOMAXILLOFACIAL JI Craniomaxillofacial Trauma Reconstr. PD DEC PY 2015 VL 8 IS 4 BP 375 EP 375 DI 10.1055/s-0035-1564297 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CX6GK UT WOS:000365799000018 PM 26576247 ER PT J AU Orr, SK Butler, KL Hayden, D Tompkins, RG Serhan, CN Irimia, D AF Orr, Sarah K. Butler, Kathryn L. Hayden, Douglas Tompkins, Ronald G. Serhan, Charles N. Irimia, Daniel TI Gene Expression of Proresolving Lipid Mediator Pathways Is Associated With Clinical Outcomes in Trauma Patients SO CRITICAL CARE MEDICINE LA English DT Article DE gene expression; lipid mediators; outcomes; resolvins; systemic inflammatory response syndrome; trauma ID INFLAMMATION-RESOLUTION; RESOLVIN D2; SURVIVAL; SEPSIS; INJURY AB Objectives: Specialized proresolving lipid mediators have emerged as powerful modulators of inflammation and activators of resolution. Animal models show significant benefits of specialized proresolving lipid mediators on survival and wound healing after major burn trauma. To date, no studies have investigated specialized proresolving lipid mediators and their relation to other lipid mediator pathways in humans after trauma. Here we determine if patients with poor outcomes after trauma have dysregulated lipid mediator pathways. Design: We studied blood leukocyte expression of 18 genes critical to the synthesis, signaling, and metabolism of specialized proresolving lipid mediators and proinflammatory lipid mediators, and we correlated these expression patterns with clinical outcomes in trauma patients from the Inflammation and the Host Response to Injury study. Setting: Seven U.S. medical trauma centers. Subjects: Ninety-six patients enrolled in the Inflammation and Host Response to Injury study, after blunt trauma and unambiguously classified as having uncomplicated or complicated recoveries. Twenty-eight healthy volunteers were enrolled as controls. Interventions: None. Measurements and Main Results: Within each patient, the 18 genes of interest were used to calculate scores for distinct families of lipid mediators, including resolvins, lipoxins, prostaglandins, and leukotrienes, as well as leukotriene to resolvin score ratios. Scores were built using a simple weighting scheme, taking into consideration both dependent and independent activities of enzymes and receptors responsible for lipid mediator biosynthesis and function. Individually, ALOX12, PTGS2, PTGES, PTGDS, ALOX5AP, LTA4H, FPR2, PTGER2, LTB4R, HPGD, PTGR1, and CYP4F3 were expressed differentially over 28 days posttrauma between patients with uncomplicated and complicated recoveries (p < 0.05). When all genes were combined into scores, patients with uncomplicated recoveries had differential and higher resolvin scores (p < 0.001) and lower leukotriene scores (p < 0.001). A final combined ratio was calculated for each patient, and posttrauma leukotriene score to resolvin score ratios were significantly lower in patients with uncomplicated clinical courses (p < 0.001). Conclusions: proresolving lipid mediator lipidomics and/or protein expression, and identifying associated therapeutic targets, may influence the clinical management of trauma patients. C1 [Orr, Sarah K.; Serhan, Charles N.] Brigham & Womens Hosp, Harvard Inst Med, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. [Orr, Sarah K.; Butler, Kathryn L.; Hayden, Douglas; Tompkins, Ronald G.; Serhan, Charles N.; Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA USA. [Butler, Kathryn L.] Massachusetts Gen Hosp, Dept Surg, Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Hayden, Douglas] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Tompkins, Ronald G.; Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg, Ctr Surg Innovat & Bioengn, Boston, MA 02114 USA. RP Irimia, D (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Surg Innovat & Bioengn, Boston, MA 02114 USA. EM dirimia@mgh.harvard.edu FU Canadian Institutes of Health Research PDF (Post-Doctoral Fellowship); National Institutes of Health (NIH); NIH [5P50GM021700-33, GM095467, GM092804]; Canadian Medical Research Council; NIH FX Dr. Orr received support from the Canadian Institutes of Health Research PDF (Post-Doctoral Fellowship-salary support for all research activities). Dr. Butler received support for article research from the National Institutes of Health (NIH). Her institution received grant support from the NIH. Dr. Hayden's institution received grant support from the NIH (5P50GM021700-33). Dr. Tompkins received support for article research from the NIH. His institution received grant support from the NIH. Dr. Serhan served as a board member for the Inflammation Research Foundation (Scientific Advisory Board member), has stock (scientific founder Resolvyx Pharma-stock of unknown value), and received support for article research from the NIH (GM095467) and Canadian Medical Research Council. His institution received grant support from the NIH, has a patent with Resolvyx, and received royalties. Dr. Irimia received support for article research from the NIH (GM092804). His institution received grant support from the NIH. NR 26 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2015 VL 43 IS 12 BP 2642 EP 2650 DI 10.1097/CCM.0000000000001312 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA CX1VB UT WOS:000365482600015 PM 26488221 ER PT J AU Ahasic, AM Tejera, P Wei, YY Su, L Mantzoros, CS Bajwa, EK Thompson, BT Christiani, DC AF Ahasic, Amy M. Tejera, Paula Wei, Yongyue Su, Li Mantzoros, Christos S. Bajwa, Ednan K. Thompson, B. Taylor Christiani, David C. TI Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-Binding Protein-3 in Critical Illness SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; critical care; insulin-like growth factor-1; insulin-like growth factor-binding protein-3; molecular epidemiology; single-nucleotide polymorphisms ID RESPIRATORY-DISTRESS-SYNDROME; IGF-I; IGFBP-3 POLYMORPHISMS; CONSENSUS CONFERENCE; BREAST-CANCER; RISK; MORTALITY; HORMONE; AMERICAN; ADULTS AB Objective: To characterize predictors of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 than chronic clinical or genetic factors. Design: Observational study nested within a large prospective study using multivariable linear regression to model circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 with acute and chronic clinical variables, and genotype from five polymorphisms in insulin-like growth factor pathway genes. Setting: ICUs from two large academic medical centers. Patients: Five hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome and available plasma from early in critical illness. Interventions: None. Measurements and Main Results: Total insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 were measured in plasma using IMMULITE assays (Siemens, Malvern, PA). We examined age, gender, body mass index, cirrhosis, and diabetes, as well as Acute Physiology, Age, and Chronic Health Evaluation III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, acute respiratory distress syndrome, and receipt of corticosteroids. Body mass index, cirrhosis, and acute respiratory distress syndrome were strongly associated with insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels; Acute Physiology, Age, and Chronic Health Evaluation III was strongly associated with insulin-like growth factor-1 levels; and age was strongly associated with insulin-like growth factor-binding protein-3. Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1: rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels. When genotypes were added to models, rs2854746 was significantly associated with plasma insulin-like growth factor-binding protein-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18. Conclusions: Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 early in critical illness. rs2854746 is also significantly associated with insulin-like growth factor-binding protein-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. Further research is needed to understand how to apply these findings to patient care. C1 [Ahasic, Amy M.] Yale Univ, Sch Med, Dept Internal Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT 06510 USA. [Tejera, Paula; Wei, Yongyue; Su, Li; Mantzoros, Christos S.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Bajwa, Ednan K.; Thompson, B. Taylor; Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Ahasic, AM (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Pulm Crit Care & Sleep Med, 333 Cedar St, New Haven, CT 06510 USA. EM amy.ahasic@yale.edu FU National Institutes of Health [R01HL60710]; American Heart Association [10FTF3440007]; National Institutes of Health (NIH); NIH; National Institutes of Health/National Heart, Lung & Blood Institute (NHLBI) [1U01HL123009-1]; NHLBI; National Institutes of Health (NHLBI) [R01HL060710, T32HL116275]; National Institutes of Health (National Cancer Institute) [P30CA006516, R01CA092824]; National Institutes of Health (National Institute of Environmental Health Sciences) [R01 ES009860, T32 ES007069]; Centers for Disease Control (National Institute for Occupational Safety Health) [R01OH002421, T42OH008416]; NIH (NHLBI) FX Supported, in part, by a grant R01HL60710 from the National Institutes of Health and a grant 10FTF3440007 from the American Heart Association.; Dr. Ahasic received support for article research from the National Institutes of Health (NIH) and the American Heart Association. Her institution received grant support from the American Heart Association (she has a career development grant [10FTF3440007] funding this research, disclosed in the article), and she received support for travel from the American Heart Association (the career development grant allows up to $3000/yr for travel to academic conferences relevant to the current research; no travel money has been received outside of this grant). Dr. Mantzoros has disclosed government work. Dr. Thompson consulted for GlaxoSmithKline (one-time acute respiratory distress syndrome [ARDS] advisory board meeting) and received support for article research form the NIH. He is currently receiving funding (1U01HL123009-1) from the National Institutes of Health/National Heart, Lung & Blood Institute (NHLBI). His institution received grant support from the NHLBI (conduct sepsis and ARDS clinical research). Dr. Christiani is currently receiving funding from the National Institutes of Health (NHLBI: R01HL060710 and T32HL116275; National Cancer Institute: P30CA006516 and R01CA092824; National Institute of Environmental Health Sciences: R01 ES009860 and T32 ES007069) and from the Centers for Disease Control (National Institute for Occupational Safety & Health: R01OH002421 and T42OH008416). His institution received grant support from the NIH (NHLBI). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 31 TC 1 Z9 1 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2015 VL 43 IS 12 BP 2651 EP 2659 DI 10.1097/CCM.0000000000001314 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA CX1VB UT WOS:000365482600016 PM 26427594 ER PT J AU Jelly, CA Alston, TA AF Jelly, Christina A. Alston, Theodore A. TI Release of Endotoxin After an Arrest SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cardiac arrest; circulatory shock; endotoxin assay; Richard Pfeiffer; vasoplegia ID SEPSIS C1 [Jelly, Christina A.; Alston, Theodore A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Crit Care & Pain Med, Boston, MA 02115 USA. RP Jelly, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Crit Care & Pain Med, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2015 VL 43 IS 12 BP 2687 EP 2688 DI 10.1097/CCM.0000000000001337 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA CX1VB UT WOS:000365482600026 PM 26575661 ER PT J AU Li, M Vienberg, SG Bezy, O O'Neill, BT Kahn, CR AF Li, Mengyao Vienberg, Sara G. Bezy, Olivier O'Neill, Brian T. Kahn, C. Ronald TI Role of PKC delta in Insulin Sensitivity and Skeletal Muscle Metabolism SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; OBESE ZUCKER RATS; GLUCOSE-TRANSPORT; PSAMMOMYS-OBESUS; OXIDATIVE STRESS; DIABETES-MELLITUS; INDUCED APOPTOSIS; TRANSGENIC MICE; RESISTANCE; ACTIVATION AB Protein kinase C (PKC)delta has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKC delta in skeletal muscle in the control of insulin sensitivity and glucose metabolism by generating mice in which PKC delta was deleted specifically in muscle using Cre-lox recombination. Deletion of PKC delta in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological levels of insulin. Likewise, in young mice, muscle-specific deletion of PKC delta did not rescue high-fat diet-induced insulin resistance or glucose intolerance. However, with an increase in age, PKC delta levels in muscle increased, and by 6 to 7 months of age, muscle-specific deletion of PKC delta improved whole-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKC delta KO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKC delta in the regulation of mitochondrial mass at older age. These data indicate an important role of PKC delta in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging. C1 [Li, Mengyao; Vienberg, Sara G.; Bezy, Olivier; O'Neill, Brian T.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02163 USA. [Vienberg, Sara G.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02163 USA. EM c.ronald.kahn@joslin.harvard.edu FU National Institutes of Health (NIH) [R01-DK-033201]; Joslin Diabetes Research Center [DK-036836]; K08 Training award from the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH [K08-DK-100543] FX This work was supported by National Institutes of Health (NIH) grant R01-DK-033201 and Joslin Diabetes Research Center grant DK-036836. B.T.O. was also funded by a K08 Training award from the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH (K08-DK-100543). NR 43 TC 3 Z9 3 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2015 VL 64 IS 12 BP 4023 EP 4032 DI 10.2337/db14-1891 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX8DN UT WOS:000365932900010 PM 26307588 ER PT J AU Lasch, S Muller, P Bayer, M Pfeilschifter, JM Luster, AD Hintermann, E Christen, U AF Lasch, Stanley Mueller, Peter Bayer, Monika Pfeilschifter, Josef M. Luster, Andrew D. Hintermann, Edith Christen, Urs TI Anti-CD3/Anti-CXCL10 Antibody Combination Therapy Induces a Persistent Remission of Type 1 Diabetes in Two Mouse Models SO DIABETES LA English DT Article ID ANTI-CD3 MONOCLONAL-ANTIBODY; ISLET-SPECIFIC EXPRESSION; PRESERVES C-PEPTIDE; CD8(+) T-CELLS; RECENT-ONSET; NOD MICE; TRANSGENIC MODEL; CONTROLLED-TRIAL; INFECTION; MELLITUS AB Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone. The combination therapy prevented islet-specific T cells from reentering the islets of Langerhans and thereby blocked the autodestructive process. In addition, the local immune balance in the pancreas was shifted toward a regulatory phenotype. A sequential temporal inactivation of T cells and blockade of T-cell migration might constitute a novel therapy for patients with type 1 diabetes. C1 [Lasch, Stanley; Mueller, Peter; Bayer, Monika; Pfeilschifter, Josef M.; Hintermann, Edith; Christen, Urs] Goethe Univ Hosp Frankfurt, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany. [Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Christen, U (reprint author), Goethe Univ Hosp Frankfurt, Pharmazentrum Frankfurt ZAFES, Frankfurt, Germany. EM christen@med.uni-frankfurt.de OI Christen, Urs/0000-0003-4165-7976 FU Else Kroner-Fresenius Foundation (EKFS); Research Training Group Translational Research Innovation-Pharma (TRIP); German Research Foundation (DFG); Goethe University Hospital Frankfurt FX This study was supported by the Else Kroner-Fresenius Foundation (EKFS), Research Training Group Translational Research Innovation-Pharma (TRIP), the German Research Foundation (DFG), and the Goethe University Hospital Frankfurt. NR 45 TC 5 Z9 6 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2015 VL 64 IS 12 BP 4198 EP 4211 DI 10.2337/db15-0479 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX8DN UT WOS:000365932900024 PM 26293506 ER PT J AU Todd, JN Dahlstrom, EH Salem, RM Sandholm, N Forsblom, C McKnight, AJ Maxwel, AP Brennan, E Sadlier, D Godson, C Groop, PH Hirschhorn, JN Florez, JC AF Todd, Jennifer N. Dahlstrom, Emma H. Salem, Rany M. Sandholm, Niina Forsblom, Carol McKnight, Amy J. Maxwel, Alexander P. Brennan, Eoin Sadlier, Denise Godson, Catherine Groop, Per-Henrik Hirschhorn, Joel N. Florez, Jose C. CA FinnDiane Study Group TI Genetic Evidence for a Causal Role of Obesity in Diabetic Kidney Disease SO DIABETES LA English DT Article ID BODY-MASS INDEX; STAGE RENAL-DISEASE; MENDELIAN RANDOMIZATION; METABOLIC SYNDROME; RISK-FACTORS; INSTRUMENTAL VARIABLES; CARDIOVASCULAR-DISEASE; UNITED-STATES; TYPE-1; COMPLICATIONS AB Obesity has been posited as an independent risk factor for diabetic kidney disease (DKD), but establishing causality from observational data is problematic. We aimed to test whether obesity is causally related to DKD using Mendelian randomization, which exploits the random assortment of genes during meiosis. In 6,049 subjects with type 1 diabetes, we used a weighted genetic risk score (GRS) comprised of 32 validated BMI loci as an instrument to test the relationship of BMI with macroalbuminuria, end-stage renal disease (ESRD), or DKD defined as presence of macroalbuminuria or ESRD. We compared these results with cross-sectional and longitudinal observational associations. Longitudinal analysis demonstrated a U-shaped relationship of BMI with development of macroalbuminuria, ESRD, or DKD over time. Cross-sectional observational analysis showed no association with overall DKD, higher odds of macroalbuminuria (for every 1 kg/m(2) higher BMI, odds ratio [OR] 1.05, 95% Cl 1.03-1.07, P < 0.001), and lower odds of ESRD (OR 0.95, 95% Cl 0.93-0.97, P < 0.001). Mendelian randomization analysis showed a 1 kg/m(2) higher BMI conferring an increased risk in macroalbuminuria (OR 1.28, 95% Cl 1.11-1.45, P = 0.001), ESRD (OR 1.43, 95% Cl 1.20-1.72, P < 0.001), and DKD (OR 1.33, 95% Cl 1.17-1.51, P < 0.001). Our results provide genetic evidence for a causal link between obesity and DKD in type 1 diabetes. As obesity prevalence rises, this finding predicts an increase in DKD prevalence unless intervention should occur. C1 [Todd, Jennifer N.; Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Todd, Jennifer N.; Salem, Rany M.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Dahlstrom, Emma H.; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik] Folkhalsan Res Ctr, Folkhalsan Inst Genet, Biomed Helsinki, Helsinki, Finland. [Dahlstrom, Emma H.; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik] Univ Helsinki, Abdominal Ctr Nephrol, Helsinki, Finland. [Dahlstrom, Emma H.; Sandholm, Niina; Forsblom, Carol; Groop, Per-Henrik] Helsinki Univ Hosp, Helsinki, Finland. [Dahlstrom, Emma H.; Sandholm, Niina] Univ Helsinki, Res Programs Unit, Diabet & Obes Res Program, Helsinki, Finland. [Salem, Rany M.; Hirschhorn, Joel N.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [McKnight, Amy J.; Maxwel, Alexander P.] Queens Univ Belfast, Ctr Publ Hlth, Nephrol Res, Belfast, Antrim, North Ireland. [Maxwel, Alexander P.] Belfast City Hosp, Reg Nephrol Unit, Belfast BT9 7AD, Antrim, North Ireland. [Brennan, Eoin; Godson, Catherine] Univ Coll Dublin, Sch Med & Med Sci, Conway Inst, Diabet Complicat Res Ctr, Dublin 2, Ireland. [Sadlier, Denise] Mater Misericordiae Univ Hosp, Dublin, Ireland. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Florez, JC (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM jcflorez@partners.org OI Maxwell, Alexander P./0000-0002-6110-7253 FU National Institutes of Health [T32-DK-007260, F32-DK-103486-01]; Nylands Nation; JDRF [3-APF-2014-111-A-N, 3-2011-70]; Waldemar von Frenckell Foundation; Folkhalsan Research Foundation; Liv och Halsa Foundation; Willhelm and Else Stockmano Foundation; Helsinki University Central Hospital Research Funds; Sigrid Juselius Foundation; Finnish Cultural Foundation; Signe and Ane Gyllenberg Foundation; Finska Lakaresallskapet; Academy of Finland [134379]; Novo Nordisk Foundation; Tekes; US-Ireland RD partnership; Diabetes UK; JDRF; National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-081923] FX J.N.T. was supported by National Institutes of Health Training grant T32-DK-007260 and grant F32-DK-103486-01. E.H.D. was supported by grants from the Nylands Nation. R.M.S was supported by JDRF grants 3-APF-2014-111-A-N and 3-2011-70. N.S. was supported by grants from the Waldemar von Frenckell Foundation. The FinnDiane Study Group was supported by grants from the Folkhalsan Research Foundation, Liv och Halsa Foundation, the Willhelm and Else Stockmano Foundation, Helsinki University Central Hospital Research Funds, the Sigrid Juselius Foundation, the Finnish Cultural Foundation, the Signe and Ane Gyllenberg Foundation, Finska Lakaresallskapet, Academy of Finland (134379), Novo Nordisk Foundation, and Tekes. A.J.M., A.P.M., D.S., and C.G. are supported by the US-Ireland R&D partnership. The Warren 3/U.K. GoKinD Study Group was jointly funded by Diabetes UK and JDRF and includes: Belfast: A.P. Maxwell, A.J. McKnight, D.A. Savage; Edinburgh: J. Walker; London: S. Thomas, G.C. Viberti; Manchester: A.J.M. Boulton; Newcastle: S. Marshall; Plymouth: A.G. Demaine, B.A. Millward; Swansea: S.C. Bain. This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK-081923 to P.-H.G., J.N.H., and J.C.F. NR 41 TC 5 Z9 6 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2015 VL 64 IS 12 BP 4238 EP 4246 DI 10.2337/db15-0254 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX8DN UT WOS:000365932900028 PM 26307587 ER PT J AU Papandonatos, GD Pan, Q Pajewski, NM Delahanty, LM Peter, I Erar, B Ahmad, S Harden, M Chen, L Fontanillas, P Wagenknecht, LE Kahn, SE Wing, RR Jablonski, KA Huggins, GS Knowler, WC Florez, JC McCaffery, JM Franks, PW AF Papandonatos, George D. Pan, Qing Pajewski, Nicholas M. Delahanty, Linda M. Peter, Inga Erar, Bahar Ahmad, Shafqat Harden, Maegan Chen, Ling Fontanillas, Pierre Wagenknecht, Lynne E. Kahn, Steven E. Wing, Rena R. Jablonski, Kathleen A. Huggins, Gordon S. Knowler, William C. Florez, Jose C. McCaffery, Jeanne M. Franks, Paul W. CA Giant Consortium Diabetes Prevention Program & The TI Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials SO DIABETES LA English DT Article ID BODY-MASS INDEX; HEAT-SHOCK-PROTEIN; CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; RISK-FACTORS; OBESITY; INDIVIDUALS; LOCI; ASSOCIATION; TRANSLATION AB Clinically relevant weight loss is achievable through lifestyle modification, but unintentional weight regain is common. We investigated whether recently discovered genetic variants affect weight loss and/or weight regain during behavioral intervention. Participants at high-risk of type 2 diabetes (Diabetes Prevention Program [DPP]; N = 917/907 intervention/comparison) or with type 2 diabetes (Look AHEAD [Action for Health in Diabetes]; N = 2,014/1,892 intervention/comparison) were from two parallel arm (lifestyle vs. comparison) randomized controlled trials. The associations of 91 established obesity-predisposing loci with weight loss across 4 years and with weight regain across years 2-4 after a minimum of 3% weight loss were tested. Each copy of the minor G allele of MTIF3 rs1885988 was consistently associated with greater weight loss following lifestyle intervention over 4 years across the DPP and Look AHEAD. No such effect was observed across comparison arms, leading to a nominally significant single nucleotide polymorphism x treatment interaction (P = 4.3 x 10(-3)). However, this effect was not significant at a study-wise significance level (Bonferroni threshold P < 5.8 x 10(-4)). Most obesity-predisposing gene variants were not associated with weight loss or regain within the DPP and Look AHEAD trials, directly or via interactions with lifestyle. C1 [Papandonatos, George D.; Erar, Bahar] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Pan, Qing; Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Pajewski, Nicholas M.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Delahanty, Linda M.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Peter, Inga] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Ahmad, Shafqat; Franks, Paul W.] Skane Univ, Univ Lund, Dept Clin Sci, Genet & Mol Epidemiol Unit,Hosp Malmo, Malmo, Sweden. [Harden, Maegan] Broad Inst, Genom Platform, Cambridge, MA USA. [Chen, Ling; Fontanillas, Pierre; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Chen, Ling; Fontanillas, Pierre; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Wagenknecht, Lynne E.] Wake Forest Sch Med, Div Publ Hlth Sci, Look AHEAD Coordinating Ctr, Winston Salem, NC USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Wing, Rena R.; McCaffery, Jeanne M.] Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. [Wing, Rena R.; McCaffery, Jeanne M.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Huggins, Gordon S.] Tufts Med Ctr, Mol Cardiol Res Inst, Ctr Translat Genom, Boston, MA USA. [Knowler, William C.] NIDDK, Phoenix, AZ USA. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Franks, Paul W.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. RP Franks, PW (reprint author), Skane Univ, Univ Lund, Dept Clin Sci, Genet & Mol Epidemiol Unit,Hosp Malmo, Malmo, Sweden. EM jeanne_mccaffery@brown.edu; paul.franks@med.lu.se OI Papandonatos, George/0000-0001-6770-932X; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK072041-02, DK056992-14S1]; Department of Veterans Affairs; Doris Duke Charitable Foundation Clinical Scientist Development Award; Swedish Heart-Lung Foundation; Novo Nordisk Foundation; Swedish Research Council; EXODIAB; Swedish Diabetes Association; NIDDK of the National Institutes of Health (NIH); NIDDK; Indian Health Service; NIH Office of Research on Minority Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; NIH Office of Research on Women's Health; American Diabetes Association; Intramural Research Program of the NIDDK FX The DPP and Look AHEAD analyses were funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01 DK072041-02 (to K.A.J. and J.C.F. [W.C.K. and P.W.F. are co-nvestigators]) and DK056992-14S1, respectively. S.E.K. is supported in part by the Department of Veterans Affairs. J.C.F. is supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award. P.W.F. was supported by grants from the Swedish Heart-Lung Foundation, the Novo Nordisk Foundation, the Swedish Research Council, EXODIAB, and the Swedish Diabetes Association.; DPP: The NIDDK of the National Institutes of Health (NIH) provided funding to the clinical centers and the coordinating center for the design and conduct of the study and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program of the National Center for Research Resources supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the NIH Office of Research on Minority Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the NIH Office of Research on Women's Health, the Department of Veterans Affairs, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the Intramural Research Program of the NIDDK. LifeScan, Health O Meter, Hoechst Marion Roussel Inc., Merck-Medco Managed Care, LLC, Merck & Co., Inc., Nike Sports Marketing, SlimFast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group, Inc., and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. provided support services under subcontract with the coordinating center. NR 32 TC 7 Z9 7 U1 2 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 2015 VL 64 IS 12 BP 4312 EP 4321 DI 10.2337/db15-0441 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX8DN UT WOS:000365932900034 PM 26253612 ER PT J AU Laxminarayan, S Reifman, J Edwards, SS Wolpert, H Steil, GM AF Laxminarayan, Srinivas Reifman, Jaques Edwards, Stephanie S. Wolpert, Howard Steil, Garry M. TI Bolus Estimation-Rethinking the Effect of Meal Fat Content SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID TYPE-1 DIABETES IMPLICATIONS; INCREASES GLUCOSE-CONCENTRATIONS; INSULIN REQUIREMENTS; DOSE CALCULATION; SENSITIVITY; MANAGEMENT; PROTEIN; OUTPUT; PUMP AB Background: Traditionally, insulin bolus calculations for managing postprandial glucose levels in individuals with type 1 diabetes rely solely on the carbohydrate content of a meal. However, recent studies have reported that other macronutrients in a meal can alter the insulin required for good postprandial control. Specifically, studies have shown that high-fat (HF) meals require more insulin than low-fat (LF) meals with identical carbohydrate content. Our objective was to assess the mechanisms underlying the higher insulin requirement observed in one of these studies. Materials and Methods: We used a combination of previously validated metabolic models to fit data from a study comparing HF and LF dinners with identical carbohydrate content in seven subjects with type 1 diabetes. For each subject and dinner type, we estimated the model parameters representing the time of peak meal-glucose appearance ((m)), insulin sensitivity (S-I), the net hepatic glucose balance, and the glucose effect at zero insulin in four time windows (dinner, early night, late night, and breakfast) and assessed the differences in model parameters via paired Wilcoxon signed-rank tests. Results: During the HF meal, the (m) was significantly delayed (mean and standard error [SE]: 102 [14] min vs. 71 [4] min; P=0.02), and S-I was significantly lower (7.25x10(-4) [1.29x10(-4)] mL/U/min vs. 8.72x10(-4) [1.08x10(-4)] mL/U/min; P=0.02). Conclusions: In addition to considering the putative delay in gastric emptying associated with HF meals, we suggest that clinicians reviewing patient records consider that the fat content of these meals may alter S-I. C1 [Laxminarayan, Srinivas; Reifman, Jaques] US Army Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Dept Def, Biotechnol High Performance Comp Software Applica, Ft Detrick, MD USA. [Edwards, Stephanie S.; Wolpert, Howard] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wolpert, Howard; Steil, Garry M.] Harvard Univ, Sch Med, Boston, MA USA. [Steil, Garry M.] Childrens Hosp, Boston, MA 02115 USA. RP Steil, GM (reprint author), Childrens Hosp Boston, ATTN Div Med Crit Care, 333 Longwood Ave, Boston, MA 02215 USA. EM garry.steil@childrens.harvard.edu FU U.S. Department of Defense [W81XWH-11-1-0421]; Military Operational Medicine Research Area Directorate of the U.S. Army Medical Research and Materiel Command, Fort Detrick, MD FX The study was supported by U.S. Department of Defense grant W81XWH-11-1-0421 to G.M.S. and by the Military Operational Medicine Research Area Directorate of the U.S. Army Medical Research and Materiel Command, Fort Detrick, MD, to S.L. and J.R. NR 22 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD DEC 1 PY 2015 VL 17 IS 12 BP 860 EP 866 DI 10.1089/dia.2015.0118 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX4DB UT WOS:000365647500004 PM 26270134 ER PT J AU Cornejo, KM Hutchinson, L Cyr, MS Nose, V McLaughlin, PJ Iafrate, AJ Sadow, PM AF Cornejo, Kristine M. Hutchinson, Lloyd Cyr, Maryann St. Nose, Vania McLaughlin, Patrick J. Iafrate, A. John Sadow, Peter M. TI MYC Analysis by Fluorescent In Situ Hybridization and Immunohistochemistry in Primary Adrenal Angiosarcoma (PAA): a Series of Four Cases SO ENDOCRINE PATHOLOGY LA English DT Article DE Primary angiosarcoma; Adrenal; MYC; Immunohistochemistry; FISH; Polysomy ID ATYPICAL VASCULAR-LESIONS; BET BROMODOMAIN INHIBITION; B-CELL LYMPHOMA; EPITHELIOID ANGIOSARCOMA; C-MYC; CUTANEOUS ANGIOSARCOMA; PROGNOSTIC-FACTORS; CORTICAL ADENOMA; GLAND; AMPLIFICATION AB Primary adrenal angiosarcomas (PAA) are rare with 36 cases reported in the English literature. MYC protein expression and gene amplification have been detected in secondary angiosarcoma (AS), and a subset of primary AS. The aim of this study was to report the clinicopathologic features of PAA and examine these tumors for MYC amplification and protein expression in a small series of four cases (resection, n = 4). Three had available material for ancillary studies and were investigated for MYC gene abnormalities and protein expression using fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Tumors occurred in three females and one male with a mean age of 69 (53-75) years. The sizes ranged from 8.5 to 15 (mean 11.5) cm and were epithelioid in morphology. All tumors had prominent necrosis, and the mitotic count ranged from 4 to 41/10 high-power fields (HPFs) (mean 20/10 HPFs, x400). Immunohistochemically, the tumor cells were positive for CD31 in 4/4 cases, CD34 in 1/4 cases, and cytokeratin in 4/4 cases. The mean follow-up period was 10.8 (3-19) months, of which three patients died of disease with distant metastases, and one patient was alive with disease. MYC nuclear staining was identified in the three cases tested. Two cases showed polysomy of chromosome 8 without MYC amplification or rearrangement. Two MYC-positive cases by IHC demonstrated copy number gain in chromosome 8, and one MYC-positive case was not associated with a chromosome 8/MYC gene abnormality. In the context of new targeted therapies, MYC positivity in PAA may be clinically valuable in treating patients with these aggressive neoplasms. C1 [Cornejo, Kristine M.; Hutchinson, Lloyd; Cyr, Maryann St.] Univ Massachusetts, Sch Med, UMass Mem Healthcare, Dept Pathol, Worcester, MA 01605 USA. [Cornejo, Kristine M.; Nose, Vania; McLaughlin, Patrick J.; Iafrate, A. John; Sadow, Peter M.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA USA. RP Cornejo, KM (reprint author), Univ Massachusetts, Sch Med, UMass Mem Healthcare, Dept Pathol, One Innovat Dr,Biotech 3, Worcester, MA 01605 USA. EM Kristine.Cornejo@umassmemorial.org NR 52 TC 1 Z9 1 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 EI 1559-0097 J9 ENDOCR PATHOL JI Endocr. Pathol. PD DEC PY 2015 VL 26 IS 4 BP 334 EP 341 DI 10.1007/s12022-015-9385-4 PG 8 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA CX0XR UT WOS:000365421300010 PM 26223194 ER PT J AU Bagai, A Peterson, ED Honeycutt, E Effron, MB Cohen, DJ Goodman, SG Anstrom, KJ Gupta, A Messenger, JC Wang, TY AF Bagai, Akshay Peterson, Eric D. Honeycutt, Emily Effron, Mark B. Cohen, David J. Goodman, Shaun G. Anstrom, Kevin J. Gupta, Anjan Messenger, John C. Wang, Tracy Y. TI In-hospital switching between adenosine diphosphate receptor inhibitors in patients with acute myocardial infarction treated with percutaneous coronary intervention: Insights into contemporary practice from the TRANSLATE-ACS study SO EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE LA English DT Article DE Adenosine diphosphate receptor inhibitor switching; safety and effectiveness; acute coronary syndrome; percutaneous coronary intervention ID ASSOCIATION TASK-FORCE; HIGH-DOSE CLOPIDOGREL; ST-SEGMENT ELEVATION; ANTIPLATELET THERAPY; PLATELET INHIBITION; PRACTICE GUIDELINES; RANDOMIZED-TRIAL; PRASUGREL; EVENTS; MANAGEMENT AB Aims: While randomized clinical trials have compared clopidogrel with higher potency adenosine diphosphate (ADP) receptor inhibitors among patients with acute myocardial infarction, little is known about the frequency, effectiveness and safety of switching between ADP receptor inhibitors in routine clinical practice. Methods and results: We studied 11,999 myocardial infarction patients treated with percutaneous coronary intervention at 230 hospitals from April 2010 to October 2012 in the TRANSLATE-ACS study. Multivariable Cox regression was used to compare six-month post-discharge risks of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, or unplanned revascularization) and Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-defined bleeding between in-hospital ADP receptor inhibitor switching versus continuation of the initially selected therapy. Among 8715 patients treated initially with clopidogrel, 994 (11.4%) were switched to prasugrel or ticagrelor; switching occurred primarily after percutaneous coronary intervention (60.9%) and at the time of hospital discharge (26.7%). Among 3284 patients treated initially with prasugrel or ticagrelor, 448 (13.6%) were switched to clopidogrel; 48.2% of switches occurred after percutaneous coronary intervention and 48.0% at hospital discharge. Switching to prasugrel or ticagrelor was not associated with increased bleeding when compared with continuation on clopidogrel (2.7% vs. 3.3%, adjusted hazard ratio 0.96, 95% confidence interval 0.64-1.42, p=0.82). Switching from prasugrel or ticagrelor to clopidogrel was not associated with increased MACE (8.9% vs. 7.7%, adjusted hazard ratio 1.06, 95% confidence interval 0.75-1.49, p=0.76) when compared with continuation on the higher potency agent. Conclusions: In-hospital ADP receptor inhibitor switching occurs in more than one in 10 myocardial infarction patients in contemporary practice. In this observational study, ADP receptor inhibitor switching does not appear to be significantly associated with increased hazard of MACE or bleeding. C1 [Bagai, Akshay; Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Peterson, Eric D.; Honeycutt, Emily; Anstrom, Kevin J.; Wang, Tracy Y.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. [Effron, Mark B.] Lilly USA LLC, Indianapolis, IN USA. [Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, KS USA. [Gupta, Anjan] Univ Wisconsin, Sch Med & Publ Hlth, Aurora Cardiovasc Serv, Aurora Sinai Med Ctr, Milwaukee, WI 53201 USA. [Gupta, Anjan] Univ Wisconsin, Sch Med & Publ Hlth, Aurora Cardiovasc Serv, Aurora St Lukes Med Ctr, Milwaukee, WI 53201 USA. [Messenger, John C.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Bagai, A (reprint author), Univ Toronto, St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM bagaia@smh.ca NR 25 TC 12 Z9 12 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2048-8726 EI 2048-8734 J9 EUR HEART J-ACUTE CA JI Eur. Heart J.-Acute Cardiovasc. Care PD DEC PY 2015 VL 4 IS 6 BP 499 EP 508 DI 10.1177/2048872614564082 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX3QB UT WOS:000365613000002 PM 25515725 ER PT J AU Johnson, DB Menzies, AM Zimmer, L Eroglu, Z Ye, F Zhao, SL Rizos, H Sucker, A Scolyer, RA Gutzmer, R Gogas, H Kefford, RF Thompson, JF Becker, JC Berking, C Egberts, F Loquai, C Goldinger, SM Pupo, GM Hugo, W Kong, XJ Garraway, LA Sosman, JA Ribas, A Lo, RS Long, GV Schadendorf, D AF Johnson, Douglas B. Menzies, Alexander M. Zimmer, Lisa Eroglu, Zeynep Ye, Fei Zhao, Shilin Rizos, Helen Sucker, Antje Scolyer, Richard A. Gutzmer, Ralf Gogas, Helen Kefford, Richard F. Thompson, John F. Becker, Juergen C. Berking, Carola Egberts, Friederike Loquai, Carmen Goldinger, Simone M. Pupo, Gulietta M. Hugo, Willy Kong, Xiangju Garraway, Levi A. Sosman, Jeffrey A. Ribas, Antoni Lo, Roger S. Long, Georgina V. Schadendorf, Dirk TI Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE BRAF; Vemurafenib; Dabrafenib; Resistance; Acquired; MAPK; NRAS; Splice; MEK1; Meta-analysis ID METASTATIC MELANOMA; RAF INHIBITION; B-RAF; MUTATIONS; VEMURAFENIB; PATHWAY; COBIMETINIB; SURVIVAL; THERAPY AB Background: Acquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance. Methods: We compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing. Results: Among 132 samples, putative resistance mechanisms were identified in 58%, including NRAS or KRAS mutations (20%), BRAF splice variants (16%), BRAF(V600E/K) amplifications (13%), MEK1/2 mutations (7%), and non-mitogen-activated protein kinase pathway alterations (11%). Marked heterogeneity was observed within tumors and patients; 18 of 19 patients (95%) with more than one progression biopsy had distinct/unknown drivers of resistance between samples. NRAS mutations were associated with vemurafenib use (p = 0.045) and intracranial metastases (p = 0.036), and MEK1/2 mutations correlated with hepatic progression (p = 0.011). Progression-free survival and overall survival were similar across resistance mechanisms. The median survival after disease progression was 6.9 months, and responses to subsequent BRAF and MEK inhibition were uncommon (2 of 15; 13%). Post-progression outcomes did not correlate with specific acquired BRAFi-resistance mechanisms. Conclusions: This is the first study to systematically characterise the clinical implications of particular acquired BRAFi-resistance mechanisms in patients with BRAF-mutant melanoma largest study to compile the landscape of resistance. Despite marked heterogeneity of resistance mechanisms within patients, NRAS mutations correlated with vemurafenib use and intracranial disease involvement. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Johnson, Douglas B.; Ye, Fei; Zhao, Shilin; Sosman, Jeffrey A.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Menzies, Alexander M.; Scolyer, Richard A.; Kefford, Richard F.; Thompson, John F.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Zimmer, Lisa; Sucker, Antje; Schadendorf, Dirk] Univ Duisburg Essen, Univ Hosp, Dept Dermatol, Essen, Germany. [Eroglu, Zeynep; Hugo, Willy; Kong, Xiangju; Ribas, Antoni; Lo, Roger S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Eroglu, Zeynep] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA. [Menzies, Alexander M.; Rizos, Helen; Kefford, Richard F.; Pupo, Gulietta M.; Long, Georgina V.] Univ Sydney, Westmead Millennium Inst, Ctr Canc Res, Westmead, NSW 2145, Australia. [Rizos, Helen; Kefford, Richard F.] Macquarie Univ, Sydney, NSW 2109, Australia. [Scolyer, Richard A.; Thompson, John F.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Menzies, Alexander M.; Scolyer, Richard A.; Kefford, Richard F.; Thompson, John F.; Long, Georgina V.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Gutzmer, Ralf] Hannover Med Sch, Skin Canc Ctr Hannover, Dept Dermatol & Allergy, Hannover, Germany. [Gogas, Helen] Univ Athens, Sch Med, Dept Med 1, GR-11527 Athens, Greece. [Becker, Juergen C.] Univ Hosp Essen, German Canc Consortium DKTK, Translat Skin Canc Res, Essen, Germany. [Berking, Carola] Univ Munich, Dept Dermatol, D-80539 Munich, Germany. [Egberts, Friederike] Univ Hosp Schleswig Holstein, Dept Dermatol, Kiel, Germany. [Loquai, Carmen] Univ Med Ctr, Dept Dermatol, Mainz, Germany. [Goldinger, Simone M.] Univ Zurich Hosp, Dept Dermatol, Zurich, Switzerland. [Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Johnson, DB (reprint author), 777 PRB,2220 Pierce Ave, Nashville, TN 37232 USA. EM douglas.b.johnson@vanderbilt.edu OI Scolyer, Richard/0000-0002-8991-0013 FU NCI NIH HHS [K12 CA0906525, P01 CA168585, K12 CA090625, P30 CA016042] NR 35 TC 27 Z9 27 U1 4 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2015 VL 51 IS 18 BP 2792 EP 2799 DI 10.1016/j.ejca.2015.08.022 PG 8 WC Oncology SC Oncology GA CX3UI UT WOS:000365624500009 PM 26608120 ER PT J AU Wu, Q Zhang, JJ Koh, W Yu, QM Zhu, XJ Amsterdam, A Davis, GE Arnaout, MA Xiong, JW AF Wu, Qing Zhang, Jiaojiao Koh, Wonshill Yu, Qingming Zhu, Xiaojun Amsterdam, Adam Davis, George E. Arnaout, M. Amin Xiong, Jing-Wei TI Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in zebrafish SO FASEB JOURNAL LA English DT Article DE tln1; itgb1b; cardiovascular development; cardiac sarcomere ID DILATED CARDIOMYOPATHY; PRESSURE-OVERLOAD; LUMEN FORMATION; BINDING DOMAIN; CELL-ADHESION; ROD DOMAIN; GENE; EXPRESSION; HEART; CONTRACTILITY AB Talin (tln) binds and activates integrins to couple extracellular matrix-bound integrins to the cytoskeleton; however, its role in heart development is not well characterized. We identified the defective gene and the resulting cardiovascular phenotypes in zebrafish tln1(fl02k) mutants. The ethylnitrosourea-induced fl02k mutant showed heart failure, brain hemorrhage, and diminished cardiac and vessel lumens at 52 h post fertilization. Positional cloning revealed a nonsense mutation of tln1 in this mutant. tln1, but neither tln2 nor -2a, was dominantly expressed in the heart and vessels. Unlike tln1 and -2 in the mouse heart, the unique tln1 expression in the heart enabled us, for the first time, to determine the critical roles of Tln1 in the maintenance of cardiac sarcomeric Z-disks and endothelial/endocardial cell integrity, partly through regulating F-actin networks in zebrafish. The similar expression profiles of tln1 and integrin beta 1b (itgb1b) and synergistic function of the 2 genes revealed that itgb1b is a potential partner for tln1 in the stabilization of cardiac Z-disks and vessel lumens. Taken together, the results of this work suggest that Tln1-mediated Itg beta 1b plays a crucial role in maintaining cardiac sarcomeric Z-disks and endothelial/endocardial cell integrity in zebrafish and may also help to gain molecular insights into congenital heart diseases. C1 [Wu, Qing; Zhu, Xiaojun; Xiong, Jing-Wei] Peking Univ, Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China. [Wu, Qing] Peking Univ, Inst Mol Med, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China. [Zhang, Jiaojiao; Yu, Qingming; Arnaout, M. Amin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA USA. [Koh, Wonshill; Davis, George E.] Univ Missouri, Sch Med, Dept Med Pharmacol, Columbia, MO USA. [Koh, Wonshill; Davis, George E.] Univ Missouri, Sch Med, Dept Physiol, Columbia, MO 65212 USA. [Amsterdam, Adam] MIT, Dept Biol, Cambridge, MA USA. RP Xiong, JW (reprint author), Peking Univ, Inst Mol Med, New Life Sci Bldg,Room 102, Beijing 100871, Peoples R China. EM jingwei_xiong@pku.edu.cn FU U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases Training Grant [T32-DK07540, DK088327, DK48549]; March of Dimes Birth Defects Foundation [1-FY2007-471]; Milton Fund from Harvard University; National Basic Research Program of China [2012CB944501, 2010CB529503]; National Natural Science Foundation of China [31430059, 81470399, 31221002, 31271549, 81270164]; NIH National Heart, Lung, and Blood Institute [HL59373]; NIH National Center for Research Resources Grant [RR012589] FX The authors thank Dr. W. Shou (Indiana University, Indianapolis, IN, USA) and members of the laboratory of J.-W.X. for providing critical comments on the manuscript, Dr. I. C. Bruce (Zhejiang University, Zheijang, China) for reading the manuscript, and Dr. Y. Hu (Peking University, Peking, China) for help with transmission electron microscopy. This work was funded by U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases Training Grant T32-DK07540 (to Q.Y.) and Grants DK088327 and DK48549 (to M.A.A.); March of Dimes Birth Defects Foundation Grant 1-FY2007-471 (to J.-W.X.); the Milton Fund from Harvard University (to J.-W.X.); the National Basic Research Program of China Grants 2012CB944501 and 2010CB529503 (to J.-W.X.); the National Natural Science Foundation of China Grants 31430059, 81470399, 31221002, 31271549, and 81270164 (to J.-W.X.); NIH National Heart, Lung, and Blood Institute Grant HL59373 (to G.E.D.); and NIH National Center for Research Resources Grant RR012589 (to M.A.A). NR 65 TC 1 Z9 1 U1 3 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD DEC PY 2015 VL 29 IS 12 BP 4989 EP 5005 DI 10.1096/fj.15-273409 PG 17 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA CX2JS UT WOS:000365523600024 PM 26310270 ER PT J AU O'Leary, TJ Dominitz, JA Chang, KM AF O'Leary, Timothy J. Dominitz, Jason A. Chang, Kyong-Mi TI Veterans Affairs Office of Research and Development: Research Programs and Emerging Opportunities in Digestive Diseases Research SO GASTROENTEROLOGY LA English DT Editorial Material ID MILITARY SERVICE MEMBERS; CARE CLINICAL-TRIAL; COLORECTAL-CANCER; UNITED-STATES; MILLENNIUM COHORT; MENTAL-HEALTH; HEPATITIS; RISK; PREVALENCE; DEPLOYMENT C1 [O'Leary, Timothy J.] US EPA, Off Res & Dev, Dept Vet Affairs, Washington, DC 20460 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Sch Med, Seattle, WA USA. [Chang, Kyong-Mi] Univ Penn, Corporal Michael J Crescenz VA Med Ctr, Philadelphia, PA 19104 USA. [Chang, Kyong-Mi] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP O'Leary, TJ (reprint author), US EPA, Off Res & Dev, Dept Vet Affairs, Washington, DC 20460 USA. FU BLRD VA [I01 BX000649]; Intramural VA [VA999999] NR 24 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2015 VL 149 IS 7 BP 1652 EP 1661 DI 10.1053/j.gastro.2015.10.021 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX6JX UT WOS:000365808100011 PM 26526712 ER PT J AU Tache, Y AF Tache, Yvette TI Personal Perspectives on Mentoring SO GASTROENTEROLOGY LA English DT Editorial Material ID MENTORSHIP; GASTROENTEROLOGY C1 [Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, CURE Digest Dis Res Ctr,Digest Dis Div, Los Angeles, CA 90095 USA. [Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Ctr Neurobiol Stress & Womens Hlth,Digest Dis Div, Los Angeles, CA 90095 USA. [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,CURE Bldg 115,Room 117, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu NR 14 TC 1 Z9 1 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2015 VL 149 IS 7 BP 1662 EP 1665 DI 10.1053/j.gastro.2015.10.037 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX6JX UT WOS:000365808100012 PM 26515791 ER PT J AU Arora, S Yan, H Cho, I Fan, HY Luo, B Gai, XW Bodian, DL Vockley, JG Zhou, Y Handorf, EA Egleston, BL Andrake, MD Nicolas, E Serebriiskii, IG Yen, TJ Hall, MJ Golemis, EA Enders, GH AF Arora, Sanjeevani Yan, Hong Cho, Iltaeg Fan, Hua-Ying Luo, Biao Gai, Xiaowu Bodian, Dale L. Vockley, Joseph G. Zhou, Yan Handorf, Elizabeth A. Egleston, Brian L. Andrake, Mark D. Nicolas, Emmanuelle Serebriiskii, Ilya G. Yen, Timothy J. Hall, Michael J. Golemis, Erica A. Enders, Greg H. TI Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas SO GASTROENTEROLOGY LA English DT Article DE Colon Cancer; Hereditary Cancer; Genomic Instability; Tumorigenesis ID PERIPHERAL-BLOOD LYMPHOCYTES; GENOME-WIDE ASSOCIATION; FANCONI-ANEMIA PATHWAY; CANCER-RISK; GERMLINE MUTATIONS; MICRONUCLEI FREQUENCY; SUSCEPTIBILITY LOCI; WERNER-SYNDROME; PROTEIN; REPAIR AB BACKGROUND & AIMS: DNA structural lesions are prevalent in sporadic colorectal cancer. Therefore, we proposed that gene variants that predispose to DNA double-strand breaks (DSBs) would be found in patients with familial colorectal carcinomas of an undefined genetic basis (UFCRC). METHODS: We collected primary T cells from 25 patients with UFCRC and matched patients without colorectal cancer (controls) and assayed for DSBs. We performed exome sequence analyses of germline DNA from 20 patients with UFCRC and 5 undiagnosed patients with polyposis. The prevalence of identified variants in genes linked to DNA integrity was compared with that of individuals without a family history of cancer. The effects of representative variants found to be associated with UFCRC was confirmed in functional assays with HCT116 cells. RESULTS: Primary T cells from most patients with UFCRC had increased levels of the DSB marker gamma(phosphorylated)histone2AX (gamma H2AX) after treatment with DNA damaging agents, compared with T cells from controls (P < .001). Exome sequence analysis identified a mean 1.4 rare variants per patient that were predicted to disrupt functions of genes relevant to DSBs. Controls (from public databases) had a much lower frequency of variants in the same genes (P < .001). Knockdown of representative variant genes in HCT116 CRC cells increased gamma H2AX. A detailed analysis of immortalized patient-derived B cells that contained variants in the Werner syndrome, RecQ helicase-like gene (WRN, encoding T705I), and excision repair cross-complementation group 6 (ERCC6, encoding N180Y) showed reduced levels of these proteins and increased DSBs, compared with B cells from controls. This phenotype was rescued by exogenous expression of WRN or ERCC6. Direct analysis of the recombinant variant proteins confirmed defective enzymatic activities. CONCLUSIONS: These results provide evidence that defects in suppression of DSBs underlie some cases of UFCRC; these can be identified by assays of circulating lymphocytes. We specifically associated UFCRC with variants in WRN and ERCC6 that reduce the capacity for repair of DNA DSBs. These observations could lead to a simple screening strategy for UFCRC, and provide insight into the pathogenic mechanisms of colorectal carcinogenesis. C1 [Arora, Sanjeevani; Yan, Hong; Yen, Timothy J.; Enders, Greg H.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA. [Arora, Sanjeevani; Egleston, Brian L.; Andrake, Mark D.; Serebriiskii, Ilya G.; Golemis, Erica A.] Fox Chase Canc Ctr, Mol Therapeut Program, Philadelphia, PA 19111 USA. [Luo, Biao] Fox Chase Canc Ctr, Inst Personalized Med, Philadelphia, PA 19111 USA. [Zhou, Yan; Handorf, Elizabeth A.; Egleston, Brian L.] Fox Chase Canc Ctr, Biostat, Philadelphia, PA 19111 USA. [Nicolas, Emmanuelle] Fox Chase Canc Ctr, Genom, Philadelphia, PA 19111 USA. [Hall, Michael J.] Fox Chase Canc Ctr, Med Oncol, Philadelphia, PA 19111 USA. [Hall, Michael J.] Fox Chase Canc Ctr, Clin Genet, Philadelphia, PA 19111 USA. [Enders, Greg H.] Fox Chase Canc Ctr, Med, Philadelphia, PA 19111 USA. [Cho, Iltaeg; Fan, Hua-Ying] Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gai, Xiaowu] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Nicolas, Emmanuelle] Inova Hlth Syst, Inova Translat Med Inst, Falls Church, VA USA. [Serebriiskii, Ilya G.] Kazan Fed Univ, Kazan, Russia. RP Golemis, EA (reprint author), Fox Chase Canc Ctr, Mol Therapeut, W406,333 Cottman Ave, Philadelphia, PA 19111 USA. EM erica.golemis@fccc.edu; greg.enders@fccc.edu FU Gianforte Family fund; National Cancer Institute [P30 CA006927]; Fox Chase Cancer Center; National Institutes of Health [GM084983, CA63366]; Russian Government FX Supported by an unrestricted gift to the Department of Medicine at Fox Chase Cancer Center by the Fuginon Corporation (G.H.E.), the Gianforte Family fund (G.H.E.), National Cancer Institute Core grant P30 CA006927, Fox Chase Cancer Center institutional funds (S.A., M.H., and G.H.E.), National Institutes of Health grants GM084983 (H.-Y.F.) and CA63366 (E.A.G.), and a subsidy of the Russian Government to Kazan Federal University (I.G.S.). NR 46 TC 3 Z9 3 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2015 VL 149 IS 7 BP 1872 EP + DI 10.1053/j.gastro.2015.08.052 PG 21 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX6JX UT WOS:000365808100040 PM 26344056 ER PT J AU Brugge, WR AF Brugge, William R. TI Cyst fluid: moving beyond the carcinoembryonic antigen SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID ENDOSCOPIC ULTRASOUND; PANCREAS; NEOPLASMS C1 [Brugge, William R.] Massachusetts Gen Hosp, Pancreas Biliary Ctr, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Pancreas Biliary Ctr, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2015 VL 82 IS 6 BP 1070 EP 1071 DI 10.1016/j.gie.2015.08.005 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX3GN UT WOS:000365585000015 PM 26264436 ER PT J AU Pont, LMEB Balvers, RK Kloezeman, JJ Nowicki, MO van den Bossche, W Kremer, A Wakimoto, H van den Hoogen, BG Leenstra, S Dirven, CMF Chiocca, EA Lawler, SE Lamfers, MLM AF Pont, L. M. E. Berghauser Balvers, R. K. Kloezeman, J. J. Nowicki, M. O. van den Bossche, W. Kremer, A. Wakimoto, H. van den Hoogen, B. G. Leenstra, S. Dirven, C. M. F. Chiocca, E. A. Lawler, S. E. Lamfers, M. L. M. TI In vitro screening of clinical drugs identifies sensitizers of oncolytic viral therapy in glioblastoma stem-like cells SO GENE THERAPY LA English DT Article ID CONDITIONALLY REPLICATIVE ADENOVIRUS; GLYCOGEN-SYNTHASE KINASE-3-BETA; MALIGNANT GLIOMA; ADJUVANT TEMOZOLOMIDE; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; CANCER; LINES; VIRUS; RADIOTHERAPY AB Oncolytic viruses (OV) have broad potential as an adjuvant for the treatment of solid tumors. The present study addresses the feasibility of clinically applicable drugs to enhance the oncolytic potential of the OV Delta24-RGD in glioblastoma. In total, 446 drugs were screened for their viral sensitizing properties in glioblastoma stem-like cells (GSCs) in vitro. Validation was done for 10 drugs to determine synergy based on the Chou Talalay assay. Mechanistic studies were undertaken to assess viability, replication efficacy, viral infection enhancement and cell death pathway induction in a selected panel of drugs. Four viral sensitizers (fluphenazine, indirubin, lofepramine and ranolazine) were demonstrated to reproducibly synergize with Delta24-RGD in multiple assays. After validation, we underscored general applicability by testing candidate drugs in a broader context of a panel of different GSCs, various solid tumor models and multiple OVs. Overall, this study identified four viral sensitizers, which synergize with Delta24-RGD and two other strains of OVs. The viral sensitizers interact with infection, replication and cell death pathways to enhance efficacy of the OV. C1 [Pont, L. M. E. Berghauser; Balvers, R. K.; Kloezeman, J. J.; van den Bossche, W.; Leenstra, S.; Dirven, C. M. F.; Lamfers, M. L. M.] Erasmus MC, Dept Neurosurg, Brain Tumor Ctr, NL-3015 GE Rotterdam, Netherlands. [Nowicki, M. O.; Chiocca, E. A.; Lawler, S. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvey Cushing Neurooncol Labs, Boston, MA 02115 USA. [van den Bossche, W.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands. [Kremer, A.] Erasmus MC, Dept Bioinformat, Rotterdam, Netherlands. [Wakimoto, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [van den Hoogen, B. G.] Erasmus MC, Dept Virosci, Rotterdam, Netherlands. [Leenstra, S.] Elisabeth Hosp, Dept Neurosurg, Tilburg, Netherlands. RP Lamfers, MLM (reprint author), Erasmus MC, Dept Neurosurg, Brain Tumor Ctr, Wytemaweg 80,Room Ee2236, NL-3015 GE Rotterdam, Netherlands. EM m.lamfers@erasmusmc.nl RI Lamfers, Martine/C-6246-2016; OI Lamfers, Martine/0000-0001-7745-9029 FU Royal Dutch Wilhelmina Fund (KWF); EUR Trustfonds, Rotterdam, The Netherlands FX This research was partially supported by a Travel Fund of the Royal Dutch Wilhelmina Fund (KWF) and a travel fund of the EUR Trustfonds, Rotterdam, The Netherlands. NR 61 TC 3 Z9 3 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD DEC PY 2015 VL 22 IS 12 BP 947 EP 959 DI 10.1038/gt.2015.72 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA CX8TA UT WOS:000365975900003 ER PT J AU Kowalczyk, MS Tirosh, I Heck, D Rao, TN Dixit, A Haas, BJ Schneider, RK Wagers, AJ Ebert, BL Regev, A AF Kowalczyk, Monika S. Tirosh, Itay Heck, Dirk Rao, Tata Nageswara Dixit, Atray Haas, Brian J. Schneider, Rebekka K. Wagers, Amy J. Ebert, Benjamin L. Regev, Aviv TI Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells SO GENOME RESEARCH LA English DT Article ID INTEGRATIVE GENOMICS VIEWER; SLAM FAMILY MARKERS; AGE-RELATED-CHANGES; SELF-RENEWAL; PROGENITOR CELLS; IN-VIVO; STOCHASTIC-MODEL; FLT3 EXPRESSION; IDENTIFICATION; HETEROGENEITY AB Both intrinsic cell state changes and variations in the composition of stem cell populations have been implicated as contributors to aging. We used single-cell RNA-seq to dissect variability in hematopoietic stem cell (HSC) and hematopoietic progenitor cell populations from young and old mice from two strains. We found that cell cycle dominates the variability within each population and that there is a lower frequency of cells in the GI phase among old compared with young long-term HSCs, suggesting that they traverse through a faster. Moreover, transcriptional changes in HSCs during aging are inversely related to those upon HSC differentiation, such that old short-term (ST) HSCs resemble young long-term (LT-HSCs), suggesting that they exist in a less differentiated state. Our results indicate both compositional changes and intrinsic, population-wide changes with age and are consistent with a model where a relationship between cell cycle progression and selfrenewal versus differentiation of HSCs is affected by aging and may contribute to the functional decline of old HSCs. C1 [Kowalczyk, Monika S.; Tirosh, Itay; Dixit, Atray; Haas, Brian J.; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Heck, Dirk; Schneider, Rebekka K.; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. [Rao, Tata Nageswara; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Rao, Tata Nageswara; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Rao, Tata Nageswara; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Wagers, Amy J.] Harvard Univ, Paul F Glenn Labs Biol Mech Aging, Sch Med, Boston, MA 02115 USA. [Wagers, Amy J.; Regev, Aviv] MIT, Howard Hughes Med Inst, Cambridge, MA 02140 USA. [Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02140 USA. RP Regev, A (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM aregev@broadinstitute.org FU European Hematology Association; EMBO Long Term Fellowship; Foundation for Polish Science; HFSP Long Term Fellowship; Rothschild Fellowship; German Cancer Foundation; Leukemia and Lymphoma Society Scholar Award; National Institutes of Health (NIH) [P01 CA066996]; HHMI; NIH CEGS Award [1P50HG006193-01]; Koch Institute Support (core) Grant from the National Cancer Institute [P30-CA14051]; Klarman Family Foundation FX We thank Alex Shalek, Rahul Satija, Orit Rozenblatt-Rosen, and Dawn Thompson for scientific discussions; Candace Guiducci for project management; Leslie Gaffney for assistance with artwork; and the Broad Genomics Platform for all sequencing work. We thank DFCI and Joslin/HSCI Flow Cytometry Cores for excellent flow cytometry support. This work was supported by an EHA Research Fellowship award from the European Hematology Association (M.S.K.), EMBO Long Term Fellowship (M.S.K.), Foundation for Polish Science (M.S.K.), HFSP Long Term Fellowship (I.T.), Rothschild Fellowship (I.T.), German Cancer Foundation (D.H.), Leukemia and Lymphoma Society Scholar Award (B.L.E.), National Institutes of Health (NIH) (P01 CA066996, B.L.E.), HHMI (A.R.), NIH CEGS Award (1P50HG006193-01, A.R.), Koch Institute Support (core) Grant from the National Cancer Institute (P30-CA14051, A.R.), and the Klarman Family Foundation (A.R.). A.J.W. is an Early Career Scientist of the Howard Hughes Medical Institute. NR 77 TC 21 Z9 22 U1 4 U2 17 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD DEC PY 2015 VL 25 IS 12 BP 1860 EP 1872 DI 10.1101/gr.192237.115 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CX6RZ UT WOS:000365830400008 PM 26430063 ER PT J AU van Zyl, T Stagner, AM Jakobiec, FA Yoon, MK AF van Zyl, Tave Stagner, Anna M. Jakobiec, Frederick A. Yoon, Michael K. TI Histopathologic features of a resolving orbital Langerhans cell histiocytosis SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Letter ID EOSINOPHILIC GRANULOMA; BONE C1 [van Zyl, Tave; Stagner, Anna M.; Jakobiec, Frederick A.; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Stagner, Anna M.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. EM Fred_Jakobiec@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X EI 1435-702X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD DEC PY 2015 VL 253 IS 12 BP 2341 EP 2343 DI 10.1007/s00417-015-3086-z PG 3 WC Ophthalmology SC Ophthalmology GA CX0ZV UT WOS:000365426900037 PM 26134307 ER PT J AU Bordon, JM Fernandez-Botran, R Wiemken, TL Peyrani, P Uriarte, SM Arnold, FW Rodriquez-Hernandez, L Rane, MJ Kelley, RR Binford, LE Uppatla, S Cavallazzi, R Blasi, F Aliberti, S Restrepo, MI Fazeli, S Mathur, A Rahmani, M Ayesu, K Ramirez, J AF Bordon, J. M. Fernandez-Botran, R. Wiemken, T. L. Peyrani, P. Uriarte, S. M. Arnold, F. W. Rodriquez-Hernandez, L. Rane, M. J. Kelley, R. R. Binford, L. E. Uppatla, S. Cavallazzi, R. Blasi, F. Aliberti, S. Restrepo, M. I. Fazeli, S. Mathur, A. Rahmani, M. Ayesu, K. Ramirez, J. TI Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response SO INFECTION LA English DT Article DE Streptococcus pneumoniae; Community-acquired pneumonia; Pneumonia severity; Pneumococcal bacteremia; Outcome; Mortality; Inflammatory response; Cytokines; Chemokines; Biomarkers; Neutrophil functional responses ID COMMUNITY-ACQUIRED-PNEUMONIA; STREPTOCOCCUS-PNEUMONIAE; HOSPITALIZED-PATIENTS; RISK-FACTORS; SEVERITY; ORGANIZATION; PATHOGENS; PROGNOSIS; DISEASE AB Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1r alpha, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines. C1 [Bordon, J. M.; Fazeli, S.; Mathur, A.; Rahmani, M.] Providence Hosp, Infect Dis Sect, Washington, DC 20017 USA. [Fernandez-Botran, R.] Univ Louisville, Sch Med, Dept Pathol & Lab Med, Louisville, KY 40292 USA. [Wiemken, T. L.; Peyrani, P.; Arnold, F. W.; Rodriquez-Hernandez, L.; Kelley, R. R.; Binford, L. E.; Uppatla, S.; Cavallazzi, R.; Ramirez, J.] Univ Louisville, Sch Med, Dept Med, Div Infect Dis, Louisville, KY 40292 USA. [Uriarte, S. M.; Rane, M. J.] Univ Louisville, Sch Med, Dept Med, Div Nephrol, Louisville, KY 40292 USA. [Blasi, F.] Univ Milan, Dept Pathophysiol & Transplantat, IRCCS Fdn Ca Granda Osped Maggiore, Milan, Italy. [Aliberti, S.] Univ Milano Bicocca, Resp Unit, Dept Hlth Sci, AO San Gerardo, Monza, Italy. [Restrepo, M. I.] South Texas Vet Hlth Care Syst, Dept Pulm Dis, San Antonio, TX USA. [Restrepo, M. I.] Univ Texas San Antonio, San Antonio, TX USA. [Ramirez, J.] Vet Adm Med Ctr, Louisville, KY 40202 USA. [Ayesu, K.] Orlando Hlth, Dept Internal Med, Orlando, FL USA. RP Bordon, JM (reprint author), Providence Hosp, Infect Dis Sect, Washington, DC 20017 USA. EM jbordon@provhosp.org RI Fernandez-Botran, Rafael/J-3659-2016; Aliberti, Stefano/K-9115-2016; OI Fernandez-Botran, Rafael/0000-0001-8138-8745; Aliberti, Stefano/0000-0002-0090-4531; Blasi, Francesco/0000-0002-2285-9970 NR 29 TC 6 Z9 8 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8126 EI 1439-0973 J9 INFECTION JI Infection PD DEC PY 2015 VL 43 IS 6 BP 729 EP 738 DI 10.1007/s15010-015-0837-z PG 10 WC Infectious Diseases SC Infectious Diseases GA CX2FG UT WOS:000365510700013 PM 26424683 ER PT J AU Trebicka, E Shanmugam, NKN Chen, KJ Su, CW Shi, HN Cherayil, BJ AF Trebicka, Estela Shanmugam, Nanda Kumar N. Chen, Kejie Su, Chien-Wen Shi, Hai Ning Cherayil, Bobby J. TI Intestinal Inflammation Leads to a Long-lasting Increase in Resistance to Systemic Salmonellosis that Requires Macrophages But Not B or T Lymphocytes at the Time of Pathogen Challenge SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE colitis; Salmonella; macrophage; neutrophil ID ENTERICA SEROVAR TYPHIMURIUM; NONTYPHOIDAL SALMONELLA; BACTERICIDAL ACTIVITY; COMMENSAL BACTERIA; INNATE IMMUNITY; ANTIBODIES; INFECTION; PROTECTION; CHILDREN; ADULTS AB Background:Intestinal inflammation is associated with systemic translocation of commensal antigens and the consequent activation of B and T lymphocytes. The long-term consequences of such immune activation are not completely understood. Methods:C57BL/6 mice were subjected to 2 courses of treatment with dextran sulfate sodium (DSS) to induce colitis. Two to 7 weeks after the DSS treatment, the mice were infected intraperitoneally with Salmonella enterica serovar Typhimurium. The outcome of infection was evaluated based on survival and tissue pathogen burden. Results:Mice that had recovered from DSS colitis displayed a significant increase in resistance to S. Typhimurium infection as indicated by improved survival and decreased tissue pathogen numbers. The colitis-induced increase in resistance to systemic salmonellosis lasted for as long as 7 weeks after discontinuing DSS and was dependent on T lymphocytes but not on B cells. Interestingly, depletion of CD4(+) and CD8(+) T cells just before the Salmonella infection did not alter the colitis-induced increase in resistance. Mice that had recovered from colitis had evidence of persistent activation of resident peritoneal macrophages and enhanced Salmonella-induced neutrophil recruitment to the peritoneum. Macrophage depletion with clodronate liposomes abrogated the colitis-induced increase in resistance to Salmonella. Conclusions:Taken together, our results indicate that DSS colitis leads to a long-lasting increase in resistance to Salmonella infection that is initiated in a T cell-dependent manner but is ultimately mediated independently of B and T cells as a result of persistent changes in innate immune cell function. C1 [Trebicka, Estela; Shanmugam, Nanda Kumar N.; Chen, Kejie; Su, Chien-Wen; Shi, Hai Ning; Cherayil, Bobby J.] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU National Institutes of Health [R01 AI089700, R01 DK082427]; National Institutes of Health grant (Nutrition and Obesity Research Center at Harvard) [P30 DK040561]; National Institutes of Health grant [U19 AI082655] FX Supported by grants from the National Institutes of Health: R01 AI089700 to B. J. Cherayil and R01 DK082427 to H. N. Shi. B. J. Cherayil and H. N. Shi received additional support from National Institutes of Health grant P30 DK040561 (the Nutrition and Obesity Research Center at Harvard). B. J. Cherayil was also supported by National Institutes of Health grant U19 AI082655. NR 30 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2015 VL 21 IS 12 BP 2758 EP 2765 DI 10.1097/MIB.0000000000000544 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX3IZ UT WOS:000365593500003 PM 26222341 ER PT J AU Shelton, E Allegretti, JR Stevens, B Lucci, M Khalili, H Nguyen, DD Sauk, J Giallourakis, C Garber, J Hamilton, MJ Tomczak, M Makrauer, F Burakoff, RB Levine, J de Silva, P Friedman, S Ananthakrishnan, A Korzenik, JR Yajnik, V AF Shelton, Edward Allegretti, Jessica R. Stevens, Betsy Lucci, Matthew Khalili, Hamed Nguyen, Deanna D. Sauk, Jenny Giallourakis, Cosmas Garber, John Hamilton, Matthew J. Tomczak, Michal Makrauer, Fredrick Burakoff, Robert B. Levine, Jonathan de Silva, Punyaganie Friedman, Sonia Ananthakrishnan, Ashwin Korzenik, Joshua R. Yajnik, Vijay TI Efficacy of Vedolizumab as Induction Therapy in Refractory IBD Patients: A Multicenter Cohort SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE vedolizumab; Crohn's disease; ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; RANDOMIZED CONTROLLED-TRIALS; ULCERATIVE-COLITIS; CROHNS-DISEASE; MAINTENANCE THERAPY; ADALIMUMAB INDUCTION; ACTIVITY INDEX; INFLIXIMAB; METAANALYSIS; PREDICTORS AB Background:Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease in a multicenter cohort of patients.Methods:Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300 mg) was administered at weeks 0, 2, 6, and 14. Efficacy was assessed using the Harvey-Bradshaw index for CD, the simple clinical colitis activity index for UC and physician assessment, along with C-reactive protein and decrease of corticosteroid therapy. Clinical response was defined as decrease in Harvey-Bradshaw index 3 and simple clinical colitis activity index 3 and remission as Harvey-Bradshaw index 4, simple clinical colitis activity index 2 and physician assessment of response and remission.Results:Our study included 172 patients (107 CD, 59 UC, 6 inflammatory bowel disease-unclassified, men 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had ostomy and 9 ileoanal pouch, and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14, respectively. Adverse events occurred in 10.5%.Conclusions:VDZ is safe and well tolerated in refractory inflammatory bowel disease patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. C1 [Shelton, Edward; Stevens, Betsy; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Ananthakrishnan, Ashwin; Yajnik, Vijay] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Shelton, Edward; Allegretti, Jessica R.; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J.; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B.; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay] Harvard Univ, Sch Med, Boston, MA USA. [Allegretti, Jessica R.; Lucci, Matthew; Hamilton, Matthew J.; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B.; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Korzenik, Joshua R.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Yajnik, V (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM vyajnik@mgh.harvard.edu FU American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; Takeda FX A. Ananthakrishnan has served on scientific advisory boards for Abbvie and Cubist. V. Yajnik has been a consultant for Janssen, UCB, Takeda and Abbvie. J. Sauk is employed by Seres Therapeutics. H. Khalili is supported by a career development award from the American Gastroenterological Association (AGA) and by National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). J. R. Korzenik is supported by funding from Takeda. The remaining authors have no conflicts of interest to disclose. NR 29 TC 17 Z9 17 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2015 VL 21 IS 12 BP 2879 EP 2885 DI 10.1097/MIB.0000000000000561 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CX3IZ UT WOS:000365593500017 PM 26288002 ER PT J AU Libman, IM Miller, KM DiMeglio, LA Bethin, KE Katz, ML Shah, A Simmons, JH Haller, MJ Raman, S Tamborlane, WV Coffey, JK Saenz, AM Beck, RW Nadeau, KJ AF Libman, Ingrid M. Miller, Kellee M. DiMeglio, Linda A. Bethin, Kathleen E. Katz, Michelle L. Shah, Avni Simmons, Jill H. Haller, Michael J. Raman, Sripriya Tamborlane, William V. Coffey, Julie K. Saenz, Ashleigh M. Beck, Roy W. Nadeau, Kristen J. CA T1D Exchange Clinic Network Metfor TI Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RESISTANCE; SENSITIVITY; COMPLICATIONS; MELLITUS AB IMPORTANCE Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. OBJECTIVE To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA(1c) 8.8% (0.7%). INTERVENTIONS Randomization to receive metformin (n = 71) (<= 2000mg/d) or placebo (n = 69). MAIN OUTCOMES AND MEASURES Primary outcome was change in HbA(1c) from baseline to 26 weeks adjusted for baseline HbA(1c). Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids. RESULTS Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA(1c) was 8.8% in each group. At 13-week follow-up, reduction in HbA(1c) was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3%[95% CI, -0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA(1c) from baseline was 0.2% in each group (mean difference, 0%[95% CI, -0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23%(16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24%(17) of participants in the metformin group and 7%(5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17%[95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36%[95% CI, 19% to 51%]; P < .001). CONCLUSIONS AND RELEVANCE Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control. C1 [Libman, Ingrid M.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Miller, Kellee M.; Saenz, Ashleigh M.; Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [DiMeglio, Linda A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Bethin, Kathleen E.] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Katz, Michelle L.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Shah, Avni] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Simmons, Jill H.] Vanderbilt Univ, Nashville, TN 37235 USA. [Haller, Michael J.] Univ Florida, Gainesville, FL USA. [Raman, Sripriya] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Tamborlane, William V.] Yale Univ, New Haven, CT USA. [Coffey, Julie K.] Univ Iowa, Iowa City, IA USA. [Nadeau, Kristen J.] Univ Colorado, Aurora, CO USA. RP Nadeau, KJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. EM T1DStats@jaeb.org FU Juvenile Diabetes Research Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [K12DK094721] FX Funding was provided by the Juvenile Diabetes Research Foundation. Part of Dr Katz's time was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094721). NR 19 TC 7 Z9 10 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 2015 VL 314 IS 21 BP 2241 EP 2250 DI 10.1001/jama.2015.16174 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CX2GT UT WOS:000365515700016 PM 26624824 ER PT J AU Molina, G Weiser, TG Lipsitz, SR Esquivel, MM Uribe-Leitz, T Azad, T Shah, N Semrau, K Berry, WR Gawande, AA Haynes, AB AF Molina, George Weiser, Thomas G. Lipsitz, Stuart R. Esquivel, Micaela M. Uribe-Leitz, Tarsicio Azad, Tej Shah, Neel Semrau, Katherine Berry, William R. Gawande, Atul A. Haynes, Alex B. TI Relationship Between Cesarean Delivery Rate and Maternal and Neonatal Mortality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEVELOPING-COUNTRIES; PREGNANCY OUTCOMES; INCOME COUNTRIES; PERINATAL HEALTH; GLOBAL SURVEY; SECTION AB IMPORTANCE Based on older analyses, the World Health Organization (WHO) recommends that cesarean delivery rates should not exceed 10 to 15 per 100 live births to optimize maternal and neonatal outcomes. OBJECTIVES To estimate the contemporary relationship between national levels of cesarean delivery and maternal and neonatal mortality. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, ecological study estimating annual cesarean delivery rates from data collected during 2005 to 2012 for all 194 WHO member states. The year of analysis was 2012. Cesarean delivery rates were available for 54 countries for 2012. For the 118 countries for which 2012 data were not available, the 2012 cesarean delivery rate was imputed from other years. For the 22 countries for which no cesarean rate data were available, the rate was imputed from total health expenditure per capita, fertility rate, life expectancy, percent of urban population, and geographic region. EXPOSURES Cesarean delivery rate. MAIN OUTCOMES AND MEASURES The relationship between population-level cesarean delivery rate and maternal mortality ratios (maternal death from pregnancy related causes during pregnancy or up to 42 days postpartum per 100 000 live births) or neonatal mortality rates (neonatal mortality before age 28 days per 1000 live births). RESULTS The estimated number of cesarean deliveries in 2012 was 22.9 million (95% CI, 22.5 million to 23.2 million). At a country-level, cesarean delivery rate estimates up to 19.1 per 100 live births (95% CI, 16.3 to 21.9) and 19.4 per 100 live births (95% CI, 18.6 to 20.3) were inversely correlated with maternal mortality ratio (adjusted slope coefficient, -10.1; 95% CI, -16.8 to -3.4; P = .003) and neonatal mortality rate (adjusted slope coefficient, -0.8; 95% CI, -1.1 to -0.5; P < .001), respectively (adjusted for total health expenditure per capita, population, percent of urban population, fertility rate, and region). Higher cesarean delivery rates were not correlated with maternal or neonatal mortality at a country level. A sensitivity analysis including only 76 countries with the highest-quality cesarean delivery rate information had a similar result: cesarean delivery rates greater than 6.9 to 20.1 per 100 live births were inversely correlated with the maternal mortality ratio (slope coefficient, -21.3; 95% CI, -32.2 to -10.5, P < .001). Cesarean delivery rates of 12.6 to 24.0 per 100 live births were inversely correlated with neonatal mortality (slope coefficient, -1.4; 95% CI, -2.3 to -0.4; P = .004). CONCLUSIONS AND RELEVANCE National cesarean delivery rates of up to approximately 19 per 100 live births were associated with lower maternal or neonatal mortality among WHO member states. Previously recommended national target rates for cesarean deliveries may be too low. C1 [Molina, George; Lipsitz, Stuart R.; Shah, Neel; Semrau, Katherine; Berry, William R.; Gawande, Atul A.; Haynes, Alex B.] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02115 USA. [Molina, George; Lipsitz, Stuart R.; Shah, Neel; Semrau, Katherine; Berry, William R.; Gawande, Atul A.; Haynes, Alex B.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Molina, George; Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Weiser, Thomas G.; Esquivel, Micaela M.; Uribe-Leitz, Tarsicio] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Azad, Tej] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Shah, Neel] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. RP Haynes, AB (reprint author), Ariadne Labs, 401 Pk Dr,Third Floor East, Boston, MA 02215 USA. EM tweiser@stanford.edu; abhaynes@mgh.harvard.edu NR 34 TC 32 Z9 34 U1 0 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 2015 VL 314 IS 21 BP 2263 EP 2270 DI 10.1001/jama.2015.15553 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CX2GT UT WOS:000365515700018 PM 26624825 ER PT J AU Buckley, EM Miller, BF Golinski, JM Sadeghian, H McAllister, LM Vangel, M Ayata, C Meehan, WP Franceschini, MA Whalen, MJ AF Buckley, Erin M. Miller, Benjamin F. Golinski, Julianne M. Sadeghian, Homa McAllister, Lauren M. Vangel, Mark Ayata, Cenk Meehan, William P., III Franceschini, Maria Angela Whalen, Michael J. TI Decreased microvascular cerebral blood flow assessed by diffuse correlation spectroscopy after repetitive concussions in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE animal models; brain trauma; optical imaging ID TRAUMATIC BRAIN-INJURY; SPORTS-RELATED CONCUSSION; COGNITIVE IMPAIRMENT; PERFUSION; SINGLE; TOMOGRAPHY; RECOVERY; DEFICITS; DISEASE; PLAYERS AB Repetitive concussions are associated with long-term cognitive dysfunction that can be attenuated by increasing the time intervals between concussions; however, biomarkers of the safest rest interval between injuries remain undefined. We hypothesize that deranged cerebral blood flow (CBF) is a candidate biomarker for vulnerability to repetitive concussions. Using a mouse model of human concussion, we examined the effect of single and repetitive concussions on cognition and on an index of CBF (CBFi) measured with diffuse correlation spectroscopy. After a single mild concussion, CBFi was reduced by 35 +/- 4% at 4 hours (P < 0.01 versus baseline) and returned to preinjury levels by 24 hours. After five concussions spaced 1 day apart, CBFi was also reduced from preinjury levels 4 hours after each concussion but had returned to preinjury levels by 72 hours after the final concussion. Interestingly, in this repetitive concussion model, lower CBFi values measured both preinjury and 4 hours after the third concussion were associated with worse performance on the Morris water maze assessed 72 hours after the final concussion. We conclude that low CBFi measured either before or early on in the evolution of injury caused by repetitive concussions could be a useful predictor of cognitive outcome. C1 [Buckley, Erin M.; Miller, Benjamin F.; Vangel, Mark; Franceschini, Maria Angela] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Golinski, Julianne M.; McAllister, Lauren M.; Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat, Div Crit Care Med, Charlestown, MA 02129 USA. [Sadeghian, Homa; Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA 02129 USA. [Meehan, William P., III] Micheli Ctr Sports Injury Prevent, Waltham, MA USA. [Meehan, William P., III] Boston Childrens Hosp, Div Sports Med, Div Emergency Med, Boston, MA USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA 02129 USA. EM mwhalen@mgh.harvard.edu FU National Football League Players Association [PO1NS 55104 06]; National Institute of Health [R01-EB001954]; Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University; MGH ECOR Fund for Medical Discovery FX This study was supported by National Football League Players Association Grant to Harvard College and PO1NS 55104 06 (MJW); National Institute of Health award R01-EB001954 (MAF); the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers; and MGH ECOR Fund for Medical Discovery (EMB). NR 40 TC 3 Z9 3 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2015 VL 35 IS 12 BP 1995 EP 2000 DI 10.1038/jcbfm.2015.161 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CX7OI UT WOS:000365891300011 PM 26154866 ER PT J AU Jung, JE Karatas, H Liu, Y Yalcin, A Montaner, J Lo, EH van Leyen, K AF Jung, Joo Eun Karatas, Hulya Liu, Yu Yalcin, Ayfer Montaner, Joan Lo, Eng H. van Leyen, Klaus TI STAT-dependent upregulation of 12/15-lipoxygenase contributes to neuronal injury after stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ischemia; lipoxygenase; neuron; STAT; transcription factor ID APOPTOSIS-INDUCING FACTOR; TRANSIENT FOCAL ISCHEMIA; OXIDATIVE STRESS; CELL-DEATH; LIPOXYGENASE; BRAIN; 15-LIPOXYGENASE; INHIBITION; DAMAGE; MICE AB Oxidative stress is a major brain injury mechanism after ischemic stroke. 12/15-lipoxygenase (12/15-LOX) is a key mediator of oxidative stress, contributing to neuronal cell death and vascular leakage. Nonetheless, the mechanism leading to its upregulation is currently unknown. We show here that Signal Transducers and Activators of Transcription (STATs), specifically STAT6 and possibly STAT1, increase transcription of 12/15-LOX in neuronal cells. Both p-STAT6 and -1 bound to specific STAT binding sites in the mouse 12/15-LOX promoter. Small interfering RNA (siRNA) knockdown showed STAT6 to be the dominant regulator, reducing 12/15-LOX promoter activation and cell death in oxidatively stressed HT22 cells. STAT6 siRNA efficiently prevented the increase of 12/15-LOX in murine primary neurons, both after induction of oxidative stress and after oxygen-glucose deprivation. Early activation of STAT6 and STAT1 in mice was consistent with a role in regulating 12/15-LOX in focal ischemia. Brains of human stroke patients showed increased p-STAT6 and p-STAT1 in the peri-infarct region, along with 12/15-LOX and markers of apoptosis. These results link STAT6 and STAT1 to the 12/15-LOX damage pathway and suggest disregulation of STAT-dependent transcription as injury mechanism in stroke. Selectively targeting STATs may thus be a novel therapeutic approach to reducing brain injury after a stroke. C1 [Jung, Joo Eun; Karatas, Hulya; Liu, Yu; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. [Yalcin, Ayfer] Ege Univ, Dept Biochem, Fac Pharm, Izmir, Turkey. [Yalcin, Ayfer] Biruni Univ, Fac Pharm, Istanbul, Turkey. [Montaner, Joan] Hosp Valle De Hebron, Lab Invest Neurovasc, Barcelona, Spain. RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, 149 13th St,Room 2401, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu RI IBIS, NEUROVASCULAR/O-1855-2015; Montaner, Joan/D-3063-2015 FU National Institutes of Health [R01 NS069939, R01 NS049430] FX The authors thank Drs C Liu, D Xu, and J Sjoberg of the Karolinska Institute, Sweden, for the human 15-LOX promoter construct. The authors thank Dr JL Witztum for a kind gift of the MDA2 antibody, and Dr J Cornicelli for the sheep antiserum to 15-LOX. Support from the National Institutes of Health (R01 NS069939 and R01 NS049430 to KvL) is gratefully acknowledged. NR 40 TC 1 Z9 1 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2015 VL 35 IS 12 BP 2043 EP 2051 DI 10.1038/jcbfm.2015.169 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CX7OI UT WOS:000365891300016 PM 26174325 ER PT J AU Fazeli, PK Lun, M Kim, SM Bredella, MA Wright, S Zhang, Y Lee, H Catana, C Klibanski, A Patwari, P Steinhauser, ML AF Fazeli, Pouneh K. Lun, Mingyue Kim, Soo M. Bredella, Miriam A. Wright, Spenser Zhang, Yang Lee, Hang Catana, Ciprian Klibanski, Anne Patwari, Parth Steinhauser, Matthew L. TI FGF21 and the late adaptive response to starvation in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR 21; PPAR-ALPHA; BROWN FAT; METABOLIC REGULATOR; ANOREXIA-NERVOSA; ACID-METABOLISM; INSULIN ACTION; HORMONE FGF21; IN-VIVO; LIVER AB In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases - markers of tissue breakdown - as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown. C1 [Fazeli, Pouneh K.; Wright, Spenser; Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Bredella, Miriam A.; Lee, Hang; Catana, Ciprian; Klibanski, Anne; Steinhauser, Matthew L.] Harvard Univ, Sch Med, Boston, MA USA. [Lun, Mingyue; Kim, Soo M.; Zhang, Yang] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Catana, Ciprian] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Patwari, Parth; Steinhauser, Matthew L.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Fazeli, PK (reprint author), 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM pkfazeli@partners.org; msteinhauser@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH [K23DK094820, K08DK090147]; Claflin Distinguished Scholar Award; Watkins Cardiovascular Leadership Award; National Institute for Biomedical Imaging and Bioengineering [5P41EB015896-17]; Harvard Clinical and Translational Science Center, National Center for Advancing Translational Science [8UL1 TR000170-05]; Harvard Clinical and Translational Science Center, National Center for Research Resources [1UL1TR001102-01, 1UL1RR025758-04] FX We thank the nurses and bionutritionists at the Clinical Research Centers of Brigham and Women's Hospital and Massachusetts General Hospital. This work was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (K23DK094820, to P.K. Fazeli and K08DK090147, to M.L. Steinhauser); a Claflin Distinguished Scholar Award (to P.K. Fazeli); a Watkins Cardiovascular Leadership Award (to M.L. Steinhauser); the National Institute for Biomedical Imaging and Bioengineering (5P41EB015896-17); the Harvard Clinical and Translational Science Center, National Center for Advancing Translational Science (8UL1 TR000170-05); and the Harvard Clinical and Translational Science Center, National Center for Research Resources (1UL1TR001102-01 and 1UL1RR025758-04). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 47 TC 16 Z9 16 U1 6 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2015 VL 125 IS 12 BP 4601 EP 4611 DI 10.1172/JCI83349 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CX6SI UT WOS:000365831300025 PM 26529252 ER PT J AU Resick, PA Wachen, JS Mintz, J Young-McCaughan, S Roache, JD Borah, AM Borah, EV Dondanville, KA Hembree, EA Litz, BT Peterson, AL AF Resick, Patricia A. Wachen, Jennifer Schuster Mintz, Jim Young-McCaughan, Stacey Roache, John D. Borah, Adam M. Borah, Elisa V. Dondanville, Katherine A. Hembree, Elizabeth A. Litz, Brett T. Peterson, Alan L. CA STRONG STAR Consortium TI A Randomized Clinical Trial of Group Cognitive Processing Therapy Compared With Group Present-Centered Therapy for PTSD Among Active Duty Military Personnel SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; active military; cognitive processing therapy; present-centered therapy; randomized clinical trial ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; PROPENSITY SCORE; PRIMARY-CARE; VETERANS; COMBAT; IRAQ; AFGHANISTAN; SYMPTOMS; EXPOSURE AB Objective: To determine whether group therapy improves symptoms of posttraumatic stress disorder (PTSD), this randomized clinical trial compared efficacy of group cognitive processing therapy (cognitive only version; CPT-C) with group present-centered therapy (PCT) for active duty military personnel. Method: Patients attended 90-min groups twice weekly for 6 weeks at Fort Hood, Texas. Independent assessments were administered at baseline, weekly before sessions, and 2 weeks, 6 months, and 12 months posttreatment. A total of 108 service members (100 men, 8 women) were randomized. Inclusion criteria included PTSD following military deployment and medication stability. Exclusion criteria included suicidal/homicidal intent or other severe mental disorders requiring immediate treatment. Follow-up assessments were administered regardless of treatment completion. Primary outcome measures were the PTSD Checklist (Stressor Specific Version; PCL-S) and Beck Depression Inventory-II. The Posttraumatic Stress Symptom Interview (PSS-1) was a secondary measure. Results: Both treatments resulted in large reductions in PTSD severity, but improvement was greater in CPT-C. CPT-C also reduced depression, with gains remaining during follow-up. In PCT, depression only improved between baseline and before Session 1. There were few adverse events associated with either treatment. Conclusions: Both CPT-C and PCT were tolerated well and reduced PTSD symptoms in group format, but only CPT-C improved depression. This study has public policy implications because of the number of active military needing PTSD treatment, and demonstrates that group format of treatment of PTSD results in significant improvement and is well tolerated. Group therapy may an important format in settings in which therapists are limited. C1 [Resick, Patricia A.] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC 27701 USA. [Wachen, Jennifer Schuster] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wachen, Jennifer Schuster] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02215 USA. [Mintz, Jim; Young-McCaughan, Stacey; Roache, John D.; Borah, Elisa V.; Dondanville, Katherine A.; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA. [Borah, Adam M.] Carl R Darnall Army Med Ctr, Dept Behav Hlth, Ft Hood, TX USA. [Hembree, Elizabeth A.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Resick, PA (reprint author), Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, 411 West Chapel Hill Rd,Suite 200, Durham, NC 27701 USA. EM patricia.resick@duke.edu FU U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program [W81XWH-08-02-109, W81XWH-08-02-0116, W81XWH-08-02-0114] FX Funding for this work was made possible by the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program awards W81XWH-08-02-109 (Alan L. Peterson), W81XWH-08-02-0116 (Patricia A. Resick), and W81XWH-08-02-0114 (Brett T. Litz). The views expressed in this article are solely those of the authors and do not reflect an endorsement by or the official policy of the U.S. Army, the Department of Defense, or the U.S. Government. The results of this study were presented in part at the International Society for Traumatic Stress Studies 29th Annual Meeting, November 7-9, 2013, Philadelphia, PA. We thank Michelle Barrera, Katina Campbell, Paul Fowler, Michelle Hall-Graham, Nicholas Holder, Kelly Leaming, and Sharon Primeaux, who supported this study as study coordinators and research assistants; Tracy Clemens, Katherine Dondanville, Kristi Pruiksma, Charity Wilkinson, and Macy Woodside, who served as therapists for this study; Tamara Britt, Lucas Brilliott, Brooke Fina, Monica Gauna, Brittany Hall-Clark, Steffany Malach, Crystal Mendoza, Susan Paschall, Veronica Vargas, and Edward Wright, who supported this study as independent evaluators; Antoinette Brundige, Susan Deason, and Gary Burk, who supported this study as part of the STRONG STAR Administrative Core; Raymond Aguilar, and Kevin Muenzler, who supported this study as part of the STRONG STAR Data and Biostatistics Core; Christopher Harte and Nathan Stein, who supported this study as part of the STRONG STAR Assessment Core; Kimberly Del Carmen and Holly Campbell-Rosen, who supported this study as grant officer representatives; and Julie R. Collins, who provided editorial support for this article. NR 49 TC 18 Z9 18 U1 8 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2015 VL 83 IS 6 BP 1058 EP 1068 DI 10.1037/ccp0000016 PG 11 WC Psychology, Clinical SC Psychology GA CX3PA UT WOS:000365610100005 PM 25939018 ER PT J AU Hassanzadeh, E Shaqdan, K Aran, S Abujudeh, HH AF Hassanzadeh, Elmira Shaqdan, Khalid Aran, Shima Abujudeh, Hani H. TI A COMPUTED TOMOGRAPHY IMAGE OF LUXATIO ERECTA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID CT C1 [Hassanzadeh, Elmira; Shaqdan, Khalid; Aran, Shima; Abujudeh, Hani H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. OI Hassanzadeh, Elmira/0000-0003-4460-698X NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD DEC PY 2015 VL 49 IS 6 BP E205 EP E207 DI 10.1016/j.jemermed.2015.02.048 PG 3 WC Emergency Medicine SC Emergency Medicine GA CX0TC UT WOS:000365408800013 PM 26409681 ER PT J AU Geng, TY Sutter, A Harland, MD Law, BA Ross, JS Lewin, D Palanisamy, A Russo, SB Chavin, KD Cowart, LA AF Geng, Tuoyu Sutter, Alton Harland, Michael D. Law, Brittany A. Ross, Jessica S. Lewin, David Palanisamy, Arun Russo, Sarah B. Chavin, Kenneth D. Cowart, L. Ashley TI SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes SO JOURNAL OF LIPID RESEARCH LA English DT Article DE sphingolipids; liver, diet and dietary lipids; lipid kinases; steatohepatitis; sphingosine-1-phosphate; lipotoxicity; sphingosine kinase 1; nonalcoholic steatohepatitis; nonalcoholic fatty liver disease ID SPHINGOSINE KINASE 1; PERFORMANCE LIQUID-CHROMATOGRAPHY; INSULIN-RESISTANCE; LIVER-DISEASE; SPHINGOLIPID METABOLISM; ENDOTHELIAL-CELLS; RETICULUM STRESS; ACTIVATION; ACIDS; MICE AB Steatohepatitis occurs in up to 20% of patients with fatty liver disease and leads to its primary disease outcomes, including fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Mechanisms that mediate this inflammation are of major interest. We previously showed that overload of saturated fatty acids, such as that which occurs with metabolic syndrome, induced sphingosine kinase 1 (SphK1), an enzyme that generates sphingosine-1-phosphate (S1P). While data suggest beneficial roles for S1P in some contexts, we hypothesized that it may promote hepatic inflammation in the context of obesity. Consistent with this, we observed 2-fold elevation of this enzyme in livers from humans with nonalcoholic fatty liver disease and also in mice with high saturated fat feeding, which recapitulated the human disease. Mice exhibited activation of NF kappa B, elevated cytokine production, and immune cell infiltration. Importantly, SphK1-null mice were protected from these outcomes. Studies in cultured cells demonstrated saturated fatty acid induction of SphK1 message, protein, and activity, and also a requirement of the enzyme for NF kappa B signaling and increased mRNA encoding TNF alpha and MCP1. Moreover, saturated fat-induced NF kappa B signaling and elevation of TNF alpha and MCP1 mRNA in HepG2 cells was blocked by targeted knockdown of S1P receptor 1, supporting a role for this lipid signaling pathway in inflammation in nonalcoholic fatty liver disease. C1 [Geng, Tuoyu; Harland, Michael D.; Law, Brittany A.; Ross, Jessica S.; Russo, Sarah B.; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Sutter, Alton; Palanisamy, Arun; Chavin, Kenneth D.] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Lewin, David] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Law, Brittany A.; Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM cowartl@musc.edu FU Veterans Affairs Merit Award; National Institutes of Health [1R01HL117233, 5P30GM103339-03, 1R01DK069369] FX This work was supported by a Veterans Affairs Merit Award, National Institutes of Health Grants 1R01HL117233 and 5P30GM103339-03 (L.A.C.), and National Institutes of Health Grant 1R01DK069369 to K.D.C. The authors acknowledge that there are no conflicts of interest to disclose. NR 41 TC 4 Z9 4 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 2015 VL 56 IS 12 BP 2359 EP 2371 DI 10.1194/jlr.M063511 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CX6XA UT WOS:000365843800012 PM 26482537 ER PT J AU Rotondo, RL Folkert, W Liebsch, NJ Chen, YLE Pedlow, FX Schwab, JH Rosenberg, AE Nielsen, GP Szymonifka, J Ferreira, A Hornicek, FJ DeLaney, TF AF Rotondo, Ronny L. Folkert, Wendy Liebsch, Norbert J. Chen, Yen-Lin E. Pedlow, Frank X. Schwab, Joseph H. Rosenberg, Andrew E. Nielsen, G. Petur Szymonifka, Jackie Ferreira, Al E. Hornicek, Francis J. DeLaney, Thomas F. TI High-dose proton-based radiation therapy in the management of spine chordomas: outcomes and clinicopathological prognostic factors SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE chordoma; spine; sacrum; radiation therapy; surgery; oncology ID SACRAL CHORDOMA; SACROCOCCYGEAL CHORDOMA; MOBILE SPINE; PHOTON/PROTON RADIOTHERAPY; SURGICAL-MANAGEMENT; LOCAL RECURRENCE; PHASE-II; SACRECTOMY; EXPERIENCE AB OBJECT Spinal chordomas can have high local recurrence rates after surgery with or without conventional dose radiation therapy (RT). Treatment outcomes and prognostic factors after high-dose proton-based RT with or without surgery were assessed. METHODS The authors conducted a retrospective review of 126 treated patients (127 lesions) categorized according to disease status (primary vs recurrent), resection (en bloc vs intralesional), margin status, and RT timing. RESULTS Seventy-one sacrococcygeal, 40 lumbar, and 16 thoracic chordomas were analyzed. Mean RT dose was 72.4 GyRBE (relative biological effectiveness). With median follow-up of 41 months, the 5-year overall survival (OS), local control (LC), locoregional control (LRC), and distant control (DC) for the entire cohort were 81%, 62%, 60%, and 77%, respectively. LC for primary chordoma was 68% versus 49% for recurrent lesions (p = 0.058). LC if treated with a component of preoperative RT was 72% versus 54% without this treatment (p = 0.113). Among primary tumors, LC and LRC were higher with preoperative RT, 85% (p = 0.019) and 79% (0.034), respectively, versus 56% and 56% if no preoperative RT was provided. Overall LC was significantly improved with en bloc versus intralesional resection (72% vs 55%, p = 0.016), as was LRC (70% vs 53%, p = 0.035). A trend was noted toward improved LC and LRC for RO/R1 margins and the absence of intralesional procedures. CONCLUSIONS High-dose proton-based RT in the management of spinal chordomas can be effective treatment. In patients undergoing surgery, those with primary chordomas undergoing preoperative RT, en bloc resection, and postoperative RT boost have the highest rate of local tumor control; among 28 patients with primary chordomas who underwent preoperative RT and en bloc resection, no local recurrences were seen. Intralesional and incomplete resections are associated with higher local failure rates and are to be avoided. C1 [Rotondo, Ronny L.; Folkert, Wendy; Liebsch, Norbert J.; Chen, Yen-Lin E.; DeLaney, Thomas F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Pedlow, Frank X.; Schwab, Joseph H.; Ferreira, Al E.; Hornicek, Francis J.] Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosenberg, Andrew E.; Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Szymonifka, Jackie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Biostat, Boston, MA USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org FU Massachusetts General Hospital on National Cancer Institute [C06 CA059267]; Federal Share FX The authors wish to acknowledge Herman-D. Suit, MD, PhD, for his thoughtful discussions during the planning and preparation of this work. Financial support for this study was received in part by the Federal Share of program income earned by Massachusetts General Hospital on National Cancer Institute grant no. C06 CA059267, Proton Therapy Research and Treatment Center. Dr. Rotondo, Ms. Kobayashi, Dr. Chen, Ms. Szymonifka, Mr. Ferreira, and Dr. DeLaney received direct or indirect support from the Federal Share. NR 23 TC 10 Z9 10 U1 1 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 EI 1547-5646 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD DEC PY 2015 VL 23 IS 6 BP 788 EP 797 DI 10.3171/2015.3.SPINE14716 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CX0FI UT WOS:000365371900016 PM 26340383 ER PT J AU Osier, ND Carlson, SW DeSana, A Dixon, CE AF Osier, Nicole D. Carlson, Shaun W. DeSana, Anthony Dixon, C. Edward TI Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals SO JOURNAL OF NEUROTRAUMA LA English DT Article DE behavior; chronic; function; histopathology; TBI ID CONTROLLED CORTICAL IMPACT; DIFFUSE AXONAL INJURY; LATERAL FLUID-PERCUSSION; CLOSED-HEAD-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MARROW STROMAL CELLS; ACUTE NEURONAL DEGENERATION; SYMPATHETIC NERVOUS-SYSTEM; MEDIAL PREFRONTAL CORTEX; CHRONIC-STAGE CONTUSION AB The purpose of this review is to survey the use of experimental animal models for studying the chronic histopathological and behavioral consequences of traumatic brain injury (TBI). The strategies employed to study the long-term consequences of TBI are described, along with a summary of the evidence available to date from common experimental TBI models: fluid percussion injury; controlled cortical impact; blast TBI; and closed-head injury. For each model, evidence is organized according to outcome. Histopathological outcomes included are gross changes in morphology/histology, ventricular enlargement, gray/white matter shrinkage, axonal injury, cerebrovascular histopathology, inflammation, and neurogenesis. Behavioral outcomes included are overall neurological function, motor function, cognitive function, frontal lobe function, and stress-related outcomes. A brief discussion is provided comparing the most common experimental models of TBI and highlighting the utility of each model in understanding specific aspects of TBI pathology. The majority of experimental TBI studies collect data in the acute postinjury period, but few continue into the chronic period. Available evidence from long-term studies suggests that many of the experimental TBI models can lead to progressive changes in histopathology and behavior. The studies described in this review contribute to our understanding of chronic TBI pathology. C1 [Osier, Nicole D.; Carlson, Shaun W.; DeSana, Anthony; Dixon, C. Edward] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. [Carlson, Shaun W.; Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. [Dixon, C. Edward] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Osier, Nicole D.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15260 USA. [DeSana, Anthony] Seton Hill Univ, Greensburg, PA USA. RP Dixon, CE (reprint author), Univ Pittsburgh, Dept Neurol Surg, 201 Hill Bldg,3434 Fifth Ave, Pittsburgh, PA 15260 USA. EM dixonec@upmc.edu FU National Institutes of Health (NIH)-NINDS [R01-NS079061, 5T32HD040686-14]; Department of Veterans Affairs [RRD B1127-I]; NIH-NINR [1F31NR014957-01, T32NR009759]; Pittsburgh Foundation; Sigma Theta Tau International Eta Chapter; International Society for Nurses in Genetics; American Association of Neuroscience Nursing/Neuroscience Nursing Foundation FX This work was supported by three federally sponsored grants: National Institutes of Health (NIH)-NINDS grants R01-NS079061 and 5T32HD040686-14, Department of Veterans Affairs grant RR&D B1127-I, and NIH-NINR grants 1F31NR014957-01 and T32NR009759. Additional support for this work was provided by grants from the following foundations and professional societies: The Pittsburgh Foundation, Sigma Theta Tau International Eta Chapter, International Society for Nurses in Genetics, and the American Association of Neuroscience Nursing/Neuroscience Nursing Foundation. The authors thank Michael Farmer for his time and assistance with the figures, Marilyn Farmer for her editorial support, as well as Lori Beck, Emad Madha, Lan Pham, and Amanda Savarese for their assistance in identifying and managing the long-term publications cited in this review. NR 309 TC 7 Z9 7 U1 7 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD DEC 1 PY 2015 VL 32 IS 23 SI SI BP 1861 EP 1882 DI 10.1089/neu.2014.3680 PG 22 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CX4TW UT WOS:000365694200004 PM 25490251 ER PT J AU Gewirtz, H AF Gewirtz, Henry TI SPECT Myocardial Perfusion Imaging: Poststress, End Systolic Images and the Ongoing Effort to Improve Diagnostic Accuracy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID EMISSION-COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; BLOOD-FLOW; QUANTITATION; STENOSIS; SIZE C1 [Gewirtz, Henry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM gewirtz.henry@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2015 VL 56 IS 12 BP 1813 EP 1814 DI 10.2967/jnumed.115.164111 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CX5EL UT WOS:000365724800002 PM 26315833 ER PT J AU McIver, DJ Grizales, AM Brownstein, JS Goldfine, AB AF McIver, David J. Grizales, Ana Maria Brownstein, John S. Goldfine, Allison B. TI Risk of Type 2 Diabetes Is Lower in US Adults Taking Chromium-Containing Supplements SO JOURNAL OF NUTRITION LA English DT Article DE chromium; diabetes; glucose intolerance; insulin resistance; dietary supplements; safety; NHANES ID TOTAL PARENTERAL-NUTRITION; PICOLINATE SUPPLEMENTATION; INSULIN SENSITIVITY; GLUCOSE-INTOLERANCE; EXERCISE PROGRAM; IMPROVE GLUCOSE; OBESE WOMEN; OLDER MEN; METABOLISM; MELLITUS AB Background: Dietary supplement use is widespread in the United States. Although it has been suggested in both in vitro and small in vivo human studies that chromium has potentially beneficial effects in type 2 diabetes (T2D), chromium supplementation in diabetes has not been investigated at the population level. Objective: The objective of this study was to examine the use and potential benefits of chromium supplementation in T2D by examining NHANES data. Methods: An individual was defined as having diabetes if he or she had a glycated hemoglobin (HbA1c) value of >= 6.5%, or reported having been diagnosed with diabetes. Data on all consumed dietary supplements from the NHANES database were analyzed, with the OR of having diabetes as the main outcome of interest based on chromium supplement use. Results: The NHANES for the years 1999-2010 included information on 62,160 individuals. After filtering the database for the required covariates (gender, ethnicity, socioeconomic status, body mass index, diabetes diagnosis, supplement usage, and laboratory HbA1c values), and when restricted to adults, the study cohort included 28,539 people. A total of 58.3% of people reported consuming a dietary supplement in the previous 30 d, 28.8% reported consuming a dietary supplement that contained chromium, and 0.7% consumed supplements that had "chromium'' in the title. Compared with nonusers, the odds of having T2D (HbA1c >= 6.5%) were lower in persons who consumed chromium-containing supplements within the previous 30 d than in those who did not (OR: 0.73; 95% CI: 0.62, 0.86; P = 0.001). Supplement use alone (without chromium) did not influence the odds of having T2D (OR: 0.89; 95% CI: 0.77, 1.03; P = 0.11). Conclusions: Over one-half the adult US population consumes nutritional supplements, and over one-quarter consumes supplemental chromium. The odds of having T2D were lower in those who, in the previous 30 d, had consumed supplements containing chromium. Given the magnitude of exposure, studies on safety and efficacy are warranted. C1 [McIver, David J.; Brownstein, John S.] Boston Childrens Hosp, Boston, MA 02115 USA. [McIver, David J.; Grizales, Ana Maria; Brownstein, John S.; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. [Grizales, Ana Maria; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP McIver, DJ (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA. EM david.mciver@childrens.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [P30-DK03836]; National Human Genome Research Institute of the NIH [U54HG007963] FX This work was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases grant P30-DK03836. Research reported in this publication was supported by the National Human Genome Research Institute of the NIH under award number U54HG007963. NR 50 TC 3 Z9 3 U1 3 U2 24 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD DEC PY 2015 VL 145 IS 12 BP 2675 EP 2682 DI 10.3945/jn.115.214569 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CX5DY UT WOS:000365723300005 PM 26446484 ER PT J AU Greer, JA MacDonald, JJ Vaughn, J Viscosi, E Traeger, L McDonnell, T Pirl, WF Temel, JS AF Greer, Joseph A. MacDonald, James J. Vaughn, Jeanne Viscosi, Elene Traeger, Lara McDonnell, Theresa Pirl, William F. Temel, Jennifer S. TI Pilot Study of a Brief Behavioral Intervention for Dyspnea in Patients With Advanced Lung Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Non-small cell; small cell; lung cancer; dyspnea ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; AMBULATORY PATIENTS; POSTURAL RELIEF; BREATHLESSNESS; PREVALENCE; MANAGEMENT; DISEASE; ANXIETY; DEPRESSION AB Context. Dyspnea is a common symptom in patients with advanced cancer that interferes with functional ability and quality of life (QOL). Although few evidence-based treatments for dyspnea exist, prior studies show support for nonpharmacological interventions that include elements of cognitive-behavioral therapy. Objectives. To examine the feasibility and utility of delivering a brief behavioral intervention for dyspnea in patients with lung cancer. Methods. For this single-group pilot study, eligible patients included those with advanced lung cancer (Stage III or IV nonsmall cell or extensive-stage small cell lung cancer) receiving outpatient cancer treatment who reported at least moderate breathlessness. The manualized intervention consisted of two sessions in which nurse practitioners taught participants breathing and relaxation techniques within the infusion clinic and encouraged home practice. Participants completed measures of breathlessness (Modified Medical Research Council Dyspnea Scale), QOL (Functional Assessment of Cancer Therapy-Lung Trial Outcome Index), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale) at baseline and within six weeks after enrollment. Results. Of the 32 patients enrolled in the study (56.3% females; mean age 63.34 [SD] = 7.96 years), 84.4% (N = 27) completed all study procedures. Comparing the baseline to postassessments, we found significant improvements in Modified Medical Research Council Dyspnea Scale (P < 0.001), Functional Assessment of Cancer Therapy-Lung Trial Outcome Index (P = 0.01), and Hospital Anxiety and Depression Scale-depression subscale (P < 0.001) scores. Conclusion. In this sample of patients with advanced lung cancer and dyspnea, we observed a high completion rate for the two-session behavioral intervention. Patients also reported improvements in dyspnea, QOL, and mood. Follow-up randomized controlled trials are needed to examine the efficacy of brief behavioral interventions for cancer-related dyspnea. (C) 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greer, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Yawkey Bldg,Suite 10B, Boston, MA 02114 USA. EM jgreer2@mgh.harvard.edu FU Barbara McCue Endowed Fund at the MGH Cancer Center FX This study was funded by the Barbara McCue Endowed Fund at the MGH Cancer Center. The authors have no disclosures. NR 36 TC 2 Z9 2 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD DEC PY 2015 VL 50 IS 6 BP 854 EP 860 DI 10.1016/j.jpainsymman.2015.06.010 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA CX7OH UT WOS:000365891100013 PM 26166181 ER PT J AU Mitchell, JC Edwards, KJ Hunt, SB Poelstra, P AF Mitchell, Joel C. Edwards, Keith J. Hunt, Scott B. Poelstra, Paul TI Relational Commitment as a Mediator of Religiousness to Marital Quality SO JOURNAL OF PSYCHOLOGY AND THEOLOGY LA English DT Article ID RELATIONSHIP STABILITY; PERSONAL RELATIONSHIPS; CLOSE RELATIONSHIPS; COUPLES; MARRIAGE; SPIRITUALITY; SATISFACTION; CONFLICT; RELIGIOSITY AB This study examined the relationship between religiousness, relational commitment, and marital quality, proposing that relational commitment would act as a mediator in the relationship between religiousness and marital quality. Using a causal step approach to testing mediation, zero-order correlates demonstrated significant relationships among all 3 variables. In examining the mediating effects of relational commitment, full mediation for religiousness on marital quality was determined by using a sequential regression analysis. Therefore, religious individuals who had higher levels of relational commitment to their spouses experienced greater marital quality than those who had lower levels of relational commitment. The theoretical and applied implications of these findings are discussed. C1 [Mitchell, Joel C.; Hunt, Scott B.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Tacoma, WA 98493 USA. [Mitchell, Joel C.; Hunt, Scott B.] Univ Washington, Tacoma, WA 98493 USA. [Edwards, Keith J.; Poelstra, Paul] Biola Univ, Rosemead Sch Psychol, La Mirada, CA 90639 USA. RP Hunt, SB (reprint author), VA Puget Sound Hlth Care Syst, 9600 Vet Dr A-116, Tacoma, WA 98493 USA. EM scott.hunt3@va.gov NR 56 TC 0 Z9 0 U1 1 U2 3 PU ROSEMEAD SCHOOL PSYCHOLOGY PI LA MIRADA PA 13800 BIOLA AVENUE, BIOLA UNIVERSITY, LA MIRADA, CA 90639-0001 USA SN 0091-6471 J9 J PSYCHOL THEOL JI J. Psychol. Theol. PD WIN PY 2015 VL 43 IS 4 BP 263 EP 270 PG 8 WC Psychology, Multidisciplinary; Religion SC Psychology; Religion GA CX6QW UT WOS:000365827400004 ER PT J AU de Caestecker, M Humphreys, BD Liu, KD Fissell, WH Cerda, J Nolin, TD Askenazi, D Mour, G Harrell, FE Pullen, N Okusa, MD Faubel, S AF de Caestecker, Mark Humphreys, Ben D. Liu, Kathleen D. Fissell, William H. Cerda, Jorge Nolin, Thomas D. Askenazi, David Mour, Girish Harrell, Frank E., Jr. Pullen, Nick Okusa, Mark D. Faubel, Sarah CA ASN AKI Advisory Grp TI Bridging Translation by Improving Preclinical Study Design in AKI SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; CISPLATIN-INDUCED NEPHROTOXICITY; CONTRAST-INDUCED NEPHROPATHY; ISCHEMIA-REPERFUSION INJURY; RANDOMIZED CONTROLLED-TRIAL; ANIMAL-MODELS; SODIUM-BICARBONATE; CARDIAC-SURGERY AB Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development. C1 [de Caestecker, Mark; Fissell, William H.] Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN 37232 USA. [Humphreys, Ben D.] Washington Univ, Sch Med, Div Renal Dis, St Louis, MO USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Cerda, Jorge] Albany Med Coll, Div Nephrol & Hypertens, Albany, NY 12208 USA. [Nolin, Thomas D.; Mour, Girish] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Nolin, Thomas D.; Mour, Girish] Univ Pittsburgh, Sch Med, Ctr Crit Care Nephrol, Pittsburgh, PA USA. [Askenazi, David] Univ Alabama Birmingham, Dept Pediat, Div Nephrol, Birmingham, AL USA. [Harrell, Frank E., Jr.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA. [Pullen, Nick] Pfizer Global Res & Dev, Inflammat & Immunol Res Unit, Cambridge, MA USA. Univ Virginia Hlth Syst, Div Nephol, Charlottesville, VA USA. Univ Virginia Hlth Syst, Ctr Immun Inflammat & Regenerat Med, Charlottesville, VA USA. [Faubel, Sarah] Univ Colorado, Div Renal, Denver, CO 80202 USA. [Faubel, Sarah] Denver Vet Affairs Med Ctr, Aurora, CO USA. RP Okusa, MD (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, 1161 21st Ave South,S3223 Med Ctr North, Nashville, TN 37232 USA. EM mark.de.caestecker@vanderbilt.edu; sarah.faubel@ucdenver.edu NR 102 TC 8 Z9 8 U1 2 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2015 VL 26 IS 12 BP 2905 EP 2916 DI 10.1681/ASN.2015070832 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CX1OR UT WOS:000365466000006 PM 26538634 ER PT J AU Batal, I De Serres, SA Safa, K Bijol, V Ueno, T Onozato, ML Iafrate, AJ Herter, JM Lichtman, AH Mayadas, TN Guleria, I Rennke, HG Najafian, N Chandraker, A AF Batal, Ibrahim De Serres, Sacha A. Safa, Kassem Bijol, Vanesa Ueno, Takuya Onozato, Maristela L. Iafrate, A. John Herter, Jan M. Lichtman, Andrew H. Mayadas, Tanya N. Guleria, Indira Rennke, Helmut G. Najafian, Nader Chandraker, Anil TI Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; DC-SIGN; TUBULAR ATROPHY; ACUTE REJECTION; ALLORECOGNITION; EXPRESSION; IMMUNITY; ANTIBODY; NETWORK; GLOMERULONEPHRITIS AB Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival. C1 [Batal, Ibrahim; Bijol, Vanesa; Herter, Jan M.; Lichtman, Andrew H.; Mayadas, Tanya N.; Rennke, Helmut G.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Batal, Ibrahim; De Serres, Sacha A.; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L.; Iafrate, A. John; Herter, Jan M.; Lichtman, Andrew H.; Mayadas, Tanya N.; Guleria, Indira; Rennke, Helmut G.; Najafian, Nader; Chandraker, Anil] Harvard Univ, Sch Med, Boston, MA USA. [De Serres, Sacha A.; Safa, Kassem; Ueno, Takuya; Guleria, Indira; Najafian, Nader; Chandraker, Anil] Brigham & Womens Hosp, Div Renal, Schuster Family Transplantat Res Ctr, Boston, MA 02115 USA. [Onozato, Maristela L.; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Batal, I (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, Renal Pathol, 630 W 168th St,VC14-238, New York, NY 02115 USA. EM ib234@columbia.edu FU American Society of Transplantation Clinical Science Fellowship Award; Pathological Society Small Grant Scheme; Clinical Trials in Organ Transplantation cooperative research program through the National Institutes of Health [U01-AI 063623]; Canadian Institutes of Health Research [KRI123890]; Fonds de recherche du Quebec Sante; American Heart Association Scientist Development Grant [11SDG5150000]; National Institutes of Health [R01-DK099507] FX This work was supported in part by a American Society of Transplantation Clinical Science Fellowship Award and Pathological Society Small Grant Scheme (to I.B.) and by a grant from the Clinical Trials in Organ Transplantation cooperative research program through the National Institutes of Health (U01-AI 063623 to N.N.). S.A.D.S. is the recipient of a Kidney Research Scientist Core Education and National Training Program New Investigator Award from Canadian Institutes of Health Research (KRI123890) and holds a scholarship from the Fonds de recherche du Quebec Sante. T.U. is a recipient of the American Heart Association Scientist Development Grant (11SDG5150000). TMN is the recipient of National Institutes of Health grant (R01-DK099507). NR 46 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2015 VL 26 IS 12 BP 3102 EP 3113 DI 10.1681/ASN.2014080804 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CX1OR UT WOS:000365466000024 PM 25855773 ER PT J AU Zhang, WR Garg, AX Coca, SG Devereaux, PJ Eikelboom, J Kavsak, P McArthur, E Thiessen-Philbrook, H Shortt, C Shlipak, M Whitlock, R Parikh, CR AF Zhang, William R. Garg, Amit X. Coca, Steven G. Devereaux, Philip J. Eikelboom, John Kavsak, Peter McArthur, Eric Thiessen-Philbrook, Heather Shortt, Colleen Shlipak, Michael Whitlock, Richard Parikh, Chirag R. CA TRIBE-AKI Consortium TI Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; SERUM CYSTATIN C; CISPLATIN NEPHROTOXICITY; CARDIOVASCULAR EVENTS; DENDRITIC CELLS; INTERLEUKIN-10; BIOMARKERS; DIALYSIS; RISK AB Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a >= 50% or >= 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% Cl), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% Cl, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% Cl, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, 'an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as bionnarkers for perioperative outcomes. C1 [Zhang, William R.; Coca, Steven G.; Parikh, Chirag R.] Yale Univ, Sch Med, Dept Internal Med, Program Appl Translat Res, New Haven, CT 06510 USA. [Garg, Amit X.; Thiessen-Philbrook, Heather] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Garg, Amit X.; McArthur, Eric] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Coca, Steven G.; Parikh, Chirag R.] Vet Affairs CT Healthcare Syst, Nephrol Sect, West Haven, CT USA. [Devereaux, Philip J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Populat Hlth Res Inst, Hamilton, ON, Canada. [Eikelboom, John] McMaster Univ, Div Cardiac Surg, Populat Hlth Res Inst, Hamilton, ON, Canada. [Shortt, Colleen] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Shlipak, Michael] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Parikh, CR (reprint author), Yale Univ, Sch Med, Nephrol Sect, 60 Temple St,Suite 6C, New Haven, CT 06510 USA. EM chirag.parikh@yale.edu FU Institute for Clinical Evaluative Sciences (ICES) - Ontario Ministry of Health and Long-Term Care (MOHLTC); National Institutes of Health (NIH) [R01-HL085757]; NIH [K23-DK080132, K24-DK090203, U01-DK082185]; O'Brien Center [P30-DK079310-07] FX This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.; This study was supported by the National Institutes of Health (NIH) (R01-HL085757 to C.R.P.) to fund the TRIBE-AKI Consortium to study novel biomarkers of AKI in cardiac surgery. S.G.C. has been supported by an NIH Career Development Award (K23-DK080132). C.R.P. is supported by the NIH (K24-DK090203) and P30-DK079310-07 O'Brien Center Grant. S.G.C., A.X.G., and C.R.P. are also members of the NIH-sponsored Assess, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Consortium (U01-DK082185). NR 60 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2015 VL 26 IS 12 BP 3123 EP 3132 DI 10.1681/ASN.2014080764 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CX1OR UT WOS:000365466000026 PM 25855775 ER PT J AU Farago, AF Le, LP Zheng, ZL Muzikansky, A Drilon, A Patel, M Bauer, TM Liu, SV Ou, SHI Jackman, D Costa, DB Multani, PS Li, GG Hornby, Z Chow-Maneval, E Luo, D Lim, JE Iafrate, AJ Shaw, AT AF Farago, Anna F. Le, Long P. Zheng, Zongli Muzikansky, Alona Drilon, Alexander Patel, Manish Bauer, Todd M. Liu, Stephen V. Ou, Sai-Hong I. Jackman, David Costa, Daniel B. Multani, Pratik S. Li, Gary G. Hornby, Zachary Chow-Maneval, Edna Luo, David Lim, Jonathan E. Iafrate, Anthony J. Shaw, Alice T. TI Durable Clinical Response to Entrectinib in NTRK1-Rearranged Non-Small Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article ID REARRANGEMENTS; FUSION AB Introduction: Chromosomal rearrangements involving neurotrophic tyrosine kinase 1 (NTRK1) occur in a subset of non-small cell lung cancers (NSCLCs) and other solid tumor malignancies, leading to expression of an oncogenic TrkA fusion protein. Entrectinib (RXDX-101) is an orally available tyrosine kinase inhibitor, including TrkA. We sought to determine the frequency of NTRK1 rearrangements in NSCLC and to assess the clinical activity of entrectinib. Methods:We screened 1378 cases of NSCLC using anchored multiplex polymerase chain reaction (AMP). A patient with an NTRK1 gene rearrangement was enrolled onto a Phase 1 dose escalation study of entrectinib in adult patients with locally advanced or metastatic tumors (NCT02097810). We assessed safety and response to treatment. Results: We identified NTRK1 gene rearrangements at a frequency of 0.1% in this cohort. A patient with stage IV lung adenocrcinoma with an SQSTM1-NTRK1 fusion transcript expression was treated with entrectinib. Entrectinib was well tolerated, with no grade 3-4 adverse events. Within three weeks of starting on treatment, the patient reported resolution of prior dyspnea and pain. Restaging CT scans demonstrated a RECIST partial response (PR) and complete resolution of all brain metastases. This patient has continued on treatment for over 6 months with an ongoing PR. Conclusions: Entrectinib demonstrated significant anti-tumor activity in a patient with NSCLC harboring an SQSTM1-NTRK1 gene rearrangement, indicating that entrectinib may be an effective therapy for tumors with NTRK gene rearrangements, including those with central nervous system metastases. C1 [Farago, Anna F.; Muzikansky, Alona; Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Le, Long P.; Zheng, Zongli; Iafrate, Anthony J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Drilon, Alexander] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Patel, Manish] Sarah Cannon Res Inst, Florida Canc Specialists, Sarasota, FL USA. [Bauer, Todd M.] PLLC, Sarah Cannon Res Inst, Tennessee Oncol, Nashville, TN USA. [Liu, Stephen V.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Ou, Sai-Hong I.] Univ Calif Irving Hlth, Orange, CA USA. [Jackman, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Multani, Pratik S.; Li, Gary G.; Hornby, Zachary; Chow-Maneval, Edna; Lim, Jonathan E.] Ignyta Inc, San Diego, CA USA. RP Farago, AF (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey Bldg,Suite 7B, Boston, MA 02114 USA. EM afarago@partners.org RI Zheng, Zongli/B-2917-2011 OI Costa, Daniel/0000-0002-0689-395X; Zheng, Zongli/0000-0003-4849-4903 FU Ignyta, Inc. [NCT02097810] FX Sources of support: The Phase 1 study of entrectinib (NCT02097810) is sponsored by Ignyta, Inc. NR 13 TC 22 Z9 23 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2015 VL 10 IS 12 BP 1670 EP 1674 DI 10.1097/01.JTO.0000473485.38553.f0 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CX3DG UT WOS:000365575100004 PM 26565381 ER PT J AU Calles, A Liao, XY Sholl, LM Rodig, SJ Freeman, GJ Butaney, M Lydon, C Dahlberg, SE Hodi, FS Oxnard, GR Jackman, DM Janne, PA AF Calles, Antonio Liao, Xiaoyun Sholl, Lynette M. Rodig, Scott J. Freeman, Gordon J. Butaney, Mohit Lydon, Christine Dahlberg, Suzanne E. Hodi, F. Stephen Oxnard, Geoffrey R. Jackman, David M. Jaenne, Pasi A. TI Expression of PD-1 and Its Ligands, PD-L1 and PD-L2, in Smokers and Never Smokers with KRAS-Mutant Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE PD-1; PD-L1; PD-L2; KRAS mutation; Lung cancer; Cancer immunotherapy ID PHASE-II; ADENOCARCINOMA; MUTATIONS; ACTIVATION; BLOCKADE; SMOKING; B7-H1; CELLS; EGFR; IMMUNOTHERAPY AB Introduction: Clinical responses to immune checkpoint blockade by anti-programmed cell death protein-1 (PD-1)/PD-L1 monoclonal antibodies in non-small-cell lung cancer (NSCLC) are associated with PD-L1 expression and smoking status. We aimed to determine the expression profile of PD-1 and its ligands, PD-L1 and PD-L2, in both smokers and never smokers patients with KRAS-mutant NSCLC. Methods: We retrospectively analyzed the clinical and molecular characteristics of 114 KRAS-mutant NSCLC patients (84 smokers and 30 never smokers) and their clinical tumor samples for the expression of PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC). We used murine monoclonal antibodies anti-PD-L1 (clone 9A11) and anti-PD-L2 (clone 9E5) to examine for tumor cell expression (0, negative; 1, weak; 2, moderate; 3, intense) and anti-PD-1 (clone EH33) for tumor-infiltrating lymphocytes. Results: PD-L1 expression was detected in 27 of 114 patients (24%; 95% confidence interval [CI], 16-33%) and associated with smoking status (current smokers, 44%; former smokers, 20%; never smokers, 13%; p = 0.03). Higher intensity of PD-L1 expression (IHC-2+/IHC-3+) was more frequently observed in smokers and associated with more pack-years. PD-L2 was positive in 54 of 114 patients (47%; 95% CI, 38-57%) and not related to smoking status. PD-1-positive tumor-infiltrating lymphocytes were present in 77 of 114 tumor specimens tested (68%; 95% CI, 59-77%) including 21 of 27 samples with PD-L1 expression and 39 of 54 samples with PD-L2-positive expression. We found that PD-L1 expression fades with the age of the specimens used for analyses decreasing beyond 3 years (p = 0.016). Conclusions: The expression of PD-1 and its ligands PD-L1 and PD-L2 is heterogeneous within KRAS-mutant NSCLC and suggests an inducible expression of PD-L1 by smoking. C1 [Calles, Antonio; Liao, Xiaoyun; Freeman, Gordon J.; Butaney, Mohit; Lydon, Christine; Hodi, F. Stephen; Oxnard, Geoffrey R.; Jackman, David M.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Liao, Xiaoyun; Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. [Sholl, Lynette M.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Freeman, Gordon J.; Oxnard, Geoffrey R.; Jackman, David M.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. [Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Oxnard, Geoffrey R.; Jackman, David M.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, LC4114,450 Brookline Ave, Boston, MA 02115 USA. EM pjanne@partners.org OI Calles, Antonio/0000-0002-2547-1947 FU Merck; Bristol-Myers Squibb; Novartis; Genentech; Ventana/Roche FX P.A.J. is a consultant/advisory board member for Astra-Zeneca. G.J.F. has an ownership interest (including patents) with Bristol-Myers Squibb, Merck, Roche, Novartis, EMD Serono, Boehringer-Ingelheim, Astra Zeneca/AmplImmune, and CoStim Pharmaceuticals and is a consultant/advisory board member for CoStim Pharmaceuticals. F.S.H. is an advisory board member for Merck, nonpaid consultant for Bristol-Myers Squibb, Novartis, Genentech, and clinical trial research support to institution from Merck, Bristol-Myers Squibb, Novartis, and Genentech. S.J.R. receives research funding from Ventana/Roche and Bristol-Meyers Squibb. G.R.O. is a consultant/advisory board member for Astra-Zeneca, Boehringer-Ingelheim, Clovis, Genentech, Novartis, and Sanofi. The rest of authors state there are no conflicts to disclose. NR 43 TC 20 Z9 23 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD DEC PY 2015 VL 10 IS 12 BP 1726 EP 1735 DI 10.1097/JTO.0000000000000687 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CX3DG UT WOS:000365575100013 PM 26473645 ER PT J AU de Moya, MA AF de Moya, Marc A. TI Addition of low-dose valproic acid to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined traumatic brain injury and hemorrhagic shock EDITORIAL CRITIQUE SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Editorial Material C1 [de Moya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP de Moya, MA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD DEC PY 2015 VL 79 IS 6 BP 919 EP 919 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CX4TD UT WOS:000365692300006 ER PT J AU Blevins, CA Weathers, FW Davis, MT Witte, TK Domino, JL AF Blevins, Christy A. Weathers, Frank W. Davis, Margaret T. Witte, Tracy K. Domino, Jessica L. TI The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PTSD CHECKLIST; MISSING DATA; FIT INDEXES; VALIDITY; SCALE; INVENTORY; CRITERIA; PREVALENCE; SYMPTOMS; MODELS AB The Posttraumatic Stress Disorder Checklist (PCL) is a widely used DSM-correspondent self-report measure of PTSD symptoms. The PCL was recently revised to reflect DSM-5 changes to the PTSD criteria. In this article, the authors describe the development and initial psychometric evaluation of the PCL for DSM-5 (PCL-5). Psychometric properties of the PCL-5 were examined in 2 studies involving trauma-exposed college students. In Study 1 (N = 278), PCL-5 scores exhibited strong internal consistency ( = .94), test-retest reliability (r = .82), and convergent (rs = .74 to .85) and discriminant (rs = .31 to .60) validity. In addition, confirmatory factor analyses indicated adequate fit with the DSM-5 4-factor model, (2)(164) = 455.83, p < .001, standardized root mean square residual (SRMR) = .07, root mean squared error of approximation (RMSEA) = .08, comparative fit index (CFI) = .86, and Tucker-Lewis index (TLI) = .84, and superior fit with recently proposed 6-factor, (2) (164) = 318.37, p < .001, SRMR = .05, RMSEA = .06, CFI = .92, and TLI = .90, and 7-factor, (2) (164) = 291.32, p < .001, SRMR = .05, RMSEA = .06, CFI = .93, and TLI = .91, models. In Study 2 (N = 558), PCL-5 scores demonstrated similarly strong reliability and validity. Overall, results indicate that the PCL-5 is a psychometrically sound measure of PTSD symptoms. Implications for use of the PCL-5 in a variety of assessment contexts are discussed. C1 [Blevins, Christy A.] VA Portland Hlth Care Syst, Portland, OR 97239 USA. [Weathers, Frank W.; Davis, Margaret T.; Witte, Tracy K.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. [Domino, Jessica L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Blevins, CA (reprint author), VA Portland Hlth Care Syst, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM christy.blevins@va.gov NR 38 TC 31 Z9 32 U1 7 U2 49 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2015 VL 28 IS 6 BP 489 EP 498 DI 10.1002/jts.22059 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX6GL UT WOS:000365799100001 PM 26606250 ER PT J AU Hammond, KW Ben-Ari, AY Laundry, RJ Boyko, EJ Samore, MH AF Hammond, Kenric W. Ben-Ari, Alon Y. Laundry, Ryan J. Boyko, Edward J. Samore, Matthew H. TI The Feasibility of Using Large-Scale Text Mining to Detect Adverse Childhood Experiences in a VA-Treated Population SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS; HEALTH; ABUSE; DEPRESSION; EXTRACTION; VETERANS; DISORDER; SERVICE; COMBAT; IMPACT AB Free text in electronic health records resists large-scale analysis. Text records facts of interest not found in encoded data, and text mining enables their retrieval and quantification. The U.S. Department of Veterans Affairs (VA) clinical data repository affords an opportunity to apply text-mining methodology to study clinical questions in large populations. To assess the feasibility of text mining, investigation of the relationship between exposure to adverse childhood experiences (ACEs) and recorded diagnoses was conducted among all VA-treated Gulf war veterans, utilizing all progress notes recorded from 2000-2011. Text processing extracted ACE exposures recorded among 44.7 million clinical notes belonging to 243,973 veterans. The relationship of ACE exposure to adult illnesses was analyzed using logistic regression. Bias considerations were assessed. ACE score was strongly associated with suicide attempts and serious mental disorders (ORs = 1.84 to 1.97), and less so with behaviorally mediated and somatic conditions (ORs = 1.02 to 1.36) per unit. Bias adjustments did not remove persistent associations between ACE score and most illnesses. Text mining to detect ACE exposure in a large population was feasible. Analysis of the relationship between ACE score and adult health conditions yielded patterns of association consistent with prior research. C1 [Hammond, Kenric W.; Laundry, Ryan J.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. [Hammond, Kenric W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Hammond, Kenric W.] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA. [Ben-Ari, Alon Y.] VA Puget Sound Hlth Care Syst, Dept Anesthesia, Seattle, WA USA. [Ben-Ari, Alon Y.] Univ Washington, Dept Anesthesia, Seattle, WA 98195 USA. [Boyko, Edward J.] Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Dept Med, Seattle, WA USA. [Samore, Matthew H.] George A Whalen VA Med Ctr, Hlth Serv Res & Dev Serv, Salt Lake City, UT USA. [Samore, Matthew H.] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. [Samore, Matthew H.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. RP Hammond, KW (reprint author), 152 VA Puget Sound,1660 S Columbian Way, Seattle, WA 98108 USA. EM khammond@uw.edu FU U.S. Department of Veterans Affairs (VA) [HIR 10-001] FX This work was supported by U.S. Department of Veterans Affairs (VA) HSR&D study, HIR 10-001. The opinions expressed here are those of the authors and do not reflect those of the VA. NR 27 TC 0 Z9 0 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2015 VL 28 IS 6 BP 505 EP 514 DI 10.1002/jts.22058 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX6GL UT WOS:000365799100003 PM 26579624 ER PT J AU Grubbs, KM Fortney, JC Pyne, JM Hudson, T Moore, WM Custer, P Schneider, R Schnurr, PP AF Grubbs, Kathleen M. Fortney, John C. Pyne, Jeffrey M. Hudson, Teresa Moore, William Mark Custer, Paul Schneider, Ronald Schnurr, Paula P. TI Predictors of Initiation and Engagement of Cognitive Processing Therapy Among Veterans With PTSD Enrolled in Collaborative Care SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PROLONGED EXPOSURE AB Collaborative care (CC) increases access to evidence-based pharmacotherapy and psychotherapy. The study aim was to identify the characteristics of rural veterans receiving a telemedicine-based CC intervention for posttraumatic stress disorder (PTSD) who initiated and engaged in cognitive processing therapy (CPT) delivered via interactive video. Veterans diagnosed with PTSD were recruited from 11 community-based outpatient clinics (N = 133).Chart abstraction identified all mental health encounters received during the 12-month study. General linear mixed models were used to identify characteristics that predicted CPT initiation and engagement (attendance at 8 or more sessions). For initiation, higher PTSD severity according to the Clinician Administered PTSD Scale (d = -0.39, p = .038) and opt-out recruitment (vs. self-referral; d = -0.49, p = .010) were negative predictors. For engagement, major depression (d = -1.32, p = .006) was a negative predictor whereas a pending claim for military service connected disability (d = 2.02, p = .008) was a positive predictor. In general, veterans enrolled in CC initiated and engaged in CPT at higher rates than usual care. Those with more severe symptoms and comorbidity, however, were at risk of not starting or completing CPT. C1 [Grubbs, Kathleen M.; Pyne, Jeffrey M.; Hudson, Teresa; Moore, William Mark] Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev, North Little Rock, AR USA. [Grubbs, Kathleen M.; Pyne, Jeffrey M.; Hudson, Teresa; Moore, William Mark] Cent Arkansas Vet Healthcare Syst, South Cent Mental Illness Educ & Clin Ctr, North Little Rock, AR USA. [Grubbs, Kathleen M.; Pyne, Jeffrey M.; Hudson, Teresa] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR 72205 USA. [Fortney, John C.] VA Puget Sound Hlth Care Syst, Ctr Innovat Vet, Ctr & Value Driven Care, Hlth Serv Res & Dev, Seattle, WA USA. [Fortney, John C.] Univ Washington, Dept Psychiat, Div Populat Hlth, Seattle, WA 98195 USA. [Custer, Paul] VA Loma Linda Hlth Care Syst, Dept Psychol, Loma Linda, CA USA. [Schneider, Ronald] Overton Brooks VA Med Ctr, Dept Psychol, Shreveport, LA USA. [Schneider, Ronald] Louisiana State Univ, Hlth Sci Ctr, Dept Psychiat, Shreveport, LA 71105 USA. [Schnurr, Paula P.] VA Med Ctr, Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Grubbs, KM (reprint author), 2121 San Diego Ave, San Diego, CA 92110 USA. EM kathleen.grubbs@va.gov NR 19 TC 0 Z9 0 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2015 VL 28 IS 6 BP 580 EP 584 DI 10.1002/jts.22049 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CX6GL UT WOS:000365799100012 PM 26625355 ER PT J AU Ko, DSC AF Ko, Dicken S. C. TI Reducing Ischemia-Reperfusion Injury in Renal Transplantation SO JOURNAL OF UROLOGY LA English DT Editorial Material ID HYDROGEN-SULFIDE C1 [Ko, Dicken S. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02138 USA. RP Ko, DSC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02138 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD DEC PY 2015 VL 194 IS 6 BP 1531 EP 1532 DI 10.1016/j.juro.2015.09.060 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CX8WT UT WOS:000365985900003 PM 26386276 ER PT J AU Barry, MJ AF Barry, Michael J. TI Patients Present with More Advanced Prostate Cancer since the USPSTF Screening Recommendations SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD DEC PY 2015 VL 194 IS 6 BP 1534 EP 1535 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CX8WT UT WOS:000365985900005 PM 26384450 ER PT J AU Lin, NU AF Lin, Nancy U. TI Better treatments needed for breast cancer brain metastases SO LANCET ONCOLOGY LA English DT Editorial Material ID PHASE-II; LAPATINIB; TRASTUZUMAB; CAPECITABINE; TRIAL C1 [Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM nlin@partners.org NR 11 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2015 VL 16 IS 16 BP 1583 EP 1584 DI 10.1016/S1470-2045(15)00477-5 PG 3 WC Oncology SC Oncology GA CX6IF UT WOS:000365803700043 PM 26596673 ER PT J AU Sundaresan, TK Haber, DA AF Sundaresan, Tilak K. Haber, Daniel A. TI Fantastic voyage: the future of cancer diagnostics SO LANCET ONCOLOGY LA English DT Editorial Material ID CELL LUNG-CANCER C1 [Sundaresan, Tilak K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. Howard Hughes Med Inst, Boston, MA 02129 USA. RP Sundaresan, TK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM dhaber@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2015 VL 16 IS 16 BP 1596 EP 1598 PG 3 WC Oncology SC Oncology GA CX6IF UT WOS:000365803700049 PM 26678190 ER PT J AU Place, AE Stevenson, KE Vrooman, LM Harris, MH Hunt, SK O'Brien, JE Supko, JG Asselin, BL Athale, UH Clavell, LA Cole, PD Kelly, KM Laverdiere, C Leclerc, JM Michon, B Schorin, MA Welch, JJG Lipshultz, SE Kutok, JL Blonquist, TM Neuberg, DS Sallan, SE Silverman, LB AF Place, Andrew E. Stevenson, Kristen E. Vrooman, Lynda M. Harris, Marian H. Hunt, Sarah K. O'Brien, Jane E. Supko, Jeffrey G. Asselin, Barbara L. Athale, Uma H. Clavell, Luis A. Cole, Peter D. Kelly, Kara M. Laverdiere, Caroline Leclerc, Jean-Marie Michon, Bruno Schorin, Marshall A. Welch, Jennifer J. G. Lipshultz, Steven E. Kutok, Jeffery L. Blonquist, Traci M. Neuberg, Donna S. Sallan, Stephen E. Silverman, Lewis B. TI Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID CHILDRENS ONCOLOGY GROUP; ERWINIA ASPARAGINASE; PEG-ASPARAGINASE; CANCER GROUP; E. COLI; DEXAMETHASONE; ADOLESCENTS; ALLERGY; PHARMACOKINETICS; PEGASPARAGINASE AB Background L-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia, and is usually administered intramuscularly. Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than the native Escherichia coli (E coli) preparation, and can be more feasibly administered intravenously. The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05-001 (DFCI 05-001) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E coli l-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia. Methods DFCI 05-001 enrolled patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia from 11 consortium sites in the USA and Canada. Patients were assigned to an initial risk group on the basis of their baseline characteristics and then underwent 32 days of induction therapy. Those who achieved complete remission after induction therapy were assigned to a final risk group and were eligible to participate in a randomised comparison of intravenous PEG-asparaginase (15 doses of 2500 IU/m(2) every 2 weeks) or intramuscular native E coli l-asparaginase (30 doses of 25 000 IU/m(2) weekly), beginning at week 7 after study entry. Randomisation (1: 1) was unmasked, and was done by a statistician-generated allocation sequence using a permuted blocks algorithm (block size of 4), stratified by final risk group. The primary endpoint of the randomised comparison was the overall frequency of asparaginase-related toxicities (defined as allergy, pancreatitis, and thrombotic or bleeding complications). Predefined secondary endpoints were disease-free survival, serum asparaginase activity, and quality of life during therapy as assessed by PedsQL surveys. All analyses were done by intention to treat. This study is registered with ClinicalTrials. gov, number NCT00400946. Findings Between April 22, 2005, and Feb 12, 2010, 551 eligible patients were enrolled. 526 patients achieved complete remission after induction, of whom 463 were randomly assigned to receive intramuscular native E coli l-asparaginase (n=231) or intravenous PEG-asparaginase (n=232). The two treatment groups did not differ significantly in the overall frequency of asparaginase-related toxicities (65 [28%] of 232 patients in the intravenous PEG-asparaginase group vs 59 [26%] of 231 patients in the intramuscular native E coli l-asparaginase group, p=0.60), or in the individual frequency of allergy (p=0.36), pancreatitis (p=0.55), or thrombotic or bleeding complications (p=0.26). Median follow-up was 6.0 years (IQR 5.0-7.1). 5-year disease-free survival was 90% (95% CI 86-94) for patients assigned to intravenous PEG-asparaginase and 89% (85-93) for those assigned to intramuscular native E coli l-asparaginase (p=0.58). The median nadir serum asparaginase activity was significantly higher in patients who received intravenous PEG-asparaginase than in those who received intramuscular native E coli l-asparaginase. Significantly more anxiety was reported by both patients and parent-proxy in the intramuscular native E coli l-asparaginase group than in the intravenous PEG-asparaginase group. Scores for other domains were similar between the groups. The most common grade 3 or worse adverse events were bacterial or fungal infections (47 [20%] of 232 in the intravenous PEG-asparaginase group vs 51 [22%] of 231 patients in the intramuscular E coli l-asparaginase group) and asparaginase-related allergic reactions (14 [6%] vs 6 [3%]). Interpretation Intravenous PEG-asparaginase was not more toxic than, was similarly efficacious to, and was associated with decreased anxiety compared with intramuscular native E coli l-asparaginase, supporting its use as the front-line asparaginase preparation in children with newly diagnosed acute lymphoblastic leukaemia. C1 [Place, Andrew E.; Vrooman, Lynda M.; Hunt, Sarah K.; O'Brien, Jane E.; Sallan, Stephen E.; Silverman, Lewis B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Stevenson, Kristen E.; Blonquist, Traci M.; Neuberg, Donna S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Place, Andrew E.; Vrooman, Lynda M.; Sallan, Stephen E.; Silverman, Lewis B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Harris, Marian H.] Harvard Univ, Sch Med, Dept Pathol, Boston Childrens Hosp, Boston, MA 02115 USA. [Supko, Jeffrey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Asselin, Barbara L.] Univ Rochester, Med Ctr, Dept Pediat, Golisano Childrens Hosp, Rochester, NY 14642 USA. [Athale, Uma H.] McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. [Clavell, Luis A.] San Jorge Childrens Hosp, Div Pediat Oncol, San Juan, PR USA. [Cole, Peter D.] Albert Einstein Coll Med, Childrens Hosp Montefiore, Div Pediat Hematol Oncol, Bronx, NY 10467 USA. [Kelly, Kara M.] Columbia Univ, New York Presbyterian Morgan Stanley Childrens Ho, Div Pediat Hematol Oncol Stem Cell Transplantat, Med Ctr, New York, NY USA. [Laverdiere, Caroline; Leclerc, Jean-Marie] Univ Montreal, Div Hematol & Oncol, Hosp St Justine, Montreal, PQ, Canada. [Michon, Bruno] Ctr Hosp Univ Quebec, Div Hematol Oncol, Quebec City, PQ, Canada. [Schorin, Marshall A.] Inova Fairfax Hosp Children, Falls Church, VA USA. [Welch, Jennifer J. G.] Brown Univ, Hasbro Childrens Hosp, Warren Alpert Med Sch, Div Pediat Hematol Oncol, Providence, RI 02912 USA. [Lipshultz, Steven E.] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Kutok, Jeffery L.] Infin Pharmaceut, Cambridge, MA USA. RP Silverman, LB (reprint author), 450 Brookline Ave,Dana Bldg Room 3-140, Boston, MA 02215 USA. EM lewis_silverman@dfci.harvard.edu FU National Cancer Institute [5P01CA068484]; Enzon Pharmaceuticals; restricted donor funds from the Dana-Farber Cancer Institute FX This study was funded by the National Cancer Institute (grant 5P01CA068484), Enzon Pharmaceuticals, and by restricted donor funds from the Dana-Farber Cancer Institute. We thank Annette Dalton, Samia Ahmed, Ani Lack, Ying Ruan, and Hongjun Wang for their contributions to the regulatory oversight, data collection, and sample preparation associated with this work. We also thank the patients and families who participated in this clinical trial. NR 25 TC 6 Z9 6 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2015 VL 16 IS 16 BP 1677 EP 1690 DI 10.1016/S1470-2045(15)00363-0 PG 14 WC Oncology SC Oncology GA CX6IF UT WOS:000365803700063 PM 26549586 ER PT J AU Alexander, S Pole, JD Gibson, P Lee, M Hesser, T Chi, SN Dvorak, CC Fisher, B Hasle, H Kanerva, J Mooricke, A Phillips, B Raetz, E Rodriguez-Galindo, C Samarasinghe, S Schmiegelow, K Tissing, W Lehrnbecher, T Sung, L AF Alexander, Sarah Pole, Jason D. Gibson, Paul Lee, Michelle Hesser, Tanya Chi, Susan N. Dvorak, Christopher C. Fisher, Brian Hasle, Henrik Kanerva, Jukka Moericke, Anja Phillips, Bob Raetz, Elizabeth Rodriguez-Galindo, Carlos Samarasinghe, Sujith Schmiegelow, Kjeld Tissing, Wim Lehrnbecher, Thomas Sung, Lillian CA Int Pediat Oncology Mortality Clas TI Classification of treatment-related mortality in children with cancer: a systematic assessment SO LANCET ONCOLOGY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DEATH CERTIFICATE COMPLETION; SAMPLE-SIZE REQUIREMENTS; PEDIATRIC ACUTE-LEUKEMIA; NORDIC COUNTRIES; CLINICAL-TRIALS; CHILDHOOD; ACCURACY; THERAPY AB Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause-of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (kappa=0.83, 95% CI 0.60-1.00) and paediatric oncologists (0.84, 0.63-1.00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0.92, 0.78-1.00). Our approach should allow comparison of treatment-related mortality across trials and across time. C1 [Alexander, Sarah; Sung, Lillian] Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada. [Pole, Jason D.] Pediat Oncol Grp Ontario, Toronto, ON, Canada. [Gibson, Paul] London Hlth Sci Ctr, Div Haematol Oncol, Childrens Hosp, London, ON, Canada. [Lee, Michelle; Hesser, Tanya] Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Program Child Hlth Evaluat Sci, Toronto, ON M5G 1X8, Canada. [Chi, Susan N.; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Dvorak, Christopher C.] Univ Calif San Francisco, Med Ctr, Div Pediat Allergy Immunol & Bone Marrow Transpla, San Francisco, CA USA. [Fisher, Brian] Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. [Hasle, Henrik] Aarhus Univ Hosp, Dept Paediat, DK-8000 Aarhus, Denmark. [Kanerva, Jukka] Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. [Moericke, Anja] Univ Med Ctr Schleswig Holstein, Dept Paediat, Kiel, Germany. [Phillips, Bob] Univ York, Ctr Reviews & Disseminat, York YO10 5DD, N Yorkshire, England. [Raetz, Elizabeth] Univ Utah, Div Pediat Hematol Oncol, Salt Lake City, UT USA. [Samarasinghe, Sujith] Great Ormond St Hosp Sick Children, Dept Paediat Haematol, London WC1N 3JH, England. [Schmiegelow, Kjeld] Rigshosp, Univ Hosp, Dept Pediat & Adolescent Med, DK-2100 Copenhagen, Denmark. [Schmiegelow, Kjeld] Univ Copenhagen, Inst Clin Med, Copenhagen, Denmark. [Tissing, Wim] Univ Groningen, Univ Med Ctr Groningen, Dept Paediat Oncol, NL-9713 AV Groningen, Netherlands. [Lehrnbecher, Thomas] Goethe Univ Frankfurt, Dept Paediat Haematol & Oncol, D-60054 Frankfurt, Germany. RP Sung, L (reprint author), Hosp Sick Children, Div Haematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM lillian.sung@sickkids.ca FU Pediatric Oncology Group of Ontario FX Financial support was provided by an Operating Grant from the Pediatric Oncology Group of Ontario who had no role in study design; data collection, analysis, or interpretation; writing of the report; or the decision to submit the paper for publication. LS had full access to all data in the study and had final responsibility for the decision to submit for publication. NR 22 TC 6 Z9 6 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2015 VL 16 IS 16 BP E604 EP E610 PG 7 WC Oncology SC Oncology GA CX6IF UT WOS:000365803700030 PM 26678213 ER PT J AU Shwartz, M Restuccia, JD Rosen, AK AF Shwartz, Michael Restuccia, Joseph D. Rosen, Amy K. TI Composite Measures of Health Care Provider Performance: A Description of Approaches SO MILBANK QUARTERLY LA English DT Article DE composite measures; performance measurement ID HOSPITAL QUALITY; COMPARE; RELIABILITY; INDICATORS; MORTALITY; PROGRAMS; SURGERY; MODEL AB ContextSince the Institute of Medicine's 2001 report Crossing the Quality Chasm, there has been a rapid proliferation of quality measures used in quality-monitoring, provider-profiling, and pay-for-performance (P4P) programs. Although individual performance measures are useful for identifying specific processes and outcomes for improvement and tracking progress, they do not easily provide an accessible overview of performance. Composite measures aggregate individual performance measures into a summary score. By reducing the amount of data that must be processed, they facilitate (1) benchmarking of an organization's performance, encouraging quality improvement initiatives to match performance against high-performing organizations, and (2) profiling and P4P programs based on an organization's overall performance. MethodsWe describe different approaches to creating composite measures, discuss their advantages and disadvantages, and provide examples of their use. FindingsThe major issues in creating composite measures are (1) whether to aggregate measures at the patient level through all-or-none approaches or the facility level, using one of the several possible weighting schemes; (2) when combining measures on different scales, how to rescale measures (using z scores, range percentages, ranks, or 5-star categorizations); and (3) whether to use shrinkage estimators, which increase precision by smoothing rates from smaller facilities but also decrease transparency. ConclusionsBecause provider rankings and rewards under P4P programs may be sensitive to both context and the data, careful analysis is warranted before deciding to implement a particular method. A better understanding of both when and where to use composite measures and the incentives created by composite measures are likely to be important areas of research as the use of composite measures grows. C1 [Shwartz, Michael; Restuccia, Joseph D.] Boston Univ, Questrom Sch Business, Boston, MA 02215 USA. [Shwartz, Michael; Restuccia, Joseph D.; Rosen, Amy K.] Boston VA Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Shwartz, M (reprint author), Boston Univ, Questrom Sch Business, Dept Operat & Technol Management, 595 Commonwealth Ave, Boston, MA 02215 USA. EM mshwartz@bu.edu FU Jayne Koskinas and Ted Giovanis Foundation FX The work reported here was supported by the Jayne Koskinas and Ted Giovanis Foundation for Health and Policy. The views expressed in this article are those of the authors and do not necessarily represent the views of the foundation. NR 47 TC 1 Z9 1 U1 7 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-378X EI 1468-0009 J9 MILBANK Q JI Milbank Q. PD DEC PY 2015 VL 93 IS 4 BP 788 EP 825 DI 10.1111/1468-0009.12165 PG 38 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CX6WZ UT WOS:000365843700013 PM 26626986 ER PT J AU Kappa, S Marien, T Hernandez, N Eisner, B Miller, N AF Kappa, S. Marien, T. Hernandez, N. Eisner, B. Miller, N. TI Prevention of infectious complications of percutaneous nephrolithotomy SO MINERVA UROLOGICA E NEFROLOGICA LA English DT Review DE Nephrostomy; percutaneous; Calculi; Infection; Sepsis; Anti-bacterial agents ID UPPER TRACT INFECTION; SYSTEMIC INFLAMMATORY RESPONSE; URINARY-TRACT; RENAL-CALCULI; SEVERE SEPSIS; PELVIC URINE; ANTIMICROBIAL PROPHYLAXIS; POSTOPERATIVE FEVER; STAGHORN CALCULI; UROLOGIC SURGERY AB Infection and sepsis is a complication of percutaneous nephrolithotomy that can lead to morbidity, mortality, and increased costs. Herein we review the current relevant literature on the topic of prevention of sepsis after percutaneous nephrolithotomy. C1 [Kappa, S.; Marien, T.; Miller, N.] Vanderbilt Univ Sch Med, Dept Urol, Nashville, TN 37273 USA. [Hernandez, N.; Eisner, B.] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA USA. RP Miller, N (reprint author), Vanderbilt Univ Sch Med, Dept Urol, 1301 Med Ctr Dr, Nashville, TN 37273 USA. EM nicole.miller@vanderbilt.edu NR 52 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0393-2249 EI 1827-1758 J9 MINERVA UROL NEFROL JI Minerva Urol. Nefrol. PD DEC PY 2015 VL 67 IS 4 BP 317 EP 323 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CX3XA UT WOS:000365631600003 PM 26364571 ER PT J AU Conlon, N Schultheis, AM Piscuoglio, S Silva, AA Guerra, E Tornos, C Reuter, VE Soslow, RA Young, RH Oliva, E Weigelt, B AF Conlon, Niamh Schultheis, Anne M. Piscuoglio, Salvatore Silva, Annacarolin. A. Guerra, Esther Tornos, Carmen Reuter, Victor E. Soslow, Robert A. Young, Robert H. Oliva, Esther Weigelt, Britta TI A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors SO MODERN PATHOLOGY LA English DT Article ID SERTOLI-CELL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; TESTIS AB Sertoli Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli Leydig cell tumors (n = 32), Sertoli cell tumors (n = 5) and gynandroblastomas (n = 5), testicular sex cord-stromal tumors (n = 15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n = 10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested two gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to occur, to include Sertoli cell tumors and gynandroblastomas. Our results suggest that DICER1 mutations may not have a role in testicular sex cord-stromal tumorigenesis. C1 [Conlon, Niamh; Schultheis, Anne M.; Piscuoglio, Salvatore; Reuter, Victor E.; Soslow, Robert A.; Weigelt, Britta] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Silva, Annacarolin. A.; Guerra, Esther; Young, Robert H.; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tornos, Carmen] SUNY Stony Brook, Med Ctr, Dept Pathol, Stony Brook, NY USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM eoliva@partners.org; weigeltb@mskcc.org OI Silva, Annacarolina/0000-0002-0067-0288; Soslow, Robert/0000-0002-7269-5898; Piscuoglio, Salvatore/0000-0003-2686-2939 FU German Cancer Aid; Susan G Komen Postdoctoral Fellowship [PDF14298348]; Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute [P30CA008748] FX We thank Russell Towers (MSKCC) for technical support. AMS is funded by a stipend from the German Cancer Aid (Dr Mildred Scheel Stiftung) and SP by a Susan G Komen Postdoctoral Fellowship Grant (PDF14298348). Research reported in this publication was supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 31 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2015 VL 28 IS 12 BP 1603 EP 1612 DI 10.1038/modpathol.2015.115 PG 10 WC Pathology SC Pathology GA CX6SG UT WOS:000365831100009 PM 26428316 ER PT J AU Miles, WO Lepesant, JMJ Bourdeaux, J Texier, M Kerenyi, MA Nakakido, M Hamamoto, R Orkin, SH Dyson, NJ Di Stefano, L AF Miles, Wayne O. Lepesant, Julie M. J. Bourdeaux, Jessie Texier, Manuela Kerenyi, Marc A. Nakakido, Makoto Hamamoto, Ryuji Orkin, Stuart H. Dyson, Nicholas J. Di Stefano, Luisa TI The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STEM-CELL DIFFERENTIATION; GENE-EXPRESSION; MESSENGER-RNA; TARGET GENE; GERM-CELLS; DROSOPHILA; NANOS; TRANSCRIPTION; PROTEINS; CANCER AB The lysine (K)-specific demethylase (LSD1) family of histone demethylases regulates chromatin structure and the transcriptional potential of genes. LSD1 is frequently deregulated in tumors, and depletion of LSD1 family members causes developmental defects. Here, we report that reductions in the expression of the Pumilio (PUM) translational repressor complex enhanced phenotypes due to dLsd1 depletion in Drosophila. We show that the PUM complex is a target of LSD1 regulation in fly and mammalian cells and that its expression is inversely correlated with LSD1 levels in human bladder carcinoma. Unexpectedly, we find that PUM posttranscriptionally regulates LSD1 family protein levels in flies and human cells, indicating the existence of feedback loops between the LSD1 family and the PUM complex. Our results highlight a new posttranscriptional mechanism regulating LSD1 activity and suggest that the feedback loop between the LSD1 family and the PUM complex may be functionally important during development and in human malignancies. C1 [Miles, Wayne O.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA USA. [Miles, Wayne O.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Lepesant, Julie M. J.; Bourdeaux, Jessie; Texier, Manuela; Di Stefano, Luisa] Univ Toulouse 3, CNRS, LBCMCP, F-31062 Toulouse, France. [Kerenyi, Marc A.; Orkin, Stuart H.] Boston Childrens Hosp, Boston, MA USA. [Kerenyi, Marc A.; Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Nakakido, Makoto; Hamamoto, Ryuji] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Di Stefano, L (reprint author), Univ Toulouse 3, CNRS, LBCMCP, F-31062 Toulouse, France. EM luisa.di-stefano@univ-tlse3.fr FU National Institutes of Public Health Service [R01 CA163698, R01 CA64402]; Fondation pour la Recherche Medicale [FRM AJE201109]; Agence Nationale de la Recherche [ANR 2012-CHEX-0002-01]; Marie Curie Career Integration Grant [PCIG13 GA 2013 618272]; Region Midi-Pyrenees [13051317]; Association de la Recherche sur le Cancer FX This work was supported by National Institutes of Public Health Service grants R01 CA163698 and R01 CA64402 to N.J.D. and by the Fondation pour la Recherche Medicale (FRM AJE201109), the Agence Nationale de la Recherche (ANR 2012-CHEX-0002-01), a Marie Curie Career Integration Grant (PCIG13 GA 2013 618272), and the Region Midi-Pyrenees (reference 13051317) to L.D.S. N.J.D. is the James and Shirley Curvey MGH Research Scholar. J.M.J.L. is supported by a postdoctoral fellowship from the Association de la Recherche sur le Cancer. NR 49 TC 1 Z9 1 U1 3 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2015 VL 35 IS 24 BP 4199 EP 4211 DI 10.1128/MCB.00755-15 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CX5BL UT WOS:000365715500009 PM 26438601 ER PT J AU Kim, KH Kim, W Howard, TP Vazquez, F Tsherniak, A Wu, JN Wang, WS Haswell, JR Walensky, LD Hahn, WC Orkin, SH Roberts, CWM AF Kim, Kimberly H. Kim, Woojin Howard, Thomas P. Vazquez, Francisca Tsherniak, Aviad Wu, Jennifer N. Wang, Weishan Haswell, Jeffrey R. Walensky, Loren D. Hahn, William C. Orkin, Stuart H. Roberts, Charles W. M. TI SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2 SO NATURE MEDICINE LA English DT Article ID METHYLTRANSFERASE EZH2; FREQUENT MUTATIONS; CELL CARCINOMA; POLYCOMB; COMPLEX; INHIBITION; LYMPHOMA; TUMORS; GENES; H3K27 AB Human cancer genome sequencing has recently revealed that genes that encode subunits of SWI/SNF chromatin remodeling complexes are frequently mutated across a wide variety of cancers, and several subunits of the complex have been shown to have bona fide tumor suppressor activity(1). However, whether mutations in SWI/SNF subunits result in shared dependencies is unknown. Here we show that EZH2, a catalytic subunit of the polycomb repressive complex 2 (PRC2), is essential in all tested cancer cell lines and xenografts harboring mutations of the SWI/SNF subunits ARID1A, PBRM1, and SMARCA4, which are several of the most frequently mutated SWI/SNF subunits in human cancer, but that co-occurrence of a Ras pathway mutation is correlated with abrogation of this dependence. Notably, we demonstrate that SWI/SNF-mutant cancer cells are primarily dependent on a non-catalytic role of EZH2 in the stabilization of the PRC2 complex, and that they are only partially dependent on EZH2 histone methyltransferase activity. These results not only reveal a shared dependency of cancers with genetic alterations in SWI/SNF subunits, but also suggest that EZH2 enzymatic inhibitors now in clinical development may not fully suppress the oncogenic activity of EZH2. C1 [Kim, Kimberly H.; Kim, Woojin; Howard, Thomas P.; Wu, Jennifer N.; Wang, Weishan; Haswell, Jeffrey R.; Walensky, Loren D.; Orkin, Stuart H.; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kim, Kimberly H.; Kim, Woojin; Howard, Thomas P.; Wu, Jennifer N.; Wang, Weishan; Haswell, Jeffrey R.; Walensky, Loren D.; Orkin, Stuart H.; Roberts, Charles W. M.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Kim, Kimberly H.; Kim, Woojin; Howard, Thomas P.; Wu, Jennifer N.; Wang, Weishan; Haswell, Jeffrey R.; Walensky, Loren D.; Orkin, Stuart H.; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Vazquez, Francisca; Tsherniak, Aviad; Wu, Jennifer N.; Hahn, William C.; Roberts, Charles W. M.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Orkin, Stuart H.; Roberts, Charles W. M.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), St Jude Childrens Res Hosp, Ctr Comprehens Canc, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM charles.roberts@stjude.org FU National Cancer Center; US National Institutes of Health [R01CA172152, R01CA113794, U01CA176058]; Claudia Adams Barr grant; National Institute of General Medical Sciences [T32GM007753]; Cure AT/RT Now foundation; Avalanna Fund; Garrett B. Smith Foundation; Miles for Mary; Leukemia & Lymphoma Society Specialized Center of Research Award Project Grant; Todd J. Schwartz Memorial Fund FX EZ005 was provided courtesy of J. Bradner (Dana-Farber Cancer Institute). Plasmids for wild-type and SET domain-truncated (SET) EZH2 were provided courtesy of M. Brown (Dana-Farber Cancer Institute). K.H.K. was supported by an award from National Cancer Center. This work was supported by US National Institutes of Health grants R01CA172152 (C.W.M.R.), R01CA113794 (C.W.M.R.) and U01CA176058 (W.C.H.). W.K. was supported by a Claudia Adams Barr grant. T.P.H. was supported by an award from the National Institute of General Medical Sciences (T32GM007753). The Cure AT/RT Now foundation, the Avalanna Fund, the Garrett B. Smith Foundation, Miles for Mary (C.W.M.R.), a Leukemia & Lymphoma Society Specialized Center of Research Award Project Grant (L.D.W.) and the Todd J. Schwartz Memorial Fund (L.D.W.) provided additional support. NR 40 TC 37 Z9 37 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD DEC PY 2015 VL 21 IS 12 BP 1491 EP + DI 10.1038/nm.3968 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CX9EV UT WOS:000366008700020 PM 26552009 ER PT J AU Menachery, VD Yount, BL Debbink, K Agnihothram, S Gralinski, LE Plante, JA Graham, RL Scobey, T Ge, XY Donaldson, EF Randell, SH Lanzavecchia, A Marasco, WA Shi, ZLL Baric, RS AF Menachery, Vineet D. Yount, Boyd L., Jr. Debbink, Kari Agnihothram, Sudhakar Gralinski, Lisa E. Plante, Jessica A. Graham, Rachel L. Scobey, Trevor Ge, Xing-Yi Donaldson, Eric F. Randell, Scott H. Lanzavecchia, Antonio Marasco, Wayne A. Shi, Zhengli-Li Baric, Ralph S. TI A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence SO NATURE MEDICINE LA English DT Article ID ACUTE RESPIRATORY SYNDROME; RECEPTOR; DISEASE; CELLS; INFECTIONS; MECHANISMS; FITNESS; VACCINE; ESCAPE; MICE AB The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations(1). Using the SARS-CoV reverse genetics system(2), we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations. C1 [Menachery, Vineet D.; Yount, Boyd L., Jr.; Debbink, Kari; Gralinski, Lisa E.; Plante, Jessica A.; Graham, Rachel L.; Scobey, Trevor; Donaldson, Eric F.; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA. [Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Agnihothram, Sudhakar] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ge, Xing-Yi; Shi, Zhengli-Li] Chinese Acad Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Peoples R China. [Randell, Scott H.] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC USA. [Randell, Scott H.] Univ N Carolina, Cyst Fibrosis Ctr, Marsico Lung Inst, Chapel Hill, NC USA. [Lanzavecchia, Antonio] Bellinzona Inst Microbiol, Inst Res Biomed, Zurich, Switzerland. [Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Baric, RS (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA. EM vineet@email.unc.edu FU National Institute of Allergy & Infectious Disease; National Institute of Aging of the US National Institutes of Health (NIH) [U19AI109761, U19AI107810, AI085524, F32AI102561, K99AG049092]; National Natural Science Foundation of China [81290341, 31470260]; USAID-EPT-PREDICT from EcoHealth Alliance; National Institute of Diabetes and Digestive and Kidney Disease of the NIH [NIH DK065988] FX Research in this manuscript was supported by grants from the National Institute of Allergy & Infectious Disease and the National Institute of Aging of the US National Institutes of Health (NIH) under awards U19AI109761 (R.S.B.), U19AI107810 (R.S.B.), AI085524 (W.A.M.), F32AI102561 (V.D.M.) and K99AG049092 (V.D.M.), and by the National Natural Science Foundation of China awards 81290341 (Z.-L.S.) and 31470260 (X.-Y.G.), and by USAID-EPT-PREDICT funding from EcoHealth Alliance (Z.-L.S.). Human airway epithelial cultures were supported by the National Institute of Diabetes and Digestive and Kidney Disease of the NIH under award NIH DK065988 (S.H.R.). We also thank M.T. Ferris (Dept. of Genetics, University of North Carolina) for the reviewing of statistical approaches and C.T. Tseng (Dept. of Microbiology and Immunology, University of Texas Medical Branch) for providing Calu-3 cells. Experiments with the full-length and chimeric SHC014 recombinant viruses were initiated and performed before the GOF research funding pause and have since been reviewed and approved for continued study by the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 27 TC 27 Z9 28 U1 4 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD DEC PY 2015 VL 21 IS 12 BP 1508 EP + DI 10.1038/nm.3985 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CX9EV UT WOS:000366008700023 PM 26552008 ER PT J AU Scarcelli, G Polacheck, WJ Nia, HT Patel, K Grodzinsky, AJ Kamm, RD Yun, SH AF Scarcelli, Giuliano Polacheck, William J. Nia, Hadi T. Patel, Kripa Grodzinsky, Alan J. Kamm, Roger D. Yun, Seok Hyun TI Noncontact three-dimensional mapping of intracellular hydromechanical properties by Brillouin microscopy SO NATURE METHODS LA English DT Article ID LIVING CELLS; STIFFNESS; MATRIX; MECHANOTRANSDUCTION; MICRORHEOLOGY; ELASTICITY AB Current measurements of the biomechanical properties of cells require physical contact with cells or lack subcellular resolution. Here we developed a label-free microscopy technique based on Brillouin light scattering that is capable of measuring an intracellular longitudinal modulus with optical resolution. The 3D Brillouin maps we obtained of cells in 2D and 3D microenvironments revealed mechanical changes due to cytoskeletal modulation and cell-volume regulation. C1 [Scarcelli, Giuliano; Patel, Kripa; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Scarcelli, Giuliano; Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Scarcelli, Giuliano] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Polacheck, William J.; Nia, Hadi T.; Grodzinsky, Alan J.; Kamm, Roger D.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Grodzinsky, Alan J.; Kamm, Roger D.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Grodzinsky, Alan J.] MIT, Dept Elect Engn, Cambridge, MA 02139 USA. [Yun, Seok Hyun] Harvard MIT Hlth Sci & Technol Program, Cambridge, MA USA. RP Scarcelli, G (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM scarc@umd.edu; syun@hms.harvard.edu OI Polacheck, William/0000-0003-2728-0746 FU National Institutes of Health [K25-EB015885, R21-EY023043, R01-EY025454, P41-EB015903, R33 CA174550]; National Science Foundation [CBET-0853773]; Human Frontier Science Program Young Investigator Grant [RGY0074/2013] FX We thank A.C. Martin, F.M. Mason, E. Moeendarbary, M.C. Gather and K. Franze for helpful discussions, as well as H. Oda, K. Sawicki and K. Berghaus for help with hydrogel measurements. This work was supported in part by the National Institutes of Health (grants K25-EB015885 and R21-EY023043 to G.S.; grants R01-EY025454 and P41-EB015903 to S.H.Y.; and grant R33 CA174550 to R.D.K.), the National Science Foundation (grant CBET-0853773 to S.H.Y.) and a Human Frontier Science Program Young Investigator Grant (RGY0074/2013 to G.S.). NR 28 TC 17 Z9 17 U1 10 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD DEC PY 2015 VL 12 IS 12 BP 1132 EP + DI 10.1038/nmeth.3616 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CX7OD UT WOS:000365890700019 PM 26436482 ER PT J AU Altrock, PM Liu, LL Michor, F AF Altrock, Philipp M. Liu, Lin L. Michor, Franziska TI The mathematics of cancer: integrating quantitative models SO NATURE REVIEWS CANCER LA English DT Review ID TUMOR-INDUCED ANGIOGENESIS; CHRONIC MYELOID-LEUKEMIA; EVOLUTIONARY GAME-THEORY; DRUG-RESISTANCE; LUNG-CANCER; PASSENGER MUTATIONS; IMMUNE-SYSTEM; BREAST-CANCER; TREE MODELS; CLINICAL-IMPLICATIONS AB Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology. C1 [Altrock, Philipp M.; Liu, Lin L.; Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Altrock, Philipp M.; Liu, Lin L.; Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Altrock, Philipp M.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA. RP Michor, F (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu NR 218 TC 23 Z9 23 U1 24 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2015 VL 15 IS 12 BP 730 EP 745 DI 10.1038/nrc4029 PG 16 WC Oncology SC Oncology GA CX6RS UT WOS:000365829700008 PM 26597528 ER PT J AU Friedman, AA Letai, A Fisher, DE Flaherty, KT AF Friedman, Adam A. Letai, Anthony Fisher, David E. Flaherty, Keith T. TI Precision medicine for cancer with next-generation functional diagnostics SO NATURE REVIEWS CANCER LA English DT Review ID CELL LUNG-CANCER; CIRCULATING TUMOR-CELLS; ACUTE MYELOID-LEUKEMIA; OVARIAN-CANCER; IN-VITRO; CHEMOTHERAPY SENSITIVITY; RESISTANCE ASSAYS; EX-VIVO; CYTOGENETIC RESPONSES; MYELOGENOUS LEUKEMIA AB Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies. Recently, several 'next-generation' functional diagnostic technologies have been reported, including novel methods for tumour manipulation, molecularly precise assays of tumour responses and device-based in situ approaches; these address the limitations of the older generation of chemosensitivity tests. The promise of these new technologies suggests a future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients. C1 [Friedman, Adam A.; Fisher, David E.; Flaherty, Keith T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Fisher, David E.] Massachusetts Gen Hosp, Dermatol & Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Letai, Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Friedman, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM aafriedman@partners.org FU NCI NIH HHS [P01 CA066996, UM1 CA186709] NR 107 TC 39 Z9 40 U1 12 U2 66 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD DEC PY 2015 VL 15 IS 12 BP 747 EP 756 DI 10.1038/nrc4015 PG 10 WC Oncology SC Oncology GA CX6RS UT WOS:000365829700009 PM 26536825 ER PT J AU Levine, RA Hagege, AA Judge, DP Padala, M Dal-Bianco, JP Aikawa, E Beaudoin, J Bischoff, J Bouatia-Naji, N Bruneval, P Butcher, JT Carpentier, A Chaput, M Chester, AH Clusel, C Delling, FN Dietz, HC Dina, C Durst, R Fernandez-Friera, L Handschumacher, MD Jensen, MO Jeunemaitre, XP Le Marec, H Le Tourneau, T Markwald, RR Merot, J Messas, E Milan, DP Neri, T Norris, RA Peal, D Perrocheau, M Probst, V Puceat, M Rosenthal, N Solis, J Schott, JJ Schwammenthal, E Slaugenhaupt, SA Song, JK Yacoub, MH AF Levine, Robert A. Hagege, Albert A. Judge, Daniel P. Padala, Muralidhar Dal-Bianco, Jacob P. Aikawa, Elena Beaudoin, Jonathan Bischoff, Joyce Bouatia-Naji, Nabila Bruneval, Patrick Butcher, Jonathan T. Carpentier, Alain Chaput, Miguel Chester, Adrian H. Clusel, Catherine Delling, Francesca N. Dietz, Harry C. Dina, Christian Durst, Ronen Fernandez-Friera, Leticia Handschumacher, Mark D. Jensen, Morten O. Jeunemaitre, Xavier P. Le Marec, Herve Le Tourneau, Thierry Markwald, Roger R. Merot, Jean Messas, Emmanuel Milan, David P. Neri, Tui Norris, Russell A. Peal, David Perrocheau, Maele Probst, Vincent Puceat, Michael Rosenthal, Nadia Solis, Jorge Schott, Jean-Jacques Schwammenthal, Ehud Slaugenhaupt, Susan A. Song, Jae-Kwan Yacoub, Magdi H. CA Leducq Mitral Transatlantic Networ TI Mitral valve disease morphology and mechanisms SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID SYSTOLIC ANTERIOR MOTION; LEFT-VENTRICULAR DYSFUNCTION; OUTFLOW TRACT OBSTRUCTION; EMBRYONIC STEM-CELLS; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; CARDIAC RESYNCHRONIZATION THERAPY; CARDIOVASCULAR MAGNETIC-RESONANCE; DYNAMIC SUBAORTIC OBSTRUCTION; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE AB Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but-even in adult life-remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular-ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease. C1 [Levine, Robert A.; Dal-Bianco, Jacob P.; Handschumacher, Mark D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Milan, David P.; Peal, David] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Delling, Francesca N.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. [Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Ctr Human Genet Res, MGH Res Inst, Boston, MA 02114 USA. [Hagege, Albert A.; Bouatia-Naji, Nabila; Bruneval, Patrick; Carpentier, Alain; Jeunemaitre, Xavier P.; Messas, Emmanuel; Perrocheau, Maele] Univ Paris 05, UMR 970, Hop Europeen Georges Pompidou, Paris, France. [Judge, Daniel P.; Dietz, Harry C.] Johns Hopkins Univ, Baltimore, MD USA. [Padala, Muralidhar] Emory Univ, Sch Med, Atlanta, GA USA. [Aikawa, Elena] Brigham & Womens Hosp, Boston, MA 02115 USA. [Beaudoin, Jonathan] Laval Hosp, Quebec City, PQ, Canada. [Bischoff, Joyce] Boston Childrens Hosp, Boston, MA USA. [Butcher, Jonathan T.] Cornell Univ, Ithaca, NY USA. [Chaput, Miguel] Univ Montreal, Montreal, PQ, Canada. [Chester, Adrian H.; Yacoub, Magdi H.] Univ London Imperial Coll Sci Technol & Med, London, England. [Clusel, Catherine] INSERM Transfert, Paris, France. [Dina, Christian; Le Marec, Herve; Le Tourneau, Thierry; Merot, Jean; Probst, Vincent; Schott, Jean-Jacques] Univ Nantes, Thorac Inst, INSERM UMR 1097, CNRS UMR 6291, Nantes, France. [Durst, Ronen] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Fernandez-Friera, Leticia; Solis, Jorge] Hosp Univ HM Monteprincipe, Madrid, Spain. [Fernandez-Friera, Leticia; Solis, Jorge] Carlos III CNIC, Ctr Nacl Invest Cardiovasc, Madrid, Spain. [Jensen, Morten O.] Univ Aarhus, Aarhus, Denmark. [Markwald, Roger R.; Norris, Russell A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Neri, Tui; Puceat, Michael] Aix Marseille Univ, INSERM UMR 910, Marseille, France. [Rosenthal, Nadia] European Mol Biol Lab, Monterotondo, Italy. [Schwammenthal, Ehud] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Song, Jae-Kwan] Asan Med Ctr, Seoul, South Korea. RP Levine, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM rlevine@partners.org RI Butcher, Jonathan/D-2280-2012; BOUATIA-NAJI, NABILA/D-5863-2013; OI Butcher, Jonathan/0000-0002-9309-6296; Bouatia-Naji, Nabila/0000-0001-5424-2134; Bischoff, Joyce/0000-0002-6367-1974; Rosenthal, Nadia/0000-0002-7599-7365 FU Leducq Foundation, Paris, France for the Leducq Mitral Transatlantic Network of Excellence [07CVD04]; Leducq Foundation Career Development Awards [10CDA01, 11CDA04]; French Society of Cardiology, Paris, France; French National Research Agency, Paris, France; French Ministry of Health, Paris, France; National Institutes of Health, Bethesda, MD [R01 HL72265, R01 HL109506, R01 HL114805, K24 HL67434, K23 HL116652, R01 HL127692, R01 HL033756, NIGMS P30 GM103342, P20 RR21949, AHA 11SDG5270006]; Doris Duke Charitable Trust, New York, NY; Ellison Foundation, Boston, MA; American Society of Echocardiography, Raleigh, NC; Austrian Health Ministry Erwin-Schrodinger Fund, Vienna; Spanish Society of Cardiology, Barcelona; Eurostars CARDIOMARK Project [E16490]; European Union, Brussels; INSERM-DGOS; Nantes University Translational Research Programs; Fondation GenaVie, Nantes, France; French Foundation of Cardiology, Paris, France; Danish Heart Foundation, Copenhagen; Fondation de la Recherche Medicale, Paris, France; Fonds de Recherche du Quebec-Sante, Montreal, Quebec, Canada; Quebec Office of the Heart and Stroke Foundation, Montreal, Quebec, Canada FX All the authors are part of the Leducq Transatlantic Network, which brings together clinical and basic scientists from multiple centres to identify mechanisms of both inherited and acquired mitral valve disease, with the aim of discovering therapies to modify the natural history favourably. The authors acknowledge support of grant 07CVD04 of the Leducq Foundation, Paris, France for the Leducq Mitral Transatlantic Network of Excellence, and Leducq Foundation Career Development Awards 10CDA01 to D.P.J. and 11CDA04 to M. Padala. Additional support came from the French Society of Cardiology, Paris, France (MVP France and REMY Registry: A.A.H., X.P.J.), the French National Research Agency, Paris, France (A.A.H., E.M.), the French Ministry of Health, Paris, France (A.A.H.; Clinical Research Hospital Program, J.-J.S., T.L.T., H.L.M., V.P.), the National Institutes of Health, Bethesda, MD, R01 HL72265 (R.A.L.), R01 HL109506 (R.A.L., E.A., J.B.), R01 HL114805 (E.A.), K24 HL67434 (R.A.L.), K23 HL116652 (F.N.D.), R01 HL127692 (S.A.S., D.P.M., R.A.L.), R01 HL033756 (R.R.M., R.A.N.), NIGMS P30 GM103342 (R.R.M., R.A.N.), P20 RR21949 (R.R.M., RAN.), AHA 11SDG5270006 (R.A.N.), the Doris Duke Charitable Trust, New York, NY (S.A.S., R.A.L.), the Ellison Foundation, Boston, MA (R.A.L.), the American Society of Echocardiography, Raleigh, NC, (J.P.D.-B.), the Austrian Health Ministry Erwin-Schrodinger Fund, Vienna (J.P.D.-B.), the Spanish Society of Cardiology, Barcelona (PROMESA: L.F.-F, J.S.), the Eurostars CARDIOMARK Project E16490, European Union, Brussels, (J.-J.S.), the INSERM-DGOS and Nantes University Translational Research Programs (J.-J.S., C.D., T.L.T.), Fondation GenaVie, Nantes, France (T.L.T.), the French Foundation of Cardiology, Paris, France (T.L.T.), the Danish Heart Foundation, Copenhagen (M.O.J.), the Fondation de la Recherche Medicale, Paris, France (M. Puceat), the Fonds de Recherche du Quebec-Sante, Montreal, Quebec, Canada (J. Beaudoin), and the Quebec Office of the Heart and Stroke Foundation, Montreal, Quebec, Canada (J. Beaudoin). NR 318 TC 17 Z9 18 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 EI 1759-5010 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD DEC PY 2015 VL 12 IS 12 BP 689 EP 710 DI 10.1038/nrcardio.2015.161 PG 22 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX2XO UT WOS:000365560300002 PM 26483167 ER PT J AU Koudriavtseva, T Plantone, D Renna, R Mandoj, C Giannarelli, D Mainero, C AF Koudriavtseva, Tatiana Plantone, Domenico Renna, Rosaria Mandoj, Chiara Giannarelli, Diana Mainero, Caterina TI Interferon-beta therapy and risk of thrombocytopenia in multiple sclerosis patients SO NEUROLOGICAL SCIENCES LA English DT Article DE Multiple sclerosis; Thrombocytopenia; Disease-modifying therapies; Beta-interferon ID HEMOLYTIC-UREMIC SYNDROME; IMMUNE THROMBOCYTOPENIA; INNATE IMMUNITY; PLATELETS; PURPURA AB Thrombocytopenia is a well-described adverse event of several disease-modifying therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased prevalence of MS has been reported in patients with immune thrombocytopenia. In this retrospective, cross-sectional, case-control study we evaluated in a heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison with sex- and age-matched controls; (2) the relationship between thrombocytopenia and patients' demographic, clinical characteristics; (3) the risk for thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean age (+/- SD) 44.5 +/- A 10.7 years] and 200 controls (56 males, mean age 45.5 +/- A 12 years) were included. Thrombocytopenia was defined as platelet count lower than normal laboratory values (130-400 x 10(9)/L). The prevalence of thrombocytopenia was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04). Thrombocytopenia was present only in relapsing-remitting MS cases, and significantly associated with lower EDSS (p = 0.002) and with a trend for shorter disease duration (p = 0.06). It was more frequent in patients on high-dose interferon-beta therapy compared with those on low-dose interferon-beta therapy, other therapies or untreated patients (p = 0.02). High-dose interferon-beta therapy was associated with more than eightfold increase in the risk for thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted for EDSS, disease duration and type of disease). The prevalence of thrombocytopenia was increased in MS patients treated with DMT. High-dose interferon-beta therapy is the variable most strongly associated with thrombocytopenia. C1 [Koudriavtseva, Tatiana; Plantone, Domenico; Renna, Rosaria] IFO, Multiple Sclerosis Ctr, Neurol Unit, Regina Elena Natl Canc Inst, I-00144 Rome, Italy. [Mandoj, Chiara] IFO, Regina Elena Natl Canc Inst, Clin Pathol, I-00144 Rome, Italy. [Giannarelli, Diana] IFO, Regina Elena Natl Canc Inst, Sci Direct, I-00144 Rome, Italy. [Mainero, Caterina] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mainero, Caterina] Harvard Univ, Sch Med, Boston, MA USA. RP Koudriavtseva, T (reprint author), IFO, Multiple Sclerosis Ctr, Neurol Unit, Regina Elena Natl Canc Inst, Via Elio Chianesi 53, I-00144 Rome, Italy. EM koudriavtseva@ifo.it NR 27 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER-VERLAG ITALIA SRL PI MILAN PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY SN 1590-1874 EI 1590-3478 J9 NEUROL SCI JI Neurol. Sci. PD DEC PY 2015 VL 36 IS 12 BP 2263 EP 2268 DI 10.1007/s10072-015-2348-1 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX4ZZ UT WOS:000365711100014 PM 26209931 ER PT J AU Mawet, J Eikermann-Haerter, K Park, KY Helenius, J Daneshmand, A Pearlman, L Avery, R Negro, A Velioglu, M Arsava, EM Ay, H Ayata, C AF Mawet, Jerome Eikermann-Haerter, Katharina Park, Kwang-Yeol Helenius, Johanna Daneshmand, Ali Pearlman, Lea Avery, Ross Negro, Andrea Velioglu, Murat Arsava, Ethem Murat Ay, Hahn Ayata, Cenk TI Sensitivity to acute cerebral ischemic injury in migraineurs A retrospective case-control study SO NEUROLOGY LA English DT Article ID STROKE; DEPOLARIZATIONS; METAANALYSIS AB Objective:Migraine, particularly with aura, is a risk factor for ischemic stroke. Recent data in migraine mutant mice suggest that cerebral hyperexcitability associated with migraine accelerates recruitment of ischemic penumbra into the core, resulting in faster infarct growth compared with wild type. We hypothesized that individuals with a history of migraine are more likely to exhibit increased recruitment of ischemic tissue into the infarct in acute stroke.Methods:In this retrospective case-control study, we identified participants with reliably documented migraine history, measured lesion volumes on diffusion-weighted and perfusion-weighted MRI obtained within 72 hours of symptom onset, calculated the proportion of ischemic tissue on perfusion-weighted imaging (PWI) hyperintense on diffusion-weighted imaging (DWI), and compared the proportion of patients with no-mismatch pattern defined as DWI lesion >83% of PWI lesion.Results:Migraineurs (n = 45) were younger, more often female, less likely to have vascular risk factors, and more often had cervical artery dissection, but otherwise did not differ from controls (n = 27). A significantly larger proportion of migraineurs had no-mismatch pattern, indicating that the entire perfusion defect was recruited into the infarct by the time of MRI (22% vs 4% of migraineurs and controls, respectively; p = 0.044). The difference was even more prominent in migraineurs with aura (36% vs 4%, p = 0.019). The association between migraine and no-mismatch pattern persisted after adjustment for time to MRI (p = 0.041).Conclusions:This case-control study supports the hypothesis that a history of migraine, particularly with aura, is associated with a no-mismatch pattern during acute ischemic stroke, consistent with data obtained in migraine mutant mice. C1 [Mawet, Jerome; Eikermann-Haerter, Katharina; Daneshmand, Ali; Pearlman, Lea; Negro, Andrea; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Park, Kwang-Yeol; Helenius, Johanna; Avery, Ross; Velioglu, Murat; Arsava, Ethem Murat; Ay, Hahn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Park, Kwang-Yeol; Helenius, Johanna; Avery, Ross; Velioglu, Murat; Arsava, Ethem Murat; Ay, Hahn; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Charlestown, MA USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA. [Mawet, Jerome] DHD Neurovasc Sorbonne Paris Cite, Lariboisiere Hosp, AP HP, Emergency Headache Ctr, Paris, France. RP Ayata, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. EM hay@mgh.harvard.edu; cayata@mgh.harvard.edu FU American Heart Association [10SDG2610275]; Claflin Distinguished Award from the Massachusetts General Hospital; NIH [NS061505, NS055104]; Fondation Leducq; Heitman Foundation; Ellison Foundation; Institut Servier; Philippe Foundation; Therese and Rene Planiol Foundation for The Study of The Brain FX Supported by the American Heart Association (10SDG2610275), the Claflin Distinguished Award from the Massachusetts General Hospital, NIH (NS061505, NS055104), Fondation Leducq, The Heitman Foundation, The Ellison Foundation, Institut Servier, Philippe Foundation, and Therese and Rene Planiol Foundation for The Study of The Brain. NR 11 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC 1 PY 2015 VL 85 IS 22 BP 1945 EP 1949 DI 10.1212/WNL.0000000000002166 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA CX4LM UT WOS:000365672400006 PM 26537055 ER PT J AU Nikolaou, NI Arntz, HR Bellou, A Beygui, F Bossaert, LL Cariou, A AF Nikolaou, N. I. Arntz, H. R. Bellou, A. Beygui, F. Bossaert, L. L. Cariou, A. TI Initial Management of acute Coronary Syndromes SO NOTFALL & RETTUNGSMEDIZIN LA German DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; HOSPITAL CARDIAC-ARREST; ASSOCIATION TASK-FORCE; ACUTE CHEST-PAIN; RANDOMIZED CONTROLLED-TRIAL; 2013 ACCF/AHA GUIDELINE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACCELERATED DIAGNOSTIC PROTOCOL; MOLECULAR-WEIGHT HEPARIN C1 [Nikolaou, N. I.] Konstantopouleio Gen Hosp, Dept Cardiol, Athens, Greece. [Arntz, H. R.] Univ Med Berlin, Dept Emergency Med, Charite, Campus Benjamin Franklin, Berlin, Germany. [Bellou, A.] Univ Rennes, Rennes, France. [Bellou, A.] Harvard Univ, Sch Med, Beth Israel Deaconnes Med Ctr, Dept Emergency Med, Boston, MA USA. [Beygui, F.] Caen Univ Hosp, Intervent Cardiol Unit, Caen, France. [Bossaert, L. L.] Univ Antwerp, Dept Med & Hlth Sci, B-2020 Antwerp, Belgium. [Cariou, A.] Cochin Univ Hosp, AP HP, Med Intens Care Unit, Paris, France. [Cariou, A.] Paris Descartes Univ, Paris, France. RP Nikolaou, NI (reprint author), Konstantopouleio Gen Hosp, Dept Cardiol, Athens, Greece. EM HRArntz@t-online.de NR 185 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1434-6222 EI 1436-0578 J9 NOTFALL RETTUNGSMED JI Notfall Rettungsmed. PD DEC PY 2015 VL 18 IS 8 BP 984 EP 1002 DI 10.1007/s10049-015-0084-y PG 19 WC Emergency Medicine SC Emergency Medicine GA CX0ZP UT WOS:000365426300011 ER PT J AU Miller, BC Maus, MV AF Miller, Brian C. Maus, Marcela V. TI CD19-Targeted CAR T Cells: A New Tool in the Fight against B Cell Malignancies SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Review DE CAR T cell; CD19; T cell therapies; Adoptive transfer; B cell; Chimeric antigen receptor; Immunotherapy ID CHIMERIC-ANTIGEN-RECEPTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CYTOKINE RELEASE SYNDROME; ADOPTIVE IMMUNOTHERAPY; CLINICAL-TRIAL; ADVERSE EVENT; CD19 ANTIGEN; IN-VIVO; PHASE-I AB Adoptive cell immunotherapy is a novel tool in the fight against cancer. Serving both effector and memory functions for the immune system, T cells make an obvious candidate for adoptive cell immunotherapy. By modifying native T cells with a chimeric antigen receptor (CAR), these cells can theoretically be targeted against any extracellular antigen. To date, the best-studied and clinically validated CAR T cells recognize CD19, a cell surface molecule on B cells and B cell malignancies. These CD19-directed T cells have shown clinical utility in chronic lymphocytic leukemia, acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphomas, with some patients achieving long-term disease remissions after treatment. This review will briefly summarize the current data supporting the use of adoptively transferred CAR T cells for the treatment of CD19-positive malignancies. Given these exciting results, the Food and Drug Administration has granted a 'breakthrough' designation for several variations of CD19-directed CAR T cells for treatment of adult and pediatric relapsed/refractory ALL. (C) 2015 S. Karger GmbH, Freiburg C1 [Miller, Brian C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Maus, Marcela V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Maus, MV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 159,Thirteenth St, Charlestown, MA 02129 USA. EM mvmaus@mgh.harvard.edu OI Maus, Marcela/0000-0002-7578-0393; Miller, Brian/0000-0001-5931-4184 FU [T32CA009172]; [K08CA166039] FX Dr. Miller is supported by T32CA009172, and Dr. Maus is supported by K08CA166039. NR 59 TC 2 Z9 2 U1 4 U2 23 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD DEC PY 2015 VL 38 IS 12 BP 683 EP 690 DI 10.1159/000442170 PG 8 WC Oncology SC Oncology GA CX4PK UT WOS:000365682600009 PM 26633875 ER PT J AU Barbu, AM Gniady, JP Vivero, RJ Friedman, AD Burns, JA AF Barbu, Anca M. Gniady, John P. Vivero, Richard J. Friedman, Aaron D. Burns, James A. TI Bedside Injection Medialization Laryngoplasty in Immediate Postoperative Patients SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE injection medialization; larynx/surgery; vocal fold paralysis ID VOCAL CORD PARALYSIS; THORACIC-SURGERY; FOLD PARALYSIS; IMMOBILITY; ASPIRATION; QUALITY; VOICE AB Objectives The morbidity of glottic insufficiency resulting from unilateral vocal fold immobility may significantly compromise postoperative recovery in patients with decreased pulmonary reserve or inability to protect their airway. Injection medialization laryngoplasty is an effective means of treating glottic insufficiency due to unilateral vocal fold immobility. The purpose of this study is to present our experience with bedside transoral injection medialization laryngoplasty in the immediate postoperative period. Study Design Case series with chart review. Setting Academic tertiary care hospital. Subjects and Methods Patient demographics, clinical characteristics, procedural details, and short-term outcome measures of oral intake were recorded in a cohort of 68 patients over 5 years with unilateral vocal cord paralysis who underwent injection medialization as a bedside procedure in the immediate postoperative period. Results Mean time to injection was 8.2 days postoperatively. At the time of injection, 40 of 68 patients were nil per os. Seventy percent (28 of 40) had their diet advanced to adequate oral intake within 5 days of injection. Greater than half of the injections (36 of 68) were performed in the intensive care unit. No complications were noted, and all patients in this cohort were able to tolerate the bedside injection. Conclusion Bedside injection medialization laryngoplasty in the immediate postoperative period via the transoral approach can be performed in patients, even in the intensive care unit, while on anticoagulation, and may be of benefit for hospitalized patients with unilateral vocal fold immobility. Further studies quantifying improvement in voice and swallowing data are merited. C1 [Barbu, Anca M.; Gniady, John P.; Vivero, Richard J.; Burns, James A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Dept Surgery,Med Sch, Boston, MA USA. [Friedman, Aaron D.] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA. RP Barbu, AM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, One Bowdoin Sq, Boston, MA 02114 USA. EM Barbu.Anca@mgh.harvard.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2015 VL 153 IS 6 BP 1007 EP 1012 DI 10.1177/0194599815601393 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CX5LS UT WOS:000365743700021 PM 26307574 ER PT J AU Chellapandian, D Shaikh, F van den Bos, C Somers, GR Astigarraga, I Jubran, R Degar, B Carret, AS Mandel, K Belletrutti, M Dix, D Visser, J Abuhadra, N Chang, T Rollins, B Whitlock, J Weitzman, S Abla, O AF Chellapandian, Deepak Shaikh, Furqan van den Bos, Cor Somers, Gino R. Astigarraga, Itziar Jubran, Rima Degar, Barbara Carret, Anne-Sophie Mandel, Karen Belletrutti, Mark Dix, David Visser, Johannes Abuhadra, Nour Chang, Tiffany Rollins, Barret Whitlock, James Weitzman, Sheila Abla, Oussama TI Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE chemotherapy; CNS neurodegeneration; diabetes insipidus; disease recurrence; Langerhans cell histiocytosis; radiotherapy ID EOSINOPHILIC GRANULOMA; INVOLVEMENT; SYSTEM; ORBIT AB Background. Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients. Methods. Ten pediatric institutions across North America and Europe contributed data of their patients with LCH and single-bone CNS-risk lesions. Clinical information on age, sex, specific craniofacial site involvement, and intracranial extension at diagnosis, therapy, and disease course was collected for all eligible patients. Results. The final analysis included 93 eligible children who were either treated with systemic therapy (chemotherapy, chemo-radiotherapy, or radiotherapy) or local therapy (biopsy, curettage, and/or intralesional steroids). Fifty-nine patients had systemic and 34 had local therapy. The 5-year event-free survival (EFS) and overall survival (OS) were 80 +/- 5% and 98 +/- 2% in the systemic therapy group versus 85 +/- 6% and 95 +/- 5% in the local therapy group. There was no statistically significant difference between either group with regard to EFS (P = 0.26) and OS (P = 0.78). On multivariable analysis, there was no significant difference among the two treatment groups after adjusting for site and intracranial soft tissue extension, nor any trend favoring systemic therapy (HR = 2.26, 95% CI = 0.77-6.70; P = 0.14). Conclusion. Systemic therapy may not reduce the risk of recurrence or late sequelae in children with LCH and single-bone CNS-risk lesions as compared to local treatment. (C) 2015 Wiley Periodicals, Inc. C1 [Chellapandian, Deepak; Shaikh, Furqan; Abuhadra, Nour; Whitlock, James; Weitzman, Sheila; Abla, Oussama] Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [van den Bos, Cor] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Pediat Oncol, NL-1105 AZ Amsterdam, Netherlands. [Somers, Gino R.] Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada. [Astigarraga, Itziar] Hosp Univ Cruces, Bio Cruces Hlth Res Inst, Serv Pediat, Baracaldo, Bizkaia, Spain. [Astigarraga, Itziar] Univ Basque Country, EHU, Dept Pediat, E-48080 Bilbao, Vizcaya, Spain. [Jubran, Rima] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Degar, Barbara] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Carret, Anne-Sophie] Univ Montreal, Dept Pediat, Div Hematol Oncol, Ctr Hosp Univ CHU St Justine, Montreal, PQ H3C 3J7, Canada. [Mandel, Karen] Univ Ottawa, Div Hematol Oncol, Childrens Hosp Eastern Ontario, Ottawa, ON, Canada. [Belletrutti, Mark] Univ Alberta, Dept Pediat, Stollery Childrens Hosp, Edmonton, AB, Canada. [Dix, David] Univ British Columbia, Dept Pediat, Vancouver, BC V6T 1W5, Canada. [Visser, Johannes] Leicester Childrens Hosp, Leicester, Leics, England. [Chang, Tiffany] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Rollins, Barret] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA USA. RP Chellapandian, D (reprint author), Hosp Sick Children, Dept Pediat, Div Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM Deepak.Chellapandian@sickkids.ca RI Chellapandian, Deepak/F-6225-2017 OI Chellapandian, Deepak/0000-0003-3518-9790 NR 14 TC 2 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2015 VL 62 IS 12 BP 2162 EP 2166 DI 10.1002/pbc.25645 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA CX0UN UT WOS:000365412600018 PM 26179251 ER PT J AU Shum, AMY Fung, DCY Corley, SM McGill, MC Bentley, NL Tan, TC Wilkins, MR Polly, P AF Shum, Angie M. Y. Fung, David C. Y. Corley, Susan M. McGill, Max C. Bentley, Nicholas L. Tan, Timothy C. Wilkins, Marc R. Polly, Patsie TI Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia SO PHYSIOLOGICAL GENOMICS LA English DT Article DE colon (C26) carcinoma; skeletal muscle; cardiac muscle; cancer cachexia; differentially expressed genes ID ADENINE-NUCLEOTIDE TRANSLOCATOR; LACTATE-DEHYDROGENASE ISOENZYME-1; GLYCOGEN-SYNTHASE KINASE-3-BETA; ANKYRIN REPEAT PROTEIN; LOSS-OF-FUNCTION; B TYPE-I; ALKALINE-PHOSPHATASE; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE AB Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response. C1 [Shum, Angie M. Y.; McGill, Max C.; Bentley, Nicholas L.; Tan, Timothy C.; Polly, Patsie] Univ New S Wales, Inflammat & Infect Res Ctr, Kensington, NSW 2052, Australia. [Shum, Angie M. Y.; McGill, Max C.; Polly, Patsie] Univ New S Wales, Fac Med, Sch Med Sci, Dept Pathol, Kensington, NSW 2052, Australia. [Corley, Susan M.; Wilkins, Marc R.] Univ New S Wales, New South Wales Syst Biol Initiat, Kensington, NSW 2052, Australia. [Fung, David C. Y.; Corley, Susan M.; Wilkins, Marc R.] Univ New S Wales, Fac Sci, Sch Biotechnol & Biomol Sci, Kensington, NSW 2052, Australia. [Bentley, Nicholas L.] Univ New S Wales, Fac Med, Sch Med Sci, Mitochondrial Bioenerget Grp,Dept Pharmacol, Kensington, NSW 2052, Australia. [Tan, Timothy C.] Blacktown Clin Sch, Blacktown, NSW, Australia. [Tan, Timothy C.] Blacktown Hosp, Blacktown, NSW, Australia. [Tan, Timothy C.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Polly, P (reprint author), Univ New S Wales, Fac Med, Sch Med Sci, Rm 420,Wallace Wurth EAST Bldg,High St, Kensington, NSW 2052, Australia. EM patsie.polly@unsw.edu.au FU University of New South Wales (UNSW) Faculty of Medicine Research Grant; New South Wales State Government Science Leveraging Fund; EIF Super Science Scheme; Australian Postgraduate Award; UNSW Research Excellence Scholarship FX This project was supported by a University of New South Wales (UNSW) Faculty of Medicine Research Grant (P. Polly), the New South Wales State Government Science Leveraging Fund and the EIF Super Science Scheme for their financial support (M. R. Wilkins). A. M. Y. Shum is a recipient of the Australian Postgraduate Award and the UNSW Research Excellence Scholarship. NR 107 TC 2 Z9 2 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 EI 1531-2267 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD DEC 1 PY 2015 VL 47 IS 12 BP 588 EP 599 DI 10.1152/physiolgenomics.00128.2014 PG 12 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA CX7RR UT WOS:000365900400002 PM 26395599 ER PT J AU Ling, D Bodugoz-Senturk, H Nanda, S Braithwaite, G Muratoglu, OK AF Ling, Doris Bodugoz-Senturk, Hatice Nanda, Salil Braithwaite, Gavin Muratoglu, Orhun K. TI Quantifying the lubricity of mechanically tough polyvinyl alcohol hydrogels for cartilage repair SO PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE LA English DT Article DE Biomaterials; polyvinyl alcohol; lubrication testing; cartilage; ligament biomechanics; orthopedic materials; polymers ID POLY(VINYL ALCOHOL); ARTICULAR-CARTILAGE; POLY(ACRYLIC ACID); SURFACE FRICTION; POLYMER GELS; POLYACRYLAMIDE; BEHAVIOR; WATER; PH AB Polyvinyl alcohol hydrogels are biocompatible and can be used as synthetic articular cartilage. Their mechanical characteristics can be tailored by various techniques such as annealing or blending with other hydrophilic polymers. In this study, we quantified the coefficient of friction of various candidate polyvinyl alcohol hydrogels against cobalt-chrome alloy or swine cartilage using a new rheometer-based method. We investigated the coefficient of friction of polyvinyl alcohol-only hydrogels and blends with polyethylene glycol, polyacrylic acid, and polyacrylamide against swine cartilage and polished cobalt-chrome surfaces. The addition of the functional groups to polyvinyl alcohol, such as acrylamide (semi-interpenetrating network) and acrylic acid (blend), significantly reduced the coefficient of friction. The coefficient of friction of the polyvinyl alcohol-only hydrogel was measured as 0.4 +/- 0.03 against cobalt-chrome alloy, and 0.09 +/- 0.004 against cartilage, while those measurements for the polyvinyl alcohol-polyacrylic acid blends and polyvinyl alcohol-polyacrylamide semi-interpenetrating network were 0.07 +/- 0.01 and 0.1 +/- 0.003 against cobalt-chrome alloy, and 0.03 +/- 0.001 and 0.02 +/- 0.001 against cartilage, respectively. There was no significant or minimal difference in the coefficient of friction between samples from different regions of the knee, or animals, or when the cartilage samples were frozen for 1 day or 2 days before testing. However, changing lubricant from deionized water to ionic media, for example, saline or simulated body fluid, increased the coefficient of friction significantly. C1 [Ling, Doris; Bodugoz-Senturk, Hatice; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bodugoz-Senturk, Hatice; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. [Nanda, Salil] Cornell Univ, Ithaca, NY USA. [Braithwaite, Gavin] Cambridge Polymer Grp, Boston, MA USA. RP Bodugoz-Senturk, H (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,GRJ1102, Boston, MA 02114 USA. EM hatbs88@gmail.com NR 34 TC 0 Z9 0 U1 5 U2 24 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0954-4119 EI 2041-3033 J9 P I MECH ENG H JI Proc. Inst. Mech. Eng. Part H-J. Eng. Med. PD DEC PY 2015 VL 229 IS 12 SI SI BP 845 EP 852 DI 10.1177/0954411915599016 PG 8 WC Engineering, Biomedical SC Engineering GA CX4MM UT WOS:000365675000003 PM 26614798 ER PT J AU Brusasco, C Corradi, F De Ferrari, A Ball, L Kacmarek, RM Pelosi, P AF Brusasco, Claudia Corradi, Francesco De Ferrari, Alessandra Ball, Lorenzo Kacmarek, Robert M. Pelosi, Paolo TI CPAP Devices for Emergency Prehospital Use: A Bench Study SO RESPIRATORY CARE LA English DT Article DE noninvasive CPAP; emergency department; ambulance; cardiogenic pulmonary edema; helmet CPAP; Boussignac; acute respiratory failure ID POSITIVE AIRWAY PRESSURE; ACUTE RESPIRATORY-FAILURE; CARDIOGENIC PULMONARY-EDEMA; CONVENTIONAL MECHANICAL VENTILATION; CONGESTIVE-HEART-FAILURE; NONINVASIVE VENTILATION; FACE MASK; SYSTEM; HELMET; METAANALYSIS AB BACKGROUND: CPAP is frequently used in prehospital and emergency settings. An air-flow output minimum of 60 L/min and a constant positive pressure are 2 important features for a successful CPAP device. Unlike hospital CPAP devices, which require electricity, CPAP devices for ambulance use need only an oxygen source to function. The aim of the study was to evaluate and compare on a bench model the performance of 3 orofacial mask devices (Ventumask, EasyVent, and Boussignac CPAP system) and 2 helmets (Ventukit and EVE Coulisse) used to apply CPAP in the prehospital setting. METHODS: A static test evaluated air-flow output, positive pressure applied, and FIO2 delivered by each device. A dynamic test assessed airway pressure stability during simulated ventilation. Efficiency of devices was compared based on oxygen flow needed to generate a minimum air flow of 60 L/min at each CPAP setting. RESULTS: The EasyVent and EVE Coulisse devices delivered significantly higher mean air-flow outputs compared with the Ventumask and Ventukit under all CPAP conditions tested. The Boussignac CPAP system never reached an air-flow output of 60 L/min. The EasyVent had significantly lower pressure excursion than the Ventumask at all CPAP levels, and the EVE Coulisse had lower pressure excursion than the Ventukit at 5, 15, and 20 cm H2O, whereas at 10 cm H2O, no significant difference was observed between the 2 devices. Estimated oxygen consumption was lower for the EasyVent and EVE Coulisse compared with the Ventumask and Ventukit. CONCLUSIONS: Air-flow output, pressure applied, F-IO2 delivered, device oxygen consumption, and ability to maintain air flow at 60 L/min differed significantly among the CPAP devices tested. Only the EasyVent and EVE Coulisse achieved the required minimum level of air-flow output needed to ensure an effective therapy under all CPAP conditions. C1 [Brusasco, Claudia; De Ferrari, Alessandra; Ball, Lorenzo; Pelosi, Paolo] Univ Genoa, Dipartimento Sci Chirurg & Diagnost Integrate, Sez Anestesia & Rianimaz, I-16132 Genoa, Italy. [De Ferrari, Alessandra; Ball, Lorenzo; Pelosi, Paolo] Azienda Osped Univ San Martino, IRCCS, Ist Sci Tumori, Genoa, Italy. [Corradi, Francesco] EO Osped Galliera, SC Anestesia & Rianimaz, Genoa, Italy. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Brusasco, C (reprint author), Univ Genoa, Dipartimento Sci Chirurg & Diagnost Integrate, Sez Anestesia & Rianimaz, Largo Rosanna Benzi 8, I-16132 Genoa, Italy. EM claudia.brusasco@gmail.com RI Corradi, Francesco/C-5207-2009; Ball, Lorenzo/K-7612-2016 OI Ball, Lorenzo/0000-0002-3876-4730 NR 37 TC 4 Z9 4 U1 1 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD DEC PY 2015 VL 60 IS 12 BP 1777 EP 1785 DI 10.4187/respcare.04134 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CX5QX UT WOS:000365758400012 PM 26420898 ER PT J AU Saddawi-Konefka, D Hung, SL Kacmarek, RM Jiang, YD AF Saddawi-Konefka, Daniel Hung, Susan L. Kacmarek, Robert M. Jiang, Yandong TI Optimizing Mask Ventilation: Literature Review and Development of a Conceptual Framework SO RESPIRATORY CARE LA English DT Review DE positive-pressure respiration; pulmonary ventilation; respiratory therapy; respiration; critical care; anesthesiology ID OBSTRUCTIVE SLEEP-APNEA; DIFFICULT AIRWAY; FACE MASK; NEUROMUSCULAR BLOCKADE; ANESTHETIZED PERSONS; EDENTULOUS PATIENTS; GENERAL-ANESTHESIA; PARALYZED PATIENTS; ENDOTRACHEAL-TUBE; LEAK COMPENSATION AB Mask ventilation is lifesaving, especially in cases of difficult intubation. Many publications have offered distinct techniques for optimizing mask ventilation. This article reviews currently available difficult mask ventilation literature and theory. We divide difficult mask ventilation into 3 broad categories based on etiology: inadequate mask seal, increased airway resistance, and decreased respiratory compliance. Published strategies for overcoming difficulty are presented and organized by etiology. C1 [Saddawi-Konefka, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA USA. [Hung, Susan L.] White Plains Hosp, Westchester Anesthesiologists, White Plains, NY USA. [Jiang, Yandong] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37235 USA. RP Jiang, YD (reprint author), Vanderbilt Univ, Med Ctr, Dept Anesthesiol, 1301 Med Ctr Dr,4648 TVC, Nashville, TN 37232 USA. EM yandong.jiang@vanderbilt.edu NR 43 TC 0 Z9 0 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD DEC PY 2015 VL 60 IS 12 BP 1834 EP 1840 DI 10.4187/respcare.04183 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CX5QX UT WOS:000365758400019 PM 26487749 ER PT J AU Quilez, ME Rodriguez-Gonzalez, R Turon, M Fernandez-Gonzalo, S Villar, J Kacmarek, RM Gomez, MN Oliva, JC Blanch, L Lopez-Aguilar, J AF Elisa Quilez, Maria Rodriguez-Gonzalez, Raquel Turon, Marc Fernandez-Gonzalo, Sol Villar, Jesus Kacmarek, Robert M. Nieves Gomez, Ma Carles Oliva, Joan Blanch, Lluis Lopez-Aguilar, Josefina TI MODERATE PEEP AFTER TRACHEAL LIPOPOLYSACCHARIDE INSTILLATION PREVENTS INFLAMMATION AND MODIFIES THE PATTERN OF BRAIN NEURONAL ACTIVATION SO SHOCK LA English DT Article DE Experimental; inflammation; mechanical ventilation; neuronal activation; PEEP ID END-EXPIRATORY PRESSURE; INDUCED LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; MECHANICAL VENTILATION; INTRATRACHEAL LIPOPOLYSACCHARIDE; RETROSPLENIAL CORTEX; HYPERCAPNIC ACIDOSIS; PNEUMONIA; MODEL; TRANSLOCATION AB Background:Ventilatory strategy and specifically positive end-expiratory pressure (PEEP) can modulate the inflammatory response and pulmonary-to-systemic translocation of lipopolysaccharide (LPS). Both inflammation and ventilatory pattern may modify brain activation, possibly worsening the patient's outcome and resulting in cognitive sequelae.Methods:We prospectively studied Sprague-Dawley rats randomly assigned to undergo 3h mechanical ventilation with 7mL/kg tidal ventilation and either 2cmH(2)O or 7cmH(2)O PEEP after intratracheal instillation of LPS or saline. Healthy nonventilated rats served as baseline. We analyzed lung mechanics, gas exchange, lung and plasma cytokine levels, lung apoptotic cells, and lung neutrophil infiltration. To evaluate brain neuronal activation, we counted c-Fos immunopositive cells in the retrosplenial cortex (RS), thalamus, supraoptic nucleus (SON), nucleus of the solitary tract (NTS), paraventricular nucleus (PVN), and central amygdala (CeA).Results:LPS increased lung neutrophilic infiltration, lung and systemic MCP-1 levels, and neuronal activation in the CeA and NTS. LPS-instilled rats receiving 7cmH(2)O PEEP had less lung and systemic inflammation and more c-Fos-immunopositive cells in the RS, SON, and thalamus than those receiving 2cmH(2)O PEEP. Applying 7cmH(2)O PEEP increased neuronal activation in the CeA and NTS in saline-instilled rats, but not in LPS-instilled rats.Conclusions:Moderate PEEP prevented lung and systemic inflammation secondary to intratracheal LPS instillation. PEEP also modified the neuronal activation pattern in the RS, SON, and thalamus. The relevance of these differential brain c-Fos expression patterns in neurocognitive outcomes should be explored. C1 [Elisa Quilez, Maria; Nieves Gomez, Ma; Blanch, Lluis; Lopez-Aguilar, Josefina] Univ Autonoma Barcelona, Inst Univ Parc Tauli, Corp Sanitaria Parc Tauli, Crit Care Ctr, Bellaterra, Spain. [Elisa Quilez, Maria; Turon, Marc; Villar, Jesus; Blanch, Lluis; Lopez-Aguilar, Josefina] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Elisa Quilez, Maria; Turon, Marc; Fernandez-Gonzalo, Sol; Nieves Gomez, Ma; Carles Oliva, Joan; Blanch, Lluis; Lopez-Aguilar, Josefina] Univ Autonoma Barcelona, Corp Sanitaria Parc Tauli, Fundacio Parc Tauli, Inst Invest & Innovacio Parc Tauli, Bellaterra, Spain. [Rodriguez-Gonzalez, Raquel] Univ Santiago de Compostela, Inst Invest Sanitaria IDIS, Dept Anesthesiol Intens Care & Pain Management, Crit Patient Translat Res Grp,Hosp Clin Univ, Santiago De Compostela, Spain. [Rodriguez-Gonzalez, Raquel; Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Turon, Marc; Fernandez-Gonzalo, Sol] Univ Autonoma Barcelona, Dept Clin & Hlth Psychol, Psychopathol & Neuropsychol Res Unit, Bellaterra, Spain. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA USA. RP Lopez-Aguilar, J (reprint author), Fundacio Parc Tauli, C Parc Tauli 1, Sabadell 08208, Spain. EM Jlopeza@tauli.cat RI Rodriguez Gonzalez, Raquel/F-1490-2013; OI Rodriguez Gonzalez, Raquel/0000-0003-4171-0263; FERNANDEZ-GONZALO, SOL/0000-0003-0267-0617 FU Corporative Research Program in Acute Lung Injury from the CIBER de Enfermedades Respiratorias; Instituto de Salud Carlos III (Madrid, Spain) [FIS PI13/02204]; I3PT-Fundacio Parc Tauli; Instituto de Salud Carlos III (Contratos postdoctorales de perfeccionamiento en investigacion en salud, Programa Sara Borrell) [CD11/00104] FX This work was supported by the Corporative Research Program in Acute Lung Injury from the CIBER de Enfermedades Respiratorias, FIS PI13/02204 Instituto de Salud Carlos III (Madrid, Spain), and I3PT-Fundacio Parc Tauli. RR-G is the recipient of a grant from Instituto de Salud Carlos III (Contratos postdoctorales de perfeccionamiento en investigacion en salud, Programa Sara Borrell CD11/00104). NR 40 TC 2 Z9 2 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD DEC PY 2015 VL 44 IS 6 BP 601 EP 608 DI 10.1097/SHK.0000000000000469 PG 8 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA CX4LZ UT WOS:000365673700013 PM 26398809 ER PT J AU Arble, DM Bass, J Behn, CD Butler, MP Challet, E Czeisler, C Depner, CM Elmquist, J Franken, P Grandner, MA Hanlon, EC Keene, AC Joyner, MJ Karatsoreos, I Kern, PA Klein, S Morris, CJ Pack, AI Panda, S Ptacek, LJ Punjabi, NM Sassone-Corsi, P Scheer, FA Saxena, R Seaquest, ER Thimgan, MS Van Cauter, E Wright, KP AF Arble, Deanna M. Bass, Joseph Behn, Cecilia Diniz Butler, Matthew P. Challet, Etienne Czeisler, Charles Depner, Christopher M. Elmquist, Joel Franken, Paul Grandner, Michael A. Hanlon, Erin C. Keene, Alex C. Joyner, Michael J. Karatsoreos, Ilia Kern, Philip A. Klein, Samuel Morris, Christopher J. Pack, Allan I. Panda, Satchidananda Ptacek, Louis J. Punjabi, Naresh M. Sassone-Corsi, Paolo Scheer, Frank A. Saxena, Richa Seaquest, Elizabeth R. Thimgan, Matthew S. Van Cauter, Eve Wright, Kenneth P. TI Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions SO SLEEP LA English DT Article DE circadian disruption; circadian rhythm; diabetes; insulin resistance; metabolism; obesity; short sleep; sleep apnea; sleep disorders ID CHRONIC INTERMITTENT HYPOXIA; POSITIVE AIRWAY PRESSURE; HIGH-FAT-DIET; HIGH CALORIC-INTAKE; INSULIN-RESISTANCE; CAROTID-BODY; WEIGHT-GAIN; FOOD-INTAKE; GLUCOSE-METABOLISM; HUMAN ADIPOCYTES AB A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in humans need to complement the elegant short-term laboratory-based human studies of simulated short sleep and shift work etc. with studies in subjects in the general population with these disorders. It is conceivable that chronic adaptations occur, and if so, the mechanisms by which they occur needs to be identified and understood. Particular areas of opportunity that are ready for translation are studies to address whether CPAP treatment of patients with pre-diabetes and obstructive sleep apnea (OSA) prevents or delays the onset of diabetes and whether temporal restricted feeding has the same impact on obesity rates in humans as it does in mice. C1 [Arble, Deanna M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Bass, Joseph] Northwestern Univ, Dept Med, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA. [Behn, Cecilia Diniz] Colorado Sch Mines, Dept Appl Math & Stat, Golden, CO 80401 USA. [Butler, Matthew P.] Oregon Hlth & Sci Univ, Oregon Inst Occupat Hlth Sci, Portland, OR 97201 USA. [Challet, Etienne] Univ Strasbourg, CNRS, Inst Cellular & Integrat Neurosci, Strasbourg, France. [Czeisler, Charles; Morris, Christopher J.; Scheer, Frank A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Czeisler, Charles; Morris, Christopher J.; Scheer, Frank A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Depner, Christopher M.; Wright, Kenneth P.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Elmquist, Joel] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Elmquist, Joel] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Elmquist, Joel] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Franken, Paul] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Grandner, Michael A.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Hanlon, Erin C.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Keene, Alex C.] Univ Nevada, Dept Biol, Reno, NV 89557 USA. [Joyner, Michael J.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA. [Karatsoreos, Ilia] Washington State Univ, Coll Vet Med, Dept Integrat Physiol & Neurosci, Pullman, WA 99164 USA. [Kern, Philip A.] Univ Kentucky, Dept Med, Div Endocrinol, Lexington, KY 40506 USA. [Kern, Philip A.] Univ Kentucky, Ctr Clin & Translat Sci, Lexington, KY USA. [Klein, Samuel] Washington Univ, Sch Med St Louis, Ctr Human Nutr, St Louis, MO USA. [Pack, Allan I.] Univ Penn, Perelman Sch Med, Div Sleep Med, Dept Med, Philadelphia, PA 19104 USA. [Pack, Allan I.] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Panda, Satchidananda] Salk Inst Biol Studies, Regulatory Biol Lab, La Jolla, CA 92037 USA. [Ptacek, Louis J.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Neurol, San Francisco, CA 94143 USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Sassone-Corsi, Paolo] Univ Calif Irvine, Sch Med, Ctr Epigenet & Metab, Irvine, CA 92717 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Saxena, Richa] Harvard Univ, Sch Med, Boston, MA USA. [Seaquest, Elizabeth R.] Univ Minnesota, Dept Med, Div Endocrinol Diabet & Metab, Minneapolis, MN 55455 USA. [Thimgan, Matthew S.] Missouri Univ Sci & Technol, Dept Biol Sci, Rolla, MO USA. [Van Cauter, Eve] Univ Chicago, Sleep Metab & Hlth Ctr, Chicago, IL 60637 USA. [Wright, Kenneth P.] Univ Colorado, Div Endocrinol Diabet & Metab, Aurora, CO USA. RP Pack, AI (reprint author), Ctr Sleep & Circadian Neurobiol, 125 South 31st St,Suite 2100, Philadelphia, PA 19104 USA. EM pack@mail.med.upenn.edu RI Diniz Behn, Cecilia/L-1643-2013; OI Arble, Deanna/0000-0002-3993-5984 FU NIDDK; Phillips Respironics FX The authors acknowledge the outstanding work by Dr. Corrine Silva and Dr. Karen Teff from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in organizing this workshop. We also acknowledge the support of the NIDDK in sponsoring the event. An unrestricted educational grant was given to the Sleep Research Society by Phillips Respironics to support travel awards for early-stage investigators. NR 123 TC 13 Z9 13 U1 1 U2 8 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2015 VL 38 IS 12 BP 1849 EP 1860 DI 10.5665/sleep.5226 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX3RH UT WOS:000365616300008 PM 26564131 ER PT J AU Maski, K Holbrook, H Manoach, D Hanson, E Kapur, K Stickgold, R AF Maski, Kiran Holbrook, Hannah Manoach, Dara Hanson, Ellen Kapur, Kush Stickgold, Robert TI Sleep Dependent Memory Consolidation in Children with Autism Spectrum Disorder SO SLEEP LA English DT Article DE autism spectrum disorder; children; cognition; memory consolidation; sleep ID LATE NOCTURNAL SLEEP; SLOW-WAVE SLEEP; DECLARATIVE MEMORY; DIAGNOSTIC INTERVIEW; DEVELOPMENTAL DELAY; TYPICAL DEVELOPMENT; AGE-CHILDREN; SPINDLES; QUESTIONNAIRE; RESTRICTION AB Study Objectives: Examine the role of sleep in the consolidation of declarative memory in children with autism spectrum disorder (ASD). Design: Case-control study. Setting: Home-based study with sleep and wake conditions. Participants: Twenty-two participants with ASD and 20 control participants between 9 and 16 y of age. Measurements and Results: Participants were trained to criterion on a spatial declarative memory task and then given a cued recall test. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with home-based polysomnography; Wake and Sleep conditions were counterbalanced. Children with ASD had poorer sleep efficiency than controls, but other sleep macroarchitectural and microarchitectural measures were comparable after controlling for age and medication use. Both groups demonstrated better memory consolidation across Sleep than Wake, although participants with ASD had poorer overall memory consolidation than controls. There was no interaction between group and condition. The change in performance across sleep, independent of medication and age, showed no significant relationships with any specific sleep parameters other than total sleep time and showed a trend toward less forgetting in the control group. Conclusion: This study shows that despite their more disturbed sleep quality, children with autism spectrum disorder (ASD) still demonstrate more stable memory consolidation across sleep than in wake conditions. The findings support the importance of sleep for stabilizing memory in children with and without neurodevelopmental disabilities. Our results suggest that improving sleep quality in children with ASD could have direct benefits to improving their overall cognitive functioning. C1 [Maski, Kiran] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Holbrook, Hannah] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Manoach, Dara] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Hanson, Ellen] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Kapur, Kush] Boston Childrens Hosp, Ctr Hlth Stat, Boston, MA USA. [Stickgold, Robert] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Stickgold, Robert] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Maski, K (reprint author), Dept Neurol, 333 Longwood Ave, Boston, MA 02115 USA. EM kiran.maski@childrens.harvard.edu FU Autism Speaks, Inc.; American Brain Foundation FX Support for this study was provided by Autism Speaks, Inc., American Brain Foundation. The authors have indicated no financial conflicts of interest. NR 46 TC 2 Z9 2 U1 5 U2 13 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD DEC 1 PY 2015 VL 38 IS 12 BP 1955 EP 1963 DI 10.5665/sleep.5248 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX3RH UT WOS:000365616300019 PM 26194566 ER PT J AU Tsai, AC Venkataramani, AS AF Tsai, Alexander C. Venkataramani, Atheendar S. TI Communal bereavement and resilience in the aftermath of a terrorist event: Evidence from a natural experiment SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE September 11 terrorist attacks; Terrorism; Stress disorders; Post-traumatic; Disasters ID POSTTRAUMATIC-STRESS-DISORDER; BEHAVIORAL RISK-FACTORS; NEW-YORK-CITY; MAJOR DEPRESSION; MENTAL-HEALTH; SEPTEMBER 11; MILITARY SERVICE; LIFE EVENTS; PSYCHOLOGICAL DISTRESS; GENERAL-POPULATION AB Rationale: Sociological analyses of the psychological distress experienced by persons indirectly exposed to traumatic stressors have been conceptualized as a form of communal bereavement, defined by Catalano and Hartig (2001) as the experience of distress among persons not attached to the deceased. Their theory predicts communal bereavement responses particularly in the setting of loss of essential state, religious, or economic institutions. Objective: To estimate the extent to which the September 11, 2001 attacks on the U.S. World Trade Center had a causal effect on psychological distress nationwide. Methods: We used a difference-in-differences framework applied to repeated cross-sectional data from more than 300,000 participants in the 2000 and 2001 Behavioral Risk Factor Surveillance System surveys. Psychological distress was measured using three questions eliciting days of poor mental health-related quality of life. The September 11 attacks served as our exposure of interest. Results: The September 11 attacks had a statistically significant, adverse, causal effect on psychological distress nationally. Both the magnitude and statistical significance of the estimated effects were larger in the New York City region compared to the rest of the country. Our estimates were robust to probes of the parallel trends assumption and potential sources of selection bias, as well as to falsification tests. However, these effects had largely resolved within four weeks. Conclusions: Contrary to findings from the medical and public health literature, we conclude that the September 11 attacks did not have lasting effects on communal bereavement. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Tsai, Alexander C.; Venkataramani, Atheendar S.] Massachusetts Gen Hosp, MGH Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.; Venkataramani, Atheendar S.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, MGH Global Hlth, 125 Nashua St,Suite 722, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health [K23MH096620]; Robert Wood Johnson Health and Society Scholars Program FX No specific funding was received for this study. ACT acknowledges salary support from U.S. National Institutes of Health K23MH096620 and the Robert Wood Johnson Health and Society Scholars Program. No funders had any role in the collection, analysis, or interpretation of data; in the writing of the article; or in the decision to submit it for publication. NR 79 TC 0 Z9 0 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2015 VL 146 SI SI BP 155 EP 163 DI 10.1016/j.socscimed.2015.10.050 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CX0EQ UT WOS:000365370100017 PM 26517292 ER PT J AU Gupta, MK Ajay, AK AF Gupta, Manoj K. Ajay, Amrendra Kumar TI Fat on sale: role of adipose-derived stem cells as anti-fibrosis agent in regenerative medicine SO STEM CELL RESEARCH & THERAPY LA English DT Editorial Material ID RABBIT EAR MODEL; THERAPIES; TISSUE AB The potential use of stem cells for cell-based tissue repair and regeneration offers alternative therapeutic strategies for various diseases. Adipose-derived stem cells (ADSCs) have emerged as a promising source of stem cells suitable for transplantation in regenerative medicine and wound repair. A recent publication in Stem Cell Research & Therapy by Zhang and colleagues reports a new finding about the anti-fibrosis role of ADSCs and conditioned media derived from them on hypertrophic scar formation in vivo. C1 [Gupta, Manoj K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Ajay, Amrendra Kumar] Brigham & Womens Hosp, Dept Med, Renal Div, Boston, MA 02115 USA. RP Gupta, MK (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. EM manoj.gupta@joslin.harvard.edu NR 12 TC 0 Z9 0 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD DEC 1 PY 2015 VL 6 AR 233 DI 10.1186/s13287-015-0246-3 PG 2 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CY1KP UT WOS:000366165400001 PM 26620570 ER PT J AU Rakian, R Block, TJ Johnson, SM Marinkovic, M Wu, JJ Dai, QX Dean, DD Chen, XD AF Rakian, Rubie Block, Travis J. Johnson, Shannan M. Marinkovic, Milos Wu, Junjie Dai, Qiuxia Dean, David D. Chen, Xiao-Dong TI Native extracellular matrix preserves mesenchymal stem cell "stemness" and differentiation potential under serum-free culture conditions SO STEM CELL RESEARCH & THERAPY LA English DT Article DE Mesenchymal stem cells; Extracellular matrix; Serum-free media; Stem cell expansion ID MARROW STROMAL CELLS; BONE-MARROW; OSTEOBLAST DIFFERENTIATION; PROGENITOR CELLS; EXPANSION; TRANSPLANTATION; PROLIFERATION; PROTEOGLYCANS; STABILITY; MIGRATION AB Introduction: Bone marrow-derived mesenchymal stem cells (BM-MSCs) for clinical use should not be grown in media containing fetal bovine serum (FBS), because of serum-related concerns over biosafety and batch-to-batch variability. Previously, we described the preparation and use of a cell-free native extracellular matrix (ECM) made by bone marrow cells (BM-ECM) which preserves stem cell properties and enhances proliferation. Here, we compare colony-forming ability and differentiation of MSCs cultured on BM-ECM with a commercially available matrix (CELLstart (TM)) and tissue culture plastic (TCP) under serum-free conditions. Methods: Primary MSCs from freshly isolated bone marrow-derived mononuclear cells or passaged MSCs (P1) were grown in serum-containing (SCM) or serum-free (SFM) media on BM-ECM, CELLstart (TM), or TCP substrates. Proliferation, cell composition (phenotype), colony-forming unit replication, and bone morphogenetic protein-2 (BMP-2) responsiveness were compared among cells maintained on the three substrates. Results: Proliferation of primary BM-MSCs was significantly higher in SCM than SFM, irrespectively of culture substrate, suggesting that the expansion of these cells requires SCM. In contrast, passaged cells cultured on BM-ECM or CELLstart (TM) in SFM proliferated to nearly the same extent as cells in SCM. However, morphologically, those on BM-ECM were smaller and more aligned, slender, and long. Cells grown for 7 days on BM-ECM in SFM were 20-40 % more positive for MSC surface markers than cells cultured on CELLstart (TM). Cells cultured on TCP contained the smallest number of cells positive for MSC markers. MSC colony-forming ability in SFM, as measured by CFU-fibroblasts, was increased 10-, 9-, and 2-fold when P1 cells were cultured on BM-ECM, CELLstart (TM), and TCP, respectively. Significantly, CFU-adipocyte and -osteoblast replication of cells grown on BM-ECM was dramatically increased over those on CELLstart (TM) (2X) and TCP (4-7X). BM-MSCs, cultured in SFM and treated with BMP-2, retained their differentiation capacity better on BM-ECM than on either of the other two substrates. Conclusions: Our findings indicate that BM-ECM provides a unique microenvironment that supports the colony-forming ability of MSCs in SFM and preserves their stem cell properties. The establishment of a robust culture system, combining native tissue-specific ECM and SFM, provides an avenue for preparing significant numbers of potent MSCs for cell-based therapies in patients. C1 [Rakian, Rubie; Block, Travis J.; Johnson, Shannan M.; Marinkovic, Milos; Dai, Qiuxia; Dean, David D.; Chen, Xiao-Dong] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Johnson, Shannan M.] Joint Base San Antonio, Periodont Grad Program, Lackland AFB, TX 78236 USA. [Wu, Junjie] Fourth Mil Med Univ, Sch Stomatol, Dept Orthodont, Xian 710032, Shaanxi Provinc, Peoples R China. [Chen, Xiao-Dong] South Texas Vet Hlth Care Syst, Res Serv, Audie Murphy VA Med Ctr, San Antonio, TX 78229 USA. RP Chen, XD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chenx4@uthscsa.edu OI Dean, David/0000-0002-4512-9065 FU VA Merit Review [1I01BX002145-01]; Baptist Health Foundation FX This research was supported by VA Merit Review (1I01BX002145-01) and Baptist Health Foundation grants to X-DC. NR 36 TC 4 Z9 5 U1 2 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-6512 J9 STEM CELL RES THER JI Stem Cell Res. Ther. PD DEC 1 PY 2015 VL 6 AR 235 DI 10.1186/s13287-015-0235-6 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CY1KH UT WOS:000366164600001 PM 26620283 ER PT J AU Du, R Zhou, J Lorenzano, S Liu, WM Charoenvimolphan, N Qian, BG Xu, J Wang, J Zhang, XM Wang, X Berndt, A Devan, WJ Valant, VJ Wang, JY Furie, KL Rosand, J Rost, N Friedlander, RM Paigen, B Weiss, ST AF Du, Rose Zhou, Jing Lorenzano, Svetlana Liu, Wenming Charoenvimolphan, Nareerat Qian, Baogang Xu, Jun Wang, Jian Zhang, Xinmu Wang, Xin Berndt, Annerose Devan, William J. Valant, Valerie J. Wang, Jinyi Furie, Karen L. Rosand, Jonathan Rost, Natalia Friedlander, Robert M. Paigen, Beverly Weiss, Scott T. TI Integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury SO STROKE LA English DT Article DE brain ischemia; cerebral infarction; genetics; models; animal; stroke ID TRANSIENT FOREBRAIN ISCHEMIA; CEREBRAL-ISCHEMIA; ENDOTHELIAL-CELLS; COLLATERAL CIRCULATION; STROKE RESEARCH; ASSOCIATION; EXPRESSION; DEATH; MICE; ANGIOGENESIS AB Background and Purpose-The extent of ischemic injury in response to cerebral ischemia is known to be affected by native vasculature. However, the nonvascular and dynamic vascular responses and their genetic basis are not well understood. Methods-We performed a genome-wide association study in 235 mice from 33 inbred strains using the middle cerebral artery occlusion model. Population structure and genetic relatedness were accounted for using the efficient mixed-model association method. Human orthologs to the genes associated with the significant and suggestive single-nucleotide polymorphisms from the mouse strain survey were examined in patients with M1 occlusions admitted with signs and symptoms of acute ischemic stroke. Results-We identified 4 genome-wide significant and suggestive single-nucleotide polymorphisms to be associated with infarct volume in mice (rs3694965, P=2.17x10(-7); rs31924033, P=5.61x10(-6); rs32249495, P=2.08x10(-7); and rs3677406, P=9.56x10(-6)). rs32249495, which corresponds to angiopoietin-1 (ANGPT1), was also significant in the recessive model in humans, whereas rs1944577, which corresponds to ZBTB7C, was nominally significant in both the additive and dominant genetic models in humans. ZBTB7C was shown to be upregulated in endothelial cells using both in vitro and in vivo models of ischemia. Conclusions-Genetic variations of ANGPT1 and ZBTB7C are associated with increased infarct size in both mice and humans. ZBTB7C may modulate the ischemic response via neuronal apoptosis and dynamic collateralization and, in addition to ANGPT1, may serve as potential novel targets for treatments of cerebral ischemia. C1 [Du, Rose; Zhou, Jing; Liu, Wenming; Charoenvimolphan, Nareerat; Qian, Baogang; Xu, Jun; Wang, Jian; Zhang, Xinmu; Wang, Xin] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Du, Rose; Weiss, Scott T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Lorenzano, Svetlana; Devan, William J.; Valant, Valerie J.; Rosand, Jonathan; Rost, Natalia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lorenzano, Svetlana] Univ Roma La Sapienza, Dept Neurol & Psychiat, I-00185 Rome, Italy. [Liu, Wenming; Wang, Jian] Northwest Agr & Forestry Univ, Dept Biol Chem, Yangling, Shaanxi, Peoples R China. [Xu, Jun] China Japan Friendship Hosp, Dept Neurosurg, Beijing, Peoples R China. [Berndt, Annerose; Paigen, Beverly] Jackson Lab, Bar Harbor, ME 04609 USA. [Berndt, Annerose] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Dept Med, Pittsburgh, PA 15260 USA. [Friedlander, Robert M.] Univ Pittsburgh, Sch Med, Dept Neurosurg, Pittsburgh, PA 15260 USA. [Devan, William J.] MD Sch Med, Quinnipiac Univ Frank H Netter, Hamden, CT USA. [Valant, Valerie J.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Furie, Karen L.] Brown Univ, Dept Neurol, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Du, R (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM rdu@partners.org RI Friedlander, Robert/A-2845-2016; OI Friedlander, Robert/0000-0003-4423-9219; Du, Rose/0000-0003-2641-6496 FU National Institutes of Health [K08NS067172]; Anspach Research Award FX This work was supported by the National Institutes of Health grant K08NS067172 and by the Anspach Research Award (Dr Du). NR 50 TC 2 Z9 2 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2015 VL 46 IS 12 BP 3514 EP 3522 DI 10.1161/STROKEAHA.115.010767 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CX2NS UT WOS:000365534400024 PM 26542693 ER PT J AU Sheth, KN Martini, SR Moomaw, CJ Koch, S Elkind, MS Sung, G Kittner, SJ Frankel, M Rosand, J Langefeld, CD Comeau, ME Waddy, SP Osborne, J Woo, D AF Sheth, Kevin N. Martini, Sharyl R. Moomaw, Charles J. Koch, Sebastian Elkind, Mitchell S. V. Sung, Gene Kittner, Steven J. Frankel, Michael Rosand, Jonathan Langefeld, Carl D. Comeau, Mary E. Waddy, Salina P. Osborne, Jennifer Woo, Daniel CA ERICH Investigators TI Prophylactic Antiepileptic Drug Use and Outcome in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study SO STROKE LA English DT Article DE cerebral hemorrhage; critical care; hematoma; seizures; stroke ID STROKE-ASSOCIATION; GUIDELINES; MANAGEMENT; ICH AB Background and Purpose-The role of antiepileptic drug (AED) prophylaxis after intracerebral hemorrhage (ICH) remains unclear. This analysis describes prevalence of prophylactic AED use, as directed by treating clinicians, in a prospective ICH cohort and tests the hypothesis that it is associated with poor outcome. Methods-Analysis included 744 patients with ICH enrolled in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study before November 2012. Baseline clinical characteristics and AED use were recorded in standardized fashion. ICH location and volume were recorded from baseline neuroimaging. We analyzed differences in patient characteristics by AED prophylaxis, and we used logistic regression to test whether AED prophylaxis was associated with poor outcome. The primary outcome was 3-month modified Rankin Scale score, with 4 to 6 considered poor outcome. Results-AEDs were used for prophylaxis in 289 (39%) of the 744 subjects; of these, levetiracetam was used in 89%. Patients with lobar ICH, craniotomy, or larger hematomas were more likely to receive prophlyaxis. Although prophylactic AED use was associated with poor outcome in an unadjusted model (odds ratio, 1.40; 95% confidence interval, 1.04-1.88; P=0.03), this association was no longer significant after adjusting for clinical and demographic characteristics (odds ratio, 1.11; 95% confidence interval, 0.74-1.65; P=0.62). Conclusions-We found no evidence that AED use (predominantly levetiracetam) is independently associated with poor outcome. A prospective study is required to assess for a more modest effect of AED use on outcome after ICH. C1 [Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Martini, Sharyl R.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Moomaw, Charles J.; Osborne, Jennifer; Woo, Daniel] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH 45221 USA. [Koch, Sebastian] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. [Elkind, Mitchell S. V.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Sung, Gene] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Frankel, Michael] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Langefeld, Carl D.; Comeau, Mary E.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Langefeld, Carl D.; Comeau, Mary E.] Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA. [Waddy, Salina P.] NINDS, Off Clin Res, Bethesda, MD 20892 USA. RP Sheth, KN (reprint author), 15 York St,LCI 1003, New Haven, CT 06510 USA. EM kevin.sheth@yale.edu FU National Institute of Neurological Disorders and Stroke [NINDS: U-01-NS069763] FX This study was supported by a grant from the National Institute of Neurological Disorders and Stroke (NINDS: U-01-NS069763). NR 13 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2015 VL 46 IS 12 BP 3532 EP 3535 DI 10.1161/STROKEAHA.115.010875 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CX2NS UT WOS:000365534400026 PM 26470777 ER PT J AU Mijalski, C Lovett, A Mahajan, R Sundararajan, S Silverman, S Feske, S AF Mijalski, Christina Lovett, Alexandra Mahajan, Rahul Sundararajan, Sophia Silverman, Scott Feske, Steven TI Cerebral Fat Embolism A Case of Rapid-Onset Coma SO STROKE LA English DT Editorial Material DE angiography; cerebrovascular disease; computed tomography; embolism; embolism, fat; stroke C1 [Mijalski, Christina; Lovett, Alexandra; Mahajan, Rahul] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mijalski, Christina; Lovett, Alexandra; Mahajan, Rahul; Feske, Steven] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Hosp Case Med Ctr, Dept Neurol, Cleveland, OH USA. RP Mijalski, C (reprint author), Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St,Suite 835, Boston, MA 02114 USA. EM cmijalski@partners.org NR 9 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD DEC PY 2015 VL 46 IS 12 BP e251 EP e253 DI 10.1161/STROKEAHA.115.011440 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA CX2NX UT WOS:000365535000001 PM 26493673 ER PT J AU Izquierdo, RE Wang, DL Huang, DN Palmas, W Weinstock, RS AF Izquierdo, Robert E. Wang, Dongliang Huang, Danning Palmas, Walter Weinstock, Ruth S. TI Case Management with a Diabetes Team Using Home Telemedicine: Acceptance of Treatment Recommendations by Primary Care Providers in IDEATel SO TELEMEDICINE AND E-HEALTH LA English DT Article DE IDEATel study; diabetes case management; telemedicine; diabetes mellitus ID COLUMBIA-UNIVERSITY INFORMATICS; ETHNICALLY DIVERSE; PROJECT; EDUCATION; OLDER; IMPLEMENTATION; PARTICIPANTS; MELLITUS; ADULTS AB Background:The Informatics for Diabetes Education and Telemedicine (IDEATel) project demonstrated that a telemedicine intervention can improve glycemic, lipid, and blood pressure control. The focus of the current study was to evaluate factors associated with primary care providers' (PCPs') decision on whether to follow recommendations from the remote diabetes team in Upstate New York.Materials and Methods:In the intervention group, diabetes educators videoconferenced with patients monthly to download and review glucose and blood pressure readings, diabetes-related issues, and laboratory data. These were reviewed with an endocrinologist, and recommendations to change therapy were sent to the PCPs. At annual visits, participants completed the Diabetes Symptom Checklist-Type 2 symptom severity score and Impact of Telemedicine surveys.Results:Factors that increase the acceptance rate of IDEATel recommendations included longer time in the study (p=0.0052), changing medication dose as opposed to starting or stopping a medication (p<0.0001), adjusting glucose-lowering agents compared with antihypertensive or antilipid medications (p<0.0001), higher total Diabetes Symptom Checklist-Type 2 symptom severity score (p=0.045), greater number of glucose readings submitted by participants (p=0.014), and high score on surveys measuring impact of telemedicine on patient's knowledge, adherence, and satisfaction (p=0.0023).Conclusions:Recommendations for change in glycemic control medications, delivered remotely by a diabetes team to PCPs, were better accepted over time. Results support the use of a team-based telemedicine program to help PCPs improve diabetes care. C1 [Izquierdo, Robert E.; Weinstock, Ruth S.] SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY 13214 USA. [Izquierdo, Robert E.; Weinstock, Ruth S.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13214 USA. [Wang, Dongliang; Huang, Danning] SUNY Upstate Med Univ, Ctr Res & Evaluat, Syracuse, NY 13214 USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. RP Izquierdo, RE (reprint author), SUNY Upstate Med Univ, Joslin Diabet Ctr, 3229 East Genesee St, Syracuse, NY 13214 USA. EM izquierr@upstate.edu NR 13 TC 1 Z9 1 U1 2 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD DEC 1 PY 2015 VL 21 IS 12 BP 980 EP 986 DI 10.1089/tmj.2014.0236 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CX4MZ UT WOS:000365676300003 PM 26114996 ER PT J AU Kauth, MR Shipherd, JC Lindsay, JA Kirsh, S Knapp, H Matza, L AF Kauth, Michael R. Shipherd, Jillian C. Lindsay, Jan A. Kirsh, Susan Knapp, Herschel Matza, Lexi TI Teleconsultation and Training of VHA Providers on Transgender Care: Implementation of a Multisite Hub System SO TELEMEDICINE AND E-HEALTH LA English DT Article DE education; military medicine; telehealth; telemedicine; transgender medicine; telepsychiatry ID SPECIALTY CARE; ACCESS AB Background:The Veterans Health Administration (VHA) is piloting a national program providing teleconsultation and training to clinicians to increase knowledge and comfort with treating transgender veterans and to expand clinical capacity. This program is based on Project ECHO and uses specialist expertise to train and educate front-line clinicians. Over time, the front-line clinicians increase knowledge and skills, enabling them to provide care locally and obviate need for patient travel. This program is innovative in its national scope, interdisciplinary team model, and multihub structure. This article describes development of the program and initial results for the first cohort of learners.Materials and Methods:Five interdisciplinary clinical teams participated in the 14-session, 7-month program. Most teams had some experience treating transgender veterans prior to participation.Results:The teams completed at least 12 of 14 sessions. Thirteen of 33 participants completed an evaluation. In general, respondents found the teleconsultation program very helpful and credited the experience with improving their team functioning. Furthermore, respondents reported a significant increase in confidence to treat transgender veterans by the end of the program (59% versus 83%). We explored whether it is possible to recruit VHA clinical teams to participate in lengthy training on a low prevalence but complex condition.Conclusions:Early results support the feasibility and effectiveness of this national VHA teleconsultation and training program for transgender care. Lessons learned from the first group of learners have been applied to two concurrent groups with positive results. C1 [Kauth, Michael R.; Shipherd, Jillian C.; Matza, Lexi] VHA Patient Care Serv, Lesbian Gay Bisexual & Transgender Program, Washington, DC USA. [Kirsh, Susan] VHA Patient Care Serv, Off Specialty Care, Washington, DC USA. [Kauth, Michael R.; Lindsay, Jan A.] VA South Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Kauth, Michael R.; Lindsay, Jan A.] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Houston, TX 77030 USA. [Kauth, Michael R.; Lindsay, Jan A.] Baylor Coll Med, Houston, TX 77030 USA. [Shipherd, Jillian C.; Matza, Lexi] VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kirsh, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Knapp, Herschel] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Kauth, MR (reprint author), Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Innovat Qual Effectiveness &, South Cent MIRECC, 2002 Holcombe Blvd,ATTN 152 VA, Houston, TX 77030 USA. EM Michael.Kauth@va.gov FU Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIn13-413] FX This material is the result of work supported with resources and the use of facilities at the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIn13-413). We would also like to thank the specialty teams for their unwavering support of transgender veterans. NR 10 TC 7 Z9 7 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD DEC 1 PY 2015 VL 21 IS 12 BP 1012 EP 1018 DI 10.1089/tmj.2015.0010 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CX4MZ UT WOS:000365676300008 PM 26171641 ER PT J AU Shore, J Vo, A Yellowlees, P Waugh, M Schneck, C Nagamoto, H Thomas, M AF Shore, Jay Vo, Alexander Yellowlees, Peter Waugh, Maryann Schneck, Christopher Nagamoto, Herbert Thomas, Marshall TI Antipsychotic-Induced Movement Disorder: Screening via Telemental Health SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telehealth; telemedicine; drug-induced movement disorder antipsychotics; telemental health; psychiatry; movement disorders ID ASYNCHRONOUS TELEPSYCHIATRY; CARE AB Background:The purpose of this brief report is to make clinical and research recommendations to advance current knowledge and practices related to the assessment of antipsychotic drug-induced movement disorders (DIMDs) via live interactive videoconferencing.Materials and Methods:The authors provide an overview of the frequent neurological side effects of antipsychotic drugs and review relevant telemedicine research. DIMD prevention is critical, but these disorders remain underdetected and under-reported. Although there are not yet formal recommendations for specific screening tools or screening frequency, baseline and annual assessments are generally agreed-upon minimums. As DIMD awareness increases and more specific guidelines are developed to steer assessments, telemental health may aid practitioners in efficiently and regularly monitoring onset and severity. Research shows that videoconferencing can be used for effective psychiatric treatments and assessment, with at least one study validating the use of videoconference assessment for a subset of movement disorders.Results and Conclusions:Clinical recommendations include developing practice-level protocols and procedures that include regular DIMD assessment (either in-person or via telemedicine) for the full spectrum of possible movement disorders for all patients taking antipsychotic medications. Research and evaluation recommendations include replicating and expanding upon the existing study using videoconferencing to assess movement disorder symptoms, using asynchronous telemental health assessments of DIMDs, and pilot-testing facial and movement recognition software to allow for clinical comparison of patients' movement patterns over time. C1 [Shore, Jay; Schneck, Christopher; Nagamoto, Herbert; Thomas, Marshall] Univ Colorado, Aurora, CO 80045 USA. [Shore, Jay; Vo, Alexander; Waugh, Maryann; Thomas, Marshall] Colorado Access, Denver, CO USA. [Yellowlees, Peter] Univ Calif Davis, Dept Psychiat, Sacramento, CA 95817 USA. [Nagamoto, Herbert] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Shore, J (reprint author), Univ Colorado, Anschutz Med Campus,13055 E 17th Ave,F800, Aurora, CO 80045 USA. EM Jay.Shore@ucdenver.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD DEC 1 PY 2015 VL 21 IS 12 BP 1027 EP 1029 DI 10.1089/tmj.2014.0242 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CX4MZ UT WOS:000365676300010 PM 26125084 ER PT J AU Folkesson, M Li, CJ Frebelius, S Swedenborg, J Wagsater, D Williams, KJ Eriksson, P Roy, J Liu, ML AF Folkesson, Maggie Li, Chunjun Frebelius, Siw Swedenborg, Jesper Wagsater, Dick Williams, Kevin Jon Eriksson, Per Roy, Joy Liu, Ming-Lin TI Proteolytically active ADAM10 and ADAM17 carried on membrane microvesicles in human abdominal aortic aneurysms SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Abdominal aortic aneurysm; ADAM10; ADAM17; intraluminal thrombus; A disintegrin and matrix metalloproteinase; membrane-bound protease; microparticles; microvesicles ID HUMAN ATHEROSCLEROTIC PLAQUES; TUMOR-NECROSIS-FACTOR; INTRALUMINAL THROMBUS; TOBACCO-SMOKE; TISSUE FACTOR; FACTOR-ALPHA; EXPRESSION; CELLS; MICROPARTICLES; DISINTEGRIN AB The intraluminal thrombus (ILT) of human abdominal aortic aneurysm (AAA) has been suggested to damage the underlying aortic wall, but previous work found scant activity of soluble proteases in the abluminal layer of the ILT, adjacent to the aneurysm. We hypothesised that transmembrane proteases carried by membrane microvesicles (MV) from dying cells remain active in the abluminal ILT. ILTs and AAA segments collected from 21 patients during surgical repair were assayed for two major transmembrane proteases, ADAM10 (a disintegrin and metalloprotease-10) and ADAM17. We also exposed cultured cells to tobacco smoke and assessed ADAM10 and ADAM17 expression and release on MVs. Immunohistochemistry showed abundant ADAM10 and ADAM17 protein in the ILT and underlying aneurysmal aorta. Domain-specific antibodies indicated both transmembrane and shed ADAM17. Importantly, ADAM10 and ADAM 17 in the abluminal ILT were enzymatically active. Electron microscopy of abluminal ILT and aortic wall showed MVs with ADAM10 and ADAM17. By flow cytometry, ADAM-positive microvesicles from abluminal ILT carried the neutrophil marker CD66, but not the platelet marker CD61. Cultured HL60 neutrophils exposed to tobacco smoke extract showed increased ADAM10 and ADAM17 content, cleavage of these molecules into active forms, and release of MVs carrying mature ADAM10 and detectable ADAM17. In conclusion, our results implicate persistent, enzymatically active ADAMs on MVs in the abluminal ILT, adjacent to the aneurysmal wall. The production of ADAM10- and ADAM17-positive MVs from smoke-exposed neutrophils provides a novel molecular mechanism for the vastly accelerated risk of AAA in smokers. C1 [Folkesson, Maggie; Wagsater, Dick] Linkoping Univ, Dept Med & Hlth, Div Drug Res, Linkoping, Sweden. [Li, Chunjun] Tianjin Med Univ, Metab Dis Hosp, Tianjin, Peoples R China. [Li, Chunjun] Tianjin Med Univ, Tianjin Inst Endocrinol, Tianjin, Peoples R China. [Frebelius, Siw; Swedenborg, Jesper; Roy, Joy] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Williams, Kevin Jon; Liu, Ming-Lin] Temple Univ, Sch Med, Dept Med, Endocrinol Sect, Philadelphia, PA 19122 USA. [Williams, Kevin Jon] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden. [Eriksson, Per] Karolinska Inst, Dept Med, Stockholm, Sweden. [Liu, Ming-Lin] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Liu, Ming-Lin] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Folkesson, M (reprint author), Linkoping Univ, Dept Med & Hlth, Div Drug Res, Linkoping, Sweden. EM maggie.m.folkesson@gmail.com; joy.roy@ki.se; mlliu02@gmail.com OI , Dick/0000-0002-3655-2419 NR 38 TC 3 Z9 4 U1 0 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD DEC PY 2015 VL 114 IS 6 BP 1165 EP 1174 DI 10.1160/TH14-10-0899 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CX5UY UT WOS:000365769200010 PM 26422658 ER PT J AU Hanske, J Sanchez, A Schmid, M Meyer, CP Abdollah, F Roghmann, F Feldman, AS Kibel, AS Sammon, JD Noldus, J Trinh, QD Eswara, JR AF Hanske, Julian Sanchez, Alejandro Schmid, Marianne Meyer, Christian P. Abdollah, Firas Roghmann, Florian Feldman, Adam S. Kibel, Adam S. Sammon, Jesse D. Noldus, Joachim Quoc-Dien Trinh Eswara, Jairam R. TI Comparison of 30-day perioperative outcomes in adults undergoing open versus minimally invasive pyeloplasty for ureteropelvic junction obstruction: analysis of 593 patients in a prospective national database SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Ureteropelvic junction obstruction; Pyeloplasty; Adult; Minimally invasive; NSQIP ID QUALITY IMPROVEMENT PROGRAM; LAPAROSCOPIC DISMEMBERED PYELOPLASTY; PEDIATRIC PYELOPLASTY; OPERATIVE OUTCOMES; AMERICAN-COLLEGE; CLINICAL PATHWAY; SURGERY; CHILDREN; TRENDS; LENGTH AB The surgical correction of ureteropelvic junction obstruction (UPJO) is indicated to prevent progression to chronic renal insufficiency. Minimally invasive surgery (MIS) has become increasingly popular as an approach to UPJO correction. We compared the perioperative outcomes between minimally invasive (MIP) and open pyeloplasty (OP) in the adult population. The current study was performed using the American College of Surgeons National Surgical Quality Improvement Program. Patients were identified using Current Procedural Terminology codes for pyeloplasty between 2005 and 2012, and were stratified according to either MIS or open approach. Patients with a diagnosis of malignant neoplasm of the kidney were excluded. Following exclusions, 593 patients remained for analysis. Primary outcomes of interest were overall perioperative complications, need for transfusions, re-intervention rate, prolonged operation time (pOT), prolonged length of stay (pLOS), readmission and mortality within 30 days of surgery. Multivariable logistic regression analyses were performed to examine the association between preoperative outcomes and surgical approach. In this study, 423 (71.3 %) patients underwent MIP and 170 (28.7 %) underwent OP. Patients who underwent MIP had a decreased risk of wound [Odds ratio (OR) 0.06, p < 0.009] and overall complications (OR 0.21, p < 0.001), transfusions (OR 0.04, p = 0.004) and pLOS [pLOS (OR 0.08, p < 0.001)]. Conversely, MIP was associated with an increased likelihood of pOT (OR 2.26, p = 0.002). Adults with UPJO undergoing MIP have a lower risk of overall complications, transfusions and pLOS compared to OP. Further studies are needed to determine whether these benefits offset the increase in expenditures, related to longer operative time and costs of disposables. C1 [Hanske, Julian; Schmid, Marianne; Meyer, Christian P.; Kibel, Adam S.; Quoc-Dien Trinh; Eswara, Jairam R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. [Hanske, Julian; Schmid, Marianne; Meyer, Christian P.; Kibel, Adam S.; Quoc-Dien Trinh; Eswara, Jairam R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hanske, Julian; Roghmann, Florian; Noldus, Joachim] Ruhr Univ Bochum, Dept Urol, Marien Hosp, D-44627 Herne, Germany. [Sanchez, Alejandro; Feldman, Adam S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Schmid, Marianne; Meyer, Christian P.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, D-20246 Hamburg, Germany. [Abdollah, Firas; Sammon, Jesse D.] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. RP Hanske, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol Surg, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM j.hanske@gmx.de; asanchez6@partners.org; dr.marianne.schmid@gmail.com; christian.p.meyer@gmail.com; firas.abdollah@gmail.com; f.roghmann@gmail.com; afeldman@partners.org; akibel@partners.org; jsammon79@gmail.com; joachim.noldus@marienhospital-herne.de; trinh.qd@gmail.com; jeswara@partners.org NR 33 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD DEC PY 2015 VL 33 IS 12 BP 2107 EP 2113 DI 10.1007/s00345-015-1586-4 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CX1ZK UT WOS:000365494300027 PM 25966662 ER PT J AU Bieniek, KF Ross, OA Cormier, KA Walton, RL Soto-Ortolaza, A Johnston, AE DeSaro, P Boylan, KB Graff-Radford, NR Wszolek, ZK Rademakers, R Boeve, BF McKee, AC Dickson, DW AF Bieniek, Kevin F. Ross, Owen A. Cormier, Kerry A. Walton, Ronald L. Soto-Ortolaza, Alexandra Johnston, Amelia E. DeSaro, Pamela Boylan, Kevin B. Graff-Radford, Neill R. Wszolek, Zbigniew K. Rademakers, Rosa Boeve, Bradley F. McKee, Ann C. Dickson, Dennis W. TI Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank SO ACTA NEUROPATHOLOGICA LA English DT Article DE Chronic traumatic encephalopathy; Traumatic brain injury; Sports; Microtubule-associated protein tau; Brain bank ID PROGRESSIVE SUPRANUCLEAR PALSY; REPETITIVE HEAD-INJURY; DEMENTIA-PUGILISTICA; TDP-43 PROTEINOPATHY; E EPSILON-4; DISEASE; DEGENERATION; EXPRESSION; DEPOSITION; HAPLOTYPE AB Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed. C1 [Bieniek, Kevin F.; Ross, Owen A.; Walton, Ronald L.; Soto-Ortolaza, Alexandra; Rademakers, Rosa; Dickson, Dennis W.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. [Bieniek, Kevin F.] Mayo Clin, Mayo Grad Sch, Rochester, MN 55905 USA. [Cormier, Kerry A.; McKee, Ann C.] VA Boston HealthCare Syst, Boston, MA 02130 USA. [Johnston, Amelia E.; DeSaro, Pamela; Boylan, Kevin B.; Graff-Radford, Neill R.; Wszolek, Zbigniew K.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Boeve, Bradley F.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [McKee, Ann C.] Boston Univ, Dept Neurol & Pathol, Alzheimers Dis Ctr, Boston, MA 02118 USA. [McKee, Ann C.] Boston Univ, CTE Program, Sch Med, Boston, MA 02118 USA. RP Dickson, DW (reprint author), Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM dickson.dennis@mayo.edu OI Bieniek, Kevin/0000-0003-4922-864X FU National Institute of Health (NIH) [P50 NS072187, R01 NS076471, R01 NS078086, UO1 NS086659-01, P30 AG13846, 0572063345-5] FX We would like to thank the patients and their families. Without their generous donation, these studies would not be possible. We would also like to thank Monica Castanedes-Casey, Virginia Philips, and Linda Rousseau for their neurohistologic assistance, Michael DeTure for brain banking, and Deann Gibson for coordination of brain donations. This study was supported by the National Institute of Health (NIH) P50 NS072187 (OAR, ZKW, RR, DWD), R01 NS076471 (RR), R01 NS078086 (OAR), UO1 NS086659-01 (ACM), P30 AG13846 (ACM; supplement 0572063345-5). Other support included an unrestricted gift from Carl Edward Bolch Jr. and Susan Bass Bolch (ZKW), Department of Veterans Affairs (ACM), Veterans Affairs Biorepository CSP 501 (ACM), Sports Legacy Institute (ACM), National Operating Committee on Standards for Athletic Equipment (ACM), the National Football League (ACM), the Andlinger Foundation (ACM), and the WWE (ACM). NR 37 TC 26 Z9 26 U1 9 U2 35 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD DEC PY 2015 VL 130 IS 6 BP 877 EP 889 DI 10.1007/s00401-015-1502-4 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CW9FU UT WOS:000365304900009 PM 26518018 ER PT J AU Miller, JB Yonekawa, Y Eliott, D Kim, IK Kim, LA Loewenstein, JI Sobrin, L Young, LH Mukai, S Vavvas, DG AF Miller, John B. Yonekawa, Yoshihiro Eliott, Dean Kim, Ivana K. Kim, Leo A. Loewenstein, John I. Sobrin, Lucia Young, Lucy H. Mukai, Shizuo Vavvas, Demetrios G. TI Long-term Follow-up and Outcomes in Traumatic Macular Holes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; SPONTANEOUS CLOSURE; SURGERY; VITRECTOMY AB PURPOSE: To review presenting characteristics, clinical course, and long-term visual and anatomic outcomes of patients with traumatic macular holes at a tertiary referral center. DESIGN: Retrospective case series. METHODS: Twenty-eight consecutive patients with traumatic macular holes at a single tertiary referral center were reviewed. In addition to visual acuities and treatments throughout the clinical course, specific dimensions of the macular hole, including diameters, height, configuration, shape, and the presence of a cuff of fluid, were examined using spectral-domain optical coherence tomography (OCT). RESULTS: Twenty-eight patients were identified with a mean initial visual acuity (VA) of logMAR 1.3 (20/400) and a mean follow-up of 2.2 years. Eleven holes (39.3%) closed spontaneously in median 5.7 weeks. Eleven underwent vitrectomy with a median time to intervention of 35.1 weeks. Median time to surgery for the 5 eyes with successful hole closure was 11.0 weeks vs 56.3 weeks for the 6 eyes that failed to close (P = .02). VA improved in closed holes (P < .01), whether spontaneously (P < .01) or via vitrectomy (P = .04), but VA did not improve in holes that did not close (P = .22). There was no relation between initial OCT dimensions and final hole closure status, although there was a trend, which did not reach statistical significance, toward small dimensions for those that closed spontaneously. CONCLUSIONS: A fairly high spontaneous closure rate was observed, with a trend toward smaller OCT dimensions. We found no relationship between hole closure and the OCT characteristics of the hole. Surgical intervention was less successful at hole closure when elected after 3 months. (C) 2015 by Elsevier Inc. All rights reserved. C1 [Miller, John B.; Yonekawa, Yoshihiro; Eliott, Dean; Kim, Ivana K.; Kim, Leo A.; Loewenstein, John I.; Sobrin, Lucia; Young, Lucy H.; Mukai, Shizuo; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu FU MUKAI FUND OF MEEI (BOSTON, MASSACHUSETTS) FX SHIZUO MUKAI: MUKAI FUND OF MEEI (BOSTON, MASSACHUSETTS). FINANCIAL DISCLOSURES: DEAN Eliott: consultant for Acucela (Tokyo, Japan), Alcon (Fort Worth, Texas), Alimera (Alpharetta, Georgia), Allergan (Dublin, Ireland), ArcticDx (Toronto, Canada), Avalanche (Menlo Park, California), Bausch & Lomb (Rochester, New York), Biogen (Cambridge, Massachusetts), Dutch Ophthalmic (Zuidland, Netherlands), Genentech (South San Francisco, California), Juvenile Diabetes Research Foundation (Wellesley, Massachusetts), Ocata Therapeutics (Marlborough, Massachusetts), Ophthotech (Princeton , New Jersey), Regeneron (Tarrytown, New York), Foundation for Fighting Blindness (Columbia, Maryland), and Thrombogenics (Leuven, Belgium); L. Sobrin: Santen (Osaka, Japan); Shizuo Mukai: Novartis (Basel, Switzerland). The following authors have no financial disclosures: John B. Miller, Yoshihiro Yonekawa, Ivana K. Kim, Leo A. Kim, John I. Loewenstein, Lucia Sobrin, Lucy H. Young, and Demetrios G. Vavvas. All authors attest that they meet the current ICMJE criteria for authorship. NR 14 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2015 VL 160 IS 6 BP 1255 EP 1258 DI 10.1016/j.ajo.2015.09.004 PG 4 WC Ophthalmology SC Ophthalmology GA CW8IS UT WOS:000365243400022 PM 26393438 ER PT J AU Laferrier, JZ Teodorski, E Cooper, RA AF Laferrier, Justin Z. Teodorski, Emily Cooper, Rory A. TI Investigation of the Impact of Sports, Exercise, and Recreation Participation on Psychosocial Outcomes in a Population of Veterans with Disabilities A Cross-sectional Study SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Psychosocial Well-being; Adaptive Sports; Recreation; Sports Participation; Rehabilitation; Disability; Self-esteem; Depression; Posttraumatic Growth; Quality of Life; Service Members; Veterans ID QUALITY-OF-LIFE; SPINAL-CORD-INJURY; PHYSICAL-ACTIVITY; MENTAL-HEALTH; CANCER SURVIVORS; CONTROLLED TRIAL; CEREBRAL-PALSY; DOSE-RESPONSE; DEPRESSION; AFGHANISTAN AB Objective The aim of this study was to investigate possible effects that participation in sports, exercise, and recreation may have on self-esteem and quality-of-life in service members/veterans with disabilities. Design Two hundred twenty service members/veterans with disabilities who were participants in one of three annual adaptive sporting events took part in this cross-sectional study. Variables of interest were years of sport, exercise, and recreation participation since the onset of disability as well as the type of activity they engaged in. Main outcome measures were self-esteem and quality-of-life. Results A positive relationship was found between participant quality-of-life and the number of years spent participating in sports, exercise, and recreation since the onset of their disability. A significant difference was found between pre-event and postevent self-esteem scores. A significant difference was also found in self-esteem scores between the levels of years of participation in sports, exercise, and recreation when averaged across activity type. Finally, there were significant differences found on self-esteem scores between the levels of type of activity averaged across years of participation. Conclusions Our results indicate that participation in sports, exercise, and recreation has a positive influence on self-esteem and quality-of-life in individuals with disabilities. C1 [Laferrier, Justin Z.; Teodorski, Emily] Univ Connecticut, Dept Kinesiol, Phys Therapy Program, Storrs, CT 06269 USA. [Laferrier, Justin Z.; Teodorski, Emily; Cooper, Rory A.] VA Rehabil Res & Dev Serv, Human Engn Res Labs, Pittsburgh, PA USA. [Laferrier, Justin Z.; Teodorski, Emily; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Laferrier, JZ (reprint author), Univ Connecticut, 358 Mansfield Rd,Unit 1101, Storrs, CT 06269 USA. FU CPPF grant through the Department of Veterans Affairs FX Funding was provided through a CPPF grant through the Department of Veterans Affairs. NR 47 TC 3 Z9 3 U1 6 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2015 VL 94 IS 12 BP 1026 EP 1034 DI 10.1097/PHM.0000000000000263 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CW7LR UT WOS:000365180800002 PM 25768065 ER PT J AU Luz, J Siddiqui, I Jain, NB Kohler, MJ Donovan, J Gerrard, P Borg-Stein, J AF Luz, Jennifer Siddiqui, Imran Jain, Nitin B. Kohler, Minna J. Donovan, Jayne Gerrard, Paul Borg-Stein, Joanne TI Resident-Perceived Benefit of a Diagnostic and Interventional Musculoskeletal Ultrasound Curriculum A Multifaceted Approach Using Independent Study, Peer Teaching, and Interdisciplinary Collaboration SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Resident Feedback; Curriculum Development; Internship and Residency; Physical and Rehabilitation Medicine; Questionnaires; Rheumatology; Musculoskeletal Ultrasound ID AMERICAN MEDICAL SOCIETY; INTEROBSERVER RELIABILITY; RHEUMATOLOGY PRACTICE; NEEDS-ASSESSMENT; SPORTS-MEDICINE; UNITED-STATES; EDUCATION; ULTRASONOGRAPHY; FELLOWS; RECOMMENDATIONS AB Musculoskeletal ultrasound (MSUS) training is now a required component of physiatry residency, but formal curriculum guidelines are not yet required or established. The authors' objective was to assess the educational value of a collaborative residency MSUS training program. The authors designed a structured MSUS training curriculum for residents based on the authors' experience and previous literature. Twenty-five residents participated in this MSUS curriculum designed by faculty and chief residents. Resident volunteers were trained by the faculty as table trainers who taught their peers in small groups. Hands-on MSUS training sessions were led by a Physical Medicine and Rehabilitation faculty MSUS expert. A Likert scale-formatted questionnaire assessed resident-perceived value of the curriculum. Response rate was 96% (22 of 23). Self-reported MSUS knowledge comparing precurriculum and postcurriculum implementation resulted in significant improvement (P = 0.001). Peer teaching was highly valued, with 86% of residents rating it very or extremely beneficial (mean [SD] score, 3.9 [1.1]). Self-guided learning, by supplemental scanning and reading, was rated beneficial or very beneficial by 73% of residents (3.0 [0.7]). The authors' successful pilot program may serve as a teaching model for other residency programs. C1 [Luz, Jennifer; Siddiqui, Imran; Borg-Stein, Joanne] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Jain, Nitin B.] Vanderbilt Univ, Med Ctr, Dept Phys Med & Rehabil, Nashville, TN USA. [Kohler, Minna J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Donovan, Jayne] Rutgers New Jersey Med Sch, Kessler Inst Rehabil, Dept Phys Med & Rehabil, Newark, NJ USA. [Gerrard, Paul] New England Rehabil Hosp Portland, Portland, ME USA. RP Luz, J (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 300 First Ave,2nd Floor, Charlestown, MA 02129 USA. FU NIAMS NIH HHS [K23 AR059199] NR 32 TC 2 Z9 3 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2015 VL 94 IS 12 BP 1095 EP 1103 DI 10.1097/PHM.0000000000000337 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CW7LR UT WOS:000365180800010 PM 26098924 ER PT J AU Manchikanti, L Atluri, S Hirsch, JA AF Manchikanti, Laxmaiah Atluri, Sairam Hirsch, Joshua A. TI COMPARISON OF TRIAMCINOLONE VS. BETAMETHASONE PROVIDES INACCURATE INFORMATION: RE: COMPARISON OF PAIN SCORE REDUCTION USING TRIAMCINOLONE VS. BETAMETHASONE IN TRANSFORAMINAL EPIDURAL STEROID INJECTIONS FOR LUMBOSACRAL RADICULAR PAIN. MCCORMICK Z ET AL. AM J PHYS MED REHABIL 2015 APR 16 [EPUB AHEAD OF PRINT] SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Letter ID LUMBAR DISC HERNIATION; 2-YEAR FOLLOW-UP; DOUBLE-BLIND TRIAL; LONG-TERM RELIEF; NECK C1 [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Atluri, Sairam] Tristate Spine Care Inst, Cincinnati, OH USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine Serv & Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. NR 12 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2015 VL 94 IS 12 BP E121 EP E122 DI 10.1097/PHM.0000000000000378 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CW7LS UT WOS:000365181000003 PM 26334423 ER PT J AU Brigham, LR Mansouri, M Abujudeh, HH AF Brigham, Leeann R. Mansouri, Mohammad Abujudeh, Hani H. TI Radiology Report Addenda: A Self-Report Approach to Error Identification, Quantification, and Classification SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE addenda; diagnostic error; errors; quality assurance AB OBJECTIVE. The purpose of this study was to analyze report addenda to assess the self-reported error rate in radiologic study interpretation, the types of errors that occur, and the distribution of error by image modality. MATERIALS AND METHODS. Addenda to all diagnostic radiology reports were compiled over a 1-year period (n = 5568). The overall error rate was based on addenda frequency relative to the total number of studies performed. Addenda written over the most recent 2-month interval (n = 851) were classified into five major categories of predominant error type: underreading, overreading, poor communication, insufficient history, and poor technique. Each category was further divided into multiple subtypes. RESULTS. Diagnostic studies at our hospital had an error rate of 0.8%. Errors of poor communication occurred most frequently (44%), followed by underreading (7%), insufficient history (21%), overreading (8%), and poor technique (1%). Analyzed by imaging modality, most errors occurred in PET (19.45 per 1000 studies), followed by MRI (13.86 per 1000 studies) and CT (12.45 per 1000 studies). CONCLUSION. Through the use of report addenda to calculate error, discrepancy between individual radiologists is removed in a reproducible and widely applicable way. This approach to error typology eliminates sample bias and in a departure from previous analyses of difficult cases shows that errors of communication are most frequent, representing a clear area for targeted improvement. C1 [Brigham, Leeann R.; Mansouri, Mohammad; Abujudeh, Hani H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mansouri, Mohammad; Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 220, Boston, MA 02114 USA. EM habujudeh@partners.org RI Mansouri, Mohammad/M-4774-2016 OI Mansouri, Mohammad/0000-0002-7472-1287 NR 9 TC 2 Z9 2 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2015 VL 205 IS 6 BP 1230 EP 1239 DI 10.2214/AJR.15.14891 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CW9LO UT WOS:000365320400025 PM 26587930 ER PT J AU Thompson, H Rybalka, A Moazzez, R Dewhirst, FE Wade, WG AF Thompson, Hayley Rybalka, Alexandra Moazzez, Rebecca Dewhirst, Floyd E. Wade, William G. TI In Vitro Culture of Previously Uncultured Oral Bacterial Phylotypes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PERIODONTAL HEALTH; SOIL BACTERIA; CULTIVATION; MICROBIOME; DIVERSITY; DISEASE AB Around a third of oral bacteria cannot be grown using conventional bacteriological culture media. Community profiling targeting 16S rRNA and shotgun metagenomics methods have proved valuable in revealing the complexity of the oral bacterial community. Studies investigating the role of oral bacteria in health and disease require phenotypic characterizations that are possible only with live cultures. The aim of this study was to develop novel culture media and use an in vitro biofilm model to culture previously uncultured oral bacteria. Subgingival plaque samples collected from subjects with periodontitis were cultured on complex mucin-containing agar plates supplemented with proteose peptone (PPA), beef extract (BEA), or Gelysate (GA) as well as on fastidious anaerobe agar plus 5% horse blood (FAA). In vitro biofilms inoculated with the subgingival plaque samples and proteose peptone broth (PPB) as the growth medium were established using the Calgary biofilm device. Specific PCR primers were designed and validated for the previously uncultivated oral taxa Bacteroidetes bacteria HOT 365 and HOT 281, Lachnospiraceae bacteria HOT 100 and HOT 500, and Clostridiales bacterium HOT 093. All agar media were able to support the growth of 10 reference strains of oral bacteria. One previously uncultivated phylotype, Actinomyces sp. HOT 525, was cultivated on FAA. Of 93 previously uncultivated phylotypes found in the inocula, 26 were detected in in vitro-cultivated biofilms. Lachnospiraceae bacterium HOT 500 was successfully cultured from biofilm material harvested from PPA plates in coculture with Parvimonas micra or Veillonella dispar/parvula after colony hybridization-directed enrichment. The establishment of in vitro biofilms from oral inocula enables the cultivation of previously uncultured oral bacteria and provides source material for isolation in coculture. C1 [Thompson, Hayley; Wade, William G.] Queen Mary Univ London, Ctr Immunol & Infect Dis, Barts & London Sch Med & Dent, London, England. [Rybalka, Alexandra; Moazzez, Rebecca] Kings Coll London, Inst Dent, London WC2R 2LS, England. [Dewhirst, Floyd E.; Wade, William G.] Forsyth Inst, Cambridge, MA USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Wade, WG (reprint author), Queen Mary Univ London, Ctr Immunol & Infect Dis, Barts & London Sch Med & Dent, London, England. EM w.wade@qmul.ac.uk OI Wade, William/0000-0003-2685-826X FU National Institute of Dental and Craniofacial Research [DE016937] FX This work has been supported in part by grant DE016937 from the National Institute of Dental and Craniofacial Research. NR 29 TC 3 Z9 3 U1 3 U2 24 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2015 VL 81 IS 24 BP 8307 EP 8314 DI 10.1128/AEM.02156-15 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA CW7XN UT WOS:000365212800006 PM 26407883 ER PT J AU Cortes-Briones, JA Cahill, JD Skosnik, PD Mathalon, DH Williams, A Sewell, RA Roach, BJ Ford, JM Ranganathan, M D'Souza, DC AF Cortes-Briones, Jose A. Cahill, John D. Skosnik, Patrick D. Mathalon, Daniel H. Williams, Ashley Sewell, R. Andrew Roach, Brian J. Ford, Judith M. Ranganathan, Mohini D'Souza, Deepak Cyril TI The Psychosis-like Effects of Delta(9)-Tetrahydrocannabinol Are Associated With Increased Cortical Noise in Healthy Humans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cannabinoids; Electroencephalogram; Neural noise; Nonlinear analysis; Psychosis; Tetrahydrocannabinol ID LEMPEL-ZIV COMPLEXITY; LONGITUDINAL DATA-ANALYSIS; SPONTANEOUS BRAIN ACTIVITY; FUNCTIONAL CONNECTIVITY; AUDITORY HALLUCINATIONS; WORKING-MEMORY; SCHIZOPHRENIA; EEG; SIGNAL; CANNABINOIDS AB BACKGROUND: Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Delta(9)-THC), the principal active constituent of cannabis. METHODS: Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Delta(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Delta(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. RESULTS: Delta(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Delta 9-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Delta(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. CONCLUSIONS: At doses that produced psychosis-like effects, Delta(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Delta(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Delta(9)-THC. C1 [Cortes-Briones, Jose A.; Cahill, John D.; Skosnik, Patrick D.; Williams, Ashley; Sewell, R. Andrew; Ranganathan, Mohini; D'Souza, Deepak Cyril] Vet Affairs Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT USA. [Cortes-Briones, Jose A.; Skosnik, Patrick D.; Williams, Ashley; Sewell, R. Andrew; Ranganathan, Mohini; D'Souza, Deepak Cyril] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. [Cortes-Briones, Jose A.; Cahill, John D.; Skosnik, Patrick D.; Sewell, R. Andrew; Ranganathan, Mohini; D'Souza, Deepak Cyril] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.; Roach, Brian J.; Ford, Judith M.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. RP D'Souza, DC (reprint author), Yale Univ, VACHS Psychiat 116A, 950 Campbell Ave, West Haven, CT 06516 USA. EM deepak.dsouza@yale.edu RI Skosnik, Patrick/D-6466-2016 FU National Institute on Drug Abuse [R21 DA020750]; National Alliance for Research on Schizophrenia and Depression Young Investigator Award; Department of Veterans Affairs; National Institute of Mental Health; National Institute of Drug Abuse; National Institute of Alcoholism and Alcohol Abuse; Yale Center for Clinical Investigation; AbbVie; Pfizer Inc. FX This research project was funded in part by grants from the National Institute on Drug Abuse (R21 DA020750 to DCD) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award to PDS.; We acknowledge support from the 1) Department of Veterans Affairs, 2) National Institute of Mental Health, 3) National Institute of Drug Abuse, 4) National Institute of Alcoholism and Alcohol Abuse, and 5) the Yale Center for Clinical Investigation. We also thank Angelina Genovese, R.N.C., M.B.A.; Michelle San Pedro, R.N.; Elizabeth O'Donnell, R.N.; Brenda Breault, R.N., B.S.N.; Sonah Yoo, R.Ph.; Rachel Galvan, R.Ph.; and Willie Ford of the Neurobiological Studies Unit at the Veterans Affairs Connecticut Healthcare System, West Haven Campus, for their central contributions to the success of this project. Finally, this manuscript is dedicated to the memory of our dear friend and colleague, the late Dr. R. Andrew Sewell.; Deepak Cyril D'Souza has received in the past 3 years and currently receives research grant support administered through Yale University School of Medicine from AbbVie and Pfizer Inc., and he is a consultant for Bristol Myers Squibb and Johnson and Johnson. Dr. Mathalon is a consultant for Bristol Myers Squibb, Roche, and Amgen. All other authors report no biomedical financial interests or potential conflicts of interest. NR 66 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2015 VL 78 IS 11 BP 805 EP 813 DI 10.1016/j.biopsych.2015.03.023 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CW5OQ UT WOS:000365046200012 PM 25913109 ER PT J AU Spitzer, TR AF Spitzer, Thomas R. TI Intersection of Hematopoietic Cell and Solid Organ Transplantation: Lessons Learned and Unanswered Questions SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID RENAL-TRANSPLANTATION; BONE-MARROW; DONOR; CHIMERISM; TOLERANCE C1 [Spitzer, Thomas R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM tspitzer@partners.org NR 15 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2015 VL 21 IS 12 BP 2037 EP 2038 DI 10.1016/j.bbmt.2015.10.003 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CW4SF UT WOS:000364981700002 PM 26463650 ER PT J AU Giralt, S Garderet, L Durie, B Cook, G Gahrton, G Bruno, B Hari, P Lokhorst, H McCarthy, P Krishnan, A Sonneveld, P Goldschmidt, H Jagannath, S Barlogie, B Mateos, M Gimsing, P Sezer, O Mikhael, J Lu, J Dimopoulos, M Mazumder, A Palumbo, A Abonour, R Anderson, K Attal, M Blade, J Bird, J Cavo, M Comenzo, R de la Rubia, J Einsele, H Garcia-Sanz, R Hillengass, J Holstein, S Johnsen, HE Joshua, D Koehne, G Kumar, S Kyle, R Leleu, X Lonial, S Ludwig, H Nahi, H Nooka, A Orlowski, R Rajkumar, V Reiman, A Richardson, P Riva, E Miguel, JS Turreson, I Usmani, S Vesole, D Bensinger, W Qazilbash, M Efebera, Y Mohty, M Gasparreto, C Gajewski, J LeMaistre, CF Bredeson, C Moreau, P Pasquini, M Kroeger, N Stadtmauer, E AF Giralt, Sergio Garderet, Laurent Durie, Brian Cook, Gordon Gahrton, Gosta Bruno, Benedetto Hari, Paremesweran Lokhorst, Henk McCarthy, Phillip Krishnan, Amrita Sonneveld, Pieter Goldschmidt, Harmut Jagannath, Sundar Barlogie, Bart Mateos, Maria Gimsing, Peter Sezer, Orhan Mikhael, Joseph Lu, Jin Dimopoulos, Meletios Mazumder, Amitabha Palumbo, Antonio Abonour, Rafat Anderson, Kenneth Attal, Michel Blade, Joan Bird, Jenny Cavo, Michele Comenzo, Raymond de la Rubia, Javier Einsele, Hermann Garcia-Sanz, Ramon Hillengass, Jens Holstein, Sarah Johnsen, Hans Erik Joshua, Douglas Koehne, Guenther Kumar, Shaji Kyle, Robert Leleu, Xavier Lonial, Sagar Ludwig, Heinz Nahi, Hareth Nooka, Anil Orlowski, Robert Rajkumar, Vincent Reiman, Anthony Richardson, Paul Riva, Eloisa Miguel, Jesus San Turreson, Ingemar Usmani, Saad Vesole, David Bensinger, William Qazilbash, Muzaffer Efebera, Yvonne Mohty, Mohamed Gasparreto, Christina Gajewski, James LeMaistre, Charles F. Bredeson, Chris Moreau, Phillipe Pasquini, Marcelo Kroeger, Nicolaus Stadtmauer, Edward TI American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Myeloma; Stem cell transplantation; Salvage therapy ID LENALIDOMIDE PLUS DEXAMETHASONE; BORTEZOMIB-THALIDOMIDE-DEXAMETHASONE; LOW-DOSE DEXAMETHASONE; RANDOMIZED PHASE-III; AUTOLOGOUS TRANSPLANTATION; ALLOGENEIC TRANSPLANTATION; COMBINATION THERAPY; FOLLOW-UP; MAINTENANCE; PROGRESSION AB In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous Ha consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease. Regarding allogeneic Ha, the expert committee agreed on the following consensus statements: (1) Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be performed in the context of a clinical trial if possible; (3) The role of postallogeneic Ha maintenance therapy needs to be explored in the context of well-designed prospective trials; and (4) Prospective randomized trials need to be performed to define the role salvage allogeneic HCT in patients with MM relapsing after primary therapy. (c) 2015 American Society for Blood and Marrow Transplantation. C1 [Giralt, Sergio; Koehne, Guenther] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, New York, NY 10065 USA. [Garderet, Laurent] Hop St Antoine, INSERM, UMRS 938, F-75571 Paris, France. [Durie, Brian] Int Myeloma Fdn, Los Angeles, CA USA. [Cook, Gordon] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. [Gahrton, Gosta; Nahi, Hareth] Karolinska Inst, Huddinge, Sweden. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Hari, Paremesweran; Pasquini, Marcelo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Lokhorst, Henk] Univ Med Ctr Utrecht, Utrecht, Netherlands. [McCarthy, Phillip; Holstein, Sarah] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Krishnan, Amrita] City Hope Canc Ctr Duarte, Duarte, CA USA. [Sonneveld, Pieter] Erasmus MC, Rotterdam, Netherlands. [Goldschmidt, Harmut; Hillengass, Jens] Heidelberg Univ, Heidelberg, Germany. [Jagannath, Sundar; Barlogie, Bart] Mt Sinai Sch Med, New York, NY USA. [Mateos, Maria; Garcia-Sanz, Ramon] Hosp Univ Salamanca, Salamanca, Spain. [Gimsing, Peter] Rigshosp, DK-2100 Copenhagen, Denmark. [Sezer, Orhan] Mem Sisli Hastanesi, Istanbul, Turkey. [Mikhael, Joseph] Mayo Clin, Scottsdale, AZ USA. [Lu, Jin] Peking Univ, Inst Hematol, Peoples Hosp, Beijing 100871, Peoples R China. [Dimopoulos, Meletios] Univ Athens, Alexandra Hosp, Athens 11528, Greece. [Mazumder, Amitabha] NYU, Sch Med, New York, NY USA. [Palumbo, Antonio] Univ Turin, Turin, Italy. [Abonour, Rafat] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Anderson, Kenneth; Richardson, Paul] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Attal, Michel] Inst Claudius Regaud, Toulouse, France. [Blade, Joan] IDIBAPS, Hosp Clin, Barcelona, Spain. [Bird, Jenny] Univ Hosp Bristol, Bristol, Avon, England. [Cavo, Michele] Univ Bologna, Sch Med, Seragnoli Inst Hematol, Bologna, Italy. [Comenzo, Raymond] Tufts Univ, Sch Med, Boston, MA 02111 USA. [de la Rubia, Javier] Hosp Dr Pesset, Valencia, Spain. [Einsele, Hermann] Klin Univ Wurzburg, Wurzburg, Germany. [Johnsen, Hans Erik] Aalborg Univ Hosp, Aalborg, Denmark. [Joshua, Douglas] Univ Sydney, Sch Med, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. [Kumar, Shaji; Kyle, Robert; Rajkumar, Vincent] Mayo Clin Rochester, Rochester, MN USA. [Leleu, Xavier] Hosp Claude Huriez, Lille, France. [Lonial, Sagar; Nooka, Anil] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Ludwig, Heinz] Wilhelminenkrebsforsch Inst, Vienna, Austria. [Orlowski, Robert; Qazilbash, Muzaffer] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Reiman, Anthony] Dalhousie Univ, Sch Med, Dalhousie, NS, Canada. [Riva, Eloisa] Hosp Clin Montevideo, Montevideo, Uruguay. [Miguel, Jesus San] Univ Navarra Clin, Navarra, Spain. [Turreson, Ingemar] Skane Univ Hosp, Malmo, Sweden. [Usmani, Saad] Levine Canc Inst, Charlotte, NC USA. [Vesole, David] John Theurer Canc Ctr, Hackensack, NJ USA. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Efebera, Yvonne] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Mohty, Mohamed] Univ Paris 06, Hosp St Antoine, Paris, France. [Gasparreto, Christina] Duke Univ Hosp, Durham, NC USA. [Gajewski, James] Oregon Hlth & Sci Univ, Portland, OR USA. [LeMaistre, Charles F.] Sarah Cannon Res Inst, Nashville, TN USA. [Bredeson, Chris] Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Moreau, Phillipe] Univ Hosp Nantes, Nantes, France. [Kroeger, Nicolaus] Univ Hamburg Hosp, Hamburg, Germany. [Stadtmauer, Edward] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Giralt, S (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave,Box 235, New York, NY 10065 USA. EM giralts@mskcc.org RI Efebera, Yvonne/E-3012-2011; richard, chrystelle/K-8595-2015; Garcia-Sanz, Ramon/B-7986-2017 OI Garcia-Sanz, Ramon/0000-0003-4120-2787 FU Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute [U10HL069294]; Blood and Marrow Transplant Clinical Trials Network from National Cancer Institute [U10HL069294]; Be The Match Foundation [U10HL069294]; SANOFI Corporation FX Blood and Marrow Transplant Clinical Trials Network U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute U10HL069294) and by the Be The Match Foundation (Grant # U10HL069294, and an Unrestricted educational grant to the International Myeloma Foundation from SANOFI Corporation. NR 67 TC 21 Z9 21 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2015 VL 21 IS 12 BP 2039 EP 2051 DI 10.1016/j.bbmt.2015.09.016 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CW4SF UT WOS:000364981700003 PM 26428082 ER PT J AU Klyuchnikov, E Bacher, U Kroger, NM Hari, PN Ahn, KW Carreras, J Bachanova, V Bashey, A Cohen, JB D'Souza, A Freytes, CO Gale, RP Ganguly, S Hertzberg, MS Holmberg, LA Kharfan-Dabaja, MA Klein, A Ku, GH Laport, GG Lazarus, HM Miller, AM Mussetti, A Olsson, RF Slavin, S Usmani, SZ Vij, R Wood, WA Maloney, DG Sureda, AM Smith, SM Hamadani, M AF Klyuchnikov, Evgeny Bacher, Ulrike Kroeger, Nicolaus M. Hari, Parameswaran N. Ahn, Kwang Woo Carreras, Jeanette Bachanova, Veronika Bashey, Asad Cohen, Jonathon B. D'Souza, Anita Freytes, Cesar O. Gale, Robert Peter Ganguly, Siddhartha Hertzberg, Mark S. Holmberg, Leona A. Kharfan-Dabaja, Mohamed A. Klein, Andreas Ku, Grace H. Laport, Ginna G. Lazarus, Hillard M. Miller, Alan M. Mussetti, Alberto Olsson, Richard F. Slavin, Shimon Usmani, Saad Z. Vij, Ravi Wood, William A. Maloney, David G. Sureda, Anna M. Smith, Sonali M. Hamadani, Mehdi TI Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Grade 1 and 2 follicular lymphoma; Reduced-intensity allogeneic hematopoietic cell transplantation; Autologous hematopoietic cell transplantation; Long-time survival ID STEM-CELL TRANSPLANTATION; PROGRESSION-FREE SURVIVAL; NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; FOLLOW-UP; ALLOGENEIC TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; RITUXIMAB; EBMT; RELAPSE AB This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P <.0001); relapse/progression: 54% versus 20% (P <.0001); progression-free survival (PFS): 41% versus 58% (P <.001), and overall survival (OS): 74% versus 66% (P =.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P <.0001) and worse PFS (RR, 2.9; P <.0001) beyond 11 months after HCT. In the first 24 months after HO', auto-HCT was associated with improved OS (RR,.41; P <.0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P =.006). A landmark analysis of patients alive and progression-free at 2 years after HO' confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P <.0001) and inferior PFS (RR, 3.2; P <.0001) and OS (RR, 2.1; P =.04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Klyuchnikov, Evgeny; Kroeger, Nicolaus M.] Univ Canc Ctr Hamburg, Dept Stem Cell Transplantat, Hamburg, Germany. [Bacher, Ulrike] Univ Gottingen, Dept Hematol & Internal Oncol, D-37073 Gottingen, Germany. [Hari, Parameswaran N.; Ahn, Kwang Woo; Carreras, Jeanette; D'Souza, Anita; Hamadani, Mehdi] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Hari, Parameswaran N.; Ahn, Kwang Woo; Carreras, Jeanette; D'Souza, Anita; Hamadani, Mehdi] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Bachanova, Veronika] Univ Minnesota, Med Ctr, Bone & Marrow Transplant Program, Minneapolis, MN 55455 USA. [Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Cohen, Jonathon B.] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Freytes, Cesar O.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Ganguly, Siddhartha] Univ Kansas, Med Ctr, Blood & Marrow Transplantat, Div Hematol & Oncol, Kansas City, KS 66103 USA. [Hertzberg, Mark S.] Prince Wales Hosp, Dept Haematol, Randwick, NSW 2031, Australia. [Holmberg, Leona A.; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kharfan-Dabaja, Mohamed A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA. [Klein, Andreas] Tufts Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA USA. [Ku, Grace H.] Univ Calif San Diego, Dept Med, Div Blood & Marrow Transplantat, San Diego, CA 92103 USA. [Laport, Ginna G.] Stanford Hosp & Clin, Div Bone Marrow Transplantat, Stanford, CA USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Miller, Alan M.] Baylor Univ, Med Ctr, Dept Oncol, Dallas, TX USA. [Mussetti, Alberto] Fdn IRCCS Ist Nazl Tumori, SC Ematol & Trapianto Midollo Osseo, Milan, Italy. [Mussetti, Alberto] Univ Milan, Milan, Italy. [Olsson, Richard F.] Karolinska Inst, Div Therapeut Immunol, Dept Lab Med, Stockholm, Sweden. [Olsson, Richard F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Slavin, Shimon] Int Ctr Cell Therapy & Canc Immunotherapy, Tel Aviv, Israel. [Usmani, Saad Z.] Carolinas HealthCare Syst, Levine Canc Inst, Dept Hematol, Med Oncol, Charlotte, NC USA. [Vij, Ravi] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA. [Wood, William A.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA. [Sureda, Anna M.] Hosp Duran & Reynals, Inst Catala Oncol, Serv Hematol, Barcelona, Spain. [Sureda, Anna M.] European Grp Blood & Marrow Transplantat, Milan, Italy. [Smith, Sonali M.] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA. RP Hamadani, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM mhamadani@mcw.edu RI Mussetti, Alberto/C-9500-2017; OI Mussetti, Alberto/0000-0002-4088-036X; D'Souza, Anita/0000-0002-1092-5643; Hari, Parameswaran/0000-0002-8800-297X FU Public Health Service grant from the National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc. FX The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a grant/cooperative agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government. NR 35 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2015 VL 21 IS 12 BP 2091 EP 2099 DI 10.1016/j.bbmt.2015.07.028 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CW4SF UT WOS:000364981700009 PM 26253007 ER PT J AU Borzecki, AM Chen, Q Restuccia, J Mull, HJ Shwartz, M Gupta, K Hanchate, A Strymish, J Rosen, A AF Borzecki, Ann M. Chen, Qi Restuccia, Joseph Mull, Hillary J. Shwartz, Michael Gupta, Kalpana Hanchate, Amresh Strymish, Judith Rosen, Amy TI Do pneumonia readmissions flagged as potentially preventable by the 3M PPR software have more process of care problems? A cross-sectional observational study SO BMJ QUALITY & SAFETY LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; 30-DAY READMISSIONS; HOSPITAL READMISSIONS; INPATIENT CARE; QUALITY; ASSOCIATION; INDICATORS; IDENTIFY; OUTCOMES; METRICS AB Background In the USA, administrative data-based readmission rates such as the Centers for Medicare and Medicaid Services' all-cause readmission measures are used for public reporting and hospital payment penalties. To improve this measure and identify better quality improvement targets, 3M developed the Potentially Preventable Readmissions (PPRs) measure. It matches clinically related index admission and readmission diagnoses that may indicate readmissions resulting from admission-or post-discharge-related quality problems. Objective To examine whether PPR software-flagged pneumonia readmissions are associated with poorer quality of care. Methods Using a retrospective observational study design and Veterans Health Administration (VA) data, we identified pneumonia discharges associated with 30-day readmissions, and then flagged cases as PPR-yes or PPR-no using the PPR software. To assess quality of care, we abstracted electronic medical records of 100 random readmissions using a tool containing explicit care processes organised into admission work-up, in-hospital evaluation/treatment, discharge readiness and post-discharge period. We derived quality scores, scaled to a maximum of 25 per section (maximum total score=100) and compared cases by total and section-specific mean scores using t tests and effect size (ES) to characterise the clinical significance of findings. Results Our abstraction sample was selected from 11 278 pneumonia readmissions (readmission rate=16.5%) during 1 October 2005-30 September 2010; 77% were flagged as PPR-yes. Contrary to expectations, total and section mean quality scores were slightly higher, although non-significantly, among PPR-yes (N=77) versus PPR-no (N=23) cases (respective total scores, 71.2 +/- 8.7 vs 65.8 +/- 11.5, p=0.14); differences demonstrated ES >0.30 overall and for admission work-up and post-discharge period sections. Conclusions Among VA pneumonia readmissions, PPR categorisation did not produce the expected quality of care findings. Either PPR-yes cases are not more preventable, or preventability assessment requires other data collection methods to capture poorly documented processes (eg, direct observation). C1 [Borzecki, Ann M.] Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Borzecki, Ann M.; Gupta, Kalpana; Hanchate, Amresh] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Chen, Qi; Restuccia, Joseph; Mull, Hillary J.; Shwartz, Michael; Hanchate, Amresh; Rosen, Amy] Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Restuccia, Joseph; Shwartz, Michael] Boston Univ, Sch Management, Boston, MA 02215 USA. [Mull, Hillary J.; Rosen, Amy] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Gupta, Kalpana; Strymish, Judith] VA Boston Healthcare Syst, Dept Infect Dis, Boston, MA USA. [Strymish, Judith] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Borzecki, AM (reprint author), Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. EM amb@bu.edu FU US Department of Veterans Affairs Health Service Research and Development Service [IIR 09-039] FX This work was funded by the US Department of Veterans Affairs Health Service Research and Development Service, grant No IIR 09-039. NR 40 TC 4 Z9 4 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD DEC PY 2015 VL 24 IS 12 BP 753 EP 763 DI 10.1136/bmjqs-2014-003911 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CW9TI UT WOS:000365340700004 PM 26283672 ER PT J AU Gatewood, MO Wemple, M Greco, S Kritek, PA Durvasula, R AF Gatewood, Medley O'Keefe Wemple, Matthew Greco, Sheryl Kritek, Patricia A. Durvasula, Raghu TI A quality improvement project to improve early sepsis care in the emergency department SO BMJ QUALITY & SAFETY LA English DT Article ID CLINICAL DECISION-SUPPORT; SEPTIC SHOCK; RANDOMIZED-TRIAL; MANAGEMENT; OUTCOMES; BUNDLE; ALERTS; IMPLEMENTATION; MORTALITY; THERAPY AB Background Sepsis causes substantial morbidity and mortality in hospitalised patients. Although many studies describe the use of protocols in the management of patients with severe sepsis and septic shock, few have addressed emergency department (ED) screening and management for patients initially presenting with uncomplicated sepsis (ie, patients without organ failure or hypotension). Objective A quality improvement task force at a large, quaternary care referral hospital sought to develop a protocol focusing on early identification of patients with uncomplicated sepsis, in addition to severe sepsis and septic shock. Intervention The three-tiered intervention consisted of (1) a nurse-driven screening tool and management protocol to identify and initiate early treatment of patients with sepsis, (2) a computer-assisted screening algorithm that generated a 'Sepsis Alert' pop-up screen in the electronic medical record for treating clinical healthcare providers and (3) automated suggested sepsis-specific order sets for initial workup and resuscitation, antibiotic selection and goal-directed therapy. Design A before and after retrospective cohort study was undertaken to determine the intervention's impact on compliance with recommended sepsis management, including serum lactate measured in the ED, 2 L of intravenous fluid administered within 2 h of triage, antibiotics administered within 3 h of triage and blood cultures drawn before antibiotic administration. Mortality rates for patients in the ED with a sepsis-designated ICD-9 code present on admission were also analysed. Results Overall bundle compliance increased by 154%, from 28% at baseline to 71% in the last quarter of the study (p<0.001). Bundle, antibiotic and intravenous fluid compliance all increased significantly after launch of the sepsis initiative (eg, bundle and intravenous fluid compliance increased by 74% and 54%, respectively; p<0.001). Bundle and antibiotic compliance both showed further significant increases after implementation of suggested order sets (31 /0 and 25% increases, respectively; p<0.001). The mortality rate for patients in the ED admitted with sepsis was 13.3% before implementation and fell to 11.1 /0 after (p=0.230); mortality in the last two quarters of the study was 9.3% (p=0.107). Conclusions The new protocol demonstrates that early screening interventions can lead to expedited delivery of care to patients with sepsis in the ED and could serve as a model for other facilities. Mortality was not significantly improved by our intervention, which included patients with uncomplicated sepsis. C1 [Gatewood, Medley O'Keefe] Univ Washington, Med Ctr, Div Emergency Med, Seattle, WA 98195 USA. [Wemple, Matthew] VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, Seattle, WA USA. [Greco, Sheryl] Univ Washington, Med Ctr, Patient Care Serv, Div Crit Care, Seattle, WA 98195 USA. [Greco, Sheryl] Univ Washington, Med Ctr, Patient Care Serv, Div Cardiol, Seattle, WA 98195 USA. [Kritek, Patricia A.] Univ Washington, Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Durvasula, Raghu] Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA. RP Gatewood, MO (reprint author), Univ Washington, Med Ctr, Div Emergency Med, Seattle, WA 98195 USA. EM medley@uw.edu NR 22 TC 5 Z9 5 U1 1 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD DEC PY 2015 VL 24 IS 12 BP 787 EP 795 DI 10.1136/bmjqs-2014-003552 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CW9TI UT WOS:000365340700008 PM 26251506 ER PT J AU Hempel, S Shekelle, PG Liu, JL Danz, MS Foy, R Lim, YW Motala, A Rubenstein, LV AF Hempel, Susanne Shekelle, Paul G. Liu, Jodi L. Danz, Margie Sherwood Foy, Robbie Lim, Yee-Wei Motala, Aneesa Rubenstein, Lisa V. TI Development of the Quality Improvement Minimum Quality Criteria Set (QI-MQCS): a tool for critical appraisal of quality improvement intervention publications SO BMJ QUALITY & SAFETY LA English DT Article ID BIAS; COMMUNITY; TRIALS; RISK AB Objective Valid, reliable critical appraisal tools advance quality improvement (QI) intervention impacts by helping stakeholders identify higher quality studies. QI approaches are diverse and differ from clinical interventions. Widely used critical appraisal instruments do not take unique QI features into account and existing QI tools (eg, Standards for QI Reporting Excellence) are intended for publication guidance rather than critical appraisal. This study developed and psychometrically tested a critical appraisal instrument, the QI Minimum Quality Criteria Set (QI-MQCS) for assessing Ql-specific features of QI publications. Methods Approaches to developing the tool and ensuring validity included a literature review, in-person and online survey expert panel input, and application to empirical examples. We investigated psychometric properties in a set of diverse QI publications (N=54) by analysing reliability measures and item endorsement rates and explored sources of disagreement between reviewers. Results The QI-MQCS includes 16 content domains to evaluate QI intervention publications: Organisational Motivation, Intervention Rationale, Intervention Description, Organisational Characteristics, Implementation, Study Design, Comparator Description, Data Sources, Timing, Adherence/Fidelity, Health Outcomes, Organisational Readiness, Penetration/Reach, Sustainability, Spread and Limitations. Median inter-rater agreement for QI-MQCS items was x 0.57 (83% agreement). Item statistics indicated sufficient ability to differentiate between publications (median quality criteria met 67%). Internal consistency measures indicated coherence without excessive conceptual overlap (absolute mean interitem correlation=0.19). The critical appraisal instrument is accompanied by a user manual detailing What to consider, Where to look and How to rate. Conclusions We developed a ready-to-use, valid and reliable critical appraisal instrument applicable to healthcare QI intervention publications, but recognise scope for continuing refinement. C1 [Hempel, Susanne; Shekelle, Paul G.; Liu, Jodi L.; Danz, Margie Sherwood; Motala, Aneesa; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA 90407 USA. [Shekelle, Paul G.] Vet Affairs West Los Angeles Med Ctr, Los Angeles, CA USA. [Danz, Margie Sherwood; Rubenstein, Lisa V.] Vet Affairs Greater Los Angeles, North Hills, CA USA. [Foy, Robbie] Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England. [Lim, Yee-Wei] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Hempel, S (reprint author), RAND Corp, RAND Hlth, 1776 Main St, Santa Monica, CA 90407 USA. EM susanne_hempel@rand.org FU Robert Wood Johnson (RWJ) Foundation [65113]; Veterans Affairs (VA) Greater Los Angeles Healthcare System; RAND Corporation; Agency for Healthcare Research and Quality (AHRQ) [1R13HS018139-01] FX The project was funded by a grant from the Robert Wood Johnson (RWJ) Foundation (ID 65113), the Veterans Affairs (VA) Greater Los Angeles Healthcare System, the RAND Corporation, and the Agency for Healthcare Research and Quality (AHRQ, 1R13HS018139-01). The funding agencies had no role in the study design, collection, analysis and interpretation of the data; the writing and the decision to submit the manuscript for publication. The findings and conclusions are those of the authors; the content of the manuscript should not be construed as the official position of the RWJ Foundation, the Department of Veteran Affairs, the RAND Corporation, or AHRQ. NR 36 TC 3 Z9 3 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD DEC PY 2015 VL 24 IS 12 BP 796 EP 804 DI 10.1136/bmjqs-2014-003151 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CW9TI UT WOS:000365340700009 PM 26311020 ER PT J AU Mitchell, DM Tuck, P Ackerman, KE Sokoloff, NC Woolley, R Slattery, M Lee, H Bouxsein, ML Misra, M AF Mitchell, Deborah M. Tuck, Padrig Ackerman, Kathryn E. Sokoloff, Natalia Cano Woolley, Ryan Slattery, Meghan Lee, Hang Bouxsein, Mary L. Misra, Madhusmita TI Altered trabecular bone morphology in adolescent and young adult athletes with menstrual dysfunction SO BONE LA English DT Article DE Bone density; Microarchitecture; Amenorrhea; Athlete ID HR-PQCT IMAGES; POSTMENOPAUSAL WOMEN; DISTAL RADIUS; PRIMARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; ELEMENT-ANALYSIS; CORTICAL BONE; MICROSTRUCTURE; STRENGTH; PLATES AB Context: Young amenorrheic athletes (AA) have lower bone mineral density (BMD) and an increased prevalence of fracture compared with eumenorrheic athletes (EA) and non-athletes. Trabecular morphology is a determinant of skeletal strength and may contribute to fracture risk. Objectives: To determine the variation in trabecular morphology among AA, EA, and non-athletes and to determine the association of trabecular morphology with fracture among AA. Design and setting: A cross-sectional study performed at an academic clinical research center. Participants: 161 girls and young women aged 14-26 years (97 AA, 32 EA, and 32 non-athletes). Main outcome measure: We measured volumetric BMD (vBMD) and skeletal microarchitecture using high-resolution peripheral quantitative computed tomography. We evaluated trabecular morphology (plate-like vs. rod-like), orientation, and connectivity by individual trabecula segmentation. Results: At the non-weight-bearing distal radius, the groups did not differ for trabecular vBMD. However, plate-like trabecular bone volume fraction (pBV/TV) was lower in AA vs. EA (p = 0.03), as were plate number (p = 0.03) and connectivity (p = 0.03). At the weight-bearing distal tibia, trabecular vBMD was higher in athletes vs. non-athletes (p = 0.05 for AA and p = 0.009 for EA vs. non-athletes, respectively). pBV/TV was higher in athletes vs. non-athletes (p = 0.04 AA and p = 0.005 EA vs. non-athletes), as were axially-aligned trabeculae, plate number, and connectivity. Among AA, those with a history of recurrent stress fracture had lower pBV/TV, axially-aligned trabeculae, plate number, plate thickness, and connectivity at the distal radius. Conclusions: Trabecular morphology and alignment differ among AA, EA, and non-athletes. These differences may be associated with increased fracture risk. (C) 2015 Published by Elsevier Inc. C1 [Mitchell, Deborah M.; Tuck, Padrig; Bouxsein, Mary L.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Mitchell, Deborah M.; Tuck, Padrig; Ackerman, Kathryn E.; Sokoloff, Natalia Cano; Woolley, Ryan; Slattery, Meghan; Lee, Hang; Bouxsein, Mary L.; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mitchell, Deborah M.; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Ackerman, Kathryn E.; Sokoloff, Natalia Cano; Woolley, Ryan; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA 02116 USA. RP Mitchell, DM (reprint author), Massachusetts Gen Hosp, Endocrine & Pediat Endocrine Units, 50 Blossom St, Boston, MA 02114 USA. EM dmmitchell@mgh.harvard.edu OI Slattery, Meghan/0000-0001-7123-0661; Woolley, Ryan/0000-0002-5179-5953; Misra, Madhusmita/0000-0002-9405-2981 FU National Institutes of Health [R01HD060827, K24HD071843]; Harvard Catalyst, the Harvard Clinical and Translational Science Center [NIH UL1 TR001102]; NIH/NCRR [1 S10 RR023405] FX This work was conducted with support from National Institutes of Health R01HD060827, K24HD071843, and by the Harvard Catalyst, the Harvard Clinical and Translational Science Center (NIH UL1 TR001102). We acknowledge funding for the HR-pQCT from a shared equipment grant (NIH/NCRR 1 S10 RR023405). We thank our research subjects and the nurses and bionutritionists at the Massachusetts General Hospital Clinical Research Center. We thank Ms. Ji Wang and Dr. X. Edward Guo from the Bone Bioengineering Lab at Columbia University for their technical assistance, and the ITS software used in this study was under an academic license from Columbia University. NR 36 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD DEC PY 2015 VL 81 BP 24 EP 30 DI 10.1016/j.bone.2015.06.021 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX0FR UT WOS:000365372800004 PM 26123592 ER PT J AU Lim, SY Rastalsky, N Choy, E Bolster, MB AF Lim, Sian Yik Rastalsky, Naina Choy, Edwin Bolster, Marcy B. TI Tibial stress reaction presenting as bilateral shin pain in a man taking denosumab for giant cell tumor of the bone SO BONE LA English DT Article DE Denosumab; Stress reaction; Atypical femoral fractures; Osteoporosis ID ATYPICAL FEMORAL FRACTURES; PATIENT RECEIVING DENOSUMAB; BISPHOSPHONATE THERAPY; DIAPHYSEAL FRACTURES; FEMUR; QUALITY; SHAFT AB Prolonged bisphosphonate use has been associated with increased risk of atypical femoral fractures. Very few cases of atypical femoral fractures have been reported with denosumab. We report a case of bilateral tibial stress reactions in a 60-year-old man with no history of osteoporosis who was on prolonged high-dose denosumab for the treatment of giant cell tumor of bone. He presented with a 3-month history of pain in his bilateral shins worsening with activity and improving with rest. Although initial radiographs were unremarkable, he was found to have changes consistent with a stress reaction on magnetic resonance imaging of the distal tibia. To our knowledge, bilateral tibial stress reactions have not been previously reported with anti-resorptive therapies (neither bisphosphonates nor denosumab). Our case is intriguing in terms of the development of stress reactions as a precursor to stress fractures which may also relate to atypical fractures. Our case suggests a possible association between denosumab use and stress reactions. Of note the indication for denosumab in our case was for the treatment of giant cell tumor of bone where the Food and Drug Administration (FDA) approved dose is substantially higher than the FDA approved dose for osteoporosis treatment. Although rare, clinicians should consider the possibility of stress fractures in patients on anti-resorptive medications such as denosumab, especially when a patient presents with new onset thigh pain, hip pain or pain over an area affecting the long bones. Evaluation by imaging of affected areas should be pursued to enable early detection and intervention, as well as prevention of morbidity and associated ongoing risk to the patient. (C) 2015 Elsevier Inc. All rights reserved. C1 [Lim, Sian Yik; Rastalsky, Naina; Bolster, Marcy B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Choy, Edwin] Massachusetts Gen Hosp, Ctr Canc, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Lim, SY (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Address-55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM sylim@partners.org FU Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital FX We wish to thank the Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital for providing assistance and support during preparation of this manuscript NR 25 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD DEC PY 2015 VL 81 BP 31 EP 35 DI 10.1016/j.bone.2015.06.017 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX0FR UT WOS:000365372800005 PM 26117225 ER PT J AU Steffens, JP Coimbra, LS Rossa, C Kantarci, A Van Dyke, TE Spolidorio, LC AF Paulo Steffens, Joao Santana Coimbra, Leila Rossa, Carlos, Jr. Kantarci, Alpdogan Van Dyke, Thomas E. Carlos Spolidorio, Luis TI Androgen receptors and experimental bone loss - an in vivo and in vitro study SO BONE LA English DT Article DE Testosterone; Androgens; Receptors, androgen; Androgen receptor antagonists; Periodontitis; Bone and bones ID SEX STEROID-METABOLISM; INTERLEUKIN-6 PRODUCTION; KNOCKOUT-MICE; CORTICAL BONE; TESTOSTERONE; MEN; ESTROGEN; MODULATE; FIBROBLASTS; DEFICIENCY AB Testosterone is a sex hormone that exhibits many functions beyond reproduction; one such function is the regulation of bone metabolism. The role played by androgen receptors during testosterone-mediated biological processes associated with bone metabolism is largely unknown. This study aims to use a periodontal disease model in vivo in order to assess the involvement of androgen receptors on microbial-induced inflammation and alveolar bone resorption in experimental bone loss. The impact of hormone deprivation was tested through both orchiectomy and chemical blockage of androgen receptor using flutamide (FLU). Additionally, the direct effect of exogenous testosterone, and the role of the androgen receptor, on osteoclastogenesis were investigated. Thirty male adult rats (n = 10/group) were subjected to: 1-orchiectomy (OCX); 2-OCX sham surgery; or 3-OCX sham surgery plus FLU, four weeks before the induction of experimental bone loss. Ten OCX sham-operated rats were not subjected to experimental bone loss and served as healthy controls. The rats were euthanized two weeks later, so as to assess bone resorption and the production of inflammatory cytokines in the gingival tissue and serum. In order to study the in vitro impact of testosterone, osteoclasts were differentiated from RAW264.7 cells and testosterone was added at increasing concentrations. Both OCX and FLU increased bone resorption, but OCX alone was observed to increase osteoclast count. IL-1 beta production was increased only in the gingival tissue of OCX animals, whereas FLU-treated animals presented a decreased expression of IL-6. Testosterone reduced the osteoclast formation in a dose-dependent manner, and significantly impacted the production of TNF-alpha; FLU partially reversed these actions. When taken together, our results indicate that testosterone modulates experimental bone loss, and that this action is mediated, at least in part, via the androgen receptor. (C) 2015 Elsevier Inc. All rights reserved. C1 [Paulo Steffens, Joao; Santana Coimbra, Leila; Carlos Spolidorio, Luis] UNESP, Sch Dent Araraquara, Dept Physiol & Pathol, BR-14801903 Araraquara, SP, Brazil. [Paulo Steffens, Joao; Kantarci, Alpdogan; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. [Paulo Steffens, Joao] Univ Fed Fluminense, Sch Dent Nova Friburgo, Dept Specif Format, BR-28625650 Nova Friburgo, RJ, Brazil. [Rossa, Carlos, Jr.] UNESP, Sch Dent Araraquara, Dept Diag & Surg, BR-14801903 Araraquara, SP, Brazil. RP Steffens, JP (reprint author), Rua Humaita 1680, BR-14801903 Araraquara, SP, Brazil. EM joaopaulosteffens@hotmail.com RI Rossa Jr, Carlos/D-8328-2012 OI Rossa Jr, Carlos/0000-0003-1705-5481 FU Sao Paulo Research Foundation (FAPESP, Sao Paulo, SP, Brazil) [2010/12021-4, 2010/09658-0]; National Council for Scientific and Technological Development (CNPq, Brasilia, DF, Brazil) [470870/2011-7]; Committee for the Improvement of Higher Education Personnel (CAPES, Brasilia, DF, Brazil) [5258-11-1]; National Institute of Health (NIH/NIDCR, Bethesda, MD, USA) [DE015566, DE020906] FX The authors would like to acknowledge the financial support from Sao Paulo Research Foundation (FAPESP, Sao Paulo, SP, Brazil, Grant #2010/12021-4 and 2010/09658-0); National Council for Scientific and Technological Development (CNPq, Brasilia, DF, Brazil, Grant # 470870/2011-7); Committee for the Improvement of Higher Education Personnel (CAPES, Brasilia, DF, Brazil, Process #5258-11-1); and the National Institute of Health (NIH/NIDCR, Bethesda, MD, USA, grants DE015566 and DE020906 to AK and TVD). NR 54 TC 1 Z9 1 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD DEC PY 2015 VL 81 BP 683 EP 690 DI 10.1016/j.bone.2015.10.001 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CX0FR UT WOS:000365372800081 PM 26450018 ER PT J AU Conlin, PR Asefzadeh, B Pasquale, LR Selyin, G Lamkin, R Cayallerano, AA AF Conlin, Paul R. Asefzadeh, Baharak Pasquale, Louis R. Selyin, Gerald Lamkin, Rebecca Cayallerano, Anthony A. TI Accuracy of a technology-assisted eye exam in evaluation of referable diabetic retinopathy and concomitant ocular diseases SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CARE; PROGRAM; TELEOPHTHALMOLOGY; TELEMEDICINE; PHOTOGRAPHY; SPECIFICITY; SENSITIVITY; ADHERENCE AB Background/aims Digital retinal imaging using store-and-forward technology is used to screen for diabetic retinopathy (DR). Its usefulness in detecting non-diabetic eye diseases is uncertain. We determined the level of agreement between teleretinal imaging supplemented with visual acuity and intraocular pressure (IOP) measurements (ie, technology-assisted eye (TAE) exam) and a comprehensive eye exam in evaluation for DR and non-diabetic ocular conditions. Methods We conducted a prospective, observational study with two parallel evaluations. Patients with diabetes (n=317) had a TAE exam and a comprehensive eye exam on the same day. A subset of participants with normal baseline exams (n=72) had follow-up exams 1 year later. We measured the level of agreement for referable ocular findings. Results Agreement for referable ocular findings was moderate (n=389, agreement: 77%; kappa: 0.55), due in part to ungradable exams (22%). However, about half of the ungradable exams had findings that warranted referral. There was substantial agreement for follow-up exams (n=72, agreement: 93%; kappa: 0.63). Among all gradable exams (n=303), the TAE exam had 86% sensitivity and 84% specificity for referable ocular findings, with high agreement (>= 94%) for DR and other major ocular diagnoses. Conclusions There was moderate-to-substantial agreement between a TAE exam and a comprehensive eye exam for referable ocular findings in patients with diabetes. Ungradable exams were a frequent marker of ocular pathology. Teleretinal imaging may be a useful evaluation for both diabetic and non-diabetic ocular conditions. C1 [Conlin, Paul R.; Asefzadeh, Baharak; Selyin, Gerald; Lamkin, Rebecca; Cayallerano, Anthony A.] Vet Affairs VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Conlin, Paul R.; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. [Asefzadeh, Baharak; Selyin, Gerald; Cayallerano, Anthony A.] New England Coll Optometry, Boston, MA USA. [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Asefzadeh, B (reprint author), VA Boston Healthcare Syst, Dept Optometry, 112,150 S Huntington Ave, Boston, MA 02130 USA. EM Baharak.Asefzadeh@va.gov FU Veterans Affairs Health Services Research & Development Service [IIR 04-045]; National Institutes of Health [K24 DK63214] FX This study was supported by research grants IIR 04-045 from the Veterans Affairs Health Services Research & Development Service and the National Institutes of Health (K24 DK63214). NR 25 TC 0 Z9 0 U1 2 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD DEC PY 2015 VL 99 IS 12 BP 1622 EP 1627 DI 10.1136/bjophthalmol-2014-306536 PG 6 WC Ophthalmology SC Ophthalmology GA CW8YJ UT WOS:000365285100008 PM 25995299 ER PT J AU Lim, LS Ng, WY Wong, D Wong, E Yeo, I Ang, CL Kim, L Vavvas, D Lee, SY AF Lim, Laurence Shen Ng, Wei Yan Wong, Doric Wong, Edmund Yeo, Ian Ang, Chong Lye Kim, Leo Vavvas, Demetrios Lee, Shu Yen TI Prognostic factor analysis of vitrectomy for myopic foveoschisis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; POSTERIOR SCLERAL REINFORCEMENT; GAS TAMPONADE; MACULAR HOLE; TRACTION MACULOPATHY; PATHOLOGICAL MYOPIA; FOVEAL DETACHMENT; VISUAL PROGNOSIS; SPECTRAL-DOMAIN; EYES AB Purpose To describe the anatomical and functional outcomes in a cohort of subjects undergoing vitrectomy for myopic foveoschisis, and to analyse the factors predicting foveal reattachment and visual improvement. Methods This retrospective case series evaluated case records and optical coherence tomography images 6 months after surgery. Multivariate linear and logistic regressions were performed to assess the factors predicting anatomical and visual improvement. Results In total, 55 eyes of 54 patients were analysed. The mean spherical equivalent refraction was -11.83 +/-4.94D. Foveal detachment was present in 63.5% of eyes preoperatively and subjects with foveal detachment had 0.70 logMAR units (95% CI 0.02 to 1.39) poorer visual acuity than subjects without (p=0.046). The mean preoperative visual acuity was 0.84+/-0.59 logMAR units and the mean postoperative visual acuity was 0.64 0.64 logMAR units (mean difference 0.20+/-0.68 logMAR units (p=0.04)). The proportion of eyes with foveal detachment was significantly lower after surgery (12.5%; p<0.001). However, the proportion of eyes with ellipsoid zone disruption was significantly higher after surgery (59.6% vs 34.0%; p<0.001). In multivariate analyses, the preoperative central foveal thickness significantly predicted postoperative visual improvement by two or more lines (OR 1.004 (95% CI 1.000 to 1.007), per pm increase; p=0.049). The presence of ellipsoid zone disruption preoperatively was associated with 0.96 logMAR (95% CI 0.2 to 1.72) poorer final acuity (p=0.02). Conclusions Eyes with myopic foveoschisis with preoperative ellipsoid disruption and thinner central foveal thickness tend to have poorer visual outcomes. While current surgical manoeuvres are effective in reattaching the fovea, they may also cause iatrogenic injury to the photoreceptors. C1 [Lim, Laurence Shen; Ng, Wei Yan; Wong, Doric; Wong, Edmund; Yeo, Ian; Ang, Chong Lye; Lee, Shu Yen] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore. [Lim, Laurence Shen] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. [Lim, Laurence Shen; Lee, Shu Yen] Duke NUS Grad Med Sch, Boston, MA USA. [Lim, Laurence Shen; Kim, Leo; Vavvas, Demetrios] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lee, SY (reprint author), Singapore Natl Eye Ctr, 11 Third Hosp Ave, Singapore 168751, Singapore. EM lee.shu.yen@snec.com.sg NR 31 TC 0 Z9 0 U1 4 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD DEC PY 2015 VL 99 IS 12 BP 1639 EP 1643 DI 10.1136/bjophthalmol-2015-306885 PG 5 WC Ophthalmology SC Ophthalmology GA CW8YJ UT WOS:000365285100011 PM 26137989 ER PT J AU Brown, RB Haq, A Stanford, CF Razzaque, MS AF Brown, Ronald B. Haq, Afrozul Stanford, Charles F. Razzaque, Mohammed S. TI Vitamin D, phosphate, and vasculotoxicity SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Review DE phosphate; blood vessels; calcification ID CHRONIC-KIDNEY-DISEASE; SOFT-TISSUE CALCIFICATION; UREMIC TUMORAL CALCINOSIS; STAGE RENAL-DISEASE; CALCIUM SUPPLEMENTATION; VASCULAR CALCIFICATION; D METABOLISM; D DEFICIENCY; CARDIOVASCULAR MORTALITY; HYPOPHOSPHATEMIC RICKETS AB Vascular calcification is a complex process that results in the ectopic deposition of calcium-phosphate hydroxyapatite. Medial and intimal vascular calcification is frequently present in patients with diabetes mellitus and chronic kidney disease (CKD), and markedly increases the morbidity and mortality of these patients. Increased serum levels of calcium and phosphate, along with the use of active vitamin D metabolites, are commonly implicated in the evolvement of vascular wall mineralization in CKD patients. Because CKD patients have lower serum levels of vitamin D, they are routinely prescribed vitamin D supplements that exert a dualistic role that is both healthful and harmful in these patients, perhaps protecting bone health, but at the expense of promoting vascular pathology. This review briefly explains how reducing the phosphate burden in CKD patients could minimize vitamin-D-associated vascular wall calcification. C1 [Brown, Ronald B.] Kansas State Univ, Coll Human Ecol, Manhattan, KS 66506 USA. [Haq, Afrozul; Stanford, Charles F.; Razzaque, Mohammed S.] VPS Healthcare, Div Res & Dev, Abu Dhabi, U Arab Emirates. [Razzaque, Mohammed S.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. RP Razzaque, MS (reprint author), VPS Healthcare, Div Res & Dev, Abu Dhabi, U Arab Emirates. EM msrazzaque@vpshealth.com NR 98 TC 5 Z9 6 U1 5 U2 6 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0008-4212 EI 1205-7541 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD DEC PY 2015 VL 93 IS 12 BP 1077 EP 1082 DI 10.1139/cjpp-2015-0083 PG 6 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA CW6VR UT WOS:000365137000007 PM 26567479 ER PT J AU Bishu, K Armstrong, EJ AF Bishu, Kalkidan Armstrong, Ehrin J. TI Endovascular revascularization of a surgically ligated superficial femoral artery: A case report SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angiography; peripheral; renal; endovascular intervention; peripheral intervention ID FAILED ANTEGRADE ANGIOPLASTY; POPLITEAL APPROACH; SUPINE PATIENT; RECANALIZATION; OCCLUSION; DISEASE; ACCESS AB We present a case of a patient with left lower extremity ischemic rest pain who initially underwent surgical profundaplasty requiring ligation of his superficial femoral artery (SFA). The patient developed continued rest pain due to diffuse disease of his profunda and inadequate collaterals. Endovascular intervention was therefore performed to the oversewn SFA. Retrograde left SFA access was obtained and the origin of the SFA was recanalized with true lumen re-entry using an ultrasound guided re-entry catheter. Angioplasty was performed at the origin of the SFA and self-expanding stents were deployed in the proximal and mid left SFA. Hemostasis at the distal left SFA access site was obtained by balloon inflation at the access site and manual compression. This case illustrates the feasibility of endovascular repair of a ligated SFA. (c) 2015 Wiley Periodicals, Inc. C1 [Bishu, Kalkidan; Armstrong, Ehrin J.] Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. [Bishu, Kalkidan; Armstrong, Ehrin J.] Univ Colorado, Sch Med, Div Cardiol, Aurora, CO USA. RP Armstrong, EJ (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM Ehrin.armstrong@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC 1 PY 2015 VL 86 IS 7 BP 1236 EP 1241 DI 10.1002/ccd.26082 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW9MS UT WOS:000365323400015 PM 26108345 ER PT J AU Razouki, Z Burgess, JF Ozonoff, A Zhao, SB Berlowitz, D Rose, AJ AF Razouki, Zayd Burgess, James F., Jr. Ozonoff, Al Zhao, Shibei Berlowitz, Dan Rose, Adam J. TI Improving Anticoagulation Measurement Novel Warfarin Composite Measure SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE atrial fibrillation; blood coagulation; international normalized ratio; stroke; warfarin ID ATRIAL-FIBRILLATION; ORAL ANTICOAGULANT; VETERANS AFFAIRS; VENOUS THROMBOEMBOLISM; THERAPEUTIC RANGE; HEALTH-CARE; QUALITY; STROKE; TIME; VARIABILITY AB Background Percent time in therapeutic range (TTR) and international normalized ratio (INR) variability both measure warfarin control and are associated with outcomes independently. Here, we examine the advantages of a warfarin composite measure (WCM), which summarizes the 2 when measuring patient outcomes. We also examine how the measure chosen would affect anticoagulation clinic performance rankings. Methods and Results We constructed WCM using an equally weighted method, adding standardized TTR to standardized log-transformed INR variability using 103 897 warfarin-experienced patients from 100 anticoagulation clinics. We examined the association of WCM with ischemic stroke, major bleeding, and fatal bleeding, using a subset of patients with atrial fibrillation (n=40 404). We divided patients into quintiles based on their level of control for TTR, log INR variability, and WCM. We calculated the hazard ratios for ischemic stroke, major bleeding, and fatal bleeding stratified by these quintiles. WCM hazard ratios for stroke and fatal bleeding showed the largest difference between excellent control and poorest control quintile compared with TTR and log INR variability, but not for major bleeding. In addition, we compared site rankings obtained using each of our 3 performance measures. Kappa scores for identifying outlier and nonoutlier clinics between WCM and its components were moderate (=0.56 for TTR and =0.62 for log INR variability) but was weak between TTR and log INR variability (=0.13). Conclusions WCM produces the largest range of risk for warfarin complications, widening the floor ceiling effects that limit the use of TTR and INR variability as separate measures. Anticoagulation clinics ranking changed considerably according to the anticoagulation measure that was selected. C1 [Razouki, Zayd] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Ozonoff, Al; Zhao, Shibei; Berlowitz, Dan; Rose, Adam J.] Bedford VA Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Burgess, James F., Jr.; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Ozonoff, Al] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Boston, MA USA. [Rose, Adam J.] Boston Univ, Gen Internal Med Sect, Dept Med, Sch Med, Boston, MA 02215 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. RP Razouki, Z (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. EM zayd.razouki@dm.duke.edu FU Office of Academic Affiliations [TPM 21-026]; Health Service Research Development [IIR-10 to 374] FX Dr Razouki is an awardee of the Office of Academic Affiliations for a Postdoctoral Training Program in Health Services Research, Durham VA Medical Center (TPM 21-026). This study was supported by the Health Service Research & Development IIR-10 to 374 (PI: Dr Rose). NR 27 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD DEC PY 2015 VL 8 IS 6 BP 600 EP 607 DI 10.1161/CIRCOUTCOMES.115.001789 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW1ZR UT WOS:000364791200011 PM 26420820 ER PT J AU Lubitz, CC Economopoulos, KP Sy, S Johanson, C Kunzel, HE Reincke, M Gazelle, GS Weinstein, MC Gaziano, TA AF Lubitz, Carrie C. Economopoulos, Konstantinos P. Sy, Stephen Johanson, Colden Kunzel, Heike E. Reincke, Martin Gazelle, G. Scott Weinstein, Milton C. Gaziano, Thomas A. TI Cost-Effectiveness of Screening for Primary Aldosteronism and Subtype Diagnosis in the Resistant Hypertensive Patients SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE blood pressure; cost-effectiveness; hyperaldosteronism; hypertension; mineralocorticoids ID LEFT-VENTRICULAR HYPERTROPHY; AMERICAN-HEART-ASSOCIATION; QUALITY-OF-LIFE; BLOOD-PRESSURE; UNITED-STATES; PRIMARY HYPERALDOSTERONISM; ARTERIAL-HYPERTENSION; CARDIOVASCULAR EVENTS; COMPUTED-TOMOGRAPHY; PREVALENCE AB Background Primary aldosteronism (PA) is a common and underdiagnosed disease with significant morbidity potentially cured by surgery. We aim to assess if the long-term cardiovascular benefits of identifying and treating surgically correctable PA outweigh the upfront increased costs in patients at the time patients are diagnosed with resistant hypertension (RH). Methods and Results A decision-analytic model compares aggregate costs and systolic blood pressure changes of 6 recommended or implemented diagnostic strategies for PA in a simulated population of at-risk RH patients. We also evaluate a 7th treat all strategy wherein all patients with RH are treated with a mineralocorticoid-receptor antagonist without further testing at RH diagnosis. Changes in systolic blood pressure are subsequently converted into gains in quality-adjusted life years (QALYs) by applying National Health and Nutrition Examination Survey data on concomitant risk factors to an existing cardiovascular disease simulation model. QALYs and lifetime costs were then used to calculate incremental cost-effectiveness ratios for the competing strategies. The incremental cost-effectiveness ratio for the strategy of computerized tomography (CT) followed by adrenal venous sampling (AVS) was $82 000/QALY compared with treat all. Incremental cost-effectiveness ratios for CT alone and AVS alone were $200 000/QALY and $492 000/QALY; the other strategies were more costly and less effective. Integrating differential patient-reported health-related quality of life adjustments for patients with PA, and incremental cost-effectiveness ratios for screening patients with CT followed by AVS, CT alone, and AVS alone were $52 000/QALY, $114 000/QALY, and $269 000/QALY gained. Conclusions CT scanning followed by AVS was a cost-effective strategy to screen for PA among patients with RH. C1 [Lubitz, Carrie C.; Economopoulos, Konstantinos P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lubitz, Carrie C.; Economopoulos, Konstantinos P.; Johanson, Colden; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Sy, Stephen; Gazelle, G. Scott; Weinstein, Milton C.; Gaziano, Thomas A.] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Kunzel, Heike E.; Reincke, Martin] Klinikum Ludwig Maximilians Univ Munchen, Med Klin & Poliklin 4, Schwerpunkt Endokrinol, Munich, Germany. [Gaziano, Thomas A.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. RP Lubitz, CC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM clubitz@partners.org FU Program in Cancer Outcomes Research Training Grant [NCI R25CA092203]; National Cancer Institute [K07CA177900]; Massachusetts General Hospital Department of Surgery; Else Kroner-Fresenius-Stiftung; National Heart, Lung, and Blood Institute [5R01HL104284] FX This study was supported by Program in Cancer Outcomes Research Training Grant (NCI R25CA092203), National Cancer Institute (K07CA177900), Massachusetts General Hospital Department of Surgery, National Heart, Lung, and Blood Institute (5R01HL104284), and by a grant of the Else Kroner-Fresenius-Stiftung to M. Reincke. NR 44 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD DEC PY 2015 VL 8 IS 6 BP 621 EP 630 DI 10.1161/CIRCOUTCOMES.115.002002 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW1ZR UT WOS:000364791200013 PM 26555126 ER PT J AU Campbell, JI Haberer, JE AF Campbell, Jeffrey I. Haberer, Jessica E. TI Cell Phone-Based and Adherence Device Technologies for HIV Care and Treatment in Resource-Limited Settings: Recent Advances SO CURRENT HIV/AIDS REPORTS LA English DT Article DE Cell phones; Electronic adherence monitoring; Technology; HIV antiretroviral therapy ID RANDOMIZED CONTROLLED-TRIAL; CROSS-SECTIONAL SURVEY; ANTIRETROVIRAL THERAPY; RURAL UGANDA; MEDICATION ADHERENCE; TEXT MESSAGES; HIV/AIDS; ACCEPTABILITY; FEASIBILITY; MANAGEMENT AB Numerous cell phone-based and adherence monitoring technologies have been developed to address barriers to effective HIV prevention, testing, and treatment. Because most people living with HIV and AIDS reside in resource-limited settings (RLS), it is important to understand the development and use of these technologies in RLS. Recent research on cell phone-based technologies has focused on HIV education, linkage to and retention in care, disease tracking, and antiretroviral therapy adherence reminders. Advances in adherence devices have focused on real-time adherence monitors, which have been used for both antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has recently been combined with cell phone-based technologies to create real-time adherence interventions using short message service (SMS). New developments in adherence technologies are exploring ingestion monitoring and metabolite detection to confirm adherence. This article provides an overview of recent advances in these two families of technologies and includes research on their acceptability and cost-effectiveness when available. It additionally outlines key challenges and needed research as use of these technologies continues to expand and evolve. C1 [Campbell, Jeffrey I.; Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Campbell, Jeffrey I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Haberer, JE (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 125 Nashua St,Suite 722, Boston, MA 02114 USA. EM jhaberer@mgh.harvard.edu RI Emchi, Karma/Q-1952-2016 FU NIH [R21AI108329, R34H100940] FX This study was supported from NIH grant numbers R21AI108329, R34H100940. NR 62 TC 1 Z9 1 U1 2 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD DEC PY 2015 VL 12 IS 4 BP 523 EP 531 DI 10.1007/s11904-015-0282-8 PG 9 WC Infectious Diseases SC Infectious Diseases GA CW4PB UT WOS:000364972500016 PM 26439917 ER PT J AU Meulstee, M Whittemore, R Watts, SA AF Meulstee, Maud Whittemore, Robin Watts, Sharon A. TI Development of an Educational Program on Prevention of Hypoglycemic Events Among Elderly Veterans With Type 2 Diabetes SO DIABETES EDUCATOR LA English DT Article ID CRITICALLY-ILL PATIENTS; GLUCOSE CONTROL; ENDOCRINE-SOCIETY; GLYCEMIC CONTROL; HYPERGLYCEMIA; ASSOCIATION; MANAGEMENT; MORTALITY; KNOWLEDGE; OUTCOMES AB Purpose The purpose of this project was to develop an evidence-based educational program to reduce hypogly-cemic events in elderly veterans with type 2 diabetes mellitus who are enrolled in the Veterans Healthcare Administration system. Updated guidelines have emphasized the importance of hypoglycemia prevention, and they recommend individualized and less stringent glycemic control. Methods A comprehensive literature review was conducted, which led to the development of evidence-based content for an educational program. Several categories and subcategories of content were identified and subsequently evaluated by a panel of experts in the field of diabetes management. Results Experts were unanimous on the importance and relevance of the categories and provided insight into the priority of subcategories of content. Results Experts were unanimous on the importance and relevance of the categories and provided insight into the priority of subcategories of content. [GRAPHICS] Conclusions Developing an evidence-based educational program for health care providers on prevention of hypoglycemia has important clinical implications. Diabetes educators can use the topical outline for patient and family teaching. This project may also serve as an example for diabetes educators on developing evidence-based educational programs. C1 [Whittemore, Robin] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Watts, Sharon A.] Cleveland VA Med Ctr, Vet Healthcare Adm, Cleveland, OH USA. [Meulstee, Maud] Vet Healthcare Adm, Boston, MA USA. RP Meulstee, M (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM maud.meulstee@yale.edu FU Yale University School of Nursing; Boston Veterans Healthcare Administration; Yale School of Nursing Capstone Committee; Yale librarian FX We thank the Yale University School of Nursing and Boston Veterans Healthcare Administration for their support. We also wish to thank the Yale School of Nursing Capstone Committee and Yale librarian for their support and scholarly expertise. The expert panel contributed significantly to this project: Dr P. R. Conlin (chief of medical service at VA Boston Healthcare System and professor of medicine at Harvard Medical School), Dr L. Haas (endocrinology clinical nurse specialist at VA Puget Sound Healthcare System and former president of the American Diabetes Association), Dr E. S. Huang (associate professor of medicine and director of the Center for Translational and Policy Research of Chronic Diseases, University of Chicago),; Dr V. Jefferson (lecturer diabetes concentration, at the Yale University School of Nursing and diabetes educator at the Yale University Health Center), and Dr M. Munshi (director of Joslin Geriatric Diabetes Program and assistant professor of medicine at Harvard Medical School). We thank Dr T. Parrino at the VA Boston Healthcare System for his continued support. NR 50 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 EI 1554-6063 J9 DIABETES EDUCATOR JI Diabetes Educ. PD DEC PY 2015 VL 41 IS 6 BP 690 EP 697 DI 10.1177/0145721715606805 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA CW8LS UT WOS:000365251700003 PM 26450221 ER PT J AU Lo Gullo, R Mishra, S Lira, DA Padole, A Otrakji, A Khawaja, RDA Pourjabbar, S Singh, S Shepard, JAO Digumarthy, SR Kalra, MK Stone, JR AF Lo Gullo, Roberto Mishra, Shelly Lira, Diego A. Padole, Atul Otrakji, Alexi Khawaja, Ranish Deedar Ali Pourjabbar, Sarvenaz Singh, Sarabjeet Shepard, Jo-Anne O. Digumarthy, Subba R. Kalra, Mannudeep K. Stone, James R. TI Quantification of interstitial fluid on whole body CT: comparison with whole body autopsy SO FORENSIC SCIENCE MEDICINE AND PATHOLOGY LA English DT Article DE Third space fluid overload; Anasarca; Whole-body CT; Virtual autopsy; Postmortem CT ID CRITICALLY-ILL PATIENTS; ACUTE KIDNEY INJURY; PLEURAL EFFUSION; OVERLOAD; BALANCE; SURVIVAL; VOLUME; MANAGEMENT; DIAGNOSIS AB Interstitial fluid accumulation can occur in pleural, pericardial, and peritoneal spaces, and subcutaneous tissue planes. The purpose of the study was to assess if whole body CT examination in a postmortem setting could help determine the presence and severity of third space fluid accumulation in the body. Our study included 41 human cadavers (mean age 61 years, 25 males and 16 females) who had whole-body postmortem CT prior to autopsy. All bodies were maintained in the morgue in the time interval between death and autopsy. Two radiologists reviewed the whole-body CT examinations independently to grade third space fluid in the pleura, pericardium, peritoneum, and subcutaneous space using a 5-point grading system. Qualitative CT grading for third space fluid was correlated with the amount of fluid found on autopsy and the quantitative CT fluid volume, estimated using a dedicated software program (Volume, Syngo Explorer, Siemens Healthcare). Moderate and severe peripheral edema was seen in 16/41 and 7/41 cadavers respectively. It is not possible to quantify anasarca at autopsy. Correlation between imaging data for third space fluid and the quantity of fluid found during autopsy was 0.83 for pleural effusion, 0.4 for pericardial effusion and 0.9 for ascites. The degree of anasarca was significantly correlated with the severity of ascites (p < 0.0001) but not with pleural or pericardial effusion. There was strong correlation between volumetric estimation and qualitative grading for anasarca (p < 0.0001) and pleural effusion (p < 0.0001). Postmortem CT can help in accurate detection and quantification of third space fluid accumulation. The quantity of ascitic fluid on postmortem CT can predict the extent of anasarca. C1 [Lo Gullo, Roberto; Mishra, Shelly; Lira, Diego A.; Padole, Atul; Otrakji, Alexi; Khawaja, Ranish Deedar Ali; Pourjabbar, Sarvenaz; Singh, Sarabjeet; Shepard, Jo-Anne O.; Digumarthy, Subba R.; Kalra, Mannudeep K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Lo Gullo, Roberto] Univ Milan, Sch Med, Dept Radiol, Milan, Italy. [Stone, James R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Lo Gullo, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM robertologullo@yahoo.it NR 25 TC 1 Z9 1 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1547-769X EI 1556-2891 J9 FORENSIC SCI MED PAT JI Forensic Sci. Med. Pathol. PD DEC PY 2015 VL 11 IS 4 BP 488 EP 496 DI 10.1007/s12024-015-9728-y PG 9 WC Medicine, Legal; Pathology SC Legal Medicine; Pathology GA CW7GZ UT WOS:000365167500003 PM 26541472 ER PT J AU Tabansky, I Messina, MD Bangeranye, C Goldstein, J Blitz-Shabbir, KM Machado, S Jeganathan, V Wright, P Najjar, S Cao, YH Sands, W Keskin, DB Stern, JNH AF Tabansky, Inna Messina, Mark D. Bangeranye, Catherine Goldstein, Jeffrey Blitz-Shabbir, Karen M. Machado, Suly Jeganathan, Venkatesh Wright, Paul Najjar, Souhel Cao, Yonghao Sands, Warren Keskin, Derin B. Stern, Joel N. H. TI Advancing drug delivery systems for the treatment of multiple sclerosis SO IMMUNOLOGIC RESEARCH LA English DT Article DE Drug delivery systems; Multiple sclerosis; Microparticles; Fusion antibodies ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DISEASE-MODIFYING THERAPIES; TARGETING DENDRITIC CELLS; REGULATORY T-CELLS; IN-VIVO; MONOCLONAL-ANTIBODY; GLATIRAMER ACETATE; INTERFERON-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; INTRACEREBRAL RECRUITMENT AB Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge. C1 [Tabansky, Inna; Stern, Joel N. H.] Rockefeller Univ, Dept Neurobiol & Behav, New York, NY 10021 USA. [Messina, Mark D.; Goldstein, Jeffrey; Blitz-Shabbir, Karen M.; Machado, Suly; Wright, Paul; Najjar, Souhel; Stern, Joel N. H.] Hofstra North Shore LIJ Sch Med, Dept Neurol, Hempstead, NY USA. [Messina, Mark D.; Bangeranye, Catherine; Goldstein, Jeffrey; Machado, Suly; Stern, Joel N. H.] Hofstra North Shore LIJ Sch Med, Dept Sci Educ, Hempstead, NY USA. [Jeganathan, Venkatesh; Cao, Yonghao; Stern, Joel N. H.] Feinstein Inst Med Res, Dept Autoimmun, North Shore LIJ Hlth Syst, Manhasset, NY USA. [Sands, Warren] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Sands, Warren] Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA. [Keskin, Derin B.] Dana Farber Harvard Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. RP Stern, JNH (reprint author), Rockefeller Univ, Dept Neurobiol & Behav, 1230 York Ave, New York, NY 10021 USA. EM jstern01@rockefeller.edu FU Bristol Myers Squibb Postdoctoral Fellowship; NIH [F32 HD081835]; Cheryl Manne Fund; HT Langbert Charitable Trust Research Fund FX We are very grateful to Leah Messina of Approach Positive Marketing for designing Figs. 1, 2, and 3 within this review. I.T. was funded by the Bristol Myers Squibb Postdoctoral Fellowship and by NIH F32 HD081835. M.M was supported by a fellowship from the Cheryl Manne Fund for the Cure of MS. J.N.H.S was funded by a grant from the HT Langbert Charitable Trust Research Fund. P.W., K.B.S., M.M., and J.N.H.S. are associates of the Northeast NMO Consortium. We also thank Marlena Kern and Gila Klein for their assistance. NR 101 TC 3 Z9 3 U1 1 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X EI 1559-0755 J9 IMMUNOL RES JI Immunol. Res. PD DEC PY 2015 VL 63 IS 1-3 SI SI BP 58 EP 69 DI 10.1007/s12026-015-8719-0 PG 12 WC Immunology SC Immunology GA CW7HH UT WOS:000365168300007 PM 26475738 ER PT J AU Minami, Y Phipps, JE Hoyt, T Milner, TE Ong, DS Soeda, T Vergallo, R Feldman, MD Jang, IK AF Minami, Yoshiyasu Phipps, Jennifer E. Hoyt, Taylor Milner, Thomas E. Ong, Daniel S. Soeda, Tsunenari Vergallo, Rocco Feldman, Marc D. Jang, Ik-Kyung TI Clinical utility of quantitative bright spots analysis in patients with acute coronary syndrome: an optical coherence tomography study SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Optical coherence tomography; Acute coronary syndrome; Stable coronary artery disease; Plaque rupture ID PLAQUE RUPTURE; ATHEROSCLEROTIC PLAQUES; VULNERABLE PLAQUE; FIBROUS CAPS; INFLAMMATION; MACROPHAGES; EROSION; LESIONS; OCT AB To investigate the clinical significance of bright spots in coronary plaque detected by optical coherence tomography (OCT) in patients with coronary artery disease. We identified 112 patients [acute coronary syndromes (ACS): n = 50, stable angina pectoris (SAP): n = 62] who underwent OCT imaging of the culprit lesion. A novel OCT algorithm was applied to detect bright spots representing the juxtaposition of a variety of plaque components including macrophages. The density of bright spots within the most superficial 250 mu m of the vessel wall was measured at the site of culprit lesion. Bright spot density in the culprit lesion was significantly higher in patients presenting with ACS compared to those presenting with SAP (0.51 +/- 0.43 % vs. 0.37 +/- 0.26 %, P = 0.04), particularly in the subgroup with ruptured culprit plaque (0.59 +/- 0.52 %). Thin-cap fibroatheroma (TCFA) was associated with a trend towards a higher density of bright spots compared to non-TCFA plaques (0.57 +/- 0.50 % vs. 0.41 +/- 0.31 %, P = 0.08). Similar results were also obtained within 1000 mu m depth. Positive linear correlation was demonstrated between bright spot density and hsCRP level (r = 0.45, P = 0.002). Using a novel algorithm, we demonstrated a significantly higher density of bright spots in the culprit lesions of patients presenting with ACS, particularly in case of plaque rupture, compared to those presenting with SAP. The density of bright spots also correlates with inflammatory status. These results suggest that the quantitative assessment of bright spot density may be useful in evaluating plaque vulnerability. C1 [Minami, Yoshiyasu; Ong, Daniel S.; Soeda, Tsunenari; Vergallo, Rocco; Jang, Ik-Kyung] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Phipps, Jennifer E.; Hoyt, Taylor; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Feldman, Marc D.] Vet Adm Hlth Care Syst, San Antonio, TX 78229 USA. [Jang, Ik-Kyung] Kyung Hee Univ, Div Cardiol, Seoul 130701, South Korea. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM IJANG@mgh.harvard.edu FU St. Jude Medical, Medtronic Corporation; Boston Scientific Corporation; Veterans Administration Merit Grant [I01 BX000397]; American Heart Association Grant [13POST17080074]; Clayton Foundation in Houston, Texas FX This study is supported by St. Jude Medical, Medtronic Corporation, Boston Scientific Corporation, Mr. and Mrs. Michael Park and Dr John Nam, Clayton Foundation in Houston, Texas, Veterans Administration Merit Grant I01 BX000397, and American Heart Association Grant 13POST17080074. NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD DEC PY 2015 VL 31 IS 8 BP 1479 EP 1487 DI 10.1007/s10554-015-0714-y PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CW9BS UT WOS:000365293900001 PM 26202158 ER PT J AU Dimitriou, D Tsai, TY Kwon, YM AF Dimitriou, Dimitris Tsai, Tsung-Yuan Kwon, Young-Min TI The effect of femoral neck osteotomy on femoral component position of a primary cementless total hip arthroplasty SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Total hip arthroplasty; Components positioning; Femoral anteversion; Offset ID IMPINGEMENT; ANTEVERSION; ORIENTATION; PLACEMENT; IMPLANT; MOTION; FEMUR AB Purpose The aim of this study was to quantify the femoral canal diameter and version at different femoral neck osteotomy locations, and to investigate the effect of the osteotomy plane on femoral component position in total hip arthroplasty (THA). Methods Preoperative and postoperative three-dimensional models were reconstructed in 15 patients (19 hips) who underwent primary cementless THA with tapered non-anatomical femoral stem. On the pre-operative models, the osteotomy plane was simulated at different levels (-5, 0, 5, and 10 mm from the femoral saddle [piriformis fossa]) and angles (30, 40, 50, and 60 degrees from the femoral anatomical axis). Medullary canal version and mediolateral diameter were measured on the osteotomy surfaces. On the postoperative models, the femoral neck osteotomy plane, stem anteversion and alignment were measured. Results The average canal diameter ranged from 22.8 to 26.3 mm at different osteotomy levels and from 20.8 to 29.0 mm at different osteotomy angles. The average canal version ranged from 11.4 to 23.2 degrees at different resection levels and from 12.8 to 21 degrees at different resection angles. The femoral stem anteversion was correlated with neck osteotomy angle (R = 0.72), whereas stem alignment in frontal plane (varus/valgus) was correlated with neck osteotomy level (R = 0.87). Conclusions The femoral neck osteotomy plane in THA affects the postoperative stem position due to the complex morphology of the proximal femoral medullary canal, suggesting that both femoral neck resection level and angle should be considered in optimizing femoral component alignment in THA patients. C1 [Dimitriou, Dimitris; Tsai, Tsung-Yuan; Kwon, Young-Min] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Dimitriou, Dimitris; Tsai, Tsung-Yuan; Kwon, Young-Min] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM ymkwon@mgh.harvard.edu OI Tsai, Tsung-Yuan/0000-0003-1522-2987; Dimitriou, Dimitris/0000-0002-9558-7080 FU Department of Orthopaedic Surgery, MGH/MAKO Surgical Corp., Davie Road, Ft. Lauderdale FX Department of Orthopaedic Surgery, MGH/MAKO Surgical Corp., 2555 Davie Road, Ft. Lauderdale, FL 33317. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD DEC PY 2015 VL 39 IS 12 BP 2315 EP 2321 DI 10.1007/s00264-015-2739-1 PG 7 WC Orthopedics SC Orthopedics GA CW7ME UT WOS:000365182500002 PM 25787684 ER PT J AU Abdullah, KG Lubelski, D Miller, J Steinmetz, MP Shin, JH Krishnaney, A Mroz, TE Benzel, EC AF Abdullah, Kalil G. Lubelski, Daniel Miller, Jacob Steinmetz, Michael P. Shin, John H. Krishnaney, Ajit Mroz, Thomas E. Benzel, Edward C. TI Progression free survival and functional outcome after surgical resection of intramedullary ependymomas SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Ependymoma; Intramedullary; Oncology; Spine tumor ID SPINAL-CORD TUMORS; RESECTABILITY; ASTROCYTOMAS; EXPERIENCE; MORBIDITY; ADULTS AB We present a 15 year institutional analysis of the factors affecting progression free survival (PFS) and overall survival (OS) in patients undergoing attempted resection of adult intramedullary spinal cord ependymomas. Intramedullary spinal cord tumors are rare but important clinical entities, and ependymomas are the most commonly encountered intramedullary tumor. In total, 53 adult patients over the span of 15 years were analyzed for OS, PFS, and the effects of plane of dissection (POD) and gross total resection (GTR) on functional and long term outcomes. The mean age was 45 years and median follow-up was 54 months. The follow-up neurological outcome and modified McCormick scale were used to determine the functional outcome. Kaplan-Meier curves were used to calculate progression and survival. The overall ability to achieve GTR was significantly correlated to identification of an intraoperative POD (p < 0.001). There was a trend towards increased PFS with the ability to achieve a GTR. There was no significant difference in the pre- and postoperative functional outcome scores. The ability to achieve a GTR is strongly correlated to the identification of a POD in ependymomas. There is a trend towards an increased probability of PFS in intramedullary spinal cord tumors when GTR is achieved. The resection of these tumors is likely to halt, but not reverse, neurological deterioration. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Abdullah, Kalil G.] Hosp Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Lubelski, Daniel; Krishnaney, Ajit; Mroz, Thomas E.; Benzel, Edward C.] Cleveland Clin, Ctr Spine Hlth, Dept Neurol Surg, Cleveland, OH 44106 USA. [Miller, Jacob] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. [Steinmetz, Michael P.] Case Western Reserve Univ, Sch Med, Dept Neurol Surg, MetroHlth Med Ctr, Cleveland, OH USA. [Shin, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Abdullah, KG (reprint author), Hosp Univ Penn, Dept Neurosurg, Third Floor Silverstein,3400 Spruce St, Philadelphia, PA 19104 USA. EM Kalil.Abdullah@uphs.upenn.edu OI Shin, John/0000-0001-7490-8108 NR 21 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2015 VL 22 IS 12 BP 1933 EP 1937 DI 10.1016/j.jocn.2015.06.017 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX0EV UT WOS:000365370600016 PM 26234635 ER PT J AU Kumar, JI Yanamadala, V Shin, JH AF Kumar, Jay I. Yanamadala, Vijay Shin, John H. TI Intramedullary spinal metastasis of a carcinoid tumor SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Carcinoid tumor; Central nervous system; Intramedullary spinal metastasis; Metastasis ID EPIDEMIOLOGY AB We report an intramedullary spinal cord metastasis from a bronchial carcinoid, and discuss its mechanisms and management. Intramedullary spinal cord metastases from any cancer are rare, and bronchial carcinoids account for only a small fraction of lung cancers. To our knowledge, an intramedullary spinal cord metastasis from a bronchial carcinoid has been described only once previously. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Yanamadala, Vijay] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yanamadala, V (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,WACC 021, Boston, MA 02115 USA. EM vyanamadala@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD DEC PY 2015 VL 22 IS 12 BP 1990 EP 1991 DI 10.1016/j.jocn.2015.07.002 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CX0EV UT WOS:000365370600033 PM 26260116 ER PT J AU Rittling, SR Singh, R AF Rittling, S. R. Singh, R. TI Osteopontin in Immune-mediated Diseases SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE immunity; Th17; B cells; autoimmunity; integrins; OPN ID INFLAMMATORY-BOWEL-DISEASE; ALCOHOLIC LIVER-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTESTINAL INFLAMMATION; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; CROHNS-DISEASE; POSTTRANSLATIONAL MODIFICATIONS; PLASMA OSTEOPONTIN AB Since its initial identification as one of the genes most highly upregulated upon T-cell activation, osteopontin (or Eta-1, as it was designated then) has been demonstrated to have many roles in the regulation of the immune response on multiple levels. It contributes to the development of immune-mediated and inflammatory diseases, and it regulates the host response to infection. In some cases, the mechanisms of these effects have been elucidated, while other mechanistic functions of the protein remain obscure. The protein itself makes these analyses complex, since it binds to a series of different integrins, and in addition to its classically secreted form, an intracellular form of osteopontin has been identified, which participates in several aspects of immune regulation. In this review, we focus on the role of osteopontin in a series of immune-related diseases, particularly those where significant advances have been made in recent years: multiple sclerosis, rheumatoid arthritis, lupus and related diseases, Sjgren's disease, colitis, and 1 area of inflammatory pathology, alcoholic and nonalcoholic liver diseases. A recurring theme in these diseases is a link between osteopontin and pathogenic T cells, particularly T helper 17 cells, where osteopontin produced by dendritic cells supports IL-17 expression, contributing to pathology. In addition, a role for osteopontin in B-cell differentiation is becoming clear. In general, osteopontin contributes to pathology in these diseases, but there are examples where it has a protective role; deciphering the mechanisms underlying these differences and the specific receptors for osteopontin will be a research challenge for the future. Aside from its newly discovered role in the development of Sjgren's disease, the role of osteopontin in inflammatory conditions in the oral cavity is still poorly understood. Elucidation of this role will be of interest. C1 [Rittling, S. R.; Singh, R.] Forsyth Inst, Cambridge, MA USA. [Rittling, S. R.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Rittling, SR (reprint author), 245 First St, Cambridge, MA 02142 USA. EM srittling@forsyth.org FU National Institute of Dental and Craniofacial Diseases of the National Institutes of Health [R01DE22380] FX This work was supported by the National Institute of Dental and Craniofacial Diseases of the National Institutes of Health (R01DE22380). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 60 TC 13 Z9 13 U1 0 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2015 VL 94 IS 12 BP 1638 EP 1645 DI 10.1177/0022034515605270 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CW9QX UT WOS:000365334400003 PM 26341976 ER PT J AU Rastan, A McKinsey, JF Garcia, LA Rocha-Singh, KJ Jaff, MR Noory, E Zeller, T AF Rastan, Aljoscha McKinsey, James F. Garcia, Lawrence A. Rocha-Singh, Krishna J. Jaff, Michael R. Noory, Elias Zeller, Thomas CA DEFINITIVE LE Investigators TI One-Year Outcomes Following Directional Atherectomy of Infrapopliteal Artery Lesions: Subgroup Results of the Prospective, Multicenter DEFINITIVE LE Trial SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE angioplasty; atherectomy; claudication; critical limb ischemia; infrapopliteal arteries; peripheral artery disease; tibial artery; peroneal artery; patency; restenosis ID SIROLIMUS-ELUTING STENTS; CRITICAL LIMB ISCHEMIA; BARE-METAL STENTS; ANGIOPLASTY; SILVERHAWK; DISEASE AB Purpose: To report a subgroup analysis of the prospective, multicenter, single-arm DEFINITIVE LE trial to assess the effectiveness of directional atherectomy for the treatment of infrapopliteal artery lesions at 1 year. Methods: In the DEFINITIVE LE trial, follow-up assessments occurred up to 1 year postprocedure. Of the 800 patients enrolled, 145 subjects with 189 infrapopliteal lesions met the criteria for this analysis. Seventy (48.3%) and 75 (51.7%) patients were suffering critical limb ischemia (CLI) and intermittent claudication, respectively; 68.3% (99/145) had diabetes. The mean lesion length was 58 +/- 44 mm (all lesions); 20.2% were occluded. The primary endpoint for patients with claudication was duplex ultrasound-derived primary patency, while for subjects with CLI it was freedom from major amputation of the target limb at 1 year. Endpoints and adverse events were independently assessed. Results: Procedure success (30% residual stenosis) was achieved in 84% of treated lesions. The 1-year primary patency rate was 84% (claudicants 89.6% and CLI patients 78%, p=0.11), and the freedom from major amputation rate was 97.1% (claudicants 100% and CLI 93.8%, p=0.03). In both claudication and CLI patients, significant improvements in Rutherford category and objective measures of walking distance and quality of life were seen at 1 year in comparison to baseline. Conclusion: This study demonstrates that directional atherectomy in infrapopliteal arteries results in promising technical and clinical results at 1 year for claudicant as well as CLI patients. C1 [Rastan, Aljoscha; Noory, Elias; Zeller, Thomas] Univ Herzzentrum Freiburg Bad Krozingen, Kardiol & Angiol 2, D-79189 Bad Krozingen, Germany. [McKinsey, James F.] Univ Hosp Columbia & Cornell, New York Presbyterian Hosp, Div Vasc Surg, New York, NY USA. [Garcia, Lawrence A.] Tufts Univ, Sch Med, Sect Intervent Cardiol, St Elizabeths Med Ctr, Boston, MA 02111 USA. [Garcia, Lawrence A.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Vasc Med, Boston, MA 02111 USA. [Rocha-Singh, Krishna J.] St Johns Hosp, Prairie Heart Inst, Springfield, IL USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Rastan, A (reprint author), Univ Herzzentrum Freiburg Bad Krozingen, Abt Kardiol & Angiol 2, Sudring 15, D-79189 Bad Krozingen, Germany. EM aljoscha.rastan@universitaets-herzzentrum.de FU Covidien FX The author(s) report receiving the following financial support for the research, authorship, and/or publication of this article: This work was supported by Covidien. NR 12 TC 2 Z9 2 U1 3 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1526-6028 EI 1545-1550 J9 J ENDOVASC THER JI J. Endovascular Ther. PD DEC PY 2015 VL 22 IS 6 BP 839 EP 846 DI 10.1177/1526602815608610 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CW9JP UT WOS:000365315300001 PM 26445814 ER PT J AU Fedorenko, IV Wargo, JA Flaherty, KT Messina, JL Smalley, KSM AF Fedorenko, Inna V. Wargo, Jennifer A. Flaherty, Keith T. Messina, Jane L. Smalley, Keiran S. M. TI BRAF Inhibition Generates a Host-Tumor Niche that Mediates Therapeutic Escape SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID RESISTANCE CAM-DR; FOCAL ADHESION KINASE; MELANOMA-CELLS; RAF INHIBITORS; STROMAL FIBROBLASTS; BINDING DOMAINS; UP-REGULATION; GROWTH; FIBRONECTIN; SURVIVAL AB The current study defines a fibroblast-derived niche that facilitates the therapeutic escape of melanoma cells from BRAF inhibition. Vemurafenib treatment led to the release of transforming growth factor-beta (TGF-beta) from the melanoma cells that increased the differentiation state of the fibroblasts, an affect associated with fibronectin deposition, increase in a-smooth muscle actin expression, and the release of neuregulin (NRG). At the same time, vemurafenib directly activated the fibroblasts through paradoxical stimulation of the mitogen-activated protein kinase pathway, causing them to secrete hepatocyte growth factor (HGF). Treatment with the BRAF/MEK inhibitor combination reversed the release of HGF. Adhesion of melanoma cells to fibronectin was critical in amplifying the fibroblast-derived NRG- and HGF-mediated PI3K/AKT (phosphatidylinositol 3'-kinase/AKT) survival signaling in the melanoma cells following BRAF inhibition. In coculture studies, combination treatment with inhibitors of BRAF/MET/HER kinase was ineffective at reversing the fibroblast-mediated therapeutic escape from BRAF inhibition. Instead, it was noted that combined BRAF/PI3K inhibition overcame fibroblast-mediated drug resistance in vitro and was associated with enhanced antitumor effects in an in vivo xenograft model. Thus, we show that melanoma cells and fibroblasts remodel their microenvironment in response to BRAF inhibition and that these adaptations allow tumor cells to evade therapy through increased PI3K/AKT survival signaling. C1 [Fedorenko, Inna V.; Smalley, Keiran S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL 33612 USA. [Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Messina, Jane L.; Smalley, Keiran S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA. RP Smalley, KSM (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM keiran.smalley@moffitt.org FU National Institutes of Health [R01 CA161107]; [P30-CA076292] FX Work in the Smalley lab is supported by R01 CA161107 from the National Institutes of Health with Core Support provided by P30-CA076292. NR 39 TC 11 Z9 11 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2015 VL 135 IS 12 BP 3115 EP 3124 DI 10.1038/jid.2015.329 PG 10 WC Dermatology SC Dermatology GA CW7LT UT WOS:000365181100031 PM 26302068 ER PT J AU Ragel, BT Ryken, TC Kalkanis, SN Ziu, M Cahill, D Olson, JJ AF Ragel, Brian T. Ryken, Timothy C. Kalkanis, Steven N. Ziu, Mateo Cahill, Daniel Olson, Jeffrey J. TI The role of biopsy in the management of patients with presumed diffuse low grade glioma A systematic review and evidence-based clinical practice guideline SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Low-grade glioma; Guidelines; Biopsy; Stereotactic biopsy ID STEREOTACTIC BRAIN BIOPSY; POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSTIC YIELD; TUMOR-BIOPSIES; FET PET; FRAMELESS; COMPLICATIONS; LESIONS; EXPERIENCE; ACCURACY AB What is the optimal role of biopsy in the initial management of presumptive low-grade glioma in adults? Adult patients with imaging suggestive of a low-grade glioma. Stereotactic biopsy is recommended when definitive surgical resection is limited by lesions that are deep-seated, not resectable, and/or located within eloquent cortex, or in patients unable to undergo craniotomy due to medical co-morbidities to obtain the critical tissue diagnosis needed for targeted treatment planning for patients with low-grade gliomas. What is the best technique for brain biopsy? Adult patients with imaging suggestive of a low-grade glioma. Frameless and frame-based stereotactic brain biopsy for low-grade gliomas are recommended based on clinical circumstances as they provide similar diagnostic yield, diagnostic accuracy, morbidity, and mortality. It is recommended the surgeon consider advanced imaging techniques (e.g., perfusion, spectroscopy, metabolic studies) to target specific regions of interest to potentially improve diagnostic accuracy. C1 [Ragel, Brian T.] Rebound Orthoped & Neurosurg, Vancouver, WA 98664 USA. [Ryken, Timothy C.] Univ Kansas, Med Ctr, Dept Neurosurg, Kansas City, KS 66103 USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Ziu, Mateo] Seton Brain & Spine Inst, Dept Neurosurg, Austin, TX USA. [Cahill, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Olson, Jeffrey J.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA USA. RP Ragel, BT (reprint author), Rebound Orthoped & Neurosurg, 200 NE Mother Joseph Pl,Suite 210, Vancouver, WA 98664 USA. EM brian.ragel@gmail.com OI Ziu, Mateo/0000-0002-3671-2638; Cahill, Daniel/0000-0003-2552-6546 FU National Cancer Institute; Genentech; Millenium FX Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millenium; and has received investigational drug provision from Merck. NR 65 TC 1 Z9 1 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2015 VL 125 IS 3 SI SI BP 481 EP 501 DI 10.1007/s11060-015-1866-2 PG 21 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CX0XD UT WOS:000365419800004 PM 26530259 ER PT J AU Aghi, MK Nahed, BV Sloan, AE Ryken, TC Kalkanis, SN Olson, JJ AF Aghi, Manish K. Nahed, Brian V. Sloan, Andrew E. Ryken, Timothy C. Kalkanis, Steven N. Olson, Jeffrey J. TI The role of surgery in the management of patients with diffuse low grade glioma A systematic review and evidence-based clinical practice guideline SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Low grade glioma; Astrocytoma; Oligodendroglioma; Surgery; Observation; Systematic review; Practice guideline ID PROGNOSTIC-FACTORS; II GLIOMAS; SURGICAL RESECTION; RADIATION-THERAPY; NATURAL-HISTORY; ELOQUENT AREAS; ADULT PATIENTS; SUPRATENTORIAL ASTROCYTOMAS; SINGLE-INSTITUTION; RANDOMIZED-TRIAL AB Should patients with imaging suggestive of low grade glioma (LGG) undergo observation versus treatment involving a surgical procedure? These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma). Surgical resection is recommended over observation to improve overall survival for patients with diffuse low-grade glioma (Level III) although observation has no negative impact on cognitive performance and quality of life (Level II). What is the impact of extent of resection on progression free survival (PFS) or overall survival (OS) in LGG patients? These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma). It is recommended that GTR or STR be accomplished instead of biopsy alone when safe and feasible so as to decrease the frequency of tumor progression recognizing that the rate of progression after GTR is fairly high. Greater extent of resection can improve OS in LGG patients. What tools are available to increase extent of resection in LGG patients? These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma). The use of intraoperative MRI should be considered as a method of increasing the extent of resection of LGGs. What is the impact of surgical resection on seizure control and accuracy of pathology in low grade glioma patients? These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma). After taking into account the patient's clinical status and tumor location, gross total resection is recommended for patients with diffuse LGG as a way to achieve more favorable seizure control. Taking into account the patient's clinical status and tumor location, surgical resection should be carried out to maximize the chance of accurate diagnosis. What tools can improve the safety of surgery for LGGs in eloquent locations? These recommendations apply to adults with imaging suggestive of a WHO grade 2 glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma). It is recommended that preoperative functional MRI and diffusion tensor imaging be utilized in the appropriate clinical setting to improve functional outcome after surgery for LGG. Intraoperative mapping is recommended for patients with diffuse LGGs in eloquent locations compared to patients with non-eloquently located diffuse LGGs as a way of preserving function. C1 [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sloan, Andrew E.] Univ Hosp Cleveland, Dept Neurosurg, Cleveland, OH 44106 USA. [Ryken, Timothy C.] Univ Kansas, Med Ctr, Dept Neurosurg, Kansas City, KS 66103 USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Olson, Jeffrey J.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA USA. RP Aghi, MK (reprint author), Univ Calif San Francisco, Dept Neurosurg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA. EM aghim@neurosurg.ucsf.edu FU National Cancer Institute; Genentech; Millenium FX Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millenium; and has received investigational drug provision from Merck. NR 68 TC 6 Z9 8 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2015 VL 125 IS 3 SI SI BP 503 EP 530 DI 10.1007/s11060-015-1867-1 PG 28 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CX0XD UT WOS:000365419800005 PM 26530265 ER PT J AU Cahill, DP Sloan, AE Nahed, BV Aldape, KD Louis, DN Ryken, TC Kalkanis, SN Olson, JJ AF Cahill, Daniel P. Sloan, Andrew E. Nahed, Brian V. Aldape, Kenneth D. Louis, David N. Ryken, Timothy C. Kalkanis, Steven N. Olson, Jeffrey J. TI The role of neuropathology in the management of patients with diffuse low grade glioma A systematic review and evidence-based clinical practice guideline SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Astrocytoma; Oligodendroglioma; Low-grade diffuse glioma; Isocitrate dehydrogenase (IDH1, IDH2); 1p/19q loss-of-heterozygosity; Methyl-guanine methyl-transferase (MGMT); Ki67/MIB1 ID CENTRAL-NERVOUS-SYSTEM; MAGNETIC-RESONANCE-SPECTROSCOPY; STEREOTAXIC BRAIN BIOPSIES; MOLECULAR-GENETIC ANALYSIS; FROZEN SECTION DIAGNOSIS; KI-67 LABELING INDEXES; CODON 132 MUTATION; DNA-REPAIR GENE; IDH1 MUTATIONS; OLIGODENDROGLIAL TUMORS AB Adult patients (age a parts per thousand yen18 years) who have suspected low-grade diffuse glioma. What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult? Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma. Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis. A resection specimen is preferred over a biopsy specimen, to minimize the potential for sampling error issues. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age a parts per thousand yen18 years) with histologically-proven WHO grade II diffuse glioma, is testing for IDH1 mutation (R132H and/or others) warranted? If so, is there a preferred method? IDH gene mutation assessment, via IDH1 R132H antibody and/or IDH1/2 mutation hotspot sequencing, is highly-specific for low-grade diffuse glioma, and is recommended as an additional test for classification and prognosis. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age a parts per thousand yen18 years) with histologically-proven WHO grade II diffuse glioma, is testing for 1p/19q loss warranted? If so, is there a preferred method? 1p/19q loss-of-heterozygosity testing, by FISH, array-CGH or PCR, is recommended as an additional test in oligodendroglial cases for prognosis and potential treatment planning. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age a parts per thousand yen18 years) with histologically-proven WHO grade II diffuse glioma, is MGMT promoter methylation testing warranted? If so, is there a preferred method? There is insufficient evidence to recommend methyl-guanine methyl-transferase (MGMT) promoter methylation testing as a routine for low-grade diffuse gliomas. It is recommended that patients be enrolled in properly designed clinical trials to assess the value of this and related markers for this target population. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age a parts per thousand yen18 years) with histologically-proven WHO grade II diffuse glioma, is Ki-67/MIB1 immunohistochemistry warranted? If so, is there a preferred method to quantitate results? Ki67/MIB1 immunohistochemistry is recommended as an option for prognostic assessment. C1 [Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sloan, Andrew E.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Nahed, Brian V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ryken, Timothy C.] Univ Kansas, Med Ctr, Dept Neurosurg, Kansas City, KS 66103 USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Olson, Jeffrey J.] Emory Clin, Dept Neurosurg, Atlanta, GA 30322 USA. RP Cahill, DP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 32 Fruit St,Yankey 9E, Boston, MA 02114 USA. EM dcahill@partners.org OI Cahill, Daniel/0000-0003-2552-6546 FU National Cancer Institute; Genentech; Millenium FX Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millenium; and has received investigational drug provision from Merck. NR 98 TC 3 Z9 3 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2015 VL 125 IS 3 SI SI BP 531 EP 549 DI 10.1007/s11060-015-1909-8 PG 19 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CX0XD UT WOS:000365419800006 PM 26530263 ER PT J AU Nahed, BV Redjal, N Brat, DJ Chi, AS Oh, K Batchelor, TT Ryken, TC Kalkanis, SN Olson, JJ AF Nahed, Brian V. Redjal, Navid Brat, Daniel J. Chi, Andrew S. Oh, Kevin Batchelor, Tracy T. Ryken, Timothy C. Kalkanis, Steven N. Olson, Jeffrey J. TI Management of patients with recurrence of diffuse low grade glioma A systematic review and evidence-based clinical practice guideline SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Low-grade gliomas; Recurrence; Surgery; Pathology; Chemotherapy; Radiation; Observation ID FRACTIONATED STEREOTACTIC REIRRADIATION; PROGRESSIVE OLIGODENDROGLIAL TUMORS; PHASE-II; VINCRISTINE CHEMOTHERAPY; ASTROCYTOMA PROGRESSION; EUROPEAN-ORGANIZATION; SALVAGE CHEMOTHERAPY; PROGNOSTIC-FACTORS; PCV CHEMOTHERAPY; RANDOMIZED-TRIAL AB These recommendations apply to adult patients with recurrent low-grade glioma (LGG) with initial pathologic diagnosis of a WHO grade II infiltrative glioma (oligodendroglioma, astrocytoma, or oligo-astrocytoma). Do pathologic and molecular characteristics predict outcome/malignant transformation at recurrence? (Level III) IDH mutation status should be determined as LGGs with IDH mutations have a shortened time to recurrence. It is unclear whether knowledge of IDH mutation status provides benefit in predicting time to progression or overall survival. (Level III) TP53 mutations occur early in LGG pathogenesis, remain stable, and are not recommended as a marker of predisposition to malignant transformation at recurrence or other measures of prognosis. (Level III) Assessment of MGMT status is recommended as an adjunct to assessing prognosis as LGGs with MGMT promoter methylation are associated with shorter PFS (in the absence of TMZ) and longer post-recurrence survival (in the presence of TMZ), ultimately producing similar overall survival to LGGs without MGMT methylationThe available retrospective reports are conflicting and comparisons between reports are limited (Level III) Assessment of CDK2NA status is recommended when possible as the loss of expression of the CDK2NA via either methylation or loss of chromosome 9p is associated with malignant progression of LGGs. (Level III) It is recommended that proliferative indices (MIB-1 or BUdR) be measured in LGGs as higher proliferation indices are associated with increased likelihood of recurrence and shorter progression free and overall survival. There is insufficient evidence to make any recommendations. What role does chemotherapy have in LGG recurrence? (Level III) Temozolomide is recommended in the therapy of recurrent LGG as it may improve clinical symptoms. Oligodendrogliomas and tumors with 1p/19q co-deletion may derive the most benefit. (Level III) PCV is recommended in the therapy of LGG at recurrence as it may improve clinical symptoms with the strongest evidence being for oligodendrogliomas. (Level III) Carboplatin is not recommended as there is no significant benefit from carboplatin as single agent therapy for recurrent LGGs. There is insufficient evidence to make any recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess these chemotherapeutic agents. What role does radiation have in LGG recurrence? (Level III) Radiation is recommended at recurrence if there was no previous radiation treatment. (Level III) It is recommended that re-irradiation be considered in the setting of LGG recurrence as it may provide benefit in disease control. There is insufficient evidence to make any specific recommendations. It is recommended that individuals with recurrent LGGs be enrolled in a properly designed clinical trial to assess the role of surgery at recurrence. C1 [Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Redjal, Navid] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Brat, Daniel J.] Emory Univ, Dept Neurosurg, Sch Med, Atlanta, GA USA. [Chi, Andrew S.; Batchelor, Tracy T.] NYU, Laura & Isaac Perlmutter Canc Ctr, Langone Med Ctr, New York, NY USA. [Oh, Kevin] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ryken, Timothy C.] Univ Kansas, Med Ctr, Dept Neurosurg, Kansas City, KS 66103 USA. [Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA. [Olson, Jeffrey J.] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA USA. RP Nahed, BV (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,Wang 745, Boston, MA 02114 USA. EM bnahed@partners.org FU National Cancer Institute; Genentech; Millenium FX Dr. Batchelor is a consultant for EMD-Serono. Dr. Kalkanis is a consultant for Arbor and Varian. Dr. Olson is a consultant for the American Cancer Society; has received research funding from the National Cancer Institute, Genentech, and Millenium; and has received investigational drug provision from Merck. NR 55 TC 4 Z9 4 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2015 VL 125 IS 3 SI SI BP 609 EP 630 DI 10.1007/s11060-015-1910-2 PG 22 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CX0XD UT WOS:000365419800009 PM 26530264 ER PT J AU Dilsizian, V Gewirtz, H Paivanas, N Kitsiou, AN Hage, FG Crone, NE Schwartz, RG AF Dilsizian, Vasken Gewirtz, Henry Paivanas, Nicholas Kitsiou, Anastasia N. Hage, Fadi G. Crone, Nathan E. Schwartz, Ronald G. TI Serious and potentially life threatening complications of cardiac stress testing: Physiological mechanisms and management strategies SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review ID CORONARY-ARTERY-DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; AMERICAN-HEART-ASSOCIATION; MYOCARDIAL BLOOD-FLOW; NEPHROGENIC SYSTEMIC FIBROSIS; POSITRON-EMISSION-TOMOGRAPHY; ADENOSINE RECEPTOR AGONISTS; BUNDLE-BRANCH BLOCK; PROGNOSTIC VALUE; HYPERTROPHIC CARDIOMYOPATHY C1 [Dilsizian, Vasken] Univ Maryland, Dept Diagnost Radiol & Nucl Med, Sch Med, Baltimore, MD 21201 USA. [Gewirtz, Henry] Harvard Univ, Dept Med, Div Cardiol, Massachusetts Gen Hosp,Med Sch, Boston, MA USA. [Paivanas, Nicholas] Univ Rochester, Dept Med, Div Cardiol, Med Ctr, Rochester, NY USA. [Kitsiou, Anastasia N.] Sismanoglio Hosp, Dept Cardiol, Athens, Greece. [Hage, Fadi G.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Crone, Nathan E.] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21218 USA. [Schwartz, Ronald G.] Univ Rochester, Dept Med, Div Cardiol & Imaging Sci Nucl Med, Med Ctr, Rochester, NY USA. RP Dilsizian, V (reprint author), Univ Maryland, Dept Diagnost Radiol & Nucl Med, Sch Med, Baltimore, MD 21201 USA. EM vdilsizian@umm.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas pharmaceutical company FX Dr. Fadi G. Hage has grant support from Astellas pharmaceutical company, and Dr. Ronald G. Schwartz serves as a consultant and is on the speakers bureau of Astellas pharmaceutical company. Other authors have reported nothing to disclose in relation to this topic and review. NR 120 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD DEC PY 2015 VL 22 IS 6 BP 1198 EP 1213 DI 10.1007/s12350-015-0141-4 PG 16 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CW9FD UT WOS:000365303100006 PM 25975944 ER PT J AU Hage, FG Ghimire, G Lester, D Mckay, J Bleich, S El-Hajj, S Iskandrian, AE AF Hage, Fadi G. Ghimire, Gopal Lester, Davis Mckay, Joshua Bleich, Steven El-Hajj, Stephanie Iskandrian, Ami E. TI The prognostic value of regadenoson myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Myocardial perfusion imaging; regadenoson; prognosis; quantitative analysis ID EMISSION COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; ADENOSINE RECEPTOR AGONIST; NUCLEAR CARDIOLOGY; DIAGNOSTIC CATHETERIZATION; HEART-DISEASE; ANGIOGRAPHY; APPROPRIATENESS; SCINTIGRAPHY; TRIAL AB Background. Regadenoson (REGA), a selective adenosine A(2A) receptor agonist, is the most widely used stress agent for SPECT myocardial perfusion imaging (MPI) in the United States. The diagnostic accuracy of REGA MPI is comparable to Adenosine MPI, but its prognostic value is not well defined. Methods. We categorized 1,400 patients (700 consecutive normal and 700 consecutive abnormal REGA-MPIs) into 4 groups based on the perfusion defect size using automated quantitative analysis: Group 1: normal perfusion; Group 2: < 10% of left ventricle; Group 3: 10%-20%; Group 4: > 20%. The primary outcome was a composite of cardiac death, myocardial infarction (MI), and late coronary revascularization (CR > 90 days after MPI). Results. Of the 1,400 patients (42% male, 37% diabetes, 21% heart failure, 26% end-stage renal disease), the primary outcome occurred in 23% (17% cardiac death, 4% MI, 6% late CR) during 46 +/- A 18 months of follow-up and 8% had early CR (within 90 days of MPI). Early CR occurred in 0.4%, 9%, 17%, and 17% and the primary outcome in 10%, 27%, 31%, and 43% in Groups 1-4, respectively (P < .001 for both). In an adjusted Cox proportional model, the hazard ratio for the primary outcome was 2.68 (1.77-4.06), 3.32 (2.28-4.83), and 4.05 (2.78-5.91) for Groups 2-4 compared to Group 1. Conclusion. REGA MPI provides powerful prognostic information that has important implications in patient management and can guide clinical practice. C1 [Hage, Fadi G.; Ghimire, Gopal; Mckay, Joshua; Bleich, Steven; Iskandrian, Ami E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Lester, Davis] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [El-Hajj, Stephanie] Louisiana State Univ, Dept Med, Baton Rouge, LA 70803 USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Dept Med, Lyons Harrison Res Bldg 314,1900 Univ BLVD, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma USA FX Drs Hage and Iskandrian have received research grants from Astellas Pharma USA. NR 28 TC 10 Z9 10 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD DEC PY 2015 VL 22 IS 6 BP 1214 EP 1221 DI 10.1007/s12350-014-0050-y PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CW9FD UT WOS:000365303100007 PM 25677160 ER PT J AU Konopnicki, S Troulis, MJ AF Konopnicki, Sandra Troulis, Maria J. TI Mandibular Tissue Engineering: Past, Present, Future SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MESENCHYMAL STEM-CELLS; PLATELET-RICH-PLASMA; HUMAN DENTAL-PULP; MORPHOGENETIC PROTEIN-2 RHBMP-2; VERTICAL RAMUS OSTEOTOMY; TRICALCIUM PHOSPHATE SCAFFOLDS; VASCULARIZED BONE-GRAFTS; IN-SITU OSTEOGENESIS; HUMAN ADIPOSE-TISSUE; MECHANICAL-PROPERTIES AB Almost 2 decades ago, the senior author's (M.T.J.) first article was with our mentor, Dr Leonard B. Kaban, a review article titled "Distraction Osteogenesis: Past, Present, Future." In 1998, many thought it would be impossible to have a remotely activated, small, curvilinear distractor that could be placed using endoscopic techniques. Currently, a U.S. patent for a curvilinear automated device and endoscopic techniques for minimally invasive access for jaw reconstruction exist. With minimally invasive access for jaw reconstruction, the burden to decrease donor site morbidity has increased. Distraction osteogenesis (DO) is an in vivo form of tissue engineering. The DO technique eliminates a donor site, is less invasive, requires a shorter operative time than usual procedures, and can be used for multiple reconstruction applications. Tissue engineering could further reduce morbidity and cost and increase treatment availability. The purpose of the present report was to review our experience with tissue engineering of bone: the past, present, and our vision for the future. The present report serves as a tribute to our mentor and acknowledges Dr Kaban for his incessant tutelage, guidance, wisdom, and boundless vision. (C) 2015 American Association of Oral and Maxillofacial Surgeons C1 [Konopnicki, Sandra] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Skeletal Biol Res Ctr, Boston, MA 02114 USA. [Konopnicki, Sandra] Lille Univ Hosp, Dept Oral Maxillofacial Surg, Lille, France. [Troulis, Maria J.] Harvard Univ, Sch Dent Med, Residency Program, Dept Oral Maxillofacial Surg,Massachusetts Gen Ho, Boston, MA 02115 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM mtroulis@partners.org NR 117 TC 1 Z9 2 U1 2 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2015 VL 73 IS 12 SU S BP S136 EP S146 DI 10.1016/j.joms.2015.05.037 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CW9WA UT WOS:000365347700019 PM 26608143 ER PT J AU Peacock, ZS Susarla, SM AF Peacock, Zachary S. Susarla, Srinivas M. TI Is the Pyriform Ligament Important for Alar Width Maintenance After Le Fort I Osteotomy? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SOFT-TISSUE CHANGES; NASAL BASE REDUCTION; MAXILLARY ADVANCEMENT; CINCH SUTURE; CONTROLLED-TRIAL; STABILITY; MORPHOLOGY; SURGERY; RELEASE AB Purpose: To determine whether identification and incorporation of the pyriform ligament in the alar cinch results in decreased alar base widening compared with standard alar cinch techniques. Materials and Methods: This was a retrospective case series and the sample was composed of patients undergoing Le Fort I osteotomy. Intraoperatively, the pyriform ligament was identified and incorporated in the alar cinch suture. Greatest alar width (GAW) measured immediately after closure was compared with GAW measured at least 5 months postoperatively. The change in alar base width was compared with that reported in the literature using other alar cinch techniques. Two case examples are reported. Results: The sample was composed of 15 patients (mean age, 27.1 yr; 27% female). The mean postoperative change in GAW was 1.0 +/- 0.6 mm (2.59 +/- 1.59%). Postoperative change in alar base width reported in the literature ranged from 0.5 to 10.8%. Conclusion: The pyriform ligament is easily identified during exposure of the maxilla and pyriform aperture and can be used to control widening of the alar base after Le Fort I osteotomy. (C) 2015 American Association of Oral and Maxillofacial Surgeons C1 [Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Susarla, Srinivas M.] Johns Hopkins Univ Hosp, Johns Hopkins Med Sch, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund, Center for Applied Clinical Investigation FX This work was supported by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund, Center for Applied Clinical Investigation. NR 28 TC 0 Z9 0 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2015 VL 73 IS 12 SU S BP S57 EP S66 DI 10.1016/j.joms.2015.04.015 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CW9WA UT WOS:000365347700009 PM 26608155 ER PT J AU Black, EM Roberts, SM Siegel, E Yannopoulos, P Higgins, LD Warner, JJP AF Black, Eric M. Roberts, Susanne M. Siegel, Elana Yannopoulos, Paul Higgins, Laurence D. Warner, Jon J. P. TI Failure after reverse total shoulder arthroplasty: what is the success of component revision? SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Reverse shoulder arthroplasty; revision reverse shoulder arthroplasty; revision shoulder; complications; reimplantation ID PROXIMAL HUMERAL FRACTURES; ROTATOR CUFF DEFICIENCY; GLENOHUMERAL ARTHRITIS; FOLLOW-UP; PROSTHESIS; HEMIARTHROPLASTY; OSTEOARTHRITIS; COMPLICATIONS; DISLOCATION; FIXATION AB Background: Complication rates remain high after reverse total shoulder arthroplasty (RTSA). Salvage options after implant failure have not been well defined. This study examines the role of reimplantation and revision RTSA after failed RTSA, reporting outcomes and complications of this salvage technique. Methods: Sixteen patients underwent component revision and reimplantation after a prior failed RTSA from 2004 to 2011. Indications included baseplate failure (7 patients, 43.8%), instability (6 patients, 37.5%), infection (2 patients, 12.5%), and humeral loosening (1 patient, 6.3%). The average age of the patient during revision surgery was 68.6 years. Outcomes information at follow-up was recorded, including visual analog scale score for pain, subjective shoulder value, American Shoulder and Elbow Surgeons score, and Simple Shoulder Test score, and these were compared with pre-revision values. Repeated surgeries and complications were noted. Results: Average time to follow-up from revision was 58.9 months (minimum, 2 years; range, 24-103 months). The average postoperative visual analog scale score for pain was 1.7/10 (7.5/10 preoperatively; P < .0001), and the subjective shoulder value was 62% (17% preoperatively; P < .0001). The average postoperative American Shoulder and Elbow Surgeons score was 66.7, and the Simple Shoulder Test score was 52.6. Fourteen patients (88%) noted that they felt "better" postoperatively than before their original RTSA and would go through the procedure again if given the option. Nine patients suffered major complications (56%), and 6 of these ultimately underwent further procedures (38% of cohort). Discussion: Salvage options after failure of RTSA remain limited. Component revision and reimplantation can effectively relieve pain and improve function compared with baseline values, and patient satisfaction levels are moderately high. However, complication rates and reoperation rates are significant. (C) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Black, Eric M.] Summit Med Grp, Dept Orthopaed Surg, Berkeley Hts, NJ USA. [Roberts, Susanne M.; Yannopoulos, Paul; Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Shoulder Serv, Boston, MA 02114 USA. [Siegel, Elana; Higgins, Laurence D.] Brigham & Womens Hosp, Dept Orthopaed Surg, Sports Med & Shoulder Serv, Boston, MA 02115 USA. RP Warner, JJP (reprint author), Yawkey Ctr Outpatient Care, 55 Fruit St,Suite 3G, Boston, MA 02114 USA. EM jwarner@mgh.harvard.edu NR 31 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD DEC PY 2015 VL 24 IS 12 BP 1908 EP 1914 DI 10.1016/j.jse.2015.05.029 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA CW6WP UT WOS:000365139400013 PM 26163279 ER PT J AU Tasigiorgos, S Economopoulos, KP Winfield, RD Sakran, JV AF Tasigiorgos, Sotirios Economopoulos, Konstantinos P. Winfield, Robert D. Sakran, Joseph V. TI Firearm Injury in the United States: An Overview of an Evolving Public Health Problem SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID GUN VIOLENCE; MENTAL-ILLNESS; VIRGINIA TECH; RESOURCE LOSS; US; DEATH; CALL; HOSPITALIZATIONS; ASSOCIATION; PREVENTION C1 [Tasigiorgos, Sotirios] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Tasigiorgos, Sotirios; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece. [Economopoulos, Konstantinos P.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. [Winfield, Robert D.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Sakran, Joseph V.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Economopoulos, KP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, 101 Merrimac St,3rd Floor,Off 340, Boston, MA 02114 USA. EM keconomopoulos@mgh.harvard.edu OI Economopoulos, Konstantinos/0000-0003-4856-0405 NR 53 TC 2 Z9 2 U1 8 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2015 VL 221 IS 6 BP 1005 EP 1014 DI 10.1016/j.jamcollsurg.2015.08.430 PG 10 WC Surgery SC Surgery GA CW9VP UT WOS:000365346600004 PM 26422747 ER PT J AU Loehrer, AP Chang, DC Hutter, MM Song, ZR Lillemoe, KD Warshaw, AL Ferrone, CR AF Loehrer, Andrew P. Chang, David C. Hutter, Matthew M. Song, Zirui Lillemoe, Keith D. Warshaw, Andrew L. Ferrone, Cristina R. TI Health Insurance Expansion and Treatment of Pancreatic Cancer: Does Increased Access Lead to Improved Care? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID DIFFERENCE-IN-DIFFERENCES; HIGH-VOLUME CENTERS; SURVIVAL; OUTCOMES; ASSOCIATION; DISPARITIES; POPULATION; INFERENCE; MORTALITY; SURGERY AB BACKGROUND: Pancreatic cancer is increasingly common and poised to become the second leading cause of cancer deaths by the year 2020. Surgical resection is the only chance for cure, yet significant disparities in resection rates exist by insurance status. The 2006 Massachusetts health care reform serves as natural experiment to evaluate the unknown impact of health insurance expansion on treatment of pancreatic cancer. STUDY DESIGN: Using the Agency for Healthcare Research and Quality's State Inpatient Databases, this cohort study examines nonelderly, adult patients with no insurance, private coverage, or government-subsidized insurance plans, who were admitted with pancreatic cancer in Massachusetts and 3 control states. The primary end point was change in pancreatic resection rates. Difference-in-difference models were used to show the impact of Massachusetts health care reform on resection rates for pancreatic cancer, controlling for confounding factors and secular trends. RESULTS: Before the Massachusetts reform, government-subsidized and self-pay patients had significantly lower rates of resection than privately insured patients. The 2006 Massachusetts health reform was associated with a 15% increased rate of admission with pancreatic cancer (p = 0.043) and a 67% increased rate of surgical resection (p = 0.043) compared with control states. Measured disparities in likelihood of resection by insurance status decreased in Massachusetts and remained unchanged in control states. CONCLUSIONS: The 2006 Massachusetts health care reform was associated with increased resection rates for pancreatic cancer compared with control states. Our findings provide hopeful evidence that increased insurance coverage can help improve equity in pancreatic cancer treatment. Additional studies are needed to evaluate the longevity of these findings and generalizability in other states. (C) 2015 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved. C1 [Loehrer, Andrew P.; Chang, David C.; Hutter, Matthew M.; Lillemoe, Keith D.; Warshaw, Andrew L.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Song, Zirui] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Loehrer, AP (reprint author), Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, 165 Cambridge St,Suite 403, Boston, MA 02114 USA. EM aloehrer@partners.org FU NIA NIH HHS [F30 AG039175, F30-AG039175] NR 33 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2015 VL 221 IS 6 BP 1015 EP 1022 DI 10.1016/j.jamcollsurg.2015.09.010 PG 8 WC Surgery SC Surgery GA CW9VP UT WOS:000365346600005 PM 26611798 ER PT J AU Almassi, GH Carr, BM Bishawi, M Shroyer, AL Quin, JA Hattler, B Wagner, TH Collins, JF Ravichandran, P Cleveland, JC Grover, FL Bakaeen, FG AF Almassi, G. Hossein Carr, Brendan M. Bishawi, Muath Shroyer, A. Laurie Quin, Jacquelyn A. Hattler, Brack Wagner, Todd H. Collins, Joseph F. Ravichandran, Pasala Cleveland, Joseph C. Grover, Frederick L. Bakaeen, Faisal G. CA Vet Affairs 517 Randomized On Off TI Resident versus attending surgeon graft patency and clinical outcomes in on- versus off-pump coronary artery bypass surgery SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article DE CABG; on-pump; off-pump; education; resident training; graft patency ID ON-PUMP; PERFORMANCE; ANASTOMOSIS; IMPROVEMENT; EXPERIENCE; SIMULATION; QUALITY; IMPACT; LEVEL; CABG AB Objective: Controversy exists regarding ideal approaches in teaching residents complex and/or new surgical techniques in part because consequences on patient outcomes are largely unknown. This study compared patient outcomes for cases in which residents (rather than attending surgeons) performed most of the distal anastomoses as primary surgeons, during on- and off-pump coronary artery bypass grafting (CABG). Methods: This preapproved substudy of the Randomized On/Off Bypass (ROOBY) trial compared clinical outcomes and 1-year graft patency for cases in which residents versus attending surgeons were the primary operator. Comparisons were made between on-pump and off-pump techniques. Results: From July 2003 through May 2007, a total of 1272 ROOBY nonemergent CABG patients were randomized at 16 Veterans Affairs centers where residents were active participants. Residents were the primary surgeon (ie, performed >= 50% of the distal anastomoses) more frequently in on-pump (77.9%) than in off-pump (67.4%) cases. Between these 2 techniques, no were found differences in baseline patient characteristics; short-term and 1-year morbidity and mortality rates were no different for residents versus attendings in CABG cases. FitzGibbon A graft patency rates were similar for resident versus attendings completed distal anastomoses for on-pump (83.0% vs 82.4%) compared with off-pump (77.2% vs 76.6%) procedures. Conclusions: In the ROOBY trial, short-term and 1-year patient outcomes and graft patency rates did not differ between resident and attending surgeons, demonstrating that with appropriate patient selection and resident supervision, residents can perform advanced, novel surgical techniques with outcomes similar to those of attending surgeons. C1 [Almassi, G. Hossein] Med Coll Wisconsin, Dept Cardiothorac Surg, Milwaukee, WI 53226 USA. [Almassi, G. Hossein] Vet Affairs Med Ctr, Milwaukee, WI USA. [Carr, Brendan M.; Shroyer, A. Laurie] Northport Vet Affairs Med Ctr, Dept Surg, Stony Brook, NY USA. [Carr, Brendan M.; Shroyer, A. Laurie] Stony Brook Sch Med, Stony Brook, NY USA. [Bishawi, Muath] Duke Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, Durham, NC USA. [Quin, Jacquelyn A.] Vet Affairs Boston Healthcare Syst, Dept Cardiac Surg, West Roxbury, MA USA. [Hattler, Brack; Cleveland, Joseph C.; Grover, Frederick L.] Vet Affairs Eastern Colorado Hlth Care Syst, Dept Cardiol, Denver, CO USA. [Hattler, Brack; Cleveland, Joseph C.; Grover, Frederick L.] Univ Colorado, Sch Med, Aurora, CO USA. [Wagner, Todd H.] Vet Affairs Palo Alto Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Wagner, Todd H.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Collins, Joseph F.] Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Collins, Joseph F.] Vet Affairs Med Ctr, Perry Point, MD USA. [Ravichandran, Pasala] Portland VA Med Ctr, Dept Surg, Portland, OR USA. [Ravichandran, Pasala] Oregon Hlth & Sci Univ, Portland, OR USA. [Bakaeen, Faisal G.] Baylor Coll Med, Cardiothorac Surg, Houston, TX 77030 USA. [Bakaeen, Faisal G.] Houston Vet Affairs Med Ctr, Houston, TX USA. RP Almassi, GH (reprint author), Med Coll Wisconsin, Cardiothorac Surg, FEC, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM halmassi@mcw.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU Offices of Research and Development; Zablocki VA Medical Center; Eastern Colorado Health Care System, Denver Department of Veterans Affairs Medical Center FX This ROOBY trial substudy was supported, in part, by the Offices of Research and Development staff and resources at the Northport VA Medical Center, the Zablocki VA Medical Center, and the Eastern Colorado Health Care System, Denver Department of Veterans Affairs Medical Center. Special appreciation is given to both Ms. Annette Wiseman and Ms. Xiaoli (Shirley) Lu for their extraordinary assistance at the Cooperative Studies Program Coordinating Center in Perry Point, Maryland. NR 28 TC 3 Z9 3 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2015 VL 150 IS 6 BP 1428 EP + DI 10.1016/j.jtcvs.2015.08.124 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CW5MX UT WOS:000365040700022 PM 26470910 ER PT J AU Rajaram, R Ju, MH Bilimoria, KY Ko, CY DeCamp, MM AF Rajaram, Ravi Ju, Mila H. Bilimoria, Karl Y. Ko, Clifford Y. DeCamp, Malcolm M. TI National evaluation of hospital readmission after pulmonary resection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article DE Patient readmission; postoperative complications; thoracic surgery; video-assisted; pulmonary surgical procedures; quality indicators; health care; pneumonectomy; Centers for Medicare and Medicaid Services; risk factors ID LENGTH-OF-STAY; SURGICAL COMPLICATIONS; RISK-FACTORS; ACS-NSQIP; SURGERY; QUALITY; RATES; PREVALENCE; LOBECTOMY; OUTCOMES AB Objectives: Our objectives were to (1) assess readmission rates and timing after pulmonary resection, (2) report the most common reasons for rehospitalization, and (3) identify risk factors for unplanned readmission after pulmonary resection. Methods: Patients who underwent pulmonary resection were identified from the 2011 American College of Surgeons National Surgical Quality Improvement Program database. We examined readmission within 30 days of surgery for all resections and 3 subgroups: open lobectomy, video-assisted thoracoscopic lobectomy, and pneumonectomy. Regression models were developed to identify factors associated with readmission. Results: In 1847 patients, there were 899 open lobectomies (49%), 724 video-assisted thoracoscopic lobectomies (39%), and 85 pneumonectomies (5%). The overall readmission rate was 9.3% with no significant difference found among patients undergoing open lobectomy (9.1%), video-assisted thoracoscopic lobectomy (8.4%), or pneumonectomy (11.8%) (P = .576). The median time from operation to readmission was similar among patients undergoing open (14 days) or video-assisted thoracoscopic lobectomy (13 days). The most common cause of readmission for all groups examined was pulmonary related. In multivariable analyses, the strongest factor associated with readmission was an inpatient complication after the initial surgery in all resections (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.05-6.04), open lobectomy (HR, 4.36; 95% CI, 2.75-6.94), and video-assisted thoracoscopic lobectomy (HR, 4.60; 95% CI, 2.65-7.97). Surgical approach was not associated with readmission (video-assisted thoracoscopic vs open lobectomy: HR, 1.07; 95% CI, 0.75-1.52). Conclusions: Experiencing a postoperative complication was strongly associated with unplanned readmission. Increased attention toward reducing postoperative complications and earlier outpatient follow-up in these patients may be a viable strategy for decreasing readmissions after pulmonary resection. C1 [Rajaram, Ravi; Ju, Mila H.; Bilimoria, Karl Y.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Rajaram, Ravi; Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, SOQIC, Chicago, IL 60611 USA. [Rajaram, Ravi; Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [DeCamp, Malcolm M.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Div Thorac Surg, Chicago, IL 60611 USA. [DeCamp, Malcolm M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP Rajaram, R (reprint author), Northwestern Univ, Sch Med, Dept Surg, 251 E Huron St Galter 3-150, Chicago, IL 60611 USA. EM Ravi-Rajaram@fsm.northwestern.edu FU American College of Surgeons Clinical Scholars in Residence Program; American Cancer Society; National Institutes of Health [5T32HL094293]; Merck; Agency for Healthcare Research and Quality [T32HS000078] FX This work was supported by the American College of Surgeons Clinical Scholars in Residence Program to RR and MHJ; American Cancer Society to KYB; National Institutes of Health 5T32HL094293 to MHJ; an unrestricted educational grant from Merck to RR; and the Agency for Healthcare Research and Quality T32HS000078 to RR. Funding sources did not have any input into the selection of research topic, study interpretation, or any resulting presentation or publication of the submitted work. NR 29 TC 5 Z9 5 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2015 VL 150 IS 6 BP 1508 EP U207 DI 10.1016/j.jtcvs.2015.05.047 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CW5MX UT WOS:000365040700040 PM 26092506 ER PT J AU Patel, VI Lancaster, RT Ergul, E Conrad, MF Bertges, D Schermerhorn, M Goodney, P Cambria, RP AF Patel, Virendra I. Lancaster, Robert T. Ergul, Emel Conrad, Mark F. Bertges, Daniel Schermerhorn, Marc Goodney, Philip Cambria, Richard P. TI Postoperative renal dysfunction independently predicts late mortality in patients undergoing aortic reconstruction SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ACUTE KIDNEY INJURY; ANEURYSM REPAIR; SERUM CREATININE; HOSPITALIZED-PATIENTS; CARDIAC-SURGERY; ACUTE DIALYSIS; FAILURE; OUTCOMES; DISEASE AB Objective: Preoperative chronic kidney disease (CKD) has been shown to predict postoperative renal complications and mortality after open aortic surgery; the impact of postoperative renal complications less severe than permanent dialysis are unknown. We evaluated the impact of postoperative renal dysfunction severity on survival using a regional quality improvement registry. Methods: Patients undergoing intact open aortic reconstruction in the Vascular Study Group of New England registry (2003-2012) were stratified by severity of postoperative renal complications; none, creatinine increase of greater than 0.5 mg/dL (incCr), or any hemodialysis (HD). Predictors of renal dysfunction and impact of renal complications on survival were analyzed using multivariable methods. Results: We included 2695 patients, of which 65% (n = 1733) underwent open abdominal aortic aneurysm repair, and 35% (n = 962) open aortoiliac reconstruction. At baseline, 15% of patients had preoperative moderate CKD and 1.2% had severe CKD. Postoperative renal complications of incCr occurred in 8.5% of patients, and 1.5% required HD. Multivariable cumlogit regression identified severe baseline CKD (odds ratio [OR], 15; 95% confidence interval [CI], 6.4-34; P <.001, moderate CKD (OR, 2.8; 95% CI, 1.9-3.3; P <.001), suprarenal clamp use (OR, 2.2; 95% CI, 1.6-2.9; P <.001), perioperative vasopressor requirements (OR, 2.2; 95% CI, 1.6-2.9; P <.001), operating time (OR, 1.004 per minute; 95% CI, 1.003-1.006; P <.001), and chronic obstructive pulmonary disease (OR, 1.5; 95% CI, 1.2-1.8; P <.001) as independent predictors of worsening strata of postoperative renal dysfunction. Multivariable logistic regression analysis showed that patient age (OR, 1.06 per year; 95% CI, 1.01-1.1; P = .01), baseline chronic obstructive pulmonary disease (OR, 1.6; 95% CI, 1.2-2.2; P <.01), incCr (OR, 3.7; 95% CI, 1.8-7.4; P = .009), and HD (OR, 4.8; 95% CI, 1.8-12.7); P = .009) independently increased 30-day mortality. Risk-adjusted multivariable Cox regression showed that incCr (hazard ratio, 1.8; 95% CI, 1.3-2.6; P <.001) and HD (hazard ratio, 4.4; 95% CI, 2.8-6.9; P <.001) increased risk of late death independent of a variety of other clinical variables, including baseline CKD. The 5-year survival was lower (log-rank P <.001) in patients with incCr (66% +/- 4%), and HD (38% +/- 10%) compared with those with no renal complications (77% +/- 1%). Conclusions: Increasing severity of postoperative renal dysfunction independently predicts increased risk of late mortality after open aortic surgery. Perioperative measures to decrease renal complications may potentially prolong the survival of patients after open aortic surgery. C1 [Patel, Virendra I.; Lancaster, Robert T.; Ergul, Emel; Conrad, Mark F.; Bertges, Daniel; Schermerhorn, Marc; Goodney, Philip; Cambria, Richard P.] VSGNE, London, England. RP Patel, VI (reprint author), Massachusetts Gen Hosp, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpatel4@partners.org FU NHLBI NIH HHS [K08 HL105676] NR 30 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2015 VL 62 IS 6 BP 1405 EP 1412 DI 10.1016/j.jvs.2015.07.084 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CW8IG UT WOS:000365242100004 PM 26598117 ER PT J AU Johnson, MR Codd, PJ Hill, WM Boettcher, T AF Johnson, Matt R. Codd, Patrick J. Hill, Westin M. Boettcher, Tara TI Ablation of Porcine Ligamentum Flavum With Ho:YAG, Q-Switched Ho:YAG, and Quadrupled Nd:YAG Lasers SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE lumbar spinal stenosis; LSS; laminectomy; nerve pain; spinal canal ID LUMBAR SPINAL STENOSIS; DISC DECOMPRESSION; YAG LASER; IRRADIATION; EFFICACY; SURGERY; EXCIMER AB Background and Objectives: Ligamentum flavum (LF) is a tough, rubbery connective tissue providing a portion of the ligamentous stability to the spinal column, and in its hypertrophied state forms a significant compressive pathology in degenerative spinal stenosis. The interaction of lasers and this biological tissue have not been thoroughly studied. Technological advances improving endoscopic surgical access to the spinal canal makes selective removal of LF using small, flexible tools such as laser-coupled fiber optics increasingly attractive for treatment of debilitating spinal stenosis. Testing was performed to assess the effect of Ho:YAG, Q-switched Ho: YAG, and frequency quadrupled Nd:YAG lasers on samples of porcine LF. The objective was to evaluate the suitability of these lasers for surgical removal of LF. Study Design/Materials and Methods: LF was resected from porcine spine within 2 hours of sacrifice and stored in saline until immediately prior to laser irradiation, which occurred within an additional 2 hours. The optical absorbance of a sample was measured over the spectral band from 190 to 2,360nm both before and after dehydration. For the experiments using the Ho:YAG (lambda = 2,080 nm, t(p) = 140 mu s, FWHM) and Q-Switched Ho:YAG (lambda = 2,080 nm, t(p) = 260 ns, FWHM) lasers, energy was delivered to the LF through a laser-fiber optic with 600 mu m core and NA = 0.39. For the experiment using the frequency quadrupled Nd:YAG laser (lambda = 266 nm, t(p) = 5 ns FWHM), rather than applying the laser energy through a laser-fiber, the energy was focused through an aperture and lens directly onto the LF. Five experiments were conducted to evaluate the effect of the given lasers on LF. First, using the Ho:YAG laser, the single-pulse laser-hole depth versus laser fluence was measured with the laser-fiber in direct contact with the LF (1 g force) and with a standoff distance of 1 mm between the laser-fiber face and the LF. Second, with the LF remaining in situ and the spine bisected along the coronal plane, the surface temperature of the LF was measured with an IR camera during irradiation with the Ho:YAG laser, with and without constant saline flush. Third, the mass loss was measured over the course of 450 Ho:YAG pulses. Fourth, hole depth and temperature were measured over 30 pulses of fixed fluence from the Ho:YAG and Q-Switched Ho:YAG lasers. Fifth, the ablation rate and surface temperature were measured as a function of fluence from the Nd:YAG laser. Several LF staining and hole-depth measurement techniques were also explored. Results: Aside from the expected absorbance peaks corresponding to the water in the LF, the most significant peaks in absorbance were located in the spectral band from 190 to 290 nm and persisted after the tissue was dehydrated. In the first experiment, using the Ho:YAG laser and with the laser-fiber in direct contact with the LF, the lowest single-pulse fluence for which LF was visibly removed was 35 J/cm(2). Testing was conducted at 6 fluences between 35 and 354 J/cm(2). Over this range the single-pulse hole depth was shown to be near linear (R-2 = 0.9374, M = 1.6), ranging from 40 to 639 mu m (N = 3). For the case where the laser-fiber face was displaced 1 mm from the LF surface, the lowest single-pulse fluence for which tissue was visibly removed was 72 J/cm(2). Testing was conducted at 4 energy densities between 72 and 180 J/cm(2). Over this range the single-pulse hole depth was shown to be near linear (R-2 = 0.8951, M = 1.4), ranging from 31 to 220 mu m (N = 3). In the second experiment, with LF in situ, constant flushing with room temperature saline was shown to drastically reduce surface temperature during exposure to Ho:YAG at 5 Hz with the laser-fiber in direct contact with the LF. Without saline, over 1 minute of treatment with a per-pulse fluence of 141 mJ/cm(2), the average maximum surface temperature measured 110 degrees C. With 10 cc's of saline flushed over 1 minute and a per-pulse laser fluence of 212 mJ/cm(2), the average maximum surface temperature was 35 degrees C. In the third experiment, mass loss was shown to be linear over 450 pulses of 600 mJ from the Ho:YAG laser (212 J/cm(2), direct contact, N = 4; 108 J/cm(2), 1 mm standoff, N = 4). With the laser-fiber in direct contact, an average of 53mg was removed (R-2 = 0.996, M = 0.117) and with 1 mm laser-fiber standoff, an average of 44 mg was removed (R-2 = 0.9988, M = 0.097). In the fourth experiment, 30 pulses of the Ho:YAG and Q-Switched Ho:YAG lasers at 1 mm standoff, and 5 Hz produced similar hole depths for the tested fluences of 9 J/cm(2) (151 and 154 mu m, respectively) and 18 J/cm(2) (470 and 442 mu m, respectively), though the Ho:YAG laser produced significantly more carbonization around the rim of the laser-hole. The increased carbonization was corroborated by higher measured LF temperature. In all tests with the Ho:YAG and Q-Switched Ho: YAG, an audible photo-acoustic affect coincided with the laser pulse. In the fifth experiment, with the frequency quadrupled Nd:YAG laser at 15 Hz for 450 pulses, ablation depth per pulse was shown to be linear for the fluence range of 0.18 - 0.73 J/cm(2) (R-2 = 0.989, M = 2.4). There was no noticeable photo-acoustic effect nor charring around the rim of the laser-hole. Conclusion: The Ho:YAG, Q-Switched Ho:YAG, and frequency quadrupled Nd:YAG lasers were shown to remove ligamentum flavum (LF). A single pulse of the Ho: YAG laser was shown to cause tearing of the tissue and a large zone of necrosis surrounding the laser-hole. Multiple pulses of the Ho:YAG and Q-Switched Ho:YAG lasers caused charring around the rim of the laser-hole, thoughthe extent of charring was more extensive with the Ho:YAG laser. Charring caused by the Ho:YAG laser was shown to be mitigated by continuously flushing the affected LF with saline during irradiation. The Nd:YAG laser was shown to ablate LF with nogross visible indication of thermal damage to surrounding LF. Lasers Surg. Med. 47:839-851, 2015. (C) 2015 Wiley Periodicals, Inc. C1 [Johnson, Matt R.; Hill, Westin M.; Boettcher, Tara] MIT, Lincoln Lab, Lexington, MA 02420 USA. [Codd, Patrick J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Johnson, MR (reprint author), MIT, Lincoln Lab, 244 Wood St, Lexington, MA 02420 USA. EM Matt.Johnson@ll.mit.edu FU Department of the Air Force [FA8721-05-C-0002] FX Contract grant sponsor: Department of the Air Force; Contract grant number: FA8721-05-C-0002. NR 32 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD DEC PY 2015 VL 47 IS 10 BP 839 EP 851 DI 10.1002/lsm.22424 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA CX0JF UT WOS:000365382000009 PM 26415136 ER PT J AU Kim, HJ Kim, S Park, YK Kim, JI Park, JM Ye, SJ AF Kim, Hee Jung Kim, Siyong Park, Yang-Kyun Kim, Jung-in Park, Jong Min Ye, Sung-Joon TI Multileaf collimator tongue-and-groove effect on depth and off-axis doses: A comparison of treatment planning data with measurements and Monte Carlo calculations SO MEDICAL DOSIMETRY LA English DT Article DE Tongue-and-groove effect; Monte Carlo; TPS; MLC ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; IMRT; VALIDATION; DOSIMETRY; IMPLEMENTATION; SIMULATION; TRANSPORT; BEAM; MLC AB To investigate how accurately treatment planning systems (TPSs) account for the tongue-and-groove (TG) effect, Monte Carlo (MC) simulations and radiochromic film (RCF) measurements were performed for comparison with TPS results. Two commercial TPSs computed the TG effect for Varian Millennium 120 multileaf collimator (MLC). The TG effect on off-axis dose profile at 3 depths of solid water was estimated as the maximum depth and the full width at half maximum (FWHM) of the dose dip at an interleaf position. When compared with the off-axis dose of open field, the maximum depth of the dose dip for MC and RCF ranged from 10.1% to 20.6%; the maximum depth of the dose dip gradually decreased by up to 8.7% with increasing depths of 1.5 to 10 cm and also by up to 4.1% with increasing off-axis distances of 0 to 13 cm. However, TPS results showed at most a 2.7% decrease for the same depth range and a negligible variation for the same off-axis distances. The FWHM of the dose dip was approximately 0.19 cm for MC and 0.17 cm for RCF, but 0.30 cm for Eclipse TPS and 0.45 cm for Pinnacle TPS. Accordingly, the integrated value of TG dose dip for TPS was larger than that for MC and RCF and almost invariant along the depths and off-axis distances. We concluded that the TG dependence on depth and off-axis doses shown in the MC and RCF results could not be appropriately modeled by the TPS versions in this study. (C) 2015 American Association of Medical Dosimetrists. C1 [Kim, Hee Jung; Park, Yang-Kyun; Kim, Jung-in; Park, Jong Min; Ye, Sung-Joon] Seoul Natl Univ, Interdisciplinary Program Radiat Appl Life Sci, Seoul, South Korea. [Kim, Hee Jung] Seoul Natl Univ, Dept Biomed Engn, Seoul, South Korea. [Kim, Hee Jung] Soonchunhyang Univ Hosp, Dept Radiat Oncol, Seoul, South Korea. [Kim, Siyong] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA. [Park, Yang-Kyun] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kim, Jung-in; Park, Jong Min; Ye, Sung-Joon] Seoul Natl Univ Hosp, Dept Radiat Oncol, Seoul 110744, South Korea. [Ye, Sung-Joon] Seoul Natl Univ, Dept Transdisciplinary Studies, Seoul, South Korea. [Ye, Sung-Joon] Seoul Natl Univ, Adv Inst Convergence Technol, Suwon, South Korea. RP Ye, SJ (reprint author), Seoul Natl Univ Hosp, Dept Radiat Oncol, 101 Daehak Ro, Seoul 110744, South Korea. EM sye@snu.ac.kr FU National Research Foundation of Korea - Korea government [490-20140029, 490-20130047] FX This work was in part supported by the National Research Foundation of Korea (490-20140029 and no. 490-20130047) Grant funded by the Korea government. NR 31 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 EI 1873-4022 J9 MED DOSIM JI Med. Dosim. PD WIN PY 2015 VL 40 IS 4 BP 271 EP 278 DI 10.1016/j.meddos.2015.01.005 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CW2EE UT WOS:000364803100001 PM 25790722 ER PT J AU Desikan, RS Schork, AJ Wang, Y Witoelar, A Sharma, M McEvoy, LK Holland, D Brewer, JB Chen, CH Thompson, WK Harold, D Williams, J Owen, MJ O'Donovan, MC Pericak-Vance, MA Mayeux, R Haines, JL Farrer, LA Schellenberg, GD Heutink, P Singleton, AB Brice, A Wood, NW Hardy, J Martinez, M Choi, SH DeStefano, A Ikram, MA Bis, JC Smith, A Fitzpatrick, AL Launer, L van Duijn, C Seshadri, S Ulstein, ID Aarsland, D Fladby, T Djurovic, S Hyman, BT Snaedal, J Stefansson, H Stefansson, K Gasser, T Andreassen, OA Dale, AM AF Desikan, R. S. Schork, A. J. Wang, Y. Witoelar, A. Sharma, M. McEvoy, L. K. Holland, D. Brewer, J. B. Chen, C-H Thompson, W. K. Harold, D. Williams, J. Owen, M. J. O'Donovan, M. C. Pericak-Vance, M. A. Mayeux, R. Haines, J. L. Farrer, L. A. Schellenberg, G. D. Heutink, P. Singleton, A. B. Brice, A. Wood, N. W. Hardy, J. Martinez, M. Choi, S. H. DeStefano, A. Ikram, M. A. Bis, J. C. Smith, A. Fitzpatrick, A. L. Launer, L. van Duijn, C. Seshadri, S. Ulstein, I. D. Aarsland, D. Fladby, T. Djurovic, S. Hyman, B. T. Snaedal, J. Stefansson, H. Stefansson, K. Gasser, T. Andreassen, O. A. Dale, A. M. CA ADNI ADGC Investigator GERAD Investigator CHARGE Investigator IPDGC Investigator TI Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus SO MOLECULAR PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; MILD COGNITIVE IMPAIRMENT; COMMON VARIANTS; RISK-FACTORS; IDENTIFIES VARIANTS; EXPRESSION; HAPLOTYPE; TAU; METAANALYSIS; NEURODEGENERATION AB We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n = 89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts = 1.65 x 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration. C1 [Desikan, R. S.; McEvoy, L. K.; Brewer, J. B.; Chen, C-H; Dale, A. M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA. [Schork, A. J.; Dale, A. M.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92037 USA. [Wang, Y.; Holland, D.; Brewer, J. B.; Dale, A. M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92037 USA. [Wang, Y.; Witoelar, A.; Djurovic, S.; Andreassen, O. A.] Univ Oslo, NORMENT, Oslo, Norway. [Wang, Y.; Witoelar, A.; Fladby, T.; Djurovic, S.; Andreassen, O. A.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Wang, Y.; Witoelar, A.; Djurovic, S.; Andreassen, O. A.] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway. [Sharma, M.; Gasser, T.] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany. [Sharma, M.] Univ Tubingen, Inst Clin Epidemiol & Appl Biometry, Tubingen, Germany. [Chen, C-H; Thompson, W. K.; Andreassen, O. A.; Dale, A. M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92037 USA. [Harold, D.; Williams, J.; Owen, M. J.; O'Donovan, M. C.] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom,Inst Psychol Med, Cardiff CF10 3AX, S Glam, Wales. [Pericak-Vance, M. A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Mayeux, R.] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Mayeux, R.] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Haines, J. L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Vanderbilt Ctr Human Genet Res, Nashville, TN 37232 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Farrer, L. A.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, L. A.; Choi, S. H.; DeStefano, A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Schellenberg, G. D.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA. [Heutink, P.] German Ctr Neurodegenerat Dis DZNE Tubingen, Tubingen, Germany. [Singleton, A. B.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Brice, A.] Univ Paris 06, Sorbonne Univ, Paris, France. [Wood, N. W.] UCL, Genet Inst, London, England. [Wood, N. W.; Hardy, J.] UCL, Dept Mol Neurosci, Inst Neurol, London, England. [Martinez, M.] CHU Purpan, CPTP, UMR1043, INSERM, Toulouse, France. [DeStefano, A.; Seshadri, S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ikram, M. A.; van Duijn, C.] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Bis, J. C.] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. [Smith, A.] Iceland Heart Assoc, Kopavogur, Iceland. [Fitzpatrick, A. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Launer, L.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Washington, DC USA. [Ulstein, I. D.] Oslo Univ Hosp, Dept Old Age Psychiat, Norwegian Ctr Dementia Res, N-0450 Oslo, Norway. [Aarsland, D.] Akershus Univ Hosp, Dept Geriatr Psychiat, Oslo, Norway. [Aarsland, D.] Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway. [Aarsland, D.] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Alzheimers Dis Res Ctr, Stockholm, Sweden. [Fladby, T.] Akershus Univ Hosp, Dept Neurol, Oslo, Norway. [Hyman, B. T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Snaedal, J.] Univ Hosp Reykjavik, Dept Geriatr Med, Reykjavik, Iceland. [Stefansson, H.; Stefansson, K.] deCODE Genet Amgen, Reykjavik, Iceland. [Stefansson, K.] Univ Iceland, Fac Med, Reykjavik, Iceland. RP Desikan, RS (reprint author), Univ Calif San Diego, Dept Radiol, 8950 Villa La Jolla Dr,Suite C101, La Jolla, CA 92037 USA. EM rdesikan@ucsd.edu; o.a.andreassen@medisin.uio.no; amdale@ucsd.edu RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Wood, Nicholas/C-2505-2009; OI Wood, Nicholas/0000-0002-9500-3348; Stefansson, Hreinn/0000-0002-9331-6666; Farrer, Lindsay/0000-0001-5533-4225; Seshadri, Sudha/0000-0001-6135-2622; Harold, Denise/0000-0001-5195-0143 FU National Institutes of Health [R01AG031224, K01AG029218, K02NS067427, T32 EB005970, UO1AG032984, U24-AG041689, R01 MH100351]; Research Council of Norway [213837, 225989, 223273, 237250/EU JPND]; South East Norway Health Authority [2013-123]; Norwegian Health Association; KG Jebsen Foundation; NIH [RC2DA029475, R01HD061414]; Robert J. Glushko and Pamela Samuelson Graduate Fellowship; ADGC; ADNI FX We would like to thank Drs. Irene Litvan, Subhojit Roy and Marilyn Albert for helpful comments on an earlier version of this manuscript. This research was supported by grants from the National Institutes of Health (R01AG031224, K01AG029218, K02NS067427, T32 EB005970, UO1AG032984, U24-AG041689, and R01 MH100351), the Research Council of Norway (#213837, #225989, #223273, #237250/EU JPND), the South East Norway Health Authority (2013-123), the Norwegian Health Association and the KG Jebsen Foundation. AJS was supported by NIH grants RC2DA029475 and R01HD061414 and the Robert J. Glushko and Pamela Samuelson Graduate Fellowship. Please see Supplementary Acknowledgements for ADGC and ADNI funding sources. NR 47 TC 20 Z9 20 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD DEC PY 2015 VL 20 IS 12 BP 1588 EP 1595 DI 10.1038/mp.2015.6 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CW7ZN UT WOS:000365218200015 PM 25687773 ER PT J AU Hawrylycz, M Miller, JA Menon, V Feng, D Dolbeare, T Guillozet-Bongaarts, AL Jegga, AG Aronow, BJ Lee, CK Bernard, A Glasser, MF Dierker, DL Menche, J Szafer, A Collman, F Grange, P Berman, KA Mihalas, S Yao, ZZ Stewart, L Barabasi, AL Schulkin, J Phillips, J Ng, L Dang, C Haynor, DR Jones, A Van Essen, DC Koch, C Lein, E AF Hawrylycz, Michael Miller, Jeremy A. Menon, Vilas Feng, David Dolbeare, Tim Guillozet-Bongaarts, Angela L. Jegga, Anil G. Aronow, Bruce J. Lee, Chang-Kyu Bernard, Amy Glasser, Matthew F. Dierker, Donna L. Menche, Joerg Szafer, Aaron Collman, Forrest Grange, Pascal Berman, Kenneth A. Mihalas, Stefan Yao, Zizhen Stewart, Lance Barabasi, Albert-Laszlo Schulkin, Jay Phillips, John Ng, Lydia Chinh Dang Haynor, David R. Jones, Allan Van Essen, David C. Koch, Christof Lein, Ed TI Canonical genetic signatures of the adult human brain SO NATURE NEUROSCIENCE LA English DT Article ID HUMAN CONNECTOME PROJECT; GENOME-WIDE ASSOCIATION; NETWORK ANALYSIS; MOUSE-BRAIN; FUNCTIONAL CONNECTIVITY; EXPRESSION PATTERNS; ALZHEIMERS-DISEASE; TRANSCRIPTOME; ORGANIZATION; GENERATION AB The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. C1 [Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Lee, Chang-Kyu; Bernard, Amy; Szafer, Aaron; Collman, Forrest; Mihalas, Stefan; Yao, Zizhen; Phillips, John; Ng, Lydia; Chinh Dang; Jones, Allan; Koch, Christof; Lein, Ed] Allen Inst Brain Sci, Seattle, WA USA. [Jegga, Anil G.; Aronow, Bruce J.] Cincinnati Childrens Hosp & Med Ctr, Div Biomed Informat, Cincinnati, OH USA. [Glasser, Matthew F.; Dierker, Donna L.; Van Essen, David C.] Washington Univ, Dept Anat & Neurobiol, St Louis, MO USA. [Menche, Joerg; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA. [Menche, Joerg; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Menche, Joerg; Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, Budapest, Hungary. [Grange, Pascal] Xian Jiaotong Liverpool Univ, Dept Math Sci, Suzhou, Jiangsu, Peoples R China. [Berman, Kenneth A.] Univ Cincinnati, Dept Elect Engn & Comp Syst, Cincinnati, OH USA. [Stewart, Lance] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Schulkin, Jay] Georgetown Univ, Dept Neurosci, Washington, DC USA. [Haynor, David R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RP Hawrylycz, M (reprint author), Allen Inst Brain Sci, Seattle, WA USA. EM mikeh@alleninstitute.org; edl@alleninstitute.org RI Grange, Pascal/I-9950-2016; Menche, Jorg/G-3994-2015; OI Grange, Pascal/0000-0002-9621-1990; Jegga, Anil/0000-0002-4881-7752; Menche, Jorg/0000-0002-1583-6404; Koch, Christof/0000-0001-6482-8067 FU Allen Institute for Brain Science; US National Institute of Drug Abuse [4R33DA027644]; D. Wall of Stanford University School of Medicine; NIH Blueprint for Neuroscience Research [1U54MH091657] FX The authors thank the Allen Institute for Brain Science founders, Paul G. Allen and Jody Allen, for their vision, encouragement and support. Research was supported by the Allen Institute for Brain Science. We also gratefully acknowledge support from the US National Institute of Drug Abuse, grant 4R33DA027644; D. Wall of Stanford University School of Medicine; and 1U54MH091657 (NIH Blueprint for Neuroscience Research). NR 44 TC 23 Z9 23 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2015 VL 18 IS 12 BP 1832 EP 1844 DI 10.1038/nn.4171 PG 13 WC Neurosciences SC Neurosciences & Neurology GA CX1LV UT WOS:000365458600022 PM 26571460 ER PT J AU Wang, DH Buckner, RL Fox, MD Holt, DJ Holmes, AJ Stoecklein, S Langs, G Pan, RQ Qian, TY Li, KC Baker, JT Stufflebeam, SM Wang, K Wang, XM Hong, B Liu, HS AF Wang, Danhong Buckner, Randy L. Fox, Michael D. Holt, Daphne J. Holmes, Avram J. Stoecklein, Sophia Langs, Georg Pan, Ruiqi Qian, Tianyi Li, Kuncheng Baker, Justin T. Stufflebeam, Steven M. Wang, Kai Wang, Xiaomin Hong, Bo Liu, Hesheng TI Parcellating cortical functional networks in individuals SO NATURE NEUROSCIENCE LA English DT Article ID RESTING-STATE FMRI; HUMAN-BRAIN; CONNECTIVITY ARCHITECTURE; INTERSUBJECT VARIABILITY; CEREBRAL-CORTEX; ORGANIZATION; STIMULATION; IDENTIFICATION; ALIGNMENT; SYSTEM AB The capacity to identify the unique functional architecture of an individual's brain is a crucial step toward personalized medicine and understanding the neural basis of variation in human cognition and behavior. Here we developed a cortical parcellation approach to accurately map functional organization at the individual level using resting-state functional magnetic resonance imaging (fMRI). A population-based functional atlas and a map of inter-individual variability were employed to guide the iterative search for functional networks in individual subjects. Functional networks mapped by this approach were highly reproducible within subjects and effectively captured the variability across subjects, including individual differences in brain lateralization. The algorithm performed well across different subject populations and data types, including task fMRI data. The approach was then validated by invasive cortical stimulation mapping in surgical patients, suggesting potential for use in clinical applications. C1 [Wang, Danhong; Buckner, Randy L.; Fox, Michael D.; Holt, Daphne J.; Stoecklein, Sophia; Pan, Ruiqi; Qian, Tianyi; Stufflebeam, Steven M.; Liu, Hesheng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Wang, Danhong; Buckner, Randy L.; Holt, Daphne J.; Holmes, Avram J.; Baker, Justin T.; Liu, Hesheng] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Fox, Michael D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat,Dept N, Boston, MA 02215 USA. [Fox, Michael D.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Stoecklein, Sophia] Univ Munich, Inst Clin Radiol, Munich, Germany. [Langs, Georg] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Computat Imaging Res Lab, Vienna, Austria. [Langs, Georg] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Qian, Tianyi; Hong, Bo] Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China. [Qian, Tianyi] Siemens Healthcare, MR Collaborat Nebraska Asia, Beijing, Peoples R China. [Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing, Peoples R China. [Baker, Justin T.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. [Stufflebeam, Steven M.] Harvard MIT Hlth Sci & Technol, Inst Med Engn & Sci, Cambridge, MA USA. [Wang, Kai] Anhui Med Univ, Affiliated Hosp 1, Dept Neurol, Hefei, Peoples R China. [Wang, Xiaomin] Capital Med Univ, Beijing Inst Brain Disorders, Beijing, Peoples R China. RP Liu, HS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM hongbo@tsinghua.edu.cn; hesheng@nmr.mgh.harvard.edu FU Human Connectome Project, WU-Minn Consortium - 16 NIH Institutes and Centers, NIH Blueprint for Neuroscience Research [1U54MH091657]; McDonnell Center for Systems Neuroscience at Washington University; Center for Brain Science Neuroinformatics Research group; Athinoula A. Martinos Center for Biomedical Imaging; Center for Human Genetic Research; NIH [K25NS069805, R01NS091604, P50MH106435, K01MH099232, R0IHD067312, P41EB015902]; OeNB [15929]; Medical Imaging Cluster of the Medical University of Vienna; National Basic Research Program of China [2011CB504100]; National Science Foundation of China [61473169]; National Program on Key Basic Research Projects of China [2011CB933204] FX The authors thank X. Peng and M. Li for technical assistance. Data set II was provided by the Human Connectome Project, WU-Minn Consortium (principal investigators, D. Van Essen and K. Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. Data set III was provided by the Brain Genomics Superstruct Project of Harvard University and the Massachusetts General Hospital (principal investigators, R.L.B., J. Roffman and J. Smoller), with support from the Center for Brain Science Neuroinformatics Research group, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Human Genetic Research. Twenty investigators at Harvard and MGH contributed data to the overall project. This work was supported by NIH grants K25NS069805 (H.L.), R01NS091604 (H.L.), P50MH106435 (R.L.B. and H.L.), K01MH099232 (A.J.H.), R0IHD067312 (G.L.), P41EB015902 (G.L.), OeNB Nr. 15929 (G.L.), Medical Imaging Cluster of the Medical University of Vienna (G.L.), National Basic Research Program of China Grant 2011CB504100 (X.W.), National Science Foundation of China Grant 61473169 (B.H.) and National Program on Key Basic Research Projects of China Grant 2011CB933204 (B.H.). NR 50 TC 25 Z9 26 U1 9 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2015 VL 18 IS 12 BP 1853 EP 1860 DI 10.1038/nn.4164 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CX1LV UT WOS:000365458600024 PM 26551545 ER PT J AU Cheloha, RW Gellman, SH Vilardaga, JP Gardella, TJ AF Cheloha, Ross W. Gellman, Samuel H. Vilardaga, Jean-Pierre Gardella, Thomas J. TI PTH receptor-1 signalling-mechanistic insights and therapeutic prospects SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID PARATHYROID-HORMONE RECEPTOR; PROTEIN-COUPLED-RECEPTOR; MALIGNANCY-ASSOCIATED HYPERCALCEMIA; NUCLEAR-LOCALIZATION SEQUENCE; MESSENGER RIBONUCLEIC-ACIDS; HETEROTRIMERIC G-PROTEINS; TARGET RESIDENCE TIME; BONE-MINERAL DENSITY; PEPTIDE RECEPTOR; POSTMENOPAUSAL WOMEN AB Parathyroid hormone/parathyroid hormone-related protein receptor (PTH/PTHrP type 1 receptor; commonly known as PTHR1) is a family B G-protein-coupled receptor (GPCR) that regulates skeletal development, bone turnover and mineral ion homeostasis. PTHR1 transduces stimuli from PTH and PTHrP into the interior of target cells to promote diverse biochemical responses. Evaluation of the signalling properties of structurally modified PTHR1 ligands has helped to elucidate determinants of receptor function and mechanisms of downstream cellular and physiological responses. Analysis of PTHR1 responses induced by structurally modified ligands suggests that PTHR1 can continue to signal through a G-protein-mediated pathway within endosomes. Such findings challenge the longstanding paradigm in GPCR biology that the receptor is transiently activated at the cell membrane, followed by rapid deactivation and receptor internalization. Evaluation of structurally modified PTHR1 ligands has further led to the identification of ligand analogues that differ from PTH or PTHrP in the type, strength and duration of responses induced at the receptor, cellular and organism levels. These modified ligands, and the biochemical principles revealed through their use, might facilitate an improved understanding of PTHR1 function in vivo and enable the treatment of disorders resulting from defects in PTHR1 signalling. This Review discusses current understanding of PTHR1 modes of action and how these findings might be applied in future therapeutic agents. C1 [Cheloha, Ross W.; Gellman, Samuel H.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. [Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Lab GPCR Biol, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM gardella@helix.mgh.harvard.edu FU Biotechnology Training Grant from NIGMS [T32 GM008349]; NIH [R01-GM056414, RO1-DK087688, R01-DK102495, P01-DK11794] FX R.W.C. was supported in part by a Biotechnology Training Grant from NIGMS (T32 GM008349). Work in the authors laboratories was supported by NIH grants R01-GM056414 (S.H.G.), RO1-DK087688, R01-DK102495 (J.-P.V.) and P01-DK11794 (T.J.G.). NR 115 TC 18 Z9 18 U1 4 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD DEC PY 2015 VL 11 IS 12 BP 712 EP 724 DI 10.1038/nrendo.2015.139 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW8AK UT WOS:000365220600002 PM 26303600 ER PT J AU Little, SE Zera, CA Clapp, MA Wilkins-Haug, L Robinson, JN AF Little, Sarah E. Zera, Chloe A. Clapp, Mark A. Wilkins-Haug, Louise Robinson, Julian N. TI A Multi-State Analysis of Early-Term Delivery Trends and the Association With Term Stillbirth SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RESPIRATORY MORBIDITY; ELECTIVE DELIVERIES; NEONATAL OUTCOMES; GESTATION; PREGNANCY AB OBJECTIVE:To investigate whether reduction in early-term deliveries was associated with increasing rates of term stillbirth.METHODS:This is a retrospective descriptive analysis of variation in term delivery timing and stillbirth from 2005 to 2011 based on birth certificate and fetal death data. Early-term deliveries (37 0/7-38 6/7 weeks of gestation) as a percentage of total term delivery and term stillbirth rates were calculated for each state, both overall and for low- and high-risk women. We analyzed whether state-level changes in early-term deliveries and term stillbirth were correlated using Pearson correlation coefficients. States were also categorized as high or low reduction (above or below the national average) and changes in stillbirth rates for these groups were analyzed using a Cochrane-Armitage test for linear trend.RESULTS:There was a decline in early-term deliveries across the United States: 1,123,467 of 3,533,233 term, singleton births occurred in the early term in 2005 (31.8%) as compared with 978,294 of 3,429,172 (28.5%) in 2011. Reductions varied widely by state. There was no change in the term stillbirth rate (123/100,000 births in 2005 compared with 130/100,000 in 2011; P=.189) nor change in the high reduction states alone. There was no correlation between state-level changes in early-term deliveries and term stillbirth. There was an increase in term stillbirths among women with diabetes (from 238/100,000 to 300/100,000 births; P=.010), independent of changes in early-term delivery timing.CONCLUSION:The reduction in early-term deliveries across the United States between 2005 and 2011 was not associated with an increase in the rate of term stillbirth.LEVEL OF EVIDENCE:II C1 Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Little, SE (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM selittle@partners.org NR 18 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2015 VL 126 IS 6 BP 1138 EP 1145 DI 10.1097/AOG.0000000000001109 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CW9EL UT WOS:000365301300004 PM 26551175 ER PT J AU Rauh-Hain, JA Pepin, KJ Meyer, LA Clemmer, JT Lu, KH Rice, LW Uppal, S Schorge, JO del Carmen, MG AF Rauh-Hain, J. Alejandro Pepin, Kristen J. Meyer, Larissa A. Clemmer, Joel T. Lu, Karen H. Rice, Laurel W. Uppal, Shitanshu Schorge, John O. del Carmen, Marcela G. TI Management for Elderly Women With Advanced-Stage, High-Grade Endometrial Cancer SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID OLD TUMOR CHARACTERISTICS; BREAST-CANCER; GREATER-THAN-OR-EQUAL-TO-70 YEARS; DATA-BASE; SURVIVAL; AGE; MORBIDITY; IMPACT; ADENOCARCINOMA; COMORBIDITY AB OBJECTIVE:To examine the treatment and survival of elderly women diagnosed with advanced-stage, high-grade endometrial cancer.METHODS:We performed a retrospective cohort study of women diagnosed between 2003 and 2011 with advanced-stage, high-grade endometrial cancers (grade 3 adenocarcinoma, carcinosarcoma, clear-cell carcinoma, and uterine serous carcinoma) using the National Cancer Database. Women were stratified by age: younger than 55, 55-64, 65-74, 75-84, and 85 years old or older. Multivariate logistic regression models and Cox proportional hazards survival methods for all-cause mortality were used for analyses.RESULTS:Twenty thousand four hundred sixty-eight patients were included, 14.9% younger than 55 years, 30.9% 55-64 years, 31.1% 65-74 years, 18.8% 75-84 years, and 4.3% 85 years old or older. Patients younger than 55 years had surgery more frequently compared with patients 75-84 years (97.2% compared with 95.8%; P<.001) and 85 years or older (97.2% compared with 94.8%; P<.001) and a higher rate of lymph node dissection (78.7% compared with 70.5%; P<.001 and 78.7% compared with 59.5%; P<.001, respectively). Women younger than 55 years old were more likely to receive chemotherapy compared with those 75-84 years (63.9% compared with 42.2%; P<.001) and 85 years old or older (63.9% compared with 22%; P<.001). After adjusting for prognostic factors, women ages 75-84 and 85 years or older were less likely to have received chemotherapy compared with women younger than 55 years (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.29-0.38 and OR 0.12, 95% CI 0.10-0.14). The same was true with surgery (OR 0.63, 95% CI 0.45-0.88 and OR 0.46, 95% CI 0.30-0.70) and radiotherapy (OR 0.61, 95% CI 0.53-0.70 and OR 0.45, 95% CI 0.37-0.56). The Cox regression model showed that in women with stage III disease, women 75-84 years had a twofold higher risk of death (hazard ratio [HR] 2.38, 95% CI 2.14-2.65) and those 85 years or older had a threefold higher risk (HR 3.16, 95% CI 2.76-3.61) compared with patients younger than 55 years. Patients with stage IV and age 75-84 years had a 24% increased risk of death (HR 1.24, 95% CI 1.11-1.40) and those 85 years or older had a 52% increased risk (HR 1.52, 95% CI 1.29-1.79).CONCLUSION:Elderly women with high-grade endometrial cancer are less likely to be treated with surgery, chemotherapy, or radiation.LEVEL OF EVIDENCE:II C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. Univ Wisconsin Hosp & Clin, Dept Obstet & Gynecol, Madison, WI 53792 USA. Univ Michigan, Div Gynecol Oncol Obstet & Gynecol, Ann Arbor, MI 48109 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX Supported by The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 31 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2015 VL 126 IS 6 BP 1198 EP 1206 DI 10.1097/AOG.0000000000001140 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CW9EQ UT WOS:000365301800007 PM 26551187 ER PT J AU Eckhard, A Dos Santos, A Liu, W Bassiouni, M Arnold, H Gleiser, C Hirt, B Harteneck, C Muller, M Rask-Andersen, H Lowenheim, H AF Eckhard, A. Dos Santos, A. Liu, W. Bassiouni, M. Arnold, H. Gleiser, C. Hirt, B. Harteneck, C. Mueller, M. Rask-Andersen, H. Loewenheim, H. TI Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-5 SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE Aquaporin; Cochlea; Water permeability; Muscarinic; Pilocarpine; Meniere's disease ID SULCUS EPITHELIAL-CELLS; RAT PAROTID-GLANDS; MENIERES-DISEASE; INNER-EAR; GUINEA-PIG; SERUM OSMOLALITY; SWEAT GLANDS; MUSCARINIC RECEPTORS; ANTIDIURETIC-HORMONE; CATION ABSORPTION AB Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as M,niSre's disease. C1 [Eckhard, A.; Dos Santos, A.; Bassiouni, M.; Arnold, H.] Univ Tubingen, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Tubingen, Germany. [Liu, W.; Rask-Andersen, H.] Univ Uppsala Hosp, Otolaryngol Sect, Dept Surg Sci, Uppsala, Sweden. [Harteneck, C.] Univ Tubingen, Dept Pharmacol & Expt Therapy, Inst Expt & Clin Pharmacol & Toxicol, Interfac Ctr Pharmacogen & Pharmaceut Res ICePhA, Tubingen, Germany. [Gleiser, C.; Hirt, B.] Univ Tubingen, Inst Anat, Tubingen, Germany. [Eckhard, A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. [Mueller, M.; Loewenheim, H.] Carl von Ossietzky Univ Oldenburg, Sch Med & Hlth Sci, European Med Sch, Univ Hosp Otorhinolaryngol, D-26122 Oldenburg, Germany. [Mueller, M.; Loewenheim, H.] Carl von Ossietzky Univ Oldenburg, Res Ctr Neurosensory Sci, D-26111 Oldenburg, Germany. [Mueller, M.; Loewenheim, H.] Carl von Ossietzky Univ Oldenburg, Cluster Excellence Hearing4all, D-26111 Oldenburg, Germany. RP Lowenheim, H (reprint author), Carl von Ossietzky Univ Oldenburg, Sch Med & Hlth Sci, European Med Sch, Univ Hosp Otorhinolaryngol, Med Campus,Steinweg 13-17, D-26122 Oldenburg, Germany. EM hubert.loewenheim@uni-oldenburg.de RI Muller, Marcus/B-3877-2016 OI Muller, Marcus/0000-0001-5881-7708 FU Institutional Strategy of the University of Tubingen (Deutsche Forschungsgemeinschaft) [ZUK 63] FX We thank Dr. Peter Bako, Dr. Karina Gutlig and Teresa Grundel for their excellent technical assistance. A. Eckhard was supported by the Institutional Strategy of the University of Tubingen (Deutsche Forschungsgemeinschaft, ZUK 63). NR 91 TC 5 Z9 5 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 EI 1432-2013 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD DEC PY 2015 VL 467 IS 12 BP 2571 EP 2588 DI 10.1007/s00424-015-1720-6 PG 18 WC Physiology SC Physiology GA CW7OA UT WOS:000365187500016 PM 26208470 ER PT J AU Ricci, JA Driscoll, DN AF Ricci, Joseph A. Driscoll, Daniel N. TI Removing the Ambiguity from the Double Bubble SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Ricci, Joseph A.; Driscoll, Daniel N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. RP Ricci, JA (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 55 Fruit St, Boston, MA 02114 USA. EM jaricci@partners.org NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2015 VL 136 IS 6 BP 864E EP 865E DI 10.1097/PRS.0000000000001794 PG 2 WC Surgery SC Surgery GA CW6PI UT WOS:000365119300001 PM 26301610 ER PT J AU Miller, MW Wolf, EJ Sadeh, N Logue, M Spielberg, JM Hayes, JP Sperbeck, E Schichman, SA Stone, A Carter, WC Humphries, DE Milberg, W McGlinchey, R AF Miller, Mark W. Wolf, Erika J. Sadeh, Naomi Logue, Mark Spielberg, Jeffrey M. Hayes, Jasmeet P. Sperbeck, Emily Schichman, Steven A. Stone, Angie Carter, Weleetka C. Humphries, Donald E. Milberg, William McGlinchey, Regina TI A novel locus in the oxidative stress-related gene ALOX12 moderates the association between PTSD and thickness of the prefrontal cortex SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Posttraumatic stress disorder; Oxidative stress; ALOX12; Cortical thickness; Factor analysis; Genetic association analysis ID REDUCED CORTICAL THICKNESS; ANTERIOR CINGULATE CORTEX; CELL-DEATH; CEREBRAL-CORTEX; 12/15-LIPOXYGENASE; 12-LIPOXYGENASE; METAANALYSIS; DISORDER; BRAIN; OLIGODENDROCYTES AB Oxidative stress has been implicated in many common age-related diseases and is hypothesized to play a role in posttraumatic stress disorder (PTSD)-related neurodegeneration (Miller and Sadeh, 2014). This study examined the influence of the oxidative stress-related genes ALOX 12 and ALOX 15 on the association between PTSD and cortical thickness. Factor analyses were used to identify and compare alternative models of the structure of cortical thickness in a sample of 218 veterans. The best-fitting model was then used for a genetic association analysis in White non-Hispanic participants (n = 146) that examined relationships between 33 single nucleotide polymorphisms (SNPs) spanning the two genes, 8 cortical thickness factors, and each SNP x PTSD interaction. Results identified a novel ALOX12 locus (indicated by two SNPs in perfect linkage disequilibrium: rs1042357 and rs10852889) that moderated the association between PTSD and reduced thickness of the right prefrontal cortex. A whole-cortex vertex-wise analysis showed this effect to be localized to clusters spanning the rostral middle frontal gyrus, superior frontal gyrus, rostral anterior cingulate cortex, and medial orbitofrontal cortex. These findings illustrate a novel factor-analytic approach to neuroimaging-genetic analyses and provide new evidence for the possible involvement of oxidative stress in PTSD-related neurodegeneration. Published by Elsevier Ltd. C1 [Miller, Mark W.; Wolf, Erika J.; Sadeh, Naomi; Hayes, Jasmeet P.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. [Miller, Mark W.; Wolf, Erika J.; Sadeh, Naomi; Spielberg, Jeffrey M.; Hayes, Jasmeet P.; Sperbeck, Emily] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Logue, Mark] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Logue, Mark] Boston Univ, Sch Med, Biomed Genet, Boston, MA 02118 USA. [Logue, Mark] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Spielberg, Jeffrey M.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Schichman, Steven A.; Stone, Angie; Carter, Weleetka C.] Cent Arkansas Vet Healthcare Syst, Res Serv, Pharmacogen Anal Lab, Little Rock, AR USA. [Humphries, Donald E.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Milberg, William; McGlinchey, Regina] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Milberg, William; McGlinchey, Regina] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders, Boston, MA USA. [Milberg, William; McGlinchey, Regina] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435; Sadeh, Naomi/0000-0002-8101-3190 FU National Institute of Mental Health (NIMH) [R21MH102834]; Translational Research Center for TBI and Stress Disorders (TRACTS); U.S. Department of Veterans Affairs (VA) Rehabilitation Research and Development (RR&D) Traumatic Brain Injury Center of Excellence at VA Boston Healthcare System [B9254-C]; Career Development Award from the VA Clinical Sciences Research and Development Program FX This research and preparation of this manuscript was supported by a National Institute of Mental Health (NIMH) grant awarded to MWM (R21MH102834, "Neuroimaging Genetics of PTSD") and the Translational Research Center for TBI and Stress Disorders (TRACTS), a U.S. Department of Veterans Affairs (VA) Rehabilitation Research and Development (RR&D) Traumatic Brain Injury Center of Excellence (B9254-C) at VA Boston Healthcare System. This research is the result of work supported with resources and the use of facilities at the Pharmacogenomics Analysis Laboratory, Research and Development Service, Central Arkansas VA Healthcare System, Little Rock, Arkansas. This work was also supported by a Career Development Award to EJW from the VA Clinical Sciences Research and Development Program. The contents of this manuscript do not represent the views of the VA, NIH or the United States Government. NR 38 TC 1 Z9 1 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD DEC PY 2015 VL 62 BP 359 EP 365 DI 10.1016/j.psyneuen.2015.09.003 PG 7 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA CW5UU UT WOS:000365062900040 PM 26372769 ER PT J AU Son, S Stevens, MM Chao, HX Thoreen, C Hosios, AM Schweitzer, LD Weng, YC Wood, K Sabatini, D Vander Heiden, MG Manalis, S AF Son, Sungmin Stevens, Mark M. Chao, Hui Xiao Thoreen, Carson Hosios, Aaron M. Schweitzer, Lawrence D. Weng, Yaochung Wood, Kris Sabatini, David Vander Heiden, Matthew G. Manalis, Scott TI Cooperative nutrient accumulation sustains growth of mammalian cells SO SCIENTIFIC REPORTS LA English DT Article ID SIZE HOMEOSTASIS; METABOLISM; PROLIFERATION; KINASE AB The coordination of metabolic processes to allow increased nutrient uptake and utilization for macromolecular synthesis is central for cell growth. Although studies of bulk cell populations have revealed important metabolic and signaling requirements that impact cell growth on long time scales, whether the same regulation influences short-term cell growth remains an open question. Here we investigate cell growth by monitoring mass accumulation of mammalian cells while rapidly depleting particular nutrients. Within minutes following the depletion of glucose or glutamine, we observe a growth reduction that is larger than the mass accumulation rate of the nutrient. This indicates that if one particular nutrient is depleted, the cell rapidly adjusts the amount that other nutrients are accumulated, which is consistent with cooperative nutrient accumulation. Population measurements of nutrient sensing pathways involving mTOR, AKT, ERK, PKA, MST1, or AMPK, or pro-survival pathways involving autophagy suggest that they do not mediate this growth reduction. Furthermore, the protein synthesis rate does not change proportionally to the mass accumulation rate over these time scales, suggesting that intracellular metabolic pools buffer the growth response. Our findings demonstrate that cell growth can be regulated over much shorter time scales than previously appreciated. C1 [Son, Sungmin; Stevens, Mark M.; Chao, Hui Xiao; Hosios, Aaron M.; Weng, Yaochung; Vander Heiden, Matthew G.; Manalis, Scott] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Stevens, Mark M.; Thoreen, Carson; Hosios, Aaron M.; Schweitzer, Lawrence D.; Sabatini, David; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA USA. [Son, Sungmin; Manalis, Scott] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Manalis, Scott] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Weng, Yaochung] MIT, Computat & Syst Biol Initiat, Cambridge, MA 02139 USA. [Thoreen, Carson; Schweitzer, Lawrence D.; Wood, Kris; Sabatini, David] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Manalis, S (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM srm@mit.edu FU Koch Institute Support (core) Grant from the National Cancer Institute, Physical Sciences Oncology Center [P30-CA14051, U54CA143874]; US National Institutes of Health [R01GM085457]; NCI Fellowship [F31CA167872]; NIH Interdepartmental Biotechnology Training Program [T32GM008334] FX This work was supported by Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute, Physical Sciences Oncology Center U54CA143874 and contract R01GM085457 from the US National Institutes of Health. L.D.S is a recipient of NCI Fellowship F31CA167872. M.M.S acknowledges support from the NIH Interdepartmental Biotechnology Training Program T32GM008334. NR 23 TC 1 Z9 1 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD DEC 1 PY 2015 VL 5 AR 17401 DI 10.1038/srep17401 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX1VN UT WOS:000365483800001 PM 26620632 ER PT J AU Cai, XM Rosand, J AF Cai, Xuemei Rosand, Jonathan TI The Evaluation and Management of Adult Intracerebral Hemorrhage SO SEMINARS IN NEUROLOGY LA English DT Article DE intracerebral hemorrhage; diagnosis; treatment; coagulopathy; surgery ID ASSOCIATION/AMERICAN STROKE ASSOCIATION; INITIAL CONSERVATIVE TREATMENT; EXTERNAL VENTRICULAR DRAINAGE; PREDICTING HEMATOMA EXPANSION; MINIMALLY INVASIVE SURGERY; HEALTH-CARE PROFESSIONALS; CEREBELLAR HEMORRHAGE; INTRAVENTRICULAR HEMORRHAGE; VENOUS THROMBOEMBOLISM; BLOOD-PRESSURE AB Intracerebral hemorrhage (ICH) is the most disabling and deadly form of stroke. Although mortality remains high, new data suggest that outcomes can be improved with standardized medical care. In this review, the authors outline the most up-to-date knowledge, including the results of the latest phase III clinical trials on the specialized care needed to treat patients with ICH. They provide an overview on how to achieve rapid diagnosis and the initial steps of intervention to reduce hematoma volume or prevent expansion by modifying potentially treatable conditions, such as underlying vascular etiologies, blood pressure control, and coagulopathies. Grading scales can help identify patients at risk for hematoma expansion and functional disabilities and guide clinical decision making. Other medical management topics important to recovery and prevention of secondary brain injury include seizure prevention and treatment, glycemic control, temperature control, and deep venous thrombosis prophylaxis and treatment. Treatment options in surgery are also possible in select patients; there are emerging studies regarding minimally invasive surgery for the management of ICH. These aggressive therapies are essential to lower themorbidity andmortality of patients presenting with ICH. C1 [Cai, Xuemei] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Cai, XM (reprint author), Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, 55 Fruit St, Boston, MA 02114 USA. EM caix@post.harvard.edu NR 85 TC 2 Z9 2 U1 1 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 2015 VL 35 IS 6 BP 638 EP 645 DI 10.1055/s-0035-1564687 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CW9VI UT WOS:000365345900006 PM 26595864 ER PT J AU Ahasic, AM Christiani, DC AF Ahasic, Amy M. Christiani, David C. TI Personalized Critical Care Medicine: How Far Away Are We? SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE personalized medicine; critical care; sepsis; ARDS; pharmacogenomics; biomarkers; genetics ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; RANDOMIZED CONTROLLED-TRIAL; ENDOTHELIAL GROWTH-FACTOR; PULMONARY-EDEMA FLUID; ALVEOLAR EPITHELIAL REPAIR; GLYCATION END-PRODUCTS; PEDIATRIC SEPTIC SHOCK; VON-WILLEBRAND-FACTOR AB Personalized medicine has typically referred to the use of genomics in clinical care. However, the concept more broadly refers to recognizing the heterogeneity of each individual patient, particularly their unique risk factors for developing disease or having poor outcomes, and using this to inform treatment decisions. Pharmacogenomics was perhaps the first major clinical application that came out of the Human Genome Project, but its translation to the critical care arena has been limited by numerous factors. Biomarkers have been widely studied in critical illnesses such as sepsis and acute respiratory distress syndrome in an attempt to aid in accurate diagnostic classification, to predict outcomes, and to assess response to therapy. Clinical use of such biomarkers has remained limited, but multi-biomarker panels have attempted to better reflect the complex physiology of critical illness, and to assist in design and recruitment for clinical trials. Genetic association and gene expression studies have been aimed at classifying risk for and severity in disease, as well as in predicting outcomes. While our understanding of the pathogenesis of critical illness has progressed significantly, the clinical utility of genetic markers remains limited. Novel methods are reaching closer to clinically applicable platforms, both for use in clinical trials and in direct patient care. Although we are not yet living in an era of personalized and precise medical care in the intensive care unit, the future is promising. C1 [Ahasic, Amy M.] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT 06520 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Sch Med, Dept Environm Genet, Harvard, MA USA. [Christiani, David C.] Massachusetts Gen Hosp, Harvard, MA USA. RP Ahasic, AM (reprint author), Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, 333 Cedar St,POB 208057, New Haven, CT 06520 USA. EM amy.ahasic@yale.edu NR 140 TC 1 Z9 1 U1 2 U2 9 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD DEC PY 2015 VL 36 IS 6 BP 809 EP 822 DI 10.1055/s-0035-1564852 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW8UV UT WOS:000365275800002 PM 26595041 ER PT J AU Meressa, D Hurtado, RM Andrews, JR Diro, E Abato, K Daniel, T Prasad, P Prasad, R Fekade, B Tedla, Y Yusuf, H Tadesse, M Tefera, D Ashenafi, A Desta, G Aderaye, G Olson, K Thim, S Goldfeld, AE AF Meressa, Daniel Hurtado, Roco M. Andrews, Jason R. Diro, Ermias Abato, Kassim Daniel, Tewodros Prasad, Paritosh Prasad, Rebekah Fekade, Bekele Tedla, Yared Yusuf, Hanan Tadesse, Melaku Tefera, Dawit Ashenafi, Abraham Desta, Girma Aderaye, Getachew Olson, Kristian Thim, Sok Goldfeld, Anne E. TI Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia-an observational cohort study SO THORAX LA English DT Article ID SOUTH-AFRICA; TUBERCULOSIS PATIENTS; ANTIRETROVIRAL THERAPY; TREATMENT OUTCOMES; CLINICAL-OUTCOMES; PROGRAM; HOSPITALIZATION; METAANALYSIS; OUTBREAK; DEFAULT AB Background In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients. Methods A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models. Results From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had >= 24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003)and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death. Conclusions We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes. C1 [Meressa, Daniel; Hurtado, Roco M.; Diro, Ermias; Abato, Kassim; Daniel, Tewodros; Prasad, Paritosh; Prasad, Rebekah; Fekade, Bekele; Yusuf, Hanan; Tadesse, Melaku; Tefera, Dawit; Ashenafi, Abraham; Desta, Girma; Olson, Kristian; Thim, Sok; Goldfeld, Anne E.] Global Hlth Comm, Addis Ababa, Ethiopia. [Meressa, Daniel; Hurtado, Roco M.; Diro, Ermias; Abato, Kassim; Daniel, Tewodros; Prasad, Paritosh; Prasad, Rebekah; Fekade, Bekele; Yusuf, Hanan; Tadesse, Melaku; Tefera, Dawit; Ashenafi, Abraham; Desta, Girma; Olson, Kristian; Thim, Sok; Goldfeld, Anne E.] Zahara Childrens Program, Addis Ababa, Ethiopia. [Hurtado, Roco M.; Tedla, Yared] St Peters TB Specialized Hosp, Addis Ababa, Ethiopia. [Hurtado, Roco M.; Andrews, Jason R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Andrews, Jason R.] Stanford Univ, Sch Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. [Diro, Ermias] Univ Gondar Hosp, Gondar, Ethiopia. [Olson, Kristian] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Aderaye, Getachew] Hallelujah Clin, Addis Ababa, Ethiopia. [Thim, Sok; Goldfeld, Anne E.] Cambodian Hlth Comm, Phnom Penh, Cambodia. [Goldfeld, Anne E.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, 200 Longwood Ave, Boston, MA 02115 USA. EM Anne.Goldfeld@childrens.harvard.edu FU Annenberg Foundation; Lilly MDR Partnership; Lilly Foundation; Ethiopian Federal Ministry of Health FX The programme received grants to GHC and its Zahara Children's Program from the Jolie-Pitt Foundation; and to GHC from the Annenberg Foundation; Lilly MDR Partnership; and Lilly Foundation; and gifts to GHC from the Blue Oak and Frankel Family Foundations, and from Jeanne Sullivan. Funds from the Ethiopian Federal Ministry of Health supported the clinical and laboratory infrastructure at St Peters and UoG and the health centres. The Stanford Center for Innovation in Global Health and the National Institutes of Health (K01 AI104411) provided support to JRA and Children's Hospital Boston provided support to AEG. NR 32 TC 6 Z9 6 U1 1 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 EI 1468-3296 J9 THORAX JI Thorax PD DEC PY 2015 VL 70 IS 12 BP 1181 EP U103 DI 10.1136/thoraxjnl-2015-207374 PG 8 WC Respiratory System SC Respiratory System GA CW7ZP UT WOS:000365218400014 PM 26506854 ER PT J AU Asnaani, A Aderka, IM Marques, L Simon, N Robinaugh, DJ Hofmann, SG AF Asnaani, Anu Aderka, Idan M. Marques, Luana Simon, Naomi Robinaugh, Donald J. Hofmann, Stefan G. TI The structure of feared social situations among race-ethnic minorities and Whites with social anxiety disorder in the United States SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE African American; collaborative psychiatric epidemiology studies; culture; ethnicity; Latino; social anxiety disorder; White ID NATIONAL-COMORBIDITY-SURVEY; MENTAL-HEALTH SURVEYS; SURVEY REPLICATION; ASIAN-AMERICAN; 12-MONTH PREVALENCE; SELF-CONSTRUALS; DSM-V; LIFETIME; EPIDEMIOLOGY; RELIABILITY AB We investigated feared social situations in individuals with social anxiety disorder from different racial and ethnic groups in the United States. The sample included 247 African Americans, 158 Latinos, and 533 non-Latino Whites diagnosed with social anxiety disorder within the past 12 months from the integrated Collaborative Psychiatric Epidemiology Studies data set. After randomly splitting the full sample, we conducted an exploratory factor analysis with half of the sample to determine the structure of feared social situations in a more diverse sample than has been used in previous studies. We found evidence for a model consisting of three feared social domains: performance/public speaking, social interaction, and observational. We then conducted a confirmatory factor analysis on the remaining half of the sample to examine whether this factor structure varied significantly between the race-ethnic groups. Analyses revealed an adequate fit of this model across all three race-ethnic groups, suggesting invariance of the factor structure between the study groups. Broader cultural contexts within which these findings are relevant are discussed, along with important implications for comprehensive, culturally sensitive assessment of social anxiety. C1 [Asnaani, Anu] Univ Penn, Dept Psychiat, Clin Psychol, Philadelphia, PA 19104 USA. [Aderka, Idan M.] Boston Univ, Boston, MA 02215 USA. [Aderka, Idan M.] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel. [Marques, Luana] Massachusetts Gen Hosp, Community Psychiat Program Res Implementat & Diss, Boston, MA 02114 USA. [Marques, Luana] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Simon, Naomi] Harvard Univ, Sch Med, Psychiat, Cambridge, MA 02138 USA. [Robinaugh, Donald J.] Harvard Univ, Sch Med, Clin Psychol, Dept Psychol, Cambridge, MA 02138 USA. [Hofmann, Stefan G.] Boston Univ, Dept Psychol & Brain Sci, Psychol, Boston, MA 02215 USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 FU National Institute of Mental Health (NIMH) [MH-078308, MH-081116]; NIMH; Department of Defense (DOD); American Foundation for Suicide Prevention FX Stefan G. Hofmann receives compensation for his work as an advisor for the Palo Alto Health Sciences and Otsuka America Pharmaceutical, Inc., and receives royalties and payments for his editorial work from various publishers. This study was partially supported by National Institute of Mental Health (NIMH) Grants MH-078308 and MH-081116 awarded to Stefan Hofmann. Naomi Simon is partially supported by a grant sponsored by the NIMH, Department of Defense (DOD), and the American Foundation for Suicide Prevention, and is also a paid consultant for Massachusetts General Hospital Psychiatry Academy, both for work unrelated to this study. NR 43 TC 0 Z9 0 U1 7 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 EI 1461-7471 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD DEC PY 2015 VL 52 IS 6 BP 791 EP 807 DI 10.1177/1363461515576823 PG 17 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA CW8LH UT WOS:000365250600012 PM 25795220 ER PT J AU Sagara, Y Barry, WT Mallory, MA Vaz-Luis, I Aydogan, F Brock, JE Winer, EP Golshan, M Metzger, O AF Sagara, Yasuaki Barry, William T. Mallory, Melissa Anne Vaz-Luis, Ines Aydogan, Fatih Brock, Jane E. Winer, Eric P. Golshan, Mehra Metzger-Filho, Otto TI Surgical Options and Locoregional Recurrence in Patients Diagnosed with Invasive Lobular Carcinoma of the Breast SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID 20-YEAR FOLLOW-UP; CONSERVING SURGERY; RANDOMIZED-TRIAL; CONSERVATION THERAPY; DUCTAL CARCINOMA; MARGIN STATUS; RE-EXCISION; CANCER; MASTECTOMY; FEATURES AB Recent consensus guidelines on margins for breast-conserving surgery (BCS) recommend the use of "no ink on tumor" as the standard for an adequate margin. The recommendations extend to invasive lobular carcinoma (ILC), but the data on this subset are limited. We reviewed our modern dataset on margin status with outcomes of ILC. We performed a retrospective cohort study on 736 patients with a diagnosis of stage I-III ILC treated at our cancer center between May 1997 and December 2007. Clinicopathologic data were extracted from the Clinical Research Information Systems Database. Margin status was defined using the latest ASCO/ASTRO/SSO consensus guideline criteria. The initial surgery performed was mastectomy in 352 patients (48 %) and BCS in 384 patients (52 %). In multivariate analysis, tumor size and multifocality were significantly associated with high rates of mastectomy and positive surgical margins at initial BCS. After initial BCS, additional surgery was performed in 92 patients (24 %). During a 72-month median follow-up period, 12 (3.1 %) ipsilateral breast tumor recurrences (IBTR) and 5 (1.3 %) other locoregional recurrences (LRR) were observed. Patients with margins with ink on tumor who did not receive further surgery were found to have significantly increased LRR [odds ratio (OR) 5.5; p = 0.02] and IBTR (OR 8.5; p = 0.006), whereas patients with close margins (1-3 mm) and margins within 1 mm were not. Our study supports the validity of using "no ink on tumor" as the standard for a negative margin for pure and mixed ILC treated with multimodality therapy. C1 [Sagara, Yasuaki; Mallory, Melissa Anne; Aydogan, Fatih; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Vaz-Luis, Ines; Winer, Eric P.; Metzger-Filho, Otto] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brock, Jane E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sagara, Y (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM yasuaki@sagara.or.jp FU NCI NIH HHS [R25 CA089017, R25CA089017] NR 29 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2015 VL 22 IS 13 BP 4280 EP 4286 DI 10.1245/s10434-015-4570-8 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA CW4JS UT WOS:000364958200026 PM 25893416 ER PT J AU Kilpatrick, LA Istrin, JJ Gupta, A Naliboff, BD Tillisch, K Labus, JS Mayer, EA AF Kilpatrick, Lisa A. Istrin, Joshua J. Gupta, Arpana Naliboff, Bruce D. Tillisch, Kirsten Labus, Jennifer S. Mayer, Emeran A. TI Sex commonalities and differences in the relationship between resilient personality and the intrinsic connectivity of the salience and default mode networks SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Resilience; NEO personality inventory; Resting state networks; Default mode network; Salience network; Sex differences ID POSTERIOR CINGULATE CORTEX; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; TEMPORO-PARIETAL JUNCTION; FUNCTIONAL CONNECTIVITY; INDEPENDENT COMPONENTS; COGNITIVE CONTROL; TRAIT RESILIENCE; LIFE EVENTS; HUMAN BRAIN; DSM-IV AB Increased resilience is associated with better health outcomes and reduced morbidity in response to injury and homeostatic perturbations. Proper functioning of the salience network (SN) and modulation of the default mode network (DMN) by SN may play a role in adaptively responding to stress. Here, we demonstrate that resilient personality in healthy subjects is associated with SN and DMN connectivity patterns and that these patterns are influenced by sex. While connectivity of SN with several brain regions including right anterior insula was significantly associated with resilient personality in both men and women, results suggest that increased functional integration of anterior DMN preferentially benefits women while increased functional integration of posterior DMN preferentially benefits men in terms of resilience. These findings may relate to previous demonstrations that men and women engage different information processing and behavioral strategies to achieve resilience and highlight the importance of considering sex in resilience research. (C) 2015 Elsevier B.V. All rights reserved. C1 [Kilpatrick, Lisa A.; Istrin, Joshua J.; Gupta, Arpana; Naliboff, Bruce D.; Tillisch, Kirsten; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Oppenheimer Family Ctr Neurobiol Stress, Los Angeles, CA USA. [Kilpatrick, Lisa A.; Gupta, Arpana; Naliboff, Bruce D.; Tillisch, Kirsten; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Naliboff, Bruce D.; Tillisch, Kirsten; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Naliboff, Bruce D.; Tillisch, Kirsten; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. [Kilpatrick, Lisa A.; Naliboff, Bruce D.; Tillisch, Kirsten; Labus, Jennifer S.; Mayer, Emeran A.] Univ Calif Los Angeles, Pain & Interocept Network PAIN, Los Angeles, CA USA. [Tillisch, Kirsten] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Kilpatrick, LA (reprint author), Oppenheimer Family Ctr Neurobiol Stress, 10833 Le Conte Ave,CHS 42-210 MC 737818, Los Angeles, CA 90095 USA. EM lisa@lisakilpatrick.com FU NIH [DK048351, DK64539, K01 DK085133, P30 DK041301] FX Supported by NIH grants DK048351, DK64539, K01 DK085133, P30 DK041301. NR 77 TC 1 Z9 1 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 EI 1873-6246 J9 BIOL PSYCHOL JI Biol. Psychol. PD DEC PY 2015 VL 112 BP 107 EP 115 DI 10.1016/j.biopsycho.2015.09.010 PG 9 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA CW5ON UT WOS:000365045800011 PM 26440126 ER PT J AU Kaplan, DE Dai, F Aytaman, A Baytarian, M Fox, R Hunt, K Knott, A Pedrosa, M Pocha, C Mehta, R Duggal, M Skanderson, M Valderrama, A Taddei, TH AF Kaplan, David E. Dai, Feng Aytaman, Ayse Baytarian, Michelle Fox, Rena Hunt, Kristel Knott, Astrid Pedrosa, Marcos Pocha, Christine Mehta, Rajni Duggal, Mona Skanderson, Melissa Valderrama, Adriana Taddei, Tamar H. CA VOCAL Study Grp TI Development and Performance of an Algorithm to Estimate the Child-Turcotte-Pugh Score From a National Electronic Healthcare Database SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Cirrhosis; Hepatocellular Carcinoma; Child-Turcotte-Pugh Score; Hepatitis C; Human; Survival; Natural History; Database ID STAGE LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; ADMINISTRATIVE DATABASES; PREDICT SURVIVAL; CIRRHOSIS; MELD; MORTALITY; MODEL; CLASSIFICATION; RECLASSIFICATION AB BACKGROUND & METHODS: The Child-Turcotte-Pugh (CTP) score is a widely used andvalidated predictor of long-term survival in cirrhosis. The CTP score is a composite of 5 subscores, 3 based on objective clinical laboratory values and 2 subjective variables quantifying the severity of ascites and hepatic encephalopathy. To date, no system to quantify CTP score from administrative databases has been validated. The Veterans Outcomes and Costs Associated with Liver Disease study is a multicenter collaborative study to evaluate the outcomes and costs of hepatocellular carcinoma in the U.S. Veterans Health Administration. We developed and validated an algorithm to calculate electronic CTP (eCTP) scores by using data from the Veterans Health Administration Corporate Data Warehouse. METHODS: Multiple algorithms for determining each CTP subscore from International Classification of Diseases version 9, Common Procedural Terminology, pharmacy, and laboratory data were devised and tested in 2 patient cohorts. For each cohort, 6 site investigators (Boston, Bronx, Brooklyn, Philadelphia, Minneapolis, and West Haven VA Medical Centers) were provided cases from which to determine validity of diagnosis, laboratory data, and clinical assessment of ascites and encephalopathy. The optimal algorithm (designated eCTP) was then applied to 30,840 cirrhotic patients alive in the first quarter of 2008 for whom 5-year overall and transplant-free survival data were available. The ability of the eCTP score and other disease severity scores (Charlson-Deyo index, Veterans Aging Cohort Study index, Model for End-Stage Liver Disease score, and Cirrhosis Comorbidity) to predict survival was then assessed by Cox proportional hazards regression. RESULTS: Spearman correlations for administrative and investigator validated laboratory data in the HCC and cirrhotic cohorts, respectively, were 0.85 and 0.92 for bilirubin, 0.92 and 0.87 for albumin, and 0.84 and 0.86 for international normalized ratio. In the HCC cohort, the overall eCTP score matched 96% of patients to within 1 point of the chart-validated CTP score (Spearman correlation, 0.81). In the cirrhosis cohort, 98% were matched to within 1 point of their actual CTP score (Spearman, 0.85). When applied to a cohort of 30,840 patients with cirrhosis, each unit change in eCTP was associated with 39% increase in the relative risk of death or transplantation. The Harrell C statistic for the eCTP (0.678) was numerically higher than those for other disease severity indices for predicting 5-year transplant-free survival. Adding other predictive models to the eCTP resulted in minimal differences in its predictive performance. CONCLUSION: We developed and validated an algorithm to extrapolate an eCTP score from data in a large administrative database with excellent correlation to actual CTP score on chart review. When applied to an administrative database, this algorithm is a highly useful predictor of survival when compared with multiple other published liver disease severity indices. C1 [Kaplan, David E.] Corporal Michael J Crescenz VA Med Ctr, Philadelphia, PA 19104 USA. [Dai, Feng; Mehta, Rajni; Duggal, Mona; Skanderson, Melissa; Taddei, Tamar H.] VA Connecticut Hlth Care Syst, West Haven, CT USA. [Aytaman, Ayse] VA New York Harbor Healthcare Syst, Brooklyn, NY USA. [Baytarian, Michelle; Pedrosa, Marcos] Boston VA Healthcare Syst, Boston, MA USA. [Fox, Rena] San Francisco VA Med Ctr, San Francisco, CA USA. [Hunt, Kristel] James J Peters VA Med Ctr, Bronx, NY USA. [Knott, Astrid; Pocha, Christine] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Valderrama, Adriana] Bayer HealthCare Pharmaceut, Tarrytown, NY USA. RP Kaplan, DE (reprint author), Corporal Michael J Crescenz VA Med Ctr, 3900 Woodland Ave,Res Bldg 21,Room A402A, Philadelphia, PA 19104 USA. EM david.kaplan2@va.gov FU Bayer Healthcare Pharmaceuticals; VA HIV, Hepatitis and Public Health Pathogens Programs in the Office of Public Health/Clinical Public Health FX Supported by unrestricted research funds from Bayer Healthcare Pharmaceuticals and the VA HIV, Hepatitis and Public Health Pathogens Programs in the Office of Public Health/Clinical Public Health. NR 31 TC 5 Z9 5 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2015 VL 13 IS 13 BP 2333 EP + DI 10.1016/j.cgh.2015.07.010 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW7PK UT WOS:000365191300024 PM 26188137 ER PT J AU White, ML Chodosh, J Jang, JS Dohlman, C AF White, Michelle L. Chodosh, James Jang, Jisun Dohlman, Claes TI Incidence of Stevens-Johnson Syndrome and Chemical Burns to the Eye SO CORNEA LA English DT Article DE cornea; keratoprosthesis; Stevens-Johnson syndrome; chemical burn; alkali burn; acid burn; incidence; penetrating keratoplasty; blindness ID TOXIC EPIDERMAL NECROLYSIS; STEM-CELL DEFICIENCY; ERYTHEMA MULTIFORME; PENETRATING KERATOPLASTY; BOSTON KERATOPROSTHESIS; KERATOLIMBAL ALLOGRAFT; CONJUNCTIVAL; MANAGEMENT; INJURIES; GLAUCOMA AB Purpose: This population-based observational study was designed to estimate the incidence and distribution of SJS-spectrum (Stevens-Johnson syndrome, toxic epidermal necrolysis, and toxic epidermal Necrolysis/Stevens-Johnson syndrome overlap) and chemical burns (alkali or acid burn of the cornea/conjunctiva) in the United States and extrapolate these numbers to the world. Methods: All patients evaluated in 961 hospital-based US emergency departments between July 1, 2010, and June 30, 2012 were identified retrospectively using the Nationwide Emergency Department Sample (NEDS) from the Agency for Healthcare Research and Quality. SJS-spectrum and chemical burn cases were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Results: A mean of 3834 new SJS-spectrum cases per year were identified in the United States, resulting in an incidence rate of 12.35 new cases per million per year. Similarly, a mean of 15,865 new chemical burn cases per year were identified, resulting in an incidence rate of 51.10 new cases per million per year. Conclusions: If the incidence of SJS-spectrum is approximately uniform the world-over, extrapolation from the US figure would amount to approximately 86,500 new cases per year in the world. Extrapolation of ocular chemical burns to the world is difficult because the incidence and severity are anticipated to be higher in the developing world than in the United States. Still, using a US incidence rate, a minimum of 357,710 burn accidents would be expected to occur worldwide every year; there are presently too few data available to calculate the degree of severity and bilaterality. C1 [White, Michelle L.; Chodosh, James; Dohlman, Claes] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jang, Jisun] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. RP White, ML (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Michelle_white@meei.harvard.edu FU Children's Hospital Ophthalmology Foundation FX The authors thank Iason S. Mantagos, MD and the Children's Hospital Ophthalmology Foundation for their collaboration in supporting this research project. NR 43 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD DEC PY 2015 VL 34 IS 12 BP 1527 EP 1533 DI 10.1097/ICO.0000000000000646 PG 7 WC Ophthalmology SC Ophthalmology GA CW2OP UT WOS:000364832200001 PM 26488629 ER PT J AU Odorcic, S Haas, W Gilmore, MS Dohlman, CH AF Odorcic, Silvia Haas, Wolfgang Gilmore, Michael S. Dohlman, Claes H. TI Fungal Infections After Boston Type 1 Keratoprosthesis Implantation: Literature Review and In Vitro Antifungal Activity of Hypochlorous Acid SO CORNEA LA English DT Article DE endophthalmitis; HOCl; keratitis; prophylaxis; yeast ID POVIDONE-IODINE; RISK-FACTORS; ENDOPHTHALMITIS; KERATITIS; OUTCOMES AB Purpose:To review the current literature describing cases of fungal keratitis and endophthalmitis after Boston keratoprosthesis (KPro) implantation and to characterize the antifungal activity of 0.01% hypochlorous acid against medically relevant fungi.Methods:A literature review of fungal keratitis or endophthalmitis in KPro patients from January 2001 to April 2015, and an in vitro time kill assay characterizing the fungicidal activity of 0.01% hypochlorous acid against fungi causing ocular infections.Results:Fifteen publications, predominantly retrospective case series, were identified. Infection rates after KPro implantation ranged from 0.009 to 0.02 fungal infections per patient-year of follow-up. The largest single-surgeon series reported an incidence of 2.4% for fungal endophthalmitis during a 10-year period. Causative organisms included both yeasts and molds. Outcomes were favorable if infections were caught early and treated appropriately; less favorable outcomes were reported in developing countries where fungal species are endemic and resources are limited. 0.01% hypochlorous acid is rapidly fungicidal, reducing the number of viable yeast cells or mold conidia by at least 99.99% within 60 seconds. The antifungal activity extended to all molds (Acremonium kiliense, Aspergillus flavus, Aspergillus fumigatus, Fusarium solani, and Mucor indicus) and yeast species (Candida albicans and Candida parapsilosis) tested.Conclusions:Fungal infections remain a lifelong concern in patients after KPro implantation. There is a growing need for a standard antifungal prophylaxis regimen, especially in the developing world. The rapid broad-spectrum in vitro fungicidal activity of 0.01% hypochlorous acid against all fungi tested makes it an attractive candidate as an antifungal prophylaxis in KPro patients. C1 [Odorcic, Silvia; Haas, Wolfgang; Gilmore, Michael S.; Dohlman, Claes H.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Gilmore, Michael S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Odorcic, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM silvia.odorcic@gmail.com FU NIAID NIH HHS [P01 AI083214] NR 24 TC 1 Z9 1 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD DEC PY 2015 VL 34 IS 12 BP 1599 EP 1605 DI 10.1097/ICO.0000000000000639 PG 7 WC Ophthalmology SC Ophthalmology GA CW2OP UT WOS:000364832200015 PM 26488624 ER PT J AU Polak, R Sforzo, GA Dill, D Phillips, EM Moore, M AF Polak, Rani Sforzo, Gary A. Dill, Diana Phillips, Edward M. Moore, Margaret TI Credentialed Chefs as Certified Wellness Coaches: Call for Action SO EATING BEHAVIORS LA English DT Article DE Coaching; Cooking; Chef; Lifestyle; Nutrition ID RANDOMIZED CLINICAL-TRIAL; FOOD PREPARATION; COOKING; INTERVENTIONS; EDUCATION; BEHAVIOR; CHOICES; ADULTS; IMPACT; SKILLS AB Beneficial relationships exist between food preparation skills and improved dietary quality, and between times spent preparing food and mortality. Food shopping, meal planning, preparation and cooking skills are valuable in supporting good health. Thus experts are proposing nutritional counseling be expanded to include these beneficial behavioral skills. Educational programs delivered by chefs have recently emerged as a way to improve engagement with nutritional guidelines. It is reasonable to assume that a chef with behavior change knowledge and skills, such as coaching, may be more effective in facilitating behavior change. We encourage chefs who wish to be involved in promoting health-related behavior change to consider continuing education in coaching knowledge and skills. We also recommend culinary schools to consider offering these courses, to aspiring chefs. Such programming will not only benefit future clients but also offers a career-enriching professional opportunity to chefs. Credentialed chefs can make a positive health impact and should be included as professionals who are eligible for the impending national certification of health and wellness coaches. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Polak, Rani; Phillips, Edward M.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Inst Lifestyle Med Phys Med & Rehabil, Boston, MA 02115 USA. [Sforzo, Gary A.] Ithaca Coll, Dept Exercise & Sport Sci, Ithaca, NY 14850 USA. [Dill, Diana] Working Together Hlth, Belmont, MA USA. [Moore, Margaret] Wellcoaches Corp, Wellesley, MA USA. [Moore, Margaret] Harvard Univ, McLean Hosp, Inst Coaching, Med Sch Affiliate, Belmont, MA 02178 USA. RP Polak, R (reprint author), Joslin Diabet Ctr, Inst Lifestyle Med, One Joslin Pl, Boston, MA 02215 USA. EM Rani.polak@joslin.harvard.edu; sforzo@ithaca.edu; Diana@WorkingTogetherForHealth.com; Edward.Phillips@joslin.harvard.edu; Margaret@Wellcoaches.com NR 31 TC 1 Z9 1 U1 4 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 EI 1873-7358 J9 EAT BEHAV JI Eat. Behav. PD DEC PY 2015 VL 19 BP 65 EP 67 DI 10.1016/j.eatbeh.2015.06.016 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA CW4UP UT WOS:000364992200014 PM 26172566 ER PT J AU Macaulay, AA VanValkenburg, SM DiGiovanni, CW AF Macaulay, Alec A. VanValkenburg, Scott M. DiGiovanni, Christopher W. TI Sport and activity restrictions following total ankle replacement: A survey of orthopaedic foot and ankle specialists SO FOOT AND ANKLE SURGERY LA English DT Article DE Total ankle replacement; Total ankle arthroplasty; Sports; Activity; Postoperative recommendations ID TOTAL JOINT ARTHROPLASTY; ATHLETIC ACTIVITY; PATIENT EXPECTATIONS; PARTICIPATION; ARTHRODESIS; CEMENTLESS; OUTCOMES AB Background: Despite an increasing utilization of total ankle replacement, surgeons have little guidance with regards to physical activity and sport participation recommendations following the procedure. Methods: Orthopaedic foot and ankle specialists were surveyed as to the activity and sports restrictions they place on their patients following ankle replacement. Fifty sports and activities were included and the results were used to derive a set of consensus recommendations. Of the 1063 surgeons that were sent the survey, 173 responded, yielding a response rate of 16.3%. Results: In general, surgeons were comfortable with aerobic or low impact sports and activities. Boot immobilized sports represented a grey area with the determination of whether or not to allow them based largely on the prior experience of the patient. High impact, cutting and jumping sports and activities were largely discouraged. Young age, high BMI and poor bone quality led surgeons to be more restrictive. Conclusions: These consensus recommendations serve as a useful guideline for surgeons and help patients set appropriate expectations for the procedure. (C) 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved. C1 [Macaulay, Alec A.; DiGiovanni, Christopher W.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [VanValkenburg, Scott M.] Upstate Bone & Joint Ctr, E Syracuse, NY 13057 USA. RP DiGiovanni, CW (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM CWDiGiovanni@MGH.Harvard.edu NR 19 TC 0 Z9 0 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1268-7731 EI 1460-9584 J9 FOOT ANKLE SURG JI Foot Ankle Surg. PD DEC PY 2015 VL 21 IS 4 BP 260 EP 265 DI 10.1016/j.fas.2015.01.014 PG 6 WC Orthopedics SC Orthopedics GA CW6HZ UT WOS:000365099800010 PM 26564728 ER PT J AU Rosenberg, PB Drye, LT Porsteinsson, AP Pollock, BG Devanand, DP Frangakis, C Ismail, Z Marano, C Meinert, CL Mintzer, JE Munro, CA Pelton, G Rabins, PV Schneider, LS Shade, DM Weintraub, D Newell, J Yesavage, J Lyketsos, CG AF Rosenberg, Paul B. Drye, Lea T. Porsteinsson, Anton P. Pollock, Bruce G. Devanand, D. P. Frangakis, Constantine Ismail, Zahinoor Marano, Christopher Meinert, Curtis L. Mintzer, Jacobo E. Munro, Cynthia A. Pelton, Gregory Rabins, Peter V. Schneider, Lon S. Shade, David M. Weintraub, Daniel Newell, Jeffery Yesavage, Jerome Lyketsos, Constantine G. CA CitAD Res Grp TI Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE Alzheimer's disease; agitation; randomized clinical trial; neuropsychiatric symptoms ID RANDOMIZED CLINICAL-TRIAL; NEUROPSYCHIATRIC SYMPTOMS; CACHE COUNTY; BEHAVIORAL DISTURBANCES; DRUG-TREATMENT; DOUBLE-BLIND; DEMENTIA; CITALOPRAM; RISK; DEPRESSION AB Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. Results: Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. Conclusions: We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial. C1 [Rosenberg, Paul B.; Marano, Christopher; Lyketsos, Constantine G.] Johns Hopkins Bayview Med Ctr, Johns Hopkins Sch Med, Div Geriatr Psychiat & Neuropsychiat, Psychiat & Behav Sci, Baltimore, MD 21224 USA. [Drye, Lea T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Alzheimers Dis Care Res & Educ Program AD CARE, Rochester, NY USA. [Pollock, Bruce G.] Univ Toronto, Campbell Inst, CAMH, Toronto, ON, Canada. [Devanand, D. P.; Pelton, Gregory] Columbia Univ, Coll Phys & Surg, Psychiat & Neurol, Div Geriatr Psychiat, New York, NY USA. [Frangakis, Constantine] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Ismail, Zahinoor] Univ Calgary, Psychiat & Neurol, Hotchkiss Brain Inst, Calgary, AB, Canada. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol & Biostat, Baltimore, MD USA. [Mintzer, Jacobo E.] Roper St Francis Healthcare, Clin Biotechnol Res Inst, Charleston, SC USA. [Munro, Cynthia A.] Johns Hopkins Bayview, Dept Neurol, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Munro, Cynthia A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Rabins, Peter V.] Johns Hopkins Univ Hosp, Johns Hopkins Sch Med, Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Psychiat Neurol & Gerontol, Los Angeles, CA 90033 USA. [Shade, David M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Pulm Med, Ctr Clin Trials, Baltimore, MD USA. [Shade, David M.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Clin Trials, Dept Epidemiol, Baltimore, MD USA. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Parkinsons Dis Res Educ & Clin Ctr PADRECC,MIRECC, Philadelphia Vet Affairs Med Ctr,Psychiat & Neuro, Philadelphia, PA 19104 USA. [Pollock, Bruce G.] Univ Toronto, Campbell Family Mental Hlth Res Inst, Div Geriatr Psychiat, Ctr Addict & Mental Hlth,Fac Med, Toronto, ON, Canada. [Ismail, Zahinoor] Univ Toronto, Psychiat, Toronto, ON, Canada. [Mintzer, Jacobo E.] Med Univ S Carolina, Dept Hlth Studies, Charleston, SC 29425 USA. [Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Newell, Jeffery] Univ So Calif, Clin Sci, Culture & Mental Hlth Lab, Los Angeles, CA USA. [Yesavage, Jerome] VA Palo Alto Hlth Care Syst, Aging Clin Res Ctr, Director Mental Illness Res Educ & Clin Ctr, Richmond, VA USA. [Yesavage, Jerome] Stanford Univ, Sch Med, Psychiat & Behav Sci, Palo Alto, CA 94304 USA. RP Rosenberg, PB (reprint author), Johns Hopkins Bayview Med Ctr, Johns Hopkins Sch Med, Div Geriatr Psychiat & Neuropsychiat, Psychiat & Behav Sci, 5300 Alpha Commons Dr 429, Baltimore, MD 21224 USA. EM prosenb9@jhmi.edu FU NIA; NIMH [R01AG031348]; NIH [P50, AG05142] FX Funding/Support: This work was supported by NIA and NIMH, R01AG031348 and in part by NIH P50, AG05142 (USC, LSS). NR 38 TC 2 Z9 3 U1 3 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD DEC PY 2015 VL 27 IS 12 BP 2059 EP 2067 DI 10.1017/S1041610215001106 PG 9 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA CW4CH UT WOS:000364938400015 PM 26305876 ER PT J AU Vanderhoek, SM Cote, CJ AF Vanderhoek, Samuel M. Cote, Charles J. TI Measurement of cardiac index and stroke volume using electrical cardiometry before and after administration of adenosine in a 6-year-old patient with supraventricular tachycardia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE Anesthesia; Arrhythmia; Monitoring; Cardiac output; Stroke volume; Pediatrics ID PROPOFOL; SEVOFLURANE; CHANNELS AB We report the case of a 6-year-old boy who developed a supraventricular tachycardia during an upper endoscopy while under general anesthesia. A noninvasive electrical cardiometry device was applied to the patient, and cardiac index and stroke volume were measured before and after the administration of adenosine. Cardiac index fell 41% (P < .0001) after adenosine was given, highlighting the known interdependence between cardiac output and heart rate in the pediatric patient. Stroke volume decreased 9% (P = .0002) after adenosine arrested the tachycardia, lending support to an increasing body of data that suggests that heart rate itself can augment contractility. (C) 2015 Elsevier Inc. All rights reserved. C1 [Vanderhoek, Samuel M.; Cote, Charles J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Vanderhoek, SM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Gray Bigelow 444,55 Fruit St, Boston, MA 02114 USA. EM svanderhoek@partners.org; cjcote@partners.org NR 10 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD DEC PY 2015 VL 27 IS 8 BP 682 EP 684 DI 10.1016/j.jclinane.2015.08.008 PG 3 WC Anesthesiology SC Anesthesiology GA CW6XT UT WOS:000365142400012 PM 26427304 ER PT J AU Venkateswaran, RV Freeman, C Chatterjee, N Kandala, J Orencole, M Vegh, EM Parks, KA Cowburn, PJ Dec, GW Singh, JP Borgquist, R AF Venkateswaran, Ramkumar V. Freeman, Carolyn Chatterjee, Neal Kandala, Jagdesh Orencole, Mary Vegh, Eszter M. Parks, Kimberly A. Cowburn, Peter J. Dec, G. William Singh, Jagmeet P. Borgquist, Rasmus TI Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Anemia; Cardiac resynchronization therapy; Heart failure; Prognostic factors; Risk stratification ID MORTALITY; MORBIDITY; DISEASE; PREVALENCE; GUIDELINES; ESC AB Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19 % female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb < 12 g/dL in women and < 13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95 % confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (a parts per thousand currency signa'1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients. C1 [Venkateswaran, Ramkumar V.; Dec, G. William] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Freeman, Carolyn; Chatterjee, Neal; Kandala, Jagdesh; Orencole, Mary; Vegh, Eszter M.; Parks, Kimberly A.; Dec, G. William; Singh, Jagmeet P.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cowburn, Peter J.] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England. [Borgquist, Rasmus] Lund Univ, Skane Univ Hosp, Arrhythmia Clin, Lund, Sweden. RP Borgquist, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. EM rasmus.borgquist@med.lu.se FU Biotronik; Boston Scientific; St. Jude Medical; Medtronic; Sorin FX Dr. Singh reports lectures, research grants, and consulting for Biotronik, Boston Scientific, St. Jude Medical, Medtronic and Sorin, as well as consulting for Respicardia and CardioInsight Inc. Dr. Parks reports consulting for Biotronic and honorary speaking for St. Jude Medical. NR 21 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X EI 1572-8595 J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD DEC PY 2015 VL 44 IS 3 BP 297 EP 304 DI 10.1007/s10840-015-0062-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW4AK UT WOS:000364933300012 PM 26453528 ER PT J AU Zhou, XY Liu, Z Shapiro, L Yang, J Burton, GF AF Zhou, Xueyuan Liu, Zhu Shapiro, Leland Yang, Jun Burton, Gregory F. TI Low-density lipoprotein receptor-related protein 1 mediates alpha 1-antitrypsin internalization in CD4(+) T lymphocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE clathrin-dependent endocytosis; endosome; lysosome; HIV-1; NF-kappa B; I kappa B alpha ID CLATHRIN-INDEPENDENT ENDOCYTOSIS; IMMUNODEFICIENCY-VIRUS TYPE-1; RAT PERITONEAL-MACROPHAGES; LYSOSOMAL PERMEABILIZATION; HIV-INFECTION; SEC RECEPTOR; COMPLEXES; EXPRESSION; APOPTOSIS; PATHWAYS AB In alpha 1-antitrypsin-deficient HIV patients, an accelerated decline of CD4(+) T cell numbers is observed, suggesting that alpha 1-antitrypsin is a potential endogenous HIV inhibitor. In infected T lymphocytes, alpha 1-antitrypsin potently blocks NF-kappa B activation and HIV-1 replication by directly interacting with I kappa B alpha in the cytosol, thereby altering its ubiquitination pattern. However, the mechanism of alpha 1-antitrypsin entry into the cytosol, where I kappa B alpha locates, remains unclear. In the present study, we investigated the mechanism of alpha 1-antitrypsin internalization in CD4(+) T cells. Thus, primary CD4(+) T cells were infected with HIV-1 and then incubated with alpha 1-antitrypsin to detect its internalization. We found that CD4(+) T cells internalized alpha 1-antitrypsin through a clathrin-dependent endocytosis process. Next, intracellular a1-antitrypsin exerted the inhibitory effect on NF-kappa B activation and HIV-1 replication. On primary CD4(+) T cells, alpha 1-antitrypsin interacted with low-density lipoprotein receptor-related protein 1 to initiate the internalization. Inside CD4(+) T lymphocytes, alpha 1-antitrypsin was transported from the endosome to the lysosome and then released into the cytosol, where it is possible for alpha 1-antitrypsin to directly interact with I kappa B alpha. These results together suggest that alpha 1-antitrypsin internalization is a clathrin-dependent and low-density lipoprotein receptor-related protein 1-mediated endocytosis process. Internalized alpha 1-antitrypsin is transported through the endosome-lysosome-cytosol routine to interact with cytosolic IkB alpha and block NF-kappa B activation and HIV-1 replication. C1 [Zhou, Xueyuan; Yang, Jun] Leidos Biomed Res Inc, Clin Serv Program, Frederick, MD 21702 USA. [Zhou, Xueyuan; Burton, Gregory F.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. [Liu, Zhu] Hainan Univ, Coll Agr, Hainan Key Lab Sustainable Utilizat Trop Bioresou, Haikou, Hainan, Peoples R China. [Shapiro, Leland] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. [Shapiro, Leland] Univ Colorado, Dept Med, Div Infect Dis, Denver, CO USA. RP Zhou, XY (reprint author), Leidos Biomed Res Inc, Clin Serv Program, Frederick, MD 21702 USA. EM xueyuan.zhou@nih.gov; zhuliu@hainu.edu.cn FU U.S. Public Health Service Grant from U.S. National Institutes of Health (NIH) National Institute of Allergy and Infectious Disease [AI91517]; Brigham Young University grant from the College of Physical and Mathematical Sciences; International Science and Technology Cooperation Project of China [2015DFR31060]; Science and Technology Program of Hainan Province [KJHZ2015-24, ZDZX2013023]; central government finance support for enhancing the comprehensive strengths of universities in Midwest China; NIH National Cancer Institute (NCI) [HHSN261200800001E] FX This work was partially supported by U.S. Public Health Service Grant AI91517 from the U.S. National Institutes of Health (NIH) National Institute of Allergy and Infectious Disease (to G.F.B.) and by a Brigham Young University grant from the College of Physical and Mathematical Sciences (to G.F.B.). This work was also partially supported by International Science and Technology Cooperation Project of China Grant 2015DFR31060 (to Z.L.); the Science and Technology Program of Hainan Province Grants KJHZ2015-24 and ZDZX2013023 (to Z.L.); and the central government finance support for enhancing the comprehensive strengths of universities in Midwest China. The work was also partially supported by the NIH National Cancer Institute (NCI) Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the reviews or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. Funding for open access was provided by NIH NCI Contract No. HHSN261200800001E. The authors thank Drs. Karen J. Merrell, John T. Prince, Richard A. Lempicki, Tomozumi Imamichi, and Ryan Taylor for their technical advice and help. NR 38 TC 2 Z9 2 U1 4 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2015 VL 98 IS 6 BP 1027 EP 1035 DI 10.1189/jlb.2A0515-209R PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA CW3SL UT WOS:000364912000018 PM 26206901 ER PT J AU Ostacher, MJ Nierenberg, AA Rabideau, D Reilly-Harrington, NA Sylvia, LG Gold, AK Shesler, LW Ketter, TA Bowden, CL Calabrese, JR Friedman, ES Iosifescu, DV Thase, ME Leon, AC Trivedi, MH AF Ostacher, Michael J. Nierenberg, Andrew A. Rabideau, Dustin Reilly-Harrington, Noreen A. Sylvia, Louisa G. Gold, Alexandra K. Shesler, Leah W. Ketter, Terence A. Bowden, Charles L. Calabrese, Joseph R. Friedman, Edward S. Iosifescu, Dan V. Thase, Michael E. Leon, Andrew C. Trivedi, Madhukar H. TI A clinical measure of suicidal ideation, suicidal behavior, and associated symptoms in bipolar disorder: Psychometric properties of the Concise Health Risk Tracking Self-Report (CHRT-SR) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Bipolar disorder; Mood disorders; Suicide; Psychometrics; Evidence-based care ID MAJOR DEPRESSIVE DISORDER; MODERATE-DOSE-USE; RATING-SCALE; ANXIETY DISORDERS; QUICK INVENTORY; MANIA; HOPELESSNESS; VALIDITY; ADULTS; CLASSIFICATION AB Objective: People with bipolar disorder are at high risk of suicide, but no clinically useful scale has been validated in this population. The aim of this study was to evaluate the psychometric properties in bipolar disorder of the 7- and 12-item versions of the Concise Health Risk Tracking Self-Report (CHRT-SR), a scale measuring suicidal ideation, suicidal behavior, and associated symptoms. Methods: The CHRT was administered to 283 symptomatic outpatients with bipolar I or II disorder who were randomized to receive lithium plus optimized personalized treatment (OPT), or OPT without lithium in a six month longitudinal comparative effectiveness trial. Participants were assessed using structured diagnostic interviews, clinician-rated assessments, and self-report questionnaires. Results: The internal consistency (Cronbach alpha) was 0.80 for the 7-item CHRT-SR and 0.90 for the 12-item CHRT-SR with a consistent factor structure, and three independent factors (current suicidal thoughts and plans, hopelessness, and perceived lack of social support) for the 7-item version. CHRT-SR scores are correlated with measures of depression, functioning, and quality of life, but not with mania scores. Conclusions: The 7- and 12-item CHRT-SR both had excellent psychometric properties in a sample of symptomatic subjects with bipolar disorder. The scale is highly correlated with depression, functioning, and quality of life, but not with mania. Future research is needed to determine whether the CHRT-SR will be able to predict suicide attempts in clinical practice. Published by Elsevier Ltd. C1 [Ostacher, Michael J.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Ostacher, Michael J.; Ketter, Terence A.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Nierenberg, Andrew A.; Reilly-Harrington, Noreen A.; Sylvia, Louisa G.; Gold, Alexandra K.; Shesler, Leah W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Nierenberg, Andrew A.; Reilly-Harrington, Noreen A.; Sylvia, Louisa G.] Harvard Univ, Sch Med, Boston, MA USA. [Rabideau, Dustin] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Calabrese, Joseph R.] Case Western Reserve Univ, Bipolar Disorders Res Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Friedman, Edward S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Iosifescu, Dan V.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Leon, Andrew C.] Weill Cornell Med Coll, Biostat Psychiat & Publ Hlth, New York, NY USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX USA. RP Ostacher, MJ (reprint author), VA Palo Alto Hlth Care Syst, 3801 Miranda Ave,Mail Code 151-T, Palo Alto, CA 94304 USA. EM ostacher@stanford.edu OI Ostacher, Michael/0000-0003-0353-7535 FU NIH [NO1MH80001] FX The study was funded by NIH NO1MH80001. ClinicalTrials.gov number NCT00667745. NR 52 TC 3 Z9 3 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2015 VL 71 BP 126 EP 133 DI 10.1016/j.jpsychires.2015.10.004 PG 8 WC Psychiatry SC Psychiatry GA CW5RI UT WOS:000365053900016 PM 26476489 ER PT J AU Sherwood, MW Nessel, CC Hellkamp, AS Mahaffey, KW Piccini, JP Suh, EY Becker, RC Singer, DE Halperin, JL Hankey, GJ Berkowitz, SD Fox, KAA Patel, MR AF Sherwood, Matthew W. Nessel, Christopher C. Hellkamp, Anne S. Mahaffey, Kenneth W. Piccini, Jonathan P. Suh, Eun-Young Becker, Richard C. Singer, Daniel E. Halperin, Jonathan L. Hankey, Graeme J. Berkowitz, Scott D. Fox, Keith A. A. Patel, Manesh R. TI Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin ROCKET AF Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE anticoagulant; atrial fibrillation; gastrointestinal bleeding; hemorrhage; risk stratification ID ORAL ANTICOAGULANTS; DABIGATRAN; POPULATION; COHORT; RISK; VARIABILITY; APIXABAN; THERAPY AB BACKGROUND Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. OBJECTIVES This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. METHODS The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. RESULTS Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban-versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. CONCLUSIONS In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation. (C) 2015 by the American College of Cardiology Foundation. C1 [Sherwood, Matthew W.; Hellkamp, Anne S.; Piccini, Jonathan P.; Becker, Richard C.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA. [Nessel, Christopher C.; Suh, Eun-Young] Janssen Pharmaceut Res & Dev, Raritan, NJ USA. [Mahaffey, Kenneth W.] Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA. [Fox, Keith A. A.] Univ Edinburgh, Dept Med, Edinburgh EH8 9YL, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Sherwood, MW (reprint author), Duke Clin Res Inst, 2400 Pratt St,POB 17969, Durham, NC 27715 USA. EM matthew.sherwood@dm.duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 NR 24 TC 16 Z9 16 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 1 PY 2015 VL 66 IS 21 BP 2271 EP 2281 DI 10.1016/j.jacc.2015.09.024 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW6HX UT WOS:000365099600001 PM 26610874 ER PT J AU Laird, JR Schneider, PA Tepe, G Brodmann, M Zeller, T Metzger, C Krishnan, P Scheinert, D Micari, A Cohen, DJ Wang, H Hasenbank, MS Jaff, MR AF Laird, John R. Schneider, Peter A. Tepe, Gunnar Brodmann, Marianne Zeller, Thomas Metzger, Christopher Krishnan, Prakash Scheinert, Dierk Micari, Antonio Cohen, David J. Wang, Hong Hasenbank, Melissa S. Jaff, Michael R. CA IN PACT SFA Trial Investigators TI Durability of Treatment Effect Using a Drug-Coated Balloon for Femoropopliteal Lesions 24-Month Results of IN.PACT SFA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE angioplasty; femoropopliteal artery; peripheral arterial disease; target lesion revascularization ID PERIPHERAL ARTERIAL-DISEASE; SUPERFICIAL FEMORAL-ARTERY; NITINOL STENT IMPLANTATION; RESILIENT RANDOMIZED-TRIAL; PACLITAXEL-ELUTING STENTS; CLINICAL IMPACT; FOLLOW-UP; IN-VIVO; ANGIOPLASTY; RESTENOSIS AB BACKGROUND Evidence from large, randomized, controlled peripheral artery disease trials reporting long-term outcomes using drug-coated balloons (DCBs) is limited. Previously, the DCB showed favorable 1-year outcomes compared with conventional percutaneous transluminal angioplasty (PTA), yet durability of the treatment effect with DCBs remains unknown. OBJECTIVES This study sought to investigate the longer-term outcomes of a paclitaxel-eluting DCB compared to PTA for femoropopliteal lesions. METHODS We enrolled 331 patients with symptomatic (Rutherford 2 to 4) femoropopliteal lesions up to 18 cm in length. Patients were randomly assigned in a 2: 1 ratio to treatment with DCB or PTA. The 24-month assessments included primary patency, freedom from clinically driven target lesion revascularization (CD-TLR), major adverse events, and quality of life and functional outcomes as assessed by the EuroQOL-5D quality-of-life questionnaire, walking impairment questionnaire, and 6-min walk test. RESULTS At 24 months, patients treated with DCB showed significantly higher primary patency when compared with PTA (78.9% vs. 50.1%; p < 0.001). The rates of CD-TLR were 9.1% and 28.3% (p < 0.001) for the DCB and PTA groups, respectively. The overall mortality rate in the DCB group was 8.1% versus 0.9% in the PTA group (p = 0.008). There were no device-or procedure-related deaths and no major amputations in either group through 24-month follow-up. The rate of vessel thrombosis was low (1.5% DCB vs. 3.8% PTA; p = 0.243), with no new events reported between 1 and 2 years. Both groups showed similar functional improvement at 2 years, although DCB patients achieved this level of function with 58% fewer reinterventions. CONCLUSIONS The 24-month outcomes from the trial demonstrate a durable and superior treatment effect of DCB versus PTA with significantly higher primary patency, lower CD-TLR, and similar functional status improvement with fewer repeat interventions. (Randomized Trial of IN. PACT Admiral Drug Eluting Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I]; NCT01175850; and IN. PACT Admiral Drug-Coated Balloon vs. Standard BalloonAngioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA][INPACTSFAII]; NCT01566461) (C) 2015 by the American College of Cardiology Foundation. C1 [Laird, John R.] Univ Calif Davis, Sacramento, CA USA. [Schneider, Peter A.] Kaiser Permanente Moanalua Med Ctr & Clin, Honolulu, HI USA. [Tepe, Gunnar] RodMed Klinikum, Rosenheim, Germany. [Brodmann, Marianne] Med Univ, Graz, Austria. [Zeller, Thomas] Univ Herzzentrum Freiburg, Bad Krozingen, Germany. [Metzger, Christopher] Wellmont Holston Valley Med Ctr, Kingsport, TN USA. [Krishnan, Prakash] Mt Sinai Med Ctr, New York, NY 10029 USA. [Scheinert, Dierk] Pk Krankenhaus, Leipzig, Germany. [Scheinert, Dierk] Univ Klinikum Leipzig, Leipzig, Germany. [Micari, Antonio] Maria Cecilia Hosp, GVM Care & Res, Cotignola, Italy. [Cohen, David J.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Wang, Hong; Hasenbank, Melissa S.] Medtronic, Santa Rosa, CA USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laird, JR (reprint author), UC Davis Vasc Ctr, Lawrence J Ellison Ambulatory Care Ctr, 4860 Y St,Suite 3400, Sacramento, CA 95817 USA. EM jrlaird@ucdavis.edu NR 31 TC 35 Z9 37 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 1 PY 2015 VL 66 IS 21 BP 2329 EP 2338 DI 10.1016/j.jacc.2015.09.063 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW6HX UT WOS:000365099600009 PM 26476467 ER PT J AU Levine, BD Baggish, AL Kovacs, RJ Link, MS Maron, MS Mitchell, JH AF Levine, Benjamin D. Baggish, Aaron L. Kovacs, Richard J. Link, Mark S. Maron, Martin S. Mitchell, Jere H. CA Amer Heart Assoc Amer Coll Cardiology TI Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 1: Classification of Sports: Dynamic, Static, and Impact A Scientific Statement From the American Heart Association and American College of Cardiology SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACC/AHA Scientific Statements; athletes; blood pressure; cardiac output; cardiovascular abnormalities; classification; oxygen saturation; sport ID ARTERIAL BLOOD-PRESSURE; NEURAL-CONTROL; EXERCISE; ALTITUDE; CIRCULATION; PERFORMANCE C1 [Levine, Benjamin D.; Mitchell, Jere H.] Univ Texas Southwestern Med Ctr, Dallas, TX 75390 USA. [Levine, Benjamin D.] Texas Hlth Presbyterian Hosp Dallas, Inst Exercise & Environm Med, Dallas, TX USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kovacs, Richard J.] Indiana Univ, Bloomington, IN 47405 USA. [Link, Mark S.] Tufts Univ, Medford, MA 02155 USA. [Maron, Martin S.] Tufts Med Ctr, Medford, MA USA. RP Levine, BD (reprint author), Univ Texas Southwestern Med Ctr, Dallas, TX 75390 USA. NR 26 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 1 PY 2015 VL 66 IS 21 BP 2350 EP 2355 DI 10.1016/j.jacc.2015.09.033 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW6HX UT WOS:000365099600012 PM 26542656 ER PT J AU Maron, BJ Levine, BD Washington, RL Baggish, AL Kovacs, RJ Maron, MS AF Maron, Barry J. Levine, Benjamin D. Washington, Reginald L. Baggish, Aaron L. Kovacs, Richard J. Maron, Martin S. CA Amer Heart Assoc Amer Coll Cardiology TI Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes A Scientific Statement From the American Heart Association and American College of Cardiology SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACC/AHA Scientific Statements; athletes; cardiovascular abnormalities; competitive athletes; preparticipation screening; sudden death ID SUDDEN CARDIAC DEATH; HYPERTROPHIC CARDIOMYOPATHY; EUROPEAN-SOCIETY; ELECTROCARDIOGRAPHIC PATTERNS; UNITED-STATES; YOUNG; SPORTS; POPULATION; PREVALENCE; CRITERIA C1 [Maron, Barry J.] Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA. [Baggish, Aaron L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Kovacs, Richard J.] Indiana Univ, Bloomington, IN 47405 USA. [Levine, Benjamin D.] Univ Texas Southwestern Med Ctr, Dallas, TX USA. [Maron, Martin S.] Tufts Med Ctr, Boston, MA 02111 USA. [Washington, Reginald L.] Rocky Mt Hosp Children, Denver, CO USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA. NR 39 TC 16 Z9 16 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 1 PY 2015 VL 66 IS 21 BP 2356 EP 2361 DI 10.1016/j.jacc.2015.09.034 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW6HX UT WOS:000365099600013 PM 26542659 ER PT J AU Estes, NAM Kovacs, RJ Baggish, AL Myerburg, RJ AF Estes, N. A. Mark, III Kovacs, Richard J. Baggish, Aaron L. Myerburg, Robert J. CA Amer Heart Assoc Amer Coll Cardiology TI Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 11: Drugs and Performance-Enhancing Substances A Scientific Statement From the American Heart Association and American College of Cardiology SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACC/AHA Scientific Statements; athletes; cardiovascular abnormalities; drugs; performance-enhancing substances ID SPORTS C1 [Estes, N. A. Mark, III] Tufts Univ, Medford, MA 02155 USA. [Baggish, Aaron L.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Kovacs, Richard J.] Indiana Univ, Bloomington, IN 47405 USA. [Myerburg, Robert J.] Univ Miami, Coral Gables, FL 33124 USA. RP Estes, NAM (reprint author), Tufts Univ, Medford, MA 02155 USA. NR 8 TC 3 Z9 3 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 1 PY 2015 VL 66 IS 21 BP 2429 EP 2433 DI 10.1016/j.jacc.2015.09.043 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW6HX UT WOS:000365099600022 PM 26542661 ER PT J AU Garaulet, M Gomez-Abelian, P Rubio-Sastre, P Madrid, JA Saxena, R Scheer, FAJL AF Garaulet, Marta Gomez-Abelian, Purificacion Rubio-Sastre, Patricia Madrid, Juan A. Saxena, Richa Scheer, Frank A. J. L. TI Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE MTNR1B; Type 2 diabetes; Glucose tolerance; Melatonin; Genetic variation ID SCALE ASSOCIATION ANALYSIS; INSULIN SENSITIVITY; SECRETION; RELEASE; INDEXES; TRAITS AB Aims. The common MTNR1B genetic variant rs10830963 is associated with an increased risk of type 2 diabetes (T2D). To date, no experimental study has tested the effect of the MTNR1B variant on glucose metabolism in humans during exposure of the melatonin receptors to their ligand. The aim of this study was to investigate whether this MTNR1B variant influenced the effect of melatonin (5 mg) on glucose tolerance assessed by an oral glucose tolerance test (OGTT; 75 g) at different times of the day (morning and evening) as compared to a placebo. Methods. Seventeen normoglycemic women (24 +/- 6 years; BMI 23.0 +/- 3.3 kg/m(2)) completed the study (11 carriers of the risk allele [CG] and 6 noncarriers [CC]). Results. The effect of melatonin on glucose tolerance depended on the genotype. In the morning, the effect of melatonin (melatonin-placebo) on the glucose area under the curve (AUC) above baseline differed significantly (P = 0.036) between the carriers and noncarriers. This effect of melatonin in the carriers was six times as large as that in the noncarriers. The MTNR1B SNP explained over one-quarter (26%) of the inter-individual differences in the effect of melatonin on glucose AUC. However, in the evening, the effect of melatonin on glucose AUG of the carriers and noncarriers did not differ significantly (P > 0.05). Conclusions. MTNR1B rs10830963 risk variant worsens the effect of melatonin on glucose tolerance, suggesting the importance of genotyping and personalized recommendations, especially in people consuming food when melatonin levels are elevated. Large-scale studies in vulnerable populations are necessary to translate these results into real-world, clinically relevant recommendations. (C) 2015 Elsevier Inc. All rights reserved. C1 [Garaulet, Marta; Gomez-Abelian, Purificacion; Rubio-Sastre, Patricia; Madrid, Juan A.] Univ Murcia, Fac Biol, Dept Physiol, E-30100 Murcia, Spain. [Garaulet, Marta; Gomez-Abelian, Purificacion; Rubio-Sastre, Patricia; Madrid, Juan A.] IMIB Arrixaca, Murcia, Spain. [Saxena, Richa] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saxena, Richa] Harvard Univ, Sch Med, Boston, MA USA. [Saxena, Richa] Broad Inst, Cambridge, MA USA. [Saxena, Richa; Scheer, Frank A. J. L.] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Boston, MA 02115 USA. [Saxena, Richa; Scheer, Frank A. J. L.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Garaulet, M (reprint author), Univ Murcia, Fac Biol, Dept Physiol, Campus Espinardo S-N, E-30100 Murcia, Spain. EM garaulet@um.es; puriki4@hotmail.com; patrirru@hotmail.com; jamadrid@um.es; fscheer@bwh.harvard.edu FU Spanish Government of Science and Innovation [BFU2011-24720, SAF2014-52480-R]; Seneca Foundation from the Government of Murcia [15123/PI/10]; NIH [R21 DK089378, R01 DK102696] FX This study was supported by grants from the Spanish Government of Science and Innovation (BFU2011-24720; SAF2014-52480-R), the Seneca Foundation from the Government of Murcia (15123/PI/10), the NIH (R21 DK089378) to Richa Saxena and Frank AJL Scheer., and NIH (R01 DK102696) to Frank AJL Scheer and Richa Saxena NR 24 TC 11 Z9 11 U1 1 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2015 VL 64 IS 12 BP 1650 EP 1657 DI 10.1016/j.metabol.2015.08.003 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CW3MI UT WOS:000364896000005 PM 26440713 ER PT J AU Lin, MT Tseng, LH Dudley, JC Riel, S Tsai, H Zheng, G Pratz, KW Levis, MJ Gocke, CD AF Lin, Ming-Tseh Tseng, Li-Hui Dudley, Jonathan C. Riel, Stacey Tsai, Harrison Zheng, Gang Pratz, Keith W. Levis, Mark J. Gocke, Christopher D. TI A Novel Tandem Duplication Assay to Detect Minimal Residual Disease in FLT3/ITD AML SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; PROGNOSTIC INFORMATION; LENGTH MUTATIONS; SEQUENCING DATA; NPM1 MUTATIONS; ADULT PATIENTS; RELAPSE; GENE; IMPACT AB Internal tandem duplication (ITD) of the fms-related tyrosine kinase 3 (FLT3) gene is associated with a poor prognosis in acute myeloid leukemia (AML) patients with a normal karyotype. The current standard polymerase chain reaction (PCR) assay for FLT3/ITD detection is not sufficiently sensitive to monitor minimal residual disease (MRD). Clone-specific assays may have sufficient sensitivity but are not practical to implement, since each clone-specific primer/probe requires clinical validation. To develop an assay for clinical molecular diagnostics laboratories to monitor MRD in FLT3/ITD AMLs. We designed a simple novel assay, tandem duplication PCR (TD-PCR), and tested its sensitivity, specificity, and clinical utility in FLT3/ITD AML patients. TD-PCR was capable of detecting a single ITD molecule and was applicable to 75 % of ITD mutants tested. TD-PCR detected MRD in bone marrow prior to patient relapse. TD-PCR also identified low-level ITD mutants not only in FLT3/ITD AMLs but also in initial diagnostic specimens that were reportedly negative by the standard assay in patients who progressed with the same ITDs detected by the TD-PCR assay. Detection of MRD by TD-PCR may guide patient selection for early clinical intervention. In contrast to clone-specific approaches, the TD-PCR assay can be more easily validated for MRD detection in clinical laboratories because it uses standardized primers and a universal positive control. In addition, our findings on multi-clonality and low-level ITDs suggest that further studies are warranted to elucidate their clinical/biological significance. C1 [Lin, Ming-Tseh; Tseng, Li-Hui; Dudley, Jonathan C.; Riel, Stacey; Tsai, Harrison; Zheng, Gang; Gocke, Christopher D.] Johns Hopkins Univ, Div Mol Pathol, Dept Pathol, Sch Med, Baltimore, MD 21287 USA. [Tseng, Li-Hui] Natl Taiwan Univ Hosp, Dept Med Genet, Taipei, Taiwan. [Dudley, Jonathan C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pratz, Keith W.; Levis, Mark J.; Gocke, Christopher D.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Gocke, CD (reprint author), Johns Hopkins Univ, Div Mol Pathol, Dept Pathol, Sch Med, Pk SB202,600 North Wolfe St, Baltimore, MD 21287 USA. EM cgocke1@jhmi.edu FU US National Institutes of Health [R21HG004315, R21HG005745]; National Cancer Institute at the National Institutes of Health [1UM1CA186691-01] FX The authors M-TL and CDG gratefully acknowledge funding received from the US National Institutes of Health (Grant Nos. R21HG004315 and R21HG005745 to CDG) and the National Cancer Institute at the National Institutes of Health (Grant No. 1UM1CA186691-01 to M-TL and CDG). NR 36 TC 1 Z9 1 U1 1 U2 5 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1177-1062 EI 1179-2000 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PD DEC PY 2015 VL 19 IS 6 BP 409 EP 417 DI 10.1007/s40291-015-0170-3 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA CW6PB UT WOS:000365118600007 PM 26446915 ER PT J AU Davis, RW Eggleston, H Johnson, F Nahrendorf, M Bock, PE Peterson, T Panizzi, P AF Davis, Richard W. Eggleston, Heather Johnson, Frances Nahrendorf, Matthias Bock, Paul E. Peterson, Tiffany Panizzi, Peter TI In Vivo Tracking of Streptococcal Infections of Subcutaneous Origin in a Murine Model SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Bioluminescence; Non-invasive imaging; Streptococcus pyogenes; Plasminogen; Streptokinase ID GROUP-A STREPTOCOCCI; M PROTEIN; PLASMINOGEN ACTIVATION; LYMPHOID-TISSUE; GLOBAL BURDEN; STREPTOKINASE; BINDING; PYOGENES; MICE; VIRULENCE AB Generation of plasmin in vivo by Streptococcus pyogenes is thought to localize the active protease complexes to the pathogen surface to aid in tissue dissemination. Here, we chose to follow cutaneous streptococcal infections by the use of non-invasive bioluminescence imaging to determine if this pathogen can be followed by this approach and the extent of bacterial spread in the absence of canonical plasminogen activation by streptokinase. Mice were injected subcutaneously with either bioluminescent strains of streptococci, namely Xen20 and Xen10 or S. pyogenes ALAB49. Bioluminescence imaging was performed daily and results were correlated with microbiological and histological analyses. Comparative analysis of chronologic non-invasive datasets indicated that Xen20 did not disseminate from the initial infection site. Contrary to this, microbiological and histological analyses of Xen20 mice for total bacterial burden indicated sepsis and widespread pathogen involvement. The use of bioluminescence in microbe-based studies requires genomic and pathologic characterization to correlate imaging results with underlying pathology. C1 [Davis, Richard W.; Eggleston, Heather; Johnson, Frances; Peterson, Tiffany; Panizzi, Peter] Auburn Univ, Harrison Sch Pharm, Dept Drug Discovery & Dev, Auburn, AL 36849 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bock, Paul E.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA. RP Panizzi, P (reprint author), Auburn Univ, Harrison Sch Pharm, Dept Drug Discovery & Dev, 4306 Walker Bldg, Auburn, AL 36849 USA. EM panizzi@auburn.edu OI Panizzi, Peter/0000-0003-0141-8807 FU National Institutes of Health through National Heart, Lung, and Blood Institute [R01 HL056181, R01 HL071544, R00 HL094533, R01 HL114477]; National Institute of Allergy and Infectious Diseases [2R44AI085840-02] FX This research was supported by the National Institutes of Health through grants provided by the National Heart, Lung, and Blood Institute, R01 HL056181 and R01 HL071544 (to P. E. B.), R00 HL094533 (to P. P.), and R01 HL114477 (to P. P. and M. N.), and the National Institute of Allergy and Infectious Diseases grant 2R44AI085840-02 (to P. P.). NR 38 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD DEC PY 2015 VL 17 IS 6 BP 793 EP 801 DI 10.1007/s11307-015-0856-2 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CW4DO UT WOS:000364941700008 PM 25921659 ER PT J AU Carlucci, G Carney, B Brand, C Kossatz, S Irwin, CP Carlin, SD Keliher, EJ Weber, W Reiner, T AF Carlucci, Giuseppe Carney, Brandon Brand, Christian Kossatz, Susanne Irwin, Christopher P. Carlin, Sean D. Keliher, Edmund J. Weber, Wolfgang Reiner, Thomas TI Dual-Modality Optical/PET Imaging of PARP1 in Glioblastoma SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE PARP1; Glioblastoma; PET; Fluorescence; Multimodality; Imaging; U87 MG ID IN-VIVO PET; OVARIAN-CANCER; BODIPY DYES; BREAST-CANCER; SINGLE-CELL; ACID; FLUORESCENCE; INHIBITORS; RESECTION; OLAPARIB AB The current study presents [F-18]PARPi-FL as a bimodal fluorescent/positron emission tomography (PET) agent for PARP1 imaging. [F-18]PARPi-FL was obtained by F-19/F-18 isotopic exchange and PET experiments, biodistribution studies, surface fluorescence imaging, and autoradiography carried out in a U87 MG glioblastoma mouse model. [F-18]PARPi-FL showed high tumor uptake in vivo and ex vivo in small xenografts (< 2 mm) with both PET and optical imaging technologies. Uptake of [F-18]PARPi-FL in blocked U87 MG tumors was reduced by 84 % (0.12 +/- 0.02 %injected dose/gram (%ID/g)), showing high specificity of the binding. PET imaging showed accumulation in the tumor (1 h p.i.), which was confirmed by ex vivo phosphor autoradiography. The fluorescent component of [F-18]PARPi-FL enables cellular resolution optical imaging, while the radiolabeled component of [F-18]PARPi-FL allows whole-body deep-tissue imaging of malignant growth. C1 [Carlucci, Giuseppe; Carney, Brandon; Brand, Christian; Kossatz, Susanne; Irwin, Christopher P.; Carlin, Sean D.; Weber, Wolfgang; Reiner, Thomas] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Carney, Brandon] CUNY Hunter Coll, Dept Chem & Biochem, New York, NY 10065 USA. [Carney, Brandon] CUNY, Grad Ctr, PhD Program Chem, New York, NY 10018 USA. [Keliher, Edmund J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weber, Wolfgang; Reiner, Thomas] Weill Cornell Med Coll, New York, NY 10065 USA. RP Reiner, T (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10065 USA. EM reinert@mskcc.org OI Carlin, Sean/0000-0002-5401-0648; Carlucci, Giuseppe/0000-0001-7494-335X; Reiner, Thomas/0000-0002-7819-5480 FU Animal Imaging Core Facility; Radiochemistry and Molecular Imaging Probe Core; Molecular Cytology Core at Memorial Sloan Kettering Cancer Center [P30 CA008748]; American Italian Cancer Foundation (AICF); Clinical and Translational Science Center (CTSC) at Weill Cornell Medical College (NIH/NCATS) [TL1TR000459]; National Science Foundation Integrative Graduate Education and Research Traineeship at Hunter College [IGERT 0965983]; NIH [K25EB016673]; Brain Tumor Center of Memorial Sloan Kettering Cancer Center; Radiology Development Fund FX The authors thank Drs. Ralph Weissleder (Harvard Medical School), NagaVaraKishore Pillarsetty (MSKCC), and Jason S. Lewis (MSKCC) for helpful discussions. They also thank Beatriz Salinas-Rodriguez for technical assistance, Valerie Longo for assisting with animal experiments, and David Gregory for critical reading of the manuscript. Support was provided by the Animal Imaging Core Facility, the Radiochemistry and Molecular Imaging Probe Core, as well as the Molecular Cytology Core at Memorial Sloan Kettering Cancer Center (P30 CA008748). This work was made possible by a financial contribution from American Italian Cancer Foundation (AICF) and the Clinical and Translational Science Center (CTSC) at Weill Cornell Medical College (NIH/NCATS Grant TL1TR000459). Finally, the authors thank the National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT 0965983 at Hunter College), the NIH (K25EB016673 for T.R.), the Brain Tumor Center of Memorial Sloan Kettering Cancer Center (for T.R.), and the Radiology Development Fund (for T.R.) for their generous funding. NR 48 TC 6 Z9 6 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD DEC PY 2015 VL 17 IS 6 BP 848 EP 855 DI 10.1007/s11307-015-0858-0 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CW4DO UT WOS:000364941700014 PM 25895168 ER PT J AU Guo, N Zhang, F Zhang, XM Guo, JX Lang, LX Kiesewetter, DO Niu, G Li, QZ Chen, XY AF Guo, Ning Zhang, Fan Zhang, Xiaomeng Guo, Jinxia Lang, Lixin Kiesewetter, Dale O. Niu, Gang Li, Quanzheng Chen, Xiaoyuan TI Quantitative Evaluation of Tumor Early Response to a Vascular-Disrupting Agent with Dynamic PET SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Dynamic PET; Vascular-disrupting agent; Integrin alpha(v)beta(3); [F-18]FPPRGD2 ID ENDOTHELIAL GROWTH-FACTOR; SOLID TUMORS; IN-VIVO; ANGIOGENESIS; CANCER; VEGF(121)/RGEL; GLIOBLASTOMA; INHIBITION AB The purpose of this study is to evaluate the early response of tumors to a vascular-disrupting agent (VDA) VEGF(121)/recombinant toxin gelonin (rGel) using dynamic [F-18]FPPRGD2 positron emission tomography (PET) and kinetic parameter estimation. Two tumor xenograft models: U87MG (highly vascularized) and A549 (moderately vascularized), were selected, and both were randomized into treatment and control groups. Sixty-minute dynamic PET scans with [F-18]FPPRGD2 that targets to integrin alpha(v)beta(3) were performed at days 0 (baseline), 1, and 3 since VEGF(121)/rGel treatment started. Dynamic PET-derived binding potential (BPND) and parametric maps were compared with tumor uptake (%ID/g) and the static PET image at 1 h after the tracer administration. The growth of U87MG tumor was obviously delayed upon VEGF(121)/rGel treatment. A549 tumor was not responsive to the same treatment. BPND of treated U87MG tumors decreased significantly at day 1 (p < 0.05), and the difference was more significant at day 3 (p < 0.01), compared with the control group. However, the tracer uptake (%ID/g) derived from static images at 1-h time point did not show significant difference between the treated and control tumors until day 3. Little difference in tracer uptake (%ID/g) or BPND was found between treated and control A549 tumors. Considering the tracer retention in tumor and the slower clearance due to damaged tumor vasculature after treatment, BPND representing the actual specific binding portion appears to be more sensitive and accurate than the semiquantitative parameters (such as %ID/g) derived from static images to assess the early response of tumor to VDA treatment. Quantitative analysis based on dynamic PET with [F-18]FPPRGD2 shows advantages in distinguishing effective from ineffective treatment during the course of VEGF(121)/rGel therapy at early stage and is therefore more sensitive in assessing therapy response than static PET. C1 [Guo, Ning; Zhang, Xiaomeng; Li, Quanzheng] Harvard Univ, Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Dept Radiol,Med Sch, Boston, MA 02114 USA. [Zhang, Fan; Guo, Jinxia] Xiamen Univ, State Key Lab Mol Vaccinol & Mol Diagnost, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. [Zhang, Fan; Guo, Jinxia; Lang, Lixin; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Li, QZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Dept Radiol,Med Sch, Boston, MA 02114 USA. EM Li.quanzheng@mgh.harvard.edu; shawn.chen@nih.gov FU National Basic Research Program of China (973 program) [2013CB733803, 2013CB733802]; National Science of Foundation of China (NSFC) [81371596, 81201086]; National Institutes of Health (NIH) [R21CA149587, R01EB013293]; Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH FX This work was supported, in part, by the National Basic Research Program of China (973 program, 2013CB733803, 2013CB733802), the National Science of Foundation of China (NSFC, 81371596, 81201086), the National Institutes of Health (NIH) R21CA149587 and R01EB013293, and the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH. NR 31 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD DEC PY 2015 VL 17 IS 6 BP 865 EP 873 DI 10.1007/s11307-015-0854-4 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CW4DO UT WOS:000364941700016 PM 25896816 ER PT J AU Placzek, MS Van de Bittner, GC Wey, HY Lukas, SE Hooker, JM AF Placzek, Michael S. Van de Bittner, Genevieve C. Wey, Hsiao-Ying Lukas, Scott E. Hooker, Jacob M. TI Immediate and Persistent Effects of Salvinorin A on the Kappa Opioid Receptor in Rodents, Monitored In Vivo with PET SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID TEST-RETEST REPRODUCIBILITY; HALLUCINOGEN SALVINORIN; ANTAGONIST RADIOTRACER; NONHUMAN-PRIMATES; RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; RADIOLIGAND BINDING; SALVIA-DIVINORUM; AGONIST AB Monitoring changes in opioid receptor binding with positron emission tomography (PET) could lead to a better understanding of tolerance and addiction because altered opioid receptor dynamics following agonist exposure has been linked to tolerance mechanisms. We have studied changes in kappa opioid receptor (KOR) binding availability in vivo with PET following kappa opioid agonist administration. Male Sprague-Dawley rats (n=31) were anesthetized and treated with the (KOR) agonist salvinorin A (0.01-1.8 mg/kg, i.v.) before administration of the KOR selective radiotracer [C-11]GR103545. When salvinorin A was administered 1 min prior to injection of the radiotracer, [C-11]GR103545 binding potential (BPND) was decreased in a dose-dependent manner, indicating receptor binding competition. In addition, the unique pharmacokinetics of salvinorin A (half-life similar to 8 min in non-human primates) allowed us to study the residual impact on KOR after the drug had eliminated from the brain. Salvinorin A was administered up to 5 h prior to [C-11]GR103545, and the changes in BPND were compared with baseline, 2.5 h, 1 h, and 1 min pretreatment times. At lower doses (0.18 mg/kg and 0.32 mg/kg) we observed no prolonged effect on KOR binding but at 0.60 mg/kg salvinorin A induced a sustained decrease in KOR binding (BPND decreased by 40-49%) which persisted up to 2.5 h post administration, long after salvinorin A had been eliminated from the brain. These data point towards an agonist-induced adaptive response by KOR, the dynamics of which have not been previously studied in vivo with PET. C1 [Placzek, Michael S.; Van de Bittner, Genevieve C.; Wey, Hsiao-Ying; Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Placzek, Michael S.; Lukas, Scott E.] Harvard Univ, Sch Med, McLean Imaging Ctr, Dept Psychiat, Belmont, MA 02178 USA. RP Hooker, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, 149 13th St, Charlestown, MA 02129 USA. EM hooker@nmr.mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program [S10RR015728, S10RR026666, S10RR017208, P41RR14075]; NIH-NIDA T32 postdoctoral fellowship [T32DA015036]; DOE Training Grant [DE-SC0008430] FX This research was carried out in whole or in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR015728, S10RR026666, and S10RR017208, P41RR14075. NIH-NIDA T32 postdoctoral fellowship T32DA015036, DOE Training Grant DE-SC0008430, and NIH-NIDA K99DA037928. The authors declare no conflict of interest. NR 54 TC 0 Z9 0 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2015 VL 40 IS 13 BP 2865 EP 2872 DI 10.1038/npp.2015.159 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CW2YE UT WOS:000364858200003 PM 26058662 ER PT J AU Gutman, DA Dunn, WD Grossmann, P Cooper, LAD Holder, CA Ligon, KL Alexander, BM Aerts, HJWL AF Gutman, David A. Dunn, William D., Jr. Grossmann, Patrick Cooper, Lee A. D. Holder, Chad A. Ligon, Keith L. Alexander, Brian M. Aerts, Hugo J. W. L. TI Somatic mutations associated with MRI-derived volumetric features in glioblastoma SO NEURORADIOLOGY LA English DT Article DE Radiogenomics; GBM; MRI; Imaging genomics; Volumetrics ID RESPONSE ASSESSMENT CRITERIA; HIGH-GRADE GLIOMAS; SURVIVAL; INFORMATION; PATTERNS; SUBTYPES; THERAPY; IMAGES; IDH1; EGFR AB MR imaging can noninvasively visualize tumor phenotype characteristics at the macroscopic level. Here, we investigated whether somatic mutations are associated with and can be predicted by MRI-derived tumor imaging features of glioblastoma (GBM). Seventy-six GBM patients were identified from The Cancer Imaging Archive for whom preoperative T1-contrast (T1C) and T2-FLAIR MR images were available. For each tumor, a set of volumetric imaging features and their ratios were measured, including necrosis, contrast enhancing, and edema volumes. Imaging genomics analysis assessed the association of these features with mutation status of nine genes frequently altered in adult GBM. Finally, area under the curve (AUC) analysis was conducted to evaluate the predictive performance of imaging features for mutational status. Our results demonstrate that MR imaging features are strongly associated with mutation status. For example, TP53-mutated tumors had significantly smaller contrast enhancing and necrosis volumes (p = 0.012 and 0.017, respectively) and RB1-mutated tumors had significantly smaller edema volumes (p = 0.015) compared to wild-type tumors. MRI volumetric features were also found to significantly predict mutational status. For example, AUC analysis results indicated that TP53, RB1, NF1, EGFR, and PDGFRA mutations could each be significantly predicted by at least one imaging feature. MRI-derived volumetric features are significantly associated with and predictive of several cancer-relevant, drug-targetable DNA mutations in glioblastoma. These results may shed insight into unique growth characteristics of individual tumors at the macroscopic level resulting from molecular events as well as increase the use of noninvasive imaging in personalized medicine. C1 [Gutman, David A.; Dunn, William D., Jr.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Gutman, David A.; Dunn, William D., Jr.; Cooper, Lee A. D.] Emory Univ, Sch Med, Biomed Informat, Atlanta, GA 30307 USA. [Holder, Chad A.] Emory Univ, Sch Med, Radiol & Imaging Sci, Atlanta, GA USA. [Cooper, Lee A. D.] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. [Grossmann, Patrick; Alexander, Brian M.; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Radiol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gutman, DA (reprint author), Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. EM dagutman@gmail.com RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU National Institute of Health [NIH-USA U24CA194354, NIH-USA U01CA190234] FX We acknowledge financial support from the National Institute of Health (NIH-USA U24CA194354, and NIH-USA U01CA190234). NR 36 TC 7 Z9 9 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-3940 EI 1432-1920 J9 NEURORADIOLOGY JI Neuroradiology PD DEC PY 2015 VL 57 IS 12 BP 1227 EP 1237 DI 10.1007/s00234-015-1576-7 PG 11 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CW8BB UT WOS:000365222500005 PM 26337765 ER PT J AU Broderick, RC Fuchs, HF Harnsberger, CR Chang, DC Sandler, BJ Jacobsen, GR Horgan, S AF Broderick, Ryan C. Fuchs, Hans F. Harnsberger, Cristina R. Chang, David C. Sandler, Bryan J. Jacobsen, Garth R. Horgan, Santiago TI Increasing the Value of Healthcare: Improving Mortality While Reducing Cost in Bariatric Surgery SO OBESITY SURGERY LA English DT Article DE Bariatric surgery; Outcomes; Value; Population database ID ACUTE APPENDICITIS; UNITED-STATES; OUTCOMES; OBESITY; POPULATION; MANAGEMENT; TRENDS; IMPACT; BYPASS; VOLUME AB Healthcare costs in the United States (U.S.) are rising. As outcomes improve, such as decreased length of stay and decreased mortality, it is expected that costs should go down. The aim of this study is to analyze hospital charges, cost of care, and mortality in bariatric surgery over time. A retrospective analysis of the Nationwide Inpatient Sample (NIS) database was performed. Adults with morbid obesity who underwent gastric bypass or sleeve gastrectomy were identified by ICD-9 codes. Multivariate analyses identified independent predictors of changes in hospital charges and in-hospital mortality. Results were adjusted for age, race, gender, Charlson comorbidity index, surgical approach (open versus laparoscopic), hospital volume, and insurance status. In order to estimate baseline surgical inflation, changes in hospital charges over time were also calculated for appendectomy. From 1998 to 2011, 209,106 patients were identified who underwent bariatric surgery. Adjusted in-hospital mortality for bariatric surgery decreased significantly by 2003 compared to 1998 (p < 0.001, OR 0.47, 95 % CI 0.22-0.92) and remained significantly decreased for the remainder of the study period. As such, a 60-80 % decrease in mortality was maintained from 2003 to 2010 compared to 1998. After adjusting for inflation, the cumulative increase in hospital charges per day of a bariatric surgery admission was 130 % from 1998 to 2011. Charges per stay increased by 2.1 % annually for bariatric surgery compared to 5.5 % for appendectomy. In-hospital mortality rate following bariatric surgery underwent a ninefold decrease since 1998 while maintaining surgical inflation costs less than appendectomy. Innovation in bariatric surgical technique and technology has resulted in improvement of outcomes while providing overall cost savings. C1 [Broderick, Ryan C.; Fuchs, Hans F.; Harnsberger, Cristina R.; Chang, David C.; Sandler, Bryan J.; Jacobsen, Garth R.; Horgan, Santiago] Univ Calif San Diego, Dept Surg, Div Minimally Invas Surg, Ctr Future Surg, San Diego, CA 92093 USA. [Fuchs, Hans F.] Univ Cologne, Dept Surg, D-50931 Cologne, Germany. [Chang, David C.] Harvard Univ, Sch Med, Dept Surg, Codman Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Broderick, RC (reprint author), Univ Calif San Diego, Dept Surg, Div Minimally Invas Surg, Ctr Future Surg, 9500 Gilman Ave,MC 0740, San Diego, CA 92093 USA. EM rbroderick@ucsd.edu; hfuchs@ucsd.edu; charnsberger@ucsd.edu; dchang8@mgh.harvard.edu; bsandler@ucsd.edu; gjacobsen@ucsd.edu; shorgan@ucsd.edu NR 24 TC 2 Z9 2 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD DEC PY 2015 VL 25 IS 12 BP 2231 EP 2238 DI 10.1007/s11695-015-1710-y PG 8 WC Surgery SC Surgery GA CW5IC UT WOS:000365027900001 PM 25986426 ER PT J AU Javorsky, BR Carroll, TB Tritos, NA Salvatori, R Heaney, AP Fleseriu, M Biller, BMK Findling, JW AF Javorsky, Bradley R. Carroll, Ty B. Tritos, Nicholas A. Salvatori, Roberto Heaney, Anthony P. Fleseriu, Maria Biller, Beverly M. K. Findling, James W. TI Discovery of Cushing's Syndrome After Bariatric Surgery: Multicenter Series of 16 Patients SO OBESITY SURGERY LA English DT Article DE Cushing's syndrome; Hypercortisolism; Preoperative screening for bariatric surgery; Hormonal causes of weight gain; Weight regain after surgery; Causes of surgical failure ID DISEASE; OBESE; DIAGNOSIS; MORTALITY; CORTISOL; SOCIETY AB The aim of this study is to demonstrate the importance of considering Cushing's syndrome (CS) as a potential etiology for weight gain and metabolic complications in patients undergoing bariatric surgery (BS). This is a retrospective chart review case series of patients (n = 16) with CS from five tertiary care centers in the USA who had BS. Median age at BS surgery was 35.5 years (median 2.5 years between BS and CS surgery). CS was not identified in 12 patients prior to BS. Four patients had CS surgery prior to BS, without recognition of recurrent or persistent CS until after BS. Median body mass index (BMI) values before BS, nadir after BS, prior to surgery for CS, and after surgery for CS were 47, 31, 38, and 35 kg/m(2), respectively. Prior to BS, 55 % of patients had hypertension and 55 % had diabetes mellitus. Only 17 % had resolution of hypertension or diabetes mellitus after BS. CS may be under-recognized in patients undergoing BS. Testing for CS should be performed prior to BS in patients with features of CS and in post-operative BS patients with persistent hypertension, diabetes mellitus, or excessive weight regain. Studies should be conducted to determine the role of prospective testing for CS in subjects considering BS. C1 [Javorsky, Bradley R.; Carroll, Ty B.; Findling, James W.] Froedtert & Med Coll Wisconsin, Endocrinol Ctr & Clin, Milwaukee, WI 53051 USA. [Tritos, Nicholas A.; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Salvatori, Roberto] Johns Hopkins Univ, Div Endocrinol Diabet & Metab, Sch Med, Baltimore, MD USA. [Salvatori, Roberto] Johns Hopkins Univ, Sch Med, Pituitary Ctr, Baltimore, MD USA. [Heaney, Anthony P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fleseriu, Maria] Oregon Hlth & Sci Univ, Northwest Pituitary Ctr, Dept Med, Portland, OR 97201 USA. [Fleseriu, Maria] Oregon Hlth & Sci Univ, Northwest Pituitary Ctr, Dept Neurol Surg, Portland, OR 97201 USA. RP Javorsky, BR (reprint author), Froedtert & Med Coll Wisconsin, Endocrinol Ctr & Clin, W129 N7055 Northfield Dr,Bldg A,Suite 203, Milwaukee, WI 53051 USA. EM bradley.javorsky@froedtert.com FU Ipsen; Pfizer; Novartis; Corcept Therapeutics; HRA Pharma; Cortendo FX There are no disclosures related specifically to this report. BJ reports no conflict of interest. TC reports personal fees from Corcept Therapeutics. NT has consulted for Pfizer and Corcept Therapeutics and has received grant support from Ipsen and Pfizer. RS reports grants and personal fees from Novartis, grants and personal fees from Ipsen, and grants and personal fees from Pfizer. AH reports no conflict of interest. MF reports grants and personal fees from Novartis, grants and personal fees from Ipsen, and grants from Corcept Therapeutics. BB reports grants and personal fees from Novartis, personal fees from HRA Pharma, and grants from Cortendo and Corcept Therapeutics. JF reports personal fees from Corcept Therapeutics and Novartis. NR 23 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 EI 1708-0428 J9 OBES SURG JI Obes. Surg. PD DEC PY 2015 VL 25 IS 12 BP 2306 EP 2313 DI 10.1007/s11695-015-1681-z PG 8 WC Surgery SC Surgery GA CW5IC UT WOS:000365027900012 PM 25917980 ER PT J AU Mattos, D Gfrerer, L Reish, RG Hughes, KS Cetrulo, C Colwell, AS Winograd, JM Yaremchuk, MJ Austen, WG Liao, EC AF Mattos, David Gfrerer, Lisa Reish, Richard G. Hughes, Kevin S. Cetrulo, Curtis Colwell, Amy S. Winograd, Jonathan M. Yaremchuk, Michael J. Austen, William G., Jr. Liao, Eric C. TI Lifetime Costs of Prophylactic Mastectomies and Reconstruction versus Surveillance SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CONTRALATERAL BREAST-CANCER; MUTATION CARRIERS; WOMEN; PREVENTION; STRATEGIES; BRCA1; OOPHORECTOMY; POPULATION; RADIATION; SURGERY AB Background: The past decade has seen an increasing prevalence of prophylactic mastectomy with decreasing ages of patients treated for breast cancer. Data are limited on the fiscal impacts of contralateral prophylactic mastectomy trends, and no study has compared bilateral prophylactic mastectomy with reconstruction to surveillance in high-risk patients. Methods: Lifetime third-party payer costs over 30 years were estimated with 2013 Medicare reimbursement rates. Costs were estimated for patients choosing contralateral or bilateral prophylactic mastectomy versus surveillance, with immediate reconstructions using a single-stage implant, tissue expander, or perforator-based free flap approach. Published cancer incidence rates predicted the percentage of surveillance patients that would require mastectomies. Sensitivity analyses were conducted that varied cost growth, discount rate, cancer incidence rate, and other variables. Lifetime costs and present values (3 percent discount rate) were estimated. Results: Lifetime prophylactic mastectomy costs were lower than surveillance costs, $1292 to $1993 lower for contralateral prophylactic mastectomy and $15,668 to $21,342 lower for bilateral prophylactic mastectomy, depending on the reconstruction. Present value estimates were slightly higher for contralateral prophylactic mastectomy over contralateral surveillance but still cost saving for bilateral prophylactic mastectomy compared with bilateral surveillance. Present value estimates are also cost saving for contralateral prophylactic mastectomy when the modeled contralateral breast cancer incidence rate is increased to at least 0.6 percent per year. Conclusions: These findings are consistent with contralateral and bilateral prophylactic mastectomy being cost saving in many scenarios, regardless of the reconstructive option chosen. They suggest that physicians and patients should continue to receive flexibility in deciding how best to proceed clinically in each case. C1 Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Liao, EC (reprint author), 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cliao@partners.org FU Musculoskeletal Transplant Foundation FX Dr. Colwell is a consultant for LifeCell and Allergan. Dr. Austen is a consultant for Mentor. Dr. Liao is the principal investigator on a research study funded by Musculoskeletal Transplant Foundation. No funds were received for this study. NR 40 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 2015 VL 136 IS 6 BP 730E EP 740E DI 10.1097/PRS.0000000000001763 PG 11 WC Surgery SC Surgery GA CW6LX UT WOS:000365110100001 PM 26595028 ER PT J AU Coe, TM Fong, ZV Wilson, SE Talamini, MA Lillemoe, KD Chang, DC AF Coe, Taylor M. Fong, Zhi Ven Wilson, Samuel E. Talamini, Mark A. Lillemoe, Keith D. Chang, David C. TI Outcomes Improvement Is Not Continuous Along the Learning Curve for Pancreaticoduodenectomy at the Hospital Level SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Pancreas-Club CY MAY 15-16, 2015 CL Washington, DC SP Pancreas Club DE Learning curve; Pancreaticoduodenectomy; Mortality; Outcomes improvement ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; HEALTH TECHNOLOGIES; OPERATIVE MORTALITY; PATIENT OUTCOMES; SURGERY; VOLUME; RESECTION; COMPLICATIONS; EXPERIENCE; SURVIVAL AB Most studies on learning curves for pancreaticoduodenectomy have been based on single-surgeon series at tertiary academic centers or are inferred indirectly from volume-outcome relationships. Our aim is to describe mortality rates associated with cumulative surgical experience among non-teaching hospitals. Observational study of a statewide inpatient database. Analysis included hospitals that began performing pancreaticoduodenectomy between 1996 and 2010, as captured by the California Office of Statewide Health Planning and Development database. Cases were numbered sequentially within each hospital. The same sequential series (e.g., first 10 cases, 11th through 20th cases) were identified across hospitals. The outcome measure was in-hospital mortality. A total of 1210 cases from 143 non-teaching hospitals were analyzed. The average age was 63 years old, and the majority of patients were non-Hispanic white. The median overall mortality rate was 9.75 %. The mortality rate for the first 10 aggregated cases was 11.3 %. This improved for subsequent cases, reaching 7.1 % for the 21st-30th cases. However, the mortality rate then increased, reaching 16.7 % by the 41st-50th cases before falling to 0.0 % by the 61st-70th cases. Initial improvement in surgical outcomes relative to cumulative surgical experience is not sustained. It is likely that factors other than surgical experience affect outcomes, such as less rigorous assessment of comorbidities or changes in support services. Vigilance regarding outcomes should be maintained even after initial improvements. C1 [Fong, Zhi Ven; Lillemoe, Keith D.; Chang, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Coe, Taylor M.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Wilson, Samuel E.] Univ Calif Irvine, Irvine Med Ctr, Dept Surg, Orange, CA 92668 USA. [Talamini, Mark A.] SUNY Stony Brook, Dept Surg, Stony Brook, NY 11794 USA. RP Chang, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02215 USA. EM dchang8@mgh.harvard.edu FU NHLBI NIH HHS [T35 HL007491] NR 32 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD DEC PY 2015 VL 19 IS 12 BP 2132 EP 2137 DI 10.1007/s11605-015-2967-0 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CW4AB UT WOS:000364932400006 PM 26438484 ER PT J AU Kapoor, N Abola, MV Jena, AB Smith, SE AF Kapoor, Neena Abola, Matthew V. Jena, Anupam B. Smith, Stacy E. TI Trends in Authorship Patterns in High-Impact Radiology Publications, 1980-2013 SO ACADEMIC RADIOLOGY LA English DT Article DE Honorary authorship; gift authorship; ethics ID RESEARCH ARTICLES; FREQUENCY; JOURNALS; CRITERIA; PROPOSAL; READERS AB Rationale and Objectives: Concerns have been raised about authorship inflation in medical literature. The purpose of this study was to determine how the number of authors per radiology article has changed over time with regard to study type and geographic factors. Materials and Methods: We collected data on study type, authorship count, and the country of the corresponding author for a sample of articles published in Radiology, American Journal of Roentgenology, and European Radiology in 1980, 1990, 2000, and 2013. Only original research and review articles were considered. We computed trends in the mean number of authors per article for each journal and compared authorship trends between study types and geographic region. The study did not involve human subjects and was therefore exempt from institutional board review at our institution. Results: A total of 682 articles were reviewed, of which 572 were original research articles (83.9%) and 110 review articles (16.1%). The overall number of authors per article doubled from 3.6 in 1980 to 7.3 in 2013 (P < .001). From 1990 to 2013, the largest absolute increase in authorship count was in Radiology (4.4-8.1, 84.1%, P < .001). The largest increase in authorship occurred in original research articles (3.7-7.8, 111%, P < .001). Although authorship counts were greatest in Asia over most study period, growth in authorship count was highest in Europe. Conclusions: Authorship count has dramatically increased in radiology journals in the last 3 decades, particularly in original research articles and in Europe. C1 [Kapoor, Neena; Smith, Stacy E.] Brigham & Womens Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02115 USA. [Kapoor, Neena; Smith, Stacy E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Abola, Matthew V.] Case Western Reserve Univ, Dept Family Med, Sch Med, Cleveland, OH 44106 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Kapoor, N (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. EM nkapoor@partners.org NR 24 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2015 VL 22 IS 12 BP 1587 EP 1591 DI 10.1016/j.acra.2015.08.013 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV9MZ UT WOS:000364612600018 PM 26419923 ER PT J AU Goyal, P Kim, J Feher, A Ma, CL Gurevich, S Veal, DR Szulc, M Wong, FJ Ratcliffe, MB Levine, RA Devereux, RB Weinsaft, JW AF Goyal, Parag Kim, Jiwon Feher, Attila Ma, Claudia L. Gurevich, Sergey Veal, David R. Szulc, Massimiliano Wong, Franklin J. Ratcliffe, Mark B. Levine, Robert A. Devereux, Richard B. Weinsaft, Jonathan W. TI Myocardial perfusion pattern for stratification of ischemic mitral regurgitation response to percutaneous coronary intervention SO CORONARY ARTERY DISEASE LA English DT Article DE mitral regurgitation; myocardial perfusion; single-photon emission computed tomography ID PAPILLARY-MUSCLE DYSFUNCTION; LONG-TERM OUTCOMES; ARTERY-DISEASE; VALVE REPAIR; IMPACT; ECHOCARDIOGRAPHY; REVASCULARIZATION; MECHANISM; RECOMMENDATIONS; ANNULOPLASTY AB ObjectiveIschemic mitral regurgitation (MR) is common, but its response to percutaneous coronary intervention (PCI) is poorly understood. This study tested the utility of myocardial perfusion imaging (MPI) for the stratification of MR response to PCI.MethodsMPI and transthoracic echocardiography (echo) were performed among patients undergoing PCI. MPI was used to assess stress/rest myocardial perfusion. MR was assessed via echo (performed before and after PCI).ResultsA total of 317 patients with abnormal myocardial perfusion on MPI underwent echo 2539 days before PCI. MR was present in 52%, among whom 24% had advanced (moderate) MR. MR was found to be associated with left ventricular (LV) chamber dilation on MPI and echo (both P<0.001). The magnitude of global LV perfusion deficits increased in relation to MR severity (P<0.01). Perfusion differences were greatest for global summed rest scores, which were 1.6-fold higher among patients with advanced MR versus those with mild MR (P=0.004), and 2.4-fold higher versus those without MR (P<0.001). In multivariate analysis, advanced MR was found to be associated with a fixed perfusion defect size on MPI [odds ratio 1.16 per segment (confidence interval 1.002-1.34), P=0.046], independent of LV volume [odds ratio 1.10 per 10ml (confidence interval 1.04-1.17), P=0.002]. Follow-up via echo (1.0 +/- 0.6 years) demonstrated MR to decrease (1 grade) in 31% of patients and increase in 12% of patients. Patients with increased MR after PCI had more severe inferior perfusion defects on baseline MPI (P=0.028), whereas defects in other distributions and LV volumes were similar (P=NS).ConclusionThe extent and distribution of single-photon emission computed tomography-evidenced myocardial perfusion defects impact MR response to revascularization. An increased magnitude of inferior fixed perfusion defects predicts post-PCI progression of MR. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Goyal, Parag; Kim, Jiwon; Feher, Attila; Ma, Claudia L.; Gurevich, Sergey; Veal, David R.; Szulc, Massimiliano; Wong, Franklin J.; Devereux, Richard B.; Weinsaft, Jonathan W.] Weill Cornell Med Coll, Greenberg Cardiol Div, Dept Med, New York, NY 10021 USA. [Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. [Ratcliffe, Mark B.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Weinsaft, JW (reprint author), Weill Cornell Med Coll, 525 East 68th St, New York, NY 10021 USA. EM jww2001@med.cornell.edu FU [K23 HL102249-01] FX This study was funded by grant K23 HL102249-01 to J.W.W. NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD DEC PY 2015 VL 26 IS 8 BP 642 EP 650 DI 10.1097/MCA.0000000000000271 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV9SQ UT WOS:000364627300003 PM 26049923 ER PT J AU Tolis, G Sundt, TM AF Tolis, George, Jr. Sundt, Thoralf M., III TI Surgical Strategies for Management of Mitral Regurgitation: Recent Evidence from Randomized Controlled Trials SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Review DE Mitral regurgitation; Ischemic mitral regurgitation; Trials; Management; Surgical treatment ID LONG-TERM SURVIVAL; VALVE REPAIR; REVASCULARIZATION; REPLACEMENT; ANNULOPLASTY AB In contrast to mitral regurgitation (MR) caused by structural abnormality of the valve ("primary" MR), about which there is increasing consensus regarding treatment, there is increasing controversy around the management of functional or "secondary" MR, of which "ischemic mitral regurgitation" (IMR) is a common cause. While the trend in the management of primary MR is increasingly aggressive, with wide agreement on the preference for repair over replacement such that debate centers on earlier and earlier repair even among asymptomatic patients, the situation is reversed in the setting of secondary MR with uncertainly beyond the mode of management (repair or replacement) to the value of intervening at all. This is, in part, because the term IMR has been somewhat loosely applied by the medical and surgical communities to include regurgitation secondary to active myocardial ischemia, as well as that resulting from a completed myocardial infarct. As a result, there is considerable variability in reported outcomes of surgical interventions for IMR. In addition, the natural history of IMR is quite adverse-more so than that of many solid organ malignancies-and its surgical treatment has traditionally carried a higher operative mortality than many cardiac surgical procedures, including similar operations for primary MR and incidental coronary artery disease. Added to this, with recent advances in both the medical and surgical treatment of heart failure improving nonoperative outcomes and simultaneously reducing operative risk compared to reports from previous decades, the landscape has been quite dynamic. Here, we review the issues surrounding surgical treatment for IMR, along with available evidence supporting different approaches, to lend an informed perspective on the divergent opinions among experts in this field and guide the appropriate management of the individual patient. C1 [Tolis, George, Jr.; Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Tolis, G (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. EM GTOLIS@mgh.harvard.edu; TSUNDT@mgh.harvard.edu FU Thrasos Therapeutics FX George Tolis, Jr. declares no conflict of interest. Thoralf M. Sundt, III declares personal fees for consultancy with Thrasos Therapeutics. NR 18 TC 0 Z9 0 U1 0 U2 2 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 EI 1534-6242 J9 CURR ATHEROSCLER REP JI Curr. Atheroscleros. Rep. PD DEC PY 2015 VL 17 IS 12 AR 67 DI 10.1007/s11883-015-0549-y PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CV8GY UT WOS:000364521700002 PM 26486511 ER PT J AU Gaier, ED Boudreault, K Rizzo, JF Falardeau, J Cestari, DM AF Gaier, Eric D. Boudreault, Katherine Rizzo, Joseph F., III Falardeau, Julie Cestari, Dean M. TI Atypical Optic Neuritis SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Optic neuritis; Ischemic optic neuropathy; Neuromyelitis optica (NMO); Sarcoidosis; Chronic relapsing inflammatory optic neuropathy; Lyme borreliosis ID RELAPSING NEUROMYELITIS-OPTICA; DEVELOPING MULTIPLE-SCLEROSIS; OCULAR LYME BORRELIOSIS; TREATMENT TRIAL; ANTI-CV2 ANTIBODIES; SPECTRUM DISORDERS; LUNG-CANCER; NMO-IGG; NEUROPATHY; SARCOIDOSIS AB Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features. C1 [Gaier, Eric D.; Boudreault, Katherine; Rizzo, Joseph F., III; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Rizzo, Joseph F., III; Cestari, Dean M.] Harvard Univ, Sch Med, Boston, MA USA. [Falardeau, Julie] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Gaier, Eric D.] Massachusetts Eye & Ear Infirm, Ophthalmol Educ, Boston, MA 02114 USA. [Boudreault, Katherine; Rizzo, Joseph F., III; Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, Boston, MA 02114 USA. [Falardeau, Julie] Oregon Hlth & Sci Univ, Casey Eye Inst, Neuroophthalmol, Portland, OR 97201 USA. RP Falardeau, J (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. EM Eric_Gaier@meei.harvard.edu; Katherine_Boudreault@meei.harvard.edu; Joseph_Rizzo@meei.harvard.edu; falardea@ohsu.edu; Dean_Cestari@meei.harvard.edu NR 70 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD DEC PY 2015 VL 15 IS 12 AR 76 DI 10.1007/s11910-015-0598-1 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CV8HC UT WOS:000364522200001 PM 26467052 ER PT J AU Zhou, J Jin, JO Patel, ES Yu, Q AF Zhou, Jing Jin, Jun-O Patel, Ekta S. Yu, Qing TI Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions SO CYTOKINE LA English DT Article DE Interleukin-6; Apoptosis; Inflammation; Sjogren's syndrome; Exocrine gland ID PRIMARY SJOGRENS-SYNDROME; NECROSIS-FACTOR-ALPHA; FAS-MEDIATED APOPTOSIS; MCL-1 UP-REGULATION; SALIVARY-GLAND; AUTOIMMUNE EXOCRINOPATHY; INTERFERON-GAMMA; CELL-LINE; SIGNALING PATHWAY; EPITHELIAL-CELLS AB Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjogren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-gamma- and TNF-alpha production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Zhou, Jing; Jin, Jun-O; Patel, Ekta S.; Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. [Zhou, Jing; Patel, Ekta S.; Yu, Qing] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Yu, Q (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA. EM jzhou@forsyth.org; junojin1@gmail.com; ektaspatel01@gmail.com; qyu@forsyth.org RI Zhou, jing/B-4718-2016 FU National Institutes of Health [P30 DE020751, R01 DE023838] FX We thank Juan Du for technical assistance in several experiments. This study was supported by the National Institutes of Health (P30 DE020751, R01 DE023838). NR 62 TC 4 Z9 4 U1 2 U2 10 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD DEC PY 2015 VL 76 IS 2 BP 244 EP 252 DI 10.1016/j.cyto.2015.07.027 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CV4NS UT WOS:000364244400018 PM 26255211 ER PT J AU Bai, XY Dinarello, CA Chan, ED AF Bai, Xiyuan Dinarello, Charles A. Chan, Edward D. TI The role of interleukin-32 against tuberculosis SO CYTOKINE LA English DT Article DE Interleukin-32; Tuberculosis; Cytokine ID MYCOBACTERIUM-TUBERCULOSIS; PROINFLAMMATORY CYTOKINE; IL-32 EXPRESSION; DISEASE; CELLS; MICE AB IL-32 is increasingly recognized to be an important host-protective molecule against tuberculosis. In this commentary, we highlight some of the potential mechanisms by which the immunomodulatory effect of IL-32 occurs against mycobacterial infections but also areas where mechanistic clarifications are needed. Published by Elsevier Ltd. C1 [Bai, Xiyuan; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80206 USA. [Bai, Xiyuan; Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Bai, Xiyuan; Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Bai, Xiyuan; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Dinarello, Charles A.] Univ Colorado, Div Infect Dis, Aurora, CO 80045 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org FU Department of Veterans Affairs Veterans Health Administration, Office of Research and Development [1 I01 BX001028-01A2]; NIH [AI15614] FX Study funded by Department of Veterans Affairs Veterans Health Administration, Office of Research and Development 1 I01 BX001028-01A2 (EDC) and NIH AI15614 (CAD). NR 20 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 EI 1096-0023 J9 CYTOKINE JI Cytokine PD DEC PY 2015 VL 76 IS 2 BP 585 EP 587 DI 10.1016/j.cyto.2015.06.013 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA CV4NS UT WOS:000364244400066 PM 26144292 ER PT J AU Bancks, MP Pletcher, MJ Kertesz, SG Sidney, S Rana, JS Schreiner, PJ AF Bancks, Michael P. Pletcher, Mark J. Kertesz, Stefan G. Sidney, Stephen Rana, Jamal S. Schreiner, Pamela J. TI Marijuana use and risk of prediabetes and diabetes by middle adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) study SO DIABETOLOGIA LA English DT Article DE Diabetes; Incidence; Longitudinal; Marijuana use; Prediabetes ID DIETARY PATTERNS; CANNABIS SMOKING; TRENDS AB Aims/hypothesis The impact of marijuana use on metabolic health is largely unknown. This study sought to clarify the cross-sectional and longitudinal associations between self-reported marijuana use, and prediabetes (defined as fasting glucose 5.6-6.9 mmol/l, 2 h glucose post OGTT 7.8-11.0 mmol/l or HbA(1c) 5.7-6.4% [39-47 mmol/mol]) and diabetes. Methods Data from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study were used to determine marijuana use and the presence of prediabetes and diabetes among participants. The association between marijuana use and the prevalence of prediabetes and diabetes was examined in 3,034 participants at CARDIA examination year 25 (2010-2011), while the incidence of prediabetes and diabetes according to previous marijuana use was assessed in 3,151 individuals who were free from prediabetes/diabetes at year 7 (1992-1993) and who returned for at least one of the four subsequent follow-up examinations over 18 years. Results The percentage of individuals who self-reported current use of marijuana declined over the course of the study's follow-up. After multivariable adjustment, higher odds of prediabetes were found for individuals who reported current use of marijuana (OR 1.65 [95% CI 1.15, 2.38]) and a lifetime use of 100 times or more (OR 1.49 [95% CI 1.06, 2.11]), compared with individuals who reported never using marijuana. There was no association between marijuana use and diabetes at CARDIA examination year 25. Over 18 years of follow-up, a greater risk of prediabetes (but not diabetes) was found for individuals who reported a lifetime use of marijuana of 100 times or more (HR 1.39 [95% CI 1.13, 1.71]), compared with individuals who had never used marijuana. Conclusions/interpretation Marijuana use in young adulthood is associated with an increased risk of prediabetes by middle adulthood, but not with the development of diabetes by this age. C1 [Bancks, Michael P.; Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Pletcher, Mark J.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Pletcher, Mark J.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Sidney, Stephen; Rana, Jamal S.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA. [Rana, Jamal S.] Kaiser Permanente No Calif, Dept Cardiol, Oakland, CA USA. [Rana, Jamal S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Bancks, MP (reprint author), Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, 1300 South Second St,Suite 300, Minneapolis, MN 55454 USA. EM banck005@umn.edu FU National Institutes of Health (NIH) [T32HL007779]; National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging (NIA); NIA; NHLBI [AG0005] FX MPB was supported by the National Institutes of Health (NIH) Training Grant T32HL007779 to conduct the current work. The CARDIA study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), the University of Minnesota (HHSN268201300028C), the Kaiser Foundation Research Institute (HHSN268201300029C) and Johns Hopkins University School of Medicine (HHSN268200900041C). The CARDIA study is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between the NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 26 TC 2 Z9 2 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2015 VL 58 IS 12 BP 2736 EP 2744 DI 10.1007/s00125-015-3740-3 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV4FC UT WOS:000364221200007 PM 26364621 ER PT J AU Letner, D Peloquin, J Durand, J Rutherford, A Yajnik, V Khalili, H Garber, J AF Letner, Dorothea Peloquin, Joanna Durand, Jacquelyn Rutherford, Anna Yajnik, Vijay Khalili, Hamed Garber, John TI Elevated Total Iron-Binding Capacity Is Associated with an Increased Risk of Celiac Disease SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Celiac disease; TIBC; Biomarkers; Iron homeostasis ID HEREDITARY HEMOCHROMATOSIS; FERRITIN; INFECTION; NETWORKS; CHILDREN; GLIADIN; MARKERS; ANEMIA AB Several lines of evidence suggest that abnormal iron homeostasis may itself play an important role in the development of celiac disease. We sought to determine whether abnormalities in iron status could be detected prior to the diagnosis of celiac disease, and to understand the relationship between altered iron indices and the natural history of celiac disease. We conducted a case-control study at two major tertiary referral hospitals. Cases were comprised of patients with celiac disease in whom iron status was assessed prior to the diagnosis. Each case was matched to five controls without known gastrointestinal disease according to age and sex. Information on potential covariates and laboratory values within 1, 1-3, and 3-5 years prior to diagnosis was collected. We used conditional logistic regression to evaluate the effect of iron indices on risk of celiac disease. We identified 157 celiac cases and 695 matched controls. Compared to participants with normal TIBC, the age-adjusted risk of celiac disease was significantly elevated among patients with elevated TIBC. For each 10 mu g/dL increase in TIBC, the risk of celiac disease increased by 4.6, 3.8, and 7.9 % within 1, 1-3, and 3-5 years prior to diagnosis, respectively. Patients with elevated pre-diagnosis TIBC were more likely to have abnormal liver enzymes and osteoporosis. Elevated TIBC is associated with an increased risk of celiac disease. Further investigation into the potential role of altered iron homeostasis may uncover important environmental factors that contribute to the development of celiac disease. C1 [Letner, Dorothea; Peloquin, Joanna; Durand, Jacquelyn; Yajnik, Vijay; Khalili, Hamed; Garber, John] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Rutherford, Anna] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02120 USA. [Peloquin, Joanna; Rutherford, Anna; Yajnik, Vijay; Khalili, Hamed; Garber, John] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Garber, J (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 7, Boston, MA 02114 USA. EM dletner@mgh.harvard.edu; jpeloquin@mgh.harvard.edu; jdurand03@gmail.com; arutherford@partners.org; vyajnik@mgh.harvard.edu; hkhalili@mgh.harvard.edu; jjgarber@mgh.harvard.edu FU Career Development Award from the Crohn's & Colitis Foundation of America; National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK094966, K23 DK099681]; Career Development Grant from the American Gastroenterological Association (AGA) FX Dr. Garber is supported by a Career Development Award from the Crohn's & Colitis Foundation of America and by the National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK094966). Dr. Khalili is supported by a Career Development Grant from the American Gastroenterological Association (AGA) and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). NR 33 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 2015 VL 60 IS 12 BP 3735 EP 3742 DI 10.1007/s10620-015-3791-9 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV8UO UT WOS:000364563600032 PM 26173503 ER PT J AU Bliss, LA Maguire, LH Chau, ZL Yang, CJ Nagle, DA Chan, AT Tseng, JF AF Bliss, Lindsay A. Maguire, Lillias H. Chau, Zeling Yang, Catherine J. Nagle, Deborah A. Chan, Andrew T. Tseng, Jennifer F. TI Readmission After Resections of the Colon and Rectum: Predictors of a Costly and Common Outcome SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Colon; Rectum; Resection; Outcomes; Readmission ID COLORECTAL SURGERY; HOSPITAL READMISSIONS; CANCER; MORTALITY; COMPLICATIONS; QUALITY; PROGRAM; VOLUME; IMPACT; RATES AB BACKGROUND: Readmission rates are a measure of surgical quality and an object of clinical and regulatory scrutiny. Despite increasing efforts to improve quality and contain cost, 6% to 25% of patients are readmitted after colorectal surgery. OBJECTIVE: The aim of this study is to define the predictors and costs of readmission following colorectal surgery. DESIGN: This is a retrospective cohort study of patients undergoing elective and nonelective colectomy and/or proctectomy in the Healthcare Cost and Utilization Project Florida State Inpatient Database 2007 to 2011. Readmission is defined as inpatient admission within 30 days of discharge. Univariate analyses were performed of sex, age, Elixhauser score, race, insurance type, procedure, indication, readmission diagnosis, cost, and length of stay. Multivariate analysis was performed by logistic regression. Sensitivity analysis of nonemergent admissions was conducted. SETTINGS: This study was conducted in Florida acute-care hospitals. PATIENTS: Patients undergoing colectomy and proctectomy from 2007 to 2011 were included. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): The primary outcomes measured were readmission and the cost of readmission. RESULTS: A total of 93,913 patients underwent colectomy; 14.7% were readmitted within 30 days. From 2007 to 2011, readmission rates remained stable (14.6%-14.2%, trend p = 0.1585). After multivariate adjustment, patient factors associated with readmission included nonwhite race, age <65, and a diagnosis code other than neoplasm or diverticular disease (p < 0.0001). Patients with Medicare or Medicaid were more likely to be readmitted than those with private insurance (p < 0.0001). Patients with longer index admissions, those with stomas, and those undergoing all procedures other than sigmoid or transverse colectomy were more likely to be readmitted (p < 0.0001). High-volume hospitals had higher rates of readmission (p < 0.0001). The most common reason for readmission was infection (32.9%). Median cost of readmission care was $7030 (intraquartile range, $4220-$13,247). Fistulas caused the most costly readmissions ($15,174; intraquartile range, $6725-$26,660). LIMITATIONS: Administrative data and retrospective design were limitations of this study. CONCLUSIONS: Readmissions rates after colorectal surgery remain common and costly. Nonprivate insurance, IBD, and high hospital volume are significantly associated with readmission. C1 [Bliss, Lindsay A.; Yang, Catherine J.; Tseng, Jennifer F.] Beth Israel Deaconess Med Ctr, Surg Outcomes Anal & Res, Boston, MA 02215 USA. [Maguire, Lillias H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chau, Zeling] UMass Mem Med Ctr, Dept Surg, Worcester, MA USA. [Nagle, Deborah A.] Beth Israel Deaconess Med Ctr, Colon & Rectal Surg, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Surg Oncol, Boston, MA 02215 USA. RP Tseng, JF (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Surg Oncol, 330 Brookline Ave,Stoneman 9, Boston, MA 02215 USA. EM jftseng@bidmc.harvard.edu FU Howard Hughes Medical Institute Early Career Award; American Surgical Association Foundation Fellowship; American Cancer Society [MSRG 10-003-01]; NIH [K24 DK098311] FX This work was supported by Howard Hughes Medical Institute Early Career Award, American Surgical Association Foundation Fellowship, American Cancer Society MSRG 10-003-01 (to J.F.T.), and NIH Award K24 DK098311 (to A.T.C.). NR 20 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD DEC PY 2015 VL 58 IS 12 BP 1164 EP 1173 DI 10.1097/DCR.0000000000000433 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CW1ZV UT WOS:000364791700008 PM 26544814 ER PT J AU Vickers, Z Damodhar, H Grummer, C Mendenhall, H Banaszynski, K Hartel, R Hind, J Joyce, A Kaufman, A Robbins, J AF Vickers, Z. Damodhar, H. Grummer, C. Mendenhall, H. Banaszynski, K. Hartel, R. Hind, J. Joyce, A. Kaufman, A. Robbins, J. TI Relationships Among Rheological, Sensory Texture, and Swallowing Pressure Measurements of Hydrocolloid-Thickened Fluids SO DYSPHAGIA LA English DT Article DE Fluid rheology; Swallowing pressure; Thickness; Mouthcoating; Sensory evaluation; Flow behavior ID COMMERCIAL THICKENERS; DYSPHAGIA DIETS; VISCOSITY; FOOD; BEVERAGES; ACCEPTANCE; PERCEPTION; AGENTS; VOLUME; FORCE AB The objective of this study was to examine the relationships among three categories of measurements (rheological, sensory texture, and swallowing pressure) from fluids thickened to two different viscosities with 15 different hydrocolloids. Fluids at viscosities of 300 and 1500 cP (at 30 s(-1)) were targeted because these are the viscosities corresponding to the barium standards used in radiographic dysphagia diagnosis. Within the low viscosity (nectar) fluids (300 cP), the sensory properties thickness, stickiness, adhesiveness, mouth coating, and number of swallows were highly positively correlated with each other and highly positively correlated with the flow behavior index, n value (an indicator of shear-thinning behavior). Within the higher viscosity (thin honey) fluids (1500 cP), the sensory textures of adhesiveness, stickiness, mouth coating, and number of swallows correlated positively with rheological measures of n value. Swallowing pressures measured in the anterior oral cavity correlated negatively with the consistency coefficient k [shear stress/(shear rate) (n) ]. Samples that were more shear thinning (lower n values, higher k values) were generally perceived as less thick, with less adhesive properties (stickiness, adhesiveness, mouthcoating, and number of swallows). This information can be useful for selecting thickeners for people with dysphagia. A desirable thickener for many dysphagic patients would be one that allowed for a safe swallow by being viscous enough to reduce airway penetration, yet pleasant to drink, having the minimal perceived thickness and mouthcoating associated with greater shear thinning. C1 [Vickers, Z.; Damodhar, H.] Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN 55112 USA. [Grummer, C.; Mendenhall, H.; Banaszynski, K.; Hartel, R.] Univ Wisconsin, Dept Food Sci, Madison, WI 53706 USA. [Hind, J.; Joyce, A.; Kaufman, A.; Robbins, J.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Hind, J.; Joyce, A.; Kaufman, A.; Robbins, J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53706 USA. RP Vickers, Z (reprint author), Univ Minnesota, Dept Food Sci & Nutr, 1334 Eckles Ave, St Paul, MN 55112 USA. EM zvickers@umn.edu OI Vickers, Zata/0000-0002-4509-7956 FU National Research Initiative Grant from the USDA Cooperative state Research, Education and Extension Service [12143]; Wm. S. Middleton Memorial Veterans Hospital Geriatric Research, Education and Clinical Center (GRECC); Minnesota Agricultural Experiment Station FX This project was supported by National Research Initiative Grant 12143 from the USDA Cooperative state Research, Education and Extension Service, and the Wm. S. Middleton Memorial Veterans Hospital Geriatric Research, Education and Clinical Center (GRECC). This manuscript was partially prepared at the William S. Middleton Veteran Affairs Hospital in Madison, WI; GRECC manuscript #2015-015. The views and content expressed in this article are solely the responsibility of the authors and do not necessarily reflect the position, policy, or official views of the Department of Veteran Affairs or the U.S. government. This research was partly supported by the Minnesota Agricultural Experiment Station. NR 45 TC 3 Z9 3 U1 10 U2 35 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X EI 1432-0460 J9 DYSPHAGIA JI Dysphagia PD DEC PY 2015 VL 30 IS 6 BP 702 EP 713 DI 10.1007/s00455-015-9647-9 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA CV8FE UT WOS:000364515500006 PM 26289079 ER PT J AU Danti, S Toschi, N Diciotti, S Tessa, C Poletti, M Del Dotto, P Lucetti, C AF Danti, S. Toschi, N. Diciotti, S. Tessa, C. Poletti, M. Del Dotto, P. Lucetti, C. TI Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE clinical phenotypes; cortical thickness and cortical folding; mild cognitive impairment; motor laterality; MR imaging; Parkinson's disease ID VERBAL FLUENCY; DEMENTIA; ASYMMETRY; DECLINE; COHORT AB Background and purpose: Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Methods: Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Results: Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. Conclusions: When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. C1 [Danti, S.; Del Dotto, P.; Lucetti, C.] Versilia Hosp, Div Neurol Unit, I-55043 Lido Di Camaiore, Lu, Italy. [Toschi, N.] Univ Roma Tor Vergata, Med Phys Sect, Dept Biomed & Prevent, Rome, Italy. [Toschi, N.] Massachusetts Gen Hosp, Dept Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Toschi, N.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Diciotti, S.] Univ Bologna, Dept Elect Elect & Informat Engn Guglielmo Marcon, Cesena, Italy. [Tessa, C.] Versilia Hosp, Div Radiol Unit, Lido Di Camaiore, Lucca, Italy. [Poletti, M.] AUSL Reggio Emilia, Dept Mental Hlth & Pathol Addict, Reggio Emilia, Italy. RP Danti, S (reprint author), Versilia Hosp, Div Neurol, AUSL 12 Viareggio,Via Aurelia 335, I-55043 Lido Di Camaiore, Lu, Italy. EM danti.sabrina@gmail.com RI Diciotti, Stefano/C-4167-2008; Toschi, Nicola/J-2555-2012 OI Diciotti, Stefano/0000-0001-8778-7819; Toschi, Nicola/0000-0003-1929-5833 NR 33 TC 6 Z9 6 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD DEC PY 2015 VL 22 IS 12 BP 1564 EP 1572 DI 10.1111/ene.12785 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CV8FA UT WOS:000364514900013 PM 26212370 ER PT J AU Gillams, A Goldberg, N Ahmed, M Bale, R Breen, D Callstrom, M Chen, MH Choi, BI de Baere, T Dupuy, D Gangi, A Gervais, D Helmberger, T Jung, EM Lee, F Lencioni, R Liang, P Livraghi, T Lu, D Meloni, F Pereira, P Piscaglia, F Rhim, H Salem, R Sofocleous, C Solomon, SB Soulen, M Tanaka, M Vogl, T Wood, B Solbiati, L AF Gillams, Alice Goldberg, Nahum Ahmed, Muneeb Bale, Reto Breen, David Callstrom, Matthew Chen, Min Hua Choi, Byung Ihn de Baere, Thierry Dupuy, Damian Gangi, Afshin Gervais, Debra Helmberger, Thomas Jung, Ernst-Michael Lee, Fred Lencioni, Riccardo Liang, Ping Livraghi, Tito Lu, David Meloni, Franca Pereira, Philippe Piscaglia, Fabio Rhim, Hyunchul Salem, Riad Sofocleous, Constantinos Solomon, Stephen B. Soulen, Michael Tanaka, Masatoshi Vogl, Thomas Wood, Brad Solbiati, Luigi TI Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, the interventional oncology sans frontiSres meeting 2013 SO EUROPEAN RADIOLOGY LA English DT Article DE Colorectal neoplasms; Liver neoplasms; Ablation techniques; Consensus; Clinical protocols AB Previous attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases. This consensus paper was discussed by an expert panel at The Interventional Oncology Sans FrontiSres 2013. A literature review was presented. Tumour characteristics, ablation technique and different clinical applications were considered and the level of consensus was documented. Specific recommendations are made with regard to metastasis size, number, and location and ablation technique. Mean 31 % 5-year survival post-ablation in selected patients has resulted in acceptance of this therapy for those with technically inoperable but limited liver disease and those with limited liver reserve or co-morbidities that render them inoperable. In the absence of RCT data, it is our aim that this consensus document will facilitate judicious selection of the patients most likely to benefit from thermal ablation and provide a unified interventional oncological perspective for the use of this technology. aEuro cent Best results require due consideration of tumour size, number, volume and location. aEuro cent Ablation technology, imaging guidance and intra-procedural imaging assessment must be optimised. aEuro cent Accepted applications include inoperable disease due to tumour distribution or inadequate liver reserve. aEuro cent Other current indications include concurrent co-morbidity, patient choice and the test-of-time approach. aEuro cent Future applications may include resectable disease, e.g. for small solitary tumours. C1 [Gillams, Alice] London Clin, Dept Imaging, London W1G 6BW, England. [Goldberg, Nahum; Ahmed, Muneeb] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bale, Reto] Univ Innsbruck Hosp, A-6020 Innsbruck, Austria. [Breen, David] Southampton Univ Hosp, Southampton, Hants, England. [Callstrom, Matthew] Mayo Clin, Rochester, MN USA. [Chen, Min Hua] Peking Univ Hosp, Beijing, Peoples R China. [Choi, Byung Ihn] Seoul Univ Hosp, Seoul, South Korea. [de Baere, Thierry] Gustave Roussy Canc Campus, Paris, France. [Gangi, Afshin] Univ Strasbourg, Strasbourg, France. [Gervais, Debra] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Helmberger, Thomas] Klinikum Bochenhausen, Munich, Germany. [Jung, Ernst-Michael] Univ Regensburg, D-93053 Regensburg, Germany. [Lee, Fred] Univ Wisconsin, Madison, WI USA. [Lencioni, Riccardo] Univ Pisa, Pisa, Italy. [Liang, Ping] Chinese Peoples Liberat Army Gen Hosp, Beijing, Peoples R China. [Livraghi, Tito] Clin Inst Humanitas, Milan, Italy. [Lu, David] Univ Calif Los Angeles, Los Angeles, CA USA. [Meloni, Franca] Univ Milan, Milan, Italy. [Pereira, Philippe] Heidelberg Univ, Heidelberg, Germany. [Piscaglia, Fabio] Univ Bologna, Bologna, Italy. [Rhim, Hyunchul] Sungkyunkwan Univ, Seoul, South Korea. [Salem, Riad] Northwestern Univ, Chicago, IL 60611 USA. [Sofocleous, Constantinos; Solomon, Stephen B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Soulen, Michael] Univ Penn, Philadelphia, PA 19104 USA. [Tanaka, Masatoshi] Yokokura Hosp, Miyama, Japan. [Vogl, Thomas] Goethe Univ Frankfurt, D-60054 Frankfurt, Germany. [Wood, Brad] NIH, Bethesda, MD 20892 USA. RP Gillams, A (reprint author), London Clin, Dept Imaging, 20 Devonshire Pl, London W1G 6BW, England. EM alliesorting@gmail.com OI meloni, maria franca/0000-0001-7485-7400 FU NCI NIH HHS [P30 CA060553] NR 0 TC 25 Z9 26 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD DEC PY 2015 VL 25 IS 12 BP 3438 EP 3454 DI 10.1007/s00330-015-3779-z PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV8FS UT WOS:000364517000004 PM 25994193 ER PT J AU Takx, RAP Sucha, D Park, J Leiner, T Hoffmann, U AF Takx, Richard A. P. Sucha, Dominika Park, Jakob Leiner, Tim Hoffmann, Udo TI Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review SO EUROPEAN RADIOLOGY LA English DT Review DE Nitroglycerin; Computed tomography; Coronary CT angiography; Coronary vasodilation; Coronary artery disease ID FRACTIONAL FLOW RESERVE; CT ANGIOGRAPHY; INTRAVASCULAR ULTRASOUND; DIAGNOSTIC PERFORMANCE; 64-MDCT ANGIOGRAPHY; GENDER-DIFFERENCES; ARTERY-DISEASE; NITRIC-OXIDE; DIAMETER; VASODILATATION AB To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. aEuro cent Sublingual nitroglycerin administration results in significant coronary artery dilatation. aEuro cent Nitroglycerin increases the number of evaluable coronary branches. aEuro cent Image quality is improved the most in smaller coronary branches. aEuro cent Nitroglycerin increases the diagnostic accuracy of coronary CT angiography. aEuro cent Most side effects are mild and do not require medical intervention. C1 [Takx, Richard A. P.; Park, Jakob; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, Boston, MA 02115 USA. [Takx, Richard A. P.; Sucha, Dominika; Leiner, Tim] Univ Med Ctr Utrecht, Dept Radiol, NL-3584 CX Utrecht, Netherlands. [Park, Jakob] Heidelberg Univ, Dept Cardiol, Heidelberg, Germany. RP Takx, RAP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, Boston, MA 02115 USA. EM rtakx@umcutrecht.nl FU German Cardiac Society; German National Academic Foundation FX The scientific guarantor of this publication is Tim Leiner. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. Jakob Park received funding from the German Cardiac Society and German National Academic Foundation. All other authors have nothing to declare. No complex statistical methods were necessary for this paper. Institutional Review Board approval and written informed consent were not necessary because the study was a systematic review. Some study subjects or cohorts have been previously reported. This study is a systematic review; as such, this is a summary of previously published material. NR 36 TC 4 Z9 4 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD DEC PY 2015 VL 25 IS 12 BP 3536 EP 3542 DI 10.1007/s00330-015-3791-3 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV8FS UT WOS:000364517000014 PM 25994194 ER PT J AU Wang, J Zhang, XH Beck, AH Collins, LC Chen, WY Tamimi, RM Hazra, A Brown, M Rosner, B Hankinson, SE AF Wang, Jun Zhang, Xuehong Beck, Andrew H. Collins, Laura C. Chen, Wendy Y. Tamimi, Rulla M. Hazra, Aditi Brown, Myles Rosner, Bernard Hankinson, Susan E. TI Alcohol Consumption and Risk of Breast Cancer by Tumor Receptor Expression SO HORMONES & CANCER LA English DT Article ID NATIONAL DEATH INDEX; POSTMENOPAUSAL WOMEN; INSULIN-RECEPTOR; PREMENOPAUSAL WOMEN; SEX-HORMONES; C-PEPTIDE; ESTROGEN; SUBTYPES; PLASMA; METAANALYSIS AB In epidemiologic studies, alcohol consumption appears more strongly associated with risk of estrogen receptor (ER)-positive than ER-negative breast cancer. However, this association has not been assessed by other potentially relevant tumor markers, such as androgen receptor (AR) or insulin receptor (IR). In the prospective Nurses' Health Study cohort, we evaluated alcohol consumption and breast cancer risk by individual tumor marker expression (i.e., ER, progesterone receptor [PR], AR, and IR) while controlling for other markers and also assessed the joint effect of these receptors. During 26 years follow-up of 106,037 women, 2552 invasive breast cancers contributed to the analysis. When all four markers were considered simultaneously, no significant heterogeneity of the alcohol and breast cancer association was observed by any of the markers. However, each increment in one drink per day was associated with 10 % (95 % confidence interval [CI] = 4 %, 15 %) and 9 % (95 % CI = 4 %, 15 %) increased risk of AR-positive and ER-positive breast cancer, respectively, while no increased risk was observed among AR-negative or ER-negative tumors. The association was independent of PR and IR expression. Assessment of the joint expression of hormone receptors revealed a significantly increased risk among AR+/ER+/PR+ (hazard ratio [HR] per drink/day = 1.11, 95 % CI = 1.06, 1.17) but not in other subgroups (e.g., AR-/ER-/PR-: HR = 0.99; 95 % CI = 0.88, 1.12). Our data suggest that the alcohol and breast cancer association may be more pronounced among ER-positive and/or AR-positive breast tumors. However, our data do not support an important role of IR in the association. C1 [Wang, Jun; Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Zhang, Xuehong; Chen, Wendy Y.; Tamimi, Rulla M.; Hazra, Aditi; Rosner, Bernard; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Zhang, Xuehong; Beck, Andrew H.; Collins, Laura C.; Chen, Wendy Y.; Tamimi, Rulla M.; Hazra, Aditi; Rosner, Bernard; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Beck, Andrew H.; Collins, Laura C.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Chen, Wendy Y.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tamimi, Rulla M.; Hazra, Aditi; Hankinson, Susan E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rosner, Bernard] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Wang, J (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, 715 N Pleasant St, Amherst, MA 01003 USA. EM junw@schoolph.umass.edu OI Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [CA166666, CA186107, CA87969]; Komen Foundation [SAC 110014] FX This study was supported by research grants CA166666, CA186107, and CA87969 from the National Institutes of Health and SAC 110014 from the Komen Foundation. We would like to thank the participants and staff of the Nurses' Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. NR 40 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-8497 EI 1868-8500 J9 HORM CANCER-US JI Horm. Cancer PD DEC PY 2015 VL 6 IS 5-6 BP 237 EP 246 DI 10.1007/s12672-015-0235-0 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA CV6RJ UT WOS:000364397600006 PM 26385458 ER PT J AU Haberer, JE Musinguzi, N Boum, Y Siedner, MJ Mocello, AR Hunt, PW Martin, JN Bangsberg, DR AF Haberer, Jessica E. Musinguzi, Nicholas Boum, Yap, II Siedner, Mark J. Mocello, A. Rain Hunt, Peter W. Martin, Jeffrey N. Bangsberg, David R. TI Duration of Antiretroviral Therapy Adherence Interruption Is Associated With Risk of Virologic Rebound as Determined by Real-Time Adherence Monitoring in Rural Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV antiretroviral therapy; real-time adherence monitoring; viral rebound ID HIV-INFECTED PATIENTS; LESS-THAN 95-PERCENT; SUB-SAHARAN AFRICA; NORTH-AMERICA; SUPPRESSION; FAILURE; RNA; LOPINAVIR/RITONAVIR; MANAGEMENT; RESISTANCE AB Background: Antiretroviral therapy (ART) adherence interruptions have been associated with viral rebound; however, the true risk is unknown because HIV RNA has never been measured during ongoing interruptions. Methods: The Uganda AIDS Rural Treatment Outcomes Study is an observational longitudinal cohort of adults initiating ART. We monitored adherence with the device that wirelessly transmits records of device openings, and routinely assessed HIV RNA quarterly. When lapses of 48+ hours between device openings were detected, we made unannounced visits to participants to investigate the cause and assess HIV RNA. Generalized estimating equation logistic regressions were used to assess factors associated with viral rebound. Results: We followed 479 participants (median: 25 months per participant). Most were women (72%), median age was 36 years, median pre-ART CD4 count was 198 cells per microliter, median pre-ART HIV RNA level was 5.0 log(10) copies per milliliter, and median duration of prior viral suppression was 13 months. A total of 587 adherence interruptions followed confirmed prior viral suppression, of which 13 (2%) had detectable viral rebound. Viral rebound was associated with duration of adherence interruption (odds ratio: 1.25 for each day beyond 48 hours; P = 0.007) and 30-day adherence before the interruption (odds ratio: 0.73; P = 0.02). Discussion: This article is the first demonstration of HIV RNA rebound during adherence interruptions objectively measured in real time. Odds of viral rebound increased by 25% with each day beyond 48 hours. Real-time adherence monitoring was feasible in a sub-Saharan African setting. Further research should assess the potential for real-time adherence interventions to sustain adherence to affordable first-line regimens. C1 [Haberer, Jessica E.; Siedner, Mark J.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Haberer, Jessica E.; Siedner, Mark J.; Bangsberg, David R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Musinguzi, Nicholas] Mbarara Univ Sci & Technol, Global Hlth Collaborat, Mbarara, Uganda. [Boum, Yap, II] EpiCtr Med Sans Frontieres, Mbarara, Uganda. [Boum, Yap, II] Mbarara Univ Sci & Technol, Dept Med Lab Sci, Mbarara, Uganda. [Mocello, A. Rain; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Hunt, Peter W.] Univ Calif San Francisco, Med, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. RP Haberer, JE (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM jhaberer@mgh.harvard.edu FU NIH [R01MH054907, K23MH087228, K23MH099916, P30AI027763, UM1CA181255] FX Supported by the NIH (R01MH054907, K23MH087228, K23MH099916, P30AI027763, and UM1CA181255). NR 26 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2015 VL 70 IS 4 BP 386 EP 392 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CV5MZ UT WOS:000364316300008 PM 26110445 ER PT J AU Mansergh, G Herbst, JH Mimiaga, MJ Holman, J AF Mansergh, Gordon Herbst, Jeffrey H. Mimiaga, Matthew J. Holman, Jeremy TI Preference for Condoms, Antiretroviral Preexposure Prophylaxis, or Both Methods to Reduce Risk for HIV Acquisition Among Uninfected US Black and Latino MSM SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Mansergh, Gordon; Herbst, Jeffrey H.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30329 USA. [Mimiaga, Matthew J.; Holman, Jeremy] John Snow Inc, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mansergh, G (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30329 USA. FU PHS HHS [200-2012-53307] NR 5 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2015 VL 70 IS 4 BP E153 EP E155 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CV5NB UT WOS:000364316500006 PM 26302430 ER PT J AU Berezina-Greene, MA Guinan, JJ AF Berezina-Greene, Maria A. Guinan, John J., Jr. TI Stimulus Frequency Otoacoustic Emission Delays and Generating Mechanisms in Guinea Pigs, Chinchillas, and Simulations SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE Coherent reflection; SFOAE; TEOAE; Cochlear mechanics ID AUDITORY-NERVE FIBERS; OLIVOCOCHLEAR-EFFERENT INHIBITION; DIFFERENT-LATENCY COMPONENTS; BASILAR-MEMBRANE RESPONSES; COCHLEAR VIBRATIONS; 2-TONE SUPPRESSION; HAIR-CELLS; TONES; HUMANS; PHASE AB According to coherent reflection theory (CRT), stimulus frequency otoacoustic emissions (SFOAEs) arise from cochlear irregularities coherently reflecting energy from basilar membrane motion within the traveling-wave peak. This reflected energy arrives in the ear canal predominantly with a single delay at each frequency. However, data from humans and animals indicate that (1) SFOAEs can have multiple delay components, (2) low-frequency SFOAE delays are too short to be accounted for by CRT, and (3) "SFOAEs" obtained with a 2nd ("suppressor") tone a parts per thousand yen2 octaves above the probe tone have been interpreted as arising from the area basal to the region of cochlear amplification. To explore these issues, we collected SFOAEs by the suppression method in guinea pigs and time-frequency analyzed these data, simulated SFOAEs, and published chinchilla SFOAEs. Time-frequency analysis revealed that most frequencies showed only one SFOAE delay component while other frequencies had multiple components including some with short delays. We found no systematic patterns in the occurrence of multiple delay components. Using a cochlear model that had significant basilar membrane motion only in the peak region of the traveling wave, simulated SFOAEs had single and multiple delay components similar to the animal SFOAEs. This result indicates that multiple components (including ones with short delays) can originate from cochlear mechanical irregularities in the SFOAE peak region and are not necessarily indicative of SFOAE sources in regions a parts per thousand yen2 octaves basal of the SFOAE peak region. We conclude that SFOAEs obtained with suppressors close to the probe frequency provide information primarily about the mechanical response in the region that receives amplification, and we attribute the too-short SFOAE delays at low frequencies to distortion-source SFOAEs and coherent reflection from multiple cochlear motions. Our findings suggest that CRT needs revision to include reflections from multiple motions in the cochlear apex. C1 [Berezina-Greene, Maria A.; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Berezina-Greene, Maria A.; Guinan, John J., Jr.] Harvard MIT HST Speech & Hearing Biosci & Technol, Cambridge, MA USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Berezina-Greene, MA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM maria.berezina@gmail.com; jjg@epl.meei.harvard.edu FU NSF GRFP; [RO1 DC000235]; [R01 DC003687]; [T32 DC00038]; [P30 DC005209] FX We thank Drs. C.A. Shera, M.C. Brown, D.C. Mountain, and K. K. Charaziak for comments on earlier versions of the manuscript. This work was supported by RO1 DC000235, R01 DC003687, T32 DC00038, P30 DC005209, and a NSF GRFP, and was part M. B-G's PhD thesis. NR 51 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2015 VL 16 IS 6 BP 679 EP 694 DI 10.1007/s10162-015-0543-7 PG 16 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CV8IT UT WOS:000364527700001 PM 26373935 ER PT J AU Shaheen, LA Valero, MD Liberman, MC AF Shaheen, Luke A. Valero, Michelle D. Liberman, M. Charles TI Towards a Diagnosis of Cochlear Neuropathy with Envelope Following Responses SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE hidden hearing loss; auditory neuropathy; acoustic overexposure; envelope following response; auditory steady-state response; auditory brainstem response; auditory nerve ID STEADY-STATE RESPONSES; AUDITORY-EVOKED-POTENTIALS; BRAIN-STEM RESPONSES; AMPLITUDE-MODULATED TONES; OUTER HAIR-CELLS; HEARING-LOSS; NERVE DEGENERATION; NOISE EXPOSURE; ROUND WINDOW; CAT COCHLEA AB Listeners with normal audiometric thresholds can still have suprathreshold deficits, for example, in the ability to discriminate sounds in complex acoustic scenes. One likely source of these deficits is cochlear neuropathy, a loss of auditory nerve (AN) fibers without hair cell damage, which can occur due to both aging and moderate acoustic overexposure. Since neuropathy can affect up to 50 % of AN fibers, its impact on suprathreshold hearing is likely profound, but progress is hindered by lack of a robust non-invasive test of neuropathy in humans. Reduction of suprathreshold auditory brainstem responses (ABRs) can be used to quantify neuropathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy is selective for AN fibers with high thresholds, and because phase locking to temporal envelopes is particularly strong in these fibers, the envelope following response (EFR) might be a more robust measure. We compared EFRs to sinusoidally amplitude-modulated tones and ABRs to tone-pips in mice following a neuropathic noise exposure. EFR amplitude, EFR phase-locking value, and ABR amplitude were all reduced in noise-exposed mice. However, the changes in EFRs were more robust: the variance was smaller, thus inter-group differences were clearer. Optimum detection of neuropathy was achieved with high modulation frequencies and moderate levels. Analysis of group delays was used to confirm that the AN population was dominating the responses at these high modulation frequencies. Application of these principles in clinical testing can improve the differential diagnosis of sensorineural hearing loss. C1 [Shaheen, Luke A.; Liberman, M. Charles] MIT, Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Shaheen, Luke A.; Valero, Michelle D.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Valero, Michelle D.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shaheen, LA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM lshaheen@mit.edu; Michelle_Valero@meei.harvard.edu; Charles_Liberman@meei.harvard.edu FU National Institute on Deafness and other Communicative Disorders [R01 DC 00188, P30 DC 05209, T32 DC 00038] FX We thank Leslie Liberman for expert assistance in cochlear immunostaining, and Yanbo Yin and Mingjie Tong for their assistance in the ouabain experiment. We thank Andrea Meredith for providing the BK knockout mice. Research supported by grants from the National Institute on Deafness and other Communicative Disorders: R01 DC 00188 (MCL), P30 DC 05209 (MCL) and T32 DC 00038 (LAS). NR 72 TC 16 Z9 16 U1 4 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2015 VL 16 IS 6 BP 727 EP 745 DI 10.1007/s10162-015-0539-3 PG 19 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA CV8IT UT WOS:000364527700004 PM 26323349 ER PT J AU Minzenberg, MJ Lesh, TA Niendam, TA Yoon, JH Cheng, YA Rhoades, RN Carter, CS AF Minzenberg, Michael J. Lesh, Tyler A. Niendam, Tara A. Yoon, Jong H. Cheng, Yaoan Rhoades, Remy N. Carter, Cameron S. TI Control-related frontal-striatal function is associated with past suicidal ideation and behaviior in patients with recent-onset psychotic major mood disorders SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar I disorder; Major depressive disorder; Psychosis; Suicide risk; Cognitive control; Frontal cortex ID PREFRONTAL CORTEX; COGNITIVE CONTROL; DEPRESSIVE DISORDER; BIPOLAR DISORDER; NEURAL CIRCUITRY; DECISION-MAKING; WORST-POINT; RISK; BRAIN; ADOLESCENTS AB Objective: Suicide is highly-prevalent in major mood disorders, yet it remains unclear how suicidal ideation and suicidal behavior relate to brain functions, especially those that support control processes. We evaluated how prefrontal cortex (PFC) activity during goal-representation (an important component of cognitive control) relates to past suicidal ideation and behavior in patients with psychotic major mood disorders. Method: 30 patients with recent-onset of either DSM-IV-TR-defined bipolar disorder type I (n=21) or major depressive disorder (n=9) with psychotic features, but neither in a major mood episode nor acutely psychotic at study, were evaluated for past suicidal ideation and behavior (Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models of brain activation accounted for current depression, psychosis and trait impulsivity. Results: Intensity of past suicidal ideation was associated with higher control-related activation in right-hemisphere regions including the ventrolateral PFC (VLPFC) and orbitofrontal cortex, rostral insula, and dorsal striatum. Among those with past suicidal ideation (n=16), past suicidal behavior (n=8) was associated with higher control-related activation in right-hemisphere regions including VLPFC, rostrolateral PFC, and frontal operculum/rostral insula: and relatively lower activity in midline parietal regions, including cuneus and precuneus. Limitations: The sample size of subjects with past suicidal behavior was modest, and all subjects were taking psychotropic medication. Conclusions: This study provides unique evidence that in early-course psychotic major mood disorders, suicidal ideation and behavior histories directly relate to PFC-based circuit function in support of cognitive control. Published by Elsevier B.V. C1 [Minzenberg, Michael J.; Cheng, Yaoan] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Minzenberg, Michael J.; Cheng, Yaoan] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Lesh, Tyler A.; Niendam, Tara A.; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Yoon, Jong H.; Rhoades, Remy N.] Stanford Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA USA. [Yoon, Jong H.; Rhoades, Remy N.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Minzenberg, MJ (reprint author), San Francisco VA Med Ctr, Outpatient Mental Hlth, 116C,4150 Clement St, San Francisco, CA 94121 USA. EM Michael.minzenberg@ucsf.edu NR 58 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC 1 PY 2015 VL 188 BP 202 EP 209 DI 10.1016/j.jad.2015.08.049 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CV3OI UT WOS:000364168100028 PM 26363618 ER PT J AU Surman, CBH Biederman, J Spencer, T Miller, CA Petty, CR Faraone, SV AF Surman, Craig B. H. Biederman, Joseph Spencer, Thomas Miller, Carolyn A. Petty, Carter R. Faraone, Stephen V. TI Neuropsychological Deficits Are Not Predictive of Deficient Emotional Self-Regulation in Adults With ADHD SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE ADHD; emotion; executive function; adult ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION DEFICITS; HYPERACTIVITY DISORDER; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; METHYLPHENIDATE; INHIBITION; DIMENSIONS; IMPACT; FMRI AB Objective: To investigate whether neuropsychological deficits account for the association between deficient emotional self-regulation (DESR) and ADHD. Method: DESR was identified in adults with and without ADHD who reported extreme frequency of items from the Barkley Current Behavior Scale (>95th percentile of control participants). A neuropsychological battery and structured diagnostic interview were administered to 113 adults with ADHD and DESR, 93 adults with ADHD without DESR, and 119 participants without ADHD or DESR. Results: Relative to adults with ADHD without DESR, adults with ADHD and DESR demonstrated lower scores on Wechsler Adult Intelligence Scale (WAIS) arithmetic but no other significant differences in neuropsychological performance. Relative to adults without ADHD, both ADHD groups demonstrated lower scores across several measures of executive function. Conclusion: Our findings do not support the hypothesis that neuropsychological deficits are linked to DESR in adults with ADHD. This finding is consistent with the hypothesis that DESR could be a manifestation of ADHD, but further study of alternate hypotheses is necessary to support this conclusion. C1 [Surman, Craig B. H.; Biederman, Joseph; Spencer, Thomas; Miller, Carolyn A.; Petty, Carter R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. EM sfaraone@childpsychresearch.org FU National Institute of Health [R01MH57934]; Shire Pharmaceuticals FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This manuscript was supported in part by grants to S. V. Faraone from the National Institute of Health (R01MH57934), and from Shire Pharmaceuticals. NR 43 TC 5 Z9 5 U1 1 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 EI 1557-1246 J9 J ATTEN DISORD JI J. Atten. Disord. PD DEC PY 2015 VL 19 IS 12 SI SI BP 1046 EP 1053 DI 10.1177/1087054713476548 PG 8 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA CV9UY UT WOS:000364634100006 PM 23503813 ER PT J AU Miller, CJ Li, MF Penfold, RB Lee, AF Smith, EG Nordberg, SS Osser, DN Bajor, L Zhang, F Bauer, MS AF Miller, Christopher J. Li, Mingfei Penfold, Robert B. Lee, Austin F. Smith, Eric G. Nordberg, Samuel S. Osser, David N. Bajor, Laura Zhang, Fang Bauer, Mark S. TI The Ascendancy of Second-Generation Antipsychotics as Frontline Antimanic Agents SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar; antipsychotic; second generation; atypical; Veteran ID RANDOMIZED CONTROLLED-TRIALS; BIPOLAR DISORDER; PRIMARY-CARE; ATYPICAL ANTIPSYCHOTICS; PRESCRIPTION PATTERNS; MAINTENANCE TREATMENT; TREAT SCHIZOPHRENIA; RACIAL DISPARITY; MEDICATIONS; VETERANS AB Introduction Knowledge of the factors affecting the adoption of new medications can enhance mental health care and guide quality improvement and policy development. Food and Drug Administration indications for treating bipolar disorder with several second-generation antipsychotics (SGAs) in the 2000s represent an opportunity to identify factors that impact the spread of a then-innovative treatment through a new population. Methods Analysis of Department of Veterans Affairs administrative data identified the population of 170,811 veterans diagnosed with bipolar disorder from 2003 to 2010. We analyzed time trends and predictors of antimanic choice (SGA vs other) among the 40,512 outpatients with bipolar disorder who initiated their first VA outpatient antimanic prescription, using multinomial logistic regression in month-by-month analyses. We conducted classwise analyses and investigated prespecified predictors among specific agents. Results In classwise analyses, SGAs supplanted lithium, valproate, and carbamazepine/oxcarbazepine as the most commonly initiated antimanics by 2007. Psychosis, but not other indices of severity, predicted SGA initiation. Demographic analyses did not identify substantial disparities in initiation of SGAs. Drug-specific analyses revealed some consideration of medical comorbidities in choosing among specific antimanic agents, although effect sizes were small. Most patients initiating an antimanic had received an antidepressant in the previous year. Discussion Second-generation antipsychotics quickly became the frontline antimanic treatment for bipolar disorder, although antidepressants most commonly predated antimanic prescriptions. Second-generation antipsychotics were used for a broad range of patients rather than being restricted to a severely ill subpopulation. The modest association of antimanic choice with relevant medical comorbidities suggests that continued attention to quality prescribing practices is warranted. C1 [Miller, Christopher J.; Nordberg, Samuel S.; Bajor, Laura; Bauer, Mark S.] VA Boston Healthcare Syst, CHOIR, Boston, MA 02130 USA. [Miller, Christopher J.; Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Li, Mingfei; Lee, Austin F.; Smith, Eric G.] Edith Nourse Rogers Mem VA Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Li, Mingfei; Lee, Austin F.] Bentley Univ, Dept Math Sci, Waltham, MA USA. [Penfold, Robert B.] Grp Hlth Res Inst, Dept Hlth Serv Res, Seattle, WA USA. [Penfold, Robert B.] Univ Washington, Dept Hlth Serv Res, Seattle, WA 98195 USA. [Lee, Austin F.] Xian Univ Finance & Econ, Sch Stat, Res Ctr Stat & Actuarial Sci Med, Xian, Peoples R China. [Lee, Austin F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Smith, Eric G.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Osser, David N.] VA Boston Healthcare Syst, Brockton, MA USA. [Zhang, Fang] Harvard Pilgrim, Dept Populat Med, Boston, MA USA. RP Miller, CJ (reprint author), VA Boston Healthcare Syst, CHOIR, 150 S,Huntington Ave,152M, Boston, MA 02130 USA. EM Christopher.Miller8@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IIR-10-314] FX This study was funded by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Grant Number IIR-10-314, "Spatiotemporal Spread of Newer Antipsychotics for Bipolar Disorder and PTSD." NR 73 TC 3 Z9 3 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2015 VL 35 IS 6 BP 645 EP 653 DI 10.1097/JCP.0000000000000405 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA CV7ZP UT WOS:000364496600005 PM 26488678 ER PT J AU Hall, DE Hanusa, BH Ling, BS Stone, RA Switzer, GE Fine, MJ Arnold, RM AF Hall, Daniel E. Hanusa, Barbara H. Ling, Bruce S. Stone, Roslyn A. Switzer, Galen E. Fine, Michael J. Arnold, Robert M. TI Using the IRB Researcher Assessment Tool to Guide Quality Improvement SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE research ethics committee; Institutional Review Board; quality improvement; engineering AB Institutional Review Boards (IRBs) are intended to protect those who participate in research. However, because there is no established measure of IRB quality, it is unclear whether these committees achieve their goal. The IRB Researcher Assessment Tool is a previously validated, internally normed, proxy measure of IRB quality that assesses 45 distinct IRB activities and functions. We administered this instrument to a sample of investigators and IRB members at a large urban VA Medical Center. We describe a systematic approach to analyze and interpret survey responses that can identify the IRB activities and functions most in need of quality improvement. The proposed approach to empirical data analysis and presentation could inform local initiatives to improve the quality of IRB review. C1 [Hall, Daniel E.; Hanusa, Barbara H.; Ling, Bruce S.; Stone, Roslyn A.; Switzer, Galen E.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Hanusa, Barbara H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Hall, Daniel E.] Univ Pittsburgh, Surg, Pittsburgh, PA 15260 USA. [Ling, Bruce S.; Fine, Michael J.; Arnold, Robert M.] Univ Pittsburgh, Med, Pittsburgh, PA 15260 USA. [Stone, Roslyn A.] Univ Pittsburgh, Grad Sch Publ Hlth, Biostat, Pittsburgh, PA 15260 USA. [Switzer, Galen E.] Univ Pittsburgh, Med & Psychiat, Pittsburgh, PA 15260 USA. RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr 151C,Bldg 30, Pittsburgh, PA 15240 USA. EM hallde@upmc.edu OI Hall, Daniel/0000-0001-6382-0522 FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [CDA 08-281, SDR 11-399-1] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (CDA 08-281 and SDR 11-399-1). NR 9 TC 0 Z9 0 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1556-2646 EI 1556-2654 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD DEC PY 2015 VL 10 IS 5 BP 460 EP 469 DI 10.1177/1556264615612195 PG 10 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA CW3EK UT WOS:000364874600005 PM 26527369 ER PT J AU Stryjewski, TP Kalish, BT Silverman, B Lehmann, LS AF Stryjewski, Tomasz P. Kalish, Brian T. Silverman, Benjamin Lehmann, Lisa Soleymani TI The Impact of Institutional Review Boards (IRBs) on Clinical Innovation: A Survey of Investigators and IRB Members SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE human subjects; IRB; multisite; protection; investigator; compliance ID MULTICENTER AB We conducted a survey to assess the perspectives of principal investigators and Institutional Review Board (IRB) members on the impact of the IRB structure on the conduct of research and innovative therapy, defined as a nonstandard treatment intended to enhance the well-being of an individual patient. Although investigators and IRB members agreed that the IRB provides adequate protection to study subjects (97% vs. 100%) and an ethically insightful review (88% vs. 100%), a third of clinical investigators felt that the IRB review process limits clinical innovation, in comparison with only 4% of IRB representatives. Limitations of the current IRB review process were explored. We propose several measures to improve the IRB review process while maintaining the protection of human research subjects, including the use of centralized IRBs, the opening of IRB meetings to investigators, the development of metrics and outcome measures for the IRB, and the promotion of guidelines that distinguish research and innovative therapy. C1 [Stryjewski, Tomasz P.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Stryjewski, Tomasz P.; Kalish, Brian T.; Silverman, Benjamin; Lehmann, Lisa Soleymani] Harvard Univ, Sch Med, Boston, MA USA. [Kalish, Brian T.] Boston Childrens Hosp, Pediat, Boston, MA USA. [Silverman, Benjamin] McLean Hosp, Boston, MA USA. [Lehmann, Lisa Soleymani] Brigham & Womens Hosp, Bioeth, Boston, MA 02115 USA. [Stryjewski, Tomasz P.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Silverman, Benjamin] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Lehmann, Lisa Soleymani] Harvard Univ, Sch Med, Med & Med Eth, Boston, MA USA. RP Lehmann, LS (reprint author), Brigham & Womens Hosp, 1620 Tremont St,BC3-002G, Boston, MA 02120 USA. EM llehmann1@partners.org FU Brigham and Women's Hospital, Department of Medicine FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Brigham and Women's Hospital, Department of Medicine. NR 18 TC 0 Z9 0 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1556-2646 EI 1556-2654 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD DEC PY 2015 VL 10 IS 5 BP 481 EP 487 DI 10.1177/1556264615614936 PG 7 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA CW3EK UT WOS:000364874600007 PM 26564945 ER PT J AU Matthiesen, MI Vela, MB Press, VG AF Matthiesen, Madeleine I. Vela, Monica B. Press, Valerie G. TI Health Literacy During Aging SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter ID POOR VISION C1 [Matthiesen, Madeleine I.] Massachusetts Gen Hosp, Med Pediat, Boston, MA 02114 USA. [Vela, Monica B.; Press, Valerie G.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Press, VG (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave,MC 5000, Chicago, IL 60637 USA. EM vpress@bsd.uchicago.edu FU NCATS NIH HHS [UL1 TR000430] NR 5 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2015 VL 30 IS 12 BP 1731 EP 1731 DI 10.1007/s11606-015-3487-z PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CV8VQ UT WOS:000364566600006 PM 26245734 ER PT J AU Hong, CS Atlas, SJ Ashburner, JM Chang, YC He, W Ferris, TG Grant, RW AF Hong, Clemens S. Atlas, Steven J. Ashburner, Jeffrey M. Chang, Yuchiao He, Wei Ferris, Timothy G. Grant, Richard W. TI Evaluating a Model to Predict Primary Care Physician-Defined Complexity in a Large Academic Primary Care Practice-Based Research Network SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; HEALTH-CARE; RISK; MANAGEMENT; HOSPITALIZATION; COORDINATION; VALIDATION; ADMISSIONS; VETERANS; PROGRAMS AB Improving the ability to risk-stratify patients is critical for efficiently allocating resources within healthcare systems. The purpose of this study was to evaluate a physician-defined complexity prediction model against outpatient Charlson score (OCS) and a commercial risk predictor (CRP). Using a cohort in which primary care physicians reviewed 4302 of their adult patients, we developed a predictive model for estimated physician-defined complexity (ePDC) and categorized our population using ePDC, OCS and CRP. 143,372 primary care patients in a practice-based research network participated in the study. For all patients categorized as complex in 2007 by one or more risk-stratification method, we calculated the percentage of total person time from 2008-2011 for which eligible cancer screening was incomplete, HbA1c was a parts per thousand yen 9 %, and LDL was a parts per thousand yen 130 mg/dl (in patients with cardiovascular disease). We also calculated the number of emergency department (ED) visits and hospital admissions per person year (ppy). There was modest agreement among individuals classified as complex using ePDC compared with OCS (36.7 %) and CRP (39.6 %). Over 4 follow-up years, eligible ePDC-complex patients had higher proportions (p < 0.001) of time with: incomplete cervical (17.8 % vs. 13.3 % for OCS; 19.4 % vs. 11.2 % for CRP), breast (21.4 % vs. 14.9 % for OCS; 22.7 % vs. 15.0 % for CRP), and colon (25.9 % vs. 18.7 % for OCS; 27.0 % vs. 18.2 % for CRP) cancer screening; HbA1c a parts per thousand yenaEuro parts per thousand 9 % (15.6 % vs. 8.1 % for OCS; 15.9 % vs. 6.9 % for CRP); and LDL a parts per thousand yenaEuro parts per thousand 130 mg/dl (12.4 % vs. 7.9 % for OCS; 11.8 % vs 9.0 % for CRP). ePDC-complex patients had higher rates (p < 0.003) of: ED visits (0.21 vs. 0.11 ppy for OCS; 0.17 vs. 0.15 ppy for CRP), and admissions in patients 45-64 and a parts per thousand yen 65 years old (0.11 vs. 0.10 ppy AND 0.24 vs. 0.21 ppy for OCS). Our measure for estimated physician-defined complexity compared favorably to commonly used risk-prediction approaches in identifying future suboptimal quality and utilization outcomes. C1 [Hong, Clemens S.; Atlas, Steven J.; Ashburner, Jeffrey M.; Chang, Yuchiao; He, Wei; Ferris, Timothy G.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Grant, Richard W.] Kaiser Permanente, Div Res, Oakland, CA USA. RP Hong, CS (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM cshong@partners.org FU Partners Community Healthcare, Inc; Massachusetts General Hospital Primary Care Practice-Based Research and Quality Improvement Network; KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health); KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [KL2 TR001100] FX Supported by a grant from Partners Community Healthcare, Inc, and institutional funding through the Massachusetts General Hospital Primary Care Practice-Based Research and Quality Improvement Network. Dr. Hong is supported by a KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100). NR 34 TC 3 Z9 3 U1 4 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2015 VL 30 IS 12 BP 1741 EP 1747 DI 10.1007/s11606-015-3357-8 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CV8VQ UT WOS:000364566600009 PM 26048275 ER PT J AU Bishu, KG Gebregziabher, M Dismuke, CE Egede, LE AF Bishu, Kinfe G. Gebregziabher, Mulugeta Dismuke, Clara E. Egede, Leonard E. TI Quantifying the Incremental and Aggregate Cost of Missed Workdays in Adults with Diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes; cost; work absenteeism ID UNITED-STATES; PRODUCTIVITY; ABSENTEEISM; US; AGREEMENT; WORKFORCE; EMPLOYEES; WORKERS; ABSENCE; BURDEN AB Although the national cost of missed workdays associated with diabetes has been estimated previously, we use the most recent available national data and methodology to update the individual and national estimates for the U.S population. We identified 14,429 employed individuals a parts per thousand yen 18 years of age in 2011 Medical Expenditure Panel Survey (MEPS) data. Diabetes and missed workdays were based on self-report, and cost was based on multiplying the daily wage rate for each individual by the number of missed days. Adjusted total national burden of missed workdays associated with diabetes was calculated using a novel two-part model to simultaneously estimate the association of diabetes with the number and cost of missed workdays. The unadjusted annual mean 2011 cost of missed workdays was $277 (95 % CI 177.0-378.0) for individuals with diabetes relative to $160 (95 % CI $130-$189) for those without. The incremental cost of missed workdays associated with diabetes was $120 (95 % CI $30.7-$209.1). Based on the US population in 2011, the unadjusted national burden of missed workdays associated with diabetes was estimated to be $2.7 billion, while the fully adjusted incremental national burden was estimated to be $1.1 billion. We provide more precise estimates of the cost burden of diabetes due to missed workdays on the U.S population. The high incremental and total cost burden of missed workdays among Americans with diabetes suggests the need for interventions to improve diabetes care management among employed individuals. C1 [Gebregziabher, Mulugeta; Dismuke, Clara E.; Egede, Leonard E.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC 29403 USA. [Bishu, Kinfe G.; Dismuke, Clara E.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX 1. This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 29 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2015 VL 30 IS 12 BP 1773 EP 1779 DI 10.1007/s11606-015-3338-y PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CV8VQ UT WOS:000364566600013 PM 25986134 ER PT J AU Leykum, LK Chesser, H Lanham, HJ Carla, P Palmer, R Ratcliffe, T Reisinger, H Agar, M Pugh, J AF Leykum, Luci K. Chesser, Hannah Lanham, Holly J. Carla, Pezzia Palmer, Ray Ratcliffe, Temple Reisinger, Heather Agar, Michael Pugh, Jacqueline TI The Association Between Sensemaking During Physician Team Rounds and Hospitalized Patients' Outcomes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE complexity science; sensemaking; length of stay; complication rates; inpatient teams ID HIGH-RELIABILITY; CARE; ORGANIZATIONS; QUALITY AB Sensemaking is the social act of assigning meaning to ambiguous events. It is recognized as a means to achieve high reliability. We sought to assess sensemaking in daily patient care through examining how inpatient teams round and discuss patients. Our purpose was to assess the association between inpatient physician team sensemaking and hospitalized patients' outcomes, including length of stay (LOS), unnecessary length of stay (ULOS), and complication rates. Eleven inpatient medicine teams' daily rounds were observed for 2 to 4 weeks. Rounds were audiotaped, and field notes taken. Four patient discussions per team were assessed using a standardized Situation, Task, Intent, Concern, Calibrate (STICC) framework. Inpatient physician teams at the teaching hospitals affiliated with the University of Texas Health Science Center at San Antonio participated in the study. Outcomes of patients admitted to the teams were included. Sensemaking was assessed based on the order in which patients were seen, purposeful rounding, patient-driven rounding, and individual patient discussions. We assigned teams a score based on the number of STICC elements used in the four patient discussions sampled. The association between sensemaking and outcomes was assessed using Kruskal-Wallis sum rank and Dunn's tests. Teams rounded in several different ways. Five teams rounded purposefully, and four based rounds on patient-driven needs. Purposeful and patient-driven rounds were significantly associated with lower complication rates. Varying the order in which patients were seen and purposefully rounding were significantly associated with lower LOS, and purposeful and patient-driven rounds associated with lower ULOS. Use of a greater number of STICC elements was associated with significantly lower LOS (4.6 vs. 5.7, p = 0.01), ULOS (0.3 vs. 0.6, p = 0.02), and complications (0.2 vs. 0.5, p = 0.0001). Improving sensemaking may be a strategy for improving patient outcomes, fostering a shared understanding of a patient's clinical trajectory, and enabling high reliability. C1 [Leykum, Luci K.; Lanham, Holly J.; Ratcliffe, Temple; Pugh, Jacqueline] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly J.; Carla, Pezzia; Ratcliffe, Temple; Pugh, Jacqueline] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Leykum, Luci K.; Lanham, Holly J.] Univ Texas Austin, McCombs Sch Business, San Antonio, TX USA. [Chesser, Hannah] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Carla, Pezzia] Univ Dallas, Dallas, TX USA. [Palmer, Ray] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Reisinger, Heather] Iowa City VA Hlth Care Syst, Iowa City, IA USA. [Agar, Michael] Ethknoworks LLC, Santa Fe, NM USA. RP Leykum, LK (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter, San Antonio, TX 78229 USA. EM Leykum@uthscsa.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CDA 07-022]; South Texas Veterans Health Care System FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 07-022). Investigator salary support is provided through this funding, and through the South Texas Veterans Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 28 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2015 VL 30 IS 12 BP 1821 EP 1827 DI 10.1007/s11606-015-3377-4 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CV8VQ UT WOS:000364566600019 PM 26014891 ER PT J AU Jones, AL Cochran, SD Leibowitz, A Wells, KB Kominski, G Mays, VM AF Jones, Audrey L. Cochran, Susan D. Leibowitz, Arleen Wells, Kenneth B. Kominski, Gerald Mays, Vickie M. TI Usual Primary Care Provider Characteristics of a Patient-Centered Medical Home and Mental Health Service Use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; primary care; mental health services; Affordable Care Act; race ID COMORBIDITY SURVEY REPLICATION; NATIONAL COMORBIDITY; PSYCHOLOGICAL DISTRESS; MAJOR DEPRESSION; UNITED-STATES; DISORDERS; EXPENDITURES; POPULATION; OUTCOMES; ILLNESS AB The benefits of the patient-centered medical home (PCMH) over and above that of a usual source of medical care have yet to be determined, particularly for adults with mental health disorders. To examine qualities of a usual provider that align with PCMH goals of access, comprehensiveness, and patient-centered care, and to determine whether PCMH qualities in a usual provider are associated with the use of mental health services (MHS). Using national data from the Medical Expenditure Panel Survey, we conducted a lagged cross-sectional study of MHS use subsequent to participant reports of psychological distress and usual provider and practice characteristics. A total of 2,358 adults, aged 18-64 years, met the criteria for serious psychological distress and reported on their usual provider and practice characteristics. We defined "usual provider" as a primary care provider/practice, and "PCMH provider" as a usual provider that delivered accessible, comprehensive, patient-centered care as determined by patient self-reporting. The dependent variable, MHS, included self-reported mental health visits to a primary care provider or mental health specialist, counseling, and psychiatric medication treatment over a period of 1 year. Participants with a usual provider were significantly more likely than those with no usual provider to have experienced a primary care mental health visit (marginal effect [ME] = 8.5, 95 % CI = 3.2-13.8) and to have received psychiatric medication (ME = 15.5, 95 % CI = 9.4-21.5). Participants with a PCMH were additionally more likely than those with no usual provider to visit a mental health specialist (ME = 7.6, 95 % CI = 0.7-14.4) and receive mental health counseling (ME = 8.5, 95 % CI = 1.5-15.6). Among those who reported having had any type of mental health visit, participants with a PCMH were more likely to have received mental health counseling than those with only a usual provider (ME = 10.0, 95 % CI = 1.0-19.0). Access to a usual provider is associated with increased receipt of needed MHS. Patients who have a usual provider with PCMH qualities are more likely to receive mental health counseling. C1 [Jones, Audrey L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Cochran, Susan D.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. [Cochran, Susan D.; Mays, Vickie M.] Univ Calif Los Angeles, Ctr Bridging Res Innovat, Training & Educ Minor Hlth Dispar Solut, Los Angeles, CA USA. [Leibowitz, Arleen] Univ Calif Los Angeles, Luskin Sch Publ Affairs, Los Angeles, CA USA. [Wells, Kenneth B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wells, Kenneth B.] Univ Calif Los Angeles, Ctr Hlth Serv & Soc, Los Angeles, CA USA. [Wells, Kenneth B.; Kominski, Gerald; Mays, Vickie M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Kominski, Gerald] Univ Calif Los Angeles, Ctr Hlth Policy Res, Los Angeles, CA USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Jones, AL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. EM Audrey.Jones3@va.gov OI Kominski, Gerald/0000-0001-5214-7133 FU Agency for Healthcare Research and Quality [1R36HS021721]; National Institutes of Health National Institute on Minority Health and Health Disparities [MD006923]; National Institute of Drug Abuse [DA20826] FX This research was supported by funding from the Agency for Healthcare Research and Quality (1R36HS021721) and from the National Institutes of Health National Institute on Minority Health and Health Disparities (MD006923) and National Institute of Drug Abuse (DA20826). Dr. Jones is supported as a VA Office of Academic Affiliations Associated Health Professions Post-Doctoral Fellow in Health Services Research at the Center for Health Equity Research and Promotion at the VA Pittsburgh Healthcare System. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 70 TC 5 Z9 5 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2015 VL 30 IS 12 BP 1828 EP 1836 DI 10.1007/s11606-015-3417-0 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CV8VQ UT WOS:000364566600020 PM 26037232 ER PT J AU Potter, J Peitzmeier, SM Bernstein, I Reisner, SL Alizaga, NM Agenor, M Pardee, DJ AF Potter, Jennifer Peitzmeier, Sarah M. Bernstein, Ida Reisner, Sari L. Alizaga, Natalie M. Agenor, Madina Pardee, Dana J. TI Cervical Cancer Screening for Patients on the Female-to-Male Spectrum: a Narrative Review and Guide for Clinicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID VAGINAL SPECULUM LUBRICATION; TRANSGENDER HEALTH; PELVIC EXAMINATION; NEEDS-ASSESSMENT; SEXUAL RISK; WOMEN; CARE; TRANSSEXUALS; CYTOLOGY; PEOPLE AB Guidelines for cervical cancer screening have evolved rapidly over the last several years, with a trend toward longer intervals between screenings and an increasing number of screening options, such as Pap/HPV co-testing and HPV testing as a primary screening. However, gynecological recommendations often do not include clinical considerations specific to patients on the female-to-male (FTM) spectrum. Both patients and providers may not accurately assess risk for HPV and other sexually transmitted infections, understand barriers to care, or be aware of recommendations for cervical cancer screening and other appropriate sexual and reproductive health services for this patient population. We review the evidence and provide guidance on minimizing emotional discomfort before, during, and after a pelvic exam, minimizing physical discomfort during the exam, and making adaptations to account for testosterone-induced anatomical changes common among FTM patients. C1 [Potter, Jennifer; Peitzmeier, Sarah M.; Reisner, Sari L.; Pardee, Dana J.] Fenway Hlth, Fenway Inst, Boston, MA 02115 USA. [Potter, Jennifer; Bernstein, Ida] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Potter, Jennifer] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Peitzmeier, Sarah M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Reisner, Sari L.; Agenor, Madina] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Alizaga, Natalie M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Agenor, Madina] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Potter, J (reprint author), Fenway Hlth, Fenway Inst, Boston, MA 02115 USA. EM jpotter@bidmc.harvard.edu FU Harvard Medical Student Center for Primary Care; Open Gate Foundation; National Cancer Institute Cancer Education Program [3R25CA057711] FX The authors would like to thank the Harvard Medical Student Center for Primary Care and the Open Gate Foundation for their generous support of this project.; M. Agenor is supported by National Cancer Institute Cancer Education Program grant 3R25CA057711. The contents of this paper are the sole responsibility of the authors and do not necessarily reflect the views of the National Institutes of Health. NR 52 TC 3 Z9 3 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2015 VL 30 IS 12 BP 1857 EP 1864 DI 10.1007/s11606-015-3462-8 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CV8VQ UT WOS:000364566600034 PM 26160483 ER PT J AU Wisse, LEM Butala, N Das, SR Davatzikos, C Dickerson, BC Vaishnavi, SN Yushkevich, PA Wolk, DA AF Wisse, Laura E. M. Butala, Nirali Das, Sandhitsu R. Davatzikos, Christos Dickerson, Bradford C. Vaishnavi, Sanjeev N. Yushkevich, Paul A. Wolk, David A. CA Alzheimer's Dis Neuroimaging TI Suspected non-AD pathology in mild cognitive impairment SO NEUROBIOLOGY OF AGING LA English DT Article DE Suspected non-AD pathology; Mild cognitive impairment; Cerebrovascular disease; Cognition; Primary age-related tauopathy; Amyloidosis ID POSITRON-EMISSION-TOMOGRAPHY; WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; CORTICAL THICKNESS; BLOOD-PRESSURE; ASSOCIATION; DEMENTIA; CORE; REGISTRATION; INTELLIGENCE AB We aim to better characterize mild cognitive impairment (MCI) patients with suspected non-Alzheimer's disease (AD) pathology (SNAP) based on their longitudinal outcome, cognition, biofluid, and neuroimaging profile. MCI participants (n = 361) from ADNI-GO/2 were designated "amyloid positive" with abnormal amyloid-beta 42 levels (AMY+) and "neurodegeneration positive" (NEU+) with abnormal hippocampal volume or hypometabolism using fluorodeoxyglucose-positron emission tomography. SNAP was compared with the other MCI groups and with AMY- controls. AMY-NEU+/SNAP, 16.6%, were older than the NEU- groups but not AMY- controls. They had a lower conversion rate to AD after 24 months than AMY+NEU+ MCI participants. SNAP-MCI participants had similar amyloid-beta 42 levels, florbetapir and tau levels, but larger white matter hyperintensity volumes than AMY- controls and AMY-NEU- MCI participants. SNAP participants performed worse on all memory domains and on other cognitive domains, than AMY-NEU- participants but less so than AMY+NEU+ participants. Subthreshold levels of cerebral amyloidosis are unlikely to play a role in SNAP-MCI, but pathologies involving the hippocampus and cerebrovascular disease may underlie the neurodegeneration and cognitive impairment in this group. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wisse, Laura E. M.; Das, Sandhitsu R.; Yushkevich, Paul A.] Univ Penn, Dept Radiol, Penn Image Comp & Sci Lab, Philadelphia, PA 19104 USA. [Butala, Nirali; Vaishnavi, Sanjeev N.; Wolk, David A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Davatzikos, Christos] Univ Penn, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat Neuroimaging, Charlestown, MA USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Charlestown, MA USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Charlestown, MA USA. RP Wisse, LEM (reprint author), Richards Med Res Labs, 3700 Hamilton Walk,6th Floor, Philadelphia, PA 19104 USA. EM Laura.Wisse@uphs.upenn.edu OI Preda, Adrian /0000-0003-3373-2438 FU National Institute on Aging [R01 AG037376, P30 AG010124, R01 AG040271]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc; Biogen Idec Inc; Bristol-Myers Squibb Company; Eisai Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd; Genentech, Inc; Fujirebio; GE Healthcare; IXICO Ltd; anssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc; Merck Co, Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc; Piramal Imaging; Servier; Synarc Inc; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; Foundation for the National Institutes of Health; Northern California Institute for Research and Education FX The study was funded by National Institute on Aging grants: R01 AG037376, P30 AG010124, and R01 AG040271. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc; Biogen Idec Inc; Bristol-Myers Squibb Company; Eisai Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc; Fujirebio; GE Healthcare; IXICO Ltd; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc; Merck & Co, Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc; Piramal Imaging; Servier; Synarc Inc; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 52 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD DEC PY 2015 VL 36 IS 12 BP 3152 EP 3162 DI 10.1016/j.neurobiolaging.2015.08.029 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CW0JZ UT WOS:000364676800004 PM 26422359 ER PT J AU Lu-Yao, GL Kim, S Moore, DF Shih, W Lin, Y DiPaola, RS Shen, S Zietman, A Yao, SL AF Lu-Yao, G. L. Kim, S. Moore, D. F. Shih, W. Lin, Y. DiPaola, R. S. Shen, S. Zietman, A. Yao, S-L TI Primary radiotherapy vs conservative management for localized prostate cancer-a population-based study SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; LONG-TERM SURVIVAL; RADICAL PROSTATECTOMY; RADIATION-THERAPY; RANDOMIZED-TRIAL; UNITED-STATES; PHASE-III; MEN; RISK; OUTCOMES AB BACKGROUND: Radiotherapy is the most common curative cancer therapy used for elderly patients with localized prostate cancer. However, the effectiveness of this approach has not been established. The purpose of this study is to evaluate the long-term outcomes of primary radiotherapy compared with conservative management in order to facilitate treatment decisions. METHOD: This population-based study consisted of 57 749 patients with T1-T2 prostate cancers diagnosed during 1992-2007. We utilized an instrumental variable (IV) analytical approach with competing risk models to evaluate the outcomes of primary radiotherapy vs conservative management. The IV was comprised of combined health service areas with high-and low-use areas corresponding to the top and bottom tertile in radiotherapy usage rates. RESULTS: In patients with low-/intermediate-risk prostate cancer, 10-year prostate cancer-specific and overall survival was similar in high-and low-radiotherapy use areas (96.1 vs 95.4% and 56.6 vs 56.3%, respectively). In patients with high-risk disease, however, areas with high-radiotherapy use had a higher 10-year cancer-specific survival (90.2 vs 88.1%, difference 2.1%; 95% CI 0.3-4.0%) and 10-year overall survival (53.3 vs 50.2%, difference 3.1%; 95% CI 1.3-6.3%). Results were similar irrespective of the type of radiotherapy used. To assess the robustness of our choice of IV, we repeated the IV analytical approach using different IVs (using the median utilization rate as the cutoff) and found the results to be similar. CONCLUSIONS: Among men 465 years of age, the benefit of primary radiotherapy for localized disease is largely confined to patients with high-risk prostate cancer (Gleason scores 7-10). C1 [Lu-Yao, G. L.; DiPaola, R. S.; Yao, S-L] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Med, Piscataway, NJ 08854 USA. [Lu-Yao, G. L.; Kim, S.; Moore, D. F.; Shih, W.; Lin, Y.; DiPaola, R. S.; Shen, S.; Yao, S-L] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Kim, S.] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ 08903 USA. [Moore, D. F.; Shih, W.; Lin, Y.] Rutgers State Univ, Sch Publ Hlth, Dept Biostat, Piscataway, NJ USA. [Zietman, A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Lu-Yao, GL (reprint author), Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Med, 195 Little Albany St,Room 5534, New Brunswick, NJ 08903 USA. EM luyaogr@cinj.rutgers.edu FU National Cancer Institute (NCI) [RC1CA145722]; Rutgers Cancer Institute of New Jersey CCSG [NCI CA-72720] FX We acknowledge the efforts of the Applied Research Branch, Division of Cancer Prevention and Population Science, National Cancer Institute, the Office of Information Services and the Office of Strategic Planning, Center for Medicare and Medicaid Services, Information Management Services and the Surveillance, Epidemiology and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. This study was approved by the NCI, CMS and Rutgers RBHS IRB. We thank Carolina Lozada and Edith Prescod for their outstanding technical and administrative assistance. The project described was supported by Award number RC1CA145722 from the National Cancer Institute (NCI) and Rutgers Cancer Institute of New Jersey CCSG core grant NCI CA-72720. NR 38 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD DEC PY 2015 VL 18 IS 4 BP 317 EP 324 DI 10.1038/pcan.2015.30 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CW2XY UT WOS:000364857600004 PM 26101187 ER PT J AU Moreira, DM Howard, LE Sourbeer, KN Amarasekara, HS Chow, LC Cockrell, DC Hanyok, BT Pratson, CL Aronson, WJ Kane, CJ Terris, MK Amling, CL Cooperberg, MR Liede, A Freedland, SJ AF Moreira, D. M. Howard, L. E. Sourbeer, K. N. Amarasekara, H. S. Chow, L. C. Cockrell, D. C. Hanyok, B. T. Pratson, C. L. Aronson, W. J. Kane, C. J. Terris, M. K. Amling, C. L. Cooperberg, M. R. Liede, A. Freedland, S. J. TI Predicting bone scan positivity in non-metastatic castration-resistant prostate cancer SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article ID ANTIGEN DOUBLING TIME; RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; SEARCH DATABASE; METASTATIC-DISEASE; SIPULEUCEL-T; NAIVE MEN; PHASE-II; THERAPY; FAILURE AB BACKGROUND: To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort. METHODS: Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations. RESULTS: A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR) = 0.98; P = 0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR = 2.03, P = 0.035; Gleason 4+3 and 8-10: OR = 1.76, P = 0.059), higher prescan PSA (OR = 2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR = 0.53; P < 0.001), higher PSA velocity (OR = 1.74; P<0.001) and more remote scan year (OR = 0.92; P = 0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA < 5, 5-14.9, 15-49.9 and >= 50 ng ml(-1), respectively (P-trend < 0.001). Men with PSADT >= 15, 9-14.9, 3-8.9 and < 3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend < 0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan. CONCLUSIONS: PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans. C1 [Moreira, D. M.] Mayo Clin, Dept Urol, Rochester, MN 55905 USA. [Howard, L. E.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Howard, L. E.; Sourbeer, K. N.; Amarasekara, H. S.; Chow, L. C.; Cockrell, D. C.; Hanyok, B. T.; Pratson, C. L.; Freedland, S. J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Howard, L. E.; Sourbeer, K. N.; Amarasekara, H. S.; Chow, L. C.; Cockrell, D. C.; Hanyok, B. T.; Pratson, C. L.; Freedland, S. J.] Duke Univ, Sch Med, Dept Surg, Div Urol, Durham, NC USA. [Howard, L. E.; Sourbeer, K. N.; Amarasekara, H. S.; Chow, L. C.; Cockrell, D. C.; Hanyok, B. T.; Pratson, C. L.; Freedland, S. J.] Duke Univ, Sch Med, Duke Prostate Ctr, Durham, NC USA. [Aronson, W. J.] W Los Angeles Vet Affairs Med Ctr, Dept Surg, Urol Sect, Los Angeles, CA 90073 USA. [Aronson, W. J.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90024 USA. [Kane, C. J.] Univ Calif San Diego, Med Ctr, Dept Surg, Div Urol, San Diego, CA 92103 USA. [Terris, M. K.] Vet Affairs Med Ctr, Div Surg, Urol Sect, Augusta, GA USA. [Terris, M. K.] Med Coll Georgia, Dept Surg, Div Urol Surg, Augusta, GA 30912 USA. [Amling, C. L.] Oregon Hlth & Sci Univ, Dept Surg, Div Urol, Portland, OR 97201 USA. [Cooperberg, M. R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Cooperberg, M. R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cooperberg, M. R.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA. [Liede, A.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA. [Freedland, S. J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. RP Moreira, DM (reprint author), Mayo Clin, Dept Urol, 200 First St SW, Rochester, MN 55905 USA. EM Moreira.Daniel@mayo.edu OI Hanyok, Brian/0000-0003-1079-8821; Terris, Martha/0000-0002-3843-7270 FU Department of Veterans Affairs, National Institutes of Health [R01CA100938]; NIH Specialized Programs of Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition; NIH [K24 CA160653]; Amgen FX This study was funded by the Department of Veterans Affairs, National Institutes of Health grant R01CA100938 (WJA), NIH Specialized Programs of Research Excellence grant P50 CA92131-01A1 (WJA), the Georgia Cancer Coalition (MKT), NIH K24 CA160653 (SJF) and Amgen. NR 22 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD DEC PY 2015 VL 18 IS 4 BP 333 EP 337 DI 10.1038/pcan.2015.25 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CW2XY UT WOS:000364857600006 PM 26171882 ER PT J AU Amri, R Bordeianou, LG Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Berger, David L. TI The conundrum of the young colon cancer patient SO SURGERY LA English DT Article ID COLORECTAL-CANCER; COST-EFFECTIVENESS; TASK-FORCE; ADULTS; RISK; SURVEILLANCE; COLONOSCOPY; OUTCOMES; DISEASE AB Background. Colonoscopy has had a major impact on the incidence and survival of colon cancer for patients who are screened, usually beginning at the age of 50. Meanwhile, the incidence rate of colon cancer is actually increasing in the patients younger than 50 while no routine screening is implemented for this age group. Methods. All patients surgically treated for colon cancer (2004-2011) without preexisting high-risk characteristics (hereditary nonpolyposis colorectal cancer, inflammatory bowel disease) were included (n = 1,015). Age-related disparities in baseline disease and outcomes were reviewed. Results. Patients younger than, 50 years of age (n = 108; 10.6%) had the greatest baseline rates of metastatic (20.4% vs 8.0%; P <.001), node-positive disease (54.6% vs 39.4%; P =.002), and greater rates of extramural vascular invasion (38.9 vs 29.4%; P =.043). Cancer-related mortality also was greatest in this group (28.7 vs 18.4%; P =.011). Multivariable Cox regression shows that patients younger than 50 are still at significantly greater risk of mortality after adjustment for effects of age, baseline AJCC staging, smoking, and comorbidity (hazard ratio: 1.57, 95% confidence interval 1.01-2.45; P =.049). Discussion. Patients younger than 50 present with the most advanced and aggressive disease, giving them the worst stage-independent prognosis of all age groups. Potential causes include age-related differences in tumor biology and underdetection by current screening efforts. This raises the question of how to address the conundrum of the young colon cancer patient, who often is the proverbial needle in a haystack of young patients, with nonspecific gastrointestinal symptoms but who would benefit considerably from early detection. C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 FU Harvard Catalyst. The Harvard Clinical and Translational Science Centre (National Centre for Research Resources); Harvard Catalyst. The Harvard Clinical and Translational Science Centre (National Centre for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard Catalyst. The Harvard Clinical and Translational Science Centre (Harvard University and its affiliated academic health care centers); Dutch Cancer Society; Dutch Digestive Society; Amsterdam University Funds; Fulbright Foundation FX This work was conducted with support from Harvard Catalyst. The Harvard Clinical and Translational Science Centre (National Centre for Research Resources and the National Centre for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health.) This work was also supported by the Dutch Cancer Society, the Dutch Digestive Society, the Amsterdam University Funds and the Fulbright Foundation. NR 29 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2015 VL 158 IS 6 BP 1697 EP 1704 DI 10.1016/j.surg.2015.07.018 PG 8 WC Surgery SC Surgery GA CV9MV UT WOS:000364612200029 PM 26298030 ER PT J AU Kaafaranil, HMA Velmahosl, GC AF Kaafaranil, Haytham M. A. Velmahosl, George C. TI Classification of Intraoperative Complications SO WORLD JOURNAL OF SURGERY LA English DT Letter ID ADVERSE EVENTS C1 [Kaafaranil, Haytham M. A.; Velmahosl, George C.] Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Kaafaranil, HMA (reprint author), Harvard Univ, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Massachusetts Gen Hosp,Med Sch, 165 Cambridge St Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.org NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD DEC PY 2015 VL 39 IS 12 BP 3032 EP 3032 DI 10.1007/s00268-015-3119-0 PG 1 WC Surgery SC Surgery GA CV8KO UT WOS:000364534100027 PM 26067638 ER PT J AU Yaffe, MJ Mittmann, N Lee, P Tosteson, ANA Trentham-Dietz, A Alagoz, O Stout, NK AF Yaffe, Martin J. Mittmann, Nicole Lee, Pablo Tosteson, Anna N. A. Trentham-Dietz, Amy Alagoz, Oguzhan Stout, Natasha K. TI Modelling mammography screening for breast cancer in the Canadian context: Modification and testing of a microsimulation model SO HEALTH REPORTS LA English DT Article DE Breast screening; incidence; microsimulation model; preventive health; sensitivity; specificity AB Background: Modelling is a flexible and efficient approach to gaining insight into the trade-offs surrounding a complex process like breast screening, which involves more variables than can be controlled in an experimental study. Data and methods: The University of Wisconsin Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation model was adapted to simulate breast cancer incidence and screening performance in Canada. The model considered effects of breast density on the sensitivity and specificity of screening. The model's ability to predict age-specific incidence of breast cancer was assessed. Results: Predictions of age-adjusted incidence over calendar years and age-specific incidence of breast cancer in Canadian women are presented. Based on standard screening strategies, ratios of in situ to invasive disease and stage distribution of disease at diagnosis are compared with data from the British Columbia provincial screening program. Interpretation: The adapted model performs well in predicting age-specific incidence and cross-sectional incidence in the absence of screening. The ratios of detection of in situ to invasive cancers and the overall stage distribution of detected cancers are in reasonable agreement with empirical data from British Columbia. C1 [Yaffe, Martin J.] Univ Toronto, Phys Sci Program, Sunnybrook Res Inst, Toronto, ON M5S 1A1, Canada. [Yaffe, Martin J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Yaffe, Martin J.] Univ Toronto, Dept Med Imaging, Toronto, ON M5S 1A1, Canada. [Mittmann, Nicole] Canc Care Ontario, Toronto, ON, Canada. [Lee, Pablo] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Trentham-Dietz, Amy; Alagoz, Oguzhan] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. [Trentham-Dietz, Amy; Alagoz, Oguzhan] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Alagoz, Oguzhan] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. [Stout, Natasha K.] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Yaffe, MJ (reprint author), Univ Toronto, Phys Sci Program, Sunnybrook Res Inst, Toronto, ON M5S 1A1, Canada. EM martin.yaffe@sri.utoronto.ca FU The Canadian Breast Cancer Foundation; National Cancer Institute through Cancer Intervention and Surveillance Modeling Network [U01 CA152958]; National Cancer Institute [UC2CA148577, HHSN261201100031C]; National Institutes of Health FX The work performed to create this report was supported by a contract from The Canadian Breast Cancer Foundation. The authors are grateful to Statistics Canada and to Dr. Michael Wolfson at the University of Ottawa for supplying key incidence data. The University of Wisconsin breast cancer simulation model was supported by grant number U01 CA152958 from the National Cancer Institute through the Cancer Intervention and Surveillance Modeling Network. Model input data on the performance of screening mammography were provided by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (BCSC), grant number UC2CA148577 and contract number HHSN261201100031C. The content of this study does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The collection of BCSC cancer data was supported by several state public health departments and cancer registries throughout the United States. A full description of these sources is available at: http://www.breastscreening.cancer.gov/work/acknowledgement.html. The authors thank the participating women, mammography facilities, and radiologists for the data they provided for this study. Procedures for requesting BCSC data and a list of the BCSC investigators are provided at: http://breastscreening.cancer.gov/. NR 14 TC 1 Z9 1 U1 0 U2 0 PU STATISTICS CANADA PI OTTAWA PA 100 TUNNEYS PASTURE DRIVEWAY, OTTAWA, ONTARIO K1A 0T6, CANADA SN 0840-6529 EI 1209-1367 J9 HEALTH REP JI Health Rep. PD DEC PY 2015 VL 26 IS 12 BP 3 EP 8 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EF0CC UT WOS:000389992100001 PM 26676233 ER PT J AU Yaffe, MJ Mittmann, N Lee, P Tosteson, ANA Trentham-Dietz, A Alagoz, O Stout, NK AF Yaffe, Martin J. Mittmann, Nicole Lee, Pablo Tosteson, Anna N. A. Trentham-Dietz, Amy Alagoz, Oguzhan Stout, Natasha K. TI Clinical outcomes of modelling mammography screening strategies SO HEALTH REPORTS LA English DT Article DE Breast screening; health outcomes; microsimulation model; preventive health ID COST-EFFECTIVENESS; BREAST-CANCER AB Background: A validated breast cancer model can be used to compare health outcomes associated with different screening strategies. Data and methods: The University of Wisconsin Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer microsimulation model was adapted to simulate breast cancer incidence, screening performance and delivery of optimal therapies in Canada. The model considered effects of breast density on incidence and screening performance. Model predictions of incidence, mortality and life-years (LY) gained for a 1960 birth cohort of women for No Screening were compared with 11 digital mammography screening strategies that varied by starting and stopping age and frequency. Results: In the absence of screening, the estimate of LYs lost from breast cancer was 360.1 per 1,000 women, and each woman diagnosed with breast cancer after age 40 who dies of breast cancer would lose an estimated average of 19.1 years. Biennial screening at ages 50 to 74 resulted in an estimated 116.3 LYs saved. Annual screening at ages 40 to 49, followed by biennial screening to age 74, resulted in an estimated 170.3 LY saved. That is, adding annual screening at ages 40 to 49 saved an additional 54 LY per 1,000 women. Screening annually at ages 40 to 74 recovered the most: 214 LY saved. More frequent screening was associated with an increased ratio of detection of ductal in situ to invasive cancers, more abnormal recalls and more negative biopsies, but a reduction in the number of women required to be screened per life saved or per LY saved. Interpretation: In general, mortality reduction was found to be associated with the total number of lifetime screens for breast cancer. However, for the same number of screens, more frequent screening after age 50 appeared to have a greater impact on breast cancer deaths averted than did beginning screening earlier. When the number of LYs saved by screening was considered, a greater impact was achieved by screening women in their 40s than by reducing the interval between screens. C1 [Yaffe, Martin J.] Univ Toronto, Phys Sci Program, Sunnybrook Res Inst, Toronto, ON M5S 1A1, Canada. [Yaffe, Martin J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Yaffe, Martin J.] Univ Toronto, Dept Med Imaging, Toronto, ON M5S 1A1, Canada. [Mittmann, Nicole] Canc Care Ontario, Toronto, ON, Canada. [Lee, Pablo] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Trentham-Dietz, Amy; Alagoz, Oguzhan] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. [Trentham-Dietz, Amy; Alagoz, Oguzhan] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Alagoz, Oguzhan] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. [Stout, Natasha K.] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Yaffe, MJ (reprint author), Univ Toronto, Phys Sci Program, Sunnybrook Res Inst, Toronto, ON M5S 1A1, Canada. EM martin.yaffe@sri.utoronto.ca FU National Cancer Institute through the Cancer Intervention and Surveillance Modeling Network (CISNET) [U01 CA152958]; National Cancer Institute [UC2CA148577, HHSN261201100031C]; Ontario Region; Canadian Breast Cancer Foundation FX The work performed to create this report was supported by a contract from The Canadian Breast Cancer Foundation, Ontario Region. The authors are grateful to Statistics Canada and to Dr. Michael Wolfson at the University of Ottawa for supplying key incidence data. The University of Wisconsin breast cancer simulation model used in this analysis was supported by grant number U01 CA152958 from the National Cancer Institute through the Cancer Intervention and Surveillance Modeling Network (CISNET). Model input data on the performance of screening mammography were provided by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (BCSC) grant number UC2CA148577 and contract number HHSN261201100031C. The content of this study does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The collection of BCSC cancer data was supported by several state public health departments and cancer registries throughout the United States. A full description of these sources is available at: http://www.breastscreening.cancer. gov/work/acknowledgement.html. The authors thank the participating women, mammography facilities, and radiologists for the data they provided for this study. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: http://breastscreening.cancer.gov/ NR 16 TC 1 Z9 1 U1 1 U2 1 PU STATISTICS CANADA PI OTTAWA PA 100 TUNNEYS PASTURE DRIVEWAY, OTTAWA, ONTARIO K1A 0T6, CANADA SN 0840-6529 EI 1209-1367 J9 HEALTH REP JI Health Rep. PD DEC PY 2015 VL 26 IS 12 BP 9 EP 15 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EF0CC UT WOS:000389992100002 PM 26676234 ER PT J AU Mittmann, N Stout, NK Lee, P Tosteson, ANA Trentham-Dietz, A Alagoz, O Yaffe, MJ AF Mittmann, Nicole Stout, Natasha K. Lee, Pablo Tosteson, Anna N. A. Trentham-Dietz, Amy Alagoz, Oguzhan Yaffe, Martin J. TI Total cost-effectiveness of mammography screening strategies SO HEALTH REPORTS LA English DT Article DE Breast screening; economic analysis; microsimulation model; preventive health ID BREAST-CANCER; IMPACT; WOMEN; US; GUIDELINES; SERVICES; AGE AB Background: Breast cancer screening technology and treatment have improved over the past decade. This analysis evaluates the total cost-effectiveness of various breast cancer screening strategies in Canada. Data and methods: Using the Wisconsin Cancer Intervention and Surveillance Monitoring Network (CISNET) breast cancer simulation model adapted to the Canadian context, costs and quality-adjusted life years (QALY) were evaluated for 11 mammography screening strategies that varied by start/stop age and screening frequency for the general population. Incremental cost-effectiveness ratios are presented, and sensitivity analyses are used to assess the robustness of model conclusions. Results: Incremental cost-effectiveness analysis showed that triennial screening at ages 50 to 69 was the most cost-effective at $94,762 per QALY. Biennial ($97,006 per QALY) and annual ($226,278 per QALY) strategies had higher incremental ratios. Interpretation: The benefits and costs of screening rise with the number of screens per woman. Decisions about screening strategies may be influenced by willingness to pay and the rate of recall for further examination after positive screens. C1 [Mittmann, Nicole] Sunnybrook Res Inst, Hlth Outcomes & PharmacoEcon HOPE Res Ctr, Toronto, ON, Canada. [Mittmann, Nicole] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Stout, Natasha K.] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lee, Pablo] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Trentham-Dietz, Amy; Alagoz, Oguzhan] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. [Trentham-Dietz, Amy; Alagoz, Oguzhan] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Alagoz, Oguzhan] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. [Yaffe, Martin J.] Sunnybrook Res Inst, Phys Sci Program, Toronto, ON, Canada. [Yaffe, Martin J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Yaffe, Martin J.] Univ Toronto, Dept Med Imaging, Toronto, ON M5S 1A1, Canada. RP Mittmann, N (reprint author), Sunnybrook Res Inst, Hlth Outcomes & PharmacoEcon HOPE Res Ctr, Toronto, ON, Canada. EM nicole.mittmann@sri.utoronto.ca FU The Canadian Breast Cancer Foundation; National Cancer Institute through Cancer Intervention and Surveillance Modeling Network (CISNET) [U01 CA152958]; National-Cancer-Institute [UC2CA148577, HHSN261201100031C]; National Institutes of Health; Canadian Breast Cancer Foundation FX The work on which this report was based was supported by a contract from The Canadian Breast Cancer Foundation. The University of Wisconsin breast cancer simulation model was supported by grant number U01 CA152958 from the National Cancer Institute through the Cancer Intervention and Surveillance Modeling Network (CISNET). Model input data on the performance of screening mammography were provided by the National-Cancer-Institute-funded Breast Cancer Surveillance Consortium (BCSC), grant number UC2CA148577 and contract number HHSN261201100031C. The content of this study does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The collection of BCSC cancer data was supported by several state public health departments and cancer registries throughout the United States. A full description of these sources is available at: http://www.breastscreening. cancer.gov/work/acknowledgement.html. The authors thank the participating women, mammography facilities, and radiologists for the data they provided. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes is provided at: http://breastscreening.cancer.gov/ NR 42 TC 2 Z9 2 U1 0 U2 0 PU STATISTICS CANADA PI OTTAWA PA 100 TUNNEYS PASTURE DRIVEWAY, OTTAWA, ONTARIO K1A 0T6, CANADA SN 0840-6529 EI 1209-1367 J9 HEALTH REP JI Health Rep. PD DEC PY 2015 VL 26 IS 12 BP 16 EP 25 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EF0CC UT WOS:000389992100003 PM 26676235 ER PT J AU Butovsky, O Jedrychowski, MP Cialic, R Murugaiyan, G Wu, PM Doykan, CE Fanek, Z Greco, DJ Kiner, O Lawson, RJ Frosch, MP Pochet, N Krichevsky, AM Gygi, SP Berry, J Cudkowicz, ME Weiner, HL AF Butovsky, Oleg Jedrychowski, Mark P. Cialic, Ron Murugaiyan, Gopal Wu, Pauline M. Doykan, Camille E. Fanek, Zain Greco, David J. Kiner, Olga Lawson, Robert J. Frosch, Matthew P. Pochet, Nathalie Krichevsky, Anna M. Gygi, Steven P. Berry, James Cudkowicz, Merit E. Weiner, Howard L. TI Targeting miR-155 restores dysfunctional microglia and ameliorates disease in the SOD1 model of ALS SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT Joint Meeting of the 20th Biennial Meeting of the International-Society-for-Developmental-Neuroscience / 5th Annual NeuroDevNet Brain Development Conference CY JUL 19-24, 2014 CL Montreal, CANADA SP Int Soc Dev Neuroscience C1 [Butovsky, Oleg; Cialic, Ron; Murugaiyan, Gopal; Wu, Pauline M.; Doykan, Camille E.; Fanek, Zain; Greco, David J.; Kiner, Olga; Krichevsky, Anna M.; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis,Med Sch, Boston, MA 02112 USA. [Jedrychowski, Mark P.; Gygi, Steven P.] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. [Lawson, Robert J.; Berry, James; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Res Inst,Med Sch, Boston, MA 02114 USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp ADRC, Boston, MA 02114 USA. [Pochet, Nathalie] Harvard Univ, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Med Sch,Broad Inst MIT & Harvard, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 EI 1873-474X J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2015 VL 47 SI SI BP 5 EP 5 DI 10.1016/j.ijdevneu.2015.04.023 PN A PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CY6QT UT WOS:000366534600013 ER PT J AU Rahbar, H Lehman, CD AF Rahbar, Habib Lehman, Constance D. TI Rethinking Preoperative Breast Magnetic Resonance Imaging SO JAMA ONCOLOGY LA English DT Editorial Material ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; CANCER; MRI C1 [Rahbar, Habib] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Lehman, Constance D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,WAC 240, Boston, MA 02114 USA. RP Lehman, CD (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,WAC 240, Boston, MA 02114 USA. EM clehman@mgh.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD DEC PY 2015 VL 1 IS 9 BP 1226 EP 1227 DI 10.1001/jamaoncol.2015.3029 PG 3 WC Oncology SC Oncology GA DW5IU UT WOS:000383678300010 PM 26401621 ER PT J AU Sweeney, CJ AF Sweeney, Christopher J. TI The Juxtaposition of Population Science and Individual Treatment Recommendations for Intermittent Androgen Deprivation Therapy SO JAMA ONCOLOGY LA English DT Editorial Material ID CARCINOMA; PROSTATE; CANCER C1 [Sweeney, Christopher J.] Harvard Med Sch, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave,D1230, Boston, MA 02115 USA. RP Sweeney, CJ (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave,D1230, Boston, MA 02115 USA. EM Christopher_Sweeney@dfci.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD DEC PY 2015 VL 1 IS 9 BP 1270 EP 1271 DI 10.1001/jamaoncol.2015.3005 PG 2 WC Oncology SC Oncology GA DW5IU UT WOS:000383678300014 PM 26379098 ER PT J AU Howitt, BE Shukla, SA Sholl, LM Ritterhouse, LL Watkins, JC Rodig, S Stover, E Strickland, KC D'Andrea, AD Wu, CJ Matulonis, UA Konstantinopoulos, PA AF Howitt, Brooke E. Shukla, Sachet A. Sholl, Lynette M. Ritterhouse, Lauren L. Watkins, Jaclyn C. Rodig, Scott Stover, Elizabeth Strickland, Kyle C. D'Andrea, Alan D. Wu, Catherine J. Matulonis, Ursula A. Konstantinopoulos, Panagiotis A. TI Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1 SO JAMA ONCOLOGY LA English DT Article ID IMMUNOTHERAPY; MUTATIONS AB IMPORTANCE Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential in endometrial cancer (EC) is unknown. OBSERVATIONS Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas data set. Evaluation of tumor-infiltrating lymphocytes (TILs) and PD-1 and PD-L1 expression was performed in 63 patients with EC referred to our institution. The predicted median (range) neoantigen load (predicted neoepitopes per sample) was proportional to the mutational load: highest in ultramutated polymerase e (POLE) tumors (8342 [628-20 440]), less in hypermutated MSI (541 [146-8063]; P <.001), and lowest in microsatellite-stable tumors (70.5 [7-1877]; P <.001). The POLE and MSI ECs exhibited higher numbers of CD3+ (44.5 vs 21.8; P =.001) and CD8+ (32.8 vs 13.5; P <.001) TILs compared with microsatellite-stable tumors. PD-1 was overexpressed in TILs (81% vs 28%; P <.001) and peritumoral lymphocytes (90% vs 28%; P <.001) of POLE and MSI tumors. PD-L1 expression was infrequently noted in tumor cells but was common in intraepithelial immune cells and more frequent in POLE and MSI tumors (39% vs 13%; P =.02). CONCLUSIONS AND RELEVANCE Polymerase e-mutated and MSI ECs are associated with high neoantigen loads and number of TILs, which is counterbalanced by overexpression of PD-1 and PD-L1. Polymerase e-mutated and MSI EC tumors may be excellent candidates for PD-1-targeted immunotherapies. C1 [Howitt, Brooke E.; Sholl, Lynette M.; Ritterhouse, Lauren L.; Watkins, Jaclyn C.; Rodig, Scott; Strickland, Kyle C.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Shukla, Sachet A.; Wu, Catherine J.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Shukla, Sachet A.; Wu, Catherine J.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Stover, Elizabeth; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.] Harvard Med Sch, Dana Farber Canc Inst, Med Gynecol Oncol Program, Boston, MA USA. [D'Andrea, Alan D.] Harvard Med Sch, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Boston, MA USA. RP Konstantinopoulos, PA (reprint author), Dana Farber Canc Inst, YC-1424,450 Brookline Ave, Boston, MA 02215 USA. EM panagiotis_konstantinopoulos@dfci.harvard.edu FU Blavatnik Family Foundation; National Institutes of Health/National Cancer Institute [1R01CA155010-04]; Susan Smith Center for Women's Cancers; Department of Defense Ovarian Cancer Academy Award [W81XWH-10-1-0585]; Center for Immuno-Oncology at the Dana-Farber Cancer Institute FX Dr Wu acknowledges support from the Blavatnik Family Foundation and National Institutes of Health/National Cancer Institute (1R01CA155010-04) for management and analysis of this study. Dr Konstantinopoulos acknowledges support from the Susan Smith Center for Women's Cancers and the Department of Defense Ovarian Cancer Academy Award W81XWH-10-1-0585 for management and analysis of this study. This work was supported, in part, by the Center for Immuno-Oncology at the Dana-Farber Cancer Institute. NR 14 TC 49 Z9 50 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD DEC PY 2015 VL 1 IS 9 BP 1319 EP 1323 DI 10.1001/jamaoncol.2015.2151 PG 5 WC Oncology SC Oncology GA DW5IU UT WOS:000383678300023 PM 26181000 ER PT J AU Lo, JA Fisher, DE Flaherty, KT AF Lo, Jennifer A. Fisher, David E. Flaherty, Keith T. TI Prognostic Significance of Cutaneous Adverse Events Associated With Pembrolizumab Therapy SO JAMA ONCOLOGY LA English DT Editorial Material ID MELANOMA; INTERLEUKIN-2; ANTI-PD-1; SAFETY AB IMPORTANCE Immunomodulatory anticancer drugs, such as the anti-programmed death-1 drug pembrolizumab, have shown promising results in trials, and more patients will receive such treatments. Little is known about cutaneous adverse events (AEs) caused by these drugs and their possible correlation with treatment response. OBJECTIVE To describe the frequency and spectrum of cutaneous AEs linked with pembrolizumab and their possible correlation with treatment response. DESIGN, SETTING, AND PARTICIPANTS A single-institution, retrospective medical record review was conducted of patients with cancer who were treated with pembro(l)izumab from March 1, 2011, to May 28, 2014. The review comprised 83 consecutive patients who were enrolled in clinical trials (NCT01295827 and NCT01866319), received at least 1 dose of pembrolizumab, and had at least 1 follow-up visit. Patients were grouped according to the following therapeutic regimen for pembrolizumab: 43 received 10mg/kg every 3 weeks, 24 received 10mg/kg every 2 weeks, and 16 received 2mg/kg every 3 weeks. Sixty-six patients were treated for melanoma, 15 patients for lung cancer, 1 patient for prostate cancer, and 1 patient for Merkel cell carcinoma. Median follow-up was 15 weeks (range, 2-105 weeks). The analysis was conducted from March 1, 2014, to September 30, 2014. MAIN OUTCOMES AND MEASURES Occurrence, severity, and type of cutaneous AEs, as well as disease progression and response to pembrolizumab treatment. RESULTS Thirty-five patients (42%) developed cutaneous AEs attributed to pembrolizumab. The most common cutaneous AEs were macular papular eruption (24 [29%]), pruritus (10 [12%]), and hypopigmentation (7 [8%]). All 7 patients who developed hypopigmentation were treated for melanoma. Survival analyses showed that patients who developed cutaneous AEs had significantly longer progression-free intervals in all 3 groups (pembrolizumab, 10 mg/kg, every 3 weeks, P <.001; pembrolizumab, 10mg/kg, every 2 weeks, P =.04; pembrolizumab, 2 mg/kg, every 3 weeks, P =.007) compared with patients who did not develop cutaneous AEs. CONCLUSIONS AND RELEVANCE Pembrolizumab therapy was associated with cutaneous AEs in 42% of patients. The development of cutaneous AEs, especially of hypopigmentation in patients with melanoma, could point toward better treatment response. C1 [Lo, Jennifer A.; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Fisher, David E.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Flaherty, KT (reprint author), 32 Fruit St,LH202, Boston, MA 02114 USA. EM kflaherty@mgh.harvard.edu FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369]; NIEHS NIH HHS [F30 ES025626]; NIGMS NIH HHS [T32 GM007753, T32GM007753] NR 7 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD DEC PY 2015 VL 1 IS 9 BP 1340 EP 1341 DI 10.1001/jamadermatol.2015.1916 PG 2 WC Oncology SC Oncology GA DW5IU UT WOS:000383678300027 PM 26270186 ER PT J AU Ahluwalia, SC Bekelman, DB Huynh, AK Prendergast, TJ Shreve, S Lorenz, KA AF Ahluwalia, Sangeeta C. Bekelman, David B. Huynh, Alexis K. Prendergast, Thomas J. Shreve, Scott Lorenz, Karl A. TI Barriers and Strategies to an Iterative Model of Advance Care Planning Communication SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE advance care planning; goals of care; patient preference; electronic health record; continuity of care; primary health care ID END-OF-LIFE; HEALTH INFORMATION EXCHANGE; VETERANS-AFFAIRS; DECISION-MAKING; INTENSIVE COMMUNICATION; CLINICAL REMINDERS; PALLIATIVE CARE; NATIONAL-SURVEY; NEAR-DEATH; DIRECTIVES AB Background: Early and repeated patient-provider conversations about advance care planning (ACP) are now widely recommended. We sought to characterize barriers and strategies for realizing an iterative model of ACP patient-provider communication. Methods: A total of 2 multidisciplinary focus groups and 3 semistructured interviews with 20 providers at a large Veterans Affairs medical center. Thematic analysis was employed to identify salient themes. Results: Barriers included variation among providers in approaches to ACP, lack of useful information about patient values to guide decision making, and ineffective communication between providers across settings. Strategies included eliciting patient values rather than specific treatment choices and an increased role for primary care in the ACP process. Conclusions: Greater attention to connecting providers across the continuum, maximizing the potential of the electronic health record, and linking patient experiences to their values may help to connect ACP communication across the continuum. C1 [Ahluwalia, Sangeeta C.] Oregon State Univ, Corvallis, OR 97331 USA. [Ahluwalia, Sangeeta C.; Huynh, Alexis K.; Lorenz, Karl A.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bekelman, David B.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA. [Bekelman, David B.] Univ Colorado, Sch Med, Aurora, CO USA. [Prendergast, Thomas J.] Portland VA Med Ctr, Portland, OR USA. [Prendergast, Thomas J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Shreve, Scott] Lebanon VA Med Ctr, Lebanon, PA USA. [Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Ahluwalia, SC (reprint author), Oregon State Univ, Coll Publ Hlth & Human Sci, 418 Waldo Hall, Corvallis, OR 97331 USA. EM sangeeta.c.ahluwalia@oregonstate.edu FU Department of Veterans Affairs Comprehensive End-of-Life Care Initiative, Office of Patient Care Services; National Palliative Care Research Center; Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St Louis, through the National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI) FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Department of Veterans Affairs Comprehensive End-of-Life Care Initiative, Office of Patient Care Services. Dr Ahluwalia is supported in part by a Career Development Grant from the National Palliative Care Research Center. The preparation of this article was supported in part by the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St Louis, through the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). NR 47 TC 5 Z9 5 U1 3 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD DEC PY 2015 VL 32 IS 8 BP 817 EP 823 DI 10.1177/1049909114541513 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CV3OR UT WOS:000364169000005 PM 24988894 ER PT J AU Zhong, QY Gelaye, B Rondon, MB Sanchez, SE Simon, GE Henderson, DC Barrios, YV Sanchez, PM Williams, MA AF Zhong, Qiu-Yue Gelaye, Bizu Rondon, Marta B. Sanchez, Sixto E. Simon, Gregory E. Henderson, David C. Barrios, Yasmin V. Mascaro Sanchez, Pedro Williams, Michelle A. TI Using the Patient Health Questionnaire (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS) to assess suicidal ideation among pregnant women in Lima, Peru SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Suicidal ideation; Antepartum depressive symptoms; PHQ-9; EPDS ID POSTPARTUM WOMEN; PRIMARY-CARE; HIGH-RISK; PREVALENCE; DEATH; DISORDERS; HOMICIDE; SYMPTOMS; THOUGHTS; VALIDITY AB We sought to examine the concordance of two suicidal ideation items from the Patient Health Questionnaire-9 (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS), to evaluate the prevalence of suicidal ideation among pregnant women, and to assess the co-occurrence of suicidal ideation with antepartum depressive symptoms. A cross-sectional study was conducted among 1,517 pregnant women attending prenatal care clinics in Lima, Peru. Item 9 of the PHQ-9 assesses suicidal ideation over the last 14 days while item 10 of the EPDS assesses suicidal ideation in the past 7 days. The two suicidal ideation items have a high concordance rate (84.2 %) but a moderate agreement (the Cohen's kappa = 0.42). Based on the PHQ-9 and the EPDS, 15.8 and 8.8 % of participants screened positive for suicidal ideation, respectively. Assessed by the PHQ-9, 51 % of participants with suicidal ideation had probable depression. In prenatal care clinics, screening for suicidal ideation is needed for women with and without depressive symptoms. Future studies are needed to identify additional predictors of antepartum suicidality, determine the appropriate duration of reporting period for suicidal ideation screening, and assess the percentage of individuals with positive responses to the two suicidal ideation items at high risk of planning and attempting suicide. C1 [Zhong, Qiu-Yue; Gelaye, Bizu; Henderson, David C.; Barrios, Yasmin V.; Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rondon, Marta B.] Cayetano Heredia Peruvian Univ, Dept Med, Lima, Peru. [Sanchez, Sixto E.] Univ Peruana Ciencias Aplicadas, Lima, Peru. [Sanchez, Sixto E.] Asociac Civil PROESA, Lima, Peru. [Simon, Gregory E.] Grp Hlth Res Inst, Seattle, WA USA. [Henderson, David C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Henderson, David C.] Harvard Univ, Sch Med, Boston, MA USA. [Mascaro Sanchez, Pedro] Univ Nacl Mayor San Marcos, Lima 14, Peru. RP Zhong, QY (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM qiz304@mail.harvard.edu OI Gelaye, Bizu/0000-0001-7934-548X FU National Institutes of Health (NIH), the Eunice Kennedy Shriver Institute of Child Health and Human Development [R01-HD-059835] FX This research was supported by an award from the National Institutes of Health (NIH), the Eunice Kennedy Shriver Institute of Child Health and Human Development (R01-HD-059835). The NIH had no further role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors wish to thank the dedicated staff members of Asociacion Civil Proyectos en Salud (PROESA), Peru, and Instituto Especializado Materno Perinatal, Peru, for their expert technical assistance with this research. The authors would like to thank Kathy Brenner for her help with revising this manuscript. NR 44 TC 9 Z9 9 U1 0 U2 14 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD DEC PY 2015 VL 18 IS 6 BP 783 EP 792 DI 10.1007/s00737-014-0481-0 PG 10 WC Psychiatry SC Psychiatry GA CV0PS UT WOS:000363953500004 PM 25369907 ER PT J AU Janssen, S Molleman, J Guitton, T Ring, D AF Janssen, Stein J. Molleman, Jeroen Guitton, Thierry G. Ring, David CA Sci Variation Grp TI What Middle Phalanx Base Fracture Characteristics are Most Reliable and Useful for Surgical Decision-making? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID INTEROBSERVER RELIABILITY; 3-DIMENSIONAL CT; CLASSIFICATION; AGREEMENT; DIAGNOSIS; FINGER; JOINTS AB Background Fracture-dislocations of the proximal interphalangeal joint are vexing because subluxation and articular damage can lead to arthrosis and the treatments are imperfect. Ideally, a surgeon could advise a patient, based on radiographs, when the risk of problems merits operative intervention, but it is unclear if middle phalanx base fracture characteristics are sufficiently reliable to be useful for surgical decision making. Questions/purposes We evaluated (1) the degree of interobserver agreement as a function of fracture characteristics, (2) the differences in interobserver agreement between experienced and less-experienced hand surgeons, and (3) what fracture characteristics and surgeon characteristics were associated with the decision for operative treatment. Methods Ninety-nine (33%) of 296 hand surgeons evaluated 21 intraarticular middle phalanx base fractures on lateral radiographs. Eighty-one surgeons (82%) were in academic practice and 57 (58%) had less than 10 years experience. Participants assessed six fracture characteristics and recommended treatment (nonoperative or operative: extension block pinning, external fixation, open reduction and internal fixation, volar plate arthroplasty, or hemihamate autograft arthroplasty) for all cases. Results With all surgeons pooled together, the interobserver agreement for fracture characteristics was substantial for assessment of a 2-mm articular step or gap (kappa, 0.73; 95% CI, 0.60-0.86; p < 0.001), subluxation or dislocation (kappa, 0.72; 95% CI, 0.58-0.86; p < 0.001), and percentage of articular surface involved (intraclass correlation coefficient [ICC], 0.67; 95% CI, 0.54-0.81; p < 0.001); moderate for comminution (kappa, 0.55; 95% CI, 0.39-0.70; p < 0.001) and stability (kappa, 0.54; 95% CI, 0.39-0.69; p < 0.001); and fair for the number of fracture fragments (ICC, 0.39; 95% CI, 0.27-0.57; p < 0.001). When recommending treatment, interobserver agreement was substantial (kappa, 0.69; 95% CI, 0.50-0.88; p < 0.001) for the recommendation to operate or not to operate, but only fair (kappa, 0.34; 95% CI, 0.21-0.47; p < 0.001) for the specific type of treatment, indicating variation in operative techniques. There were no differences in agreement for any of the fracture characteristics or treatment preference between less-experienced and more-experienced surgeons, although statistical power on this comparison was low. None of the surgeon characteristics was associated with the decision for operative treatment, whereas all fracture characteristics were, except for stable and uncertain joint stability. Articular step or gap (beta, 0.90; R-squared, 0.89; 95% CI, 0.75-1.05; p < 0.001), likelihood of subluxation or dislocation (beta, 0.80; R-squared, 0.76; 95% CI, 0.59-1.02; p < 0.001), and unstable fractures (beta, 0.88; R-squared, 0.81; 95% CI, 0.67-1.1; p < 0.001), are most strongly associated with the decision for operative treatment. Conclusions We found that assessment of a step or gap and likelihood of subluxation were most reliable and are strongly associated with the decision for operative treatment. Surgeons largely agree on which fractures might benefit from surgery, and the variation seems to be with the operative technique. Efforts at improving the care of these fractures should focus on the comparative effectiveness of the various operative treatment options. C1 [Janssen, Stein J.; Molleman, Jeroen; Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Guitton, Thierry G.] Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 23 TC 4 Z9 4 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2015 VL 473 IS 12 BP 3943 EP 3950 DI 10.1007/s11999-015-4394-7 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CV3GF UT WOS:000364146300044 PM 26084850 ER PT J AU Lopez, L Cook, N Hicks, L AF Lopez, Lenny Cook, Nakela Hicks, Leroi TI IMPROVED QUALITY OF CARE FOR CARDIOVASCULAR DISEASE FOR LATINOS SEEN IN HIGH PROPORTION LATINO VS LOW PROPORTION LATINO CLINICS SO ETHNICITY & DISEASE LA English DT Article DE Health Care Disparities; Quality of Health Care; Coronary Disease; Congestive Heart Failure; Cardiology Consultation ID COMMUNITY-HEALTH CENTERS; CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; 2011 PERFORMANCE-MEASURES; PATIENT ACTIVATION; HEART-FAILURE; RACIAL DISPARITIES; PHYSICIAN; MANAGEMENT; SPECIALTY AB Background: Primary care practices that concentrate linguistically and culturally appropriate services for Latinos may result in higher cardiology consultation rates and improved process measure performance for patients with coronary artery disease (CAD) and congestive heart failure (CHF). Methods: Multivariable Cox proportional-hazards regression was used to assess differences in referral at high proportion (HP) vs low proportion (LP) practices. Multivariable Poisson regression was used to assess the frequency of follow-up consultation. Results: Among the 9,761 patients, 9,168 had CAD, 4,444 had CHF, and 3,851 had both conditions. Latinos comprised 11% of the CAD cohort and 11% of the CHF cohort. Multivariable analyses showed higher consultation rates for Latinos at HP practices for CAD and CHF. Blacks and Whites at HP practices had no significant differences in rates of consultation compared to those in LP practices. Latinos at HP practices had 25% more consultations for CAD and 23% more consultations for CHF than Latinos at LP practices. Latinos at HP clinics had higher overall mean quality performance on clinical measures for both CAD and CHF. Latinos at an LP clinic had the largest improvement in quality performance with consultation. Conclusions: Among Latinos with CAD or CHF receiving care within a single large academic care network, Latino patients at HP practices have higher rates of cardiologist consultation and performance on CVD process measures compared to Latino patients at LP practices. Elucidating the essential components of individual practice environments that pro-vide higher quality of care for Latinos will allow for well designed systems to reduce health care disparities. C1 [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lopez, Lenny] Harvard Univ, Sch Med, Boston, MA USA. [Cook, Nakela] NHLBI, Bethesda, MD 20892 USA. [Hicks, Leroi] Christiana Care Hlth Syst, Dept Med, Newark, DE USA. [Hicks, Leroi] Christiana Care Hlth Syst, Value Inst, Newark, DE USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM llopez1@partners.org FU Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program; Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [U54-GM104941] FX The authors would like to thank Lina Pabon-Nau, MD for her assistance in the early stages of this project. Dr. Lenny Lopez acknowledges the support of the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program. This funding body was not involved in the design, data collection, analysis, interpretation nor the preparation of the manuscript.; Dr. Hicks' effort was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number U54-GM104941 (PI: Binder-Macleod). NR 37 TC 0 Z9 1 U1 0 U2 4 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2015 VL 25 IS 1 BP 3 EP 10 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KV UT WOS:000363717600003 PM 25812245 ER PT J AU Smith, JA Frueh, BC Campbell, J Egede, L AF Smith, Jeffrey A. Frueh, B. Christopher Campbell, Jennifer Egede, Leonard TI RACIAL DIFFERENCES IN DIABETES AMONG UNION FORCES DURING THE US CIVIL WAR SO ETHNICITY & DISEASE LA English DT Editorial Material DE Diabetes; Military; Civil War ID ETHNIC-DIFFERENCES; UNITED-STATES; VETERANS; END AB Diabetes is the seventh leading cause of death in the United States and disproportionately affects ethnic minorities. While research examining health disparities is well-established, an historical understanding of how the disparities evolved over time may be warranted. This article examined racial differences in prevalence of diabetes and associated mortality in Blacks and Whites during the US Civil War. Data were extracted from the Medical and Surgical History of the War of Rebellion, 18611865, representing segregated White and Black Union Forces who served during the war. Data were collapsed by war theater (Atlantic, Central, Pacific). Results by race show that, from 1861 to 1866, the rates of Whites diagnosed with diabetes ranged overall from 0% to .11% and was distributed throughout the war theaters as: Atlantic 0.3% to .05%; Central 0.3% to .08%, and Pacific 0% to .11%. For Blacks, Atlantic ranged from .02% to .07% and Central .03% to .06%. None were reported for Pacific. Mortality was approximately .01% for both Blacks and Whites. These data suggest no racial differences in diabetes prevalence and mortality existed between Blacks and Whites during this time, implying that disparities may have evolved more recently. C1 [Smith, Jeffrey A.] Univ Hawaii, Dept Hist, Hilo, HI 96720 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Campbell, Jennifer; Egede, Leonard] Med Univ S Carolina, Charleston, SC 29425 USA. [Egede, Leonard] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Egede, L (reprint author), Med Univ S Carolina, Ctr Hlth Disparities Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu NR 12 TC 0 Z9 0 U1 0 U2 3 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2015 VL 25 IS 1 BP 104 EP 107 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KV UT WOS:000363717600018 PM 25812260 ER PT J AU Noerager, BD Xu, X Davis, VA Jones, CW Okafor, S Whitehead, A Blalock, JE Jackson, PL AF Noerager, Brett D. Xu, Xin Davis, Virginia A. Jones, Caleb W. Okafor, Svetlana Whitehead, Alicia Blalock, J. Edwin Jackson, Patricia L. TI A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation SO INFLAMMATION LA English DT Article DE acrolein; neutrophils; inflammation; chronic obstructive pulmonary disease ID OBSTRUCTIVE PULMONARY-DISEASE; BRONCHIAL EPITHELIAL-CELLS; PROLINE-GLYCINE-PROLINE; CIGARETTE-SMOKE; CYSTIC-FIBROSIS; ALPHA,BETA-UNSATURATED ALDEHYDES; AIRWAY INFLAMMATION; RELEASE; CHEMOATTRACTANT; MACROPHAGES AB Neutrophils (PMNs) are key mediators of inflammatory processes throughout the body. In this study, we investigated the role of acrolein, a highly reactive aldehyde that is ubiquitously present in the environment and produced endogenously at sites of inflammation, in mediating PMN-mediated degradation of collagen facilitating proline-glycine-proline (PGP) production. We treated peripheral blood neutrophils with acrolein and analyzed cell supernatants and lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE), assessed their ability to break down collagen and release PGP, and assayed for the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP. Acrolein treatment induced elevated production and functionality of collagen-degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and triaminopeptidase activity declined with increasing concentrations of acrolein thereby sparing PGP from enzymatic destruction. These findings suggest that acrolein exacerbates the acute inflammatory response mediated by neutrophils and sets the stage for chronic pulmonary and systemic inflammation. C1 [Noerager, Brett D.; Davis, Virginia A.] Univ Montevallo, Dept Biol Chem & Math, Montevallo, AL 35115 USA. [Xu, Xin; Jones, Caleb W.; Blalock, J. Edwin; Jackson, Patricia L.] Univ Alabama Birmingham, Dept Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Jones, Caleb W.; Okafor, Svetlana; Whitehead, Alicia] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Blalock, J. Edwin; Jackson, Patricia L.] Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL 35294 USA. [Jackson, Patricia L.] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA. [Jackson, Patricia L.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Noerager, BD (reprint author), Univ Montevallo, Dept Biol Chem & Math, Montevallo, AL 35115 USA. EM noeragerb@montevallo.edu OI Blalock, J. Edwin/0000-0001-5303-8123 FU NIH [HL07783, HL090999, HL087824]; Cystic Fibrosis Foundation [R464-CR11]; NIH/NIDDK [P30 DKO72482] FX JEB is funded through NIH (HL07783, HL090999, and HL087824). PLJ is supported by Cystic Fibrosis Foundation R464-CR11 "Research Development Program-Component II" and NIH/NIDDK P30 DKO72482. The authors wish to thank Dr. Mike Wells for thoughtful input on many drafts of the manuscript. NR 41 TC 3 Z9 3 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 EI 1573-2576 J9 INFLAMMATION JI Inflammation PD DEC PY 2015 VL 38 IS 6 BP 2279 EP 2287 DI 10.1007/s10753-015-0213-2 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA CV4GA UT WOS:000364223800029 PM 26208604 ER PT J AU Ferguson, ND Thompson, BT AF Ferguson, Niall D. Thompson, B. Taylor TI Prone positioning and neuromuscular blocking agents are part of standard care in severe ARDS patients: no SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; METAANALYSIS; WEAKNESS; TRIALS C1 [Ferguson, Niall D.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Hlth Network, Dept Med, Div Respirol, Toronto, ON, Canada. [Ferguson, Niall D.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Ferguson, Niall D.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Thompson, B. Taylor] Harvard Univ, Sch Med, Boston, MA USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. EM tthompson1@partners.org OI Ferguson, Niall/0000-0002-6213-5264 FU NHLBI NIH HHS [U01 HL123009] NR 15 TC 2 Z9 2 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2015 VL 41 IS 12 BP 2198 EP 2200 DI 10.1007/s00134-015-4043-3 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA CV0WO UT WOS:000363974600022 PM 26399891 ER PT J AU Foley, OW Birrer, N Rauh-Hain, JA Clark, RM DiTavi, E del Carmen, MG AF Foley, Olivia W. Birrer, Nicole Rauh-Hain, J. Alejandro Clark, Rachel M. DiTavi, Elizabeth del Carmen, Marcela G. TI Effect of Educational Intervention on Cervical Cancer Prevention and Screening in Hispanic Women SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Cervical cancer; HPV; Prevention; Education; Screening ID HUMAN-PAPILLOMAVIRUS; MULTIPLE IMPUTATION; HPV VACCINATION; YOUNG-ADULTS; FOLLOW-UP; KNOWLEDGE; ATTITUDES; AWARENESS; BELIEFS; SAMPLE AB To evaluate the effect of an educational intervention on four domains of health care utilization and cervical cancer prevention and screening in a Hispanic population. Data collected from a survey were used to design education strategies focused on four domains of interest. A second survey was conducted to measure the impact of the intervention. Following the intervention, respondents were more likely to have any knowledge of human papillomavirus (HPV). Respondents living in the United States (US) for < 5 years were more likely to have had a Papanicolaou smear in the preceding 3 years (p = 0.0314), to report knowledge of HPV vaccination (p = 0.0258), and to be willing to vaccinate themselves (p = 0.0124) and their children (p = 0.0341) after the intervention. Educational interventions designed to meet the needs identified by the sample group led to an increase in HPV awareness throughout the entire population surveyed and an increase in health care service utilization and HPV vaccine acceptance for women living in the US for < 5 years. These tools should be promoted to reduce the cervical cancer burden on vulnerable populations. C1 [Foley, Olivia W.; Birrer, Nicole; Rauh-Hain, J. Alejandro; Clark, Rachel M.; DiTavi, Elizabeth; del Carmen, Marcela G.] Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02114 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Massachusetts General Hospital Clinician-Teacher Development Award; Deborah Kelly Center for Outcomes Research Award FX This work was funded by Massachusetts General Hospital Clinician-Teacher Development Award and the Deborah Kelly Center for Outcomes Research Award. NR 23 TC 1 Z9 1 U1 3 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 EI 1573-3610 J9 J COMMUN HEALTH JI J. Community Health PD DEC PY 2015 VL 40 IS 6 BP 1178 EP 1184 DI 10.1007/s10900-015-0045-x PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CV0XU UT WOS:000363978000017 PM 26026277 ER PT J AU Mehta, AB Syeda, SN Wiener, RS Walkey, AJ AF Mehta, Anuj B. Syeda, Sohera N. Wiener, Renda Soylemez Walkey, Allan J. TI Epidemiological trends in invasive mechanical ventilation in the United States: A population-based study SO JOURNAL OF CRITICAL CARE LA English DT Article DE Mortality/trends; Epidemiology; Respiratory insufficiency/mortality; Respiratory insufficiency/epidemiology; United States/epidemiology ID ACUTE RESPIRATORY-FAILURE; OBSTRUCTIVE PULMONARY-DISEASE; CONGESTIVE-HEART-FAILURE; INTENSIVE-CARE-UNIT; NONINVASIVE VENTILATION; ADMINISTRATIVE DATA; VALIDATED METHODS; CRITICAL ILLNESS; MORTALITY; OUTCOMES AB Purpose: Epidemiological trends for invasive mechanical ventilation (IMV) have not been clearly defined. We sought to define trends for IMV in the United States and assess for disease-specific variation for 3 common causes of respiratory failure: pneumonia, heart failure (HF), and chronic obstructive pulmonary disease (COPD). Methods: We calculated national estimates for utilization of nonsurgical IMV cases from the Nationwide Inpatient Sample from 1993 to 2009 and compared trends for COPD, HF, and pneumonia. Results: We identified 8309344 cases of IMV from 1993 to 2009. Utilization of IMV for nonsurgical indications increased from 178.9 per 100000 in 1993 to 310.9 per 100000 US adults in 2009. Pneumonia cases requiring IMV showed the largest increase (103.6%), whereas COPD cases remained relatively stable (2.5% increase) and HF cases decreased by 55.4%. Similar demographic and clinical changes were observed for pneumonia, COPD, and HF, with cases of IMV becoming younger, more ethnically diverse, and more frequently insured by Medicaid. Outcome trends for patients differed based on diagnosis. Adjusted hospital mortality decreased over time for cases of pneumonia (odds ratio [OR] per 5 years, 0.89; 95% confidence interval [CI], 0.88-0.90) and COPD (OR per 5 years, 0.97; 95% CI, 0.97-0.98) but increased for HF (OR per 5 years, 1.10; 95% CI, 1.09-1.12). Conclusion: Utilization of IMV in the US increased from 1993 to 2009 with a decrease in overall mortality. However, trends in utilization and outcomes of IMV differed markedly based on diagnosis. Unlike favorable outcome trends in pneumonia and COPD, hospital mortality for HF has not improved. Further studies to investigate the outcome gap between HF and other causes of respiratory failure are needed. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mehta, Anuj B.; Syeda, Sohera N.; Wiener, Renda Soylemez; Walkey, Allan J.] Boston Univ, Ctr Pulm, Sch Med, Div Pulm & Crit Care Med,Dept Med, Boston, MA 02215 USA. [Syeda, Sohera N.] VA Boston Healthcare Syst, Boston, MA USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. RP Mehta, AB (reprint author), 72 E Concord St R304, Boston, MA 02118 USA. EM anuj.mehta2@bmc.org OI Walkey, Allan/0000-0003-4685-6894; Wiener, Renda/0000-0001-7712-2135 FU National Institutes of Health [T32 86308]; National Institutes of Health's National Heart, Lung, and Blood Institute [K01HL116768] FX Supported in part by National Institutes of HealthT32 86308 (ABM) and National Institutes of Health's National Heart, Lung, and Blood InstituteK01HL116768 (AJW). NR 36 TC 4 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2015 VL 30 IS 6 BP 1217 EP 1221 DI 10.1016/j.jcrc.2015.07.007 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA CV0MX UT WOS:000363945900013 PM 26271686 ER PT J AU Piva, S Dora, G Minelli, C Michelini, M Turla, F Mazza, S D'Ottavi, P Moreno-Duarte, I Sottini, C Eikermann, M Latronico, N AF Piva, Simone Dora, Giancarlo Minelli, Cosetta Michelini, Mariachiara Turla, Fabio Mazza, Stefania D'Ottavi, Patrizia Moreno-Duarte, Ingrid Sottini, Caterina Eikermann, Matthias Latronico, Nicola TI The Surgical Optimal Mobility Score predicts mortality and length of stay in an Italian population of medical, surgical, and neurologic intensive care unit patients SO JOURNAL OF CRITICAL CARE LA English DT Article DE Early mobilization; Rehabilitation; Safety; Mortality; Validation; Neurologic patients ID CRITICALLY-ILL PATIENTS; QUALITY IMPROVEMENT PROJECT; PHYSICAL-THERAPY; WEAKNESS; VALIDATION; SAFETY; SCALE; COMA; ICU AB Purpose: We validated the Italian version of Surgical Optimal Mobility Score (SOMS) and evaluated its ability to predict intensive care unit (ICU) and hospital length of stay (LOS), and hospital mortality in a mixed population of ICU patients. Materials and Methods: We applied the Italian version of SOMS in a consecutive series of prospectively enrolled, adult ICU patients. Surgical Optimal Mobility Score level was assessed twice a day by ICU nurses and twice a week by an expert mobility team. Zero-truncated Poisson regression was used to identify predictors for ICU and hospital LOS, and logistic regression for hospital mortality. All models were adjusted for potential confounders. Results: Of 98 patients recruited, 19 (19.4%) died in hospital, of whom 17 without and 2 with improved mobility level achieved during the ICU stay. SOMS improvement was independently associated with lower hospital mortality (odds ratio, 0.07; 95% confidence interval [CI], 0.01-0.42) but increased hospital LOS (odds ratio, 1.21; 95% CI: 1.10-1.33). A higher first-morning SOMS on ICU admission, indicating better mobility, was associated with lower ICU and hospital LOS (rate ratios, 0.89 [95% CI, 0.80-0.99] and 0.84 [95% CI, 0.79-0.89], respectively). Conclusions: The first-morning SOMS on ICU admission predicted ICU and hospital LOS in a mixed population of ICU patients. SOMS improvement was associated with reduced hospital mortality but increased hospital LOS, suggesting the need of optimizing hospital trajectories after ICU discharge. (C) 2015 Elsevier Inc. All rights reserved. C1 [Piva, Simone; Turla, Fabio; Mazza, Stefania; Latronico, Nicola] Spedali Civili Univ Hosp, Dept Anesthesia Crit Care Med & Emergency, I-25123 Brescia, Italy. [Dora, Giancarlo; Sottini, Caterina] Spedali Civili Univ Hosp, Dept Phys Med & Rehabil, I-25123 Brescia, Italy. [Minelli, Cosetta] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Michelini, Mariachiara; D'Ottavi, Patrizia; Latronico, Nicola] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Brescia, Italy. [Moreno-Duarte, Ingrid; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Moreno-Duarte, Ingrid; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. RP Latronico, N (reprint author), Spedali Civili Univ Hosp, Dept Anesthesia Crit Care Med & Emergency, Piazzale Osped Civili 1, I-25123 Brescia, Italy. EM nicola.latronico@unibs.it OI Piva, Simone/0000-0002-5483-8007 NR 30 TC 3 Z9 3 U1 3 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2015 VL 30 IS 6 BP 1251 EP 1257 DI 10.1016/j.jcrc.2015.08.002 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA CV0MX UT WOS:000363945900019 PM 26315654 ER PT J AU Stehman, CR Moromizato, T McKane, CK Mogensen, KM Gibbons, FK Christopher, KB AF Stehman, Christine R. Moromizato, Takuhiro McKane, Caitlin K. Mogensen, Kris M. Gibbons, Fiona K. Christopher, Kenneth B. TI Association between blood alcohol concentration and mortality in critical illness SO JOURNAL OF CRITICAL CARE LA English DT Article DE Alcohol; Ethanol; Critical care; Intensive care; Mortality; Sepsis ID ACUTE ETHANOL EXPOSURE; TRAUMATIC BRAIN-INJURY; ISCHEMIA-REPERFUSION INJURY; LOCALLY WEIGHTED REGRESSION; NEIGHBORHOOD POVERTY RATE; CELL DISTRIBUTION WIDTH; GEOCODING PROJECT US; ADULT INTENSIVE-CARE; HOSPITAL MORTALITY; UNITED-STATES AB Objective: In animal models of renal, intestinal, liver, cardiac, and cerebral ischemia, alcohol exposure is shown to reduce ischemia-reperfusion injury. Inpatient mortality of trauma patients is shown to be decreased in a dose-dependent fashion relative to blood alcohol concentration (BAC) at hospital admission. In this study, we examined the association between BAC at hospital admission and risk of 30-day mortality in critically ill patients. Design: We performed a 2-center observational study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. Setting: Medical and surgical intensive care units in 2 teaching hospitals in Boston, Massachusetts. Patients: We studied 11850 patients, 18 years or older, who received critical care between 1997 and 2007. The exposure of interest was the BAC determined in the first 24 hours of hospital admission and categorized a priori as BAC less than 10mg/dL (below level of detection), 10 to 80 mg/dL, 80 to 160 mg/dL, and greater than 160 mg/dL. The primary outcome was all-cause mortality in the 30 days after critical care initiation. Secondary outcomes included 90- and 365-day mortality after critical care initiation. Mortality was determined using the US Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both BAC and mortality. Adjustment included age, sex, race (white or nonwhite), type (surgical vs medical), Deyo-Charlson index, sepsis, acute organ failure, trauma, and chronic liver disease. Results: Thirty-day mortality of the cohort was 13.7%. Compared to patients with BAC levels less than 10 mg/dL, patients with levels greater than or equal to 10 mg/dL had lower odds of 30-day mortality; for BAC levels 10 to 79.9 mg/dL, the OR was 0.53 (95% confidence interval [CI], 0.40-0.70); for BAC levels 80 to 159.9 mg/dL, it was 0.36 (95% CI, 0.26-0.49); and for BAC levels greater than or equal to 160 mg/dL, it was 0.35 (95% CI, 0.27-0.44). After multivariable adjustment, the OR of 30-day mortality was 0.97 (0.72-1.31), 0.79 (0.57-1.10), and 0.69 (0.54-0.90), respectively. When the cohort was analyzed with sepsis as the outcome of interest, the multivariable adjusted odds of sepsis in patients with BAC 80 to 160 mg/dL or greater than 160mg/dL were 0.72 (0.50-1.04) or 0.68 (0.51-0.90), respectively, compared to those with BAC less than 10mg/dL. In a subset of patients with blood cultures drawn (n = 4065), the multivariable adjusted odds of bloodstream infection in patients with BAC 80 to 160mg/dL or greater than 160 mg/dL were 0.53 (0.27-1.01) or 0.49 (0.29-0.83), respectively, compared to those with BAC less than 10 mg/dL. Conclusions: Analysis of 11850 adult patients showed that having a detectable BAC at hospitalization was associated with significantly decreased odds of 30-day mortality after critical care. Furthermore, BAC greater than 160 mg/dL is associated with significantly decreased odds of developing sepsis and bloodstream infection. (C) 2015 Elsevier Inc. All rights reserved. C1 [Stehman, Christine R.] Indiana Univ Sch Med, Dept Emergency Med, Indianapolis, IN 46202 USA. [Moromizato, Takuhiro] Okinawa Hokubu Prefectural Hosp, Dept Med, Okinawa, Japan. [McKane, Caitlin K.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA. [Mogensen, Kris M.] Brigham & Womens Hosp, Dept Nutr, Boston, MA 02115 USA. [Gibbons, Fiona K.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Christopher, Kenneth B.] Brigham & Womens Hosp, Dept Med, Div Renal, Nathan E Hellman Mem Lab, Boston, MA 02115 USA. RP Christopher, KB (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, 75 Francis St,MRB 418, Boston, MA 02115 USA. EM kbchristopher@partners.org OI Mogensen, Kris/0000-0001-9510-3018 NR 99 TC 1 Z9 1 U1 3 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2015 VL 30 IS 6 BP 1382 EP 1389 DI 10.1016/j.jcrc.2015.08.023 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA CV0MX UT WOS:000363945900041 PM 26483354 ER PT J AU Ambrus, DB Benjamin, EJ Bajwa, EK Hibbert, KA Walkey, AJ AF Ambrus, Daniel B. Benjamin, Emelia J. Bajwa, Ednan K. Hibbert, Kathryn A. Walkey, Allan J. TI Risk factors and outcomes associated with new-onset atrial fibrillation during acute respiratory distress syndrome (vol 30, pg 994, 2015) SO JOURNAL OF CRITICAL CARE LA English DT Correction C1 [Ambrus, Daniel B.] Umass Mem Med Ctr, Dept Internal Med, Sect Hosp Med, Worcester, MA USA. [Ambrus, Daniel B.] Boston Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med & Prevent Med, Boston, MA 02118 USA. [Bajwa, Ednan K.; Hibbert, Kathryn A.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Walkey, Allan J.] Boston Univ, Sch Med, Ctr Pulm, Dept Med,Sect Pulm & Crit Care, Boston, MA 02118 USA. RP Walkey, AJ (reprint author), Boston Univ, Sch Med, 72 E Newton St,R 304, Boston, MA 02118 USA. EM alwalkey@bu.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD DEC PY 2015 VL 30 IS 6 BP 1421 EP 1421 DI 10.1016/j.jcrc.2015.10.003 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA CV0MX UT WOS:000363945900061 PM 26719064 ER PT J AU Barrows, RJ Barsuglia, J Paholpak, P Eknoyan, D Sabodash, V Lee, GJ Mendez, MF AF Barrows, Robin J. Barsuglia, Joseph Paholpak, Pongsatorn Eknoyan, Donald Sabodash, Valeriy Lee, Grace J. Mendez, Mario F. TI Executive Abilities as Reflected by Clock Hand Placement: Frontotemporal Dementia Versus Early-Onset Alzheimer Disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Alzheimer disease; frontotemporal dementia; executive functioning ID MILD COGNITIVE IMPAIRMENT; TENSOR-BASED MORPHOMETRY; DRAWING-TEST; QUALITATIVE ANALYSES; BEHAVIORAL VARIANT; DIAGNOSTIC-CRITERIA; WORKING-MEMORY; OLDER-ADULTS; TASK; CONNECTIVITY AB The clock-drawing test (CDT) is widely used in clinical practice to diagnose and distinguish patients with dementia. It remains unclear, however, whether the CDT can distinguish among the early-onset dementias. Accordingly, we examined the ability of both quantitative and qualitative CDT analyses to distinguish behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer disease (eAD), the 2 most common neurodegenerative dementias with onset <65 years of age. We hypothesized that executive aspects of the CDT would discriminate between these 2 disorders. The study compared 15 patients with bvFTD and 16 patients with eAD on the CDT using 2 different scales and correlated the findings with neuropsychological testing and magnetic resonance imaging. The total CDT scores did not discriminate bvFTD and eAD; however, specific analysis of executive hand placement items successfully distinguished the groups, with eAD exhibiting greater errors than bvFTD. The performance on those executive hand placement items correlated with measures of naming as well as visuospatial and executive function. On tensor-based morphometry of the magnetic resonance images, executive hand placement correlated with right frontal volume. These findings suggest that lower performance on executive hand placement items occurs with involvement of the right dorsolateral frontal-parietal network for executive control in eAD, a network disproportionately affected in AD of early onset. Rather than the total performance on the clock task, the analysis of specific errors, such as executive hand placement, may be useful for early differentiation of eAD, bvFTD, and other conditions. C1 [Barrows, Robin J.; Barsuglia, Joseph; Paholpak, Pongsatorn; Sabodash, Valeriy; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Barrows, Robin J.; Barsuglia, Joseph; Paholpak, Pongsatorn; Eknoyan, Donald; Sabodash, Valeriy; Mendez, Mario F.] Greater Los Angeles VA Healthcare Syst, West Los Angeles, CA USA. [Paholpak, Pongsatorn] Khon Kaen Univ, Fac Med, Dept Psychiat, Khon Kaen, Thailand. [Eknoyan, Donald] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Lee, Grace J.] Loma Linda Univ, Dept Psychol, Sch Behav Hlth, Loma Linda, CA 92350 USA. RP Barrows, RJ (reprint author), VA Greater Los Angeles Healthcare Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM drbarrowsrobinjoyce@gmail.com FU National Institute of Aging [5R01AG034499-05] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Aging (grant number 5R01AG034499-05). NR 52 TC 2 Z9 3 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2015 VL 28 IS 4 BP 239 EP 248 DI 10.1177/0891988715598228 PG 10 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA CV1AX UT WOS:000363986300002 PM 26251109 ER PT J AU Chang, TE Brill, CD Traeger, L Bedoya, CA Inamori, A Hagan, PN Flaherty, K Hails, K Yeung, A Trinh, NH AF Chang, Trina E. Brill, Charlotte D. Traeger, Lara Bedoya, C. Andres Inamori, Aya Hagan, Patrick N. Flaherty, Katherine Hails, Katherine Yeung, Albert Nhi-Ha Trinh TI Association of Race, Ethnicity and Language with Participation in Mental Health Research Among Adult Patients in Primary Care SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Depression; Latino Americans; Asian Americans; Minority groups; Patient selection ID TUSKEGEE LEGACY PROJECT; CANCER CLINICAL-TRIALS; AFRICAN-AMERICANS; MINORITY PARTICIPATION; MEDICAL-RESEARCH; ASIAN-AMERICANS; OLDER-ADULTS; WILLINGNESS; DEPRESSION; BARRIERS AB Racial and ethnic minorities remain underrepresented in clinical psychiatric research, but the reasons are not fully understood and may vary widely between minority groups. We used the Z-test of independent proportions and binary logistic regression to examine the relationship between race, ethnicity or primary language and participation in screening as well as interest in further research participation among primary care patients being screened for a depression study. Minorities were less likely than non-Hispanic Whites to complete the initial screening survey. Latinos and Blacks were more likely to agree to be contacted for research than non-Hispanic Whites. Among Latinos, primary language was associated with willingness to be contacted for research. Associations between research participation and race, ethnicity and language are complex and vary across different enrollment steps. Future research should consider stages of the research enrollment process separately to better understand barriers and identify targets for intervention. C1 [Chang, Trina E.; Brill, Charlotte D.; Inamori, Aya; Hails, Katherine; Yeung, Albert; Nhi-Ha Trinh] Massachusetts Gen Hosp, DCRP, Boston, MA 02114 USA. [Traeger, Lara; Bedoya, C. Andres] Massachusetts Gen Hosp, Behav Med Program, Boston, MA 02114 USA. [Hagan, Patrick N.] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA. [Flaherty, Katherine] ABT Associates Inc, Cambridge, MA 02138 USA. RP Chang, TE (reprint author), Massachusetts Gen Hosp, DCRP, 1 Bowdoin Sq,6th Fl, Boston, MA 02114 USA. EM techang@partners.org FU Robert Wood Johnson Foundation's program, 'Finding Answers: Disparities Research for Change' (RWJF) [66709]; Harvard Medical School's Center of Excellence Health Disparities Post Graduate Fellowship (HDPG); Disparities Mentorship and Professional Support (D-MaPS) Enrichment Award from Harvard Catalyst Health Disparities Research Program FX The authors would like to thank the professional and support staff at the participating sites for their commitment and participation in the study: MGH Charlestown Healthcare Center, MGH Chelsea Healthcare Center, MGH Internal Medicine Associates, and MGH Revere Healthcare Center. The authors would also like to thank Drs. Joseph Betancourt and Alexander Green from the MGH Disparities Solutions Center for their contributions to the conception and design of the study, Jennifer Riconda and the MGH Development Office for their support of the grant, Dr. Jerrold Rosenbaum the chief of the MGH Department of Psychiatry for his support of the study, Dr. Susan Regan with the MGH Medical Practices Evaluation Center for her statistical support of the study, and Soo Jeong Yoon and Jenny Man for their technical assistance in the study. This manuscript was made possible through the support of the Robert Wood Johnson Foundation's program, 'Finding Answers: Disparities Research for Change' (RWJF Grant Number 66709); Harvard Medical School's Center of Excellence Health Disparities Post Graduate Fellowship (HDPG); Disparities Mentorship and Professional Support (D-MaPS) Enrichment Award from the Harvard Catalyst Health Disparities Research Program; and the MGH Department of Psychiatry. NR 39 TC 2 Z9 2 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 EI 1557-1920 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD DEC PY 2015 VL 17 IS 6 SI SI BP 1660 EP 1669 DI 10.1007/s10903-014-0130-8 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CV0YS UT WOS:000363980500009 PM 25398517 ER PT J AU Cummings, BM Cowl, AS Yager, PH El Saleeby, CM Shank, ES Noviski, N AF Cummings, Brian M. Cowl, Allison S. Yager, Phoebe H. El Saleeby, Chadi M. Shank, Erik S. Noviski, Natan TI Cardiovascular Effects of Continuous Dexmedetomidine Infusion Without a Loading Dose in the Pediatric Intensive Care Unit SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article DE dexmedetomidine; pediatrics; critical care; safety ID SEDATION; CHILDREN; WITHDRAWAL; PROPOFOL; MRI AB Background: Use of dexmedetomidine in pediatric critical care is common, despite lack of prospective studies on its hemodynamic effects. Objective: To describe cardiovascular effects in critically ill children treated with a constant continuous infusion of dexmedetomidine without a loading dose at highest Food and Drug Administration-approved adult dose. Methods: Prospective, pilot study of 17 patients with dexmedetomidine infused at a rate of 0.7 g/kg/h for 6 to 24 hours. Heart rate (HR) and blood pressure (BP) values over time were analyzed by a random effects mixed model. Results: Patients with median age of 1.6 years (1 month to 17 years) and median weight of 11.8 kg (2.8-84 kg) received an infusion for a mean of 16 7.2 hours. There were no cardiac conduction abnormalities. One patient required discontinuation of infusion for predetermined low HR termination criteria at hour 13 of infusion; there was no clinical compromise and it coincided with planned extubation. Decreased HR of 20% from baseline was found in 35% of patients. The mean HR reduction was largest at hour 13 of infusion with a decrease of 13 +/- 17 bpm from baseline, but HR changes over time were not statistically significant. Blood pressure effects included a decrease in 12% and an increase in 29%. There was a small but statistically significant increase in systolic BP of 0.4 mm Hg/h of infusion, P < .001. Conclusion: A continuous infusion of 0.7 g/kg/h of dexmedetomidine without a loading dose for up to 24 hours in critically ill children had tolerable effects on HR and BP. C1 [Cummings, Brian M.; Yager, Phoebe H.; Noviski, Natan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Crit Care Med, Boston, MA 02114 USA. [Cowl, Allison S.] Univ Connecticut, Connecticut Childrens Med Ctr, Pediat Crit Care, Hartford, CT 06112 USA. [El Saleeby, Chadi M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Infect Dis,Pediat, Boston, MA 02114 USA. [Shank, Erik S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care & Pain Med,Pediat Anesthesia,Anesthesia, Boston, MA 02114 USA. RP Cummings, BM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Crit Care Med, 175 Cambridge St, Boston, MA 02114 USA. EM bmcummings@partners.org FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award) [8UL1TR000170-05]; Harvard University FX The author(s) received no financial support for the research, authorship, and/or publication of this article: This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and its affiliated academic health care centers). NR 25 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0885-0666 EI 1525-1489 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD DEC PY 2015 VL 30 IS 8 BP 512 EP 517 DI 10.1177/0885066614538754 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA CV3XK UT WOS:000364199700007 PM 24923492 ER PT J AU Slade, EP Goldman, HH Dixon, LB Gibbons, B Stuart, EA AF Slade, Eric P. Goldman, Howard H. Dixon, Lisa B. Gibbons, Brent Stuart, Elizabeth A. TI Assessing the Representativeness of Medical Expenditure Panel Survey Inpatient Utilization Data for Individuals With Psychiatric and Nonpsychiatric Conditions SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE mental health; psychiatric inpatient hospitalization; serious mental illness; measurement error; stigma ID SERIOUS MENTAL-ILLNESS; HEALTH; SERVICES; DEPRESSION; HIV; COMORBIDITY; ASSOCIATION; PREVALENCE; ACCURACY; SAMPLE AB Sampling and reporting biases in the Medical Expenditure Panel Survey (MEPS) survey could render data on inpatient utilization that are not representative for individuals with severe psychiatric conditions. The authors assessed the representativeness of MEPS data on psychiatric inpatient utilization, by comparing MEPS estimates of total annual psychiatric and nonpsychiatric inpatient admissions and bed days, and mean length of stay, for nonelderly U.S. adults in calendar years 2005 to 2010 (N = 9,288) to estimates from the Nationwide Inpatient Sample (NIS), a nationally representative inpatient care database derived from hospitals' administrative records (N = 21,934,378). Compared with the NIS, the MEPS indicated 34% as many psychiatric admissions and 86% as many nonpsychiatric admissions, while mean psychiatric length of stay was greater in MEPS than in NIS. In MEPS data, underrepresentation of psychiatric inpatient utilization at community hospitals may result in measurement distortions for commonly used statistics on psychiatric inpatient utilization and costs. C1 [Slade, Eric P.] US Dept Vet Affairs, Baltimore, MD USA. [Slade, Eric P.; Goldman, Howard H.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Dixon, Lisa B.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Dixon, Lisa B.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Gibbons, Brent] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Stuart, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Slade, EP (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Div Res Serv, 737 W Lombard St, Baltimore, MD 21201 USA. EM eslade@psych.umaryland.edu FU National Institute of Mental Health/National Institutes of Health Common Fund [R21-MH096285] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: National Institute of Mental Health/National Institutes of Health Common Fund R21-MH096285. NR 32 TC 0 Z9 0 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD DEC PY 2015 VL 72 IS 6 BP 736 EP 755 DI 10.1177/1077558715592745 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CV6YF UT WOS:000364417500005 PM 26149973 ER PT J AU Thierauf, J Veit, JA Affolter, A Bergmann, C Grunow, J Laban, S Lennerz, JK Grunmuller, L Mauch, C Plinkert, PK Hess, J Hoffmann, TK AF Thierauf, Julia Veit, Johannes A. Affolter, Annette Bergmann, Christoph Gruenow, Jennifer Laban, Simon Lennerz, Jochen K. Gruenmueller, Lisa Mauch, Cornelia Plinkert, Peter K. Hess, Jochen Hoffmann, Thomas K. TI Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck SO MELANOMA RESEARCH LA English DT Article DE head and neck cancer; immunohistochemistry; mucosal melanoma; PD-L1; PD-1 ID IMMUNE CHECKPOINTS; CELL-CARCINOMA; LIGAND 1; CANCER; SAFETY; RADIOTHERAPY; NIVOLUMAB; MPDL3280A; MEMBRANES; ANTI-PD-1 AB Mucosal melanoma of the head and neck is a rare and aggressive tumor entity with a poor prognosis. The standard treatment is radical tumor resection, with or without adjuvant radiation, where conventional chemotherapies in advanced stage or recurrent diseases have shown little benefit. Overexpression of the programmed cell death ligand 1 (PD-L1) is a common feature in human cancer. Although PD-L1 is an acknowledged prognostic biomarker for dismal prognosis in other tumors of the head and neck, expression and clinical relevance of PD-L1 in mucosal melanoma have not been addressed so far. We assessed PD-L1 expression using immunohistochemical staining in 23 tumor samples from patients with primary mucosal melanoma and correlated expression status with clinicopathological and outcome data. Tumors were derived from the nasal cavity (43.5%), nasal sinuses (43.5%), and the conjunctiva (13%). All patients had undergone surgery; 39% of all patients received adjuvant radiation and 13% were administered systemic interferon therapy. The probability of 1- and 5-year overall survival was 87 and 34.8%, respectively. The mean overall survival was 51 months and the mean recurrence-free survival was 23 months. Immunohistochemical staining showed PD-L1 expression in 13% (3/23) of mucosal melanoma. In contrast, prominent PD-L1 staining was detected in 100% of tissue sections from a control group of cutaneous melanoma (n=9). PD-L1 expression in mucosal melanoma was not correlated with age, sex, nor anatomical localization of the tumor. Interestingly, patients with PD-L1-positive mucosal melanoma had a significantly longer recurrence-free survival (P=0.026). In contrast to cutaneous melanoma and some other malignancies, a relevant PD-L1 overexpression in mucosal melanoma could not be confirmed. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved. C1 [Thierauf, Julia; Veit, Johannes A.; Laban, Simon; Hoffmann, Thomas K.] Univ Med Ctr Ulm, Dept Otorhinolaryngol Head & Neck Surg, Ulm, Germany. [Lennerz, Jochen K.; Gruenmueller, Lisa] Univ Med Ctr Ulm, Inst Pathol, Ulm, Germany. [Bergmann, Christoph] Univ Med Ctr Essen, Dept Otorhinolaryngol Head & Neck Surg, Essen, Germany. [Affolter, Annette] Univ Med Ctr Heidelberg, Inst Pathol, Heidelberg, Germany. [Affolter, Annette; Gruenow, Jennifer; Plinkert, Peter K.; Hess, Jochen] Univ Med Ctr Heidelberg, Sect Expt & Translat Head & Neck Oncol, Dept Otorhinolaryngol Head & Neck Surg, Heidelberg, Germany. [Hess, Jochen] German Canc Res Ctr, Res Grp Mol Mech Head & Neck Tumors, Heidelberg, Germany. [Mauch, Cornelia] Univ Med Ctr Cologne, Dept Dermatol & Venerol, Cologne, Germany. [Lennerz, Jochen K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Thierauf, J (reprint author), Univ Med Ctr Ulm, Dept Otorhinolaryngol Head & Neck Surg, Ulm, Germany. EM thieraufjulia@gmail.com NR 35 TC 8 Z9 8 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0960-8931 EI 1473-5636 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 2015 VL 25 IS 6 BP 503 EP 509 DI 10.1097/CMR.0000000000000197 PG 7 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA CV5MC UT WOS:000364313800006 PM 26352784 ER PT J AU Driscoll, KA Volkening, LK Haro, H Ocean, G Wang, YX Jackson, CC Clougherty, M Hale, DE Klingensmith, GJ Laffel, L Deeb, LC Siminerio, LM AF Driscoll, Kimberly A. Volkening, Lisa K. Haro, Heidi Ocean, Gesnyr Wang, Yuxia Jackson, Crystal Crismond Clougherty, Marilyn Hale, Daniel E. Klingensmith, Georgeanna J. Laffel, Lori Deeb, Larry C. Siminerio, Linda M. TI Are children with type 1 diabetes safe at school? Examining parent perceptions SO PEDIATRIC DIABETES LA English DT Article DE parents' perceptions; safety; school environment; type 1 diabetes ID SELF-MANAGEMENT; PERSPECTIVES; METAANALYSIS; CARE AB ObjectiveTo describe parent perceptions of children's diabetes care at school including: availability of licensed health professionals; staff training; logistics of provision of care; and occurrence and treatment of hypo- and hyperglycemia; and to examine parents' perceptions of their children's safety and satisfaction in the school environment. Research design and methodsA survey was completed by parents of children with type 1 diabetes from permissive (trained, non-medical school personnel permitted to provide diabetes care; N = 237) and non-permissive (only licensed health care professionals permitted to provide diabetes care; N = 198) states. ResultsMost parents reported that schools had nurses available for the school day; teachers and coaches should be trained; nurses, children, and parents frequently provided diabetes care; and hypo- and hyperglycemia occurred often. Parents in permissive states perceived children to be as safe and were as satisfied with care as parents in non-permissive states. ConclusionsTraining non-medical staff will probably maximize safety of children with diabetes when a school nurse is not available. C1 [Driscoll, Kimberly A.; Ocean, Gesnyr; Wang, Yuxia; Deeb, Larry C.] Florida State Univ, Coll Med, Dept Behav Sci & Social Med, Tallahassee, FL 32306 USA. [Volkening, Lisa K.; Laffel, Lori] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Haro, Heidi; Klingensmith, Georgeanna J.] Univ Colorado, Dept Pediat, Sch Med, Barbara Davis Ctr, Aurora, CO USA. [Jackson, Crystal Crismond] Govt Affairs & Advocacy, Amer Diabet Assoc, Alexandria, VA USA. [Clougherty, Marilyn] Childrens Hosp Pittsburgh, Pediat Endocrinol, Pittsburgh, PA 15213 USA. [Hale, Daniel E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Siminerio, Linda M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Driscoll, KA (reprint author), Florida State Univ, Coll Med, Dept Behav Sci & Social Med, 1115 West Call St, Tallahassee, FL 32306 USA. EM kimberly.driscoll@med.fsu.edu OI Driscoll, Kimberly/0000-0002-3006-4633 FU American Diabetes Association FX This study was supported by the American Diabetes Association. NR 14 TC 8 Z9 8 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X EI 1399-5448 J9 PEDIATR DIABETES JI Pediatr. Diabetes PD DEC PY 2015 VL 16 IS 8 BP 613 EP 620 DI 10.1111/pedi.12204 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA CV0GW UT WOS:000363929400008 PM 25266418 ER PT J AU Chen, F Du, Y Esposito, E Liu, Y Guo, SZ Wang, XY Lo, E Xing, CH Ji, XM AF Chen, Fan Du, Yang Esposito, Elga Liu, Yi Guo, Shuzhen Wang, Xiaoying Lo, Eng H. Xing, Changhong Ji, Xunming TI Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126 SO TRANSLATIONAL STROKE RESEARCH LA English DT Article DE Focal cerebral ischemia; miR-126; Exosome; Biomarker; Reperfusion injury ID VASCULAR INTEGRITY; ENDOTHELIAL-CELLS; ACUTE STROKE; MICRORNA; EXPRESSION; MIR-126; BRAIN; BIOMARKERS; ANGIOGENESIS; MECHANISM AB Emerging data suggest that exosomal microRNA (miRNA) may provide potential biomarkers in acute ischemic stroke. However, the effects of ischemia-reperfusion on total versus exosomal miRNA responses in circulating blood remain to be fully defined. Here, we quantified levels of miR-126 in whole serum versus exosomes extracted from serum and compared these temporal profiles against reperfusion and outcomes in a rat model of acute focal cerebral ischemia. First, in vitro experiments confirmed the vascular origin and changes in miR-126 in brain endothelial cultures subjected to oxygen-glucose deprivation. Then in vivo experiments were performed by inducing permanent or transient focal cerebral ischemia in rats, and total serum and exosomal miR-126 levels were quantified, along with measurements of infarction and neurological outcomes. Exosomal levels of miR-126 showed a transient reduction at 3 h post-ischemia that appeared to normalize back close to pre-ischemic baselines after 24 h. There were no detectable differences in exosomal miR-126 responses in permanent or transient ischemia. Serum miR-126 levels appeared to differ in permanent versus transient ischemia. Significant reductions in serum miR-126 were detected at 3 h after permanent ischemia but not transient ischemia. By 24 h, serum miR-126 levels were back close to baseline in both permanent and transient ischemia. Overall, there were no correlations between serum miR-126 and exosomal miR-126. This proof-of-concept study suggests that changes in serum miR-126 may be able to distinguish severe permanent ischemia from milder injury after transient ischemia. C1 [Chen, Fan; Liu, Yi; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Beijing, Peoples R China. [Chen, Fan; Du, Yang; Esposito, Elga; Liu, Yi; Guo, Shuzhen; Wang, Xiaoying; Lo, Eng H.; Xing, Changhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02134 USA. [Du, Yang] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China. RP Xing, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02134 USA. EM Xing.Changhong@mgh.harvard.edu; jixunming@vip.163.com FU NIH; National Natural Science Foundation of China FX Supported in part by grants from NIH and National Natural Science Foundation of China. NR 46 TC 4 Z9 5 U1 5 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 EI 1868-601X J9 TRANSL STROKE RES JI Transl. Stroke Res. PD DEC PY 2015 VL 6 IS 6 BP 478 EP 484 DI 10.1007/s12975-015-0429-3 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CV3JE UT WOS:000364154700010 PM 26449616 ER PT J AU Rieken, M Shariat, SF Kluth, LA Fajkovic, H Rink, M Karakiewicz, PI Seitz, C Briganti, A Roupret, M Loidl, W Trinh, QD Bachmann, A Pourmand, G AF Rieken, Malte Shariat, Shahrokh F. Kluth, Luis A. Fajkovic, Harun Rink, Michael Karakiewicz, Pierre I. Seitz, Christian Briganti, Alberto Roupret, Morgan Loidl, Wolfgang Trinh, Quoc-Dien Bachmann, Alexander Pourmand, Gholamreza TI Association of Cigarette Smoking and Smoking Cessation with Biochemical Recurrence of Prostate Cancer in Patients Treated with Radical Prostatectomy SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Radical prostatectomy; Smoking; Biochemical recurrence ID UNITED-STATES; TOBACCO USE; RISK; MORTALITY; OUTCOMES; COHORT; HEALTH; IMPACT; LUNG AB Background: Cigarette smoking seems to be associated with prostate cancer (PCa) incidence and mortality. Objective: To elucidate the association between pretreatment smoking status, cumulative smoking exposure, and time since smoking cessation and the risk of biochemical recurrence (BCR) of PCa in patients treated with radical prostatectomy (RP). Design, setting, and participants: Retrospective analysis of 6538 patients with pathologically node-negative PCa treated with RP between 2000 and 2011. Clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation were collected. Intervention: RP without neoadjuvant therapy. Outcome measurements and statistical analysis: Univariable and multivariable Cox regression analyses assessed the association between smoking and risk of PCa BCR. Results and limitations: Of 6538 patients, 2238 (34%), 2086 (32%), and 2214 (34%) were never, former, and current smokers, respectively. Median follow-up for patients not experiencing BCR was 28 mo (interquartile range 14-42). RP Gleason score (p=0.3), extracapsular extension (p=0.2), seminal vesicle invasion (p = 0.8), and positive surgical margins (p = 0.9) were comparable among the three groups. In multivariable Cox regression analysis, former smokers (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.30-2.04; p < 0.001) and current smokers (HR 1.80, 95% CI 1.45-2.24; p < 0.001) had a higher risk of PCa BCR compared with non-smokers. Smoking cessation for >= 10 yr mitigated the risk of BCR in multivariable analyses (HR 0.96, 95% CI 0.68-1.37; p = 0.84). In multivariable analysis, no significant association between cumulative smoking exposure and risk of BCR could be detected. Limitations of the study include the retrospective design and potential recall bias regarding smoking history. Conclusion: Smoking seems to be associated with a higher risk of PCa BCR after RP. The effects of smoking appear to be mitigated by >= 10 yr of cessation. Smokers should be counseled regarding the detrimental effects of smoking on PCa prognosis. Patient summary: We investigated the effect of smoking on the risk of prostate cancer recurrence in patients with treated with surgery. We found that former smokers and current smokers were at higher risk of cancer recurrence compared to patients who never smoked; the detrimental effect of smoking was mitigated after 10 yr or more of smoking cessation. We conclude that smokers should be counseled regarding the detrimental effects on prostate cancer outcomes. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Rieken, Malte; Shariat, Shahrokh F.; Kluth, Luis A.] New York Presbyterian Hosp, Dept Urol, Weill Cornell Med Coll, New York, NY USA. [Rieken, Malte; Bachmann, Alexander] Univ Basel Hosp, Dept Urol, CH-4031 Basel, Switzerland. [Shariat, Shahrokh F.; Fajkovic, Harun; Seitz, Christian] Med Univ Vienna, Dept Urol, A-1090 Vienna, Austria. [Shariat, Shahrokh F.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA. [Kluth, Luis A.; Rink, Michael] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Karakiewicz, Pierre I.] Univ Montreal, Dept Urol, Montreal, PQ, Canada. [Briganti, Alberto] Ist Sci San Raffaele, Urol Res Inst, Dept Urol, I-20132 Milan, Italy. [Roupret, Morgan] Hosp Pitie Salpetriere, Dept Urol, Paris, France. [Loidl, Wolfgang] Krankenhaus Barmherzige Schwestern Linz, Prostate Canc Ctr, Linz, Austria. [Trinh, Quoc-Dien] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pourmand, Gholamreza] Univ Tehran Med Sci, Urol Res Ctr, Tehran, Iran. RP Shariat, SF (reprint author), Med Univ Vienna, Dept Urol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM sfshariat@gmail.com NR 24 TC 8 Z9 8 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD DEC PY 2015 VL 68 IS 6 BP 949 EP 956 DI 10.1016/j.eururo.2015.05.038 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CU4EB UT WOS:000363478500017 PM 26050111 ER PT J AU Martin, NE Stowell, C Huland, H AF Martin, Neil E. Stowell, Caleb Huland, Hartwig TI Reply to Steven MacLennan, Paula R. Williamson, and Thomas B. Lam's Letter to the Editor re: Neil E. Martin, Laura Massey, Caleb Stowell, et al. Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer. Eur Urol 2015; 67: 460-7 SO EUROPEAN UROLOGY LA English DT Letter C1 [Martin, Neil E.; Stowell, Caleb] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Martin, Neil E.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Huland, Hartwig] Univ Med Ctr Hamburg Eppendorf, Martini Klin, Hamburg, Germany. RP Martin, NE (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM nmartin@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 2 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD DEC PY 2015 VL 68 IS 6 BP E125 EP E126 DI 10.1016/j.eururo.2015.08.016 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA CU4EB UT WOS:000363478500002 PM 26320381 ER PT J AU Miller, A Moon, B Anders, S Walden, R Brown, S Montella, D AF Miller, Anne Moon, Brian Anders, Shilo Walden, Rachel Brown, Steven Montella, Diane TI Integrating computerized clinical decision support systems into clinical work: A meta-synthesis of qualitative research SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Computerized clinical decision support; Workflow integration; Clinical decision making; Meta-synthesis; Qualitative research; Human-system interaction; Human computer interaction; Usability ID ELECTRONIC HEALTH RECORDS; INTENSIVE INSULIN THERAPY; MEANINGFUL USE; METASYNTHESIS; PERFORMANCE; ALERTS AB Purpose: Computerized clinical decision support systems (CDSS) are an emerging means for improving healthcare safety, quality and efficiency, but meta-analyses findings are mixed. This meta-synthesis aggregates qualitative research findings as possible explanations for variable quantitative research outcomes. Inclusion criteria: Qualitative studies published between 2000 and 2013 in English, involving physicians, registered and advanced practice nurses' experience of CDSS use in clinical practice were included. Search strategy: PubMed and CINAHL databases were searched. Study titles and abstracts were screened against inclusion criteria. Retained studies were appraised against quality criteria. Findings were extracted iteratively from studies in the 4th quartile of quality scores. Two reviewers constructed themes inductively. A third reviewer applied the defined themes deductively achieving 92% agreement. Results: 3798 unique records were returned; 56 met inclusion criteria and were reviewed against quality criteria. 9 studies were of sufficiently high quality for synthetic analysis. Five major themes (clinician-patient-system integration; user interface usability; the need for better 'algorithms'; system maturity; patient safety) were defined. Conclusions: Despite ongoing development, CDSS remains an emerging technology. Lack of understanding about and lack of consideration for the interaction between human decision makers and CDSS is a major reason for poor system adoption and use. Further high-quality qualitative research is needed to better understand human-system interaction issues. These issues may continue to confound quantitative study results if not addressed. (C) 2015 Published by Elsevier Ireland Ltd. C1 [Miller, Anne; Anders, Shilo; Walden, Rachel; Brown, Steven; Montella, Diane] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. [Moon, Brian] Perigean Technol, Fredericksburg, VA USA. [Miller, Anne; Brown, Steven; Montella, Diane] US Dept Vet Affairs, Fredericksburg, VA USA. RP Miller, A (reprint author), Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA. EM Anne.miller@vanderbilt.edu OI Walden, Rachel/0000-0003-4140-9446 FU United States Department of Veteran's Affairs FX This project was funded by the United States Department of Veteran's Affairs. It was conceived as part of a broader program of research coordinated by the Knowledge Based System's Group within the Department of Veteran's Affair's Office of Informatics and Analytics. NR 35 TC 2 Z9 3 U1 2 U2 25 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD DEC PY 2015 VL 84 IS 12 BP 1009 EP 1018 DI 10.1016/j.ijmedinf.2015.09.005 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CU9IL UT WOS:000363858100002 PM 26391601 ER PT J AU Almario, CV Chey, WD Iriana, S Dailey, F Robbins, K Patel, AV Reid, M Whitman, C Fuller, G Bolus, R Dennis, B Encarnacion, R Martinez, B Soares, J Modi, R Agarwal, N Lee, A Kubomoto, S Sharma, G Bolus, S Chang, L Spiegel, BMR AF Almario, Christopher V. Chey, William D. Iriana, Sentia Dailey, Francis Robbins, Karen Patel, Anish V. Reid, Mark Whitman, Cynthia Fuller, Garth Bolus, Roger Dennis, Buddy Encarnacion, Rey Martinez, Bibiana Soares, Jennifer Modi, Rushaba Agarwal, Nikhil Lee, Aaron Kubomoto, Scott Sharma, Gobind Bolus, Sally Chang, Lin Spiegel, Brennan M. R. TI Computer versus physician identification of gastrointestinal alarm features SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE Alarm features; Checklists; Patient-provider portal ID SAFETY CHECKLISTS; GUIDELINES; MANAGEMENT; RECORDS; DISEASE; DIAGNOSIS; SYMPTOMS; QUALITY; CANCER; SYSTEM AB Objective: It is important for clinicians to inquire about "alarm features" as it may identify those at risk for organic disease and who require additional diagnostic workup. We developed a computer algorithm called Automated Evaluation of Gastrointestinal Symptoms (AEGIS) that systematically collects patient gastrointestinal (GI) symptoms and alarm features, and then "translates" the information into a history of present illness (HPI). Our study's objective was to compare the number of alarms documented by physicians during usual care vs. that collected by AEGIS. Methods: We performed a cross-sectional study with a paired sample design among patients visiting adult GI clinics. Participants first received usual care by their physicians and then completed AEGIS. Each individual thus contributed both a physician-documented and computer-generated HPI. Blinded physician reviewers enumerated the positive alarm features (hematochezia, melena, hematemesis, unintentional weight loss, decreased appetite, and fevers) mentioned in each HPI. We compared the number of documented alarms within patient using the Wilcoxon signed-rank test. Results: Seventy-five patients had both physician and AEGIS HPIs. AEGIS identified more patients with positive alarm features compared to physicians (53% vs. 27%; p<.001). AEGIS also documented more positive alarms (median 1, interquartile range [IQR] 0-2) vs. physicians (median 0, IQR 0-1; p<.001). Moreover, clinicians documented only 30% of the positive alarms self-reported by patients through AEGIS. Conclusions: Physicians documented less than one-third of red flags reported by patients through a computer algorithm. These data indicate that physicians may under report alarm features and that computerized "checklists" could complement standard HPIs to bolster clinical care. (C) 2015 Published by Elsevier Ireland Ltd. C1 [Almario, Christopher V.; Iriana, Sentia; Dailey, Francis; Robbins, Karen; Patel, Anish V.; Whitman, Cynthia; Fuller, Garth; Martinez, Bibiana; Soares, Jennifer; Modi, Rushaba; Agarwal, Nikhil; Lee, Aaron; Kubomoto, Scott; Sharma, Gobind; Spiegel, Brennan M. R.] Cedars Sinai Med Ctr, Div Gastroenterol, Los Angeles, CA 90048 USA. [Almario, Christopher V.; Reid, Mark; Martinez, Bibiana; Soares, Jennifer; Modi, Rushaba; Agarwal, Nikhil; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. [Almario, Christopher V.; Modi, Rushaba; Agarwal, Nikhil; Chang, Lin] Univ Calif Los Angeles, Div Digest Dis, Los Angeles, CA USA. [Almario, Christopher V.; Reid, Mark; Whitman, Cynthia; Fuller, Garth; Bolus, Roger; Martinez, Bibiana; Soares, Jennifer; Bolus, Sally; Spiegel, Brennan M. R.] CS CORE, Los Angeles, CA 90048 USA. [Chey, William D.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Dennis, Buddy; Encarnacion, Rey] Univ Calif Los Angeles, CTRL, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), CS CORE, 116 Robertson Blvd,4th Floor, Los Angeles, CA 90048 USA. EM Brennan.Spiegel@cshs.org FU National Institutes of Health through the NIH Roadmap for Medical Research Grant [AR052177]; National Institutes of Health T32 training grant [NIH T32DK07180-40] FX NIH/NIAMS U01 AR057936A, the National Institutes of Health through the NIH Roadmap for Medical Research Grant (AR052177). Dr. Almario was supported by a National Institutes of Health T32 training grant (NIH T32DK07180-40) during his gastroenterology and health services research training at UCLA. Support for the My GI Health portal used in this study was obtained from Ironwood Pharmaceuticals. The above funding sources did not play any role in the conduct of this study. NR 24 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD DEC PY 2015 VL 84 IS 12 BP 1111 EP 1117 DI 10.1016/j.ijmedinf.2015.07.006 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CU9IL UT WOS:000363858100013 PM 26254875 ER PT J AU Oldenburg, CE Perez-Brumer, AG Reisner, SL Mimiaga, MJ AF Oldenburg, Catherine E. Perez-Brumer, Amaya G. Reisner, Sari L. Mimiaga, Matthew J. TI Transactional Sex and the HIV Epidemic Among Men Who have Sex with Men (MSM): Results From a Systematic Review and Meta-analysis SO AIDS AND BEHAVIOR LA English DT Review DE Men who have sex with men; HIV; Transactional sex; Meta-analysis ID SEXUALLY-TRANSMITTED INFECTIONS; CHI-MINH CITY; RISK-FACTORS; ANAL INTERCOURSE; SAN-FRANCISCO; SOUTH-AFRICA; PREVALENCE; WORKERS; SYPHILIS; BEHAVIOR AB Engagement in transactional sex has been hypothesized to increase risk of HIV among MSM, however conflicting evidence exists. We conducted a systematic review and meta-analysis comparing HIV prevalence among MSM who engaged in transactional sex to those who did not (33 studies in 17 countries; n = 78,112 MSM). Overall, transactional sex was associated with a significant elevation in HIV prevalence (OR 1.34, 95 % CI 1.11-1.62). Latin America (OR 2.28, 95 % CI 1.87-2.78) and Sub-Saharan Africa (OR 1.72, 95 % CI 1.02-2.91) were the only regions where this elevation was noted. Further research is needed to understand factors associated with sex work and subsequent HIV risk in Latin America and Sub-Saharan Africa. C1 [Oldenburg, Catherine E.; Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Perez-Brumer, Amaya G.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA. [Reisner, Sari L.; Mimiaga, Matthew J.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Oldenburg, CE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM ceo242@mail.harvard.edu FU National Institute of Allergy and Infectious Disease T32 NRSA Grant [T32AI007535]; National Institute on Drug Abuse T32 NRSA Grant [T32DA013911]; Eunice Kennedy Shriver National Institute of Child Health & Human Development T32 NRSA Grant [T32HD049339]; National Institutes of Health FX CEO is supported by a National Institute of Allergy and Infectious Disease T32 NRSA Grant (T32AI007535; PI: Seage) and a National Institute on Drug Abuse T32 NRSA Grant (T32DA013911; PI: Flanigan). APB is supported by a Eunice Kennedy Shriver National Institute of Child Health & Human Development T32 NRSA Grant (T32HD049339; PI: Nathanson). Support for this work came from the National Institutes of Health. NR 51 TC 10 Z9 10 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD DEC PY 2015 VL 19 IS 12 BP 2177 EP 2183 DI 10.1007/s10461-015-1010-5 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CT8CL UT WOS:000363042500004 PM 25652233 ER PT J AU Matthews, LT Smit, JA Moore, L Milford, C Greener, R Mosery, FN Ribaudo, H Bennett, K Crankshaw, TL Kaida, A Psaros, C Safren, SA Bangsberg, DR AF Matthews, L. T. Smit, J. A. Moore, L. Milford, C. Greener, R. Mosery, F. N. Ribaudo, H. Bennett, K. Crankshaw, T. L. Kaida, A. Psaros, C. Safren, S. A. Bangsberg, D. R. TI Periconception HIV Risk Behavior Among Men and Women Reporting HIV-Serodiscordant Partners in KwaZulu-Natal, South Africa SO AIDS AND BEHAVIOR LA English DT Article DE Safer conception; Serodiscordant couples; South Africa; PMTCT ID SUB-SAHARAN AFRICA; REPRODUCTIVE DECISION-MAKING; RANDOMIZED CONTROLLED-TRIAL; TO-CHILD TRANSMISSION; HEALTH-CARE NEEDS; ANTIRETROVIRAL THERAPY; PREEXPOSURE PROPHYLAXIS; DISCORDANT COUPLES; POSITIVE WOMEN; CAPE-TOWN AB HIV-infected men and women who choose to conceive risk infecting their partners. To inform safer conception programs we surveyed HIV risk behavior prior to recent pregnancy amongst South African, HIV-infected women (N = 209) and men (N = 82) recruited from antenatal and antiretroviral clinics, respectively, and reporting an uninfected or unknown-HIV-serostatus pregnancy partner. All participants knew their HIV-positive serostatus prior to the referent pregnancy. Only 11 % of women and 5 % of men had planned the pregnancy; 40 % of women and 27 % of men reported serostatus disclosure to their partner before conception. Knowledge of safer conception strategies was low. Around two-thirds reported consistent condom use, 41 % of women and 88 % of men reported antiretroviral therapy, and a third of women reported male partner circumcision prior to the referent pregnancy. Seven women (3 %) and two men (2 %) reported limiting sex without condoms to peak fertility. None reported sperm washing or manual insemination. Safer conception behaviors including HIV-serostatus disclosure, condom use, and ART at the time of conception were not associated with desired pregnancy. In light of low pregnancy planning and HIV-serostatus disclosure, interventions to improve understandings of serodiscordance and motivate mutual HIV-serostatus disclosure and pregnancy planning are necessary first steps before couples or individuals can implement specific safer conception strategies. C1 [Matthews, L. T.; Bangsberg, D. R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Matthews, L. T.; Bangsberg, D. R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Smit, J. A.; Moore, L.; Milford, C.; Greener, R.; Mosery, F. N.] Univ Witwatersrand, Fac Hlth Sci, MatCH Res Maternal Adolescent & Child Hlth Rese, Dept Obstet & Gynaecol, Durban, South Africa. [Smit, J. A.] Univ KwaZulu Natal, Fac Hlth Sci, Sch Pharm & Pharmacol, Durban, South Africa. [Ribaudo, H.] Harvard Univ, Sch Med, Ctr Biostat AIDS Res, Boston, MA USA. [Bennett, K.] Bennett Stat Consulting Inc, Ballston Lake, NY USA. [Crankshaw, T. L.] Univ KwaZulu Natal, Hlth Econ & HIV & AIDS Res Div HEARD, Durban, South Africa. [Kaida, A.] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada. [Psaros, C.; Safren, S. A.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med, Boston, MA 02114 USA. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthews@partners.org FU Harvard University CFAR [P30 AI060354]; Harvard Global Health Institute; Burroughs-Wellcome/American Society for Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases; NIH [NIMH 87227, 094214, NIMH 096651]; [NIMH 095655] FX We thank the participants and study staff for their contributions to this work. Lynn Matthews is supported by a K23 award (NIMH 095655) and received funding for this Project from the Harvard University CFAR (P30 AI060354), Harvard Global Health Institute, and the Burroughs-Wellcome/American Society for Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases. Additional support was provided by the NIH including K24 awards (NIMH 87227 and 094214) and K23 award (NIMH 096651). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 97 TC 2 Z9 2 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD DEC PY 2015 VL 19 IS 12 BP 2291 EP 2303 DI 10.1007/s10461-015-1050-x PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA CT8CL UT WOS:000363042500015 PM 26080688 ER PT J AU Workman, AD Palmer, JN Adappa, ND Cohen, NA AF Workman, Alan D. Palmer, James N. Adappa, Nithin D. Cohen, Noam A. TI The Role of Bitter and Sweet Taste Receptors in Upper Airway Immunity SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review DE T2R38; Bitter taste receptor; Sweet taste receptor; Solitary chemosensory cell; Airway immune function; Upper airway immunity ID SOLITARY CHEMOSENSORY CELLS; UPPER RESPIRATORY-INFECTION; CHRONIC RHINOSINUSITIS; NITRIC-OXIDE; PSEUDOMONAS-AERUGINOSA; INDIVIDUAL-DIFFERENCES; INNATE IMMUNITY; SINUS SURGERY; UMAMI TASTES; EPITHELIUM AB Over the past several years, taste receptors have emerged as key players in the regulation of innate immune defenses in the mammalian respiratory tract. Several cell types in the airway, including ciliated epithelial cells, solitary chemosensory cells, and bronchial smooth muscle cells, all display chemoresponsive properties that utilize taste receptors. A variety of bitter products secreted by microbes are detected with resultant downstream inflammation, increased mucous clearance, antimicrobial peptide secretion, and direct bacterial killing. Genetic variation of bitter taste receptors also appears to play a role in the susceptibility to infection in respiratory disease states, including that of chronic rhinosinusitis. Ongoing taste receptor research may yield new therapeutics that harness innate immune defenses in the respiratory tract and may offer alternatives to antibiotic treatment. The present review discusses taste receptor-protective responses and analyzes the role these receptors play in mediating airway immune function. C1 [Workman, Alan D.; Palmer, James N.; Adappa, Nithin D.; Cohen, Noam A.] Univ Penn, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Workman, Alan D.; Palmer, James N.; Adappa, Nithin D.; Cohen, Noam A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Monell Smell & Taste Ctr, Philadelphia, PA USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM gnoam.cohen@gmail.com OI Cohen, Noam/0000-0002-9462-3932 FU NIDCD NIH HHS [R01 DC013588] NR 85 TC 6 Z9 6 U1 3 U2 21 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 EI 1534-6315 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD DEC PY 2015 VL 15 IS 12 AR 72 DI 10.1007/s11882-015-0571-8 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA CU1AT UT WOS:000363252100005 PM 26492878 ER PT J AU Alderman, T Addington, J Bearden, C Cannon, TD Cornblatt, BA McGlashan, TH Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Woods, SW Cadenhead, KS AF Alderman, Tracy Addington, Jean Bearden, Carrie Cannon, Tyrone D. Cornblatt, Barbara A. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Cadenhead, Kristin S. TI Negative symptoms and impaired social functioning predict later psychosis in Latino youth at clinical high risk in the North American prodromal longitudinal studies consortium SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Article DE clinical high risk; Latino; prodrome; psychosis ID SCHIZOPHRENIA; STRESS; 1ST; REACTIVITY; DISORDERS; VALIDITY; EPISODE; SAMPLE; ADULTS; PHASE AB AimExamining ethnically related variables in evaluating those at risk for psychosis is critical. This study investigated sociodemographic and clinical characteristics of Latino versus non-Latino clinical high-risk (CHR) subjects and healthy control (HC) subjects in the first North American Prodrome Longitudinal Study. MethodsFifty-six Latino CHR subjects were compared to 25 Latino HC and 423 non-Latino CHR subjects across clinical and demographic variables. Thirty-nine of the 56 CHR subjects completed at least one subsequent clinical evaluation over the 2.5-year period with 39% developing a psychotic illness. Characteristics of Latino CHR subjects who later converted to psychosis (converters') were compared to those who did not (non-converters'). ResultsLatino CHR subjects were younger than non-Latino CHR subjects and had less education than Latino HC subjects and non-Latino CHR counterparts. Latino CHR converters had higher scores than Latino non-converters on the Structured Interview for Prodromal Syndromes total negative symptoms that were accounted for by decreased expression of emotion and personal hygiene/social attentiveness subsections. Latino CHR converters scored lower on the global functioning:social scale, indicating worse social functioning than Latino non-converters. ConclusionBased on this sample, Latino CHR subjects may seek treatment earlier and have less education than non-Latino CHR subjects. Deficits in social functioning and impaired personal hygiene/social attentiveness among Latino CHR subjects predicted later psychosis and may represent important areas for future study. Larger sample sizes are needed to more thoroughly investigate the observed ethnic differences and risk factors for psychosis in Latino youth. C1 [Alderman, Tracy; Tsuang, Ming T.; Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Cadenhead, Kristin S.] San Diego Vet Affairs Med Ctr, San Diego, CA USA. [Bearden, Carrie; Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol & Psychiat & Biobehav Sci, Los Angeles, CA USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Walker, Elaine F.] Emory Univ, Dept Psychol & Psychiat, Atlanta, GA 30322 USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. RP Alderman, T (reprint author), Univ Calif San Diego, Cognit Assessment & Risk Evaluat Program, 9500 Gilman Dr,Mail Code 0810, La Jolla, CA 92093 USA. EM talderman@ucsd.edu FU National Institute of Mental Health (NIMH) [U01 MH081944-01] FX The authors would like to acknowledge the National Institute of Mental Health (NIMH): U01 MH081944-01. NR 36 TC 4 Z9 4 U1 2 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD DEC PY 2015 VL 9 IS 6 BP 467 EP 475 DI 10.1111/eip.12128 PG 9 WC Psychiatry SC Psychiatry GA CU4CH UT WOS:000363473300005 PM 24576057 ER PT J AU Kurgan, S Onder, C Altingoz, SM Bagis, N Uyanik, M Serdar, MA Kantarci, A AF Kurgan, S. OEnder, C. Altingoz, S. M. Bagis, N. Uyanik, M. Serdar, M. A. Kantarci, A. TI High sensitivity detection of salivary 8-hydroxy deoxyguanosine levels in patients with chronic periodontitis SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE 8-hydroxy deoxyguanosine; ELISA; generalized chronic periodontitis; LC-MS; MS; oxidative stress ID TANDEM MASS-SPECTROMETRY; OXIDATIVE DNA-DAMAGE; LINKED-IMMUNOSORBENT-ASSAY; PERFORMANCE LIQUID-CHROMATOGRAPHY; GINGIVAL CREVICULAR FLUID; ANTIOXIDANT CAPACITY; PROTEIN OXIDATION; HUMAN URINE; 8-HYDROXY-2'-DEOXYGUANOSINE 8-OHDG; BIOMARKER EVIDENCE AB BackgroundInflammation is associated with hydroxyl radical damage to DNA as a result of oxidative stress. 8-Hydroxy deoxyguanosine (8-OHdG) is a marker of this process and its levels in saliva could be linked to the severity of periodontal inflammation. The aim of this study was to test the sensitivity of liquid chromatography with tandem mass spectrometry (LC-MS/MS) in comparison to enzyme-linked immune sorbent assay (ELISA) for the detection of 8-OHdG in saliva in patients with chronic periodontitis before and after periodontal treatment. MethodsSaliva samples were collected from 23 patients (eight females and 15 males; 46.15.1years of age) with generalized chronic periodontitis and 25 (15 females and 10 males; 44.96.8years of age) periodontally healthy individuals. Patients received initial periodontal treatment consisting of scaling and root planing and were evaluated at baseline and after 6wk of completion of non-surgical therapy. Salivary 8-OHdG levels were measured using ELISA and LC-MS/MS before and after the treatment. Clinically, plaque index, gingival index, clinical attachment level, bleeding on probing, gingival recession and probing pocket depth were measured at baseline and after 6wk. ResultsSalivary levels of 8-OHdG decreased significantly after the non-surgical periodontal treatment (p<0.001). Statistically significant positive correlations were observed between plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing values and LC-MS/MS and ELISA levels of 8-OHdG (p<0.001). ConclusionLC-MS/MS is a reliable and sensitive method for evaluating salivary 8-OHdG levels to monitor the treatment response of periodontitis. C1 [Kurgan, S.; OEnder, C.; Altingoz, S. M.; Bagis, N.] Ankara Univ, Dept Periodontol, Fac Dent, TR-06500 Ankara, Turkey. [Uyanik, M.] Gulhane Mil Med Acad, Dept Med Biochem, Ankara, Turkey. [Serdar, M. A.] Acibadem Univ, Sch Med, Dept Med Biochem, Ankara, Turkey. [Kantarci, A.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. RP Kurgan, S (reprint author), Ankara Univ, Dept Periodontol, Sch Dent, TR-06500 Ankara, Turkey. EM sivgeakgun@gmail.com RI Uyanik, Metin/L-7360-2015 OI Uyanik, Metin/0000-0001-7083-0454 FU Ankara University Scientific Research Projects Office [08B3334005] FX We would like to thank Prof. Dr. Meral Gunhan for her valuable contribution to this study. The authors declare that they have no conflict of interests. This study was supported by the Ankara University Scientific Research Projects Office (08B3334005). NR 66 TC 2 Z9 2 U1 3 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 EI 1600-0765 J9 J PERIODONTAL RES JI J. Periodont. Res. PD DEC PY 2015 VL 50 IS 6 BP 766 EP 774 DI 10.1111/jre.12263 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CU6QT UT WOS:000363658300009 PM 25662588 ER PT J AU Gerke, TA Martin, NE Ding, ZH Nuttall, EJ Stack, EC Giovannucci, E Lis, RT Stampfer, MJ Kantoff, PW Parmigiani, G Loda, M Mucci, LA AF Gerke, Travis A. Martin, Neil E. Ding, Zhihu Nuttall, Elizabeth J. Stack, Edward C. Giovannucci, Edward Lis, Rosina T. Stampfer, Meir J. Kantoff, Phillip W. Parmigiani, Giovanni Loda, Massimo Mucci, Lorelei A. TI Evaluating a 4-marker signature of aggressive prostate cancer using time-dependent AUC SO PROSTATE LA English DT Article DE prognostic biomarkers; biomarker validation; prostate cancer ID RADICAL PROSTATECTOMY; PHYSICIANS HEALTH; PROGNOSTIC MODEL; PROGRESSION; EXPRESSION; DISEASE; COHORT; VALIDATION; BIOMARKERS; MARKERS AB BACKGROUNDWe previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer. METHODSUsing data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n=276). Based on these models, we generated prognostic risk scores in an independent population, the Health Professionals Follow-up Study (HPFS; n=347) to evaluate external validity. In each cohort, men were followed prospectively from cancer diagnosis through 2011 for development of distant metastasis or cancer mortality. We measured protein tumor expression of PTEN, SMAD4, SPP1, and CCND1 on tissue microarrays. RESULTSDuring a median of 11.9 and 14.3 years follow-up in the PHS and HPFS cohorts, 24 and 32 men (9%) developed lethal disease. When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. CONCLUSIONSAlthough the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in aggressive prostate tumors and highlight the challenges that may result from overfitting in discovery-based research. Prostate 75:1926-1933, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Gerke, Travis A.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gerke, Travis A.] Univ Florida, Dept Epidemiol, Gainesville, FL USA. [Martin, Neil E.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Martin, Neil E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ding, Zhihu] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02115 USA. [Nuttall, Elizabeth J.; Lis, Rosina T.; Loda, Massimo] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Stack, Edward C.; Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir J.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA. [Kantoff, Phillip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Gerke, TA (reprint author), Univ Florida, Dept Epidemiol, ScD, POB 100231, Gainesville, FL 32610 USA. EM tgerke@ufl.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU National Institutes of Health [UM1CA16755201, P50CA090381, R01CA133891, R01CA136578, R01CA141298, U01MMHCC]; Metamark Genetics, Inc; Belfer Institute for Applied Cancer Science; Prostate Cancer Foundation; National Research Service Award [T32 CA009001 NCI] FX Grant sponsor: National Institutes of Health research; Grant numbers: UM1CA16755201; P50CA090381; R01CA133891; R01CA136578; R01CA141298; U01MMHCC; Grant sponsor: Metamark Genetics, Inc, the Belfer Institute for Applied Cancer Science and the Prostate Cancer Foundation; Grant sponsor: National Research Service Award; Grant number: T32 CA009001 NCI (Gerke). NR 21 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD DEC 1 PY 2015 VL 75 IS 16 BP 1926 EP 1933 DI 10.1002/pros.23090 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA CU0PK UT WOS:000363219300012 PM 26469352 ER PT J AU Nemes, S Burstrom, K Zethraeus, N Eneqvist, T Garellick, G Rolfson, O AF Nemes, Szilard Burstrom, Kristina Zethraeus, Niklas Eneqvist, Ted Garellick, Goran Rolfson, Ola TI Assessment of the Swedish EQ-5D experience-based value sets in a total hip replacement population SO QUALITY OF LIFE RESEARCH LA English DT Article DE EQ-5D; Experience-based value sets; Visual analogue scale; Time trade-off; Swedish Hip Arthroplasty Register; Total hip replacement; Quality register ID PATIENT-REPORTED OUTCOMES; QUALITY-OF-LIFE; HEALTH STATES; ARTHROPLASTY REGISTER; VALUATION; SCORES; CARE AB All patients undergoing elective total hip replacement (THR) in Sweden are asked to complete a survey, including the EQ-5D. Thus far, EQ-5D values have been presented using the UK TTO value set based on hypothetical values. Shift to the use of the recently introduced Swedish experience-based value set, derived from a representative Swedish population, is an appealing alternative. To investigate how accurate the Swedish experience-based VAS value set predicts observed EQ VAS values and to compare correlations between Swedish and UK value sets including two provisional value sets derived from the THR population. Pre- and one-year postoperative data from 56,062 THR patients from the Swedish Hip Arthroplasty Register were used. Agreement between the observed and the predicted EQ VAS values was assessed with correlation. Based on pre- and postoperative data, we constructed two provisional VAS value sets. Correlations between observed and calculated values using the Swedish VAS value set were moderate (r = 0.46) in preoperative data and high (r = 0.72) in postoperative data. Correlations between UK and register-based value sets were constantly lower compared to Swedish value sets. Register-based values and Swedish values were highly correlated. The Swedish value sets are more accurate in terms of representation of the Swedish THR patients than the currently used UK TTO value set. We find it feasible to use the experience-based Swedish value sets for further presentation of EQ-5D values in the Swedish THR population. C1 [Nemes, Szilard; Eneqvist, Ted; Garellick, Goran; Rolfson, Ola] Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Nemes, Szilard; Eneqvist, Ted; Garellick, Goran; Rolfson, Ola] Univ Gothenburg, Sahlgrenska Acad, Dept Orthopaed, Gothenburg, Sweden. [Burstrom, Kristina; Zethraeus, Niklas] Karolinska Inst, Dept Learning Informat Management & Eth, Med Management Ctr, Stockholm, Sweden. [Burstrom, Kristina] Karolinska Inst, Dept Publ Hlth Sci, Equ & Hlth Policy Res Grp, Stockholm, Sweden. [Burstrom, Kristina] Stockholm Cty Council, Hlth Care Serv, Stockholm, Sweden. [Zethraeus, Niklas] Dent & Pharmaceut Benefits Agcy, Stockholm, Sweden. [Rolfson, Ola] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Nemes, S (reprint author), Swedish Hip Arthroplasty Register, Gothenburg, Sweden. EM szilard.nemes@registercentrum.se OI Rolfson, Ola/0000-0001-6534-1242 FU Swedish National Board of Health and Welfare; Swedish Association of Local Authorities and Regions; County Council of the Western Region of Sweden; Dr Felix Neuberghs Foundation; Wangstedts Foundation; Goran Bauer Foundation; Gothenburg Medical Association; Swedish Medical Association FX We would like to acknowledge helpful comments at the EuroQol Scientific Plenary Meeting 2014. This study is an analysis of the databases in the Swedish Hip Arthroplasty Register, which is funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions, and the County Council of the Western Region of Sweden. Research grants from Dr Felix Neuberghs Foundation, Wangstedts Foundation, Goran Bauer Foundation, Gothenburg Medical Association, and Swedish Medical Association have contributed financially to this study. The publication of the results is not contingent on the sponsor's approval. All valuable discussions in the Health Outcomes and Economic Evaluation Research Group and in the Equity and Health Policy Research Group at Karolinska Institutet are gratefully acknowledged, as well as suggestions received at the 31st EuroQol Plenary Meeting in Stockholm 2014. We would like to express our sincere thanks and appreciation to all orthopedic surgeons and administrators involved in the collection and registration of PROMs data for THR patients in Sweden for their devoted work. We would also like to thank the anonymous reviewers and the editor for their constructive and valuable comments and suggestions. NR 28 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD DEC PY 2015 VL 24 IS 12 BP 2963 EP 2970 DI 10.1007/s11136-015-1020-9 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA CU1CG UT WOS:000363256300018 PM 26038221 ER PT J AU Kamin, HS McCarthy, AE Abel, MR Jellinek, MS Baer, L Murphy, JM AF Kamin, Hayley S. McCarthy, Alyssa E. Abel, Madelaine R. Jellinek, Michael S. Baer, Lee Murphy, J. Michael TI Using a Brief Parent-Report Measure to Track Outcomes for Children and Teens with Internalizing Disorders SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Child psychiatry; Pediatrics; Depression; Anxiety disorders; Outcome assessment ID PEDIATRIC SYMPTOM CHECKLIST; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH-CARE; COGNITIVE-BEHAVIORAL INTERVENTION; PSYCHOMETRIC PROPERTIES; PSYCHOSOCIAL PROBLEMS; DEPRESSIVE-DISORDERS; COLLABORATIVE CARE; ANXIETY DISORDERS; UNITED-KINGDOM AB The Pediatric Symptom Checklist (PSC) is a widely-used, parent-completed measure of children's emotional and behavioral functioning. Previous research has shown that the PSC and its subscales are generally responsive to patient progress over the course of psychiatric treatment. In this naturalistic study, we examined the performance and utility of the five-item PSC Internalizing Subscale (PSC-IS) as an assessment of routine treatment in outpatient pediatric psychiatry. Parents and clinicians of 1,593 patients aged 17 or younger completed standardized measures at intake and three-month follow-up appointments. Comparisons between PSC-IS scores and clinician-reported diagnoses, internalizing symptoms, and overall functioning showed acceptable levels of agreement. Change scores on the PSC-IS were also larger among patients with internalizing diagnoses than those with non-internalizing diagnoses. As a brief measure of internalizing symptoms, the PSC may be particularly useful to mental health clinicians treating youth with depression and anxiety as a quality assurance or treatment outcome measure. C1 [Kamin, Hayley S.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [McCarthy, Alyssa E.] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. [Abel, Madelaine R.; Jellinek, Michael S.; Baer, Lee; Murphy, J. Michael] Massachusetts Gen Hosp, Child Psychiat Serv, Div Child & Adolescent Psychiat, Dept Psychiat, Boston, MA 02114 USA. [Jellinek, Michael S.; Baer, Lee; Murphy, J. Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Jellinek, Michael S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Div Child & Adolescent Psychiat, Dept Psychiat, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org FU Fuss Family Fund FX A portion of Dr. Murphy's time for the planning and data analysis for this study was made possible by a grant from the Fuss Family Fund. The support of the Fuss Family Fund is hereby gratefully acknowledged. NR 67 TC 2 Z9 2 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X EI 1573-3327 J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD DEC PY 2015 VL 46 IS 6 BP 851 EP 862 DI 10.1007/s10578-014-0525-8 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CT7WL UT WOS:000363025200003 PM 25476666 ER PT J AU Evans, SC Fite, PJ Hendrickson, ML Rubens, SL Mages, AK AF Evans, Spencer C. Fite, Paula J. Hendrickson, Michelle L. Rubens, Sonia L. Mages, Anna K. TI The Role of Reactive Aggression in the Link Between Hyperactive-Impulsive Behaviors and Peer Rejection in Adolescents SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE Attention-deficit/hyperactivity disorder (ADHD) symptoms; Hyperactive-impulsive behaviors; Proactive and reactive aggression; Peer rejection; Adolescents ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; PROACTIVE AGGRESSION; TEACHER RATINGS; LATINO/HISPANIC CHILDREN; DEPRESSIVE SYMPTOMS; DISRUPTIVE BEHAVIOR; CRITERION VALIDITY; HISPANIC CHILDREN; CONDUCT DISORDER AB Attention-deficit/hyperactivity disorder (ADHD) symptoms and aggressive behaviors are both associated with peer rejection, but little is known the nature of this association with respect to the two symptom dimensions of hyperactivity-impulsivity and inattention and different types of aggression. The present study examines the relations between dimensions of ADHD symptomatology, proactive and reactive aggression, and peer rejection in adolescence. Teacher-reported data were obtained for 200 high school students (grades 9-12; 48 % female; predominately Latino). In structural equation modeling path analyses, the indirect effects of reactive aggression accounted for the link between hyperactivity-impulsivity and peer rejection. Within the same model, neither inattention nor proactive aggression were associated with peer rejection. These findings suggest that reactive aggression may be a key mechanism through which hyperactive-impulsive behavior is associated with peer rejection. Future research and intervention efforts should address the role of reactive aggression among youth with ADHD symptomatology. C1 [Evans, Spencer C.; Fite, Paula J.; Hendrickson, Michelle L.; Mages, Anna K.] Univ Kansas, Clin Child Psychol Program, Dole Human Dev Ctr, Lawrence, KS 66045 USA. [Rubens, Sonia L.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Evans, SC (reprint author), Univ Kansas, Clin Child Psychol Program, Dole Human Dev Ctr, 1000 Sunnyside Ave, Lawrence, KS 66045 USA. EM spencerevans@ku.edu NR 70 TC 5 Z9 5 U1 3 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-398X EI 1573-3327 J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD DEC PY 2015 VL 46 IS 6 BP 903 EP 912 DI 10.1007/s10578-014-0530-y PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CT7WL UT WOS:000363025200008 PM 25552242 ER PT J AU Oliveira, AL Azevedo, DC Eajazi, A Palmer, WE Kwon, YM Bredella, MA Torriani, M AF Oliveira, Adriana L. Azevedo, Debora C. Eajazi, Alireza Palmer, William E. Kwon, Young-Min Bredella, Miriam A. Torriani, Martin TI Assessment of total hip arthroplasty as a predisposing factor for ischiofemoral impingement SO SKELETAL RADIOLOGY LA English DT Article DE Ischiofemoral; Impingement; Quadratus femoris; Hip; MRI; Total hip arthroplasty ID LESSER TROCHANTER; QUADRATUS FEMORIS; PAIN AB To examine the effect of total hip arthroplasty (THA) on ischiofemoral (IF) and quadratus femoris (QF) spaces with the hypothesis that THA does not affect ischiofemoral relationships. The study was IRB approved and complied with HIPAA guidelines. We identified consecutive MR examinations (pelvis and/or hip) obtained at our institution in adults (a parts per thousand yen18 years old) screened for THA-related complications. Native hips from the same individuals served as controls. We collected medical record data including age, gender, surgical history, and THA designs. Two radiologists independently measured the IF-RAD and IF-MRI (IF space on radiographs and MR imaging, respectively) and QF space (on MR imaging). Groups were compared using ANCOVA controlled for gender. The study group comprised 250 hips (132 subjects; 162 post-THA and 88 native hips). Subjects were aged 59 +/- 10 years, with 66 males and 66 females. Comparison of IF-MRI and QF spaces between native and post-THA hips showed no differences (P > 0.12) and IF-RAD was higher in post-THA subjects (P = 0.01). No differences in the IF-MRI and QF spaces were present between native hips and different THA designs (P > 0.4). IF-RAD of metal-on-metal THA was higher than that of native hips (P = 0.01) and trended higher than ceramic-on-polyethylene THA (P = 0.08), with the remaining comparisons showing no significant differences (P > 0.4). Radiographic- and MRI-based measures in patients with standard THA do not show narrowing of IF and QF spaces. C1 [Oliveira, Adriana L.; Azevedo, Debora C.; Eajazi, Alireza; Palmer, William E.; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Oliveira, Adriana L.; Azevedo, Debora C.; Eajazi, Alireza; Palmer, William E.; Kwon, Young-Min; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Kwon, Young-Min] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. EM mtorriani@mgh.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2015 VL 44 IS 12 BP 1755 EP 1760 DI 10.1007/s00256-015-2229-y PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CT8BR UT WOS:000363040500005 PM 26260537 ER PT J AU Chang, CY Huang, AJ Bredella, MA Torriani, M Halpern, EF Rosenthal, DI Springfield, DS AF Chang, Connie Y. Huang, Ambrose J. Bredella, Miriam A. Torriani, Martin Halpern, Elkan F. Rosenthal, Daniel I. Springfield, Dempsey S. TI Percutaneous CT-guided needle biopsies of musculoskeletal tumors: a 5-year analysis of non-diagnostic biopsies SO SKELETAL RADIOLOGY LA English DT Article DE Nondiagnostic; CT-guided biopsy; Percutaneous; Frozen pathology ID RESULTS CLINICALLY USEFUL; SOFT-TISSUE SARCOMA; CORE BIOPSY; ASPIRATION-CYTOLOGY; DIAGNOSTIC-ACCURACY; THYROID-NODULES; LESIONS; UTILITY; BONE; EXPERIENCE AB To study non-diagnostic CT-guided musculoskeletal biopsies and take steps to minimize them. Specifically we asked: (1) What malignant diagnoses have a higher non-diagnostic rate? (2) What factors of a non-diagnostic biopsy may warrant more aggressive pursuit? (3) Do intra-procedural frozen pathology (FP) or point-of-care (POC) cytology reduce the non-diagnostic biopsy rate? This study was IRB-approved and HIPAA-compliant. We retrospectively reviewed 963 consecutive CT-guided musculoskeletal biopsies. We categorized pathology results as malignant, benign, or non-diagnostic and recorded use of FP or POC cytology. Initial biopsy indication, final diagnosis, method of obtaining the final diagnosis of non-diagnostic biopsies, age of the patient, and years of biopsy attending experience were recorded. Groups were compared using Pearson's chi(2) test or Fisher's exact test. In all, 140 of 963 (15 %) biopsies were non-diagnostic. Lymphoma resulted in more non-diagnostic biopsies (P < 0.0001). While 67% of non-diagnostic biopsies yielded benign diagnoses, 33% yielded malignant diagnoses. Patients whose percutaneous biopsy was indicated due to the clinical context without malignancy history almost always generated benign results (96 %). Whereas 56% of biopsies whose indication was an imaging finding of a treatable lesion were malignant, 20% of biopsies whose indication was a history of malignancy were malignant. There was no statistically significant difference in the nondiagnostic biopsy rates of pediatric versus adult patients (P = 0.8) and of biopsy attendings with fewer versus more years of experience (P = 0.5). The non-diagnostic rates of biopsies with FP (8 %), POC cytology (25 %), or neither (24 %) were significantly different (P < 0.0001). Lymphoma is the malignant diagnosis most likely to result in a non-diagnostic biopsy. If the clinical and radiologic suspicion for malignancy is high, repeat biopsy is warranted. If the clinical context suggests a benign lesion, a non-diagnostic biopsy may be considered reassuring. Frozen pathology may decrease the non-diagnostic biopsy rate. C1 [Chang, Connie Y.; Huang, Ambrose J.; Bredella, Miriam A.; Torriani, Martin; Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Springfield, Dempsey S.] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Chang, CY (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St Yawkey 6E, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu; ajhuang@mgh.harvard.edu; mbredella@mgh.harvard.edu; mtorriani@mgh.harvard.edu; elk@ita-mgh.org; dirosenthal@mgh.harvard.edu; dsprin1927@gmail.com NR 38 TC 1 Z9 1 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2015 VL 44 IS 12 BP 1795 EP 1803 DI 10.1007/s00256-015-2235-0 PG 9 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CT8BR UT WOS:000363040500010 PM 26338069 ER PT J AU Chang, CY Simeone, FJ Huang, AJ AF Chang, Connie Y. Simeone, F. Joseph Huang, Ambrose J. TI Battery-powered bone drill: caution needed in densely blastic lesions SO SKELETAL RADIOLOGY LA English DT Article DE CT-guided biopsy; Tumor; Metastases ID PORCINE MANDIBULAR CONDYLE; TISSUE STIFFNESS; MUSCULOSKELETAL NEOPLASMS; OPEN BIOPSY; ACCURACY; DEVICE; MINERALIZATION; TUMORS AB Image-guided biopsies play an important role for pathologic diagnosis of bone tumors. Recently, motorized, battery powered bone marrow biopsy devices have been used to biopsy focal bone lesions with high accuracy. We present here two cases of densely blastic metastases where the biopsy sample could not be removed from the needle. These two cases suggest that if the lesion is densely blastic, then the sample should be small (< 5 mm) to ensure that the biopsy specimen will not be stuck within the biopsy needle. C1 [Chang, Connie Y.; Simeone, F. Joseph; Huang, Ambrose J.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. RP Chang, CY (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu; fsimeone@mgh.harvard.edu; ajhuang@mgh.harvard.edu NR 21 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2015 VL 44 IS 12 BP 1845 EP 1848 DI 10.1007/s00256-015-2241-2 PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA CT8BR UT WOS:000363040500017 PM 26315889 ER PT J AU Cheng, BQ Zhang, YY Wang, A Dong, YL Xie, ZC AF Cheng, Baiqi Zhang, Yiying Wang, Arthur Dong, Yuanlin Xie, Zhongcong TI Vitamin C Attenuates Isoflurane-Induced Caspase-3 Activation and Cognitive Impairment SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Isoflurane; Vitamin C; Caspase-3; Cognitive function ID BETA-PROTEIN-LEVELS; ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; OXIDATIVE STRESS; RISK-FACTOR; ANESTHESIA; SURGERY; CELLS; ACID; DEMENTIA AB Anesthetic isoflurane has been reported to induce caspase-3 activation. The underlying mechanism(s) and targeted intervention(s), however, remain largely to be determined. Vitamin C (VitC) inhibits oxidative stress and apoptosis. We therefore employed VitC to further determine the up-stream mechanisms and the down-stream consequences of the isoflurane-induced caspase-3 activation. H4 human neuroglioma cells overexpressed human amyloid precursor protein (H4-APP cells) and rat neuroblastoma cells were treated either with (1) 2 % isoflurane or (2) with the control condition, plus saline or 400 mu M VitC for 3 or 6 h. Western blot analysis and fluorescence assay were utilized at the end of the experiments to determine caspase-3 activation, levels of reactive oxygen species and ATP, and mitochondrial function. The interaction of isoflurane (1.4 % for 2 h) and VitC (100 mg/kg) on cognitive function in mice was also assessed in the fear conditioning system. Here, we show for the first time that the VitC treatment attenuated the isoflurane-induced caspase-3 activation. Moreover, VitC mitigated the isoflurane-induced increases in the levels of reactive oxygen species, opening of mitochondrial permeability transition pore, reduction in mitochondrial membrane potential, and the reduction in ATP levels in the cells. Finally, VitC ameliorated the isoflurane-induced cognitive impairment in the mice. Pending confirmation from future studies, these results suggested that VitC attenuated the isoflurane-induced caspase-3 activation and cognitive impairment by inhibiting the isoflurane-induced oxidative stress, mitochondrial dysfunction, and reduction in ATP levels. These findings would promote further research into the underlying mechanisms and targeted interventions of anesthesia neurotoxicity. C1 [Cheng, Baiqi; Zhang, Yiying; Wang, Arthur; Dong, Yuanlin; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Cheng, Baiqi; Zhang, Yiying; Wang, Arthur; Dong, Yuanlin; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Cheng, Baiqi] Jilin Univ, Coll Life Sci, Minist Educ, Key Lab Mol Enzymol & Engn, Changchun 130023, Peoples R China. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu FU National Institutes of Health, Bethesda, Maryland [R21AG038994, R01GM088801, R01AG041274]; Alzheimer's Association, Chicago, Illinois; Cure Alzheimer's Fund, Wellesley, Massachusetts FX This study was supported by R21AG038994, R01GM088801, and R01AG041274 from the National Institutes of Health, Bethesda, Maryland; Investigator-Initiated Research grant from Alzheimer's Association, Chicago, Illinois; and Cure Alzheimer's Fund, Wellesley, Massachusetts, to Zhongcong Xie. The Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital and Harvard Medical School, generously provided the cost of inhalation anesthetic isoflurane. NR 42 TC 8 Z9 8 U1 1 U2 20 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD DEC PY 2015 VL 52 IS 3 BP 1580 EP 1589 DI 10.1007/s12035-014-8959-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CS2LW UT WOS:000361903400042 PM 25367886 ER PT J AU Pardee, AB AF Pardee, Arthur B. TI Bioregulation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID BREAST-CANCER CELLS; ESCHERICHIA-COLI; FEEDBACK MECHANISM; DNA; BIOMARKERS; INHIBITORS; PROTEIN; BIOSYNTHESIS; METASTASIS; PROTEASOME AB During the 20th century great progress was made in genetics and biochemistry, and these were combined into a molecular biological understanding of functions of macromolecules. Further great discoveries will be made about bioregulations, applicable to scientific problems such as cell development and evolution, and to illnesses including heart disease through defective control of cholesterol production, and to neurological cell-based diseases. The "War Against Cancer" is still far from won. The present generation of scientists can develop clinical applications from recent basic science discoveries. (C) 2015 Wiley Periodicals, Inc. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM arthur_pardee@dfci.harvard.edu NR 63 TC 0 Z9 0 U1 1 U2 76 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 2015 VL 230 IS 12 BP 2898 EP 2902 DI 10.1002/jcp.25059 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA CQ1SC UT WOS:000360378000006 PM 26031897 ER PT J AU Campbell, JI Kanters, S Bennett, JE Thorlund, K Tsai, AC Mills, EJ Siedner, MJ AF Campbell, Jeffrey I. Kanters, Steve Bennett, John E. Thorlund, Kristian Tsai, Alexander C. Mills, Edward J. Siedner, Mark J. TI Comparative Effectiveness of Induction Therapy for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: A Network Meta-Analysis SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE cryptococcal meningitis; HIV/AIDS; induction therapy; network meta-analysis; therapeutics ID HIGH-DOSE FLUCONAZOLE; RANDOMIZED CONTROLLED-TRIAL; LIPOSOMAL AMPHOTERICIN-B; EARLY FUNGICIDAL ACTIVITY; AIDS PATIENTS; PLUS FLUCYTOSINE; IN-VITRO; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; ORAL FLUCONAZOLE AB Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin- fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine + triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis. C1 [Campbell, Jeffrey I.; Tsai, Alexander C.; Siedner, Mark J.] Harvard Univ, Sch Med, Boston, MA USA. [Kanters, Steve; Mills, Edward J.] Univ Ottawa, Fac Hlth Sci, Vancouver, BC, Canada. [Kanters, Steve] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada. [Bennett, John E.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Thorlund, Kristian] McMaster Univ, Fac Hlth Sci, Hamilton, ON, Canada. [Tsai, Alexander C.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Mills, Edward J.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Siedner, MJ (reprint author), MGH Ctr Global Hlth, 100 Cambridge St,15th Flr, Boston, MA 02114 USA. EM msiedner@mgh.harvard.edu NR 70 TC 0 Z9 0 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD WIN PY 2015 VL 2 IS 1 DI 10.1093/ofid/ofv010 PG 11 WC Infectious Diseases SC Infectious Diseases GA CP5KQ UT WOS:000359921100007 ER PT J AU Konstantopoulos, C Ribaudo, H Ragland, K Bangsberg, DR Li, JZ AF Konstantopoulos, Christina Ribaudo, Heather Ragland, Kathleen Bangsberg, David R. Li, Jonathan Z. TI Antiretroviral Regimen and Suboptimal Medication Adherence Are Associated With Low-Level Human Immunodeficiency Virus Viremia SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE adherence; antiretroviral therapy; low-level viremia ID DRUG-RESISTANCE; HIV-1-INFECTED PATIENTS; HIV-1 REPLICATION; VIRAL LOAD; THERAPY; INTERMITTENT; POPULATION; INHIBITORS; PROTEASE AB Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification. C1 [Konstantopoulos, Christina; Li, Jonathan Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Konstantopoulos, Christina] Meharry Med Coll, Nashville, TN 37208 USA. [Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Ragland, Kathleen] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Li, JZ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 65 Landsdowne St,Rm 421, Cambridge, MA 02139 USA. EM jli22@partners.org NR 16 TC 3 Z9 3 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD WIN PY 2015 VL 2 IS 1 DI 10.1093/ofid/ofu119 PG 4 WC Infectious Diseases SC Infectious Diseases GA CP5KQ UT WOS:000359921100016 ER PT J AU Kuhlen, JL Blumenthal, KG Sokol, CL Balekian, DS Weil, AA Varughese, CA Shenoy, ES Banerji, A AF Kuhlen, James L., Jr. Blumenthal, Kimberly G. Sokol, Caroline L. Balekian, Diana S. Weil, Ana A. Varughese, Christy A. Shenoy, Erica S. Banerji, Aleena TI Ceftaroline Desensitization Procedure in a Pregnant Patient With Multiple Drug Allergies SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE beta-lactam; ceftaroline; cross-reactivity; desensitization procedure; drug allergy ID CARBOPLATIN HYPERSENSITIVITY; SAFETY; VANCOMYCIN; PENICILLIN; PREVENTION; MANAGEMENT; OUTCOMES AB Validated skin testing is lacking for many drugs, including ceftaroline. The cross-reactivity between ceftaroline and other beta-lactam antibiotics is unknown. We report a case of a pregnant patient with cystic fibrosis and multiple drug allergies who required ceftaroline for methicillin-resistant Staphylococcus aureus pneumonia and underwent an uncomplicated empiric desensitization procedure. C1 [Kuhlen, James L., Jr.; Blumenthal, Kimberly G.; Sokol, Caroline L.; Balekian, Diana S.; Banerji, Aleena] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Kuhlen, James L., Jr.; Blumenthal, Kimberly G.; Sokol, Caroline L.; Balekian, Diana S.; Weil, Ana A.; Shenoy, Erica S.; Banerji, Aleena] Harvard Univ, Sch Med, Boston, MA USA. [Blumenthal, Kimberly G.; Shenoy, Erica S.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Sokol, Caroline L.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. [Weil, Ana A.; Varughese, Christy A.; Shenoy, Erica S.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Varughese, Christy A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Shenoy, Erica S.] Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. RP Kuhlen, JL (reprint author), Massachusetts Gen Hosp, Cox Allergy Associates 201, Boston, MA 02114 USA. EM jkuhlen@partners.org NR 23 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD WIN PY 2015 VL 2 IS 1 DI 10.1093/ofid/ofv027 PG 4 WC Infectious Diseases SC Infectious Diseases GA CP5KQ UT WOS:000359921100017 ER PT J AU Li, JZ Arnold, KB Lo, J Dugast, AS Plants, J Ribaudo, HJ Cesa, K Heisey, A Kuritzkes, DR Lauffenburger, DA Alter, G Landay, A Grinspoon, S Pereyra, F AF Li, Jonathan Z. Arnold, Kelly B. Lo, Janet Dugast, Anne-Sophie Plants, Jill Ribaudo, Heather J. Cesa, Kevin Heisey, Andrea Kuritzkes, Daniel R. Lauffenburger, Douglas A. Alter, Galit Landay, Alan Grinspoon, Steven Pereyra, Florencia TI Differential Levels of Soluble Inflammatory Markers by Human Immunodeficiency Virus Controller Status and Demographics SO OPEN FORUM INFECTIOUS DISEASES LA English DT Article DE antiretroviral therapy; gender; HIV elite controllers; inflammation; low-level viremia ID HIV-1 ELITE CONTROLLERS; NON-AIDS EVENTS; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; IMMUNOSUPPRESSIVE ROLE; VIRAL REPLICATION; IMMUNE ACTIVATION; INFECTED PATIENTS; LIFE EXPECTANCY; CLINICAL-TRIAL AB Background. Human immunodeficiency virus (HIV)-1 elite controllers (ECs) represent an ideal population to study the effects of HIV persistence on chronic inflammation in the absence of antiretroviral therapy (ART). Methods. Twenty inflammatory markers measured in cohorts of ECs, HIV suppressed noncontrollers, and HIV-uninfected controls were compared using rank-based tests and partial least squares discriminant analysis (PLSDA). Spearman correlations were determined among the inflammatory markers, residual viremia by the single-copy assay, and CD4(+) T cell slope. Results. Significant differences were seen between cohorts in 15 of the soluble inflammatory markers. Human immunodeficiency virus-1 ECs were found to have the highest levels for all of the markers with the exception of RANTES. In particular, median levels of 7 inflammatory markers (soluble CD14 [sCD14], interferon [IFN]-gamma, IFN-gamma-inducible protein [IP]-10, interleukin [IL]-4, IL-10, sCD40L, and granulocyte-macrophage colony-stimulating factor) were twice as high in the HIV-1 ECs compared with either of the HIV-suppressed or uninfected groups. Multivariate PLSDA analysis of inflammatory markers improved differentiation between the patient cohorts, discerning gender differences in inflammatory profile amongst individuals on suppressive ART. Soluble markers of inflammation in ECs were not associated with either levels of residual HIV-1 viremia or CD4(+) T cell decline. Conclusions. Despite maintaining relatively low levels of viremia, HIV-1 ECs had elevated levels of a set of key inflammatory markers. Additional studies are needed to determine whether ECs may benefit from ART and to further evaluate the observed gender differences. C1 [Li, Jonathan Z.; Heisey, Andrea; Kuritzkes, Daniel R.; Pereyra, Florencia] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Arnold, Kelly B.; Lauffenburger, Douglas A.] MIT, Cambridge, MA 02139 USA. [Lo, Janet; Cesa, Kevin; Grinspoon, Steven; Pereyra, Florencia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dugast, Anne-Sophie; Alter, Galit] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Plants, Jill; Landay, Alan] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Li, JZ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 65 Landsdowne St,Rm 435, Cambridge, MA 02139 USA. EM jli22@partners.org NR 49 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD WIN PY 2015 VL 2 IS 1 DI 10.1093/ofid/ofu117 PG 10 WC Infectious Diseases SC Infectious Diseases GA CP5KQ UT WOS:000359921100023 ER PT J AU Weil, AA Hohmann, EL AF Weil, Ana A. Hohmann, Elizabeth L. TI Fecal Microbiota Transplant: Benefits and Risks SO OPEN FORUM INFECTIOUS DISEASES LA English DT Editorial Material ID CLOSTRIDIUM-DIFFICILE INFECTION; INSULIN SENSITIVITY; GUT MICROBIOME; OBESITY C1 [Weil, Ana A.; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Weil, Ana A.; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Boston, MA USA. RP Weil, AA (reprint author), Massachusetts Gen Hosp, Infect Dis, 55 Fruit St,GRJ 520, Boston, MA 02114 USA. EM aweil@partners.org NR 16 TC 4 Z9 4 U1 1 U2 35 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 2328-8957 J9 OPEN FORUM INFECT DI JI Open Forum Infect. Dis. PD WIN PY 2015 VL 2 IS 1 DI 10.1093/ofid/ofv005 PG 2 WC Infectious Diseases SC Infectious Diseases GA CP5KQ UT WOS:000359921100037 ER PT J AU Guercio, BJ Donovan, NJ Ward, A Schultz, A Lorius, N Amariglio, RE Rentz, DM Johnson, KA Sperling, RA Marshall, GA AF Guercio, Brendan J. Donovan, Nancy J. Ward, Andrew Schultz, Aaron Lorius, Natacha Amariglio, Rebecca E. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Marshall, Gad A. TI Apathy is Associated With Lower Inferior Temporal Cortical Thickness in Mild Cognitive Impairment and Normal Elderly Individuals SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID BETA-AMYLOID DEPOSITION; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; FUNCTIONAL IMPAIRMENT; ATROPHY; DEMENTIA; INVENTORY; SPECT; PROGRESSION; TOMOGRAPHY AB Apathy is a common neuropsychiatric symptom in Alzheimer's disease dementia and amnestic mild cognitive impairment and is associated with cortical atrophy in Alzheimer's disease dementia. This study investigated possible correlations between apathy and cortical atrophy in 47 individuals with mild cognitive impairment and 19 clinically normal elderly. Backward elimination multivariate linear regression was used to evaluate the cross-sectional relationship between scores on the Apathy Evaluation Scale and thickness of several cortical regions and covariates. Lower inferior temporal cortical thickness was predictive of greater apathy. Greater anterior cingulate cortical thickness was also predictive of greater apathy, suggesting an underlying reactive process. C1 [Guercio, Brendan J.; Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Guercio, Brendan J.; Donovan, Nancy J.; Lorius, Natacha; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Donovan, Nancy J.; Ward, Andrew; Lorius, Natacha; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Ward, Andrew; Schultz, Aaron; Lorius, Natacha; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Marshall, GA (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. EM gamarshall@partners.org OI Ward, Andrew/0000-0001-6948-4814 FU Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694, R01 AG037497]; Harvard Medical School Scholars in Medicine Office; [R01 AG027435]; [K23 AG033634]; [K24 AG035007] FX This research was supported by R01 AG027435, K23 AG033634, K24 AG035007, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), and the Harvard Aging Brain Study (P01 AGO36694, R01 AG037497). Authors have also received research salary support from the Harvard Medical School Scholars in Medicine Office. NR 42 TC 8 Z9 9 U1 1 U2 55 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2015 VL 27 IS 1 BP E22 EP E27 DI 10.1176/appi.neuropsych.13060141 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CI2WE UT WOS:000354607600005 PM 25716491 ER PT J AU Ascierto, PA Atkins, M Bifulco, C Botti, G Cochran, A Davies, M Demaria, S Dummer, R Ferrone, S Formenti, S Gajewski, TF Garbe, C Khleif, S Kiessling, R Lo, R Lorigan, P Mc Arthur, G Masucci, G Melero, I Mihm, M Palmieri, G Parmiani, G Puzanov, I Romero, P Schilling, B Seliger, B Stroncek, D Taube, J Tomei, S Zarour, HM Testori, A Wang, E Galon, J Ciliberto, G Mozzillo, N Marincola, FM Thurin, M AF Ascierto, Paolo A. Atkins, Michael Bifulco, Carlo Botti, Gerardo Cochran, Alistair Davies, Michael Demaria, Sandra Dummer, Reinhard Ferrone, Soldano Formenti, Silvia Gajewski, Thomas F. Garbe, Claus Khleif, Samir Kiessling, Rolf Lo, Roger Lorigan, Paul Mc Arthur, Grant Masucci, Giuseppe Melero, Ignacio Mihm, Martin Palmieri, Giuseppe Parmiani, Giorgio Puzanov, Igor Romero, Pedro Schilling, Bastian Seliger, Barbara Stroncek, David Taube, Janis Tomei, Sara Zarour, Hassane M. Testori, Alessandro Wang, Ena Galon, Jerome Ciliberto, Gennaro Mozzillo, Nicola Marincola, Francesco M. Thurin, Magdalena TI Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014 SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article AB The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma. C1 [Ascierto, Paolo A.; Botti, Gerardo; Ciliberto, Gennaro; Mozzillo, Nicola] Fdn G Pascale, Ist Nazl Tumori, Naples, Italy. [Atkins, Michael] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Bifulco, Carlo] Providence Canc Ctr, Earle A Chiles Res Inst, Translat Mol Pathol, Portland, OR USA. [Cochran, Alistair] Univ Calif Los Angeles, David Geffen Sch Med, John Wayne Canc Inst, Dept Pathol & Lab Med, Santa Monica, CA USA. [Cochran, Alistair] Univ Calif Los Angeles, David Geffen Sch Med, John Wayne Canc Inst, Dept Surg, Santa Monica, CA USA. [Davies, Michael] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Demaria, Sandra] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY USA. [Demaria, Sandra] Weill Cornell Med Coll, Dept Pathol, New York, NY USA. [Dummer, Reinhard] Univ Hosp Zurich, Dept Dermatol, Skin Canc Unit, CH-8091 Zurich, Switzerland. [Ferrone, Soldano] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Formenti, Silvia] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY USA. [Gajewski, Thomas F.] Univ Chicago Med, Dept Med, Immunol & Canc Program, Chicago, IL USA. [Gajewski, Thomas F.] Univ Chicago Med, Dept Pathol, Immunol & Canc Program, Chicago, IL USA. [Garbe, Claus] Univ Tubingen, Dept Dermatol, Ctr Dermato Oncol, Tubingen, Germany. [Khleif, Samir] Georgia Regents Univ, Georgia Regents Univ Canc Ctr, Augusta, GA USA. [Kiessling, Rolf] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Lo, Roger] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lo, Roger] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Lo, Roger] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Lorigan, Paul] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England. [Mc Arthur, Grant] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Mc Arthur, Grant] Univ Melbourne, Melbourne, Vic 3010, Australia. [Masucci, Giuseppe] Karolinska Hosp, Dept Oncol Pathol, S-10401 Stockholm, Sweden. [Melero, Ignacio] Ctr Invest Med Aplicada, Navarra, Spain. [Melero, Ignacio] Univ Navarra Clin, Navarra, Spain. [Mihm, Martin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Palmieri, Giuseppe] CNR, Unit Canc Genet, Inst Biomol Chem, Sassari, Italy. [Parmiani, Giorgio] Ist Sci San Raffaele, Div Mol Oncol, Unit Bioimmunotherapy Solid Tumors, I-20132 Milan, Italy. [Puzanov, Igor] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Romero, Pedro] Ludwig Canc Res Ctr, Lausanne, Switzerland. [Romero, Pedro] Univ Lausanne, Lausanne, Switzerland. [Schilling, Bastian] Univ Duisburg Essen, West German Canc Ctr, Univ Hosp,W, Dept Dermatol, Essen, Germany. [Seliger, Barbara] Univ Halle Wittenberg, Inst Med Immunol, D-06108 Halle, Germany. [Stroncek, David] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Taube, Janis] Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. [Tomei, Sara] Sidra Med & Res Ctr, Div Translat Med, Doha, Qatar. [Zarour, Hassane M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Zarour, Hassane M.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA. [Zarour, Hassane M.] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15260 USA. [Testori, Alessandro] Ist Europeo Oncol, Milan, Italy. [Wang, Ena] Sidra Med & Res Ctr, Div Translat Med, Doha, Qatar. [Galon, Jerome] Univ Paris 05, Sorbonne Paris Cite, Ctr Rech Cordeliers, INSERM,UMRS1138,Lab Integrat Canc Immunol, Paris, France. [Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar. [Thurin, Magdalena] NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA. [Schilling, Bastian] German Canc Consortium DKTK, Essen, Germany. RP Ascierto, PA (reprint author), Fdn G Pascale, Ist Nazl Tumori, Naples, Italy. EM paolo.ascierto@gmail.com OI Demaria, Sandra/0000-0003-4426-0499; Palmieri, Giuseppe/0000-0002-4350-2276; MELERO BERMEJO, IGNACIO/0000-0002-1360-348X; Lorigan, Paul/0000-0002-8875-2164 FU Fondazione Melanoma Onlus; Society of ImmunoTherapy of Cancer (SITC) FX The meeting was supported by Fondazione Melanoma Onlus and the Society of ImmunoTherapy of Cancer (SITC). A special thanks to 3P Solution of Napoli for their support and cooperation in organizing the meeting and especially to Lucia Politi. NR 0 TC 4 Z9 4 U1 3 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD NOV 30 PY 2015 VL 13 AR 374 DI 10.1186/s12967-015-0736-1 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CX6ES UT WOS:000365794600002 PM 26619946 ER PT J AU Xie, E Kotha, A Biaco, T Sedani, N Zou, J Stashenko, P Duncan, MJ Campos-Neto, A Cayabyab, MJ AF Xie, Emily Kotha, Abhiroop Biaco, Tracy Sedani, Nikita Zou, Jonathan Stashenko, Phillip Duncan, Margaret J. Campos-Neto, Antonio Cayabyab, Mark J. TI Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance SO PLOS ONE LA English DT Article ID IN-VIVO; GASTROINTESTINAL-TRACT; TRANSGENIC MICE; SIV INFECTION; CAVITY; REPLICATION; PULLULANASE; INDUCTION; DEPLETION; DELETION AB The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis) that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases. C1 [Xie, Emily; Kotha, Abhiroop; Biaco, Tracy; Sedani, Nikita; Zou, Jonathan; Stashenko, Phillip; Campos-Neto, Antonio; Cayabyab, Mark J.] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA 02115 USA. [Xie, Emily; Kotha, Abhiroop; Biaco, Tracy; Sedani, Nikita; Zou, Jonathan; Stashenko, Phillip; Campos-Neto, Antonio; Cayabyab, Mark J.] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA. [Duncan, Margaret J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Stashenko, Phillip; Campos-Neto, Antonio; Cayabyab, Mark J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Cayabyab, MJ (reprint author), Forsyth Inst, Global Infect Dis Res Ctr, 245 First St, Cambridge, MA 02115 USA. EM mcayabyab@forsyth.org FU National Institute of Dental and Craniofacial Research [RO3 DE022525] FX This work was supported by a grant (RO3 DE022525) from the National Institute of Dental and Craniofacial Research. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 2 Z9 2 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 30 PY 2015 VL 10 IS 11 AR e0143422 DI 10.1371/journal.pone.0143422 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX7NW UT WOS:000365889800036 PM 26618634 ER PT J AU Hebenstreit, CL Madden, E Koo, KH Maguen, S AF Hebenstreit, Claire L. Madden, Erin Koo, Kelly H. Maguen, Shira TI Minimally adequate mental health care and latent classes of PTSD symptoms in female Iraq and Afghanistan veterans SO PSYCHIATRY RESEARCH LA English DT Article DE Women; Veterans; Service utilization; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSES; UNITED-STATES; DEPRESSION; DIAGNOSES; WAR; VA; SERVICES; EXPOSURE; ILLNESS AB Female veterans of Operations Enduring and Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) represent a growing segment of Department of Veterans Affairs (VA) health care users. A retrospective analysis used national VA medical records to identify factors associated with female OEF/OIF/OND veterans' completion of minimally adequate care (MAC) for PTSD, defined as the completion of at least nine mental health outpatient visits within a 15-week period or at least twelve consecutive weeks of medication use. The sample included female OEF/OIF/OND veterans with PTSD who initiated VA health care between 2007-2013, and were seen in outpatient mental health (N=2183). Multivariable logistic regression models examined factors associated with completing MAC for PTSD, including PTSD symptom expression (represented by latent class analysis), sociodemographic, military, clinical, and VA access factors. Within one year of initiating mental health care, 48.3% of female veterans completed MAC. Race/ethnicity, age, PTSD symptom class, additional psychiatric diagnoses, and VA primary care use were significantly associated with completion of MAC for PTSD. Results suggest that veterans presenting for PTSD treatment should be comprehensively evaluated to identify factors associated with inadequate completion of care. Treatments that are tailored to PTSD symptom class may help to address potential barriers. Published by Elsevier Ireland Ltd. C1 [Hebenstreit, Claire L.; Madden, Erin; Koo, Kelly H.; Maguen, Shira] San Francisco VA Med Ctr, Gen Med, San Francisco, CA 94121 USA. [Hebenstreit, Claire L.; Koo, Kelly H.; Maguen, Shira] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Hebenstreit, CL (reprint author), San Francisco VA Med Ctr, Gen Med, 4150 Clement St, San Francisco, CA 94121 USA. EM Claire.hebenstreit@va.gov FU San Francisco VA Medical Center; University of California, San Francisco; U.S. Department of Defense [W81XWH-11-2-0189]; VA Advanced Fellowship Program in Women's Health FX This research has been supported by the San Francisco VA Medical Center, the University of California, San Francisco, the U.S. Department of Defense Award Grant (W81XWH-11-2-0189), and the VA Advanced Fellowship Program in Women's Health. NR 39 TC 1 Z9 1 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 30 PY 2015 VL 230 IS 1 BP 90 EP 95 DI 10.1016/j.psychres.2015.08.028 PG 6 WC Psychiatry SC Psychiatry GA CS5SK UT WOS:000362138100014 PM 26330305 ER PT J AU Mpondo, BCT Neilson, E AF Mpondo, Bonaventura C. T. Neilson, Eric TI Renal dysfunction among HIV-infected patients starting antiretroviral therapy in Mwanza, Tanzania SO AIDS LA English DT Letter ID SCHISTOSOMA-MANSONI; DISEASE; AFRICA; ADULTS; RISK C1 [Mpondo, Bonaventura C. T.] Univ Dodoma, Coll Hlth & Allied Sci, Sch Med & Dent, Dept Internal Med, Dodoma, Tanzania. [Neilson, Eric] Massachusetts Gen Hosp, Ctr Global Hlth, Peace Corps SEED Global Hlth Serv Partnership, Boston, MA 02114 USA. RP Mpondo, BCT (reprint author), Univ Dodoma, Dodoma, Tanzania. EM boniempondo@gmail.com NR 17 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD NOV 28 PY 2015 VL 29 IS 18 BP 2531 EP 2532 DI 10.1097/QAD.0000000000000877 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DB4NV UT WOS:000368490800002 PM 26372486 ER PT J AU Murray, CJL Barber, RM Foreman, KJ Ozgoren, AA Abd-Allah, F Abera, SF Aboyans, V Abraham, JP Abubakar, I Abu-Raddad, LJ Abu-Rmeileh, NM Achoki, T Ackerman, IN Ademi, Z Adou, AK Adsuar, JC Afshin, A Agardh, EE Alam, SS Alasfoor, D Albittar, MI Alegretti, MA Alemu, ZA Alfonso-Cristancho, R Alhabib, S Ali, R Alla, F Allebeck, P Almazroa, MA Alsharif, U Alvarez, E Alvis-Guzman, N Amare, AT Ameh, EA Amini, H Ammar, W Anderson, HR Anderson, BO Antonio, CAT Anwari, P Arnlov, J Arsenijevic, VSA Artaman, A Asghar, RJ Assadi, R Atkins, LS Avila, MA Awuah, B Bachman, VF Badawi, A Bahit, MC Balakrishnan, K Banerjee, A Barker-Collo, SL Barquera, S Barregard, L Barrero, LH Basu, A Basu, S Basulaiman, MO Beardsley, J Bedi, N Beghi, E Bekele, T Bell, ML Benjet, C Bennett, DA Bensenor, IM Benzian, H Bernabe, E Bertozzi-Villa, A Beyene, TJ Bhala, N Bhalla, A Bhutta, ZA Bienhoff, K Bikbov, B Biryukov, S Blore, JD Blosser, CD Blyth, FM Bohensky, MA Bolliger, IW Basara, BB Bornstein, NM Bose, D Boufous, S Bourne, RRA Boyers, LN Brainin, M Brayne, CE Brazinova, A Breitborde, NJK Brenner, H Briggs, AD Brooks, PM Brown, JC Brugha, TS Buchbinder, R Buckle, GC Budke, CM Bulchis, A Bulloch, AG Campos-Nonato, IR Carabin, H Carapetis, JR Cardenas, R Carpenter, DO Caso, V Castaneda-Orjuela, CA Castro, RE Catala-Lopez, F Cavalleri, F Cavlin, A Chadha, VK Chang, JC Charlson, FJ Chen, HL Chen, WQ Chiang, PP Chimed-Ochir, O Chowdhury, R Christensen, H Christophi, CA Cirillo, M Coates, MM Coffeng, LE Coggeshall, MS Colistro, V Colquhoun, SM Cooke, GS Cooper, C Cooper, LT Coppola, LM Cortinovis, M Criqui, MH Crump, JA Cuevas-Nasu, L Danawi, H Dandona, L Dandona, R Dansereau, E Dargan, PI Davey, G Davis, A Davitoiu, DV Dayama, A De Leo, D Degenhardt, L Del Pozo-Cruz, B Dellavalle, RP Deribe, K Derrett, S Des Jarlais, DC Dessalegn, M Dharmaratne, SD Dherani, MK Diaz-Torne, C Dicker, D Ding, EL Dokova, K Dorsey, ER Driscoll, TR Duan, L Duber, HC Ebel, BE Edmond, KM Elshrek, YM Endres, M Ermakov, SP Erskine, HE Eshrati, B Esteghamati, A Estep, K Faraon, EJA Farzadfar, F Fay, DF Feigin, VL Felson, DT Fereshtehnejad, SM Fernandes, JG Ferrari, AJ Fitzmaurice, C Flaxman, AD Fleming, TD Foigt, N Forouzanfar, MH Fowkes, FGR Paleo, UF Franklin, RC Furst, T Gabbe, B Gaffikin, L Gankpe, FG Geleijnse, JM Gessner, BD Gething, P Gibney, KB Giroud, M Giussani, G Dantes, HG Gona, P Gonzalez-Medina, D Gosselin, RA Gotay, CC Goto, A Gouda, HN Graetz, N Gugnani, HC Gupta, R Gupta, R Gutierrez, RA Haagsma, J Hafezi-Nejad, N Hagan, H Halasa, YA Hamadeh, RR Hamavid, H Hammami, M Hancock, J Hankey, GJ Hansen, GM Hao, YT Harb, HL Haro, JM Havmoeller, R Hay, SI Hay, RJ Heredia-Pi, IB Heuton, KR Heydarpour, P Higashi, H Hijar, M Hoek, HW Hoffman, HJ Hosgood, HD Hossain, M Hotez, PJ Hoy, DG Hsairi, M Hu, GQ Huang, C Huang, JJ Husseini, A Huynh, C Iannarone, ML Iburg, KM Innos, K Inoue, M Islami, F Jacobsen, KH Jarvis, DL Jassal, SK Jee, SH Jeemon, P Jensen, PN Jha, V Jiang, GH Jiang, Y Jonas, JB Juel, K Kan, HD Karch, A Karema, CK Karimkhani, C Karthikeyan, G Kassebaum, NJ Kaul, A Kawakami, N Kazanjan, K Kemp, AH Kengne, AP Keren, A Khader, YS Khalifa, SEA Khan, EA Khan, G Khang, YH Kieling, C Kim, D Kim, S Kim, Y Kinfu, Y Kinge, JM Kivipelto, M Knibbs, LD Knudsen, AK Kokubo, Y Kosen, S Krishnaswami, S Defo, BK Bicer, BK Kuipers, EJ Kulkarni, C Kulkarni, VS Kumar, GA Kyu, HH Lai, T Lalloo, R Lallukka, T Lam, H Lan, Q Lansingh, VC Larsson, A Lawrynowicz, AEB Leasher, JL Leigh, J Leung, R Levitz, CE Li, B Li, YC Li, YM Lim, SS Lind, M Lipshultz, SE Liu, SW Liu, Y Lloyd, BK Lofgren, KT Logroscino, G Looker, KJ Lortet-Tieulent, J Lotufo, PA Lozano, R Lucas, RM Lunevicius, R Lyons, RA Ma, S Macintyre, MF Mackay, MT Majdan, M Malekzadeh, R Marcenes, W Margolis, DJ Margono, C Marzan, MB Masci, JR Mashal, MT Matzopoulos, R Mayosi, BM Mazorodze, TT Mcgill, NW Mcgrath, JJ Mckee, M McLain, A Meaney, PA Medina, C Mehndiratta, MM Mekonnen, W Melaku, YA Meltzer, M Memish, ZA Mensah, GA Meretoja, A Mhimbira, FA Micha, R Miller, TR Mills, EJ Mitchell, PB Mock, CN Ibrahim, NM Mohammad, KA Mokdad, AH Mola, GLD Monasta, L Hernandez, JCM Montico, M Montine, TJ Mooney, MD Moore, AR Moradi-Lakeh, M Moran, AE Mori, R Moschandreas, J Moturi, WN Moyer, ML Mozaffarian, D Msemburi, WT Mueller, UO Mukaigawara, M Mullany, EC Murdoch, ME Murray, J Murthy, KS Naghavi, M Naheed, A Naidoo, KS Naldi, L Nand, D Nangia, V Narayan, KMV Nejjari, C Neupane, SP Newton, CR Ng, M Ngalesoni, FN Nguyen, G Nisar, MI Nolte, S Norheim, OF Norman, RE Norrving, B Nyakarahuka, L Oh, IH Ohkubo, T Ohno, SL Olusanya, BO Opio, JN Ortblad, K Ortiz, A Pain, AW Pandian, JD Panelo, CIA Papachristou, C Park, EK Park, JH Patten, SB Patton, GC Paul, VK Pavlin, BI Pearce, N Pereira, DM Perez-Padilla, R Perez-Ruiz, F Perico, N Pervaiz, A Pesudovs, K Peterson, CB Petzold, M Phillips, MR Phillips, BK Phillips, DE Piel, FB Plass, D Poenaru, D Polinder, S Pope, D Popova, S Poulton, RG Pourmalek, F Prabhakaran, D Prasad, NM Pullan, RL Qato, DM Quistberg, DA Rafay, A Rahimi, K Rahman, SU Raju, M Rana, SM Razavi, H Reddy, KS Refaat, A Remuzzi, G Resnikoff, S Ribeiro, AL Richardson, L Richardus, JH Roberts, DA Rojas-Rueda, D Ronfani, L Roth, GA Rothenbacher, D Rothstein, DH Rowley, JT Roy, N Ruhago, GM Saeedi, MY Saha, S Sahraian, MA Sampson, UKA Sanabria, JR Sandar, L Santos, IS Satpathy, M Sawhney, M Scarborough, P Schneider, IJ Schottker, B Schumacher, AE Schwebel, DC Scott, JG Seedat, S Sepanlou, SG Serina, PT Servan-Mori, EE Shackelford, KA Shaheen, A Shahraz, S Levy, TS Shangguan, S She, J Sheikhbahaei, S Shi, PL Shibuya, K Shinohara, Y Shiri, R Shishani, K Shiue, I Shrime, MG Sigfusdottir, ID Silberberg, DH Simard, EP Sindi, S Singh, A Singh, JA Singh, L Skirbekk, V Slepak, EL Sliwa, K Soneji, S Soreide, K Soshnikov, S Sposato, LA Sreeramareddy, CT Stanaway, JD Stathopoulou, V Stein, DJ Stein, MB Steiner, C Steiner, TJ Stevens, A Stewart, A Stovner, LJ Stroumpoulis, K Sunguya, BF Swaminathan, S Swaroop, M Sykes, BL Tabb, KM Takahashi, K Tandon, N Tanne, D Tanner, M Tavakkoli, M Taylor, HR Te Ao, BJ Tediosi, F Temesgen, AM Templin, T Ten Have, M Tenkorang, EY Terkawi, AS Thomson, B Thorne-Lyman, AL Thrift, AG Thurston, GD Tillmann, T Tonelli, M Topouzis, F Toyoshima, H Traebert, J Tran, BX Trillini, M Truelsen, T Tsilimbaris, M Tuzcu, EM Uchendu, US Ukwaja, KN Undurraga, EA Uzun, SB Van Brakel, WH Van De Vijver, S van Gool, CH Van Os, J Vasankari, TJ Venketasubramanian, N Violante, FS Vlassov, VV Vollset, SE Wagner, GR Wagner, J Waller, SG Wan, X Wang, HD Wang, JL Wang, LH Warouw, TS Weichenthal, S Weiderpass, E Weintraub, RG Wang, WZ Werdecker, A Westerman, R Whiteford, HA Wilkinson, JD Williams, TN Wolfe, CD Wolock, TM Woolf, AD Wulf, S Wurtz, B Xu, GL Yan, LJL Yano, Y Ye, PP Yentur, GK Yip, P Yonemoto, N Yoon, SJ Younis, MZ Yu, CH Zaki, ME Zhao, Y Zheng, YF Zonies, D Zou, XN Salomon, JA Lopez, AD Vos, T AF Murray, Christopher J. L. Barber, Ryan M. Foreman, Kyle J. Ozgoren, Ayse Abbasoglu Abd-Allah, Foad Abera, Semaw F. Aboyans, Victor Abraham, Jerry P. Abubakar, Ibrahim Abu-Raddad, Laith J. Abu-Rmeileh, Niveen M. Achoki, Tom Ackerman, Ilana N. Ademi, Zanfina Adou, Arsene K. Adsuar, Jose C. Afshin, Ashkan Agardh, Emilie E. Alam, Sayed Saidul Alasfoor, Deena Albittar, Mohammed I. Alegretti, Miguel A. Alemu, Zewdie A. Alfonso-Cristancho, Rafael Alhabib, Samia Ali, Raghib Alla, Francois Allebeck, Peter Almazroa, Mohammad A. Alsharif, Ubai Alvarez, Elena Alvis-Guzman, Nelson Amare, Azmeraw T. Ameh, Emmanuel A. Amini, Heresh Ammar, Walid Anderson, H. Ross Anderson, Benjamin O. Antonio, Carl Abelardo T. Anwari, Palwasha Arnlov, Johan Arsenijevic, Valentina S. Arsic Artaman, Al Asghar, Rana J. Assadi, Reza Atkins, Lydia S. Avila, Marco A. Awuah, Baffour Bachman, Victoria F. Badawi, Alaa Bahit, Maria C. Balakrishnan, Kalpana Banerjee, Amitava Barker-Collo, Suzanne L. Barquera, Simon Barregard, Lars Barrero, Lope H. Basu, Arindam Basu, Sanjay Basulaiman, Mohammed O. Beardsley, Justin Bedi, Neeraj Beghi, Ettore Bekele, Tolesa Bell, Michelle L. Benjet, Corina Bennett, Derrick A. Bensenor, Isabela M. Benzian, Habib Bernabe, Eduardo Bertozzi-Villa, Amelia Beyene, Tariku J. Bhala, Neeraj Bhalla, Ashish Bhutta, Zulfiqar A. Bienhoff, Kelly Bikbov, Boris Biryukov, Stan Blore, Jed D. Blosser, Christopher D. Blyth, Fiona M. Bohensky, Megan A. Bolliger, Ian W. Basara, Berrak Bora Bornstein, Natan M. Bose, Dipan Boufous, Soufiane Bourne, Rupert R. A. Boyers, Lindsay N. Brainin, Michael Brayne, Carol E. Brazinova, Alexandra Breitborde, Nicholas J. K. Brenner, Hermann Briggs, Adam D. Brooks, Peter M. Brown, Jonathan C. Brugha, Traolach S. Buchbinder, Rachelle Buckle, Geoffrey C. Budke, Christine M. Bulchis, Anne Bulloch, Andrew G. Campos-Nonato, Ismael R. Carabin, Helene Carapetis, Jonathan R. Cardenas, Rosario Carpenter, David O. Caso, Valeria Castaneda-Orjuela, Carlos A. Castro, Ruben E. Catala-Lopez, Ferran Cavalleri, Fiorella Cavlin, Alanur Chadha, Vineet K. Chang, Jung-Chen Charlson, Fiona J. Chen, Honglei Chen, Wanqing Chiang, Peggy P. Chimed-Ochir, Odgerel Chowdhury, Rajiv Christensen, Hanne Christophi, Costas A. Cirillo, Massimo Coates, Matthew M. Coffeng, Luc E. Coggeshall, Megan S. Colistro, Valentina Colquhoun, Samantha M. Cooke, Graham S. Cooper, Cyrus Cooper, Leslie T. Coppola, Luis M. Cortinovis, Monica Criqui, Michael H. Crump, John A. Cuevas-Nasu, Lucia Danawi, Hadi Dandona, Lalit Dandona, Rakhi Dansereau, Emily Dargan, Paul I. Davey, Gail Davis, Adrian Davitoiu, Dragos V. Dayama, Anand De Leo, Diego Degenhardt, Louisa Del Pozo-Cruz, Borja Dellavalle, Robert P. Deribe, Kebede Derrett, Sarah Des Jarlais, Don C. Dessalegn, Muluken Dharmaratne, Samath D. Dherani, Mukesh K. Diaz-Torne, Cesar Dicker, Daniel Ding, Eric L. Dokova, Klara Dorsey, E. Ray Driscoll, Tim R. Duan, Leilei Duber, Herbert C. Ebel, Beth E. Edmond, Karen M. Elshrek, Yousef M. Endres, Matthias Ermakov, Sergey P. Erskine, Holly E. Eshrati, Babak Esteghamati, Alireza Estep, Kara Faraon, Emerito Jose A. Farzadfar, Farshad Fay, Derek F. Feigin, Valery L. Felson, David T. Fereshtehnejad, Seyed-Mohammad Fernandes, Jefferson G. Ferrari, Alize J. Fitzmaurice, Christina Flaxman, Abraham D. Fleming, Thomas D. Foigt, Nataliya Forouzanfar, Mohammad H. Fowkes, F. Gerry R. Paleo, Urbano Fra Franklin, Richard C. Fuerst, Thomas Gabbe, Belinda Gaffikin, Lynne Gankpe, Fortune G. Geleijnse, Johanna M. Gessner, Bradford D. Gething, Peter Gibney, Katherine B. Giroud, Maurice Giussani, Giorgia Gomez Dantes, Hector Gona, Philimon Gonzalez-Medina, Diego Gosselin, Richard A. Gotay, Carolyn C. Goto, Atsushi Gouda, Hebe N. Graetz, Nicholas Gugnani, Harish C. Gupta, Rahul Gupta, Rajeev Gutierrez, Reyna A. Haagsma, Juanita Hafezi-Nejad, Nima Hagan, Holly Halasa, Yara A. Hamadeh, Randah R. Hamavid, Hannah Hammami, Mouhanad Hancock, Jamie Hankey, Graeme J. Hansen, Gillian M. Hao, Yuantao Harb, Hilda L. Maria Haro, Josep Havmoeller, Rasmus Hay, Simon I. Hay, Roderick J. Heredia-Pi, Ileana B. Heuton, Kyle R. Heydarpour, Pouria Higashi, Hideki Hijar, Martha Hoek, Hans W. Hoffman, Howard J. Hosgood, H. Dean Hossain, Mazeda Hotez, Peter J. Hoy, Damian G. Hsairi, Mohamed Hu, Guoqing Huang, Cheng Huang, John J. Husseini, Abdullatif Huynh, Chantal Iannarone, Marissa L. Iburg, Kim M. Innos, Kaire Inoue, Manami Islami, Farhad Jacobsen, Kathryn H. Jarvis, Deborah L. Jassal, Simerjot K. Jee, Sun Ha Jeemon, Panniyammakal Jensen, Paul N. Jha, Vivekanand Jiang, Guohong Jiang, Ying Jonas, Jost B. Juel, Knud Kan, Haidong Karch, Andre Karema, Corine K. Karimkhani, Chante Karthikeyan, Ganesan Kassebaum, Nicholas J. Kaul, Anil Kawakami, Norito Kazanjan, Konstantin Kemp, Andrew H. Kengne, Andre P. Keren, Andre Khader, Yousef S. Khalifa, Shams Eldin A. Khan, Ejaz A. Khan, Gulfaraz Khang, Young-Ho Kieling, Christian Kim, Daniel Kim, Sungroul Kim, Yunjin Kinfu, Yohannes Kinge, Jonas M. Kivipelto, Miia Knibbs, Luke D. Knudsen, Ann Kristin Kokubo, Yoshihiro Kosen, Soewarta Krishnaswami, Sanjay Defo, Barthelemy Kuate Bicer, Burcu Kucuk Kuipers, Ernst J. Kulkarni, Chanda Kulkarni, Veena S. Kumar, G. Anil Kyu, Hmwe H. Lai, Taavi Lalloo, Ratilal Lallukka, Tea Lam, Hilton Lan, Qing Lansingh, Van C. Larsson, Anders Lawrynowicz, Alicia E. B. Leasher, Janet L. Leigh, James Leung, Ricky Levitz, Carly E. Li, Bin Li, Yichong Li, Yongmei Lim, Stephen S. Lind, Maggie Lipshultz, Steven E. Liu, Shiwei Liu, Yang Lloyd, Belinda K. Lofgren, Katherine T. Logroscino, Giancarlo Looker, Katharine J. Lortet-Tieulent, Joannie Lotufo, Paulo A. Lozano, Rafael Lucas, Robyn M. Lunevicius, Raimundas Lyons, Ronan A. Ma, Stefan Macintyre, Michael F. Mackay, Mark T. Majdan, Marek Malekzadeh, Reza Marcenes, Wagner Margolis, David J. Margono, Christopher Marzan, Melvin B. Masci, Joseph R. Mashal, Mohammad T. Matzopoulos, Richard Mayosi, Bongani M. Mazorodze, Tasara T. Mcgill, Neil W. Mcgrath, John J. Mckee, Martin McLain, Abigail Meaney, Peter A. Medina, Catalina Mehndiratta, Man Mohan Mekonnen, Wubegzier Melaku, Yohannes A. Meltzer, Michele Memish, Ziad A. Mensah, George A. Meretoja, Atte Mhimbira, Francis A. Micha, Renata Miller, Ted R. Mills, Edward J. Mitchell, Philip B. Mock, Charles N. Ibrahim, Norlinah Mohamed Mohammad, Karzan A. Mokdad, Ali H. Mola, Glen L. D. Monasta, Lorenzo Montanez Hernandez, Julio C. Montico, Marcella Montine, Thomas J. Mooney, Meghan D. Moore, Ami R. Moradi-Lakeh, Maziar Moran, Andrew E. Mori, Rintaro Moschandreas, Joanna Moturi, Wilkister N. Moyer, Madeline L. Mozaffarian, Dariush Msemburi, William T. Mueller, Ulrich O. Mukaigawara, Mitsuru Mullany, Erin C. Murdoch, Michele E. Murray, Joseph Murthy, Kinnari S. Naghavi, Mohsen Naheed, Aliya Naidoo, Kovin S. Naldi, Luigi Nand, Devina Nangia, Vinay Narayan, K. M. Venkat Nejjari, Chakib Neupane, Sudan P. Newton, Charles R. Ng, Marie Ngalesoni, Frida N. Nguyen, Grant Nisar, Muhammad I. Nolte, Sandra Norheim, Ole F. Norman, Rosana E. Norrving, Bo Nyakarahuka, Luke Oh, In-Hwan Ohkubo, Takayoshi Ohno, Summer L. Olusanya, Bolajoko O. Opio, John Nelson Ortblad, Katrina Ortiz, Alberto Pain, Amanda W. Pandian, Jeyaraj D. Panelo, Carlo Irwin A. Papachristou, Christina Park, Eun-Kee Park, Jae-Hyun Patten, Scott B. Patton, George C. Paul, Vinod K. Pavlin, Boris I. Pearce, Neil Pereira, David M. Perez-Padilla, Rogelio Perez-Ruiz, Fernando Perico, Norberto Pervaiz, Aslam Pesudovs, Konrad Peterson, Carrie B. Petzold, Max Phillips, Michael R. Phillips, Bryan K. Phillips, David E. Piel, Frederic B. Plass, Dietrich Poenaru, Dan Polinder, Suzanne Pope, Daniel Popova, Svetlana Poulton, Richie G. Pourmalek, Farshad Prabhakaran, Dorairaj Prasad, Noela M. Pullan, Rachel L. Qato, Dima M. Quistberg, D. Alex Rafay, Anwar Rahimi, Kazem Rahman, Sajjad U. Raju, Murugesan Rana, Saleem M. Razavi, Homie Reddy, K. Srinath Refaat, Amany Remuzzi, Giuseppe Resnikoff, Serge Ribeiro, Antonio L. Richardson, Lee Richardus, Jan Hendrik Roberts, D. Allen Rojas-Rueda, David Ronfani, Luca Roth, Gregory A. Rothenbacher, Dietrich Rothstein, David H. Rowley, Jane T. Roy, Nobhojit Ruhago, George M. Saeedi, Mohammad Y. Saha, Sukanta Sahraian, Mohammad Ali Sampson, Uchechukwu K. A. Sanabria, Juan R. Sandar, Logan Santos, Itamar S. Satpathy, Maheswar Sawhney, Monika Scarborough, Peter Schneider, Ione J. Schoettker, Ben Schumacher, Austin E. Schwebel, David C. Scott, James G. Seedat, Soraya Sepanlou, Sadaf G. Serina, Peter T. Servan-Mori, Edson E. Shackelford, Katya A. Shaheen, Amira Shahraz, Saeid Levy, Teresa Shamah Shangguan, Siyi She, Jun Sheikhbahaei, Sara Shi, Peilin Shibuya, Kenji Shinohara, Yukito Shiri, Rahman Shishani, Kawkab Shiue, Ivy Shrime, Mark G. Sigfusdottir, Inga D. Silberberg, Donald H. Simard, Edgar P. Sindi, Shireen Singh, Abhishek Singh, Jasvinder A. Singh, Lavanya Skirbekk, Vegard Slepak, Erica Leigh Sliwa, Karen Soneji, Samir Soreide, Kjetil Soshnikov, Sergey Sposato, Luciano A. Sreeramareddy, Chandrashekhar T. Stanaway, Jeffrey D. Stathopoulou, Vasiliki Stein, Dan J. Stein, Murray B. Steiner, Caitlyn Steiner, Timothy J. Stevens, Antony Stewart, Andrea Stovner, Lars J. Stroumpoulis, Konstantinos Sunguya, Bruno F. Swaminathan, Soumya Swaroop, Mamta Sykes, Bryan L. Tabb, Karen M. Takahashi, Ken Tandon, Nikhil Tanne, David Tanner, Marcel Tavakkoli, Mohammad Taylor, Hugh R. Te Ao, Braden J. Tediosi, Fabrizio Temesgen, Awoke M. Templin, Tara Ten Have, Margreet Tenkorang, Eric Y. Terkawi, Abdullah S. Thomson, Blake Thorne-Lyman, Andrew L. Thrift, Amanda G. Thurston, George D. Tillmann, Taavi Tonelli, Marcello Topouzis, Fotis Toyoshima, Hideaki Traebert, Jefferson Tran, Bach X. Trillini, Matias Truelsen, Thomas Tsilimbaris, Miltiadis Tuzcu, Emin M. Uchendu, Uche S. Ukwaja, Kingsley N. Undurraga, Eduardo A. Uzun, Selen B. Van Brakel, Wim H. Van De Vijver, Steven van Gool, Coen H. Van Os, Jim Vasankari, Tommi J. Venketasubramanian, N. Violante, Francesco S. Vlassov, Vasiliy V. Vollset, Stein Emil Wagner, Gregory R. Wagner, Joseph Waller, Stephen G. Wan, Xia Wang, Haidong Wang, Jianli Wang, Linhong Warouw, Tati S. Weichenthal, Scott Weiderpass, Elisabete Weintraub, Robert G. Wang Wenzhi Werdecker, Andrea Westerman, Ronny Whiteford, Harvey A. Wilkinson, James D. Williams, Thomas N. Wolfe, Charles D. Wolock, Timothy M. Woolf, Anthony D. Wulf, Sarah Wurtz, Brittany Xu, Gelin Yan, Lijing L. Yano, Yuichiro Ye, Pengpeng Yentur, Goekalp K. Yip, Paul Yonemoto, Naohiro Yoon, Seok-Jun Younis, Mustafa Z. Yu, Chuanhua Zaki, Maysaa E. Zhao, Yong Zheng, Yingfeng Zonies, David Zou, Xiaonong Salomon, Joshua A. Lopez, Alan D. Vos, Theo CA GBD 2013 DALYs Collaborator HALE Collaborator TI Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition SO LANCET LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; LOW SOCIOECONOMIC-STATUS; SELF-RATED HEALTH; SYSTEMATIC ANALYSIS; MORTALITY TRENDS; NONCOMMUNICABLE DISEASES; ECONOMIC-DEVELOPMENT; CHANGING RELATION; EUROPEAN-UNION; RISK-FACTORS AB Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6.2 years (95% UI 5.6-6.6), from 65.3 years (65.0-65.6) in 1990 to 71.5 years (71.0-71.9) in 2013, HALE at birth rose by 5.4 years (4.9-5.8), from 56.9 years (54.5-59.1) to 62.3 years (59.7-64.8), total DALYs fell by 3.6% (0.3-7.4), and age-standardised DALY rates per 100 000 people fell by 26.7% (24.6-29.1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. C1 [Murray, Christopher J. L.; Barber, Ryan M.; Foreman, Kyle J.; Achoki, Tom; Afshin, Ashkan; Bachman, Victoria F.; Bertozzi-Villa, Amelia; Bienhoff, Kelly; Biryukov, Stan; Blore, Jed D.; Bolliger, Ian W.; Brown, Jonathan C.; Bulchis, Anne; Coates, Matthew M.; Coffeng, Luc E.; Coggeshall, Megan S.; Dandona, Lalit; Dansereau, Emily; Dicker, Daniel; Duber, Herbert C.; Estep, Kara; Fitzmaurice, Christina; Flaxman, Abraham D.; Fleming, Thomas D.; Forouzanfar, Mohammad H.; Gonzalez-Medina, Diego; Graetz, Nicholas; Haagsma, Juanita; Hamavid, Hannah; Hancock, Jamie; Hansen, Gillian M.; Hay, Simon I.; Heuton, Kyle R.; Higashi, Hideki; Huynh, Chantal; Iannarone, Marissa L.; Kassebaum, Nicholas J.; Kyu, Hmwe H.; Levitz, Carly E.; Lim, Stephen S.; Lind, Maggie; Lofgren, Katherine T.; Lozano, Rafael; Macintyre, Michael F.; Margono, Christopher; McLain, Abigail; Mokdad, Ali H.; Mooney, Meghan D.; Moradi-Lakeh, Maziar; Moyer, Madeline L.; Msemburi, William T.; Mullany, Erin C.; Naghavi, Mohsen; Ng, Marie; Nguyen, Grant; Ohno, Summer L.; Ortblad, Katrina; Pain, Amanda W.; Phillips, Bryan K.; Phillips, David E.; Richardson, Lee; Roberts, D. 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RI Rahimi, Kazem/Q-1279-2015; Adsuar, Jose C/C-6558-2008; Pereira, David/M-9286-2013; Ribeiro, Antonio/C-2707-2009; Haro, Josep Maria/D-1423-2011; Degenhardt, Louisa/D-4515-2012; Hankey, Graeme /H-4968-2014; Kaul, Anil/B-2075-2016; Carabin, Helene/B-7600-2016; Whiteford, Harvey/A-4840-2009; Charlson, Fiona/F-5290-2011; Patten, Scott/B-4434-2011; Monasta, Lorenzo/B-1388-2012; Sepanlou, Sadaf/H-9343-2016; Bolliger, Ian/C-4207-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Naldi, Luigi/K-6343-2016; Thrift, Amanda/I-6251-2012; Weiderpass, Elisabete/M-4029-2016; Dokova, Klara/N-2448-2016; Jacobsen, Kathryn/B-5857-2008; Nolte, Sandra/B-7498-2008; Tonelli, Marcello/B-3028-2009; Lalloo, Ratilal/O-5624-2014; Tillmann, Taavi/R-6026-2016; Salomon, Joshua/D-3898-2009; Santos, Itamar/K-7055-2012; Patton, George/B-5246-2013; Scott, James/D-5900-2012; Brenner, Hermann/B-4627-2017; Majdan, Marek/K-5017-2012; Alsharif, Ubai/C-6527-2017; Amini, Heresh/B-3076-2010; Lotufo, Paulo/A-9843-2008; Karch, Andre/D-6973-2017; 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Deribe, Kebede/0000-0002-8526-6996; Taylor, Hugh/0000-0002-9437-784X; Khang, Young-Ho/0000-0002-9585-8266; Stein, Dan/0000-0001-7218-7810; Mitchell, Philip/0000-0002-7954-5235; Vlassov, Vasiliy/0000-0001-5203-549X; Soreide, Kjetil/0000-0001-7594-4354; Tediosi, Fabrizio/0000-0001-8671-9400; Miller, Ted/0000-0002-0958-2639; Giussani, Giorgia/0000-0003-2460-3095; Leung, Ricky/0000-0002-2852-6771; Kieling, Christian/0000-0001-7691-4149; Hay, Simon/0000-0002-0611-7272; Sreeramareddy, Chandrashekhar/0000-0002-5693-7631; Xu, Gelin/0000-0002-6194-0341; Goto, Atsushi/0000-0003-0669-654X; Soshnikov, Sergey/0000-0002-6983-7066; assadi, reza/0000-0002-5016-2994; Heydarpour, Pouria/0000-0001-5644-7555; Rahimi, Kazem/0000-0002-4807-4610; Adsuar, Jose C/0000-0001-7203-3168; Pereira, David/0000-0003-0384-7592; Ribeiro, Antonio/0000-0002-2740-0042; Haro, Josep Maria/0000-0002-3984-277X; Degenhardt, Louisa/0000-0002-8513-2218; Hankey, Graeme /0000-0002-6044-7328; Whiteford, Harvey/0000-0003-4667-6623; Charlson, Fiona/0000-0003-2876-5040; Patten, Scott/0000-0001-9871-4041; Monasta, Lorenzo/0000-0001-7774-548X; Sepanlou, Sadaf/0000-0002-3669-5129; Bolliger, Ian/0000-0001-8055-297X; LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Naldi, Luigi/0000-0002-3160-2835; Thrift, Amanda/0000-0001-8533-4170; Weiderpass, Elisabete/0000-0003-2237-0128; Jacobsen, Kathryn/0000-0002-4198-6246; Nolte, Sandra/0000-0001-6185-9423; Lalloo, Ratilal/0000-0001-5822-1269; Tillmann, Taavi/0000-0002-8428-3719; Salomon, Joshua/0000-0003-3929-5515; Santos, Itamar/0000-0003-3212-8466; Patton, George/0000-0001-5039-8326; Scott, James/0000-0002-0744-0688; Brenner, Hermann/0000-0002-6129-1572; Majdan, Marek/0000-0001-8037-742X; Alsharif, Ubai/0000-0002-4024-3950; Amini, Heresh/0000-0002-4825-1322; Lotufo, Paulo/0000-0002-4856-8450; Karch, Andre/0000-0003-3014-8543; Franklin, Richard/0000-0003-1864-4552; Ermakov, Sergey/0000-0003-1072-1162; Higashi, Hideki/0000-0002-5534-0905; Gibney, Katherine/0000-0001-5851-5339; Leasher, Janet/0000-0002-8779-5162; Davis, Adrian/0000-0001-7134-7528; Banerjee, Amitava/0000-0001-8741-3411; Hotez, Peter/0000-0001-8770-1042; Undurraga, Eduardo/0000-0002-4425-1253; Balakrishnan, Kalpana/0000-0002-5905-1801; Montico, Marcella/0000-0003-0377-8232; Vlassov, Valentin/0000-0003-2845-2992; Mhimbira, Francis/0000-0001-8989-6832; Olusanya, Bolajoko/0000-0002-3826-0583; Castaneda-Orjuela, Carlos/0000-0002-8735-6223; Heredia-Pi, Ileana Beatriz/0000-0002-9998-9239 FU Bill & Melinda Gates Foundation; Graduate School of Medical Sciences, University Medical Center Groningen (UMCG); National Health and Medical Research Council; National Natural Sciences Foundation of China; German National Cohort Consortium; Brien Holden Vision Institute; National Health and Medical Research Council Public Health (Australian) Early Career Fellowship; Wellcome Trust Fellowship in Public Health and Tropical Medicine [099876]; National Natural Science Foundation for Young Scholars of China [81200051]; Research Fund for the Doctoral Program of Higher Education of China [20110071120060]; Science Foundation for Young Scholars in Zhongshan Hospital [2012ZSQN04]; Scientific Project for Fudan University [20520133474]; Australian National Health and Medical Research Council Senior Principal Research Fellow; Swiss National Science Foundation [PBBSP3-146869, P300P3-154634]; Korean Health Technology R&D Project (Ministry of Health & Welfare, Republic of Korea) [HI13C0729]; CGIAR Research Program on Aquatic Agricultural Systems FX Bill & Melinda Gates Foundation.; On behalf of the GBD 2010 Genitourinary Diseases Expert Group, GR, NoP, and BB would like to acknowledge that their activities within the GBD 2013 have been made on the behalf of the International Society of Nephrology (ISN). ATA received institutional support and grants from the Graduate School of Medical Sciences, University Medical Center Groningen (UMCG). JM has received support from the National Health and Medical Research Council. LLY is also supported by the National Natural Sciences Foundation of China. UOM would like to acknowledge his funding by the German National Cohort Consortium. RB was provided funding support by the Brien Holden Vision Institute. INA would like to acknowledge her funding support from the National Health and Medical Research Council Public Health (Australian) Early Career Fellowship. KD is supported by a Wellcome Trust Fellowship in Public Health and Tropical Medicine (grant number 099876). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. JS was supported by the National Natural Science Foundation for Young Scholars of China, (number 81200051); Research Fund for the Doctoral Program of Higher Education of China (number 20110071120060); Science Foundation for Young Scholars in Zhongshan Hospital (number 2012ZSQN04); and the Scientific Project for Fudan University (number 20520133474). RB is funded by an Australian National Health and Medical Research Council Senior Principal Research Fellow. TF is grateful to the Swiss National Science Foundation for an Early and an Advanced Postdoc Mobility fellowship (project numbers PBBSP3-146869 and P300P3-154634). SJY and IHO received funding for their work in a grant from the Korean Health Technology R&D Project (Ministry of Health & Welfare, Republic of Korea; grant number HI13C0729). ALT-L was supported by the CGIAR Research Program on Aquatic Agricultural Systems. NR 60 TC 213 Z9 229 U1 80 U2 251 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD NOV 28 PY 2015 VL 386 IS 10009 BP 2145 EP 2191 DI 10.1016/S0140-6736(15)61340-X PG 47 WC Medicine, General & Internal SC General & Internal Medicine GA CX8YW UT WOS:000365992600030 ER PT J AU Brown, M Kuperberg, GR AF Brown, Meredith Kuperberg, Gina R. TI A Hierarchical Generative Framework of Language Processing: Linking Language Perception, Interpretation, and Production Abnormalities in Schizophrenia SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Review DE schizophrenia; language; generative models; speech perception; thought disorder; auditory verbal hallucinations ID AUDITORY VERBAL HALLUCINATIONS; SUPERIOR TEMPORAL GYRUS; CONTINUOUS SPEECH RECOGNITION; FORMAL THOUGHT-DISORDER; SEVERE MENTAL-ILLNESS; COGNITIVE REMEDIATION; 1ST-EPISODE SCHIZOPHRENIA; FUNCTIONAL CONNECTIVITY; NEUROCOGNITIVE DEFICITS; COMMUNICATION DISORDERS AB Language and thought dysfunction are central to the schizophrenia syndrome. They are evident in the major symptoms of psychosis itself, particularly as disorganized language output (positive thought disorder) and auditory verbal hallucinations (AVHs), and they also manifest as abnormalities in both high-level semantic and contextual processing and low-level perception. However, the literatures characterizing these abnormalities have largely been separate and have sometimes provided mutually exclusive accounts of aberrant language in schizophrenia. In this review, we propose that recent generative probabilistic frameworks of language processing can provide crucial insights that link these four lines of research. We first outline neural and cognitive evidence that real-time language comprehension and production normally involve internal generative circuits that propagate probabilistic predictions to perceptual cortices predictions that are incrementally updated based on prediction error signals as new inputs are encountered. We then explain how disruptions to these circuits may compromise communicative abilities in schizophrenia by reducing the efficiency and robustness of both high-level language processing and low-level speech perception. We also argue that such disruptions may contribute to the phenomenology of thought-disordered speech and false perceptual inferences in the language system (i.e., AVHs). This perspective suggests a number of productive avenues for future research that may elucidate not only the mechanisms of language abnormalities in schizophrenia, but also promising directions for cognitive rehabilitation. C1 [Brown, Meredith; Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Brown, Meredith; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Brown, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM mbrown@alum.mit.edu FU NSF [SMA-1513806]; NM [R01MH071635] FX This work was supported by NSF grant SMA-1513806 to MB and NM grant R01MH071635 to GK. NR 291 TC 1 Z9 1 U1 9 U2 18 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD NOV 27 PY 2015 VL 9 AR 643 DI 10.3389/fnhum.2015.00643 PG 23 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA CY7DU UT WOS:000366569200001 PM 26640435 ER PT J AU Yang, LH Guell, M Niu, D George, H Lesha, E Grishin, D Aach, J Shrock, E Xu, WH Poci, J Cortazio, R Wilkinson, RA Fishman, JA Church, G AF Yang, Luhan Gueell, Marc Niu, Dong George, Haydy Lesha, Emal Grishin, Dennis Aach, John Shrock, Ellen Xu, Weihong Poci, Juergen Cortazio, Rebeca Wilkinson, Robert A. Fishman, Jay A. Church, George TI Genome-wide inactivation of porcine endogenous retroviruses (PERVs) SO SCIENCE LA English DT Article ID HUMAN-CELLS; TRANSGENIC PIGS; NO EVIDENCE; XENOTRANSPLANTATION; INFECTION; DNA AB The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation. C1 [Yang, Luhan; Gueell, Marc; Niu, Dong; George, Haydy; Lesha, Emal; Grishin, Dennis; Aach, John; Shrock, Ellen; Poci, Juergen; Cortazio, Rebeca; Church, George] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02138 USA. [Yang, Luhan; Gueell, Marc; Church, George] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. [Yang, Luhan; Gueell, Marc; Church, George] eGenesis Biosci, Boston, MA 02115 USA. [Niu, Dong] Zhejiang Univ, Coll Anim Sci, Hangzhou 310058, Zhejiang, Peoples R China. [Wilkinson, Robert A.; Fishman, Jay A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Boston, MA 02115 USA. [Xu, Weihong] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yang, LH (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02138 USA. EM luhan.yang@egenesisbio.com; gchurch@genetics.med.harvard.edu OI Guell, Marc/0000-0003-4000-7912; Lesha, Emal/0000-0002-8902-3537 FU Human Frontier Science Program Long Term fellowship; NIH [P50 HG005550] FX We thank Z. Herbert and M. Vangala at the Dana-Farber Genomics Core Facility for assistance with RNA analysis, Y. Shen and O. Castanon for volunteering in laboratory research, and S. Broder for scientific advice. M.G. is funded by a Human Frontier Science Program Long Term fellowship. This study was funded by NIH grant P50 HG005550. L.Y., G.C., and M.G. are inventors on a patent filed by Harvard University that covers the work in this manuscript. L.Y., G.C., and M.G. are founding members of eGenesisBio. Pig cells are available from G.C. under a materials transfer agreement with Harvard University. NR 20 TC 64 Z9 74 U1 27 U2 145 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 27 PY 2015 VL 350 IS 6264 BP 1101 EP 1104 DI 10.1126/science.aad1191 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CY5BJ UT WOS:000366422600046 PM 26456528 ER PT J AU Auld, AF Shiraishi, RW Mbofana, F Couto, A Fetogang, EB El-Halabi, S Lebelonyane, R Pilatwe, PT Hamunime, N Okello, V Mutasa-Apollo, T Mugurungi, O Murungu, J Dzangare, J Kwesigabo, G Wabwire-Mangen, F Mulenga, M Hachizovu, S Ettiegne-Traore, V Mohamed, F Bashorun, A Nhan, DT Hai, NH Quang, TH Van Onacker, JD Francois, K Robin, EG Desforges, G Farahani, M Kamiru, H Nuwagaba-Biribonwoha, H Ehrenkranz, P Denison, JA Koole, O Tsui, S Torpey, K Mukadi, YD van Praag, E Menten, J Mastro, TD Hamilton, CD Abiri, OO Griswold, M Pierre, E Xavier, C Alfredo, C Jobarteh, K Letebele, M Agolory, S Baughman, AL Mutandi, G Preko, P Ryan, C Ao, T Gonese, E Herman-Roloff, A Ekra, KA Kouakou, JS Odafe, S Onoru, D Dalhatu, I Debem, HH Nguyen, DB Yen, LN Abdul-Quader, AS Pelletier, V Williams, SG Behel, S Bicego, G Swaminathan, M Dokubo, EK Adjorlolo-Johnson, G Marlink, R Lowrance, D Spira, T Colebunders, R Bangsberg, D Zee, A Kaplan, J Ellerbrock, TV AF Auld, Andrew F. Shiraishi, Ray W. Mbofana, Francisco Couto, Aleny Fetogang, Ernest Benny El-Halabi, Shenaaz Lebelonyane, Refeletswe Pilatwe, Tlhagiso Pilatwe Hamunime, Ndapewa Okello, Velephi Mutasa-Apollo, Tsitsi Mugurungi, Owen Murungu, Joseph Dzangare, Janet Kwesigabo, Gideon Wabwire-Mangen, Fred Mulenga, Modest Hachizovu, Sebastian Ettiegne-Traore, Virginie Mohamed, Fayama Bashorun, Adebobola Do Thi Nhan Nguyen Huu Hai Tran Huu Quang Van Onacker, Joelle Deas Francois, Kesner Robin, Ermane G. Desforges, Gracia Farahani, Mansour Kamiru, Harrison Nuwagaba-Biribonwoha, Harriet Ehrenkranz, Peter Denison, Julie A. Koole, Olivier Tsui, Sharon Torpey, Kwasi Mukadi, Ya Diul van Praag, Eric Menten, Joris Mastro, Timothy D. Hamilton, Carol Dukes Abiri, Oseni Omomo Griswold, Mark Pierre, Edna Xavier, Carla Alfredo, Charity Jobarteh, Kebba Letebele, Mpho Agolory, Simon Baughman, Andrew L. Mutandi, Gram Preko, Peter Ryan, Caroline Ao, Trong Gonese, Elizabeth Herman-Roloff, Amy Ekra, Kunomboa A. Kouakou, Joseph S. Odafe, Solomon Onoru, Dennis Dalhatu, Ibrahim Debem, Henry H. Nguyen, Duc B. Le Ngoc Yen Abdul-Quader, Abu S. Pelletier, Valerie Williams, Seymour G. Behel, Stephanie Bicego, George Swaminathan, Mahesh Dokubo, E. Kainne Adjorlolo-Johnson, Georgette Marlink, Richard Lowrance, David Spira, Thomas Colebunders, Robert Bangsberg, David Zee, Aaron Kaplan, Jonathan Ellerbrock, Tedd V. TI Lower Levels of Antiretroviral Therapy Enrollment Among Men with HIV Compared with Women-12 Countries, 2002-2013 SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT LA English DT Article ID GENDER; VIETNAM; AFRICA C1 [Auld, Andrew F.; Shiraishi, Ray W.; Behel, Stephanie; Bicego, George; Swaminathan, Mahesh; Dokubo, E. Kainne; Spira, Thomas; Zee, Aaron; Kaplan, Jonathan; Ellerbrock, Tedd V.] CDC, Ctr Global Hlth, Div Global HIV AIDS, Atlanta, GA 30333 USA. [Mbofana, Francisco; Couto, Aleny] Natl Inst Hlth, Maputo, Mozambique. [Fetogang, Ernest Benny; El-Halabi, Shenaaz; Lebelonyane, Refeletswe; Pilatwe, Tlhagiso Pilatwe] Minist Hlth, Gaborone, Botswana. [Hamunime, Ndapewa] Minist Hlth & Social Serv, Windhoek, Namibia. [Okello, Velephi] Minist Hlth, Basel, Switzerland. [Mutasa-Apollo, Tsitsi; Mugurungi, Owen; Murungu, Joseph; Dzangare, Janet] Minist Hlth, Harare, Zimbabwe. [Kwesigabo, Gideon] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Wabwire-Mangen, Fred] Makerere Univ, Infect Dis Inst, Coll Hlth Sci, Kampala, Uganda. [Mulenga, Modest; Hachizovu, Sebastian] Trop Dis Res Ctr, Harare, Zimbabwe. [Ettiegne-Traore, Virginie] Minist Hlth, Yamoussoukro, Cote Ivoire. [Mohamed, Fayama] Directorate Gen Budget & Finance, Yamoussoukro, Cote Ivoire. [Bashorun, Adebobola] Minist Hlth, Abuja, Nigeria. [Do Thi Nhan; Nguyen Huu Hai] Vietnam Author HIV AIDS Control, Hanoi, Vietnam. [Tran Huu Quang] Hanoi Sch Publ Hlth, Hanoi, Vietnam. [Van Onacker, Joelle Deas; Francois, Kesner; Robin, Ermane G.; Desforges, Gracia] Programme Natl Lutte Sida MSPP, Port Au Prince, Haiti. [Farahani, Mansour] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Kamiru, Harrison; Nuwagaba-Biribonwoha, Harriet] ICAP, New York, NY USA. [Ehrenkranz, Peter] Gates Fdn, Seattle, WA USA. [Denison, Julie A.; Tsui, Sharon] FHI 360, Social & Behav Hlth Sci, Washington, DC USA. [Koole, Olivier; Menten, Joris; Colebunders, Robert] Inst Trop Med, Dept Clin Sci, Louvain, Belgium. [Torpey, Kwasi] FHI 360, Lusaka, Zambia. [Mukadi, Ya Diul] FHI 360, Port Au Prince, Haiti. [van Praag, Eric] FHI 360, Dodoma, Tanzania. [Mastro, Timothy D.; Hamilton, Carol Dukes] FHI 360, Global Hlth Populat & Nutr, Durham, NC USA. [Abiri, Oseni Omomo; Preko, Peter] Univ Texas Houston, Sch Biomed Informat, Houston, TX USA. [Griswold, Mark; Pierre, Edna] Natl Alliance State & Terr AIDS Directors, Washington, DC USA. [Xavier, Carla; Alfredo, Charity; Jobarteh, Kebba] CDC, Div Global HIV AIDS, Ctr Global Hlth, Maputo, Mozambique. [Letebele, Mpho; Agolory, Simon; Baughman, Andrew L.; Mutandi, Gram] CDC, Div Global HIV AIDS, Ctr Global Hlth, Gaborone, Botswana. [Agolory, Simon; Baughman, Andrew L.; Mutandi, Gram] CDC, Div Global HIV AIDS, Ctr Global Hlth, Windhoek, Namibia. [Ryan, Caroline; Ao, Trong] CDC, Div Global HIV AIDS, Ctr Global Hlth, Basel, Switzerland. [Gonese, Elizabeth; Herman-Roloff, Amy] CDC, Div Global HIV AIDS, Ctr Global Hlth, Harare, Zimbabwe. [Ekra, Kunomboa A.; Kouakou, Joseph S.] CDC, Div Global HIV AIDS, Ctr Global Hlth, Yamoussoukro, Cote Ivoire. [Odafe, Solomon; Onoru, Dennis; Dalhatu, Ibrahim; Debem, Henry H.] CDC, Div Global HIV AIDS, Ctr Global Hlth, Abuja, Nigeria. [Nguyen, Duc B.; Le Ngoc Yen; Abdul-Quader, Abu S.] CDC, Div Global HIV AIDS, Ctr Global Hlth, Hanoi, Vietnam. [Pelletier, Valerie] CDC, Div Global HIV AIDS, Ctr Global Hlth, Port Au Prince, Haiti. [Williams, Seymour G.] CDC, Div Global Hlth Protect, Ctr Global Hlth, Durban, South Africa. [Adjorlolo-Johnson, Georgette] Elizabeth Glaser Pediat AIDS Fdn, Los Angeles, CA USA. [Lowrance, David] CDC, Ctr Global Hlth, Div Global Hlth Protect, Port Au Prince, Haiti. [Bangsberg, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Auld, AF (reprint author), CDC, Ctr Global Hlth, Div Global HIV AIDS, Atlanta, GA 30333 USA. EM aauld@cdc.gov NR 10 TC 6 Z9 7 U1 2 U2 4 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 0149-2195 EI 1545-861X J9 MMWR-MORBID MORTAL W JI MMWR-Morb. Mortal. Wkly. Rep. PD NOV 27 PY 2015 VL 64 IS 46 BP 1281 EP 1286 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CX9DJ UT WOS:000366004900002 PM 26605861 ER PT J AU Graham, DB Root, DE AF Graham, Daniel B. Root, David E. TI Resources for the design of CRISPR gene editing experiments SO GENOME BIOLOGY LA English DT Review ID PLURIPOTENT STEM-CELLS; OFF-TARGET SITES; SEQUENCE-SPECIFIC CONTROL; ZINC-FINGER TARGETER; GENOME-WIDE ANALYSIS; FUNCTIONAL GENOMICS; GUIDE-RNA; MAMMALIAN-CELLS; MOUSE MODELS; CAS9 AB CRISPR-based approaches have quickly become a favored method to perturb genes to uncover their functions. Here, we review the key considerations in the design of genome editing experiments, and survey the tools and resources currently available to assist users of this technology. C1 [Graham, Daniel B.; Root, David E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Graham, Daniel B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Graham, Daniel B.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Root, DE (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM droot@broadinstitute.org FU Functional Genomics Consortium FX We thank the members of Broad Institute's Genetic Perturbation Platform for helpful discussions and the Functional Genomics Consortium for support. NR 107 TC 12 Z9 13 U1 14 U2 71 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD NOV 27 PY 2015 VL 16 AR 260 DI 10.1186/s13059-015-0823-x PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CX3BU UT WOS:000365571300001 PM 26612492 ER PT J AU Kuijten, MMP Degeling, MH Chen, JW Wojtkiewicz, G Waterman, P Weissleder, R Azzi, J Nicolay, K Tannous, BA AF Kuijten, Maayke M. P. Degeling, M. Hannah Chen, John W. Wojtkiewicz, Gregory Waterman, Peter Weissleder, Ralph Azzi, Jamil Nicolay, Klaas Tannous, Bakhos A. TI Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging SO SCIENTIFIC REPORTS LA English DT Article ID TEMPERATURE-SENSITIVE LIPOSOMES; MAGNETIC-RESONANCE; PARAMAGNETIC LIPOSOMES; CONTRAST AGENTS; DRUG-DELIVERY; HYPERTHERMIA; FLUORESCENCE; RELEASE; SYSTEM; CANCER AB Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging. C1 [Kuijten, Maayke M. P.; Degeling, M. Hannah; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. [Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Kuijten, Maayke M. P.; Degeling, M. Hannah; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Kuijten, Maayke M. P.; Nicolay, Klaas] Eindhoven Univ Technol, Dept Biomed Engn, Biomed NMR, NL-5600 MB Eindhoven, Netherlands. [Degeling, M. Hannah] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. [Azzi, Jamil] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr,Renal Div, Boston, MA 02114 USA. [Azzi, Jamil] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02114 USA. RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Boston, MA 02114 USA. EM btannous@hms.harvard.edu FU NIH/NCI [4R00CA126839, P50CA86355]; NIH/NINDS [R01-NS070835, R01-NS072167, P30NS045776]; Fulbright scholarship; Saal van Zwanenberg Foundation; Dutch Brain Foundation (Hersenstichting Nederland); Dutch Cancer Foundation (KWF Kankerbestrijding); VSBfonds; Dr. Hendrik Muller Vaderlandschfonds; Hersenstichting brain fund; Jo Keur (Leiden hospital) FX This work was supported by grant from NIH/NCI 4R00CA126839 (BAT), and P50CA86355 (RW and BAT), as well as NIH/NINDS R01-NS070835 (JWC), R01-NS072167 (JWC), and P30NS045776 (BAT). Maayke Kuijten was supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, the Dutch Brain Foundation (Hersenstichting Nederland) and the Dutch Cancer Foundation (KWF Kankerbestrijding). Marja H. Degeling was supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSBfonds, Dr. Hendrik Muller Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), the Hersenstichting brain fund as well as the Jo Keur (Leiden hospital). The authors would like to thank Dr. Darell D. Bigner (Duke University Medical Center) for providing the antibody against EGFRvIII, Dr. Casey Maguire (MGH) for biotinylation of this antibody and Dr. Miguel Sena Esteves (Universisty of Massachusetts Medical Center) for providing the retrovirus vector expressing EGFRvIII. NR 35 TC 1 Z9 1 U1 11 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 27 PY 2015 VL 5 AR 17220 DI 10.1038/srep17220 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX0MY UT WOS:000365392200001 PM 26610702 ER PT J AU Churpek, JE Pyrtel, K Kanchi, KL Shao, J Koboldt, D Miller, CA Shen, D Fulton, R O'Laughlin, M Fronick, C Pusic, I Uy, GL Braunstein, EM Levis, M Ross, J Elliott, K Heath, S Jiang, A Westervelt, P DiPersio, JF Link, DC Walter, MJ Welch, J Wilson, R Ley, TJ Godley, LA Graubert, TA AF Churpek, Jane E. Pyrtel, Khateriaa Kanchi, Krishna-Latha Shao, Jin Koboldt, Daniel Miller, Christopher A. Shen, Dong Fulton, Robert O'Laughlin, Michelle Fronick, Catrina Pusic, Iskra Uy, Geoffrey L. Braunstein, Evan M. Levis, Mark Ross, Julie Elliott, Kevin Heath, Sharon Jiang, Allan Westervelt, Peter DiPersio, John F. Link, Daniel C. Walter, Matthew J. Welch, John Wilson, Richard Ley, Timothy J. Godley, Lucy A. Graubert, Timothy A. TI Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia SO BLOOD LA English DT Article ID CLONAL HEMATOPOIESIS; AUTOSOMAL-DOMINANT; MONOMAC SYNDROME; GATA2 MUTATIONS; THROMBOCYTOPENIA; MALIGNANCIES; HAPLOINSUFFICIENCY; ERYTHROLEUKEMIA; TRANSFORMATION; SEQUENCE AB Familial clustering of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) can be caused by inherited factors. We screened 59 individuals from 17 families with 2 or more biological relatives with MDS/AML for variants in 12 genes with established roles in predisposition to MDS/AML, and identified a pathogenic germ line variant in 5 families (29%). Extending the screen with a panel of 264 genes that are recurrently mutated in de novo AML, we identified rare, nonsynonymous germ line variants in 4 genes, each segregating with MDS/AML in 2 families. Somatic mutations are required for progression to MDS/AML in these familial cases. Using a combination of targeted and exome sequencing of tumor and matched normal samples from 26 familial MDS/AML cases and asymptomatic carriers, we identified recurrent frameshift mutations in the cohesin-associated factor PDS5B, co-occurrence of somatic ASXL1 mutations with germ line GATA2 mutations, and recurrent mutations in other known MDS/AML drivers. Mutations in genes that are recurrently mutated in de novo AML were underrepresented in the familial MDS/AML cases, although the total number of somatic mutations per exome was the same. Lastly, clonal skewing of hematopoiesis was detected in 67% of young, potential biomarker that could be used for surveillance in these high-risk families. C1 [Churpek, Jane E.; Godley, Lucy A.] Univ Chicago, Hematol Oncol Sect, Ctr Clin Canc Genet, Chicago, IL 60637 USA. [Pyrtel, Khateriaa; Shao, Jin; Koboldt, Daniel; Elliott, Kevin; Heath, Sharon; Westervelt, Peter; DiPersio, John F.; Link, Daniel C.; Walter, Matthew J.; Welch, John; Wilson, Richard; Ley, Timothy J.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Kanchi, Krishna-Latha; Koboldt, Daniel; Miller, Christopher A.; Fulton, Robert; O'Laughlin, Michelle; Fronick, Catrina; Wilson, Richard; Ley, Timothy J.] Washington Univ, Genome Inst, St Louis, MO USA. [Koboldt, Daniel; Pusic, Iskra; Uy, Geoffrey L.; Jiang, Allan; Westervelt, Peter; DiPersio, John F.; Link, Daniel C.; Walter, Matthew J.; Welch, John; Ley, Timothy J.] Washington Univ, Div Oncol, Dept Med, St Louis, MO USA. [Shen, Dong] Medimmune AstraZeneca, Gaithersburg, MD USA. [Braunstein, Evan M.; Levis, Mark] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Ross, Julie] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Graubert, Timothy A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Graubert, TA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 North Grove St,Lawrence House 204, Boston, MA 02114 USA. EM tgraubert@partners.org FU National Institutes of Health National Cancer Institute [CA101937, CA157439, K12 CA139160]; Cancer Research Foundation; Children's Research Fund FX This work was supported by National Institutes of Health National Cancer Institute grants CA101937 (T.J.L.), CA157439 (J.R.), and K12 CA139160 (J.E.C.); the Cancer Research Foundation (L.A.G., J.E.C.); and the Children's Research Fund (J.R.). NR 39 TC 18 Z9 19 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 26 PY 2015 VL 126 IS 22 BP 2484 EP 2490 DI 10.1182/blood-2015-04-641100 PG 7 WC Hematology SC Hematology GA CY4RF UT WOS:000366395200009 PM 26492932 ER PT J AU Eaton, BR MacDonald, SM Yock, TI Tarbell, NJ AF Eaton, Bree R. MacDonald, Shannon M. Yock, Torunn I. Tarbell, Nancy J. TI Secondary Malignancy Risk Following Proton Radiation Therapy SO FRONTIERS IN ONCOLOGY LA English DT Review DE proton; radiotherapy; radiation; second malignancy ID CHILDHOOD-CANCER SURVIVOR; INITIAL CLINICAL-OUTCOMES; BIOL-PHYS 2006/65/1-7; INDUCED 2ND CANCERS; LOW-GRADE GLIOMAS; COST-EFFECTIVENESS; 5-YEAR SURVIVORS; PEDIATRIC TUMORS; LATE MORTALITY; X-RAY AB Radiation-induced secondary malignancies are a significant, yet uncommon cause of morbidity and mortality among cancer survivors. Secondary malignancy risk is dependent upon multiple factors including patient age, the biological and genetic predisposition of the individual, the volume and location of tissue irradiated, and the dose of radiation received. Proton therapy (PRT) is an advanced particle therapy with unique dosimetric properties resulting in reduced entrance dose and minimal to no exit dose when compared with standard photon radiation therapy. Multiple dosimetric studies in varying cancer subtypes have demonstrated that PRT enables the delivery of adequate target volume coverage with reduced integral dose delivered to surrounding tissues, and modeling studies taking into account dosimetry and radiation cell biology have estimated a significantly reduced risk of radiation-induced secondary malignancy with PRT. Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in proton treated cohorts is awaited. This article reviews the current dosimetric and clinical literature evaluating the incidence of and risk factors associated with radiation-induced secondary malignancy following PRT. C1 [Eaton, Bree R.; MacDonald, Shannon M.; Yock, Torunn I.; Tarbell, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Eaton, BR (reprint author), Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. EM brupper@emory.edu NR 37 TC 4 Z9 4 U1 3 U2 5 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD NOV 26 PY 2015 VL 5 AR 261 DI 10.3389/fonc.2015.00261 PG 6 WC Oncology SC Oncology GA CX6LA UT WOS:000365811100001 PM 26636040 ER PT J AU Neumann, T Benajiba, L Goring, S Stegmaier, K Schmidt, B AF Neumann, Theresa Benajiba, Lina Goering, Stefan Stegmaier, Kimberly Schmidt, Boris TI Evaluation of Improved Glycogen Synthase Kinase-3 alpha Inhibitors in Models of Acute Myeloid Leukemia SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DISCOVERY; TARGET; GSK3 AB The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML) may require alpha-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3 alpha selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3 alpha/beta with the highest GSK-3 alpha selectivity reported to dtae. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3 alpha targeting in AML cell lines was achieved with compound 27, resulting in a strong differrentiation phenotype and colony formation impairment, confirming the potential of GSK-3 alpha inhibition in AML therapy. C1 [Neumann, Theresa; Goering, Stefan; Schmidt, Boris] Tech Univ Darmstadt, Clemens Schopf Inst Organ Chem & Biochem, D-64287 Darmstadt, Germany. [Benajiba, Lina; Stegmaier, Kimberly] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Schmidt, B (reprint author), Tech Univ Darmstadt, Clemens Schopf Inst Organ Chem & Biochem, D-64287 Darmstadt, Germany. EM Schmidt_boris@t-online.de RI Schmidt, Boris/D-3293-2009 OI Schmidt, Boris/0000-0003-1662-2392 FU Hans und Ilse Breuer-Stiftung; [R01 CA140292] FX The authors thank the students Martin Brodrecht, Anne Schieferdecker, and David Fiebig (Technische Universitat Darmstadt), who supported this work. The authors thank Dennis Bensinger (Technische Universitat Darmstadt) for help with scripting. We thank the Hans und Ilse Breuer-Stiftung for financial support. KS. is a Leukemia and Lymphoma Society Scholar, and this work was supported in part by Grant R01 CA140292. NR 26 TC 2 Z9 2 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD NOV 26 PY 2015 VL 58 IS 22 BP 8907 EP 8919 DI 10.1021/acs.jmedchem.5b01200 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CX9DG UT WOS:000366004600012 PM 26496242 ER PT J AU Cho, JL McDermott, S Tsibris, AM Mark, EJ AF Cho, Josalyn L. McDermott, Shaunagh Tsibris, Athe M. Mark, Eugene J. TI Case 37-2015: A 76-Year-Old Man with Fevers, Leukopenia, and Pulmonary Infiltrates Disseminated Mycobacterium bovis infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GRANULOMATOUS LUNG-DISEASE; HOT-TUB LUNG; HYPERSENSITIVITY PNEUMONITIS; NONTUBERCULOUS MYCOBACTERIA; MILIARY TUBERCULOSIS; RADIOLOGIC FEATURES; CLINICAL-FEATURES; AVIUM COMPLEX; DIAGNOSIS; HISTOPATHOLOGY C1 [Cho, Josalyn L.; Tsibris, Athe M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McDermott, Shaunagh] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cho, Josalyn L.; Tsibris, Athe M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [McDermott, Shaunagh] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cho, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 26 PY 2015 VL 373 IS 22 BP 2162 EP 2172 DI 10.1056/NEJMcpc1504839 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CW9YT UT WOS:000365354800013 PM 26605931 ER PT J AU Sharma, A Phillips, AJ Juppner, H AF Sharma, Amita Phillips, Alfred J. Jueppner, Harald TI Hypoplastic Metatarsals - Beyond Cosmesis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Sharma, Amita; Jueppner, Harald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Phillips, Alfred J.] St Elizabeth Hosp, Brighton, MA USA. RP Sharma, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM asharma5@partners.org FU NIDDK NIH HHS [P01DK11794, P01 DK011794, R01DK46718-20, R01 DK046718] NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 26 PY 2015 VL 373 IS 22 BP 2189 EP 2190 DI 10.1056/NEJMc1508520 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CW9YT UT WOS:000365354800026 PM 26605941 ER PT J AU Maheswaran, S Haber, DA AF Maheswaran, Shyamala Haber, Daniel A. TI CELL FATE Transition loses its invasive edge SO NATURE LA English DT Editorial Material ID STEM-CELLS; CANCER; PROGRESSION; EMT C1 [Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu; dhaber@mgh.harvard.edu NR 11 TC 6 Z9 7 U1 1 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 26 PY 2015 VL 527 IS 7579 BP 452 EP 453 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW9XW UT WOS:000365352500031 PM 26560026 ER PT J AU Nunez, JK Harrington, LB Kranzusch, PJ Engelman, AN Doudna, JA AF Nunez, James K. Harrington, Lucas B. Kranzusch, Philip J. Engelman, Alan N. Doudna, Jennifer A. TI Foreign DNA capture during CRISPR-Cas adaptive immunity SO NATURE LA English DT Article ID SPACER ACQUISITION; BACTERIAL IMMUNITY; SYSTEM; PROKARYOTES; ELEMENTS; REPEATS; DEFENSE; RNA; BACTERIOPHAGE; ENDONUCLEASE AB Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30-40-base-pair lengths into clustered regularly interspaced short palindromic repeat (CRISPR) loci as spacer segments(1-6). The universally conserved Cas1-Cas2 integrase complex catalyses spacer acquisition using a direct nucleophilic integration mechanism similar to retroviral integrases and transposases(7-13). How the Cas1-Cas2 complex selects foreign DNA substrates for integration remains unknown. Here we present X-ray crystal structures of the Escherichia coli Cas1-Cas2 complex bound to cognate 33-nucleotide protospacer DNA substrates. The protein complex creates a curved binding surface spanning the length of the DNA and splays the ends of the protospacer to allow each terminal nucleophilic 3'-OH to enter a channel leading into the Cas1 active sites. Phosphodiester backbone interactions between the protospacer and the proteins explain the sequence-nonspecific substrate selection observed in vivo(2-4). Our results uncover the structural basis for foreign DNA capture and the mechanism by which Cas1-Cas2 functions as a molecular ruler to dictate the sequence architecture of CRISPR loci. C1 [Nunez, James K.; Harrington, Lucas B.; Kranzusch, Philip J.; Doudna, Jennifer A.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Kranzusch, Philip J.; Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. [Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. [Engelman, Alan N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Innovat Genom Initiat, Berkeley, CA 94720 USA. [Doudna, Jennifer A.] Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA. RP Doudna, JA (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. EM doudna@berkeley.edu FU UC Office of the President; Multicampus Research Programs; Program for Breakthrough Biomedical Research - Sandler Foundation; US National Science Foundation [1244557]; NIH [AI070042]; US National Science Foundation Graduate Research Fellowships; UC Berkeley Chancellor's Graduate Fellowship; [MR-15-328599] FX We thank G. Meigs and the 8.3.1 beamline staff at the Advanced Light Source for assistance with data collection, J. Chen for input on experimental design and members of the Doudna laboratory for comments and discussions. The 8.3.1 beamline is supported by UC Office of the President, Multicampus Research Programs and Initiatives grant MR-15-328599 and Program for Breakthrough Biomedical Research, which is partially funded by the Sandler Foundation. This project was funded by US National Science Foundation grant No. 1244557 to J.A.D. and by NIH grant AI070042 to A.N.E. J.K.N. and L.B.H. are supported by US National Science Foundation Graduate Research Fellowships and J.K.N. by a UC Berkeley Chancellor's Graduate Fellowship. P.J.K. is supported as a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. J.A.D. is an Investigator of the Howard Hughes Medical Institute and a member of the Center for RNA Systems Biology. NR 29 TC 25 Z9 28 U1 13 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 26 PY 2015 VL 527 IS 7579 BP 535 EP + DI 10.1038/nature15760 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW9XW UT WOS:000365352500052 PM 26503043 ER PT J AU Brautigam, H Moreno, CL Steele, JW Bogush, A Dickstein, DL Kwok, JBJ Schofield, PR Thinakaran, G Mathews, PM Hof, PR Gandy, S Ehrlich, ME AF Brautigam, Hannah Moreno, Cesar L. Steele, John W. Bogush, Alexey Dickstein, Dara L. Kwok, John B. J. Schofield, Peter R. Thinakaran, Gopal Mathews, Paul M. Hof, Patrick R. Gandy, Sam Ehrlich, Michelle E. TI Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1-/- phenotype and forms complexes with wildtype PS1 and nicastrin SO SCIENTIFIC REPORTS LA English DT Article ID GAMMA-SECRETASE ACTIVITY; ALZHEIMERS-DISEASE; MUTATIONS; PLAQUES; MOUSE; ASPARTATES; INSIGHTS; MUTANT; MICE AB The presenilin 1 (PSEN1) L271V mutation causes early-onset familial Alzheimer's disease by disrupting the alternative splicing of the PSEN1 gene, producing some transcripts harboring the L271V point mutation and other transcripts lacking exon 8 (PS1(Delta exon8)). We previously reported that PS1 L271V increased amyloid beta (A beta) 42/40 ratios, while PS1(Delta exon8) reduced A beta 42/40 ratios, indicating that the former and not the exon 8 deletion transcript is amyloidogenic. Also, PS1(Delta exon8) did not rescue A beta generation in PS1/2 double knockout cells indicating its identity as a severe loss-of-function splice form. PS1(Delta exon8) is generated physiologically raising the possibility that we had identified the first physiological inactive PS1 isoform. We studied PS1(Delta exon8) in vivo by crossing PS1(Delta exon8) transgenics with either PS1-null or Dutch APP(E693Q) mice. As a control, we crossed APP(E693Q) with mice expressing a deletion in an adjacent exon (PS1(Delta exon9)). PS1(Delta exon8) did not rescue embryonic lethality or Notch-deficient phenotypes of PS1-null mice displaying severe loss of function in vivo. We also demonstrate that this splice form can interact with wildtype PS1 using cultured cells and - co-immunoprecipitation (co-IP)/bimolecular fluorescence complementation. Further co-IP demonstrates that PS1(Delta exon8) interacts with nicastrin, participating in the gamma-secretase complex formation. These data support that catalytically inactive PS1(Delta exon8) is generated physiologically and participates in protein-protein interactions. C1 [Brautigam, Hannah; Moreno, Cesar L.; Dickstein, Dara L.; Hof, Patrick R.; Gandy, Sam] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Brautigam, Hannah; Moreno, Cesar L.; Dickstein, Dara L.; Hof, Patrick R.; Gandy, Sam] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Moreno, Cesar L.; Steele, John W.; Gandy, Sam; Ehrlich, Michelle E.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Moreno, Cesar L.; Ehrlich, Michelle E.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Moreno, Cesar L.; Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Brautigam, Hannah; Steele, John W.; Dickstein, Dara L.; Hof, Patrick R.; Gandy, Sam; Ehrlich, Michelle E.] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Brautigam, Hannah; Dickstein, Dara L.; Hof, Patrick R.; Gandy, Sam; Ehrlich, Michelle E.] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA. [Brautigam, Hannah; Moreno, Cesar L.; Dickstein, Dara L.; Hof, Patrick R.; Ehrlich, Michelle E.] Icahn Sch Med Mt Sinai, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA. [Brautigam, Hannah] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Steele, John W.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92037 USA. [Steele, John W.] OrPhi Therapeut, Dept Preclin Biol, Carlsbad, CA 92008 USA. [Bogush, Alexey] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. [Kwok, John B. J.; Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia. [Kwok, John B. J.; Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Thinakaran, Gopal] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA. [Thinakaran, Gopal] Univ Chicago, Dept Neurol & Pathol, Chicago, IL 60637 USA. [Mathews, Paul M.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Mathews, Paul M.] Nathan Kline Inst Ctr Dementia Res, Orangeburg, NY 10962 USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. EM samuel.gandy@mssm.edu OI moreno, cesar/0000-0002-0876-0341; Mathews, Paul/0000-0003-1742-7687 FU NIH [F31 AG039890, F31 AG042299, P50 AG005138, P01 AG0717617, U01 AG046170, I01 RX000684, R01NS075685, R34 AG049649] FX This work was supported by NIH grants F31 AG039890 (HB), F31 AG042299 (CLM), P50 AG005138 (to Mary Sano with SG, PRH, DLD, MEE), P01 AG0717617 (PM) U01 AG046170 (SG), I01 RX000684 (SG), R01NS075685 (SG), and R34 AG049649 (SG). A portion of this work was used in a dissertation by HB in partial fulfillment of requirements for the PhD degree at the Icahn School of Medicine at Mount Sinai in New York. We thank Drs Miguel Gama Sosa and Gregory Elder for PS1 +/- mice. We also thank: Dr. Chang-Deng Hu, Purdue University for BiFC vectors; Dr. Mark Baxter for advice on statistical analysis; Drs Maitane Ortiz-Virumbrales and Rachel Lane for technical assistance; Jennifer Short and William G.M. Janssen for advice with confocal imaging; Carlos Thomas and Ari Stock for assistance with embryo photographs; and members of the Dickstein, Hof, Ehrlich, and Gandy laboratories for advice and discussion. NR 25 TC 1 Z9 1 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 26 PY 2015 VL 5 AR 17042 DI 10.1038/srep17042 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX0LR UT WOS:000365388600001 PM 26608390 ER PT J AU Paiva, C Godbersen, JC Soderquist, RS Rowland, T Kilmarx, S Spurgeon, SE Brown, JR Srinivasa, SP Danilov, AV AF Paiva, Cody Godbersen, J. Claire Soderquist, Ryan S. Rowland, Taylor Kilmarx, Sumner Spurgeon, Stephen E. Brown, Jennifer R. Srinivasa, Sreesha P. Danilov, Alexey V. TI Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells SO PLOS ONE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; ER STRESS; IN-VIVO; FLAVOPIRIDOL; ACTIVATION; DEATH; TRANSCRIPTION; DINACICLIB; RESISTANCE; CANCER AB CDK (cyclin-dependent kinase) inhibitors have shown remarkable activity in CLL, where its efficacy has been linked to inhibition of the transcriptional CDKs (7 and 9) and deregulation of RNA polymerase and short-lived pro-survival proteins such as MCL1. Furthermore, ER (endoplasmic reticulum) stress has been implicated in CDK inhibition in CLL. Here we conducted a pre-clinical study of a novel orally active kinase inhibitor P1446A in CLL B-cells. P1446A inhibited CDKs at nanomolar concentrations and induced rapid apoptosis of CLL cells in vitro, irrespective of chromosomal abnormalities or IGHV mutational status. Apoptosis preceded inactivation of RNA polymerase, and was accompanied by phosphorylation of stress kinases JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase). Pharmacologic inhibitors of JNK/p38 MAPK conferred protection from P1446A-mediated apoptosis. Treatment with P1446A led to a dramatic induction of NOXA in a JNKdependent manner, and sensitized CLL cells to ABT-737, a BH3-mimetic. We observed concurrent activation of apoptosis stress-inducing kinase 1 (ASK1) and its interaction with inositol-requiring enzyme 1 (IRE1) and tumor necrosis factor receptor-associated factor 2 (TRAF2) in CLL cells treated with P1446A, providing insights into upstream regulation of JNK in this setting. Consistent with previous reports on limited functionality of ER stress mechanism in CLL cells, treatment with P1446A failed to induce an extensive unfolded protein response. This study provides rationale for additional investigations of P1446A in CLL. C1 [Paiva, Cody; Rowland, Taylor; Spurgeon, Stephen E.; Danilov, Alexey V.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Godbersen, J. Claire; Kilmarx, Sumner] Dartmouth Coll, Hanover, NH 03755 USA. [Soderquist, Ryan S.] Duke Univ, Durham, NC USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Srinivasa, Sreesha P.] Piramal Healthcare Ltd, Bombay, Maharashtra, India. RP Danilov, AV (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. EM danilov@ohsu.edu FU Piramal Healthcare Ltd.; Lymphoma Research Foundation; Leukemia Lymphoma Society; American Cancer Society FX This study was in part funded by Piramal Healthcare Ltd., which provided salary support for Sreesha Srinivasa, a co-author on this study, as well as research materials. In addition, Alexey V. Danilov's salary was in part paid by the Lymphoma Research Foundation Clinical Investigator Career development award. JRB is supported by the Leukemia Lymphoma Society and the American Cancer Society and is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. The above funding organizations did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and research materials. NR 61 TC 3 Z9 3 U1 5 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 25 PY 2015 VL 10 IS 11 AR e0143685 DI 10.1371/journal.pone.0143685 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX7ES UT WOS:000365865300100 PM 26606677 ER PT J AU Wang, RP Dai, GP Takahashi, E AF Wang, Rongpin Dai, Guangping Takahashi, Emi TI High Resolution MRI Reveals Detailed Layer Structures in Early Human Fetal Stages: In Vitro Study with Histologic Correlation SO FRONTIERS IN NEUROANATOMY LA English DT Article DE human fetal brain; cerebral wall; neurogenesis; structural mri; histology ID INCREASINGLY IMPORTANT TOOL; MAGNETIC-RESONANCE; BRAIN-DEVELOPMENT; GANGLIONIC EMINENCE; PRENATAL-DIAGNOSIS; WHITE-MATTER; PATHWAYS; SUBPLATE; CEREBRUM; PRETERM AB An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI) studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW), which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. 12-weighted imaging was performed on fetal brain specimens ranging from 10 GVV to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW). Early second trimester (15-18 GVV) was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high resolution structural imaging and color-coding processing with histological analysis may be a potential tool for studying detailed structures of typical developing fetal brains, as well as fetal brains with developmental disorders as references for clinical MRI. C1 [Wang, Rongpin; Takahashi, Emi] Harvard Univ, Sch Med, Dept Med, Div Newborn Med,Boston Childrens Hosp, Boston, MA USA. [Wang, Rongpin] Guizhou Prov Peoples Hosp, Dept Radiol, Guiyang, Peoples R China. [Dai, Guangping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Wang, RP (reprint author), Guizhou Prov Peoples Hosp, Dept Radiol, Guiyang, Peoples R China. EM wangrongpin@126.com FU Boston Children's Hospital (BCH); Guizhou Provincial People's Hospital; NICHD [R01HD078561, R21HD069001, R03NS091587] FX This work was supported by Boston Children's Hospital (BCH), Guizhou Provincial People's Hospital, and NICHD (R01HD078561, R21HD069001, R03NS091587; ET). The authors thank Donald Siwek and Dairy R. Ricketts, Boston University School of Medicine for providing the fetal brain specimens from the Departmental collection, Ying Huang in the Center for Molecular Oncologic Pathology of Dana-Farber Cancer Institute for technical assistance, Borjan Gagoski at BCH for discussion, and Molly Wilkinson and Ashley Ruyan Lim at BCH for editorial assistance. NR 33 TC 2 Z9 2 U1 1 U2 3 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-5129 J9 FRONT NEUROANAT JI Front. Neuroanat. PD NOV 25 PY 2015 VL 9 AR 150 DI 10.3380/fnana.2015.00150 PG 9 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA CX6ZN UT WOS:000365850300002 PM 26834575 ER PT J AU Banks, WA Gray, AM Erickson, MA Salameh, TS Damodarasamy, M Sheibani, N Meabon, JS Wing, EE Morofuji, Y Cook, DG Reed, MJ AF Banks, William A. Gray, Alicia M. Erickson, Michelle A. Salameh, Therese S. Damodarasamy, Mamatha Sheibani, Nader Meabon, James S. Wing, Emily E. Morofuji, Yoichi Cook, David G. Reed, May J. TI Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE Blood-brain barrier; Neurovascular unit; Neuroinflammation; Brain endothelial cells; Indomethacin; Lipopolysaccharide ID ENDOTHELIAL-CELLS; N-ACETYLCYSTEINE; NITRIC-OXIDE; IN-VITRO; CUTTING EDGE; PERMEABILITY; RECEPTOR; ACTIVATION; TRANSPORT; ENDOTOXIN AB Background: Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, but many mechanistic questions remain. Methods: We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using C-14-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co-or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to C-14-sucrose and radioactive albumin. Results: In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with C-14-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and C-14-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes. Conclusions: The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is to be dependent on COX but not on oxidative stress. Based on in vivo and in vitro measures of neuroinflammation, it appears that astrocytes, microglia/macrophages, and pericytes play little role in the LPS-mediated disruption of the BBB. C1 [Banks, William A.; Erickson, Michelle A.; Salameh, Therese S.; Wing, Emily E.; Morofuji, Yoichi; Cook, David G.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Banks, William A.; Erickson, Michelle A.; Damodarasamy, Mamatha; Morofuji, Yoichi; Reed, May J.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Gray, Alicia M.] Univ Washington, Sch Med, Seattle, WA USA. [Sheibani, Nader] Univ Wisconsin, Sch Med & Publ Hlth, Ophthalmol & Visual Sci, Madison, WI USA. [Meabon, James S.] VA Puget Sound Hlth Care Syst, Mental Hlth Res Educ & Clin Ctr, Seattle, WA USA. [Morofuji, Yoichi] Nagasaki Univ, Dept Neurosurg, Nagasaki 852, Japan. RP Banks, WA (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU VA; [R01 AG029839] FX We would like to thank Dr. Jessica Hamerman (University of Washington) for TREM2 KO mouse materials and the rat anti-TREM2 antibody. Supported by the VA and R01 AG029839 (WAB). NR 59 TC 13 Z9 14 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD NOV 25 PY 2015 VL 12 AR 223 DI 10.1186/s12974-015-0434-1 PG 15 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CX5ZU UT WOS:000365781800001 PM 26608623 ER PT J AU Jung, M Mody, M Saito, DN Tomoda, A Okazawa, H Wada, Y Kosaka, H AF Jung, Minyoung Mody, Maria Saito, Daisuke N. Tomoda, Akemi Okazawa, Hidehiko Wada, Yuji Kosaka, Hirotaka TI Sex Differences in the Default Mode Network with Regard to Autism Spectrum Traits: A Resting State fMRI Study SO PLOS ONE LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; FUNCTIONAL CONNECTIVITY MRI; LOW-FREQUENCY OSCILLATIONS; QUOTIENT AQ; HUMAN BRAIN; GENDER-DIFFERENCES; DISORDER; AMPLITUDE; MOTION; SCHIZOPHRENIA AB Autism spectrum traits exist on a continuum and are more common in males than in females, but the basis for this sex difference is unclear. To this end, the present study draws on the extreme male brain theory, investigating the relationship between sex difference and the default mode network (DMN), both known to be associated with autism spectrum traits. Resting-state functional magnetic resonance imaging (MRI) was carried out in 42 females (mean age +/- standard deviation, 22.4 +/- 4.2 years) and 43 males (mean age +/- standard deviation, 23.8 +/- 3.9 years) with typical development. Using a combination of different analyses (viz., independent component analysis (ICA), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and seed-based analyses), we examined sex differences in the DMN and the relationship to autism spectrum traits as measured by autism-spectrum quotient (AQ) scores. We found significant differences between female and male subjects in DMN brain regions, with seed-based analysis revealing a significant negative correlation between default-mode resting state functional connectivity of the anterior medial prefrontal cortex seed (aMPFC) and AQ scores in males. However, there were no relationships between DMN sex differences and autism spectrum traits in females. Our findings may provide important insight into the skewed balance of functional connectivity in males compared to females that could serve as a potential biomarker of the degree of autism spectrum traits in line with the extreme male brain theory. C1 [Jung, Minyoung; Saito, Daisuke N.; Tomoda, Akemi; Okazawa, Hidehiko; Wada, Yuji; Kosaka, Hirotaka] Univ Fukui, Res Ctr Child Mental Dev, Eiheiji, Fukui, Japan. [Jung, Minyoung; Mody, Maria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Saito, Daisuke N.; Tomoda, Akemi; Okazawa, Hidehiko; Wada, Yuji; Kosaka, Hirotaka] Osaka Univ, United Grad Sch Child Dev, Dept Child Dev, Dev Emot Intelligence,Div Dev Higher Brain Funct, Eiheiji, Fukui, Japan. [Saito, Daisuke N.; Tomoda, Akemi; Okazawa, Hidehiko; Wada, Yuji; Kosaka, Hirotaka] Kanazawa Univ, Eiheiji, Fukui, Japan. [Saito, Daisuke N.; Tomoda, Akemi; Okazawa, Hidehiko; Wada, Yuji; Kosaka, Hirotaka] Hamamatsu Univ Sch Med, Eiheiji, Fukui, Japan. [Saito, Daisuke N.; Tomoda, Akemi; Okazawa, Hidehiko; Wada, Yuji; Kosaka, Hirotaka] Chiba Univ, Eiheiji, Fukui, Japan. [Saito, Daisuke N.; Tomoda, Akemi; Okazawa, Hidehiko; Wada, Yuji; Kosaka, Hirotaka] Univ Fukui, Eiheiji, Fukui, Japan. [Saito, Daisuke N.; Okazawa, Hidehiko] Univ Fukui, Biomed Imaging Res Ctr, Eiheiji, Fukui, Japan. [Wada, Yuji; Kosaka, Hirotaka] Univ Fukui, Fac Med Sci, Dept Neuropsychiat, Eiheiji, Fukui, Japan. RP Kosaka, H (reprint author), Univ Fukui, Res Ctr Child Mental Dev, Eiheiji, Fukui, Japan. EM hirotaka@u-fukui.ac.jp RI Okazawa, Hidehiko/B-2795-2016 OI Okazawa, Hidehiko/0000-0001-7046-3383 FU Japan Society for the Promotion of Science [26118505] FX This research was funded in part by Research Fellowships for Young Scientists and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (26118505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 1 Z9 1 U1 4 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 24 PY 2015 VL 10 IS 11 AR e0143126 DI 10.1371/journal.pone.0143126 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX7DU UT WOS:000365862600030 PM 26600385 ER PT J AU Tamehiro, N Park, MH Hawxhurst, V Nagpal, K Adams, ME Zannis, VI Golenbock, DT Fitzgerald, ML AF Tamehiro, Norimasa Park, Min Hi Hawxhurst, Victoria Nagpal, Kamalpreet Adams, Marv E. Zannis, Vassilis I. Golenbock, Douglas T. Fitzgerald, Michael L. TI LXR Agonism Upregulates the Macrophage ABCA1/Syntrophin Protein Complex That Can Bind ApoA-I and Stabilized ABCA1 Protein, but Complex Loss Does Not Inhibit Lipid Efflux SO BIOCHEMISTRY LA English DT Article ID CASSETTE TRANSPORTER A1; CHOLESTEROL EFFLUX; ABCA1-DEFICIENT MACROPHAGES; HEART-DISEASE; ATHEROSCLEROSIS; MICE; ASSOCIATION; RECEPTOR; CAPACITY; CELLS AB Macrophage ABCA1 effluxes lipid and has anti-inflammatory activity. The syntrophins, which are cytoplasmic PDZ protein scaffolding factors, can bind ABCA1 and modulate its activity. However, many of the data assessing the function of the ABCA1-syntrophin interaction are based on overexpression in nonmacrophage cells. To assess endogenous complex function in macrophages, we derived immortalized macrophages from Abca1(+/+) and Abca1(-/-) mice and show their phenotype recapitulates primary macrophages. Abca1(+/+) lines express the CD11B and F4/80 macrophage markers and markedly upregulate cholesterol efflux in response to LXR nuclear hormone agonists. In contrast, immortalized Abca1(-/-) macrophages show no efflux to apoA-I. In response to LPS, Abca1(-/-) macrophages display pro-inflammatory changes, including an increased level of expression of cell surface CD 14, and 11-26-fold higher levels of IL-6 and IL-12 mRNA. Given recapitulation of phenotype, we show with these lines that the ABCA1-syntrophin protein complex is upregulated by LXR agonists and can bind apoA-I. Moreover, in immortalized macrophages, combined alpha 1/beta 2-syntrophin loss modulated ABCA1 cell surface levels and induced pro-inflammatory gene expression. However, loss of all three syntrophin isoforms known to bind ABCA1 did not impair lipid efflux in immortalized or primary macrophages. Thus, the ABCA1-syntrophin protein complex is not essential for ABCA1 macrophage lipid efflux but does directly interact with apoA-I and can modulate the pool of cell surface ABCA1 stabilized by apoA-I. C1 [Tamehiro, Norimasa; Park, Min Hi; Hawxhurst, Victoria; Fitzgerald, Michael L.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, Lipid Metab Unit, Boston, MA 02114 USA. [Nagpal, Kamalpreet; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, Worcester, MA 01605 USA. [Adams, Marv E.] Univ Washington, Seattle, WA 98195 USA. [Zannis, Vassilis I.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Fitzgerald, ML (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, Lipid Metab Unit, 185 Cambridge St,7th Floor 7150, Boston, MA 02114 USA. EM mfitzgerald@ccib.mgh.harvard.edu FU American Heart Association [09GRNT2260352]; National Institutes of Health [HL074136, HL101274, HL112661] FX This work was funded by grants to M.L.F. from the American Heart Association (09GRNT2260352) and the National Institutes of Health (HL074136, HL101274, and HL112661). NR 38 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 24 PY 2015 VL 54 IS 46 BP 6931 EP 6941 DI 10.1021/acs.biochem.5b00894 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CX1NY UT WOS:000365464100008 PM 26506427 ER PT J AU Tsai, TT Rehring, TF Rogers, RK Shetterly, SM Wagner, NM Gupta, R Jazaeri, O Hedayati, N Jones, WS Patel, MR Ho, PM Go, AS Magid, DJ AF Tsai, Thomas T. Rehring, Thomas F. Rogers, R. Kevin Shetterly, Susan M. Wagner, Nicole M. Gupta, Rajan Jazaeri, Omid Hedayati, Nasim Jones, W. Schuyler Patel, Manesh R. Ho, P. Michael Go, Alan S. Magid, David J. TI The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease SO CIRCULATION LA English DT Article DE comparative effectiveness research; lower extremity bypass surgery; peripheral arterial disease ID QUALITY-OF-LIFE; WALKING IMPAIRMENT QUESTIONNAIRE; RANDOMIZED CONTROLLED-TRIAL; INTERMITTENT CLAUDICATION; OCCLUSIVE DISEASE; LIMB ISCHEMIA; EXERCISE; ENDARTERECTOMY; MULTICENTER; STENOSIS AB Background Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia. Methods and Results In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.32.7% and 19.0 +/- 3.5% at 1 and 3 years versus 5.2 +/- 2.4% and 8.3 +/- 3.1%, log-rank P<0.001) and critical limb ischemia (19.1 +/- 4.8% and 31.6 +/- 6.3% at 1 and 3 years versus 10.8 +/- 2.5% and 16.0 +/- 3.2%, log-rank P<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%, P<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection. Conclusions In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations. C1 [Tsai, Thomas T.; Rehring, Thomas F.; Shetterly, Susan M.; Wagner, Nicole M.; Ho, P. Michael; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80231 USA. [Tsai, Thomas T.; Rehring, Thomas F.; Rogers, R. Kevin; Gupta, Rajan; Jazaeri, Omid; Ho, P. Michael; Magid, David J.] Univ Colorado, Denver, CO 80202 USA. [Hedayati, Nasim] UC Davis Hlth Syst, Davis, CA USA. [Jones, W. Schuyler; Patel, Manesh R.] Duke Clin Res Inst, Durham, NC USA. [Ho, P. Michael] Denver VA Med Ctr, Denver, CO USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Tsai, TT (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, 10065 East Harvard Suite 300, Denver, CO 80231 USA. EM thomas.tsai@coloradooutcomes.org FU Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program [290201000008I] FX This project was funded under Contract No. 290201000008I from the Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services. NR 27 TC 3 Z9 3 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 24 PY 2015 VL 132 IS 21 BP 1999 EP 2011 DI 10.1161/CIRCULATIONAHA.114.013440 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CX3DB UT WOS:000365574600010 PM 26362632 ER PT J AU Podrid, PJ AF Podrid, Philip J. TI ECG Challenge: November 24, 2015 SO CIRCULATION LA English DT Editorial Material C1 [Podrid, Philip J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Podrid, Philip J.] Harvard Univ, Sch Med, Boston, MA USA. [Podrid, Philip J.] VA Boston Healthcare Syst, Boston, MA USA. RP Podrid, PJ (reprint author), West Roxbury VA Hosp, Cardiol Sect, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM ppodrid@circulationjournal.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 24 PY 2015 VL 132 IS 21 BP 2034 EP 2034 DI 10.1161/CIRCULATIONAHA.115.020092 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CX3DB UT WOS:000365574600013 ER PT J AU Brownell, AL Kuruppu, D Kil, KE Jokivarsi, K Poutiainen, P Zhu, AJ Maxwell, M AF Brownell, Anna-Liisa Kuruppu, Darshini Kil, Kun-Eek Jokivarsi, Kimmo Poutiainen, Pekka Zhu, Aijun Maxwell, Michelle TI PET imaging studies show enhanced expression of mGluR5 and inflammatory response during progressive degeneration in ALS mouse model expressing SOD1-G93A gene SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE ALS; Glutamate; mGluR5; Inflammation; [F-18]FPEB; [C-11]PBR28 ID AMYOTROPHIC-LATERAL-SCLEROSIS; METABOTROPIC GLUTAMATE RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; RADIOLIGAND BINDING; SPINAL-CORD; IN-VITRO; BRAIN; NEUROTOXICITY; NEUROINFLAMMATION; ANTIBIOTICS AB Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disorder. Genetic studies have linked mutation of the gene SOD1 to ALS pathology as well as several other pathological processes including modulation of glutamatergic function and inflammatory processes. Since therapeutic approaches for ALS are focused on glutamatergic function, we investigated modulation of glutamate transport based on its receptor function as well as excitotoxicity-induced inflammatory response. Methods: In vivo positron emission tomography (PET) imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) using [F-18]FPEB ([F-18]3 fluoro 5 (2-pyridylethynyl)benzonitrile) and inflammatory response using [C-11]PBR28 (peripheral benzodiazepine receptor ligand 28) were done in an early and a late phase of neurodegeneration in four ALS mice expressing SOD1-G93A gene and four control base mice (C57/BL6). Accumulation of [F-18]FPEB and [C-11]PBR28 were quantitated in several brain areas and spinal cord to determine degeneration-induced modulation. The studies were completed with immunohistochemical analyses of mGluR5 and inflammatory response. Results: These studies showed enhanced binding potential of [F-18]FPEB in several brain areas including striatum, hippocampus, and frontal cortex. In the whole brain, the binding potential increased 49 +/- 9 % from base mice to ALS-type mice and further enhanced 23 +/- 4 % during disease progression. Also, in the spinal cord 6-22 %, enhanced accumulation of [F-18]FPEB was observed during progression of the disease. The accumulation of [C-11] PBR28 increased by 110 +/- 33 % in the whole brain during progression of the disease indicating significant inflammatory process. [C-11]PBR28 accumulation enhanced 89-264 % in the spinal cord and 204 % in the lungs. The end point immunohistochemical analyses verified the enhanced mGluR5 expression and inflammation. Conclusions: These results confirm the role of glutamate and inflammation in ALS-type pathology. These data also support the hypothesis that excessive glutamate may contribute to inflammation in the chronic neurodegenerative processes in ALS. C1 [Brownell, Anna-Liisa; Kil, Kun-Eek; Jokivarsi, Kimmo; Poutiainen, Pekka; Zhu, Aijun] Massachusetts Gen Hosp, Imaging, Athinoula A Martinos Biomed Imaging Ctr, Charlestown, MA 02129 USA. [Kuruppu, Darshini] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA USA. [Maxwell, Michelle] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Imaging, Athinoula A Martinos Biomed Imaging Ctr, 149 13th St, Charlestown, MA 02129 USA. EM abrownell@mgh.harvard.edu FU NIH [NIBIB-R01EB012864, NIMH-R01MH91684]; [1S10RR029495-01]; [1S10RR026666-01]; [1S10RR023452-01] FX These studies were conducted by support of NIH grants NIBIB-R01EB012864 and NIMH-R01MH91684 to ALB. The following supporting instrument grants (1S10RR029495-01, 1S10RR026666-01, and 1S10RR023452-01) to ALB are also acknowledged. NR 38 TC 5 Z9 5 U1 5 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD NOV 24 PY 2015 VL 12 AR 217 DI 10.1186/s12974-015-0439-9 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CX5ZO UT WOS:000365781200003 PM 26597638 ER PT J AU Uosaki, H Cahan, P Lee, DI Wang, SN Miyamoto, M Fernandez, L Kass, DA Kwon, C AF Uosaki, Hideki Cahan, Patrick Lee, Dong I. Wang, Songnan Miyamoto, Matthew Fernandez, Laviel Kass, David A. Kwon, Chulan TI Transcriptional Landscape of Cardiomyocyte Maturation SO CELL REPORTS LA English DT Article ID CELL-DERIVED CARDIOMYOCYTES; PLURIPOTENT STEM-CELLS; CARDIAC REGENERATION; DEFINED FACTORS; PROMOTES; HEART; PROLIFERATION; DELETION; MOUSE; BIOCONDUCTOR AB Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of the CM maturation that is subsequently required to generate adult myocytes remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStat CM that indexes CM maturation status. MatStat CM reveals that pluripotent-stem-cell-derived CMs mature early in culture but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation. C1 [Uosaki, Hideki; Lee, Dong I.; Wang, Songnan; Miyamoto, Matthew; Fernandez, Laviel; Kass, David A.; Kwon, Chulan] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. [Uosaki, Hideki; Wang, Songnan; Miyamoto, Matthew; Fernandez, Laviel; Kwon, Chulan] Johns Hopkins Inst Cell Engn, Baltimore, MD 21205 USA. [Cahan, Patrick] Boston Childrens Hosp, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA. [Cahan, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cahan, Patrick] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Cahan, Patrick] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Kwon, C (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. EM ckwon13@jhmi.edu OI Cahan, Patrick/0000-0003-3652-2540 FU Magic that Matters Fund; NHLBI/NIH [R01HL111198]; MSCRF [MSCRFI-1622]; Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad; Japan Society for the Promotion of Science; NIDDK/NIH [K01DK096013]; National Health Service-NHLBI [HL-119012, HL-107153]; Fondation Leducq FX The authors thank D.A.K. and C.K. laboratory members for helpful discussions and G. Howard for editorial assistance. This work was supported by the Magic that Matters Fund and grants from NHLBI/NIH (R01HL111198) and MSCRF (MSCRFI-1622) to C.K. H.U. was supported by the Japan Heart Foundation/Bayer Yakuhin Research Grant Abroad and fellowships from the Japan Society for the Promotion of Science and MSCRF. P.C. was supported by NIDDK/NIH (K01DK096013). D.A.K. was supported by National Health Service-NHLBI grants HL-119012, HL-107153, and Fondation Leducq. NR 55 TC 4 Z9 5 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 24 PY 2015 VL 13 IS 8 BP 1705 EP 1716 DI 10.1016/j.celrep.2015.10.032 PG 12 WC Cell Biology SC Cell Biology GA CX0RR UT WOS:000365404900019 PM 26586429 ER PT J AU Chin, CR Perreira, JM Savidis, G Portmann, JM Aker, AM Feeley, EM Smith, MC Brass, AL AF Chin, Christopher R. Perreira, Jill M. Savidis, George Portmann, Jocelyn M. Aker, Aaron M. Feeley, Eric M. Smith, Miles C. Brass, Abraham L. TI Direct Visualization of HIV-1 Replication Intermediates Shows that Capsid and CPSF6 Modulate HIV-1 Intra-nuclear Invasion and Integration SO CELL REPORTS LA English DT Article ID HIV-1-INFECTED CELLS; DNA INTEGRATION; HOST PROTEINS; IDENTIFICATION; INFECTION; HYBRIDIZATION; INHIBITION; MODEL; ENTRY; ASSAY AB Direct visualization of HIV-1 replication would improve our understanding of the viral life cycle. We adapted established technology and reagents to develop an imaging approach, ViewHIV, which allows evaluation of early HIV-1 replication intermediates, from reverse transcription to integration. These methods permit the simultaneous evaluation of both the capsid protein (CA) and viral DNA genome (vDNA) components of HIV-1 in both the cytosol and nuclei of single cells. ViewHIV is relatively rapid, uses readily available reagents in combination with standard confocal microscopy, and can be done with virtually any HIV-1 strain and permissive cell lines or primary cells. Using ViewHIV, we find that CA enters the nucleus and associates with vDNA in both transformed and primary cells. We also find that CA's interaction with the host polyadenylation factor, CPSF6, enhances nuclear entry and potentiates HIV-1' s depth of nuclear invasion, potentially aiding the virus's integration into gene-dense regions. C1 [Chin, Christopher R.; Perreira, Jill M.; Savidis, George; Portmann, Jocelyn M.; Aker, Aaron M.; Smith, Miles C.; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA. [Feeley, Eric M.; Brass, Abraham L.] MIT & Harvard Univ, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. RP Brass, AL (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01655 USA. EM abraham.brass@umassmed.edu FU University of Massachusetts Center for AIDS Research; Bill and Melinda Gates Foundation; Burroughs Wellcome Fund; NIH [1R01AI091786] FX We thank Q. Nugyen, S. Lai, and A. Patel of Panomics for their support and helpful discussions; J. Luban, F. Diaz-Griffero, M. Lichterfeld, R. Baker, and K. Ullman for discussions and reagents; and University of Massachusetts Medical School (A. Dauphin, B. Hobbs, C. Barry, L. Benson, T. Brailey, and R. Fish). This work was funded by a grant from the University of Massachusetts Center for AIDS Research and the Bill and Melinda Gates Foundation to A.L.B. A.L.B. is grateful to the Burroughs Wellcome Fund and the NIH (1R01AI091786) for their support. NR 36 TC 15 Z9 15 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 24 PY 2015 VL 13 IS 8 BP 1717 EP 1731 DI 10.1016/j.celrep.2015.10.036 PG 15 WC Cell Biology SC Cell Biology GA CX0RR UT WOS:000365404900020 PM 26586435 ER PT J AU Gross, JG Glassman, AR Jampol, LM Inusah, S Aiello, LP Antoszyk, AN Baker, CW Berger, BB Bressler, NM Browning, D Elman, MJ Ferris, FL Friedman, SM Marcus, DM Melia, M Stockdale, CR Sun, JK Beck, RW AF Gross, Jeffrey G. Glassman, Adam R. Jampol, Lee M. Inusah, Seidu Aiello, Lloyd Paul Antoszyk, Andrew N. Baker, Carl W. Berger, Brian B. Bressler, Neil M. Browning, David Elman, Michael J. Ferris, Frederick L., III Friedman, Scott M. Marcus, Dennis M. Melia, Michele Stockdale, Cynthia R. Sun, Jennifer K. Beck, Roy W. CA Diabet Retinopathy Clin Res Networ TI Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MACULAR EDEMA; RESEARCH-NETWORK; VISUAL-ACUITY; BEVACIZUMAB; AFLIBERCEPT; PROTOCOL AB IMPORTANCE Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. C1 [Gross, Jeffrey G.] Carolina Retina Ctr PA, Columbia, SC USA. [Glassman, Adam R.; Inusah, Seidu; Melia, Michele; Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Jampol, Lee M.; Stockdale, Cynthia R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Aiello, Lloyd Paul; Sun, Jennifer K.] Harvard Univ, Joslin Diabet Ctr, Beetham Eye Inst, Dept Ophthalmol, Boston, MA 02115 USA. [Antoszyk, Andrew N.; Browning, David] Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA. [Baker, Carl W.] Paducah Retinal Ctr, Paducah, KY USA. [Berger, Brian B.] Retina Res Ctr, Austin, TX USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Elman, Michael J.] Elman Retina Grp PA, Baltimore, MD USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. [Friedman, Scott M.] Florida Retina Consultants, Lakeland, FL USA. [Marcus, Dennis M.] Southeast Retina Ctr PC, Augusta, GA USA. RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. EM drcrstat2@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services [EY14231, EY23207, EY18817]; Genentech FX This study was supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services (grants EY14231, EY23207, and EY18817). Genentech provided ranibizumab for the study and funds to the DRCR.net to defray the study's clinical site costs. NR 23 TC 36 Z9 37 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 24 PY 2015 VL 314 IS 20 BP 2137 EP 2146 DI 10.1001/jama.2015.15217 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CW9XQ UT WOS:000365351900017 ER PT J AU Ventura, MI Edwards, JD Barnes, DE AF Ventura, Maria I. Edwards, Jerri D. Barnes, Deborah E. TI More than just a movement disorder Why cognitive training is needed in Parkinson disease SO NEUROLOGY LA English DT Editorial Material ID SYMPTOMS; PERFORMANCE AB Parkinson disease (PD) is a movement disorder with cardinal motor symptoms of resting tremor, bradykinesia, freezing of gait, and rigidity.(1) Most PD treatments aim to manage motor symptoms through pharmacologic and surgical interventions such as deep brain stimulation. Although these treatments can improve or slow decline in motor symptoms, they can also have adverse side effects, such as debilitating motor fluctuations, and costs are an estimated $25 billion per year in the United States alone.(2,3) In addition, nonmotor symptoms, including cognitive impairments, can be as troublesome as motor symptoms, but are not responsive to current PD treatments.(4) Results from an extensive review by Seppi et al.(4) show a lack of evidence for the effectiveness of pharmacologic treatments for cognitive decline in PD, with the exception of rivastigmine for the treatment of dementia. Cognitive difficulties in domains such as speed of processing, memory, and visuospatial and attentional executive functioning are common in PD, may appear before motor symptom onset, and can affect approximately 25% of patients at disease onset.(5) Even subtle cognitive decline can negatively affect quality of life. Furthermore, those experiencing cognitive difficulties early in disease progression are at higher risk for cognitive decline, with 80% developing dementia.(6) Therefore, there is a great need to explore nonpharmacologic, noninvasive interventions that are effective in treating cognitive symptoms in order to help patients with PD maintain daily functioning, independence and quality of life. C1 [Ventura, Maria I.] Univ Calif San Francisco, Dept Geriatr, San Francisco, CA 94143 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94117 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Stat, San Francisco, CA 94143 USA. [Edwards, Jerri D.] Univ S Florida, Sch Aging Studies, Tampa, FL USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94117 USA. EM Deborah.Barnes@ucsf.edu FU NIA NIH HHS [T32 AG000212] NR 10 TC 0 Z9 0 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 24 PY 2015 VL 85 IS 21 BP 1828 EP 1829 DI 10.1212/WNL.0000000000002158 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CW9HJ UT WOS:000365309500002 PM 26519546 ER PT J AU Kaup, AR Nettiksimmons, J LeBlanc, ES Yaffe, K AF Kaup, Allison R. Nettiksimmons, Jasmine LeBlanc, Erin S. Yaffe, Kristine TI Memory complaints and risk of cognitive impairment after nearly 2 decades among older women SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; DECLINE; BIOMARKERS; DEMENTIA; ADULTS AB Objectives:To investigate the association between subjective memory complaints (SMCs) and long-term risk of cognitive impairment in aging because most previous studies have followed individuals for only a few years.Methods:Participants were 1,107 cognitively normal, community-dwelling older women (aged 65 years and older at baseline) in a prospective study of aging. SMCs were assessed shortly after baseline and repeatedly over time with the yes/no question, Do you feel you have more problems with memory than most? Cognitive status 18 years later (normal or impaired with mild cognitive impairment or dementia) was determined by an expert panel. Using logistic regression, we investigated the association between SMCs over time and risk of cognitive impairment, adjusting for demographics, baseline cognition, and characteristics that differed between those with and without SMCs.Results:At baseline, 8.0% of participants (n = 89) endorsed SMCs. Baseline SMCs were associated with increased risk of cognitive impairment 18 years later (adjusted odds ratio [OR] = 1.7, 95% confidence interval 1.1-2.8). Results were unchanged after excluding participants with depression. The association between SMCs and cognitive impairment was greatest at the last SMC assessment time point (18 years before diagnosis: adjusted OR = 1.7 [1.1-2.9]; 14 years before diagnosis: adjusted OR = 1.6 [0.9-2.7]; 10 years before diagnosis: adjusted OR = 1.9 [1.1-3.1]; 4 years before diagnosis: adjusted OR = 3.0 [1.8-5.0]).Conclusions:SMCs are associated with cognitive impairment nearly 2 decades later among older women. SMCs may be a very early symptom of an insidious neurodegenerative disease process, such as Alzheimer disease. C1 [Kaup, Allison R.] Univ Calif San Francisco, Res Serv, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Kaup, Allison R.; Nettiksimmons, Jasmine; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [LeBlanc, Erin S.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. RP Kaup, AR (reprint author), Univ Calif San Francisco, Res Serv, San Francisco, CA 94143 USA. EM allison.kaup@ucsf.edu FU NIH; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576]; NIA grant [K24AG031155]; US Department of Veterans Affairs, Rehabilitation Research and Development Service [1IK2RX001629]; Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment; Medical Research Service of the San Francisco Veterans Affairs Medical Center; Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) FX The Study of Osteoporotic Fractures (SOF) is supported by NIH funding. The National Institute on Aging (NIA) provides support under the following grants: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. The research described here was also supported in part by NIA grant K24AG031155 (awarded to Kristine Yaffe, MD); by Career Development Award 1IK2RX001629 (awarded to Allison Kaup, PhD) from the US Department of Veterans Affairs, Rehabilitation Research and Development Service; and the Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC). The contents of this manuscript do not represent the views of the US Department of Veterans Affairs or the United States Government. NR 25 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 24 PY 2015 VL 85 IS 21 BP 1852 EP 1858 DI 10.1212/WNL.0000000000002153 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CW9HJ UT WOS:000365309500007 PM 26511452 ER PT J AU Berkowitz, AL Milligan, TA Cho, TA AF Berkowitz, Aaron L. Milligan, Tracey A. Cho, Tracey A. TI DEVELOPMENT OF A TRACK IN GLOBAL AND HUMANITARIAN HEALTH FOR NEUROLOGY RESIDENTS SO NEUROLOGY LA English DT Article AB Neurology trainee interest in global health is rapidly increasing, but few neurology residency programs have formal opportunities for residents to pursue training in global health.(1) Residents who participate in rotations abroad are at times inadequately prepared or insufficiently supported, which can lead to a detrimental burden on the host institution and negatively impact residents' experiences.(2) We report the development of a track in global and humanitarian health aimed to provide a structured curriculum in the practice of neurology in resource-limited settings for neurology residents. C1 [Berkowitz, Aaron L.; Milligan, Tracey A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. [Cho, Tracey A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Berkowitz, AL (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA. EM aberkowitz3@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 24 PY 2015 VL 85 IS 21 BP 1894 EP 1895 DI 10.1212/WNL.0000000000002154 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CW9HU UT WOS:000365310600003 PM 26598431 ER PT J AU Ellis, L Loda, M AF Ellis, Leigh Loda, Massimo TI Advanced neuroendocrine prostate tumors regress to stemness SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID MOUSE MODEL; CANCER; INHIBITION; CELLS C1 [Ellis, Leigh] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Dept Med Oncol, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London SE1 9RT, England. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 2015 VL 112 IS 47 BP 14406 EP 14407 DI 10.1073/pnas.1519151112 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IY UT WOS:000365173100029 PM 26578812 ER PT J AU Sun, S Payer, B Namekawa, S An, JY Press, W Catalan-Dibene, J Sunwoo, H Lee, JT AF Sun, Sha Payer, Bernhard Namekawa, Satoshi An, Jee Young Press, William Catalan-Dibene, Jovani Sunwoo, Hongjae Lee, Jeannie T. TI Xist imprinting is promoted by the hemizygous (unpaired) state in the male germ line SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Xist; imprinting; X inactivation; transgenerational inheritance; meiotic silencing by unpaired DNA ID X-CHROMOSOME INACTIVATION; EARLY MOUSE DEVELOPMENT; DOSAGE COMPENSATION; RNA; TSIX; GENE; EXPRESSION; MICE; MAMMALS; SPERMATOGENESIS AB The long noncoding X-inactivation-specific transcript (Xist gene) is responsible for mammalian X-chromosome dosage compensation between the sexes, the process by which one of the two X chromosomes is inactivated in the female soma. Xist is essential for both the random and imprinted forms of X-chromosome inactivation. In the imprinted form, Xist is paternally marked to be expressed in female embryos. To investigate the mechanism of Xist imprinting, we introduce Xist transgenes (Tg) into the male germ line. Although ectopic high-level Xist expression on autosomes can be compatible with viability, transgenic animals demonstrate reduced fitness, subfertility, defective meiotic pairing, and other germ-cell abnormalities. In the progeny, paternal-specific expression is recapitulated by the 200-kb Xist Tg. However, Xist imprinting occurs efficiently only when it is in an unpaired or unpartnered state during male meiosis. When transmitted from a hemizygous father (+/Tg), the Xist Tg demonstrates paternal-specific expression in the early embryo. When transmitted by a homozygous father (Tg/Tg), the Tg fails to show imprinted expression. Thus, Xist imprinting is directed by sequences within a 200-kb X-linked region, and the hemizygous (unpaired) state of the Xist region promotes its imprinting in the male germ line. C1 [Sun, Sha; Payer, Bernhard; An, Jee Young; Press, William; Sunwoo, Hongjae; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Sun, Sha; Payer, Bernhard; An, Jee Young; Press, William; Sunwoo, Hongjae; Lee, Jeannie T.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02114 USA. [Sun, Sha; Catalan-Dibene, Jovani] Univ Calif Irvine, Sch Biol Sci, Dept Dev & Cell Biol, Irvine, CA 92697 USA. [Namekawa, Satoshi] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Div Reprod Sci, Cincinnati, OH 45229 USA. [Namekawa, Satoshi] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA. [Lee, Jeannie T.] Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Payer, Bernhard/0000-0002-4694-2082 FU NIH [R01-GM58839]; UCI FX We thank members of the Lee laboratory for valuable discussions and suggestions, the University of California, Irvine (UCI) Optical Biology Core Facility for use of the Zeiss LSM780 system, and the UCI Transgenic Mouse Facility for assistance with mouse embryos. This work was funded by NIH Grant R01-GM58839 (to J.T.L.) and by start-up funds from UCI (to S.S.). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 56 TC 5 Z9 6 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 2015 VL 112 IS 47 BP 14415 EP 14422 DI 10.1073/pnas.1519528112 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IY UT WOS:000365173100032 PM 26489649 ER PT J AU Weissleder, R Nahrendorf, M AF Weissleder, Ralph Nahrendorf, Matthias TI Advancing biomedical imaging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE imaging; intravital microscopy; inflammation ID ACUTE MYOCARDIAL-INFARCTION; IRON-OXIDE NANOPARTICLES; IN-VIVO; MAGNETIC-RESONANCE; LUNG-CANCER; STEM-CELLS; FOLATE RECEPTOR; MASS CYTOMETRY; QUANTUM DOTS; SINGLE-CELL AB Imaging reveals complex structures and dynamic interactive processes, located deep inside the body, that are otherwise difficult to decipher. Numerous imaging modalities harness every last inch of the energy spectrum. Clinical modalities include magnetic resonance imaging (MRI), X-ray computed tomography (CT), ultrasound, and light-based methods [endoscopy and optical coherence tomography (OCT)]. Research modalities include various light microscopy techniques (confocal, multiphoton, total internal reflection, superresolution fluorescence microscopy), electron microscopy, mass spectrometry imaging, fluorescence tomography, bioluminescence, variations of OCT, and optoacoustic imaging, among a few others. Although clinical imaging and researchmicroscopy are often isolated from one another, we argue that their combination and integration is not only informative but also essential to discovering new biology and interpreting clinical datasets in which signals invariably originate from hundreds to thousands of cells per voxel. C1 [Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL122208] NR 82 TC 8 Z9 8 U1 13 U2 67 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 2015 VL 112 IS 47 BP 14424 EP 14428 DI 10.1073/pnas.1508524112 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IY UT WOS:000365173100034 PM 26598657 ER PT J AU McLaren, PJ Coulonges, C Bartha, I Lenz, TL Deutsch, AJ Bashirova, A Buchbinder, S Carrington, MN Cossarizza, A Dalmau, J De Luca, A Goedert, JJ Gurdasani, D Haas, DW Herbeck, JT Johnson, EO Kirk, GD Lambotte, O Luo, M Mallal, S van Manen, D Martinez-Picado, J Meyer, L Miro, J Mullins, JI Obel, N Poli, G Sandhu, MS Schuitemaker, H Shea, PR Theodorou, I Walker, BD Weintrob, AC Winkler, CA Wolinsky, SM Raychaudhuri, S Goldstein, DB Telenti, A de Bakker, PIW Zagury, JF Fellay, J AF McLaren, Paul J. Coulonges, Cedric Bartha, Istvan Lenz, Tobias L. Deutsch, Aaron J. Bashirova, Arman Buchbinder, Susan Carrington, Mary N. Cossarizza, Andrea Dalmau, Judith De Luca, Andrea Goedert, James J. Gurdasani, Deepti Haas, David W. Herbeck, Joshua T. Johnson, Eric O. Kirk, Gregory D. Lambotte, Olivier Luo, Ma Mallal, Simon van Manen, Daniele Martinez-Picado, Javier Meyer, Laurence Miro, JoseM. Mullins, James I. Obel, Niels Poli, Guido Sandhu, Manjinder S. Schuitemaker, Hanneke Shea, Patrick R. Theodorou, Ioannis Walker, Bruce D. Weintrob, Amy C. Winkler, Cheryl A. Wolinsky, Steven M. Raychaudhuri, Soumya Goldstein, David B. Telenti, Amalio de Bakker, Paul I. W. Zagury, Jean-Francois Fellay, Jacques TI Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV-1 control; GWAS; heritability; infectious disease; genomics ID GENOME-WIDE ASSOCIATION; DISEASE PROGRESSION; AFRICAN-AMERICANS; INFECTION; HLA; AIDS; CCR5; DETERMINANTS; RESTRICTION; HAPLOTYPES AB Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between similar to 8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5 Delta 32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward. C1 [McLaren, Paul J.; Bartha, Istvan; Fellay, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, Global Hlth Inst, CH-1015 Lausanne, Switzerland. [McLaren, Paul J.; Bartha, Istvan; Fellay, Jacques] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Coulonges, Cedric; Zagury, Jean-Francois] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, EA4627, Lab Genom Bioinformat & Applicat, F-75003 Paris, France. [Coulonges, Cedric; Meyer, Laurence; Theodorou, Ioannis; Zagury, Jean-Francois] French Agcy Res AIDS & Hepatitis, ANRS Genom Grp, F-75013 Paris, France. [Lenz, Tobias L.] Max Planck Inst Evolutionary Biol, Dept Evolutionary Ecol, Evolutionary Immunogen, D-24306 Plon, Germany. [Deutsch, Aaron J.] Harvard Univ, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. [Deutsch, Aaron J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Deutsch, Aaron J.; Raychaudhuri, Soumya] Brigham & Womens Hosp, Dept Med, Div Genet & Rheumatol, Boston, MA 02115 USA. [Deutsch, Aaron J.; Raychaudhuri, Soumya] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Bashirova, Arman; Carrington, Mary N.; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02129 USA. [Bashirova, Arman; Carrington, Mary N.; Walker, Bruce D.] Harvard, Boston, MA 02129 USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, Bridge HIV 1, San Francisco, CA 94102 USA. [Carrington, Mary N.] Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Cossarizza, Andrea] Univ Modena & Reggio Emilia, Sch Med, Dept Surg Med Dent & Morphol Sci, I-41121 Modena, Italy. [Dalmau, Judith; Martinez-Picado, Javier] Univ Autonoma Barcelona, AIDS Res Inst IrsiCaixa, Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona 08916, Spain. [De Luca, Andrea] Siena Univ Hosp, Univ Div Infect Dis, I-53100 Siena, Italy. Univ Siena, Dept Med Biotechnol, I-53100 Siena, Italy. [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA. [Gurdasani, Deepti; Sandhu, Manjinder S.] Wellcome Trust Sanger Inst, Human Genet, Hinxton CB10 1SA, England. [Gurdasani, Deepti; Sandhu, Manjinder S.] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. [Haas, David W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Herbeck, Joshua T.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. [Johnson, Eric O.] RTI Int, Behav Hlth Epidemiol, Res Triangle Pk, NC 27709 USA. [Kirk, Gregory D.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. [Lambotte, Olivier] INSERM, U1012, F-94270 Le Kremlin Bicetre, France. [Lambotte, Olivier] Univ Paris 11, F-94270 Le Kremlin Bicetre, France. [Lambotte, Olivier] Hop Bicetre, AP HP, Dept Internal Med & Infect Dis, F-94270 Le Kremlin Bicetre, France. [Luo, Ma] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0J6, Canada. [Luo, Ma] Natl Microbiol Lab, Winnipeg, MB R3E 3P6, Canada. [Mallal, Simon] Murdoch Univ, Inst Immunol & Infect Dis, Perth, WA 6150, Australia. [Mallal, Simon] Pathwest, Perth, WA 6150, Australia. [van Manen, Daniele; Schuitemaker, Hanneke] Univ Amsterdam, Acad Med Ctr, Ctr Infect Dis & Immun Amsterdam, NL-1105 AZ Amsterdam, Netherlands. [Martinez-Picado, Javier] Inst Catalana Recerca & Estudis Avancats, Barcelona 08916, Spain. [Meyer, Laurence] INSERM, Ctr Rech Epidemiol & Sante Populat, U1018, F-94270 Le Kremlin Bicetre, Bicetre, France. [Meyer, Laurence] Univ Paris 11, Fac Med Paris Sud, UMRS 1018, F-94270 Le Kremlin Bicetre, Bicetre, France. [Meyer, Laurence] Hop Bicetre, AP HP, Epidemiol & Publ Hlth Serv, F-94270 Le Kremlin Bicetre, Bicetre, France. [Miro, JoseM.] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, Infect Dis Serv, E-08036 Barcelona, Spain. [Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Obel, Niels] Copenhagen Univ Hosp, Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark. [Poli, Guido] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy. [Poli, Guido] Univ Vita Salute San Raffaele, Sch Med, I-20132 Milan, Italy. [Shea, Patrick R.; Goldstein, David B.] Columbia Univ, Inst Genom Med, New York, NY 10032 USA. [Theodorou, Ioannis] INSERM, UMRS 945, F-75014 Paris, France. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Weintrob, Amy C.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Winkler, Cheryl A.] Leidos Biomed Res Inc, Bas Res Lab, Mol Genet Epidemiol Sect, Ctr Canc Res,NCI,Frederick Natl Lab, Frederick, MD 21702 USA. [Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England. [Telenti, Amalio] J Craig Venter Inst, La Jolla, CA 92037 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands. RP Fellay, J (reprint author), Ecole Polytech Fed Lausanne, Sch Life Sci, Global Hlth Inst, CH-1015 Lausanne, Switzerland. EM Jacques.Fellay@epfl.ch RI SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; Lenz, Tobias/D-1387-2009; Dalmau, Judith/I-7065-2016; Martinez-Picado, Javier/G-5507-2012; Fellay, Jacques/A-6681-2009; OI Deutsch, Aaron/0000-0001-6750-5335; Shea, Patrick/0000-0001-6804-5131; Lenz, Tobias/0000-0002-7203-0044; Dalmau, Judith/0000-0001-7513-3711; Martinez-Picado, Javier/0000-0002-4916-2129; Fellay, Jacques/0000-0002-8240-939X; McLaren, Paul/0000-0001-6019-7018; Wolinsky, Steven/0000-0002-9625-6697 FU Howard Hughes Medical Institute; NIAID NIH HHS [K24 AI118591]; NIDA NIH HHS [U01 DA036297] NR 39 TC 6 Z9 6 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 2015 VL 112 IS 47 BP 14658 EP 14663 DI 10.1073/pnas.1514867112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IY UT WOS:000365173100073 PM 26553974 ER PT J AU Gao, X Zhao, YC Stemmer-Rachamimov, AO Liu, H Huang, PG Chin, SM Selig, MK Plotkin, SR Jain, RK Xu, L AF Gao, Xing Zhao, Yingchao Stemmer-Rachamimov, Anat O. Liu, Hao Huang, Peigen Chin, ShanMin Selig, Martin K. Plotkin, Scott R. Jain, Rakesh K. Xu, Lei TI Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NF2 schwannoma model; anti-VEGF; neurological function; radiation ID ENDOTHELIAL GROWTH-FACTOR; ADVANCED RECTAL-CANCER; PHASE-I TRIAL; NEUROFIBROMATOSIS TYPE-2; VESTIBULAR SCHWANNOMA; KINASE INHIBITOR; MOUSE MODELS; TUMOR-GROWTH; BEVACIZUMAB; CAPECITABINE AB Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS. C1 [Gao, Xing; Zhao, Yingchao; Liu, Hao; Huang, Peigen; Chin, ShanMin; Jain, Rakesh K.; Xu, Lei] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gao, Xing; Zhao, Yingchao; Stemmer-Rachamimov, Anat O.; Liu, Hao; Huang, Peigen; Chin, ShanMin; Selig, Martin K.; Plotkin, Scott R.; Jain, Rakesh K.; Xu, Lei] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Gao, Xing] Cent S Univ, Xiangya Hosp, Dept Oral & Maxillofacial Surg, Changsha 410008, Hunan, Peoples R China. [Zhao, Yingchao] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Ctr Canc, Wuhan 430023, Hubei, Peoples R China. [Stemmer-Rachamimov, Anat O.; Selig, Martin K.] Massachusetts Gen Hosp, Mol Pathol Div, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Xu, L (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM lei@steele.mgh.harvard.edu FU Children's Tumor Foundation Clinical Research Award; American Cancer Society Research Scholar Award; CTF Drug Discovery Initiative; Ira Spiro Award; NIH/National Cancer Institute [P01CA080214, P50CA165962]; Outstanding Investigator Grant [R35CA197743] FX We thank Carolyn Smith and Sylvie Roberge for their superb technical support, Dr. Gino Ferraro for consultation on neurobiological studies, and Meenal Datta and Dr. Yves Boucher for editorial help. This study was supported by a Children's Tumor Foundation Clinical Research Award (to L.X. and S.R.P.), American Cancer Society Research Scholar Award (to L.X.), CTF Drug Discovery Initiative (L.X.), Ira Spiro Award (to L.X.), NIH/National Cancer Institute P01CA080214 and P50CA165962 (to R.K.J.), and Outstanding Investigator Grant R35CA197743 (to R.K.J.). NR 52 TC 1 Z9 2 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 24 PY 2015 VL 112 IS 47 BP 14676 EP 14681 DI 10.1073/pnas.1512570112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IY UT WOS:000365173100076 PM 26554010 ER PT J AU Chen, DZ Craft, D Yang, L AF Chen, Danny Z. Craft, David Yang, Lin TI A circular matrix-merging algorithm with application in Volumetric Intensity-Modulated Arc Therapy SO THEORETICAL COMPUTER SCIENCE LA English DT Article DE Matrix merging; Dynamic programming; kappa-Link shortest path; Volumetric intensity modulated Arc therapy ID SHOOT IMRT DELIVERY; MULTILEAF COLLIMATORS; HELICAL TOMOTHERAPY; RADIATION-THERAPY; VMAT; OPTIMIZATION; GENERATION; EFFICIENCY; QUALITY; PATH AB In this paper, we study an optimization problem, called the circular matrix-merging (CMM) problem: Given a cyclic sequence of n non-negative matrices that are associated with some locations on a circle and an operation that merges two consecutive matrices into one matrix at the expense of some merging error, merge the n matrices into the minimum number of matrices under the constraint of a threshold of the total merging error. This problem arises in Volumetric Intensity-Modulated Arc Therapy (VMAT) for radiation cancer treatment, where the circular structure represents a delivery arc path of 360 degrees around the patient and the matrices represent the radiation fluence maps at selected delivery angles on that path. By computing the minimum k matrices, the CMM algorithm produces a most efficient delivery plan that meets clinical requirements. Based on dynamic programming and computing a set of k-link shortest paths, we present a polynomial time algorithm for the CMM problem, improving the quality and efficiency of VMAT delivery. (C) 2015 Elsevier B.V. All rights reserved. C1 [Chen, Danny Z.; Yang, Lin] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA. [Craft, David] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Craft, David] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yang, L (reprint author), Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA. EM dchen@nd.edu; dcraft@partners.org; lyang5@nd.edu OI Yang, Lin/0000-0001-7593-7066 FU NSF [CCF-1217906] FX This research was supported in part by NSF under Grant CCF-1217906. NR 19 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3975 EI 1879-2294 J9 THEOR COMPUT SCI JI Theor. Comput. Sci. PD NOV 23 PY 2015 VL 607 SI SI BP 126 EP 134 DI 10.1016/j.tcs.2015.04.028 PN 2 PG 9 WC Computer Science, Theory & Methods SC Computer Science GA CZ0AM UT WOS:000366767500002 ER PT J AU Ito, F Ku, AW Bucsek, MJ Muhitch, JB Vardam-Kaur, T Kim, M Fisher, DT Camoriano, M Khoury, T Skitzki, JJ Gollnick, SO Evans, SS AF Ito, Fumito Ku, Amy W. Bucsek, Mark J. Muhitch, Jason B. Vardam-Kaur, Trupti Kim, Minhyung Fisher, Daniel T. Camoriano, Marta Khoury, Thaer Skitzki, Joseph J. Gollnick, Sandra O. Evans, Sharon S. TI Immune Adjuvant Activity of Pre-Resectional Radiofrequency Ablation Protects against Local and Systemic Recurrence in Aggressive Murine Colorectal Cancer SO PLOS ONE LA English DT Article ID RENAL-CELL CARCINOMA; RADIO-FREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; T-CELLS; ANTITUMOR IMMUNITY; THERMAL ABLATION; TUMOR VACCINE; SPONTANEOUS REGRESSION; BREAST-CARCINOMA; LIVER METASTASES AB Purpose While surgical resection is a cornerstone of cancer treatment, local and distant recurrences continue to adversely affect outcome in a significant proportion of patients. Evidence that an alternative debulking strategy involving radiofrequency ablation (RFA) induces antitumor immunity prompted the current investigation of the efficacy of performing RFA prior to surgical resection (pre-resectional RFA) in a preclinical mouse model. Experimental Design Therapeutic efficacy and systemic immune responses were assessed following pre-resectional RFA treatment of murine CT26 colon adenocarcinoma. Results Treatment with pre-resectional RFA significantly delayed tumor growth and improved overall survival compared to sham surgery, RFA, or resection alone. Mice in the pre-resectional RFA group that achieved a complete response demonstrated durable antitumor immunity upon tumor re-challenge. Failure to achieve a therapeutic benefit in immunodeficient mice confirmed that tumor control by pre-resectional RFA depends on an intact adaptive immune response rather than changes in physical parameters that make ablated tumors more amenable to a complete surgical excision. RFA causes a marked increase in intratumoral CD8(+) T lymphocyte infiltration, thus substantially enhancing the ratio of CD8(+) effector T cells: FoxP3(+) regulatory T cells. Importantly, pre-resectional RFA significantly increases the number of antigen-specific CD8(+) T cells within the tumor microenvironment and tumor-draining lymph node but had no impact on infiltration by myeloid-derived suppressor cells, M1 macrophages or M2 macrophages at tumor sites or in peripheral lymphoid organs (i.e., spleen). Finally, pre-resectional RFA of primary tumors delayed growth of distant tumors through a mechanism that depends on systemic CD8(+) T cell-mediated antitumor immunity. Conclusion Improved survival and antitumor systemic immunity elicited by pre-resectional RFA support the translational potential of this neoadjuvant treatment for cancer patients with high-risk of local and systemic recurrence. C1 [Ito, Fumito; Ku, Amy W.; Bucsek, Mark J.; Muhitch, Jason B.; Vardam-Kaur, Trupti; Kim, Minhyung; Fisher, Daniel T.; Camoriano, Marta; Evans, Sharon S.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. [Ito, Fumito; Kim, Minhyung; Skitzki, Joseph J.] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Ito, Fumito] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Muhitch, Jason B.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA. [Vardam-Kaur, Trupti] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab,Dept Radiat Oncol, Boston, MA USA. [Khoury, Thaer] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. [Gollnick, Sandra O.] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA. RP Evans, SS (reprint author), Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. EM sharon.evans@roswellpark.org FU National Institutes of Health [CA79765, AI082039, CA098156, CA109480, P30CA016056]; Jennifer Linscott Tietgen Family Foundation FX This work was supported by grants from the National Institutes of Health (CA79765 and AI082039 to S.S. Evans; CA098156 and CA109480 to S.O. Gollnick; and P30CA016056 to Roswell Park Cancer Institute); and the Jennifer Linscott Tietgen Family Foundation (J.J. Skitzki and S.S. Evans). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 2 Z9 2 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 23 PY 2015 VL 10 IS 11 AR e0143370 DI 10.1371/journal.pone.0143370 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX7AW UT WOS:000365853900101 PM 26599402 ER EF