FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Malhotra, A Neilan, TG Sarmiento, K AF Malhotra, Atul Neilan, Tomas G. Sarmiento, Kathleen TI Obstructive Sleep Apnea and Atrial Fibrillation Is the Link Real? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE animal; atrial pressure; connexin-43; lung; models; pulmonary veins; rats; ventricular remodeling ID CATHETER ABLATION; RECURRENCE; PRESSURE; TRIAL; RISK; REDUCTION; OBESITY; CPAP C1 [Malhotra, Atul] Univ Calif San Diego, Pulm Crit Care & Sleep Med Div, La Jolla, CA 92037 USA. [Neilan, Tomas G.] UCSD Vet Affairs Med Syst, La Jolla, CA USA. [Sarmiento, Kathleen] Harvard Univ, Massachusetts Gen Hosp, Div Radiol, Dept Med,Cardiac MR PET CT Program, Boston, MA USA. RP Malhotra, A (reprint author), Univ Calif San Diego, 9300 Campus Pointe Dr, La Jolla, CA 92037 USA. EM amalhotra@ucsd.edu FU NHLBI NIH HHS [K24 HL093218, R01 HL085188] NR 20 TC 0 Z9 1 U1 0 U2 2 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 NOV 11 PY 2014 VL 64 IS 19 BP 2024 EP 2025 DI 10.1016/j.jacc.2014.07.990 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT0HI UT WOS:000344617200008 PM 25440098 ER PT J AU Shoamanesh, A Martinez-Ramirez, S Oliveira, J Reijmer, Y Falcone, GJ Ayres, A Schwab, K Goldstein, JN Rosand, J Gurol, ME Viswanathan, A Greenberg, SM AF Shoamanesh, Ashkan Martinez-Ramirez, Sergi Oliveira-Filho, Jamary Reijmer, Yael Falcone, Guido J. Ayres, Alison Schwab, Kristin Goldstein, Joshua N. Rosand, Jonathan Gurol, M. Edip Viswanathan, Anand Greenberg, Steven M. TI Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID LOBAR INTRACEREBRAL HEMORRHAGE; APOLIPOPROTEIN-E EPSILON-2; CENTRAL-NERVOUS-SYSTEM; PREVALENCE; ASSOCIATION; POPULATION; GENOTYPE; ALLELE; SIGN AB Objective: We sought to explore the mechanisms leading to cerebral amyloid angiopathy (CAA)-related cortical superficial siderosis (cSS) by examining its neuroimaging and genetic association with cerebral microbleeds (CMBs). Methods: MRI scans of >4 subjects with probable or definite CAA participating in a longitudinal research study were graded for cSS presence and severity (focal, restricted to <= 3 sulci vs disseminated, $4 sulci), and CMB count. APOE epsilon variants were directly genotyped. We performed cross-sectional analysis comparing CMB counts and APOE epsilon 2 and epsilon 4 allele frequency between subjects with no, focal, or disseminated cSS. Results: cSS was present in 48% (n = 40) of the population. APOE epsilon 2 was overrepresented among participants with focal (odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-29.3, p = 0.008) and disseminated (OR 11.5, 95% CI 2.8-46.2, p = 0.001) cSS relative to individuals without cSS. CMB counts decreased with increasing severity of cSS (median: 41, 38, and 15 for no cSS, focal cSS, and disseminated cSS, respectively, p = 0.09). The highest CMB count tertile was associated with APOE epsilon 4 (OR 3.0, 95% CI 1.4-6.6, p = 0.006) relative to the lowest tertile. Conclusions: Among individuals with advanced CAA, cSS tends to occur in individuals with relatively lower CMB counts and with a distinct pattern of APOE genotypes. These results suggest that CAA-related cSS and CMBs may arise from distinct vasculopathic mechanisms. C1 [Shoamanesh, Ashkan; Martinez-Ramirez, Sergi; Oliveira-Filho, Jamary; Reijmer, Yael; Falcone, Guido J.; Ayres, Alison; Schwab, Kristin; Goldstein, Joshua N.; Rosand, Jonathan; Gurol, M. Edip; Viswanathan, Anand; Greenberg, Steven M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program, Boston, MA 02115 USA. RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemorrhag Stroke Res Program, Boston, MA 02115 USA. EM sgreenberg@mgh.harvard.edu RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016 OI Falcone, Guido/0000-0002-6407-0302 FU NIH [R01 AG26484, R01 NS070834] FX This work is supported by grants from the NIH (R01 AG26484 and R01 NS070834). NR 21 TC 17 Z9 17 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 11 PY 2014 VL 83 IS 20 BP 1838 EP 1843 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AT3SR UT WOS:000344854400013 PM 25320098 ER PT J AU Waugh, JL AF Waugh, Jeff L. TI Education in medical billing benefits both neurology trainees and academic departments SO NEUROLOGY LA English DT Article ID RESIDENTS; CURRICULUM; DOCUMENTATION; PHYSICIANS; KNOWLEDGE; BUSINESS; SERVICES AB The objective of residency training is to produce physicians who can function independently within their chosen subspecialty and practice environment. Skills in the business of medicine, such as clinical billing, are widely applicable in academic and private practices but are not commonly addressed during formal medical education. Residency and fellowship training include limited exposure to medical billing, but our academic department's performance of these skills was inadequate: in 56% of trainee-generated outpatient notes, documentation was insufficient to sustain the chosen billing level. We developed a curriculum to improve the accuracy of documentation and coding and introduced practice changes to address our largest sources of error. In parallel, we developed tools that increased the speed and efficiency of documentation. Over 15 months, we progressively eliminated note devaluation, increased the mean level billed by trainees to nearly match that of attending physicians, and increased outpatient revenue by $34,313/trainee/year. Our experience suggests that inclusion of billing education topics into the formal medical curriculum benefits both academic medical centers and trainees. C1 [Waugh, Jeff L.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Waugh, Jeff L.] Massachusetts Gen Hosp, Pediat Movement Disorders Clin, Boston, MA 02114 USA. RP Waugh, JL (reprint author), Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. EM Jeff.Waugh@childrens.harvard.edu NR 23 TC 3 Z9 3 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 11 PY 2014 VL 83 IS 20 BP 1856 EP 1861 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AT3SR UT WOS:000344854400016 PM 25298311 ER PT J AU Ebrahimkhani, MR Daneshmand, A Mazumder, A Allocca, M Calvo, JA Abolhassani, N Jhun, I Muthupalani, S Ayata, C Samson, LD AF Ebrahimkhani, Mohammad R. Daneshmand, Ali Mazumder, Aprotim Allocca, Mariacarmela Calvo, Jennifer A. Abolhassani, Nona Jhun, Iny Muthupalani, Sureshkumar Ayata, Cenk Samson, Leona D. TI Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA repair; base excision; Aag/Mpg DNA glycosylase; ischemia reperfusion; liver ID METHYLPURINE-DNA GLYCOSYLASE; POLY(ADP-RIBOSE) POLYMERASE-1; CHRONIC INFLAMMATION; CELL-DEATH; DAMAGE; MICE; MECHANISMS; PARP-1; HMGB1; PROTECTS AB Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag(-/-) mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag(-/-) mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly (ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag(-/-) liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury. C1 [Ebrahimkhani, Mohammad R.; Mazumder, Aprotim; Allocca, Mariacarmela; Calvo, Jennifer A.; Abolhassani, Nona; Jhun, Iny; Samson, Leona D.] MIT, Ctr Environm Hlth Sci, David H Koch Inst Integrat Canc Res, Dept Biol Engn, Cambridge, MA 02139 USA. [Ebrahimkhani, Mohammad R.; Mazumder, Aprotim; Allocca, Mariacarmela; Calvo, Jennifer A.; Abolhassani, Nona; Jhun, Iny; Samson, Leona D.] MIT, Ctr Environm Hlth Sci, David H Koch Inst Integrat Canc Res, Dept Biol, Cambridge, MA 02139 USA. [Daneshmand, Ali; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Muthupalani, Sureshkumar] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit, Boston, MA 02114 USA. RP Samson, LD (reprint author), MIT, Ctr Environm Hlth Sci, David H Koch Inst Integrat Canc Res, Dept Biol Engn, Cambridge, MA 02139 USA. EM lsamson@mit.edu FU National Institutes of Health [R01-CA055042, R01-CA149261, P30-ES02109, R01-NS055104]; Ellison Medical Foundation; Heitman Foundation; Ellison Foundation FX We thank Catherine A. Moroski-Erkul and Lindsey W. Eichinger for technical help with mouse colonies during the study, the Swanson Biotechnology Center, the David H. Koch Institute for Integrative Cancer Research, and the Center for Environmental Health Sciences Bioanalytical Core Facility. This work was supported by National Institutes of Health Grants R01-CA055042, R01-CA149261, and P30-ES02109 and the Ellison Medical Foundation (to L. D. S.); National Institutes of Health Grant R01-NS055104 (to C. A.); and the Heitman Foundation and the Ellison Foundation (C. A.). L. D. S. is an American Cancer Society Research Professor. NR 60 TC 13 Z9 13 U1 1 U2 10 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 11 PY 2014 VL 111 IS 45 BP E4878 EP E4886 DI 10.1073/pnas.1413582111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS8WW UT WOS:000344526800012 PM 25349415 ER PT J AU Tan, L Wang, J Tanizaki, J Huang, ZF Aref, AR Rusan, M Zhu, SJ Zhang, YY Ercan, D Liao, RG Capelletti, M Zhou, WJ Hur, W Kim, N Sim, T Gaudet, S Barbie, DA Yeh, JRJ Yun, CH Hammerman, PS Mohammadi, M Janne, PA Gray, NS AF Tan, Li Wang, Jun Tanizaki, Junko Huang, Zhifeng Aref, Amir R. Rusan, Maria Zhu, Su-Jie Zhang, Yiyun Ercan, Dalia Liao, Rachel G. Capelletti, Marzia Zhou, Wenjun Hur, Wooyoung Kim, NamDoo Sim, Taebo Gaudet, Suzanne Barbie, David A. Yeh, Jing-Ruey Joanna Yun, Cai-Hong Hammerman, Peter S. Mohammadi, Moosa Jaenne, Pasi A. Gray, Nathanael S. TI Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE drug discovery; cancer drug resistance; kinase inhibitor; structure-based drug design ID FACTOR RECEPTOR 4; GROWTH-FACTOR RECEPTORS; TYROSINE KINASE; LUNG-CANCER; SELECTIVE INHIBITOR; COLORECTAL-CANCER; DRUG-RESISTANCE; HEPATOCELLULAR-CARCINOMA; REGULATES PROLIFERATION; ACQUIRED-RESISTANCE AB The human FGF receptors (FGFRs) play critical roles in various human cancers, and several FGFR inhibitors are currently under clinical investigation. Resistance usually results from selection for mutant kinases that are impervious to the action of the drug or from up-regulation of compensatory signaling pathways. Preclinical studies have demonstrated that resistance to FGFR inhibitors can be acquired through mutations in the FGFR gatekeeper residue, as clinically observed for FGFR4 in embryonal rhabdomyosarcoma and neuroendocrine breast carcinomas. Here we report on the use of a structure-based drug design to develop two selective, next-generation covalent FGFR inhibitors, the FGFR irreversible inhibitors 2 (FIIN-2) and 3 (FIIN-3). To our knowledge, FIIN-2 and FIIN-3 are the first inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. Because of the conformational flexibility of the reactive acrylamide substituent, FIIN-3 has the unprecedented ability to inhibit both the EGF receptor (EGFR) and FGFR covalently by targeting two distinct cysteine residues. We report the cocrystal structure of FGFR4 with FIIN-2, which unexpectedly exhibits a "DFG-out" covalent binding mode. The structural basis for dual FGFR and EGFR targeting by FIIN3 also is illustrated by crystal structures of FIIN-3 bound with FGFR4 V550L and EGFR L858R. These results have important implications for the design of covalent FGFR inhibitors that can overcome clinical resistance and provide the first example, to our knowledge, of a kinase inhibitor that covalently targets cysteines located in different positions within the ATP-binding pocket. C1 [Tan, Li; Zhou, Wenjun; Hur, Wooyoung; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Aref, Amir R.; Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yiyun; Yeh, Jing-Ruey Joanna] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Tan, Li; Zhou, Wenjun; Hur, Wooyoung; Gaudet, Suzanne; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Wang, Jun; Tanizaki, Junko; Aref, Amir R.; Rusan, Maria; Ercan, Dalia; Liao, Rachel G.; Capelletti, Marzia; Barbie, David A.; Hammerman, Peter S.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tanizaki, Junko; Ercan, Dalia; Capelletti, Marzia; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Gaudet, Suzanne] Dana Farber Canc Inst, Ctr Syst Canc Biol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Huang, Zhifeng; Mohammadi, Moosa] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA. [Huang, Zhifeng] Wenzhou Med Univ, Sch Pharm, Wenzhou 325035, Peoples R China. [Rusan, Maria] Aarhus Univ, Dept Clin Med, DK-8200 Aarhus, Denmark. [Zhu, Su-Jie; Yun, Cai-Hong] Peking Univ, Hlth Sci Ctr, Beijing 100191, Peoples R China. [Zhang, Yiyun; Yeh, Jing-Ruey Joanna] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Liao, Rachel G.; Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02141 USA. [Hur, Wooyoung; Sim, Taebo] Korea Inst Sci & Technol, Chem Kin Res Ctr, Seoul 136791, South Korea. [Kim, NamDoo] Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Taegu 706010, South Korea. [Sim, Taebo] Korea Univ, Korean Inst Sci & Technol, Grad Sch Converging Sci & Technol, Seoul 136713, South Korea. RP Hammerman, PS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM Peter_Hammerman@dfci.harvard.edu; Moosa.Mohammadi@nyumc.org; pasi_janne@dfci.harvard.edu; nathanael_gray@dfci.harvard.edu OI Liao, Rachel/0000-0002-7830-1976; Mohammadi, Moosa/0000-0003-2434-9437 FU Lung Specialized Programs of Research Excellence [5 P50 CA090578-10]; National Institute of Dental and Craniofacial Research [R01 DE13686] FX We thank Liping Wang for technical assistance and Dr. Sara Buhrlage for proofreading. This work was supported by Lung Specialized Programs of Research Excellence Grant 5 P50 CA090578-10 (to P.A.J. and N.S.G.) and National Institute of Dental and Craniofacial Research Grant R01 DE13686 (to M. M.). NR 95 TC 31 Z9 32 U1 5 U2 44 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 11 PY 2014 VL 111 IS 45 BP E4869 EP E4877 DI 10.1073/pnas.1403438111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS8WW UT WOS:000344526800011 PM 25349422 ER PT J AU Shinozaki, S Chang, K Sakai, M Shimizu, N Yamada, M Tanaka, T Nakazawa, H Ichinose, F Yamada, Y Ishigami, A Ito, H Ouchi, Y Starr, ME Saito, H Shimokado, K Stamler, JS Kaneki, M AF Shinozaki, Shohei Chang, Kyungho Sakai, Michihiro Shimizu, Nobuyuki Yamada, Marina Tanaka, Tomokazu Nakazawa, Harumasa Ichinose, Fumito Yamada, Yoshitsugu Ishigami, Akihito Ito, Hideki Ouchi, Yasuyoshi Starr, Marlene E. Saito, Hiroshi Shimokado, Kentaro Stamler, Jonathan S. Kaneki, Masao TI Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65 SO SCIENCE SIGNALING LA English DT Article ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; INSULIN-RESISTANCE; PARKINSONS-DISEASE; CELL-DEATH; HISTONE DEACETYLASE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; NEURODEGENERATIVE DISEASES; NITROSATIVE STRESS; GUANYLYL CYCLASE AB Inflammation increases the abundance of inducible nitric oxide synthase (iNOS), leading to enhanced production of nitric oxide (NO), which can modify proteins by S-nitrosylation. Enhanced NO production increases the activities of the transcription factors p53 and nuclear factor kappa B (NF-kappa B) in several models of disease-associated inflammation. S-Nitrosylation inhibits the activity of the protein deacetylase SIRT1. SIRT1 limits apoptosis and inflammation by deacetylating p53 and p65 (also known as RelA), a subunit of NF-kappa B. We showed in multiple cultured mammalian cell lines that NO donors or inflammatory stimuli induced S-nitrosylation of SIRT1 within CXXC motifs, which inhibited SIRT1 by disrupting its ability to bind zinc. Inhibition of SIRT1 reduced deacetylation and promoted activation of p53 and p65, leading to apoptosis and increased expression of proinflammatory genes. In rodent models of systemic inflammation, Parkinson's disease, or aging-related muscular atrophy, S-nitrosylation of SIRT1 correlated with increased acetylation of p53 and p65 and activation of p53 and NF-kappa B target genes, suggesting that S-nitrosylation of SIRT1 may represent a proinflammatory switch common to many diseases and aging. C1 [Shinozaki, Shohei; Chang, Kyungho; Sakai, Michihiro; Shimizu, Nobuyuki; Yamada, Marina; Tanaka, Tomokazu; Nakazawa, Harumasa; Ichinose, Fumito; Kaneki, Masao] Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp,Dept Anesthesia Crit Care, Charlestown, MA 02129 USA. [Shinozaki, Shohei; Shimokado, Kentaro] Tokyo Med & Dent Univ, Grad Sch, Dept Geriatr & Vasc Med, Tokyo 1138519, Japan. [Chang, Kyungho; Yamada, Yoshitsugu] Univ Tokyo, Grad Sch Med, Dept Anesthesiol, Tokyo 1138655, Japan. [Chang, Kyungho; Yamada, Yoshitsugu] Univ Tokyo, Grad Sch Med, Pain Relief Ctr, Tokyo 1138655, Japan. [Ishigami, Akihito; Ito, Hideki] Tokyo Metropolitan Inst Gerontol, Tokyo 1730015, Japan. [Ouchi, Yasuyoshi] Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Tokyo 1138655, Japan. [Ouchi, Yasuyoshi] Federat Natl Publ Serv Personnel Mutual Aid Assoc, Tokyo 1050001, Japan. [Starr, Marlene E.; Saito, Hiroshi] Univ Kentucky, Dept Surg, Coll Med, Lexington, KY 40536 USA. [Stamler, Jonathan S.] Case Western Reserve Univ, Inst Transformat Mol Med, Cleveland, OH 44106 USA. [Stamler, Jonathan S.] Case Western Reserve Univ, Harrington Discovery Inst, Cleveland, OH 44106 USA. [Stamler, Jonathan S.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp,Dept Anesthesia Crit Care, Charlestown, MA 02129 USA. EM mkaneki@helix.mgh.harvard.edu FU NIH [R01-DK-058127, R01-GM-099921, 5P01-HL-075443-08, R01-AG-039732]; American Diabetes Association [7-08-RA-77]; Shriners Hospitals for Children [71000, 85800]; Defense Advanced Research Project Agency [N66001-13-C-4054]; JSPS [25860231]; Takeda Scientific Foundation; Atherosclerosis Research Foundation; MEXT [24108007, 21592304] FX This work was supported by grants from the NIH (R01-DK-058127), American Diabetes Association (7-08-RA-77), and Shriners Hospitals for Children (71000, 85800) to M.K.; NIH (R01-GM-099921, 5P01-HL-075443-08) and Defense Advanced Research Project Agency (N66001-13-C-4054) to J.S.; NIH (R01-AG-039732) to H.S.; JSPS KAKENHI (25860231) and Takeda Scientific Foundation to S.S.; Atherosclerosis Research Foundation to K.S.; MEXT KAKENHI (24108007) to N.S.; and MEXT KAKENHI (21592304) to K.C. NR 102 TC 20 Z9 22 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1945-0877 EI 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD NOV 11 PY 2014 VL 7 IS 351 AR ra106 DI 10.1126/scisignal.2005375 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AT7EQ UT WOS:000345100200001 PM 25389371 ER PT J AU Astill, RG Piantoni, G Raymann, RJEM Vis, JC Coppens, JE Walker, MP Stickgold, R Van Der Werf, YD Van Someren, EJW AF Astill, Rebecca G. Piantoni, Giovanni Raymann, Roy J. E. M. Vis, Jose C. Coppens, Joris E. Walker, Matthew P. Stickgold, Robert Van Der Werf, Ysbrand D. Van Someren, Eus J. W. TI Sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE children; learning; motor skill; memory; sleep; spindles; slow waves; frequency ID MEMORY CONSOLIDATION; INTELLECTUAL ABILITY; DECLARATIVE MEMORY; EEG; OSCILLATIONS; ADOLESCENCE; CHILDHOOD; SEQUENCE; BRAIN; ELECTROENCEPHALOGRAM AB Background and Aim: The role of sleep in the enhancement of motor skills has been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children. Hypothesis: We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics. Methods: 30 children (19 females, 10.7 +/- 0.8 years of age; mean +/- SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography (PSG) night. Initial and delayed performance were assessed over 12 h of wake; 12 h with sleep; and 24 h with wake and sleep. For the 12 h with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions. Analyses: Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy. Results and Conclusions: Children enhance their accuracy only over an interval with sleep. Unlike previously reported in adults, children enhance their speed independent of sleep, a capacity that may to be lost in adulthood. Individual differences in the dominant frequency of spindles and slow waves were predictive for performance: children performed better if they had less slow spindles, more fast spindles and faster slow waves. On the other hand, overnight enhancement of accuracy was most pronounced in children with more slow spindles and slower slow waves, i.e., the ones with an initial lower performance. Associations of spindle and slow wave characteristics with initial performance may confound interpretation of their involvement in overnight enhancement. Slower frequencies of characteristic sleep events may mark slower learning and immaturity of networks involved in motor skills. C1 [Astill, Rebecca G.; Piantoni, Giovanni; Raymann, Roy J. E. M.; Vis, Jose C.] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Sleep & Cognit, NL-1105 BA Amsterdam, Netherlands. [Astill, Rebecca G.] Slotervaartziekenhuis, Amsterdam Sleep Ctr, Dept Clin Neurophysiol, Amsterdam, Netherlands. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Vis, Jose C.] Sleepvision, Berg En Dal, Netherlands. [Coppens, Joris E.] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Technol & Software Dev, NL-1105 BA Amsterdam, Netherlands. [Walker, Matthew P.] Univ Calif Berkeley, Dept Psychol, Sleep & Neuroimaging Lab, Berkeley, CA 94720 USA. [Stickgold, Robert] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Stickgold, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Van Der Werf, Ysbrand D.] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Emot & Cognit, NL-1105 BA Amsterdam, Netherlands. [Van Der Werf, Ysbrand D.] VU Univ & Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [Van Someren, Eus J. W.] VU Univ & Med Ctr, Ctr Neurogen & Cognit Res, Dept Integrat Neurophysiol, Amsterdam, Netherlands. [Van Someren, Eus J. W.] VU Univ & Med Ctr, Ctr Neurogen & Cognit Res, Dept Med Psychol, Amsterdam, Netherlands. RP Van Someren, EJW (reprint author), Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Sleep & Cognit, Meibergdreef 4, NL-1105 BA Amsterdam, Netherlands. EM e.van.someren@nin.knaw.nl FU Netherlands Organization of Scientific Research; Netherlands Institute for Neuroscience; Baer Bed; Medcare; IBM; Amstel Botel; Cambridge Neurotechnology; J&J Pharmaceutical Research and Development; Nederlandse Vereniging voor Slaap-Waak Onderzock; Onderzoeksschool Neurowetenschappen Amsterdam; Philips; SEIN Zwolle; Gelre ziekenhuizen Zutphen; OLVG Amsterdam; Sint Lucas Andreas Ziekenhuis Amsterdam; Spaarne Ziekenhuis Hoofddorp; Zaans Medisch Centrum Zaandam; Netherlands Organization of Scientific Research (NWO): VICI Innovation [453-07-001]; National Initiative Brain and Cognition Research Program "Innovative learning materials and methods" [056-32-013] FX Data were obtained during "The Great Sleep Experiment" event, organized and sponsored by Netherlands Organization of Scientific Research and the Netherlands Institute for Neuroscience, and sponsored by Baer Bed, Medcare, IBM, Amstel Botel, Cambridge Neurotechnology, J&J Pharmaceutical Research and Development, Nederlandse Vereniging voor Slaap-Waak Onderzock, Onderzoeksschool Neurowetenschappen Amsterdam, Philips, SEIN Zwolle, Gelre ziekenhuizen Zutphen, OLVG Amsterdam, Sint Lucas Andreas Ziekenhuis Amsterdam, Spaarne Ziekenhuis Hoofddorp and Zaans Medisch Centrum Zaandam. This work was further supported by grants from the Netherlands Organization of Scientific Research (NWO): VICI Innovation (Grant 453-07-001), and National Initiative Brain and Cognition Research Program "Innovative learning materials and methods" (Grant 056-32-013). NR 74 TC 9 Z9 9 U1 0 U2 15 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD NOV 11 PY 2014 VL 8 AR 910 DI 10.3389/fnhum.2014.00910 PG 13 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AS8UH UT WOS:000344522900001 PM 25426055 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Antiangiogenesis Strategies Revisited: From Starving Tumors to Alleviating Hypoxia SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III TRIAL; METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA; ANTI-ANGIOGENIC THERAPY; ADVANCED HEPATOCELLULAR-CARCINOMA; PANCREATIC NEUROENDOCRINE TUMORS; BREAST-CANCER; BLOOD-VESSELS; VASCULAR NORMALIZATION AB Ten antiangiogenic drugs targeting VEGF or its receptors are approved for cancer treatment. However, these agents, intended to block tumors' blood supply, may cause hypoxia, which may fuel tumor progression and treatment resistance. Emerging clinical data suggest that patients whose tumor perfusion or oxygenation increases in response to these agents may actually survive longer. Hence, strategies aimed at alleviating tumor hypoxia while improving perfusion may enhance the outcome of radiotherapy, chemotherapy, and immunotherapy. Here I summarize lessons learned from preclinical and clinical studies over the past decade and propose strategies for improving antiangiogenic therapy outcomes for malignant and nonmalignant diseases. C1 [Jain, Rakesh K.] Harvard Univ, Sch Med, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Jain, Rakesh K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU Enlight; Ophthotech; SynDevRx; NIH [P01CA080124, R01CA163815]; Proton Beam/Federal Share Program; Department of Defense Breast Cancer Innovator Award; National Foundation for Cancer Research FX R.K.J. would like to thank colleagues and collaborators for their contributions to the areas of tumor microenvironment and antiangiogenesis therapy for more than three decades. In addition, R.K.J. would like to thank Dan G. Duda and Giorgio Seano for their help in manuscript preparation: Dan G. Duda for preparing Figure 1 and Table 1; Trupti Vardam for preparing Table 3; Giorgio Seano for preparing Table 2 and Figures 2,3, and 4; and James Baish, Tracy T. Batchelor, Ana Batista, Peter Carmeliet, Vikash Chauhan, Helen Chen, Elisabeth de Vries, Dai Fukumura, Steven Isakoff, Robert S. Kerbel, Lance L. Munn, Kamila Naxerova, Mei Rosa Ng, Timothy P. Padera, Sara Tolaney, and Lei Xu for many helpful comments. R.K.J. received consultant fees from Enlight, Ophthotech, and SynDevRx. R.K.J. owns equity in Enlight, Ophthotech, SynDevRx, and XTuit and serves on the Board of Directors of XTuit and the Boards of Trustees of H&Q Healthcare Investors, H&Q Life Sciences Investors, and the Tekla Healthcare Opportunities Fund. This work was supported by the NIH (P01CA080124 and R01CA163815), the Proton Beam/Federal Share Program, the Department of Defense Breast Cancer Innovator Award, and the National Foundation for Cancer Research. NR 172 TC 157 Z9 162 U1 12 U2 76 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD NOV 10 PY 2014 VL 26 IS 5 BP 605 EP 622 DI 10.1016/j.ccell.2014.10.006 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AT5KA UT WOS:000344980900007 PM 25517747 ER PT J AU Riggi, N Knoechel, B Gillespie, SM Rheinbay, E Boulay, G Suva, ML Rossetti, NE Boonseng, WE Oksuz, O Cook, EB Formey, A Patel, A Gymrek, M Thapar, V Deshpande, V Ting, DT Hornicek, FJ Nielsen, GP Stamenkovic, I Aryee, MJ Bernstein, BE Rivera, MN AF Riggi, Nicolo Knoechel, Birgit Gillespie, Shawn M. Rheinbay, Esther Boulay, Gaylor Suva, Mario L. Rossetti, Nikki E. Boonseng, Wannaporn E. Oksuz, Ozgur Cook, Edward B. Formey, Aurelie Patel, Anoop Gymrek, Melissa Thapar, Vishal Deshpande, Vikram Ting, David T. Hornicek, Francis J. Nielsen, G. Petur Stamenkovic, Ivan Aryee, Martin J. Bernstein, Bradley E. Rivera, Miguel N. TI EWS-FLI1 Utilizes Divergent Chromatin Remodeling Mechanisms to Directly Activate or Repress Enhancer Elements in Ewing Sarcoma SO CANCER CELL LA English DT Article ID MESENCHYMAL STEM-CELLS; IN-VIVO; HUMAN GENOME; TRANSCRIPTION; ONCOGENE; CANCER; GENE; LINEAGE; FUSION; MICROSATELLITES AB The aberrant transcription factor EWS-FLI1 drives Ewing sarcoma, but its molecular function is not completely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements, which lack evolutionary conservation and regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors. These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets, such as the kinase VRK1. Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation. C1 [Riggi, Nicolo; Knoechel, Birgit; Gillespie, Shawn M.; Rheinbay, Esther; Boulay, Gaylor; Suva, Mario L.; Rossetti, Nikki E.; Boonseng, Wannaporn E.; Oksuz, Ozgur; Cook, Edward B.; Deshpande, Vikram; Nielsen, G. Petur; Aryee, Martin J.; Bernstein, Bradley E.; Rivera, Miguel N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Riggi, Nicolo; Knoechel, Birgit; Gillespie, Shawn M.; Rheinbay, Esther; Boulay, Gaylor; Suva, Mario L.; Rossetti, Nikki E.; Boonseng, Wannaporn E.; Oksuz, Ozgur; Cook, Edward B.; Aryee, Martin J.; Bernstein, Bradley E.; Rivera, Miguel N.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Riggi, Nicolo; Knoechel, Birgit; Gillespie, Shawn M.; Rheinbay, Esther; Boulay, Gaylor; Suva, Mario L.; Rossetti, Nikki E.; Boonseng, Wannaporn E.; Oksuz, Ozgur; Cook, Edward B.; Patel, Anoop; Deshpande, Vikram; Hornicek, Francis J.; Nielsen, G. Petur; Aryee, Martin J.; Bernstein, Bradley E.; Rivera, Miguel N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Riggi, Nicolo; Knoechel, Birgit; Gillespie, Shawn M.; Rheinbay, Esther; Boulay, Gaylor; Suva, Mario L.; Aryee, Martin J.; Bernstein, Bradley E.; Rivera, Miguel N.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Knoechel, Birgit] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Knoechel, Birgit] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Knoechel, Birgit] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gillespie, Shawn M.; Patel, Anoop; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Formey, Aurelie; Stamenkovic, Ivan] Univ Lausanne, Fac Biol & Med, Ctr Hosp Univ Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. [Patel, Anoop] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Gymrek, Melissa] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Gymrek, Melissa] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gymrek, Melissa] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Thapar, Vishal; Ting, David T.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Thapar, Vishal; Ting, David T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM bernstein.bradley@mgh.harvard.edu; mnrivera@mgh.harvard.edu OI /0000-0002-6086-3903; Ting, David/0000-0002-3261-2322 FU NIH [HL007574-30]; St. Baldrick's fellowship; Swiss National Science Foundation [P3SMP3_148408]; Nuovo Soldati Foundation; Fond de perfectionnement CHUV; Howard Hughes Medical Institute; National Human Genome Research Institute (ENCODE) [U54 HG006991]; Hyundai Hope on Wheels; Burroughs Wellcome Fund; Affymetrix FX We thank R. Issner, X. Zhang, C. Epstein, N. Shoresh, T. Durham, H. Whitton, M. Hatan, and the Broad Genome Sequencing Platform for technical assistance and L. Gaffney and L. Solomon for help with illustrations. B.K. was supported by a NIH T32 Training Grant (HL007574-30) and a St. Baldrick's fellowship. N.R. was supported by the Swiss National Science Foundation (Grant P3SMP3_148408), by the Nuovo Soldati Foundation, and by the Fond de perfectionnement CHUV. This work was supported by the Howard Hughes Medical Institute (to B.E.B. and MNR), by the National Human Genome Research Institute (ENCODE U54 HG006991) (to B.E.B.), by Hyundai Hope on Wheels (to M.N.R.), and by the Burroughs Wellcome Fund (to B.E.B., M.N.R, and D.T.T.). M.N.R., D.T.T., and V.D. receive research support from Affymetrix. B.E.B. is a scientific advisory board member for Syros Pharmaceuticals and a founder and scientific advisor for HiFiBio SAS. NR 48 TC 42 Z9 43 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD NOV 10 PY 2014 VL 26 IS 5 BP 668 EP 681 DI 10.1016/j.ccell.2014.10.004 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AT5KA UT WOS:000344980900011 PM 25453903 ER PT J AU Bresler, SC Weiser, DA Huwe, PJ Park, JH Krytska, K Ryles, H Laudenslager, M Rappaport, EF Wood, AC McGrady, PW Hogarty, MD London, WB Radhakrishnan, R Lemmon, MA Mosse, YP AF Bresler, Scott C. Weiser, Daniel A. Huwe, Peter J. Park, Jin H. Krytska, Kateryna Ryles, Hannah Laudenslager, Marci Rappaport, Eric F. Wood, Andrew C. McGrady, Patrick W. Hogarty, Michael D. London, Wendy B. Radhakrishnan, Ravi Lemmon, Mark A. Mosse, Yael P. TI ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma SO CANCER CELL LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; RECEPTOR TYROSINE KINASE; CELL LUNG-CANCER; NON-HODGKINS-LYMPHOMA; CRIZOTINIB RESISTANCE; MISSENSE MUTATIONS; GENE; EML4-ALK; TUMORS; FUSION AB Genetic studies have established anaplastic lymphoma kinase (ALK), a cell surface receptor tyrosine kinase, as a tractable molecular target in neuroblastoma. We describe comprehensive genomic, biochemical, and computational analyses of ALK mutations across 1,596 diagnostic neuroblastoma samples. ALK tyrosine kinase domain mutations occurred in 8% of samples-at three hot spots and 13 minor sites-and correlated significantly with poorer survival in high- and intermediate-risk neuroblastoma. Biochemical and computational studies distinguished oncogenic (constitutively activating) from nononcogenic mutations and allowed robust computational prediction of their effects. The mutated variants also showed differential in vitro crizotinib sensitivities. Our studies identify ALK genomic status as a clinically important therapeutic stratification tool in neuroblastoma and will allow tailoring of ALK-targeted therapy to specific mutations. C1 [Bresler, Scott C.; Park, Jin H.; Lemmon, Mark A.] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Bresler, Scott C.; Huwe, Peter J.; Park, Jin H.; Radhakrishnan, Ravi; Lemmon, Mark A.] Univ Penn, Perelman Sch Med, Grad Grp Biochem & Mol Biophys, Philadelphia, PA 19104 USA. [Bresler, Scott C.] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA. [Weiser, Daniel A.; Hogarty, Michael D.; Mosse, Yael P.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Weiser, Daniel A.; Krytska, Kateryna; Ryles, Hannah; Laudenslager, Marci; Wood, Andrew C.; Hogarty, Michael D.; Mosse, Yael P.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Weiser, Daniel A.; Krytska, Kateryna; Ryles, Hannah; Laudenslager, Marci; Wood, Andrew C.; Hogarty, Michael D.; Mosse, Yael P.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Rappaport, Eric F.] Childrens Hosp Philadelphia, Nucle Acid Core Facil, Philadelphia, PA 19104 USA. [Huwe, Peter J.; Radhakrishnan, Ravi] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [McGrady, Patrick W.; London, Wendy B.] Univ Florida, Childrens Oncol Grp, Stat & Data Ctr, Dept Biostat, Gainesville, FL 32611 USA. [London, Wendy B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [London, Wendy B.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. RP Lemmon, MA (reprint author), Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. EM mlemmon@mail.med.upenn.edu; mosse@email.chop.edu RI Weiser, Daniel/B-6160-2016; OI Weiser, Daniel/0000-0001-6673-5323; Lemmon, Mark/0000-0002-3379-5319 FU NIH [R01-CA140198, T32-GM008275]; U.S. Army Peer Reviewed Medical Research Program [W81XWH-10-1-0212/3]; European Commission [FP7-ICT-2011-9-600841]; Great Rivers Affiliate of the American Heart Association [11PRE7670020]; NSF; Institute for Translational Medicine and Therapeutics of the University of Pennsylvania by NCRR [UL1RR024134]; National Partnership for Advanced Computational Infrastructure from XSEDE [MCB060006] FX This work was supported in part by NIH Grant R01-CA140198 (to Y.P.M.), by U.S. Army Peer Reviewed Medical Research Program Grants W81XWH-10-1-0212/3 (to M.A.L. and Y.P.M), by European Commission Grant FP7-ICT-2011-9-600841 (to R.R.), by Predoctoral Fellowship 11PRE7670020 from the Great Rivers Affiliate of the American Heart Association (to J.H.P.), by NIH Training Grant in Structural Biology T32-GM008275 (to S.C.B), by an NSF graduate research fellowship (to P.J.H.), and by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania (supported by NCRR Grant UL1RR024134). Computational resources were provided in part by the National Partnership for Advanced Computational Infrastructure under Grant MCB060006 from XSEDE (to R.R.). We thank the members of the M.A.L., Y.P.M., Ferguson, and R.R. laboratories for valuable discussions and Pfizer for their gift of crizotinib. Y.P.M. is the inventor of a patent filed by the Children's Hospital of Philadelphia (WO/2009/103061 or PCT/US2009/034288: Methods and Compositions for Identifying, Diagnosing, and Treating Neuroblastoma). NR 45 TC 46 Z9 47 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD NOV 10 PY 2014 VL 26 IS 5 BP 682 EP 694 DI 10.1016/j.ccell.2014.09.019 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AT5KA UT WOS:000344980900012 PM 25517749 ER PT J AU Ott, PA Hamid, O Pavlick, AC Kluger, H Kim, KB Boasberg, PD Simantov, R Crowley, E Green, JA Hawthorne, T Davis, TA Sznol, M Hwu, P AF Ott, Patrick A. Hamid, Omid Pavlick, Anna C. Kluger, Harriet Kim, Kevin B. Boasberg, Peter D. Simantov, Ronit Crowley, Elizabeth Green, Jennifer A. Hawthorne, Thomas Davis, Thomas A. Sznol, Mario Hwu, Patrick TI Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GLYCOPROTEIN NONMETASTATIC B; T-CELL-ACTIVATION; METASTATIC MELANOMA; BREAST-CANCER; DC-HIL; PROGNOSTIC INDICATOR; THERAPEUTIC TARGET; IMPROVED SURVIVAL; CLINICAL-TRIALS; GPNMB AB Purpose The antibody-drug conjugate glembatumumab vedotin links a fully human immunoglobulin G2 monoclonal antibody against the melanoma-related glycoprotein NMB (gpNMB) to the potent cytotoxin monomethyl auristatin E. This study evaluated the safety and activity of glembatumumab vedotin in patients with advanced melanoma. Patients and Methods Patients received glembatumumab vedotin every 3 weeks (schedule 1) in a dose escalation and phase II expansion at the maximum-tolerated dose (MTD). Dosing during 2 of 3 weeks (schedule 2) and weekly (schedule 3) was also assessed. The primary end points were safety and pharmacokinetics. The secondary end points included antitumor activity, gpNMB expression, and immunogenicity. Results One hundred seventeen patients were treated using schedule 1 (n = 79), schedule 2 (n = 15), or schedule 3 (n = 23). The MTDs were 1.88, 1.5, and 1.0 mg/kg for schedules 1, 2, and 3, respectively. Grade 3/4 treatment-related toxicities that occurred in two or more patients included rash, neutropenia, fatigue, neuropathy, arthralgia, myalgia, and diarrhea. Three treatment-related deaths (resulting from pneumococcal sepsis, toxic epidermal necrolysis, and renal failure) occurred at doses exceeding the MTDs. In the schedule 1 phase II expansion cohort (n = 34), five patients (15%) had a partial response and eight patients (24%) had stable disease for >= 6 months. The objective response rate (ORR) was 2 of 6 (33%) for the schedule 2 MTD and 3 of 12 (25%) for the schedule 3 MTD. Rash was correlated with a greater ORR and improved progression-free survival. Conclusion Glembatumumab vedotin is active in advanced melanoma. The schedule 1 MTD (1.88 mg/kg once every 3 weeks) was associated with a promising ORR and was generally well tolerated. More frequent dosing was potentially associated with a greater ORR but increased toxicity. (C) 2014 by American Society of Clinical Oncology C1 [Ott, Patrick A.; Pavlick, Anna C.] NYU, Inst Canc, New York, NY USA. [Hamid, Omid; Boasberg, Peter D.] Angeles Clin & Res Inst, Los Angeles, CA USA. [Kluger, Harriet; Sznol, Mario] Yale Canc Ctr, New Haven, CT USA. [Kim, Kevin B.; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Simantov, Ronit; Crowley, Elizabeth; Green, Jennifer A.; Hawthorne, Thomas; Davis, Thomas A.] Celldex Therapeut, Hampton, NJ USA. RP Ott, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM patrick_ott@dfci.harvard.edu FU Celldex Therapeutics; Bristol-Myers Squibb; Genentech; Merck FX Omid Hamid, Celldex Therapeutics; Anna C. Pavlick, Bristol-Myers Squibb, Genentech, Merck NR 44 TC 23 Z9 23 U1 1 U2 12 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 NOV 10 PY 2014 VL 32 IS 32 BP 3659 EP + DI 10.1200/JCO.2013.54.8115 PG 11 WC Oncology SC Oncology GA AT3UI UT WOS:000344860000016 PM 25267741 ER PT J AU Leighl, NB Rekhtman, N Biermann, WA Huang, J Mino-Kenudson, M Ramalingam, SS West, H Whitlock, S Somerfield, MR AF Leighl, Natasha B. Rekhtman, Natasha Biermann, William A. Huang, James Mino-Kenudson, Mari Ramalingam, Suresh S. West, Howard Whitlock, Sara Somerfield, Mark R. TI Molecular Testing for Selection of Patients With Lung Cancer for Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Guideline SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB Purpose The College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) guideline on molecular testing for the selection of patients with lung cancer for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors was considered for endorsement. Methods American Society of Clinical Oncology (ASCO) staff reviewed the CAP/IASLC/AMP guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. Results The ASCO panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and present options that will be acceptable to patients. The CAP/IASLC/AMP guideline comprises 37 recommendations (evidence grade A or B), expert consensus opinions, or suggestions that address the following five principal questions: (1) When should molecular testing be performed? (2) How should EGFR testing be performed? (3) How should ALK testing be performed? (4) Should other genes be routinely tested in lung adenocarcinoma? (5) How should molecular testing be implemented and operationalized? Conclusion The ASCO review panel endorses the CAP/IASLC/AMP guideline. This guideline represents an important advance toward standardization of EGFR and ALK testing practices and is of major clinical relevance in advancing the care of patients with lung cancer. In the Discussion section, the ASCO review panel highlights three evolving areas: advances in ALK testing methodology, considerations for selecting appropriate populations for molecular testing, and emergence of other targetable molecular alterations. (C) 2014 by American Society of Clinical Oncology C1 [Leighl, Natasha B.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Rekhtman, Natasha; Huang, James] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Biermann, William A.] Einstein Med Ctr Montgomery, East Norriton, PA USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA. [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [West, Howard] Swedish Canc Inst, Seattle, WA USA. [Whitlock, Sara] Free Breathe, Madison, WI USA. [Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. RP Leighl, NB (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org FU Bristol-Myers Squibb FX Bristol-Myers Squibb NR 4 TC 69 Z9 80 U1 2 U2 11 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 NOV 10 PY 2014 VL 32 IS 32 BP 3673 EP + DI 10.1200/JCO.2014.57.3055 PG 9 WC Oncology SC Oncology GA AT3UI UT WOS:000344860000018 PM 25311215 ER PT J AU Braun, D Gorfine, M Parmigiani, G AF Braun, Danielle Gorfine, Malka Parmigiani, Giovanni TI Misreported Family Histories and Underestimation of Risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CANCER; VALIDATION; BRCAPRO; MUTATION; MODELS C1 [Braun, Danielle; Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gorfine, Malka] Technion Israel Inst Technol, Haifa, Israel. RP Braun, D (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA053996, T32 CA009337] NR 9 TC 2 Z9 2 U1 0 U2 1 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 NOV 10 PY 2014 VL 32 IS 32 BP 3682 EP + DI 10.1200/JCO.2014.57.4848 PG 3 WC Oncology SC Oncology GA AT3UI UT WOS:000344860000021 PM 25199751 ER PT J AU Smith, MR Halabi, S Small, EJ AF Smith, Matthew R. Halabi, Susan Small, Eric J. TI Is Time to First Skeletal-Related Event the Best Primary End Point in the Assessment of Bisphosphonate Efficacy in Patients With Castration-Sensitive Prostate Cancer? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CONTROLLED-TRIAL; ZOLEDRONIC ACID; MEN C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Halabi, Susan] Duke Univ, Med Ctr, Durham, NC USA. [Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 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 NOV 10 PY 2014 VL 32 IS 32 BP 3685 EP 3685 DI 10.1200/JCO.2014.57.3808 PG 1 WC Oncology SC Oncology GA AT3UI UT WOS:000344860000024 PM 25225438 ER PT J AU Marinkovic, K Courtney, MG Witzel, T Dale, AM Halgren, E AF Marinkovic, Ksenija Courtney, Maureen G. Witzel, Thomas Dale, Anders M. Halgren, Eric TI Spatio-temporal dynamics and laterality effects of face inversion, feature presence and configuration, and face outline SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE magnetoencephalography; faces; fusiform gyrus; temporal cortex; laterality; dual route model; face inversion ID HUMAN EXTRASTRIATE CORTEX; DEPTH-RECORDED POTENTIALS; EVENT-RELATED POTENTIALS; TEMPORAL-LOBE EPILEPSY; SURFACE-BASED ANALYSIS; HUMAN NEURAL SYSTEMS; HUMAN FUSIFORM GYRUS; WORD FORM AREA; HUMAN BRAIN; CORTICAL SURFACE AB Although a crucial role of the fusiform gyrus (FG) in face processing has been demonstrated with a variety of methods, converging evidence suggests that face processing involves an interactive and overlapping processing cascade in distributed brain areas. Here we examine the spatio-temporal stages and their functional tuning to face inversion, presence and configuration of inner features, and face contour in healthy subjects during passive viewing. Anatomically-constrained magnetoencephalography (aMEG) combines high-density whole-head MEG recordings and distributed source modeling with high-resolution structural M RI. Each person's reconstructed cortical surface served to constrain noise-normalized minimum norm inverse source estimates. The earliest activity was estimated to the occipital cortex at similar to 100 ms after stimulus onset and was sensitive to an initial coarse level visual analysis. Activity in the right-lateralized ventral temporal area (inclusive of the FG) peaked at similar to 160 ms and was largest to inverted faces. Images containing facial features in the veridical and rearranged configuration irrespective of the facial outline elicited intermediate level activity. The M160 stage may provide structural representations necessary for downstream distributed areas to process identity and emotional expression. However, inverted faces additionally engaged the left ventral temporal area at similar to 180 ms and were uniquely subserved by bilateral processing. This observation is consistent with the dual route model and spared processing of inverted faces in prosopagnosia. The subsequent deflection, peaking at similar to 240 ms in the anterior temporal areas bilaterally, was largest to normal, upright faces. It may reflect initial engagement of the distributed network subserving individuation and familiarity. These results support dynamic models suggesting that processing of unfamiliar faces in the absence of a cognitive task is subserved by a distributed and interactive neural circuit. C1 [Marinkovic, Ksenija; Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Marinkovic, Ksenija] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Courtney, Maureen G.] Boston Univ, Ctr Memory & Brain, Cognit Neuroimaging Lab, Boston, MA 02215 USA. [Witzel, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Boston, MA USA. [Dale, Anders M.; Halgren, Eric] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Marinkovic, K (reprint author), San Diego State Univ, Dept Psychol, 5500 Campanile Dr, San Diego, CA 92182 USA. EM kmarinkovic@mail.sdsu.edu RI Witzel, Thomas/P-1402-2014 FU NIH [N518741, AA016624, RR14075, P01 HD033113] FX We are grateful to Rupali P. Dhond, Sharelle Baldwin, Jeremy Jordin, Dave Post, Brendan Cox, Kim Paulson, Jeffrey Lewine, and Bruce Fischl. This work was supported by NIH (N518741, AA016624, RR14075, P01 HD033113). NR 134 TC 0 Z9 1 U1 6 U2 20 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD NOV 10 PY 2014 VL 8 AR UNSP 868 DI 10.3389/fnhum.2014.00868 PG 12 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AS7RH UT WOS:000344452100001 PM 25426044 ER PT J AU Snavely, AC Harrington, DP Li, Y AF Snavely, Anna C. Harrington, David P. Li, Yi TI A latent variable transformation model approach for exploring dysphagia SO STATISTICS IN MEDICINE LA English DT Article DE latent variables; semiparametric modeling; multiple outcomes; dysphagia ID LOCALLY ADVANCED HEAD; NECK-CANCER; CONTINUOUS OUTCOMES; TRAIT MODELS; CHEMORADIATION; DISCRETE AB Multiple outcomes are often collected in applications where the quantity of interest cannot be measured directly or is difficult or expensive to measure. In a head and neck cancer study conducted at Dana-Farber Cancer Institute, the investigators wanted to determine the effect of clinical and treatment factors on unobservable dysphagia through collected multiple outcomes of mixed types. Latent variable models are commonly adopted in this setting. These models stipulate that multiple collected outcomes are conditionally independent given the latent factor. Mixed types of outcomes (e.g., continuous vs. ordinal) and censored outcomes present statistical challenges, however, as a natural analog of the multivariate normal distribution does not exist for mixed data. Recently, Lin et al. proposed a semiparametric latent variable transformation model for mixed outcome data; however, it may not readily accommodate event time outcomes where censoring is present. In this paper, we extend the work of Lin et al. by proposing both semiparametric and parametric latent variable models that allow for the estimation of the latent factor in the presence of measurable outcomes of mixed types, including censored outcomes. Both approaches allow for a direct estimate of the treatment (or other covariate) effect on the unobserved latent variable, greatly enhancing the interpretability of the models. The semiparametric approach has the added advantage of allowing the relationship between the measurable outcomes and latent variables to be unspecified, rendering more robust inference. The parametric and semiparametric models can also be used together, providing a comprehensive modeling strategy for complicated latent variable problems. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Snavely, Anna C.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Snavely, Anna C.] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Harrington, David P.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Harrington, David P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Yi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. RP Snavely, AC (reprint author), UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA. EM anna_snavely@med.unc.edu NR 29 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD NOV 9 PY 2014 VL 33 IS 25 BP 4337 EP 4352 DI 10.1002/sim.6239 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AQ6DK UT WOS:000342898500002 PM 24974798 ER PT J AU Kouyos, RD Metcalf, CJE Birger, R Klein, EY zur Wiesch, PA Ankomah, P Arinaminpathy, N Bogich, TL Bonhoeffer, S Brower, C Chi-Johnston, G Cohen, T Day, T Greenhouse, B Huijben, S Metlay, J Mideo, N Pollitt, LC Read, AF Smith, DL Standley, C Wale, N Grenfell, B AF Kouyos, Roger D. Metcalf, C. Jessica E. Birger, Ruthie Klein, Eili Y. zur Wiesch, Pia Abel Ankomah, Peter Arinaminpathy, Nimalan Bogich, Tiffany L. Bonhoeffer, Sebastian Brower, Charles Chi-Johnston, Geoffrey Cohen, Ted Day, Troy Greenhouse, Bryan Huijben, Silvie Metlay, Joshua Mideo, Nicole Pollitt, Laura C. Read, Andrew F. Smith, David L. Standley, Claire Wale, Nina Grenfell, Bryan TI The path of least resistance: aggressive or moderate treatment? SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE drug resistance; evolution; treatment strategies ID DRUG-RESISTANCE; ANTIBIOTIC-RESISTANCE; ANTIRETROVIRAL THERAPY; IN-VITRO; PLASMODIUM-FALCIPARUM; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; TUBERCULOSIS TREATMENT; EVOLUTIONARY DYNAMICS; MALARIA PARASITES AB The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution. C1 [Kouyos, Roger D.; Metcalf, C. Jessica E.; Birger, Ruthie; Klein, Eili Y.; Arinaminpathy, Nimalan; Bogich, Tiffany L.; Brower, Charles; Grenfell, Bryan] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Kouyos, Roger D.] Univ Zurich, Univ Hosp Zurich, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland. [Metcalf, C. Jessica E.; Smith, David L.] Univ Oxford, Dept Zool, Oxford, England. [zur Wiesch, Pia Abel; Cohen, Ted] Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Div Global Hlth Equ, Boston, MA 02115 USA. [zur Wiesch, Pia Abel; Cohen, Ted] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ankomah, Peter] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Bonhoeffer, Sebastian] Swiss Fed Inst Technol, Inst Integrat Biol, Zurich, Switzerland. [Chi-Johnston, Geoffrey] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Klein, Eili Y.] Johns Hopkins Univ, Dept Emergency Med, Ctr Adv Modeling, Baltimore, MD USA. [Day, Troy] Queens Univ, Dept Math, Kingston, ON, Canada. [Day, Troy] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. [Greenhouse, Bryan] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA. [Pollitt, Laura C.; Read, Andrew F.; Wale, Nina] Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA USA. [Pollitt, Laura C.; Read, Andrew F.; Wale, Nina] Penn State Univ, Dept Biol, State Coll, PA USA. [Pollitt, Laura C.; Read, Andrew F.] Penn State Univ, Dept Entomol, State Coll, PA USA. [Metlay, Joshua] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Mideo, Nicole] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON, Canada. [Bogich, Tiffany L.; Read, Andrew F.; Grenfell, Bryan] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Arinaminpathy, Nimalan] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England. [Standley, Claire] George Washington Univ, Dept Hlth Policy, Washington, DC USA. [Pollitt, Laura C.] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh, Midlothian, Scotland. [Huijben, Silvie] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res, Barcelona, Spain. [Brower, Charles] Ctr Dis Dynam Econ & Policy, Washington, DC USA. RP Birger, R (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. EM rbirger@princeton.edu RI Birger, Ruthie/F-2416-2014; Bonhoeffer, Sebastian/A-2735-2008; Kouyos, Roger/G-6226-2014; Smith, David/L-8850-2013; OI Birger, Ruthie/0000-0002-2960-5084; Bonhoeffer, Sebastian/0000-0001-8052-3925; Kouyos, Roger/0000-0002-9220-8348; Bogich, Tiffany/0000-0002-8143-5289; Smith, David/0000-0003-4367-3849; Greenhouse, Bryan/0000-0003-0287-9111; Klein, Eili/0000-0002-1304-5289 FU RAPIDD program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Science and Technology Directorate, Department of Homeland Security [HSHQDC-12-C-00058] FX This work emerged from a meeting funded by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health; Science and Technology Directorate, Department of Homeland Security; contract HSHQDC-12-C-00058. We thank C. Ovenden for comments on an earlier draft. NR 63 TC 20 Z9 20 U1 3 U2 19 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 EI 1471-2954 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD NOV 7 PY 2014 VL 281 IS 1794 AR 20140566 DI 10.1098/rspb.2014.0566 PG 8 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA CE0RL UT WOS:000351512500002 PM 25253451 ER PT J AU Hafler, BP Klein, ZA Zhou, ZJ Strittmatter, SM AF Hafler, Brian P. Klein, Zoe A. Zhou, Z. Jimmy Strittmatter, Stephen M. TI Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice SO BRAIN RESEARCH LA English DT Article DE Neurodegeneration; Progranulin; Autofluorescent storage material; Neuronal ceroid lipofuscinosis ID NEURONAL CEROID-LIPOFUSCINOSIS; LYSOSOMAL STORAGE DISEASES; ENZYME REPLACEMENT THERAPY; GENE; EXPRESSION; PROTEIN; MODEL; CELL AB Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Gm-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn(-/-) mice develop degenerative pathology similar to features of human CLN11. (C) 2014 Elsevier B.V. All rights reserved. C1 [Hafler, Brian P.; Zhou, Z. Jimmy] Yale Univ, Sch Med, Dept Ophthalmol & Visual Sci, New Haven, CT 06510 USA. [Klein, Zoe A.; Strittmatter, Stephen M.] Yale Univ, Sch Med, Cellular Neurosci Neurodegenerat & Repair Program, Dept Neurol, New Haven, CT 06510 USA. [Klein, Zoe A.; Strittmatter, Stephen M.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Zhou, Z. Jimmy] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Zhou, Z. Jimmy] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. RP Hafler, BP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM brian_hafler@meei.harvard.edu OI Strittmatter, Stephen/0000-0001-8188-3092 FU NIH [R01 NS074319]; Yale Department of Ophthalmology and Visual Science; Kavli Institute for Neuroscience at Yale University FX This work was supported by the NIH R01 NS074319, the Yale Department of Ophthalmology and Visual Science, and the Kavli Institute for Neuroscience at Yale University. NR 32 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 7 PY 2014 VL 1588 BP 168 EP 174 DI 10.1016/j.brainres.2014.09.023 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AU2SX UT WOS:000345468900018 PM 25234724 ER PT J AU Welch, JLM Utter, DR Rossetti, BJ Welch, DBM Eren, AM Borisy, GG AF Welch, Jessica L. Mark Utter, Daniel R. Rossetti, Blair J. Welch, David B. Mark Eren, A. Murat Borisy, Gary G. TI Dynamics of tongue microbial communities with single-nucleotide resolution using oligotyping SO FRONTIERS IN MICROBIOLOGY LA English DT Article DE human microbiome; oral microbiota; 16S ribosomal RNA; Haemophilus; Neisseria; Streptococcus; Veillonella ID OPERATIONAL TAXONOMIC UNIT; HUMAN ORAL MICROBIOME; BACTERIAL COMMUNITIES; GUT MICROBIOTA; ECOLOGY AB The human mouth is an excellent system to study the dynamics of microbial communities and their interactions with their host. We employed oligotyping to analyze, with single-nucleotide resolution, oral microbial 16S ribosomal RNA (rRNA) gene sequence data from a time course sampled from the tongue of two individuals, and we interpret our results in the context of oligotypes that we previously identified in the oral data from the Human Microbiome Project. Our previous work established that many of these oligotypes had dramatically different distributions between individuals and across oral habitats, suggesting that they represented functionally different organisms. Here we demonstrate the presence of a consistent tongue microbiome but with rapidly fluctuating proportions of the characteristic taxa. In some cases closely related oligotypes representing strains or variants within a single species displayed fluctuating relative abundances over time, while in other cases an initially dominant oligotype was replaced by another oligotype of the same species. We use this high temporal and taxonomic level of resolution to detect correlated changes in oligotype abundance that could indicate which taxa likely interact synergistically or occupy similar habitats, and which likely interact antagonistically or prefer distinct habitats. For example, we found a strong correlation in abundance over time between two oligotypes from different families of Gamma Proteobacteria, suggesting a close functional or ecological relationship between them. In summary, the tongue is colonized by a microbial community of moderate complexity whose proportional abundance fluctuates widely on time scales of days. The drivers and functional consequences of these community dynamics are not known, but we expect they will prove tractable to future, targeted studies employing taxonomically resolved analysis of high-throughput sequencing data sampled at appropriate temporal intervals and spatial scales. C1 [Welch, Jessica L. Mark; Utter, Daniel R.; Welch, David B. Mark; Eren, A. Murat; Borisy, Gary G.] Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, Woods Hole, MA 02543 USA. [Welch, Jessica L. Mark; Utter, Daniel R.; Rossetti, Blair J.; Borisy, Gary G.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. RP Welch, JLM (reprint author), Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, 7 MBL St, Woods Hole, MA 02543 USA. EM jmarkwelch@mbl.edu OI Eren, A. Murat/0000-0001-9013-4827 FU National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research Grant [DE022586]; Woods Hole Partnership Education Program; G. Unger Vetlesen Foundation; NSF [DBI-1262592] FX We thank two reviewers for their careful reading and comments, which greatly improved the manuscript. Supported by National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research Grant DE022586 (to Gary G. Borisy). Daniel R. Utter was supported by the Woods Hole Partnership Education Program; A. Murat Eren was supported by a G. Unger Vetlesen Foundation grant to the Marine Biological Laboratory; David B. Mark Welch was supported by NSF DBI-1262592. NR 38 TC 2 Z9 2 U1 3 U2 16 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PD NOV 7 PY 2014 VL 5 AR 568 DI 10.3389/fmicb.2014.00568 PG 15 WC Microbiology SC Microbiology GA AU5NB UT WOS:000345652700001 ER PT J AU Amabile, N Cheng, S Renard, JM Larson, MG Ghorbani, A McCabe, E Griffin, G Guerin, C Ho, JE Shaw, SY Cohen, KS Vasan, RS Tedgui, A Boulanger, CM Wang, TJ AF Amabile, Nicolas Cheng, Susan Renard, Jean Marie Larson, Martin G. Ghorbani, Anahita McCabe, Elizabeth Griffin, Gabriel Guerin, Coralie Ho, Jennifer E. Shaw, Stanley Y. Cohen, Kenneth S. Vasan, Ramachandran S. Tedgui, Alain Boulanger, Chantal M. Wang, Thomas J. TI Association of circulating endothelial microparticles with cardiometabolic risk factors in the Framingham Heart Study SO EUROPEAN HEART JOURNAL LA English DT Article DE Microparticles; Cardiovascular risk factors; Endothelium ID TYPE-2 DIABETES-MELLITUS; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; METABOLIC SYNDROME; PROGENITOR CELLS; HYPERTENSIVE PATIENTS; SCIENTIFIC STATEMENT; DENSITY-LIPOPROTEIN; CARDIOVASCULAR RISK; DYSFUNCTION AB Objective To examine the relation of endothelial microparticles (EMPs) with cardiometabolic risk in the community. Background Circulating EMPs are small membrane vesicles released after endothelial cell injury. Endothelial microparticles are reportedly increased among individuals with a high burden of cardiovascular risk factors. However, prior investigations have been Limited to small, highly selected samples. Methods We studied 844 individuals without a history of cardiovascular disease in the Framingham Offspring cohort (mean age 66 +/- 9 years, 57% women). We used standardized flow cytometry methods to identify and quantify circulating CD144+ and CD31+/CD41 - EMPs. We then used multivariable regression analyses to investigate the relations of EMP phenotypes with cardiovascular and metabolic risk factors. Results In multivariable analyses, the following cardiovascular risk factors were associated with one or more of the circulating EMP populations: hypertension (P = 0.025 for CD144+,), elevated triglycerides (P = 0.002 for CD144+, P < 0.0001 for CD31+/CD41), and metabolic syndrome (P < 0.0001 for CD 144+,). Overall, each tertile increase in the Framingham risk score corresponded to a 9% increase in log-CD31+/CD41 EMPs (P = 0.022). Furthermore, the presence of hypertriglyceridaemic waist status was associated with 38% higher levels of CD144+ EM Ps (P < 0.0001) and 46% higher levels of CD31+/CD41 EMPs (P< 0.0001). Conclusion In a large community-based sample, circulating EMP levels were associated with the presence of cardiometabolic risk factors, particularly dyslipidaemia. These data underscore the potential influence of high-risk metabolic profiles on endothelial integrity. C1 [Amabile, Nicolas; Renard, Jean Marie; Guerin, Coralie; Tedgui, Alain; Boulanger, Chantal M.] INSERM, Paris Cardiovasc Res Ctr PARCC, U970, F-75737 Paris 15, France. [Amabile, Nicolas; Renard, Jean Marie; Guerin, Coralie; Tedgui, Alain; Boulanger, Chantal M.] Univ Paris 05, Sorbonne Paris Cite, UMR S970, Paris, France. [Cheng, Susan; Larson, Martin G.; Ho, Jennifer E.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Larson, Martin G.; McCabe, Elizabeth] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ghorbani, Anahita; McCabe, Elizabeth; Ho, Jennifer E.; Shaw, Stanley Y.; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Griffin, Gabriel] Duke Univ, Sch Med, Durham, NC USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Cohen, Kenneth S.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN 37232 USA. RP Boulanger, CM (reprint author), INSERM, Paris Cardiovasc Res Ctr PARCC, U970, 56 Rue Leblanc, F-75737 Paris 15, France. EM chantal.boulanger@inserm.fr; thomas.j.wang@vanderbilt.edu OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, R01-HL083197]; Institut National de la Sante et de la Recherche Medicale (INSERM); National Institutes of Health [R01-HL-08675]; Clinical Research Program grant from the American Heart Association; Ellison Foundation; [ANR-2010-EMMA-041]; [R01-HL93328] FX This work was supported in part by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), grant R01-HL083197 (T.J.W.), Institut National de la Sante et de la Recherche Medicale (INSERM), and ANR-2010-EMMA-041(C.M.B.) and R01-HL93328 (R.S.V.). Additional support was provided by National Institutes of Health grant R01-HL-08675. S.C. is supported in part by a Clinical Research Program grant from the American Heart Association and the Ellison Foundation. NR 45 TC 34 Z9 35 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD NOV 7 PY 2014 VL 35 IS 42 SI SI BP 2972 EP 2979 DI 10.1093/eurheartj/ehu153 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU1FX UT WOS:000345367500013 PM 24742886 ER PT J AU Cho, JA Zhang, X Miller, GM Lencer, WI Nery, FC AF Cho, Jin A. Zhang, Xuan Miller, Gregory M. Lencer, Wayne I. Nery, Flavia C. TI 4-Phenylbutyrate Attenuates the ER Stress Response and Cyclic AMP Accumulation in DYT1 Dystonia Cell Models SO PLOS ONE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; DEPENDENT PROTEIN-KINASE; CYCLOHYDROLASE-I GENE; TORSION DYSTONIA; TYROSINE-HYDROXYLASE; CHEMICAL CHAPERONES; HUNTINGTONS-DISEASE; PHARMACOLOGICAL STRATEGY; DOPAMINE-RECEPTORS; CERVICAL DYSTONIA AB Dystonia is a neurological disorder in which sustained muscle contractions induce twisting and repetitive movements or abnormal posturing. DYT1 early-onset primary dystonia is the most common form of hereditary dystonia and is caused by deletion of a glutamic acid residue (302/303) near the carboxyl-terminus of encoded torsinA. TorsinA is localized primarily within the contiguous lumen of the endoplasmic reticulum (ER) and nuclear envelope (NE), and is hypothesized to function as a molecular chaperone and an important regulator of the ER stress-signaling pathway, but how the mutation in torsinA causes disease remains unclear. Multiple lines of evidence suggest that the clinical symptoms of dystonia result from abnormalities in dopamine (DA) signaling, and possibly involving its down-stream effector adenylate cyclase that produces the second messenger cyclic adenosine-3', 5'-monophosphate (cAMP). Here we find that mutation in torsinA induces ER stress, and inhibits the cyclic adenosine-3', 5'-monophosphate (cAMP) response to the adenylate cyclase agonist forskolin. Both defective mechanins are corrected by the small molecule 4-phenylbutyrate (4-PBA) that alleviates ER stress. Our results link torsinA, the ER-stress-response, and cAMP-dependent signaling, and suggest 4-PBA could also be used in dystonia treatment. Other pharmacological agents known to modulate the cAMP cascade, and ER stress may also be therapeutic in dystonia patients and can be tested in the models described here, thus supplementing current efforts centered on the dopamine pathway. C1 [Cho, Jin A.; Lencer, Wayne I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol Cell Biol, Boston, MA USA. [Zhang, Xuan; Nery, Flavia C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci,Dept Neurol, Boston, MA 02114 USA. [Zhang, Xuan; Nery, Flavia C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, Boston, MA USA. [Zhang, Xuan; Nery, Flavia C.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. [Miller, Gregory M.] Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. [Miller, Gregory M.] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. [Lencer, Wayne I.] Harvard Univ, Sch Med, Harvard Digest Dis Ctr, Boston, MA USA. RP Nery, FC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci,Dept Neurol, Boston, MA 02114 USA. EM nery.flavia@mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke [NS037409]; Harvard Digestive Diseases Center [P30 DK34854]; CCFA; [DK48106]; [DK084424]; [DK090603]; [DK083894] FX This work was supported by the National Institute of Neurological Disorders and Stroke, Grant NS037409 (F.C.N.; investigator); DK48106 (W.I.L., PI), DK084424 (W.I.L., PI), DK090603 (W.I.L., PI) and the Harvard Digestive Diseases Center P30 DK34854 (W.I.L., PI); DK083894 (W.I.L., PI) and CCFA Fellowship (J.A.C.; postdoc). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 80 TC 7 Z9 7 U1 1 U2 8 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 7 PY 2014 VL 9 IS 11 AR e110086 DI 10.1371/journal.pone.0110086 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AT3WF UT WOS:000344863100010 PM 25379658 ER PT J AU Zheng, XJ Demirci, FY Barmada, MM Richardson, GA Lopez, OL Sweet, RA Kamboh, MI Feingold, E AF Zheng, Xiaojing Demirci, F. Yesim Barmada, M. Michael Richardson, Gale A. Lopez, Oscar L. Sweet, Robert A. Kamboh, M. Ilyas Feingold, Eleanor TI A Rare Duplication on Chromosome 16p11.2 Is Identified in Patients with Psychosis in Alzheimer's Disease SO PLOS ONE LA English DT Article ID COPY NUMBER VARIATION; MENTAL-RETARDATION; SEIZURE DISORDER; DOWN-REGULATION; SCHIZOPHRENIA; RISK; MICRODELETION; DELETIONS; AUTISM; ASSOCIATION AB Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis. C1 [Zheng, Xiaojing; Feingold, Eleanor] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Demirci, F. Yesim; Barmada, M. Michael; Kamboh, M. Ilyas; Feingold, Eleanor] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Richardson, Gale A.; Sweet, Robert A.; Kamboh, M. Ilyas] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.; Sweet, Robert A.; Kamboh, M. Ilyas] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Richardson, Gale A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Zheng, Xiaojing] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. RP Zheng, XJ (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. EM xiaojinz@email.unc.edu OI Demirci, F. Yesim/0000-0001-6907-9843; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460; Feingold, Eleanor/0000-0003-2898-6484 FU National Institute on Aging [AG030653, AG041718, AG005133, AG027224]; NanoString award; NIMH Grant [T32 MH015169] FX This study was supported by the National Institute on Aging grants AG030653, AG041718 (MIK), AG005133 (OLL), and AG027224 (RAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs or the United States Government. Funding for experimental validation was provided by NanoString award. This work was conducted in partial fulfillment of requirements for the first author's doctoral degree, supported by NIMH Grant T32 MH015169 (G.A.R., Program Director). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 2 Z9 4 U1 3 U2 8 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 7 PY 2014 VL 9 IS 11 AR e111462 DI 10.1371/journal.pone.0111462 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AT3WF UT WOS:000344863100030 PM 25379732 ER PT J AU Lee, LK Sahani, DV AF Lee, Leslie K. Sahani, Dushyant V. TI Autoimmune pancreatitis in the context of IgG4-related disease: Review of imaging findings SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Autoimmune pancreatitis; IgG4-related disease; Pancreatic cancer; Imaging; Computed tomography; Magnetic resonance; Positron emission tomography; Review ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE CHOLANGIOPANCREATOGRAPHY; DUAL-PHASE CT; FDG-PET; SCLEROSING CHOLANGITIS; DIAGNOSTIC-CRITERIA; RETROPERITONEAL FIBROSIS; RADIOLOGICAL FEATURES; SYSTEMIC-DISEASE; SERUM IGG4 AB Current understanding of autoimmune pancreatitis (AIP) recognizes a histopathological subtype of the disease to fall within the spectrum of IgG4-related disease. Along with clinical, laboratory, and histopathological data, imaging plays an important role in the diagnosis and management of AIP, and more broadly, within the spectrum of IgG4-related disease. In addition to the defined role of imaging in consensus diagnostic protocols, an array of imaging modalities can provide complementary data to address specific clinical concerns. These include contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging for pancreatic parenchymal lesion localization and characterization, endoscopic retrograde and magnetic resonance cholangiopancreatography (ERCP and MRCP) to assess for duct involvement, and more recently, positron emission tomography (PET) imaging to assess for extra-pancreatic sites of involvement. While the imaging appearance of AIP varies widely, certain imaging features are more likely to represent AIP than alternate diagnoses, such as pancreatic cancer. While nonspecific, imaging findings which favor a diagnosis of AIP rather than pancreatic cancer include: delayed enhancement of affected pancreas, mild dilatation of the main pancreatic duct over a long segment, the "capsule" and "penetrating duct" signs, and responsiveness to corticosteroid therapy. Systemic, extra-pancreatic sites of involvement are also often seen in AIP and IgG4-related disease, and typically respond to corticosteroid therapy. Imaging by CT, MR, and PET also play a role in the diagnosis and monitoring after treatment of involved sites. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Lee, Leslie K.; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol,Med Sch, Boston, MA 02114 USA. RP Lee, LK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol,Med Sch, 55 Fruit St,White Bldg 270, Boston, MA 02114 USA. EM llee22@partners.org NR 84 TC 5 Z9 7 U1 2 U2 6 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 7 PY 2014 VL 20 IS 41 BP 15177 EP 15189 DI 10.3748/wjg.v20.i41.15177 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AT7KL UT WOS:000345115100019 PM 25386067 ER PT J AU Kim, T Kim, S Park, YK Youn, KK Keall, P Lee, R AF Kim, Taeho Kim, Siyong Park, Yang-Kyun Youn, Kaylin K. Keall, Paul Lee, Rena TI Motion management within two respiratory-gating windows: feasibility study of dual quasi-breath-hold technique in gated medical procedures SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE quasi-breath-hold biofeedback; respiratory motion management; duty-cycle ID AUDIOVISUAL BIOFEEDBACK; RADIOTHERAPY; LUNG; MRI; IMPACT; CANCER; IMAGES AB A dual quasi-breath-hold (DQBH) technique is proposed for respiratory motion management (a hybrid technique combining breathing-guidance with breath-hold task in the middle). The aim of this study is to test a hypothesis that the DQBH biofeedback system improves both the capability of motion management and delivery efficiency. Fifteen healthy human subjects were recruited for two respiratory motion measurements (free breathing and DQBH biofeedback breathing for 15 min). In this study, the DQBH biofeedback system utilized the abdominal position obtained using an real-time position management (RPM) system (Varian Medical Systems, Palo Alto, USA) to audio-visually guide a human subject for 4 s breath-hold at EOI and 90% EOE (EOE90%) to improve delivery efficiency. We investigated the residual respiratory motion and the delivery efficiency (duty-cycle) of abdominal displacement within the gating window. The improvement of the abdominal motion reproducibility was evaluated in terms of cycle-to-cycle displacement variability, respiratory period and baseline drift. The DQBH biofeedback system improved the abdominal motion management capability compared to that with free breathing. With a phase based gating (mean +/- std: 55 +/- 5%), the averaged root mean square error (RMSE) of the abdominal displacement in the dual-gating windows decreased from 2.26 mm of free breathing to 1.16 mm of DQBH biofeedback (p-value = 0.007). The averaged RMSE of abdominal displacement over the entire respiratory cycles reduced from 2.23 mm of free breathing to 1.39 mm of DQBH biofeedback breathing in the dual-gating windows (p-value = 0.028). The averaged baseline drift dropped from 0.9 mm min(-1) with free breathing to 0.09 mm min(-1) with DQBH biofeedback (p-value = 0.048). The averaged duty-cycle with an 1 mm width of displacement bound increased from 15% of free breathing to 26% of DQBH biofeedback (p-value = 0.003). The study demonstrated that the DQBH biofeedback system has the potential to significantly reduce the residual respiratory motion with the improved duty cycle during the respiratory gating procedure. C1 [Kim, Taeho; Kim, Siyong; Youn, Kaylin K.] Mayo Clin, Dept Radiat Oncol, Jacksonville, FL 32224 USA. [Kim, Taeho; Lee, Rena] Ewha Womans Univ, Dept Radiat Oncol, Seoul, South Korea. [Kim, Taeho] Univ Virginia, Dept Radiat Oncol, Charlottesville, VA 22903 USA. [Kim, Siyong] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23284 USA. [Park, Yang-Kyun] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Keall, Paul] Univ Sydney, Sydney Med Sch, Radiat Phys Lab, Sydney, NSW 2006, Australia. RP Kim, T (reprint author), Mayo Clin, Dept Radiat Oncol, Jacksonville, FL 32224 USA. EM renalee@ewha.ac.kr FU Industrial Strategic Technology Development Program - Ministry of Knowledge Economy (MKE, Korea) [10035527] FX This study was supported by the Industrial Strategic Technology Development Program (10035527) funded by the Ministry of Knowledge Economy (MKE, Korea). NR 23 TC 1 Z9 1 U1 0 U2 14 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 7 PY 2014 VL 59 IS 21 BP 6583 EP 6594 DI 10.1088/0031-9155/59/21/6583 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA AQ8QD UT WOS:000343092900019 PM 25321091 ER PT J AU Jacobson, C LaCasce, A AF Jacobson, Caron LaCasce, Ann TI How I treat Burkitt lymphoma in adults SO BLOOD LA English DT Review ID STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMAS; ACUTE LYMPHOBLASTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; C-MYC; INTENSIVE CHEMOTHERAPY; AFRICAN CHILDREN; GERMINAL CENTER; UNITED-STATES; CODOX-M/IVAC AB 4 Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is almost uniformly associated with translocations involving the gene for MYC on chromosome 8. The 3 subtypes of BL, endemic, sporadic, and immunodeficiency-associated, differ from epidemiologic and clinical perspectives but may be genetically similar. Prompt administration of multiagent immunochemotherapy regimens is associated with favorable outcomes for the majority of patients. Survival is inferior in older patients, likely reflecting increased therapy-related toxicity, possibly resulting in decreased treatment intensity. Central nervous system prophylaxis, tumor lysis prevention and treatment, and management of infectious complications from myelosuppressive regimens are critical. Prognosis of refractory or relapsed disease is poor and patients are best treated on clinical trials when available. C1 [Jacobson, Caron; LaCasce, Ann] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP LaCasce, A (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ann_lacasce@dfci.harvard.edu NR 60 TC 8 Z9 8 U1 0 U2 2 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 6 PY 2014 VL 124 IS 19 BP 2913 EP 2920 DI 10.1182/blood-2014-06-538504 PG 8 WC Hematology SC Hematology GA AY3CD UT WOS:000347461200007 PM 25258344 ER PT J AU Stadtmauer, EA Sullivan, KM Marty, FM Dadwal, SS Papanicolaou, GA Shea, TC Mossad, SB Andreadis, C Young, JAH Buadi, FK El Idrissi, M Heineman, TC Berkowitz, EM AF Stadtmauer, Edward A. Sullivan, Keith M. Marty, Francisco M. Dadwal, Sanjeet S. Papanicolaou, Genovefa A. Shea, Thomas C. Mossad, Sherif B. Andreadis, Charalambos Young, Jo-Anne H. Buadi, Francis K. El Idrissi, Mohamed Heineman, Thomas C. Berkowitz, Elchonon M. TI A phase 1/2 study of an adjuvanted varicella-zoster virus subunit vaccine in autologous hematopoietic cell transplant recipients SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HERPES-ZOSTER; GLYCOPROTEIN-E; ACYCLOVIR PROPHYLAXIS; IMMUNE-RESPONSES; OLDER-ADULTS; RISK-FACTORS; INFECTION; PATHOGENESIS; IMMUNOGENICITY AB Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B-or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 mu g varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01(B), 3 doses of gE adjuvanted with AS01(E), 1 dose of saline followed by 2 doses of gE/AS01(B), or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4(+) T cells expressing >= 2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01(B) 3-dose group than in the gE/AS01(B) 2-dose group but not higher than in the gE/AS01(E) 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218. C1 [Stadtmauer, Edward A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sullivan, Keith M.] Duke Univ, Med Ctr, Durham, NC USA. [Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marty, Francisco M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dadwal, Sanjeet S.] City Hope Natl Med Ctr, Duarte, CA USA. [Papanicolaou, Genovefa A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shea, Thomas C.] Univ North Carolina Hosp, Chapel Hill, NC USA. [Mossad, Sherif B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Andreadis, Charalambos] Univ Calif Med Ctr, San Francisco, CA USA. [Young, Jo-Anne H.] Univ Minnesota, Minneapolis, MN USA. [Buadi, Francis K.] Mayo Clin, Rochester, MN USA. [El Idrissi, Mohamed] GlaxoSmithKline Vaccines, Wavre, Belgium. [Heineman, Thomas C.; Berkowitz, Elchonon M.] GlaxoSmithKline Vaccines, King Of Prussia, PA USA. RP Stadtmauer, EA (reprint author), Abramson Canc Ctr, West Perelman Ctr Adv Med 2, 34th & Civ Ctr Bldg, Philadelphia, PA 19104 USA. EM stadtmae@uphs.upenn.edu OI Papanicolaou, Genovefa/0000-0002-2891-079X FU GlaxoSmithKline Vaccines FX This work was supported by GlaxoSmithKline Vaccines. NR 38 TC 22 Z9 24 U1 0 U2 3 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 6 PY 2014 VL 124 IS 19 BP 2921 EP 2929 DI 10.1182/blood-2014-04-573048 PG 9 WC Hematology SC Hematology GA AY3CD UT WOS:000347461200008 PM 25237196 ER PT J AU Saez, B Ferraro, F Yusuf, RZ Cook, CM Yu, VWC Pardo-Saganta, A Sykes, SM Palchaudhuri, R Schajnovitz, A Lotinun, S Lymperi, S Mendez-Ferrer, S del Toro, R Day, R Vasic, R Acharya, SS Baron, R Lin, CP Yamaguchi, Y Wagers, AJ Scadden, DT AF Saez, Borja Ferraro, Francesca Yusuf, Rushdia Z. Cook, Colleen M. Yu, Vionnie W. C. Pardo-Saganta, Ana Sykes, Stephen M. Palchaudhuri, Rahul Schajnovitz, Amir Lotinun, Sutada Lymperi, Stefania Mendez-Ferrer, Simon del Toro, Raquel Day, Robyn Vasic, Radovan Acharya, Sanket S. Baron, Roland Lin, Charles P. Yamaguchi, Yu Wagers, Amy J. Scadden, David T. TI Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning SO BLOOD LA English DT Article ID BONE-MARROW MICROENVIRONMENT; MORPHOGEN GRADIENT FORMATION; HEMATOPOIETIC STEM; STEM/PROGENITOR CELLS; PROGENITOR CELLS; INTEGRIN VLA-4; NICHE; MAINTENANCE; TRANSPLANTATION; MODULATION AB The glycosyltransferase gene, Ext1, is essential for heparan sulfate production. Induced deletion of Ext1 selectively in Mx1-expressing bone marrow (BM) stromal cells, a known population of skeletal stem/progenitor cells, in adult mice resulted in marked changes in hematopoietic stem and progenitor cell (HSPC) localization. HSPC egressed from BM to spleen after Ext1 deletion. This was associated with altered signaling in the stromal cells and with reduced vascular cell adhesion molecule 1 production by them. Further, pharmacologic inhibition of heparan sulfate mobilized qualitatively more potent and quantitatively more HSPC from the BM than granulocyte colony-stimulating factor alone, including in a setting of granulocyte colony-stimulating factor resistance. The reduced presence of endogenous HSPC after Ext1 deletion was associated with engraftment of transfused HSPC without any toxic conditioning of the host. Therefore, inhibiting heparan sulfate production may provide a means for avoiding the toxicities of radiation or chemotherapy in HSPC transplantation for nonmalignant conditions. C1 [Saez, Borja; Ferraro, Francesca; Yusuf, Rushdia Z.; Cook, Colleen M.; Yu, Vionnie W. C.; Palchaudhuri, Rahul; Schajnovitz, Amir; Lymperi, Stefania; Day, Robyn; Vasic, Radovan; Acharya, Sanket S.; Wagers, Amy J.; Scadden, David T.] Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. [Saez, Borja; Ferraro, Francesca; Yusuf, Rushdia Z.; Cook, Colleen M.; Yu, Vionnie W. C.; Pardo-Saganta, Ana; Palchaudhuri, Rahul; Schajnovitz, Amir; Lymperi, Stefania; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Saez, Borja; Ferraro, Francesca; Yusuf, Rushdia Z.; Cook, Colleen M.; Yu, Vionnie W. C.; Pardo-Saganta, Ana; Palchaudhuri, Rahul; Schajnovitz, Amir; Lymperi, Stefania; Lin, Charles P.; Wagers, Amy J.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA. [Sykes, Stephen M.] Fox Chase Canc Ctr, Res Inst, Philadelphia, PA 19111 USA. [Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Mendez-Ferrer, Simon; del Toro, Raquel] Ctr Nacl Invest Cient, Madrid, Spain. [Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 USA. [Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Yamaguchi, Yu] Sanford Burnham Med Res Inst, La Jolla, CA USA. [Wagers, Amy J.] Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Wagers, Amy J.] Howard Hughes Med Inst, Cambridge, MA USA. RP Scadden, DT (reprint author), 7 Divin Ave,Sherman Fairchild Bldg 258B, Cambridge, MA 02138 USA. EM david_scadden@harvard.edu OI Yu, Vionnie W. C./0000-0002-6658-0285; Mendez-Ferrer, Simon/0000-0002-9805-9988; del Toro Estevez, Raquel/0000-0002-1379-7990 FU National Institutes of Health, National Heart, Lung, and Blood Institute [HL044851, HL97794, HL097748, HL100402, HL099997]; American Society of Hematology Scholar Award FX This work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute grants HL044851, HL97794, and HL097748 (to D.T.S.) and HL100402 and HL099997 (to A.J.W. and D.T.S.). B.S. is a recipient of the American Society of Hematology Scholar Award and a former Scholar of the Chamber of Industry and Commerce of Navarra. NR 46 TC 11 Z9 11 U1 0 U2 7 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 6 PY 2014 VL 124 IS 19 BP 2937 EP 2947 DI 10.1182/blood-2014-08-593426 PG 11 WC Hematology SC Hematology GA AY3CD UT WOS:000347461200010 PM 25202142 ER PT J AU Suglia, SF Clark, CJ Boynton-Jarrett, R Kressin, NR Koenen, KC AF Suglia, Shakira F. Clark, Cari J. Boynton-Jarrett, Renee Kressin, Nancy R. Koenen, Karestan C. TI Child maltreatment and hypertension in young adulthood SO BMC PUBLIC HEALTH LA English DT Article DE Child maltreatment; Hypertension; Violence; Stress; Blood pressure ID BLOOD-PRESSURE; PSYCHOSOCIAL STRESS; SEX-DIFFERENCES; JOB STRAIN; ABUSE; WOMEN; HEALTH; MEN; DEPRESSION; SAMPLES AB Background: Maltreatment during childhood and adolescence has been associated with chronic conditions in adulthood including cardiovascular disease. However, less is known about the effects of childhood maltreatment on cardiovascular risk factors prior to development of cardiovascular disease, or whether these effects are evident in young adulthood. Furthermore, few studies have examined sex differences and most studies have relied on self-reported outcome measures that are subject to misclassification. Methods: We examined the relationship between child maltreatment and hypertension in young adulthood in the National Longitudinal Study of Adolescent Health, a nationally representative school-based sample of US adolescents. Participants retrospectively (mean age 29.9, n = 11384) reported on their experiences of child maltreatment prior to the 6th grade (prior to age 11) during follow-up. Child neglect, physical and sexual violence as well as a measure of social services visits to the home were examined. Blood pressure was measured during an in-home visit. Hypertension was defined as measured SBP of at least 140 mmHg or DBP of at least 90 mmHG measured in adulthood, or self-reported use of antihypertensive medications. Results: In adjusted models, women who experienced sexual abuse in early childhood had a higher prevalence of hypertension (Prevalence Ratio (PR) 1.43 95% CI 1.00, 2.05) compared to women who did not experience sexual abuse. Among men, experiencing sexual abuse was not statistically significantly associated with hypertension. Experiencing neglect, physical abuse or having visitations by social services at home during childhood was not associated with hypertension among either women or men. Conclusion: Sexual abuse in early childhood is associated with hypertension in young women. C1 [Suglia, Shakira F.; Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Clark, Cari J.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Boynton-Jarrett, Renee] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Senior Vet Affairs Hlth Serv Res & Dev Res Career, Boston, MA 02130 USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Suglia, SF (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10032 USA. EM sfs2150@cumc.columbia.edu FU William T Grant Foundation; Department of Veterans Affairs, Health Services Research & Development Service [RCS 02-066-1]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921]; [7K01HL103199-03]; [1R03HD068045-01A1]; [KL2TR000113]; [K12HD43444] FX Dr. Suglia was supported by Grant Number 7K01HL103199-03. Dr. Clark was supported by grant numbers 1R03HD068045-01A1 and KL2TR000113. Dr. Boynton-Jarrett was supported by the William T Grant Foundation and Grant Number K12HD43444. Dr. Kressin is supported in part by a Senior Research Career Scientist award from the Department of Veterans Affairs, Health Services Research & Development Service (RCS 02-066-1).; This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://www.cpc.unc.edu/addhealth). No direct support was received from grant P01-HD31921 for this analysis. NR 31 TC 8 Z9 8 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD NOV 6 PY 2014 VL 14 AR 1149 DI 10.1186/1471-2458-14-1149 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AU1CE UT WOS:000345357900001 PM 25374338 ER PT J AU Mandal, PK Ferreira, LMR Collins, R Meissner, TB Boutwell, CL Friesen, M Vrbanac, V Garrison, BS Stortchevoi, A Bryder, D Musunuru, K Brand, H Tager, AM Allen, TM Talkowski, ME Rossi, DJ Cowan, CA AF Mandal, Pankaj K. Ferreira, Leonardo M. R. Collins, Ryan Meissner, Torsten B. Boutwell, Christian L. Friesen, Max Vrbanac, Vladimir Garrison, Brian S. Stortchevoi, Alexei Bryder, David Musunuru, Kiran Brand, Harrison Tager, Andrew M. Allen, Todd M. Talkowski, Michael E. Rossi, Derrick J. Cowan, Chad A. TI Efficient Ablation of Genes in Human Hematopoietic Stem and Effector Cells using CRISPR/Cas9 SO CELL STEM CELL LA English DT Article ID ZINC-FINGER NUCLEASES; OFF-TARGET ACTIVITY; CD4 T-CELLS; MAMMALIAN-CELLS; CCR5 GENE; GENOME; HIV-1; DNA; SYSTEMS; TALEN AB Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9-mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4(+) T cells and CD34(+) hematopoietic stem and progenitor cells (HSPCs). Use of single RNA guides led to highly efficient mutagenesis in HSPCs but not in T cells. A dual guide approach improved gene deletion efficacy in both cell types. HSPCs that had undergone genome editing with CRISPR/Cas9 retained multilineage potential. We examined predicted on-and off-target mutations via target capture sequencing in HSPCs and observed low levels of off-target mutagenesis at only one site. These results demonstrate that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy. C1 [Mandal, Pankaj K.; Ferreira, Leonardo M. R.; Meissner, Torsten B.; Friesen, Max; Garrison, Brian S.; Musunuru, Kiran; Rossi, Derrick J.; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Mandal, Pankaj K.; Garrison, Brian S.; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA 02116 USA. [Ferreira, Leonardo M. R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Collins, Ryan; Stortchevoi, Alexei; Brand, Harrison; Talkowski, Michael E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Mol Neurogenet Unit, Boston, MA 02114 USA. [Boutwell, Christian L.; Vrbanac, Vladimir; Tager, Andrew M.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Vrbanac, Vladimir; Tager, Andrew M.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Vrbanac, Vladimir; Tager, Andrew M.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Garrison, Brian S.; Rossi, Derrick J.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Bryder, David] Lund Univ, Immunol Sect, Inst Expt Med Res, S-22184 Lund, Sweden. [Musunuru, Kiran; Rossi, Derrick J.; Cowan, Chad A.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Musunuru, Kiran] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Musunuru, Kiran; Talkowski, Michael E.; Cowan, Chad A.] Broad Inst, Cambridge, MA 02142 USA. [Talkowski, Michael E.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Rossi, DJ (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM derrick.rossi@childrens.harvard.edu; chad_cowan@harvard.edu RI Allen, Todd/F-5473-2011; mandal, pankaj/B-4885-2016; OI Ferreira, Leonardo/0000-0003-2491-9866; Collins, Ryan/0000-0003-1268-9995 FU Portuguese Foundation for Science and Technology; National Institutes of Health [P01-AI104715, MH095867, R01HL107630, U01DK072473, R01DK097768, U01HL100408]; Simons Foundation; March of Dimes; Leona M. and Harry B. Helmsley Charitable Trust; Jane Brock-Wilson Fund; Harvard Stem Cell Institute; Harvard University FX This work was supported in part by a fellowship from the Portuguese Foundation for Science and Technology (L. M. R. F.); the National Institutes of Health P01-AI104715 (T. M. A.), MH095867 (M. E. T.), R01HL107630 (D.J.R.), U01DK072473 (D.J.R.), R01DK097768 (C. A. C.), and U01HL100408 (C. A. C.); the Simons Foundation (M. E. T); the March of Dimes (M. E. T.); the Leona M. and Harry B. Helmsley Charitable Trust (D.J.R.); the Jane Brock-Wilson Fund (D.J.R. and T. M. A.); the Harvard Stem Cell Institute (D.J.R. and C. A. C.); and Harvard University (C. A. C.). D.J.R. is a New York Stem Cell Foundation Robertson Investigator. We thank Jennifer Shay and Carrie Hanscom for excellent technical support and the staff of the HSCRB-HSCI Flow Cytometry Core for assistance. NR 52 TC 91 Z9 96 U1 15 U2 62 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 EI 1875-9777 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 6 PY 2014 VL 15 IS 5 BP 643 EP 652 DI 10.1016/j.stem.2014.10.004 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA AT5XH UT WOS:000345012700016 PM 25517468 ER PT J AU Khera, AV Mehta, NN AF Khera, Amit V. Mehta, Nehal N. TI Single-cell transcriptomics: an emerging tool in the study of cardiometabolic disease SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material DE Transcriptomics; Single-cell; Next generation sequencing; Cardiometabolic diseases ID PREIMPLANTATION GENETIC DIAGNOSIS; EXPRESSION C1 [Khera, Amit V.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA. RP Mehta, NN (reprint author), NHLBI, Sect Inflammat & Cardiometab Dis, Bldg 10, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov NR 17 TC 1 Z9 1 U1 1 U2 3 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 6 PY 2014 VL 12 AR 312 DI 10.1186/s12967-014-0312-0 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AT8TK UT WOS:000345204600001 PM 25377125 ER PT J AU Pugh, TJ Yu, W Yang, J Field, AL Ambrogio, L Carter, SL Cibulskis, K Giannikopoulos, P Kiezun, A Kim, J McKenna, A Nickerson, E Getz, G Hoffher, S Messinger, YH Dehner, LP Roberts, CWM Rodriguez-Galindo, C Williams, GM Rossi, CT Meyerson, M Hill, DA AF Pugh, T. J. Yu, W. Yang, J. Field, A. L. Ambrogio, L. Carter, S. L. Cibulskis, K. Giannikopoulos, P. Kiezun, A. Kim, J. McKenna, A. Nickerson, E. Getz, G. Hoffher, S. Messinger, Y. H. Dehner, L. P. Roberts, C. W. M. Rodriguez-Galindo, C. Williams, G. M. Rossi, C. T. Meyerson, M. Hill, D. A. TI Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences SO ONCOGENE LA English DT Article ID INTEGRATIVE GENOMICS VIEWER; COPY-NUMBER ALTERATION; EMBRYONAL RHABDOMYOSARCOMA; HUMAN CANCERS; MUTATIONS; TUMORS; REGISTRY; GENES AB Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer. C1 [Pugh, T. J.; Ambrogio, L.; Carter, S. L.; Cibulskis, K.; Giannikopoulos, P.; Kiezun, A.; Kim, J.; McKenna, A.; Nickerson, E.; Getz, G.; Meyerson, M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Pugh, T. J.; Roberts, C. W. M.; Rodriguez-Galindo, C.; Meyerson, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Pugh, T. J.; Roberts, C. W. M.; Rodriguez-Galindo, C.; Meyerson, M.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Yu, W.; Yang, J.; Field, A. L.; Hoffher, S.; Rossi, C. T.; Hill, D. A.] George Washington Univ, Dept Integrat Syst Biol, Washington, DC USA. [Yu, W.; Yang, J.; Field, A. L.; Hoffher, S.; Hill, D. A.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Yu, W.; Yang, J.; Field, A. L.; Hoffher, S.; Hill, D. A.] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Messinger, Y. H.; Williams, G. M.] Childrens Hosp, Minneapolis, MN USA. [Messinger, Y. H.; Williams, G. M.] Clin Minnesota, Minneapolis, MN USA. [Dehner, L. P.] Washington Univ, Med Ctr, Dept Pathol & Immunol, St Louis, MO USA. [Roberts, C. W. M.; Rodriguez-Galindo, C.] Boston Childrens Hosp, Boston, MA USA. [Roberts, C. W. M.; Rodriguez-Galindo, C.] Dana Farber Childrens Canc Ctr, Boston, MA USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Mailstop Dana 1540, Boston, MA 02215 USA. EM matthew_meyerson@dfci.harvard.edu; dashill@childrensnational.org OI Kiezun, Adam/0000-0002-6634-1073 FU Carlos Slim Health Institute in Mexico; Canadian Institutes of Health Research Fellowship; National Cancer Institute [R01CA143167]; National Heart, Lung and Blood Institute [R01HL109265, R01HL111190] FX Sequence data used for this analysis are available from dbGaP under accession phs000543. The work was conducted as part of the Slim Initiative for Genomic Medicine, a project funded by the Carlos Slim Health Institute in Mexico. We would like to acknowledge the technical expertise and data generation efforts of The Broad Institute Genomics Platform and Cancer Genome Analysis group. TJP was supported by a Canadian Institutes of Health Research Fellowship. DAH is supported by National Cancer Institute (R01CA143167), and National Heart, Lung and Blood Institute (R01HL109265 and R01HL111190). We thank the members of the Ogawa Laboratory for shared insights during reporting of genomic findings of PPB.34 NR 34 TC 30 Z9 30 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD NOV 6 PY 2014 VL 33 IS 45 BP 5295 EP 5302 DI 10.1038/onc.2014.150 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AT7MD UT WOS:000345120400007 PM 24909177 ER PT J AU Lim, ET Liu, YFP Chan, YL Tiinamaija, T Karajamaki, A Madsen, E Altshuler, DM Raychaudhuri, S Groop, L Fannick, J Hirschhorn, JN Katsanis, N Daly, MJ AF Lim, Elaine T. Liu, Yangfan P. Chan, Yingleong Tiinamaija, Tuomi Karajamaki, AnnMari Madsen, Erik Altshuler, David M. Raychaudhuri, Soumya Groop, Leif Fannick, Jason Hirschhorn, Joel N. Katsanis, Nicholas Daly, Mark J. CA Go-T2D Consortium TI A Novel Test for Recessive Contributions to Complex Diseases Implicates Bardet-Biedl Syndrome Gene BBS10 in Idiopathic Type 2 Diabetes and Obesity SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ALZHEIMERS-DISEASE; VARIANTS; ASSOCIATION; DISRUPTION; CILIOPATHY; MUTATIONS; AUTISM; GWAS AB Rare-variant association studies in common, complex diseases are customarily conducted under an additive risk model in both single-variant and burden testing. Here, we describe a method to improve detection of rare recessive variants in complex diseases termed RAFT (recessive-allele-frequency-based test). We found that RAFT outperforms existing approaches when the variant influences disease risk in a recessive manner on simulated data. We then applied our method to 1,791 Finnish individuals with type 2 diabetes (T2D) and 2,657 matched control subjects. In BBS10, we discovered a rare variant (c.1189A>G [p.Ile397Val]; rs202042386) that confers risk of T2D in a recessive state (p = 1.38 x 10(-6)) and would be missed by conventional methods. Testing of this variant in an established in vivo zebrafish model confirmed the variant to be pathogenic. Taken together, these data suggest that RAFT can effectively reveal rare recessive contributions to complex diseases overlooked by conventional association tests. C1 [Lim, Elaine T.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. [Lim, Elaine T.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Lim, Elaine T.; Chan, Yingleong; Altshuler, David M.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lim, Elaine T.; Chan, Yingleong; Altshuler, David M.; Raychaudhuri, Soumya; Fannick, Jason; Hirschhorn, Joel N.; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Liu, Yangfan P.; Madsen, Erik; Katsanis, Nicholas] Duke Univ, Med Ctr, Ctr Human Dis Modeling, Durham, NC 27710 USA. [Chan, Yingleong; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Chan, Yingleong; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Chan, Yingleong; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Tiinamaija, Tuomi] Univ Helsinki, Cent Hosp, Dept Internal Med Diabetol, Helsinki 00029, Finland. [Tiinamaija, Tuomi] Univ Helsinki, Folkhalsan Res Ctr, Inst Diabet Genet, FIN-00014 Helsinki, Finland. [Tiinamaija, Tuomi] Univ Helsinki, Res Program Diabet & Obes, FIN-00014 Helsinki, Finland. [Karajamaki, AnnMari] Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa 65130, Finland. [Karajamaki, AnnMari] Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa 65100, Finland. [Altshuler, David M.; Fannick, Jason] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol,Dept Med, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Univ Manchester, Ctr Musculoskeletal Res, Inst Inflammat & Repair, Arthrit Res UK Epidemiol Unit, Manchester M13 9PT, Lancs, England. [Groop, Leif] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland. [Groop, Leif] Lund Univ, Skane Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, S-20502 Malmo, Sweden. [Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP Lim, ET (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. EM tengting.lim@childrens.harvard.edu; mjdaly@atgu.mgh.harvard.edu OI Tuomi, Tiinamaija/0000-0002-8306-6202; Katsanis, Nicholas/0000-0002-2480-0171 FU NIH [R37GM04360, R01HD04260, R01DK072301, R01DK075972]; Lung GO Sequencing Project [HL-102923]; WHI Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010] FX The Botnia PPP and Direva studies are supported by grants from Academy of Finland and the Juselius and Folkhalsan Foundations. The in vivo functional study is supported by NIH grants R37GM04360, R01HD04260, R01DK072301, and R01DK075972 (N.K.). The authors would like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010). Finally, the authors would also like to thank anonymous reviewers 1 and 2 for their words of encouragement and insightful, detailed feedback, which have helped improve this manuscript substantially. NR 39 TC 6 Z9 6 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV 6 PY 2014 VL 95 IS 5 BP 509 EP 520 DI 10.1016/j.ajhg.2014.09.015 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AT3OY UT WOS:000344845000003 PM 25439097 ER PT J AU Gusev, A Lee, SH Trynka, G Finucane, H Vilhjalmsson, BJ Xu, H Zang, CZ Ripke, S Bulik-Sullivan, B Stahl, E Kahler, AK Hultman, CM Purcell, SM McCarroll, SA Daly, M Pasaniuc, B Sullivan, PF Neale, BM Wray, NR Raychaudhuri, S Price, AL AF Gusev, Alexander Lee, S. Hong Trynka, Gosia Finucane, Hilary Vilhjalmsson, Bjarni J. Xu, Han Zang, Chongzhi Ripke, Stephan Bulik-Sullivan, Brendan Stahl, Eli Kaehler, Anna K. Hultman, Christina M. Purcell, Shaun M. McCarroll, Steven A. Daly, Mark Pasaniuc, Bogdan Sullivan, Patrick F. Neale, Benjamin M. Wray, Naomi R. Raychaudhuri, Soumya Price, Alkes L. CA Psychiat Genomics Consortium SWE-SCZ Consortium TI Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; PRIOR INFORMATION; GENETIC-VARIATION; DNA ELEMENTS; LARGE-SCALE; SNPS; SCHIZOPHRENIA; LOCI; EXPRESSION AB Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (h(g)(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of h(g)(2) from imputed SNPs (5.1 x enrichment; p = 3.7 x 10(-17)) and 38% (SE = 4%) of h(g)(2) from genotyped SNPs (1.6 x enrichment, p = 1.0 x 10(-4)). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of h(g)(2) despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease. C1 [Gusev, Alexander; Vilhjalmsson, Bjarni J.; Xu, Han; Zang, Chongzhi; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lee, S. Hong; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Trynka, Gosia; Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Trynka, Gosia; Ripke, Stephan; Bulik-Sullivan, Brendan; Purcell, Shaun M.; Daly, Mark; Neale, Benjamin M.; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Trynka, Gosia; Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Trynka, Gosia; Raychaudhuri, Soumya] Partners Ctr Personalized Genet Med, Boston, MA 02115 USA. [Trynka, Gosia; Daly, Mark; Neale, Benjamin M.; Raychaudhuri, Soumya; Price, Alkes L.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Finucane, Hilary] MIT, Dept Math, Cambridge, MA 02142 USA. [Xu, Han; Zang, Chongzhi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ripke, Stephan; Bulik-Sullivan, Brendan; Purcell, Shaun M.; Daly, Mark; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan; Bulik-Sullivan, Brendan; Purcell, Shaun M.; McCarroll, Steven A.; Daly, Mark; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Stahl, Eli; Purcell, Shaun M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Kaehler, Anna K.; Hultman, Christina M.; Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. [Pasaniuc, Bogdan] Univ Calif Los Angeles, Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England. RP Gusev, A (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM agusev@hsph.harvard.edu; aprice@hsph.harvard.edu RI Stroup, Thomas/F-9188-2014; Pantelis, Christos/H-7722-2014; Melle, Ingrid /B-4858-2011; Domenici, Enrico/K-8194-2016; Ruderfer, Douglas/M-5795-2016; Zang, Chongzhi/D-1445-2011; McQuillin, Andrew/C-1623-2008; Lee, Sang Hong/A-2569-2011; Wray, Naomi/C-8639-2015; McDonald, Colm/C-1430-2009; Webb, Bradley/B-1459-2009; Hansen, Thomas/O-5965-2014; Hammer, Christian/C-5827-2014; Zai, Clement/G-7379-2015; Vilhjalmsson, Bjarni/K-3971-2014; SCHALL, ULRICH/G-7452-2013; Collier, David/D-1649-2011; Mattheisen, Manuel/B-4949-2012; Slominsky, Petr/B-4640-2016; So, Hon-Cheong/I-1100-2016 OI murray, robin/0000-0003-0829-0519; Visscher, Peter/0000-0002-2143-8760; Knight, Joanne/0000-0002-7148-1660; McIntosh, Andrew/0000-0002-0198-4588; Dinan, Timothy/0000-0002-2316-7220; Corvin, Aiden/0000-0001-6717-4089; Crowley, James/0000-0001-9051-1557; Stroup, Thomas/0000-0002-3123-0672; Myin-Germeys, Inez/0000-0002-3731-4930; Franke, Lude/0000-0002-5159-8802; Escott-Price, Valentina/0000-0003-1784-5483; Murphy, Kieran/0000-0003-2930-4465; Julia Cano, Antonio/0000-0001-6064-3620; Moran, Jennifer/0000-0002-5664-4716; Walters, James/0000-0002-6980-4053; Grove, Jakob/0000-0003-2284-5744; Suvisaari, Jaana/0000-0001-7167-0990; Buxbaum, Joseph/0000-0001-8898-8313; Bruggeman, Richard/0000-0002-3238-8471; O'Neill, Francis Anthony/0000-0002-7531-7657; /0000-0002-8114-7615; Adolfsson, Rolf/0000-0001-9785-8473; Golimbet, Vera/0000-0002-9960-7114; Jonsson, Erik/0000-0001-8368-6332; Donohoe, Gary/0000-0003-3037-7426; Pantelis, Christos/0000-0002-9565-0238; Melle, Ingrid /0000-0002-9783-548X; Domenici, Enrico/0000-0001-7436-6919; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Golimbet, Vera/0000-0002-0114-4300; Esko, Tonu/0000-0003-1982-6569; Lee, Sang Hong/0000-0001-9701-2718; Wray, Naomi/0000-0001-7421-3357; Webb, Bradley/0000-0002-0576-5366; Hansen, Thomas/0000-0001-6703-7762; Hammer, Christian/0000-0003-4548-7548; Vilhjalmsson, Bjarni/0000-0003-2277-9249; Collier, David/0000-0003-4087-1559; Mattheisen, Manuel/0000-0002-8442-493X; Slominsky, Petr/0000-0003-3530-0655; FU Wellcome Trust [076113]; NIH [R01 MH101244, R03 HG006731, 1U01HG0070033]; Doris Duke Clinical Scientist Development Award; NIH fellowship [F32 GM106584]; Rubicon grant from the Netherlands Organization for Scientific Research; Fannie and John Hertz Foundation; Australian Research Council [DE130100614, FT0991360]; National Health and Medical Research Council [613602, 1050218] FX This study made use of data generated by the Wellcome Trust Case Control Consortium (WTCCC) and the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the WTCCC data is available at www.wtccc.org.uk. Funding for the WTCCC project was provided by the Wellcome Trust under award 076113. We thank Manolis Kellis, Abhishek Sarkar, Joe Pickrell, X. Shirley Liu, Nick Patterson, Sara Lindstrom, Peter Kraft, and Shamil Sunyaev for helpful discussions and Amy Williams for assistance with HApI-UR. This research was funded by NIH grants R01 MH101244, R03 HG006731, and 1U01HG0070033, the Doris Duke Clinical Scientist Development Award, and NIH fellowship F32 GM106584. G.T. was supported by the Rubicon grant from the Netherlands Organization for Scientific Research. H.F. was supported by the Fannie and John Hertz Foundation. We also acknowledge grant funding from the Australian Research Council (DE130100614 and FT0991360) and the National Health and Medical Research Council (613602 and 1050218). NR 80 TC 97 Z9 97 U1 2 U2 39 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV 6 PY 2014 VL 95 IS 5 BP 535 EP 552 DI 10.1016/j.ajhg.2014.10.004 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA AT3OY UT WOS:000344845000005 PM 25439723 ER PT J AU Sarma, K Cifuentes-Rojas, C Ergun, A del Rosario, A Jeon, Y White, F Sadreyev, R Lee, JT AF Sarma, Kavitha Cifuentes-Rojas, Catherine Ergun, Ayla del Rosario, Amanda Jeon, Yesu White, Forest Sadreyev, Ruslan Lee, Jeannie T. TI ATRX Directs Binding of PRC2 to Xist RNA and Polycomb Targets SO CELL LA English DT Article ID X-CHROMOSOME INACTIVATION; REPRESSIVE COMPLEX 2; LONG NONCODING RNAS; SYNDROME PROTEIN; STEM-CELLS; CHROMATIN; GENE; DOMAIN; REPEAT; LOCALIZATION AB X chromosome inactivation (XCI) depends on the long noncoding RNA Xist and its recruitment of Polycomb Repressive Complex 2 (PRC2). PRC2 is also targeted to other sites throughout the genome to effect transcriptional repression. Using XCI as a model, we apply an unbiased proteomics approach to isolate Xist and PRC2 regulators and identified ATRX. ATRX unexpectedly functions as a high-affinity RNA-binding protein that directly interacts with RepA/Xist RNA to promote loading of PRC2 in vivo. Without ATRX, PRC2 cannot load onto Xist RNA nor spread in cis along the X chromosome. Moreover, epigenomic profiling reveals that genomewide targeting of PRC2 depends on ATRX, as loss of ATRX leads to spatial redistribution of PRC2 and derepression of Polycomb responsive genes. Thus, ATRX is a required specificity determinant for PRC2 targeting and function. C1 [Sarma, Kavitha; Cifuentes-Rojas, Catherine; Jeon, Yesu; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Sarma, Kavitha; Cifuentes-Rojas, Catherine; Ergun, Ayla; Jeon, Yesu; Sadreyev, Ruslan; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sarma, Kavitha; Cifuentes-Rojas, Catherine; Ergun, Ayla; Jeon, Yesu; Sadreyev, Ruslan; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Sadreyev, Ruslan; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sadreyev, Ruslan; Lee, Jeannie T.] Harvard Univ, Sch Med, Boston, MA USA. [del Rosario, Amanda] MIT, Dept Bioengn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU National Institutes of Health Grants [F32-GM090765, F32-GM101828, RO1-GM090278] FX We thank Ulandt Kim for next generation sequencing, all lab members for helpful advice, and Drs.David Picketts (Ottawa Hospital Research Institute) and Xiaolu Yang (University of Pennsylvania) for the kind gift of ATRX plasmids. This work was supported by National Institutes of Health Grants F32-GM090765 (to K.S.), F32-GM101828 (to CCR), and RO1-GM090278 (to J.T.L.).J.T.L.is an Investigator of the Howard Hughes Medical Institute. NR 57 TC 54 Z9 56 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 6 PY 2014 VL 159 IS 4 BP 869 EP 883 DI 10.1016/j.cell.2014.10.019 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AS8TY UT WOS:000344522000018 PM 25417162 ER PT J AU Matoba, S Liu, YT Lu, FL Iwabuchi, KA Shen, L Inoue, A Zhang, Y AF Matoba, Shogo Liu, Yuting Lu, Falong Iwabuchi, Kumiko A. Shen, Li Inoue, Azusa Zhang, Yi TI Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation SO CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; CLONED BOVINE EMBRYOS; PREIMPLANTATION EMBRYOS; SIGNIFICANT IMPROVEMENT; DEACETYLASE INHIBITOR; LYSINE 9; HETEROCHROMATIN; GENOME; OOCYTES; CLONING AB Mammalian oocytes can reprogram somatic cells into a totipotent state enabling animal cloning through somatic cell nuclear transfer (SCNT). However, the majority of SCNT embryos fail to develop to term due to undefined reprogramming defects. Here, we identify histone H3 lysine 9 trimethylation (H3K9me3) of donor cell genome as a major barrier for efficient reprogramming by SCNT. Comparative transcriptome analysis identified reprogramming resistant regions (RRRs) that are expressed normally at 2-cell mouse embryos generated by in vitro fertilization (IVF) but not SCNT. RRRs are enriched for H3K9me3 in donor somatic cells and its removal by ectopically expressed H3K9me3 demethylase Kdm4d not only reactivates the majority of RRRs, but also greatly improves SCNT efficiency. Furthermore, use of donor somatic nuclei depleted of H3K9 methyltransferases markedly improves SCNT efficiency. Our study thus identifies H3K9me3 as a critical epigenetic barrier in SCNT-mediated reprogramming and provides a promising approach for improving mammalian cloning efficiency. C1 [Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zhang, Y (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA. EM yzhang@genetics.med.harvard.edu RI Lu, Falong/Q-3013-2016 FU NIH [U01DK089565]; Japan Society for the Promotion of Science (JSPS) FX We thank Drs.Shinpei Yamaguchi, Luis M.Tuesta, and Hao Wu for critical reading of the manuscript.This project is supported by NIH U01DK089565 (to Y.Z.).S.M.and K.A.I.are supported by postdoctoral fellowship from the Japan Society for the Promotion of Science (JSPS).Y.Z.is an investigator of the Howard Hughes Medical Institute. NR 43 TC 47 Z9 51 U1 8 U2 59 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 6 PY 2014 VL 159 IS 4 BP 884 EP 895 DI 10.1016/j.cell.2014.09.055 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AS8TY UT WOS:000344522000019 PM 25417163 ER PT J AU Drawnel, FM Boccardo, S Prummer, M Delobel, F Graff, A Weber, M Gerard, R Badi, L Kam-Thong, T Bu, L Jiang, X Hoflack, JC Kiialainen, A Jeworutzki, E Aoyama, N Carlson, C Burcin, M Gromo, G Boehringer, M Stahlberg, H Hall, BJ Magnone, MC Kolaja, K Chien, KR Bailly, J Iacone, R AF Drawnel, Faye M. Boccardo, Stefano Prummer, Michael Delobel, Frederic Graff, Alexandra Weber, Michael Gerard, Regine Badi, Laura Kam-Thong, Tony Bu, Lei Jiang, Xin Hoflack, Jean-Christophe Kiialainen, Anna Jeworutzki, Elena Aoyama, Natsuyo Carlson, Coby Burcin, Mark Gromo, Gianni Boehringer, Markus Stahlberg, Henning Hall, Benjamin J. Magnone, Maria Chiara Kolaja, Kyle Chien, Kenneth R. Bailly, Jacques Iacone, Roberto TI Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells SO CELL REPORTS LA English DT Article ID CARDIOMYOCYTES; HEART; DIFFERENTIATION; MATURATION; MECHANISMS; STRESS AB Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. C1 [Drawnel, Faye M.; Boccardo, Stefano; Prummer, Michael; Delobel, Frederic; Weber, Michael; Gerard, Regine; Badi, Laura; Kam-Thong, Tony; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Hall, Benjamin J.; Magnone, Maria Chiara; Bailly, Jacques; Iacone, Roberto] Roche Innovat Ctr Basel, Roche Pharma Res Early Dev, CH-4070 Basel, Switzerland. [Boccardo, Stefano] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Graff, Alexandra; Stahlberg, Henning] Univ Basel, Biozentrum, Dept Biosystems Sci & Engn, Ctr Cell Imaging & Nano Analyt, CH-4058 Basel, Switzerland. [Bu, Lei; Jiang, Xin] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Aoyama, Natsuyo; Carlson, Coby; Kolaja, Kyle] Cellular Dynam Int, Madison, WI 53711 USA. [Chien, Kenneth R.] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. [Chien, Kenneth R.] Karolinska Inst, Dept Med Huddinge, S-17177 Stockholm, Sweden. [Chien, Kenneth R.] Harvard Univ, Harvard Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Iacone, R (reprint author), Roche Innovat Ctr Basel, Roche Pharma Res Early Dev, CH-4070 Basel, Switzerland. EM roberto.iacone@roche.com RI Prummer, Michael/G-6464-2011; Stahlberg, Henning/H-1868-2011 OI Prummer, Michael/0000-0001-9896-3929; Stahlberg, Henning/0000-0002-1185-4592 FU Roche Postdoctoral Fellowship Program FX This work was supported by the Roche Postdoctoral Fellowship Program (to F. M. D., E. J., and S. B.). The authors would like to thank Inga Clausen and Nicholas Flint for technical assistance, Prof. Adam Cohen for useful advice, and Dr. Blake Anson and Dr. Ravi Jagasia for valuable comments on the manuscript. NR 25 TC 35 Z9 35 U1 4 U2 35 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 6 PY 2014 VL 9 IS 3 BP 810 EP 820 DI 10.1016/j.celrep.2014.09.055 PG 11 WC Cell Biology SC Cell Biology GA AS7ZI UT WOS:000344470000004 PM 25437537 ER PT J AU Fergusson, JR Smith, KE Fleming, VM Rajoriya, N Newell, EW Simmons, R Marchi, E Bjorkander, S Kang, YH Swadling, L Kurioka, A Sahgal, N Lockstone, H Baban, D Freeman, GJ Sverremark-Ekstrom, E Davis, MM Davenport, MP Venturi, V Ussher, JE Willberg, CB Klenerman, P AF Fergusson, Joannah R. Smith, Kira E. Fleming, Vicki M. Rajoriya, Neil Newell, Evan W. Simmons, Ruth Marchi, Emanuele Bjorkander, Sophia Kang, Yu-Hoi Swadling, Leo Kurioka, Ayako Sahgal, Natasha Lockstone, Helen Baban, Dilair Freeman, Gordon J. Sverremark-Ekstrom, Eva Davis, Mark M. Davenport, Miles P. Venturi, Vanessa Ussher, James E. Willberg, Christian B. Klenerman, Paul TI CD161 Defines a Transcriptional and Functional Phenotype across Distinct Human T Cell Lineages SO CELL REPORTS LA English DT Article ID HUMAN TH17 CELLS; HUMAN NKR-P1A; MULTIPLE-SCLEROSIS; CUTTING EDGE; ALPHA-CHAIN; MAIT CELLS; B-CELLS; EXPRESSION; RECEPTOR; LYMPHOCYTES AB The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a population known as mucosal-associated invariant T (MAIT) cells. To understand whether different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, which can be extended to CD161+ CD4+ and CD161+TCR gamma delta+ T cells. Furthermore, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161-expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both T cell receptor (TCR) expression and cell lineage. C1 [Fergusson, Joannah R.; Smith, Kira E.; Fleming, Vicki M.; Rajoriya, Neil; Simmons, Ruth; Marchi, Emanuele; Kang, Yu-Hoi; Swadling, Leo; Kurioka, Ayako; Ussher, James E.; Willberg, Christian B.; Klenerman, Paul] Univ Oxford, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. [Fleming, Vicki M.] Oxford Univ Hosp NHS Trust, Dept Microbiol & Infect Dis, Oxford OX3 9DU, England. [Newell, Evan W.; Davis, Mark M.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Newell, Evan W.] Singapore Immunol Network SIgN, Agcy Sci Technol & Res A STAR, Singapore 138632, Singapore. [Bjorkander, Sophia; Sverremark-Ekstrom, Eva] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden. [Sahgal, Natasha; Lockstone, Helen; Baban, Dilair] Univ Oxford, Wellcome Trust Ctr Human Genet, Bioinformat & Stat Genet Core, Oxford OX3 7BN, England. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Davenport, Miles P.; Venturi, Vanessa] Prince Wales Hosp, Dept Hematol, Kensington, NSW 2052, Australia. [Ussher, James E.] Univ Otago, Dept Microbiol & Immunol, Dunedin 9054, New Zealand. [Klenerman, Paul] John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 9TU, England. RP Klenerman, P (reprint author), Univ Oxford, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. EM paul.klenerman@ndm.ox.ac.uk RI Sverremark-Ekstrom, Eva/A-2305-2016; OI Sverremark-Ekstrom, Eva/0000-0001-6271-8681; Fergusson, Joannah/0000-0001-9223-1209; Willberg, Christian/0000-0001-5299-9344 FU Wellcome Trust IITM Programme [092871/Z/10/Z]; Wellcome Trust [WT091663MA]; Medical Research Council; NIHR Biomedical Research Centre (Oxford); Nuffield Department of Clinical Medicine (Oxford); James Martin School for the 21st Century (Oxford); NIH [NIAD U19AI 082630]; Oxford Dominions Trust FX The authors would like to thank T. Hansen for the kind provision of the MR1-blocking antibody, N. Rust for sorting expertise, C. Marchant for technical support, and all members of the laboratory for helpful discussion and support. J.R.F is supported by the Wellcome Trust IITM Programme (092871/Z/10/Z). This work was also supported by the Wellcome Trust (WT091663MA), the Medical Research Council, the NIHR Biomedical Research Centre (Oxford), the Nuffield Department of Clinical Medicine (Oxford), the James Martin School for the 21st Century (Oxford), the NIH (NIAD U19AI 082630), and the Oxford Dominions Trust. NR 46 TC 38 Z9 38 U1 2 U2 10 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 6 PY 2014 VL 9 IS 3 BP 1075 EP 1088 DI 10.1016/j.celrep.2014.09.045 PG 14 WC Cell Biology SC Cell Biology GA AS7ZI UT WOS:000344470000028 PM 25437561 ER PT J AU Brehme, M Voisine, C Rolland, T Wachi, S Soper, JH Zhu, YT Orton, K Villella, A Garza, D Vidal, M Ge, H Morimoto, RI AF Brehme, Marc Voisine, Cindy Rolland, Thomas Wachi, Shinichiro Soper, James H. Zhu, Yitan Orton, Kai Villella, Adriana Garza, Dan Vidal, Marc Ge, Hui Morimoto, Richard I. TI A Chaperome Subnetwork Safeguards Proteostasis in Aging and Neurodegenerative Disease SO CELL REPORTS LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; GENE-EXPRESSION CHANGES; CAENORHABDITIS-ELEGANS; POSTMITOTIC NEURONS; POLYGLUTAMINE AGGREGATION; MOLECULAR CHAPERONES; PROTEIN AGGREGATION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; CELLULAR TOXICITY AB Chaperones are central to the proteostasis network (PN) and safeguard the proteome from misfolding, aggregation, and proteotoxicity. We categorized the human chaperome of 332 genes into network communities using function, localization, interactome, and expression data sets. During human brain aging, expression of 32% of the chaperome, corresponding to ATP-dependent chaperone machines, is repressed, whereas 19.5%, corresponding to ATP-independent chaperones and co-chaperones, are induced. These repression and induction clusters are enhanced in the brains of those with Alzheimer's, Huntington's, or Parkinson's disease. Functional properties of the chaperome were assessed by perturbation in C. elegans and human cell models expressing A beta, polyglutamine, and Huntingtin. Of 219 C. elegans orthologs, knockdown of 16 enhanced both Ab and polyQ-associated toxicity. These correspond to 28 human orthologs, of which 52% and 41% are repressed, respectively, in brain aging and disease and 37.5% affected Huntingtin aggregation in human cells. These results identify a critical chaperome subnetwork that functions in aging and disease. C1 [Brehme, Marc; Wachi, Shinichiro; Soper, James H.; Zhu, Yitan; Villella, Adriana; Garza, Dan; Ge, Hui] Proteostasis Therapeut Inc, Cambridge, MA 02139 USA. [Brehme, Marc; Rolland, Thomas; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Brehme, Marc; Rolland, Thomas; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Brehme, Marc; Rolland, Thomas; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Brehme, Marc; Voisine, Cindy; Orton, Kai; Morimoto, Richard I.] Northwestern Univ, Rice Inst Biomed Res, Dept Mol Biosci, Evanston, IL 60208 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. EM marc_vidal@dfci.harvard.edu; hui.ge@novartis.com; r-morimoto@northwestern.edu RI Brehme, Marc/G-8697-2015 OI Brehme, Marc/0000-0003-0694-331X FU Proteostasis Therapeutics, grants from the National Institutes of Health (NIGMS); Proteostasis Therapeutics, grants from the National Institutes of Health (NIA); Proteostasis Therapeutics, grants from the National Institutes of Health (NIMH); Proteostasis Therapeutics, grants from the National Institutes of Health (NHGRI) [P50HG004233]; Ellison Medical Foundation; Daniel F. and Ada L. Rice Foundation FX The authors thank the members of the R.I.M. laboratory, the Center for Cancer Systems Biology (CCSB), and Proteostasis Therapeutics for their support and critical reading of the manuscript. These studies were supported by Proteostasis Therapeutics, grants from the National Institutes of Health (NIGMS, NIA, and NIMH to R.I.M. and NHGRI P50HG004233 to M.V.), the Ellison Medical Foundation, a foundation that requests to be anonymous, and the Daniel F. and Ada L. Rice Foundation to R.I.M. M.V. is a "Chercheur Qualifie Honoraire" from the Fonds de la Recherche Scientifique (Wallonia-Brussels Federation, Belgium). NR 61 TC 50 Z9 50 U1 3 U2 21 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 6 PY 2014 VL 9 IS 3 BP 1135 EP 1150 DI 10.1016/j.celrep.2014.09.042 PG 16 WC Cell Biology SC Cell Biology GA AS7ZI UT WOS:000344470000033 PM 25437566 ER PT J AU Orlando, DA Chen, MW Brown, VE Solanki, S Choi, YJ Olson, ER Fritz, CC Bradner, JE Guenther, MG AF Orlando, David A. Chen, Mei Wei Brown, Victoria E. Solanki, Snehakumari Choi, Yoon J. Olson, Eric R. Fritz, Christian C. Bradner, James E. Guenther, Matthew G. TI Quantitative ChIP-Seq Normalization Reveals Global Modulation of the Epigenome SO CELL REPORTS LA English DT Article ID MIXED-LINEAGE LEUKEMIA; HISTONE MODIFICATION; CHROMATIN; METHYLATION; THERAPY; GENOME; CELLS; GENE; TRANSCRIPTION; REGULATORS AB Epigenomic profiling by chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) is a prevailing methodology used to investigate chromatin-based regulation in biological systems such as human disease, but the lack of an empirical methodology to enable normalization among experiments has limited the precision and usefulness of this technique. Here, we describe a method called ChIP with reference exogenous genome (ChIP-Rx) that allows one to perform genome-wide quantitative comparisons of histone modification status across cell populations using defined quantities of a reference epigenome. ChIP-Rx enables the discovery and quantification of dynamic epigenomic profiles across mammalian cells that would otherwise remain hidden using traditional normalization methods. We demonstrate the utility of this method for measuring epigenomic changes following chemical perturbations and show how reference normalization of ChIP-seq experiments enables the discovery of disease-relevant changes in histone modification occupancy. C1 [Orlando, David A.; Chen, Mei Wei; Brown, Victoria E.; Solanki, Snehakumari; Choi, Yoon J.; Olson, Eric R.; Fritz, Christian C.; Guenther, Matthew G.] Syros Pharmaceut, Watertown, MA 02472 USA. [Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Orlando, DA (reprint author), Syros Pharmaceut, 480 Arsenal St, Watertown, MA 02472 USA. EM dorlando@syros.com; mguenther@syros.com NR 41 TC 29 Z9 30 U1 2 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 6 PY 2014 VL 9 IS 3 BP 1163 EP 1170 DI 10.1016/j.celrep.2014.10.018 PG 8 WC Cell Biology SC Cell Biology GA AS7ZI UT WOS:000344470000035 PM 25437568 ER PT J AU Gandhi, M Gandhi, RT AF Gandhi, Monica Gandhi, Rajesh T. TI Single-Pill Regimens for HIV-1 Infection REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Gandhi, Monica] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gandhi, M (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM rgandhi@partners.org NR 3 TC 2 Z9 2 U1 0 U2 1 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 6 PY 2014 VL 371 IS 19 BP 1845 EP 1846 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AS3IH UT WOS:000344170300023 PM 25372099 ER PT J AU Hohmann, EL AF Hohmann, Elizabeth L. TI Case 25-2014: A Man with Ulcerative Colitis and Bloody Diarrhea REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehohmann@partners.org NR 1 TC 0 Z9 0 U1 0 U2 2 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 6 PY 2014 VL 371 IS 19 BP 1848 EP 1849 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AS3IH UT WOS:000344170300029 PM 25372107 ER PT J AU Ashcroft, P Altrock, PM Galla, T AF Ashcroft, Peter Altrock, Philipp M. Galla, Tobias TI Fixation in finite populations evolving in fluctuating environments SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE evolutionary dynamics; fluctuating environments; stochastic processes ID EVOLUTIONARY GAMES; DYNAMICS; COOPERATION; EMERGENCE; STRATEGIES; MECHANICS; SELECTION; SURVIVAL; CONFLICT; YEAST AB The environment in which a population evolves can have a crucial impact on selection. We study evolutionary dynamics in finite populations of fixed size in a changing environment. The population dynamics are driven by birth and death events. The rates of these events may vary in time depending on the state of the environment, which follows an independent Markov process. We develop a general theory for the fixation probability of a mutant in a population of wild-types, and for mean unconditional and conditional fixation times. We apply our theory to evolutionary games for which the payoff structure varies in time. The mutant can exploit the environmental noise; a dynamic environment that switches between two states can lead to a probability of fixation that is higher than in any of the individual environmental states. We provide an intuitive interpretation of this surprising effect. We also investigate stationary distributions when mutations are present in the dynamics. In this regime, we find two approximations of the stationary measure. One works well for rapid switching, the other for slowly fluctuating environments. C1 [Ashcroft, Peter; Galla, Tobias] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England. [Altrock, Philipp M.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA. [Altrock, Philipp M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Altrock, Philipp M.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Galla, T (reprint author), Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England. EM tobias.galla@manchester.ac.uk OI Ashcroft, Peter/0000-0003-4067-7692; Galla, Tobias/0000-0003-3402-2163 FU EPSRC; Deutsche Akademie der Naturforscher Leopoldina [LPDS 2012-12] FX P.A. acknowledges support from the EPSRC. P.M.A. gratefully acknowledges the financial support from Deutsche Akademie der Naturforscher Leopoldina, grant no. LPDS 2012-12. NR 52 TC 4 Z9 4 U1 3 U2 27 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD NOV 6 PY 2014 VL 11 IS 100 AR 20140663 DI 10.1098/rsif.2014.0663 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO5KF UT WOS:000341383000008 PM 25165604 ER PT J AU Shi, ZY Wu, YJ Li, C Fu, SK Li, GD Zhu, YB Swain, CA Marcantonio, ER Xie, ZC Shen, Y AF Shi, Zhongyong Wu, Yujie Li, Cheng Fu, Shukun Li, Guodong Zhu, Yingbo Swain, Celeste A. Marcantonio, Edward R. Xie, Zhongcong Shen, Yuan TI Using the Chinese version of Memorial Delirium Assessment Scale to describe postoperative delirium after hip surgery SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE memorial delirium assessment scale; confusion assessment method; postoperative delirium; hip surgery; Chinese ID CONFUSION ASSESSMENT METHOD; CLINICAL UTILITY; ALZHEIMERS-DISEASE; RANDOMIZED-TRIAL; FRACTURE REPAIR; OLDER-ADULTS; IMPACT; VALIDATION; DEMENTIA; PREVALENCE AB OBJECTIVE: Memorial Delirium Assessment Scale (MDAS) assesses severity of delirium. However, whether the MDAS can be used in a Chinese population is unknown. Moreover, the optimal postoperative MDAS cutoff point for describing postoperative delirium in Chinese remains largely to be determined. We therefore performed a pilot study to validate MDAS in the Chinese language and to determine the optimal postoperative MDAS cutoff point for delirium. METHODS: Eighty-two patients (80 +/- 6 years, 21.9% male), who had hip surgery under general anesthesia, were enrolled. The Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) were administered to the patients before surgery. The CAM and MDAS were performed on the patients on the first, second and fourth postoperative days. The reliability and validity of the MDAS were determined. A receiver operating characteristic (ROC) curve was used to determine the optimal Chinese version MDAS cutoff point for the identification of delirium. RESULTS: The Chinese version of the MDAS had satisfactory internal consistency (a = 0.910). ROC analysis obtained an average optimal MDAS cutoff point of 7.5 in describing the CAM-defined postoperative delirium, with an area under the ROC of 0.990 (95% CI 0.977-1.000, P < 0.001). CONCLUSIONS: The Chinese version of the MDAS had good reliability and validity. The patients whose postoperative Chinese version MDAS cutoff point score was 7.5 would likely have postoperative delirium. These results have established a system for a larger scale study in the future. C1 [Shi, Zhongyong; Wu, Yujie; Shen, Yuan] Tongji Univ, Peoples Hosp 10, Dept Psychiat, Shanghai 200072, Peoples R China. [Li, Cheng; Fu, Shukun] Tongji Univ, Peoples Hosp 10, Dept Anesthesiol, Shanghai 200072, Peoples R China. [Li, Guodong] Tongji Univ, Peoples Hosp 10, Dept Orthoped Surg, Shanghai 200072, Peoples R China. [Zhu, Yingbo] Tongji Univ, Sch Med, Shanghai 200072, Peoples R China. [Swain, Celeste A.; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA USA. [Swain, Celeste A.; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. RP Shen, Y (reprint author), Tongji Univ, Peoples Hosp 10, Dept Psychiat, 301 Yanchang Rd,Bldg 9,Floor 4th,Room 4405, Shanghai 200072, Peoples R China. EM kmsharonshen@gmail.com NR 30 TC 2 Z9 2 U1 1 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-4365 J9 FRONT AGING NEUROSCI JI Front. Aging Neurosci. PD NOV 5 PY 2014 VL 6 AR 297 DI 10.3389/fnagi.2014.00297 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AY9NO UT WOS:000347878000001 PM 25414664 ER PT J AU Ibinson, JW Ezaru, CS Cormican, DS Mangione, MP AF Ibinson, James W. Ezaru, Catalin S. Cormican, Daniel S. Mangione, Michael P. TI GlideScope Use improves intubation success rates: an observational study using propensity score matching SO BMC ANESTHESIOLOGY LA English DT Article DE Airway management; Direct laryngoscopy; Difficult intubation ID DIFFICULT TRACHEAL INTUBATION; DIRECT LARYNGOSCOPY; VIDEO LARYNGOSCOPE; AIRWAY MANAGEMENT; VIDEOLARYNGOSCOPE; COMPLICATIONS; PERFORMANCE; PERFORATION; BLADE; TRIAL AB Background: Rigid video laryngoscopes are popular alternatives to direct laryngoscopy for intubation, but further large scale prospective studies comparing these devices to direct laryngoscopy in routine anesthesiology practice are needed. We hypothesized that the first pass success rate with one particular video laryngoscope, the GlideScope, would be higher than the success rate with direct laryngoscopy. Methods: 3831 total intubation attempts were tracked in an observational study comparing first-pass success rate using a Macintosh or Miller-style laryngoscope with the GlideScope. Propensity scoring was then used to select 626 subjects matched between the two groups based on their morphologic traits. Results: Comparing the GlideScope and direct laryngoscopy groups suggested that intubation would be more difficult in the GlideScope group based on the Mallampati class, cervical range of motion, mouth opening, dentition, weight, and past intubation history. Thus, a propensity score based on these factors was used to balance the groups into two 313 patient cohorts. Direct laryngoscopy was successful in 80.8% on the first-pass intubation attempt, while the GlideScope was successful in 93.6% (p < 0.001; risk difference of 0.128 with a 95% CI of 0.0771 - 0.181). Conclusion: A greater first-attempt success rate was found when using the GlideScope versus direct laryngoscopy. In addition, the GlideScope was found to be 99% successful for intubation after initial failure of direct laryngoscopy, helping to reduce the incidence of failed intubation. C1 [Ibinson, James W.; Ezaru, Catalin S.; Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Ibinson, James W.; Ezaru, Catalin S.; Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Cormican, Daniel S.] Univ Pittsburgh, Med Ctr, Dept Anesthesiol, Pittsburgh, PA USA. RP Mangione, MP (reprint author), Univ Pittsburgh, Sch Med, Dept Anesthesiol, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. EM mangionemp@anes.upmc.edu OI Ibinson, James/0000-0002-5525-5225 FU NIH [T32GM075770]; Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA FX The authors would like to thank the Anesthesiologists and the Certified Registered Nurse Anesthetists of the VA Pittsburgh Healthcare System for their dedicated efforts toward the collection of the data for this project. During a portion of his work on this project, Dr Ibinson was supported by NIH Grant Number T32GM075770. This material is also the result of work supported with resources and the use of facilities at the VA Pittsburgh Health Care System. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. Other support includes the Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA. NR 22 TC 5 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2253 J9 BMC ANESTHESIOL JI BMC Anesthesiol. PD NOV 5 PY 2014 VL 14 AR 101 DI 10.1186/1471-2253-14-101 PG 8 WC Anesthesiology SC Anesthesiology GA AX4XS UT WOS:000346932800001 PM 25400507 ER PT J AU Cannon, WD Garrett, WE Hunter, RE Sweeney, HJ Eckhoff, DG Nicandri, GT Hutchinson, MR Johnson, DD Bisson, LJ Bedi, A Hill, JA Koh, JL Reinig, KD AF Cannon, W. Dilworth Garrett, William E., Jr. Hunter, Robert E. Sweeney, Howard J. Eckhoff, Donald G. Nicandri, Gregg T. Hutchinson, Mark R. Johnson, Donald D. Bisson, Leslie J. Bedi, Asheesh Hill, James A. Koh, Jason L. Reinig, Karl D. TI Improving Residency Training in Arthroscopic Knee Surgery with Use of a Virtual-Reality Simulator A Randomized Blinded Study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OPERATING-ROOM; LAPAROSCOPIC SKILLS; PARADIGM SHIFT; PERFORMANCE; ACQUISITION AB Background: There is a paucity of articles in the surgical literature demonstrating transfer validity (transfer of training). The purpose of this study was to assess whether skills learned on the ArthroSim virtual-reality arthroscopic knee simulator transferred to greater skill levels in the operating room. Methods: Postgraduate year-3 orthopaedic residents were randomized into simulator-trained and control groups at seven academic institutions. The experimental group trained on the simulator, performing a knee diagnostic arthroscopy procedure to a predetermined proficiency level based on the average proficiency of five community-based orthopaedic surgeons performing the same procedure on the simulator. The residents in the control group continued their institution-specific orthopaedic education and training. Both groups then performed a diagnostic knee arthroscopy procedure on a live patient. Video recordings of the arthroscopic surgery were analyzed by five pairs of expert arthroscopic surgeons blinded to the identity of the residents. A proprietary global rating scale and a procedural checklist, which included visualization and probing scales, were used for rating. Results: Forty-eight (89%) of the fifty-four postgraduate year-3 residents from seven academic institutions completed the study. The simulator-trained group averaged eleven hours of training on the simulator to reach proficiency. The simulator-trained group performed significantly better when rated according to our procedural checklist (p = 0.031), including probing skills (p = 0.016) but not visualization skills (p = 0.34), compared with the control group. The procedural checklist weighted probing skills double the weight of visualization skills. The global rating scale failed to reach significance (p = 0.061) because of one extreme outlier. The duration of the procedure was not significant. This lack of a significant difference seemed to be related to the fact that residents in the control group were less thorough, which shortened their time to completion of the arthroscopic procedure. Conclusions: We have demonstrated transfer validity (transfer of training) that residents trained to proficiency on a high-fidelity realistic virtual-reality arthroscopic knee simulator showed a greater skill level in the operating room compared with the control group. C1 Univ Calif San Francisco, San Francisco, CA 94158 USA. Northwestern Univ, Chicago, IL 60611 USA. NYU, Hosp Joint Dis, New York, NY USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Minneapolis, MN USA. Univ Iowa, Iowa City, IA USA. Univ Washington, Seattle, WA 98195 USA. RP Cannon, WD (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 1500 Owens St, San Francisco, CA 94158 USA. EM cannond@orthosurg.ucsf.edu RI Koh, Jason/D-1925-2015 OI Koh, Jason/0000-0002-1814-5051 NR 29 TC 22 Z9 22 U1 3 U2 6 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV 5 PY 2014 VL 96A IS 21 BP 1798 EP 1806 DI 10.2106/JBJS.N.00058 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AW7UA UT WOS:000346468500014 PM 25378507 ER PT J AU Hodi, FS Lee, SL McDermott, DF Rao, UN Butterfield, LH Tarhini, AA Leming, P Puzanov, I Shin, D Kirkwood, JM AF Hodi, F. Stephen Lee, Sandra McDermott, David F. Rao, Uma N. Butterfield, Lisa H. Tarhini, Ahmad A. Leming, Philip Puzanov, Igor Shin, Donghoon Kirkwood, John M. TI Ipilimumab Plus Sargramostim vs Ipilimumab Alone for Treatment of Metastatic Melanoma A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Correction AB IMPORTANCE Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade with ipilimumab prolongs survival in patients with metastatic melanoma. CTLA-4 blockade and granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine combinations demonstrate therapeutic synergy in preclinical models. A key unanswered question is whether systemic GM-CSF (sargramostim) enhances CTLA-4 blockade. OBJECTIVE To compare the effect of ipilimumab plus sargramostim vs ipilimumab alone on overall survival (OS) in patients with metastatic melanoma. DESIGN, SETTING, AND PARTICIPANTS The Eastern Cooperative Oncology Group (ECOG) conducted a US-based phase 2 randomized clinical trial from December 28, 2010, until July 28, 2011, of patients (N = 245) with unresectable stage III or IV melanoma, at least 1 prior therapy, no central nervous system metastases, and ECOG performance status of 0 or 1. INTERVENTIONS Patients were randomized to receive ipilimumab, 10mg/kg, intravenously on day 1 plus sargramostim, 250 mu g subcutaneously, on days 1 to 14 of a 21-day cycle (n = 123) vs ipilimumab alone (n = 122). Ipilimumab treatment included induction for 4 cycles followed by maintenance every fourth cycle. MAIN OUTCOMES AND MEASURES Primary end point: comparison of length of OS. Secondary end point: progression-free survival (PFS), response rate, safety, and tolerability. RESULTS ResultsMedian follow-up was 13.3 months (range, 0.03-19.9). Median OS as of December 2012 for ipilimumab plus sargramostim was 17.5 months (95%CI, 14.9-not reached) vs 12.7 months (95%CI, 10.0-not reached) for ipilimumab. The 1-year survival rate for ipilimumab plus sargramostim was 68.9% (95%CI, 60.6%-85.5%) compared to 52.9% (95%CI, 43.6%-62.2%) for ipilimumab alone (stratified log-rank 1-sided P = .01; mortality hazard ratio 0.64 [1-sided 90% repeated CI, not applicable-0.90]). A planned interim analysis was conducted at 69.8%of expected events (104 observed with 149 expected deaths). Planned interim analysis using the O'Brien-Fleming boundary was crossed for improvement in OS. There was no difference in PFS. Median PFS for ipilimumab plus sargramostim was 3.1 months (95%CI, 2.9-4.6) vs 3.1 months (95%CI, 2.9-4.0) for ipilimumab alone. Grade 3 to 5 adverse events occurred in 44.9%(95%CI; 35.8%-54.4%) of patients in the ipilimumab plus sargramostim group vs 58.3%(95%CI, 49.0%-67.2%) of patients in the ipilimumab-alone group (2-sided P = .04). CONCLUSION AND RELEVANCE Among patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone resulted in longer OS and lower toxicity, but no difference in PFS. These findings require confirmation in larger studies with longer follow-up. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 2 U2 5 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 5 PY 2014 VL 312 IS 17 BP A1744 EP A1744 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AS3QX UT WOS:000344194500031 ER PT J AU Spainhour, JCG Janech, MG Schwacke, JH Velez, JCQ Ramakrishnan, V AF Spainhour, John Christian G. Janech, Michael G. Schwacke, John H. Velez, Juan Carlos Q. Ramakrishnan, Viswanathan TI The Application of Gaussian Mixture Models for Signal Quantification in MALDI-ToF Mass Spectrometry of Peptides SO PLOS ONE LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; ASSISTED-LASER-DESORPTION/IONIZATION; COMPLEX PROTEIN MIXTURES; ABSOLUTE QUANTIFICATION; ENDOTHELIAL-CELLS; LC-MS; PROTEOMICS; IDENTIFICATION; ENZYME; PLASMA AB Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled with stable isotope standards (SIS) has been used to quantify native peptides. This peptide quantification by MALDI-TOF approach has difficulties quantifying samples containing peptides with ion currents in overlapping spectra. In these overlapping spectra the currents sum together, which modify the peak heights and make normal SIS estimation problematic. An approach using Gaussian mixtures based on known physical constants to model the isotopic cluster of a known compound is proposed here. The characteristics of this approach are examined for single and overlapping compounds. The approach is compared to two commonly used SIS quantification methods for single compound, namely Peak Intensity method and Riemann sum area under the curve (AUC) method. For studying the characteristics of the Gaussian mixture method, Angiotensin II, Angiotensin-2-10, and Angiotenisn-1-9 and their associated SIS peptides were used. The findings suggest, Gaussian mixture method has similar characteristics as the two methods compared for estimating the quantity of isolated isotopic clusters for single compounds. All three methods were tested using MALDI-TOF mass spectra collected for peptides of the renin-angiotensin system. The Gaussian mixture method accurately estimated the native to labeled ratio of several isolated angiotensin peptides (5.2% error in ratio estimation) with similar estimation errors to those calculated using peak intensity and Riemann sum AUC methods (5.9% and 7.7%, respectively). For overlapping angiotensin peptides, (where the other two methods are not applicable) the estimation error of the Gaussian mixture was 6.8%, which is within the acceptable range. In summary, for single compounds the Gaussian mixture method is equivalent or marginally superior compared to the existing methods of peptide quantification and is capable of quantifying overlapping (convolved) peptides within the acceptable margin of error. C1 [Spainhour, John Christian G.; Ramakrishnan, Viswanathan] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Janech, Michael G.; Velez, Juan Carlos Q.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Velez, Juan Carlos Q.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Schwacke, John H.] Sci Res Corp, N Charleston, SC USA. RP Spainhour, JCG (reprint author), Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. EM jcs21@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Janech, Michael/0000-0002-3202-4811 FU National Institute of General Medicine [5T32GM74934-8]; National Institutes of Health [5DK080944] FX JCGS was supported under a training grant from the National Institute of General Medicine (5T32GM74934-8) http://www.nigms.nih.gov/Pages/default.aspx. JCQV was supported by a grant from the National Institutes of Health (5DK080944) http://www.nih.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 2 Z9 2 U1 1 U2 13 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 5 PY 2014 VL 9 IS 11 AR e111016 DI 10.1371/journal.pone.0111016 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS9IQ UT WOS:000344556900032 PM 25372836 ER PT J AU Choy, E Butrynski, JE Harmon, DC Morgan, JA George, S Wagner, AJ D'Adamo, D Cote, GM Flamand, Y Benes, CH Haber, DA Baselga, JM Demetri, GD AF Choy, Edwin Butrynski, James E. Harmon, David C. Morgan, Jeffrey A. George, Suzanne Wagner, Andrew J. D'Adamo, David Cote, Gregory M. Flamand, Yael Benes, Cyril H. Haber, Daniel A. Baselga, Jose M. Demetri, George D. TI Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy SO BMC CANCER LA English DT Article ID SINGLE INSTITUTION; TUMORS; RECURRENCE; SURVIVAL; CHILDREN; RELAPSE AB Background: Preclinical studies have documented antitumor activity of PARP inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study aimed to translate that observation into a clinical trial to assess the efficacy and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing sarcoma (EWS) progressing after prior chemotherapy. Methods: In this nonrandomized phase II trial, adult participants with radiographically measureable metastatic EWS received olaparib tablets, 400 mg orally twice daily, until disease progression or drug intolerance. Tumor measurements were determined by CT or MRI at 6 and 12 weeks after starting olaparib administration, and then every 8 weeks thereafter. Tumor response determinations were made according to RECIST 1.1, and adverse event determinations were made according to CTCAE, version 4.0. A total of 22 participants were planned to be enrolled using a conventional 2-step phase II study design. If no objective responses were observed after 12 participants had been followed for at least 3 months, further accrual would be stopped. Results: 12 participants were enrolled, and all were evaluable. There were no objective responses (PR/CR), 4 SD (duration 10.9, 11.4, 11.9, and 17.9 wks), and 8 PD as best response. Of the SD, 2 had minor responses (-9% and -11.7% by RECIST 1.1). The median time to disease progression was 5.7 weeks. Further enrollment was therefore discontinued. No significant or unexpected toxicities were observed with olaparib, with only a single case each of grade 3 anemia and grade 3 thrombocytopenia observed. Conclusions: This study is the first report of a prospective phase II trial to evaluate the safety and efficacy of a PARP inhibitor in patients with advanced Ewing sarcoma after failure of standard chemotherapy. Olaparib administration was safe and well tolerated when administered to this small heavily pre-treated cohort at the 400 mg BID dose, although the median duration of dosing was for only 5.7 weeks. No significant responses or durable disease control was seen, and the short average interval to disease progression underscores the aggressiveness of this disease. Other studies to combine cytotoxic chemotherapy with PARP inhibition in EWS are actively ongoing. C1 [Choy, Edwin; Harmon, David C.; Cote, Gregory M.; Haber, Daniel A.; Baselga, Jose M.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Butrynski, James E.; Morgan, Jeffrey A.; George, Suzanne; Wagner, Andrew J.; D'Adamo, David; Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Flamand, Yael] Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA. [Choy, Edwin; Harmon, David C.; Cote, Gregory M.; Benes, Cyril H.; Haber, Daniel A.; Baselga, Jose M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. RP Choy, E (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. EM echoy@mgh.harvard.edu OI Cote, Gregory/0000-0003-0181-886X FU Jennifer Hunter Yates Foundation; Ludwig Center at Dana-Farber / Harvard Cancer Center; Brian MacIsaac Sarcoma Fund; National Cancer Institute of the National Institutes of Health [U54CA168512] FX This study was supported by the Jennifer Hunter Yates Foundation, Ludwig Center at Dana-Farber / Harvard Cancer Center, the Brian MacIsaac Sarcoma Fund, and the National Cancer Institute of the National Institutes of Health under Award Number U54CA168512. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 14 TC 23 Z9 24 U1 1 U2 6 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 NOV 5 PY 2014 VL 14 AR 813 DI 10.1186/1471-2407-14-813 PG 6 WC Oncology SC Oncology GA AS8NZ UT WOS:000344506600001 PM 25374341 ER PT J AU Sperling, R Mormino, E Johnson, K AF Sperling, Reisa Mormino, Elizabeth Johnson, Keith TI The Evolution of Preclinical Alzheimer's Disease: Implications for Prevention Trials SO NEURON LA English DT Review ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; NORMAL OLDER INDIVIDUALS; AMYLOID-BETA DEPOSITION; NEUROFIBRILLARY TANGLE PATHOLOGY; INTRINSIC NETWORK CONNECTIVITY; CEREBROSPINAL-FLUID BIOMARKERS; ACCELERATED CORTICAL ATROPHY; ADULT LIFE-SPAN; IN-VIVO MODEL AB As the field begins to test the concept of a "preclinical'' stage of neurodegenerative disease, when the pathophysiological process has begun in the brain, but clinical symptoms are not yet manifest, a number of intriguing questions have already arisen. In particular, in preclinical Alzheimer's disease (AD), the temporal relationship of amyloid markers to markers of neurodegeneration and their relative utility in the prediction of cognitive decline among clinically normal older individuals remains to be fully elucidated. Secondary prevention trials in AD have already begun in both genetic at-risk and amyloid at-risk cohorts, with several more trials in the planning stages, and should provide critical answers about whether intervention at this very early stage of disease can truly bend the curve of clinical progression. This review will highlight recent progress in cognitive, imaging, and biomarker outcomes in the field of preclinical AD, and the remaining gaps in knowledge. C1 [Sperling, Reisa] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA. [Sperling, Reisa; Mormino, Elizabeth; Johnson, Keith] Massachusetts Gen Hosp, Harvard Aging Brain Study, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Sperling, Reisa; Johnson, Keith] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sperling, R (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu FU National Institute on Aging [P01AG036694, R01 AG046396, R01 AG027435, K24 AG035007, F32AG044054]; Alzheimer's Association; Janssen; Eli Lilly; Bright Focus Foundation; Harvard NeuroDiscovery Center; National Institutes on Aging; Geoffrey Beene Global Neurodiscovery Challenge; Avid Pharmaceuticals; Biogen Idec; Merck; NIH FX The authors are supported by the National Institute on Aging (P01AG036694; R01 AG046396; R01 AG027435; K24 AG035007; and F32AG044054) and the Alzheimer's Association. The authors want to acknowledge the invaluable contributions of the NIA-AA Preclinical Workgroup. The authors also wish to thank Nayiri Arzoumanian for assistance with editing the manuscript, and all of the research participants who have contributed to our findings. R. S. has served as a consultant for Merck, Eisai, Janssen, Boehringer-Ingelheim, Isis, Lundbeck, Roche, and Genetech. She has research support from Janssen, Eli Lilly, Alzheimer's Association, Bright Focus Foundation, Harvard NeuroDiscovery Center, and the National Institutes on Aging. E. M. has received a financial award from the Geoffrey Beene Global Neurodiscovery Challenge. K.J. has served as a consultant for Piramal, Lilly/Avid, GEHC, Biogen Idec, Isis, Lundbeck, Janssen, and Siemens, and has research support from Avid Pharmaceuticals, Biogen Idec, Merck, Alzheimer's Association, Harvard NeuroDiscovery Center, and the NIH. NR 156 TC 61 Z9 64 U1 6 U2 43 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD NOV 5 PY 2014 VL 84 IS 3 BP 608 EP 622 DI 10.1016/j.neuron.2014.10.038 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AS3HK UT WOS:000344168100014 PM 25442939 ER PT J AU Laughney, AM Kim, E Sprachman, MM Miller, MA Kohler, RH Yang, KS Orth, JD Mitchison, TJ Weissleder, R AF Laughney, Ashley M. Kim, Eunha Sprachman, Melissa M. Miller, Miles A. Kohler, Rainer H. Yang, Katy S. Orth, James D. Mitchison, Timothy J. Weissleder, Ralph TI Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; P-GLYCOPROTEIN INHIBITOR; MULTIDRUG-RESISTANCE; IN-VIVO; ANTICANCER DRUGS; OVARIAN-CANCER; MDR1 GENE; EXPRESSION; NANOPARTICLES; DOXORUBICIN AB Eribulin mesylate was developed as a potent microtubule-targeting cytotoxic agent to treat taxane-resistant cancers, but recent clinical trials have shown that it eventually fails in many patient subpopulations for unclear reasons. To investigate its resistance mechanisms, we developed a fluorescent analog of eribulin with pharmacokinetic (PK) properties and cytotoxic activity across a human cell line panel that are sufficiently similar to the parent drug to study its cellular PK and tissue distribution. Using intravital imaging and automated tracking of cellular dynamics, we found that resistance to eribulin and the fluorescent analog depended directly on the multidrug resistance protein 1 (MDR1). Intravital imaging allowed for real-time analysis of in vivo PK in tumors that were engineered to be spatially heterogeneous for taxane resistance, whereby an MDR1-mApple fusion protein distinguished resistant cells fluorescently. In vivo, MDR1-mediated drug efflux and the three-dimensional tumor vascular architecture were discovered to be critical determinants of drug accumulation in tumor cells. We furthermore show that standard intravenous administration of a third-generation MDR1 inhibitor, HM30181, failed to rescue drug accumulation; however, the same MDR1 inhibitor encapsulated within a nanoparticle delivery system reversed the multidrug-resistant phenotype and potentiated the eribulin effect in vitro and in vivo in mice. Our work demonstrates that in vivo assessment of cellular PK of an anticancer drug is a powerful strategy for elucidating mechanisms of drug resistance in heterogeneous tumors and evaluating strategies to overcome this resistance. C1 [Laughney, Ashley M.; Kim, Eunha; Sprachman, Melissa M.; Miller, Miles A.; Kohler, Rainer H.; Yang, Katy S.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Orth, James D.; Mitchison, Timothy J.; Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH/National Cancer Institute grant [5T32CA079443]; [R01CA164448]; [PO1-CA139980]; [U54-CA151884] FX This work was funded in part by grants R01CA164448, PO1-CA139980, and U54-CA151884. A.M.L., M.M.S., M.A.M., and K.S.Y. were sponsored by NIH/National Cancer Institute grant 5T32CA079443. NR 41 TC 16 Z9 16 U1 3 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD NOV 5 PY 2014 VL 6 IS 261 AR 261ra152 DI 10.1126/scitranslmed.3009318 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AS4GR UT WOS:000344232400005 PM 25378644 ER PT J AU Hodi, FS Lee, S McDermott, DF Rao, UN Butterfield, LH Tarhini, AA Leming, P Puzanov, I Shin, D Kirkwood, JM AF Hodi, F. Stephen Lee, Sandra McDermott, David F. Rao, Uma N. Butterfield, Lisa H. Tarhini, Ahmad A. Leming, Philip Puzanov, Igor Shin, Donghoon Kirkwood, John M. TI Ipilimumab Plus Sargramostim vs Ipilimumab Alone for Treatment of Metastatic Melanoma A Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; INFLAMMATORY-BOWEL-DISEASE; RESISTANT PROSTATE-CANCER; BONE-MARROW CULTURES; GM-CSF; COMBINATION IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; ANTIBODY BLOCKADE AB IMPORTANCE Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade with ipilimumab prolongs survival in patients with metastatic melanoma. CTLA-4 blockade and granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccine combinations demonstrate therapeutic synergy in preclinical models. A key unanswered question is whether systemic GM-CSF (sargramostim) enhances CTLA-4 blockade. OBJECTIVE To compare the effect of ipilimumab plus sargramostim vs ipilimumab alone on overall survival (OS) in patients with metastatic melanoma. DESIGN, SETTING, AND PARTICIPANTS The Eastern Cooperative Oncology Group (ECOG) conducted a US-based phase 2 randomized clinical trial from December 28, 2010, until July 28, 2011, of patients (N = 245) with unresectable stage III or IV melanoma, at least 1 prior therapy, no central nervous system metastases, and ECOG performance status of 0 or 1. INTERVENTIONS Patients were randomized to receive ipilimumab, 10mg/kg, intravenously on day 1 plus sargramostim, 250 mu g subcutaneously, on days 1 to 14 of a 21-day cycle (n = 123) vs ipilimumab alone (n = 122). Ipilimumab treatment included induction for 4 cycles followed by maintenance every fourth cycle. MAIN OUTCOMES AND MEASURES Primary end point: comparison of length of OS. Secondary end point: progression-free survival (PFS), response rate, safety, and tolerability. RESULTS Median follow-up was 13.3 months (range, 0.03-19.9). As of December 2012, median OS and 1-year survival for the ipilimumab plus sargramostim group vs ipilimumab alone were significantly different. [GRAPHICS] A planned interim analysis was conducted at 69.8% of expected events (104 observed of 149 expected deaths) and the O'Brien-Fleming boundary was crossed for improvement in OS. There was no difference in PFS. Adverse events were more common in the ipilimumab-only group. CONCLUSION AND RELEVANCE Among patients with unresectable stage III or IV melanoma, treatment with ipilimumab plus sargramostim vs ipilimumab alone resulted in longer OS and lower toxicity, but no difference in PFS. These findings require confirmation in larger studies with longer follow-up. Copyright 2014 American Medical Association. All rights reserved. C1 [Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Lee, Sandra; Shin, Donghoon] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Lee, Sandra; McDermott, David F.; Shin, Donghoon] Harvard Univ, Sch Med, Boston, MA USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Rao, Uma N.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Butterfield, Lisa H.; Tarhini, Ahmad A.; Kirkwood, John M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Leming, Philip] Christ Hosp Canc Ctr, Cincinnati, OH USA. [Leming, Philip] Univ Cincinnati, Dept Med, Cincinnati, OH USA. [Puzanov, Igor] Vanderbilt Univ, Dept Med, Div Hematol & Oncol, Nashville, TN USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu FU Public Health Service [CA23318, CA66636, CA21115, CA80775, CA39229, CA49957, CA32291]; NCI FX Funding/Support: This study was coordinated by ECOG (Robert L. Comis, MD, Chair); supported in part by Public Health Service grants CA23318, CA66636, CA21115, CA80775, CA39229, CA49957, CA32291; and the NCI; NIH; the US Department of Health and Human Services; Bristol-Myers Squibb; and Genzyme. NR 40 TC 92 Z9 94 U1 3 U2 14 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 5 PY 2014 VL 312 IS 17 BP 1744 EP 1753 DI 10.1001/jama.2014.13943 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AS3QX UT WOS:000344194500012 PM 25369488 ER PT J AU Maddox, TM Stanislawski, MA Grunwald, GK Bradley, SM Ho, PM Tsai, TT Patel, MR Sandhu, A Valle, J Magid, DJ Leon, B Bhatt, DL Fihn, SD Rumsfeld, JS AF Maddox, Thomas M. Stanislawski, Maggie A. Grunwald, Gary K. Bradley, Steven M. Ho, P. Michael Tsai, Thomas T. Patel, Manesh R. Sandhu, Amneet Valle, Javier Magid, David J. Leon, Benjamin Bhatt, Deepak L. Fihn, Stephan D. Rumsfeld, John S. TI Nonobstructive Coronary Artery Disease and Risk of Myocardial Infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; SECONDARY PREVENTION THERAPIES; CLINICAL-ASSESSMENT; MORTALITY RISK; CART PROGRAM; INSIGHTS; OUTCOMES; ANGINA; STRATIFICATION; IMPLEMENTATION AB IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: >= 1 stenosis >= 20% but no stenosis >= 70%; obstructive CAD: any stenosis >= 70% or left main [LM] stenosis >= 50%) and distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among 37 674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20 899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24%(n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56%(n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18%(n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47%(n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1-or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients. Copyright 2014 American Medical Association. All rights reserved. C1 [Maddox, Thomas M.; Stanislawski, Maggie A.; Grunwald, Gary K.; Bradley, Steven M.; Ho, P. Michael; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Maddox, Thomas M.; Grunwald, Gary K.; Bradley, Steven M.; Ho, P. Michael; Sandhu, Amneet; Valle, Javier; Leon, Benjamin; Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Grunwald, Gary K.; Magid, David J.] Colorado Sch Publ Hlth, Aurora, CO USA. [Tsai, Thomas T.; Magid, David J.] Kaiser Permanente Colorado, Denver, CO USA. [Patel, Manesh R.] Duke Univ, Durham, NC USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Heart & Vasc Ctr, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Fihn, Stephan D.] US Dept Vet Affairs, Off Analyt & Business Intelligence, Washington, DC USA. RP Maddox, TM (reprint author), Denver VA Med Ctr, Div Cardiol, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.maddox@va.gov FU VA Health Services Research and Development career development awards FX The CART program is an operational program of the Department of Veterans Affairs Office of Information and Analytics. Drs Maddox and Bradley are supported with VA Health Services Research and Development career development awards. NR 40 TC 51 Z9 53 U1 4 U2 10 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 5 PY 2014 VL 312 IS 17 BP 1754 EP 1763 DI 10.1001/jama.2014.14681 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AS3QX UT WOS:000344194500013 PM 25369489 ER PT J AU Smith, JG Luk, K Schulz, CA Engert, JC Do, R Hindy, G Rukh, G Dufresne, L Almgren, P Owens, DS Harris, TB Peloso, GM Kerr, KF Wong, Q Smith, AV Budoff, MJ Rotter, JI Cupples, LA Rich, S Kathiresan, S Orho-Melander, M Gudnason, V O'Donnell, CJ Post, WS Thanassoulis, G AF Smith, J. Gustav Luk, Kevin Schulz, Christina-Alexandra Engert, James C. Do, Ron Hindy, George Rukh, Gull Dufresne, Line Almgren, Peter Owens, David S. Harris, Tamara B. Peloso, Gina M. Kerr, Kathleen F. Wong, Quenna Smith, Albert V. Budoff, Matthew J. Rotter, Jerome I. Cupples, L. Adrienne Rich, Stephen Kathiresan, Sekar Orho-Melander, Marju Gudnason, Vilmundur O'Donnell, Christopher J. Post, Wendy S. Thanassoulis, George CA CHARGE Extracoronary TI Association of Low-Density Lipoprotein Cholesterol-Related Genetic Variants With Aortic Valve Calcium and Incident Aortic Stenosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MENDELIAN RANDOMIZATION; HEART-DISEASE; EARLY LESION; RISK; PROGRESSION; CALCIFICATION; ATHEROSCLEROSIS; STATINS; DESIGN; TRIAL AB IMPORTANCE Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression. OBJECTIVE To evaluate whether genetic data are consistent with an association between LDL-C, high-density lipoprotein cholesterol (HDL-C), or triglycerides (TG) and aortic valve disease. DESIGN, SETTING, AND PARTICIPANTS Using a Mendelian randomization study design, we evaluated whether weighted genetic risk scores (GRSs), a measure of the genetic predisposition to elevations in plasma lipids, constructed using single-nucleotide polymorphisms identified in genome-wide association studies for plasma lipids, were associated with aortic valve disease. We included community-based cohorts participating in the CHARGE consortium (n = 6942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2527), Age Gene/Environment Study-Reykjavik (2000-2012; n = 3120), and the Malmo Diet and Cancer Study (MDCS, 1991-2010; n = 28 461). MAIN OUTCOMES AND MEASURES Aortic valve calcium quantified by computed tomography in CHARGE and incident aortic stenosis in the MDCS. RESULTS The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years, aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). Plasma LDL-C, but not HDL-C or TG, was significantly associated with incident aortic stenosis (hazard ratio [HR] per mmol/L, 1.28; 95% CI, 1.04-1.57; P = .02; aortic stenosis incidence: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). The LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of aortic valve calcium in CHARGE (odds ratio [OR] per GRS increment, 1.38; 95% CI, 1.09-1.74; P = .007) and with incident aortic stenosis in MDCS (HR per GRS increment, 2.78; 95% CI, 1.22-6.37; P = .02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively). In sensitivity analyses excluding variants weakly associated with HDL-C or TG, the LDL-C GRS remained associated with aortic valve calcium (P = .03) and aortic stenosis (P = .009). In instrumental variable analysis, LDL-C was associated with an increase in the risk of incident aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P = .02). CONCLUSIONS AND RELEVANCE Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation. Copyright 2014 American Medical Association. All rights reserved. C1 [Smith, J. Gustav] Lund Univ, Dept Cardiol, Lund, Sweden. [Smith, J. Gustav] Skane Univ Hosp, Dept Heart Failure & Valvular Dis, Lund, Sweden. [Smith, J. Gustav; Schulz, Christina-Alexandra; Hindy, George; Rukh, Gull; Almgren, Peter; Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Smith, J. Gustav; Peloso, Gina M.; Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Luk, Kevin; Engert, James C.; Dufresne, Line; Thanassoulis, George] McGill Univ, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. [Engert, James C.; Thanassoulis, George] Res Inst, Dept Med, Montreal, PQ H3A 1A1, Canada. [Smith, J. Gustav; Do, Ron; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Smith, J. Gustav; Do, Ron; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. [Owens, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Kerr, Kathleen F.; Wong, Quenna] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Budoff, Matthew J.; Rotter, Jerome I.] Harbor UCLA, Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, L. Adrienne; O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Rich, Stephen] Univ Virginia, Charlottesville, VA USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bethesda, MD 20892 USA. [Post, Wendy S.] Johns Hopkins Univ, Dept Internal Med, Div Cardiol, Baltimore, MD USA. RP Thanassoulis, G (reprint author), McGill Univ, Ctr Hlth, 687 Pine Ave W H4-55, Montreal, PQ H3A 1A1, Canada. EM george.thanassoulis@mcgill.ca RI Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; Kerr, Kathleen/A-2893-2013; Hindy, George/H-1864-2016; OI Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Hindy, George/0000-0002-7257-9299; Owens, David/0000-0002-7293-9688 FU Swedish Cancer Society; Swedish Medical Research Council; Swedish Dairy Association; Albert Pahlsson Foundation; Gunnar Nilsson Foundation; Malmo city council; Swedish Heart-Lung Foundation; Swedish National Health Service; Crafoord Foundation; Skane University Hospital; Thorsten Westerstrom Foundation; National Institute on Aging [N01-AG-12100]; National Eye Institute; National Institute on Deafness and Other Communication Disorders; National Heart, Lung, and Blood Institute (NHLBI); National Institute on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); Althingi (Icelandic parliament); NHLBI [N02-HL-64278, UL1 RR024156, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, N01-HC-25195]; American College of Cardiology Foundation/Merck Adult Cardiology Research Fellowship Award; GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease Young Investigator Award; Clinician-Scientist Salary Award from the Fonds de la Recherche du Quebec-Sante; RI-MUHC/Merck Research Competition; Canadian Institutes of Health Research [MOP-119380, MOP-126033]; [N01-HC-95159]; [N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167]; [N01-HC-95168]; [N01-HC-95169]; [N01-HC-65226]; [R01 HL071739] FX The Malmo Diet and Cancer study was supported by the Swedish Cancer Society, the Swedish Medical Research Council, the Swedish Dairy Association, the Albert Pahlsson and Gunnar Nilsson Foundations, and the Malmo city council. Dr J. G. Smith was supported by the Swedish Heart-Lung Foundation, governmental funding of clinical research within the Swedish National Health Service, the Crafoord Foundation, Skane University Hospital, and the Thorsten Westerstrom Foundation. The Age, Gene/Environment Susceptibility-Reykjavik Study was supported by a grant from the National Institute on Aging (N01-AG-12100) and by the National Eye Institute, the National Institute on Deafness and Other Communication Disorders, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (Icelandic parliament). The MESA, MESA CARe, and the MESA SHARe project were supported by contracts N01-HC-95159 through 95169, N01-HC-65226, and N02-HL-64278 and grants from the NHLBI (UL1 RR024156, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259). Computed tomographic measures in MESA were supported by a grant to Dr Budoff (R01 HL071739). The Framingham Heart Study was supported by contracts from the NHLBI (N01-HC-25195, N02-HL-64278) with Affymetrix for genotyping services. Dr Kathiresan was supported by the American College of Cardiology Foundation/Merck Adult Cardiology Research Fellowship Award and the GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease Young Investigator Award. Dr Thanassoulis was supported by a Clinician-Scientist Salary Award from the Fonds de la Recherche du Quebec-Sante and operating grants from the RI-MUHC/Merck Research Competition and the Canadian Institutes of Health Research (MOP-119380 and MOP-126033). NR 30 TC 35 Z9 38 U1 2 U2 14 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 5 PY 2014 VL 312 IS 17 BP 1764 EP 1771 DI 10.1001/jama.2014.13959 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AS3QX UT WOS:000344194500014 PM 25344734 ER PT J AU Youngster, I Russell, GH Pindar, C Ziv-Baran, T Sauk, J Hohmann, EL AF Youngster, Ilan Russell, George H. Pindar, Christina Ziv-Baran, Tomer Sauk, Jenny Hohmann, Elizabeth L. TI Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VANCOMYCIN; EPIDEMIOLOGY; FIDAXOMICIN; METRONIDAZOLE; METAANALYSIS; RECURRENCE; GUIDELINES; CHILDREN; DISEASE; COST AB IMPORTANCE Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use. OBJECTIVE To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C difficile infection. DESIGN, SETTING, AND PARTICIPANTS Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C difficile infection requiring hospitalization were enrolled. INTERVENTIONS Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80 degrees C (-112 degrees F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months. MAIN OUTCOMES AND MEASURES The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements. RESULTS No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02). CONCLUSIONS AND RELEVANCE This preliminary study among patients with relapsing C difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness. Copyright 2014 American Medical Association. All rights reserved. C1 [Youngster, Ilan; Pindar, Christina; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Youngster, Ilan; Russell, George H.; Sauk, Jenny; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Boston, MA USA. [Youngster, Ilan] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02445 USA. [Russell, George H.] Boston Childrens Hosp, Dept Gastroenterol & Nutr, Boston, MA 02445 USA. [Ziv-Baran, Tomer] Tel Aviv Univ, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel. [Sauk, Jenny] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Youngster, I (reprint author), Boston Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02445 USA. EM ilan.youngster@childrens.harvard.edu RI Youngster, Ilan/J-5047-2014 OI Youngster, Ilan/0000-0001-5233-1213 FU National Center for Research Resources, National Institutes of Health [8UL1TR000170-05]; National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05]; Harvard University FX The study was funded by internal hospital division funds. Dr Youngster received career support from Harvard Catalyst, the Harvard Clinical and Translational Science Center, funded by the 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 154 Z9 167 U1 6 U2 66 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 5 PY 2014 VL 312 IS 17 BP 1772 EP 1778 DI 10.1001/jama.2014.13875 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AS3QX UT WOS:000344194500015 PM 25322359 ER PT J AU Kalantarian, S Ay, H Gollub, RL Lee, H Retzepi, K Mansour, M Ruskin, JN AF Kalantarian, Shadi Ay, Hakan Gollub, Randy L. Lee, Hang Retzepi, Kallirroi Mansour, Moussa Ruskin, Jeremy N. TI Association Between Atrial Fibrillation and Silent Cerebral Infarctions A Systematic Review and Meta-analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BRAIN INFARCTS; CARDIOVASCULAR HEALTH; COMPUTED-TOMOGRAPHY; RISK-FACTOR; STROKE; PREVALENCE; DEMENTIA; DISEASE; PROJECTIONS; PATTERNS AB Background: Atrial fibrillation (AF) is a common cause of stroke. Silent cerebral infarctions (SCIs) are known to occur in the presence and absence of AF, but the association between these disorders has not been well-defined. Purpose: To estimate the association between AF and SCIs and the prevalence of SCIs in stroke-free patients with AF. Data Sources: Searches of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE from inception to 8 May 2014 without language restrictions and manual screening of article references. Study Selection: Observational studies involving adults with AF and no clinical history of stroke or prosthetic valves who reported SCIs. Data Extraction: Study characteristics and study quality were assessed in duplicate. Data Synthesis: Eleven studies including 5317 patients with mean ages from 50.0 to 83.6 years reported on the association between AF and SCIs. Autopsy studies were heterogeneous and low-quality; therefore, they were excluded from the meta-analysis of the risk estimates. When computed tomography (CT) and magnetic resonance imaging (MRI) studies were combined, AF was associated with SCIs in patients with no history of symptomatic stroke (odds ratio, 2.62 [95% CI, 1.81 to 3.80]; I-2 = 32.12%; P for heterogeneity = 0.118). This association was independent of AF type (paroxysmal vs. persistent). The results were not altered significantly when the analysis was restricted to studies that met at least 70% of the maximum possible quality score (odds ratio, 3.06 [CI, 2.24 to 4.19]). Seventeen studies reported the prevalence of SCIs. The overall prevalence of SCI lesions on MRI and CT among patients with AF was 40% and 22%, respectively. Limitation: Most studies were cross-sectional, and autopsy studies were heterogeneous and not sufficiently sensitive to detect small lesions. Conclusion: Atrial fibrillation is associated with more than a 2-fold increase in the odds for SCI. C1 Inst Heart Vasc & Stroke Care, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM jruskin@partners.org OI Gollub, Randy L./0000-0002-9434-4044 FU Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital FX Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital. NR 44 TC 20 Z9 21 U1 1 U2 10 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 NOV 4 PY 2014 VL 161 IS 9 BP 650 EP U158 DI 10.7326/M14-0538 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA AX9TE UT WOS:000347244100006 PM 25364886 ER PT J AU Groeneweg, JW Foster, R Growdon, WB Verheijen, RHM Rueda, BR AF Groeneweg, Jolijn W. Foster, Rosemary Growdon, Whitfield B. Verheijen, Rene H. M. Rueda, Bo R. TI Notch signaling in serous ovarian cancer SO JOURNAL OF OVARIAN RESEARCH LA English DT Review DE Ovarian serous carcinoma; Notch; Gamma secretase inhibitor; Patient derived xenograft models ID GAMMA-SECRETASE INHIBITOR; ADVANCED SOLID TUMORS; EPITHELIAL-MESENCHYMAL TRANSITION; ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL-CYCLE ARREST; STEM-CELLS; PHASE-I; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; MOLECULAR PATHOGENESIS AB Ovarian cancer is the most lethal of all gynecologic malignancies because women commonly present with advanced stage disease and develop chemotherapy refractory tumors. While cytoreductive surgery followed by platinum based chemotherapy are initially effective, ovarian tumors have a high propensity to recur highlighting the distinct need for novel therapeutics to improve outcomes for affected women. The Notch signaling pathway plays an established role in embryologic development and deregulation of this signaling cascade has been linked to many cancers. Recent genomic profiling of serous ovarian carcinoma revealed that Notch pathway alterations are among the most prevalent detected genomic changes. A growing body of scientific literature has confirmed heightened Notch signaling activity in ovarian carcinoma, and has utilized in vitro and in vivo models to suggest that targeting this pathway with gamma secretase inhibitors (GSIs) leads to anti-tumor effects. While it is currently unknown if Notch pathway inhibition can offer clinical benefit to women with ovarian cancer, several GSIs are currently in phase I and II trials across many disease sites including ovary. This review will provide background on Notch pathway function and will focus on the pre-clinical literature that links altered Notch signaling to ovarian cancer progression. C1 [Groeneweg, Jolijn W.; Foster, Rosemary; Growdon, Whitfield B.; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Groeneweg, Jolijn W.; Foster, Rosemary; Growdon, Whitfield B.; Rueda, Bo R.] Harvard Univ, Sch Med, Boston, MA USA. [Foster, Rosemary; Growdon, Whitfield B.; Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Verheijen, Rene H. M.] Univ Med Ctr Utrecht, Dept Gynecol Oncol, Div Woman & Baby, Utrecht, Netherlands. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. EM brueda@MGH.Harvard.edu NR 136 TC 17 Z9 19 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1757-2215 J9 J OVARIAN RES JI J. Ovarian Res. PD NOV 4 PY 2014 VL 7 AR 95 DI 10.1186/s13048-014-0095-1 PG 12 WC Reproductive Biology SC Reproductive Biology GA AW2DC UT WOS:000346097500001 PM 25366565 ER PT J AU Chow, FC He, W Bacchetti, P Regan, S Feske, SK Meigs, JB Grinspoon, SK Triant, VA AF Chow, Felicia C. He, Wei Bacchetti, Peter Regan, Susan Feske, Steven K. Meigs, James B. Grinspoon, Steven K. Triant, Virginia A. TI Elevated rates of intracerebral hemorrhage in individuals from a US clinical care HIV cohort SO NEUROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; POPULATION-BASED COHORT; MYOCARDIAL-INFARCTION RATES; CORONARY-HEART-DISEASE; T-CELL COUNT; RISK-FACTORS; INFECTED PATIENTS; CEREBROVASCULAR EVENTS; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION AB Objective: To compare rates of intracerebral hemorrhage (ICH) in HIV-infected and uninfected individuals in a large clinical care cohort and to assess risk factors associated with ICH. Methods: We identified incident ICH in HIV-infected and uninfected control cohorts from the Partners Health Care system using ICD-9-CM codes. We constructed Cox proportional hazards models to estimate adjusted hazard ratios for HIV infection and other predictors of ICH. Results: The incidence rate of ICH was 2.29 per 1,000 person-years in HIV-infected individuals compared with 1.23 per 1,000 person-years in uninfected individuals, with an unadjusted incidence rate ratio of 1.85 (95% confidence interval 1.37-2.47, p < 0.001). In a multivariable model, HIV infection was independently associated with a higher hazard of ICH, although its effect diminished with increasing age. Female sex was associated with a lower hazard of ICH in the uninfected cohort but not in the HIV cohort. CD4 count <200 x 10(6) cells/L and anticoagulant use were predictive of ICH. Conclusions: HIV infection conferred an increased adjusted hazard of ICH, which was more pronounced in young patients and in women. C1 [Chow, Felicia C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Feske, Steven K.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [He, Wei; Regan, Susan; Meigs, James B.; Triant, Virginia A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Grinspoon, Steven K.; Triant, Virginia A.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Triant, Virginia A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Chow, FC (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. EM chowf@sfgh.ucsf.edu FU NIH [5T32MH090847, K24 DK080140, P30 DK040561, K01 AI073109] FX Supported in part by NIH grants 5T32MH090847 (F. C. C.), K24 DK080140 (J.B.M.), P30 DK040561 (S. K. G.), and K01 AI073109 (V.A.T.). NR 40 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 4 PY 2014 VL 83 IS 19 BP 1705 EP 1711 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AT2NK UT WOS:000344771200007 PM 25280902 ER PT J AU Atassi, N Berry, J Shui, A Zach, N Sherman, A Sinani, E Walker, J Katsovskiy, I Schoenfeld, D Cudkowicz, M Leitner, M AF Atassi, Nazem Berry, James Shui, Amy Zach, Neta Sherman, Alexander Sinani, Ervin Walker, Jason Katsovskiy, Igor Schoenfeld, David Cudkowicz, Merit Leitner, Melanie TI The PRO-ACT database Design, initial analyses, and predictive features SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; URIC-ACID LEVELS; PLACEBO-CONTROLLED TRIAL; DISEASE PROGRESSION; CLINICAL-TRIAL; PARKINSON-DISEASE; OXIDATIVE STRESS; DOUBLE-BLIND; ALS; SURVIVAL AB Objective: To pool data from completed amyotrophic lateral sclerosis (ALS) clinical trials and create an open-access resource that enables greater understanding of the phenotype and biology of ALS. Methods: Clinical trials data were pooled from 16 completed phase II/III ALS clinical trials and one observational study. Over 8 million de-identified longitudinally collected data points from over 8,600 individuals with ALS were standardized across trials and merged to create the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. This database includes demographics, family histories, and longitudinal clinical and laboratory data. Mixed effects models were used to describe the rate of disease progression measured by the Revised ALS Functional Rating Scale (ALSFRS-R) and vital capacity (VC). Cox regression models were used to describe survival data. Implementing Bonferroni correction, the critical p value for 15 different tests was p = 0.003. Results: The ALSFRS-R rate of decline was 1.02 (+/-2.3) points per month and the VC rate of decline was 2.24% of predicted (+/-6.9) per month. Higher levels of uric acid at trial entry were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.02). Higher levels of creatinine at baseline were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.01). Finally, higher body mass index (BMI) at baseline was associated with longer survival (p < 0.0001). Conclusion: The PRO-ACT database is the largest publicly available repository of merged ALS clinical trials data. We report that baseline levels of creatinine and uric acid, as well as baseline BMI, are strong predictors of disease progression and survival. C1 [Atassi, Nazem; Berry, James; Sherman, Alexander; Sinani, Ervin; Walker, Jason; Katsovskiy, Igor; Cudkowicz, Merit] Massachusetts Gen Hosp, Dept Neurol, NCRI, Boston, MA 02114 USA. [Shui, Amy; Schoenfeld, David] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Zach, Neta; Leitner, Melanie] Prize4Life, Cambridge, MA USA. RP Atassi, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, NCRI, Boston, MA 02114 USA. EM natassi@partners.org FU ALS Therapy Alliance (ATA) FX The authors thank the ALS Therapy Alliance (ATA) for funding this project, the companies that donated clinical trials data, and the Northeast ALS (NEALS) consortium for providing a number of de-identified clinical trials datasets. NR 39 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 4 PY 2014 VL 83 IS 19 BP 1719 EP 1725 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AT2NK UT WOS:000344771200009 PM 25298304 ER PT J AU Stewart, EH Davis, B Clemans-Taylor, BL Littenberg, B Estrada, CA Centor, RM AF Stewart, Emily H. Davis, Brian Clemans-Taylor, B. Lee Littenberg, Benjamin Estrada, Carlos A. Centor, Robert M. TI Rapid Antigen Group A Streptococcus Test to Diagnose Pharyngitis: A Systematic Review and Meta-Analysis SO PLOS ONE LA English DT Article ID PEDIATRIC EMERGENCY-DEPARTMENT; THROAT CULTURE; TEST ACCURACY; CHILDHOOD PHARYNGITIS; SPECTRUM BIAS; SENSITIVITY; MANAGEMENT; PERFORMANCE; VALIDATION; PYOGENES AB Background: Pharyngitis management guidelines include estimates of the test characteristics of rapid antigen streptococcus tests (RAST) using a non-systematic approach. Objective: To examine the sensitivity and specificity, and sources of variability, of RAST for diagnosing group A streptococcal (GAS) pharyngitis. Data Sources: MEDLINE, Cochrane Reviews, Centre for Reviews and Dissemination, Scopus, SciELO, CINAHL, guidelines, 2000-2012. Study Selection: Culture as reference standard, all languages. Data Extraction and Synthesis: Study characteristics, quality. Main Outcome(s) and Measure(s): Sensitivity, specificity. Results: We included 59 studies encompassing 55,766 patients. Forty three studies (18,464 patients) fulfilled the higher quality definition (at least 50 patients, prospective data collection, and no significant biases) and 16 (35,634 patients) did not. For the higher quality immunochromatographic methods in children (10,325 patients), heterogeneity was high for sensitivity (inconsistency [I-2] 88%) and specificity (I-2 86%). For enzyme immunoassay in children (342 patients), the pooled sensitivity was 86% (95% CI, 79-92%) and the pooled specificity was 92% (95% CI, 88-95%). For the higher quality immunochromatographic methods in the adult population (1,216 patients), the pooled sensitivity was 91% (95% CI, 87 to 94%) and the pooled specificity was 93% (95% CI, 92 to 95%); however, heterogeneity was modest for sensitivity (I-2 61%) and specificity (I-2 72%). For enzyme immunoassay in the adult population (333 patients), the pooled sensitivity was 86% (95% CI, 81-91%) and the pooled specificity was 97% (95% CI, 96 to 99%); however, heterogeneity was high for sensitivity and specificity (both, I-2 88%). Conclusions: RAST immunochromatographic methods appear to be very sensitive and highly specific to diagnose group A streptococcal pharyngitis among adults but not in children. We could not identify sources of variability among higher quality studies. The present systematic review provides the best evidence for the wide range of sensitivity included in current guidelines. C1 [Stewart, Emily H.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Davis, Brian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Clemans-Taylor, B. Lee; Centor, Robert M.] Univ Alabama, Huntsville, AL 35899 USA. [Littenberg, Benjamin] Univ Vermont, Burlington, VT USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham, AL 35233 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] Vet Affairs Qual Scholar Program, Birmingham, AL USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham, AL 35233 USA. EM cestrada@uab.edu FU Justin Rogers Foundation FX RMC received funding from Justin Rogers Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 82 TC 10 Z9 10 U1 1 U2 8 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 4 PY 2014 VL 9 IS 11 AR e111727 DI 10.1371/journal.pone.0111727 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS6XG UT WOS:000344402000094 PM 25369170 ER PT J AU Xanthakis, V Enserro, DM Murabito, JM Polak, JF Wollert, KC Januzzi, JL Wang, TJ Tofler, G Vasan, RS AF Xanthakis, Vanessa Enserro, Danielle M. Murabito, Joanne M. Polak, Joseph F. Wollert, Kai C. Januzzi, James L. Wang, Thomas J. Tofler, Geoffrey Vasan, Ramachandran S. TI Ideal Cardiovascular Health Associations With Biomarkers and Subclinical Disease and Impact on Incidence of Cardiovascular Disease in the Framingham Offspring Study SO CIRCULATION LA English DT Article DE American Heart Association; biological markers; cardiovascular diseases; risk ID LIFE-STYLE; US ADULTS; RISK; PREVALENCE; MORTALITY; EVENTS; INDIVIDUALS; BURDEN; STROKE; DEATH AB Background-The American Heart Association Cardiovascular Health score (CVH score) is inversely associated with cardiovascular disease (CVD) incidence, but the mechanisms underlying this association warrant exploration. Methods and Results-We related the CVH score to circulating biomarkers and prevalent subclinical CVD (defined as >= 1 of the following: increased carotid intima-media thickness or stenosis, left ventricular hypertrophy [by ECG or echocardiography], left ventricular systolic dysfunction, microalbuminuria, and a reduced ankle-brachial index) in 2680 Framingham Study participants (mean age, 58 years; 55% women). After adjustment for age and sex, an ideal CVH score (nonsmoking status, ideal body mass index, regular physical activity, healthy diet, and an optimal profile of serum cholesterol, blood pressure, and glucose; 1 point for each) was associated with higher circulating concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide and B-type natriuretic peptide) and lower blood concentrations of plasminogen activator inhibitor-1, aldosterone, C-reactive protein, D-dimer, fibrinogen, homocysteine, and growth differentiation factor-15 levels (P<0.001 for all), as well as lower odds of subclinical disease (odds ratio, 0.74 per 1-unit increase in CVH score; 95% confidence interval, 0.68-0.80). The incidence of CVD (267 events over 16 years) was inversely associated with the CVH score in age-and sex-adjusted models (hazard ratio, 0.77 per 1-unit increase in CVH score; 95% confidence interval, 0.70-0.86), which was slightly attenuated upon adjustment for biomarkers and subclinical disease (hazard ratio, 0.87; 95% confidence interval, 0.78-0.97). Conclusion-In our prospective community-based study, the inverse association between an ideal cardiovascular health score and CVD incidence was partly attributable to its favorable impact on CVD biomarker levels and subclinical disease. C1 [Xanthakis, Vanessa; Murabito, Joanne M.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Xanthakis, Vanessa; Enserro, Danielle M.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Xanthakis, Vanessa; Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, Boston, MA 02118 USA. [Polak, Joseph F.] Tufts Univ, Med Ctr, Dept Radiol, Boston, MA 02111 USA. [Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany. [Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Div Cardiol, Nashville, TN USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. RP Xanthakis, V (reprint author), Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, 801 Massachusetts Ave,Ste 470, Boston, MA 02118 USA. EM vanessax@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU AHA [13CRP14090010]; National Heart, Lung, and Blood Institute [N01-HC-25915]; DeSanctis Clinical Scholar Endowment FX This work was supported by AHA Clinical Research Program award 13CRP14090010 (Dr Xanthakis) and by contract N01-HC-25915 (from the National Heart, Lung, and Blood Institute). Dr Januzzi is supported in part by the DeSanctis Clinical Scholar Endowment. Dr Xanthakis (Section of Preventive Medicine and Epidemiology, Boston University School of Medicine) had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 26 TC 40 Z9 42 U1 0 U2 9 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 4 PY 2014 VL 130 IS 19 BP 1676 EP + DI 10.1161/CIRCULATIONAHA.114.009273 PG 29 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AS1UJ UT WOS:000344067000010 PM 25274000 ER PT J AU Egan, BM Li, JX Hutchison, FN Ferdinand, KC AF Egan, Brent M. Li, Jiexiang Hutchison, Florence N. Ferdinand, Keith C. TI Hypertension in the United States, 1999 to 2012 Progress Toward Healthy People 2020 Goals SO CIRCULATION LA English DT Article DE Healthy People Programs; hypertension; nutrition surveys; population characteristics ID DISEASE RISK-FACTORS; BODY-MASS-INDEX; BLOOD-PRESSURE; NATIONAL-HEALTH; RESISTANT HYPERTENSION; ADULTS; PREVALENCE; AWARENESS; TRENDS; INSURANCE AB Background-To reduce the cardiovascular disease burden, Healthy People 2020 established US hypertension goals for adults to (1) decrease the prevalence to 26.9% and (2) raise treatment to 69.5% and control to 61.2%, which requires controlling 88.1% on treatment. Methods and Results-To assess the current status and progress toward these Healthy People 2020 goals, time trends in National Health and Nutrition Examination Surveys 1999 to 2012 data in 2-year blocks were assessed in adults >= 18 years of age age-adjusted to US 2010. From 1999 to 2000 to 2011 to 2012, prevalent hypertension was unchanged (30.1% versus 30.8%, P=0.32). Hypertension treatment (59.8% versus 74.7%, P<0.001) and proportion of treated adults controlled (53.3%-68.9%, P=0.0015) increased. Hypertension control to <140/< 90 mm Hg rose every 2 years from 1999 to 2000 to 2009 to 2010 (32.2% versus 53.8%, P<0.001) before declining to 51.2% in 2011 to 2012. Modifiable factor(s) significant in multivariable logistic regression modeling include: (1) increasing body mass index with prevalent hypertension (odds ratio [OR], 1.44); (2) lack of health insurance (OR, 1.68) and <2 healthcare visits per year (OR, 4.24) with untreated hypertension; (3) healthcare insurance (OR, 1.69), >= 2 healthcare visits per year (OR, 3.23), and cholesterol treatment (OR, 1.90) with controlled hypertension. Conclusions-The National Health and Nutrition Examination Survey 1999 to 2012 analysis suggests that Healthy People 2020 goals for hypertension ([1] prevalence shows no progress, [2] treatment was exceeded, and [3] control) have flattened below target. Findings are consistent with evidence that (1) obesity prevention and treatment could reduce prevalent hypertension, and (2) healthcare insurance, >= 2 healthcare visits per year, and guideline-based cholesterol treatment could improve hypertension control. C1 [Egan, Brent M.] Care Coordinat Inst, Greenville, SC 29601 USA. [Egan, Brent M.] Univ S Carolina, Sch Med Greenville, Greenville Hlth Syst, Greenville, SC USA. [Li, Jiexiang] Coll Charleston, Dept Math, Charleston, SC 29424 USA. [Hutchison, Florence N.] Med Univ S Carolina, Charleston, SC 29425 USA. [Hutchison, Florence N.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Ferdinand, Keith C.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Egan, BM (reprint author), Care Coordinat Inst, 300 East McBee Ave,4th Floor, Greenville, SC 29601 USA. EM began@ccihealth.org FU National Institutes of Health [HL105880]; United States Army [W81XWH-10-2-0057]; Centers for Disease Control, Atlanta, GA (Community Transformation Grant thru the South Carolina Department of Health and Environmental Control [SC DHEC]; State of South Carolina, Columbia, SC FX This work was supported in part by National Institutes of Health grant HL105880; United States Army, W81XWH-10-2-0057, Centers for Disease Control, Atlanta, GA (Community Transformation Grant thru the South Carolina Department of Health and Environmental Control [SC DHEC]), and the State of South Carolina, Columbia, SC. NR 36 TC 33 Z9 33 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 4 PY 2014 VL 130 IS 19 BP 1692 EP + DI 10.1161/CIRCULATIONAHA.114.010676 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AS1UJ UT WOS:000344067000012 PM 25332288 ER PT J AU Vurro, M Crowell, AM Pezaris, JS AF Vurro, Milena Crowell, Anne Marie Pezaris, John S. TI Simulation of thalamic prosthetic vision: reading accuracy, speed, and acuity in sighted humans SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE visual prosthesis; artificial sight; neuroprosthesis; neurotechnology ID LATERAL GENICULATE-NUCLEUS; VISUAL PROSTHESIS; ARTIFICIAL VISION; ELECTRICAL-STIMULATION; RETINITIS-PIGMENTOSA; PSYCHOPHYSICS; MICROSTIMULATION; EYE; CONTRAST; GLAUCOMA AB The psychophysics of reading with artificial sight has received increasing attention as visual prostheses are becoming a real possibility to restore useful function to the blind through the coarse, pseudo-pixelized vision they generate. Studies to date have focused on simulating retinal and cortical prostheses; here we extend that work to report on thalamic designs. This study examined the reading performance of normally sighted human subjects using a simulation of three thalamic visual prostheses that varied in phosphene count, to help understand the level of functional ability afforded by thalamic designs in a task of daily living. Reading accuracy, reading speed, and reading acuity of 20 subjects were measured as a function of letter size, using a task based on the MNREAD chart. Results showed that fluid reading was feasible with appropriate combinations of letter size and phosphene count, and performance degraded smoothly as font size was decreased, with an approximate doubling of phosphene count resulting in an increase of 0.2 logMAR in acuity. Results here were consistent with previous results from our laboratory. Results were also consistent with those from the literature, despite using naive subjects who were not trained on the simulator, in contrast to other reports. C1 [Vurro, Milena; Crowell, Anne Marie; Pezaris, John S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Pezaris, JS (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,M-C THR 425, Boston, MA 02114 USA. EM pezaris.john@mgh.harvard.edu FU National Eye Institute of the National Institutes of Health [R01EY019679]; NEMA Foundation; Rappaport Foundation; 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) [UL1TR001102]; Harvard University FX Research reported in this publication was supported by the National Eye Institute of the National Institutes of Health under Award R01EY019679, The NEMA Foundation, The Rappaport Foundation, 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 UL1TR001102), and Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent official view of the sponsors. NR 59 TC 5 Z9 5 U1 1 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD NOV 4 PY 2014 VL 8 AR 816 DI 10.3389/fnhum.2014.00816 PG 14 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AS1ON UT WOS:000344050200001 PM 25408641 ER PT J AU White, JP Wrann, CD Rao, RR Nair, SK Jedrychowski, MP You, JS Martinez-Redondo, V Gygi, SP Ruas, JL Hornberger, TA Wu, ZD Glass, DJ Piao, XH Spiegelman, BM AF White, James P. Wrann, Christiane D. Rao, Rajesh R. Nair, Sreekumaran K. Jedrychowski, Mark P. You, Jae-Sung Martinez-Redondo, Vicente Gygi, Steven P. Ruas, Jorge L. Hornberger, Troy A. Wu, Zhidan Glass, David J. Piao, Xianhua Spiegelman, Bruce M. TI G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GPR56; mTOR; G alpha 12/13; muscle hypertrophy; overload ID GROWTH-FACTOR RECEPTOR; SKELETAL-MUSCLE; PATHWAY; PGC-1-ALPHA; EXERCISE; INCREASE; MTOR AB Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1 alpha 4) is a protein isoform derived by alternative splicing of the PGC1 alpha mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1 alpha 4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1 alpha 4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1 alpha 4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on G alpha 12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise. C1 [White, James P.; Wrann, Christiane D.; Rao, Rajesh R.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [White, James P.; Wrann, Christiane D.; Rao, Rajesh R.; Jedrychowski, Mark P.; Gygi, Steven P.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Nair, Sreekumaran K.] Mayo Clin, Div Endocrinol, Endocrine Res Unit, Rochester, MN 55905 USA. [You, Jae-Sung; Hornberger, Troy A.] Univ Wisconsin, Sch Vet Med, Dept Comparat Biosci, Madison, WI 53706 USA. [Martinez-Redondo, Vicente; Ruas, Jorge L.] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. [Wu, Zhidan; Glass, David J.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Piao, Xianhua] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med,Div Newborn Med, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM Bruce_Spiegelman@dfci.harvard.edu OI Hornberger, Troy/0000-0002-2349-1899; Ruas, Jorge/0000-0002-1110-2606 FU American Cancer Society [PF-13-385-01-TBE]; German Research Foundation [WR 157/3-1]; Irvington Institute Fellowship Program of the Cancer Research Institute; National Institutes of Health (NIH) [AR057347, DK061562]; Novartis FX We thank the Harvard Histology Core Facility for assistance with embedding and processing muscle tissue. J.P.W. was supported by Postdoctoral Fellowship PF-13-385-01-TBE from the American Cancer Society. C. D. W. was supported by Fellowship WR 157/3-1 from the German Research Foundation. R. R. R. was supported by the Irvington Institute Fellowship Program of the Cancer Research Institute. T. A. H. was supported by National Institutes of Health (NIH) Grant AR057347. This project was supported by NIH Grant DK061562 and a grant from Novartis (to B.M.S.). NR 26 TC 14 Z9 14 U1 0 U2 6 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 4 PY 2014 VL 111 IS 44 BP 15756 EP 15761 DI 10.1073/pnas.1417898111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS2CY UT WOS:000344088100043 PM 25336758 ER PT J AU Zhao, R Deibler, RW Lerou, PH Ballabeni, A Heffner, GC Cahan, P Unternaehrer, JJ Kirschner, MW Daley, GQ AF Zhao, Rui Deibler, Richard W. Lerou, Paul H. Ballabeni, Andrea Heffner, Garrett C. Cahan, Patrick Unternaehrer, Juli J. Kirschner, Marc W. Daley, George Q. TI A nontranscriptional role for Oct4 in the regulation of mitotic entry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pluripotent stem cells; mitotic entry; Oct4; Cdk1; CDC25 ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; CYCLIN-A; TRANSCRIPTION FACTOR; RETINOBLASTOMA PROTEIN; GENOMIC INSTABILITY; MAMMALIAN EMBRYO; DEFINED FACTORS; SELF-RENEWAL; COMPLEX AB Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin-Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry. C1 [Zhao, Rui; Heffner, Garrett C.; Cahan, Patrick; Unternaehrer, Juli J.; Daley, George Q.] Harvard Univ, Stem Cell Transplantat Program,Harvard Stem Cell, Div Pediat Hematol Oncol,Sch Med,Dana Farber Canc, Manton Ctr Orphan Dis Res,Boston Childrens Hosp,S, Boston, MA 02115 USA. [Zhao, Rui; Heffner, Garrett C.; Cahan, Patrick; Unternaehrer, Juli J.; Daley, George Q.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Deibler, Richard W.; Ballabeni, Andrea; Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Lerou, Paul H.] Harvard Univ, Brigham & Womens Hosp, Dept Newborn Med,Sch Med, Div Genet,Dept Med,Div Newborn Med,Boston Childre, Boston, MA 02115 USA. [Lerou, Paul H.] Harvard Univ, Brigham & Womens Hosp, Dept Med,Sch Med, Div Genet,Div Newborn Med,Boston Childrens Hosp, Boston, MA 02115 USA. [Lerou, Paul H.] Harvard Univ, Harvard Stem Cell Inst, Sch Med, Boston, MA 02115 USA. RP Kirschner, MW (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM marc@hms.harvard.edu; george.daley@childrens.harvard.edu OI Cahan, Patrick/0000-0003-3652-2540 FU NIH National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium [UO1-HL100001]; National Institute of Diabetes and Digestive and Kidney Diseases [R24DK092760]; Alex's Lemonade Stand; Doris Duke Medical Foundation; Harvard Stem Cell Institute; NIH [R01GM026875, R01GM039023, RC4GM096319, K99HD061981]; Charles H. Hood Foundation; NHLBI [T32HL007623]; Microarray Core Facility at the Children's Hospital Boston [NIH-P50-NS40828, NIH-P30-HD18655] FX We thank Drs. Stuart Orkin and Jianlong Wang for the BirA bioOct4 ES cells, Cristina Cardoso for the GFP-PCNA construct, and Duanqing Pei for the NLS(-)-mOct4GFP construct. G.Q.D. is supported by NIH National Heart, Lung, and Blood Institute (NHLBI) Progenitor Cell Biology Consortium Grant UO1-HL100001; National Institute of Diabetes and Digestive and Kidney Diseases Grant R24DK092760; Alex's Lemonade Stand; the Doris Duke Medical Foundation; and the Harvard Stem Cell Institute. G.Q.D. is an affiliate member of the Broad Institute and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. M.W.K. is supported by NIH Grants R01GM026875, R01GM039023, and RC4GM096319. P.H.L. is supported by NIH Grant K99HD061981, the Harvard Stem Cell Institute, and the Charles H. Hood Foundation. G.C.H. and P.C. are supported by NHLBI Grant T32HL007623. Microarray experiments were performed by the Microarray Core Facility at the Children's Hospital Boston (Grants NIH-P50-NS40828 and NIH-P30-HD18655). NR 51 TC 10 Z9 10 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 4 PY 2014 VL 111 IS 44 BP 15768 EP 15773 DI 10.1073/pnas.1417518111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AS2CY UT WOS:000344088100045 PM 25324523 ER PT J AU Bratcher, PE Gaggar, A AF Bratcher, Preston E. Gaggar, Amit TI Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA SO PLOS ONE LA English DT Article ID INTERSTITIAL LUNG-DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; CLINICAL-SIGNIFICANCE; SYSTEMIC-SCLEROSIS; SERUM-LEVELS; RADIATION PNEUMONITIS; RHEUMATOID-ARTHRITIS; BIOMARKER PROFILES; CIRCULATING LEVELS AB Background: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature. In order to determine the source of these variations, factors influencing the measurement by ELISA were explored. Materials and Methods: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw. Recombinant SP-D was diluted into different matrices and used for a standard curve. Samples were analyzed by capture ELISA using one of two distinct detection antibodies. Results: The type of matrix had some effects on detection of recombinant SP-D. The type of anticoagulant used and dilution factor had very little effect, except for in plasma collected in EDTA vacutainers. The extent of variation in published values seemed to be due to the ELISA configuration employed, and, in agreement with this, we found that by switching the detection antibody, there was a 50% decrease in the extrapolated SP-D value of serum and plasma samples. Storage of samples resulted in slight changes in measured SP-D levels. Conclusions: The ELISA configuration employed to measure circulating levels of SP-D has a significant effect on the extrapolated values. In both configurations tested, the use of EDTA as a coagulant resulted in inconsistent values, and we, therefore, suggest the avoidance of this anticoagulant when assaying for SP-D by ELISA. While the demonstrated effects of several factors on measurement of SP-D may not account for all the disparities amongst the previous studies, they stress that variations in methodologies for measuring the same protein can result in very inconsistent results. C1 [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35294 USA. [Gaggar, Amit] US Dept Vet Affairs, Med Serv, Med Ctr, Birmingham, AL USA. [Bratcher, Preston E.; Gaggar, Amit] Univ Alabama Birmingham, Program Protease & Matrix Biol, Birmingham, AL 35294 USA. RP Bratcher, PE (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. EM bratcher@uab.edu FU National Institutes of Health [HL102371, 5T32HL105346-02] FX This work is supported by the National Institutes of Health (HL102371 to AG and 5T32HL105346-02 to PEB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 92 TC 4 Z9 4 U1 1 U2 3 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 3 PY 2014 VL 9 IS 11 AR e111466 DI 10.1371/journal.pone.0111466 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU4DB UT WOS:000345558100068 PM 25365324 ER PT J AU Li, SY Zhai, X Rong, PJ McCabe, MF Wang, X Zhao, JJ Ben, H Wang, SX AF Li, Shaoyuan Zhai, Xu Rong, Peijing McCabe, Michael F. Wang, Xing Zhao, Jingjun Ben, Hui Wang, Shuxing TI Therapeutic Effect of Vagus Nerve Stimulation on Depressive-Like Behavior, Hyperglycemia and Insulin Receptor Expression in Zucker Fatty Rats SO PLOS ONE LA English DT Article ID ACUPUNCTURE; MELATONIN; DISORDER; OBESITY; MEMORY; TRIAL AB Depression and type 2 diabetes (T2D) are common comorbid diseases and highly prevalent in the clinical setting with an unclarified mechanism. Zucker diabetic fatty (ZDF, fa/fa) rats natively develop T2D with hyperglycemia and hyperinsulinemia. Here we studied whether ZDF rats also innately develop depression, what a correlation is between depression and T2D, whether insulin receptor (IR) expression is involved in, and whether transcutaneous auricular vagus nerve stimulation (taVNS) would be beneficial in amelioration of the comorbidity. Six week old male ZDF and Zucker lean (ZL, fa/+) littermates were randomly divided into naive (ZDF, n = 6; ZL, n = 7) and taVNS (ZDF-taVNS, n = 8; ZL-taVNS, n = 6) groups. Once daily 30 min-taVNS sessions were administrated under anesthesia for 34 consecutive days in taVNS groups. Blood glucose levels were tested weekly, and plasma glycosylated hemoglobin (HbAlc) level and immobility time in forced swimming test were determined on day 35 in all groups. The expression of insulin receptor (IR) in various tissues was also detected by immunostaining and Western blot. We found that naive ZDF rats developed hyperglycemia steadily. These ZDF rats showed a strong positive correlation between longer immobility time and higher plasma HbAlC level. Long term taVNS treatment simultaneously prevented the development of depression-like behavior and progression of hyperglycemia in ZDF rats. The expression of IR in various tissues of naive ZDF rats is lower than in naive ZL and long-term taVNS treated ZDF rats. Collectively, our results indicate that in ZDF rats, i) depression and T2D develop simultaneously, ii) immobility time and HbAlc concentrations are highly and positively correlated, iii) a low expression of IR may be involved in the comorbidity of depression and T2D, and iv) taVNS is antidiabetic and antidepressive possibly through IR expression upregulation. C1 [Li, Shaoyuan; Zhai, Xu; Rong, Peijing; Zhao, Jingjun; Ben, Hui; Wang, Shuxing] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Dept Physiol, Beijing, Peoples R China. [Li, Shaoyuan; Wang, Xing; Wang, Shuxing] Xinxiang Med Univ, Dept Anat, Xinxiang, Henan, Peoples R China. [McCabe, Michael F.; Wang, Shuxing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Wang, Shuxing] Guangdong Entomol Inst, Primate Res Ctr, Guangzhou, Guangdong, Peoples R China. [Wang, Shuxing] Guangdong Landau Biotechnol Co Ltd, Guangzhou, Guangdong, Peoples R China. RP Rong, PJ (reprint author), China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Dept Physiol, Beijing, Peoples R China. EM rongpj@hotmail.com; 13718103762@139.com FU National Natural Science Foundation of China [81271243]; National Basic Research Program of China (973 Program) [2012CB518503]; Project Supported National Science and Technology Ministry [2012BAF14B10] FX This work was supported by National Natural Science Foundation of China, 81271243; National Basic Research Program of China (973 Program), 2012CB518503; and Project Supported National Science and Technology Ministry, 2012BAF14B10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 3 Z9 3 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 3 PY 2014 VL 9 IS 11 AR e112066 DI 10.1371/journal.pone.0112066 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU4DB UT WOS:000345558100144 PM 25365428 ER PT J AU Merlin, JS Walcott, M Ritchie, C Herbey, I Kertesz, SG Chamot, E Saag, M Turan, JM AF Merlin, Jessica S. Walcott, Melonie Ritchie, Christine Herbey, Ivan Kertesz, Stefan G. Chamot, Eric Saag, Michael Turan, Janet M. TI 'Two Pains Together': Patient Perspectives on Psychological Aspects of Chronic Pain while Living with HIV SO PLOS ONE LA English DT Article ID PRIMARY-CARE PATIENTS; CHRONIC BACK-PAIN; MUSCULOSKELETAL PAIN; NONCANCER PAIN; OPIOID USE; GENERAL-POPULATION; DEPRESSION; MANAGEMENT; COMORBIDITY; ADULTS AB Objective: Chronic pain is common in HIV-infected individuals. Understanding HIV-infected patients' chronic pain experience not just from a biological, but also from a psychological perspective, is a critical first step toward improving care for this population. Our objective was to explore HIV-infected patients' perspectives on psychological aspects of chronic pain using in-depth qualitative interviews. Methods: Investigators engaged in an iterative process of independent and group coding until theme saturation was reached. Results: Of the 25 patients with chronic pain interviewed, 20 were male, 15 were younger than age 50, and 15 were African-American. Key themes that emerged included the close relationship between mood and pain; mood and pain in the context of living with HIV; use of alcohol/drugs to self-medicate for pain; and the challenge of receiving prescription pain medications while dealing with substance use disorders. Conclusions: The results suggest that psychological approaches to chronic pain treatment may be well received by HIV-infected patients. C1 [Merlin, Jessica S.; Walcott, Melonie; Herbey, Ivan; Saag, Michael] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Merlin, Jessica S.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL USA. [Ritchie, Christine] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. [Ritchie, Christine] Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kertesz, Stefan G.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL USA. [Chamot, Eric; Turan, Janet M.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL USA. RP Merlin, JS (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. EM jmerlin@uab.edu FU University of Alabama at Birmingham (UAB) Center for AIDS Research (CFAR); National Institutes of Health funded program [P30 A1027767]; Agency for Healthcare Research and Quality [1K12HS02169401]; National Institute on Aging [7K07AG031779]; Mary Fisher CARE Fund at UAB FX This research was supported by the University of Alabama at Birmingham (UAB) Center for AIDS Research (CFAR), an National Institutes of Health funded program (P30 A1027767) that was made possible by the following institutes: National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Mental Health, National Institute on Aging, and the NIH Office of AIDS Research. JSM is supported by 1K12HS02169401 (Agency for Healthcare Research and Quality). CSR is supported by 7K07AG031779 (National Institute on Aging). Funding was also provided by the Mary Fisher CARE Fund at UAB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 3 Z9 3 U1 0 U2 3 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 3 PY 2014 VL 9 IS 11 AR e111765 DI 10.1371/journal.pone.0111765 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU4DB UT WOS:000345558100116 PM 25365306 ER PT J AU Blackburn, J Liu, S Dobrinski, K Martinez, S Moore, F Lobbardi, R Langenau, D AF Blackburn, Jessica Liu, Sali Dobrinski, Kimberly Martinez, Sarah Moore, Finola Lobbardi, Riadh Langenau, David TI Clonal evolution enhances leukemia propagating cell activity in T-cell acutelymphoblastic leukemia through AKT/mTORC1 pathway activation SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Blackburn, Jessica; Liu, Sali; Dobrinski, Kimberly; Martinez, Sarah; Moore, Finola; Lobbardi, Riadh; Langenau, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA PR06 DI 10.1158/1557-3125.MODORG-PR06 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600089 ER PT J AU Blackburn, J Liu, S Dobrinski, K Martinez, S Moore, F Lobbardi, R Langenau, D AF Blackburn, Jessica Liu, Sali Dobrinski, Kimberly Martinez, Sarah Moore, Finola Lobbardi, Riadh Langenau, David TI Clonal evolution enhances leukemia propagating cell activity in T-cell acutelymphoblastic leukemia through AKT/mTORC1 pathway activation SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Blackburn, Jessica; Liu, Sali; Dobrinski, Kimberly; Martinez, Sarah; Moore, Finola; Lobbardi, Riadh; Langenau, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA A08 AR A08 DI 10.1158/1557-3125.MODORG-A08 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600008 ER PT J AU Chorzalska, A Xiong, XL Lunardi, A White, JR Sawicki, JA Bratslavsky, G Pandolfi, PP Kotula, L AF Chorzalska, Anna Xiong, Xiaoling Lunardi, Andrea White, Julie R. Sawicki, Janet A. Bratslavsky, Gennady Pandolfi, Pier Paolo Kotula, Leszek TI Abi1 levels regulate prostate tumor progression in mice downstream from Pten inactivation SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Chorzalska, Anna; Xiong, Xiaoling] New York Blood Ctr, New York, NY 10021 USA. [Lunardi, Andrea; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [White, Julie R.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sawicki, Janet A.] Lankenau Inst Med Res, Wynnewood, PA USA. [Bratslavsky, Gennady; Kotula, Leszek] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA B06 DI 10.1158/1557-3125.MODORG-B06 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600040 ER PT J AU Gutierrez, A Pan, L Groen, R Baleydier, F Kentsis, A Marineau, J Grebliunaite, R Kozakewich, E Reed, C Pflumio, F Poglio, S Uzan, B Clemons, P Verplank, L An, F Burbank, J Norton, S Tolliday, N Steen, H Weng, AP Yuan, HP Bradner, JE Mitsiades, C Look, AT Aster, JC AF Gutierrez, Alejandro Pan, Li Groen, Richard Baleydier, Frederic Kentsis, Alex Marineau, Jason Grebliunaite, Ruta Kozakewich, Elena Reed, Casie Pflumio, Francoise Poglio, Sandrine Uzan, Benjamin Clemons, Paul Verplank, Lynn An, Frank Burbank, Jason Norton, Stephanie Tolliday, Nicola Steen, Hanno Weng, Andrew P. Yuan, Huipin Bradner, James E. Mitsiades, Constantine Look, A. Thomas Aster, Jon C. TI A new class of drugs active in T-ALL is revealed in a zebrafish screen SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Gutierrez, Alejandro; Groen, Richard; Kentsis, Alex; Marineau, Jason; Grebliunaite, Ruta; Kozakewich, Elena; Reed, Casie; Bradner, James E.; Mitsiades, Constantine; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pan, Li; Baleydier, Frederic; Aster, Jon C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Pflumio, Francoise; Poglio, Sandrine; Uzan, Benjamin] INSERM, Fontenay Aux Roses, France. [Pflumio, Francoise; Poglio, Sandrine; Uzan, Benjamin] Univ Paris Sud, Fontenay Aux Roses, France. [Clemons, Paul; Verplank, Lynn; An, Frank; Burbank, Jason; Norton, Stephanie; Tolliday, Nicola] Broad Inst, Cambridge, MA USA. [Gutierrez, Alejandro; Kentsis, Alex; Steen, Hanno; Look, A. Thomas] Boston Childrens Hosp, Boston, MA USA. [Weng, Andrew P.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Yuan, Huipin] Univ Twente, NL-7500 AE Enschede, Netherlands. [Groen, Richard] Univ Utrecht, Utrecht, Netherlands. [Baleydier, Frederic] Hosp Civils Lyon, Lyon, France. [Pflumio, Francoise; Poglio, Sandrine; Uzan, Benjamin] Univ Paris Diderot, Paris, France. RI Pflumio, Francoise/E-2074-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA IA8 DI 10.1158/1557-3125.MODORG-IA8 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600075 ER PT J AU Hahn, WC AF Hahn, William C. TI Functional genomics and cancer vulnerabilities SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA IA14 DI 10.1158/1557-3125.MODORG-IA14 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600080 ER PT J AU Kaufman, CK Mosimann, C White, R Matos, D Zon, LI AF Kaufman, Charles K. Mosimann, Christian White, Richard Matos, Dominic Zon, Leonard I. TI From melanocyte to melanoma: Identifying key molecular events at the onset of cancer SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Kaufman, Charles K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mosimann, Christian] Univ Zurich, Zurich, Switzerland. [White, Richard] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Matos, Dominic; Zon, Leonard I.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA PR10 DI 10.1158/1557-3125.MODORG-PR10 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600093 ER PT J AU Li, CG Lee, PS Sun, Y Gu, XX Zhang, E Wu, CL Parkhitko, A Aurrichio, N Morrison, T Blenis, J Xu, KF Henske, EP Levy, B Kwiatkowski, D Yu, J AF Li, Chenggang Lee, Po-Shun Sun, Yang Gu, Xiaoxiao Zhang, Erik Wu, Chin-Lee Parkhitko, Andrey Aurrichio, Neil Morrison, Tasha Blenis, John Xu, Kai-Feng Henske, Elizabeth Petri Levy, Bruce Kwiatkowski, David Yu, Jane TI Aspirin inhibits cyclooxygenase 2-mediated prostaglandin production and tumorigenesisin a preclinical model of tuberous sclerosis complex SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Li, Chenggang; Sun, Yang; Zhang, Erik; Parkhitko, Andrey; Aurrichio, Neil; Morrison, Tasha; Henske, Elizabeth Petri; Levy, Bruce; Kwiatkowski, David; Yu, Jane] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Po-Shun] Vertex Pharmaceut, Boston, MA USA. [Gu, Xiaoxiao; Blenis, John] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Chin-Lee] Mass Gen Hosp, Boston, MA USA. [Xu, Kai-Feng] Peking Union Med Coll, Beijing 100021, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA B09 DI 10.1158/1557-3125.MODORG-B09 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600042 ER PT J AU Lobbardi, R Abdelfattah, N Martinez, B Pinder, J Toiber, D Blackburn, JS De Waard, M Dellaire, G Mostoslavsky, R Langenau, DM AF Lobbardi, Riadh Abdelfattah, Nouran Martinez, Barbara Pinder, Jordan Toiber, Deborah Blackburn, Jessica S. De Waard, Manon Dellaire, Graham Mostoslavsky, Raul Langenau, David M. TI A large-scale transgenic screen in zebrafish identifies TOX as a novel oncogene in T-cell acute lymphoblastic leukemia SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Lobbardi, Riadh; Abdelfattah, Nouran; Blackburn, Jessica S.; Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA USA. [Martinez, Barbara; Toiber, Deborah; Mostoslavsky, Raul] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Pinder, Jordan; Dellaire, Graham] Dalhousie Univ, Dept Pathol, Halifax, NS, Canada. [Pinder, Jordan; Dellaire, Graham] Dept Biochem & Mol Biol, Halifax, NS, Canada. [De Waard, Manon] Leiden Univ, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA B12 DI 10.1158/1557-3125.MODORG-B12 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600043 ER PT J AU Roderick, JE Tesell, J Gutierrez, A Look, T Qi, J Bradner, JE Kelliher, MA AF Roderick, Justine E. Tesell, Jessica Gutierrez, Alejandro Look, Thomas Qi, Jun Bradner, James E. Kelliher, Michelle A. TI Targeting NOTCH1 and C-MYC in humanized models of relapsed and induction failure pediatric T-ALL SO MOLECULAR CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translational Impact of Model Organisms in Cancer CY NOV 05-08, 2013 CL San Diego, CA SP Amer Assoc Canc Res C1 [Roderick, Justine E.; Tesell, Jessica; Kelliher, Michelle A.] UMass Med Sch, Worcester, MA USA. [Gutierrez, Alejandro] Bostons Childrens Hosp, Boston, MA USA. [Look, Thomas; Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD NOV PY 2014 VL 12 SU 11 MA PR02 DI 10.1158/1557-3125.MODORG-PR02 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CQ9IW UT WOS:000360928600087 ER PT J AU Drendall, CI Barry, W Ramos, C Tolbert, N Geradts, J Petricoin, E Seewaldt, V AF Drendall, Catherine Ibarra Barry, William Ramos, Corinne Tolbert, Nora Geradts, Joseph Petricoin, Emanuel Seewaldt, Victoria TI Feasibility study: Protein profiling of primary breast cancers from premenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract C1 [Drendall, Catherine Ibarra; Tolbert, Nora; Geradts, Joseph; Seewaldt, Victoria] Duke Univ, Med Ctr, Durham, NC USA. [Barry, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramos, Corinne] Theranost Hlth Inc, Rockville, MD USA. [Petricoin, Emanuel] George Mason Univ, Manassas, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 23 IS 11 SU S MA C16 DI 10.1158/1538-7755.DISP13-C16 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CP4JA UT WOS:000359846600151 ER PT J AU Oluloro, A Oluloro, A Winkfield, KM Svoboda, L Waldman, LT Lathan, CS AF Oluloro, Ann Oluloro, Ann Winkfield, Karen M. Svoboda, Ludmila Waldman, Laura Tesler Lathan, Christopher S. TI Addressing cancer disparities through use of a novel community-based oncology program SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract C1 [Oluloro, Ann; Winkfield, Karen M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Oluloro, Ann; Svoboda, Ludmila; Waldman, Laura Tesler; Lathan, Christopher S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 23 IS 11 SU S MA A27 DI 10.1158/1538-7755.DISP13-A27 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CP4JA UT WOS:000359846600022 ER PT J AU Ahmad, I Ouyang, XS Wani, WY Zhang, JH AF Ahmad, Israr Ouyang, Xiaosen Wani, Willayat Y. Zhang, Jianhua TI NRBF-2 Regulates Autophagic Flux and Plays an Important Role in Neuronal Survival SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 [Ahmad, Israr; Ouyang, Xiaosen; Wani, Willayat Y.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Ctr Free Radical Biol & Med, Birmingham, AL 35294 USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Birmingham, AL USA. 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 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 2014 VL 76 SU 1 MA 18 BP S21 EP S21 DI 10.1016/j.freeradbiomed.2014.10.466 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CO9WA UT WOS:000359525800038 ER PT J AU Dohi, K Kovac, A Erickson, M Kraemer, BC Ogawa, T Banks, WA AF Dohi, Kenji Kovac, Andrej Erickson, Michelle Kraemer, Brian C. Ogawa, Takeki Banks, William A. TI Hydrogen in Drinking Water Reduces Brain Edema after Traumatic Brain Injury in Mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 [Dohi, Kenji; Ogawa, Takeki] Jikei Univ, Tokyo, Japan. [Dohi, Kenji; Kovac, Andrej; Erickson, Michelle; Kraemer, Brian C.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Kraemer, Brian C.; Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. 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 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 2014 VL 76 SU 1 MA 23 BP S22 EP S22 DI 10.1016/j.freeradbiomed.2014.10.471 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CO9WA UT WOS:000359525800043 ER PT J AU Janes, J Liu, C Straub, A Kim-Shapiro, DB AF Janes, John Liu, Chen Straub, Adam Kim-Shapiro, Daniel B. TI Computational Modeling of NO Bioavailability in the Myoendothelial Junction SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 [Janes, John; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Liu, Chen] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. [Straub, Adam] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15260 USA. [Straub, Adam] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15260 USA. 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 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 2014 VL 76 SU 1 MA 8 BP S16 EP S16 DI 10.1016/j.freeradbiomed.2014.10.494 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CO9WA UT WOS:000359525800028 ER PT J AU Boardman, CR Sonnenberg, A AF Boardman, Charles R. Sonnenberg, Amnon TI Magical Thinking SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Editorial Material ID RECTAL-CANCER; APPROPRIATENESS; ENDOSCOPY; COLON; RISK C1 [Boardman, Charles R.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 11 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 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD NOV PY 2014 VL 5 AR e63 DI 10.1038/ctg.2014.15 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CJ5MI UT WOS:000355531300002 PM 25393587 ER PT J AU Villar, J Kacmarek, RM AF Villar, J. Kacmarek, R. M. TI It does not matter whether you are an elephant or a shrew: all mammals' tidal volumes are similarly scaled! SO MINERVA ANESTESIOLOGICA LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; INDUCED LUNG INJURY; VENTILATION; MORTALITY C1 [Villar, J.] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, J.] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria 35010, Spain. [Kacmarek, R. M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, R. M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA. RP Villar, J (reprint author), Hosp Univ Dr Negrin, Barranco de la Ballena S-N 4th Floor,South Wing, Las Palmas Gran Canaria 35010, Spain. EM jesus.villar54@gmail.com NR 14 TC 2 Z9 2 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 EI 1827-1596 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD NOV PY 2014 VL 80 IS 11 BP 1149 EP 1151 PG 3 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA CJ3FN UT WOS:000355368900001 PM 24714700 ER PT J AU Barouch, D AF Barouch, Dan TI Antibody-Based Vaccines and Therapeutics for HIV-1 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 16th Annual International Meeting of the Institute-of-Human-Virology (IHV) CY SEP 14-14, 2014 CL Univ Maryland Sch Med, Baltimore, MD SP Inst Human Virol HO Univ Maryland Sch Med C1 [Barouch, Dan] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 2014 VL 67 SU 3 MA B-107 BP 46 EP 46 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CH6BF UT WOS:000354119800021 ER PT J AU Frank, D AF Frank, David TI Strategies for Targeting Cancer Pathways: Oncogenic Transcription Factors as Convergence Points for Molecular Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract CT 16th Annual International Meeting of the Institute-of-Human-Virology (IHV) CY SEP 14-14, 2014 CL Univ Maryland Sch Med, Baltimore, MD SP Inst Human Virol HO Univ Maryland Sch Med C1 [Frank, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 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 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV PY 2014 VL 67 SU 3 MA C-108 BP 53 EP 53 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CH6BF UT WOS:000354119800032 ER PT J AU Hasegawa, K Sullivan, AF Hirashima, ET Gaeta, TJ Fee, C Turner, SJ Massaro, S Camargo, CA AF Hasegawa, Kohei Sullivan, Ashley F. Hirashima, Eva Tovar Gaeta, Theodore J. Fee, Christopher Turner, Stuart J. Massaro, Susan Camargo, Carlos A., Jr. CA Multictr Airway Res Collaboration TI A Multicenter Observational Study of US Adults with Acute Asthma: Who Are the Frequent Users of the Emergency Department? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Acute asthma; Emergency department; Epidemiology exacerbation; Health care utilization; Racial disparity; Socioeconomic status ID UNITED-STATES; DISPARITIES; POPULATION; PREDICTORS; VISITS; CARE AB BACKGROUND: Despite the substantial burden of asthma-related emergency department (ED) visits, there have been no recent multicenter efforts to characterize this high-risk population. OBJECTIVE: We aimed to characterize patients with asthma according to their frequency of ED visits and to identify factors associated with frequent ED visits. METHODS: A multicenter chart review study of 48 EDs across 23 US states. We identified ED patients ages 18 to 54 years with acute asthma during 2011 and 2012. Primary outcome was frequency of ED visits for acute asthma in the past year, excluding the index ED visit. RESULTS: Of the 1890 enrolled patients, 863 patients (46%) had 1 or more (frequent) ED visits in the past year. Specifically, 28% had 1 to 2 visits, 11% had 3 to 5 visits, and 7% had 6 or more visits. Among frequent ED users, guideline-recommended management was suboptimal. For example, of patients with 6 or more ED visits, 85% lacked evidence of prior evaluation by an asthma specialist, and 43% were not treated with inhaled corticosteroids. In a multivariable model, significant predictors of frequent ED visits were public insurance, no insurance, and markers for chronic asthma severity (all P < .05). Stronger associations were found among those with a higher frequency of asthma-related ED visits (eg, 6 or more ED visits). CONCLUSION: This multicenter study of US adults with acute asthma demonstrated many frequent ED users and suboptimal preventive management in this high-risk population. Future reductions in asthma morbidity and associated health care utilization will require continued efforts to bridge these major gaps in asthma care. (C) 2014 American Academy of Allergy, Asthma & Immunology C1 [Hasegawa, Kohei; Sullivan, Ashley F.; Hirashima, Eva Tovar; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Gaeta, Theodore J.] New York Methodist Hosp, Dept Emergency Med, Brooklyn, NY USA. [Fee, Christopher] Univ Calif San Francisco, Med Ctr, Dept Emergency Med, San Francisco, CA USA. [Turner, Stuart J.; Massaro, Susan] Novartis Pharmaceut, E Hanover, NJ USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM khasegawa1@partners.org RI Shapiro, Nathan/F-1718-2016; OI Pallin, Daniel/0000-0002-8517-9702 FU Novartis Pharmaceuticals Corporation FX Funded by a grant from Novartis Pharmaceuticals Corporation to Massachusetts General Hospital (PI, C. A. Camargo). The sponsor had no role in the conduct of the study, nor collection, management, or analysis of the data. NR 24 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD NOV-DEC PY 2014 VL 2 IS 6 BP 733 EP + DI 10.1016/j.jaip.2014.06.012 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA CH7HW UT WOS:000354207600015 PM 25439365 ER PT J AU Iammatteo, M Blumenthal, KG Saff, R Long, AA Banerji, A AF Iammatteo, Melissa Blumenthal, Kimberly G. Saff, Rebecca Long, Aidan A. Banerji, Aleena TI Safety and Outcomes of Test Doses for the Evaluation of Adverse Drug Reactions: A 5-Year Retrospective Review SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Test dose; Graded challenge; Drug provocation test; Adverse drug reaction; Hypersensitivity reaction; Drug allergy ID PROVOCATION TESTS; HYPERSENSITIVITY REACTIONS; ALLERGIC REACTIONS; ORAL CHALLENGE; BETA-LACTAMS; DIAGNOSIS; MANAGEMENT; ANTIBIOTICS; PENICILLIN; UPDATE AB BACKGROUND: Graded challenges are the criterion standard for evaluating adverse drug reactions (ADR). Evidence-based guidelines regarding the optimal number of steps for challenges are lacking. OBJECTIVE: To determine the safety and outcomes of 1- or 2-step test doses among patients with ADRs seen by the allergy/immunology consult service and to compare the outcomes of 1- or 2-step test doses with multistep challenges performed during the same time period. METHODS: We conducted a retrospective chart review of all 1- or 2-step test doses and multistep challenges at a single academic center between 2008 and 2013. Patient demographics, symptoms of initial ADRs, and outcomes of test doses and multistep challenges were reviewed. ADRs were classified by type and were graded by severity. Outcomes of 1- or 2-step test doses were compared with multistep challenges. RESULTS: We identified 456 patients who underwent 497 one- or 2-step test doses (mean age, 51 years; 67.5% female patients). The most common drugs that prompted test doses were beta-lactams (62%). The majority of patients (n = 444 [89%]) did not experience any ADRs during test doses. ADRs that occurred during test doses (n = 53 [11%]) were most commonly non-immune-mediated (45%) or IgE-mediated (32%), with grade 1 or 2 severity (100%). Forty-nine percent of ADRs during test doses did not receive any treatment. The ADR rate during multistep challenges (10/82 [12%]) was similar to test doses. CONCLUSION: One-or 2-step test doses were safe for evaluation of ADRs. Multistep challenges did not confer added safety. Furthermore, 1- or 2-step test doses did not raise concern for induction of tolerance. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology C1 [Iammatteo, Melissa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Blumenthal, Kimberly G.; Saff, Rebecca; Long, Aidan A.; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Iammatteo, M (reprint author), Massachusetts Gen Hosp, Dept Med, Gray Bigelow 740,55 Fruit St, Boston, MA 02114 USA. EM miammatteo@partners.org NR 26 TC 10 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD NOV-DEC PY 2014 VL 2 IS 6 BP 768 EP 774 DI 10.1016/j.jaip.2014.08.001 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA CH7HW UT WOS:000354207600019 PM 25439369 ER PT J AU Manchikanti, L Benyamin, RM Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin M. Falco, Frank J. E. Hirsch, Joshua A. TI Metamorphosis of Medicine in the United States: A Carrot and Stick Policy of Electronic Medical Records SO PAIN PHYSICIAN LA English DT Editorial Material ID HEALTH-CARE; ICD-10; READY C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 35 TC 14 Z9 14 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD NOV-DEC PY 2014 VL 17 IS 6 BP E671 EP E680 PG 10 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CF8DE UT WOS:000352785000002 PM 25415782 ER PT J AU Manchikanti, L Benyamin, RM Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin M. Falco, Frank J. E. Hirsch, Joshua A. TI Metamorphosis of Medicine in the United States: Is Information Technology a White Knight or Killer Whale? SO PAIN PHYSICIAN LA English DT Editorial Material ID HEALTH-CARE; ICD-10; READY C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Urbana, IL 61801 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 39 TC 11 Z9 11 U1 0 U2 0 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD NOV-DEC PY 2014 VL 17 IS 6 BP E663 EP E670 PG 8 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CF8DE UT WOS:000352785000001 PM 25415781 ER PT J AU Manchikanti, L Falco, FJE Pampati, V Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Pampati, Vidyasagar Hirsch, Joshua A. TI Lumbar Interlaminar Epidural Injections Are Superior to Caudal Epidural Injections in Managing Lumbar Central Spinal Stenosis SO PAIN PHYSICIAN LA English DT Article DE Caudal epidural; lumbar interlaminar; transforaminal epidural; steroids; local anesthetic; central spinal stenosis; radiculitis ID OUTCOMES-RESEARCH-TRIAL; INTERVENTIONAL PAIN MANAGEMENT; ESTIMATE REIMBURSEMENT AMOUNTS; 2-YEAR FOLLOW-UP; CHRONIC LOW-BACK; STEROID INJECTIONS; DEGENERATIVE-SPONDYLOLISTHESIS; MEDICARE-POPULATION; DISC-HERNIATION; DOUBLE-BLIND AB Background: Epidural injections are performed to manage lumbar central spinal stenosis pain utilizing caudal, interlaminar, and transforaminal approaches. The literature on the efficacy of epidural injections in managing lumbar central spinal stenosis pain is sparse; lacking multiple, high quality randomized trials with long-term follow-up. Methods: Two randomized controlled trials of the caudal and lumbar interlaminar approaches that assessed 220 patients with lumbar central spinal stenosis were analyzed. Results: The analysis found efficacy for both caudal and interlaminar approaches in managing chronic pain and disability from central spinal stenosis was demonstrated. In the patients responsive to treatment, those with at least 3 weeks of improvement with the first 2 procedures, 51% reported significant improvement with caudal epidural injections, whereas it was 84% with local anesthetic only with interlaminar epidurals, 57% with caudal and 83% with lumbar interlaminar with local anesthetic with steroid. The response rate was 38% with caudal and 72% with lumbar interlaminar with local anesthetic only and 44% with caudal and 73% with lumbar interlaminar with local anesthetic with steroid when all patients were considered. In the interlaminar approach, results were superior for pain relief and functional status with fewer nonresponsive patients compared to the caudal approach. Limitations: The data was derived from 2 previously published randomized, controlled trials rather than comparing 2 techniques in one randomized controlled trial. Further, the randomized controlled trials were active control trials without a placebo. Conclusions: The results of this assessment showed significant improvement in patients suffering with chronic lumbar spinal stenosis with caudal and interlaminar epidural approaches with local anesthetic only, or with steroids in a long-term follow-up of up to 2 years, in contemporary interventional pain management setting, with the interlaminar approach providing significantly better results. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Falco, Frank J. E.] Temple Univ, Sch Med, Dept PM&R, Philadelphia, PA 19122 USA. [Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Minimally Invas Spine Surg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Serv & Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 74 TC 9 Z9 10 U1 3 U2 3 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD NOV-DEC PY 2014 VL 17 IS 6 BP E691 EP E702 PG 12 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA CF8DE UT WOS:000352785000004 PM 25415784 ER PT J AU Armstrong, TS Vera-Bolanos, E Gilbert, M Yuan, Y Wani, K Wu, JM Omuro, A Lieberman, F Robins, HI Gerstner, E Wu, J Wen, P Mikkelsen, T Aldape, K Mendoza, T AF Armstrong, Terri S. Vera-Bolanos, Elizabeth Gilbert, Mark Yuan, Ying Wani, Khalida Wu, Jimin Omuro, Antonio Lieberman, Frank Robins, H. Ian Gerstner, Elizabeth Wu, Jing Wen, Patrick Mikkelsen, Tom Aldape, Ken Mendoza, Tito CA CERN Fdn TI A PHASE II STUDY OF LAPATINIB AND DOSE-DENSE TEMOZOLOMIDE (TMZ) FOR ADULTS WITH RECURRENT EPENDYMOMA: PATIENT REPORTED OUTCOMES(PRO) FROM A CERN CLINICAL TRIAL SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Houston, Sch Nursing, Houston, TX 77030 USA. [Vera-Bolanos, Elizabeth; Gilbert, Mark; Yuan, Ying; Wani, Khalida; Wu, Jimin; Aldape, Ken; Mendoza, Tito] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Omuro, Antonio] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA. [Robins, H. Ian] Univ Wisconsin, Madison, WI USA. [Gerstner, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wen, Patrick] Dana Farber Canc Ctr, Boston, MA USA. [Wu, Jing] Univ N Carolina, Chapel Hill, NC USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [CERN Fdn] CERN Fdn, Dayton, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-07 DI 10.1093/neuonc/nou237.7 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200037 ER PT J AU Arvold, N Cefalu, M Wang, Y Zigler, C Schrag, D Dominici, F AF Arvold, Nils Cefalu, Matthew Wang, Yun Zigler, Cory Schrag, Deborah Dominici, Francesca TI RADIOTHERAPY WITH VS WITHOUT TEMOZOLOMIDE IN OLDER PATIENTS WITH GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Arvold, Nils; Schrag, Deborah] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cefalu, Matthew; Wang, Yun; Zigler, Cory; Dominici, Francesca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-08 DI 10.1093/neuonc/nou237.8 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200038 ER PT J AU Bandopadhayay, P Chi, S Janeway, K Pinches, N Malkin, H Manley, P Goumnerova, L Chang, M Kieran, M Harris, M Ramkissoon, S Ligon, K AF Bandopadhayay, Pratiti Chi, Susan Janeway, Katherine Pinches, Nathan Malkin, Hayley Manley, Peter Goumnerova, Liliana Chang, Michael Kieran, Mark Harris, Marian Ramkissoon, Shakti Ligon, Keith TI CLINICAL TARGETED EXOME-BASED SEQUENCING FOR CHILDREN DIAGNOSED WITH BRAIN TUMORS: INITIAL RESULTS OF AN INSTITUTE-WIDE PROJECT ON PERSONALIZED MEDICINE SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Bandopadhayay, Pratiti; Chi, Susan; Janeway, Katherine; Pinches, Nathan; Malkin, Hayley; Manley, Peter; Chang, Michael; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ligon, Keith] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goumnerova, Liliana; Harris, Marian] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA GE-02 DI 10.1093/neuonc/nou256.2 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200388 ER PT J AU Boockvar, J Bodhinayake, I Brooks, C Chen, J Schwartz, J Rowinsky, E Reardon, D AF Boockvar, John Bodhinayake, Imithri Brooks, Chris Chen, Janice Schwartz, Jonathan Rowinsky, Eric Reardon, David TI INITIATION OF CLINICAL STUDIES WITH SL-701, A SYNTHETIC MULTI-PEPTIDE VACCINE WITH ENHANCED IMMUNOSTIMULATORY PROPERTIES TARGETING MULTIPLE GLIOMA-ASSOCIATED ANTIGENS, IN ADULTS WITH FIRST RECURRENCE OF GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Boockvar, John; Bodhinayake, Imithri] Weill Cornell Med Coll, New York, NY USA. [Brooks, Chris; Chen, Janice; Schwartz, Jonathan; Rowinsky, Eric] Stemline Therapeut Inc, New York, NY USA. [Reardon, David] Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA IT-02 DI 10.1093/neuonc/nou258.2 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200442 ER PT J AU Brastianos, P Taylor-Weiner, A Manley, P Jones, R Dias-Santagata, D Thorner, A Rodriguez, F Bernardo, L Schubert, L Stewart, C Kieran, M Louis, D Getz, G Santagata, S AF Brastianos, Priscilla Taylor-Weiner, Amaro Manley, Peter Jones, Robert Dias-Santagata, Dora Thorner, Aaron Rodriguez, Fausto Bernardo, Lindsay Schubert, Laura Stewart, Chip Kieran, Mark Louis, David Getz, Gad Santagata, Sandro TI EXOME SEQUENCING REVEALS BRAF MUTATIONS IN PAPILLARY CRANIOPHARYNGIOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Brastianos, Priscilla; Taylor-Weiner, Amaro; Stewart, Chip; Getz, Gad] Broad Inst Harvard & MIT, Cambridge, MA USA. [Brastianos, Priscilla; Dias-Santagata, Dora; Bernardo, Lindsay; Louis, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Manley, Peter; Thorner, Aaron; Schubert, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thorner, Aaron; Schubert, Laura] Ctr Canc Genome Discovery, Boston, MA USA. [Rodriguez, Fausto] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Manley, Peter; Louis, David; Santagata, Sandro] Harvard Univ, Sch Med, Boston, MA USA. [Jones, Robert; Santagata, Sandro] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kieran, Mark] Boston Childrens Hosp, Boston, MA USA. Childrens Hosp Pennsylvania, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA GE-05 DI 10.1093/neuonc/nou256.5 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200391 ER PT J AU Brastianos, P Carter, S Santagata, S Taylor-Weiner, A Jones, R Van Allen, E Horowitz, P Ligon, K Cahill, D Dunn, I Van Hummelen, P Lin, N Curry, W Stemmer-Rachamimov, A Beroukhim, R Batchelor, T Baselga, J Louis, D Getz, G Hahn, W AF Brastianos, Priscilla Carter, Scott Santagata, Sandro Taylor-Weiner, Amaro Jones, Robert Van Allen, Eli Horowitz, Peleg Ligon, Keith Cahill, Daniel Dunn, Ian Van Hummelen, Paul Lin, Nancy Curry, William Stemmer-Rachamimov, Anat Beroukhim, Rameen Batchelor, Tracy Baselga, Jose Louis, David Getz, Gad Hahn, William TI GENOMIC CHARACTERIZATION OF BRAIN METASTASES REVEALS BRANCHED EVOLUTION AND METASTASIS-SPECIFIC MUTATIONS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Brastianos, Priscilla; Santagata, Sandro; Jones, Robert; Van Allen, Eli; Horowitz, Peleg; Ligon, Keith; Cahill, Daniel; Dunn, Ian; Lin, Nancy; Curry, William; Stemmer-Rachamimov, Anat; Beroukhim, Rameen; Batchelor, Tracy; Louis, David; Hahn, William] Harvard Univ, Sch Med, Boston, MA USA. [Brastianos, Priscilla; Cahill, Daniel; Curry, William; Stemmer-Rachamimov, Anat; Batchelor, Tracy; Louis, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Van Allen, Eli; Van Hummelen, Paul; Lin, Nancy; Beroukhim, Rameen; Hahn, William] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carter, Scott; Taylor-Weiner, Amaro; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA USA. [Santagata, Sandro; Jones, Robert; Horowitz, Peleg; Ligon, Keith; Dunn, Ian] Brigham & Womens Hosp, Boston, MA 02115 USA. [Van Hummelen, Paul] Ctr Canc Genome Discovery, Boston, MA USA. Vall DHebron Univ Hosp, Barcelona, Spain. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA BM-07 DI 10.1093/neuonc/nou240.7 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200129 ER PT J AU Brenner, A Cohen, Y Vredenburgh, J Peters, K Blumenthal, D Bokstein, F Breitbart, E Bangio, L Sher, N Harats, D Wen, P AF Brenner, Andrew Cohen, Yael Vredenburgh, James Peters, Katherine Blumenthal, Deborah Bokstein, Felix Breitbart, Eyal Bangio, Livnat Sher, Naamit Harats, Dror Wen, Patrick TI PHASE 1-2 DOSE-ESCALATION STUDY OF VB-111, AN ANTI-ANGIOGENIC GENE THERAPY, AS MONOTHERAPY AND IN COMBINATION WITH BEVACIZUMAB, IN PATIENTS WITH RECURRENT GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Brenner, Andrew] UTHSCSA, Canc Therapy & Res Ctr, San Antonio, TX USA. [Cohen, Yael; Bokstein, Felix; Breitbart, Eyal; Bangio, Livnat; Sher, Naamit; Harats, Dror] VBL Therapeut, Or Yehuda, Israel. [Vredenburgh, James] St Francis Hosp & Med Ctr, Hartford, CT USA. [Peters, Katherine] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA. [Blumenthal, Deborah; Wen, Patrick] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA NT-07 DI 10.1093/neuonc/nou265.7 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200637 ER PT J AU Calligaris, D Loginov, D Machaidze, R Alberta, JA Stiles, CD Love, JC Agar, NYR AF Calligaris, David Loginov, Denis Machaidze, Revaz Alberta, John A. Stiles, Charles D. Love, J. Christopher Agar, Nathalie Y. R. TI A MASS SPECTROMETRY IMAGING PLATFORM TO STUDY DRUG-SUSCEPTIBILITY OF BRAIN TUMORS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Calligaris, David; Machaidze, Revaz; Agar, Nathalie Y. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Loginov, Denis; Love, J. Christopher] MIT, Cambridge, MA 02139 USA. [Alberta, John A.; Stiles, Charles D.; Agar, Nathalie Y. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA NI-10 DI 10.1093/neuonc/nou264.10 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200560 ER PT J AU Chandra, V Ou, YM Evans, J Kalpathy-Cramer, J Dietrich, J Chi, A Wen, P Rosen, B Batchelor, T Gerstner, E AF Chandra, Vyshak Ou, Yangming Evans, John Kalpathy-Cramer, Jayashree Dietrich, Jorg Chi, Andrew Wen, Patrick Rosen, Bruce Batchelor, Tracy Gerstner, Elizabeth TI PHASE II STUDY OF TIVOZANIB, AN ORAL VEGFR INHIBITOR, IN PATIENTS WITHRECURRENT GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Dietrich, Jorg; Chi, Andrew; Batchelor, Tracy; Gerstner, Elizabeth] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Chandra, Vyshak; Ou, Yangming; Evans, John; Kalpathy-Cramer, Jayashree; Rosen, Bruce; Gerstner, Elizabeth] MGH HST Martinos Ctr Biomed Imaging, Boston, MA USA. [Wen, Patrick] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-16 DI 10.1093/neuonc/nou237.16 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200046 ER PT J AU Chen, C Kozono, D Li, J Nitta, M Sampetrean, O Gonda, D Kushwaha, D Vandenberg, S Ramakrishnan, V Zhu, S Furnari, F Matsui, H Harismendy, O Cavenee, W Mao, Y Becher, O Kwon, CH Ligon, K Saya, H Carter, B AF Chen, Clark Kozono, David Li, Jie Nitta, Masayuki Sampetrean, Oltea Gonda, David Kushwaha, Deepa Vandenberg, Scott Ramakrishnan, Valya Zhu, Shan Furnari, Frank Matsui, Hiroko Harismendy, Olivier Cavenee, Webster Mao, Ying Becher, Oren Kwon, Chang-Hyuk Ligon, Keith Saya, Hideyuki Carter, Bob TI EPIGENETIC REGULATION OF GLIOBLASTOMA TUMORIGENICITY: A HYBRID MODEL SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Kozono, David; Ligon, Keith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sampetrean, Oltea; Saya, Hideyuki] Keio Univ, Tokyo, Japan. [Mao, Ying] Huashan Hosp, Shanghai, Peoples R China. [Nitta, Masayuki; Furnari, Frank; Cavenee, Webster] Ludwig Inst Canc Res, La Jolla, CA USA. [Chen, Clark; Li, Jie; Gonda, David; Kushwaha, Deepa; Vandenberg, Scott; Ramakrishnan, Valya; Zhu, Shan; Matsui, Hiroko; Harismendy, Olivier; Carter, Bob] Univ Calif San Diego, La Jolla, CA 92093 USA. [Becher, Oren] Duke Univ, Durham, NC USA. [Kwon, Chang-Hyuk] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA CB-04 DI 10.1093/neuonc/nou241.4 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200164 ER PT J AU Emblem, K Pinho, M Chandra, V Gerstner, E Stufflebeam, S Sorenson, G Harris, G Freedman, R Sohl, J Younger, J Krop, I Winer, E Lin, N AF Emblem, Kyrre Pinho, Marco Chandra, Vyshak Gerstner, Elizabeth Stufflebeam, Steve Sorenson, Greg Harris, Gordon Freedman, Rachel Sohl, Jessica Younger, Jerry Krop, Ian Winer, Eric Lin, Nancy TI BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Freedman, Rachel; Sohl, Jessica; Krop, Ian; Winer, Eric; Lin, Nancy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerstner, Elizabeth; Harris, Gordon; Younger, Jerry] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Emblem, Kyrre; Pinho, Marco; Chandra, Vyshak; Gerstner, Elizabeth; Stufflebeam, Steve] MGH HST Martinos Ctr Biomed Imaging, Boston, MA USA. [Emblem, Kyrre] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. [Pinho, Marco] UT Southwestern Med Ctr, Dallas, TX USA. [Sorenson, Greg] Siemens Healthcare USA, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA NI-23 DI 10.1093/neuonc/nou264.22 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200567 ER PT J AU Esaki, S Rabkin, SD Martuza, RL Wakimoto, H AF Esaki, Shinichi Rabkin, Samuel D. Martuza, Robert L. Wakimoto, Hiroaki TI TRANSIENT FASTING ENHANCES REPLICATION AND THERAPEUTIC ACTIVITY OF ONCOLYTIC HSV IN GLIOBLASTOMA THERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Esaki, Shinichi; Rabkin, Samuel D.; Martuza, Robert L.; Wakimoto, Hiroaki] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Esaki, Shinichi; Rabkin, Samuel D.; Martuza, Robert L.; Wakimoto, Hiroaki] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA ET-17 DI 10.1093/neuonc/nou255.17 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200333 ER PT J AU Gan, HK Fichtel, L Lassman, AB Merrell, R van den Bent, M Kumthekar, P Scott, AM Pedersen, M Gomez, E Fischer, J Ames, W Xiong, H Dudley, M Munasinghe, W Roberts-Rapp, L Ansell, P Holen, K Reardon, DA AF Gan, Hui K. Fichtel, Lisa Lassman, Andrew B. Merrell, Ryan van den Bent, Martin Kumthekar, Priya Scott, Andrew M. Pedersen, Michelle Gomez, Erica Fischer, JuDee Ames, William Xiong, Hao Dudley, Matt Munasinghe, Wijith Roberts-Rapp, Lisa Ansell, Peter Holen, Kyle Reardon, David A. TI A PHASE 1 STUDY EVALUATING ABT-414 WITH TEMOZOLOMIDE (TMZ) OR CONCURRENT RADIOTHERAPY (RT) AND TMZ IN GLIOBLASTOMA (GBM) SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Gan, Hui K.; Scott, Andrew M.] Austin Hlth & Ludwig Inst Canc Res, Heidelberg, Vic, Australia. [Fichtel, Lisa] South Texas Oncol & Hematol, San Antonio, TX USA. [Lassman, Andrew B.] Columbia Univ, Med Ctr, New York, NY USA. [Lassman, Andrew B.] Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Merrell, Ryan] Northshore Univ Hlth Syst, Ctr Comprehens Canc, Evanston, IL USA. [van den Bent, Martin] Erasmus MC Canc Ctr, Rotterdam, Netherlands. [Kumthekar, Priya] Northwestern Univ, Chicago, IL 60611 USA. [Pedersen, Michelle; Gomez, Erica; Fischer, JuDee; Ames, William; Xiong, Hao; Dudley, Matt; Munasinghe, Wijith; Roberts-Rapp, Lisa; Ansell, Peter; Holen, Kyle] AbbVie Inc, N Chicago, IL USA. [Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA ET-19 DI 10.1093/neuonc/nou255.19 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200335 ER PT J AU Gilbert, M Yuan, Y Wani, K Wu, JM Omuro, A Lieberman, F Robins, HI Gerstner, E Wu, J Wen, P Mikkelsen, T Armstrong, T Aldape, K AF Gilbert, Mark Yuan, Ying Wani, Khalida Wu, Jimin Omuro, Antonio Lieberman, Frank Robins, H. Ian Gerstner, Elizabeth Wu, Jing Wen, Patrick Mikkelsen, Tom Armstrong, Terri Aldape, Ken TI A PHASE II STUDY OF LAPATINIB AND DOSE-DENSE TEMOZOLOMIDE (TMZ) FOR ADULTS WITH RECURRENT EPENDYMOMA: A CERN CLINICAL TRIAL SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Gilbert, Mark; Yuan, Ying; Wani, Khalida; Wu, Jimin; Armstrong, Terri; Aldape, Ken] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Omuro, Antonio] Memoral Sloan Kettering Canc Ctr, New York, NY USA. [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA. [Robins, H. Ian] Univ Wisconsin, Madison, WI USA. [Gerstner, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wen, Patrick] Dana Farber Canc Ctr, Boston, MA USA. [Wu, Jing] Univ N Carolina, Chapel Hill, NC USA. [Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA. [Armstrong, Terri] Univ Texas Hlth Sci Ctr Houston, Sch Nursing, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-23 DI 10.1093/neuonc/nou237.23 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200053 ER PT J AU Jonas, O Sengupta, S Calligaris, D Poe, M Methuku, K Francois, JP Cook, J Agar, N Pomeroy, S Langer, R AF Jonas, Oliver Sengupta, Soma Calligaris, David Poe, Michael Methuku, Kashi Francois, Jessica Pierre Cook, James Agar, Nathalie Pomeroy, Scott Langer, Robert TI A NOVEL TROJAN HORSE FOR IN-VIVO SENSITIVITY TESTING OF MEDULLOBLASTOMA THERAPIES SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Jonas, Oliver; Langer, Robert] MIT, Boston, MA USA. [Sengupta, Soma] BIDMC, Boston, MA USA. [Calligaris, David; Agar, Nathalie] Brigham & Womens Hosp, Boston, MA 02115 USA. [Poe, Michael; Methuku, Kashi; Cook, James] UW Milwaukee, Milwaukee, WI USA. [Sengupta, Soma; Francois, Jessica Pierre; Pomeroy, Scott] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA ET-24 DI 10.1093/neuonc/nou255.24 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200340 ER PT J AU Kim, H Zheng, S Amini, S Virk, S Mikkelsen, T Brat, D Sougnez, C Muller, F Hu, J Sloan, A Cohen, M Van Meir, E Scarpace, L Lander, E Gabriel, S Getz, G Meyerson, M Chin, L Barnholtz-Sloan, J Verhaak, R AF Kim, Hoon Zheng, Siyuan Amini, Seyed Virk, Selene Mikkelsen, Tom Brat, Daniel Sougnez, Carrie Muller, Florian Hu, Jian Sloan, Andrew Cohen, Mark Van Meir, Erwin Scarpace, Lisa Lander, Eric Gabriel, Stacey Getz, Gad Meyerson, Matthew Chin, Lynda Barnholtz-Sloan, Jill Verhaak, Roel TI ALTERATION OF THE p53 PATHWAY AND ANCESTRAL PROGENITORS ARE ASSOCIATED WITH TUMOR RECURRENCE IN GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Kim, Hoon; Zheng, Siyuan; Amini, Seyed; Verhaak, Roel] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Virk, Selene; Sloan, Andrew; Cohen, Mark; Barnholtz-Sloan, Jill] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA. [Mikkelsen, Tom; Scarpace, Lisa] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Mikkelsen, Tom; Scarpace, Lisa] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 USA. [Brat, Daniel] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Van Meir, Erwin] Emory Univ, Dept Neurosurg & Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. [Van Meir, Erwin] Emory Univ, Sch Med, Atlanta, GA USA. [Sougnez, Carrie; Lander, Eric; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA USA. [Muller, Florian; Hu, Jian; Chin, Lynda; Verhaak, Roel] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Sloan, Andrew] Univ Hosp Case Med Ctr, Case Western Reserve Sch Med, Brain Tumor & Neurooncol Ctr, Dept Neurosurg, Cleveland, OH USA. [Cohen, Mark] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH USA. Univ So Calif, Epigenome Ctr, Los Angeles, CA USA. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA GE-17 DI 10.1093/neuonc/nou256.17 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200402 ER PT J AU Kushwaha, D Ramakrishnan, V Ng, K Steed, T Nguyen, T Futalan, D Akers, J Tao, J Chowdhury, D Carter, B Chen, C AF Kushwaha, Deepa Ramakrishnan, Valya Ng, Kimberly Steed, Tyler Thien Nguyen Futalan, Diahnn Akers, Johnny Tao, Jiang Chowdhury, Dipanjan Carter, Bob Chen, Clark TI A GENOME-WIDE miRNA SCREEN REVEALED MIR-603 AS A MGMT-REGULATING miRNA IN GLIOBLASTOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Kushwaha, Deepa; Ramakrishnan, Valya; Ng, Kimberly; Steed, Tyler; Thien Nguyen; Futalan, Diahnn; Akers, Johnny; Carter, Bob; Chen, Clark] Univ Calif San Diego, La Jolla, CA 92093 USA. [Chowdhury, Dipanjan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tao, Jiang] Tiantan Med Ctr, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA MR-02 DI 10.1093/neuonc/nou262.2 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200498 ER PT J AU Lafay-Cousin, L Chi, S Smith, A Wells, E Madden, J Margol, A Ramaswamy, V Owen, E Strother, D Dhall, G Foreman, N Packer, R Bouffet, E AF Lafay-Cousin, Lucie Chi, Susan Smith, Amy Wells, Elizabeth Madden, Jennifer Margol, Ashley Ramaswamy, Vijay Owen, Emily Strother, Douglas Dhall, Girish Foreman, Nicholas Packer, Roger Bouffet, Eric TI VERY ENCOURAGING LONG TERM SURVIVAL AND NEUROCOGNITIVE OUTCOME OF YOUNG CHILDREN TREATED FOR MEDULLOBLASTOMA WITH SEQUENTIAL HIGH DOSE CHEMOTHERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Lafay-Cousin, Lucie; Strother, Douglas] Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada. [Chi, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Amy; Owen, Emily] Arnold Palmer Hosp, Orlando, FL USA. [Wells, Elizabeth; Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Madden, Jennifer; Foreman, Nicholas] Colorado Children Hosp, Denver, CO USA. [Ramaswamy, Vijay; Bouffet, Eric] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Margol, Ashley; Dhall, Girish] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA PT-08 DI 10.1093/neuonc/nou266.8 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200700 ER PT J AU Lee, E Muzikansky, A Kesari, S Wong, E Fadul, C Reardon, D Norden, A Nayak, L Rinne, M Alexander, B Arvold, N Doherty, L LaFrankie, D Pulverenti, J Smith, K Gaffey, S Kenney, A Hammond, S Drappatz, J Wen, P AF Lee, Eudocia Muzikansky, Alona Kesari, Santosh Wong, Eric Fadul, Camilo Reardon, David Norden, Andrew Nayak, Lakshmi Rinne, Mikael Alexander, Brian Arvold, Nils Doherty, Lisa LaFrankie, Debra Pulverenti, Julee Smith, Katrina Gaffey, Sarah Kenney, Alexandra Hammond, Samantha Drappatz, Jan Wen, Patrick TI A RANDOMIZED, PLACEBO-CONTROLLED PILOT TRIAL OF ARMODAFINIL FOR FATIGUE IN PATIENTS WITH GLIOMAS UNDERGOING RADIOTHERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Lee, Eudocia; Reardon, David; Norden, Andrew; Nayak, Lakshmi; Rinne, Mikael; Alexander, Brian; Arvold, Nils; Doherty, Lisa; LaFrankie, Debra; Pulverenti, Julee; Smith, Katrina; Gaffey, Sarah; Kenney, Alexandra; Wen, Patrick] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kesari, Santosh] Univ Calif San Diego, San Diego, CA 92103 USA. [Wong, Eric] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Fadul, Camilo] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Drappatz, Jan] Univ Pittsburgh, Pittsburgh, PA USA. [Hammond, Samantha] City Hope Beckman Res Inst, Duarte, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA SM-03 DI 10.1093/neuonc/nou277.3 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200817 ER PT J AU Ma, D Galanis, E Peller, P Ligon, K Giannini, C Sarkaria, J AF Ma, Daniel Galanis, Eva Peller, Patrick Ligon, Keith Giannini, Caterina Sarkaria, Jann TI GENETIC PROFILING FOR EARLY EVEROLIMUS SENSITIVITY IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS ENROLLED ON NCCTG N057K SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Ma, Daniel; Galanis, Eva; Peller, Patrick; Giannini, Caterina; Sarkaria, Jann] Mayo Clin, Rochester, MN USA. [Ligon, Keith] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ligon, Keith] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA BI-20 DI 10.1093/neuonc/nou239.20 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200110 ER PT J AU Nigim, F Cavanaugh, J Patel, AP Curry, WT Kasper, EM Chi, AS Martuza, RL Rabkin, SD Wakimoto, H AF Nigim, Fares Cavanaugh, Jill Patel, Anoop P. Curry, William T., Jr. Kasper, Ekkehard M. Chi, Andrew S. Martuza, Robert L. Rabkin, Samuel D. Wakimoto, Hiroaki TI HIF-1A TARGETING IN AN ORTHOTOPIC XENOGRAFT MODEL THAT RECAPITULATES THE HYPOXIC MICROENVIRONMENT OF GLIOBLASTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P.; Curry, William T., Jr.; Chi, Andrew S.; Martuza, Robert L.; Rabkin, Samuel D.; Wakimoto, Hiroaki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kasper, Ekkehard M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AI-21 DI 10.1093/neuonc/nou238.21 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200022 ER PT J AU Ohla, V Kasper, E Doostkam, S Volk, B Ostertag, C AF Ohla, Victoria Kasper, Ekkehard Doostkam, Soroush Volk, B. Ostertag, Christian TI GLIOMATOSIS CEREBRI: DIAGNOSIS, MANAGEMENT AND OUTCOMES IN THE LARGEST SERIES FROM A SINGLE EUROPEAN INSTITUTION SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Ohla, Victoria; Kasper, Ekkehard] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Ohla, Victoria; Doostkam, Soroush; Volk, B.; Ostertag, Christian] Univ Freiburg, D-79106 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA NI-63 DI 10.1093/neuonc/nou264.61 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200603 ER PT J AU Peters, K Reardon, D Randazzo, D Dutton, S Edwards, A Lipp, E Herndon, J McSherry, F Desjardins, A Ranjan, T Vlahovic, G Friedman, H AF Peters, Katherine Reardon, David Randazzo, Dina Dutton, Shelley Edwards, Ashley Lipp, Eric Herndon, James, II McSherry, Frances Desjardins, Annick Ranjan, Tulika Vlahovic, Gordana Friedman, Henry TI VORINOSTAT AND BEVACIZUMAB FOR RECURRENT HIGH-GRADE GLIOMA: INTERIM ANALYSIS OF A PHASE II CLINICAL TRIAL SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Peters, Katherine; Randazzo, Dina; Dutton, Shelley; Edwards, Ashley; Lipp, Eric; Herndon, James, II; McSherry, Frances; Desjardins, Annick; Ranjan, Tulika; Vlahovic, Gordana; Friedman, Henry] Duke Univ, Med Ctr, Durham, NC USA. [Reardon, David] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-46 DI 10.1093/neuonc/nou237.45 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200074 ER PT J AU Raizer, J Pentsova, E Omuro, A Lin, N Nayak, L Quant, E Kumthekar, P AF Raizer, Jeffrey Pentsova, Elena Omuro, Antonio Lin, Nancy Nayak, Lakshmi Quant, Eudocia Kumthekar, Priya TI PHASE I TRIAL OF INTRATHECAL TRASTUZUMAB IN HER2 POSITIVE LEPTOMENINGEAL METASTASES SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Raizer, Jeffrey; Kumthekar, Priya] Northwestern Univ, Chicago, IL 60611 USA. [Pentsova, Elena; Omuro, Antonio] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lin, Nancy; Nayak, Lakshmi; Quant, Eudocia] Dana Farber Canc Inst, Boston, MA 02115 USA. OI Omuro, Antonio/0000-0003-4299-3664 NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-47 DI 10.1093/neuonc/nou237.46 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200075 ER PT J AU Ratner, N Keng, V Patmore, DM Kendall, JK Jousma, E Choi, K Fan, DH Schwartz, EB Fuchs, JR Zou, YS Kim, MO Dombi, E Levy, DE Cancelas, JA Stemmer-Rachamimov, A Spinner, RJ Largaespada, DA AF Ratner, Nancy Keng, Vincent Patmore, Deanna M. Kendall, Jed K. Jousma, Edwin Choi, Kwangmin Fan, Danhua Schwartz, Eric B. Fuchs, James R. Zou, Yuanshu Kim, Mi-Ok Dombi, Eva Levy, David E. Cancelas, Jose A. Stemmer-Rachamimov, Anat Spinner, Robert J. Largaespada, David A. TI EGFR-STAT3 ACTIVATES beta-CATENIN SIGNALING TO DRIVE NEUROFIBROMA INITIATION IN NF1, AND PLAYS A ROLE IN TUMOR MAINTENANCE SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Ratner, Nancy; Patmore, Deanna M.; Kendall, Jed K.; Jousma, Edwin; Choi, Kwangmin; Kim, Mi-Ok; Cancelas, Jose A.] Cincinnati Childrens, Cincinnati, OH USA. [Keng, Vincent; Fan, Danhua; Schwartz, Eric B.; Fuchs, James R.; Zou, Yuanshu; Largaespada, David A.] Univ Minnesota, Minneapolis, MN USA. [Spinner, Robert J.] Mayo Clin, Rochester, MN USA. [Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dombi, Eva] NCI, Pediat Branch, Bethesda, MD 20892 USA. [Levy, David E.] NYU, Sch Med, New York, NY USA. RI Kim, Mi-Ok/O-9626-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA PM-18 DI 10.1093/neuonc/nou268.18 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200694 ER PT J AU Razis, E Vlahovic, G Recht, L Wheeler, H Reardon, D Fisher, PG Owen, S Nicholas, K Paradise, E Yellin, M Davis, T Weller, M Stupp, R Hottinger, AF AF Razis, Evangelia Vlahovic, Gordana Recht, Lawrence Wheeler, Helen Reardon, David Fisher, Paul G. Owen, Scott Nicholas, Kelly Paradise, Elsa Yellin, Michael Davis, Thomas Weller, Michael Stupp, Roger Hottinger, Andreas F. TI VACCINATION AGAINST EPIDERMAL GROWTH FACTOR RECEPTOR VARIANT III IN GLIOBLASTOMA: THE RINDOPEPIMUT COMPASSIONATE USE EXPERIENCE SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Razis, Evangelia] Hygeia Hosp, Athens, Greece. [Vlahovic, Gordana] Duke Univ, Durham, NC USA. [Recht, Lawrence; Fisher, Paul G.] Stanford Univ Med Ctr, Palo Alto, CA USA. [Wheeler, Helen] Sydney Neuro Oncol Grp, Sydney, NSW, Australia. [Reardon, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Owen, Scott] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Nicholas, Kelly] Univ Chicago, Chicago, IL 60637 USA. [Paradise, Elsa; Yellin, Michael; Davis, Thomas] Celldex Therapeut Inc, Hampton, NJ USA. [Weller, Michael; Stupp, Roger] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. [Stupp, Roger; Hottinger, Andreas F.] CHU Vaudois, CH-1011 Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA IT-28 DI 10.1093/neuonc/nou258.26 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200466 ER PT J AU Shaw, A Mehra, R Tan, DSW Felip, E Chow, LQM Camidge, DR Vansteenkiste, J Sharma, S De Pas, T Riely, GJ Solomon, BJ Wolf, J Thomas, M Schuler, M Liu, G Santoro, A Geraldes, M Sen, P Boral, AJ Yovine, A Kim, DW AF Shaw, Alice Mehra, Ranee Tan, Daniel S. W. Felip, Enriqueta Chow, Laura Q. M. Camidge, D. Ross Vansteenkiste, Johan Sharma, Sunil De Pas, Tommaso Riely, Gregory J. Solomon, Benjamin J. Wolf, Juergen Thomas, Michael Schuler, Martin Liu, Geoffrey Santoro, Armando Geraldes, Margarida Sen, Paramita Boral, Anthony J. Yovine, Alejandro Kim, Dong-Wan TI CERITINIB (LDK378) FOR TREATMENT OF PATIENTS WITH ALK-REARRANGED (ALK plus ) NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN METASTASES (BM) IN THE ASCEND-1 TRIAL SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Shaw, Alice] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mehra, Ranee] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Tan, Daniel S. W.] Natl Canc Ctr Singapore, Singapore, Singapore. [Felip, Enriqueta] Vall dHebron Univ, Barcelona, Spain. [Chow, Laura Q. M.] Univ Washington, Seattle, WA 98195 USA. [Camidge, D. Ross] Univ Colorado, Denver, CO 80202 USA. [Vansteenkiste, Johan] Univ Hosp KU Leuven, Leuven, Belgium. [Sharma, Sunil] Huntsman Canc Inst, Salt Lake City, UT USA. [De Pas, Tommaso] Inst Europeo Oncol, Milan, Italy. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Wolf, Juergen] Univ Hosp Cologne, Cologne, Germany. [Thomas, Michael] Heidelberg Univ, Thoraxklin, Translat Lung Res Ctr Heidelberg, Heidelberg, Germany. [Schuler, Martin] Univ Duisburg Essen, West German Canc Ctr, Essen, Germany. [Schuler, Martin] German Canc Consortium DKTK, Heidelberg, Germany. [Liu, Geoffrey] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Santoro, Armando] IRCCS Inst Clin Humanitas, Milan, Italy. [Geraldes, Margarida] Novartis Pharmaceut, E Hanover, NJ USA. [Sen, Paramita; Boral, Anthony J.] Novartis Inst BioMed Res, Cambridge, MA USA. [Boral, Anthony J.] Novartis Pharma AG, Basel, Switzerland. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea. NR 0 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA BM-32 DI 10.1093/neuonc/nou240.32 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200150 ER PT J AU Shih, H Sherman, J Nachtigall, L Colvin, M Fullerton, B Winrich, B Batchelor, T Thornton, L Daartz, J Mancuso, S Oh, K Curry, W Loeffler, J Yeap, B AF Shih, Helen Sherman, Janet Nachtigall, Lisa Colvin, Mary Fullerton, Barbara Winrich, Barbara Batchelor, Tracy Thornton, Lauren Daartz, Juliane Mancuso, Sarah Oh, Kevin Curry, William Loeffler, Jay Yeap, Beow TI PROSPECTIVE EARLY RESULTS OF LOW GRADE GLIOMA PATIENTS TREATED WITH PROTON THERAPY SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Shih, Helen; Sherman, Janet; Nachtigall, Lisa; Colvin, Mary; Fullerton, Barbara; Winrich, Barbara; Batchelor, Tracy; Thornton, Lauren; Daartz, Juliane; Mancuso, Sarah; Oh, Kevin; Curry, William; Loeffler, Jay; Yeap, Beow] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-52 DI 10.1093/neuonc/nou237.51 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200080 ER PT J AU Tateishi, K Lelic, N Ho, QH Esakl, S Iafrate, JA Cahill, DP Chi, AS Wakimoto, H AF Tateishi, Kensuke Lelic, Nina Ho, Quan H. Esakl, Shinichi Iafrate, John A. Cahill, Daniel P. Chi, Andrew S. Wakimoto, Hiroaki TI NAD plus SYNTHESIS INHIBITION AS A THERAPEUTIC STRATEGY FOR GLIOBLASTOMA WITH MYC AMPLIFICATION SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Tateishi, Kensuke; Lelic, Nina; Esakl, Shinichi; Cahill, Daniel P.; Wakimoto, Hiroaki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Chi, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Ho, Quan H.; Iafrate, John A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Tateishi, Kensuke; Lelic, Nina; Ho, Quan H.; Iafrate, John A.; Cahill, Daniel P.; Chi, Andrew S.; Wakimoto, Hiroaki] Translat Neurooncol Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA NT-33 DI 10.1093/neuonc/nou265.31 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200660 ER PT J AU Verreault, M Levasseur, C Schmitt, C Guehennec, J Labussiere, M Marie, Y Haidar, S Mokhtari, K Hoang-Xuan, K Sanson, M Ligon, K Delattre, JY Idbaih, A AF Verreault, Maite Levasseur, Camille Schmitt, Charlotte Guehennec, Jeremy Labussiere, Marianne Marie, Yannick Haidar, Sam Mokhtari, Karima Hoang-Xuan, Khe Sanson, Marc Ligon, Keith Delattre, Jean-Yves Idbaih, Ahmed TI HIGHLY SELECTIVE ACTIVITY OF MDM2 INHIBITOR RG7112 AGAINST MDM2-AMPLIFIED/TP53 WILD-TYPE GLIOBLASTOMAS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 19th Annual Scientific Meeting of the Society-for-Neuro-Oncology CY NOV 13-16, 2014 CL Miami, FL SP Soc Neuro Oncol C1 [Verreault, Maite; Levasseur, Camille; Schmitt, Charlotte; Guehennec, Jeremy; Labussiere, Marianne; Marie, Yannick; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Delattre, Jean-Yves; Idbaih, Ahmed] INSERM, U1127, F-7501 Paris, France. [Verreault, Maite; Levasseur, Camille; Schmitt, Charlotte; Guehennec, Jeremy; Labussiere, Marianne; Marie, Yannick; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Delattre, Jean-Yves; Idbaih, Ahmed] CNRS, UMR 7225, F-75013 Paris, France. [Verreault, Maite; Levasseur, Camille; Schmitt, Charlotte; Guehennec, Jeremy; Labussiere, Marianne; Marie, Yannick; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Delattre, Jean-Yves; Idbaih, Ahmed] Univ Paris 06, Sorbonne Univ, UMR S 1127, F-75013 Paris, France. [Verreault, Maite; Levasseur, Camille; Schmitt, Charlotte; Guehennec, Jeremy; Labussiere, Marianne; Marie, Yannick; Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Delattre, Jean-Yves; Idbaih, Ahmed] ICM, F-750133 Paris, France. [Haidar, Sam; Ligon, Keith] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Haidar, Sam; Ligon, Keith] Brigham & Womens Hosp & Childrens, Div Neuropathol, Dept Pathol, Boston, MA USA. [Mokhtari, Karima; Hoang-Xuan, Khe; Sanson, Marc; Delattre, Jean-Yves; Idbaih, Ahmed] Hop La Pitie Salpetriere, AP HP, Serv Neuropathol R Escourolle, Serv Neurol, F-75013 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA ET-62 DI 10.1093/neuonc/nou255.59 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200386 ER PT J AU Wefel, J Noll, K Rao, G Cahill, D AF Wefel, Jeffrey Noll, Kyle Rao, Ganesh Cahill, Daniel TI RELATIONSHIPS BETWEEN NEUROCOGNITIVE FUNCTIONING AND IDH1 GENETIC MUTATION STATUS IN MALIGNANT ASTROCYTOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Wefel, Jeffrey; Noll, Kyle; Rao, Ganesh] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cahill, Daniel] Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA NC-15 DI 10.1093/neuonc/nou263.15 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200546 ER PT J AU Wen, P Reardon, D Phuphanich, S Aiken, R Landolfi, J Curry, W Zhu, JJ Glantz, M Peereboom, D Markert, J Larocca, R O'Rourke, D Fink, K Kim, L Gruber, M Lesser, G Pan, E Kesari, S Yu, J AF Wen, Patrick Reardon, David Phuphanich, Surasak Aiken, Robert Landolfi, Joseph Curry, William Zhu, Jay-Jiguang Glantz, Michael Peereboom, David Markert, James Larocca, Renato O'Rourke, Donald Fink, Karen Kim, Lyndon Gruber, Michael Lesser, Glenn Pan, Ed Kesari, Santosh Yu, John TI A RANDOMIZED DOUBLE BLIND PLACEBO-CONTROLLED PHASE 2 TRIAL OF DENDRITIC CELL (DC) VACCINE ICT-107 FOLLOWING STANDARD TREATMENT IN NEWLY DIAGNOSED PATIENTS WITH GBM SO NEURO-ONCOLOGY LA English DT Meeting Abstract C1 [Wen, Patrick; Reardon, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [Phuphanich, Surasak; Yu, John] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Aiken, Robert] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Landolfi, Joseph] JFK Med Ctr, Edison, NJ USA. [Curry, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhu, Jay-Jiguang] Mem Herman Texas Med Ctr, Houston, TX USA. [Glantz, Michael] Penn State Hershey Med Ctr, Hershey, PA USA. [Peereboom, David] Cleveland Clin, Cleveland, OH 44106 USA. [Markert, James] Univ Alabama Birmingham, Med Ctr, Birmingham, AL 35294 USA. [Larocca, Renato] Norton Canc Inst, Louisville, KY USA. [O'Rourke, Donald] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Fink, Karen] Baylor Charles A Sammons Canc Ctr, Neurooncol Associates, Dallas, TX USA. [Kim, Lyndon] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Gruber, Michael] NYU, Med Ctr, New York, NY 10016 USA. [Lesser, Glenn] Wake Forest Baptist Med Ctr, Winston Salem, NC USA. [Pan, Ed] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Kesari, Santosh] Moores UCSD Canc Ctr, San Diego, CA USA. NR 0 TC 2 Z9 2 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2014 VL 16 SU 5 MA AT-60 DI 10.1093/neuonc/nou237.59 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CC6CM UT WOS:000350452200088 ER PT J AU Richmond, JM Essien, K Currimbhoy, S Pandya, A Bangari, D Youd, M Groom, JR Luster, AD Harris, JE AF Richmond, J. M. Essien, K. Currimbhoy, S. Pandya, A. Bangari, D. Youd, M. Groom, J. R. Luster, A. D. Harris, J. E. TI Targeting the IFN-gamma-CXCL10 axis in keratinocytes to develop novel treatments for vitiligo SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT Inflammatory Skin Disease Summit - The Translational Revolution CY NOV 19-21, 2014 CL Austrian Acad Sci, Vienna, AUSTRIA HO Austrian Acad Sci C1 [Richmond, J. M.; Essien, K.; Harris, J. E.] Univ Massachusetts, Sch Med, Dept Med, Div Dermatol, Worcester, MA USA. [Currimbhoy, S.; Pandya, A.] Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. [Bangari, D.; Youd, M.] Genzyme, Framingham, MA USA. [Groom, J. R.] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. [Groom, J. R.] Univ Melbourne, Melbourne, Vic, Australia. [Luster, A. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0906-6705 EI 1600-0625 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2014 VL 23 SU 2 SI SI MA P002 BP 1 EP 1 PG 1 WC Dermatology SC Dermatology GA CB9PD UT WOS:000349963100003 ER PT J AU Kinkel, RP Simon, JH O'Connor, P Hyde, R Pace, A AF Kinkel, R. P. Simon, J. H. O'Connor, P. Hyde, R. Pace, A. TI Early MRI activity predicts treatment nonresponse with intramuscular interferon beta-1a in clinically isolated syndrome SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Multiple sclerosis; Magnetic resonance imaging; Intramuscular interferon beta-1a; Treatment response; Clinically isolated syndrome; Clinically definite multiple sclerosis ID RELAPSING MULTIPLE-SCLEROSIS; 1ST DEMYELINATING EVENT; 10-YEAR FOLLOW-UP; DIAGNOSTIC-CRITERIA; NATURAL-HISTORY; OPTIC NEURITIS; DISABILITY; MS; DEFINITE; RISK AB Objective: Determine whether MRI activity 6 months after treatment initiation in the Controlled High-Risk Subjects Avonex (R) Multiple Sclerosis Prevention Study (CHAMPS) predicted progression to clinically definite multiple sclerosis (CDMS) over the subsequent 30 months in intramuscular interferon beta-1a (IM IFN beta-1a)-treated patients vs placebo-treated patients. Methods: CHAMPS patients were randomized to once-weekly IM 30 mu g or placebo for up to 36 months. MRI was performed every 6 months until CDMS confirmation. Patient groups were defined based on new T2 and/or Gd + lesions at 6 months. Results: Thirteen IM IFN beta-1a patients (6.7%) and 24 placebo patients (12.6%) developed CDMS prior to month 6 and did not undergo the 6-month MRI. At 6 months, 29.7% of IM IFN beta-1a-treated patients vs 40.9% of placebo-treated patients were defined as having high MRI activity levels (>= 2 new T2 and/or >= 2 Gd+ lesions). In this subgroup, estimated cumulative probabilities of CDMS were similar between groups (HR=0.88 [0.44-1.77], p=0.7227). A significant treatment response was seen for patients with <2 new T2 and <2 Gd+ lesions at 6 months (HR=0.39 [0.19-0.82], p=0.0120). Conclusion: MRI scans 6 months after IM IFN beta-1 a initiation in CIS patients predict early treatment non-response. Standardized scanning and monitoring may facilitate early disease management. (C) 2014 Elsevier B.V. All rights reserved. C1 [Kinkel, R. P.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Simon, J. H.] Portland VA Med Ctr, Portland, OR 97239 USA. [O'Connor, P.] St Michaels Hosp, Multiple Sclerosis Clin, Toronto, ON M5B 1W8, Canada. [Hyde, R.; Pace, A.] Biogen Idec Inc, Cambridge, MA 02142 USA. RP Kinkel, RP (reprint author), Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr,MC 0662, La Jolla, CA 92093 USA. EM rkinkel@ucsd.edu; jacksimon1@me.com; OCONNORP@smh.toronto.on.ca; Robert.Hyde@biogenidec.com; Amy.Pace@biogenidec.com FU Biogen Idec FX Biogen Idec provided funding for editorial support in the development of this paper; Christopher Barnes of Infusion Communications wrote the first draft of the manuscript based on input from authors, Joshua Safran and Shannon Davis from Infusion Communications copyedited the manuscript, and Colin Mitchell of Biogen Idec styled the manuscript per journal requirements. Biogen Idec reviewed and provided feedback on the paper to the authors. The authors had full editorial control of the paper and provided their final approval of all content. NR 39 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD NOV PY 2014 VL 3 IS 6 BP 712 EP 719 DI 10.1016/j.msard.2014.08.003 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CB5KO UT WOS:000349666100008 PM 25891550 ER PT J AU Mahoney, KM Atkins, MB AF Mahoney, Kathleen M. Atkins, Michael B. TI Prognostic and Predictive Markers for the New Immunotherapies SO ONCOLOGY-NEW YORK LA English DT Article ID RENAL-CELL CARCINOMA; ADVANCED MELANOMA PATIENTS; T-CELLS; METASTATIC MELANOMA; GENE SIGNATURE; CANCER; IPILIMUMAB; EXPRESSION; ANTIBODY; SAFETY AB Blocking the programmed cell death 1 (PD-1) pathway with monoclonal antibodies has shown promising antitumor responses in clinical trials, with less toxicity than has been seen with prior immune therapies such as interleukin 2 and ipilimumab. Pembrolizumab, an anti-PD-1 antibody, recently gained US Food and Drug Administration (FDA) accelerated approval for the treatment of patients with ipilimumab-refractory melanoma, while nivolumab, another anti-PD-1 antibody, and MPDL3280A, an anti-programmed cell death 1 ligand (PD-L1) antibody, have been granted FDA "breakthrough designation" for treatment of subsets of patients with refractory Hodgkin lymphoma and metastatic bladder cancer, respectively. Encouraging antitumor activity has also been seen with these agents in patients with other malignancies, including non-small-cell lung cancer and head and neck cancer, tumors not previously thought to be immune-responsive. PD-L1 expression has emerged as a potential predictive biomarker for PD-1-directed therapy. Multiple, distinct, companion assays for PD-L1 positivity have been developed, but there is as yet no comparison, standardization, or prospective validation of these assays. PD-L1 expression on tumor cells and/or the tumor-immune infiltrate is likely only part of the predictive model necessary for selecting patients predisposed to respond to monotherapy. Additional predictive biomarkers are necessary to identify patients most likely to benefit from PD-1-based combination therapy, since tumor cell PD-L1 expression appears to have limited predictive value in this setting. C1 [Mahoney, Kathleen M.] Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02215 USA. [Mahoney, Kathleen M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mahoney, Kathleen M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mahoney, Kathleen M.; Atkins, Michael B.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. [Atkins, Michael B.] Georgetown Univ, Sch Med, Georgetown Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Atkins, Michael B.] MedStar Georgetown Univ Hosp, Div Hematol Oncol, Washington, DC USA. RP Mahoney, KM (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM kmmah5@bidmc.harvard.edu NR 71 TC 48 Z9 51 U1 0 U2 10 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2014 VL 28 SU 3 BP 39 EP 48 PG 10 WC Oncology SC Oncology GA CB9JH UT WOS:000349947300004 PM 25384886 ER PT J AU Wisneski, AD Mookhoek, A Chitsaz, S Hope, MD Guccione, JM Ge, L Tseng, EE AF Wisneski, Andrew D. Mookhoek, Aart Chitsaz, Sam Hope, Michael D. Guccione, Julius M. Ge, Liang Tseng, Elaine E. TI Patient-Specific Finite Element Analysis of Ascending Thoracic Aortic Aneurysm SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID WALL STRESS; MECHANICAL-PROPERTIES; INTIMAL TEARS; VALVE; DISSECTION; ROOT AB Background and aim of the study: Rupture/dissection of ascending thoracic aortic aneurysm (aTAA) is a cardiovascular emergency. Elective surgical repair is primarily based on maximum diameter, but complications have occurred under the size limits for surgical intervention. aTAA wall stress may be a better predictor of patient-specific rupture risk, but cannot be directly measured in vivo. The study aim was to develop an aTAA computational model associated with tricuspid aortic valve (TAV) to determine patient-specific wall stresses. Methods: A TAV-associated aTAA was excised intact during surgery. Zero-pressure geometry was generated from microcomputed tomography, and an opening angle was used to calculate residual stress. Material properties determined from stress-strain data were incorporated into an Ogden hyperelastic model. Wall stress distribution and magnitudes at systemic pressure were determined using finite element analyses (FEA) in LS-DYNA. Results: Regional material property differences were noted: the left aTAA region had a higher stiffness compared to the right, and anterior/posterior walls. During systole, the mean principal wall stresses were 172.0 kPa (circumferential) and 71.9 kPa (longitudinal), while peak wall stresses were 545.1 kPa (circumferential) and 430.1 kPa (longitudinal). Elevated wall stress pockets were seen in anatomic left and right aTAA regions. Conclusion: A validated computational approach was demonstrated to determine aTAA wall stresses in a patient-specific fashion, taking into account the required zero-stress geometry, wall thickness, material properties and residual stress. Regions of maximal wall stress may indicate the sites most prone to rupture. The creation of a patient-specific aTAA model based on a surgical specimen is necessary to serve as the 'gold standard' for comparing models based on in-vivo data alone. Validated data using the surgical specimen are essential for establishing wall stress and rupture-risk relationships. C1 [Wisneski, Andrew D.; Chitsaz, Sam; Guccione, Julius M.; Ge, Liang; Tseng, Elaine E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Hope, Michael D.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Hope, Michael D.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mookhoek, Aart] Erasmus Univ, Med Ctr, Dept Cardiothorac Surg, Rotterdam, Netherlands. RP Tseng, EE (reprint author), UCSF Med Ctr, Div Cardiothorac Surg, 500 Parnassus Ave,Suite 405W,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org FU American Heart Association Western States Affiliate Medical Student Fellowship FX These studies were supported by an American Heart Association Western States Affiliate Medical Student Fellowship. NR 24 TC 2 Z9 2 U1 1 U2 6 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD NOV PY 2014 VL 23 IS 6 BP 765 EP 772 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CB4BM UT WOS:000349573200015 PM 25790625 ER PT J AU Syme, M Caalaman, E Lichtenberg, PA Moye, J Mona, L AF Syme, M. Caalaman, E. Lichtenberg, P. A. Moye, J. Mona, L. TI SEXUALITY AND CONSENT IN LONG-TERM CARE: A QUALITATIVE INVESTIGATION OF CURRENT POLICIES, PROCEDURES, AND UNMET NEEDS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Syme, M.] San Diego State Univ, San Diego, CA 92182 USA. [Syme, M.; Caalaman, E.] Univ San Diego, San Diego, CA 92110 USA. [Lichtenberg, P. A.] Wayne State Univ, Detroit, MI USA. [Moye, J.] VA Boston Healthcare Syst, Boston, MA USA. [Mona, L.] VA Long Beach Healthcare Syst, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 75 EP 75 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501073 ER PT J AU Wang, JM Lee, L Spiro, A AF Wang, J. M. Lee, L. Spiro, A. TI COGNITIVE FUNCTIONING AND ALL-CAUSE MORTALITY: THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wang, J. M.; Lee, L.; Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Wang, J. M.; Lee, L.; Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Lee, L.; Spiro, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, A.] Boston Univ, Sch Dent Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 81 EP 81 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501096 ER PT J AU Quach, L Driver, J Cho, K Dugan, E Gagnon, DR AF Quach, L. Driver, J. Cho, K. Dugan, E. Gagnon, D. R. TI MORTALITY AND COMORBIDITY AMONG CENTENARIANS IN THE VETERANS ADMINISTRATION HEALTH CARE SYSTEM DURING 1997-2012 SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Quach, L.; Driver, J.; Cho, K.; Gagnon, D. R.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Quach, L.; Dugan, E.] Univ Massachusetts, Dept Gerontol, Boston, MA 02125 USA. [Driver, J.; Cho, K.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Driver, J.; Cho, K.] Harvard Univ, Sch Med, Boston, MA USA. [Gagnon, D. R.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 84 EP 84 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501107 ER PT J AU Zhang, N Zhang, Y Van Remmen, H Fischer, KE Austad, SN Shoelson, SE Hussey, S Musi, N AF Zhang, N. Zhang, Y. Van Remmen, H. Fischer, K. E. Austad, S. N. Shoelson, S. E. Hussey, S. Musi, N. TI NFKB INHIBITION IMPROVES GLUCOSE METABOLISM, BUT ACCELERATES SARCOPENIA AND IMPAIRS EXERCISE TOLERANCE, IN AGED MICE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Zhang, N.; Zhang, Y.; Van Remmen, H.; Fischer, K. E.; Austad, S. N.; Musi, N.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shoelson, S. E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Hussey, S.] Univ S Florida, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 90 EP 90 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501134 ER PT J AU Caprio, TV Hung, WW Howe, JL Sun, D Deering, J Kochersberger, G Fell, S AF Caprio, T. V. Hung, W. W. Howe, J. L. Sun, D. Deering, J. Kochersberger, G. Fell, S. TI CASE-BASED TELECONFERENCE MODEL FOR GERIATRICS CONSULTATION AND EDUCATION: OUTREACH TO RURAL PRIMARY CARE PROVIDERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Caprio, T. V.; Kochersberger, G.] Univ Rochester, Rochester, NY USA. [Caprio, T. V.; Kochersberger, G.; Fell, S.] Canandaigua VA Med Ctr, Canandaigua, NY USA. [Hung, W. W.; Howe, J. L.; Sun, D.; Deering, J.] James J Peters VA Med Ctr, Bronx, NY USA. [Hung, W. W.; Howe, J. L.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 120 EP 120 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501270 ER PT J AU Rossi, MI Powers, BB Edmonds, N Dolbee, C Hennon, J Homer, MC AF Rossi, M. I. Powers, B. Brott Edmonds, N. Dolbee, C. Hennon, J. Homer, M. C. TI TELEDEMENTIA CLINIC: CLINICAL VIDEO TELEHEALTH TO DIAGNOSE & SUPPORT RURAL VETERANS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rossi, M. I.; Powers, B. Brott; Edmonds, N.; Dolbee, C.; Hennon, J.; Homer, M. C.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Rossi, M. I.; Hennon, J.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 120 EP 120 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501269 ER PT J AU Roiland, R Porter, J Polnaszek, B Hovanes, ML Jensen, LL Kind, A AF Roiland, R. Porter, J. Polnaszek, B. Hovanes, M. L. Jensen, L. L. Kind, A. TI FRAILTY AND TRANSITIONAL CARE OUTCOMES IN HOSPITALIZED, OLDER VETERANS: A FEASIBILITY STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Roiland, R.; Porter, J.; Hovanes, M. L.; Jensen, L. L.; Kind, A.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Porter, J.; Hovanes, M. L.; Kind, A.] Univ Madison Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI USA. [Polnaszek, B.] Univ Madison Sch Med & Publ Hlth, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 149 EP 149 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501414 ER PT J AU Regier, NG Naik, AD Moye, J AF Regier, N. G. Naik, A. D. Moye, J. TI A COMPARISON OF THE EFFECTS OF CANCER, CANCER TREATMENTS, AND EMOTIONAL FACTORS ON COGNITION IN YOUNGER AND OLDER VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Regier, N. G.; Moye, J.] VA Boston Healthcare Syst, Boston, MA USA. [Naik, A. D.] Baylor Coll Med, Houston, TX 77030 USA. [Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 171 EP 171 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337501519 ER PT J AU Feng, MC Mulligan, E Moye, J AF Feng, M. C. Mulligan, E. Moye, J. TI CHARACTERISTICS ASSOCIATED WITH SYMPTOM IMPROVEMENT AMONG OLDER ADULTS IN PSYCHOTHERAPY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Feng, M. C.; Mulligan, E.; Moye, J.] VA Boston Healthcare Syst, Jamaica Plain, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 185 EP 185 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337502058 ER PT J AU Mulligan, E Naik, AD Moye, J AF Mulligan, E. Naik, A. D. Moye, J. TI SOCIAL ISOLATION FOLLOWING ORAL-DIGESTIVE CANCER PREDICTS DEPRESSIVE SYMPTOMS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Mulligan, E.; Moye, J.] VA Boston Healthcare Syst, Brockton, MA USA. [Mulligan, E.; Moye, J.] Harvard Univ, Sch Med, Boston, MA USA. [Naik, A. D.] Michael E Debakey VA Med Ctr, Houston, TX USA. [Naik, A. D.] Baylor Coll Med, Houson, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 186 EP 186 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337502062 ER PT J AU Cahana-Amitay, D Lee, L Spiro, A AF Cahana-Amitay, D. Lee, L. Spiro, A. TI PROFILES OF LANGUAGE PERFORMANCE IN AGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cahana-Amitay, D.; Spiro, A.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Lee, L.; Spiro, A.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 192 EP 192 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337502084 ER PT J AU Lee, L Kubzansky, LD Mehta, AJ Schwartz, J Spiro, A AF Lee, L. Kubzansky, L. D. Mehta, A. J. Schwartz, J. Spiro, A. TI PATTERNS OF EARLY EXPERIENCES AND TRAJECTORIES OF INFLAMMATORY MARKERS: THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Lee, L.; Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Lee, L.; Spiro, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lee, L.; Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Spiro, A.] Boston Univ, Sch Dent Med, Boston, MA 02215 USA. [Kubzansky, L. D.; Mehta, A. J.; Schwartz, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2014 VL 54 SU 2 BP 205 EP 205 PG 1 WC Gerontology SC Geriatrics & Gerontology GA AW5TU UT WOS:000346337502142 ER PT J AU Spira, JL Lathan, CE Bleiberg, J Tsao, JW AF Spira, James L. Lathan, Corinna E. Bleiberg, Joseph Tsao, Jack W. TI The Impact of Multiple Concussions on Emotional Distress, Post-Concussive Symptoms, and Neurocognitive Functioning in Active Duty United States Marines Independent of Combat Exposure or Emotional Distress SO JOURNAL OF NEUROTRAUMA LA English DT Article DE adult brain injury; behavioral assessments; cognitive function; head trauma; military injury ID TRAUMATIC BRAIN-INJURY; PROFESSIONAL FOOTBALL PLAYERS; DEPLOYED MILITARY PERSONNEL; HEAD-INJURY; RECURRENT CONCUSSION; NEUROPSYCHOLOGICAL OUTCOMES; POSTCONCUSSION SYNDROME; NCAA CONCUSSION; IRAQ; PERFORMANCE AB Controversy exists as to whether the lingering effects of concussion on emotional, physical, and cognitive symptoms is because of the effects of brain trauma or purely to emotional factors such as post-traumatic stress disorder or depression. This study examines the independent effects of concussion on persistent symptoms. The Defense Automated Neurobehavioral Assessment, a clinical decision support tool, was used to assess neurobehavioral functioning in 646 United States Marines, all of whom were fit for duty. Marines were assessed for concussion history, post-concussive symptoms, emotional distress, neurocognitive functioning, and deployment history. Results showed that a recent concussion or ever having experienced a concussion was associated with an increase in emotional distress, but not with persistent post-concussive symptoms (PPCS) or neurocognitive functioning. Having had multiple lifetime concussions, however, was associated with greater emotional distress, PPCS, and reduced neurocognitive functioning that needs attention and rapid discrimination, but not for memory-based tasks. These results are independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. Results supported earlier findings that a previous concussion is not generally associated with post-concussive symptoms independent of covariates. In contrast with other studies that failed to find a unique contribution for concussion to PPCS, however, evidence of recent and multiple concussion was seen across a range of emotional distress, post-concussive symptoms, and neurocognitive functioning in this study population. Results are discussed in terms of implications for assessing concussion on return from combat. C1 [Spira, James L.] US Dept Vet Affairs, Natl Ctr PTSD, Pacific Isl Div, Honolulu, HI 96819 USA. [Spira, James L.] Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. [Lathan, Corinna E.] AnthroTronix Inc, Silver Spring, MD USA. [Bleiberg, Joseph] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence Psychol Hlth & Traum, Bethesda, MD USA. [Tsao, Jack W.] US Navy Bur Med & Surg Falls Church, Traumat Brain Injury Program, Wounded Ill & Injured Directorate, Falls Church, VA USA. RP Spira, JL (reprint author), US Dept Vet Affairs, Natl Ctr PTSD, 3375 Koapaka St,I-560, Honolulu, HI 96819 USA. EM James.Spira@va.gov OI Bleiberg, Joseph/0000-0003-0867-5494 FU U.S. Navy Bureau of Medicine and Surgery, Wounded, Ill, and Injured Directorate FX This work was supported by the U.S. Navy Bureau of Medicine and Surgery, Wounded, Ill, and Injured Directorate, as well as with resources and the use of facilities at the US Department of Veterans Affairs, National Center for PTSD, Pacific Islands Health Care System. NR 56 TC 8 Z9 8 U1 0 U2 7 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 NOV 1 PY 2014 VL 31 IS 22 BP 1823 EP 1834 DI 10.1089/neu.2014.3363 PG 12 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CB4ZO UT WOS:000349637400002 PM 25003552 ER PT J AU Haley, KP Blanz, EJ Gaddy, JA AF Haley, Kathryn Patricia Blanz, Eric Joshua Gaddy, Jennifer Angeline TI High Resolution Electron Microscopy of the Helicobacter pylori Cag Type IV Secretion System Pili Produced in Varying Conditions of Iron Availability SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Infection; Issue 93; Helicobacter pylori; iron acquisition; cag pathogenicity island; type IV secretion; pili ID CHEMICALLY-DEFINED MEDIA; IN-VIVO; DISEASE; DEFICIENCY; INFECTION; GENE AB Helicobacter pylori is a helical-shaped, gram negative bacterium that colonizes the human gastric niche of half of the human population(1,2). H. pylori is the primary cause of gastric cancer, the second leading cause of cancer-related deaths worldwide(3). One virulence factor that has been associated with increased risk of gastric disease is the Cag-pathogenicity island, a 40-kb region within the chromosome of H. pylori that encodes a type IV secretion system and the cognate effector molecule, CagA(4,5). The Cag-T4SS is responsible for translocating CagA and peptidoglycan into host epithelial cells(5,6). The activity of the Cag-T4SS results in numerous changes in host cell biology including upregulation of cytokine expression, activation of proinflammatory pathways, cytoskeletal remodeling, and induction of oncogenic cell-signaling networks(5-8). The Cag-T4SS is a macromolecular machine comprised of sub-assembly components spanning the inner and outer membrane and extending outward from the cell into the extracellular space. The extracellular portion of the Cag-T4SS is referred to as the "pilus" (5). Numerous studies have demonstrated that the Cag-T4SS pili are formed at the host-pathogen interface(9,10). However, the environmental features that regulate the biogenesis of this important organelle remain largely obscure. Recently, we reported that conditions of low iron availability increased the Cag-T4SS activity and pilus biogenesis. Here we present an optimized protocol to grow H. pylori in varying conditions of iron availability prior to co-culture with human gastric epithelial cells. Further, we present the comprehensive protocol for visualization of the hyper-piliated phenotype exhibited in iron restricted conditions by high resolution scanning electron microscopy analyses. C1 [Haley, Kathryn Patricia; Blanz, Eric Joshua; Gaddy, Jennifer Angeline] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37235 USA. [Gaddy, Jennifer Angeline] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Washington, DC USA. RP Gaddy, JA (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37235 USA. EM jennifer.a.gaddy@vanderbilt.edu FU Department of Veterans Affairs Career Development Award [1IK2BX001701]; CTSA from the National Center for Advancing Translational Sciences [UL1TR000445]; NIH [CA68485, DK20593, DK58404, DK59637, EY08126] FX This research was supported by the Department of Veterans Affairs Career Development Award 1IK2BX001701 and the CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Scanning electron microscopy experiments were performed in part through the use of the VUMC Cell Imaging Shared Resource, supported by NIH grants CA68485, DK20593, DK58404, DK59637 and EY08126. NR 25 TC 4 Z9 4 U1 0 U2 1 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD NOV PY 2014 IS 93 AR e52122 DI 10.3791/52122 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB0JH UT WOS:000349311400061 PM 25489938 ER PT J AU Oto, J Chenelle, CT Su, ZB Sun, MQ Jiang, YD Kacmarek, RM AF Oto, Jun Chenelle, Christopher T. Su, Zhenbo Sun, Mary Q. Jiang, Yandong Kacmarek, Robert M. TI Ventilation Efficacy of Video-Laryngoscopes Equipped With a Ventilation Feature SO RESPIRATORY CARE LA English DT Article DE video-laryngoscope; ventilation catheter; endotracheal intubation; difficult airway; emergency ventilation; jet ventilation ID DIFFICULT AIRWAY MANAGEMENT; FREQUENCY JET VENTILATION; LARYNGEAL MASK AIRWAY; ENDOTRACHEAL INTUBATION; TRACHEAL INTUBATION; ADULT AIRWAY; EMERGENCY; COMPLICATIONS; RESUSCITATION; UNSUCCESSFUL AB INTRODUCTION: Achieving effective ventilation is challenging for anesthesia care providers and emergency medical personnel, as difficult mask ventilation and difficult intubation frequently occur. The aim of this study was to determine whether video-laryngoscopes equipped with a ventilation feature can produce effective ventilation. METHODS: An intubation mannequin with its trachea connected to a model lung with compliance 50 (normal compliance: C50) and 20 mL/cm 1120 (low compliance: C20) was used. Ventilation was established via a ventilation catheter (inner diameter 3.5 mm, 50 cm length) extending to the tip of the video-laryngoscope blade. Three different views of the vocal cords (grade 1, vocal cords fully visualized; grade 2, partial vocal cord visualization; grade 3, only epiglottis visualized) were tested. Ventilation was provided by jet ventilator (Jet). The Jet was operated at 10, 15, and 20 psi (Jet10, Jet15, and Jet20). Effective tidal volume (V-T) was defined as a V-T greater than anatomical dead space (150 mL). RESULTS: In C50, Jet15 and Jet20 generated effective V-T in all vocal cord views (for Jet15: grade 1, 663 +/- 33 mL; grade 2, 363 +/- 25 mL; and grade 3, 198 +/- 9 mL; for Jet20: grade 1, 1,005 +/- 114 mL; grade 2, 484 +/- 38 mL; grade 3, 268 +/- 8 mL, respectively). In C20, Jet15 and Jet20 generated effective V-T in grades 1 and 2 (Jet15: grade 1, 288 +/- 8 mL; grade 2, 160 +/- 20 mL; grade 3, 81 +/- 7 mL; Jet20: grade 1, 421 +/- 20 mL; grade 2, 222 +/- 16 mL; grade 3, 111 +/- 8 mL, respectively). Jet10 achieved effective V-T in grade 1 and 2 (grade 1, 354 +/- 6 mL; grade 2, 223 +/- 37 mL, respectively) in C50 and grade 1 (163 +/- 12 mL) in C20. CONCLUSIONS: Video-laryngoscopes equipped with a ventilation feature provided effective V-T in simulated clinical scenarios. Further clinical study is required to validate these findings. C1 [Oto, Jun; Chenelle, Christopher T.; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Su, Zhenbo; Sun, Mary Q.; Jiang, Yandong] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org OI Chenelle, Christopher/0000-0002-1499-9973 FU Covidien; Hollister FX Dr Kacmarek received a research grant from Covidien and Hollister and has received an honorarium for lecturing from Maquet. All other authors declare no conflicts of interest. NR 30 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 59 IS 11 BP 1636 EP 1642 DI 10.4187/respcare.03169 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA8WF UT WOS:000349200900005 PM 25161299 ER PT J AU Vargas, M Servillo, G Tessitore, G Aloj, F Brunetti, I Arditi, E Salami, D Kacmarek, RM Pelosi, P AF Vargas, Maria Servillo, Giuseppe Tessitore, Gaetano Aloj, Fulvio Brunetti, Iole Arditi, Enrico Salami, Dorino Kacmarek, Robert M. Pelosi, Paolo TI Double Lumen Endotracheal Tube for Percutaneous Tracheostomy SO RESPIRATORY CARE LA English DT Article DE tracheostomy; double lumen endotracheal tube; airway management; intensive care ID FLEXIBLE FIBEROPTIC BRONCHOSCOPY; MEAN AIRWAY PRESSURE; MECHANICAL VENTILATION; LUNG MODEL; RESISTANCE AB BACKGROUND: Percutaneous dilational tracheostomy is normally a bronchoscope-guided procedure. The insertion of a bronchoscope into an endotracheal tube (ETT) affects resistance, flow, and alveolar pressure. To improve airway management and ventilation during percutaneous tracheostomy, we developed a double lumen endotracheal tube (DLET). The aim of this in vitro study was to compare the linear constant of the Rohrer equation (K-1), the nonlinear constant of the Rohrer equation (K-2), the inspiratory and expiratory airway resistance, and ventilatory and airway pressures using the DLET with different standard sized ETTs. METHODS: A trachea and lung model was used to compare the DLET to ETTs with 7, 7.5, and 8 mm inner diameters with and without a bronchoscope (4.5 mm external diameter), and 4 and 5 mm inner diameter ventilation tubes (F-4, F-5) of a translaryngeal tracheostomy. For each device, the pressure drop across the device and the Rohrer equation linear constant (K-1) and nonlinear constant (K-2) were calculated during a continuous flow of 10-90 L/min, the inspiratory and expiratory airway resistance values were calculated during volume controlled mechanical ventilation, and respiratory airway pressure values were calculated during volume and pressure controlled mechanical ventilation. RESULTS: DLET had lower K-2, pressure drop, and inspiratory and expiratory airway resistance compared with conventional ETTs plus fiberoptic bronchoscope. Furthermore, during mechanical ventilation, DLET had a lower value of peak pressure, mean pressure, and intrinsic PEEP than the other ETTs plus fiberoptic bronchoscope. CONCLUSIONS: Use of the DLET during percutaneous dilational tracheostomy allows fiberoptic bronchoscopy without imposing excessive airway resistance. Reduced tube resistance during this procedure may confer additional safety in what is well known to be a hazardous procedure. C1 [Vargas, Maria; Servillo, Giuseppe; Tessitore, Gaetano] Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, I-80100 Naples, Italy. [Aloj, Fulvio] Ist Ricovero & Cura Carattere Sci Neuromd, Anaesthesia & Intens Care Unit, Pozzilli, Italy. [Brunetti, Iole; Arditi, Enrico; Salami, Dorino; Pelosi, Paolo] Univ Genoa, Azienda Osped Univ San Martino IST, Ist Ricovero & Cura Carattere Sci, Dept Anesthesia & Intens Care, 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. [Pelosi, Paolo] Univ Genoa, Azienda Osped Univ San Martino IST, Ist Ricovero & Cura Carattere Sci, Dept Surg & Integrated Sci, Genoa, Italy. RP Vargas, M (reprint author), Univ Naples Federico II, Dept Neurosci & Reprod & Odontostomatol Sci, Via Pansini 16, I-80100 Naples, Italy. EM vargas.maria82@gmail.com RI Vargas, Maria/H-6876-2014; Servillo, Giuseppe/M-9132-2016 OI Vargas, Maria/0000-0001-7652-970X; Servillo, Giuseppe/0000-0002-4618-3434 NR 21 TC 9 Z9 9 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 NOV PY 2014 VL 59 IS 11 BP 1652 EP 1659 DI 10.4187/respcare.03161 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA8WF UT WOS:000349200900007 PM 25161301 ER PT J AU Hess, DR AF Hess, Dean R. TI Respiratory Mechanics in Mechanically Ventilated Patients SO RESPIRATORY CARE LA English DT Article DE auto-PEEP; chest wall; compliance; esophageal pressure; mechanical ventilation; plateau pressure; resistance; respiratory mechanics; work of breathing ID END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; CHEST-WALL MECHANICS; DISTRESS-SYNDROME; ESOPHAGEAL PRESSURE; TRANSPULMONARY PRESSURE; SUPPORT VENTILATION; AIRWAY PRESSURE; VOLUME CURVES; DEPENDENT PATIENTS AB Respiratory mechanics refers to the expression of lung function through measures of pressure and flow. From these measurements, a variety of derived indices can be determined, such as volume, compliance, resistance, and work of breathing. Plateau pressure is a measure of end-inspiratory distending pressure. It has become increasingly appreciated that end-inspiratory transpulmonary pressure (stress) might be a better indicator of the potential for lung injury than plateau pressure alone. This has resulted in a resurgence of interest in the use of esophageal manometry in mechanically ventilated patients. End-expiratory transpulmonary pressure might also be useful to guide the setting of PEEP to counterbalance the collapsing effects of the chest wall. The shape of the pressure-time curve might also be useful to guide the setting of PEEP (stress index). This has focused interest in the roles of stress and strain to assess the potential for lung injury during mechanical ventilation. This paper covers both basic and advanced respiratory mechanics during mechanical ventilation. C1 [Hess, Dean R.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 66 TC 7 Z9 10 U1 0 U2 7 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 NOV PY 2014 VL 59 IS 11 BP 1773 EP 1794 DI 10.4187/respcare.03410 PG 22 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CA8WF UT WOS:000349200900019 PM 25336536 ER PT J AU Heeg, B Van Agthoven, M van Beurden-Tan, C Liwing, J Mellqvist, UH Plesner, T Logman, F Aschan, J Einsele, H Treur, M Barendse, M Richardson, PG Palumbo, A Nahi, H Sonneveld, P AF Heeg, B. Van Agthoven, M. van Beurden-Tan, C. Liwing, J. Mellqvist, U. H. Plesner, T. Logman, F. Aschan, J. Einsele, H. Treur, M. Barendse, M. Richardson, P. G. Palumbo, A. Nahi, H. Sonneveld, P. TI TREATMENT SEQUENCING SURVIVAL MODEL FOR PATIENTS WITH MULTIPLE MYELOMA INELIGIBLE FOR STEM CELL TRANSPLANTATION (SCT) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Heeg, B.; Treur, M.] Pharmerit Int, Rotterdam, Netherlands. [Van Agthoven, M.] Janssen Cilag BV, Tilburg, Netherlands. [van Beurden-Tan, C.; Sonneveld, P.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Liwing, J.; Aschan, J.; Barendse, M.] Janssen Cilag AB, Sollentuna, Sweden. [Mellqvist, U. H.] Dept Hematol, Gothenburg, Sweden. [Plesner, T.] Vejle Hosp, Vejle, Denmark. [Logman, F.] Eastbridge Pharma BV, Utrecht, Netherlands. [Einsele, H.] Med Klin 2, Wurzburg, Germany. [Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palumbo, A.] Univ Turin, Turin, Italy. [Nahi, H.] Karolinska Univ Hosp, Solna, Sweden. 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 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD NOV PY 2014 VL 17 IS 7 MA PCN24 BP A617 EP A618 PG 3 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AX4QT UT WOS:000346917302219 PM 27202167 ER PT J AU Muldoon, MF Ryan, CM Yao, JK Conklin, SM Manuck, SB AF Muldoon, Matthew F. Ryan, Christopher M. Yao, Jeffrey K. Conklin, Sarah M. Manuck, Stephen B. TI Long-Chain Omega-3 Fatty Acids and Optimization of Cognitive Performance SO MILITARY MEDICINE LA English DT Article ID N-3 FATTY-ACIDS; HEART-RATE-VARIABILITY; RANDOMIZED CONTROLLED-TRIAL; HEALTHY-YOUNG ADULTS; ETHYL-EICOSAPENTAENOIC ACID; FISH-OIL SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; DOCOSAHEXAENOIC ACID; DOUBLE-BLIND; OLDER-ADULTS AB Low consumption of the omega-3 fatty acids, eicosapentaenoic and docosahexaenonic acids, is linked to delayed brain development and, in late life, increased risk for Alzheimer's disease. The current review focuses on cognitive functioning during midlife and summarizes available scientific evidence relevant to the hypothesis that adequate dietary consumption of the long-chain omega-3 fatty acids is necessary for optimal cognitive performance. Taken together, the findings suggest that raising the currently low consumption among healthy adults may improve some aspects of cognitive performance. Nonetheless, evidence from randomized clinical trials is comparatively sparse and leaves unclear: (a) whether such effects are clinically significant, (b) whether effects of eicosapentaenoic acid and DHA differ, (c) which dimensions of cognitive function are affected, (d) the dose-response relationships, or (e) the time course of the response. Clarification of these issues through both laboratory and clinical investigations is a priority given the broad implications for public health, as well as for military personnel and other positions of high performance demand and responsibility. C1 [Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Inst Heart & Vasc, Pittsburgh, PA 15260 USA. [Ryan, Christopher M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15206 USA. [Conklin, Sarah M.] Allegheny Coll, Dept Psychol & Neurosci, Meadville, PA 16335 USA. [Manuck, Stephen B.] Univ Pittsburgh, Dept Psychol, Behav Physiol Lab, Pittsburgh, PA 15260 USA. RP Muldoon, MF (reprint author), Univ Pittsburgh, Sch Med, Inst Heart & Vasc, Old Engn Hall,Room 506, Pittsburgh, PA 15260 USA. FU IsodiNatura FX Dr. Conklin, Dr. Yao, and Dr. Muldoon report receipt of a $9,000 research grant in 2008 from IsodiNatura to support serum fatty acid determinations. NR 122 TC 2 Z9 2 U1 1 U2 16 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD NOV PY 2014 VL 179 IS 11 SU S BP 95 EP 105 DI 10.7205/MILMED-D-14-00168 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CA7LS UT WOS:000349099400007 PM 25373092 ER PT J AU Chan, SH Burgess, JF Clark, JA Mayo-Smith, MF AF Chan, Stephanie H. Burgess, James F., Jr. Clark, Jack A. Mayo-Smith, Michael F. TI Experience of the Veterans Health Administration in Massachusetts After State Health Care Reform SO MILITARY MEDICINE LA English DT Article AB Starting in 2006, Massachusetts enacted a series of health insurance reforms that successfully led to 96.6% of its population being covered by 2011. As the rest of the nation undertakes similar reforms, it is unknown how the Veterans Health Administration (VHA), one of many important Federal health care programs, will be affected. Our state-level study approach assessed the effects of health reform on utilization of VHA services in Massachusetts from 2005 to 2011. Models were adjusted for state-level demographic and economic characteristics, including health insurance rates, unemployment rates, median household income, poverty rates, and percent of population 65 years and older. No statistically significant associative change was observed in Massachusetts relative to other states over this time period. The findings raise important questions about the continuing role of VHA in American health care as health insurance coverage is one of many factors that influence decisions on where to seek health care. C1 [Chan, Stephanie H.; Mayo-Smith, Michael F.] VA New England Healthcare Syst, Dept Vet Affairs, Bedford, MA 01730 USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Burgess, James F., Jr.; Clark, Jack A.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Clark, Jack A.] Edith Nourse Rogers Mem VA Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. RP Chan, SH (reprint author), VA New England Healthcare Syst, Dept Vet Affairs, 200 Springs Rd, Bedford, MA 01730 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD NOV PY 2014 VL 179 IS 11 BP 1288 EP 1292 DI 10.7205/MILMED-D-14-00093 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA CA7LK UT WOS:000349098600025 PM 25373056 ER PT J AU Cahan, P Morris, SA Collins, JJ Daley, GQ AF Cahan, Patrick Morris, Samantha A. Collins, James J. Daley, George Q. TI Defining cellular identity through network biology SO CELL CYCLE LA English DT Editorial Material C1 [Cahan, Patrick; Morris, Samantha A.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cahan, Patrick; Morris, Samantha A.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Collins, James J.] Boston Univ, Dept Biomed Engn, Howard Hughes Med Inst, Boston, MA 02215 USA. [Collins, James J.] Boston Univ, Ctr Synthet Biol, Boston, MA 02215 USA. [Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Cahan, Patrick/0000-0003-3652-2540 FU NIDDK NIH HHS [K01 DK096013, R24 DK092760] NR 1 TC 4 Z9 4 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2014 VL 13 IS 21 BP 3313 EP 3314 DI 10.4161/15384101.2014.972918 PG 2 WC Cell Biology SC Cell Biology GA AZ6FA UT WOS:000348313100001 PM 25485572 ER PT J AU Taplin, ME Chi, KN Chu, F Cochran, J Edenfield, WJ Antonarakis, ES Emmenegger, U Heath, EI Hussain, A Njar, VC Koletsky, A Lipsitz, D Nordquist, L Pili, R Rettig, M Sartor, O Shore, ND Marrinucci, D Mamlouk, K Montgomery, B AF Taplin, M. E. Chi, K. N. Chu, F. Cochran, J. Edenfield, W. J. Antonarakis, E. S. Emmenegger, U. Heath, E. I. Hussain, A. Njar, V. C. Koletsky, A. Lipsitz, D. Nordquist, L. Pili, R. Rettig, M. Sartor, O. Shore, N. D. Marrinucci, D. Mamlouk, K. Montgomery, B. TI Activity of galeterone in castrate-resistant prostate cancer (CRPC) with C-terminal AR loss: Results from ARMOR2 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Taplin, M. E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Chi, K. N.] BC Canc Agcy, Genitourinary Oncol, Vancouver, BC, Canada. [Chu, F.] San Bernadino Urol Associates, Urol, San Bernardino, CA USA. [Cochran, J.] Urol Clin North Texas, Urol, Dallas, TX USA. [Edenfield, W. J.] Canc Ctr Carolinas, Greenville, SC USA. [Antonarakis, E. S.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. [Emmenegger, U.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Heath, E. I.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Hussain, A.; Njar, V. C.] Univ Maryland, Baltimore, MD 21201 USA. [Koletsky, A.] Ctr Hematol Oncol, Boca Raton, FL USA. [Lipsitz, D.] Carolina Urol, Urol, Concord, NC USA. [Nordquist, L.] Urol Canc Ctr, Omaha, NE USA. [Nordquist, L.] GU Res Network LLC, Oncol, Omaha, NE USA. [Pili, R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Rettig, M.] Inst Urol Oncol, Los Angeles, CA USA. [Sartor, O.] Tulane Univ, New Orleans, LA 70118 USA. [Shore, N. D.] Carolina Urol Res Ctr Atlantic Urol Clin, Myrtle Beach, SC USA. [Marrinucci, D.] EPIC Sci, Sci, San Diego, CA USA. [Mamlouk, K.] Tokai Pharma, Med Affairs, Cambridge, MA USA. [Montgomery, B.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 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 NOV PY 2014 VL 50 SU 6 MA 4 BP 8 EP 8 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700005 ER PT J AU Castel, P Juric, D Griffith, M Griffith, OL Won, HH Ainscough, B Ellis, H Ebbesen, S Gopakumar, I Quadt, C Peters, M Solit, D Lowe, SW Mardis, ER Berger, MF Scaltriti, M Baselga, J AF Castel, P. Juric, D. Griffith, M. Griffith, O. L. Won, H. H. Ainscough, B. Ellis, H. Ebbesen, S. Gopakumar, I. Quadt, C. Peters, M. Solit, D. Lowe, S. W. Mardis, E. R. Berger, M. F. Scaltriti, M. Baselga, J. TI Loss of PTEN leads to acquired resistance to the PI3Ka inhibitor BYL719: a case of convergent evolution under selective therapeutic pressure SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Castel, P.; Won, H. H.; Ellis, H.; Gopakumar, I.; Solit, D.; Berger, M. F.; Scaltriti, M.; Baselga, J.] Mem Sloan Kettering Canc Ctr, HOPP, New York, NY 10021 USA. [Juric, D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Griffith, M.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Griffith, O. L.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Ainscough, B.; Mardis, E. R.] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA. [Ebbesen, S.; Lowe, S. W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Quadt, C.; Peters, M.] Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 50 SU 6 MA 75 BP 29 EP 29 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700076 ER PT J AU Garon, EG Rizvi, NA LeighI, NB Hui, R Eder, JP Patnaik, A Aggarwal, C Horn, L Balmanoukian, AS Gubens, MA Felip-Font, E Costa, EC Soria, JC Ahn, MJ Arkenau, HT Lee, JS Robinet, G Lubiniecki, GM Zhang, J Emancipator, K Rutledge, R Dolled-Filhart, M Gandhi, L AF Garon, E. G. Rizvi, N. A. Leigh, N. B., I Hui, R. Eder, J. P. Patnaik, A. Aggarwal, C. Horn, L. Balmanoukian, A. S. Gubens, M. A. Felip-Font, E. Carceny Costa, E. Soria, J. C. Ahn, M. J. Arkenau, H. T. Lee, J. S. Robinet, G. Lubiniecki, G. M. Zhang, J. Emancipator, K. Rutledge, R. Dolled-Filhart, M. Gandhi, L. TI Correlation of clinical activity of pembrolizumab (MK-3475) with immunohistochemical staining for programmed death-1 ligand (PD-L1) in >= 50% of tumor cells in a prospective non-small cell lung cancer (NSCLC) validation population SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Garon, E. G.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Rizvi, N. A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Leigh, N. B., I] Princess Margaret Canc Ctr, Dept Med, Toronto, ON, Canada. [Hui, R.] Univ Sydney, Dept Med Oncol, Westmead Hosp, Sydney, NSW 2006, Australia. [Eder, J. P.] Yale Univ, Dept Med Oncol, New Haven, CT USA. [Patnaik, A.] South Texas Accelerated Res Therapeut, Clin Res, San Antonio, TX USA. [Aggarwal, C.] Univ Penn, Abramson Canc Ctr, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Horn, L.] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. [Balmanoukian, A. S.] Angeles Clin & Res Inst, Dept Lung & Thorac Canc, Los Angeles, CA USA. [Gubens, M. A.] Univ Calif San Francisco, Thorac Tumours Grp, San Francisco, CA 94143 USA. [Felip-Font, E.] Hosp Gen Univ Vail dHebron, Dept Med Oncol, Barcelona, Spain. [Carceny Costa, E.] Catalan Inst Oncol Badalona, Badalona, Spain. [Soria, J. C.] Gustave Roussy, Drug Dev Dept DITEP, Villejuif, France. [Ahn, M. J.] Samsung Med Ctr, Dept Internal Med, Samsung, South Korea. [Arkenau, H. T.] Sarah Cannon Res UK, London, England. [Lubiniecki, G. M.] Seoul Natl Univ, Bundang Hosp, Dept Hematol Oncol, Songnam, South Korea. [Robinet, G.] Hop Morvan, Inst Cancerol, Brest, France. [Lubiniecki, G. M.] Merck & Co Inc, Clin Res, N Wales, PA USA. [Zhang, J.] Merck & Co Inc, BARDS, N Wales, PA USA. [Gandhi, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Emancipator, K.] Merck & Co Inc, Mol Biomarkers & Diagnost, Whitehouse Stn, NJ USA. [Rutledge, R.] Merck & Co Inc, Oncol Clin Res, Whitehouse Stn, NJ USA. [Dolled-Filhart, M.] Merck & Co Inc, Mol Biomarkers & Diagnost, Whitehouse Stn, NJ USA. RI Zhang, Jin/E-8298-2017 NR 0 TC 0 Z9 0 U1 0 U2 7 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 NOV PY 2014 VL 50 SU 6 MA 127 BP 44 EP 45 PG 2 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700128 ER PT J AU Daud, A Hamid, O Robert, C Hodi, FS Wolchok, JD Hwu, WJ Weber, JS Kefford, R Hersey, P Joshua, AM Joseph, R Gangadhar, TC Dronca, R Patnaik, A Zarour, H Gerigich, K Lunceford, J Emacipator, K Dolled-Filhart, M Li, X Kang, P Ebbinghaus, S Ribas, A AF Daud, A. Hamid, O. Robert, C. Hodi, F. S. Wolchok, J. D. Hwu, W. J. Weber, J. S. Kefford, R. Hersey, P. Joshua, A. M. Joseph, R. Gangadhar, T. C. Dronca, R. Patnaik, A. Zarour, H. Gerigich, K. Lunceford, J. Emacipator, K. Dolled-Filhart, M. Li, X. Kang, P. Ebbinghaus, S. Ribas, A. TI Relationship between programmed death ligand 1 (PD-L1) expression and clinical outcome in patients (pts) with melanoma (MEL) treated with pembrolizumab (pembro; MK-3475) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Daud, A.] Univ Calif San Francisco, Med Div Hematol & Med Oncol, San Francisco, CA 94143 USA. [Hamid, O.] Angeles Clin & Res Inst, Melanoma Ctr, Los Angeles, CA USA. [Robert, C.] Gustave Roussy, Villejuif Paris Sud, France. [Robert, C.] INSERM, U981, Villejuif Paris Sud, France. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolchok, J. D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hwu, W. J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Weber, J. S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Kefford, R.] Westmead Hosp, Crown Princess Mary Canc Ctr, Sydney, NSW, Australia. [Kefford, R.] Australia Univ Sydney, Melanoma Inst, Sydney, NSW, Australia. [Hersey, P.] Univ Sydney, Sydney, NSW 2006, Australia. [Joshua, A. M.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Joseph, R.] Mayo Clin, Jacksonville, FL 32224 USA. [Gangadhar, T. C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Dronca, R.] Mayo Clin, Rochester, MN USA. [Patnaik, A.] South Texas Accelerated Res Therapeut, Phase Res 1, San Antonio, TX USA. [Zarour, H.] Univ Pittsburgh, Pittsburgh, PA USA. [Gerigich, K.; Lunceford, J.; Emacipator, K.; Dolled-Filhart, M.; Li, X.; Kang, P.; Ebbinghaus, S.] Merck & Co Inc, Mol Biomarkers & Diagnost, Whitehouse Stn, NJ USA. [Ribas, A.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 1 U2 8 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 NOV PY 2014 VL 50 SU 6 MA 140 BP 48 EP 49 PG 2 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700141 ER PT J AU Castro, C Peterson, V Ullal, A Agasti, S Tuang, S Miller, N Birrer, M Weissleder, R AF Castro, C. Peterson, V. Ullal, A. Agasti, S. Tuang, S. Miller, N. Birrer, M. Weissleder, R. TI Leveraging a novel DNA barcoding platform for integrated profiling and pharmacodynamic readouts SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Castro, C.] Massachusetts Gen Hosp, Ctr Canc, Med Ctr Syst Biol, Boston, MA USA. [Peterson, V.; Ullal, A.; Agasti, S.; Tuang, S.; Miller, N.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Birrer, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol Radiol, Boston, MA 02114 USA. NR 0 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 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2014 VL 50 SU 6 MA 161 BP 54 EP 54 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700162 ER PT J AU Williams, M Sims, D Lih, J Datta, A Hamilton, S Iafrate, AJ Sklar, J Sadis, S Takabe, N Tricoli, J Doroshow, J Conley, B AF Williams, M. Sims, D. Lih, J. Datta, A. Hamilton, S. Iafrate, A. J. Sklar, J. Sadis, S. Takabe, N. Tricoli, J. Doroshow, J. Conley, B. TI Development of a targeted NGS assay system for patient enrollment to the NCI-MATCH study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Williams, M.; Sims, D.; Lih, J.; Datta, A.] NCI, Mol Charterizat & Clin Assay Dev Lab, Frederick, MD 21701 USA. [Hamilton, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Iafrate, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sklar, J.] Yale Univ, Med Ctr, New Haven, CT USA. [Sadis, S.] Life Technol, Compendia, Foster City, CA USA. [Takabe, N.] NCI, CTEP, Bethesda, MD 20892 USA. [Tricoli, J.; Conley, B.] NCI, CDP, Shady Grove, MD USA. [Doroshow, J.] NCI, DCTD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2014 VL 50 SU 6 MA 232 BP 78 EP 78 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700233 ER PT J AU Johnson, S Johnson, N Chi, D Primack, B Cruz, C Stover, D Greifenberg, AK Cao, S O'Connor, K Baselga, J Balmana, J Serra, V Geyer, M D'Andrea, A Lim, E Shapiro, GI AF Johnson, S. Johnson, N. Chi, D. Primack, B. Cruz, C. Stover, D. Greifenberg, A. K. Cao, S. O'Connor, K. Baselga, J. Balmana, J. Serra, V. Geyer, M. D'Andrea, A. Lim, E. Shapiro, G. I. TI Reversal of primary and acquired PARP-inhibitor resistance in BRCA-mutated triple-negative breast cancers by inhibition of transcriptional cyclin-dependent kinases (CDKs) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Johnson, S.; Stover, D.; O'Connor, K.; Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnson, N.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Chi, D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Primack, B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Cruz, C.; Balmana, J.; Serra, V.] Vall dHebron Inst Oncol, Expt Therapeut Grp, Barcelona, Spain. [Greifenberg, A. K.; Geyer, M.] Max Planck Inst Mol Physiol, Dept Phys Biochem, Bonn, Germany. [Cao, S.; D'Andrea, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baselga, J.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Lim, E.] Ludwig Inst Canc Res, Olivia Newton John Canc Wellness Ctr, Melbourne, Vic 3050, Australia. NR 0 TC 0 Z9 0 U1 4 U2 4 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 NOV PY 2014 VL 50 SU 6 MA 238 BP 80 EP 80 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700239 ER PT J AU Chen, J Amato, K Wang, S Youngblood, V Brantley-Sieders, D Cook, R Tan, L Gray, N AF Chen, J. Amato, K. Wang, S. Youngblood, V. Brantley-Sieders, D. Cook, R. Tan, L. Gray, N. TI Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Chen, J.; Amato, K.; Wang, S.; Youngblood, V.; Brantley-Sieders, D.; Cook, R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Tan, L.; Gray, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 50 SU 6 MA 297 BP 98 EP 98 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700298 ER PT J AU Krishnan, B Hanna, SC Wilson, HL Bailey, ST Damrauer, JS Simamura, T Levine, RL Wong, KK Johnson, GL Kim, WY AF Krishnan, B. Hanna, S. C. Wilson, H. L. Bailey, S. T. Damrauer, J. S. Simamura, T. Levine, R. L. Wong, K. K. Johnson, G. L. Kim, W. Y. TI Tyk2-src dependence of kidney cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Krishnan, B.; Hanna, S. C.; Wilson, H. L.; Bailey, S. T.; Damrauer, J. S.; Johnson, G. L.; Kim, W. Y.] Univ N Carolina, Chapel Hill, NC USA. [Krishnan, B.; Wilson, H. L.; Bailey, S. T.; Damrauer, J. S.; Kim, W. Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Dept Pharmacol, Chapel Hill, NC USA. [Simamura, T.] Loyola Univ Chicago, Inst Oncol, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, Leukemia Serv, Dept Med, New York, NY 10021 USA. [Wong, K. K.] Harvard Univ, Sch Med, Dept Med, Dana Farber Harvard Canc Ctr,Dept Med Oncol, Boston, MA USA. [Wong, K. K.] Lowe Ctr Thorac Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 50 SU 6 MA 299 BP 98 EP 98 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700300 ER PT J AU Schalck, A Frederick, DT Hammond, MR Ferreiro-Neira, I Cooper, ZA Cusack, JC Lawrence, DP Flaherty, KT Wargo, JA Sullivan, RJ AF Schalck, A. Frederick, D. T. Hammond, M. R. Ferreiro-Neira, I. Cooper, Z. A. Cusack, J. C. Lawrence, D. P. Flaherty, K. T. Wargo, J. A. Sullivan, R. J. TI Optimal sequencing schedules for combining BRAF inhibition with BCL-2 inhibition SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Schalck, A.; Frederick, D. T.; Hammond, M. R.; Lawrence, D. P.; Flaherty, K. T.; Sullivan, R. J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA. [Ferreiro-Neira, I.; Cusack, J. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cooper, Z. A.; Wargo, J. A.] MDACC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2014 VL 50 SU 6 MA 314 BP 102 EP 102 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700315 ER PT J AU Tolcher, A Goss, G Gordon, M Gandhi, L Papadopoulos, KP Rasco, D Pedersen, M Fischer, J Ames, W Xiong, H Dudley, M Munasinghe, W Ansell, P Holen, K Vokes, E AF Tolcher, A. Goss, G. Gordon, M. Gandhi, L. Papadopoulos, K. P. Rasco, D. Pedersen, M. Fischer, J. Ames, W. Xiong, H. Dudley, M. Munasinghe, W. Ansell, P. Holen, K. Vokes, E. TI A phase 1/2 study evaluating the safety, pharmacokinetics and efficacy of ABT-414 in subjects with advanced solid tumors likely to over-express the epidermal growth factor receptor (EGFR) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Tolcher, A.; Papadopoulos, K. P.; Rasco, D.] START, San Antonio, TX USA. [Goss, G.] Ottawa Hosp Canc Ctr, Ottawa, ON, Canada. [Gordon, M.] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Gandhi, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fischer, J.; Ames, W.; Xiong, H.; Dudley, M.; Munasinghe, W.; Ansell, P.; Holen, K.] AbbVie, N Chicago, IL USA. [Vokes, E.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 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 NOV PY 2014 VL 50 SU 6 MA 342 BP 111 EP 111 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700343 ER PT J AU de Weger, V Lolkema, MP Dickson, M Le Cesne, A Wagner, A Merqui-Roelvink, M Varga, A Tap, W Schwartz, G Demetri, G Zheng, W Tuffal, G Mace, S Miao, H Schellens, JHM de Jonge, M AF de Weger, V. Lolkema, M. P. Dickson, M. Le Cesne, A. Wagner, A. Merqui-Roelvink, M. Varga, A. Tap, W. Schwartz, G. Demetri, G. Zheng, W. Tuffal, G. Mace, S. Miao, H. Schellens, J. H. M. de Jonge, M. TI A first-in-human (FIH) safety and pharmacological study of SAR405838, a novel HDM2 antagonist, in patients with solid malignancies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [de Weger, V.; Merqui-Roelvink, M.; Schellens, J. H. M.] Netherlands Canc Inst, Amsterdam, Netherlands. [Lolkema, M. P.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Lolkema, M. P.; de Jonge, M.] Erasmus MC Canc Inst, Rotterdam, Netherlands. [Dickson, M.; Tap, W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Le Cesne, A.; Varga, A.] Gustave Roussy, Villejuif, France. [Wagner, A.; Demetri, G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schwartz, G.] Columbia Univ, Med Ctr, New York, NY USA. [Zheng, W.; Miao, H.] Sanofi Oncol, Cambridge, MA USA. [Tuffal, G.] Sanofi R&D, DSAR, Montpellier, France. [Mace, S.] Sanofi Oncol, Vitry Sur Seine, France. NR 0 TC 3 Z9 3 U1 0 U2 5 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 NOV PY 2014 VL 50 SU 6 MA 378 BP 121 EP 122 PG 2 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700379 ER PT J AU Choueiri, TK Escudier, B Pal, SK Jonasch, E Heng, D Powles, T Arkenau, HT Clark, E D'Cruz, C Frigault, M Nash, AF Morgan, SR AF Choueiri, T. K. Escudier, B. Pal, S. Kumar Jonasch, E. Heng, D. Powles, T. Arkenau, H. T. Clark, E. D'Cruz, C. Frigault, M. Nash, A. F. Morgan, S. R. TI cMet: Proof-of-concept clinical trial with volitinib in patients with advanced papillary renal cell cancer (PRCC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Choueiri, T. K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Escudier, B.] Inst Gustave Roussy, Immunotherapy Unit, Villejuif, France. [Pal, S. Kumar] City Hope Natl Med Ctr, Comprehens Canc Ctr Duarte, Duarte, CA USA. [Jonasch, E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Heng, D.] Tom Baker Canc Clin, Calgary, AB, Canada. [Powles, T.] St Bartholomews Hosp, Med Oncol Ctr, London, England. [Arkenau, H. T.] Sarah Cannon Res Inst, London, England. [Clark, E.; D'Cruz, C.; Frigault, M.] AstraZeneca, Boston, MA USA. [Nash, A. F.; Morgan, S. R.] AstraZeneca, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 0 U1 2 U2 3 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 NOV PY 2014 VL 50 SU 6 MA 395 BP 126 EP 127 PG 2 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700396 ER PT J AU Corcoran, R Coffee, EM Van Allen, E Ahronian, LG Wagle, N Kwak, EL Faris, JE Iafrate, AJ Garraway, LA Engelman, JA AF Corcoran, R. Coffee, E. M. Van Allen, E. Ahronian, L. G. Wagle, N. Kwak, E. L. Faris, J. E. Iafrate, A. J. Garraway, L. A. Engelman, J. A. TI Clinical acquired resistance to combined RAF/EGFR or RAF/MEK inhibition in BRAF mutant colorectal cancer (CRC) patients through MAPK pathway alterations SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Corcoran, R.; Coffee, E. M.; Ahronian, L. G.; Kwak, E. L.; Faris, J. E.; Iafrate, A. J.; Engelman, J. A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Van Allen, E.; Wagle, N.; Garraway, L. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2014 VL 50 SU 6 MA 428 BP 141 EP 141 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700429 ER PT J AU Enderle, D Brinkmann, K Koestler, T Bentink, S Flaherty, KT Skog, J Noerholm, M AF Enderle, D. Brinkmann, K. Koestler, T. Bentink, S. Flaherty, K. T. Skog, J. Noerholm, M. TI Monitoring therapy response and resistance mutations in circulating RNA and DNA of plasma from patients with malignant melanoma SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Enderle, D.; Brinkmann, K.; Koestler, T.; Bentink, S.; Noerholm, M.] Exosome Diagnost GmbH, Martinsried, Germany. [Flaherty, K. T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Skog, J.] Exosome Diagnost Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 50 SU 6 MA 454 BP 149 EP 149 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700455 ER PT J AU Kwak, EL Juric, D Cleary, JM Cote, G Hilton, JF Flaherty, KT Wood, K Rance, C Barrett, S Shapiro, GI AF Kwak, E. L. Juric, D. Cleary, J. M. Cote, G. Hilton, J. F. Flaherty, K. T. Wood, K. Rance, C. Barrett, S. Shapiro, G. I. TI Treatment of advanced solid tumors with golvatinib (E7050) in combination with lenvatinib (E7080) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Kwak, E. L.; Juric, D.; Cote, G.; Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cleary, J. M.; Hilton, J. F.; Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wood, K.] Eisai Europe Ltd, Hatfield, Herts, England. [Rance, C.; Barrett, S.] Eisai Inc, Woodcliff Lake, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2014 VL 50 SU 6 MA 484 BP 158 EP 158 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700485 ER PT J AU Bardia, A Chavez-MacGregor, C Modi, S Campone, M Ma, B Kittaneh, M Dirix, L Motta, M Zhang, V Bhansali, S Fjaellskog, ML Oliveira, M AF Bardia, A. Chavez-MacGregor, C. Modi, S. Campone, M. Ma, B. Kittaneh, M. Dirix, L. Motta, M. Zhang, V. Bhansali, S. Fjaellskog, M. L. Oliveira, M. TI Triple blockade with LEE011, everolimus, and exemestane in women with ER+/HER2-advanced/metastatic breast cancer: results from a Phase Ib clinical trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Bardia, A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Chavez-MacGregor, C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Modi, S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Campone, M.] Inst Cancerol Ouest Rene Gauducheau, St Herblain, France. [Ma, B.] Chinese Univ Hong Kong, Dept Clin Oncol, Phase Clin Trial Ctr 1, Hong Kong, Hong Kong, Peoples R China. [Kittaneh, M.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Dirix, L.] Sint Augustinus Hosp, Antwerp, Belgium. [Motta, M.; Zhang, V.; Fjaellskog, M. L.] Novartis Inst Biomed Res, Cambridge, MA USA. [Bhansali, S.] Novartis Pharmaceut, Oncol, E Hanover, NJ USA. [Oliveira, M.] Vail dHebron Univ Hosp VHIO, Barcelona, Spain. NR 0 TC 2 Z9 2 U1 3 U2 3 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 NOV PY 2014 VL 50 SU 6 MA 500 BP 163 EP 163 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700501 ER PT J AU Soucheray, M Kikuchi, E Pulido, I Akbay, E Becker, JH Christensen, CL Johnson, N Patel, TB Carretero, J Wong, KK Shimamura, T AF Soucheray, M. Kikuchi, E. Pulido, I. Akbay, E. Becker, J. H. Christensen, C. L. Johnson, N. Patel, T. B. Carretero, J. Wong, K. K. Shimamura, T. TI Strategies to overcome resistance to BET bromodomain inhibitor in KRAS/LKB1 mutant NSCLC SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Soucheray, M.; Becker, J. H.] Loyola Univ Chicago, Oncol Res Inst, Maywood, IL USA. [Kikuchi, E.; Akbay, E.; Wong, K. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Johnson, N.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Patel, T. B.] Loyola Univ Chicago, Maywood, IL USA. [Shimamura, T.] Loyola Univ, Med Ctr, Oncol Res Inst, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2014 VL 50 SU 6 MA 593 BP 191 EP 191 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700594 ER PT J AU Pollyea, DA de Botton, S Fathi, AT Stein, EM Tallman, MS Agresta, S Bowden, C Fan, B Prah, M Yang, H Yen, K Stone, RM AF Pollyea, D. A. de Botton, S. Fathi, A. T. Stein, E. M. Tallman, M. S. Agresta, S. Bowden, C. Fan, B. Prah, M. Yang, H. Yen, K. Stone, R. M. TI Clinical safety and activity in a phase I trial of AG-120, a first in class, selective, potent inhibitor of the IDH1-mutant protein, in patients with IDH1 mutant positive advanced hematologic malignancies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Pollyea, D. A.] Univ Colorado, Ctr Canc, Aurora, CO USA. Inst Gustave Roussy, Villejuif, France. [Fathi, A. T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Stein, E. M.; Tallman, M. S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Agresta, S.; Bowden, C.; Fan, B.; Prah, M.; Yang, H.; Yen, K.] Agios Pharmaceut, Cambridge, MA USA. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 2 U2 4 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 NOV PY 2014 VL 50 SU 6 MA 1LBA BP 195 EP 195 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700597 ER PT J AU Soria, J Sequist, LV Goldman, JW Wakelee, HA Gadgeel, SM Varga, A Yu, HA Solomon, BJ Ou, SH Papadimitrakopoulou, V Oxnard, GR Horn, L Dziadziuszko, R Chao, B Spira, AI Liu, S Mekhail, T Matheny, S Litten, J Camidge, RD AF Soria, J. Sequist, L. V. Goldman, J. W. Wakelee, H. A. Gadgeel, S. M. Varga, A. Yu, H. A. Solomon, B. J. Ou, S. H. Papadimitrakopoulou, V. Oxnard, G. R. Horn, L. Dziadziuszko, R. Chao, B. Spira, A. I. Liu, S. Mekhail, T. Matheny, S. Litten, J. Camidge, R. D. TI Interim phase 2 results of study CO-1686-008: A phase 1/2 study of the irreversible, mutant selective, EGFR inhibitor rociletinib (CO-1686) in patients with advanced non small cell lung cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Soria, J.; Varga, A.] Inst Gustave Roussy, Villejuif, France. [Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldman, J. W.] UCLA Santa Monica Hematol Oncol, Santa Monica, CA USA. [Wakelee, H. A.] Stanford Canc Inst, Stanford, CA USA. [Gadgeel, S. M.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Yu, H. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Solomon, B. J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Ou, S. H.] Univ Calif Irvine, Irvine, CA USA. [Papadimitrakopoulou, V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Oxnard, G. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Horn, L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dziadziuszko, R.] Med Univ Gdansk, Dept Radiotherapy & Oncol, Gdansk, Poland. [Chao, B.] Ohio State Univ, Div Med Oncol, Columbus, OH 43210 USA. [Spira, A. I.] Virginia Canc Specialists, Fairfax, VA USA. [Liu, S.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Mekhail, T.] Florida Hosp, Orlando, FL USA. [Matheny, S.; Litten, J.] Clovis Oncol, Boulder, CO USA. [Camidge, R. D.] Univ Colorado, Ctr Canc, Aurora, CO USA. NR 0 TC 2 Z9 2 U1 3 U2 8 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 NOV PY 2014 VL 50 SU 6 MA 10LBA BP 199 EP 199 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700606 ER PT J AU Tabernero, J van Geel, R Bendell, JC Spreafico, A Schuler, M Yoshino, T Delord, JP Yamada, Y Lolkema, MP Fans, JE Eskens, FALM Sharma, S Yaeger, R Lenz, HJ Wainberg, Z Avsar, E Chatterjee, A Jaeger, S Demuth, T Schellens, JHM AF Tabernero, J. van Geel, R. Bendell, J. C. Spreafico, A. Schuler, M. Yoshino, T. Delord, J. P. Yamada, Y. Lolkema, M. P. Fans, J. E. Eskens, F. A. L. M. Sharma, S. Yaeger, R. Lenz, H. J. Wainberg, Z. Avsar, E. Chatterjee, A. Jaeger, S. Demuth, T. Schellens, J. H. M. TI Phase I study of the selective BRAFV600 inhibitor encorafenib (LGX818) combined with cetuximab and with or without the a-specific PI3K inhibitor alpelisib (BYL719) in patients with advanced BRAF mutant colorectal cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 18-21, 2014 CL European Org Res & Treatment Canc, Barcelona, SPAIN SP Natl Canc Inst, Amer Assoc Canc Res HO European Org Res & Treatment Canc C1 [Tabernero, J.] Vall DHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain. [van Geel, R.; Schellens, J. H. M.] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands. [Bendell, J. C.] Sarah Cannon Res Inst, Dept Oncol, Nashville, TN USA. [Spreafico, A.] Princess Margaret Canc Ctr, Dept Oncol, Toronto, ON, Canada. [Schuler, M.] Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany. [Yoshino, T.] Natl Canc Ctr Hosp East, Dept Gastroenterol & Gastrointestinal Oncol, Chiba, Japan. [Delord, J. P.] Inst Claudius Regaud, Dept Med, Toulouse, France. [Yamada, Y.] Natl Canc Ctr, Div Gastrointestinal Oncol, Tokyo, Japan. [Lolkema, M. P.] Univ Med Ctr Utrecht, Dept Med Oncol, Utrecht, Netherlands. [Fans, J. E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Eskens, F. A. L. M.] Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands. [Sharma, S.] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Yaeger, R.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Lenz, H. J.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Wainberg, Z.] UCLA Med Ctr, Dept Med, Santa Monica, CA USA. [Avsar, E.; Chatterjee, A.] Novartis Pharmaceut, Oncol Translat Med, E Hanover, NJ USA. [Jaeger, S.] Novartis Inst Biomed Res, Cambridge, MA USA. [Demuth, T.] Novartis Pharma AG, Oncol Translat Med, Basel, Switzerland. NR 0 TC 3 Z9 3 U1 1 U2 2 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 NOV PY 2014 VL 50 SU 6 MA 11LBA BP 199 EP 199 PG 1 WC Oncology SC Oncology GA AY7RC UT WOS:000347755700607 ER PT J AU Fromson, JA Iodice, KE Donelan, K Birnbaum, RJ AF Fromson, John A. Iodice, Kristin E. Donelan, Karen Birnbaum, Robert J. TI Supporting the Returning Veteran: Building Linkages Between Clergy and Health Professionals SO JOURNAL OF PSYCHIATRIC PRACTICE LA English DT Article DE veterans healthcare; clergy; medical education; psychiatrists; posttraumatic stress disorder; traumatic brain injury ID POSTTRAUMATIC-STRESS; BARRIERS; CARE; AFGHANISTAN; IRAQ AB Objective. Rather than seeking psychiatric services, veterans often turn to clergy members as first responders to cope with exposure to traumatic events. The goal of this study was to evaluate clergy preparedness to assist with these issues and to determine if an educational symposium geared toward this population would increase preparedness and collaboration with psychiatrists. Methods. A pre- and post-conference survey was administered to clergy members who attended an educational symposium on the benefits of collaboration between psychiatry and spirituality for service members. Results. Analyses found that clergy frequently self-reported difficulties recognizing symptoms of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and identifying resources. After attending a symposium on the topic, follow-up data indicated significant increases in the clergy's preparedness to address traumatic events. Conclusions. Educational programs may assist clergy in filling knowledge gaps related to recognizing symptoms of PTSD and TBI and providing resources to veterans and their family members. C1 [Fromson, John A.; Iodice, Kristin E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Birnbaum, Robert J.] Partners Hlthcare, Boston, MA USA. RP Fromson, JA (reprint author), Brigham & Womens Faulkner Hosp, Dept Psychiat, 1153 Ctr St, Boston, MA 02130 USA. EM jfromson@bics.bwh.harvard.edu FU Red Sox Foundation-Massachusetts General Hospital Home Base Program; Massachusetts General Hospital Psychiatry Academy FX This research was sponsored by the Red Sox Foundation-Massachusetts General Hospital Home Base Program and the Massachusetts General Hospital Psychiatry Academy. The findings of this study were presented at a poster session of the Mysell Research Colloquium, Harvard Medical School, on March 30, 2011 in Boston, MA. NR 15 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 1527-4160 EI 1538-1145 J9 J PSYCHIATR PRACT JI J. Psychiatr. Pract. PD NOV PY 2014 VL 20 IS 6 BP 479 EP 483 DI 10.1097/01.pra.0000456598.89234.76 PG 5 WC Psychiatry SC Psychiatry GA CA0CR UT WOS:000348583000010 PM 25406054 ER PT J AU Teshiba, R Kawano, S Wang, LL He, LJ Naranjo, A London, WB Seeger, RC Gastier-Foster, JM Look, AT Hogarty, MD Cohn, SL Maris, JM Park, JR Shimada, H AF Teshiba, Risa Kawano, Shinya Wang, Larry L. He, Lejian Naranjo, Arlene London, Wendy B. Seeger, Robert C. Gastier-Foster, Julie M. Look, A. Thomas Hogarty, Michael D. Cohn, Susan L. Maris, John M. Park, Julie R. Shimada, Hiroyuki TI Age-Dependent Prognostic Effect by Mitosis-Karyorrhexis Index in Neuroblastoma: A Report from the Children's Oncology Group SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE age cut-off; International Neuroblastoma Pathology Classification; mitosis-karyorrhexis index; neuroblastoma; prognosis ID N-MYC; PATHOLOGY CLASSIFICATION; NEURO-BLASTOMA; CANCER-GROUP; INTERNATIONAL CRITERIA; EMBRYONIC LETHALITY; TUMORS; SUBSETS; GANGLIONEUROBLASTOMA; EXPRESSION AB Prognostic effects of Mitosis-Karyorrhexis Index (MKI) used in the International Neuroblastoma Pathology Classification (INPC) are age-dependent. A total of 4,282 neuroblastomas reviewed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory (8/1/2001-3/31/2012) included 2,365 low-MKI (L-MKI), 1,068 intermediate-MKI (I-MKI), and 849 high-MKI (H-MKI) tumors. Cox proportional hazards models were fit to determine age cut-offs at which the relative risk of event/death was maximized in each MKI class. Backward-selected Cox models were fit to determine the prognostic strength of the age cut-offs for survival in the presence of other prognostic factors. The age cut-offs used in the INPC for L-MKI tumors (<60 months, n = 2,710, 84.0% +/- 1.0% event-free survival [EFS], 93.8 +/- 0.7% overall survival [OS] vs >= 60 months, n = 195, 49.8% +/- 4.6% EFS, 71.7% +/- 4.1% OS; P < 0.0001) and I-MKI tumors (<18 months, n = 568, 83.8% +/- 2% EFS, 93.7% +/- 1.3% OS vs >= 18 months, n = 500, 51.4% +/- 2.9% EFS, 66.7% +/- 2.7% OS; P < 0.0001) were within the effective range for distinguishing prognostic groups. As for H-MKI tumors (no cut-off age in the INPC, 51.0% +/- 2.2% EFS, 64.4% +/- 2.1% OS), a new cut-off of 3-4 months was suggested (<4 months, n = 38, 82.3% +/- 8.4% EFS, 81.8% +/- 8.5% OS vs >= 4 months, n = 811, 49.6% +/- 2.2% EFS, 63.7% +/- 2.1% OS, P = 0.0034 and 0.0437, respectively). Multivariate analyses revealed that cut-offs of 60 and 18 months for L-MKI and I-MKI tumors, respectively, were independently prognostic. However, the cut-off of 4 months for H-MKI tumors did not reach statistical significance in the presence of other factors. The age cut-offs for MKI classes (60 months for L-MKI, 18 months for I-MKI, no cut-off for H-MKI) in the current INPC are reasonable and effective for distinguishing prognostic groups with increased risk of event/death for older patients. C1 [Teshiba, Risa; Kawano, Shinya; Wang, Larry L.; He, Lejian; Shimada, Hiroyuki] Childrens Hosp Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. [Teshiba, Risa; Kawano, Shinya; Wang, Larry L.; He, Lejian; Seeger, Robert C.; Shimada, Hiroyuki] Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA. [Naranjo, Arlene] Univ Florida, Childrens Oncol Grp Stat, Dept Biostat, Gainesville, FL 32607 USA. [Naranjo, Arlene] Univ Florida, Ctr Data, Gainesville, FL 32607 USA. [London, Wendy B.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA 02215 USA. [London, Wendy B.] Harvard Univ, Sch Med, Childrens Oncol Grp Stat, Boston Childrens Hosp, Boston, MA 02215 USA. [London, Wendy B.] Harvard Univ, Sch Med, Ctr Data, Boston Childrens Hosp, Boston, MA 02215 USA. [London, Wendy B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Seeger, Robert C.] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43205 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Hogarty, Michael D.; Maris, John M.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Cohn, Susan L.] Univ Chicago, Dept Pediat, Div Hematol Oncol, Chicago, IL 60637 USA. [Park, Julie R.] Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98105 USA. [Park, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98105 USA. RP Shimada, H (reprint author), Childrens Hosp Los Angeles, Dept Pathol & Lab Med, 4650 Sunset Blvd,MS 43, Los Angeles, CA 90027 USA. EM hshimada@chla.usc.edu OI Cohn, Susan/0000-0001-5749-7650 FU National Institute of Health [U10 CA98413, U10 CA98543] FX This work was partly supported by grants from the National Institute of Health (U10 CA98413 and U10 CA98543). NR 33 TC 4 Z9 5 U1 1 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 EI 1615-5742 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD NOV-DEC PY 2014 VL 17 IS 6 BP 441 EP 449 DI 10.2350/14-06-1505-OA.1 PG 9 WC Pathology; Pediatrics SC Pathology; Pediatrics GA CA0LN UT WOS:000348609300005 PM 25207821 ER PT J AU Partridge, A AF Partridge, A. TI "Oncobrain" - is it real and what can be done? SO BREAST LA English DT Meeting Abstract C1 [Partridge, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD NOV PY 2014 VL 23 SU 1 MA IN11 BP S5 EP S6 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AY5EC UT WOS:000347594900012 ER PT J AU Rosenberg, S Ruddy, K Tamimi, R Gelber, S Schapira, L Come, S Borges, V Larsen, B Garber, J Partridge, A AF Rosenberg, S. Ruddy, K. Tamimi, R. Gelber, S. Schapira, L. Come, S. Borges, V. Larsen, B. Garber, J. Partridge, A. TI BRCA1/BRCA2 (BRCA) testing in young women with breast cancer: patterns; motivations and implications for treatment decisions SO BREAST LA English DT Meeting Abstract C1 [Rosenberg, S.; Larsen, B.; Garber, J.; Partridge, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ruddy, K.] Mayo Clin, Dept Med Oncol, Rochester, MN USA. [Tamimi, R.] Brigham & Womens Hosp, Dept Channing Div Network Med, Boston, MA 02115 USA. [Gelber, S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Schapira, L.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Come, S.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Borges, V.] Univ Colorado, Ctr Canc, Dept Med Oncol, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD NOV PY 2014 VL 23 SU 1 MA PO18 BP S8 EP S8 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AY5EC UT WOS:000347594900016 ER PT J AU Sachdev, R Rosenberg, SM Ruddy, KJ Schapira, L Come, S Borges, V Larsen, B Gelber, S Tamimi, RM Partridge, AH AF Sachdev, R. Rosenberg, S. M. Ruddy, K. J. Schapira, L. Come, S. Borges, V. Larsen, B. Gelber, S. Tamimi, R. M. Partridge, A. H. TI Cognitive coping in young women with breast cancer SO BREAST LA English DT Meeting Abstract C1 [Sachdev, R.; Rosenberg, S. M.; Larsen, B.; Partridge, A. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ruddy, K. J.] Mayo Clin, Dept Med Oncol, Rochester, MN USA. [Schapira, L.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Come, S.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Borges, V.] Univ Colorado, Dept Med Oncol, Aurora, CO USA. [Gelber, S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tamimi, R. M.] Brigham & Womens Hosp, Dept Channing, Div Network Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD NOV PY 2014 VL 23 SU 1 MA HM32 BP S13 EP S13 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AY5EC UT WOS:000347594900030 ER PT J AU Tritos, NA AF Tritos, Nicholas A. TI The role of pasireotide in the treatment of acromegaly SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Editorial Material ID HYPERGLYCEMIA; MANAGEMENT; THERAPY C1 [Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Tritos, Nicholas A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. EM ntritos@partners.org NR 10 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD NOV PY 2014 VL 2 IS 11 BP 855 EP 856 DI 10.1016/S2213-8587(14)70175-5 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AY8BP UT WOS:000347779800003 PM 25260837 ER PT J AU Dai, Y Clark, J Zheng, KN Kujoth, GC Prolla, TA Simon, DK AF Dai, Ying Clark, Joanne Zheng, Kangni Kujoth, Gregory C. Prolla, Tomas A. Simon, David K. TI Somatic mitochondrial DNA mutations do not increase neuronal vulnerability to MPTP in young POLG mutator mice SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Aging; Parkinson's disease; mtDNA mutations; Oxidative stress; Neurodegeneration; Tyrosine hydroxylase ID SUBSTANTIA-NIGRA NEURONS; PARKINSONS-DISEASE; DELETIONS; NEURODEGENERATION; DYSFUNCTION; MECHANISMS AB Mitochondrial DNA (mtDNA) mutations are hypothesized to play a pathogenic role in aging and age-related neurodegenerative diseases such as Parkinson's disease (PD). In support of this, high levels of somatic mtDNA mutations in "POLG mutator" mice carrying a proofreading-deficient form of mtDNA polymerase gamma (Polg(D257A)) lead to a premature aging phenotype. However, the relevance of this finding to the normal aging process has been questioned as the number of mutations is greater even in young POLG mutator mice, which shows no overt phenotype, than levels achieved during normal aging in mice. Vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) increases with age, and we hypothesized that this may result in part from the accumulation with age of somatic mtDNA mutations. If correct, then levels of mutations in young (2-3 month old) POLG mutator mice should be sufficient to increase vulnerability to MPTP. In contrast, we find that susceptibility to MPTP in both heterozygous and homozygous POLG mutator mice at this young age is not different from that of wild type littermate controls as measured by levels of tyrosine hydroxylase positive (TH+) striatal terminals, striatal dopamine and its metabolites, a marker of oxidative damage, or stereological counts of TH+ and total substantia nigra neurons. These unexpected results do not support the hypothesis that somatic mtDNA mutations contribute to the age-related vulnerability of dopaminergic neurons to MPTP. It remains possible that somatic mtDNA mutations influence vulnerability to other stressors, or require additional time for the deleterious consequences to manifest. Furthermore, the impact of the higher levels of mutations present at older ages in these mice was not assessed in our study, although a prior study also failed to detect an increase in vulnerability to MPTP in older mice. With these caveats, the current data do not provide evidence for a role of somatic mtDNA mutations in determining the vulnerability to MPIP. (C) 2014 Elsevier Inc. All rights reserved. C1 [Dai, Ying; Clark, Joanne; Zheng, Kangni; Simon, David K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA. [Zheng, Kangni] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kujoth, Gregory C.] Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. [Prolla, Tomas A.] Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA. RP Dai, Y (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Room CLS 628, Brookline, MA 02445 USA. EM ydai@bidmc.harvard.edu FU National Institute on Aging [1R03AG035223-01] FX This work was supported by the National Institute on Aging (1R03AG035223-01; DKS). NR 22 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 2014 VL 46 BP 62 EP 67 DI 10.1016/j.ntt.2014.10.004 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA AZ1NR UT WOS:000348006100009 PM 25450660 ER PT J AU Alberti, CF Shahar, A Crundall, D AF Alberti, Concetta F. Shahar, Amit Crundall, David TI Are experienced drivers more likely than novice drivers to benefit from driving simulations with a wide field of view? SO TRANSPORTATION RESEARCH PART F-TRAFFIC PSYCHOLOGY AND BEHAVIOUR LA English DT Article ID HAZARD PERCEPTION; OF-VIEW; VISUAL INFORMATION; RISK PERCEPTION; EYE-MOVEMENTS; ATTENTION; SEARCH AB This study aimed to further our understanding of the impact of a restricted field of view on visual search and hazard perception, by comparing novice and experienced driver performance in a driving simulator as a function of the available field of view. Participants encountered a series of virtual hazards during their drive while viewing the world under narrow or wide field of view conditions. The results showed that all drivers were more likely to avoid the hazards when presented with a wide view, even though the hazards only occurred in an area of the screen that was visible in both the wide and narrow view conditions. Experienced drivers also tended to have fewer crashes, and this appeared to be related to a greater speed reduction 10 metres before the hazard. This speed reduction was greatest in the wide field of view condition suggesting that additional information from wider eccentricities was useful in safely navigating the hazardous events. Gaze movement recording revealed that only experienced drivers made overt use of wider eccentricities, and this was typically in advance of any visual cues that might help identify the hazard. This suggests that either early overt attention to wider eccentricities, or continuous covert attention to these extra-foveal regions on approach to the hazard, is responsible for the safer behaviour of experienced drivers when presented with a wide field of view. We speculate about the possible underlying mechanism and discuss possible consequences for HP tests. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Alberti, Concetta F.; Shahar, Amit; Crundall, David] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England. RP Alberti, CF (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Schepens Eye Res Inst,Med Sch, 20 Staniford St, Boston, MA 02141 USA. EM conce.alberti@gmail.com OI Crundall, David/0000-0002-6030-3631 NR 37 TC 3 Z9 3 U1 4 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1369-8478 EI 1873-5517 J9 TRANSPORT RES F-TRAF JI Transp. Res. Pt. F-Traffic Psychol. Behav. PD NOV PY 2014 VL 27 BP 124 EP 132 DI 10.1016/j.trf.2014.09.011 PN A PG 9 WC Psychology, Applied; Transportation SC Psychology; Transportation GA AY7SC UT WOS:000347758200012 ER PT J AU Goehler, A Gazelle, GS AF Goehler, Alexander Gazelle, G. Scott TI Examining the Use of Comparative and Cost-Effectiveness Analyses in Radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE comparative effectiveness analysis; cost-effectiveness analysis; modeling; patient-related outcomes; value demonstration ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; SERVICES TASK-FORCE; ACUTE CHEST-PAIN; CORONARY CT ANGIOGRAPHY; LUNG-CANCER MORTALITY; MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT; DECISION-SUPPORT; HEALTH; OUTCOMES AB OBJECTIVE. This article explores key principles of comparative effectiveness analysis-in particular, how radiologic comparative and cost-effectiveness studies differ from other clinical trials. Exemplary studies are reviewed to show how comparative effectiveness has been implemented in radiology and how future studies might be conducted. Finally, the article closes with a discussion of several additional key themes relevant to quality and value in clinical radiology going forward. CONCLUSION. Comparative effectiveness is likely to require a paradigm shift in thinking within the discipline. For new radiologic applications to be accepted, we will need to show at least a significant change in treatment planning and at best a meaningful change in patient outcomes. This shift will require a forward-thinking approach to robust evidence generation for new imaging modalities or indications and the inclusion of other modes of value demonstration such as clinical decision support and intelligent data mining. C1 [Goehler, Alexander] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06520 USA. [Goehler, Alexander; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Goehler, Alexander; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Goehler, Alexander] Univ Duisburg Essen, Alfried Krupp von Bohlen & Halbach Fdn, Inst Hlth Syst Management, Essen, Germany. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Goehler, A (reprint author), Yale Univ, Sch Med, Dept Radiol, 333 Cedar St,POB 208042, New Haven, CT 06520 USA. EM agoehler@post.harvard.edu NR 52 TC 5 Z9 5 U1 0 U2 2 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 NOV PY 2014 VL 203 IS 5 BP 939 EP 944 DI 10.2214/AJR.14.12887 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2JM UT WOS:000347415700029 PM 25341130 ER PT J AU Lam, DL Pandharipande, PV Lee, JM Lehman, CD Lee, CI AF Lam, Diana L. Pandharipande, Pari V. Lee, Janie M. Lehman, Constance D. Lee, Christoph I. TI Imaging-Based Screening: Understanding the Controversies SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE false-positive; incidental findings; overdiagnosis; screening ID MANAGING INCIDENTAL FINDINGS; SERVICES TASK-FORCE; FLEISCHNER SOCIETY GUIDELINES; RADIATION-INDUCED CANCER; GENE MUTATION CARRIERS; COST-CONSCIOUS CARE; BREAST-CANCER; WHITE PAPER; COMMITTEE II; LUNG-CANCER AB OBJECTIVE. The goals of this article are to provide an overview of controversial aspects of imaging-based screening and to elucidate potential risks that may offset anticipated benefits. CONCLUSION. Current controversial topics associated with imaging-based screening include false-positive results, incidental findings, overdiagnosis, radiation risks, and costs. Alongside the benefits of screening, radiologists should be prepared to discuss these additional diagnostic consequences with providers and patients to better guide shared decision making regarding imaging-based screening. C1 [Lam, Diana L.; Lee, Janie M.; Lehman, Constance D.; Lee, Christoph I.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98109 USA. [Pandharipande, Pari V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Inst Technol Assessment, Boston, MA USA. [Lee, Christoph I.] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. RP Lee, CI (reprint author), Univ Washington, Sch Med, Dept Radiol, 825 Eastlake Ave E,G3-200, Seattle, WA 98109 USA. EM stophlee@uw.edu FU GE Healthcare; National Institutes of Health, National Cancer Institute [K07CA133097]; Medical Imaging and Technology Alliance; Association of University Radiologists FX C. I. Lee is funded in part by GE Healthcare and the Association of University Radiologists (GERRAF award) and has been a paid consultant for GE Healthcare. P. V. Pandharipande is funded in part by the National Institutes of Health, National Cancer Institute (award number K07CA133097) and is also funded by the Medical Imaging and Technology Alliance for unrelated research. C. D. Lehman has been a paid consultant for GE Healthcare, Bayer HealthCare, and Philips Healthcare. D. L. Lam and J. M. Lee have no disclosures. The research content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, GE Healthcare, or the Association of University Radiologists. NR 64 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 NOV PY 2014 VL 203 IS 5 BP 952 EP 956 DI 10.2214/AJR.14.13049 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2JM UT WOS:000347415700031 PM 25341132 ER PT J AU Mangano, MD Rahman, A Choy, G Sahani, DV Boland, GW Gunn, AJ AF Mangano, Mark D. Rahman, Arifeen Choy, Garry Sahani, Dushyant V. Boland, Giles W. Gunn, Andrew J. TI Radiologists' Role in the Communication of Imaging Examination Results to Patients: Perceptions and Preferences of Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE patient-centered radiology; quality improvement; radiology reporting ID REFERRING PHYSICIAN; ACCESS; STYLE AB OBJECTIVE. It has been suggested that radiology reporting practices would be improved if radiologists were to discuss the results of an examination directly with the patient. The attitudes and preferences of patients with regard to direct communication with the radiologist are not well-defined. The purpose of this study was to survey patients about their preferred method of receiving radiologic results. MATERIALS AND METHODS. An anonymous survey was distributed to adult patients undergoing contrast-enhanced CT or MRI over a 2-week period in June 2013. RESULTS. The response rate was 58.4% (642 responses). For normal examination results, the preferred mode of communication was a telephone call from the ordering physician (34.1%); only 12% of respondents opted for a telephone call from the radiologist, and 2.6% chose a face-to-face meeting with the radiologist. For abnormal test results, the preferred mode of communication was also a telephone call from the ordering physician (49.8%); 14.4% of respondents selected a telephone call from the radiologist, and 8.3% chose a face-to-face meeting with the radiologist. Patients preferred receiving very detailed versions of radiology reports for both normal (46.4%) and abnormal (81.8%) test results. Patients also expressed a desire to have access to at least key images from their examinations. CONCLUSION. Patients prefer receiving both normal and abnormal examination results from the physicians who ordered the examination rather than the radiologist. They also prefer to receive very detailed examination results rather than a brief summary in lay terms. C1 [Mangano, Mark D.; Rahman, Arifeen; Gunn, Andrew J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Mangano, Mark D.; Rahman, Arifeen; Gunn, Andrew J.] Harvard Med, Boston, MA 02114 USA. [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol & Teleradiol, Boston, MA 02114 USA. [Choy, Garry; Sahani, Dushyant V.; Boland, Giles W.] Harvard Univ, Sch Med, Boston, MA USA. [Sahani, Dushyant V.; Boland, Giles W.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Gunn, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. EM agunnmd@gmail.com NR 25 TC 13 Z9 13 U1 0 U2 2 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 NOV PY 2014 VL 203 IS 5 BP 1034 EP 1039 DI 10.2214/AJR.14.12470 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2JM UT WOS:000347415700042 PM 25341142 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Reply to "Tomosynthesis Assisting in Localization of Breast Lesions for Ultrasound Targeting Seen on One Mammographic View Only" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02163 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02163 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 203 IS 5 BP W556 EP W556 DI 10.2214/AJR.14.12957 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2JM UT WOS:000347415700018 PM 25341176 ER PT J AU Tsapaki, V Rehani, MM AF Tsapaki, Virginia Rehani, Madan M. TI I Perform More Than 100 Interventional Procedures Every Year but Have Never Seen Radiation-Induced Skin Injury: Am I Missing Something? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE deterministic effects; interventional procedures; radiation-induced skin injuries; radiation protection; tissue reactions C1 [Tsapaki, Virginia] Konstantopoulio Gen Hosp, Athens, Greece. [Rehani, Madan M.] Massachusetts Gen Hosp, Boston, MA 02214 USA. [Rehani, Madan M.] Harvard Univ, Sch Med, Boston, MA 02214 USA. RP Rehani, MM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02214 USA. EM madan.rehani@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 203 IS 5 BP W462 EP W463 DI 10.2214/AJR.13.11765 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2JM UT WOS:000347415700001 PM 25341159 ER PT J AU Walker, CM Digumarthy, SR AF Walker, Christopher M. Digumarthy, Subba R. TI Reply to "Can Morphologic Characteristics of the Reversed Halo Sign Narrow the Differential Diagnosis of Pulmonary Infections?" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter C1 [Walker, Christopher M.] Univ Missouri, St Lukes Hosp Kansas City, Kansas City, MO 64110 USA. [Digumarthy, Subba R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Walker, CM (reprint author), Univ Missouri, St Lukes Hosp Kansas City, Kansas City, MO 64110 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2014 VL 203 IS 5 BP W559 EP W559 DI 10.2214/AJR.14.12996 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AY2JM UT WOS:000347415700020 PM 25341178 ER PT J AU Chang, EW Gardecki, J Pitman, M Wilsterman, EJ Patel, A Tearney, GJ Iftimia, N AF Chang, Ernest W. Gardecki, Joseph Pitman, Martha Wilsterman, Eric J. Patel, Ankit Tearney, Guillermo J. Iftimia, Nicusor TI Low coherence interferometry approach for aiding fine needle aspiration biopsies SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE low coherence interferometry; fine-needle aspiration biopsy; tissue-type differentiation; breast cancer biopsy aiding capabilities ID BREAST-TUMOR MARGINS; TOMOGRAPHY; LESIONS; FEASIBILITY; DIAGNOSIS; ACCURACY; MASSES AB We present portable preclinical low-coherence interference (LCI) instrumentation for aiding fine needle aspiration biopsies featuring the second-generation LCI-based biopsy probe and an improved scoring algorithm for tissue differentiation. Our instrument and algorithm were tested on 38 mice with cultured tumor mass and we show the specificity, sensitivity, and positive predictive value of tumor detection of over 0.89, 0.88, and 0.96, respectively. (C) The Authors. Published by SPIE C1 [Chang, Ernest W.; Patel, Ankit; Iftimia, Nicusor] Phys Sci Inc, Andover, MA 01810 USA. [Gardecki, Joseph; Wilsterman, Eric J.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Pitman, Martha] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr Dr, Andover, MA 01810 USA. EM iftimia@psicorp.com NR 24 TC 1 Z9 1 U1 0 U2 1 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV PY 2014 VL 19 IS 11 AR 116005 DI 10.1117/1.JBO.19.11.116005 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AY2TM UT WOS:000347442000028 PM 25375634 ER PT J AU Fredriksen-Goldsen, KI Simoni, JM Kim, HJ Lehavot, K Walters, KL Yang, J Hoy-Ellis, CP Muraco, A AF Fredriksen-Goldsen, Karen I. Simoni, Jane M. Kim, Hyun-Jun Lehavot, Keren Walters, Karina L. Yang, Joyce Hoy-Ellis, Charles P. Muraco, Anna TI The Health Equity Promotion Model: Reconceptualization of Lesbian, Gay, Bisexual, and Transgender (LGBT) Health Disparities SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE health equity; health disparities; mental and physical health; sexual orientation; sexual identity; gender identity; lesbain; gay; bisexual; transgender; minority health ID OF-THE-LITERATURE; SEXUAL ORIENTATION; MENTAL-HEALTH; PSYCHOLOGICAL DISTRESS; UNITED-STATES; OLDER-ADULTS; LIFE-COURSE; PSYCHIATRIC-DISORDERS; ALLOSTATIC LOAD; RISK BEHAVIORS AB National health initiatives emphasize the importance of eliminating health disparities among historically disadvantaged populations. Yet, few studies have examined the range of health outcomes among lesbian, gay, bisexual, and transgender (LGBT) people. To stimulate more inclusive research in the area, we present the Health Equity Promotion Model-a framework oriented toward LGBT people reaching their full mental and physical health potential that considers both positive and adverse health-related circumstances. The model highlights (a) heterogeneity and intersectionality within LGBT communities; (b) the influence of structural and environmental context; and (c) both health-promoting and adverse pathways that encompass behavioral, social, psychological, and biological processes. It also expands upon earlier conceptualizations of sexual minority health by integrating a life course development perspective within the health-promotion model. By explicating the important role of agency and resilience as well as the deleterious effect of social structures on health outcomes, it supports policy and social justice to advance health and well-being in these communities. Important directions for future research as well as implications for health-promotion interventions and policies are offered. C1 [Fredriksen-Goldsen, Karen I.; Kim, Hyun-Jun; Walters, Karina L.; Hoy-Ellis, Charles P.] Univ Washington, Sch Social Work, Seattle, WA 98105 USA. [Simoni, Jane M.; Yang, Joyce] Univ Washington, Dept Psychol, Seattle, WA 98105 USA. [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. [Muraco, Anna] Loyola Marymount Univ, Dept Sociol, Los Angeles, CA 90045 USA. RP Fredriksen-Goldsen, KI (reprint author), Univ Washington, Sch Social Work, 4101 15th Ave NE,Box 354900, Seattle, WA 98105 USA. EM fredrikk@u.washington.edu OI Simoni, Jane/0000-0002-8711-1576 FU National Institute on Aging [2R01AG026526-03A1]; Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment; VA Puget Sound Health Care System, Seattle, Washington FX This research was supported in part by grants from the National Institute on Aging (2R01AG026526-03A1). The views expressed in this article are those of the authors and do not necessarily reflect the views of the National Institutes of Health, National Institute of Aging, University of Washington, Department of Veterans Affairs, or Loyola Marymount University. In addition, Keren Lehavot's contribution to this article is supported by resources from the Department of Veterans Affairs Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment and the VA Puget Sound Health Care System, Seattle, Washington. NR 124 TC 19 Z9 19 U1 6 U2 42 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0002-9432 EI 1939-0025 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD NOV PY 2014 VL 84 IS 6 BP 653 EP 663 DI 10.1037/ort0000030 PG 11 WC Psychiatry; Social Work SC Psychiatry; Social Work GA AX4TM UT WOS:000346924100008 PM 25545433 ER PT J AU Landers, S Closson, EF Oldenburg, CE Holcomb, R Spurlock, S Mimiaga, MJ AF Landers, Stewart Closson, Elizabeth F. Oldenburg, Catherine E. Holcomb, Richard Spurlock, Shannon Mimiaga, Matthew J. TI HIV Prevention Needs Among Street-Based Male Sex Workers in Providence, Rhode Island SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DRUG-USE; BISEXUAL MEN; SAN-FRANCISCO; CONDOM USE; INFECTION; ABUSE; RISK; GAY; IDENTIFICATION; TRANSMISSION AB We examined data derived from a needs assessment of the personal and social characteristics and HIV risk behavior of street-based male sex workers, in Providence, Rhode Island, who engage in transactional sexual intercourse with other men. Substance use, injected drugs, needle sharing, and psychosocial distress were highly prevalent among the sample. History of physical, sexual, and emotional abuse was associated with increased risk of condomless anal sexual intercourse with paying male clients. C1 [Landers, Stewart; Spurlock, Shannon; Mimiaga, Matthew J.] John Snow Inc, Boston, MA 02210 USA. [Closson, Elizabeth F.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Oldenburg, Catherine E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Holcomb, Richard] Project Weber, Providence, RI USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Landers, S (reprint author), John Snow Inc, 44 Farnsworth St, Boston, MA 02210 USA. EM landers@jsi.com NR 22 TC 1 Z9 1 U1 2 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2014 VL 104 IS 11 BP E100 EP E102 DI 10.2105/AJPH.2014.302188 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AX8UR UT WOS:000347184400017 PM 25211761 ER PT J AU DeSalvo, MN Douw, L Takaya, S Liu, HS Stufflebeam, SM AF DeSalvo, Matthew N. Douw, Linda Takaya, Shigetoshi Liu, Hesheng Stufflebeam, Steven M. TI Task-dependent reorganization of functional connectivity networks during visual semantic decision making SO BRAIN AND BEHAVIOR LA English DT Article DE Connectomics; default mode network; functional magnetic resonance imaging; graph theory; language; memory; resting state ID DEFAULT-MODE NETWORK; INDEPENDENT COMPONENT ANALYSIS; WORKING-MEMORY PERFORMANCE; HUMAN BRAIN; PREFRONTAL CORTEX; MRI; REST; MODULATION; ACTIVATION; RETRIEVAL AB Introduction: Functional MRI is widely used to study task-related changes in neuronal activity as well as resting-state functional connectivity. In this study, we explore task-related changes in functional connectivity networks using fMRI. Dynamic connectivity may represent a new measure of neural network robustness that would impact both clinical and research efforts. However, prior studies of task-related changes in functional connectivity have shown apparently conflicting results, leading to several competing hypotheses regarding the relationship between task-related and resting-state brain networks. Methods: We used a graph theory-based network approach to compare functional connectivity in healthy subjects between the resting state and when performing a clinically used semantic decision task. We analyzed fMRI data from 21 healthy, right-handed subjects. Results: While three nonoverlapping, highly intraconnected functional modules were observed in the resting state, an additional language-related module emerged during the semantic decision task. Both overall and within-module connectivity were greater in default mode network (DMN) and classical language areas during semantic decision making compared to rest, while between-module connectivity was diffusely greater at rest, revealing a more widely distributed pattern of functional connectivity at rest. Conclusions: The results of this study suggest that there are differences in network topology between resting and task states. Specifically, semantic decision making is associated with a reduction in distributed connectivity through hub areas of the DMN as well as an increase in connectivity within both default and language networks. C1 [DeSalvo, Matthew N.; Douw, Linda; Takaya, Shigetoshi; Liu, Hesheng; Stufflebeam, Steven M.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [DeSalvo, Matthew N.; Douw, Linda; Takaya, Shigetoshi; Liu, Hesheng; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP DeSalvo, MN (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM mnd12@nmr.mgh.harvard.edu FU National Institutes of Health [P41-RR14075, R01-NS037462, R0-1NS069696, 5R01-NS060918]; NCRR; NIH Human Connectome Project; Mental Illness and Neuroscience Discovery Institute; NWO (Dutch Organization for Scientific Research) Rubicon grant; Epilepsy Foundation; RSNA Research Medical Student Grant [RMS 1310]; Japan Epilepsy Research Foundation FX This work was supported by the National Institutes of Health (Grants P41-RR14075, R01-NS037462, R0-1NS069696, 5R01-NS060918), NCRR, the NIH Human Connectome Project, the Mental Illness and Neuroscience Discovery Institute, the NWO (Dutch Organization for Scientific Research) Rubicon grant, the Epilepsy Foundation, RSNA Research Medical Student Grant (RMS 1310), and the Japan Epilepsy Research Foundation. NR 37 TC 6 Z9 6 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2162-3279 J9 BRAIN BEHAV JI Brain Behav. PD NOV PY 2014 VL 4 IS 6 BP 877 EP 885 DI 10.1002/brb3.286 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AX5NZ UT WOS:000346974700011 PM 25365802 ER PT J AU Walkey, AJ Hammill, BG Curtis, LH Benjamin, EJ AF Walkey, Allan J. Hammill, Bradley G. Curtis, Lesley H. Benjamin, Emelia J. TI Long-term Outcomes Following Development of New-Onset Atrial Fibrillation During Sepsis SO CHEST LA English DT Article ID MEDICARE BENEFICIARIES; ADMINISTRATIVE DATA; RISK-FACTORS; UNITED-STATES; STROKE; MORTALITY; HEART; TRENDS; ANTICOAGULATION; STRATIFICATION AB BACKGROUND: New-onset atrial fibrillation (AF) is associated with adverse outcomes during a sepsis hospitalization; however, long-term outcomes following hospitalization with sepsis-associated new-onset AF are unclear. METHODS: We used a Medicare 5% sample to identify patients who survived hospitalization with sepsis between 1999 and 2010. AF status was defined as no AF, prior AF, or new-onset AF based on AF claims during and prior to a sepsis hospitalization. We used competing risk models to determine 5-year risks of AF occurrence, heart failure, ischemic stroke, and mortality aft er the sepsis hospitalization, according to AF status during the sepsis admission. RESULTS: We identified 138,722 sepsis survivors, of whom 95,536 (69%) had no AF during sepsis, 33,646 (24%) had prior AF, and 9,540 (7%) had new-onset AF during sepsis. AF occurrence following sepsis hospitalization was more common among patients with new-onset AF during sepsis (54.9%) than in patients with no AF during sepsis (15.5%). Compared with patients with no AF during sepsis, those with new-onset AF during sepsis had greater 5-year risks of hospitalization for heart failure (11.2% vs 8.2%; multivariable-adjusted hazard ratio [HR], 1.25; 95% CI, 1.16-1.34), ischemic stroke (5.3% vs 4.7%; HR, 1.22; 95% CI, 1.10-1.36), and death (74.8% vs 72.1%; HR, 1.04; 95% CI, 1.01-1.07). CONCLUSIONS: Most sepsis survivors with new-onset AF during sepsis have AF occur aft er discharge from the sepsis hospitalization and have increased long-term risks of heart failure, ischemic stroke, and death. Our findings may have implications for posthospitalization surveillance of patients with new-onset AF during a sepsis hospitalization. C1 [Walkey, Allan J.] Boston Univ, Sch Publ Hlth, Ctr Pulm, Boston, MA USA. [Walkey, Allan J.] Boston Univ, Sch Publ Hlth, Dept Med, Pulm & Crit Care Med Sect, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Med, Sect Cardiovasc Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Med, Sect Prevent Med, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hammill, Bradley G.; Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Curtis, Lesley H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. RP Walkey, AJ (reprint author), 72 E Concord St,R-304, Boston, MA 02118 USA. EM alwalkey@bu.edu OI Walkey, Allan/0000-0003-4685-6894; Benjamin, Emelia/0000-0003-4076-2336 FU US National Institutes of Health, National Heart, Lung, and Blood Institute [K01 HL116768, R01 HL102214, R01 HL092577, R01NS17950] FX This study was funded by the US National Institutes of Health, National Heart, Lung, and Blood Institute [K01 HL116768 (to Dr Walker) and R01 HL102214, R01 HL092577, R01NS17950 (to Dr Benjamin)]. NR 28 TC 24 Z9 24 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2014 VL 146 IS 5 BP 1187 EP 1195 DI 10.1378/chest.14-0003 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AX9HZ UT WOS:000347215500035 PM 24723004 ER PT J AU Shostak, E Majid, A Channick, C AF Shostak, Eugene Majid, Adnan Channick, Colleen TI A 54-Year-Old Woman With Postextubation Stridor SO CHEST LA English DT Editorial Material ID FIBRINOUS TRACHEAL PSEUDOMEMBRANE; TRACHEOBRONCHITIS AB A 54-year-old woman developed a witnessed generalized tonic clonic seizure at work. Paramedics recorded a blood glucose level of 30 mg/dL. Despite normalizing the blood glucose level, the patient's mental status did not improve, and she was intubated in the field. Given the limited view of the glottis, a tracheal tube introducer (Bougie) was used to facilitate intubation. C1 [Shostak, Eugene; Majid, Adnan] Beth Israel Deaconess Med Ctr, Dept Intervent Pulmonol, Boston, MA 02215 USA. [Shostak, Eugene; Channick, Colleen] Massachusetts Gen Hosp, Dept Intervent Pulmonol, Boston, MA 02114 USA. [Channick, Colleen] Massachusetts Gen Hosp, Special Procedures Unit, Boston, MA 02114 USA. RP Channick, C (reprint author), Special Procedures Unit, 55 Fruit St,Bigelow 952, Boston, MA 02114 USA. EM cchannick@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2014 VL 146 IS 5 BP E163 EP E166 DI 10.1378/chest.13-3077 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AX9HZ UT WOS:000347215500005 PM 25367484 ER PT J AU Olshen, A Tang, M Cortes, J Gonen, M Hughes, T Branford, S Quintas-Cardama, A Michor, F AF Olshen, Adam Tang, Min Cortes, Jorge Gonen, Mithat Hughes, Timothy Branford, Susan Quintas-Cardama, Alfonso Michor, Franziska TI Dynamics of chronic myeloid leukemia response to dasatinib, nilotinib, and high-dose imatinib SO HAEMATOLOGICA LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; EARLY CHRONIC-PHASE; TYROSINE KINASE INHIBITORS; CYTOGENETIC RESPONSES; RESISTANCE; THERAPY; INTOLERANCE; MESYLATE; EFFICACY; MUTATION AB Treatment with the tyrosine kinase inhibitor imatinib is the standard of care for newly diagnosed patients with chronic myeloid leukemia. In recent years, several second-generation inhibitors-such as dasatinib and nilotinib have become available: these promise to overcome some of the mutations associated with acquired resistance to imatinib. Despite eliciting similar clinical responses, the molecular effects of these agents on different subpopulations of leukemic cells remain incompletely understood. Furthermore, the consequences of using high-dose imatinib therapy have not been investigated in detail. Here we utilized clinical data from patients treated with dasatinib, nilotinib, or high-dose imatinib, together with a statistical data analysis and mathematical modeling approach, to investigate the molecular treatment response of leukemic cells to these agents. We found that these drugs elicit very similar responses if administered front-line. However, patients display significantly different kinetics when treated second-line, both in terms of differences between front-line and second-line treatment for the same drug, and among agents when used as second-line. We then utilized a mathematical framework describing the behavior of four differentiation levels of leukemic cells during therapy to predict the treatment response kinetics for the different cohorts of patients. The dynamics of BCR-ABL1 clearance observed in our study suggest that the use of standard or high-dose imatinib or a second-generation tyrosine kinase inhibitor such as nilotinib or dasatinib elicits similar responses when administered as front-line therapy for patients with chronic myeloid leukemia in chronic phase. C1 [Olshen, Adam] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tang, Min; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tang, Min; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cortes, Jorge; Quintas-Cardama, Alfonso] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Branford, Susan; Quintas-Cardama, Alfonso] SA Pathol, Dept Genet & Mol Pathol, Rundle Mall, SA, Australia. [Hughes, Timothy; Branford, Susan] Univ Adelaide, Adelaide, SA 5005, Australia. RP Michor, F (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 665 Huntington Ave, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu NR 25 TC 1 Z9 1 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD NOV PY 2014 VL 99 IS 11 BP 1701 EP 1709 DI 10.3324/haematol.2013.085977 PG 9 WC Hematology SC Hematology GA AX6EO UT WOS:000347016300010 PM 25216683 ER PT J AU Seabury, SA Helland, E Jena, AB AF Seabury, Seth A. Helland, Eric Jena, Anupam B. TI Medical Malpractice Reform: Noneconomic Damages Caps Reduced Payments 15 Percent, With Varied Effects By Specialty SO HEALTH AFFAIRS LA English DT Article ID DEFENSIVE MEDICINE; TORT REFORMS; CLAIMS; PHYSICIANS; LITIGATION; LIABILITY; RISK; FREQUENCY; IMPACT; PEDIATRICIANS AB The impact of medical malpractice reforms on the average size of malpractice payments in specific physician specialties is unknown and subject to debate. We analyzed a national sample of malpractice claims for the period 1985-2010, merged with information on state liability reforms, to estimate the impact of state noneconomic damages caps on average malpractice payment size for physicians overall and for ten different specialty categories. We then compared how the effects differed according to the restrictiveness of the cap ($ 250,000 versus $ 500,000). We found that, overall, noneconomic damages caps reduced average payments by $ 42,980 (15 percent), compared to having no cap at all. A more restrictive $ 250,000 cap reduced average payments by $ 59,331 (20 percent), and a less restrictive $ 500,000 cap had no significant effect, compared to no cap at all. The effect of the caps overall varied according to specialty, with the largest impact being on claims involving pediatricians and the smallest on claims involving surgical subspecialties and ophthalmologists. C1 [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA 90089 USA. [Seabury, Seth A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Helland, Eric] Claremont Mckenna Coll, Claremont, CA 91711 USA. [Helland, Eric] RAND Corp, Santa Monica, CA USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Boston, MA USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seabury, SA (reprint author), Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA 90089 USA. EM seabury@usc.edu FU RAND Institute for Civil Justice (ICJ); National Institute on Aging [7R01AG031544]; ICJ; Office of the Director, National Institutes of Health (NIH Early Independence Award) [1DP5OD017897-01] FX Seth Seabury received funding from the RAND Institute for Civil Justice (ICJ) and grant support from the National Institute on Aging (Grant No. 7R01AG031544). Eric Helland received funding from the ICJ. Anupam Jena received an award from the Office of the Director, National Institutes of Health (NIH Early Independence Award No. 1DP5OD017897-01). The Physician Insurers Association of America provided data for this study through an agreement with the RAND Corporation. The association was not involved in the design or conduct of the study or in the interpretation and reporting of findings. [Published online October 22, 2014.] NR 45 TC 3 Z9 3 U1 0 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV PY 2014 VL 33 IS 11 BP 2048 EP 2056 DI 10.1377/hlthaff.2014.0492 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AX8LT UT WOS:000347161700023 PM 25339633 ER PT J AU Villarreal, G Chatterjee, A Oh, SS Oh, DJ Kang, MH Rhee, DJ AF Villarreal, Guadalupe, Jr. Chatterjee, Ayan Oh, Sarah S. Oh, Dong-Jin Kang, Min Hyung Rhee, Douglas J. TI Canonical Wnt Signaling Regulates Extracellular Matrix Expression in the Trabecular Meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE Wnt signaling; beta-catenin; TCF4; miR-29; extracellular matrix; trabecular meshwork; glaucoma; TGF-beta 2; SPARC ID OPEN-ANGLE GLAUCOMA; LOWER INTRAOCULAR-PRESSURES; AQUEOUS-HUMOR; MICE EXHIBIT; BETA-CATENIN; OUTFLOW; CELLS; TGF-BETA-2; STATINS; PATHWAY AB PURPOSE. Canonical Wnt signaling has emerged as a critical regulator of aqueous outflow facility and intraocular pressure (IOP). In this study, we examine the role of canonical Wnt signaling on extracellular matrix (ECM) expression in the trabecular meshwork (TM) and explore the molecular mechanisms involved. METHODS. beta-catenin localization in human TM tissue was examined using immunofluorescent staining. Primary human TM cells were incubated with lithium chloride (LiCl) and the effect on active beta-catenin expression was assessed by immunoblot. Adenovirus expressing a dominant-negative TCF4 mutant that lacks a beta-catenin binding domain was used. Changes in the levels of the microRNA-29 (miR-29) family and ECM proteins were determined by real-time quantitative PCR and immunoblot analysis, respectively. RESULTS. beta-catenin was expressed throughout the TM, with localization primarily to the plasma membrane. Incubation of TM cells with lithium chloride increased the expression of active beta-catenin. Lithium chloride treatment upregulated miR-29b expression, and suppressed the levels of various ECM proteins under both basal and TGF-beta 2 stimulatory conditions. Infection of TM cells with a dominant-negative TCF4 mutant induced ECM levels without a significant change in the expression of the miR-29 family. CONCLUSIONS. Collectively, our data identify the canonical Wnt signaling pathway as an important modulator of ECM expression in the TM and provide a mechanistic framework for its regulation of outflow facility and IOP. C1 [Villarreal, Guadalupe, Jr.; Chatterjee, Ayan; Oh, Sarah S.; Oh, Dong-Jin; Kang, Min Hyung; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Rhee, DJ (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Case Med Ctr, Dept Ophthalmol & Visual Sci, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM DougRhee@aol.com FU Fight for Sight Summer Student Fellowship; Howard Hughes Medical Institute Research Training Fellowship for Medical Students; National Eye Institute [EY 019654-01]; MEEI Vision-Core Grant [EY 014104] FX Supported by Fight for Sight Summer Student Fellowship (GV); Howard Hughes Medical Institute Research Training Fellowship for Medical Students (AC); National Eye Institute EY 019654-01 (DJR); and EY 014104 (MEEI Vision-Core Grant). NR 51 TC 9 Z9 9 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2014 VL 55 IS 11 BP 7433 EP 7440 DI 10.1167/iovs.13-12652 PG 8 WC Ophthalmology SC Ophthalmology GA AX9IR UT WOS:000347217300051 PM 25352117 ER PT J AU Yamaguchi, T Calvacanti, BM Cruzat, A Qazi, Y Ishikawa, S Osuka, A Lederer, J Hamrah, P AF Yamaguchi, Takefumi Calvacanti, Bernardo M. Cruzat, Andrea Qazi, Yureeda Ishikawa, Shizu Osuka, Akinori Lederer, James Hamrah, Pedram TI Correlation Between Human Tear Cytokine Levels and Cellular Corneal Changes in Patients With Bacterial Keratitis by In Vivo Confocal Microscopy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE infectious keratitis; dendritic cells; corneal infection; tears; cytokines ID DENDRITIC CELLS; MICROBIAL KERATITIS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; IL-6 RECEPTOR; INFLAMMATION; INTERLEUKIN-6; EXPRESSION; DISEASE; KERATOCONUS AB PURPOSE. We investigated bilateral tear cytokine levels in patients with unilateral bacterial keratitis (BK) as associated with in vivo confocal microscopic (IVCM) alterations in corneal nerves and dendritiform immune cells (DCs). METHODS. A total of 54 (13 BK, 13 contralateral, 28 healthy controls) tear samples was collected prospectively and analyzed by multiplex microbeads assay. The IVCM of the central cornea was performed on the same day, and assessed for corneal nerve and DC alterations. RESULTS. Interleukin-1 beta, IL-6, and IL-8 were significantly elevated only in affected eyes (66.6 +/- 26.8, 7174 +/- 2430, and 810 +/- 315 Pg/mL, respectively; P = 0.04, P < 0.001, and P < 0.001, respectively), compared to healthy controls (13.0 +/- 4.0, 171.8 +/- 32.1, and 56.5 +/- 33.8 Pg/mL). Levels of chemokine ligand 2 (CCL-2), IL-10, and IL-17a were elevated only in contralateral eyes (813 +/- 478, 86.7 +/- 38.3, and 3350 +/- 881 Pg/mL, respectively; P = 0.02, P = 0.01, and P = 0.04, respectively), compared to controls (73.7 +/- 25.3, 17.5 +/- 4.9, and 1350 +/- 337 Pg/mL). Triggering receptor expressed on myeloid cells (TREM)-1 was significantly elevated in affected (551 +/- 231 Pg/mL, P = 0.02) and contralateral unaffected (545 +/- 298 Pg/mL, P = 0.03) eyes compared to controls (31.3 +/- 12.4 pg/mL). The density of DCs was significantly increased in affected (226.9 +/- 37.3 cells/mm(2), P < 0.001) and unaffected (122.3 +/- 23.7 cells/mm(2), P < 0.001) eyes compared to controls (22.7 +/- 5.9 cells/mm(2)). Sub-basal nerve density significantly decreased in affected (3337 +/- 1615 mu m/mm(2), P < 0.001) and contralateral (13,230 +/- 1635 mu m/mm(2), P < 0.001) eyes compared to controls (21,200 +/- 545 mu m/mm(2)). Levels of IL-1 beta, IL-6, and IL-8 were significantly correlated with DC density (R = 0.40, R = 0.55, and R = 0.31, all P < 0.02) and nerve density (R = -0.30, R = -0.53, and R = -0.39, all P < 0.01). CONCLUSIONS. Proinflammatory tear cytokines are elevated bilaterally in patients with unilateral BK, and are correlated strongly with alterations in DCs and nerve density as detected by IVCM. C1 [Yamaguchi, Takefumi; Calvacanti, Bernardo M.; Cruzat, Andrea; Qazi, Yureeda; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Cornea Serv,Massachusetts Eye & Ear Infirm,Ocular, Boston, MA 02114 USA. [Yamaguchi, Takefumi; Hamrah, Pedram] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Schepens Eye Res I, Boston, MA 02114 USA. [Ishikawa, Shizu; Osuka, Akinori; Lederer, James] Harvard Univ, Sch Med, Brigham Womens Hosp, Dept Surg, Boston, MA 02114 USA. RP Hamrah, P (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst Mass Eye & Ear, 20 Staniford St, Boston, MA 02114 USA. EM pedram_hamrah@meei.harvard.edu OI Osuka, Akinori/0000-0002-7575-7927 FU NIH [K08-EY020575, L30-EY021919]; Research to Prevent Blindness Career Development Award; Uehara Memorial Foundation FX Supported by NIH Grants K08-EY020575 (PH) and L30-EY021919 (PH), Research to Prevent Blindness Career Development Award (PH), and an Uehara Memorial Foundation Fellowship (TY). The authors alone are responsible for the content and writing of the paper. NR 58 TC 6 Z9 7 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2014 VL 55 IS 11 BP 7457 EP 7466 DI 10.1167/iovs.14-15411 PG 10 WC Ophthalmology SC Ophthalmology GA AX9IR UT WOS:000347217300054 PM 25324281 ER PT J AU Walker, A AF Walker, Allan TI Intestinal Colonization and Programming of the Intestinal Immune Response SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE intestinal colonization; intestinal defenses; probiotics ID GUT MICROBIOTA; DISEASE; SYSTEM; HEALTH; INFLAMMATION; HOMEOSTASIS; PROBIOTICS; TOLERANCE; BACTERIA AB Initial bacterial colonization of the gut is a vital component of the development of the gastrointestinal tract, particularly mucosal immune protection, during the neonatal period. Newborn infants in their protected intrauterine environment are suddenly thrust into a highly contaminated extrauterine state. Although mucosal host defenses have developed in utero during fetal maturation because of the stimulation of ingested trophic factors in amniotic fluid, actual active protection only occurs when colonizing bacteria stimulate the gut mucosal barrier. Colonization evolves over a period of about 1 year and is dependent on the mode of delivery, use of perinatal antibiotics, age at birth, and infant feeding. A fully colonized gut consists of 10(14) bacteria, establishes a symbiotic relationship with the host and insures normal development and immune homeostasis. Colonizing bacteria can also affect the epithelial mucosal barrier and the innate and adaptive immune systems. Disruption of normal colonization, dysbiosis, is associated with increased expression of disease. Evidence exists that the use of probiotics with dysbiosis may prevent disease expression. C1 [Walker, Allan] Harvard Univ, Mucosal Immunol & Biol Res Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat,Med Sch,MassGen Hosp Children, Boston, MA USA. RP Walker, A (reprint author), Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, 114 16th St 114-3501, Charlestown, MA 02129 USA. EM wwalker@partners.org FU National Institute of Health (NIH) [P30 DK040561, P01 DK033506]; National Institute of Child Health and Human Development, Bethesda, MD [R01 HD012437, R01 HD059126] FX Supported by National Institute of Health (NIH) grants: National Institute of Digestive, Diabetes and Kidney Diseases P30 DK040561, P01 DK033506; and National Institute of Child Health and Human Development, R01 HD012437, R01 HD059126, Bethesda, MD. NR 21 TC 5 Z9 5 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2014 VL 48 SU 1 BP S8 EP S11 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AX9UA UT WOS:000347246300004 PM 25291135 ER PT J AU Atukunda, EC Siedner, MJ Obua, C Mugyenyi, GR Twagirumukiza, M Agaba, AG AF Atukunda, Esther C. Siedner, Mark J. Obua, Celestino Mugyenyi, Godfrey R. Twagirumukiza, Marc Agaba, Amon G. TI Sublingual Misoprostol versus Intramuscular Oxytocin for Prevention of Postpartum Hemorrhage in Uganda: A Double-Blind Randomized Non-Inferiority Trial SO PLOS MEDICINE LA English DT Article ID 3RD STAGE; RISK-FACTORS; BLOOD-LOSS; LABOR; MANAGEMENT; STATEMENT; FEVER AB Background: Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 mu g, for prevention of PPH during active management of labor. Methods and Findings: We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 mu g of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss >= 500 ml within 24 h of delivery. Secondary outcomes included measured blood loss >= 1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol and oxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a regional referral hospital with capacity for emergency surgery and blood transfusion. High-risk women were excluded from participation. Conclusions: Misoprostol 600 mu g is inferior to oxytocin 10 IU for prevention of primary PPH in active management of labor. These data support use of oxytocin in settings where it is available. While not powered to do so, the study found no significant differences in rate of severe PPH, need for blood transfusion, postpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol. C1 [Atukunda, Esther C.; Mugyenyi, Godfrey R.; Agaba, Amon G.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Obua, Celestino] Makerere Univ, Coll Hlth Sci, Sch Biomed Sci, Dept Pharmacol & Therapeut, Kampala, Uganda. [Twagirumukiza, Marc] Univ Ghent, Fac Med & Hlth Sci, Dept Pharmacol, B-9000 Ghent, Belgium. RP Atukunda, EC (reprint author), Mbarara Univ Sci & Technol, Mbarara, Uganda. EM estheratukunda@gmail.com FU Father Bash Foundation; Divine Mercy Hospital [FBF PS1981] FX Funding for this study was provided by the Father Bash Foundation and Divine Mercy Hospital scholarship awards to ECA (FBF PS1981). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 2 Z9 2 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD NOV PY 2014 VL 11 IS 11 AR e1001752 DI 10.1371/journal.pmed.1001752 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AX5YX UT WOS:000347001600001 PM 25369200 ER PT J AU Bi, WL Chiocca, EA AF Bi, Wenya Linda Chiocca, E. Antonio TI Image-Guided Maximal Resection of Intrinsic Tumors SO WORLD NEUROSURGERY LA English DT Editorial Material DE Brain tumor resection; Intraoperative MRI ID SURVIVAL CLINICAL ARTICLE; GLIOBLASTOMA; EXTENT C1 [Chiocca, E. Antonio] Harvard Univ, Sch Med, Inst Neurosci, Dept Neurosurg,Brigham & Womens Faulkner Hosp, Boston, MA 02138 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Inst Neurosci, Dept Neurosurg,Brigham & Womens Faulkner Hosp, Boston, MA 02138 USA. EM eachiocca@partners.org NR 5 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 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD NOV PY 2014 VL 82 IS 5 BP 604 EP 605 DI 10.1016/j.wneu.2014.04.070 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AX9XK UT WOS:000347252300043 PM 24802845 ER PT J AU Jho, DH Biller, BMK Agarwalla, PK Swearingen, B AF Jho, David H. Biller, Beverly M. K. Agarwalla, Pankaj K. Swearingen, Brooke TI Pituitary Apoplexy: Large Surgical Series with Grading System SO WORLD NEUROSURGERY LA English DT Article DE Hemorrhagic macroadenoma; Pituitary adenoma; Pituitary apoplexy; Transsphenoidal surgery ID CLINICAL-FEATURES; TUMOR APOPLEXY; MANAGEMENT; ADENOMAS; HEMORRHAGE; OUTCOMES; SURGERY AB BACKGROUND: Pituitary apoplexy is an infrequent occurrence that can require timely treatment. The term "pituitary apoplexy" as used in the literature describes a heterogeneous spectrum. There is controversy about which subsets require urgent as opposed to elective surgical treatment or even medical treatment alone. We present a retrospective series of 109 consecutive cases of pituitary apoplexy from a single institution from 1992-2012 and develop a comprehensive classification system to analyze outcome. METHODS: Surgical and endocrine consult databases were reviewed to analyze patterns of presentation, imaging, treatment, and outcomes. RESULTS: Most of the patients in this series presented clinically with "classic" pituitary apoplexy (97%), had magnetic resonance imaging for evaluation (99%), underwent transsphenoidal surgery as their primary treatment (93%), and were found to have pituitary adenomas on histopathology (90%). We categorized patients into 5 grades based on clinical presentation. Tumor volume, cavernous sinus involvement, suprasellar extension, and need for ongoing endocrine replacement correlated with grade. Long-term endocrine replacement at follow-up was required in 62%-68% of patients with a higher grade compared with 0-23% of patients with a lower grade. Higher grade patients tended to undergo earlier surgery after symptom onset. Symptoms resolved or improved with treatment in 92%-100% of patients across all grades with good general outcomes for visual deficits and ocular motility problems, validating management decisions overall. CONCLUSIONS: We offer a simple yet comprehensive grading system to classify the clinical spectrum of pituitary apoplexy, which has implications for management, outcomes, and categorization for future studies. C1 [Jho, David H.] Allegheny Gen Hosp, Dept Neurosurg, Pittsburgh, PA 15212 USA. [Jho, David H.] Allegheny Gen Hosp, Neuroendoscopy Dept, Pittsburgh, PA 15212 USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Agarwalla, Pankaj K.; Swearingen, Brooke] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. EM bswearingen@partners.org NR 32 TC 9 Z9 10 U1 0 U2 1 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 NOV PY 2014 VL 82 IS 5 BP 781 EP 790 DI 10.1016/j.wneu.2014.06.005 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AX9XK UT WOS:000347252300080 PM 24915069 ER PT J AU Brent, GA AF Brent, Gregory A. TI Perchlorate Exposure in Pregnancy and Cognitive Outcomes in Children: It's Not Your Mother's Thyroid SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID THIOCYANATE EXPOSURE; HORMONE; WOMEN; ASSOCIATION; POSTPARTUM; MANAGEMENT; WATER C1 [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Dept Med, 111,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gbrent@ucla.edu FU NIDDK NIH HHS [R01 DK098576, R01 DK98576] NR 22 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP 4066 EP 4068 DI 10.1210/jc.2014-3673 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100020 PM 25372124 ER PT J AU Faje, AT Sullivan, R Lawrence, D Tritos, NA Fadden, R Klibanski, A Nachtigall, L AF Faje, Alexander T. Sullivan, Ryan Lawrence, Donald Tritos, Nicholas A. Fadden, Riley Klibanski, Anne Nachtigall, Lisa TI Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients With Metastatic Melanoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AUTOIMMUNE HYPOPHYSITIS; ADVERSE EVENTS; PHASE-II; CANCER; COMBINATION; ANTIBODY AB Context: Ipilimumab (Ipi) is approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Little is known about Ipi-induced hypophysitis (IH), an important treatment complication. Objective: The objectives of the study were as follows: 1) to examine the prevalence of IH, 2) to characterize the clinical course and treatment outcomes in IH, 3) to identify the risk factors for the development of IH, and 4) to determine optimal strategies for the management of IH. Design: This was a retrospective review. Setting: The study was conducted at a tertiary referral center. Subjects: One hundred fifty-four adult patients with metastatic melanoma were evaluated at Massachusetts General Hospital and were treated with Ipi between March 2008 and December 2013. Intervention(s): The intervention included treatment with Ipi. Main Outcome Measure(s): Pituitary magnetic resonance imaging, pituitary hormone assessment, and patient survival were measured. Results: IH was diagnosed in 17 patients (11%). Male gender (P = .02) and older age (P = .005), but not the cumulative dose of Ipi, were risk factors for IH. All patients with IH had anterior hypopituitarism (none had diabetes insipidus). Hypopituitarism was persistent in most individuals (76%). Diffuse pituitary enlargement was observed exclusively in all cases of IH and, upon retrospective review of magnetic resonance imaging scans, this finding preceded the clinical diagnosis of hypophysitis in eight patients. Pituitary enlargement resolved rapidly (within 40 d in seven of seven patients). Median survival in patients with IH was 19.4 vs 8.8 months (P = .05) in the remainder of the cohort. Conclusions: Male gender and older age are risk factors for IH. Pituitary enlargement is sensitive and specific for IH in the appropriate setting, can precede the clinical diagnosis, and resolves rapidly. Anterior pituitary function recovery is uncommon. The incidence of hypophysitis may positively predict survival in melanoma patients treated with Ipi. C1 [Faje, Alexander T.; Tritos, Nicholas A.; Klibanski, Anne; Nachtigall, Lisa] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Faje, Alexander T.; Tritos, Nicholas A.; Klibanski, Anne; Nachtigall, Lisa] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sullivan, Ryan; Lawrence, Donald; Fadden, Riley] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. RP Faje, AT (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM afaje@partners.org NR 19 TC 43 Z9 43 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP 4078 EP 4085 DI 10.1210/jc.2014-2306 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100022 PM 25078147 ER PT J AU McNabb, B Vittinghoff, E Eastell, R Schwartz, AV Bauer, DC Ensrud, K Barrett-Connor, E Black, DM AF McNabb, Brian Vittinghoff, Eric Eastell, Richard Schwartz, Ann V. Bauer, Douglas C. Ensrud, Kristine Barrett-Connor, Elizabeth Black, Dennis M. TI A Model of BMD Changes After Alendronate Discontinuation to Guide Postalendronate BMD Monitoring SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FRACTURE INTERVENTION TRIAL; LONG-TERM EXTENSION; POSTMENOPAUSAL OSTEOPOROSIS; RANDOMIZED-TRIAL; ZOLEDRONIC ACID; BISPHOSPHONATE THERAPY; VERTEBRAL FRACTURES; WOMEN; BONE; FLEX AB Context: Women stopping alendronate are commonly monitored with serial bone mineral density (BMD) measurements, yet no information exists on how frequently or for whom these measurements should be performed. Objective: The objective of the study was to develop a tool to guide post-alendronate BMD monitoring. Design: A predictive model was constructed to estimate the time until a given percentage of women's BMD T-scores drop below a given threshold that indicates a management change (such as retreatment) would be considered. This model was then used to estimate the time it would take for groups of women defined by their baseline BMDs to drop below the given threshold. Setting: Data were derived from the Fracture Intervention Trial Long Term Extension (FLEX), the largest multicenter clinical trial of its type to date. Participants: Four hundred four women who had received an average of 5.1 years of alendronate during the Fracture Intervention Trial and were subsequently observed for 5 treatment-free years (on placebo) during the FLEX trial were used to estimate the change in BMD over time. Results: If a management change such as alendronate reinitiation would be considered when BMDT-score drops below -2.5, the model shows that women with total hip BMD greater than -1.9 T-scores at the time of alendronate discontinuation have less than a 20% probability that at follow-up, monitoring BMD will be below the threshold within 5 years. The model performed similarly, and results are provided over a range of management change thresholds from -1.75 to -3 T-scores. Conclusions: Using the tool developed in this analysis, it is possible to estimate when BMD repeat measurement after alendronate discontinuation could potentially be useful. Measuring BMD within 5 years after alendronate discontinuation is unlikely to change management for women with total hip BMD 0.6 T-scores above a prespecified retreatment threshold within the range of -1.75 to -3 T-scores. C1 [McNabb, Brian] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA 94121 USA. [McNabb, Brian; Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94117 USA. [McNabb, Brian] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94117 USA. [Vittinghoff, Eric; Schwartz, Ann V.; Bauer, Douglas C.; Black, Dennis M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94117 USA. [Eastell, Richard] Univ Sheffield, Dept Human Metab, Acad Unit Bone Metab, Sheffield S10 2JF, S Yorkshire, England. [Ensrud, Kristine] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Ensrud, Kristine] Vet Affairs Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92093 USA. RP McNabb, B (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Mailing Code 111A1, San Francisco, CA 94121 USA. EM brian.mcnabb@ucsf.edu FU Veterans Affairs Advanced Women's Health Fellowship FX B.M. is supported by the Veterans Affairs Advanced Women's Health Fellowship. NR 30 TC 2 Z9 2 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP 4094 EP 4100 DI 10.1210/jc.2014-1193 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100024 PM 25127011 ER PT J AU Huh, JY Mougios, V Kabasakalis, A Fatouros, I Siopi, A Douroudos, II Filippaios, A Panagiotou, G Park, KH Mantzoros, CS AF Huh, Joo Young Mougios, Vassilis Kabasakalis, Athanasios Fatouros, Ioannis Siopi, Aikaterina Douroudos, Ioannis I. Filippaios, Andreas Panagiotou, Grigorios Park, Kyung Hee Mantzoros, Christos S. TI Exercise-Induced Irisin Secretion Is Independent of Age or Fitness Level and Increased Irisin May Directly Modulate Muscle Metabolism Through AMPK Activation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FNDC5 GENE-EXPRESSION; HUMAN SKELETAL-MUSCLE; ADIPOSE-TISSUE; MESSENGER-RNA; IN-VITRO; HUMANS; OBESITY; BROWN; ASSOCIATION; RESISTANCE AB Context: Irisin has been proposed to be a myokine mediating the effect of exercise on adipocyte browning. The physiology of irisin in humans is not completely understood. Objective: To study the physiology of irisin in healthy individuals with different age and fitness levels and to explore the direct effects of irisin on muscle metabolism. Design, Setting, and Subjects: Treadmill exercise studies were conducted to measure circulating irisin at baseline and in response to exercise among old and young, physically active and sedentary individuals. Also, high- and moderate-intensity swimming was performed in adolescent men and women to study the effect of exercise intensity and the time course of irisin induction by acute bouts of exercise. Human myotubes were treated with recombinant irisin, and the effect on gene expression, cell signaling, and metabolism was examined. Results: Baseline circulating irisin was lower in old (vs young) and physically active (vs sedentary) subjects. Despite differences in basal levels, the percentage increase of irisin by acute bouts of exercise was not related to age or fitness level. The time course study revealed that circulating irisin increased immediately after high-intensity interval exercise and declined 1 hour thereafter. In vitro experiments showed that irisin facilitates glucose and lipid metabolism in human muscle through AMP kinase phosphorylation. Conclusions: Despite the differences in basal irisin levels, exercise-induced irisin secretion is independent of age or fitness level. Increased irisin can directly modulate muscle metabolism through AMP kinase activation. C1 [Huh, Joo Young; Filippaios, Andreas; Panagiotou, Grigorios; Park, Kyung Hee; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mougios, Vassilis; Kabasakalis, Athanasios; Siopi, Aikaterina] Aristotle Univ Thessaloniki, Sch Phys Educ & Sports Sci, Thessaloniki 54124, Greece. [Fatouros, Ioannis; Douroudos, Ioannis I.] Democritus Univ Thrace, Dept Phys Educ & Sport Sci, Komotini 69100, Greece. [Park, Kyung Hee] Hallym Univ, Sacred Heart Hosp, Dept Family Med, Gyeonggi Do 431796, South Korea. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Boston, MA 02130 USA. EM cmantzor@bidmc.harvard.edu OI Panagiotou, Grigorios/0000-0003-0690-1478; Park, Kyung Hee/0000-0001-9806-0076 FU Clinical Science Research and Development Service of the VA Office of Research and Development; Bodosakis Foundation (Greece) FX This work was supported by an award from the Clinical Science Research and Development Service of the VA Office of Research and Development. Part of this study was supported by a donation received from the Bodosakis Foundation (Greece) for instrument purchase. NR 34 TC 28 Z9 30 U1 3 U2 24 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP E2154 EP E2161 DI 10.1210/jc.2014-1437 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100056 PM 25119310 ER PT J AU McFadden, DG Dias-Santagata, D Sadow, PM Lynch, KD Lubitz, C Donovan, SE Zheng, ZL Le, L Iafrate, AJ Daniels, GH AF McFadden, David G. Dias-Santagata, Dora Sadow, Peter M. Lynch, Kerry D. Lubitz, Carrie Donovan, Samuel E. Zheng, Zongli Le, Long Iafrate, A. J. Daniels, Gilbert H. TI Identification of Oncogenic Mutations and Gene Fusions in the Follicular Variant of Papillary Thyroid Carcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THERAPEUTIC TARGET; CANCER; BRAF; ALK; KINASE; PATTERNS; SURVIVAL AB Background: The diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) is increasingly common. Recent studies have suggested that FVPTC is heterogeneous and comprises multiple tumor types with distinct biological behaviors and underlying genetics. Objectives: The purpose of this work was to identify the prevalence of mutations and gene fusions in known oncogenes in a panel representative of the common spectrum of FVPTC diagnosed at an academic medical center and correlate the clinical and pathological features obtained at the initial diagnosis with the tumor genotype. Materials and Methods: We performed SNaPshot genotyping on a panel of 129 FVPTCs of >= 1 cm for 90 point mutations or small deletions in known oncogenes and tumor suppressors and identified gene fusions using an anchored multiplex PCR assay targeting a panel of rearranged oncogenes. Results: We identified a mutation or gene fusion in 70% (89 of 127) of cases. Mutations targeting the RAS family of oncogenes were the most frequently observed class of alterations, present in 36% (46 of 127) of cases, followed by BRAF mutation, present in 30% (38 of 127). We also detected oncogenic rearrangements not previously associated with FVPTC, including TFG-ALK and CREB3L2-PPAR gamma. BRAF mutation was significantly associated with unencapsulated tumor status. Conclusions: These data support the hypothesis that FVPTC is composed of distinct biological entities, with one class being identified by BRAF mutation and support the use of clinical genotyping assays that detect a diverse array of rearrangements involving ALK and PPAR gamma. Additional studies are necessary to identify genetic drivers in the 30% of FVPTCs with no known oncogenic alteration and to better predict behavior in tumors with known genotypes. C1 [McFadden, David G.; Donovan, Samuel E.; Daniels, Gilbert H.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. [Dias-Santagata, Dora; Sadow, Peter M.; Lynch, Kerry D.; Zheng, Zongli; Le, Long; Iafrate, A. J.] Massachusetts Gen Hosp, Dept Med, Dept Pathol, Boston, MA 02114 USA. [Lubitz, Carrie] Massachusetts Gen Hosp, Ctr Canc, Dept Surg, Boston, MA 02114 USA. [Lubitz, Carrie] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP McFadden, DG (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 730-S, Boston, MA 02114 USA. EM mcfadden.david@mgh.harvard.edu RI zheng, zongli/B-2917-2011 OI zheng, zongli/0000-0003-4849-4903 FU Ellison Foundation; National Cancer Institute (Career Development Award) [K08-CA160658]; National Cancer Institute program in Cancer Outcomes Research Training Grant [R25 CA092203]; Massachusetts General Hospital Department of Surgery; Massachusetts General Hospital American Cancer Society Institutional Research Grant FX This work was supported by a grant award to G.H.D. from the Ellison Foundation. D.G.M. is supported by the National Cancer Institute (Career Development Award K08-CA160658). C.C.L. is supported by the National Cancer Institute program in Cancer Outcomes (Research Training Grant (R25 CA092203), Massachusetts General Hospital Department of Surgery and a Massachusetts General Hospital American Cancer Society Institutional Research Grant. NR 25 TC 12 Z9 12 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2014 VL 99 IS 11 BP E2457 EP E2462 DI 10.1210/jc.2014-2611 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AX1ZN UT WOS:000346743100095 PM 25148236 ER PT J AU Munn, LL Padera, TP AF Munn, Lance L. Padera, Timothy P. TI Imaging the lymphatic system SO MICROVASCULAR RESEARCH LA English DT Article DE Imaging; Lymphatic vessels; Technologies; Lymph node; Lymphatic function; Lymphatic metastasis; Lymphography; Fluorescence; Models; Clinical ID POSITRON-EMISSION-TOMOGRAPHY; NEAR-INFRARED FLUORESCENCE; CELL LUNG-CANCER; TRANSBRONCHIAL NEEDLE ASPIRATION; GUIDED INDOCYANINE GREEN; STAGE BREAST-CANCER; MAGNETIC-RESONANCE; NODE METASTASIS; COMPUTED-TOMOGRAPHY; IN-VIVO AB Visualization of the lymphatic system is clinically necessary during diagnosis or treatment of many conditions and diseases; it is used for identifying and monitoring lymphedema, for detecting metastatic lesions during cancer staging and for locating lymphatic structures so they can be spared during surgical procedures. Imaging lymphatic anatomy and function also plays an important role in experimental studies of lymphatic development and function, where spatial resolution and accessibility are better. Here, we review technologies for visualizing and imaging the lymphatic system for clinical applications. We then describe the use of lymphatic imaging in experimental systems as well as some of the emerging technologies for improving these methodologies. (C) 2014 Elsevier Inc. All rights reserved. C1 [Munn, Lance L.; Padera, Timothy P.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM Imunn@mgh.harvard.edu; tpadera@mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Padera, Timothy/0000-0002-3453-9384 FU National Institutes of Health [R01CA149285, R00-CA137167, R21-AI097745, DP2-OD008780] FX This work was funded in part by National Institutes of Health grants R01CA149285 (LLM) and R00-CA137167, R21-AI097745 and DP2-OD008780 (TPP). NR 154 TC 6 Z9 6 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 EI 1095-9319 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 2014 VL 96 SI SI BP 55 EP 63 DI 10.1016/j.mvr.2014.06.006 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AX4IB UT WOS:000346895500009 PM 24956510 ER PT J AU Marshall, AL AF Marshall, Ariela L. TI Diagnosis, Treatment, and Prevention of Venous Thromboembolism in Pregnancy SO POSTGRADUATE MEDICINE LA English DT Article DE thrombosis; venous thromboembolism; anticoagulation; pregnancy ID MOLECULAR-WEIGHT HEPARIN; MASSIVE PULMONARY-EMBOLISM; DEEP-VEIN THROMBOSIS; OF-THE-LITERATURE; ANTIPHOSPHOLIPID ANTIBODIES; POSTPARTUM PERIOD; RISK-FACTORS; UNFRACTIONATED HEPARIN; ANTICOAGULANT-THERAPY; HEART-VALVES AB Pregnancy and the puerperium put women at increased risk of venous thromboembolism (VTE) due to both baseline maternal risk factors and the development of pregnancy-related prothrombotic anatomic and physiologic changes. Pregnant women are at an approximately 5-fold increased risk of VTE compared with nonpregnant women, and the risk of VTE increases further (to >= 20-fold) in puerperium; risk remains increased until approximately 12 weeks postpartum. Pregnancy-related VTE accounts for about 10% of maternal deaths in the developed world. Clinicians should promptly evaluate any signs or symptoms suspicious for VTE, generally starting with ultrasound of the lower extremities. For treatment of women with established VTE, low molecular weight heparins (LMWHs) are preferred due to a favorable safety and efficacy profile. Unfractionated heparin (UFH) and potentially fondaparinux are alternatives. Warfarin should be avoided in the antepartum period due to teratogenicity, and the non-vitamin K oral anticoagulants are currently not recommended due to the lack of data. Low molecular weight heparin, UFH, and warfarin are all acceptable in the postpartum period and for breast-feeding women, but the non-vitamin K oral anticoagulants should be avoided. Prophylaxis (generally with LMWH or in some cases UFH) is recommended for women at highest risk of pregnancy-related VTE, such as those with inherited thrombophilias and a strong family or personal history of VTE. Prophylaxis with LMWH and aspirin is recommended for women with antiphospholipid syndrome. Clinicians should engage in multidisciplinary discussion, particularly around the time of delivery, to manage the details of anticoagulation in their pregnant patients. C1 Dana Farber Canc Inst, Dept Hematol & Med Oncol, Boston, MA 02115 USA. RP Marshall, AL (reprint author), Dana Farber Canc Inst, Dept Hematol & Med Oncol, Boston, MA 02115 USA. NR 79 TC 6 Z9 10 U1 1 U2 14 PU JTE MULTIMEDIA PI WEST CONSHOHOCKEN PA 18 ELIZABETH ST, STE 110, WEST CONSHOHOCKEN, PA 19428 USA SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD NOV PY 2014 VL 126 IS 7 DI 10.3810/pgm.2014.11.2830 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AX2WA UT WOS:000346801800003 PM 25387211 ER PT J AU Li, XB Fryml, L Rodriguez, JJ Taylor, J Borckardt, JJ Short, B Sahlem, G Roberts, D George, MS AF Li, Xingbao Fryml, Leah Rodriguez, Julia Jaskwich Taylor, Joseph Borckardt, Jeff J. Short, Baron Sahlem, Greg Roberts, Donna George, Mark S. TI Safe Management of a Bipolar Depressed Patient With Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) Over 7 Years and > 2 Million Stimuli SO BRAIN STIMULATION LA English DT Letter ID MAJOR DEPRESSION; TMS; MULTISITE C1 [Li, Xingbao; Fryml, Leah; Rodriguez, Julia Jaskwich; Taylor, Joseph; Borckardt, Jeff J.; Short, Baron; Sahlem, Greg; Roberts, Donna; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Brain Stimulat Div, Charleston, SC 29425 USA. [George, Mark S.] Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Li, XB (reprint author), MUSC, IOP, 502 N,67 President St, Charleston, SC 29425 USA. EM lixi@musc.edu NR 7 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD NOV-DEC PY 2014 VL 7 IS 6 SI SI BP 919 EP 921 DI 10.1016/j.brs.2014.09.005 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AW7OZ UT WOS:000346455200027 PM 25440291 ER PT J AU Zhu, B Edson-Heredia, E Guo, J Maeda-Chubachi, T Shen, W Kimball, AB AF Zhu, B. Edson-Heredia, E. Guo, J. Maeda-Chubachi, T. Shen, W. Kimball, A. B. TI Itching is a significant problem and a mediator between disease severity and quality of life for patients with psoriasis: results from a randomized controlled trial SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID PLAQUE PSORIASIS; INDEX PASI; PRURITUS; AREA; MODERATE; OUTCOMES; DLQI AB Background In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity. Objectives To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL. Methods Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results. Results Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P < 0.01). Multiple hierarchical linear regression analyses showed a statistically significant (P < 0.01) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P < 0.05) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score. Conclusions Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis. C1 [Zhu, B.; Edson-Heredia, E.; Maeda-Chubachi, T.; Shen, W.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Guo, J.] InVentiv Hlth Clin, Indianapolis, IN USA. [Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM havardskinstudies@partners.org FU Eli Lilly and Company FX Funding for this study was provided by Eli Lilly and Company. NR 17 TC 8 Z9 8 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2014 VL 171 IS 5 BP 1215 EP 1219 DI 10.1111/bjd.13065 PG 5 WC Dermatology SC Dermatology GA AW9TK UT WOS:000346600000018 PM 24749812 ER PT J AU Shim, EH Livi, CB Rakheja, D Tan, J Benson, D Parekh, V Kho, EY Ghosh, AP Kirkman, R Velu, S Dutta, S Chenna, B Rea, SL Mishur, RJ Li, QH Johnson-Pais, TL Guo, L Bae, S Wei, S Block, K Sudarshan, S AF Shim, Eun-Hee Livi, Carolina B. Rakheja, Dinesh Tan, Jubilee Benson, Daniel Parekh, Vishwas Kho, Eun-Young Ghosh, Arindam P. Kirkman, Richard Velu, Sadanan Dutta, Shilpa Chenna, Balachandra Rea, Shane L. Mishur, Robert J. Li, Qiuhua Johnson-Pais, Teresa L. Guo, Lining Bae, Sejong Wei, Shi Block, Karen Sudarshan, Sunil TI L-2-Hydroxyglutarate: An Epigenetic Modifier and Putative Oncometabolite in Renal Cancer SO CANCER DISCOVERY LA English DT Article ID CELL CARCINOMA; ALPHA-KETOGLUTARATE; MYELOID CANCERS; MUTATIONS; 2-HYDROXYGLUTARATE; ACIDURIA; TET2; DEHYDROGENASE; EXPRESSION; HISTONE AB Through unbiased metabolomics, we identified elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglutaratre (2-OG)-dependent dioxygenases that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifically the d enantiomer, can result from gain-of-function mutations of isocitrate dehydrogenase (IDH1, IDH2) found in several different tumors. In contrast, kidney tumors demonstrate elevations of the l enantiomer of 2HG (l-2HG). High-2HG tumors demonstrate reduced DNA levels of 5-hydroxymethylcytosine (5hmC), consistent with 2HG-mediated inhibition of ten-eleven translocation (TET) enzymes, which convert 5-methylcytosine (5mC) to 5hmC. l-2HG elevation is mediated in part by reduced expression of l-2HG dehydrogenase (L2HGDH). L2HGDH reconstitution in RCC cells lowers l-2HG and promotes 5hmC accumulation. In addition, L2HGDH expression in RCC cells reduces histone methylation and suppresses in vitro tumor phenotypes. Our report identifies l-2HG as an epigenetic modifier and putative oncometabolite in kidney cancer. C1 [Shim, Eun-Hee; Tan, Jubilee; Benson, Daniel; Kho, Eun-Young; Ghosh, Arindam P.; Kirkman, Richard; Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Rakheja, Dinesh] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Parekh, Vishwas; Wei, Shi] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Velu, Sadanan; Dutta, Shilpa; Chenna, Balachandra] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Rea, Shane L.; Mishur, Robert J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Li, Qiuhua; Johnson-Pais, Teresa L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Guo, Lining] Metabolon, Durham, NC USA. [Bae, Sejong] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Block, Karen] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Sudarshan, S (reprint author), Univ Alabama Birmingham, 1105 Fac Off Tower,510 20th St South, Birmingham, AL 35294 USA. EM sudarshan@uab.edu OI CHENNA, BALA CHANDRA/0000-0002-2660-5302 FU NIH [P30 CA013148, K08 CA138774, R01 NCI CA131272]; Urology Care Foundation; Astellas Pharrna Rising Star Award; American Cancer Society [RSG-12-127-01 CNE]; Clinical & Translational Science Awards/Institute for Integration of Medicine and Science [UL1RR025767]; Cancer Prevention Research Institute of Texas [RP120190] FX The research reported its this article was supported by the NIH (P30 CA013148). S. Sudarshan was supported by the NIH (K08 CA138774), the Urology Care Foundation, the Astellas Pharrna Rising Star Award, and the American Cancer Society (RSG-12-127-01 CNE). K. Block was supported by the NIH (R01 NCI CA131272). S. Sudarshan and C.B. Livi were supported by the Clinical & Translational Science Awards/Institute for Integration of Medicine and Science (UL1RR025767). C.B. Livi and K. Block were supported by the Cancer Prevention Research Institute of Texas (RP120190). NR 37 TC 32 Z9 32 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD NOV PY 2014 VL 4 IS 11 BP 1290 EP 1298 DI 10.1158/2159-8290.CD-13-0696 PG 9 WC Oncology SC Oncology GA AW8GY UT WOS:000346500700024 PM 25182153 ER PT J AU Sullivan, JP Nahed, BV Madden, MW Oliveira, SM Springer, S Bhere, D Chi, AS Wakimoto, H Rothenberg, SM Sequist, LV Kapur, R Shah, K Iafrate, AJ Curry, WT Loeffler, JS Batchelor, TT Louis, DN Toner, M Maheswaran, S Haber, DA AF Sullivan, James P. Nahed, Brian V. Madden, Marissa W. Oliveira, Samantha M. Springer, Simeon Bhere, Deepak Chi, Andrew S. Wakimoto, Hiroaki Rothenberg, S. Michael Sequist, Lecia V. Kapur, Ravi Shah, Khalid Iafrate, A. John Curry, William T. Loeffler, Jay S. Batchelor, Tracy T. Louis, David N. Toner, Mehmet Maheswaran, Shyamala Haber, Daniel A. TI Brain Tumor Cells in Circulation Are Enriched for Mesenchymal Gene Expression SO CANCER DISCOVERY LA English DT Article ID GLIOBLASTOMA STEM-CELLS; HETEROGENEITY; METASTASIS; HYPOXIA; GLIOMAS AB Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local invasion and angiogenic recruitment, yet metastatic dissemination is extremely rare. Here, we adapted a microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence of circulating brain tumor cells (CTC). Staining and scoring criteria for GBM CTCs were first established using orthotopic patient-derived xenografts (PDX), and then applied clinically: CTCs were identified in at least one blood specimen from 13 of 33 patients (39%; 26 of 87 samples). Single GBM CTCs isolated from both patients and mouse PDX models demonstrated enrichment for mesenchymal over neural differentiation markers compared with primary GBMs. Within primary GBMs, RNA in situ hybridization identified a subpopulation of highly migratory mesenchymal tumor cells, and in a rare patient with disseminated GBM, systemic lesions were exclusively mesenchymal. Thus, a mesenchymal subset of GBM cells invades the vasculature and may proliferate outside the brain. C1 [Sullivan, James P.; Nahed, Brian V.; Madden, Marissa W.; Oliveira, Samantha M.; Springer, Simeon; Chi, Andrew S.; Wakimoto, Hiroaki; Rothenberg, S. Michael; Sequist, Lecia V.; Iafrate, A. John; Curry, William T.; Loeffler, Jay S.; Batchelor, Tracy T.; Louis, David N.; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Sullivan, James P.; Rothenberg, S. Michael; Sequist, Lecia V.; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Nahed, Brian V.; Wakimoto, Hiroaki; Curry, William T.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Bhere, Deepak; Chi, Andrew S.; Shah, Khalid; Batchelor, Tracy T.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Kapur, Ravi; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Engn Med, Boston, MA USA. [Shah, Khalid] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Iafrate, A. John; Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Toner, Mehmet; Maheswaran, Shyamala] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM maheswaran@helix.mgh.harvard.edu; haber@helix.mgh.harvard.edu FU NIH [K12CA090354, P50CA165962]; NIHLRP; B*Cured; Voices Against Brain Cancer; Stand Up To Cancer Dream Team Translational Cancer Research Grant [SU2C-AACR-DT0309]; Stand Up To Cancer is a program of the Entertainment Industry Foundation; Howard Hughes Medical Institute FX This work was funded by grants from the NIH K12CA090354, P50CA165962, and NIHLRP (to T.T. Batchelor, D.A. Haber, and B.V. Nahed); B*Cured (to B.N. Nahed); Voices Against Brain Cancer (to B.V. Nahed.); a Stand Up To Cancer Dream Team Translational Cancer Research Grant (SU2C-AACR-DT0309, to D.A. Haber, M. Toner, and S. Maheswaran; Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research); and Howard Hughes Medical Institute (to D.A. Haber). NR 31 TC 29 Z9 29 U1 5 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD NOV PY 2014 VL 4 IS 11 BP 1299 EP 1309 DI 10.1158/2159-8290.CD-14-0471 PG 11 WC Oncology SC Oncology GA AW8GY UT WOS:000346500700025 PM 25139148 ER PT J AU Crompton, BD Stewart, C Taylor-Weiner, A Alexe, G Kurek, KC Calicchio, ML Kiezun, A Carter, SL Shukla, SA Mehta, SS Thorner, AR de Torres, C Lavarino, C Sunol, M McKenna, A Sivachenko, A Cibulskis, K Lawrence, MS Stojanov, P Rosenberg, M Ambrogio, L Auclair, D Seepo, S Blumenstiel, B DeFelice, M Imaz-Rosshandler, I Celis, ASCY Rivera, MN Rodriguez-Galindo, C Fleming, MD Golub, TR Getz, G Mora, J Stegmaier, K AF Crompton, Brian D. Stewart, Chip Taylor-Weiner, Amaro Alexe, Gabriela Kurek, Kyle C. Calicchio, Monica L. Kiezun, Adam Carter, Scott L. Shukla, Sachet A. Mehta, Swapnil S. Thorner, Aaron R. de Torres, Carmen Lavarino, Cinzia Sunol, Mariona McKenna, Aaron Sivachenko, Andrey Cibulskis, Kristian Lawrence, Michael S. Stojanov, Petar Rosenberg, Mara Ambrogio, Lauren Auclair, Daniel Seepo, Sara Blumenstiel, Brendan DeFelice, Matthew Imaz-Rosshandler, Ivan Schwarz-Cruz y Celis, Angela Rivera, Miguel N. Rodriguez-Galindo, Carlos Fleming, Mark D. Golub, Todd R. Getz, Gad Mora, Jaume Stegmaier, Kimberly TI The Genomic Landscape of Pediatric Ewing Sarcoma SO CANCER DISCOVERY LA English DT Article ID SISTER-CHROMATID COHESION; TRANSCRIPTION FACTOR; BLADDER-CANCER; SEQUENCING DATA; MUTATIONAL PROCESSES; TUMOR-SUPPRESSOR; CELL-CYCLE; RNA-SEQ; FAMILY; GENES AB Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date, with only EWS-ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS-ETS fusions in this disease. SIGNIFICANCE: We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS-ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma. (C) 2014 AACR. C1 [Crompton, Brian D.; Alexe, Gabriela; Mehta, Swapnil S.; Thorner, Aaron R.; Rodriguez-Galindo, Carlos; Golub, Todd R.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Crompton, Brian D.; Alexe, Gabriela; Mehta, Swapnil S.; Thorner, Aaron R.; Rodriguez-Galindo, Carlos; Golub, Todd R.; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA. [Stewart, Chip; Taylor-Weiner, Amaro; Alexe, Gabriela; Kiezun, Adam; Carter, Scott L.; McKenna, Aaron; Sivachenko, Andrey; Cibulskis, Kristian; Lawrence, Michael S.; Stojanov, Petar; Rosenberg, Mara; Ambrogio, Lauren; Auclair, Daniel; Seepo, Sara; Blumenstiel, Brendan; DeFelice, Matthew; Rivera, Miguel N.; Golub, Todd R.; Getz, Gad; Stegmaier, Kimberly] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Alexe, Gabriela] Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA. [Kurek, Kyle C.; Calicchio, Monica L.; Fleming, Mark D.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Shukla, Sachet A.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [de Torres, Carmen; Lavarino, Cinzia; Sunol, Mariona; Mora, Jaume] Hosp San Juan Dios, Dept Pediat Oncol, Barcelona, Spain. [Stojanov, Petar] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Imaz-Rosshandler, Ivan; Schwarz-Cruz y Celis, Angela] Inst Nacl Med Genom, Mexico City, DF, Mexico. [Rivera, Miguel N.; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Stegmaier, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D630, Boston, MA 02215 USA. EM kimberly_stegmaier@dfci.harvard.edu FU Stand Up To Cancer Innovative Research Grant [SU2C-AACR-IRG0509]; Cookies for Kids' Cancer; Golf Fights Cancer; Brian MacIsaac Sarcoma Foundation; Hyundai Hope on Wheels; Bear Necessities Pediatric Cancer Foundation; St. Baldrick's Foundation; Asociacion Pablo Ugarte; Xarxa de Bancs de tumors de Catalunya; Instituto de Salud Carlos III Ministerio de Sanidad y Politica Social Direccion de Terapias Avanzadas y Trasplantes Orden [SAS/2481/2009 TRA-130] FX This work was conducted as parr of the Slim Initiative for Genomic Medicine (SIGMA), a joint U.S.-Mexico project founded by the Carlos Slim Health Institute. This work was also supported by a Stand Up To Cancer Innovative Research Grant, grant number SU2C-AACR-IRG0509 (Stand. Up To Cancer is is program of the Entertainment Industry Foundation administered by the American Association for Cancer Research), Cookies for Kids' Cancer, Golf Fights Cancer, Brian MacIsaac Sarcoma Foundation (to K. Stegmaier), Hyundai Hope on Wheels, Bear Necessities Pediatric Cancer Foundation, St. Baldrick's Foundation (to B.D. Crompton), Asociacion Pablo Ugarte, Xarxa de Bancs de tumors de Catalunya, and Instituto de Salud Carlos III Ministerio de Sanidad y Politica Social Direccion de Terapias Avanzadas y Trasplantes Orden SAS/2481/2009 TRA-130 (to J. Mora). NR 73 TC 58 Z9 59 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD NOV PY 2014 VL 4 IS 11 BP 1326 EP 1341 DI 10.1158/2159-8290.00-13-1037 PG 16 WC Oncology SC Oncology GA AW8GY UT WOS:000346500700027 PM 25186949 ER PT J AU Varetti, G Pellman, D Gordon, DJ AF Varetti, Gianluca Pellman, David Gordon, David J. TI Aurea Mediocritas: The Importance of a Balanced Genome SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID MEROTELIC KINETOCHORE ORIENTATION; ACUTE MYELOID-LEUKEMIA; SPINDLE CHECKPOINT INACTIVATION; CHROMOSOME SEGREGATION ERRORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; AGING-ASSOCIATED PHENOTYPES; MAMMALIAN TISSUE-CELLS; COPY-NUMBER ALTERATION; HUMAN CANCER-CELLS; PHASE-II TRIAL AB Aneuploidy, defined as an abnormal number of chromosomes, is a hallmark of cancer. Paradoxically, aneuploidy generally has a negative impact on cell growth and fitness in nontransformed cells. In this work, we review recent progress in identifying how aneuploidy leads to genomic and chromosomal instability, how cells can adapt to the deleterious effects of aneuploidy, and how aneuploidy contributes to tumorigenesis in different genetic contexts. Finally, we also discuss how aneuploidy might be a target for anticancer therapies. C1 [Varetti, Gianluca; Pellman, David; Gordon, David J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Varetti, Gianluca; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM David_Pellman@dfci.harvard.edu NR 146 TC 4 Z9 4 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD NOV PY 2014 VL 6 IS 11 AR a015842 DI 10.1101/cshperspect.a015842 PG 20 WC Cell Biology SC Cell Biology GA AW7MW UT WOS:000346449000004 PM 25237130 ER PT J AU Hettmer, S Li, ZZ Billin, AN Barr, FG Cornelison, DDW Ehrlich, AR Guttridge, DC Hayes-Jordan, A Helman, LJ Houghton, PJ Khan, J Langenau, DM Linardic, CM Pal, R Partridge, TA Pavlath, GK Rota, R Schafer, BW Shipley, J Stillman, B Wexler, LH Wagers, AJ Keller, C AF Hettmer, Simone Li, Zhizhong Billin, Andrew N. Barr, Frederic G. Cornelison, D. D. W. Ehrlich, Alan R. Guttridge, Denis C. Hayes-Jordan, Andrea Helman, Lee J. Houghton, Peter J. Khan, Javed Langenau, David M. Linardic, Corinne M. Pal, Ranadip Partridge, Terence A. Pavlath, Grace K. Rota, Rossella Schaefer, Beat W. Shipley, Janet Stillman, Bruce Wexler, Leonard H. Wagers, Amy J. Keller, Charles TI Rhabdomyosarcoma: Current Challenges and Their Implications for Developing Therapies SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID CHILDRENS ONCOLOGY GROUP; SOFT-TISSUE SARCOMAS; EMBRYONAL RHABDOMYOSARCOMA; PEDIATRIC RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA; PHASE-2 TRIAL; CANCER; CELLS; CHEMOTHERAPY; CHILDHOOD AB Rhabdomyosarcoma (RMS) represents a rare, heterogeneous group of mesodermal malignancies with skeletal muscle differentiation. One major subgroup of RMS tumors (so-called "fusion-positive" tumors) carries exclusive chromosomal translocations that join the DNA-binding domain of the PAX3 or PAX7 gene to the transactivation domain of the FOXO1 (previously known as FKHR) gene. Fusion-negative RMS represents a heterogeneous spectrum of tumors with frequent RAS pathway activation. Overtly metastatic disease at diagnosis is more frequently found in individuals with fusion-positive than in those with fusion-negative tumors. RMS is the most common pediatric soft-tissue sarcoma, and approximately 60% of all children and adolescents diagnosed with RMS are cured by currently available multimodal therapies. However, a curative outcome is achieved in <30% of high-risk individuals with RMS, including all those diagnosed as adults, those diagnosed with fusion-positive tumors during childhood (including metastatic and nonmetastatic tumors), and those diagnosed with metastatic disease during childhood (including fusion-positive and fusion-negative tumors). This white paper outlines current challenges in RMS research and their implications for developing more effective therapies. Urgent clinical problems include local control, systemic disease, need for improved risk stratification, and characterization of differences in disease course in children and adults. Biological challenges include definition of the cellular functions of PAX-FOXO1 fusion proteins, clarification of disease heterogeneity, elucidation of the cellular origins of RMS, delineation of the tumor microenvironment, and identification of means for rational selection and testing of new combination therapies. To streamline future therapeutic developments, it will be critical to improve access to fresh tumor tissue for research purposes, consider alternative trial designs to optimize early clinical testing of candidate drugs, coalesce advocacy efforts to garner public and industry support, and facilitate collaborative efforts between academia and industry. C1 [Hettmer, Simone] Univ Hosp Berlin, Charite, D-10439 Berlin, Germany. [Li, Zhizhong] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. [Li, Zhizhong] Novartis Inst Biomed Res, San Diego, CA 92121 USA. [Billin, Andrew N.] GlaxoSmithKline, Durham, NC 27709 USA. [Barr, Frederic G.; Helman, Lee J.; Khan, Javed] NCI, Bethesda, MD 20892 USA. [Cornelison, D. D. W.] Univ Missouri, Columbia, MO 65211 USA. [Ehrlich, Alan R.] Focus Rhabdo, New York, NY USA. [Guttridge, Denis C.] Ohio State Univ, Columbus, OH 43210 USA. [Hayes-Jordan, Andrea] Univ Texas Houston, Sch Med, Houston, TX 77030 USA. [Houghton, Peter J.] Nationwide Childrens Res Inst, Columbus, OH 43205 USA. [Langenau, David M.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Linardic, Corinne M.] Duke Univ, Sch Med, Durham, NC 27710 USA. [Pal, Ranadip] Texas Tech Univ, Dept Elect & Comp Engn, Lubbock, TX 79409 USA. [Partridge, Terence A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pavlath, Grace K.] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Rota, Rossella] Osped Pediat Bambino Gesu, Dept Oncohematol, I-00165 Rome, Italy. [Schaefer, Beat W.] Univ Childrens Hosp, CH-8032 Zurich, Switzerland. [Shipley, Janet] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Stillman, Bruce] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Wexler, Leonard H.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Wagers, Amy J.] Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Keller, Charles] Oregon Hlth & Sci Univ, Pediat Canc Biol Program, Dept Pediat, Pape Family Pediat Res Inst, Portland, OR 97239 USA. [Keller, Charles] Childrens Canc Therapy Dev Inst, Ft Collins, CO 80524 USA. RP Wagers, AJ (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. EM amy_wagers@harvard.edu; charles@cc-TDI.org RI Khan, Javed/P-9157-2014; OI Khan, Javed/0000-0002-5858-0488; Billin, Andrew/0000-0001-7752-0934; Rota, Rossella/0000-0002-9408-7711 FU Michelle Paternoster Foundation for Sarcoma Research; Christina Renna Foundation Inc.; Friends of T.J. Foundation FX The authors are grateful to the Michelle Paternoster Foundation for Sarcoma Research, the Christina Renna Foundation Inc., and the Friends of T.J. Foundation for lending their voice and financial support, and to the staff at the Banbury Center at Cold Spring Harbor Laboratory, NY for their interest and for hosting the RMS meeting in May 2014. NR 41 TC 9 Z9 9 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD NOV PY 2014 VL 4 IS 11 AR a025650 DI 10.1101/cshperspect.a025650 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AW8OQ UT WOS:000346522200001 PM 25368019 ER PT J AU Engel, CC Bray, RM Jaycox, LH Freed, MC Zatzick, D Lane, ME Brambilla, D Olmsted, KR Vandermaas-Peeler, R Litz, B Tanielian, T Belsher, BE Evatt, DP Novak, LA Unutzer, J Katon, WJ AF Engel, Charles C. Bray, Robert M. Jaycox, Lisa H. Freed, Michael C. Zatzick, Doug Lane, Marian E. Brambilla, Donald Olmsted, Kristine Rae Vandermaas-Peeler, Russ Litz, Brett Tanielian, Terri Belsher, Bradley E. Evatt, Daniel P. Novak, Laura A. Unuetzer, Juergen Katon, Wayne J. TI Implementing collaborative primary care for depression and posttraumatic stress disorder: Design and sample for a randomized trial in the US military health system SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE PTSD; Depression; Collaborative care; Primary care; Implementation; Military ID DISEASE MANAGEMENT PROGRAMS; REDUCING SUICIDAL IDEATION; ABBREVIATED PTSD CHECKLIST; COGNITIVE-BEHAVIOR THERAPY; REENGINEERING SYSTEMS; SCREENING INSTRUMENT; ANXIETY DISORDERS; SOMATIC SYMPTOMS; CHRONIC PAIN; METAANALYSIS AB Background: War-related trauma, posttraumatic stress disorder (PTSD), depression and suicide are common in US military members. Often, those affected do not seek treatment due to stigma and barriers to care. When care is sought, it often fails to meet quality standards. A randomized trial is assessing whether collaborative primary care improves quality and outcomes of PTSD and depression care in the US military health system. Objective: The aim of this study is to describe the design and sample for a randomized effectiveness trial of collaborative care for PTSD and depression in military members attending primary care. Methods: The STEPS-UP Trial (STepped Enhancement of PTSD Services Using Primary Care) is a 6 installation (18 clinic) randomized effectiveness trial in the US military health system. Study rationale, design, enrollment and sample characteristics are summarized. Findings: Military members attending primary care with suspected PTSD, depression or both were referred to care management and recruited for the trial (2592), and 1041 gave permission to contact for research participation. Of those, 666 (64%) met eligibility criteria, completed baseline assessments, and were randomized to 12 months of usual collaborative primary care versus STEPS-UP collaborative care. Implementation was locally managed for usual collaborative care and centrally managed for STEPS-UP. Research reassessments occurred at 3-, 6-, and 12-months. Baseline characteristics were similar across the two intervention groups. Conclusions: STEPS-UP will be the first large scale randomized effectiveness trial completed in the US military health system, assessing how an implementation model affects collaborative care impact on mental health outcomes. It promises lessons for health system change. (C) 2014 Elsevier Inc. All rights reserved. C1 [Engel, Charles C.; Jaycox, Lisa H.; Tanielian, Terri] RAND Corp, Arlington, VA 22202 USA. [Bray, Robert M.; Lane, Marian E.; Brambilla, Donald; Olmsted, Kristine Rae; Vandermaas-Peeler, Russ] RTI Int, Res Triangle Pk, NC USA. [Freed, Michael C.; Belsher, Bradley E.; Evatt, Daniel P.; Novak, Laura A.] Deployment Hlth Clin Ctr, Bethesda, MD USA. [Engel, Charles C.; Freed, Michael C.; Belsher, Bradley E.] Univ Hlth Sci, Uniformed Serv, Bethesda, MD USA. [Zatzick, Doug; Unuetzer, Juergen; Katon, Wayne J.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Litz, Brett] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Litz, Brett] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Engel, CC (reprint author), RAND Corp, 1200 South Hayes St, Arlington, VA 22202 USA. NR 63 TC 9 Z9 9 U1 6 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2014 VL 39 IS 2 BP 310 EP 319 DI 10.1016/j.cct.2014.10.002 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AW8XJ UT WOS:000346542400015 PM 25311446 ER PT J AU Oreskovic, NM Blossom, J Robinson, AI Chen, MHL Uscanga, DK Mendoza, JA AF Oreskovic, Nicolas M. Blossom, Jeff Robinson, Alyssa I. Chen, Minghua L. Uscanga, Doris K. Mendoza, Jason A. TI The influence of the built environment on outcomes from a "walking school bus study": a cross-sectional analysis using geographical information systems SO GEOSPATIAL HEALTH LA English DT Article DE built environment; children; geographical information systems; active commuting; physical activity; United States of America ID CHILDRENS PHYSICAL-ACTIVITY; GLOBAL POSITIONING SYSTEMS; NEIGHBORHOOD; TRAVEL; YOUTH; US; ASSOCIATION; ADOLESCENTS; TRANSPORT; WEIGHT AB Active commuting to school increases children's daily physical activity. The built environment is associated with children's physical activity levels in cross-sectional studies. This study examined the role of the built environment on the outcomes of a " walking school bus" study. Geographical information systems was used to map out and compare the built environments around schools participating in a pilot walking school bus randomised controlled trial, as well as along school routes. Multi-level modelling was used to determine the built environment attributes associated with the outcomes of active commuting to school and accelerometer-determined moderate-to-vigorous physical activity (MPVA). There were no differences in the surrounding built environments of control (n = 4) and intervention (n = 4) schools participating in the walking school bus study. Among school walking routes, park space was inversely associated with active commuting to school (beta = -0.008, SE = 0.004, P = 0.03), while mixed-land use was positively associated with daily MPVA (beta = 60.0, SE = 24.3, P = 0.02). There was effect modification such that high traffic volume and high street connectivity were associated with greater moderate-to-vigorous physical activity. The results of this study suggest that the built environment may play a role in active school commuting outcomes and daily physical activity. C1 [Oreskovic, Nicolas M.; Robinson, Alyssa I.; Chen, Minghua L.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Oreskovic, Nicolas M.] Harvard Univ, Sch Med, Boston, MA USA. [Blossom, Jeff] Harvard Ctr Geog Anal, Cambridge, MA USA. [Uscanga, Doris K.; Mendoza, Jason A.] Seattle Childrens Hosp, Seattle Childrens Res Inst, Seattle, WA USA. [Mendoza, Jason A.] Univ Washington, Seattle, WA 98195 USA. RP Oreskovic, NM (reprint author), Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM noreskovic@mgh.harvard.edu OI Oreskovic, Nicolas/0000-0001-8702-8636 FU National Institutes of Health/National Heat, Lung, and Blood Institutes [K23HL103841]; Active Living Research of the Robert Wood Johnson Foundation [63773]; National Institutes of Health/National Cancer Institute [K07CA131178, R21CA133418]; United States Department of Agriculture [6250-51000-053] FX N.M. Oreskovic was supported by a grant from the National Institutes of Health/National Heat, Lung, and Blood Institutes (K23HL103841). J.A. Mendoza was supported by grants from Active Living Research of the Robert Wood Johnson Foundation (grant 63773), the National Institutes of Health/National Cancer Institute (K07CA131178 and R21CA133418), and the United States Department of Agriculture (Cooperative Agreement 6250-51000-053). This work was presented in part as a poster at the Pediatric Academic Societies meeting, May 2013; Washington, D. C. NR 36 TC 2 Z9 2 U1 2 U2 10 PU UNIV NAPLES FEDERICO II PI NAPLES PA FAC VET MED, DEP PATHOLOGY & ANIMAL HEALTH, VET PARASITOLOGY, VIA DELLA VETERINARIA 1, NAPLES, 80137, ITALY SN 1827-1987 EI 1970-7096 J9 GEOSPATIAL HEALTH JI Geospatial Health PD NOV PY 2014 VL 9 IS 1 BP 37 EP 44 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AW8LE UT WOS:000346512600004 PM 25545924 ER PT J AU Jalian, HR Avram, MM AF Jalian, H. Ray Avram, Mathew M. TI Mid-Level Practitioners in Dermatology A Need for Further Study and Oversight SO JAMA DERMATOLOGY LA English DT Editorial Material ID LASER-SURGERY; CARE C1 [Jalian, H. Ray] Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. [Avram, Mathew M.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avram, Mathew M.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Jalian, HR (reprint author), Univ Calif Los Angeles, Div Dermatol, 2020 Santa Monica Blvd,Ste 570, Santa Monica, CA 90404 USA. EM HJalian@mednet.ucla.edu NR 9 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD NOV PY 2014 VL 150 IS 11 BP 1149 EP 1151 DI 10.1001/jamadermatol.2014.1922 PG 3 WC Dermatology SC Dermatology GA AW4EP UT WOS:000346234300003 PM 25110861 ER PT J AU Katz, KA Reid, EE Chren, MM AF Katz, Kenneth A. Reid, Erika E. Chren, Mary-Margaret TI The Good, the Bad, and the Ugly of Free Drug Samples Reply SO JAMA DERMATOLOGY LA English DT Letter ID PATTERNS C1 [Katz, Kenneth A.] Permanente Med Grp Inc, Dept Dermatol, Pleasanton, CA 94588 USA. [Reid, Erika E.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Chren, Mary-Margaret] San Francisco VA Med Ctr, San Francisco, CA USA. RP Katz, KA (reprint author), Permanente Med Grp Inc, Dept Dermatol, 7601 Stoneridge Dr,Second Floor,S Bldg, Pleasanton, CA 94588 USA. EM Kenneth.Katz@gmail.com 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 2168-6068 EI 2168-6084 J9 JAMA DERMATOL JI JAMA Dermatol. PD NOV PY 2014 VL 150 IS 11 BP 1238 EP 1238 DI 10.1001/jamadermatol.2014.1815 PG 1 WC Dermatology SC Dermatology GA AW4EP UT WOS:000346234300033 PM 25188905 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Defining a New Role for the National Cancer Institute Cooperative Groups: More Science, Fewer Trials SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), 10 North Grove St, Boston, MA 02114 USA. EM bchabner@partners.org NR 4 TC 0 Z9 0 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD NOV PY 2014 VL 19 IS 11 BP 1113 EP 1114 DI 10.1634/theoncologist.2014-0359 PG 2 WC Oncology SC Oncology GA AW9TZ UT WOS:000346601600002 PM 25326160 ER PT J AU Bertagnolli, MM Canetta, R Nass, SJ AF Bertagnolli, Monica M. Canetta, Renzo Nass, Sharyl J. TI Expanding Public-Private Collaborations to Enhance Cancer Drug Development: A Report of the Institute of Medicine's Workshop Series, "Implementing a National Cancer Clinical Trials System for the 21st Century" SO ONCOLOGIST LA English DT Article DE Clinical trials; Drug development; National Cancer Institute; Institute of Medicine ID SURGICAL ADJUVANT BREAST; FOLLOW-UP; CHEMOTHERAPY; RADIOTHERAPY; TAMOXIFEN; AGE AB Since their inception in the 1950s, the National Cancer Institute-funded cancer cooperative groups have been important contributors to cancer clinical and translational research. In 2010, a committee appointed by the Institute of Medicine (IOM) of the National Academy of Sciences completed a consensus review on the status of the U.S. publicly funded cancer clinical trials system. This report identified a need to reinvigorate the cooperative groups and provided recommendations for improving their effectiveness. Follow-up workshops to monitor progress were conducted by the IOM's National Cancer Policy Forum and the American Society of Clinical Oncology (ASCO) in 2011 and 2013. One of the key recommendations of the IOM report was a call for greater collaboration among stakeholders in cancer research. In particular, more active engagement and better alignment of incentives among the cooperative groups, the National Cancer Institute, the U. S. Food and Drug Administration, and the biopharmaceutical industry were identified as essential to achieving the promise of oncology drug development. This review, based on presentations and discussion during the IOM-ASCO workshops, outlines the progress and remaining challenges of these collaborations. C1 [Bertagnolli, Monica M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Canetta, Renzo] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Nass, Sharyl J.] Natl Acad, Inst Med, Natl Canc Policy Forum, Washington, DC USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 27 TC 1 Z9 1 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD NOV PY 2014 VL 19 IS 11 BP 1179 EP 1185 DI 10.1634/theoncologist.2014-0240 PG 7 WC Oncology SC Oncology GA AW9TZ UT WOS:000346601600014 PM 25326161 ER PT J AU Ganguly, K Abrams, GM AF Ganguly, Karunesh Abrams, Gary M. TI Neurologic Rehabilitation Preface SO SEMINARS IN NEUROLOGY LA English DT Editorial Material C1 [Ganguly, Karunesh; Abrams, Gary M.] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA USA. [Ganguly, Karunesh; Abrams, Gary M.] UCSF, Dept Neurol, San Francisco, CA USA. RP Ganguly, K (reprint author), Neurol & Rehabil Serv, 1700 Owens St, San Francisco, CA 94158 USA. EM karunesh.ganguly@ucsf.edu NR 0 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 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD NOV PY 2014 VL 34 IS 5 BP 483 EP 483 DI 10.1055/s-0034-1396001 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AW6YL UT WOS:000346411500002 PM 25520019 ER PT J AU Tsu, AP Abrams, GM Byl, NN AF Tsu, Adelyn P. Abrams, Gary M. Byl, Nancy N. TI Poststroke Upper Limb Recovery SO SEMINARS IN NEUROLOGY LA English DT Article DE stroke; upper limb rehabilitation; stroke management ID RANDOMIZED CONTROLLED-TRIAL; UPPER-EXTREMITY FUNCTION; SKILL ACQUISITION PROGRAM; ROBOT-ASSISTED THERAPY; STROKE REHABILITATION; MOTOR IMAGERY; COPENHAGEN STROKE; CLINICAL-TRIAL; BOBATH CONCEPT; OUTCOMES AB Upper limb recovery after a stroke is suboptimal. Only a few individuals achieve full functional use of the hemiparetic arm. Complex primary and secondary impairments may affect recovery of upper limb function in stroke survivors. In addition, multiple personal, social, behavioral, economic, and environmental factors may interact to positively or negatively influence recovery during the different stages of rehabilitation. The current management of upper limb dysfunction poststroke has become more evidence based. In this article, we review the standard of care for upper limb poststroke rehabilitation, the evidence supporting the treatment modalities that currently exist and the exciting new developments in the therapeutic pipeline. C1 [Tsu, Adelyn P.; Abrams, Gary M.] San Francisco VA Med Ctr, Dept Neurol, Rehabil Serv, San Francisco, CA 94121 USA. [Tsu, Adelyn P.; Abrams, Gary M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Byl, Nancy N.] Univ Calif San Francisco, Dept Phys Therapy & Rehabil Sci, San Francisco, CA 94143 USA. RP Tsu, AP (reprint author), San Francisco VA Med Ctr, Dept Neurol, Rehabil Serv, San Francisco, CA 94121 USA. EM adelyn.tsu@ucsf.edu NR 72 TC 1 Z9 2 U1 2 U2 10 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 NOV PY 2014 VL 34 IS 5 BP 485 EP 495 DI 10.1055/s-0034-1396002 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AW6YL UT WOS:000346411500003 PM 25520020 ER PT J AU Dinney, CPN Hansel, D McConkey, D Shipley, W Hagan, M Dreicer, R Lerner, S Czerniak, B Waldman, F Groshen, S True, LD Petricoin, E Theodorescu, D Hruszkewycz, A Bajorin, D AF Dinney, Colin P. N. Hansel, Donna McConkey, David Shipley, William Hagan, Michael Dreicer, Robert Lerner, Seth Czerniak, Bogdan Waldman, Fred Groshen, Susan True, Lawrence D. Petricoin, Emanuel Theodorescu, Dan Hruszkewycz, Andrew Bajorin, Dean TI Novel neoadjuvant therapy paradigms for bladder cancer: Results from the National Cancer Center Institute Forum SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Review DE Bladder cancer; Neoadjuvant chemotherapy; Radiation ID COMBINED-MODALITY THERAPY; LONG-TERM OUTCOMES; CELL LUNG-CANCER; RADICAL CYSTECTOMY; BREAST-CANCER; PROTEIN MICROARRAYS; DRUG DISCOVERY; CHEMOTHERAPY; RADIOTHERAPY; EXPRESSION AB Objective: To bridge gaps in translational science and develop the concepts for 2 novel biomarker-driven clinical trials: one in the presurgical setting and the other in the setting of bladder preservation with chemoradiation. Methods and materials: The National Cancer Institute sponsored a forum, "Novel Neoadjuvant Therapy for Bladder Cancer," which brought leading clinical and laboratory-based scientists together with the advocacy community. Results: The group designed a neoadjuvant clinical trial to compare the clinical efficacy of the two frontline chemotherapy regimens (gemcitabine plus cisplatin versus MVAC) and the ability of a gene expression profiling-based algorithm (CoXEN) to predict complete pathological response. The trial was recently opened under the leadership of the Southwest Oncology Group (SWOG, S1314), receiving support for the biomarker studies from the NCI's BISQFP resource. A second clinical trial was planned that will examine the relationship between expression of the DNA repair protein MRE11 and complete response in patients treated with concurrent 5-fiurouracil/mitomycin C plus radiation. Conclusion: The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapies for muscle-invasive urothelial cancer. The goal is to use this framework to develop comparable trials with immunotherapy in non-muscle invasive cancers and to exploit the neoadjuvant platform to develop targeted therapy in muscle-invasive disease. (C) 2014 Elsevier Inc. All rights reserved. C1 [Dinney, Colin P. N.; McConkey, David] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Hansel, Donna] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. [Shipley, William] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hagan, Michael] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA. [Dreicer, Robert] Cleveland Clin, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. [Lerner, Seth] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. [Czerniak, Bogdan] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Waldman, Fred] Quest Diagnost, San Juan Capistrano, CA USA. [Groshen, Susan] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [True, Lawrence D.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. [Petricoin, Emanuel] George Mason Univ, Ctr Appl Prote & Mol Med, Fairfax, VA 22030 USA. [Theodorescu, Dan] Univ Colorado, Dept Urol Surg, Denver, CO 80202 USA. [Hruszkewycz, Andrew] NCI, Bethesda, MD 20892 USA. [Bajorin, Dean] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. RP Dinney, CPN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. EM cdinney@mdanderson.org FU National Cancer Institute of the National Institutes of Health; SPORE in Genitourinary Cancer at The University of Texas MD Anderson Cancer Center [P50 CA91846]; Clinical and Translational Science Center at the Weill Medical College of Cornell University [UL1-RR024996] FX This Workshop was supported by resources from the National Cancer Institute of the National Institutes of Health. Dr. Colin Dinney wishes to acknowledge grant support from the SPORE in Genitourinary Cancer at The University of Texas MD Anderson Cancer Center (P50 CA91846). Dr. Dean Bajorin wishes to acknowledge support from the Clinical and Translational Science Center at the Weill Medical College of Cornell University (UL1-RR024996). NR 60 TC 10 Z9 10 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV PY 2014 VL 32 IS 8 BP 1108 EP 1115 DI 10.1016/j.urolonc.2013.10.021 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX0EZ UT WOS:000346627300004 PM 25443274 ER PT J AU Mahal, BA Ziehr, DR Aizer, AA Hyatt, AS Sammon, JD Schmid, M Choueiri, TK Hu, JC Sweeney, CJ Beard, CJ D'Amico, AV Martin, NE Lathan, C Kim, SP Trinh, QD Nguyen, PL AF Mahal, Brandon A. Ziehr, David R. Aizer, Ayal A. Hyatt, Andrew S. Sammon, Jesse D. Schmid, Marianne Choueiri, Toni K. Hu, Jim C. Sweeney, Christopher J. Beard, Clair J. D'Amico, Anthony V. Martin, Neil E. Lathan, Christopher Kim, Simon P. Quoc-Dien Trinh Nguyen, Paul L. TI Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE African American; Insurance; Affordable Care Act; Prostatic neoplasm; Cancer; Disparities ID LOCALIZED PROSTATE-CANCER; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; RADIATION-THERAPY; CARE; TRIAL; RADIOTHERAPY; MORTALITY; OUTCOMES; STROKE AB Objectives: Treating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP. Materials and methods: The Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level > 20 ng/ml or Gleason score 8-10 or stage > cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy. Results: Compared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95%.CI: 0.56-0.64; P < 0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P-interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27-0.54, P < 0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57-0.66, P < 0.001) among insured men. Conclusions: AA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mahal, Brandon A.; Ziehr, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Hyatt, Andrew S.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Hyatt, Andrew S.; Choueiri, Toni K.; Sweeney, Christopher J.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Lathan, Christopher; Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Sammon, Jesse D.] Henry Ford Hosp, Vattikuti Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Schmid, Marianne; Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Div Urol, Sch Med, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.; Lathan, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hu, Jim C.] UCLA Med Ctr, Dept Urol, Los Angeles, CA USA. [Kim, Simon P.] Yale Univ, Dept Urol, Canc Outcomes & Publ Policy Effectiveness Res Ctr, New Haven, CT USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Prostate Cancer Foundation; Fitz's Cancer Warriors FX This work is supported by David and Cynthia Chapin, the Prostate Cancer Foundation, Fitz's Cancer Warriors, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. NR 28 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV PY 2014 VL 32 IS 8 BP 1285 EP 1291 DI 10.1016/j.urolonc.2014.04.014 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX0EZ UT WOS:000346627300028 PM 24846344 ER PT J AU Ravi, P Karakiewicz, PI Roghmann, F Gandaglia, G Choueiri, TK Menon, M McKay, RR Nguyen, PL Sammon, JD Sukumar, S Varda, B Chang, SL Kibel, AS Sun, M Trinh, QD AF Ravi, Praful Karakiewicz, Pierre I. Roghmann, Florian Gandaglia, Giorgio Choueiri, Toni K. Menon, Mani McKay, Rana R. Nguyen, Paul L. Sammon, Jesse D. Sukumar, Shyam Varda, Briony Chang, Steven L. Kibel, Adam S. Sun, Maxine Quoc-Dien Trinh TI Mental health outcomes in elderly men with prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Anxiety; Depression; SEER; Medicare; Prostate cancer ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; ERECTILE DYSFUNCTION; DEPRESSIVE SYMPTOMS; FUNCTIONAL OUTCOMES; POSTTREATMENT; CARCINOMA AB Objective: To examine the burden of mental health issues (MHI), namely anxiety, depressive disorders, and suicide, in a population-based cohort of older men with localized prostate cancer and to evaluate associations with primary treatment modality. Patients and methods: A total of 50,856 men, who were 65 years of age or older with clinically localind prostate cancer diagnosed between 1992 and 2005 and without a diagnosis of mental illness at baseline, were abstracted from the Surveillance, Epidemiology, and End Results Medicare database. The primary outcome of interest was the development of Mill (anxiety, major depressive disorder, depressive disorder not elsewhere classified, neurotic depression, adjustment disorder with depressed mood, and suicide) after the diagnosis of prostate cancer. Results: A total of 10,389 men (20.4%) developed MHI during the study period. Independent risk factors for MET included age >= 75 years (hazard ratio [HR] =. 1.29); higher comorbidity (Charlson comorbidity index >= 3, HR = 1.63); rural hospital location (HR = 1.14); being single, divorced, or widowed (HR = 1.12); later year of diagnosis (HR = 1.05); and urinary incontinence (HR = 1.47). Black race (HR = 0.79), very high-income status (HR = 0.87), and definitive treatment (radical prostatectomy [RP], HR = 0.79; radiotherapy [RT], HR = 0.85, all P < 0.001) predicted a lower risk of MHI. The rates of MHI at 10 years were 29.7%, 29.0%, and 22.6% in men undergoing watchful waiting (WW), RT, and RP, respectively. Conclusion: Older men with localized prostate cancer had a significant burden of MM. Men treated with RP or RT were at a lower risk of developing MET, compared with those undergoing WW, with median time to development of MHI being significantly greater in those undergoing RP compared with those undergoing RT or WW. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ravi, Praful] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, London, England. [Karakiewicz, Pierre I.; Roghmann, Florian; Gandaglia, Giorgio; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Roghmann, Florian] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany. [Choueiri, Toni K.; McKay, Rana R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Oncol, Boston, MA 02115 USA. [Menon, Mani; Sammon, Jesse D.] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Sukumar, Shyam] Univ Minnesota, Dept Urol, Minneapolis, MN USA. [Varda, Briony; Chang, Steven L.; Kibel, Adam S.; Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Div Urol Surg, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Ravi, P (reprint author), Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, London, England. EM prafulravi1987@gmail.com FU Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital FX This work is supported by the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital. NR 30 TC 9 Z9 9 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV PY 2014 VL 32 IS 8 BP 1333 EP 1340 DI 10.1016/j.urolonc.2014.05.005 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AX0EZ UT WOS:000346627300034 PM 25153773 ER PT J AU Williams-Sanchez, V McArdle, RA Wilson, RH Kidd, GR Watson, CS Bourne, AL AF Williams-Sanchez, Victoria McArdle, Rachel A. Wilson, Richard H. Kidd, Gary R. Watson, Charles S. Bourne, Andrea L. TI Validation of a Screening Test of Auditory Function Using the Telephone SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Diagnostic techniques and procedures; hearing loss; hearing test; screening; sensitivity and specificity; telephone; validation studies ID QUALITY-OF-LIFE; IN-NOISE TEST; HEARING-LOSS; OLDER-ADULTS; ELDERLY POPULATION; PRIMARY-CARE; TASK-FORCE; SPEECH; WORDS; LISTENERS AB Background: Several European countries have demonstrated successful use of telephone screening tests for auditory function. The screening test consists of spoken three-digit sequences presented in a noise background. The speech-to-noise ratios of the stimuli are determined by an adaptive tracking method that converges on the level required to achieve 50% correct recognition. Purpose: A version of the three-digit telephone screening protocol for the United States was developed: the US National Hearing Test (NHT). The objective of the current study was to determine the sensitivity and specificity as well as the feasibility of the NHT for use within the Department of Veterans Affairs (VA). Research Design and Study Sample: Using a multisite study design with convenience sampling, we used the NHT to collect data from 693 participants (1379 ears) from three geographical areas of the United States (Florida, Tennessee, and California). Data Collection and Analysis: The NHT procedures were as follows: the participants (1) called a toll-free telephone number, (2) entered their assigned ear-specific identification code, (3) listened to 40-sets of digit triplets presented in speech-spectrum background noise, and (4) entered in the numbers that they heard on the telephone key pad. The NHT was performed on each ear, either at home or in a VA clinic. In addition to collecting data from the experimental task, we gathered demographic data and the data from other standard-of-care tests (i.e., audiometric thresholds and speech recognition tests in quiet and in noise). Results: A total of 505 participants completed the NHT at a VA clinic, whereas 188 completed the test at home. Although the ear-specific NHT and mean pure-tone threshold all correlated significantly (p < 0.001), there were more modest correlations in the low- and high-frequency ranges with the highest correlation seen with the 2000 Hz mean pure-tone threshold. When the NHT 50% point or threshold was compared with the three-frequency PTA at 500, 1000, and 2000 Hz, the sensitivity was 0.87 and specificity was 0.54. When comparing the NHT with the four-frequency PTA at 500, 1000, 2000, and 4000 Hz, the sensitivity was 0.81 and specificity increased to 0.65. The NHT also correlated strongly with other speech-in-noise measures. Conclusions: The NHT was found to correlate with other audiometric measures, including pure-tone thresholds and speech recognition tests in noise, at sufficiently high correlation values to support its use as a screening test of auditory function. C1 [Williams-Sanchez, Victoria; McArdle, Rachel A.] Bay Pines VA HealthCare Syst, Bay Pines, FL 37710 USA. [Williams-Sanchez, Victoria; McArdle, Rachel A.] Univ S Florida, Dept Commun Sci & Disorders, Tampa, FL USA. [Wilson, Richard H.] James H Quillen VA Med Ctr, Mountain Home, TN USA. [Wilson, Richard H.] E Tennessee State Univ, Dept Audiol & Speech Language Pathol, Johnson City, TN USA. [Kidd, Gary R.; Watson, Charles S.] Commun Disorders Technol Inc, Bloomington, IN USA. [Kidd, Gary R.; Watson, Charles S.] Indiana Univ, Bloomington, IN USA. [Bourne, Andrea L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Williams-Sanchez, V (reprint author), Bay Pines VA HealthCare Syst, Audiol 126,POB 5005, Bay Pines, FL 37710 USA. EM vawilli2@mail.usf.edu FU National Institutes of Health/National Institute on Deafness and Other Communication Disorders [R43DC009719]; Rehabilitation Research and Development Service, VA; Auditory and Vestibular Dysfunction Research Enhancement Award Program (REAP); Senior Research Career Scientist award FX The screening test used in this study was developed with funding provided by National Institutes of Health/National Institute on Deafness and Other Communication Disorders grant R43DC009719 to Communication Disorders Technology, Inc. (CDT), Bloomington, IN. Charles Watson is a stockholder of CDT and might benefit financially from the licensing, sale, or other commercial use of that test. The Rehabilitation Research and Development Service, VA, also supported this work through a Career Development Award to Rachel A. McArdle and a Merit Review, the Auditory and Vestibular Dysfunction Research Enhancement Award Program (REAP), and a Senior Research Career Scientist award to Richard H. Wilson. NR 58 TC 5 Z9 7 U1 3 U2 3 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD NOV-DEC PY 2014 VL 25 IS 10 BP 937 EP 951 DI 10.3766/jaaa.25.10.3 PG 15 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AW7RE UT WOS:000346461400003 PM 25514447 ER PT J AU Killeen, DE Sedaghat, AR Cunnane, ME Gray, ST AF Killeen, Daniel E. Sedaghat, Ahmad R. Cunnane, Mary E. Gray, Stacey T. TI Objective radiographic density measurements of sinus opacities are not strong predictors of noninvasive fungal disease SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID PARANASAL SINUSES; CHRONIC RHINOSINUSITIS; COMPUTED-TOMOGRAPHY; DIAGNOSIS; BALLS AB Background: High-density paranasal sinus opacities are often deemed consistent with fungal elements. No studies of objective quantitative radiographic density measures have been performed to support this assertion. Methods: A consecutive series of 120 patients with chronic rhinosinusitis who underwent maxillary antrostomy with microbiological evaluation of contents within 60 days of sinus computed tomography scanning was investigated. Radiographic density characteristics of opacities in cultured maxillary sinuses (minimum, maximum, average, and standard deviation of Hounsfield units [ HUstd]) were recorded. Receiver operator characteristic (ROC) curves were used to analyze the accuracy of radiographic characteristics in predicting fungal opacities. Results: Of 133 maxillary sinus opacities, 22 were ultimately consistent with noninvasive fungal disease: 11 allergic fungal rhinosinusitis and 11 fungal balls. Fungal balls had higher-density components and were more heterogeneous and allergic fungal mucin was generally more radiodense. These findings were reflected by statistically significant ROC curves for maximum HU (p = 0.019) and HUstd (p = 0.023) for fungal balls and for average HU (p = 0.002) for allergic fungal mucin. A maximum HU cutoff of 334.0 detected fungal balls with 90.9% sensitivity and 72.7% specificity. An average HU cutoff of 42.9 HU detected allergic fungal mucin with 100% sensitivity and 46.3% specificity, although specificity improved to 73.2% with inclusion of nasal polyposis as a second requirement. Conclusion: Higher average HU more accurately predicts allergic fungal mucin whereas heterogeneity/high-density components more accurately predict fungal balls. No objective radiographic density measure, in isolation, is both sensitive and specific in predicting noninvasive fungal sinusitis. C1 [Killeen, Daniel E.; Sedaghat, Ahmad R.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otorhinolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Gray, Stacey T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02115 USA. [Cunnane, Mary E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02115 USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otorhinolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD NOV-DEC PY 2014 VL 28 IS 6 BP 483 EP 486 DI 10.2500/ajra.2014.28.4104 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA AW2ML UT WOS:000346122200012 PM 25514484 ER PT J AU Ojserkis, R McKay, D Badour, CL Feldner, MT Arocho, J Dutton, C AF Ojserkis, Rachel McKay, Dean Badour, Christal L. Feldner, Matthew T. Arocho, Justin Dutton, Courtney TI Alleviation of Moral Disgust, Shame, and Guilt in Posttraumatic Stress Reactions: An Evaluation of Comprehensive Distancing SO BEHAVIOR MODIFICATION LA English DT Article DE disgust; moral disgust; guilt; shame; trauma; acceptance and commitment therapy ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; LIFE EVENTS CHECKLIST; TRAUMA-RELATED GUILT; PSYCHOMETRIC PROPERTIES; MENTAL CONTAMINATION; COMMITMENT THERAPY; INDIVIDUAL-DIFFERENCES; PROLONGED EXPOSURE AB Research suggests that moral disgust, shame, and guilt are present in posttraumatic psychopathology. However, it is unclear that these emotional states are responsive to empirically supported interventions for posttraumatic stress symptoms (PTSS). This study explored the relations among moral disgust, shame, guilt, and PTSS, and examined comprehensive distancing (CD) as a novel intervention for these emotional states in undergraduates with elevated PTSS. Participants were randomly assigned to use a CD or a cognitive challenge task in response to personalized scripts of a traumatic event. Both interventions were associated with decreases in disgust, moral disgust, shame, and guilt. Contrary to predictions, there were no significant differences between the exercises in the reduction of negative emotions. In addition, PTSS severity was correlated with trauma-related guilt as well as state guilt and shame, but not trait or state measures of disgust or moral disgust. This proof of concept project sets the stage for further research examining CD as an alternative or adjunctive intervention for posttraumatic stress reactions with strong features of moral disgust, shame, and guilt. C1 [Ojserkis, Rachel; McKay, Dean; Arocho, Justin] Fordham Univ, Bronx, NY 10458 USA. [Badour, Christal L.; Dutton, Courtney] Univ Arkansas, Fayetteville, AR 72701 USA. [Feldner, Matthew T.] Univ Arkansas, Dept Psychol Sci, Fayetteville, AR 72701 USA. [Badour, Christal L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Badour, Christal L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Feldner, Matthew T.] Laureate Inst Brain Res, Tulsa, OK USA. RP Ojserkis, R (reprint author), Fordham Univ, Dept Psychol, 441 E Fordham Rd, Bronx, NY 10458 USA. EM rojserkis@fordham.edu NR 118 TC 2 Z9 2 U1 4 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 EI 1552-4167 J9 BEHAV MODIF JI Behav. Modificat. PD NOV PY 2014 VL 38 IS 6 BP 801 EP 836 DI 10.1177/0145445514543465 PG 36 WC Psychology, Clinical SC Psychology GA AW0YH UT WOS:000346016700002 PM 25037054 ER PT J AU Boockvar, K AF Boockvar, Kenneth TI Impact of Depression and Mental Illness on Outcomes of Medical Illness in Older Adults SO CLINICAL THERAPEUTICS LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; CARE; SYMPTOMS; RISK; IMPAIRMENT; MORTALITY; DISEASE; SINGLE C1 [Boockvar, Kenneth] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Boockvar, Kenneth] James J Peters VA Med Ctr, Bronx, NY USA. [Boockvar, Kenneth] Jewish Home Lifecare, New York, NY USA. RP Boockvar, K (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. OI Boockvar, Kenneth/0000-0003-1165-5558 NR 25 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1486 EP 1488 DI 10.1016/j.clinthera.2014.10.010 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900002 PM 25455929 ER PT J AU Zahradnik, EK Grossman, H AF Zahradnik, Erin K. Grossman, Hillel TI Palliative Care as a Primary Therapeutic Approach in Advanced Dementia: A Narrative Review SO CLINICAL THERAPEUTICS LA English DT Review DE palliative care; dementia; Alzheimer's disease; geriatrics; geriatric psychiatry ID RANDOMIZED CONTROLLED-TRIAL; HOSPITALIZED OLDER-ADULTS; NURSING-HOME RESIDENTS; CELL LUNG-CANCER; ALZHEIMER-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL SYMPTOMS; TERMINALLY-ILL; DIGNITY THERAPY; CACHE COUNTY AB Purpose: The goal of this narrative review was to identify and summarize the ways in which palliative care could benefit patients who have advanced dementia. Methods: This case-based discussion article examines current literature on palliative care for dementia. Findings: Dementia is an incurable, progressive disease that affects millions of subjects. The prevalence has grown in the last decade and is projected to continue on this trajectory. In the later stages of dementia, subjects require increasing levels of care due to severe cognitive and functional impairment. Although the field of palliative medicine focuses on improving the quality of life of patients with life-limiting illnesses, many patients with advanced dementia do not receive palliative care services. (C) 2014 Elsevier HS Journals, Inc. All rights reserved. C1 [Zahradnik, Erin K.; Grossman, Hillel] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Grossman, Hillel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Zahradnik, EK (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM erin.zahradnik@mssm.edu NR 71 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1512 EP 1517 DI 10.1016/j.clinthera.2014.10.006 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900004 PM 25457122 ER PT J AU Garrido, MM Prigerson, HG Penrod, JD Jones, SC Boockyar, KS AF Garrido, Melissa M. Prigerson, Holly G. Penrod, Joan D. Jones, Shatice C. Boockyar, Kenneth S. TI Benzodiazepine and Sedative-hypnotic Use Among Older Seriously Ill Veterans: Choosing Wisely? SO CLINICAL THERAPEUTICS LA English DT Article DE Benzodiazepine; inappropriate; sedative-hypnotic; veterans ID INAPPROPRIATE MEDICATION USE; RECEIVING PALLIATIVE CARE; BEERS CRITERIA; HEALTH-CARE; ELDERLY-PATIENTS; ADULTS; RISK; CANCER; SETTINGS; EXPOSURE AB Purpose: The 2014 American Geriatrics Society's Choosing Wisely list cautions against the use of any benzodiazepines or other sedative-hypnotics (BSHs) as initial treatments for agitation, insomnia, or delirium in older adults. Because these symptoms are prevalent among hospitalized patients, seriously ill older adults are at risk of receiving these potentially inappropriate medications. The objectives of this study were to understand the extent to which potentially inappropriate BSHs are being used in hospitalized, seriously ill, older veterans and to understand what clinical and sociodemographic characteristics are associated with potentially inappropriate BSH use. Methods: We reviewed medical records of 222 veterans aged >= 65 years who were hospitalized in an acute care facility in the New York New Jersey metropolitan region in fiscal years 2009 and 2010. Veterans had diagnoses of advanced cancer, chronic obstructive pulmonary disease, congestive heart failure, and/or HIV/AIDS and received inpatient palliative care. Associations among potentially inappropriate BSH use (BSHs for indications other than alcohol withdrawal and current generalized anxiety disorder or one-time use before a medical procedure) and clinical and sociodemographic characteristics were examined with multivariable logistic regression. Findings: One-fifth of the sample was prescribed a potentially inappropriate BSH during the index hospitalization during the study period (n = 47). The most commonly prescribed potentially inappropriate medications were zolpidem (n = 26 [11.7%]) and lorazepam (n = 19 [8.9%]). Hispanic ethnicity was significantly associated with prescription of potentially inappropriate BSHs among the entire sample (adjusted odds ratio [AOR] = 3.79; 95% CI, 1.32-10.88) and among patients who survived until discharge (n = 164; AOR = 5.28; 95% CI, 1.64-17.07). Among patients who survived until discharge, black patients were less likely to be prescribed potentially inappropriate BSHs than white patients (AOR = 0.35; 95% CI, 0.13 0.997), and patients who had past-year BSH prescriptions were more likely to be prescribed a potentially inappropriate BSH than patients without past-year BSH use. Implications: The potentially inappropriate BSHs documented in our sample included short-and intermediate-acting benzodiazepines, medications that were not identified as potentially inappropriate for older adults until after these data were collected. Few long-acting benzodiazepines were recorded, suggesting that the older veterans in our sample were receiving medications according to the guidelines in place at the time of hospitalization. Clinicians may be able to reduce prescriptions of newly identified inappropriate BSHs by being aware of medications patients received before hospitalization and by being cognizant of racial/ethnic disparities in symptom management. Future studies should explore reasons for disparities in BSH prescriptions. Published by Elsevier HS Journals, Inc. C1 [Garrido, Melissa M.; Penrod, Joan D.; Jones, Shatice C.; Boockyar, Kenneth S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Garrido, Melissa M.; Penrod, Joan D.; Boockyar, Kenneth S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY USA. [Boockyar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. RP Garrido, MM (reprint author), James J Peters VA Med Ctr, 4A-17,130 Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [CDA 11-201/CDP 12255]; Greenwall Foundation; National Palliative Care Research Center FX Dr. Garrido is supported by CDA 11-201/CDP 12255, Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service. Dr. Boockvar is supported by the Greenwall Foundation. Data were collected with support from the National Palliative Care Research Center. NR 34 TC 5 Z9 6 U1 1 U2 5 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1547 EP 1554 DI 10.1016/j.clinthera.2014.10.007 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900008 PM 25453732 ER PT J AU Redding, SE Liu, S Hung, WW Boockvar, KS AF Redding, Sarah E. Liu, Sophia Hung, William W. Boockvar, Kenneth S. TI Opioid Interruptions, Pain, and Withdrawal Symptoms in Nursing Home Residents SO CLINICAL THERAPEUTICS LA English DT Article DE opioid; withdrawal; pain management; nursing homes ID ADVERSE EVENTS; DRUG; RELIABILITY; MORPHINE; SCALE; CARE; MDS AB Purpose: Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Methods: Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for >= 1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre-and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Findings: Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P < 0.015). In patients with interruptions, there were statistically insignificant changes in mean (SD) pain score (difference 0.50 [2.66]; 95% CI, 3.16 to 2.16) and withdrawal-score (difference 0.91 [3.12]; 95% CI, 4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with patients without interruptions, patients with interruptions experienced larger increases in pain scores during the follow-up periods (difference 0.09 points per day; 95% CI, 0.01 to 0.019; P = 0.08). In particular, patients who received the highest quartile of opioid dose before interruption experienced increases in pain scores over time that were 0.22 points per day larger (95% CI, 0.02 to 0.41; P = 0.03) than those without interruption. Withdrawal scores were not associated with opioid interruption regardless of dose before interruption. Published by Elsevier HS Journals, Inc. C1 [Redding, Sarah E.; Liu, Sophia; Hung, William W.; Boockvar, Kenneth S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Hung, William W.; Boockvar, Kenneth S.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Boockvar, Kenneth S.] Jewish Home Lifecare, New York, NY USA. RP Boockvar, KS (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU Veterans Affairs Health Services Research and Development Service [RCD 03-027-1, REA 08-260]; Greenwall Foundation FX This study was supported by Veterans Affairs Health Services Research and Development Service grants RCD 03-027-1 and REA 08-260. The study sponsor had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the mandscript for publication. One author (K. Boockvar) is also supported by the Greenwall Foundation. The contents do not represent the views of the US Department of Veterans Affairs or the United States Government. NR 21 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD NOV PY 2014 VL 36 IS 11 BP 1555 EP 1563 DI 10.1016/j.clinthera.2014.10.013 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AU9YX UT WOS:000345948900009 PM 25455930 ER PT J AU Harris, RC Fries, MH Boyle, A Adeniji-Adele, H Cherian, Z Klein, N John, AS AF Harris, Rachel C. Fries, Melissa H. Boyle, Annelee Adeniji-Adele, Hassan Cherian, Zacharia Klein, Nancy John, Anitha S. TI Multidisciplinary Management of Pregnancy in Complex Congenital Heart Disease: A Model for Coordination of Care SO CONGENITAL HEART DISEASE LA English DT Article DE Complex Congenital Heart Disease; Pregnancy; Multidisciplinary; Delivery Plan ID HIGH-RISK; WOMEN; OUTCOMES; ANTICOAGULATION; VALVES AB With advancements in medical care, many women with complex congenital heart disease (CHD) are now living into adulthood and childbearing years. The strains of pregnancy and parturition can be dangerous in such patients, and careful interdisciplinary plans must be made to optimize maternal and fetal health through this process. Several large studies have been published regarding risk prediction and medical management of pregnancy in complex CHD, though few case studies detailing clinical care plans have been published. The objective of this report is to describe the process of developing a detailed pregnancy and delivery care plan for three women with complex CHD, including perspectives from the multidisciplinary specialists involved in the process. This article demonstrates that collaboration between specialists in the fields of cardiology, anesthesiology, high-risk obstetrics, maternal fetal medicine, and neonatology results in clinically successful individualized treatment plans for the management of pregnancy in complex CHD. Multidisciplinary collaboration is a crucial element in the management of pregnancy in complex CHD. We provide a template used in three cases which can serve as a model for the design of future care plans. C1 [Harris, Rachel C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Fries, Melissa H.; Boyle, Annelee] Washington Hosp Ctr, Dept Obstet & Gynecol, Washington, DC 20010 USA. [Adeniji-Adele, Hassan] Washington Hosp Ctr, Dept Anesthesiol, Washington, DC 20010 USA. [Cherian, Zacharia] Washington Hosp Ctr, Dept Neonatol, Washington, DC 20010 USA. [Klein, Nancy; John, Anitha S.] George Washington Univ, Div Cardiol, Sch Med, Childrens Natl Med Ctr, Washington, DC USA. RP John, AS (reprint author), Childrens Natl Med Ctr, Div Pediat Cardiol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM anjohn@cnmc.org NR 24 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-079X EI 1747-0803 J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD NOV-DEC PY 2014 VL 9 IS 6 BP E204 EP E211 DI 10.1111/chd.12163 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AW3JA UT WOS:000346181300006 PM 24447432 ER PT J AU Urdaneta, RA Seemann, R Dragan, LF Lubelski, W Leary, J Chuang, SK AF Urdaneta, Rainier A. Seemann, Rudolf Dragan, Lrina-Florentina Lubelski, William Leary, Joseph Chuang, Sung-Kiang TI A Retrospective Radiographic Study on the Effect of Natural Tooth-Implant Proximity and an Introduction to the Concept of a Bone-Loading Platform Switch SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE adjacent structures; platform switching; retrospective cohort study; single-tooth implants; tooth-implant distance ID LOCKING-TAPER IMPLANTS; DENTAL IMPLANTS; ADJACENT TEETH; PROSTHESES; ROOT; REPLACEMENT; OVERLOAD; MM AB Purpose: The aim of this study was to evaluate the effect of tooth-implant proximity using an implant system with a double platform shift that was designed to load bone coronal to the implant-abutment interface. Materials and Methods: A retrospective cohort study was conducted between January 2008 and December 2009. The sample was composed of patients who had received at least one 5-mm-wide hydroxyapatite-coated single-tooth Bicon implant that had been placed adjacent to at least one natural tooth. Descriptive statistics and univariate and multivariate linear mixed-effects regression models, adjusted for multiple implants in the same patient, were utilized. The primary predictor variable was the horizontal distance between implant and adjacent tooth, and the primary outcome variable was the change in peri-implant bone levels over time. Results: Two hundred six subjects who received 235 plateau root-form implants were followed for an average of 42 months. Tooth-implant distance ranged between 0 and 14.6 mm. Out of 235 implants, 43 implants were placed < 1 mm to an adjacent natural tooth on mesial and/or distal sides. The proximity of a plateau root-form implant was not associated with complications on the adjacent tooth such as bone loss, root resorption, endodontic treatment, pain, or extraction. The proximity of an adjacent tooth was not a risk factor for the failure of a plateau root-form implant. After adjusting for other covariates in a multivariate model, the proximity of a natural tooth did not have a statistically significant effect on peri-implant bone levels (P = .13). The extraction of an adjacent tooth was associated with a significant increase in peri-implant bone loss (P = .008). Conclusion: The placement of a plateau root-form implant with a sloping shoulder in close proximity to an adjacent tooth did not cause damage to that tooth or lead to bone loss or the failure of the implant. C1 [Urdaneta, Rainier A.] Implant Dent Ctr, Boston, MA USA. [Seemann, Rudolf] Univ Vienna, A-1010 Vienna, Austria. [Dragan, Lrina-Florentina] Tufts Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02111 USA. [Lubelski, William] Bicon, Boston, MA USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Urdaneta, RA (reprint author), 25 Prairie Ave, Auburndale, MA 02466 USA. EM rainieru@yahoo.com NR 38 TC 1 Z9 1 U1 2 U2 6 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD NOV-DEC PY 2014 VL 29 IS 6 BP 1412 EP 1424 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AW2MI UT WOS:000346121900023 PM 25397804 ER PT J AU Friedland, B Metson, R AF Friedland, Bernard Metson, Ralph TI A Guide to Recognizing Maxillary Sinus Pathology and for Deciding on Further Preoperative Assessment Prior to Maxillary Sinus Augmentation SO INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY LA English DT Article ID COMPUTED-TOMOGRAPHY; PANORAMIC RADIOGRAPHY; INCIDENTAL FINDINGS; DENTAL IMPLANTS; ENT ASSESSMENT; PREVALENCE; ABNORMALITIES; LIFT; DISEASE AB Dentists contemplating sinus augmentation frequently take a cone beam computed tomography (CBCT) scan as part of the work-up. Maxillary sinus pathology is common, and such dentists will be faced with pathologic sinus findings. Not all sinus pathology needs to be treated. The purpose of this article is twofold: to describe the most common sinus findings as seen on a CBCT scan and a way to recognize them, as well as to provide an algorithm for decision making on when further evaluation of the sinus is necessary. C1 [Friedland, Bernard] Harvard Univ, Sch Dent Med, Div Oral & Maxillofacial Radiol, Boston, MA 02115 USA. [Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Friedland, B (reprint author), Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. EM bernard_friedland@hms.harvard.edu NR 25 TC 0 Z9 0 U1 0 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0198-7569 EI 1945-3388 J9 INT J PERIODONT REST JI Int. J. Periodontics Restor. Dent. PD NOV-DEC PY 2014 VL 34 IS 6 BP 807 EP 815 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AW0AT UT WOS:000345953600013 PM 25411736 ER PT J AU Gulur, P Cohen, AR Watt, L Lau, ME El Saleeby, C AF Gulur, Padma Cohen, Ari R. Watt, Lisa Lau, Mary E. El Saleeby, Chadi TI Elevated Lidocaine Serum Concentration After Subcutaneous Lidocaine Administration Using a Needle-Free Device in Pediatric Patients SO PEDIATRIC EMERGENCY CARE LA English DT Article DE J-Tip; needle-free device; lidocaine; lidocaine toxicity; drug toxicity ID VENOUS CANNULATION; DELIVERY; SYSTEM AB We report several cases in which pediatric patients at our institution have elevated lidocaine levels in toxicology screens after subcutaneous injection of lidocaine using a needle-free device. The purpose of this article is to report 4 cases in which pediatric patients have elevated lidocaine levels in toxicology screens after J-Tip administration. In particular, the article highlights 2 cases in which children younger than 3 years had lidocaine levels in the toxic range. Although the literature has reported the device to be effective with no significant untoward effects in children as young as 3 years, it seems that no information is available for children younger than 3 years. From a quality assurance/safety perspective, a summary is provided as our institutional response to concerns raised over what is typically thought to be a benign and beneficial intervention in children. C1 [Gulur, Padma; Watt, Lisa; Lau, Mary E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gulur, Padma; Cohen, Ari R.; El Saleeby, Chadi] Harvard Univ, Sch Med, Boston, MA USA. [Cohen, Ari R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [El Saleeby, Chadi] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 15 Parkman St,WACC 330, Boston, MA 02114 USA. EM pgulur@yahoo.com NR 4 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 EI 1535-1815 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD NOV PY 2014 VL 30 IS 11 BP 829 EP 831 PG 3 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA AU9KP UT WOS:000345911800015 PM 25198765 ER PT J AU Bot, AGJ Bossen, JKJ Herndon, JH Ruchelsman, DE Ring, D Vranceanu, AM AF Bot, Arjan G. J. Bossen, Jeroen K. J. Herndon, James H. Ruchelsman, David E. Ring, David Vranceanu, Ana-Maria TI Informed Shared Decision-Making and Patient Satisfaction SO PSYCHOSOMATICS LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; IDIOPATHIC ARM PAIN; LOW-BACK-PAIN; PERCEIVED DISABILITY; DOCTOR QUESTIONNAIRE; ORTHOPEDIC-SURGEONS; SURGICAL PRACTICE; HEALTH-STATUS; COMMUNICATION; HYPOCHONDRIASIS AB Background: Evidence suggests that when patients have a role in medical decisions they are more satisfied with their health care. Objective: To assess predictors of patient satisfaction, ratings' of the provider's informed shared decision-making (ISDM), and disability among patients with orthopedic pain complaints. Research Design: A total of 130 patients with nontraumatic painful conditions of the upper extremity were enrolled Medical encounters were audio recorded and coded by 2 independent coders. Eight ISDM elements and a total ISDM score were evaluated. Bivariate and multivariable analyses were used to answer the study questions. Measures: Participants' completed the Princess Margaret Hospital Patient Satisfaction with their Doctor Questionnaire to measure satisfaction; the Disabilities of Arm, Shoulder and Hand questionnaire; the Patient Health Questionnaire-9 to measure depression; the Whiteley Index to assess heightened illness concerns; and the pain catastrophizing scale to assess coping strategies in response to pain. Results: Less health anxiety, female gender, the ISDM element Identify choice, and any specific diagnosis determined 22% of the variation in satisfaction. Less health anxiety and unemployed unable to work compared with full-time working status were associated with a better rating of shared decision-making on the ISDM. Catastrophic thinking, female gender, symptoms of depression, and any specific diagnosis were associated with greater disability. Catastrophic thinking and symptoms of depression were the greatest contributors to the variation in disability. Conclusions: Psychologic factors are the strongest determinants of patient action, ratings of shared decision-making on the ISDM, and upper-extremity disability. Health anxiety is the most important,factor in ratings of patient satisfaction and ISD M whereas depression and catastrophizing are salient predictors' of disability, Level of Evidence: Prognostic level 1. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. Massachusetts Gen Hosp, Dept Behav Med, Benson Henry Mind Body Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 34 TC 5 Z9 5 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2014 VL 55 IS 6 BP 586 EP 594 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AW3JG UT WOS:000346182000008 PM 24836165 ER PT J AU Bot, AGJ Bekkers, S Herndon, JH Mudgal, CS Jupiter, JB Ring, D AF Bot, Arjan G. J. Bekkers, Stijn Herndon, James H. Mudgal, Chaitanya S. Jupiter, Jesse B. Ring, David TI Determinants of Disability After Proximal Interphalangeal Joint Sprain or Dislocation SO PSYCHOSOMATICS LA English DT Article ID DEPRESSION; TRIAL; PAIN AB Background: Sprain or dislocation of the proximal interphalangeal joint may be a useful example of the counterintuitive aspects of recovery as the prognosis if excellent, but protectiveness in response to discomfort often hinders the stretching exercises that are a key component of the recovery process. Objective: The aim of this study was to investigate the relationship between disability and pain self-efficacy in this context. Methods: A total of 82 patients (54 men and 28 women) were enrolled in this prospective study. Finger motion was measured, and the patients completed measures of upper limb specific disability ( the shortened version of the Disabilities of the Arm., Shoulder and Hand questionnaire), symptoms of depression (Patient Health Questionnaire-9), effective coping strategies in response to pain (the Pain Self-Efficacy Questionnaire), and a pain scale at enrollment. Results: Patients were enrolled a mean of 48 days after injury. The final multivariable model accounting for greater disability included lower self efficacy, greater symptoms of depression, and gender (Women have more disability). Lower self-efficacy was also the strongest predictor of pain intensity and finger stillness. Conclusions: Effective coping strategies such as self-efficacy facilitate recovery (less disability, pain, and stiffness) after proximal interphalangeal joint sprain/dislocation. Level of Evidence: Prognostic level I. C1 [Bot, Arjan G. J.; Bekkers, Stijn; Herndon, James H.; Mudgal, Chaitanya S.; Jupiter, Jesse B.; Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dring@partners.org FU Anna fonds; VSB-fonds; Prins Bernhard Cultuurfonds/Banning-de Jong fonds; Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage; Skeletal Dynamics; AONA FX A.G.J.B. received funding from "Anna fonds," "VSB-fonds," and "Prins Bernhard Cultuurfonds/Banning-de Jong fonds." S.B. received funding from Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage.; James H. Herndon M.D., M.B.A., is a board member of the Trustee of the journal of Bone and joint Surgery and is a consultant at CMO and Wiserhealth. Chaitanya S. Mudgal, MD., receives payment for lectures, including service on speakers bureaus, and is a member of AONA faculty where he receives a stipend. Jesse B. Jupiter, M.D. is a consultant at AO foundation and receives no payment. He also received grants from AO foundation and has stock options in OHK Medical Devices, Inc., although he has not been paid to date. David Ring, M.D., Ph. D. has applied for study-specific grants from Skeletal Dynamics; is a consultant at Wright Medical, Skeletal Dynamics, and Biomet; has received honoraria from AO North America and AO International; has received royalties from Wright Medical; has contracted royalties from Biomet and Skeletal Dynamics; and has stock options in Illuminos. He is the Deputy Editor for Review Articles, journal of Hand Surgery, American Volume; Hand and Wrist, journal of Orthopaedic Trauma; and Hand for Clinical Orthopaedics' and Related Research. He is also the Assistant Editor for journal of Shoulder and Elbow Surgery NR 15 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2014 VL 55 IS 6 BP 595 EP 601 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AW3JG UT WOS:000346182000009 PM 25034813 ER PT J AU Vaduganathan, M McCullough, SA Fraser, TN Stern, TA AF Vaduganathan, Muthiah McCullough, Stephen A. Fraser, Traci N. Stern, Theodore A. TI Death Due to Munchausen Syndrome: A Case of Idiopathic Recurrent Right Ventricular Failure and a Review of the Literature SO PSYCHOSOMATICS LA English DT Article ID FACTITIOUS DISORDERS; SUDDEN-DEATH; FOLLOW-UP; DIAGNOSIS C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Vaduganathan, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM muthu@md.northwestern.edu NR 16 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2014 VL 55 IS 6 BP 668 EP 672 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AW3JG UT WOS:000346182000017 PM 25262044 ER PT J AU Zhao, GP Moore, DJ Kim, JI Lee, KM O'Connor, M Yang, MZ Marshall, AF Lei, J Schuetz, C Markmann, JF Deng, SP AF Zhao, Gaoping Moore, Daniel J. Kim, James I. Lee, Kang Mi O'Connor, Matthew Yang, Maozhu Marshall, Andrew F. Lei, Ji Schuetz, Christian Markmann, James F. Deng, Shaoping TI An immunosufficient murine model for the study of human islets SO XENOTRANSPLANTATION LA English DT Article DE human islet; transplant model; transplant tolerance; Treg; xenograft ID XENOREACTIVE NATURAL ANTIBODIES; N-GLYCOLYLNEURAMINIC ACID; NON-GAL ANTIBODIES; GENE-KNOCKOUT PIGS; ALPHA-1,3-GALACTOSYLTRANSFERASE GENE; XENOGRAFT SURVIVAL; ENDOTHELIAL-CELLS; FLOW-CYTOMETRY; HUMAN XENOTRANSPLANTATION; HYPERACUTE REJECTION AB For the sake of therapy of diabetes, it is critical to understand human beta cell function in detail in health and disease. Current studies of human beta cell physiology in vivo are mostly limited to immunodeficient mouse models, which possess significant technical limitations. This study aimed to create a new model for the study of human islets through induction of transplant tolerance in immunosufficient mice. B6 diabetic mice were transplanted with human islets and treated with anti-CD45RB. To assess whether anti-CD45RB-induced transplant tolerance requires B cells, B6 recipients received additional anti-CD20 or B6 mu MT-/- mice were used. For some anti-CD45RB-treated B6 mu MT-/- mice, additional anti-CD25 mAb was applied at the early or late stage post-transplant. Immunohistology was performed to show the Foxp3 cells in grafted anti-CD45RB/anti-CD20-treated Foxp3-GFP B6 mice. The results showed that anti-CD45RB alone allowed indefinite graft survival in 26.6% of B6 mice, however 100% of xenografts were accepted in mice treated simultaneously with anti-CD20, and 88.9% of xenografts accepted in anti-CD45RB-treated mu MT-/- mice. These mu MT-/- mice accepted the islets from another human donor but rejected the islets from baboon. Additional administration of anti-CD25 mAb at the time of transplantation resulted in 100% rejection, whereas 40% of grafts were rejected while the antibody was administrated at days 60 post-transplant. Immunohistologic examination showed Foxp3+ cells accumulated around grafts. We conclude that induction of tolerance to human islets in an immunosufficient mouse model could be generated by targeting murine CD45RB and CD20. This new system will facilitate study of human islets and accelerate the dissection of the critical mechanisms underlying islet health in human disease. C1 [Zhao, Gaoping; Kim, James I.; Lee, Kang Mi; O'Connor, Matthew; Yang, Maozhu; Lei, Ji; Schuetz, Christian; Markmann, James F.; Deng, Shaoping] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Zhao, Gaoping; Yang, Maozhu; Deng, Shaoping] Sichuan Acad Med Sci, Dept Surg, Sichuan Prov Key Lab Translat Med Organ Transplan, Chengdu, Sichuan Provinc, Peoples R China. [Zhao, Gaoping; Yang, Maozhu; Deng, Shaoping] Sichuan Prov Peoples Hosp, Chengdu, Sichuan Provinc, Peoples R China. [Zhao, Gaoping; Yang, Maozhu; Deng, Shaoping] Univ Elect Sci & Technol China, Sch Med, Chengdu 610054, Sichuan Provinc, Peoples R China. [Moore, Daniel J.; Marshall, Andrew F.] Vanderbilt Univ, Ian Burr Div Endocrinol & Diabet, Dept Pediat & Pathol Microbiol & Immunol, Nashville, TN 37235 USA. RP Deng, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, 55 Fruit St, Boston, MA 02114 USA. EM sdeng10@yahoo.com RI Moore, Daniel/A-4924-2008; Schuetz, Christian/K-5234-2013 OI Moore, Daniel/0000-0002-6889-9345; Schuetz, Christian/0000-0002-6828-4543 FU National Natural Science Foundation of China [81172832]; Sichuan Youth Science and Technology Foundation [2013JQ0020]; Special Program for Sichuan Youth Science and Technology Innovation Research Team; NIH [K08DK090146, R03DK097410]; [R01AI057851] FX This work was supported by R01AI057851 (J.F.M.), by the National Natural Science Foundation of China (No. 81172832), Sichuan Youth Science and Technology Foundation (2013JQ0020) and Special Program for Sichuan Youth Science and Technology Innovation Research Team to G.Z., and by NIH K08DK090146 and R03DK097410 (D.J.M.). NR 58 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV-DEC PY 2014 VL 21 IS 6 BP 567 EP 573 DI 10.1111/xen.12126 PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA AW2YF UT WOS:000346151800009 PM 25041432 ER PT J AU Briet, JP Bot, AGJ Hageman, MGJS Menendez, ME Mudgal, CS Ring, DC AF Briet, Jan Paul Bot, Arjan G. J. Hageman, Michiel G. J. S. Menendez, Mariano E. Mudgal, Chaitanya S. Ring, David C. TI The Pain Self-Fifficacy Questionnaire: Validation of an Abbreviated Two-Item Questionnaire SO PSYCHOSOMATICS LA English DT Article ID PATIENT-REPORTED OUTCOMES; CONTROLLED-TRIAL; HEALTH-CARE; ARM PAIN; VALIDITY; DEPRESSION; DISABILITIES; RELIABILITY; EXPERIENCES; IMPUTATION AB Background: The Pain Self-Efficacy Questionnaire (PSEQ) is a validated tool to assess pain self-efficacy and is strongly correlated with disability. Reducing the number of questions of the original PSEQ to screen for self-efficacy will result in more efficient screening and less burden for the patient. Objective: The aim of this study;vas to prospectively validate the shortened version of the PSEQ. Method: Overall, 249 new and follow-up patients visiting our outpatient orthopedic hand surgery clinic were prospectively enrolled and asked to complete the PSEQ, short version of the Disabilities of the Arm Shoulder and Hand, and 2-question version of the Patient Health Questionnaire (PHQ-2) depression questionnaires. The patients completed the questionnaires in the office and online 2 weeks after their visit. At the follow-up visit, the PSEQ was substituted with the 2-question version of the Pain Self:Efficacy Questionnaire (PSEQ-2). The factors associated with higher short forms of the Disabilities of the Arm, Shoulder and Hand scores were investigated in a bivariate and multivariable analysis. Paired t-test was used to compare the mean values of the short and long questionnaires at enrollment. Results: There was a large correlation (r = 0.90; p < 0.001) between the original PSEQ and the PSEQ-2 at enrollment The Cronbach alpha were comparable for the PSEQ and the PSEQ-2 (alpha = 0.95 compared with alpha = 0.91). There was a small but statistically significant difference between the average scores of the PSEQ and PSEQ-2 (4.4 vs 4.8: p <0.001), For the shortened PSEQ, a smaller but still large correlation was found with the short,forms of the Disabilities of the Arm, Shoulder and Hand r = 0.71 vs r = 0.61). Both the PSEQ-2 and the PSEQ were the most important predictors of the short forms of the Disabilities of the Arm, Shoulder and Hand scores. A substantial test-retest reliability was found for the PSEQ-2 (0.66). Conclusion: The PSEQ-2 can be used to quickly assess patients' pain self-efficacy. C1 [Briet, Jan Paul; Bot, Arjan G. J.; Hageman, Michiel G. J. S.; Menendez, Mariano E.; Mudgal, Chaitanya S.; Ring, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM Dring@partners.org FU "AnnaFonds Travel grant" (Dutch Orthopaedic travel grant); "VSB-fonds," a nonmedical study grant; "Prins Bernhard Cultuurfonds Banning-de Jong funds," a nonmedical study grant; "Marti keuning Eckhardt fonds," a non-medical study grant; "Spinoza fonds," a nonmedical study grant; Skeletal Dynamics; AO North America FX Aijan G.J. Bot received "AnnaFonds Travel grant" (Dutch Orthopaedic travel grant), "VSB-fonds," a nonmedical study grant, and "Prins Bernhard Cultuurfonds Banning-de Jong funds," a nonmedical study grant, for excellent Dutch students. Michiel G.J.S Hageman received "Marti keuning Eckhardt fonds," a non-medical study grant, "Spinoza fonds," a nonmedical study grant, and "AnnaFonds Travel grant" ( Dutch Orthopaedic travel grant). Chaitanya S. Mudgal, M.D., received Payment for Lectures from the AONA faculty(stipend). David Ring received study-specific grants from Skeletal Dynamics (pending) and is Consultant at Wright Medical, Skeletal Dynamics, and Biomet and received Honoraria from AO North America, and AO International. He has received Royalties from Wright Medical and has Royalties contracted from Biomet and Skeletal Dynamics and has stock options for Illuminos. He has received funding for Hand Surgery Fellowship from AO North America. He is the Deputy Editor for review articles, Journal of Hand Surgery, American; Deputy Editor for Hand and Wrist, Journal of Orthopaedic Trauma; and Assistant Editor, Journal of Shoulder and Elbow Surgery. NR 35 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2014 VL 55 IS 6 BP 578 EP 585 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AW3JG UT WOS:000346182000007 PM 25016359 ER PT J AU Dou, XW Charness, ME AF Dou, Xiaowei Charness, Michael E. TI Effect of Lipid Raft Disruption on Ethanol Inhibition of L1 Adhesion SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Fetal Alcohol Spectrum Disorders; L1 Neural Cell Adhesion Molecule; Lipid Raft; Ethanol ID DETERGENT-RESISTANT MEMBRANES; CELL-CELL ADHESION; NEURITE OUTGROWTH; MOLECULE L1; NEURONAL MIGRATION; GROWTH; ENDOCYTOSIS; ANTAGONISM; CAVEOLAE; GUIDANCE AB BackgroundAlcohol causes fetal alcohol spectrum disorders in part by disrupting the function of the neural cell adhesion molecule L1. Alcohol inhibits L1-mediated cell-cell adhesion in diverse cell types and inhibits L1-mediated neurite outgrowth in cerebellar granule neurons (CGNs). A recent report indicates that ethanol (EtOH) induces the translocation of L1 into CGN lipid rafts and that disruption of lipid rafts prevents EtOH inhibition of L1-mediated neurite outgrowth. The same butanol-pentanol cutoff was noted for alcohol-induced translocation of L1 into lipid rafts that was reported previously for alcohol inhibition of L1 adhesion, suggesting that EtOH might inhibit L1 adhesion by shifting L1 into lipid rafts. MethodsThe NIH/3T3 cell line, 2A2-L1(s), is a well-characterized EtOH-sensitive clonal cell line that stably expresses human L1. Cells were treated with 25mM EtOH, 5M filipin, or both. Lipid rafts were enriched in membrane fractions by preparation of detergent-resistant membrane (DRMs) fractions. Caveolin-1 was used as a marker of lipid rafts, and L1 and Src were quantified by Western blotting in lipid-raft-enriched membrane fractions and by immunohistochemistry. ResultsEtOH (25mM) increased the percentage of L1, but not Src, in 2A2-L1(s) membrane fractions enriched in lipid rafts. Filipin, an agent known to disrupt lipid rafts, decreased the percentage of caveolin and L1 in DRMs from 2A2-L1(s) cells. Filipin also blocked EtOH-induced translocation of L1 into lipid rafts from 2A2-L1(s) cells but did not significantly affect L1 adhesion or EtOH inhibition of L1 adhesion. ConclusionsThese findings indicate that EtOH does not inhibit L1 adhesion in NIH/3T3 cells by inducing the translocation of L1 into lipid rafts. C1 [Dou, Xiaowei; Charness, Michael E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. RP Charness, ME (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA 02132 USA. EM michael_charness@hms.harvard.edu FU Medical Research Service; Department of Veterans Affairs; NIAAA [RO1AA12974, U24AA014811 (CIFASD)] FX We thank Carrie E. Menkari for excellent technical assistance. Supported by the Medical Research Service, Department of Veterans Affairs and NIAAA RO1AA12974 and U24AA014811 (CIFASD). NR 31 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2014 VL 38 IS 11 BP 2707 EP 2711 DI 10.1111/acer.12556 PG 5 WC Substance Abuse SC Substance Abuse GA AU5AW UT WOS:000345620400004 PM 25421507 ER PT J AU Durazzo, TC Pennington, DL Schmidt, TP Meyerhoff, DJ AF Durazzo, Timothy C. Pennington, David L. Schmidt, Thomas P. Meyerhoff, Dieter J. TI Effects of Cigarette Smoking History on Neurocognitive Recovery Over 8 Months of Abstinence in Alcohol-Dependent Individuals SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Cigarette Smoking; Cognition; Recovery; Longitudinal ID BRAIN; DISORDERS; HMO AB BackgroundThis study compared the rate and extent of recovery on measures of learning and memory, processing speed, and working memory in treatment-seeking alcohol-dependent individuals (ALC) who were never smokers (nvsALC), former smokers (fsALC), and active smokers (asALC) over the first 8months of sustained abstinence from alcohol. Assessments after 1week, 1month, and 8months of abstinence in ALC enabled a comparison of the rates of neurocognitive changes from 1 week to 1 month versus 1 to 8months of abstinence. MethodsALC and never-smoking controls were administered standardized measures of auditory-verbal and visuospatial learning and memory, processing speed, and working memory. Controls completed a baseline assessment and a follow-up approximately 9months later. ResultsOver 8months of abstinence, asALC showed poorer recovery than nvsALC on visuospatial learning, and both fsALC and asALC recovered less than nvsALC on processing speed measures. The corresponding recovery rates for the ALC group, as a whole, were greater from 1 week to 1 month than from 1 to 8months of abstinence; these findings were largely driven by improvements in nvsALC. The recovery levels for fsALC on most measures were similar to those in asALC. Additionally, over 8months, asALC showed significantly less improvement with increasing age than nvsALC on measures of processing speed and learning and memory. At 8months of abstinence, asALC were inferior to controls and nvsALC on multiple measures, fsALC performed worse than nvsALC on several tests, but nvsALC were not different from controls on any measure. ConclusionsOverall, ALC showed rapid improvement on measures of visuospatial learning and processing speed during the first month of abstinence from alcohol. Results also provide robust evidence that smoking status influenced the rate and level of neurocognitive recovery over 8months of abstinence in this ALC cohort. C1 [Durazzo, Timothy C.; Pennington, David L.; Schmidt, Thomas P.; Meyerhoff, Dieter J.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Pennington, David L.; Meyerhoff, Dieter J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [DA24136, AA10788] FX This work was supported by grants from the National Institutes of Health (DA24136 to TCD and AA10788 to DJM) administered by the Northern California Institute for Research and Education and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. NR 28 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2014 VL 38 IS 11 BP 2816 EP 2825 DI 10.1111/acer.12552 PG 10 WC Substance Abuse SC Substance Abuse GA AU5AW UT WOS:000345620400016 PM 25336410 ER PT J AU Conway, KMC Romitti, PA Holmes, L Olney, RS Richardson, SD AF Conway, Kristin M. Caspers Romitti, Paul A. Holmes, Lewis Olney, Richard S. Richardson, Sandra D. CA Natl Birth Defects Prevention TI Maternal Periconceptional Alcohol Consumption and Congenital Limb Deficiencies SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE limb deficiencies; congenital; maternal exposure; pregnancy; alcohol drinking; folic acid ID BIRTH-DEFECTS PREVENTION; URINARY FOLATE EXCRETION; FOR-GESTATIONAL-AGE; REDUCTION DEFECTS; ACUTE ETHANOL; CHOLESTEROL DEFICIENCY; PRETERM BIRTH; UNITED-STATES; PREGNANCY; EXPOSURE AB Background: Women of childbearing age report high rates of alcohol consumption, which may result in alcohol exposure during early pregnancy. Epidemiological research on congenital limb deficiencies (LDs) and periconceptional exposure to alcohol is inconclusive. Methods: Data from the National Birth Defects Prevention Study (NBDPS) were examined for associations between LDs and patterns of maternal periconceptional (1 month before conception through the first trimester) alcohol consumption among LD case (n=906) and unaffected control (n=8352) pregnancies with expected delivery dates from 10/1997 through 12/2007. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated from unconditional logistic regression analysis for all LDs combined, specific LD subtypes (preaxial/terminal transverse), and LD anatomic groups (upper/lower limbs); interactions with folic acid (FA) supplementation were tested. Results: When compared with nondrinkers, inverse associations were found between all LDs combined, preaxial, and upper LDs and any reported periconceptional alcohol consumption (aORs ranged from 0.56-0.83), drinking without binging (aORs: 0.53-0.75), and binge drinking (4 drinks/occasion) (aORs: 0.64-0.94); however, none of the binge drinking aORs were statistically significant. Stratification by alcohol type showed inverse associations between all LDs combined, preaxial, transverse, and upper and lower LDs for drinking without binging of wine only (aORs: 0.39-0.67) and between all LDs combined and upper LDs for drinking without binging of combinations of alcohol (aORs: 0.63-0.87). FA did not modify observed associations. Conclusion: Maternal periconceptional alcohol consumption did not emerge as a teratogen for selected LDs in the NBDPS. Future studies should evaluate additional rare LDs among more highly exposed populations. Birth Defects Research (Part A) 100:863-876, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Conway, Kristin M. Caspers; Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA 52242 USA. [Holmes, Lewis] Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. [Olney, Richard S.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Richardson, Sandra D.] Bur Environm & Occupat Epidemiol, Congenital Malformat Registry, New York State Dept Hlth, Albany, NY USA. RP Romitti, PA (reprint author), Univ Iowa, Dept Epidemiol, Coll Publ Hlth, S416 CPHB,145 N Riverside Dr, Iowa City, IA 52242 USA. EM paul-romitti@uiowa.edu FU Centers for Disease Control and Prevention [U01/DD000492]; Birth Defects Study To Evaluate Pregnancy exposureS [U01/DD001035] FX This work was supported by cooperative agreements from the Centers for Disease Control and Prevention to the Iowa Center for Birth Defects Research and Prevention participating in the National Birth Defects Prevention Study (U01/DD000492) and the Birth Defects Study To Evaluate Pregnancy exposureS (U01/DD001035). NR 55 TC 1 Z9 1 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD NOV PY 2014 VL 100 IS 11 SI SI BP 863 EP 876 DI 10.1002/bdra.23292 PG 14 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AU6CQ UT WOS:000345690600008 ER PT J AU Aldwin, CM Jeong, YJ Igarashi, H Choun, S Spiro, A AF Aldwin, Carolyn M. Jeong, Yu-Jin Igarashi, Heidi Choun, Soyoung Spiro, Avron, III TI Do hassles mediate between life events and mortality in older men? Longitudinal findings from the VA Normative Aging Study SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Stressful life events; Hassles; Mortality; Trajectories; Aging ID DAILY STRESSORS; DEVELOPMENTAL TRAJECTORIES; SOCIAL SUPPORT; HEALTH; DISEASE; DISPARITIES; REACTIVITY; EXPOSURE; ABUSE; RISK AB We investigated whether hassles mediated the effect of life events on mortality in a sample of 1293 men (M-age = 65.58, SD =7.01), participants in the VA Normative Aging Study. We utilized measures of stressful life events (SLE) and hassles from 1989 to 2004, and men were followed for mortality until 2010. For life events and hassles, previous research identified three and four patterns of change over time, respectively, generally indicating low, moderate, and high trajectories, with one moderate, non-linear pattern for hassles (shallow U curve). Controlling for demographics and health behaviors, we found that those with moderate SLE trajectories (38%) more likely to die than those with low SLE trajectories, HR = 1.42, 95% CI [1.16, 3.45]. Including the hassles classes showed that those with the moderate non-linear hassles trajectory were 63% more likely to die than those with low hassles trajectory, HR = 1.63, 95% CI [1.19, 2.23], while those with consistently high hassles trajectory were over 3 times more likely to die, HR = 3.30, 95% CI [1.58, 6.89]. However, the HR for moderate SLE trajectory decreased only slightly to 1.38, 95% CI [1.13, 1.68], suggesting that the two types of stress have largely independent effects on mortality. Research is needed to determine the physiological and behavioral pathways through which SLE and hassles differentially affect mortality. (C) 2014 Elsevier Inc. All rights reserved. C1 [Aldwin, Carolyn M.; Igarashi, Heidi; Choun, Soyoung] Oregon State Univ, Corvallis, OR 97331 USA. [Jeong, Yu-Jin] Chonbuk Natl Univ, Jeonju Si, Jeollabuk Do, South Korea. [Spiro, Avron, III] VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Aldwin, CM (reprint author), Oregon State Univ, Corvallis, OR 97331 USA. EM Carolyn.Aldwin@oregonstate.edu FU NIH [R01 AG032037, AG002287, AG018436]; CSR&D Service, US Department of Veterans Affairs; VA CSP/ERIC FX This study was funded by NIH grants R01 AG032037, AG002287, and AG018436, as well as a Merit Review and a Senior Research Career Scientist Award from the CSR&D Service, US Department of Veterans Affairs. The VA Normative Aging Study is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) and is supported by VA CSP/ERIC. The views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NR 56 TC 3 Z9 3 U1 4 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV PY 2014 VL 59 SI SI BP 74 EP 80 DI 10.1016/j.exger.2014.06.019 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AU6FE UT WOS:000345698100012 PM 24995936 ER PT J AU Lefkowits, C Sukumvanich, P Claxton, R Courtney-Brooks, M Kelley, JL McNeil, MA Goodman, A AF Lefkowits, Carolyn Sukumvanich, Paniti Claxton, Rene Courtney-Brooks, Madeleine Kelley, Joseph L. McNeil, Melissa A. Goodman, Annekathryn TI Needs assessment of palliative care education in gynecologic oncology fellowship: We're not teaching what we think is most important SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Palliative care; Communication; Education ID OF-LIFE CARE; COMMUNICATION-SKILLS; ADVANCE DIRECTIVES; CANCER-PATIENTS; OVARIAN-CANCER; BAD-NEWS; END; SATISFACTION; DISCUSSIONS; MEDICINE AB Objectives. We sought to characterize gynecologic oncology fellowship directors' perspectives on (1) inclusion of palliative care (PC) topics in current fellowship curricula, (2) relative importance of PC topics and (3) interest in new PC curricular materials. Methods. An electronic survey was distributed to fellowship directors, assessing current teaching of 16 PC topics meeting ABOG/ASCO objectives, relative importance of PC topics and interest in new PC curricular materials. Descriptive and correlative statistics were used. Results. Response rate was 63% (29/46). 100% of programs had coverage of some PC topic in didactics in the past year and 48% (14/29) have either a required or elective PC rotation. Only 14% (4/29) have a written PC curriculum. Rates of explicit teaching of PC topics ranged from 36% (fatigue) to 93% (nausea). Four of the top five most important PC topics for fellowship education were communication topics. There was no correlation between topics most frequently taught and those considered most important (r(s) = 0.11, p = 0.69). All fellowship directors would consider using new PC curricular materials. Educational modalities of greatest interest include example teaching cases and PowerPoint slides. Conclusions. Gynecologic oncology fellowship directors prioritize communication topics as the most important PC topics for fellows to learn. There is no correlation between which PC topics are currently being taught and which are considered most important. Interest in new PC curricular materials is high, representing an opportunity for curricular development and dissemination. Future efforts should address identification of optimal methods for teaching communication to gynecologic oncology fellows. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lefkowits, Carolyn; Sukumvanich, Paniti; Courtney-Brooks, Madeleine; Kelley, Joseph L.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol,Med Ctr, Pittsburgh, PA 15213 USA. [Claxton, Rene] Univ Pittsburgh, Sect Palliat Care & Med Eth, Div Gen Internal Med, Dept Med,Med Ctr, Pittsburgh, PA 15213 USA. [McNeil, Melissa A.] Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15213 USA. [Goodman, Annekathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP Lefkowits, C (reprint author), UPMC, Magee Womens Hosp, Div Gynecol Oncol, 300 Halket St, Pittsburgh, PA 15213 USA. EM caseylefflowitscj@upmc.edu NR 55 TC 3 Z9 3 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2014 VL 135 IS 2 BP 255 EP 260 DI 10.1016/j.ygyno2014.08.016 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AU4TW UT WOS:000345605200015 PM 25135001 ER PT J AU Lefkowits, C Sukumvanich, P Claxton, R Courtney-Brooks, M Kelley, I McNeil, MA Goodman, AK AF Lefkowits, C. Sukumvanich, P. Claxton, R. Courtney-Brooks, M. Kelley, Il. McNeil, M. A. Goodman, A. K. TI Needs assessment of palliative care education in gynecologic oncology fellowship: We're not teaching what we think is most important SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Lefkowits, C.; Sukumvanich, P.; Courtney-Brooks, M.; Kelley, Il.] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Div Gynecol Oncol, Pittsburgh, PA 15213 USA. [Claxton, R.] UPMC, Dept Internal Med, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. [McNeil, M. A.] UPMC, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Goodman, A. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2014 VL 135 IS 2 BP 390 EP 390 DI 10.1016/j.ygyno.2014.07.029 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AU4TW UT WOS:000345605200055 ER PT J AU Goldman, JM AF Goldman, Julian M. TI Solving the Interoperability Challenge Safe and reliable information exchange requires more from product designers SO IEEE PULSE LA English DT Article C1 [Goldman, Julian M.] Partners Hlth Care Boston, Boston, MA 02199 USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldman, JM (reprint author), Partners Hlth Care Boston, Boston, MA 02199 USA. EM jmgoldman@mgh.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 2154-2287 J9 IEEE PULSE JI IEEE Pulse PD NOV-DEC PY 2014 VL 5 IS 6 BP 37 EP 39 DI 10.1109/MPUL.2014.2355307 PG 3 WC Engineering, Biomedical SC Engineering GA AU5CF UT WOS:000345624000009 PM 25415883 ER PT J AU Bogenschutz, MP Donovan, DM Mandler, RN Perl, HI Forcehimes, AA Crandall, C Lindblad, R Oden, NL Sharma, G Metsch, L Lyons, MS McCormack, R Konstantopoulos, WM Douaihy, A AF Bogenschutz, Michael P. Donovan, Dennis M. Mandler, Raul N. Perl, Harold I. Forcehimes, Alyssa A. Crandall, Cameron Lindblad, Robert Oden, Neal L. Sharma, Gaurav Metsch, Lisa Lyons, Michael S. McCormack, Ryan Konstantopoulos, Wendy Macias Douaihy, Antoine TI Brief Intervention for Patients With Problematic Drug Use Presenting in Emergency Departments A Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID SCREENING-TEST; TRAUMA CENTER; ALCOHOL; DISORDERS; MISUSE; RISK; CARE AB IMPORTANCE Medical treatment settings such as emergency departments (EDs) present important opportunities to address problematic substance use. Currently, EDs do not typically intervene beyond acute medical stabilization. OBJECTIVE To contrast the effects of a brief intervention with telephone boosters (BI-B) with those of screening, assessment, and referral to treatment (SAR) and minimal screening only (MSO) among drug-using ED patients. DESIGN, SETTING, AND PARTICIPANTS Between October 2010 and February 2012, 1285 adult ED patients from 6 US academic hospitals, who scored 3 or greater on the 10-item Drug Abuse Screening Test (indicating moderate to severe problems related to drug use) and who were currently using drugs, were randomized to MSO (n = 431), SAR (n = 427), or BI-B (n = 427). Follow-up assessments were conducted at 3, 6, and 12 months by blinded interviewers. INTERVENTIONS Following screening, MSO participants received only an informational pamphlet. The SAR participants received assessment plus referral to addiction treatment if indicated, and the BI-B participants received assessment and referral as in SAR, plus a manual-guided counseling session based on motivational interviewing principles and up to 2 "booster" sessions by telephone during the month following the ED visit. MAIN OUTCOMES AND MEASURES Outcomes evaluated at follow-up visits included self-reported days using the patient-defined primary problem drug, days using any drug, days of heavy drinking, and drug use based on analysis of hair samples. The primary outcome was self-reported days of use of the patient-defined primary problem drug during the 30-day period preceding the 3-month follow-up. RESULTS Follow-up rates were 89%, 86%, and 81% at 3, 6, and 12 months, respectively. For the primary outcome, estimated differences in number of days of use (95% CI) were as follows: MSO vs BI-B, 0.72 (-0.80 to 2.24), P (adjusted) = .57; SAR vs BI-B, 0.70 (-0.83 to 2.23), P (adjusted) = .57; SAR vs MSO, -0.02 (-1.53 to 1.50), P (adjusted) = .98. There were no significant differences between groups in self-reported days using the primary drug, days using any drug, or heavy drinking days at 3, 6, or 12 months. At the 3-month follow-up, participants in the SAR group had a higher rate of hair samples positive for their primary drug of abuse (265 of 280 [95%]) than did participants in the MSO group (253 of 287 [88%]) or the BI-B group (244 of 275 [89%]). Hair analysis differences between groups at other time points were not significant. CONCLUSIONS AND RELEVANCE In this sample of drug users seeking emergency medical treatment, a relatively robust brief intervention did not improve substance use outcomes. More work is needed to determine how drug use disorders may be addressed effectively in the ED. C1 [Bogenschutz, Michael P.; Forcehimes, Alyssa A.] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. [Bogenschutz, Michael P.; Forcehimes, Alyssa A.] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA. [Donovan, Dennis M.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98195 USA. [Donovan, Dennis M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Mandler, Raul N.; Perl, Harold I.] NIDA, Bethesda, MD 20892 USA. [Crandall, Cameron] Univ New Mexico, Hlth Sci Ctr, Dept Emergency Med, Albuquerque, NM 87131 USA. [Lindblad, Robert; Oden, Neal L.; Sharma, Gaurav] EMMES Corp, Rockville, MD USA. [Metsch, Lisa] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Lyons, Michael S.] Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA. [McCormack, Ryan] NYU, Sch Med, Dept Emergency Med, New York, NY USA. [Konstantopoulos, Wendy Macias] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Konstantopoulos, Wendy Macias] Harvard Univ, Sch Med, Boston, MA USA. [Douaihy, Antoine] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Bogenschutz, MP (reprint author), Univ New Mexico, Hlth Sci Ctr, Ctr Psychiat Res, Dept Psychiat, MSC11 6035,1 Univ New Mexico, Albuquerque, NM 87131 USA. EM mbogenschutz@salud.unm.edu OI Bogenschutz, Michael/0000-0003-4530-3470; McCormack, Ryan/0000-0002-7210-4736 FU EMMES Corporation [NIDA: HHSN271200900034C]; [U10DA015833]; [U10DA013714]; [U10DA013720]; [U10DA013732]; [U10DA013046]; [U10DA015831]; [U10DA020036]; [U10DA013035] FX The study was supported by the following grants from NIDA: HHSN271200900034C (EMMES Corporation); U10DA015833 (Principal Investigator [PI], Michael P. Bogenschutz); U10DA013714 (PI, Dennis M. Donovan); U10DA013720 (PIs, Jose Szapocznik, PhD, and Lisa Metsch); U10DA013732 (PI, Theresa Winhusen); U10DA013046 (PI, John Rotrosen); U10DA015831 (PIs, Roger D. Weiss and Kathleen M. Carroll, PhD); U10DA020036 (PI, Dennis C. Daley); and U10DA013035 (PIs, John Rotrosen and Edward V. Nunes). NR 28 TC 26 Z9 26 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV PY 2014 VL 174 IS 11 BP 1736 EP 1745 DI 10.1001/jamainternmed.2014.4052 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KA UT WOS:000345909900010 PM 25179753 ER PT J AU Lee, JS Nsa, W Hausmann, LRM Trivedi, AN Bratzler, DW Auden, D Mor, MK Baus, K Larbi, FM Fine, MJ AF Lee, Jonathan S. Nsa, Wato Hausmann, Leslie R. M. Trivedi, Amal N. Bratzler, Dale W. Auden, Dana Mor, Maria K. Baus, Kristie Larbi, Fiona M. Fine, Michael J. TI Quality of Care for Elderly Patients Hospitalized for Pneumonia in the United States, 2006 to 2010 SO JAMA INTERNAL MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; ALL-CAUSE MORTALITY; PNEUMOCOCCAL VACCINATION; INFLUENZA VACCINATION; PERFORMANCE-MEASURES; MEDICARE PATIENTS; ADULTS; OUTCOMES; METAANALYSIS; ASSOCIATIONS AB IMPORTANCE Nearly every US acute care hospital reports publicly on adherence to recommended processes of care for patients hospitalized with pneumonia. However, it remains uncertain how much performance of these process measures has improved over time or whether performance is associated with superior patient outcomes. OBJECTIVES To describe trends in processes of care, mortality, and readmission for elderly patients hospitalized for pneumonia and to assess the independent associations between processes and outcomes of care. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study conducted from January 1, 2006, to December 31, 2010, at 4740 US acute care hospitals. The cohort included 1 818 979 cases of pneumonia in elderly (>= 65 years), Medicare fee-for-service patients who were eligible for at least 1 of 7 pneumonia inpatient processes of care tracked by the Centers for Medicare & Medicaid Services (CMS). MAIN OUTCOMES AND MEASURES Annual performance rates for 7 pneumonia processes of care and an all-or-none composite of these measures; and 30-day, all-cause mortality and hospital readmission, adjusted for patient and hospital characteristics. RESULTS Adjusted annual performance rates for all 7 CMS processes of care (expressed in percentage points per year) increased significantly from 2006 to 2010, ranging from 1.02 for antibiotic initiation within 6 hours to 5.30 for influenza vaccination (P < .001). All 7 measures were performed in more than 92% of eligible cases in 2010. The all-or-none composite demonstrated the largest adjusted relative increase over time (6.87 percentage points per year; P < .001) and was achieved in 87.4% of cases in 2010. Adjusted annual mortality decreased by 0.09 percentage points per year (P < .001), driven primarily by decreasing mortality in the subgroup not treated in the intensive care unit (ICU) (-0.18 percentage points per year; P < .001). Adjusted annual readmission rates decreased significantly by 0.25 percentage points per year (P < .001). All 7 processes of care were independently associated with reduced 30-day mortality, and 5 were associated with reduced 30-day readmission. CONCLUSIONS AND RELEVANCE Performance of processes of care for elderly patients hospitalized for pneumonia improved substantially from 2006 to 2010. Adjusted 30-day mortality declined slightly over time primarily owing to improved survival among non-ICU patients, and all individual processes of care were independently associated with reduced mortality. C1 [Lee, Jonathan S.; Hausmann, Leslie R. M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Nsa, Wato; Auden, Dana] Oklahoma Fdn Med Qual, Oklahoma City, OK USA. [Hausmann, Leslie R. M.; Mor, Maria K.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Trivedi, Amal N.] Brown Univ, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Bratzler, Dale W.] Univ Oklahoma, Hlth Sci Ctr, Coll Med & Publ Hlth, Oklahoma City, OK USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Baus, Kristie; Larbi, Fiona M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr 151C, Pittsburgh, PA 15240 USA. EM michael.fine@va.gov FU CMS, an agency of the US Department of Health and Human Services [HHSM-500-2011-OK10C] FX The analyses on which this study is based were performed under contract No. HHSM-500-2011-OK10C funded by the CMS, an agency of the US Department of Health and Human Services. NR 48 TC 12 Z9 12 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV PY 2014 VL 174 IS 11 BP 1806 EP 1814 DI 10.1001/jamainternmed.2014.4501 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KA UT WOS:000345909900021 PM 25201438 ER PT J AU Sammon, JD Pucheril, D Diaz, M Kibel, AS Kantoff, PW Menon, M Trinh, QD AF Sammon, Jesse D. Pucheril, Daniel Diaz, Mireya Kibel, Adam S. Kantoff, Philip W. Menon, Mani Quoc-Dien Trinh TI Contemporary Nationwide Patterns of Self-reported Prostate-Specific Antigen Screening SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Sammon, Jesse D.; Pucheril, Daniel; Diaz, Mireya; Menon, Mani; Quoc-Dien Trinh] Henry Ford Hlth Syst, Ctr Outcomes Res Analyt & Evaluat, Vattikuti Urol Inst, Detroit, MI USA. [Kibel, Adam S.; Quoc-Dien Trinh] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02115 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Trinh, QD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 45 Francis St,ASB 2-3, Boston, MA 02115 USA. EM trinh.qd@gmail.com NR 6 TC 15 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV PY 2014 VL 174 IS 11 BP 1839 EP 1841 DI 10.1001/jamainternmed.2014.4117 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AU9KA UT WOS:000345909900027 PM 25179266 ER PT J AU McCarthy, AM Kontos, D Synnestvedt, M Tan, KS Heitjan, DF Schnall, M Conant, EF AF McCarthy, Anne Marie Kontos, Despina Synnestvedt, Marie Tan, Kay See Heitjan, Daniel F. Schnall, Mitchell Conant, Emily F. TI Screening Outcomes Following Implementation of Digital Breast Tomosynthesis in a General-Population Screening Program SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SERVICES TASK-FORCE; MAMMOGRAPHY; CANCER; PERFORMANCE AB Background Early data on breast cancer screening utilizing digital breast tomosynthesis (DBT) combined with digital mammography (DM) have shown improvements in false-positive and false-negative screening rates compared with DM alone. However, these trials were performed at sites where conventional mammographic screening was concurrently performed, possibly leading to selection biases or with complex, multireader algorithms not reflecting general clinical practice. Our study reports the impact on screening outcomes for DBT screening implemented in an entire clinic population. Methods Recall rates, cancer detection, and positive predictive values of screening were compared for 15 571 women screened with DBT and 10 728 screened with DM alone prior to DBT implementation at a single breast imaging center. Generalized linear mixed-effects models were used to estimate the odds ratio (OR) for recall rate adjusted for age, race, presence of prior mammograms, breast density and reader. All statistical tests were two-sided. Results DBT screening showed a statistically significant reduction in recalls compared to DM alone. For the entire population, there were 16 fewer recalls (8.8% vs 10.4%, P <.001, adjusted OR = 0.80, 95% confidence interval [CI] = 0.74 to 0.88, P <.001) and 0.9 additional cancers detected per 1000 screened with DBT compared to DM alone. There was a statistically significant increase in PPV1 (6.2% vs 4.4%, P = .047). In women younger than age 50 years screened with DBT, there were 17 fewer recalls (12.3% vs 14.0%, P = .02) and 3.6 additional cancer detected per 1000 screened (5.7 vs 2.2 per 1000, P = .02). Conclusions Our data support the clinical implementation of DBT in breast cancer screening; however, larger prospective trials are needed to validate our findings in specific patient subgroups. C1 [McCarthy, Anne Marie; Synnestvedt, Marie] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Kontos, Despina; Synnestvedt, Marie; Conant, Emily F.] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. [Tan, Kay See; Heitjan, Daniel F.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [McCarthy, Anne Marie] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [McCarthy, Anne Marie] Harvard Univ, Sch Med, Boston, MA USA. RP Conant, EF (reprint author), Univ Penn, Perelman Sch Med, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM emily.conant@uphs.upenn.edu FU U54 grant from the National Cancer Institute at the National Institutes of Health: Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) Network [U54CA163313] FX This work was supported by a U54 grant from the National Cancer Institute at the National Institutes of Health: Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) Network (U54CA163313). NR 22 TC 14 Z9 14 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD NOV PY 2014 VL 106 IS 11 AR dju316 DI 10.1093/jnci/dju316 PG 7 WC Oncology SC Oncology GA AU7IG UT WOS:000345773500024 ER PT J AU Munoz, D Near, AM van Ravesteyn, NT Lee, SJ Schechter, CB Alagoz, O Berry, DA Burnside, ES Chang, YJ Chisholm, G de Koning, HJ Ergun, MA Heijnsdijk, EAM Huang, H Stout, NK Sprague, BL Trentham-Dietz, A Mandelblatt, JS Plevritis, SK AF Munoz, Diego Near, Aimee M. van Ravesteyn, Nicolien T. Lee, Sandra J. Schechter, Clyde B. Alagoz, Oguzhan Berry, Donald A. Burnside, Elizabeth S. Chang, Yaojen Chisholm, Gary de Koning, Harry J. Ergun, Mehmet Ali Heijnsdijk, Eveline A. M. Huang, Hui Stout, Natasha K. Sprague, Brian L. Trentham-Dietz, Amy Mandelblatt, Jeanne S. Plevritis, Sylvia K. TI Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BRCA1/2 MUTATION CARRIERS; CIRCULATING TUMOR-CELLS; RANDOMIZED-TRIALS; UNITED-STATES; HORMONE-THERAPY; MAMMOGRAPHY; CHEMOTHERAPY; TRASTUZUMAB; RISK; SURVIVAL AB Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100 000 women (model range = 13-21) and 5 per 100 000 women (model range = 3-6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%-87.8% vs 85.7%-96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. C1 [Munoz, Diego] Stanford Univ, Sch Med, Div Biomed Informat Res, Stanford, CA 94305 USA. [Munoz, Diego; Plevritis, Sylvia K.] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. [Near, Aimee M.; Chang, Yaojen; Mandelblatt, Jeanne S.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Near, Aimee M.; Chang, Yaojen; Mandelblatt, Jeanne S.] Georgetown Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Washington, DC USA. [van Ravesteyn, Nicolien T.; de Koning, Harry J.; Heijnsdijk, Eveline A. M.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Lee, Sandra J.; Huang, Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lee, Sandra J.; Huang, Hui] Harvard Univ, Sch Med, Boston, MA USA. [Schechter, Clyde B.] Albert Einstein Coll Med, Dept Family & Social Med, Bronx, NY 10467 USA. [Schechter, Clyde B.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Alagoz, Oguzhan; Ergun, Mehmet Ali] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI USA. [Burnside, Elizabeth S.; Trentham-Dietz, Amy] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Berry, Donald A.; Chisholm, Gary] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Stout, Natasha K.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Sprague, Brian L.] Univ Vermont, Coll Med, Dept Surg, Burlington, VT 05405 USA. RP Plevritis, SK (reprint author), Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. EM sylvia.plevritis@stanford.edu RI Burnside, Elizabeth/M-9414-2014 OI Burnside, Elizabeth/0000-0002-6600-435X FU National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network [U01 CA152958]; National Cancer Institute [HHSN261 201100031C] FX This research was supported by grant number U01 CA152958 from the National Cancer Institute as part of the Cancer Intervention and Surveillance Modeling Network. Data were provided by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (HHSN261 201100031C). NR 47 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD NOV PY 2014 VL 106 IS 11 AR dju289 DI 10.1093/jnci/dju289 PG 9 WC Oncology SC Oncology GA AU7IG UT WOS:000345773500009 ER PT J AU Lyles, CR Schafer, AL Seligman, HK AF Lyles, Courtney R. Schafer, Anne L. Seligman, Hilary K. TI Income, Food Insecurity, and Osteoporosis among Older Adults in the 2007-2008 National Health and Nutrition Examination Survey (NHANES) SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Aging; disparities; osteoporosis; socioeconomic factors; nutrition; food insecurity ID BONE-MINERAL DENSITY; BODY-MASS INDEX; FRACTURE RISK; SOCIOECONOMIC-STATUS; UNITED-STATES; VITAMIN-D; METAANALYSIS; WOMEN; ASSOCIATION; EPIDEMIOLOGY AB Background. Low SES is associated with risk and protective factors for osteoporosis. However, there has been little examination of SES and osteoporosis in the U.S. Methods. We conducted a cross-sectional study of adults aged 50 or older in 2007-2008 NHANES, examining two predictors of SES: income and food insecurity. Our outcome was osteoporosis assessed from bone scans. Adjusted regression models (overall and gender-stratified) controlled for age, gender, race/ethnicity, education, BMI, smoking, alcohol consumption, physical activity, calcium and vitamin D, and medication use. Results. Of 2403 participants, 5% had osteoporosis. In adjusted models, there was a higher risk of osteoporosis in low-income (OR; 95% CI: 1.90;1.07-3.37) and food-insecure populations (3.48;1.43-8.48). There was a stronger association with food insecurity among women (4.91;2.40-10.0) than men (0.46;0.07-3.01). Conclusions. Income and food insecurity may have significant implications not just for immediate nutritional outcomes, but also for conditions such as osteoporosis that develop over the lifespan. C1 [Lyles, Courtney R.; Seligman, Hilary K.] San Francisco Gen Hosp, UCSF Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Lyles, Courtney R.; Seligman, Hilary K.] UCSF Ctr Vulnerable Populat, San Francisco, CA USA. [Schafer, Anne L.] UCSF Dept Med, Div Endocrinol & Metab, San Francisco, CA USA. [Schafer, Anne L.] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, VA USA. RP Lyles, CR (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Ctr Vulnerable Populat, 1001 Potrero Ave Bldg 10,W13,Box 1364, San Francisco, CA 94110 USA. FU AHRQ HHS [K99HS022408]; NCRR NIH HHS [KL2RR024130] NR 42 TC 1 Z9 1 U1 1 U2 9 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 EI 1548-6869 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2014 VL 25 IS 4 BP 1530 EP 1541 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AU6SN UT WOS:000345732200007 PM 25418225 ER PT J AU Griffis, HM Kilaru, AS Werner, RM Asch, DA Hershey, JC Hill, S Ha, YP Sellers, A Mahoney, K Merchant, RM AF Griffis, Heather M. Kilaru, Austin S. Werner, Rachel M. Asch, David A. Hershey, John C. Hill, Shawndra Ha, Yoonhee P. Sellers, Allison Mahoney, Kevin Merchant, Raina M. TI Use of Social Media Across US Hospitals: Descriptive Analysis of Adoption and Utilization SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE social media; Internet; health information ID HEALTH-CARE; PATIENT RATINGS; QUALITY; ASSOCIATIONS; INTERNET; ONLINE AB Background: Use of social media has become widespread across the United States. Although businesses have invested in social media to engage consumers and promote products, less is known about the extent to which hospitals are using social media to interact with patients and promote health. Objective: The aim was to investigate the relationship between hospital social media extent of adoption and utilization relative to hospital characteristics. Methods: We conducted a cross-sectional review of hospital-related activity on 4 social media platforms: Facebook, Twitter, Yelp, and Foursquare. All US hospitals were included that reported complete data for the Centers for Medicare and Medicaid Services Hospital Consumer Assessment of Healthcare Providers and Systems survey and the American Hospital Association Annual Survey. We reviewed hospital social media webpages to determine the extent of adoption relative to hospital characteristics, including geographic region, urban designation, bed size, ownership type, and teaching status. Social media utilization was estimated from user activity specific to each social media platform, including number of Facebook likes, Twitter followers, Foursquare check-ins, and Yelp reviews. Results: Adoption of social media varied across hospitals with 94.41% (3351/3371) having a Facebook page and 50.82% (1713/3371) having a Twitter account. A majority of hospitals had a Yelp page (99.14%, 3342/3371) and almost all hospitals had check-ins on Foursquare (99.41%, 3351/3371). Large, urban, private nonprofit, and teaching hospitals were more likely to have higher utilization of these accounts. Conclusions: Although most hospitals adopted at least one social media platform, utilization of social media varied according to several hospital characteristics. This preliminary investigation of social media adoption and utilization among US hospitals provides the framework for future studies investigating the effect of social media on patient outcomes, including links between social media use and the quality of hospital care and services. C1 [Griffis, Heather M.; Sellers, Allison] Univ Penn, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Kilaru, Austin S.] Highland Hosp, Dept Emergency Med, Oakland, CA USA. [Werner, Rachel M.] Univ Penn, Perelman Sch Med, Ctr Hlth Equity Res & Promot, Philadelphia VA Med Ctr,Div Gen Internal Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Philadelphia VA Med Ctr, Penn Med Ctr Healthcare Innovat, Philadelphia, PA 19104 USA. [Hershey, John C.; Hill, Shawndra] Univ Penn, Wharton Sch, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Ha, Yoonhee P.] Univ Penn, Perelman Sch Med, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. [Mahoney, Kevin] Univ Penn, Penn Med, Philadelphia, PA 19104 USA. [Merchant, Raina M.] Univ Penn, Dept Emergency Med, Penn Social Media & Hlth Innovat Lab, Philadelphia, PA 19104 USA. RP Merchant, RM (reprint author), Univ Penn, Dept Emergency Med, Penn Social Media & Hlth Innovat Lab, 423 Guardian Dr,Room 1022, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu NR 22 TC 12 Z9 12 U1 3 U2 29 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD NOV PY 2014 VL 16 IS 11 AR e264 DI 10.2196/jmir.3758 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AU5FJ UT WOS:000345632300043 PM 25431831 ER PT J AU Owusu-Darko, S Rauh-Hain, JA Horowitz, NS Goodman, A Schorge, JO del Carmen, MG AF Owusu-Darko, Sharon Rauh-Hain, J. Alejandro Horowitz, Neil S. Goodman, Annekathryn Schorge, John O. del Carmen, Marcela G. TI Comparison of Outcomes in Patients with Early-stage Mucinous Endometrial Cancer and Those with Endometrioid Endometrial Cancer, With and Without Adjuvant Therapy SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE endometrial cancer; endometrioid endometrial cancer; gynecological malignancies; hyperestrogenism; mucinous endometrial cancer ID SIMULATING MICROGLANDULAR HYPERPLASIA; GYNECOLOGIC-ONCOLOGY-GROUP; UTERINE CORPUS; IMMUNOHISTOCHEMICAL FEATURES; ADENOCARCINOMA; CARCINOMA; EMPHASIS; CERVIX AB OBJECTIVE: To compare risk factors, treatment, and outcomes in patients with stage I/II mucinous endometrial cancer (MEC) relative to those of patients with endometrioid endometrial cancer (EEC). STUDY DESIGN: We conducted a case-control study of patients with MEC and EEC. Patients with stage IA, IB, or II MEC treated at the 2 institutions between 01/01/ 1996 and 01/01/2007 were identified. Each MEC case was matched with 2 EEC controls by age, stage, grade, and year of diagnosis. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. RESULTS: A total of 34 patients with MEC were compared to 68 controls with EEC. All patients were treated by hysterectomy and bilateral salpingo-oophorectomy. Use of adjuvant radiation therapy was similar between cases and controls. The 5-year disease-free survival (DFS) rates were not significantly different in patients with MEC when compared to those with EEC (89% vs. 92%, respectively, p =0.2). The 5-year OS rates for patients with MEC and the control group were 95% and 96%, respectively (p =0.1). CONCLUSION: Patients with early-stage MEC and EEC have similar DFS and overall survival. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 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 mdeclarmen@partners.org NR 29 TC 0 Z9 1 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD NOV-DEC PY 2014 VL 59 IS 11-12 BP 527 EP 533 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW1HO UT WOS:000346041000002 PM 25552123 ER PT J AU Rauh-Hain, JA Goodman, A Boruta, DM Schorge, JO Horowitz, NS del Carmen, MG AF Rauh-Hain, J. Alejandro Goodman, Annekathryn Boruta, David M. Schorge, John O. Horowitz, Neil S. del Carmen, Marcela G. TI Endometrial Stromal Sarcoma A Clinicopathologic Study of 29 Patients SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE endometrial carcinoma; endometrial stromal sarcoma; hormones; late disease recurrence; surgery ID PROGNOSTIC-SIGNIFICANCE; DNA-PLOIDY; TUMOR SIZE; GRADE; UTERUS; LYMPHADENECTOMY; EXPRESSION; ESTROGEN; STAGE AB OBJECTIVE: To analyze clinicopathological characteristics, treatment, and survival in patients with endometrial stromal sarcoma (ESS). STUDY DESIGN: Patients with ESS were identified from the tumor registry of the two participating institutions. Categorical variables were evaluated by chi(2) analysis or Fisher's exact test. Survival estimates were plotted utilizing the Kaplan-Meier method. The log-rank test was utilized to quantify survival differences on univariate analysis. RESULTS: A total of 29 patients with ESS were included: 14 (48%) patients with stage I, 1 (3.4%) with stage II, 5 (17%) with stage III, and 9 (31%) with stage IV disease. Median age was 44 (range, 25-62). Most patients were treated by hysterectomy and salpingo-oophorectomy. Sixteen patients (55%) received adjuvant therapy after surgery. The most common type of adjuvant therapy was hormonal treatment. Median follow-up was 84 months (range, 1-382 months). Four patients with stage I (36%), 2 with stage III (18%), and 5 (46%) with stage IV developed disease recurrences. In 8 cases (73%) the recurrence site was the abdomen and pelvis, and in 3 cases (27%) the recurrence site was the lung. CONCLUSION: ESS is an indolent tumor with propensity for late recurrence. Age, early tumor stage (stage I), lymph node dissection, and adjuvant therapy did not affect disease-free or overall survival. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM mdeclarmen@partners.org NR 26 TC 1 Z9 1 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD NOV-DEC PY 2014 VL 59 IS 11-12 BP 547 EP 552 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AW1HO UT WOS:000346041000005 PM 25552126 ER PT J AU LaBuzetta, JN Yoo, AJ Ali, S Fitzpatrick, K Leslie-Mazwi, T Hirsch, JA Schwamm, L Rost, N AF LaBuzetta, Jamie Nicole Yoo, Albert J. Ali, Syed Fitzpatrick, Kaitlin Leslie-Mazwi, Thabele Hirsch, Joshua A. Schwamm, Lee Rost, Natalia TI Determinants of Early Outcomes in Patients with Acute Ischemic Stroke and Proximal Artery Occlusion SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; tPA; endovascular treatment; outcome; proximal artery occlusion ID TISSUE-PLASMINOGEN-ACTIVATOR; INTRAVENOUS THROMBOLYSIS; INTRAARTERIAL THERAPY; ENDOVASCULAR THERAPY; EARLY RECANALIZATION; INFARCT VOLUME; REVASCULARIZATION; THROMBECTOMY; TIME; METAANALYSIS AB Background: Proximal artery occlusions (PAO) recanalize in only a small percentage of acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV tPA) alone, yet the benefits of adjunctive or substitutive intra-arterial therapy (IAT) in this patient subgroup are not well established. We evaluated early poststroke outcomes in a cohort of AIS patients with PAO categorized as "likely to benefit'' (LTB) from IAT using prespecified criteria. Methods: Using a prespecified protocol, 193 patients from our institutional stroke database admitted between January 1, 2007, and December 31, 2011, were prospectively deemed LTB from IAT. Logistic regression was used to determine independent predictors of favorable (discharge to home or acute rehabilitation) versus unfavorable (discharge to skilled nursing facility, hospice, or in-hospital mortality) outcome. Results: Of the patients included, 29.5% received IV tPA only, 11.4% underwent IAT only, and 37.8% had both. Overall in-hospital mortality was 19.2%. In a univariate analysis, age (odds ratio [OR], .95; 95% confidence interval [CI],.93-. 98), IV tPA (OR, 2.3; 95% CI, 1.2-4.3), and history of atrial fibrillation (OR, .5; 95% CI,.28-. 97) were associated with outcome. Effect of IAT was not statistically significant (OR, 1.3; 95% CI,.7-2.3; P = .4). In multivariate analysis, the only independent predictor of favorable outcome was IV tPA administration (OR, 2.4; 95% CI, 1.2-5.0). The odds of favorable poststroke outcome were significantly lowered (OR, .3; 95% CI,.1-. 6; P =.0006) in those receiving neither IV tPA nor IAT. Conclusions: In AIS patients with PAO thought most likely to benefit from IAT, IV tPA independently predicted favorable outcomes. These data reinforce the recommendation to provide early IV tPA to all eligible patients. C1 [LaBuzetta, Jamie Nicole; Fitzpatrick, Kaitlin; Leslie-Mazwi, Thabele; Schwamm, Lee; Rost, Natalia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Yoo, Albert J.; Ali, Syed; Leslie-Mazwi, Thabele; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rost, N (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM nrost@partners.org FU National Institute of Neurological Disorders and Stroke (NINDS); American Heart Association Get With The Guidelines-Stroke (GWTG-Stroke); Penumbra Inc; NIH/NINDS [K23 NS064052, R01NS082285]; Genzyme Co. FX This study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), and the American Heart Association Get With The Guidelines-Stroke (GWTG-Stroke). Dr Albert Yoo receives research support from Penumbra Inc and NIH/NINDS. Dr Joshua Hirsch is a shareholder in Intratech. Dr Lee Schwamm is on the CoAxia Advisory Board, the Lundbeck DIAS 4 Intl Steering Committee, and is a Medtronic advisor on device design. He has been involved with RTI Health for economic models of imaging in thrombolysis. He is a stroke systems consultant for the Massachusetts Department of Public Health. Dr Natalia Rost receives research support from the NIH/NINDS (K23 NS064052 and R01NS082285) and Genzyme Co. NR 34 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD NOV-DEC PY 2014 VL 23 IS 10 BP 2527 EP 2532 DI 10.1016/j.jstrokecerebrovasdis.2014.03.020 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AU5ME UT WOS:000345650300019 PM 25238927 ER PT J AU Maschmeyer, G Patterson, TF AF Maschmeyer, Georg Patterson, Thomas F. TI Our 2014 approach to breakthrough invasive fungal infections SO MYCOSES LA English DT Article DE Breakthrough fungal infection; liposomal AmB; fluconazole; posaconazole; voriconazole; echinocandins ID ACUTE MYELOID-LEUKEMIA; MINIMUM INHIBITORY CONCENTRATIONS; STEM-CELL TRANSPLANTATION; IN-VITRO ACTIVITY; AMPHOTERICIN-B; POSACONAZOLE PROPHYLAXIS; ASPERGILLUS-TERREUS; CANDIDA-GLABRATA; DRUG-RESISTANCE; HEMATOLOGICAL MALIGNANCIES AB Evidence-based clinical pathways to direct antifungal treatment options in patients with breakthrough fungal infections during current systemic antifungal therapy are not available. Nonetheless, for defined settings of such breakthrough infections approaches to management can be recommended based on clinical, epidemiological, pharmacological and in vitro susceptibility data. C1 [Maschmeyer, Georg] Charite, Klinikum Ernst von Bergmann, Dept Hematol Oncol & Palliat Care, Acad Teaching Hosp, D-14467 Potsdam, Germany. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio Ctr Med Mycol, Div Infect Dis, San Antonio, TX 78229 USA. RP Maschmeyer, G (reprint author), Charite, Klinikum Ernst von Bergmann, Dept Hematol Oncol & Palliat Care, Acad Teaching Hosp, Charlottenstr 72, D-14467 Potsdam, Germany. EM gmaschmeyer@klinikumevb.de NR 55 TC 6 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0933-7407 EI 1439-0507 J9 MYCOSES JI Mycoses PD NOV PY 2014 VL 57 IS 11 BP 645 EP 651 DI 10.1111/myc.12213 PG 7 WC Dermatology; Mycology SC Dermatology; Mycology GA AU5LP UT WOS:000345648900001 PM 24963554 ER PT J AU Gao, JX Liu, YY D'Souza, RM Barabasi, AL AF Gao, Jianxi Liu, Yang-Yu D'Souza, Raissa M. Barabasi, Albert-Laszlo TI Target control of complex networks SO NATURE COMMUNICATIONS LA English DT Article ID CONTROLLABILITY; EMERGENCE; DYNAMICS AB Controlling large natural and technological networks is an outstanding challenge. It is typically neither feasible nor necessary to control the entire network, prompting us to explore target control: the efficient control of a preselected subset of nodes. We show that the structural controllability approach used for full control overestimates the minimum number of driver nodes needed for target control. Here we develop an alternate 'k-walk' theory for directed tree networks, and we rigorously prove that one node can control a set of target nodes if the path length to each target node is unique. For more general cases, we develop a greedy algorithm to approximate the minimum set of driver nodes sufficient for target control. We find that degree heterogeneous networks are target controllable with higher efficiency than homogeneous networks and that the structure of many real-world networks are suitable for efficient target control. C1 [Gao, Jianxi; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Gao, Jianxi; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Liu, Yang-Yu; Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [D'Souza, Raissa M.] Univ Calif Davis, Complex Sci Ctr, Dept Mech & Aerosp Engn, Davis, CA 95616 USA. [D'Souza, Raissa M.] Univ Calif Davis, Dept Comp Sci, Davis, CA 95616 USA. [D'Souza, Raissa M.] Santa Fe Inst, Santa Fe, NM 87501 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu RI gao, jianxi/I-1300-2013; Gao, Jianxi/C-8494-2015 OI gao, jianxi/0000-0002-3952-208X; Gao, Jianxi/0000-0002-3952-208X FU US Army Research Laboratory; US Army Research Office [W911NF-09-2-0053]; MURI award [W911NF-13-1-0340]; John Templeton Foundation [51977]; Defense Threat Reduction Agency Basic Research Grant [HDTRA1-10-1-0100] FX We gratefully acknowledge support from the US Army Research Laboratory and the US Army Research Office under Cooperative Agreement W911NF-09-2-0053 and MURI award W911NF-13-1-0340, The John Templeton Foundation ID #51977, as well as the Defense Threat Reduction Agency Basic Research Grant No. HDTRA1-10-1-0100. We thank Tao Jia, Jean-Jacques Slotine and Gang Yan for discussions. NR 40 TC 36 Z9 37 U1 4 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD NOV PY 2014 VL 5 AR 5415 DI 10.1038/ncomms6415 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU5CN UT WOS:000345624800036 PM 25388503 ER PT J AU Pathania, S Bade, S Le Guillou, M Burke, K Reed, R Bowman-Colin, C Su, Y Ting, DT Polyak, K Richardson, AL Feunteun, J Garber, JE Livingston, DM AF Pathania, Shailja Bade, Sangeeta Le Guillou, Morwenna Burke, Karly Reed, Rachel Bowman-Colin, Christian Su, Ying Ting, David T. Polyak, Kornelia Richardson, Andrea L. Feunteun, Jean Garber, Judy E. Livingston, David M. TI BRCA1 haploinsufficiency for replication stress suppression in primary cells SO NATURE COMMUNICATIONS LA English DT Article ID DNA-DAMAGE RESPONSE; STRAND BREAK REPAIR; GENOMIC INSTABILITY; CANCER SUSCEPTIBILITY; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; ANTICANCER BARRIER; MUTATION CARRIERS; TUMOR SUPPRESSION; EPITHELIAL-CELLS AB BRCA1-a breast and ovarian cancer suppressor gene-promotes genome integrity. To study the functionality of BRCA1 in the heterozygous state, we established a collection of primary human BRCA1(+/+) and BRCA1(mut/+) mammary epithelial cells and fibroblasts. Here we report that all BRCA1(mut/+) cells exhibited multiple normal BRCA1 functions, including the support of homologous recombination-type double-strand break repair (HR-DSBR), checkpoint functions, centrosome number control, spindle pole formation, Slug expression and satellite RNA suppression. In contrast, the same cells were defective in stalled replication fork repair and/or suppression of fork collapse, that is, replication stress. These defects were rescued by reconstituting BRCA1(mut/+) cells with wt BRCA1. In addition, we observed 'conditional' haploinsufficiency for HR-DSBR in BRCA1(mut/+) cells in the face of replication stress. Given the importance of replication stress in epithelial cancer development and of an HR defect in breast cancer pathogenesis, both defects are candidate contributors to tumorigenesis in BRCA1-deficient mammary tissue. C1 [Pathania, Shailja; Burke, Karly; Bowman-Colin, Christian; Ting, David T.; Polyak, Kornelia; Garber, Judy E.; Livingston, David M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Pathania, Shailja; Bade, Sangeeta; Reed, Rachel; Bowman-Colin, Christian; Su, Ying; Polyak, Kornelia; Richardson, Andrea L.; Garber, Judy E.; Livingston, David M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Le Guillou, Morwenna; Feunteun, Jean] Univ Paris 11, CNRS UMR8200, F-94805 Villejuif, France. [Ting, David T.] Massachusetts Gen Hosp, Dept Hematol Oncol, Charlestown, MA 02129 USA. [Richardson, Andrea L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Pathania, S (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM shailja_pathania@dfci.harvard.edu; david_livingston@dfci.harvard.edu OI Ting, David/0000-0002-3261-2322 FU National Institutes of Health [PO1CA80111-15]; Susan G. Komen Foundation for the Cure [SAC110022]; Breast Cancer Research Foundation; Susan G. Komen for the Cure [CCR13264590]; La Ligue Francaise contre le Cancer; National Cancer Institute (contract BRACAPS) FX We express our deep gratitude to the women who donated their tissues for these studies. We are extremely grateful to Ildi Hajdu for teaching us the DNA fibre assay and analysis. We also thank Stoil Dimitrov and Jorge Ernesto Gonzalez for help and advice in setting up the comet assay and the CellProfiler pipeline for comet data analysis, and Manish Neupane for pMIG-hTERT and pBABE-hygro-hTERT plasmids. We thank Aaron R. Thorner and Paul Van Hummelen from the DFCI Center for Cancer Genome Discovery (CCGD) for help with genotyping the BRCA1 mutations. We also thank multiple members of the Livingston laboratory for valuable discussions. This work was supported in part by grants to D. M. L from the National Institutes of Health (PO1CA80111-15), the Susan G. Komen Foundation for the Cure (SAC110022), the Breast Cancer Research Foundation, and a generous gift from Richard and Ann Solomon. S. P. was also supported by a grant from Susan G. Komen for the Cure (CCR13264590). This work was also supported in part by La Ligue Francaise contre le Cancer and The National Cancer Institute (contract BRACAPS) to J.F. NR 68 TC 29 Z9 29 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD NOV PY 2014 VL 5 AR 5496 DI 10.1038/ncomms6496 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU9LA UT WOS:000345913000001 PM 25400221 ER PT J AU Valentino, MD McGuire, AM Rosch, JW Bispo, PJM Burnham, C Sanfilippo, CM Carter, RA Zegans, ME Beall, B Earl, AM Tuomanen, EI Morris, TW Haas, W Gilmore, MS AF Valentino, Michael D. McGuire, Abigail Manson Rosch, Jason W. Bispo, Paulo J. M. Burnham, Corinna Sanfilippo, Christine M. Carter, Robert A. Zegans, Michael E. Beall, Bernard Earl, Ashlee M. Tuomanen, Elaine I. Morris, Timothy W. Haas, Wolfgang Gilmore, Michael S. TI Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster SO NATURE COMMUNICATIONS LA English DT Article ID GROUP-B STREPTOCOCCI; OPHTHALMIC SUSPENSION 0.6-PERCENT; C-PROTEIN COMPLEX; BACTERIAL CONJUNCTIVITIS; ANTIMICROBIAL RESISTANCE; STAPHYLOCOCCUS-AUREUS; PNEUMOCOCCAL VACCINE; SPECIES DEFINITION; EPITHELIAL-CELLS; FAMILY ADHESINS AB Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the United States. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with other unencapsulated nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not been described in encapsulated pneumococci. These findings suggest that the unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis strategy substantially different from that described for S. pneumoniae at other infection sites. C1 [Valentino, Michael D.; Bispo, Paulo J. M.; Haas, Wolfgang; Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Valentino, Michael D.; Bispo, Paulo J. M.; Haas, Wolfgang; Gilmore, Michael S.] Harvard Univ, Dept Microbiol & Immunobiol, Sch Med, Boston, MA 02115 USA. [Valentino, Michael D.; McGuire, Abigail Manson; Earl, Ashlee M.; Gilmore, Michael S.] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA. [Rosch, Jason W.; Burnham, Corinna; Carter, Robert A.; Tuomanen, Elaine I.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Sanfilippo, Christine M.; Tuomanen, Elaine I.] Bausch & Lomb Inc, Rochester, NY 14609 USA. [Zegans, Michael E.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH 03755 USA. [Beall, Bernard] Ctr Dis Control & Prevent, Streptococcus Lab, Atlanta, GA 30333 USA. RP Gilmore, MS (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St C703, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu RI Manson, Abigail/B-7132-2016; OI Manson, Abigail/0000-0002-3800-0714; Earl, Ashlee/0000-0001-7857-9145; Tuomanen, Elaine/0000-0003-0349-8716 FU NIH, Molecular Basis for Ocular Surface Tropism in Conjunctivitis [EY024285]; Harvard wide Program on Antibiotic Resistance [AI083214, HHSN272200900018C]; NIH fellowship [EY007145]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES) [9775-13-7] FX Portions of this project were supported by NIH grants EY024285, Molecular Basis for Ocular Surface Tropism in Conjunctivitis and by the Harvard wide Program on Antibiotic Resistance, AI083214. HHSN272200900018C supported the involvement of A.M.M. Additional support for this project was obtained from the ALSAC organization of St Jude Children's Research Hospital (J.W.R., C.B., R.A.C. and E.I.T.). In addition, portions of this project were supported by Bausch and Lomb Inc. (C.M.S., W.H., T.W.M. and M.S.G.). M.D.V. was supported in part by NIH fellowship through EY007145. P.J.M.B. was supported by a grant from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES #9775-13-7). We gratefully thank Drs F. Lebreton, D. Van Tyne and M. Martin for their helpful comments throughout the course of this work and during manuscript preparation. Funding agencies had no role in study design, data analysis, decision to publish or preparation of the manuscript. NR 69 TC 9 Z9 9 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD NOV PY 2014 VL 5 AR 5411 DI 10.1038/ncomms6411 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AU5CN UT WOS:000345624800032 PM 25388376 ER PT J AU Cohn, N Jackendoff, R Holcomb, PJ Kuperberg, GR AF Cohn, Neil Jackendoff, Ray Holcomb, Phillip J. Kuperberg, Gina R. TI The grammar of visual narrative: Neural evidence for constituent structure in sequential image comprehension SO NEUROPSYCHOLOGIA LA English DT Article DE Constituent structure; Grammar; Narrative; Visual language; Comics; ERPs ID EVENT-RELATED POTENTIALS; BRAIN POTENTIALS; LANGUAGE COMPREHENSION; SEMANTIC INTEGRATION; SYNTACTIC ANALYSIS; ERP; SEGMENTATION; PERCEPTION; PREDICTION; MUSIC AB Constituent structure has long been established as a central feature of human language. Analogous to how syntax organizes words in sentences, a narrative grammar organizes sequential images into hierarchic constituents. Here we show that the brain draws upon this constituent structure to comprehend wordless visual narratives. We recorded neural responses as participants viewed sequences of visual images (comics strips) in which blank images either disrupted individual narrative constituents or fell at natural constituent boundaries. A disruption of either the first or the second narrative constituent produced a left-lateralized anterior negativity effect between 500 and 700 ms. Disruption of the second constituent also elicited a posteriorly-distributed positivity (P600) effect. These neural responses are similar to those associated with structural violations in language and music. These findings provide evidence that comprehenders use a narrative structure to comprehend visual sequences and that the brain engages similar neurocognitive mechanisms to build structure across multiple domains. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cohn, Neil; Jackendoff, Ray; Holcomb, Phillip J.; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Jackendoff, Ray] Tufts Univ, Dept Philosophy, Medford, MA 02155 USA. [Jackendoff, Ray] Tufts Univ, Ctr Cognit Studies, Medford, MA 02155 USA. [Cohn, Neil] Univ Calif San Diego, Dept Cognit Sci, Dept 0526, La Jolla, CA 92093 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Cohn, N (reprint author), Univ Calif San Diego, Dept Cognit Sci, Dept 0526, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM neilcohn@visuallanguagelab.com FU NIMH, USA [R01 MH071635]; NICHD, USA [HD25889]; NARSAD; Sidney Baer Trust; Tufts Center for Cognitive Studies FX This work was supported by NIMH, USA (R01 MH071635), NICHD, USA (HD25889) and NARSAD (with the Sidney Baer Trust), as well as funding from the Tufts Center for Cognitive Studies. We thank Suzi Grossman, Chelsey Ott, and Patrick Bender for aid in stimuli creation and experimentation, and Fantagraphics Books for their donation of The Complete Peanuts. NR 90 TC 13 Z9 13 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD NOV PY 2014 VL 64 BP 63 EP 70 DI 10.1016/j.neuropsychologia.2014.09.018 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA AU6TL UT WOS:000345734500007 PM 25241329 ER PT J AU Denny, BT Fan, J Liu, X Guerreri, S Mayson, SJ Rimsky, L New, AS Siever, LJ Koenigsberg, HW AF Denny, Bryan T. Fan, Jin Liu, Xun Guerreri, Stephanie Mayson, Sarah Jo Rimsky, Liza New, Antonia S. Siever, Larry J. Koenigsberg, Harold W. TI Insula-amygdala functional connectivity is correlated with habituation to repeated negative images SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE habituation; emotion; functional connectivity; insula; amygdala ID GILL-WITHDRAWAL REFLEX; OLD-WORLD MONKEY; EMOTION REGULATION; FACIAL EXPRESSIONS; BRAIN; APLYSIA; DISHABITUATION; PICTURES; CORTEX; METAANALYSIS AB Behavioral habituation during repeated exposure to aversive stimuli is an adaptive process. However, the way in which changes in self-reported emotional experience are related to the neural mechanisms supporting habituation remains unclear. We probed these mechanisms by repeatedly presenting negative images to healthy adult participants and recording behavioral and neural responses using functional magnetic resonance imaging. We were particularly interested in investigating patterns of activity in insula, given its significant role in affective integration, and in amygdala, given its association with appraisal of aversive stimuli and its frequent coactivation with insula. We found significant habituation behaviorally along with decreases in amygdala, occipital cortex and ventral prefrontal cortex (PFC) activity with repeated presentation, whereas bilateral posterior insula, dorsolateral PFC and precuneus showed increased activation. Posterior insula activation during image presentation was correlated with greater negative affect ratings for novel presentations of negative images. Further, repeated negative image presentation was associated with increased functional connectivity between left posterior insula and amygdala, and increasing insula-amygdala functional connectivity was correlated with increasing behavioral habituation. These results suggest that habituation is subserved in part by insula-amygdala connectivity and involves a change in the activity of bottom-up affective networks. C1 [Denny, Bryan T.; Fan, Jin; Guerreri, Stephanie; Mayson, Sarah Jo; Rimsky, Liza; New, Antonia S.; Siever, Larry J.; Koenigsberg, Harold W.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Fan, Jin] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Fan, Jin] CUNY Queens Coll, Dept Psychol, New York, NY 11367 USA. [Liu, Xun] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [New, Antonia S.; Siever, Larry J.; Koenigsberg, Harold W.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Koenigsberg, HW (reprint author), James J Peters VA Med Ctr, Mental Hlth Patient Care Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM HWarrenK@nyc.rr.com RI Liu, Xun/C-2400-2009; Fan, Jin/A-6716-2009 OI Liu, Xun/0000-0003-1366-8926; Fan, Jin/0000-0001-9630-8330 FU National Institute of Mental Health [R01 MH077813]; National Center for Research Resources, National Institutes of Health for the Mount Sinai General Clinical Research Center [5M01 RR00071]; James J Peters Veterans Affairs Medical Center FX This work was supported by a grant from the National Institute of Mental Health (R01 MH077813 to Dr Koenigsberg); by the National Center for Research Resources, National Institutes of Health for the Mount Sinai General Clinical Research Center (5M01 RR00071) and by the James J Peters Veterans Affairs Medical Center. NR 51 TC 8 Z9 8 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD NOV PY 2014 VL 9 IS 11 BP 1660 EP 1667 DI 10.1093/scan/nst160 PG 8 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AU8LA UT WOS:000345846800003 PM 24170933 ER PT J AU Foster-Chang, SA Manning, ML Chandler, L AF Foster-Chang, Sarah A. Manning, Mary L. Chandler, Laura TI Tuberculosis Screening of New Hospital Employees Compliance, Clearance to Work Time, and Cost Using Tuberculin Skin Test and Interferon-Gamma Release Assays SO WORKPLACE HEALTH & SAFETY LA English DT Article ID HEALTH-CARE WORKERS; QUANTIFERON-TB GOLD; LATENT TUBERCULOSIS; UNITED-STATES; DIAGNOSIS; INFECTION; ACCEPTABILITY; GUIDELINES; SPOT.TB; PROGRAM AB Selection of the most suitable test(s) for detection of Mycobacterium tuberculosis (TB) infection should be based on purpose, setting, effectiveness, and cost. Two tests are available to screen for latent TB: the tuberculin skin test (TST) and the more recent interferon-gamma release assays (IGRAs). Based on the administrative, logistic, and technical ease of use, an IGRA trial was initiated by the occupational health department at an urban Veteran's Administration health care facility for TB screening of new employees. As a result, new employees completing the pre-placement process within the organization's designated 14 days increased from 77% to 97%, new employee clearance to work time decreased from 13.18 to 5.91 days, and new employee TB screening costs were reduced by 40%. The IGRA is an acceptable alternative to the TST and has significant potential to improve the process of pre-placement TB screening. C1 [Foster-Chang, Sarah A.; Chandler, Laura] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Foster-Chang, Sarah A.] Natl VA Occupat & Environm Med Consult Grp, Natl VA Occupat Hlth Program, Philadelphia, PA USA. [Chandler, Laura] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Manning, Mary L.] Thomas Jefferson Univ, Jefferson Sch Nursing, Philadelphia, PA 19107 USA. RP Foster-Chang, SA (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave,1B153, Philadelphia, PA 19104 USA. EM Sarah.Foster-Chang@va.gov NR 36 TC 1 Z9 1 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2165-0799 EI 2165-0969 J9 WORKPLACE HEALTH SAF JI Workplace Health Saf. PD NOV PY 2014 VL 62 IS 11 BP 460 EP 467 DI 10.3928/21650799-20140902-02 PG 8 WC Nursing SC Nursing GA AW0BU UT WOS:000345956200004 PM 25207587 ER PT J AU Cheng, J Jiang, JB Zhao, JX Wang, ZR Sun, YG Ma, HL Fan, KH Yin, W Sun, N Wang, ZW Zhao, X Li, HQ AF Cheng, Jing Jiang, Junbing Zhao, Junxing Wang, Zhirui Sun, Yaogui Ma, Haili Fan, Kuohai Yin, Wei Sun, Na Wang, Zhiwei Zhao, Xin Li, Hongquan TI Cloning and bioinformatics analysis of a full-length cDNA of porcine CR1-like gene SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA English DT Editorial Material ID COMPLEMENT RECEPTOR-TYPE-1; C3B/C4B RECEPTOR; ERYTHROCYTE; PROTEIN; GLYCOSYLATION; SEQUENCE; DOMAINS C1 [Cheng, Jing; Jiang, Junbing; Zhao, Junxing; Sun, Yaogui; Ma, Haili; Fan, Kuohai; Yin, Wei; Sun, Na; Wang, Zhiwei; Zhao, Xin; Li, Hongquan] Shanxi Agr Univ, Coll Anim Sci & Vet Med, Taigu 030801, Peoples R China. [Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02148 USA. [Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02148 USA. [Wang, Zhirui] MGH DF HCC Recombinant Prot Express & Purificat C, Boston, MA 02148 USA. RP Li, HQ (reprint author), Shanxi Agr Univ, Coll Anim Sci & Vet Med, Taigu 030801, Peoples R China. EM livets@163.com NR 15 TC 1 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1672-9145 EI 1745-7270 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD NOV PY 2014 VL 46 IS 11 BP 997 EP 1000 DI 10.1093/abbs/gmu084 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AU2ZX UT WOS:000345483900010 PM 25236667 ER PT J AU Barnes, DE Cenzer, IS Yaffe, K Ritchie, CS Lee, SJ AF Barnes, Deborah E. Cenzer, Irena S. Yaffe, Kristine Ritchie, Christine S. Lee, Sei J. CA Alzheimer's Dis Neuroimaging Initi TI A point-based tool to predict conversion from mild cognitive impairment to probable Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Mild cognitive impairment; Prognostic modeling; Risk factors; Aged; Human; Magnetic resonance imaging; Neuropsychological tests; Disease progression ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; OLDER-ADULTS; AD; DEMENTIA; MRI; MCI; BIOMARKERS; RISK AB Background: Our objective in this study was to develop a point-based tool to predict conversion from amnestic mild cognitive impairment (MCI) to probable Alzheimer's disease (AD). Methods: Subjects were participants in the first part of the Alzheimer's Disease Neuroimaging Initiative. Cox proportional hazards models were used to identify factors associated with development of AD, and a point score was created from predictors in the final model. Results: The final point score could range from 0 to 9 (mean 4.8) and included: the Functional Assessment Questionnaire (2-3 points); magnetic resonance imaging (MRI) middle temporal cortical thinning (1 point); MRI hippocampal subcortical volume (1 point); Alzheimer's Disease Cognitive Scale cognitive subscale (2-3 points); and the Clock Test (1 point). Prognostic accuracy was good (Harrell's c = 0.78; 95% CI 0.75, 0.81); 3-year conversion rates were 6% (0-3 points), 53% (4-6 points), and 91% (7-9 points). Conclusions: A point-based risk score combining functional dependence, cerebral MRI measures, and neuropsychological test scores provided good accuracy for prediction of conversion from amnestic MCI to AD. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Cenzer, Irena S.; Yaffe, Kristine; Ritchie, Christine S.; Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Cenzer, Irena S.; Ritchie, Christine S.; Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Ritchie, Christine S.] Jewish Home San Francisco, San Francisco, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM deborah.barnes@ucsf.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec, Inc.; Bristol-Myers Squibb Company; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche, Ltd.; Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Piramal Imaging; Servier; Synarc, Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; Northern California Institute for Research and Education; NIH [P30 AGO 10129, K01 AG030514]; S.D. Bechtel, Jr. Foundation; National Institutes of Health; Department of Veterans Affairs; Department of Defense; NARSAD; University of California School of Medicine, S.D.; NIH; Commonwealth Fund; Retirement Research Foundation; American Federation of Aging Research through the Beeson Career Development Award [K23AG040779]; [K24-AG031155] FX The authors thank Dr. John Boscardin, Professor of Medicine and Epidemiology & Biostatistics at the University of California, San Francisco, for guidance on statistical methods as well as the study participants. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: the Alzheimer's Association; the Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec, Inc.; Bristol-Myers Squibb Company; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche, Ltd., and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Piramal Imaging; Servier; Synarc, Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research provides 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 Neuroimaging at the University of California, Los Angeles. This research was also supported by NIH Grants P30 AGO 10129 and K01 AG030514. This study was supported by the S.D. Bechtel, Jr. Foundation. Dr. Yaffe was supported in part by Grant K24-AG031155.; Dr. Barnes reports research support from the National Institutes of Health, Alzheimer's Association, Department of Veterans Affairs, Department of Defense, NARSAD, University of California School of Medicine, S.D. Bechtel, Jr. Foundation, UCSF Osher Center for Integrative Medicine, and UCB Pharma, Inc., and serves as a study design consultant for the UCSF Clinical and Translational Sciences Institute. Dr. Yaffe reports serving on data safety monitoring boards for Takeda, Inc., and a study sponsored by the NIH and has served as a consultant for Novartis, Inc. Dr. Ritchie reports research funding from the National Institutes of Health, the Commonwealth Fund, the Retirement Research Foundation, programmatic funding support from the S.D. Bechtel, Jr. Foundation, and royalties from UptoDate. Dr. Lee reports funding from the National Institute on Aging and the American Federation of Aging Research through the Beeson Career Development Award (K23AG040779) and the S.D. Bechtel, Jr. Foundation. NR 50 TC 7 Z9 7 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 646 EP 655 DI 10.1016/j.jalz.2013.12.014 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800009 PM 24495339 ER PT J AU Dodge, HH Zhu, J Harvey, D Saito, N Silbert, LC Kaye, JA Koeppe, RA Albin, RL AF Dodge, Hiroko H. Zhu, Jian Harvey, Danielle Saito, Naomi Silbert, Lisa C. Kaye, Jeffrey A. Koeppe, Robert A. Albin, Roger L. CA Alzheimer's Dis Neuroimaging Inita TI Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE ADNI; Cognitive declines; Biomarker; Biomarker progressions; ADNI-mem; ADNI-exe; MCI; FDG-PET; MRI volume ID NEUROIMAGING INITIATIVE ADNI; SMALL-VESSEL DISEASE; WHITE-MATTER; CORTICAL THICKNESS; CLINICAL CHARACTERIZATION; PATHOLOGICAL CASCADE; HYPOTHETICAL MODEL; DYNAMIC BIOMARKERS; EXECUTIVE FUNCTION; PROCESSING SPEED AB Background: It is unknown which commonly used Alzheimer disease (AD) biomarker values baseline or progression best predict longitudinal cognitive decline. Methods: 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. Results: About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. Conclusions: For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Dodge, Hiroko H.; Silbert, Lisa C.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Dodge, Hiroko H.; Albin, Roger L.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Dodge, Hiroko H.; Albin, Roger L.] Univ Michigan, Michigan Alzheimers Dis Ctr, Ann Arbor, MI USA. [Zhu, Jian] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Harvey, Danielle; Saito, Naomi] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Silbert, Lisa C.; Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. [Koeppe, Robert A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Albin, Roger L.] Vet Affairs Ann Arbor Healthcare Syst, Neurol Serv & Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. RP Dodge, HH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. EM dodgeh@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Drug Discovery Foundation; Bio-Clinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly; F. Hoffmann-La Roche Ltd; Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; National Institutes of Health grant [P30 AG010129]; National Institute on Aging [P30 AG008017, 1R01AG036772, R13 AG030995]; Michigan Alzheimer's Disease Center Pilot Grant FX Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Bio-Clinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; 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; 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 California, Los Angeles. This research was also supported by National Institutes of Health grant (P30 AG010129). Additional funding includes National Institute on Aging (P30 AG008017, 1R01AG036772, and R13 AG030995) and Michigan Alzheimer's Disease Center Pilot Grant. NR 37 TC 6 Z9 6 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 690 EP 703 DI 10.1016/j.jalz.2014.04.513 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800014 PM 25022534 ER PT J AU Samieri, C Proust-Lima, C Glymour, MM Okereke, OI Amariglio, RE Sperling, RA Rentz, DM Grodstein, F AF Samieri, Cecilia Proust-Lima, Cecile Glymour, Maria M. Okereke, Olivia I. Amariglio, Rebecca E. Sperling, Reisa A. Rentz, Dorene M. Grodstein, Francine TI Subjective cognitive concerns, episodic memory, and the APOE epsilon 4 allele SO ALZHEIMERS & DEMENTIA LA English DT Article DE Memory; Apolipoprotein E4; Subjective cognitive concerns ID ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; OLDER-ADULTS; SELF-APPRAISAL; COMPLAINTS; IMPAIRMENT; DECLINE; ASSOCIATION; COMMUNITY; INDIVIDUALS AB Background: Subjective cognitive concerns may represent a simple method to assess likelihood of memory decline among apolipoprotein E (APOE) epsilon 4 carriers. Methods: We examined the relationship of self-reported subjective cognitive concerns, using seven specific cognitive concerns, with memory and memory decline over 6 years among APOE epsilon 4 carriers and non-carriers from the Nurses' Health Study. Results: In both groups, increasing subjective cognitive concern score predicted worse baseline memory and faster rates of subsequent memory decline, after adjustment for age, education and depression. The relation with baseline memory appeared statistically stronger in APOE epsilon 4 carriers (P-interaction = 0.03). For memory decline, mean differences in slopes of episodic memory (95% CI) for 4 to 7 versus no concern = -0.05 (-0.10, 0.01) standard units in APOE epsilon 4 carriers, and -0.04 (-0.08, -0.01) standard units in non-carriers. Conclusions: APOE epsilon 4 carriers with self-assessed cognitive concerns appear to have worse memory, and possibly accelerated memory decline. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Samieri, Cecilia; Okereke, Olivia I.; Grodstein, Francine] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Samieri, Cecilia; Okereke, Olivia I.; Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.; Grodstein, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Samieri, Cecilia; Proust-Lima, Cecile] Ctr INSERM U897 Epidemiol Biostat, INSERM, Bordeaux, France. [Samieri, Cecilia; Proust-Lima, Cecile] Univ Bordeaux, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France. [Glymour, Maria M.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Glymour, Maria M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Okereke, Olivia I.; Grodstein, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Okereke, Olivia I.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Okereke, Olivia I.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Samieri, C (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM cecilia.samieri@channing.harvard.edu RI Okereke, Olivia/R-9934-2016; Samieri, Cecilia/E-3334-2014; Proust-Lima, Cecile/E-6670-2014 OI Samieri, Cecilia/0000-0001-9809-7506; FU NIH National Cancer Institute [P01 CA87969]; Fulbright Research Scholar award; PRES Universite de Bordeaux; National Institutes of Health [R21 AG034385, K08 AG029813, PO1AG036694, 5RO1AG027435, RO1AG037497, U19AG10483, K24AG035007]; Alzheimer's Association [NIRG-12-243012, SGCOG-13-282201] FX This study was funded by grants from the NIH National Cancer Institute (P01 CA87969). Dr Samieri was supported by a Fulbright Research Scholar award and a grant from the PRES Universite de Bordeaux. Dr Glymour was supported by National Institutes of Health grant R21 AG034385. Dr Okereke was supported by National Institutes of Health grant K08 AG029813. Dr. Amariglio is supported in part by National Institutes of Health grants PO1AG036694, 5RO1AG027435, RO1AG037497 and by the Alzheimer's Association NIRG-12-243012. Drs. Rentz and Sperling are supported by National Institutes of Health grants PO1AG036694, 5RO1AG027435, RO1AG037497, U19AG10483, K24AG035007, and by the Alzheimer's Association SGCOG-13-282201. NR 41 TC 4 Z9 4 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 752 EP 759 DI 10.1016/j.jalz.2014.06.012 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800020 PM 25256133 ER PT J AU Cosentino, S Zahodne, LB Brandt, J Blacker, D Albert, M Dubois, B Stern, Y AF Cosentino, Stephanie Zahodne, Laura B. Brandt, Jason Blacker, Deborah Albert, Marilyn Dubois, Bruno Stern, Yaakov TI Social cognition in Alzheimer's disease: A separate construct contributing to dependence SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Social cognition; Cognition; Dependence ID VARIANT FRONTOTEMPORAL DEMENTIA; BEHAVIORAL-VARIANT; PATIENT DEPENDENCE; EXECUTIVE FUNCTION; PREDICTORS; DISSOCIATION; MULTICENTER; PROGRESSION; EMOTION; MODELS AB The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD. Participants were monitored every 6 months for 5.5 years. Results from multivariate latent growth curve models adjusted for sex, age, education, depression, and recruitment site revealed that social cognition and general cognition were unrelated cross-sectionally and throughout time. However, baseline levels of each were related independently to dependence, and change values of,each were related independently to change in dependence. These findings highlight the separability of social and general cognition in AD. Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Cosentino, Stephanie; Zahodne, Laura B.; Stern, Yaakov] Columbia Univ Coll Phys & Surg, Dept Neurol, Cognit Neurosci Div, New York, NY 10032 USA. [Cosentino, Stephanie; Zahodne, Laura B.; Stern, Yaakov] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis, New York, NY 10032 USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Brandt, Jason; Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dubois, Bruno] Sorbonne Univ, Univ Paris 06, Parktown, South Africa. [Dubois, Bruno] INSERM, Inst Cerveau & Moelle Epiniere, UMRS 975, Paris, France. [Dubois, Bruno] Inst Memoire & Malad Alzheimer, Paris, France. [Dubois, Bruno] Grp Hosp Pitie Salpetriere, Ctr References Demences Rares, F-75634 Paris, France. RP Cosentino, S (reprint author), Columbia Univ Coll Phys & Surg, Dept Neurol, Cognit Neurosci Div, 630 W 168th St, New York, NY 10032 USA. EM sc2460@cumc.columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU National Institute on Aging (NIA) [R01 AG007370, T32 AG000261]; Paul B. Beeson Career Development Award in Aging [K23 AG032899]; National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000040, UL1 RR024156] FX The Predictors study is supported by a National Institute on Aging (NIA) grant (R01 AG007370) to Dr. Stern. Dr. Cosentino is supported by a Paul B. Beeson Career Development Award in Aging (K23 AG032899). Dr. Zahodne is supported by an NIA grant (T32 AG000261). This publication was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health (through grant no. UL1 TR000040), formerly the National Center for Research Resources (grant no. UL1 RR024156). NR 49 TC 5 Z9 5 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 818 EP 826 DI 10.1016/j.jalz.2013.12.021 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800027 PM 24656839 ER PT J AU Jessen, F Amariglio, RE van Boxtel, M Breteler, M Ceccaldi, M Chetelat, G Dubois, B Dufouil, C Ellis, KA van der Flier, WM Glodzik, L van Harten, AC de Leon, MJ McHugh, P Mielke, MM Molinuevo, JL Mosconi, L Osorio, RS Perrotin, A Petersen, RC Rabin, LA Rami, L Reisberg, B Rentz, DM Sachdev, PS de la Sayette, V Saykin, AJ Scheltens, P Shulman, MB Slavin, MJ Sperling, RA Stewart, R Uspenskaya, O Vellas, B Visser, PJ Wagner, M AF Jessen, Frank Amariglio, Rebecca E. van Boxtel, Martin Breteler, Monique Ceccaldi, Mathieu Chetelat, Gael Dubois, Bruno Dufouil, Carole Ellis, Kathryn A. van der Flier, Wiesje M. Glodzik, Lidia van Harten, Argonde C. de Leon, Mony J. McHugh, Pauline Mielke, Michelle M. Molinuevo, Jose Luis Mosconi, Lisa Osorio, Ricardo S. Perrotin, Audrey Petersen, Ronald C. Rabin, Laura A. Rami, Lorena Reisberg, Barry Rentz, Dorene M. Sachdev, Perminder S. de la Sayette, Vincent Saykin, Andrew J. Scheltens, Philip Shulman, Melanie B. Slavin, Melissa J. Sperling, Reisa A. Stewart, Robert Uspenskaya, Olga Vellas, Bruno Visser, Pieter Jelle Wagner, Michael CA SCD I Working Grp TI A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Subjective cognitive decline; Preclinical Alzheimer's disease; Mild cognitive impairment; Prodromal Alzheimer's disease; Research criteria ID BETA-AMYLOID DEPOSITION; MEMORY COMPLAINTS; OLDER-ADULTS; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; PROSPECTIVE COHORT; IMPAIRMENT; DEMENTIA; RECOMMENDATIONS AB There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Jessen, Frank; Wagner, Michael] Univ Bonn, Dept Psychiat, Bonn, Germany. [Jessen, Frank; Wagner, Michael] Univ Bonn, Clin Treatment & Res Ctr Neurodegenerat Dis KBFZ, Bonn, Germany. [Jessen, Frank; Breteler, Monique; Wagner, Michael] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Amariglio, Rebecca E.; Rentz, Dorene M.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp,Dept Neurol, Boston, MA USA. [van Boxtel, Martin; Visser, Pieter Jelle] Maastricht Univ, Sch Mental Hlth & Neurosci MHeNS, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. [Ceccaldi, Mathieu] Univ Marseille, Inst Neurosci Syst, Marseille, France. [Chetelat, Gael; Perrotin, Audrey; de la Sayette, Vincent] INSERM, U1077, Caen, France. [Chetelat, Gael; Perrotin, Audrey; de la Sayette, Vincent] Univ Caen Basse Normandie, UMR S1077, Caen, France. [Chetelat, Gael; Perrotin, Audrey; de la Sayette, Vincent] Ecole Prat Hautes Etud, UMR S1077, Caen, France. [Chetelat, Gael; Perrotin, Audrey; de la Sayette, Vincent] CHU Caen, U1077, F-14000 Caen, France. [Dubois, Bruno] Univ Paris 06, Paris, France. [Dufouil, Carole] INSERM, CIC EC7, U708, Bordeaux, France. [Dufouil, Carole] Bordeaux Univ, Bordeaux, France. [Ellis, Kathryn A.] Univ Melbourne, Dept Psychiat, Acad Unit Psychiat Old Age, Melbourne, Vic, Australia. [van der Flier, Wiesje M.; van Harten, Argonde C.; Scheltens, Philip; Visser, Pieter Jelle] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Alzheimer Ctr, Amsterdam, Netherlands. [Glodzik, Lidia; de Leon, Mony J.; McHugh, Pauline; Mosconi, Lisa; Osorio, Ricardo S.; Reisberg, Barry; Shulman, Melanie B.] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10016 USA. [Mielke, Michelle M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Molinuevo, Jose Luis; Rami, Lorena] Hosp Clin Barcelona, IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain. [Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Rabin, Laura A.] CUNY, Brooklyn Coll, New York, NY 10021 USA. [Rabin, Laura A.] CUNY, Grad Ctr, New York, NY USA. [Reisberg, Barry] NYU, Sch Med, Silberstein Aging & Dementia Res Ctr, New York, NY USA. [Sachdev, Perminder S.] Univ New S Wales, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Saykin, Andrew J.] Indiana Univ, Sch Med, Dept Radiol & Imaging Sci, Indianapolis, IN USA. [Slavin, Melissa J.] Univ New S Wales, UNSW Med, Sch Psychiat, Dementia Collaborat Res Ctr, Sydney, NSW, Australia. [Stewart, Robert] Kings Coll London, Inst Psychiat, London, England. [Uspenskaya, Olga] Grp Hosp Pitie Salpetriere, Alzheimers Inst, F-75634 Paris, France. [Vellas, Bruno] Univ Toulouse 3, Toulouse Univ Hosp, Dept Internal Med & Geriatr, UMR INSERM 1027, F-31062 Toulouse, France. RP Jessen, F (reprint author), Univ Bonn, Dept Psychiat, Bonn, Germany. EM frank.jessen@ukb.uni-bonn.de RI Visser, Pieter/C-8541-2015; de la Sayette, Vincent/L-8074-2015; Wagner, Michael/E-2325-2011; Chetelat, Gael/G-2316-2015; OI Visser, Pieter/0000-0001-8008-9727; Wagner, Michael/0000-0003-2589-6440; Reisberg, Barry/0000-0002-9104-7423; Molinuevo, Jose Luis/0000-0003-0485-6001; de Leon, Mony/0000-0003-2245-4380; Sachdev, Perminder/0000-0002-9595-3220; Stewart, Robert/0000-0002-4435-6397 FU NCATS NIH HHS [UL1 TR001108]; NIA NIH HHS [R01 AG019771, K23 AG044431, K24 AG035007, P30 AG008051, P30 AG010133] NR 61 TC 118 Z9 121 U1 13 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2014 VL 10 IS 6 BP 844 EP 852 DI 10.1016/j.jalz.2014.01.001 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AU0KD UT WOS:000345310800030 PM 24798886 ER PT J AU Abtahian, F Hawkins, BM Ryan, DP Cefalo, P Nasser, NJ MacKay, C Jaff, MR Weinberg, I AF Abtahian, Farhad Hawkins, Beau M. Ryan, David P. Cefalo, Philip Nasser, Nicola J. MacKay, Cheryl Jaff, Michael R. Weinberg, Ido TI Inferior Vena Cava Filter Usage, Complications, and Retrieval Rate in Cancer Patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Cancer; Deep venous thrombosis; Inferior vena cava; Malignancy; Pulmonary embolism ID DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; PULMONARY-EMBOLISM; MALIGNANT-DISEASE; PLACEMENT; ANTICOAGULATION; EXPERIENCE; OUTCOMES; TRENDS AB BACKGROUND: Venous thromboembolism contributes significantly to morbidity and mortality in cancer patients. Because cancer patients frequently have contraindications to anticoagulation, inferior vena cava filters are commonly placed. The use, safety, and retrieval of retrievable inferior vena cava filters in cancer patients have not been well studied. METHODS: A retrospective review of retrievable inferior vena cava filter use at a tertiary referral hospital was conducted between January 1, 2009 and December 31, 2011. Indications for inferior vena cava filter placement, anticoagulation practices, complications, filter retrieval, and patient outcomes were analyzed for patients with and without active cancer and for cancer subtypes, including localized and metastatic cases. RESULTS: Of 666 patients receiving retrievable inferior vena cava filters during this time period, 247 (37.1%) had active cancer. Of these, 151 (22.7%) had carcinoma, 92 (13.8%) had sarcoma, and 115 (17.3%) had metastatic disease. Overall, follow-up was available for a median of 401.0 (interquartile range: 107.5-786.5) days. Indwelling filter-related complications occurred in 19.8% of patients without cancer and 17.7% with an active cancer (P = .50). Patients with cancer were less likely to have the filter retrieved (28.0% vs 42.0%, P < .001). In multivariable analysis, cancer was not associated with filter-related complications but was associated with a lower rate of filter retrieval. CONCLUSIONS: In a modern cohort of patients undergoing retrievable inferior vena cava filter placement, active diagnosis of cancer is not associated with a significant increase in filter-related complications, but is associated with a reduced rate of filter retrieval. (C) 2014 Elsevier Inc. All rights reserved. C1 [Abtahian, Farhad] Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA. [Hawkins, Beau M.] Univ Oklahoma, Coll Med, Dept Med, Oklahoma City, OK 73190 USA. [Ryan, David P.] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. [Cefalo, Philip] Spaulding Rehabil Hosp, Dept Med, Boston, MA USA. [Nasser, Nicola J.] Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada. [MacKay, Cheryl; Jaff, Michael R.; Weinberg, Ido] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, 55 Fruit St, Boston, MA 02114 USA. EM iweinberg@partners.org NR 32 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD NOV PY 2014 VL 127 IS 11 BP 1111 EP 1117 DI 10.1016/j.amjmed.2014.06.025 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AU3KQ UT WOS:000345512400023 PM 24997415 ER PT J AU Badheka, AO Shah, N Ghatak, A Patel, NJ Chothani, A Mehta, K Singh, V Patel, N Grover, P Deshmukh, A Panaich, SS Savani, GT Bhalara, V Arora, S Rathod, A Desai, H Kar, S Alfonso, C Palacios, IF Grines, C Schreiber, T Rihal, CS Makkar, R Cohen, MG O'Neill, W de Marchena, E AF Badheka, Apurva O. Shah, Neeraj Ghatak, Abhijit Patel, Nileshkumar J. Chothani, Ankit Mehta, Kathan Singh, Vikas Patel, Nilay Grover, Peeyush Deshmukh, Abhishek Panaich, Sidakpal S. Savani, Ghanshyambhai T. Bhalara, Vipulkumar Arora, Shilpkumar Rathod, Ankit Desai, Harit Kar, Saibal Alfonso, Carlos Palacios, Igor F. Grines, Cindy Schreiber, Theodore Rihal, Charanjit S. Makkar, Raj Cohen, Mauricio G. O'Neill, William de Marchena, Eduardo TI Balloon Mitral Valvuloplasty in the United States: A 13-Year Perspective SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Balloon; Complications; Cost; Hospital stay; Mitral valve; Mortality; Valvuloplasty ID FOLLOW-UP; NATIONAL HEART; COMMISSUROTOMY; VALVOTOMY; STENOSIS; REGISTRY; COMPLICATIONS; IMMEDIATE; EXPERIENCE; TRENDS AB BACKGROUND: Incidence and prevalence of mitral stenosis is declining in the US. We performed this study to determine recent trends in utilization, complications, mortality, length of stay, and cost associated with balloon mitral valvuloplasty. METHODS: Utilizing the nationwide inpatient sample database from 1998 to 2010, we identified patients using the International Classification of Diseases, 9th Revision, Clinical Modification procedure code for "percutaneous valvuloplasty." Patients >= 18 years of age with mitral stenosis were included. Patients with concomitant aortic, tricuspid, or pulmonic stenosis were excluded. Primary outcome included death and procedural complications. RESULTS: A total of 1308 balloon mitral valvuloplasties (weighted n = 6540) were analyzed. There was a 7.5% decrease in utilization of the procedure from 24.6 procedures/10 million population in 1998-2001 to 22.7 procedures/10 million population in 2008-2010 (P for trend = .098). We observed a 15.9% overall procedural complication rate and 1.7% mortality rate. The procedural complication rates have increased in recent years (P = .001), corresponding to increasing age and burden of comorbidities in patients. The mean cost per admission for balloon mitral valvuloplasty has gone up significantly over the 10 years, from $11,668 +/- 1046 in 2001 to $23,651 +/- 301 in 2010 (P < .001). CONCLUSIONS: In a large cross-sectional study of balloon mitral valvuloplasty in the US, we have reported trends of decreasing overall utilization and increasing procedural complication rates and cost over a period of 13 years. (C) 2014 Elsevier Inc. All rights reserved. C1 [Badheka, Apurva O.; Patel, Nilay; Panaich, Sidakpal S.; Bhalara, Vipulkumar; Arora, Shilpkumar; Grines, Cindy; Schreiber, Theodore] Detroit Med Ctr, Detroit, MI USA. [Shah, Neeraj; Patel, Nileshkumar J.] Staten Isl Univ Hosp, Staten Isl, NY 10305 USA. [Ghatak, Abhijit; Singh, Vikas; Grover, Peeyush; Savani, Ghanshyambhai T.; Desai, Harit; Alfonso, Carlos; Cohen, Mauricio G.; de Marchena, Eduardo] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Chothani, Ankit] MedStar Washington Hosp Ctr, Washington, DC USA. [Mehta, Kathan] UPMC Shadyside Hosp, Pittsburgh, PA USA. [Deshmukh, Abhishek] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Rathod, Ankit; Kar, Saibal; Makkar, Raj] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Palacios, Igor F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rihal, Charanjit S.] Mayo Clin, Rochester, MN USA. [O'Neill, William] Henry Ford Hosp, Detroit, MI 48202 USA. RP de Marchena, E (reprint author), Univ Miami, Miller Sch Med, Dominion Towers,1400 NW 10th Ave,Suite 206A, Miami, FL 33136 USA. EM emarchen@med.miami.edu OI Cohen, Mauricio/0000-0003-2038-6070 NR 32 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD NOV PY 2014 VL 127 IS 11 AR 1126.e1 DI 10.1016/j.amjmed.2014.05.015 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AU3KQ UT WOS:000345512400025 PM 24859718 ER PT J AU Eaves, L Keller, M Medland, S Neale, B AF Eaves, Lindon Keller, Matthew Medland, Sarah Neale, Benjamin TI Methodological developments in the analysis of behavior genetics data SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 44th Annual Meeting of the Behavior-Genetics-Association CY JUN 18-21, 2014 CL Charlottesville, VA SP Behav Genet Assoc C1 [Eaves, Lindon] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Keller, Matthew] Univ Colorado, Boulder, CO 80309 USA. [Medland, Sarah] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Neale, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Medland, Sarah/C-7630-2013 OI Medland, Sarah/0000-0003-1382-380X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 EI 1573-3297 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2014 VL 44 IS 6 SI SI BP 656 EP 657 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA AT9ZU UT WOS:000345283700048 ER PT J AU Milad, MR Rosenbaum, BL Simon, NM AF Milad, Mohammed R. Rosenbaum, Blake L. Simon, Naomi M. TI Neuroscience of fear extinction: Implications for assessment and treatment of fear-based and anxiety related disorders SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Fear conditioning; vmPFC; Amygdala; Exposure therapy; Yohimbine; DCS ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; COGNITIVE-BEHAVIORAL THERAPY; ANTERIOR CINGULATE CORTEX; D-CYCLOSERINE ENHANCEMENT; EXPOSURE THERAPY; CONDITIONED FEAR; PANIC DISORDER AB Current exposure-based therapies aimed to reduce pathological fear and anxiety are now amongst the most effective interventions for trauma and anxiety related disorders. Nevertheless, they can be further improved to enhance initial and long-term outcomes. It is now widely accepted that a greater understanding of the neurobiological mechanisms of fear extinction is needed to further develop and identify novel effective targeted treatments as well as prevention strategies for fear-based and anxiety-related disorders. Guided by elegant mechanistic, cellular, and molecular preclinical reports, data from imaging studies are beginning to shape our understanding of how fear is quelled in the human brain. In this article, we briefly review the neural circuits underlying fear extinction in rodents and healthy humans. We then review how these circuits may fail to extinguish fear in patients with anxiety disorders. We end with a discussion examining how fear extinction research may lead to significant advances of current therapeutics for anxiety disorders. (C) 2014 Elsevier Ltd. All rights reserved.U C1 [Milad, Mohammed R.; Rosenbaum, Blake L.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Charlestown, MA 02129 USA. [Simon, Naomi M.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders,Med Sch, Boston, MA 02114 USA. RP Milad, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, 149 13th St, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu NR 100 TC 19 Z9 19 U1 8 U2 31 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD NOV PY 2014 VL 62 SI SI BP 17 EP 23 DI 10.1016/j.brat.2014.08.006 PG 7 WC Psychology, Clinical SC Psychology GA AU2TS UT WOS:000345471000003 PM 25204715 ER PT J AU Tirumani, SH Tirumani, H Jagannathan, JP Shinagare, AB Hornick, JL George, S Wagner, AJ Ramaiya, NH AF Tirumani, S. H. Tirumani, H. Jagannathan, J. P. Shinagare, A. B. Hornick, J. L. George, S. Wagner, A. J. Ramaiya, N. H. TI MDCT features of succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumours SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID PROGNOSTIC-FACTORS; MUTATIONS; GIST; RECURRENCE; SDHA; KIT AB Objective: To describe the multidetector CT (MDCT) features and metastatic pattern of succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumours (GISTs). Methods: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study, we retrospectively identified 34 patients (20 females; mean age, 34 years; range, 12-59 years) with histopathology-confirmed SDH-deficient GIST, who were seen at our institution from 1999 through 2012. MDCT of primary tumour in 8 patients and follow-up imaging in all 34 patients over median follow-up of 106 months [interquartile range (IQR), 52-175 months] were reviewed by two radiologists in consensus. Clinical information was extracted from electronic medical records. Results: Primary tumour in all 34 patients was located in the stomach. Mean tumour size (n=58) was 9.6 cm (range, 8-14 cm). Primary tumours were lobulated, variable in growth pattern, hypo-(1/ 8) to isodense (7/ 8) and similar in enhancement to the skeletal muscle. Two were multifocal, four of eight had necrosis and one of eight had haemorrhage. Tumour rupture with haemoperitoneum and tumour-bowel fistula was noted in one patient each. During follow-up, 12/ 34 patients developed tumour in surgical bed, and 28/ 34 patients developed metastases. Most common sites of metastases were the liver (24/ 34), peritoneum (20/ 34) and lymph nodes (18/ 34). Carney triad and Carney-Stratakis syndrome were noted in 5/ 34 and 1/ 34 patients, respectively. At the time of writing, six patients had deceased at a median interval of 109 months (IQR, 54-126 months). Conclusion: SDH-deficient GISTs occur in young patients, commonly arise in stomach, can be multifocal and may be associated with Carney triad or Carney-Stratakis syndrome. They frequently metastasize to lymph nodes in addition to the liver and peritoneum and are associated with indolent course despite metastatic spread. Advances in knowledge: The presence of features unusual for conventional GIST on imaging should alert the radiologist for the possibility of SDH-deficient GIST, especially, because SDH-deficient GISTs are resistant to imatinib. Young age at diagnosis, prolonged survival, association with Carney triad and Carney-Stratakis syndrome and occurrence of concurrent renal cell carcinoma and thyroid malignancies necessitates long-term follow-up of patients with SDH-deficient GISTs. C1 [Tirumani, S. H.; Jagannathan, J. P.; Shinagare, A. B.; Ramaiya, N. H.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Tirumani, S. H.; Tirumani, H.; Jagannathan, J. P.; Shinagare, A. B.; Ramaiya, N. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, J. L.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [George, S.; Wagner, A. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [George, S.; Wagner, A. J.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. EM stirumani@partners.org NR 19 TC 4 Z9 5 U1 0 U2 3 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PD NOV PY 2014 VL 87 IS 1043 AR UNSP 20140476 DI 10.1259/bjr.20140476 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU2CI UT WOS:000345423200017 PM 25189191 ER PT J AU Plastaras, JP Dionisi, F Wo, JY AF Plastaras, John P. Dionisi, Francesco Wo, Jennifer Y. TI Gastrointestinal Cancer Nonliver Proton Therapy for Gastrointestinal Cancers SO CANCER JOURNAL LA English DT Review DE Multimodality therapy; gastrointestinal (GI) cancers; toxicity; radiation therapy (RT); proton radiotherapy (PRT) ID PHASE-III TRIAL; ADVANCED RECTAL-CANCER; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; INTENSITY-MODULATED RADIOTHERAPY; DOSE-VOLUME RELATIONSHIPS; DISTAL ESOPHAGEAL CANCER; RESECTED GASTRIC-CANCER; NORMAL-TISSUE EXPOSURE; BEAM THERAPY; RADIATION-THERAPY AB Multimodality therapy for gastrointestinal (GI) cancers carries considerable risk for toxicity; even single-modality radiation therapy in this population carries with it a daunting side effect profile. Supportive care can certainly mitigate some of the morbidity, but there remain numerous associated acute and late complications that can compromise the therapy and ultimately the outcome. Gastrointestinal cancers inherently occur amid visceral organs that are particularly sensitive to radiotherapy, creating a very narrow therapeutic window for aggressive cell kill with minimal normal tissue damage. Radiation therapy is a critical component of locoregional control, but its use has historically been limited by toxicity concerns, both real and perceived. Fundamental to this is the fact that long-term clinical experience with radiation in GI cancers derives almost entirely from 2-dimensional radiation (plain x-ray-based planning) and subsequently 3-dimensional conformal radiation. The recent use of intensity-modulated photon-based techniques is not well represented in most of the landmark chemoradiation trials. Furthermore, the elusive search for efficacious but tolerable local therapy in GI malignancies raises the possibility that proton radiotherapy's physical and dosimetric differences relative to conventional therapy may make it better suited to the challenge. In many sites, local recurrences after chemoradiation pose a particular challenge, and reirradiation in these sites may be done successfully with proton radiotherapy. C1 [Plastaras, John P.] Univ Penn, Philadelphia, PA 19104 USA. [Dionisi, Francesco] Azienda Prov Serv Sanit, Trento, Italy. [Wo, Jennifer Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Plastaras, JP (reprint author), Perelman Ctr Adv Med, Dept Radiat Oncol, TRC 4 W 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM John.Plastaras2@uphs.upenn.edu NR 70 TC 2 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD NOV-DEC PY 2014 VL 20 IS 6 SI SI BP 378 EP 386 PG 9 WC Oncology SC Oncology GA AU3NZ UT WOS:000345521700003 PM 25415682 ER PT J AU Eaton, BR Yock, T AF Eaton, Bree R. Yock, Torunn TI The Use of Proton Therapy in the Treatment of Benign or Low-Grade Pediatric Brain Tumors SO CANCER JOURNAL LA English DT Review DE Proton; radiation; pediatric; brain tumors; benign; low grade ID CONFORMAL RADIATION-THERAPY; OPTIC PATHWAY GLIOMAS; QUALITY-OF-LIFE; CLINICAL-OUTCOMES; CHILDHOOD CRANIOPHARYNGIOMA; COST-EFFECTIVENESS; IMAGING CHANGES; PHOTON THERAPY; RADIOTHERAPY; CHILDREN AB Radiation therapy (RT) plays a critical role in the local tumor control of benign and low-grade central nervous system tumors in children but is not without the risk of long-term treatment-related sequelae. Proton therapy (PRT) is an advanced RT modality with a unique dose-deposition pattern that allows for treatment of a target volume with reduced scatter dose delivered to normal tissues compared with conventional photon RT and is now increasingly utilized in children with the hope of mitigating radiation-induced late effects. This article reviews the current literature evaluating the use of PRT in benign and low-grade pediatric central nervous system tumors such as low-grade glioma, craniopharyngioma, and ependymoma. Multiple dosimetric studies support the use of PRT by demonstrating the ability of PRT to better spare critical structures important for cognitive development, endocrine function, and hearing preservation and to reduce the total body dose associated with second malignancy risk. Early clinical data demonstrate that PRT is well tolerated with rates of local tumor control comparable to conventional photon RT series, and long-term clinical data are awaited. C1 [Eaton, Bree R.; Yock, Torunn] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Yock, T (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 55 Fruit St,Room 110, Boston, MA 02114 USA. EM tyock@mgh.harvard.edu NR 49 TC 2 Z9 4 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD NOV-DEC PY 2014 VL 20 IS 6 SI SI BP 403 EP 408 PG 6 WC Oncology SC Oncology GA AU3NZ UT WOS:000345521700007 PM 25415686 ER PT J AU Ben-Josef, G Ott, LS Spivack, SB Wang, CQ Ross, JS Shah, SJ Curtis, JP Kim, N Krumholz, HM Bernheim, SM AF Ben-Josef, Gal Ott, Lesli S. Spivack, Steven B. Wang, Changqin Ross, Joseph S. Shah, Sachin J. Curtis, Jeptha P. Kim, Nancy Krumholz, Harlan M. Bernheim, Susannah M. TI Payments for Acute Myocardial Infarction Episodes-of-Care Initiated at Hospitals With and Without Interventional Capabilities SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE acute inferior myocardial infarction; cost and cost analysis; insurance, health reimbursement; percutaneous coronary intervention ID PERCUTANEOUS CORONARY INTERVENTION; SITE CARDIAC-CATHETERIZATION; OUTCOMES; IMPACT; FACILITIES AB Background-It is unknown whether hospitals with percutaneous coronary intervention (PCI) capability provide costlier care than hospitals without PCI capability for patients with acute myocardial infarction. The growing number of PCI hospitals and higher rate of PCI use may result in higher costs for episodes-of-care initiated at PCI hospitals. However, higher rates of transfers and postacute care procedures may result in higher costs for episodes-of-care initiated at non-PCI hospitals. Methods and Results-We identified all 2008 acute myocardial infarction admissions among Medicare fee-for-service beneficiaries by principal discharge diagnosis and classified hospitals as PCI- or non-PCI-capable on the basis of hospitals' 2007 PCI performance. We added all payments from admission through 30 days postadmission, including payments to hospitals other than the admitting hospital. We calculated and compared risk-standardized payment for PCI and non-PCI hospitals using 2-level hierarchical generalized linear models, adjusting for patient demographics and clinical characteristics. PCI hospitals had a higher mean 30-day risk-standardized payment than non-PCI hospitals (PCI, $20340; non-PCI, $19713; P<0.001). Patients presenting to PCI hospitals had higher PCI rates (39.2% versus 13.2%; P<0.001) and higher coronary artery bypass graft rates (9.5% versus 4.4%; P<0.001) during index admissions, lower transfer rates (2.2% versus 25.4%; P<0.001), and lower revascularization rates within 30 days (0.15% versus 0.27%; P<0.0001) than those presenting to non-PCI hospitals. Conclusions-Despite higher PCI and coronary artery bypass graft rates for Medicare patients initially presenting to PCI hospitals, PCI hospitals were only $627 costlier than non-PCI hospitals for the treatment of patients with acute myocardial infarction in 2008. C1 [Ben-Josef, Gal] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Ben-Josef, Gal] Boston Med Ctr, Dept Pediat, Boston, MA USA. [Ott, Lesli S.; Wang, Changqin; Ross, Joseph S.; Curtis, Jeptha P.; Kim, Nancy; Krumholz, Harlan M.; Bernheim, Susannah M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06510 USA. [Ross, Joseph S.; Kim, Nancy; Bernheim, Susannah M.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. [Curtis, Jeptha P.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Ross, Joseph S.; Krumholz, Harlan M.; Bernheim, Susannah M.] Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Spivack, Steven B.] Univ N Carolina, Gillings Sch Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Shah, Sachin J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Bernheim, SM (reprint author), Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM susannah.bernheim@yale.edu FU National Heart, Lung, and Blood Institute in Bethesda, Maryland [1U01HL105270-04]; National Institute on Aging [K08 AG032886-05]; American Federation for Aging Research through Paul B. Beeson Career Development Award Program; American Heart Association; National Research Service Award from National Institutes of Health; Centers for Medicare and Medicaid Services, an agency of the US Department of Health and Human Services [HHSM-500-2008-0025I/HHSM-500-T0001, 000008] FX This study is supported by grant 1U01HL105270-04 (Center for Cardiovascular Outcomes Research at Yale University) from the National Heart, Lung, and Blood Institute in Bethesda, Maryland. Dr Ross is supported by grant K08 AG032886-05 from the National Institute on Aging and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program. Dr Ben-Josef received support for this project from the American Heart Association Student Scholarship in Cardiovascular Disease and the National Research Service Award from the National Institutes of Health. The work for this article was supported in part by Contract Number HHSM-500-2008-0025I/HHSM-500-T0001, Modification No. 000008, entitled Measure & Instrument Development and Support (MIDS)-Development and Re-evaluation of the CMS Hospital Outcomes and Efficiency Measures, funded by the Centers for Medicare and Medicaid Services, an agency of the US Department of Health and Human Services. The content of this work does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. We assume full responsibility for the accuracy and completeness of the ideas presented. NR 10 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2014 VL 7 IS 6 BP 882 EP + DI 10.1161/CIRCOUTCOMES.114.000927 PG 22 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU0BY UT WOS:000345289300013 PM 25387777 ER PT J AU Ovbiagele, B Smith, EE Schwamm, LH Grau-Sepulveda, MV Saver, JL Bhatt, DL Hernandez, AF Peterson, ED Fonarow, GC AF Ovbiagele, Bruce Smith, Eric E. Schwamm, Lee H. Grau-Sepulveda, Maria V. Saver, Jeffrey L. Bhatt, Deepak L. Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. TI Chronic Kidney Disease and Bleeding Complications After Intravenous Thrombolytic Therapy for Acute Ischemic Stroke SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE glomerular filtration rate; hemorrhage; prognosis; renal Insufficiency, chronic ID TISSUE-PLASMINOGEN ACTIVATOR; INTRACRANIAL HEMORRHAGE; RENAL DYSFUNCTION; RT-PA; RISK; IMPROVEMENT; IMPAIRMENT; MANAGEMENT AB Background-The safety of intravenous thrombolysis in ischemic stroke (IS) patients with chronic kidney disease (CKD) is uncertain. We assessed whether CKD is associated with bleeding complications after intravenous tissue-type plasminogen activator administration to patients with IS. Methods and Results-Data were analyzed from 44 410 patients with IS treated with intravenous tissue-type plasminogen activator in the Get With The Guidelines-Stroke Program. Glomerular filtration rate based on admission serum creatinine was categorized as dichotomous (presence of CKD as <60) or as distinct categories: normal (>= 90), mild (>= 60-<90), moderate (>= 30-< 60), severe (>= 15-<30), and kidney failure (<15 or dialysis). Primary outcomes evaluated were symptomatic intracranial hemorrhage and serious systemic hemorrhage; secondary outcomes were in-hospital mortality, independent functional status. There were 15 191 of 44 410 (34%) intravenous tissue-type plasminogen activator-treated IS patients with CKD. Presence of CKD (versus no CKD) was not associated with risk-adjusted symptomatic intracranial hemorrhage (adjusted odds ratio, 1.0; 95% confidence interval: 0.91-1.10) or serious systemic hemorrhage (adjusted odds ratio, 0.97; 95% confidence interval: 0.80-1.18) and did not significantly vary by kidney dysfunction stage for either of these primary end points in multivariable analyses. Compared with patients with normal kidney function, those with CKD were more likely to die in the hospital (adjusted odds ratio, 1.22; 95% confidence interval: 1.14-1.32) and have an unfavorable discharge functional status (adjusted odds ratio, 1.13; 95% CI: 1.07-1.19). Conclusions-Presence of CKD among patients with IS treated with intravenous tissue-type plasminogen activator is associated with higher unadjusted odds of symptomatic intracranial hemorrhage or serious systemic hemorrhage, but this is explained by non-CKD related factors. C1 [Ovbiagele, Bruce] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Outcomes Res & Assessment Grp, Durham, NC USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Ovbiagele, B (reprint author), Med Univ S Carolina, Dept Neurosci, 96 Jonathan Lucas St,CSB 301,MSC 606, Charleston, SC 29425 USA. EM ovibes@musc.edu RI Hernandez, Adrian F./A-7818-2016; OI Saver, Jeffrey/0000-0001-9141-2251; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU American Heart Association; American Stroke Association; Pfizer (New York, NY); Merck-Schering Plough Partnership (North Wales, PA) FX The Get With the Guidelines Program is funded by the American Heart Association and the American Stroke Association. The program is also supported, in part, by unrestricted educational grants to the American Heart Association by Pfizer (New York, NY) and the Merck-Schering Plough Partnership (North Wales, PA), who did not participate in the design, analysis, or article preparation and did not require approval of this article for submission. NR 17 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2014 VL 7 IS 6 BP 929 EP 935 DI 10.1161/CIRCOUTCOMES.114.001144 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU0BY UT WOS:000345289300019 PM 25249561 ER PT J AU Cunningham, JW Wiviott, SD AF Cunningham, Jonathan W. Wiviott, Stephen D. TI Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit SO CLINICAL CARDIOLOGY LA English DT Review ID CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; LIFE-STYLE INTERVENTION; VALVULAR HEART-DISEASE; PULMONARY-HYPERTENSION; BARIATRIC SURGERY; OVERWEIGHT ADULTS; CLINICAL-TRIAL; PHASE-3 TRIAL AB Obesity is a major correlate of cardiovascular disease. Weight loss improves cardiovascular risk factors and has the potential to improve outcomes. Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. In clinical trials, these drugs cause weight loss and improve glucose tolerance, lipid profile, and, with the exception of bupropion plus naltrexone, blood pressure. However, their effect on cardiovascular outcomes is unknown. In defining appropriate roles for these drugs in preventive cardiology, it is important to remember the checkered history of drugs for obesity. New weight-loss drugs share the serotonergic and sympathomimetic mechanisms that proved harmful in the cases of Fen-Phen and sibutramine, respectively, albeit with significant differences. Given these risks, randomized cardiovascular outcomes trials are needed to establish the safety, and potential benefit, of these drugs. This review will discuss the history of pharmacotherapy for obesity, existing efficacy and safety data for the novel weight-loss drugs, and issues in the design of postapproval clinical trials. C1 [Cunningham, Jonathan W.; Wiviott, Stephen D.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM swiviott@partners.org FU Brigham and Women's Hospital from Eisai Pharmaceuticals; AstraZeneca; Merck; Arena Pharmaceuticals; Boston Clinical Research Institute; Bristol-Myers Squibb; Daiichi-Sankyo; Eli Lilly; ICON Medical Imaging; Johnson Johnson; Medscape; WebMD FX Dr. Wiviott receives funds for research through Brigham and Women's Hospital from Eisai Pharmaceuticals, AstraZeneca, and Merck. Dr. Wiviott has received consulting fees or speaking honoraria from Arena Pharmaceuticals, AstraZeneca, the Boston Clinical Research Institute, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, ICON Medical Imaging, Johnson & Johnson, Medscape, and WebMD. NR 57 TC 11 Z9 11 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD NOV PY 2014 VL 37 IS 11 BP 693 EP 699 DI 10.1002/clc.22304 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU0YI UT WOS:000345347700007 PM 25223901 ER PT J AU Ananthakrishnan, AN Khalili, H Konijeti, GG Higuchi, LM de Silva, P Fuchs, CS Richter, JM Schernhammer, ES Chan, AT AF Ananthakrishnan, Ashwin N. Khalili, Hamed Konijeti, Gauree G. Higuchi, Leslie M. de Silva, Punyanganie Fuchs, Charles S. Richter, James M. Schernhammer, Eva S. Chan, Andrew T. TI Sleep Duration Affects Risk for Ulcerative Colitis: A Prospective Cohort Study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Circadian Clock; Population; Epidemiology; Risk Factor; Inflammation. ID INFLAMMATORY-BOWEL-DISEASE; CORONARY-HEART-DISEASE; ROTATING SHIFT WORK; SELF-REPORTED SLEEP; LONG-TERM INTAKE; CROHNS-DISEASE; CARDIOVASCULAR-DISEASE; ENVIRONMENTAL-FACTORS; POSTMENOPAUSAL WOMEN; METABOLIC SYNDROME AB BACKGROUND & AIMS: Sleep deprivation is associated with production of inflammatory cytokines. Disturbed sleep quality has been associated with increased risk of disease flare in patients with Crohn's disease (CD) or ulcerative colitis (UC). However, the association between sleep and risk of incident CD and UC has not been previously examined. METHODS: We conducted a prospective study of women who were enrolled in the Nurses' Health Study (NHS) I since 1976 and NHS II since 1989 and followed through detailed biennial questionnaires with > 90% follow-up. We examined the association of sleep duration reported in 1986 in NHS I and 2001 in NHS II with incident CD and UC, diagnosed through 2010, in NHS I and 2009 in NHS II. Cox proportional hazards models adjusting for potential confounders were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Among 151,871 women, we confirmed 191 cases of CD (incidence, 8/100,000 person-years) and 230 cases of UC (incidence, 10/100,000 person-years) over 2,292,849 person-years. Compared with women with reported usual sleep durations of 7-8 h/day (incidence, 8/100,000 person-years), women with reported sleep duration < 6 h/day (11/100,000 person-years) or > 9 h/day (20/100,000 person-years) had a higher incidence of UC (P <.05). The multivariate hazard ratios for UC were 1.51 (95% CI, 1.10-2.09) for sleep durations < 6 h/day and 2.05 (95% CI, 1.44-2.92) for sleep durations > 9 h/day, compared with sleep durations of 7-8 h/day. In contrast, sleep duration did not modify risk of CD. Duration of rotating night shift work was not associated with CD or UC. CONCLUSIONS: On the basis of data from the NHS I and II, less than 6 hours sleep/day and more than 9 hours sleep/day are each associated with an increased risk of UC. Further studies are needed to evaluate sleep as a modifiable risk factor in the pathogenesis and progression of IBD. C1 [Ananthakrishnan, Ashwin N.; Khalili, Hamed; Konijeti, Gauree G.; Richter, James M.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Khalili, Hamed; Konijeti, Gauree G.; Higuchi, Leslie M.; Fuchs, Charles S.; Richter, James M.; Schernhammer, Eva S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Higuchi, Leslie M.; Fuchs, Charles S.] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [de Silva, Punyanganie] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Fuchs, Charles S.; Schernhammer, Eva S.; Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schernhammer, Eva S.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU American Gastroenterological Association; Broad Medical Research Program of the Broad Foundation; National Institutes of Health [K24 DK098311, P01 CA87969, P30 DK043351, K08 DK064256, K23 DK091742, K23 DK099681, UM1 CA176276] FX Supported by a Research Scholars Award of the American Gastroenterological Association (A.N.A, H.K), the Broad Medical Research Program of the Broad Foundation (A.T.C), and the National Institutes of Health (K24 DK098311, P01 CA87969, P30 DK043351, K08 DK064256, K23 DK091742, K23 DK099681, and UM1 CA176276). NR 67 TC 8 Z9 8 U1 5 U2 12 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 NOV PY 2014 VL 12 IS 11 BP 1879 EP 1886 DI 10.1016/j.cgh.2014.04.021 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AU1WE UT WOS:000345407400022 PM 24780288 ER PT J AU Ananthakrishnan, AN Cagan, A Gainer, VS Cheng, SC Cai, TX Scoville, E Konijeti, GG Szolovits, P Shaw, SY Churchill, S Karlson, EW Murphy, SN Kohane, I Liao, KP AF Ananthakrishnan, Ashwin N. Cagan, Andrew Gainer, Vivian S. Cheng, Su-Chun Cai, Tianxi Scoville, Elizabeth Konijeti, Gauree G. Szolovits, Peter Shaw, Stanley Y. Churchill, Susanne Karlson, Elizabeth W. Murphy, Shawn N. Kohane, Isaac Liao, Katherine P. TI Thromboprophylaxis Is Associated With Reduced Post-hospitalization Venous Thromboembolic Events in Patients With Inflammatory Bowel Diseases SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE CD; UC; Clot; Vein; Vascular ID POPULATION-BASED COHORT; CROHNS-DISEASE; RISK-FACTORS; INHERITED THROMBOPHILIA; PULMONARY-EMBOLISM; CO-MORBIDITY; PROPHYLAXIS; THROMBOSIS; CANCER; GLUCOCORTICOIDS AB BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs) have increased risk for venous thromboembolism (VTE); those who require hospitalization have particularly high risk. Few hospitalized patients with IBD receive thromboprophylaxis. We analyzed the frequency of VTE after IBD-related hospitalization, risk factors for post-hospitalization VTE, and the efficacy of prophylaxis in preventing post-hospitalization VTE. METHODS: In a retrospective study, we analyzed data from a multi-institutional cohort of patients with Crohn's disease or ulcerative colitis and at least 1 IBD-related hospitalization. Our primary outcome was a VTE event. All patients contributed person-time from the date of the index hospitalization to development of VTE, subsequent hospitalization, or end of follow-up. Our main predictor variable was pharmacologic thromboprophylaxis. Cox proportional hazard models adjusting for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: From a cohort of 2788 patients with at least 1 IBD-related hospitalization, 62 patients developed VTE after discharge (2%). Incidences of VTE at 30, 60, 90, and 180 days after the index hospitalization were 3.7/1000, 4.1/1000, 5.4/1000, and 9.4/1000 person-days, respectively. Pharmacologic thromboprophylaxis during the index hospital stay was associated with a significantly lower risk of post-hospitalization VTE (HR, 0.46; 95% CI, 0.22-0.97). Increased numbers of comorbidities (HR, 1.30; 95% CI, 1.16-1.47) and need for corticosteroids before hospitalization (HR, 1.71; 95% CI, 1.02-2.87) were also independently associated with risk of VTE. Length of hospitalization or surgery during index hospitalization was not associated with post-hospitalization VTE. CONCLUSIONS: Pharmacologic thromboprophylaxis during IBD-related hospitalization is associated with reduced risk of post-hospitalization VTE. C1 [Ananthakrishnan, Ashwin N.; Scoville, Elizabeth; Konijeti, Gauree G.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Karlson, Elizabeth W.; Murphy, Shawn N.; Kohane, Isaac; Liao, Katherine P.] Harvard Univ, Sch Med, Boston, MA USA. [Cagan, Andrew; Gainer, Vivian S.; Murphy, Shawn N.] Partners HealthCare, Res IS & Comp, Charlestown, MA USA. [Cheng, Su-Chun; Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Szolovits, Peter] MIT, Cambridge, MA 02139 USA. [Churchill, Susanne; Kohane, Isaac] Brigham & Womens Hosp, Natl Ctr Biomed Comp i2b2, Boston, MA 02115 USA. [Karlson, Elizabeth W.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Kohane, Isaac] Childrens Hosp, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU NIH [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01 AR049880]; U.S. National Institutes of Health [K23 DK097142] FX Supported by NIH U54-LM008748. A.N.A is supported by funding from the U.S. National Institutes of Health (K23 DK097142). K.P.L. is supported by NIH K08 AR060257 and the Harold and Duval Bowen fund. E.W.K is supported by grants from the NIH (K24 AR052403, P60 AR047782, R01 AR049880). NR 35 TC 8 Z9 8 U1 1 U2 6 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 NOV PY 2014 VL 12 IS 11 BP 1905 EP 1910 DI 10.1016/j.cgh.2014.02.034 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AU1WE UT WOS:000345407400026 PM 24632349 ER PT J AU Smoller, J AF Smoller, Jordan TI PSYCHIATRIC GENETICS AND THE FUTURE OF PERSONALIZED TREATMENT SO DEPRESSION AND ANXIETY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; DE-NOVO MUTATIONS; MAJOR DEPRESSIVE DISORDER; BIPOLAR DISORDER; RISK LOCI; SCHIZOPHRENIA; IDENTIFICATION; METAANALYSIS; VARIANTS; OUTCOMES C1 [Smoller, Jordan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Smoller, Jordan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Smoller, Jordan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smoller, Jordan] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Smoller, Jordan] Massachusetts Gen Hosp, Clin Res Program, Genet & Genom Unit, Boston, MA 02114 USA. [Smoller, Jordan] Massachusetts Gen Hosp, Partners HealthCare Biobank, Boston, MA 02114 USA. [Smoller, Jordan] Broads Stanley Ctr Psychiat Res, Cambridge, MA USA. [Smoller, Jordan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Smoller, J (reprint author), Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu FU NIMH NIH HHS [K24 MH094614, K24MH094614] NR 26 TC 3 Z9 3 U1 0 U2 3 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 NOV PY 2014 VL 31 IS 11 BP 893 EP 898 DI 10.1002/da.22322 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AU0OB UT WOS:000345321500001 PM 25407575 ER PT J AU Perlis, RH AF Perlis, Roy H. TI USE OF LARGE DATA SETS AND THE FUTURE OF PERSONALIZED TREATMENT SO DEPRESSION AND ANXIETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIALS; SUICIDE; RISK; DEPRESSION; PREDICTORS; PSYCHIATRY; DISORDER C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg MGH,185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM rperlis@partners.org NR 14 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2014 VL 31 IS 11 BP 916 EP 919 DI 10.1002/da.22321 PG 4 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AU0OB UT WOS:000345321500007 PM 25407581 ER PT J AU Wyman, MF Kallio, P Allred, E Meyer, D AF Wyman, Mary F. Kallio, Peter Allred, Emily Meyer, Deborah TI A group-based brief intervention for surgery patients with high-risk substance use SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Substance use disorder; Surgery; Brief intervention; Health behavior; Veterans ID ALCOHOL-USE DISORDERS; MAJOR NONCARDIAC SURGERY; SELF-REPORTED DRINKING; EMERGENCY-DEPARTMENT; HEALTH-CARE; AT-RISK; AUDIT-C; CONSUMPTION; ABUSE; COMPLICATIONS AB Objective: This study examined the feasibility and efficacy of a psychosocial intervention to address high-risk substance use in patients scheduled for elective surgery. Method: A group-format intervention, based on motivational interviewing principles, was provided prior to elective surgery to 107 participants with at-risk substance use, identified using the Alcohol Use Disorders Identification Test - Condensed (AUDIT-C) and self-report of illicit drug use. Patient satisfaction was assessed with an anonymous survey. Within-subject comparisons of substance use at baseline and at a postoperative follow-up evaluation were conducted. A control group of 67 surgery patients reporting high-risk substance use completed baseline assessments and received usual care. Medical outcomes and measures of utilization were compared between groups. Results: Patient satisfaction with the brief intervention was high. A paired t test comparing average pre- and post-AUDIT-C scores showed significant reduction in substance use postsurgery (t=9.94, P=.000), and participants reported intention to maintain reduced substance use levels. Between-group analyses revealed no significant differences in medical complications or utilization. Conclusion: Findings suggest that a group-based intervention for substance use disorder can be implemented as part of preoperative care and may contribute to decreased substance use prior to and following surgery. Further work is needed to identify methods to reduce adverse medical outcomes in surgical patients. Published by Elsevier Inc. C1 [Wyman, Mary F.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Wyman, Mary F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Psychiat, Madison, WI 53706 USA. [Kallio, Peter; Allred, Emily; Meyer, Deborah] Zablocki Vet Affairs Med Ctr, Milwaukee, WI USA. RP Wyman, MF (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM mary.wyman@va.gov NR 29 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 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 637 EP 643 DI 10.1016/j.genhosppsych.2014.08.002 PG 7 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400016 PM 25264340 ER PT J AU Walker, RJ Gebregziabher, M Martin-Harris, B Egede, LE AF Walker, Rebekah J. Gebregziabher, Mulugeta Martin-Harris, Bonnie Egede, Leonard E. TI Independent effects of socioeconomic and psychological social determinants of health on self-care and outcomes in Type 2 diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Diabetes; Social determinants; Socioeconomic; Psychological; Self-care ID OF-THE-LITERATURE; PSYCHOMETRIC PROPERTIES; GLYCEMIC CONTROL; VALIDITY; SCALE; DEPRESSION; DISTRESS; ADULTS; QUESTIONNAIRE; METAANALYSIS AB Objective: The purpose of this study was to investigate the independent effects of socioeconomic and psychological social determinants of health on diabetes knowledge, self-care, diabetes outcomes and quality of life. Research design and methods: Cross-sectional sample of 615 adults from two adult primary care clinics in the southeastern United States. Primary outcome variables were diabetes knowledge, self-care behaviors (diet, exercise, medication adherence, blood sugar testing, foot care) and diabetes outcomes (HbA1c, low-density lipoprotein, blood pressure, physical component summary score of SF12 quality of life, mental component summary score of SF12 quality of life). Covariates included age, sex, race/ethnicity, marital status, health literacy and comorbidity. Linear regression models were used to assess independent associations controlling for covariates. Results: In final adjusted models, significant associations for HbA1c included education [beta=-0.72, 95% confidence interval (CI): -1.36 to -0.08], income (beta=-0.66, CI: -1.30 to -0.16), self-efficacy (beta=-0.12, CI: -0.15 to -0.08) and diabetes distress (beta=0.43, CI: 0.14 to 0.72). Significant associations for self-care included medication adherence with diabetes distress (beta=-0.58, CI: -0.91 to -0.25) and perceived stress (beta=-0.12, CI: -0.18 to -0.05) and exercise with depression (beta=-0.06, CI: -0.10 to-0.01) and self-efficacy (beta=0.06, CI: 0.01 to 0.10). Significant associations for quality of life included depression (beta=-0.08, CI: -0.12 to -0.03), serious psychological distress (beta=-0.09, CI: -0.12 to -0.05), social support (beta=0.01, CI: 0.001 to 0.02) and perceived stress (beta=-0.12, CI: -0.19 to -0.06). Conclusions: Social determinants of health were significantly associated with diabetes self-care and outcomes with socioeconomic factors being most often associated with diabetes outcomes and psychological factors, specifically self-efficacy and perceived stress being most often associated with self-care and quality of life. (C) 2014 Elsevier Inc. All rights reserved. C1 [Walker, Rebekah J.; Gebregziabher, Mulugeta; Egede, Leonard E.] Ralph H Johnson VAMC, Charleston VA HSR & D COIN, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Walker, Rebekah J.; Martin-Harris, Bonnie] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Publ Hlth Sci, Charleston, SC 29425 USA. [Martin-Harris, Bonnie] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU The National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 40 TC 12 Z9 12 U1 6 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 662 EP 668 DI 10.1016/j.genhosppsych.2014.06.011 PG 7 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400020 PM 25103544 ER PT J AU Leibovici, V Murad, S Cooper-Kazaz, R Tetro, T Keuthen, NJ Hadayer, N Czarnowicki, T Odlaug, BL AF Leibovici, Vera Murad, Sari Cooper-Kazaz, Rena Tetro, Tamar Keuthen, Nancy J. Hadayer, Noa Czarnowicki, Tali Odlaug, Brian L. TI Excoriation (skin picking) disorder in Israeli University students: prevalence and associated mental health correlates SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Skin picking disorder; Prevalence; University students; Comorbidity; Health correlates ID OBSESSIVE-COMPULSIVE DISORDER; BODY DYSMORPHIC DISORDER; GENDER-DIFFERENCES; TRICHOTILLOMANIA; PHENOMENOLOGY; POPULATION; SAMPLE AB Objective: The purpose of the study was to examine the prevalence of excoriation (skin picking) disorder (SPD) and associated physical and mental health correlates in a sample of Israeli university students. Methods: Five thousand Israeli students were given questionnaires screening for SPD, depression, obsessive-compulsive disorder, body dysmorphic disorder and disruptive, impulse control and conduct disorders. A total of 2176 participants (43.6%) responded and were included in the analysis. Mean age was 25.1 +/- 4.8 (range 17-60) years, and 64.3% were female. Results: The proportion of students who were screened positive for SPD was 3.03%, with a nearly equal gender distribution (3.0% in females and 3.1% in males). There was a trend toward significantly higher rates of psychiatric problems such as generalized anxiety, compulsive sexual behavior and eating disorders in these students. Within the group of students screening positive for SPD, alcohol intake was higher in male students, while female students perceived themselves as less attractive. No association was found between depression and SPD. A high prevalence rate of skin picking was found within first-degree family members of the participants screening positive for SPD. Conclusions: Clinicians and public health officials within university settings should screen for SPD as it is common and associated with psychosocial dysfunction. (C) 2014 Elsevier Inc. All rights reserved. C1 [Leibovici, Vera; Murad, Sari; Tetro, Tamar; Hadayer, Noa; Czarnowicki, Tali] Hadassah Hebrew Univ, Med Ctr, Dept Dermatol, Jerusalem, Israel. [Cooper-Kazaz, Rena] Talbia Psychiat Clin, Clalit Hlth Serv, Jerusalem, Israel. [Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Odlaug, Brian L.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark. RP Leibovici, V (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Dermatol, Jerusalem, Israel. EM vleibovici@hadassah.org.il OI Odlaug, Brian/0000-0001-5407-0686 FU Trichotillomania Learning Center FX Dr. Vera Leibovici, Dr. Sari Murad, Dr. Rena Kazaz-Cooper, Dr. Tamar Tetro, Dr. Noa Hadayer and Dr. Tali Czarnowicki have nothing to disclose. Dr. Nancy Keuthen has received funding from the Trichotillomania Learning Center and is on the scientific advisory boards of the Trichotillomania Learning Center and the International Obsessive Compulsive Disorders Foundation. She is a stock shareholder of Pfizer Inc., Merck & Co. Inc., and Johnson & Johnson, and receives royalties from New Harbinger. Brian Odlaug has received a research grant from the Trichotillomania Learning Center, is a consult for Lundbeck Pharmaceuticals, and has received honoraria and royalties from Oxford University Press. NR 24 TC 2 Z9 2 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 686 EP 689 DI 10.1016/j.genhosppsych.2014.07.008 PG 4 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400024 PM 25150776 ER PT J AU Chang, G Weiss, AP Orav, EJ Rauch, SL AF Chang, Grace Weiss, Anthony P. Orav, Endel John Rauch, Scott L. TI Predictors of frequent emergency department use among patients with psychiatric illness SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Utilization; Prediction; Mental disorder; Emergency department ID LENGTH-OF-STAY; CASE-MANAGEMENT; CARE; VISITS; CONSULTATION; ATTENDERS; SERVICES; CONTACTS AB Objective: To identify the patient characteristics associated with frequent emergency department (ED) use and develop a tool to predict risk for returning in the next month. Method: Prospective cohort study of 863 adults with psychiatric illness presenting to one of four general hospital EDs. ED visits and relevant clinical information in the year before and one month after the index visit were abstracted. Results: One hundred sixty-seven of the patients (19%) were considered frequent users. Characteristics associated with frequent user status were homelessness, cocaine-positive toxicology screen, Medicare insurance, a personality disorder and hepatobiliary disease (all P<.05). Patients scoring in the highest risk category had nearly five times the odds of returning to the ED in the month subsequent to the index visit. Conclusions: Psychiatric patients with frequent ED use are a heterogeneous group, but there are specific target conditions which, if confirmed, may facilitate reduced ED use and be replaced by more appropriate treatment. Published by Elsevier Inc. C1 [Chang, Grace; Weiss, Anthony P.; Orav, Endel John; Rauch, Scott L.] Partners Psychiat & Mental Hlth, Div Hlth Serv Res, Boston, MA 02115 USA. [Chang, Grace; Weiss, Anthony P.; Orav, Endel John; Rauch, Scott L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chang, Grace; Orav, Endel John] Brigham Womens Hosp, Boston, MA 02115 USA. [Weiss, Anthony P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02478 USA. RP Chang, G (reprint author), 940 Belmont St, Brockton, MA 02301 USA. EM grace.chang2@va.gov; weissan@upstate.edu; eorav@partners.org; srauch@partners.org FU Partners Psychiatry and Mental Health Division of Health Services Research; [K24 AA 000289] FX The authors wish to acknowledge the contributions of Dr. Eric Goepfert, Ms. Sally Paustian and Ms Jennifer Smallwood. This study was supported by the Partners Psychiatry and Mental Health Division of Health Services Research and K24 AA 000289 (GC). NR 36 TC 2 Z9 2 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 716 EP 720 DI 10.1016/j.genhosppsych.2014.09.010 PG 5 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400030 PM 25312277 ER PT J AU Hershenberg, R Mavandadi, S Klaus, JR Oslin, DW Sayers, SL AF Hershenberg, Rachel Mavandadi, Shahrzad Klaus, Johanna R. Oslin, David W. Sayers, Steven L. TI Veteran preferences for romantic partner involvement in depression treatment SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Depression; Veterans; Social support; Treatment ID FAMILY INVOLVEMENT; PRIMARY-CARE; PRIME-MD; VALIDITY; UTILITY AB Objective: The objective was to examine Veterans' preferences for romantic partner involvement in depression treatment and patient characteristics that are associated with the likelihood of preferred involvement. Method: One hundred seventy-nine Veterans who met criteria for major or minor depression reported if they wanted their partners to give them medication reminders, accompany them to appointments, and speak with their treatment provider. Results: Greater depression severity and wanting a partner to be less critical and more encouraging were associated with greater preferences for involvement. Conclusion: Veterans may view their partners' involvement in depression treatment as one opportunity for partners to decrease blame or understand more about their problems. Published by Elsevier Inc. C1 Philadelphia VA Med Ctr, Educ & Clin Ctr, VISN Mental Illness Res 4, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Sayers, SL (reprint author), Philadelphia VA Med Ctr, VISN MIRECC 4, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM steven.sayers@va.gov FU VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA FX Please do not cite without permission from the authors. This paper was prepared with the support of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA. The views expressed in the article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. There were no conflicts of interest related to this project or its authors. We would like to thank Shirley Leong for consultation on the preparation of this manuscript. 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 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2014 VL 36 IS 6 BP 757 EP 759 DI 10.1016/j.genhosppsych.2014.08.001 PG 3 WC Psychiatry SC Psychiatry GA AU2GK UT WOS:000345434400038 PM 25219288 ER PT J AU Dunn, EC Winning, A Zaika, N Subramanian, SV AF Dunn, Erin C. Winning, Ashley Zaika, Natalya Subramanian, S. V. TI Does poor health predict moving, move quality, and desire to move?: A study examining neighborhood selection in US adolescents and adults SO HEALTH & PLACE LA English DT Article DE Desire to move; Health; Move quality; Moving; Neighborhood selection ID RESIDENTIAL-MOBILITY; MIGRATION; INEQUALITIES; OPPORTUNITY; DEPRESSION; DEPRIVATION; DISORDER; OUTCOMES; POVERTY; STRESS AB To date, research has rarely considered the role of health in shaping characteristics of the neighborhood, including mobility patterns. We explored whether individual health status shapes and constrains where individuals live. Using the National Longitudinal Study of Adolescent Health data, we examined whether 16 health indicators predicted moving, move quality, and desire to move. 3.8% of adolescents (n=490) reported a move in the past year In the unadjusted models, 10 health indicators were associated with moving; the magnitude of association for these health indicators was similar to socio-demographic characteristics. 7 of these health-moving associations persisted after adjusting for covariates. Health was also associated with moving quality, with a greater number of past year health problems in the child being associated with moving to a lower income neighborhood and parent disability or poor health being associated with moving to a higher income neighborhood. Almost every poor health status indicator was associated with a greater desire to move. Findings suggest that health status influences moving, and a reciprocal framework is more appropriate for examining health neighborhood linkages. (c) 2014 Elsevier Ltd. All rights reserved, C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Dunn, Erin C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. [Dunn, Erin C.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Winning, Ashley; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Zaika, Natalya] Tufts Univ, Eliot Pearson Dept Child Dev, Medford, MA 02155 USA. RP Subramanian, SV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA. EM SVSUBRAM@hsph.harvard.edu FU Robert Wood Johnson Investigator Award in Health Policy Research FX SVS is supported by a Robert Wood Johnson Investigator Award in Health Policy Research. NR 43 TC 3 Z9 3 U1 6 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8292 EI 1873-2054 J9 HEALTH PLACE JI Health Place PD NOV PY 2014 VL 30 BP 154 EP 164 DI 10.1016/j.healthplace.2014.08.007 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AU3PZ UT WOS:000345527200020 PM 25282124 ER PT J AU Garanto, A Duijkers, L Xiao, R Bennett, J Vandenberghe, LH Collin, RWJ AF Garanto, Alejandro Duijkers, Lonneke Xiao, Ru Bennett, Jean Vandenberghe, Luk H. Collin, Rob W. J. TI AAV-mediated antisense oligonucleotide delivery is an effective therapeutic approach for CEP290-associated LCA SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT ESGCT and NVGCT Collaborative Congress CY OCT 23-26, 2014 CL The Hague, NETHERLANDS SP European Soc Gene & Cell Therapy, Netherlands Soc Gene & Cell Therapy C1 [Garanto, Alejandro; Duijkers, Lonneke; Collin, Rob W. J.] Radboud UMC, Dept Human Genet, Nijmegen, Netherlands. [Garanto, Alejandro; Collin, Rob W. J.] Radboud UMC, Radboud Inst Mol Life Sci, Nijmegen, Netherlands. [Xiao, Ru; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Schepens Eye Res Inst, Boston, MA 02114 USA. [Bennett, Jean] Univ Penn Sch Med, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA USA. [Bennett, Jean] Univ Penn Sch Med, Scheie Eye Inst, Ctr Adv Retinal & Ophthalm Therapeut, Philadelphia, PA USA. NR 0 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 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 2014 VL 25 IS 11 MA P074 BP A80 EP A80 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AT2OR UT WOS:000344774700241 ER PT J AU Joung, JK AF Joung, J. Keith TI Targeted Genome and Epigenome Editing Using Engineered CRISPR-Cas and TALE Technologies SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT ESGCT and NVGCT Collaborative Congress CY OCT 23-26, 2014 CL The Hague, NETHERLANDS SP European Soc Gene & Cell Therapy, Netherlands Soc Gene & Cell Therapy C1 [Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 2014 VL 25 IS 11 MA INV047 BP A10 EP A10 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AT2OR UT WOS:000344774700027 ER PT J AU Kahraman, S Dirice, E Altunbas, HA Sanlioglu, AD AF Kahraman, S. Dirice, E. Altunbas, H. A. Sanlioglu, A. D. TI Both Soluble TRAIL and Adenovirus-Mediated Endogenous Expression of TRAIL Induces Proliferation in Min6 Mouse Pancreatic Beta Cells SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT ESGCT and NVGCT Collaborative Congress CY OCT 23-26, 2014 CL The Hague, NETHERLANDS SP European Soc Gene & Cell Therapy, Netherlands Soc Gene & Cell Therapy C1 [Kahraman, S.; Sanlioglu, A. D.] Akdeniz Univ, Gene & Cell Therapy Ctr, TR-07058 Antalya, Turkey. [Dirice, E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Altunbas, H. A.] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, TR-07058 Antalya, Turkey. RI Altunbas, Hasan/C-4199-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 2014 VL 25 IS 11 MA P122 BP A95 EP A95 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AT2OR UT WOS:000344774700288 ER PT J AU Tsai, SQ Wyvekens, N Khayter, C Foden, JA Thapar, V Reyon, D Goodwin, MJ Aryee, MJ Joung, JK AF Tsai, Shengdar Q. Wyvekens, Nicolas Khayter, Cyd Foden, Jennifer A. Thapar, Vishal Reyon, Deepak Goodwin, Mathew J. Aryee, Martin J. Joung, J. Keith TI Dimeric CRISPR/Cas-based nucleases for high-precision genome editing in human cells SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT ESGCT and NVGCT Collaborative Congress CY OCT 23-26, 2014 CL The Hague, NETHERLANDS SP European Soc Gene & Cell Therapy, Netherlands Soc Gene & Cell Therapy C1 [Tsai, Shengdar Q.; Wyvekens, Nicolas; Khayter, Cyd; Foden, Jennifer A.; Thapar, Vishal; Reyon, Deepak; Goodwin, Mathew J.; Aryee, Martin J.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Tsai, Shengdar Q.; Wyvekens, Nicolas; Khayter, Cyd; Foden, Jennifer A.; Thapar, Vishal; Reyon, Deepak; Aryee, Martin J.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Tsai, Shengdar Q.; Wyvekens, Nicolas; Khayter, Cyd; Foden, Jennifer A.; Goodwin, Mathew J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Tsai, Shengdar Q.; Reyon, Deepak; Aryee, Martin J.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wyvekens, Nicolas] Univ Freiburg, Sch Med, D-79106 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 2 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 2014 VL 25 IS 11 MA P025 BP A120 EP A121 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AT2OR UT WOS:000344774700365 ER PT J AU Williams, DA AF Williams, David A. TI Update on gene therapy trials for severe combined immunodeficiency and Wiskott-Aldrich Syndrome SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT ESGCT and NVGCT Collaborative Congress CY OCT 23-26, 2014 CL The Hague, NETHERLANDS SP European Soc Gene & Cell Therapy, Netherlands Soc Gene & Cell Therapy C1 [Williams, David A.] Boston Childrens Hosp, Boston, MA USA. [Williams, David A.] Dana Farber Canc Inst, Boston, MA USA. [Williams, David A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 2014 VL 25 IS 11 MA INV073 BP A16 EP A17 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AT2OR UT WOS:000344774700051 ER PT J AU Zinn, E Khaychuk, V Sarkar, D Carvalho, L Pacouret, S Morris, H Plovie, E Vandenberghe, LH AF Zinn, E. Khaychuk, V. Sarkar, D. Carvalho, L. Pacouret, S. Morris, H. Plovie, E. Vandenberghe, Luk H. TI Pre-existing immunity to AAV overcome by in silico ancestral capsid design SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT ESGCT and NVGCT Collaborative Congress CY OCT 23-26, 2014 CL The Hague, NETHERLANDS SP European Soc Gene & Cell Therapy, Netherlands Soc Gene & Cell Therapy C1 [Zinn, E.; Khaychuk, V.; Sarkar, D.; Carvalho, L.; Pacouret, S.; Plovie, E.; Vandenberghe, Luk H.] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Zinn, E.; Khaychuk, V.; Sarkar, D.; Carvalho, L.; Pacouret, S.; Plovie, E.; Vandenberghe, Luk H.] Schepens Eye Res Inst, Boston, MA USA. [Zinn, E.; Khaychuk, V.; Sarkar, D.; Carvalho, L.; Pacouret, S.; Morris, H.; Plovie, E.; Vandenberghe, Luk H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ocular Genom Inst, Singapore, Singapore. [Pacouret, S.] Grenoble Inst Technol, Grenoble, France. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 2014 VL 25 IS 11 MA INV040 BP A8 EP A8 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AT2OR UT WOS:000344774700021 ER PT J AU Lindsay, RW Bhama, P Hadlock, TA AF Lindsay, Robin W. Bhama, Prabhat Hadlock, Tessa A. TI Quality-of-Life Improvement After Free Gracilis Muscle Transfer for Smile Restoration in Patients With Facial Paralysis SO JAMA FACIAL PLASTIC SURGERY LA English DT Article ID MOTOR-NERVE; VALIDATION; EXCURSION; FACE; REANIMATION; CHILDREN; OUTCOMES AB IMPORTANCE Facial paralysis can contribute to disfigurement, psychological difficulties, and an inability to convey emotion via facial expression. In patients unable to perform a meaningful smile, free gracilis muscle transfer (FGMT) can often restore smile function. However, little is known about the impact on disease-specific quality of life. OBJECTIVE To determine quantitatively whether FGMT improves quality of life in patients with facial paralysis. DESIGN, SETTING, AND PARTICIPANTS Prospective evaluation of 154 FGMTs performed at a facial nerve center on 148 patients with facial paralysis. The Facial Clinimetric Evaluation (FaCE) survey and Facial Assessment by Computer Evaluation software (FACE-gram) were used to quantify quality-of-life improvement, oral commissure excursion, and symmetry with smile. INTERVENTION Free gracilis muscle transfer. MAIN OUTCOMES AND MEASURES Change in FaCE score, oral commissure excursion, and symmetry with smile. RESULTS There were 127 successful FGMTs on 124 patients and 14 failed procedures on 13 patients. Mean (SD) FaCE score increased significantly after successful FGMT (42.30 [15.9] vs 58.5 [17.60]; paired 2-tailed t test, P < .001). Mean (SD) FACE scores improved significantly in all subgroups (nonflaccid cohort, 37.8 [19.9] vs 52.9 [19.3]; P = .02; flaccid cohort, 43.1 [15.1] vs 59.6 [17.2]; P < .001; trigeminal innervation cohort, 38.9 [14.6] vs 55.2 [18.2]; P < .001; cross-face nerve graft cohort, 47.3 [16.6] vs 61.7 [16.9]; P < .001) except the failure cohort (36.5 [20.8] vs 33.5 [17.9]; Wilcoxon signed-rank test, P = .15). Analysis of 40 patients' photographs revealed a mean (SD) preoperative and postoperative excursion on the affected side of -0.88 (3.79) and 7.68 (3.38), respectively (P < .001); symmetry with smile improved from a mean (SD) of 13.8 (7.46) to 4.88 (3.47) (P < .001). CONCLUSIONS AND RELEVANCE Free gracilis muscle transfer has become a mainstay in the management armamentarium for patients with severe reduction in oral commissure movement after facial nerve insult and recovery. We found a quantitative improvement in quality of life after FGMT in patients who could not recover a meaningful smile after facial nerve insult. Quality-of-life improvement was not statistically different between donor nerve groups or facial paralysis types. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lindsay, RW (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. EM robin_lindsay@meei.harvard.edu FU Leslie Bernstein Grant from American Academy of Facial Plastic and Reconstructive Surgery FX The work was supported in part by the Leslie Bernstein Grant from the American Academy of Facial Plastic and Reconstructive Surgery. NR 21 TC 15 Z9 15 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6076 EI 2168-6092 J9 JAMA FACIAL PLAST SU JI JAMA Facial Plast. Surg. PD NOV-DEC PY 2014 VL 16 IS 6 BP 419 EP 424 DI 10.1001/jamafacial.2014.679 PG 6 WC Surgery SC Surgery GA AU2IT UT WOS:000345442100008 PM 25275339 ER PT J AU Chhabra, KR Sherry, NA Keamy, DG AF Chhabra, Karan R. Sherry, Nicole A. Keamy, Donald G., Jr. TI Anosmia in a 9-Year-Old Boy SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID KALLMANN-SYNDROME C1 [Chhabra, Karan R.] Rutgers Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. [Sherry, Nicole A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keamy, Donald G., Jr.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chhabra, KR (reprint author), Rutgers Robert Wood Johnson Med Sch, 675 Hoes Ln W, Piscataway, NJ 08854 USA. EM krchhabra@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD NOV PY 2014 VL 140 IS 11 BP 1083 EP 1084 DI 10.1001/jamaoto.2014.2081 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AU2JE UT WOS:000345443200019 PM 25257649 ER PT J AU Graham, LA Singletary, BA Richman, JS Maddox, TM Itani, KMF Hawn, MT AF Graham, Laura A. Singletary, Brandon A. Richman, Joshua S. Maddox, Thomas M. Itani, Kamal M. F. Hawn, Mary T. TI Improved Adverse Postoperative Outcomes With Revised American College of Cardiology/American Heart Association Guidelines for Patients With Cardiac Stents SO JAMA SURGERY LA English DT Article ID DRUG-ELUTING STENTS; NONCARDIAC SURGERY; CORONARY STENTS; ANTIPLATELET THERAPY; BARE-METAL; PERIOPERATIVE MANAGEMENT; LATE THROMBOSIS; RISK; IMPLANTATION; EVENTS AB IMPORTANCE In 2007, the American College of Cardiology/American Heart Association guidelines were revised for patients with cardiac stents in need of subsequent surgery to recommend delaying elective noncardiac surgery by 365 days in patients with drug-eluting stents (DESs). OBJECTIVE To examine the effect of the guidelines on postoperative major adverse cardiac events (MACEs) in subsequent noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS Patients receiving a cardiac stent between fiscal years 2005 and 2010 were identified by International Classification of Diseases, Ninth Revision diagnosis codes in the Veterans Affairs Medical SAS data sets. The Veterans Affairs Surgical Quality Improvement Program data were used to identify subsequent operations in the 2 years following stenting. The preguideline period was defined as fiscal years 2005 through 2007 and the postguideline period was defined as fiscal years 2008 through 2010. Surgery patients admitted through the emergency department or transferred from another hospital were excluded from analyses. Overall, 16 634 elective noncardiac operations were identified (8034 [48.3%] in the preguideline period; 8600 [51.7%] in the postguideline period). MAIN OUTCOMES AND MEASURES Composite 30-day postoperative MACEs. We used chi(2) tests to examine differences in bivariate frequencies and used logistic models to examine adjusted associations with 2-year postoperative MACEs. RESULTS The median time to surgery was 364 days (interquartile range, 184-528 days). A total of 11 026 operations (66.3%) followed DES placement, and 5608 (33.7%) followed bare metal stent placement. After the guidelines' publication, surgery timing increased following DES placement from 323 to 404 days (P < .001) and decreased following bare metal stent placement from 402 to 309 days (P < .001). In addition, postoperative MACE rates decreased from 4.2% to 3.3%(P = .002). After adjusting for cardiac risk factors and procedure characteristics, there was an overall absolute risk reduction of 0.9% for MACEs (odds ratio = 0.74; 95% CI, 0.62-0.89). On further examination of trends across time, MACE rates with DES placement began to decrease prior to the guidelines' publication from 5.5% in 2005 to 4.3% in 2006 and remained stable through 2010. In contrast, MACE rates with bare metal stent placement increased from 4.3% in 2005 to 8.0% in 2007 but decreased to 4.8% following the guidelines' publication. CONCLUSIONS AND RELEVANCE After the guidelines' publication, noncardiac surgery was delayed in patients with DESs but not bare metal stents. With a 26% reduction in MACEs following the guidelines, it would appear that the guidelines did improve postoperative outcomes; however, when examined over time, it becomes evident that there are many more factors influencing management of patients with cardiac stents in need of subsequent surgery. C1 [Graham, Laura A.; Singletary, Brandon A.; Richman, Joshua S.; Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Graham, Laura A.; Singletary, Brandon A.; Richman, Joshua S.; Hawn, Mary T.] Univ Alabama Birmingham, Sect Gastrointestinal Surg, Dept Surg, Birmingham, AL 35294 USA. [Maddox, Thomas M.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, Denver, CO USA. [Itani, Kamal M. F.] Boston Univ, Dept Surg, Vet Affairs Boston Healthcare Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Hawn, MT (reprint author), Univ Alabama Birmingham, Sect Gastrointestinal Surg, Dept Surg, 1922 Seventh Ave S,KB 428, Birmingham, AL 35294 USA. EM mhawn@uab.edu FU VA Health Services Research and Development [IIR 09-347]; VA Health Services Research and Development FX This study is funded by grant IIR 09-347 from VA Health Services Research and Development. Drs Richman and Maddox are supported by career development awards from VA Health Services Research and Development. NR 23 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1113 EP 1120 DI 10.1001/jamasurg.2014.2044 PG 8 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800005 PM 25188466 ER PT J AU Ernst, KF Hall, DE Schmid, KK Seever, G Lavedan, P Lynch, TG Johanning, JM AF Ernst, Katherine F. Hall, Daniel E. Schmid, Kendra K. Seever, Georgia Lavedan, Pierre Lynch, Thomas G. Johanning, Jason Michael TI Surgical Palliative Care Consultations Over Time in Relationship to Systemwide Frailty Screening SO JAMA SURGERY LA English DT Article ID UNIT; SERVICES; OUTCOMES; PROJECT; TRAUMA AB IMPORTANCE The need for integrating palliative care into surgical services has been established within the surgical literature. The ability to effectively screen, obtain an appropriately timed consultation, and determine the effect of consultation remains problematic. OBJECTIVE To examine surgical palliative care consultations over time and their relationship to the initiation and implementation of a systemwide frailty-screening program. DESIGN, SETTING, AND PARTICIPANTS We reviewed all surgical palliative care consultations performed between January 1, 2006, and August 31, 2013, and abstracted the referring service (medicine/surgery), date of surgery (if any), date of death (if any), and all variables required to calculate a frailty score using the risk analysis index. We examined changes in mortality and referral patterns before and after implementation of the frailty-screening program using multivariable logistic regression. EXPOSURES Surgical palliative care consultations, including frailty screening. MAIN OUTCOMES AND MEASURES The primary study outcomes were 30-, 180-, and 360-day mortality. RESULTS From 2006 to 2013, a total of 310 palliative care consultations were ordered for surgical patients: 160 before initiation of frailty screening (January 1, 2011) and 150 after initiation of the program. The groups had similar demographics, comorbidities, and frailty scores. After initiation, we observed dramatically decreased mortality at 30, 180, and 360 days (21.3% vs 31.9%, 44.0% vs 70.6%, and 66.0% vs 78.8%, respectively; all P < .05). This coincided with an increased rate of palliative care consultations from 32 per year to 56 per year. After initiation of the program, consultations were more likely to be requested by surgeons (56.7% vs 24.4%; P < .05) and were more likely to occur before the index operation (52.0% vs 26.3%; P < .05). Implementation of the screening program was associated with a 33% reduction in 180-day mortality (odds ratio [OR], 0.37; 95% CI, 0.22-0.62; P < .001) even after controlling for age, frailty, and whether the patients had surgery. Modeled mortality was also reduced when the palliative care consultation was ordered by a surgeon (OR, 0.50; CI, 0.30-0.83; P = .007) or ordered before the operation (OR, 0.52; CI, 0.30-0.90; P = .02). CONCLUSIONS AND RELEVANCE Our data suggest that a systematic frailty-screening program effectively identifies at-risk surgical patients and is associated with a significant reduction in mortality for patients undergoing palliative care consultation. Analysis also suggests that preoperative palliative care consultations ordered by surgeons are associated with reduced mortality rates. C1 [Ernst, Katherine F.] Univ Nebraska Med Ctr, Coll Med, Omaha, NE 68105 USA. [Hall, Daniel E.] Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Schmid, Kendra K.] Univ Nebraska Med Ctr, Dept Biostat, Coll Publ Hlth Masters Programs, Omaha, NE 68105 USA. [Seever, Georgia; Lavedan, Pierre; Johanning, Jason Michael] Nebraska Western Iowa Vet Affairs Med Ctr, Dept Surg, Omaha, NE USA. [Lynch, Thomas G.] Vet Hlth Adm, Washington, DC USA. [Johanning, Jason Michael] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68105 USA. RP Johanning, JM (reprint author), Univ Nebraska Med Ctr, 4101 Woolworth Ave, Omaha, NE 68105 USA. EM jason.johanning@va.gov OI Hall, Daniel/0000-0001-6382-0522 FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Health Services Research and Development [CDA 08-281] FX This research was supported in part by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Health Services Research and Development (CDA 08-281). NR 16 TC 11 Z9 11 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1121 EP 1126 DI 10.1001/jamasurg.2014.1393 PG 6 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800006 PM 25207603 ER PT J AU Quin, J Lucke, J Hattler, B Gupta, S Baltz, J Bishawi, M Almassi, GH Grover, FL Collins, J Shroyer, AL AF Quin, Jacquelyn Lucke, John Hattler, Brack Gupta, Sandeep Baltz, Janet Bishawi, Muath Almassi, G. Hossein Grover, Frederick L. Collins, Joseph Shroyer, A. Laurie TI Surgeon Judgment and Utility of Transit Time Flow Probes in Coronary Artery Bypass Grafting Surgery SO JAMA SURGERY LA English DT Article ID ON-PUMP; FAILURE AB IMPORTANCE Transit time flow (TTF) probes may be useful for predicting long-term graft patency and assessing grafts intraoperatively in patients undergoing coronary artery bypass grafting (CABG); however, studies of TTF probe use are limited. OBJECTIVE To examine 1-year graft patency and intraoperative revision rates in patients undergoing CABG based on intraoperative TTF assessment. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of a multicenter randomized clinical trial conducted at 18 Veterans Affairs hospitals using the Randomized On/Off Bypass (ROOBY) Trial data set. Of the original 2203 patients undergoing CABG surgery with or without cardiopulmonary bypass from February 1, 2002, through May 31, 2008, we studied a subset of 1607 who underwent TTF probe analysis of 1 or more grafts during surgery. EXPOSURES Use of TTF probes to assess graft flow and pulsatility index (PI) values. The decision to revise a graft was based on the judgment of the attending surgeon. MAIN OUTCOMES AND MEASURES Rates of 1-year FitzGibbon grade A patency and intraoperative revision were compared based on TTF measurements (<20 [low flow] vs >= 20 mL/min [normal flow]) and PI values (<3, 3-5, and >5). RESULTS We measured TTF and/or PI in 2738 grafts, and 1-year patency was determined in 1710 (62.5%) of these grafts. FitzGibbon grade A patency occurred significantly less often in grafts with a TTF with low flow (259 of 363 [71.3%]) than in those with normal flow (1174 of 1347 [87.2%]; P < .01). FitzGibbon grade A patency was also inversely correlated with increasing PI values, as found in 936 of 1093 grafts (85.6%) with a PI less than 3, 136 of 182 grafts (74.7%) with a PI of 3 to 5, and 91 of 134 grafts (67.9%) with a PI greater than 5 (P <= .01). Intraoperative graft revision was more frequent in grafts with low flow (44 of 568 [7.7%]) than in those with normal flow (8 of 2170 [0.4%]; P < .01). Graft revision was also more frequent as PI increased (12 of 1827 [0.7%] with a PI < 3, 9 of 307 [2.9%] with a PI 3-5, and 9 of 155 [5.8%] with a PI >5; P < .01). CONCLUSIONS AND RELEVANCE Intraoperative TTF probe data may be helpful in predicting long-term patency and in the decision of whether to revise a questionable graft for patients undergoing CABG surgery. C1 [Quin, Jacquelyn] Vet Affairs Boston Healthcare Syst, Surg Serv, West Roxbury, MA 02132 USA. [Lucke, John] Charles George VA Med Ctr, Surg Serv, Asheville, NC USA. [Hattler, Brack] Dept VA Eastern Colorado Hlth Care Syst, Med Serv, Denver, CO USA. [Hattler, Brack] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA. [Gupta, Sandeep; Bishawi, Muath; Shroyer, A. Laurie] Northport VA Med Ctr, Surg Serv, Stony Brook, NY USA. [Gupta, Sandeep; Bishawi, Muath; Shroyer, A. Laurie] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Baltz, Janet; Grover, Frederick L.; Shroyer, A. Laurie] Dept VA Eastern Colorado Hlth Care Syst, Surg Serv, Denver, CO USA. [Almassi, G. Hossein; Shroyer, A. Laurie] Milwaukee VA Med Ctr, Surg Serv, Milwaukee, WI USA. [Grover, Frederick L.] Univ Colorado, Dept Surg, Sch Med, Aurora, CO USA. [Collins, Joseph] Coordinating Ctr, Cooperat Studies Program, Perry Point, MD USA. [Collins, Joseph] VA Med Ctr, Perry Point, MD USA. RP Quin, J (reprint author), Vet Affairs Boston Healthcare Syst, Surg Serv, 1400 VFW Pkwy,Mail Code 112, West Roxbury, MA 02132 USA. EM jacquelyn.quin@va.gov RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU Cooperative Studies Program (CSP) of the Department of VA Office of Research and Development FX This study was supported by the Cooperative Studies Program (CSP) of the Department of VA Office of Research and Development. NR 17 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1182 EP 1187 DI 10.1001/jamasurg.2014.1891 PG 6 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800015 PM 25251332 ER PT J AU Chen, Q Tsai, TC Mull, HJ Rosen, AK Itani, KMF AF Chen, Qi Tsai, Thomas C. Mull, Hillary J. Rosen, Amy K. Itani, Kamal M. F. TI Using a Composite Readmission Measure to Assess Surgical Quality in the Veterans Health Administration: How Well Does It Correlate With Established Surgical Measures? SO JAMA SURGERY LA English DT Letter C1 [Chen, Qi; Mull, Hillary J.; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Tsai, Thomas C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Tsai, Thomas C.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Mull, Hillary J.; Rosen, Amy K.; Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, Boston, MA 02130 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Chen, Q (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave, Boston, MA 02130 USA. EM qi.chen2@va.gov NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1206 EP 1207 DI 10.1001/jamasurg.2014.1095 PG 2 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800022 PM 25207493 ER PT J AU Kerfoot, BP Kissane, N AF Kerfoot, B. Price Kissane, Nicole TI The Use of Gamification to Boost Residents' Engagement in Simulation Training SO JAMA SURGERY LA English DT Letter C1 [Kerfoot, B. Price] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Kerfoot, B. Price] Harvard Univ, Sch Med, Boston, MA USA. [Kissane, Nicole] Boston Med Ctr, Boston, MA USA. [Kissane, Nicole] Boston Univ, Boston, MA 02215 USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,151DIA, Boston, MA 02130 USA. EM price.kerfoot@gmail.com NR 5 TC 9 Z9 9 U1 5 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1208 EP 1209 DI 10.1001/jamasurg.2014.1779 PG 2 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800023 PM 25229631 ER PT J AU Mull, HJ Chen, Q Shwartz, M Itani, KMF Rosen, AK AF Mull, Hillary J. Chen, Qi Shwartz, Michael Itani, Kamal M. F. Rosen, Amy K. TI Measuring Surgical Quality: Which Measure Should We Trust? SO JAMA SURGERY LA English DT Letter ID CARE C1 [Mull, Hillary J.; Chen, Qi; Shwartz, Michael; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA. [Mull, Hillary J.; Itani, Kamal M. F.; Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Shwartz, Michael] Boston Univ, Sch Management, Dept Operat & Technol Management, Boston, MA 02215 USA. [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, Boston, MA 02130 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Mull, HJ (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave,152M, Boston, MA 02130 USA. EM hillary.mull@va.gov FU Intramural VA [VA999999] 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 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2014 VL 149 IS 11 BP 1210 EP 1212 DI 10.1001/jamasurg.2014.373 PG 3 WC Surgery SC Surgery GA AU2JI UT WOS:000345443800025 PM 25250973 ER PT J AU Stern, JE Luke, B Hornstein, MD Cabral, H Gopal, D Diop, H Kotelchuck, M AF Stern, Judy E. Luke, Barbara Hornstein, Mark D. Cabral, Howard Gopal, Daksha Diop, Hafsatou Kotelchuck, Milton TI The effect of father's age in fertile, subfertile, and assisted reproductive technology pregnancies: A population based cohort study SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE Paternal age; Maternal age; Subfertility; ART; IVF; Preterm delivery; Birthweight ID PATERNAL AGE; MATERNAL AGE; SEMEN QUALITY; BIRTH-DEFECTS; DNA-DAMAGE; SPERM; ASSOCIATION; INFERTILITY; OUTCOMES; AUTISM AB To compare ages of mothers and of fathers at delivery in couples who are fertile, subfertile, and subfertile treated with assisted reproductive technology (ART) and to characterize birth outcomes in the ART population according to paternal age. Live birth deliveries in Massachusetts between July, 2004 and December, 2008 were identified from vital records and categorized by maternal fertility status and treatment as ART, subfertile or fertile. The ART births were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database to obtain cycle-specific treatment data. Parental ages were obtained from birth certificates. Age of mothers and fathers were compared using ANOVA for continuous measures and chi (2) for categories. Risks of prematurity (< 37 weeks), low birthweight (< 2,500 g), and low birthweight z-score (small for gestatational age, SGA) were modeled using logistic regression by categories of paternal age as adjusted odds ratios and 95 % CI. The study population included 9,092 ART, 6,238 subfertile, and 318,816 fertile deliveries. Paternal ages in the ART and subfertile groups were similar and differed significantly from those of the fertile group. Maternal age in the ART and subfertile groups averaged 5-6 years older than their fertile counterparts and fathers averaged 4-5 years older with twice as many being older than 37. The risks for prematurity, low birthweight and SGA did not increase with increasing paternal age. Fathers in ART- treated and subfertile couples are older than in their fertile counterparts. Older paternal age was not assoicated with increased risk for prematurity, low birthweight, or SGA. C1 [Stern, Judy E.] Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH 03755 USA. [Luke, Barbara] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA. [Hornstein, Mark D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Cabral, Howard] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gopal, Daksha] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Diop, Hafsatou] Massachusetts Dept Publ Hlth, Boston, MA USA. [Kotelchuck, Milton] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. RP Stern, JE (reprint author), Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH 03755 USA. EM judy.e.stern@dartmouth.edu FU [R01HD064595]; [R01HD067270] FX This work was supported by R01HD064595 and R01HD067270. The views expressed in this article are those of the authors and do not necessarily represent the official view of the National Institutes of Health. NR 30 TC 5 Z9 5 U1 1 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 EI 1573-7330 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD NOV PY 2014 VL 31 IS 11 BP 1437 EP 1444 DI 10.1007/s10815-014-0327-8 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA AU1UR UT WOS:000345406000006 PM 25193289 ER PT J AU Seifarth, H Schlett, CL Lehman, SJ Bamberg, F Donnelly, P Januzzi, JL Koenig, W Truong, QA Hoffmann, U AF Seifarth, Harald Schlett, Christopher L. Lehman, Sam J. Bamberg, Fabian Donnelly, Patrick Januzzi, James L. Koenig, Wolfgang Truong, Quynh A. Hoffmann, Udo TI Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Coronary artery disease; Coronary atherosclerotic plaque; Plaque progression; Cardiac biomarker; Coronary CT angiography ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ACUTE CHEST-PAIN; MYOCARDIAL-INFARCTION; ATHEROSCLEROTIC PLAQUE; ARTERY-DISEASE; INTRAVASCULAR-ULTRASOUND; CARDIOVASCULAR EVENTS; FOLLOW-UP; LESIONS; ASSAY AB Background: Elevated levels of inflammatory biomarkers are associated with increased cardiovascular morbidity and mortality. Objective: We sought to determine whether elevated concentrations of high-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) predict progression of coronary artery disease (CAD) as determined by coronary CT angiography (coronary CTA). Methods: Patients presenting to the emergency department with acute chest pain who initially showed no evidence of an acute coronary syndrome underwent baseline and follow-up coronary CTA (median follow-up, 23.9 months) using identical acquisition and reconstruction parameters. Coronary CTA data of each major coronary artery were co-registered. Cross-sections were assessed for the presence of calcified and noncalcified plaques. Progression of atherosclerotic plaque and change of plaque composition from noncalcified to calcified plaque was evaluated and correlated to levels of hs-TnT and hs-CRP at the time of the baseline CT. Results: Fifty-four patients (mean age, 54.1 years; 59% male) were included, and 6775 cross-sections were compared. CAD was detected in 12.2 +/- 21.2 cross-sections per patient at baseline. Prevalence of calcified plaque increased by 1.5 +/- 2.4 slices per patient (P < .0001) over the follow-up period. On average, 1.6 +/- 3.6 slices with new noncalcified plaque were found per patient (P < .0001) and 0.7 +/- 1.7 slices with pre-existing noncalcified plaque had progressed to calcified plaque (P < .0001). After multivariate adjustment, change of overall CAD burden was predicted by baseline hs-TnT and hs-CRP (r = 0.29; P = .039 and r = 0.40; P = .004). Change of plaque composition was associated with baseline hs-TnT (r = 0.29; P = .03). Conclusion: Concentrations of hs-TnT and hs-CRP are weakly associated with a significant increase in CAD burden and change in plaque composition over 24 months independent of baseline risk factors. (C) 2014 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Seifarth, Harald; Schlett, Christopher L.; Lehman, Sam J.; Bamberg, Fabian; Donnelly, Patrick; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Seifarth, Harald; Schlett, Christopher L.; Lehman, Sam J.; Bamberg, Fabian; Donnelly, Patrick; Januzzi, James L.; Truong, Quynh A.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Seifarth, Harald] Esslingen Hosp, Dept Diagnost & Intervent Radiol, Esslingen, Germany. [Schlett, Christopher L.] Univ Heidelberg Hosp, Dept Diagnost & Intervent Radiol, Heidelberg, Germany. [Januzzi, James L.; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med & Cardiol 2, D-89069 Ulm, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St, Boston, MA 02114 USA. EM uhoffmann@partners.org FU National Institutes of Health [R01 HL080053, T32HL076136, L30HL093896]; Siemens Medical Solutions and GE Healthcare; Deutsche Forschungsgemeinschaft [SE 2029/1-1]; German Federal Ministry of Education and Research; Foundation of German Business; Roche Diagnostics; Siemens; Critical Diagnostics; Balson Scholar Fund; National Institutes of Health; GE Healthcare and Siemens Medical Systems FX This work was supported by the National Institutes of Health (R01 HL080053; Udo Hoffmann [principal investigator]) and in part by Siemens Medical Solutions and GE Healthcare. Dr Harald Seifarth was supported by Deutsche Forschungsgemeinschaft (grant SE 2029/1-1). Dr Christopher L. Schlett is supported in part by grants from the German Federal Ministry of Education and Research, as well as the Foundation of German Business. Dr James L. Januzzi reports having received research grant support from Roche Diagnostics, Siemens, and Critical Diagnostics and assay/reagent support from Siemens. He was also supported in part by the Balson Scholar Fund. Dr Quynh A. Truong is supported by National Institutes of Health (grants T32HL076136 and L30HL093896). Dr Udo Hoffmann has received grant support for the ROMICAT 1 and 2 trials from the National Institutes of Health and research grant support from GE Healthcare and Siemens Medical Systems. NR 30 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD NOV-DEC PY 2014 VL 8 IS 6 BP 452 EP 458 DI 10.1016/j.jcct.2014.09.005 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AU4CP UT WOS:000345556900008 PM 25467832 ER PT J AU Blanke, P Dvir, D Cheung, A Ye, J Levine, RA Precious, B Berger, A Stub, D Hague, C Murphy, D Thompson, C Munt, B Moss, R Boone, R Wood, D Pache, G Webb, J Leipsic, J AF Blanke, Philipp Dvir, Danny Cheung, Anson Ye, Jian Levine, Robert A. Precious, Bruce Berger, Adam Stub, Dion Hague, Cameron Murphy, Darra Thompson, Christopher Munt, Brad Moss, Robert Boone, Robert Wood, David Pache, Gregor Webb, John Leipsic, Jonathon TI A simplified D-shaped model of the mitral annulus to facilitate CT-based sizing before transcatheter mitral valve implantation SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Mitral regurgitation; Mitral annulus; Transcatheter mitral valve implantation; Transapical mitral valve replacement; Computed tomography ID COMPUTED-TOMOGRAPHY; 3-DIMENSIONAL ECHOCARDIOGRAPHY; REGURGITATION; REPLACEMENT; CARDIOMYOPATHY; RECONSTRUCTION; VALIDATION; GEOMETRY; PROLAPSE; ANATOMY AB Background: The nonplanar, saddle-shaped structure of the mitral annulus has been well established through decades of anatomic and echocardiographic study. Its relevance for mitral annular assessment for transcatheter mitral valve implantation is uncertain. Objective: Our objectives are to define the methodology for CT-based simplified "D-shaped" mitral annular assessment for transcatheter mitral valve implantation and compare these measurements to traditional "saddle-shaped" mitral annular assessment. Methods: The annular contour was manually segmented, and fibrous trigones were identified using electrocardiogram-gated diastolic CT data sets of 28 patients with severe functional mitral regurgitation, yielding annular perimeter, projected area, trigone-to-trigone (TT) distance, and septal-lateral distance. In contrast to the traditional saddle-shaped annulus, the D-shaped annulus was defined as being limited anteriorly by the TT distance, excluding the aortomitral continuity. Hypothetical left ventricular outflow tract (LVOT) clearance was assessed. Results: Projected area, perimeter, and septal-lateral distance were found to be significantly smaller for the D-shaped annulus (11.2 +/- 2.7 vs 13.0 +/- 3.0 cm(2); 124.1 +/- 15.1 vs 136.0 +/- 15.5 mm; and 32.1 perpendicular to 4.0 vs 40.1 perpendicular to 4.9 mm, respectively; P < .001). TT distances were identical (32.7 +/- 4.1 mm). Hypothetical LVOT clearance was significantly lower for the saddle-shaped annulus than for the D-shaped annulus (10.7 +/- 2.2 vs 17.5 +/- 3.0 mm; P < .001). Conclusion: By truncating the anterior horn of the saddle-shaped annular contour at the TT distance, the resulting more planar and smaller D-shaped annulus projects less onto the LVOT, yielding a significantly larger hypothetical LVOT clearance than the saddle-shaped approach. CT-based mitral annular assessment may aid preprocedural sizing, ensuring appropriate patient and device selection. (C) 2014 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Blanke, Philipp; Dvir, Danny; Cheung, Anson; Ye, Jian; Precious, Bruce; Berger, Adam; Stub, Dion; Hague, Cameron; Murphy, Darra; Thompson, Christopher; Munt, Brad; Moss, Robert; Boone, Robert; Wood, David; Webb, John; Leipsic, Jonathon] Univ British Columbia, St Pauls Hosp, Ctr Heart Valve Innovat, Vancouver, BC V5Z 1M9, Canada. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Pache, Gregor] Univ Freiburg, Dept Radiol, Sect Cardiovasc Radiol, D-79106 Freiburg, Germany. RP Leipsic, J (reprint author), Univ British Columbia, St Pauls Hosp, Ctr Heart Valve Innovat, Vancouver, BC V5Z 1M9, Canada. EM jleipsic@providencehealth.bc.ca RI Thompson, Christopher/F-3967-2010 OI Thompson, Christopher/0000-0001-9206-376X FU NHLBI NIH HHS [K24 HL067434, R01 HL038176, R01 HL072265, R01 HL109506] NR 19 TC 18 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD NOV-DEC PY 2014 VL 8 IS 6 BP 459 EP 467 DI 10.1016/j.jcct.2014.09.009 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AU4CP UT WOS:000345556900009 PM 25467833 ER PT J AU Yanamadala, V Walcott, BP Fecci, PE Rozman, P Kumar, JI Nahed, BV Swearingen, B AF Yanamadala, Vijay Walcott, Brian P. Fecci, Peter E. Rozman, Peter Kumar, Jay I. Nahed, Brian V. Swearingen, Brooke TI Reversal of warfarin associated coagulopathy with 4-factor prothrombin complex concentrate in traumatic brain injury and intracranial hemorrhage SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Fresh frozen plasma; Intracranial hemorrhage; Prothrombin complex concentrate; Subdural hematoma; Warfarin ID PLASMA AB Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or FCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and FCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p = 0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p < 0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p <0.05). In this preliminary experience, FCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R25 NS065743] NR 10 TC 3 Z9 3 U1 1 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 NOV PY 2014 VL 21 IS 11 BP 1881 EP 1884 DI 10.1016/j.jocn.2014.05.001 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AU4TK UT WOS:000345604100007 PM 24953825 ER PT J AU Spencer, AE Uchida, M Kenworthy, T Keary, CJ Biederman, J AF Spencer, Andrea E. Uchida, Mai Kenworthy, Tara Keary, Christopher J. Biederman, Joseph TI Glutamatergic Dysregulation in Pediatric Psychiatric Disorders: A Systematic Review of the Magnetic Resonance Spectroscopy Literature SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; ANTERIOR CINGULATE CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DORSOLATERAL PREFRONTAL CORTEX; COGNITIVE-BEHAVIORAL THERAPY; AUTISM SPECTRUM DISORDERS; GAMMA-AMINOBUTYRIC-ACID; H-1 MR SPECTROSCOPY; MAJOR DEPRESSION AB Objective: As the major excitatory neurotransmitter in the brain, glutamate plays a critical role in normal brain function; thus, its dysregulation could lead to psychopathology in youth. A growing body of literature has investigated the role of glutamate in the pathophysiology of childhood psychiatric disorders through magnetic resonance spectroscopy (MRS). The aim of this study was to review the existing literature to gauge the specificity of such findings. Data Sources: PubMed was searched for all scientific, peer-reviewed articles published in English that included MRS measurements of glutamatergic metabolites in pediatric psychiatric populations through August 14, 2013. Study Selection: 50 articles were included in this review. These studies included measurements of glutamate or related metabolites with MRS in children with psychiatric disorders. Data Extraction: All relevant data (eg, population; number, sex, and age of subjects; method of comparison; treatment history; MRS Tesla; brain regions of interest; glutamatergic findings; other findings; and comorbidities) were extracted from the included articles. The direction and significance of glutamate dysregulation and brain region(s) examined were used to compare the studies. Results: Most consistently, increases in glutamatergic metabolites were found in the anterior cingulate cortex (ACC) and other regions in youth with attention-deficit/hyperactivity disorder (ADHD). Limited data suggested increases in glutamatergic metabolites in youth with autism spectrum disorders, emotional dysregulation, and high risk for schizophrenia and decreases in youth with major depression, bipolar disorder, and obsessive-compulsive disorder. There was limited but consistent evidence for normalization of glutamatergic levels with treatment, particularly in bipolar disorder and ADHD. Conclusions: A relatively small number of studies have examined the role of glutamatergic dysregulation in pediatric psychiatric disorders. Some consistencies can be found, but interpretation of the data is limited by differences in methodology, including age of subjects, severity of current symptoms, treatment, and scanning parameters. (C) Copyright 2014 Physicians Postgraduate Press, Inc. C1 [Spencer, Andrea E.; Uchida, Mai; Kenworthy, Tara; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Keary, Christopher J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Spencer, Andrea E.; Uchida, Mai; Keary, Christopher J.; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), 55 Fruit St,WRN 705, Boston, MA 02215 USA. EM jbiederman@partners.org FU Pediatric Psychopharmacology Research Council Fund, Massachusetts General Hospital FX This work was supported by the Pediatric Psychopharmacology Research Council Fund, Massachusetts General Hospital. NR 95 TC 5 Z9 6 U1 4 U2 21 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2014 VL 75 IS 11 BP 1226 EP + DI 10.4088/JCP.13r08767 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU4EK UT WOS:000345561900022 PM 25271988 ER PT J AU Mischoulon, D Price, LH Carpenter, LL Tyrka, AR Papakostas, GI Fava, M AF Mischoulon, David Price, Lawrence H. Carpenter, Linda L. Tyrka, Audrey R. Papakostas, George I. Fava, Maurizio TI Failed Studies Should Not Be Used to Malign Good Treatments Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID MAJOR DEPRESSIVE DISORDER; S-ADENOSYL METHIONINE; CLINICAL-TRIAL; DOUBLE-BLIND; ESCITALOPRAM; PLACEBO C1 [Mischoulon, David; Papakostas, George I.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Mischoulon, David; Papakostas, George I.; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Price, Lawrence H.; Carpenter, Linda L.; Tyrka, Audrey R.] Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA. [Price, Lawrence H.; Carpenter, Linda L.; Tyrka, Audrey R.] Butler Hosp, Lab Clin & Translat Neurosci, Providence, RI 02906 USA. [Price, Lawrence H.; Carpenter, Linda L.; Tyrka, Audrey R.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. EM dmischoulon@partners.org FU NCCIH NIH HHS [R01 AT001742, R01AT001638] NR 5 TC 1 Z9 1 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2014 VL 75 IS 11 BP E1328 EP E1329 DI 10.4088/JCP.14lr09266a PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU4EK UT WOS:000345561900013 PM 25470103 ER PT J AU Jacobs, MA Weinstein, S Hope, TA Aslam, R Yee, J Coakley, F AF Jacobs, Melissa A. Weinstein, Stefanie Hope, Thomas A. Aslam, Rizwan Yee, Judy Coakley, Fergus TI Neuroendocrine Tumors: Beyond the Abdomen SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Review DE lesion descriptors; breast carcinoma; BIRADS classification; scoring system; magnetic resonance imaging; specificity ID MERKEL CELL-CARCINOMA; MEDULLARY-THYROID CARCINOMA; RADIOLOGIC-PATHOLOGICAL CORRELATION; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; LYMPH-NODE BIOPSY; OF-THE-LITERATURE; F-18-FDG PET-CT; PROGNOSTIC-FACTORS; OLFACTORY NEUROBLASTOMA AB Several classification systems for neuroendocrine tumors (NETs) exist, which use variable terminology and criteria for grading and staging. This variability in terminology can cause confusion and difficulty in recognizing which tumors are, in fact, members of this heterogeneous group of malignancies. The largest group of NETs, the gastroenteropancreatic NETs, has been well described and characterized; however, there are less-recognized extra-abdominal NETs that can arise from nearly any organ in the body. In this article, the clinical features and imaging appearances of the extra-abdominal NETs will be reviewed, compared, and contrasted. This diverse group consists of paragangliomas, Merkel cell carcinomas, esthesioneuroblastomas, NETs of the lung, and medullary thyroid carcinomas. Recognition of these tumors as part of the larger group of NETs is important for understanding how best to approach imaging for their diagnosis, staging, and potential treatment. Familiarity with the computed tomographic and magnetic resonance imaging appearances and the role of radionuclide imaging of these heterogeneous groups aids in the correct diagnosis and in treatment planning. C1 [Jacobs, Melissa A.; Coakley, Fergus] Oregon Hlth & Sci Univ, Dept Radiol, Pittsburgh, PA USA. [Weinstein, Stefanie; Hope, Thomas A.; Aslam, Rizwan; Yee, Judy] UCSF Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. [Weinstein, Stefanie; Hope, Thomas A.; Aslam, Rizwan; Yee, Judy] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Weinstein, S (reprint author), UCSF Med Ctr, Dept Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM Stefanie.Weinstein@ucsf.edu NR 111 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2014 VL 38 IS 6 BP 898 EP 914 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AU2EW UT WOS:000345430200015 PM 25162290 ER PT J AU Hershenberg, R Davila, J Leong, SH AF Hershenberg, Rachel Davila, Joanne Leong, Shirley H. TI DEPRESSIVE SYMPTOMS IN WOMEN AND THE PREFERENCE AND EMOTIONAL BENEFITS OF DISCUSSING POSITIVE LIFE EVENTS SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID SELF-VERIFICATION STRIVINGS; THINGS GO RIGHT; INTERPERSONAL BENEFITS; NEGATIVE FEEDBACK; SEX-DIFFERENCES; GOOD-NEWS; RESPONSES; RUMINATION; GIRLS; MOOD AB Discussing positive life events with other people-a process referred to as capitalization-generally enhances positive emotions and well-being. We examined current symptoms of depression as an individual difference factor likely to be associated with the preference and emotional benefits of capitalization in a sample of women with a range of depressive symptoms. Specifically, when given a choice to capitalize on a positive life event or discuss a negative life event, we hypothesized that women with greater symptoms of depression would be more likely to choose to discuss a negative event. Next, regardless of preference, all participants completed a capitalization interaction with a highly supportive confederate. We tested competing hypotheses regarding the emotional consequences of capitalization, as greater depressive symptoms could interfere with the emotional benefit or, alternatively, could be associated with enhanced emotional benefits. As predicted, findings suggested that depressive symptoms were associated with a greater preference to discuss a negative rather than positive event. Notably, when examining change in emotion following capitalization, findings supported the benefit hypothesis. Together, findings suggested that women with greater depressive symptoms were less inclined to capitalize but, when prompted to do so, experienced greater improvements in current levels of positive and negative emotion. Clinical implications and ideas for continued systematic study of depression and this positive emotion regulation strategy are discussed. C1 [Hershenberg, Rachel; Leong, Shirley H.] Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Philadelphia, PA 19104 USA. [Davila, Joanne] SUNY Stony Brook, Stony Brook, NY USA. RP Hershenberg, R (reprint author), Philadelphia VA Med Ctr, VISN MIRECC 4, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM rhersh@mail.med.upenn.edu NR 51 TC 1 Z9 1 U1 2 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD NOV PY 2014 VL 33 IS 9 BP 767 EP 788 PG 22 WC Psychology, Clinical; Psychology, Social SC Psychology GA AU3BC UT WOS:000345486900001 ER PT J AU Ejaz, A Spolverato, G Kim, Y Dodson, R Sicklick, JK Pitt, HA Lillemoe, KD Cameron, JL Pawlik, TM AF Ejaz, Aslam Spolverato, Gaya Kim, Yuhree Dodson, Rebecca Sicklick, Jason K. Pitt, Henry A. Lillemoe, Keith D. Cameron, John L. Pawlik, Timothy M. TI Long-Term Health-Related Quality of Life after Iatrogenic Bile Duct Injury Repair SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; MANAGEMENT; COMPLICATIONS; STRICTURES; OUTCOMES; DISEASE; SF-36 AB BACKGROUND: Data on the effect of bile duct injuries (BDI) on health-related quality of life (HRQOL) are not well defined. We sought to assess long-term HRQOL after BDI repair in a large cohort of patients spanning a 23-year period. STUDY DESIGN: We identified and mailed HRQOL questionnaires to all patients treated for major BDI after laparoscopic cholecystectomy between January 1, 1990 and December 31, 2012 at Johns Hopkins Hospital. RESULTS: We identified 167 patients alive at the time of the study who met the inclusion criteria. Median age at BDI was 42 years (interquartile range 31 to 54 years); the majority of patients were female (n = 131 [78.4%]) and of white race (n = 137 [83.0%]). Most patients had Bismuth level 2 (n = 56 [33.7%]) or Bismuth level 3 (n = 40 [24.1%]) BDI. Surgical repair most commonly involved a Roux-en-Y hepaticojejunostomy (n = 142 [86.1%]). Sixty-two patients (37.1%) responded to the HRQOL questionnaire. Median follow-up was 169 months (interquartile range 125 to 222 months). At the time of BDI, mental health was most affected, with patients commonly reporting a depressed mood (49.2%) or low energy level (40.0%). These symptoms improved significantly after definitive repair (both p < 0.05). Limitations in physical activity and general health remained unchanged before and after surgical repair (both p > 0.05). CONCLUSIONS: Mental health concerns were more commonplace vs physical or general health issues among patients with BDI followed long term. Optimal multidisciplinary management of BDI can help restore HRQOL to preinjury levels. (C) 2014 by the American College of Surgeons C1 [Ejaz, Aslam; Spolverato, Gaya; Kim, Yuhree; Dodson, Rebecca; Cameron, John L.; Pawlik, Timothy M.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. [Ejaz, Aslam] Univ Illinois Hosp, Dept Surg, Chicago, IL USA. [Ejaz, Aslam] Univ Illinois, Hlth Sci Ctr, Chicago, IL 60612 USA. [Sicklick, Jason K.] Univ Calif San Diego, Sch Med, Dept Surg, La Jolla, CA 92093 USA. [Pitt, Henry A.] Temple Univ, Sch Med, Dept Surg, Philadelphia, PA 19122 USA. [Lillemoe, Keith D.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pawlik, TM (reprint author), Johns Hopkins Univ Hosp, Dept Surg, 600 N Wolfe St,Blalock 688, Baltimore, MD 21287 USA. EM tpawlik1@jhmi.edu NR 33 TC 6 Z9 7 U1 1 U2 1 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 NOV PY 2014 VL 219 IS 5 BP 923 EP U384 DI 10.1016/j.jamcollsurg.2014.04.024 PG 20 WC Surgery SC Surgery GA AU2EM UT WOS:000345429100012 PM 25127511 ER PT J AU Phillips, EA Nimeh, T Braga, J Lerner, LB AF Phillips, Elizabeth A. Nimeh, Tony Braga, Julie Lerner, Lori B. TI Does a Surgical Career Affect a Woman's Childbearing and Fertility? A Report on Pregnancy and Fertility Trends among Female Surgeons SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental Surgical Problems CY OCT 06-10, 2013 CL Washington, DC SP Amer Coll Surg ID LIFE-STYLE FACTORS; WOMEN; INFERTILITY; RESIDENCY; STRESS; EXPERIENCE; MANAGEMENT; AGE AB BACKGROUND: Increases in pregnancy complication rates and use of assisted reproductive technology (ART) have been demonstrated in female urologists and orthopaedic surgeons when compared with the general US population. To determine if childbearing differences exist across specialties, we evaluated female surgeons in all fields, particularly with regard to fertility. STUDY DESIGN: An anonymous, 199-item survey was distributed via specialty female surgeon interest groups and word of mouth to general surgery, gynecology, neurosurgery, ophthalmology, orthopaedics, otolaryngology, plastic surgery, podiatry, and urology. The 1,021 responses were analyzed and compared with Centers for Disease Control National Survey for Family Growth and National Institute of Health data to identify differences between populations. RESULTS: Of women surgeons, 32% reported fertility difficulty; 84% of whom underwent infertility workup. Seventy-six percent of these women used ART to attempt pregnancy. In comparison, only 10.9% of women in the general US population report infertility, and 11% seek infertility services. Of all babies born to female surgeons, at least 13% were conceived using ART. Surgeons had 1.4 biological children, less than the national average. Age at first pregnancy was 33 years, compared with a national average of 23. If ART was implemented, surgeon age at first birth increased to 35.4 years. Highest rates of infertility existed in otolaryngology (29%), general surgery (22%), and orthopaedics (18%). CONCLUSIONS: Female surgeons have first pregnancies later in life, fewer children, and report more issues with infertility. Assisted reproductive technology is implemented more often by female surgeons than the general population. Differences in fertility exist between specialties and warrant additional study. (C) 2014 by the American College of Surgeons C1 [Phillips, Elizabeth A.] Boston Med Ctr, Dept Urol, Boston, MA 02118 USA. [Nimeh, Tony; Lerner, Lori B.] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Braga, Julie] Dartmouth Hitchcock, Dept Obstet & Gynecol, Lebanon, NH USA. RP Phillips, EA (reprint author), Boston Med Ctr, Dept Urol, 725 Albany St,Suite 3B, Boston, MA 02118 USA. EM elizabeth.phillips@bmc.org NR 35 TC 5 Z9 5 U1 2 U2 4 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 NOV PY 2014 VL 219 IS 5 BP 944 EP 950 DI 10.1016/j.jamcollsurg.2014.07.936 PG 7 WC Surgery SC Surgery GA AU2EM UT WOS:000345429100014 PM 25260684 ER PT J AU Hyder, JA Roy, N Wakeam, E Hernandez, R Kim, SP Bader, AM Cima, RR Nguyen, LL AF Hyder, Joseph A. Roy, Nathalie Wakeam, Elliot Hernandez, Roland Kim, Simon P. Bader, Angela M. Cima, Robert R. Nguyen, Louis L. TI Performance Measurement in Surgery Through the National Quality Forum SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PERIOPERATIVE SURGICAL HOME; IMPROVEMENT PROGRAM; POSTOPERATIVE COMPLICATIONS; AMERICAN-COLLEGE; INFORMED-CONSENT; HOSPITAL QUALITY; DECISION-MAKING; RISK CALCULATOR; UNITED-STATES; CARE AB BACKGROUND: Performance measurement has become central to surgical practice. We systematically reviewed all endorsed performance measures from the National Quality Forum, the national clearing house for performance measures in health care, to identify measures relevant to surgical practice and describe measure stewardship, measure types, and identify gaps in measurement. STUDY DESIGN: Performance measures current to June 2014 were categorized by denominator statement as either assessing surgical practice in specific or as part of a mixed medical and surgical population. Measures were further classified by surgical specialty, Donabedian measure type, patients, disease and events targeted, reporting eligibility, and measure stewards. RESULTS: Of 637 measures, 123 measures assessed surgical performance in specific and 123 assessed surgical performance in aggregate. Physician societies (51 of 123, 41.5%) were more common than government agencies (32 of 123, 26.0%) among measure stewards for surgical measures, in particular, the Society for Thoracic Surgery (n = 32). Outcomes measures rather than process measures were common among surgical measures (62 of 123, 50.4%) compared with aggregate medical/surgical measures (46 of 123, 37.4%). Among outcomes measures, death alone was the most commonly specified outcome (24 of 62, 38.7%). Only 1 surgical measure addressed patient-centered care and only 1 measure addressed hospital readmission. We found 7 current surgical measures eligible for value-based purchasing. CONCLUSIONS: Surgical society stewards and outcomes measure types, particularly for cardiac surgery, were well represented in the National Quality Forum. Measures addressing patient-centered outcomes and the value of surgical decision-making were not well represented and may be suitable targets for measure innovation. (C) 2014 by the American College of Surgeons C1 [Hyder, Joseph A.] Mayo Clin, Dept Anesthesiol, Div Resp & Crit Care Med, Rochester, MN 55905 USA. [Cima, Robert R.] Mayo Clin, Dept Surg, Rochester, MN 55905 USA. [Cima, Robert R.] Mayo Clin, Ctr Sci Hlth Care Delivery, Rochester, MN 55905 USA. [Hyder, Joseph A.; Wakeam, Elliot; Hernandez, Roland; Bader, Angela M.; Nguyen, Louis L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Hernandez, Roland; Nguyen, Louis L.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Bader, Angela M.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Roy, Nathalie] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Roy, Nathalie; Nguyen, Louis L.] Harvard Univ, Sch Med, Boston, MA USA. [Wakeam, Elliot; Bader, Angela M.] Toronto Gen Hosp, Dept Surg, Toronto, ON, Canada. [Kim, Simon P.] Yale Univ, Sch Med, Dept Urol, New Haven, CT USA. RP Hyder, JA (reprint author), Mayo Clin, Dept Anesthesiol, 200 1st St SW, Rochester, MN 55905 USA. EM hyder.joseph@mayo.edu NR 40 TC 2 Z9 2 U1 2 U2 6 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 NOV PY 2014 VL 219 IS 5 BP 1037 EP 1046 DI 10.1016/j.jamcollsurg.2014.06.018 PG 10 WC Surgery SC Surgery GA AU2EM UT WOS:000345429100025 PM 25260680 ER PT J AU Spira, AP Stone, KL Rebok, GW Punjabi, NM Redline, S Ancoli-Israel, S Yaffe, K AF Spira, Adam P. Stone, Katie L. Rebok, George W. Punjabi, Naresh M. Redline, Susan Ancoli-Israel, Sonia Yaffe, Kristine TI Sleep-Disordered Breathing and Functional Decline in Older Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sleep; apnea; function; IADLs; older women ID MILD COGNITIVE IMPAIRMENT; DAYTIME SLEEPINESS; STROKE; ADULTS; APNEA; HEALTH; DISTURBANCES; EPIDEMIOLOGY; DEMENTIA; OUTCOMES AB ObjectivesTo determine the association between sleep-disordered breathing (SDB) and decline in instrumental activities of daily living (IADLs) and mobility in older women. DesignProspective cohort. SettingMinneapolis and Pittsburgh sites of the Study of Osteoporotic Fractures, participants' homes. ParticipantsWomen with a mean agestandard deviation of 82.33.2 (N=302). MeasurementsParticipants completed a single night of unattended polysomnography and provided data regarding difficulty with IADLs and mobility. They repeated IADL and mobility measures 5.0 +/- 0.7years later. ResultsAfter adjustment for age, obesity, Mini-Mental State Examination score, depressive symptoms, history of hypertension and chronic obstructive pulmonary disease, and number of IADL impairments at baseline, women with an apnea-hypopnea index (AHI) of 15 or greater at baseline had more than twice the odds of an increase in number of IADL difficulties (adjusted odds ratio (aOR)=2.22, 95% confidence interval (CI)=1.09-4.53) and of incident IADL difficulty (aOR=2.43, 95% CI=1.00-5.92), of women with an AHI less than 5. There was no association between AHI and mobility difficulty. Women in the middle and highest tertiles of oxygen desaturation index had more than double the odds as those in the lowest tertile of an increase in number of IADL difficulties (middle tertile aOR=2.64, 95% CI=1.38-5.04, highest tertile aOR=2.17, 95% CI=1.13-4.17) and approximately three times the odds of incident IADL difficulty (middle tertile aOR=2.84, 95% CI=1.27-6.36, highest tertile aOR=3.07, 95% CI=1.31-7.18). Neither sleep fragmentation nor sleep duration was associated with IADL outcomes. ConclusionSDB and associated hypoxemia are risk factors for functional decline in older women. Research is needed to determine whether treatment of SDB prevents functional decline. C1 [Spira, Adam P.; Rebok, George W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Stone, Katie L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Punjabi, Naresh M.] Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Redline, Susan] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Spira, AP (reprint author), 624 N Broadway,Hampton House,Rm 794, Baltimore, MD 21205 USA. EM aspira@jhu.edu FU Mentored Research Scientist Development Award from the NIA [1K01AG033195]; NIH; NIA; NIH [2R01-HL075078]; ResMed; NIH National Heart, Lung, and Blood Institute; California Pacific Medical Center; ResMed Foundation; National Institute of Mental Health; National Institute of Diabetes and Digestive and Kidney Diseases; Department of Defense; Department of Veterans Affairs; Alzheimer's Association; National Institutes of Health (NIH) [AG026720, AG05394, AG05407, AR35582, AR35583, AR35584, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, HL40489, K24AG031155] FX Dr. Adam Spira is supported by Mentored Research Scientist Development Award 1K01AG033195 from the NIA. Dr. Katie Stone reports that NIH funding has been obtained for this work. Dr. George Rebok is supported by grants from the NIA. Dr. Naresh Punjabi is supported by NIH grant 2R01-HL075078 and has received grant support from ResMed for a multicenter clinical trial on the effects of positive airway pressure therapy for sleep apnea in individuals with type 2 diabetes mellitus. Dr. Susan Redline is supported by grants from the NIH National Heart, Lung, and Blood Institute and has received a subcontract from California Pacific Medical Center for work in this study. She also has received a research grant from the ResMed Foundation to support ancillary data collection for a NIH-funded clinical trial. She is a member of the board of directors for the American Academy of Sleep Medicine. Dr. Redline is the first incumbent of an endowed professorship donated to the Harvard Medical School by Dr. Peter Farrell, the founder and Board Chairman of ResMed, through a charitable remainder trust instrument, with annual support equivalent to the endowment payout provided to the Harvard Medical School during Dr. Farrell's lifetime by the ResMed Company through an irrevocable gift agreement. Dr. Ancoli-Israel is supported by grants from NIH and is a consultant for Ferring Pharmaceuticals, Inc., Merck, NeuroVigil, Inc., and Purdue Pharma LP. Dr. Kristine Yaffe has received grants from the NIA, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Department of Defense, Department of Veterans Affairs, Alzheimer's Association, and an anonymous donor. She has served on data safety monitoring boards for Pfizer and Medivation and has received honoraria from Novartis as an advisory board member. She is a member of the boards of the Beeson Program, the National Institute of Mental Health, and the National Heart, Lung and Blood Institute.; Supported by National Institutes of Health (NIH) Grants AG026720, AG05394, AG05407, AR35582, AR35583, AR35584, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, 2 R01 AG027574-22A1, HL40489, K24AG031155. The content is solely the responsibility of the authors and does not necessarily represent the official views of National Institute on Aging (NIA) or NIH. NR 23 TC 2 Z9 2 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2040 EP 2046 DI 10.1111/jgs.13108 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700002 PM 25376169 ER PT J AU Sowa, GA Perera, S Bechara, B Agarwal, V Boardman, J Huang, W Camacho-Soto, A Vo, N Kang, J Weiner, D AF Sowa, Gwendolyn A. Perera, Subashan Bechara, Bernard Agarwal, Vikas Boardman, John Huang, Wan Camacho-Soto, Alejandra Vo, Nam Kang, James Weiner, Debra TI Associations Between Serum Biomarkers and Pain and Pain-Related Function in Older Adults with Low Back Pain: A Pilot Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE low back pain; biomarkers; imaging ID HUMAN INTERVERTEBRAL DISC; KNEE OSTEOARTHRITIS; PHYSICAL FUNCTION; LUMBAR DISC; MATRIX METALLOPROTEINASES; ASYMPTOMATIC VOLUNTEERS; RHEUMATOID-ARTHRITIS; INFLAMMATORY MARKERS; MOLECULAR MARKERS; URINE BIOMARKERS AB ObjectivesTo examine the relationship between serum biomarkers and self-reported pain intensity and pain-related function, in addition to the contribution of magnetic resonance imaging (MRI) findings of lumbar spine degenerative changes, in older adults with chronic low back pain. DesignSingle-center cross-sectional cohort study. SettingAcademic medical center. ParticipantsIndividuals aged 60 and older with axial low back pain without radiculopathy or previously diagnosed osteoarthritis of the knee or hip or pain outside the low back that is more severe than the back pain (n=43). MeasurementsTo examine pain-related impairment, pain was measured on a pain thermometer and the McGill Pain Questionnaire Short Form was administered. To examine pain-related function or activity limitation, the Roland Morris Disability Questionnaire, Short Physical Performance Battery (SPPB), and repetitive trunk rotation were used. Single plasma samples were obtained before and after physical performance tests and analyzed for inflammatory markers (E-selectin and regulated on activation, normal T cell expressed and secreted (RANTES)), inhibitors of catabolic enzymes (tissue inhibitor of metalloproteinases-1 (TIMP-1)), markers of matrix turnover (C- telopeptide of type II collagen (CTX-II) and aggrecan chondroitin sulfate 846 (CS846)), and stress biomarkers (neuropeptide Y (NPY)). Conventional nongadolinium lumbar MRI was performed and analyzed quantitatively and clinically. ResultsComposite MRI measurements did not show significant correlation with pain or pain-related function. Basal levels and changes in serum biomarkers in response to activity, particularly NPY and RANTES, demonstrated associations with pain and pain-related function in addition to the explanatory power of MRI-based results. ConclusionSerum biomarkers may be a metric for assessment of active disease in older adults, in whom imaging changes are ubiquitous. In addition, changing levels of biomarkers in response to activity suggests that they may be useful as metrics to measure treatment responses in future studies and may reflect potential targets for use in designing personalized treatment for older adults with low back pain. C1 [Sowa, Gwendolyn A.; Huang, Wan; Camacho-Soto, Alejandra] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Sowa, Gwendolyn A.; Bechara, Bernard; Huang, Wan; Camacho-Soto, Alejandra; Vo, Nam; Kang, James] Univ Pittsburgh, Dept Orthopaed, Ferguson Lab Orthopaed Res, Pittsburgh, PA 15213 USA. [Perera, Subashan; Weiner, Debra] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Agarwal, Vikas; Boardman, John] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Weiner, Debra] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. [Weiner, Debra] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15213 USA. [Weiner, Debra] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15213 USA. [Weiner, Debra] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Sowa, GA (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 201, Pittsburgh, PA 15213 USA. EM sowaga@upmc.edu FU Dennis W. Jahnigen Career Development Scholars Award; American Geriatrics Society; Pittsburgh Claude D. Pepper Older Americans Independence Center [AG024827] FX Funded by the Dennis W. Jahnigen Career Development Scholars Award, the American Geriatrics Society, and the Pittsburgh Claude D. Pepper Older Americans Independence Center (AG024827). NR 50 TC 10 Z9 11 U1 4 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2047 EP 2055 DI 10.1111/jgs.13102 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700003 PM 25367206 ER PT J AU Brown, RT Pierluissi, E Guzman, D Kessell, ER Goldman, LE Sarkar, U Schneidermann, M Critchfield, JM Kushel, MB AF Brown, Rebecca T. Pierluissi, Edgar Guzman, David Kessell, Eric R. Goldman, L. Elizabeth Sarkar, Urmimala Schneidermann, Michelle Critchfield, Jeffrey M. Kushel, Margot B. TI Functional Disability in Late-Middle-Aged and Older Adults Admitted to a Safety-Net Hospital SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE disability; physical function; middle-aged; aged ID UNITED-STATES; INSTRUMENTAL ACTIVITIES; SOCIOECONOMIC-STATUS; HEALTH; VALIDITY; OUTCOMES; DECLINE; POPULATION; INDEX; RELIABILITY AB ObjectivesTo determine the prevalence of preadmission functional disability in late-middle-aged and older safety-net inpatients and to identify characteristics associated with functional disability by age. DesignCross-sectional analysis. SettingSafety-net hospital in San Francisco, California. ParticipantsEnglish-, Spanish-, and Chinese-speaking community-dwelling individuals aged 55 and older admitted to a safety-net hospital with anticipated return to the community (N=699). MeasurementsAt hospital admission, participants reported their need for help performing five activities of daily living (ADLs) and seven instrumental activities of daily living (IADLs) 2weeks before admission. ADL disability was defined as needing help performing one or more ADLs and IADL disability as needing help performing two or more IADLs. Participant characteristics were assessed, including sociodemographic characteristics, health status, health-related behaviors, and health-seeking behaviors. ResultsOverall, 28.3% of participants reported that they had an ADL disability 2weeks before admission, and 40.4% reported an IADL disability. The prevalence of preadmission ADL disability was 28.9% of those aged 55 to 59, 20.7% of those aged 60 to 69, and 41.2% of those aged 70 and older (P<.001). The prevalence of IADL disability had a similar distribution. The characteristics associated with functional disability differed according to age; in participants aged 55 to 59, African Americans had a higher odds of ADL and IADL disability, whereas in participants aged 60 to 69 and aged 70 and older, inadequate health literacy was associated with functional disability. ConclusionPreadmission functional disability is common in individuals aged 55 and older admitted to a safety-net hospital. Late-middle-aged individuals admitted to safety-net hospitals may benefit from models of acute care currently used for older adults that prevent adverse outcomes associated with functional disability. C1 [Brown, Rebecca T.; Pierluissi, Edgar] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, Rebecca T.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Pierluissi, Edgar; Kessell, Eric R.; Schneidermann, Michelle; Critchfield, Jeffrey M.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Guzman, David; Goldman, L. Elizabeth; Sarkar, Urmimala; Kushel, Margot B.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. San Francisco Gen Hosp & Trauma Ctr, San Francisco, CA USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, 181G,4150 Clement St, San Francisco, CA 94121 USA. EM rebecca.brown@ucsf.edu FU Gordon and Betty Moore Foundation; National Center for Advancing Translational Sciences, National Institutes of Health (NIH) through the University of California at San Francisco Clinical and Translational Sciences Institute [KL2TR000143]; National Institute on Aging (NIA), NIH [K23 AG045290]; National NIA, NIH [T32 AG000212, P30AG044281] FX This work was funded in part by the Gordon and Betty Moore Foundation (Mr. Guzman and Drs. Kessell, Goldman, Sarkar, Schneidermann, Critchfield, and Kushel); Grant KL2TR000143 from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) through the University of California at San Francisco Clinical and Translational Sciences Institute (Dr. Brown); Grant K23 AG045290 from the National Institute on Aging (NIA), NIH; and Grants T32 AG000212 (Dr. Brown) and P30AG044281 (Dr. Brown) from the National NIA, NIH. These funding sources had no role in the preparation, review, or approval of the manuscript. The opinions expressed in this manuscript may not represent those of the Department of Veterans Affairs. NR 50 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2056 EP 2063 DI 10.1111/jgs.13103 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700004 PM 25367281 ER PT J AU Tschirhart, EC Du, QL Kelley, AS AF Tschirhart, Evan C. Du, Qingling Kelley, Amy S. TI Factors Influencing the Use of Intensive Procedures at the End of Life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE end-of-life decisions; terminal care; intensive care; Medicare ID ADVANCE DIRECTIVES; MEDICARE EXPENDITURES; SUSTAINING TREATMENTS; REGIONAL-VARIATIONS; CANCER-PATIENTS; LAST YEAR; CARE; ILLNESS; DETERMINANTS; PREFERENCES AB ObjectivesTo examine individual and regional factors associated with the use of intensive medical procedures in the last 6months of life. DesignRetrospective cohort study. SettingThe Health and Retirement Study (HRS), a longitudinal nationally representative cohort of older adults. ParticipantsHRS decedents aged 66 and older (N=3,069). MeasurementsMultivariable logistic regression was used to evaluate associations between individual and regional factors and receipt of five intensive procedures: intubation and mechanical ventilation, tracheostomy, gastrostomy tube insertion, enteral and parenteral nutrition, or cardiopulmonary resuscitation in the last 6months of life. ResultsApproximately 18% of subjects (n=546) underwent at least one intensive procedure in the last 6months of life. Characteristics significantly associated with lower odds of an intensive procedure included aged 85-94 (vs 65-74, adjusted odds ratio (AOR)=0.67, 95% confidence interval (CI)=0.51-0.90), Alzheimer's disease (AOR=0.71, 95% CI=0.54-0.94), cancer (AOR=0.60, 95% CI=0.43-0.85), nursing home residence (AOR=0.70, 95% CI=0.50-0.97), and having an advance directive (AOR=0.71, 95% CI=0.57-0.89). In contrast, living in a region with higher hospital care intensity (AOR=2.16, 95% CI=1.48-3.13) and black race (AOR=2.02, 95% CI=1.52-2.69) each doubled one's odds of undergoing an intensive procedure. ConclusionIndividual characteristics and regional practice patterns are important determinants of intensive procedure use in the last 6months of life. The effect of nonclinical factors highlights the need to better align treatments with individual preferences. C1 [Tschirhart, Evan C.; Du, Qingling; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Tschirhart, EC (reprint author), 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM evan.tschirhart@mssm.edu FU Medical Student Training in Aging Research Program, American Federation for Aging Research and National Institute on Aging [1K23AG040774-01A1] FX This work was supported by the Medical Student Training in Aging Research Program, American Federation for Aging Research and National Institute on Aging (1K23AG040774-01A1). NR 37 TC 8 Z9 9 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2088 EP 2094 DI 10.1111/jgs.13104 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700008 PM 25376084 ER PT J AU Ramaswamy, R Williams, A Clark, EM Kelley, AS AF Ramaswamy, Ravishankar Williams, Alicia Clark, Elizabeth M. Kelley, Amy S. TI Communication Skills Curriculum for Foreign Medical Graduates in an Internal Medicine Residency Program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE communication skills; foreign medical graduates; internal medicine residency ID FELLOWS AB Effective communication is an important aspect of caring for the elderly, who are more likely to have multimorbidity, limited health literacy, and psychosocial barriers to care. About half of Internal Medicine (IM) trainees in the United States are foreign medical graduates, and may not have been exposed to prior communication skills education. This novel communication skills curriculum for IM interns aimed to increase trainees' confidence and use of specific communication tools with older adults, particularly in delivering bad news and conducting family meetings. The workshop consisted of two interactive sessions in a small group with two learners and one or two facilitators, during the 4-week geriatrics block in IM internship training year. Twenty-three IM interns at an urban Veterans Affairs Medical Center were surveyed at the beginning and at the end of the 4-week block and 3months after completion of the workshop about their knowledge, confidence, and skill in communication and asked about challenges to effective communication with older adults. The primary outcome measure was change in self-reported confidence and behavior in communication at 4weeks. On a 4-point Likert scale, there was average improvement of 0.70 in self-reported confidence in communication, which was sustained 3months after completion of the workshop. Participants reported several patient, physician, and system barriers to effective communication. Communication skills education in a small-group setting and the opportunity for repeated practice and self-reflection resulted in a sustained increase in overall confidence in IM interns in communication with older adults and may help overcome certain patient- and physician-specific communication barriers. C1 [Ramaswamy, Ravishankar; Kelley, Amy S.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Williams, Alicia] Columbia Univ, Bassett Med Ctr, Cooperstown, NY USA. [Clark, Elizabeth M.] Montefiore Med Ctr, Dept Med, Div Geriatr, Bronx, NY 10467 USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ Ctr, Bronx, NY USA. [Kelley, Amy S.] James J Peters Vet Affairs Med Ctr, Ctr Clin, Bronx, NY USA. RP Ramaswamy, R (reprint author), Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, One Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM ravishankar.ramaswamy@mssm.edu FU Hartford Centers of Excellence career development award; American Federation for Aging Research; National Institute on Aging [1K23AG0407 74-01A1] FX Dr. Ramaswamy is supported by the Hartford Centers of Excellence career development award. Dr. Kelley is supported by the American Federation for Aging Research and National Institute on Aging (1K23AG0407 74-01A1). NR 19 TC 2 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2153 EP 2158 DI 10.1111/jgs.13094 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700018 PM 25354834 ER PT J AU Brown, RT Ahalt, C Steinman, MA Kruger, K Williams, BA AF Brown, Rebecca T. Ahalt, Cyrus Steinman, Michael A. Kruger, Kelly Williams, Brie A. TI Police on the Front Line of Community Geriatric Health Care: Challenges and Opportunities SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatrics; police; public health policy ID NURSING-HOME PLACEMENT; OLDER-ADULTS; CRIME VICTIMIZATION; RESIDENTS; KNOWLEDGE; POPULATION; VALIDATION; ATTITUDES; VICTIMS; SERVICE AB As the population ages, police increasingly serve as first responders to incidents involving older adults in which aging-related health plays a critical role. The goals of this study were to assess police officers' knowledge of aging-related health, to identify challenges police experience in their encounters with older adults, and to describe their recommendations for how to address those challenges. This was a mixed-methods study of 141 San Francisco police officers recruited from mandatory police trainings between 2011 and 2013. Descriptive statistics were used to analyze 141 self-administered questionnaires, and principles of grounded theory were used to analyze open-ended questionnaire responses and 11 additional qualitative interviews. Eighty-nine percent of officers reported interacting with older adults at least monthly. Although 84% of police reported prior training in working with older adults, only 32% rated themselves as knowledgeable about aging-related health. Participants described themselves as first responders to medical and social emergencies involving older adults and identified several challenges, including identifying and responding to aging-related conditions and ensuring appropriate medical and social service handoffs. To address these challenges, officers recommended developing trainings focused on recognizing and responding to aging-related conditions and improving police knowledge of community resources for older adults. They also called for enhanced communication and collaboration between police and clinicians. These findings suggest that, because they assume a front-line role in responding to older adults with complex medical and social needs, many police may benefit from additional knowledge about aging-related health and community resources. Collaboration between police and healthcare providers presents an important opportunity to develop geriatrics training and interprofessional systems of care to support police work with a rapidly aging population. C1 [Brown, Rebecca T.; Ahalt, Cyrus; Steinman, Michael A.; Williams, Brie A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Brown, Rebecca T.; Steinman, Michael A.; Williams, Brie A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Kruger, Kelly] San Francisco Police Dept, San Francisco, CA USA. RP Brown, RT (reprint author), San Francisco VA Med Ctr, 181G,4150 Clement St, San Francisco, CA 94121 USA. EM rebecca.brown@ucsf.edu FU National Institute on Aging (NIA), National Institutes of Health (NIH) [T32 AG000212]; National Center for Advancing Translational Sciences, NIH, through the University of California at San Francisco (UCSF) Clinical and Translational Sciences Institute [KL2TR000143]; NIA, NIH [P30AG044281, 1K23 AG030999]; John A. Hartford Foundation; Jacob & Valeria Langeloth Foundation; UCSF Program for the Aging Century; UCSF University Community Partnership Grant from NIA, NIH [K23 AG033102]; American Federation for Aging Research FX This work was supported by Grant T32 AG000212 from the National Institute on Aging (NIA), National Institutes of Health (NIH) (Dr. Brown), Grant KL2TR000143 from the National Center for Advancing Translational Sciences, NIH, through the University of California at San Francisco (UCSF) Clinical and Translational Sciences Institute (Dr. Brown), Grant P30AG044281 from the NIA, NIH (Drs. Brown, Steinman, and Williams), the John A. Hartford Foundation (Drs. Brown and Williams), the Jacob & Valeria Langeloth Foundation (Dr. Williams and Mr. Ahalt), the UCSF Program for the Aging Century (Drs. Brown and Williams and Mr. Ahalt), the UCSF University Community Partnership Grant, Grant K23 AG033102 from NIA, NIH (Dr. Williams), and Grant 1K23 AG030999 from NIA, NIH and the American Federation for Aging Research (Dr. Steinman). The opinions expressed in this manuscript may not represent those of the Department of Veterans Affairs. NR 31 TC 0 Z9 0 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2014 VL 62 IS 11 BP 2191 EP 2198 DI 10.1111/jgs.13093 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AU3GO UT WOS:000345500700024 PM 25378267 ER PT J AU Marina, A von Frankenberg, AD Suvag, S Callahan, HS Kratz, M Richards, TL Utzschneider, KM AF Marina, Anna von Frankenberg, Anize Delfino Suvag, Seda Callahan, Holly S. Kratz, Mario Richards, Todd L. Utzschneider, Kristina M. TI Effects of Dietary Fat and Saturated Fat Content on Liver Fat and Markers of Oxidative Stress in Overweight/Obese Men and Women under Weight-Stable Conditions SO NUTRIENTS LA English DT Article DE non-alcoholic fatty liver; dietary fat; saturated fat; oxidative stress ID NONALCOHOLIC STEATOHEPATITIS; INSULIN SENSITIVITY; EXERCISE INTERVENTION; LIPID-PEROXIDATION; DISEASE; RESISTANCE; SEVERITY; TRIAL AB Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNF alpha, IFN-gamma) and oxidative stress (urinary F2-alpha isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change -2.13% (-3.74%, -0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-a isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress. C1 [Marina, Anna; von Frankenberg, Anize Delfino; Suvag, Seda; Kratz, Mario; Utzschneider, Kristina M.] Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98195 USA. [Callahan, Holly S.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Kratz, Mario] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kratz, Mario] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Richards, Todd L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Endocrinol, Seattle, WA 98108 USA. RP Utzschneider, KM (reprint author), Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, 1959 NE Pacific St, Seattle, WA 98195 USA. EM annam45@hotmail.com; anize.frankenberg@gmail.com; sedasuv@yahoo.com; hcal@uw.edu; mkratz@fhcrc.org; toddr@u.washington.edu; kutzschn@u.washington.edu FU Department of Veteran Affairs; Diabetes Research Center [P30DK017047]; Institute for Translational Health Sciences [UL1TR000423]; Nutrition Obesity Research Center [P30 DK035816]; Diagnostic Imaging Sciences Center at the University of Washington; Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) FX We are grateful to the study participants for their contribution and time. This study was supported by funding and resources from the Department of Veteran Affairs, the Diabetes Research Center (P30DK017047), the Institute for Translational Health Sciences (UL1TR000423), the Nutrition Obesity Research Center (P30 DK035816), the Diagnostic Imaging Sciences Center at the University of Washington, and the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES). NR 30 TC 8 Z9 8 U1 2 U2 9 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD NOV PY 2014 VL 6 IS 11 BP 4678 EP 4690 DI 10.3390/nu6114678 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AU3RM UT WOS:000345531300004 PM 25353663 ER PT J AU Morasco, BJ O'Hearn, D Turk, DC Dobscha, SK AF Morasco, Benjamin J. O'Hearn, Daniel Turk, Dennis C. Dobscha, Steven K. TI Associations Between Prescription Opioid Use and Sleep Impairment among Veterans with Chronic Pain SO PAIN MEDICINE LA English DT Article DE Opioids; Sleep; Chronic Pain; Pittsburgh Sleep Quality Index ID CHRONIC NONCANCER PAIN; QUALITY-OF-LIFE; HEPATITIS-C; BACK-PAIN; THERAPY; DISORDERS; INSOMNIA; APNEA; COMORBIDITY; MEDICATIONS AB ObjectiveChronic pain is associated with impairments in sleep; however, the relationship between prescription opioid status and sleep is unclear. The primary aim of this study was to examine differences in self-reported sleep quality between groups of patients who varied based on chronic pain and prescription opioid status. DesignThis is a cross-sectional study with retrospective review of patient medical records. SettingThe study was performed in a single VA medical center located in the Pacific Northwest. SubjectsParticipants with chronic pain and a current prescription for opioid medications (N=72), chronic pain and no opioid prescription (N=104), or who did not report current chronic pain or opioid prescription (N=91) were included. MethodsAll participants completed self-report questionnaires assessing demographic characteristics, sleep parameters, pain-related variables, and psychiatric symptoms. Data on prescription opioid use were extracted from patients' medical records. ResultsIn unadjusted analyses, patients with chronic pain who were prescribed opioids were more likely to have sleep apnea diagnoses in their medical record and reported more impairment on sleep global score and across four sleep parameter subscales (subjective sleep quality, sleep latency, sleep disturbance, and use of sleeping medications). In linear regression analyses controlling for demographic and clinical covariates, prescription opioid status was associated with sleep latency, and opioid dose was significantly associated with sleep latency and sleep global score. ConclusionsPrescription opioid status and dose were associated with impairment in self-reported sleep. For patients with chronic pain, consideration should be given to use of nonpharmacological interventions to improve sleep. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Ctr Improve Vet Involvement Care, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [O'Hearn, Daniel] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse [DA023467, DA034083]; U.S. Food & Drug Administration [FD004508] FX This study was supported in part by awards from the National Institute on Drug Abuse (DA023467, DA034083) and from the U.S. Food & Drug Administration (FD004508). This material is also the result of work supported with resources and the use of facilities at the Portland VA Medical Center. NR 54 TC 3 Z9 3 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD NOV PY 2014 VL 15 IS 11 BP 1902 EP 1910 DI 10.1111/pme.12472 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AU4EI UT WOS:000345561700010 PM 24930962 ER PT J AU Manchikanti, L Benyamin, RM Candido, KD Hirsch, JA AF Manchikanti, Laxmaiah Benyamin, Ramsin M. Candido, Kenneth D. Hirsch, Joshua A. TI Cohen et al. Reach Inappropriate Conclusions on the Effect of Sedation on the Accuracy and Treatment Outcomes for Diagnostic Injections SO PAIN MEDICINE LA English DT Letter ID 2-YEAR FOLLOW-UP; LOW-BACK-PAIN; RADIOFREQUENCY DENERVATION; EPIDURAL INJECTIONS; COST-EFFECTIVENESS; CONTROLLED-TRIAL; DOUBLE-BLIND C1 [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Manchikanti, Laxmaiah] Pain Management Ctr, Paducah, KY USA. [Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin M.] Univ Illinois, Coll Med, Dept Surg, Urbana, IL 61801 USA. [Candido, Kenneth D.] Advocate Illinois Mason Med Ctr, Dept Anesthesiol, Chicago, IL USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Manchikanti, L (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. NR 18 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD NOV PY 2014 VL 15 IS 11 BP 1978 EP 1980 DI 10.1111/pme.12561 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AU4EI UT WOS:000345561700019 PM 25288045 ER PT J AU Hamza, TH Hill-Burns, EM Scott, WK Vance, JM Factor, SA Zabetian, CP Payami, H AF Hamza, Taye H. Hill-Burns, Erin M. Scott, William K. Vance, Jeffrey M. Factor, Stewart A. Zabetian, Cyrus P. Payami, Haydeh TI Glutamate Receptor Gene GRIN2A, Coffee, and Parkinson Disease SO PLOS GENETICS LA English DT Editorial Material ID CAFFEINE; RISK; SMOKING C1 [Hamza, Taye H.; Hill-Burns, Erin M.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12205 USA. [Hamza, Taye H.] New England Res Inst Inc, Watertown, MA USA. [Scott, William K.; Vance, Jeffrey M.] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA. [Scott, William K.; Vance, Jeffrey M.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Payami, Haydeh] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA. RP Hamza, TH (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY 12205 USA. EM haydeh.payami@health.ny.gov OI Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [P50 NS071674, R01 NS036960, R01 NS067469] NR 11 TC 3 Z9 4 U1 1 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2014 VL 10 IS 11 AR e1004774 DI 10.1371/journal.pgen.1004774 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA AU2NL UT WOS:000345455200025 PM 25411979 ER PT J AU Coutinho, ML Matsunaga, J Wang, LC Moctezuma, AD Lewis, MS Babbitt, JT Aleixo, JAG Haake, DA AF Coutinho, Mariana L. Matsunaga, James Wang, Long-Chieh de la Pena Moctezuma, Alejandro Lewis, Michael S. Babbitt, Jane T. Aleixo, Jose Antonio G. Haake, David A. TI Kinetics of Leptospira interrogans Infection in Hamsters after Intradermal and Subcutaneous Challenge SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID CELL MONOLAYERS; ICTEROHAEMORRHAGIAE; MODEL; DISSEMINATION; VIRULENCE; ETIOLOGY; DISEASE; CATTLE; WATER; HOST AB Background: Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection. Methodology/Principal Findings: Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7. Conclusions/Significance: The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2610 6 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis. C1 [Coutinho, Mariana L.; Matsunaga, James; Wang, Long-Chieh; Lewis, Michael S.; Babbitt, Jane T.; Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Coutinho, Mariana L.; Aleixo, Jose Antonio G.] Univ Fed Pelotas, Ctr Desenvolvimento Tecnol, Pelotas, Brazil. [Coutinho, Mariana L.] Univ Fed Rio Grande do Sul, Fac Vet, Porto Alegre, RS, Brazil. [Matsunaga, James; Babbitt, Jane T.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [de la Pena Moctezuma, Alejandro] Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecnia, CEIEPAA, Tequisquiapan, Queretaro, Mexico. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90024 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Immunol, Los Angeles, CA USA. [Haake, David A.] Univ Calif Los Angeles, Dept Mol Genet, Los Angeles, CA USA. RP Coutinho, ML (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu FU VA Medical Research Funds (United States Office of Veterans Affairs) [1I01BX002003, 5I01BX000119]; National Institute of Allergy and Infectious Diseases [R01 AI034431]; Brazilian Conselho Nacional de Pesquisa [201549/2008-5]; Direccion General de Asuntos del Personal Academico, UNAM FX This study was supported by VA Medical Research Funds (United States Office of Veterans Affairs Project Numbers 1I01BX002003 to DAH and 5I01BX000119 to JM; http://www.research.va.gov/), the National Institute of Allergy and Infectious Diseases (Grant #R01 AI034431 to DAH; http://www.niaid.nih.gov/), the Brazilian Conselho Nacional de Pesquisa (process number 201549/2008-5), the Direccion General de Asuntos del Personal Academico, UNAM (to AdlPM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 9 Z9 9 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD NOV PY 2014 VL 8 IS 11 AR e3307 DI 10.1371/journal.pntd.0003307 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AU3LF UT WOS:000345514000036 PM 25411782 ER PT J AU Sugimoto, JD Koepke, AA Kenah, EE Halloran, ME Chowdhury, F Khan, AI LaRocque, RC Yang, Y Ryan, ET Qadri, F Calderwood, SB Harris, JB Longini, IM AF Sugimoto, Jonathan D. Koepke, Amanda A. Kenah, Eben E. Halloran, M. Elizabeth Chowdhury, Fahima Khan, Ashraful I. LaRocque, Regina C. Yang, Yang Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. Harris, Jason B. Longini, Ira M., Jr. TI Household Transmission of Vibrio cholerae in Bangladesh SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID ABO BLOOD-GROUPS; INFECTIOUS-DISEASE; EPIDEMIC CHOLERA; EL TOR; CONTACTS; IMMUNITY; SUSCEPTIBILITY; PHILIPPINES; VACCINES; DIARRHEA AB Background: Vibrio cholerae infections cluster in households. This study's objective was to quantify the relative contribution of direct, within-household exposure (for example, via contamination of household food, water, or surfaces) to endemic cholera transmission. Quantifying the relative contribution of direct exposure is important for planning effective prevention and control measures. Methodology/Principal Findings: Symptom histories and multiple blood and fecal specimens were prospectively collected from household members of hospital-ascertained cholera cases in Bangladesh from 2001-2006. We estimated the probabilities of cholera transmission through 1) direct exposure within the household and 2) contact with community-based sources of infection. The natural history of cholera infection and covariate effects on transmission were considered. Significant direct transmission (p-value<0.0001) occurred among 1414 members of 364 households. Fecal shedding of O1 El Tor Ogawa was associated with a 4.9% (95% confidence interval: 0.9%-22.8%) risk of infection among household contacts through direct exposure during an 11-day infectious period (mean length). The estimated 11-day risk of O1 El Tor Ogawa infection through exposure to community-based sources was 2.5% (0.8%-8.0%). The corresponding estimated risks for O1 El Tor Inaba and O139 infection were 3.7% (0.7%-16.6%) and 8.2% (2.1%-27.1%) through direct exposure, and 3.4% (1.7%-6.7%) and 2.0% (0.5%-7.3%) through community-based exposure. Children under 5 years-old were at elevated risk of infection. Limitations of the study may have led to an underestimation of the true risk of cholera infection. For instance, available covariate data may have incompletely characterized levels of pre-existing immunity to cholera infection. Transmission via direct exposure occurring outside of the household was not considered. Conclusions: Direct exposure contributes substantially to endemic transmission of symptomatic cholera in an urban setting. We provide the first estimate of the transmissibility of endemic cholera within prospectively-followed members of households. The role of direct transmission must be considered when planning cholera control activities. C1 [Sugimoto, Jonathan D.; Koepke, Amanda A.; Kenah, Eben E.; Halloran, M. Elizabeth; Yang, Yang; Longini, Ira M., Jr.] Univ Florida, Dept Biostat, Ctr Stat & Quantitat Infect Dis, Gainesville, FL 32611 USA. [Sugimoto, Jonathan D.] Univ Florida, Dept Epidemiol, Gainesville, FL USA. [Sugimoto, Jonathan D.; Kenah, Eben E.; Yang, Yang; Longini, Ira M., Jr.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. [Sugimoto, Jonathan D.; Koepke, Amanda A.; Halloran, M. Elizabeth] Fred Hutchinson Canc Res Ctr, Ctr Stat & Quantitat Infect Dis, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Koepke, Amanda A.] Univ Washington, Dept Stat, Seattle, WA 98195 USA. [Kenah, Eben E.; Yang, Yang; Longini, Ira M., Jr.] Univ Florida, Dept Biostat, Gainesville, FL USA. [Halloran, M. Elizabeth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chowdhury, Fahima; Khan, Ashraful I.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, CVS, Mohakhali Dhaka, Bangladesh. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [LaRocque, Regina C.; Ryan, Edward T.; Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Sugimoto, JD (reprint author), Univ Florida, Dept Biostat, Ctr Stat & Quantitat Infect Dis, Gainesville, FL 32611 USA. EM ilongini@ufl.edu FU International Centre for Diarrhoeal Disease Research, Bangladesh; Swedish International Development Cooperation Agency [HN01AV]; Physician-Scientist Early Career Award from the Howard Hughes Medical Institute; National Institutes of Health [U01-AI058935, U01-AI077883, R01-AI106878, R01-AI099243]; Fogarty/Ellison Fellowship in Global Health [D43-TW005572, F32-GM085945, R03-A1063079]; Models of Infectious Disease Agent Study [U01-GM070749]; Ecology of Cholera grant - National Institutes of Health [R01-A139129] FX The following funding sources supported the cholera field, microbiologic and immune evaluations, including the household analysis: the International Centre for Diarrhoeal Disease Research, Bangladesh;; the Swedish International Development Cooperation Agency (www.sida.se) (HN01AV) [FQ]; a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute (https://www.hhmi.org) [RCL]; and the following grants from the National Institutes of Health (www.nih.gov): U01-AI058935 [SBC, ETR, FQ, RCL, JBH, FC, AIK]; U01-AI077883 [ETR, FQ]; R01-AI106878 [ETR, FQ]; R01-AI099243 [JBH]; a Fogarty/Ellison Fellowship in Global Health (D43-TW005572) [FQ]; F32-GM085945 [FQ]; R03-A1063079 [FQ]. The following funding sources supported the household analysis: the Models of Infectious Disease Agent Study (U01-GM070749) [JDS, MEH, IML] and the Ecology of Cholera (R01-A139129) grant [ALK, MEH, IML] funded by the National Institutes of Health (www.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The corresponding author had full access to the data. All authors were responsible for the decision to submit for publication. NR 36 TC 4 Z9 4 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD NOV PY 2014 VL 8 IS 11 AR e3314 DI 10.1371/journal.pntd.0003314 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AU3LF UT WOS:000345514000041 PM 25411971 ER PT J AU Stineman, MG Streim, JE Pan, Q Kurichi, JE Rose, SMSF Xie, DW AF Stineman, Margaret G. Streim, Joel E. Pan, Qiang Kurichi, Jibby E. Rose, Sophia Miryam Schuessler-Fiorenza Xie, Dawei TI Activity Limitation Stages Empirically Derived for Activities of Daily Living (ADL) and Instrumental ADL in the US Adult Community-Dwelling Medicare Population SO PM&R LA English DT Article ID HOME ACCESSIBILITY FEATURES; HEALTH-CARE UTILIZATION; SELF-RATED HEALTH; FUNCTIONAL DISABILITY; ELDERLY-PEOPLE; INDEPENDENCE; IMPACT; REHABILITATION; IMPROVEMENT; MORTALITY AB Background: Stages quantify severity like conventional measures but further specify the activities that people are still able to perform without difficulty. Objective: To develop Activity Limitation Stages for defining and monitoring groups of adult community-dwelling Medicare beneficiaries. Design: Cross-sectional. Setting: Community. Participants: There were 14,670 respondents to the 2006 Medicare Current Beneficiary Survey. Methods: Stages were empirically derived for the Activities of Daily Living (ADLs) and the Instrumental Activities of Daily Living (IADLs) by profiling the distribution of performance difficulties as reported by beneficiaries or their proxies. Stage prevalence estimates were determined, and associations with demographic and health variables were examined for all community-dwelling Medicare beneficiaries. Main Outcome Measurements: ADL and IADL stage prevalence. Results: Stages (0-IV) define 5 groups across the separate ADL and IADL domains according to hierarchically organized profiles of retained abilities and difficulties. For example, at ADL-I, people are guaranteed to be able to eat, toilet, dress, and bathe/shower without difficulty, whereas they experience limitations getting in and out of bed or chairs and/or difficulties walking. In 2006, an estimated 6.0, 2.9, 2.2, and 0.5 million beneficiaries had mild (ADL-I), moderate (ADL-II), severe (ADL-III), and complete (ADL-IV) difficulties, respectively, with estimates for IADL stages even higher. ADL and IADL stages showed expected associations with age and health-related concepts, supporting construct validity. Stages showed the strongest associations with conditions that impair cognition. Conclusions: Stages as aggregate measures reveal the ADLs and IADLs that people are still able to do without difficulty, along with those activities in which they report having difficulty, consequently emphasizing how groups of people with difficulties can still participate in their own lives. Over the coming decades, stages applied to populations served by vertically integrated clinical practices could facilitate large-scale planning, with the goal of maximizing personal autonomy among groups of community-dwelling people with disabilities. C1 [Stineman, Margaret G.; Pan, Qiang; Xie, Dawei] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Stineman, Margaret G.] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Streim, Joel E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Streim, Joel E.; Rose, Sophia Miryam Schuessler-Fiorenza] Philadelphia Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Kurichi, Jibby E.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rose, Sophia Miryam Schuessler-Fiorenza] VA Healthcare Syst Palo Alto, Spinal Cord Injury Serv, Palo Alto, CA USA. RP Kurichi, JE (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 423 Guardian Dr,907 Blockley Hall, Philadelphia, PA 19104 USA. EM jkurichi@mail.med.upenn.edu RI Schussler-Fiorenza Rose, Sophia Miryam/E-6411-2013 OI Schussler-Fiorenza Rose, Sophia Miryam/0000-0002-6311-6671 FU National Institute of Aging of the National Institutes of Health [AG032420-01A1, R01 AG 040105-01A1] FX The research for this manuscript was supported by grants from the National Institute of Aging of the National Institutes of Health (AG032420-01A1 and R01 AG 040105-01A1). NR 42 TC 9 Z9 9 U1 2 U2 6 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 NOV PY 2014 VL 6 IS 11 BP 976 EP 987 DI 10.1016/j.pmrj.2014.05.001 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AU4YJ UT WOS:000345614000003 PM 24798263 ER PT J AU DiVita, MA Mix, JM Goldstein, R Gerrard, P Niewczyk, P Ryan, CM Kowalske, K Zafonte, R Schneider, JC AF DiVita, Margaret A. Mix, Jacqueline M. Goldstein, Richard Gerrard, Paul Niewczyk, Paulette Ryan, Colleen M. Kowalske, Karen Zafonte, Ross Schneider, Jeffrey C. TI Rehabilitation Outcomes Among Burn Injury Patients With a Second Admission to an Inpatient Rehabilitation Facility SO PM&R LA English DT Article ID ACUTE-CARE; RISK-FACTORS; STROKE REHABILITATION; FIM INSTRUMENT; PREDICTORS; RELIABILITY; POPULATION; MORTALITY; DEATH AB Background: Burn survivors tend to have complex medical issues requiring rehabilitation to improve overall function and quality of life. A subset of burn patients treated in inpatient rehabilitation facilities (IRFs) may require more than 1 rehabilitation stay for the same injury. Objective: To compare the rehabilitation outcomes among burn patients admitted to an IRF who were discharged to acute care and then readmitted to an IRF with burn patients admitted to an IRF only 1 time. Design: Retrospective cohort study. Setting: Inpatient rehabilitation facilities. Participants: Burn injury patients aged 18 years or more who were admitted to IRFs between 2002 and 2011. Methods: We performed a secondary analysis of data from Uniform Data System for Medical Rehabilitation, a national data repository. Outcomes of the repeaters' second stay (n = 188) were compared to the nonrepeaters' first and only stay (n = 6,855), using linear regression and logistic regression to determine whether repeater status was associated with rehabilitation outcomes. Main Outcome Measurements: Functional status (using the Functional Independence Measure [FIM] instrument) at admission, discharge and change, length of stay, FIM efficiency (total FIM points gained per day), and discharge disposition. Results: Repeater status was inversely associated with discharge FIM total (coefficient - -3.42, 95% confidence interval - -5.76, = 1.07) and FIM change (coefficient = 4.05, 95% CI = 6.34, 1.75) in linear regression models. No other significant differences were found, and those differences in discharge FIM total and FIM change were small. Conclusions: Differences found in rehabilitation outcomes between the repeater and nonrepeater groups were small and may not reflect clinically meaningful differences. Burn injury patients who required a second IRF admission had rehabilitation outcomes similar to those of burn injury patients who did not require a second IRF admission, emphasizing the value of inpatient rehabilitation for burn injury IRF readmissions. C1 [DiVita, Margaret A.; Mix, Jacqueline M.; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY 14228 USA. [DiVita, Margaret A.] SUNY Coll Cortland, Dept Hlth, Cortland, NY 13045 USA. [Goldstein, Richard; Gerrard, Paul; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sumner Redstone Burn Ctr,Surg Serv, Boston, MA USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children Boston, Boston, MA USA. [Kowalske, Karen] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. RP DiVita, MA (reprint author), Uniform Data Syst Med Rehabil, 270 Northpointe Pkwy, Amherst, NY 14228 USA. EM margaret.divita@cortland.edu OI DiVita, Margaret/0000-0002-4878-2959 FU NIH; NIDRR; DOD FX Disclosures outside this publication: board membership (no money), ACRM, IBIA; grants/grants pending (money to institution), NIH, NIDRR, DOD; royalties (money to author), Elsevier, Demos; payment for development of educational presentations (money to author), Oakstone NR 20 TC 1 Z9 1 U1 1 U2 2 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 NOV PY 2014 VL 6 IS 11 BP 999 EP 1007 DI 10.1016/j.pmrj.2014.05.010 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AU4YJ UT WOS:000345614000006 PM 24880057 ER PT J AU Grubaugh, AL Gros, KS Davidson, TM Frueh, BC Ruggiero, KJ AF Grubaugh, Anouk L. Gros, Kirstin Stauffacher Davidson, Tatiana M. Frueh, B. Christopher Ruggiero, Kenneth J. TI Providers' Perspectives Regarding the Feasibility and Utility of an Internet-Based Mental Health Intervention for Veterans SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE Internet-based intervention; web-based intervention; PTSD; mental health; veterans; qualitative ID POSTTRAUMATIC-STRESS-DISORDER; CARE; IRAQ; AFGHANISTAN; BARRIERS; COMBAT; PTSD; DISSEMINATION; PERCEPTIONS; DEPLOYMENT AB Although support for Internet-based interventions (IBIs) has grown significantly in the past decade, few interventions are designed specifically for veterans with posttraumatic stress disorder and other mental health problems. Additionally, research guiding IBI development is limited. We solicited feedback from providers familiar with the needs and preferences of Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) veterans with mental health problems to inform the development of an IBI. Thematic interviews were conducted with 17 Veterans Affairs providers to (a) gain insight into the unique problems and needs of OIF/OEF veterans, (b) obtain feedback on the content and presentation of the IBI, and (c) generate suggestions regarding the effective delivery of the IBI. Providers were receptive to the use of IBIs and were vocal in their need for novel approaches and tools to address the mental health needs of their patients. They noted several advantages to IBIs such as their ability to circumvent access-to-care barriers and their ease of use and likely appeal to OIF/OEF veterans. They also noted challenges associated with IBIs, including obtaining sufficient motivation and buy-in from veterans given the distal nature of IBIs. Finally, providers offered several recommendations regarding the content and design of the IBI, as well as strategies for effective marketing and dissemination. Provider feedback was valuable in the development of an IBI that is responsive to the mental health needs of OIF/OEF veterans and in learning about how best to promote IBIs. Similar approaches can be used by stakeholders interested in developing IBIs for novel populations and settings. C1 [Grubaugh, Anouk L.; Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Grubaugh, Anouk L.; Gros, Kirstin Stauffacher; Davidson, Tatiana M.; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Honolulu, HI 96822 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. RP Grubaugh, AL (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM grubaugh@musc.edu NR 25 TC 1 Z9 1 U1 0 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD NOV PY 2014 VL 6 IS 6 BP 624 EP 631 DI 10.1037/a0035772 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU2NC UT WOS:000345454200005 ER PT J AU Weaver, TL Resick, PA AF Weaver, Terri L. Resick, Patricia A. TI Injury Dimensions in Female Victims of Intimate Partner Violence: Expanding the Examination of Associations With Symptoms of Posttraumatic Stress Disorder SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE PTSD; depression; injury; violence; body image ID BODY DYSMORPHIC DISORDER; WOMEN; METAANALYSIS; IMAGE; RISK; TRAUMA AB This study examined the types, frequency, and location of acute and residual injuries (violence-related marks or scars) of 345 victims of moderate-severe intimate partner violence (IPV). Acute facial injuries were common with facial bruising reported by 83%, facial lacerations reported by 44%, and damaged teeth reported by 20% of the sample. Fifty-six percent of the sample reported at least 1 mark or scar resulting from their acute injury. Having an IPV-related residual injury was associated with reports of significantly more severe forms of past-year violence (physical assault and 2 forms of psychological maltreatment), total number of acute injuries, and symptoms of posttraumatic stress disorder (PTSD) and depression. Moreover, positive residual injury status and 2 forms of psychological maltreatment predicted significant and unique variance in PTSD (but not depression), controlling for length of abuse and severity of physical assault. Within the residual injury subsample, body image distress associated with the residual injury and 1 form of psychological maltreatment predicted significant variance in PTSD (but not depression), controlling for length of abuse, severity of physical assault, and number of acute injuries. Implications for the multiple dimensions of injury were discussed. C1 [Weaver, Terri L.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. RP Weaver, TL (reprint author), St Louis Univ, Dept Psychol, 224 Grand Blvd, St Louis, MO 63103 USA. EM weavert@slu.edu NR 29 TC 0 Z9 0 U1 2 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD NOV PY 2014 VL 6 IS 6 BP 683 EP 690 DI 10.1037/a0036063 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU2NC UT WOS:000345454200012 ER PT J AU Yilmaz, E Hough, KA Gebhart, GF Williams, BA Gold, MS AF Yilmaz, Eser Hough, Karen A. Gebhart, Gerald F. Williams, Brian A. Gold, Michael S. TI Mechanisms Underlying Midazolam-Induced Peripheral Nerve Block and Neurotoxicity SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID TRANSLOCATOR PROTEIN TSPO; ROOT GANGLION NEURONS; INTRATHECAL MIDAZOLAM; BUPIVACAINE IMPROVES; GABA(A) RECEPTORS; RAT; ANALGESIA; INFLAMMATION; ANESTHETICS; ADJUVANTS AB Background and Objectives: The benzodiazepine midazolam has been reported to facilitate the actions of spinally administrated local anesthetics. Interestingly, despite the lack of convincing evidence for the presence of gamma-aminobutyric acid type A (GABA(A)) receptors along peripheral nerve axons, midazolam also has been shown to have analgesic efficacy when applied alone to peripheral nerves. These observations suggest midazolam-induced nerve block is due to another site of action. Furthermore, because of evidence indicating that midazolam has equal potency at the benzodiazepine site on the GABA(A) receptor and the 18-kd translocator protein (TSPO), it is possible that at least the nerve-blocking actions of midazolam are mediated by this alternative site of action. Methods: We used the benzodiazepine receptor antagonist flumazenil, and the TSPO antagonist PK11195, with midazolam on rat sciatic nerves and isolated sensory neurons to determine if either receptor mediates midazolam-induced nerve block and/or neurotoxicity. Results: Midazolam (300 mu M)-induced block of nerve conduction was reversed by PK11195 (3 mu M), but not flumazenil (30 mu M). Midazolam-induced neurotoxicity was blocked by neither PK11195 nor flumazenil. Midazolam also causes the release of Ca2+ from internal stores in sensory neurons, and there was a small but significant attenuation of midazolam-induced neurotoxicity by the Ca2+ chelator, BAPTA. BAPTA (30 mu M) significantly attenuated midazolam-induced nerve block. Conclusions: Our results indicate that processes underlying midazolam-induced nerve block and neurotoxicity are separable, and suggest that selective activation of TSPO may facilitate modality-selective nerve block while minimizing the potential for neurotoxicity. C1 [Yilmaz, Eser; Hough, Karen A.; Gebhart, Gerald F.; Williams, Brian A.; Gold, Michael S.] Univ Pittsburgh, Sch Med, Ctr Pain Res, Pittsburgh, PA USA. [Yilmaz, Eser; Hough, Karen A.; Gebhart, Gerald F.; Williams, Brian A.; Gold, Michael S.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Williams, Brian A.] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Gold, MS (reprint author), 3500 Terrace St,Room E1440 BST, Pittsburgh, PA 15139 USA. EM msg22@pitt.edu OI Gold, Michael/0000-0002-2083-6206 FU Department of Defense [OR090012] FX This research is supported by the Department of Defense grant OR090012 to B.A.W., M.S.G., and G.F.G. NR 25 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD NOV-DEC PY 2014 VL 39 IS 6 BP 525 EP 533 DI 10.1097/AAP.0000000000000176 PG 9 WC Anesthesiology SC Anesthesiology GA AT4SZ UT WOS:000344933500014 PM 25304479 ER PT J AU Nishio, I AF Nishio, Isuta TI Cervical Transforaminal Epidural Steroid Injections A Proposal for Optimizing the Preprocedural Evaluation With Available Imaging SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article ID VERTEBRAL ARTERY; COMPLICATIONS; HYPOPLASIA AB Cervical transforaminal epidural steroid injection (CTFESI) has been used to treat cervical radicular pain; however, rare but serious complications such as cerebellar or spinal cord infarction have been reported. The most probable causes of the serious complications include vertebral artery trauma, spasm, or accidental arterial injection of particulate steroid. Several recommendations have been made to improve the safety of CTFESI; however, evaluation and risk assessment of the patient's anatomy by the interventionist have not been sufficiently emphasized. Significant correlations between foraminal narrowing and proximity of the vertebral artery to the target of needle have been reported. This correlation is particularly problematic for interventionists because patients considered or referred for CTFESI are more likely to have foraminal narrowing at the level concerned. Without knowing the patient's anatomy, a common practice of rotating the C-arm obliquely to obtain a full view of the target foramen may carry significant risk of needle's encounter with the vertebral artery. Risk assessment through careful preprocedural review of the patient's magnetic resonance imaging by the interventionist is a worthwhile practice to optimize safety. Special attention should be paid to the vital structures such as the vertebral artery, neural foramen, and carotid artery. A preprocedural roadmap for the safest predicted needle trajectory can be created by simulation using the patient's available magnetic resonance imaging scans. These considerations may guide and help the interventionist to minimize the risk of inadvertent needle placement involving vital structures such as the vertebral artery or carotid artery. C1 [Nishio, Isuta] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98108 USA. RP Nishio, I (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-112 Anes, Seattle, WA 98108 USA. EM nishioi@uw.edu NR 17 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD NOV-DEC PY 2014 VL 39 IS 6 BP 546 EP 549 DI 10.1097/AAP.0000000000000164 PG 4 WC Anesthesiology SC Anesthesiology GA AT4SZ UT WOS:000344933500017 PM 25304477 ER PT J AU Atmanli, A Hu, DJ Domian, IJ AF Atmanli, Ayhan Hu, Dongjian Domian, Ibrahim J. TI Molecular Etching: A Novel Methodology for the Generation of Complex Micropatterned Growth Surfaces for Human Cellular Assays SO ADVANCED HEALTHCARE MATERIALS LA English DT Article ID EXTRACELLULAR-MATRIX; IN-VITRO; STEM-CELLS; HEART; PROTEINS; SHEETS; TISSUE; DIFFERENTIATION; CARDIOMYOCYTES; EXPANSION C1 [Atmanli, Ayhan; Hu, Dongjian; Domian, Ibrahim J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Atmanli, Ayhan; Hu, Dongjian; Domian, Ibrahim J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Domian, Ibrahim J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Domian, IJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM domian@mgh.harvard.edu FU National Science Foundation under NSF award [ECS-0335765]; National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) [U01HL100408-01, NIH/NHLBI 1K08 HL091209] FX This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the National Science Foundation under NSF award no. ECS-0335765. CNS is part of Harvard University. This work was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) [U01HL100408-01 and NIH/NHLBI 1K08 HL091209]. NR 39 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 EI 2192-2659 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD NOV PY 2014 VL 3 IS 11 BP 1759 EP 1764 DI 10.1002/adhm.201400010 PG 6 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA AT3TJ UT WOS:000344857000007 PM 24805162 ER PT J AU Jindai, K Kunzer, B Van, TT Striker, R AF Jindai, Kazuaki Kunzer, Bethaney Van, Tam T. Striker, Rob TI Human immunodeficiency virus testing pitfalls and clinical suspicion SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ACUTE HIV-INFECTION; PERFORMANCE; ALGORITHM AB Universal human immunodeficiency virus (HIV) screening was recommended in 2012, and major improvements in HIV testing have occurred in the past decade, but identification of HIV infected individuals remains inadequate in the United States. We report the case of a seronegative HIV-infected man who despite clinical and laboratory findings of acquired immunodeficiency syndrome, repeatedly tested nonreactive to third-generation HIV enzyme immunoassays (EIAs) and Western blot testing. Serologic diagnosis in this case required fourth-generation EIA testing due to the seronegativity of standard testing. The fourth-generation HIV EIA was positive presumably because it detects p24 HIV antigen as well as antibodies, unlike rapid HIV tests and third-generation HIV EIAs. This case highlights not only the importance of frontline providers to understand the different testing methodologies for HIV screening and their limitations but the importance of clinical suspicion as well. C1 [Jindai, Kazuaki; Kunzer, Bethaney; Striker, Rob] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Infect Dis Sect, Madison, WI 53706 USA. [Van, Tam T.] Univ Wisconsin, Wisconsin State Lab Hyg, Madison, WI 53706 USA. [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Jindai, K (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Infect Dis Sect, Madison, WI 53706 USA. EM rstriker@wisc.edu NR 10 TC 0 Z9 0 U1 1 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 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2014 VL 32 IS 11 AR 1442.e1 DI 10.1016/j.ajem.2014.04.017 PG 2 WC Emergency Medicine SC Emergency Medicine GA AT4ZC UT WOS:000344951600056 PM 24856744 ER PT J AU Gupta, AC Chandra, RV Yoo, AJ Leslie-Mazwi, TM Bell, DL Mehta, BP Vanderboom, TL Rabinov, JD Larvie, M Hirsch, JA AF Gupta, A. C. Chandra, R. V. Yoo, A. J. Leslie-Mazwi, T. M. Bell, D. L. Mehta, B. P. Vanderboom, T. L. Rabinov, J. D. Larvie, M. Hirsch, J. A. TI Safety and Effectiveness of Sacroplasty: A Large Single-Center Experience SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SACRAL INSUFFICIENCY FRACTURES; PERCUTANEOUS SACROPLASTY; PALLIATION; GUIDANCE; PAIN AB BACKGROUND AND PURPOSE: Sacral insufficiency fractures are a common cause of severe low back pain and immobilization in patients with osteoporosis or cancer. Current practice guideline recommendations range from analgesia and physical therapy to resection with surgical fixation. We sought to assess the safety and effectiveness of sacroplasty, an emerging minimally invasive treatment. MATERIALS AND METHODS: We performed a retrospective review of institutional databases for percutaneous sacroplasty performed between January 2004 and September 2013. Demographic and procedural data and pre- and posttreatment Visual Analog Scale, Functional Mobility Scale, and Analgesic Scale scores were reviewed. Overall response was rated by using a 4-point scale (1, complete resolution of pain; 2, improvement of pain; 3, no change; 4, worsened pain) assessed at short-term follow-up. RESULTS: Fifty-three patients were included; most (83%) were female. Fracture etiology was cancer-related (55%), osteoporotic insufficiency (30%), and minor trauma (15%). No major complication or procedure-related morbidity occurred. There were statistically significant decreases in the Visual Analog Scale (P < .001), Functional Mobility Scale (P < .001), and Analgesic Scale scores (P < .01) in 27 patients with recorded data: pretreatment Visual Analog Scale (median [interquartile range], 9.0 [8.0-10.0]); Functional Mobility Scale, 3.0 (2.0-3.0); and Analgesic Scale scores, 3.0(3.0-4.0) were reduced to 3.0 (0.0-5.8),1.0 (0.25-2.8), and 3.0(2.0-3.8) posttreatment. When we used the overall 4-point score at a mean of 27 days, 93% (n = 45) reported complete resolution or improvement in overall pain. CONCLUSIONS: In this single-center cohort, sacroplasty was a safe and effective procedure. There were significant short-term gains in pain relief, increased mobility, and decreased dependence on pain medication. C1 [Gupta, A. C.; Yoo, A. J.; Leslie-Mazwi, T. M.; Bell, D. L.; Mehta, B. P.; Vanderboom, T. L.; Rabinov, J. D.; Larvie, M.; Hirsch, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Chandra, R. V.] Monash Hlth, Dept Radiol, Melbourne, Vic, Australia. Monash Univ, Dept Surg, Melbourne, Vic 3004, Australia. RP Hirsch, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Gray 241,55 Fruit St, Boston, MA 02114 USA. EM jahirsch@partners.org FU CareFusion FX Joshua A. Hirsch-RELATED: Consulting Fees or Honoraria: from CareFusion, a company that makes augmentation products that could be used in sacroplasty; Stocks/Stock Options: He also holds stocks/stock options in Intratech. NR 19 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI DENVILLE PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA SN 0195-6108 EI 1936-959X J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 2014 VL 35 IS 11 BP 2202 EP 2206 DI 10.3174/ajnr.A4027 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AT8QQ UT WOS:000345197700032 PM 25012675 ER PT J AU Sethi, RKV Kozin, ED Remenschneider, AK Lee, DJ Gray, ST Shrime, MG Gliklich, RE AF Sethi, Rosh K. V. Kozin, Elliott D. Remenschneider, Aaron K. Lee, Daniel J. Gray, Stacey T. Shrime, Mark G. Gliklich, Richard E. TI Subspecialty emergency room as alternative model for otolaryngologic care: Implications for emergency health care delivery SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article AB Purpose: A dedicated otolaryngology emergency room (ER) represents a specialized surgical evaluation and treatment setting that may be an alternative triage pathway for acute otolaryngologic complaints. We aim to characterize practice patterns in this setting and to provide insight into the epidemiology of all-corner, urgent otolaryngologic complaints in the United States. Methods and methods: Electronic medical records were reviewed for all patients who registered for otolaryngologic care and received a diagnosis in the Massachusetts Eye and Ear Infirmary ER between January 2011 and September 2013. Descriptive analysis was performed to characterize utilization and diagnostic patterns. Predictors of " inpatient admission were identified using multivariable regression. Geocoding analysis was performed to characterize catchment area. Results: A total of 12,234 patient visits were evaluated with a mean age of 44.7. Auditory and vestibular problems constituted the most frequent diagnoses (50.0%). The majority of patients were discharged home (92.3%). Forty-three percent of patients underwent a procedure in the ER; the most common procedure was diagnostic nasolaryngoscopy (52%). Predictors of inpatient admission were post-operative complaint (odds ratio [OR] 7.3, P < 0.0001), arrival overnight (OR 3.3, P < 0.0001), and laryngeal complaint (OR 2.4, P < 0.0001). Patients traveled farther for evaluation of hearing loss (11 miles) and less for common diagnoses including impacted cerumen (7.1 miles) (P < 0.0001). Conclusion: In this report, we investigate practice patterns of a dedicated otolaryngology emergency room to explore an alternative to standard acute otolaryngologic health care delivery mechanisms. We identify key predictors of inpatient admission. This study has implications for emergency health care delivery models. C) 2014 Elsevier Inc. All rights reserved. C1 [Sethi, Rosh K. V.; Kozin, Elliott D.; Remenschneider, Aaron K.; Lee, Daniel J.; Gray, Stacey T.; Gliklich, Richard E.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Sethi, Rosh K. V.; Kozin, Elliott D.; Remenschneider, Aaron K.; Lee, Daniel J.; Gray, Stacey T.; Shrime, Mark G.; Gliklich, Richard E.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. RP Kozin, ED (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM Elliott_kozin@meei.harvard.edu RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 FU NIDCD NIH HHS [T32 DC000020] NR 23 TC 6 Z9 6 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 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2014 VL 35 IS 6 BP 758 EP 765 DI 10.1016/j.amjoto.2014.06.013 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA AT9RF UT WOS:000345263200014 PM 25106951 ER PT J AU Prieto-Centurion, V Rolle, AJ Au, DH Carson, SS Henderson, AG Lee, TA Lindenauer, PK McBurnie, MA Mularski, RA Naureckas, ET Vollmer, WM Joese, BJ Krishnan, JA AF Prieto-Centurion, Valentin Rolle, Andrew J. Au, David H. Carson, Shannon S. Henderson, Ashley G. Lee, Todd A. Lindenauer, Peter K. McBurnie, Mary A. Mularski, Richard A. Naureckas, Edward T. Vollmer, William M. Joese, Binoy J. Krishnan, Jerry A. CA CONCERT Consortium TI Multicenter Study Comparing Case Definitions Used to Identify Patients with Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE COPD; spirometry; ICD-9-CM; comparative effectiveness; case definitions ID AIRWAY-OBSTRUCTION; UNITED-STATES; PRIMARY-CARE; COPD; EXACERBATIONS; DIAGNOSIS; VALIDITY; SPIROMETRY; HOSPITALIZATIONS; PREVENTION AB Rationale: Clinical trials in chronic obstructive pulmonary disease (COPD) usually require evidence of airflow obstruction and clinical risk factors. International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes or patient-reported physician diagnoses are often used for epidemiologic studies and performance improvement programs. Objectives: To evaluate agreement between these case definitions for COPD and to assess the comparability of study populations identified as having COPD not using the clinical trial reference standard. Methods: We recruited patients from the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter clinical registry in a cross-sectional study. Demographics, clinical, and post-bronchodilator spirometry data were collected at an in-person study visit. The kappa statistic (kappa) was used to evaluate agreement. A multivariable logistic regression model was used to identify patient characteristics associated with meeting the trial reference standard. Measurements and Main Results: A total of 998 (82.8%) of 1,206 study participants met at least one case definition for COPD (of the 998: 91% using ICD-9 codes, 73% using patient reported physician diagnosis, 56% using trial reference standard); agreement between case definitions was poor (kappa = 0.20-0.26). Lack of airflow obstruction was the principal (89%) reason patients identified as having COPD did not meet the trial reference standard. Patients who were black (vs white), obese (vs normal weight), or had depression (vs. not) were less likely to meet the trial reference standard (odds ratio [95% CI], 0.37 [0.26-0.53], 0.51 [0.34-0.75], 0.53 [0.40-0.71], respectively). Conclusions: Findings highlight concerns about the applicability of findings in clinical trials to patients meeting other case definitions for COPD. C1 [Prieto-Centurion, Valentin; Rolle, Andrew J.; Krishnan, Jerry A.] Univ Illinois, Div Pulm Crit Care Sleep & Allergy, Chicago, IL 60612 USA. [Lee, Todd A.] Univ Illinois, Dept Pharm Syst Outcomes & Policy, Chicago, IL 60612 USA. [Au, David H.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Carson, Shannon S.; Henderson, Ashley G.] Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA. [Lindenauer, Peter K.] Baystate Med Ctr, Dept Med, Springfield, MA 01199 USA. [Lindenauer, Peter K.] Baystate Med Ctr, Ctr Qual Care Res, Springfield, MA 01199 USA. [Lindenauer, Peter K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [McBurnie, Mary A.; Mularski, Richard A.; Vollmer, William M.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. [Naureckas, Edward T.] Univ Chicago Med, Sect Pulm & Crit Care, Chicago, IL USA. [Joese, Binoy J.; Krishnan, Jerry A.] Univ Illinois Hosp & Hlth Sci Syst, Populat Hlth Sci Program, Chicago, IL USA. RP Prieto-Centurion, V (reprint author), Univ Illinois, 912 South Wood St,MC 719, Chicago, IL 60612 USA. EM vprieto@uic.edu FU National Heart, Lung, and Blood Institute [RC2 HL101618]; National Institutes of Health [2T32HL082547]; Patient-Centered Outcomes Research Institute [IH-12-11-4365, CE-1304-6490, PPRN-1306-04748] FX Supported by the National Heart, Lung, and Blood Institute (RC2 HL101618) for CONCERT; National Institutes of Health T32 (2T32HL082547) institutional training grant (V.P.-C.); and Patient-Centered Outcomes Research Institute contracts IH-12-11-4365, CE-1304-6490, and PPRN-1306-04748 (J.A.K.). NR 31 TC 8 Z9 8 U1 1 U2 6 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 NOV 1 PY 2014 VL 190 IS 9 BP 989 EP 995 DI 10.1164/rccm.201406-1166OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AT8RN UT WOS:000345199900009 PM 25192554 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, Marcos I. Anzueto, Antonio TI Azithromycin: We're There! Reply SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID EXACERBATIONS; PREVENTION C1 [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX 78258 USA. Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX USA. RP Restrepo, MI (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78258 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 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 NOV 1 PY 2014 VL 190 IS 9 BP 1075 EP 1076 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AT8RN UT WOS:000345199900021 PM 25360733 ER PT J AU Morii, T Ohtsuka, K Ohnishi, H Mochizuki, K Yoshiyama, A Aoyagi, T Hornicek, FJ Ichimura, S AF Morii, Takeshi Ohtsuka, Kouki Ohnishi, Hiroaki Mochizuki, Kazuo Yoshiyama, Akira Aoyagi, Takayuki Hornicek, Francis J. Ichimura, Shoichi TI BH3 Mimetics Inhibit Growth of Chondrosarcoma - A Novel Targeted-therapy for Candidate Models SO ANTICANCER RESEARCH LA English DT Article DE Chondrosarcoma; apoptosis; BH3 mimetics; Bcl2 ID BCL-2 FAMILY; DRUG-RESISTANCE; PERIPHERAL CHONDROSARCOMA; ABT-737; CELLS; EXPRESSION; APOPTOSIS; TUMORS; CHEMORESISTANCE; OSTEOSARCOMA AB Background: Chondrosarcoma is refractory to conventional chemotherapy. BH-3 mimetics ABT-737 and ABT-263 are synthetic small-molecule inhibitors of anti-apoptotic proteins B-cell lymphoma-2 (Bcl2) and Bcl-xL, which play a critical role in survival of chondrosarcoma cells. Materials and Methods: Clumdrosarcoma cell lines SW-1353 and CS-1 were used as the disease model. We used immunoblotting to assess the expression of target molecules Bcl2 and Bel-xL, and the apoptotic inducers Bcl2-associated X (Bax) and Bcl2-antagonist/killer Bak). In vitro growth inluhition by BH-3 tnimetics was confirmed by photomicroscopic cell counting and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetharypheny1)-2-(4- sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Apoptotic induction was confirmed by Enzyme-Linked ImmunoSorbent Assay (ELLS'A). In vivo growth inhibition was assessed in a non-obese diabetic/severe combined immutodeficient (NOD/SCID) mouse model. Results: Expression of the target and effector molecules was confirmed in chondrosarcoma cell lines. BH3 mimetics significantly inhibited cell growth and induced apoptosis in vitro. Administration of ABT-263 inhibited chondrosarcotna growth and improved survival in a mouse model. Conclusion: BH3 mimetics represent a novel treatment modality for chondrosarcoma. C1 [Morii, Takeshi; Mochizuki, Kazuo; Yoshiyama, Akira; Aoyagi, Takayuki; Ichimura, Shoichi] Kyorin Univ, Dept Orthopaed Surg, Fac Med, Mitaka, Tokyo 1618611, Japan. [Ohtsuka, Kouki; Ohnishi, Hiroaki] Kyorin Univ, Dept Lab Med, Fac Med, Mitaka, Tokyo 1618611, Japan. [Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Morii, T (reprint author), Kyorin Univ, Dept Orthopaed Surg, Fac Med, 6-20-2 Shinkawa, Mitaka, Tokyo 1618611, Japan. EM t-morii@gh3.so-net.ne.jp FU Health and Labour Sciences Research Expenses for Commission, Applied Research for Innovative Treatment of Cancer from the Ministry of Health, Labor and Welfare [H26-084]; Kyorin University School of Medicine FX We are grateful to Ms. Mizuho Kosuge and Ms. Miyukii Murayama for their skilful technical assistance. This study was supported in part by the Health and Labour Sciences Research Expenses for Commission, Applied Research for Innovative Treatment of Cancer from the Ministry of Health, Labor and Welfare H26-084) and by a Research Encouragement Award by Kyorin University School of Medicine. NR 28 TC 2 Z9 2 U1 1 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD NOV PY 2014 VL 34 IS 11 BP 6423 EP 6430 PG 8 WC Oncology SC Oncology GA AT5CN UT WOS:000344961300021 PM 25368242 ER PT J AU Pursnani, A Mayrhofer, T Ferencik, M Hoffmann, U AF Pursnani, Amit Mayrhofer, Thomas Ferencik, Maros Hoffmann, Udo TI The 2013 ACC/AHA cardiovascular prevention guidelines improve alignment of statin therapy with coronary atherosclerosis as detected by coronary computed tomography angiography SO ATHEROSCLEROSIS LA English DT Article DE Prevention; Guidelines; Atherosclerosis; Computed tomography; Statin ID ESC/EAS GUIDELINES; PROGNOSTIC VALUE; DISEASE; DYSLIPIDAEMIAS; METAANALYSIS; CHOLESTEROL; MANAGEMENT; RISK AB The recently released 2013 ACC/AHA guidelines for management of blood cholesterol have substantially increased the number of adults who are eligible for preventive statin therapy. We sought to determine whether eligibility for statin therapy as determined by the 2013 ACC/AHA guideline recommendation is better aligned with the actual presence of coronary artery disease (CAD) as detected by coronary CT angiography (CCTA) when compared to prior guidelines including the 2004 NCEP ATP III and 2011 ESC/EAS guidelines. In this secondary analysis of the prospective observational ROMICAT I (Rule Out Myocardial Infarction with Computer Assisted Tomography) cohort study, we included all men and women aged 40-79 years presenting with acute chest pain but not diagnosed with acute coronary syndrome nor on admission statin. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy by the 2013 ACC/AHA, the 2004 NCEP ATP III, and the 2011 ESC/EAS guidelines. We determined the presence and severity of CAD as detected by CCTA. The 2013 ACC/AHA algorithm identified nearly twice as many individuals as eligible for statins (n = 77/189; 41%) as compared to the 2004 ATP III criteria: (n = 41/189; 22%), (p < .0001) In addition, the 2013 ACC/AHA guidelines were more sensitive for treatment of CCTA-detected CAD than the 2004 ATP III guidelines [53.4% (42.5-64.1) vs 27.3% (18.3-37.8), p < .001] and the 2011 ESC/EAE guidelines [53.4% (42.5-64.1) vs 34.1% (24.3-45.0), p < .001]. However, the specificity of these guidelines was modestly reduced compared to the 2004 ATP III guidelines [70.3 (60.4-79.0) vs 83.2 (74.4-89.9), p < .001] and the 2011 ESC/EAE guidelines [70.3 (60.4-79.0) vs 86.1 (77.8-92.2), p < .001], suggesting increased treatment of subjects without CCTA-detected CAD. Overall, the 2013 ACC/AHA guidelines are more sensitive to identify patients who have CAD detected by CCTA eligible for statin therapy as compared with prior guidelines, with an acceptable trade-off in specificity for recommending statin therapy in those without CAD. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Pursnani, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM amit.pursnani@gmail.com FU National Heart, Lung, and Blood Institute [R01 HL080053, 5K24HL113128]; NIH [T32 HL076136]; American Heart Association [13FTF16450001] FX This work was supported by grants from the National Heart, Lung, and Blood Institute (R01 HL080053 and 5K24HL113128) Dr. Pursnani received support from NIH T32 HL076136. Dr. Ferencik was supported by a grant from the American Heart Association (13FTF16450001). NR 17 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2014 VL 237 IS 1 BP 314 EP 318 DI 10.1016/j.atherosclerosis.2014.09.023 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AT5WT UT WOS:000345011300048 PM 25299966 ER PT J AU Odden, MC Shlipak, MG Whitson, HE Katz, R Kearney, PM Defilippi, C Shastri, S Sarnak, MJ Siscovick, DS Cushman, M Psaty, BM Newman, AB AF Odden, Michelle C. Shlipak, Michael G. Whitson, Heather E. Katz, Ronit Kearney, Patricia M. defilippi, Chris Shastri, Shani Sarnak, Mark J. Siscovick, David S. Cushman, Mary Psaty, Bruce M. Newman, Anne B. TI Risk factors for cardiovascular disease across the spectrum of older age: The Cardiovascular Health Study SO ATHEROSCLEROSIS LA English DT Article DE Aging; Epidemiology; Risk factors ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; BODY-MASS INDEX; BLOOD-PRESSURE; MORTALITY RISK; CYSTATIN-C; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; FOLLOW-UP; ASSOCIATION AB Objective: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age. Methods: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP). Results: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45). Conclusions: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Odden, Michelle C.] Oregon State Univ, Sch Biol & Populat Hlth Sci, Corvallis, OR 97331 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Whitson, Heather E.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Whitson, Heather E.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. [Whitson, Heather E.] Geriatr Res Educ & Clin Ctr, Durham VA Med Ctr, Durham, NC USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Kearney, Patricia M.] Natl Univ Ireland Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland. [defilippi, Chris] Univ Maryland, Div Cardiovasc Med, Baltimore, MD 21201 USA. [Shastri, Shani] Univ Texas SW Med Ctr Dallas, Div Nephrol, Dallas, TX 75390 USA. [Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. [Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Odden, MC (reprint author), Oregon State Univ, Sch Biol & Populat Hlth Sci, 141B Milam Hall, Corvallis, OR 97331 USA. EM Michelle.Odden@oregonstate.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, N01HC85239, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging (NIA) [R01AG023629, R01AG027002, K01AG039387, K23AG032867, P30AG028716, R01AG043438]; American Heart Association Western States Affiliate [11CRP7210088] FX This research was supported by contracts HHSN268201200036C, N01HC85239, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 and R01AG027002 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm.; Dr. Odden is supported by the American Heart Association Western States Affiliate (11CRP7210088) and the National Institute on Aging (K01AG039387). Dr. Whitson is supported by the National Institute on Aging K23AG032867, P30AG028716, and R01AG043438. NR 39 TC 12 Z9 13 U1 2 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2014 VL 237 IS 1 BP 336 EP 342 DI 10.1016/j.atherosclerosis.2014.09.012 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AT5WT UT WOS:000345011300050 PM 25303772 ER PT J AU Giedt, RJ Sprachman, MM Yang, KS Weissleder, R AF Giedt, Randy J. Sprachman, Melissa M. Yang, Katherine S. Weissleder, Ralph TI Imaging Cellular Distribution of Bcl Inhibitors Using Small Molecule Drug Conjugates SO BIOCONJUGATE CHEMISTRY LA English DT Article ID FAMILY PROTEINS; CYTOCHROME-C; IN-VIVO; APOPTOSIS; DEATH; MITOCHONDRIA; POTENT; CELLS; BAX; DEXAMETHASONE AB Overexpression of anti-apoptotic proteins such as Bcl-2 is a cellular mechanism to evade apoptosis; consequently, Bcl-2 inhibitors are being developed as anticancer agents. In this work, we have synthesized a fluorescent version of ABT-199 in an effort to visualize a drug surrogate by high resolution imaging. We show that this fluorescent conjugate has comparable Bcl-2 binding efficacy and cell line potency to the parent compound and can be used as an imaging agent in several cancer cell types. We anticipate that this agent will be a valuable tool for studying the single-cell distribution and pharmacokinetics of ABT-199 as well the broader group of BH3-mimetics. C1 [Giedt, Randy J.; Sprachman, Melissa M.; Yang, Katherine S.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH [T32CA79443]; [1R01CA164448]; [P01-CA139980] FX R.J.G. and M.M.S. were supported by an NIH grant T32CA79443, and this project was funded via 1R01CA164448 and P01-CA139980. We are grateful to Dr. Rainer Kohler for imaging assistance and Dr. Thomas Reiner, Dr. Bjorn Askevold, and Dr. Eunha Kim for many helpful discussions. The crystal structure graphic of Bcl-2 used in the TOC graphic was generated using CCP4 mg Molecular Graphics Software.27 NR 27 TC 2 Z9 2 U1 3 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV PY 2014 VL 25 IS 11 BP 2081 EP 2085 DI 10.1021/bc500433k PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA AU0JK UT WOS:000345309000019 PM 25333750 ER PT J AU Li, ZX Roussakis, E Koolen, PGL Ibrahim, AMS Kim, K Rose, LF Wu, J Nichols, AJ Baek, Y Birngruber, R Apiou-Sbirlea, G Matyal, R Huang, T Chan, R Lin, SJ Evans, CL AF Li, Zongxi Roussakis, Emmanuel Koolen, Pieter G. L. Ibrahim, Ahmed M. S. Kim, Kuylhee Rose, Lloyd F. Wu, Jesse Nichols, Alexander J. Baek, Yunjung Birngruber, Reginald Apiou-Sbirlea, Gabriela Matyal, Robina Huang, Thomas Chan, Rodney Lin, Samuel J. Evans, Conor L. TI Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID LIMB ISCHEMIA; SKIN; PHOSPHORESCENCE; HYPOXIA; TENSION; BURNS; INDICATORS; COMPLEXES; SYSTEMS; PROBES AB Oxygen plays an important role in wound healing, as it is essential to biological functions such as cell proliferation, immune responses and collagen synthesis. Poor oxygenation is directly associated with the development of chronic ischemic wounds, which affect more than 6 million people each year in the United States alone at an estimated cost of $25 billion. Knowledge of oxygenation status is also important in the management of burns and skin grafts, as well as in a wide range of skin conditions. Despite the importance of the clinical determination of tissue oxygenation, there is a lack of rapid, user-friendly and quantitative diagnostic tools that allow for non-disruptive, continuous monitoring of oxygen content across large areas of skin and wounds to guide care and therapeutic decisions. In this work, we describe a sensitive, colorimetric, oxygen-sensing paint-on bandage for two-dimensional mapping of tissue oxygenation in skin, burns, and skin grafts. By embedding both an oxygen-sensing porphyrin-dendrimer phosphor and a reference dye in a liquid bandage matrix, we have created a liquid bandage that can be painted onto the skin surface and dries into a thin film that adheres tightly to the skin or wound topology. When captured by a camera-based imaging device, the oxygen-dependent phosphorescence emission of the bandage can be used to quantify and map both the pO(2) and oxygen consumption of the underlying tissue. In this proof-of-principle study, we first demonstrate our system on a rat ischemic limb model to show its capabilities in sensing tissue ischemia. It is then tested on both ex vivo and in vivo porcine burn models to monitor the progression of burn injuries. Lastly, the bandage is applied to an in vivo porcine graft model for monitoring the integration of full-and partial-thickness skin grafts. (C) 2014 Optical Society of America C1 [Li, Zongxi; Roussakis, Emmanuel; Nichols, Alexander J.; Baek, Yunjung; Apiou-Sbirlea, Gabriela; Evans, Conor L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Charlestown, MA 02129 USA. [Koolen, Pieter G. L.; Ibrahim, Ahmed M. S.; Kim, Kuylhee; Lin, Samuel J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Plast Surg, Charlestown, MA 02129 USA. [Rose, Lloyd F.; Wu, Jesse; Chan, Rodney] US Army, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Nichols, Alexander J.; Evans, Conor L.] Harvard Univ, Program Biophys, Boston, MA 02115 USA. [Nichols, Alexander J.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Baek, Yunjung] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea. [Birngruber, Reginald] Med Univ Lubeck, Inst Biomed Opt, D-23562 Lubeck, Germany. [Matyal, Robina; Huang, Thomas] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Li, ZX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 149 13th St, Charlestown, MA 02129 USA. EM evans.conor@mgh.harvard.edu RI Birngruber, Reginald/Q-2342-2016 FU Air Force Office for Scientific Research [FA9550-13-1-0068]; National Institute of Health [1 DP2 OD007096-1] FX The authors would like to thank Joachim Pruessner (Api) for his help with diagram design and creation. This research is sponsored in part by the Air Force Office for Scientific Research, under grant number: FA9550-13-1-0068. The authors also gratefully acknowledge funding from the National Institute of Health, under grant number: 1 DP2 OD007096-1. Information on the New Innovator Award Program is at http://nihroadmap.nih.gov/newinnovator/. NR 39 TC 11 Z9 12 U1 4 U2 29 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 NOV 1 PY 2014 VL 5 IS 11 BP 3748 EP 3764 DI 10.1364/BOE.5.003748 PG 17 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AT4UR UT WOS:000344939400001 PM 25426308 ER PT J AU Nam, AS Chico-Calero, I Vakoc, BJ AF Nam, Ahhyun S. Chico-Calero, Isabel Vakoc, Benjamin J. TI Complex differential variance algorithm for optical coherence tomography angiography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID SWEPT SEMICONDUCTOR-LASER; BLOOD-FLOW; INTENSITY; CONTRAST; OCT AB We describe a complex differential variance (CDV) algorithm for optical coherence tomography based angiography. The algorithm exploits both the intensity and phase changes of optical coherence tomography (OCT) signals from flowing blood to achieve high vascular contrast, and also intrinsically reject undesirable phase signals originating from small displacement axial bulk tissue motion and instrument synchronization errors. We present this algorithm within a broader discussion of the properties of OCT signal dynamics. The performance of the algorithm is compared against two other existing algorithms using both phantom measurements and in vivo data. We show that the algorithm provides better contrast for a given number of measurements and equivalent spatial averaging. (C) 2014 Optical Society of America C1 [Nam, Ahhyun S.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Nam, Ahhyun S.; Chico-Calero, Isabel; Vakoc, Benjamin J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Chico-Calero, Isabel; Vakoc, Benjamin J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Vakoc, Benjamin J.] Harvard Mit Div Hlth Sci & Technol, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Nam, AS (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM snam@mit.edu FU Center for Biomedical OCT Research and Translation - National Center for Research Resources [P41EB015903]; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health; NIH [R01CA163528]; Graduate Student Fellowship of Wellman Center for Photomedicine; Kwanjeong Educational Foundation FX This project was supported by the Center for Biomedical OCT Research and Translation through Grant Number P41EB015903, awarded by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. This work was also supported by NIH grant R01CA163528. Ahhyun S. Nam was partially supported by Graduate Student Fellowship of Wellman Center for Photomedicine and Kwanjeong Educational Foundation. NR 23 TC 13 Z9 14 U1 0 U2 8 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 NOV 1 PY 2014 VL 5 IS 11 BP 3822 EP 3832 DI 10.1364/BOE.5.003822 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AT4UR UT WOS:000344939400006 PM 25426313 ER PT J AU Lechowicz, MJ Lazarus, HM Carreras, J Laport, GG Cutler, CS Wiernik, PH Hale, GA Maharaj, D Gale, RP Rowlings, PA Freytes, CO Miller, AM Vose, JM Maziarz, RT Montoto, S Maloney, DG Hari, PN AF Lechowicz, M. J. Lazarus, H. M. Carreras, J. Laport, G. G. Cutler, C. S. Wiernik, P. H. Hale, G. A. Maharaj, D. Gale, R. P. Rowlings, P. A. Freytes, C. O. Miller, A. M. Vose, J. M. Maziarz, R. T. Montoto, S. Maloney, D. G. Hari, P. N. TI Allogeneic hematopoietic cell transplantation for mycosis fungoides and Sezary syndrome SO BONE MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; INTERNATIONAL-SOCIETY; CUTANEOUS-LYMPHOMAS; ORGANIZATION; PROPOSAL; BLOOD AB We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P = 0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22-44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free. C1 [Lechowicz, M. J.] Emory Univ Hosp, Atlanta, GA 30322 USA. [Lazarus, H. M.] Univ Hosp, Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Carreras, J.; Hari, P. N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Laport, G. G.] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA. [Cutler, C. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wiernik, P. H.] Our Lady Mercy Med Ctr, Bronx, NY USA. [Hale, G. A.] Childrens Hosp, Pediatr Hematol Oncol BMT, St Petersburg, FL USA. [Maharaj, D.] South Florida Bone Marrow Stem Cell Transplant In, Boynton Beach, FL USA. [Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Sect Hematol, London, England. [Rowlings, P. A.] Univ Newcastle, HAPS Pathol North, Calvary Mater Newcastle, Callaghan, NSW 2308, Australia. [Freytes, C. O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Miller, A. M.] Baylor Univ, Med Ctr, Dallas, TX USA. [Vose, J. M.] Nebraska Med Ctr, Div Hematol Oncol, Omaha, NE USA. [Maziarz, R. T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Montoto, S.] Queen Mary Univ London, Barts Canc Inst, London, England. [Maloney, D. G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200W Wisconsin Ave,Suite 5500, Milwaukee, WI 53226 USA. EM phari@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X FU Public Health Service Grant/Cooperative Agreement from the National Cancer Institute (NCI) [U24 CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [U10 HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; 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 U10 HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from 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; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; 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.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; 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, or any other agency of the U.S. Government. NR 15 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2014 VL 49 IS 11 BP 1360 EP 1365 DI 10.1038/bmt.2014.161 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AT4RC UT WOS:000344927400003 PM 25068422 ER PT J AU Wey, HY Phillips, KA McKay, DR Laird, AR Kochunov, P Davis, MD Glahn, DC Duong, T Fox, PT AF Wey, Hsiao-Ying Phillips, Kimberley A. McKay, D. Reese Laird, Angela R. Kochunov, Peter Davis, M. Duff Glahn, David C. Duong, Timothy Q. Fox, Peter T. TI Multi-region hemispheric specialization differentiates human from nonhuman primate brain function SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Brain evolution; Brain connectivity; Functional connectivity; Resting-state networks; Primates; fMRI ID RESTING-STATE NETWORKS; PRIMARY MOTOR CORTEX; MONKEYS CEBUS-APELLA; CEREBRAL ASYMMETRY; PREFRONTAL CORTEX; PLANUM TEMPORALE; GENETIC-CONTROL; CONNECTIVITY; ARCHITECTURE; CHIMPANZEES AB The human behavioral repertoire greatly exceeds that of nonhuman primates. Anatomical specializations of the human brain include an enlarged neocortex and prefrontal cortex (Semendeferi et al. in Am J Phys Anthropol 114:224-241, 2001), but regional enlargements alone cannot account for these vast functional differences. Hemispheric specialization has long believed to be a major contributing factor to such distinctive human characteristics as motor dominance, attentional control and language. Yet structural cerebral asymmetries, documented in both humans and some nonhuman primate species, are relatively minor compared to behavioral lateralization. Identifying the mechanisms that underlie these functional differences remains a goal of considerable interest. Here, we investigate the intrinsic connectivity networks in four primate species (humans, chimpanzees, baboons, and capuchin monkeys) using resting-state fMRI to evaluate the intra- and inter- hemispheric coherences of spontaneous BOLD fluctuation. All three nonhuman primate species displayed lateralized functional networks that were strikingly similar to those observed in humans. However, only humans had multi-region lateralized networks, which provide fronto-parietal connectivity. Our results indicate that this pattern of within-hemisphere connectivity distinguishes humans from nonhuman primates. C1 [Wey, Hsiao-Ying; Phillips, Kimberley A.; McKay, D. Reese; Laird, Angela R.; Kochunov, Peter; Davis, M. Duff; Duong, Timothy Q.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying; McKay, D. Reese; Laird, Angela R.; Kochunov, Peter; Davis, M. Duff; Duong, Timothy Q.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Phillips, Kimberley A.] Trinity Univ, Dept Psychol, San Antonio, TX 78212 USA. [Phillips, Kimberley A.; Kochunov, Peter; Davis, M. Duff; Duong, Timothy Q.; Fox, Peter T.] Texas Biomed Res Inst, Southwest Natl Primate Res Ctr, San Antonio, TX USA. [McKay, D. Reese; Glahn, David C.] Yale Univ, Olin Neuropsychiat Res Ctr, Inst Living, New Haven, CT USA. [McKay, D. Reese; Glahn, David C.] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Kochunov, Peter] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Davis, M. Duff] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. RP Phillips, KA (reprint author), Trinity Univ, Dept Psychol, 1 Trinity Pl, San Antonio, TX 78212 USA. EM kimberley.phillips@trinity.edu RI Fox, Peter/B-4725-2010; OI Fox, Peter/0000-0002-0465-2028; Phillips, Kimberley/0000-0002-5517-3596 FU American Heart Association Established Investigator Award [0940104 N]; National Institute of Health [NINDS R15 NS070717-01, NIA R01 AG29412-5, NINDS R01 NS45879]; Clinical Translational Science Award's imaging supplement [UL1RR025767]; American Heart Association [11PRE5670005]; Translational Science Training Grant from the Institute for Integration of Medicine and Science, University of Texas Health Science Center; National Center for Research Resources [P51RR13986]; Office of Research Infrastructure Programs/OD [P51OD011133] FX This work was supported by the American Heart Association Established Investigator Award (0940104 N to T. Q. D.), National Institute of Health (NINDS R15 NS070717-01 to K. A. P.; NIA R01 AG29412-5 to M. D. D.; NINDS R01 NS45879 to T. Q. D.) and Clinical Translational Science Award's imaging supplement (parent grant UL1RR025767) to K. A. P. and T. Q. D., and H.Y.W. H.Y.W. was supported by a Predoctoral Fellowship (11PRE5670005) from the American Heart Association and by a Translational Science Training Grant from the Institute for Integration of Medicine and Science, University of Texas Health Science Center. This project was also supported by the National Center for Research Resources (P51RR13986) and is currently supported by the Office of Research Infrastructure Programs/OD (P51OD011133) to M. D. D. We thank Nicholas Holder for technical assistance, and Drs. Kathy Brasky and Mel de la Garza for essential veterinary support. NR 42 TC 10 Z9 10 U1 4 U2 16 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD NOV PY 2014 VL 219 IS 6 BP 2187 EP 2194 DI 10.1007/s00429-013-0620-9 PG 8 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA AT4AL UT WOS:000344879200024 PM 23928747 ER PT J AU Wey, HY Phillips, KA McKay, DR Laird, AR Kochunov, P Davis, MD Glahn, DC Blangero, J Duong, TQ Fox, PT AF Wey, Hsiao-Ying Phillips, Kimberley A. McKay, D. Reese Laird, Angela R. Kochunov, Peter Davis, M. Duff Glahn, David C. Blangero, John Duong, Timothy Q. Fox, Peter T. TI Multi-region hemispheric specialization differentiates human from nonhuman primate brain function (vol 219, pg 2187, 2014) SO BRAIN STRUCTURE & FUNCTION LA English DT Correction C1 [Wey, Hsiao-Ying; Phillips, Kimberley A.; McKay, D. Reese; Laird, Angela R.; Kochunov, Peter; Davis, M. Duff; Duong, Timothy Q.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying; McKay, D. Reese; Laird, Angela R.; Kochunov, Peter; Davis, M. Duff; Duong, Timothy Q.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Phillips, Kimberley A.] Trinity Univ, Dept Psychol, San Antonio, TX 78212 USA. [Phillips, Kimberley A.; Kochunov, Peter; Davis, M. Duff; Duong, Timothy Q.; Fox, Peter T.] Texas Biomed Res Inst, Southwest Natl Primate Res Ctr, San Antonio, TX USA. [McKay, D. Reese; Glahn, David C.] Yale Univ, Olin Neuropsychiatry Res Ctr, Inst Living, New Haven, CT USA. [McKay, D. Reese; Glahn, David C.] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. [Laird, Angela R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. [Kochunov, Peter] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Davis, M. Duff] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Blangero, John] Texas Biomed Res Inst, Dept Genet, San Antonio, TX 78245 USA. RP Phillips, KA (reprint author), Trinity Univ, Dept Psychol, 1 Trinity Pl, San Antonio, TX 78212 USA. EM kimberley.phillips@trinity.edu RI Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 NR 1 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD NOV PY 2014 VL 219 IS 6 BP 2195 EP 2195 DI 10.1007/s00429-013-0635-2 PG 1 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA AT4AL UT WOS:000344879200025 ER PT J AU White, SL Hirth, R Mahillo, B Dominguez-Gil, B Delmonico, FL Noel, L Chapman, J Matesanz, R Carmona, M Alvarez, M Nunez, JR Leichtman, A AF White, Sarah L. Hirth, Richard Mahillo, Beatriz Dominguez-Gil, Beatriz Delmonico, Francis L. Noel, Luc Chapman, Jeremy Matesanz, Rafael Carmona, Mar Alvarez, Marina Nunez, Jose R. Leichtman, Alan TI The global diffusion of organ transplantation: trends, drivers and policy implications SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID RENAL REPLACEMENT THERAPY; MEDICAL TECHNOLOGIES; DONATION; EXPERIENCE; DATABASE; TOURISM; CHINA; MODEL AB Rising incomes, the spread of personal insurance, lifestyle factors adding to the burden of illness, ageing populations, globalization and skills transfer within the medical community have increased worldwide demand for organ transplantation. The Global Observatory on Donation and Transplantation, which was built in response to World Health Assembly resolution WHA57.18, has conducted ongoing documentation of global transplantation activities since 2007. In this paper, we use the Global Observatory's data to describe the current distribution of - and trends in - transplantion activities and to evaluate the role of health systems factors and macroeconomics in the diffusion of transplantation technology. We then consider the implications of our results for health policies relating to organ donation and transplantation. Of the World Health Organization's Member States, most now engage in organ transplantation and more than a third performed deceased donor transplantation in 2011. In general, the Member States that engage in organ transplantation have greater access to physician services and greater total health spending per capita than the Member States where organ transplantation is not performed.The provision of deceased donor transplantation was closely associated with high levels of gross national income per capita. There are several ways in which governments can support the ethical development of organ donation and transplantation programmes. Specifically, they can ensure that appropriate legislation, regulation and oversight are in place, and monitor donation and transplantation activities, practices and outcomes. Moreover, they can allocate resources towards the training of specialist physicians, surgeons and transplant coordinators, and implement a professional donor-procurement network. C1 [White, Sarah L.] Univ Sydney, Charles Perkins Ctr, Sydney Med Sch, Sydney, NSW 2006, Australia. [Hirth, Richard] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Mahillo, Beatriz; Dominguez-Gil, Beatriz; Matesanz, Rafael; Carmona, Mar; Alvarez, Marina] Org Nacl Trasplantes, Madrid, Spain. [Delmonico, Francis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Noel, Luc; Nunez, Jose R.] World Hlth Org, Serv Delivery & Safety, Geneva, Switzerland. [Chapman, Jeremy] Westmead Hosp, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia. [Leichtman, Alan] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP White, SL (reprint author), Univ Sydney, Charles Perkins Ctr, Sydney Med Sch, Sydney, NSW 2006, Australia. EM sarah.white@sydney.edu.au FU World Health Organization [001] NR 29 TC 18 Z9 18 U1 2 U2 15 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 EI 1564-0604 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD NOV PY 2014 VL 92 IS 11 BP 826 EP 835 DI 10.2471/BLT.14.137653 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AT9SW UT WOS:000345267300017 PM 25378744 ER PT J AU Wilbur, DC AF Wilbur, David C. TI Digital Pathology: Get on Board-The Train Is Leaving the Station SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID IMAGING-SYSTEM AB The digital revolution clearly is underway, and the new technologies will affect the practice of pathology in general. In the coming years, cytology will be particularly affected by these technologic advances. C1 [Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM dwilbur@partners.org NR 16 TC 3 Z9 3 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD NOV PY 2014 VL 122 IS 11 BP 791 EP 795 DI 10.1002/cncy.21479 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA AT9DO UT WOS:000345228400003 PM 25236488 ER PT J AU Chebib, I Yaeger, K Mino-Kenudson, M Pitman, MB AF Chebib, Ivan Yaeger, Kurt Mino-Kenudson, Mari Pitman, Martha B. TI The Role of Cytopathology and Cyst Fluid Analysis in the Preoperative Diagnosis and Management of Pancreatic Cysts > 3 cm SO CANCER CYTOPATHOLOGY LA English DT Article DE pancreas; cyst; intraductal; mucinous; papillary; neoplasm; cytology; endoscopic ultrasound; fine needle aspiration biopsy ID PAPILLARY MUCINOUS NEOPLASMS; INTERNATIONAL-CONSENSUS-GUIDELINES; FINE-NEEDLE-ASPIRATION; EPITHELIAL ATYPIA; TUMORS; MALIGNANCY; OPERATE AB BACKGROUNDPancreatic cyst size >3 cm is a worrisome rather than high-risk feature for malignancy based on the 2012 International Guidelines for the management of mucinous cysts. The value of cytology in preoperative evaluation and surgical triage is unclear. METHODSAll pancreatic cysts >3 cm resected over a 7-year period were evaluated for clinical, radiologic, and pathologic information. Performance of cytology for the detection of malignancy and surgical triage compared with imaging was assessed. RESULTSThere were 93 histologically confirmed cysts, 52 of which were mucinous and 41 of which were nonmucinous. Of these, 37% were malignant, including 16 nonmucinous malignancies and 18 mucinous cysts (12 with invasive carcinoma, 6 with high-grade dysplasia). Thirty-nine cysts (41% malignant, 59% benign) were not subject to endoscopic ultrasound-fine needle aspiration (EUS-FNA) prior to resection (average size, 6.0 cm). Fifty-four were evaluated by EUS-FNA, with 35 available for review (average size, 5.4 cm). Cytology/cyst fluid analysis had the highest specificity (88.9%) compared with imaging, whereas magnetic resonance imaging (MRI) showed the highest sensitivity (100%). MRI had the highest predictive value for mucinous (100%) versus nonmucinous cysts (100%). MRI and EUS were able to predict malignancy from the presence of high-risk imaging features in all cases. Some benign cases also showed high-risk imaging features on MRI (28.6%), computed tomography (32.3%), and EUS (45.8%). Cytology correctly classified 5 of 6 benign cysts with high-risk imaging as benign. CONCLUSIONSPreoperative evaluation of pancreatic cysts >3 cm is warranted, as many are nonmucinous cysts and not high-grade. Cytology is more specific than imaging for the detection of malignancy in cysts >3 cm. Cancer (Cancer Cytopathol) 2014;122:804-809. (c) 2014 American Cancer Society. Fine-needle aspiration of pancreatic cysts >3 cm adds value to imaging studies, especially when compared with computed tomography. Cytology is more specific for the detection of malignancy than imaging for cysts >3 cm. C1 [Chebib, Ivan] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Chebib, Ivan] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chebib, I (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 125 Warren Bldg,55 Fruit St, Boston, MA 02114 USA. EM ichebib@partners.org NR 27 TC 8 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD NOV PY 2014 VL 122 IS 11 BP 804 EP 809 DI 10.1002/cncy.21460 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA AT9DO UT WOS:000345228400005 PM 25044974 ER PT J AU Allott, EH Howard, LE Cooperberg, MR Kane, CJ Aronson, WJ Terris, MK Amling, CL Freedland, SJ AF Allott, Emma H. Howard, Lauren E. Cooperberg, Matthew R. Kane, Christopher J. Aronson, William J. Terris, Martha K. Amling, Christopher L. Freedland, Stephen J. TI Serum Lipid Profile and Risk of Prostate Cancer Recurrence: Results from the SEARCH Database SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; METABOLIC SYNDROME; HDL CHOLESTEROL; STATIN USE; COHORT; GRADE; ASSOCIATION; PREVENTION; MORTALITY; OBESITY AB Background: Evidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance. Methods: We conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines. Results: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10mg/dl, 1.03; 95% confidence interval (CI), 1.01-1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01-1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41-0.91), respectively. Conclusions: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively. Impact: These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence. (C) 2014 AACR. C1 [Allott, Emma H.; Howard, Lauren E.; Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol, Durham, NC 27710 USA. [Allott, Emma H.] Duke Canc Inst, Canc Prevent Detect & Control Program, Durham, NC USA. [Allott, Emma H.; Howard, Lauren E.; Freedland, Stephen J.] Vet Affairs Med Ctr Durham, Div Urol, Durham, NC USA. [Howard, Lauren E.] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Cooperberg, Matthew R.] UCSF Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA USA. [Kane, Christopher J.] Univ Calif San Diego Hlth Syst, Dept Urol, San Diego, CA USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. RP Freedland, SJ (reprint author), Duke Univ, Sch Med, DUMC 2626,571 Res Dr, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI [5R25-CA126938-03]; NIH [1-R01-CA131235-01A1, 1K24CA160653] FX This study was supported by grants from the NCI (5R25-CA126938-03; to E.H. Allott) and NIH (1-R01-CA131235-01A1 and 1K24CA160653; to S.J. Freedland). NR 33 TC 18 Z9 18 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 NOV PY 2014 VL 23 IS 11 BP 2349 EP 2356 DI 10.1158/1055-9965.EPI-14-0458 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AT9YL UT WOS:000345279600017 PM 25304929 ER PT J AU Zhao, Y Wei, QY Hu, LM Chen, F Hu, ZB Heist, RS Su, L Amos, CI Shen, HB Christiani, DC AF Zhao, Yang Wei, Qingyi Hu, Lingming Chen, Feng Hu, Zhibin Heist, Rebecca S. Su, Li Amos, Christopher I. Shen, Hongbing Christiani, David C. TI Polymorphisms in MicroRNAs Are Associated with Survival in Non-Small Cell Lung Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; PLATINUM-BASED CHEMOTHERAPY; GENETIC-VARIANTS; CLINICAL-OUTCOMES; EXPRESSION; MIRNA; RISK; CHINESE; SNPS AB Background: MicroRNAs (miRNA) play important roles in the regulation of eukaryotic gene expression and are involved in human carcinogenesis. Single-nucleotide polymorphisms (SNP) in miRNA sequence may alter miRNA functions in gene regulation, which, in turn, may affect cancer risk and disease progression. Methods: We conducted an analysis of associations of 142 miRNA SNPs with non-small cell lung cancer (NSCLC) survival using data from a genome-wide association study (GWAS) in a Caucasian population from the Massachusetts General Hospital (Boston, MA) including 452 early-stage and 526 late-stage NSCLC cases. Replication analyses were further performed in two external populations, one Caucasian cohort from The University of Texas MD Anderson Cancer Center (Houston, TX) and one Han Chinese cohort from Nanjing, China. Results: We identified seven significant SNPs in the discovery set. Results from the independent Caucasian cohort demonstrated that the C allele of rs2042253 (hsa-miRNA-5197) was significantly associated with decreased risk for death among the patients with late-stage NSCLC (discovery set: HR, 0.80; P = 0.007; validation set: HR, 0.86; P = 0.035; combined analysis: HR, 0.87; P = 0.007). Conclusions: These findings provide evidence that some miRNA SNPs are associated with NSCLC survival and can be used as predictive biomarkers. Impact: This study provided an estimate of outcome probability for survival experience of patients with NSCLC, which demonstrates that genetic factors, as well as classic nongenetic factors, may be used to predict individual outcome. (C)2014 AACR. C1 [Zhao, Yang; Hu, Lingming; Chen, Feng; Hu, Zhibin; Shen, Hongbing; Christiani, David C.] Nanjing Med Univ, Nanjing, Jiangsu, Peoples R China. [Wei, Qingyi] Duke Univ, Duke Canc Inst, Durham, NC USA. [Heist, Rebecca S.; Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Room 1407,Bldg 1,665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU NIH [R01CA092824, P50CA090578, P30ES000002]; Natural Scientific Funding of China [NSFC] [30901232, 81373102, 81072389]; Natural Scientific Funding of China [NIH] [5R01CA092824]; Scientific Research Grants for High Education of Jiangsu Province [12KJB310003]; National Science Foundation for Distinguished Young Scholars of China [81225020] FX This study was supported by NIH grants (R01CA092824, P50CA090578, and P30ES000002 to D.C. Christiani), the Natural Scientific Funding of China [NSFC; 30901232, 81373102, and NIH grants 5R01CA092824 (PI, D. C. Christiani) to Y. Zhao; NSFC 81072389 to F. Chen], Scientific Research Grants for High Education of Jiangsu Province (12KJB310003 to Y. Zhao), and The National Science Foundation for Distinguished Young Scholars of China (81225020 to Z. Hu). NR 54 TC 9 Z9 9 U1 4 U2 17 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 NOV PY 2014 VL 23 IS 11 BP 2503 EP 2511 DI 10.1158/1055-9965.EPI-14-0389 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AT9YL UT WOS:000345279600034 PM 25103824 ER PT J AU Epplein, M Bostick, RM Mu, LN Ogino, S Braithwaite, D Kanetsky, PA AF Epplein, Meira Bostick, Roberd M. Mu, Lina Ogino, Shuji Braithwaite, Dejana Kanetsky, Peter A. TI Challenges and Opportunities in International Molecular Cancer Prevention Research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID COLORECTAL-CANCER; PATHOLOGICAL EPIDEMIOLOGY; MICROSATELLITE INSTABILITY; PIK3CA MUTATION; SCIENCE; SURVIVAL; SMOKING; FIELD; RISK AB The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries. (C) 2014 AACR. C1 [Epplein, Meira] Vanderbilt Univ, Div Epidemiol, Sch Med, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA. [Epplein, Meira] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. [Bostick, Roberd M.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Bostick, Roberd M.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Mu, Lina] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Braithwaite, Dejana] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kanetsky, Peter A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. RP Epplein, M (reprint author), Vanderbilt Univ, Div Epidemiol, Sch Med, 2525 West End Ave,6th Floor, Nashville, TN 37203 USA. EM meira.epplein@vanderbilt.edu OI Epplein, Meira/0000-0001-5646-6430 FU National Cancer Institute, NIH [K07 CA151782, R01 C174853, R01 CA151993, P30 CA138292]; National Institute of Environmental Health Science, NIH [R01 ES018846] FX M. Epplein was supported by the National Cancer Institute, NIH (K07 CA151782 and R01 C174853). S. Ogino was funded in part by the National Cancer Institute, NIH (R01 CA151993). R.M. Bostick was supported in part by the National Cancer Institute, NIH (P30 CA138292). L. Mu was funded by the National Institute of Environmental Health Science, NIH (R01 ES018846). NR 30 TC 9 Z9 9 U1 2 U2 7 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 NOV PY 2014 VL 23 IS 11 BP 2613 EP 2617 DI 10.1158/1055-9965.EPI-14-0848 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AT9YL UT WOS:000345279600051 PM 25277796 ER PT J AU Vergallo, R Papafaklis, MI Yonetsu, T Bourantas, CV Andreou, I Wang, Z Fujimoto, JG McNulty, I Lee, H Biasucci, LM Crea, F Feldman, CL Michalis, LK Stone, PH Jang, IK AF Vergallo, Rocco Papafaklis, Michail I. Yonetsu, Taishi Bourantas, Christos V. Andreou, Ioannis Wang, Zhao Fujimoto, James G. McNulty, Iris Lee, Hang Biasucci, Luigi M. Crea, Filippo Feldman, Charles L. Michalis, Lampros K. Stone, Peter H. Jang, Ik-Kyung TI Endothelial Shear Stress and Coronary Plaque Characteristics in Humans Combined Frequency-Domain Optical Coherence Tomography and Computational Fluid Dynamics Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; optical coherence tomography; shear stress ID ATHEROSCLEROTIC PLAQUE; NATURAL-HISTORY; WALL SHEAR; INTRAVASCULAR ULTRASOUND; ARTERIES; LESIONS; QUANTIFICATION; PROGRESSION; THICKNESS; RUPTURE AB Background-Despite the exposure of the entire vasculature to the atherogenic effects of systemic risk factors, atherosclerotic plaques preferentially develop at sites with disturbed flow. This study aimed at exploring in vivo the relationship between local endothelial shear stress (ESS) and coronary plaque characteristics in humans using computational fluid dynamics and frequency-domain optical coherence tomography. Methods and Results-Three-dimensional coronary artery reconstruction was performed in 21 patients (24 arteries) presenting with acute coronary syndrome using frequency-domain optical coherence tomography and coronary angiography. Each coronary artery was divided into sequential 3-mm segments and analyzed for the assessment of local ESS and plaque characteristics. A total of 146 nonculprit segments were evaluated. Compared with segments with higher ESS [>= 1 Pascal (Pa)], those with low ESS (<1 Pa) showed higher prevalence of lipid-rich plaques (37.5% versus 20.0%; P=0.019) and thin-cap fibroatheroma (12.5% versus 2.0%; P=0.037). Overall, lipid plaques in segments with low ESS had thinner fibrous cap (115 mu m [63-166] versus 170 mu m [107-219]; P=0.004) and higher macrophage density (normalized standard deviation: 8.4% [4.8-12.6] versus 6.2% [4.2-8.8]; P=0.017). Segments with low ESS showed more superficial calcifications (minimum calcification depth: 93 mu m [50-140] versus 152 mu m [105-258]; P=0.049) and tended to have higher prevalence of spotty calcifications (26.0% versus 12.0%; P=0.076). Conclusions-Coronary regions exposed to low ESS are associated with larger lipid burden, thinner fibrous cap, and higher prevalence of thin-cap fibroatheroma in humans. Frequency-domain optical coherence tomography-based assessment of ESS and wall characteristics may be useful in identifying vulnerable coronary regions. C1 [Vergallo, Rocco; Yonetsu, Taishi; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr,Dept Med, Boston, MA USA. [Papafaklis, Michail I.; Andreou, Ioannis; Feldman, Charles L.; Stone, Peter H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA. [Bourantas, Christos V.] Erasmus MC, Dept Intervent Cardiol, Rotterdam, Netherlands. [Wang, Zhao; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Wang, Zhao; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Biasucci, Luigi M.; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, I-00168 Rome, Italy. [Michalis, Lampros K.] Univ Ioannina, Sch Med, Dept Cardiol, GR-45110 Ioannina, Greece. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org RI Wang, Zhao/E-3515-2015; OI Wang, Zhao/0000-0002-3628-5699; Papafaklis, Michail/0000-0002-5646-0378; biasucci, luigi m/0000-0002-6921-6497; Andreou, Ioannis/0000-0002-2912-1928 FU LightLab Imaging/St. Jude Medical; Italian Society of Cardiology; Enrico ed Enrica Sovena Foundation; George D. Behrakis Research Fellowship; Dr John Nam Research Fellowship FX This work was supported by LightLab Imaging/St. Jude Medical (I.K. Jang); the 2013 Italian Society of Cardiology Award for Research Abroad, and the Enrico ed Enrica Sovena Foundation (R. Vergallo); the George D. Behrakis Research Fellowship (M.I. Papafaklis and I. Andreou); the Dr John Nam Research Fellowship, and the generous support of Mr and Mrs Michael A. Park. NR 28 TC 21 Z9 23 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2014 VL 7 IS 6 BP 905 EP 911 DI 10.1161/CIRCIMAGING.114.001932 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AU0CA UT WOS:000345289500010 PM 25190591 ER PT J AU Taqueti, VR Di Carli, MF Jerosch-Herold, M Sukhova, GK Murthy, VL Folco, EJ Kwong, RY Ozaki, CK Belkin, M Nahrendorf, M Weissleder, R Libby, P AF Taqueti, Viviany R. Di Carli, Marcelo F. Jerosch-Herold, Michael Sukhova, Galina K. Murthy, Venkatesh L. Folco, Eduardo J. Kwong, Raymond Y. Ozaki, C. Keith Belkin, Michael Nahrendorf, Matthias Weissleder, Ralph Libby, Peter TI Increased Microvascularization and Vessel Permeability Associate With Active Inflammation in Human Atheromata SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerotic plaque; inflammation; molecular imaging; neovascularization ID POSITRON-EMISSION-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE INFLAMMATION; GENE-EXPRESSION; F-18-FDG PET; MACROPHAGES; CELLS; QUANTIFICATION; THERAPY; DENSITY; DISEASE AB Background-Studies have shown the feasibility of imaging plaques with 2-deoxy-2-[F-18]fluoroglucose (FDG) positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging with inconsistent results. We sought to investigate the relationship between markers of inflammatory activation, plaque microvascularization, and vessel wall permeability in subjects with carotid plaques using a multimodality approach combining FDG positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging, and histopathology. Methods and Results-Thirty-two subjects with carotid stenoses underwent noninvasive imaging with FDG positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging, 46.9% (n=15) before carotid endarterectomy. We measured FDG uptake (target: background ratio [TBR]) by positron emission tomography and K-trans (reflecting microvascular permeability and perfusion) by magnetic resonance imaging and correlated imaging with immunohistochemical markers of macrophage content (CD68), activated inflammatory cells (major histocompatibility complex class II), and microvessels (CD31) in plaque and control regions. TBR and K-trans correlated significantly with tertiles of CD68(+) (P=0.009 and P=0.008, respectively), major histocompatibility complex class II+ (P=0.003 and P<0.001, respectively), and CD31(+) (P=0.004 and P=0.008, respectively). Regions of plaques were associated with increased CD68(+) (P=0.002), major histocompatibility complex class II+ (P=0.002), CD31(+) (P=0.02), TBR (P<0.0001), and K-trans (P<0.0001), as compared with those without plaques. Microvascularization correlated with macrophage content (r(s)=0.52; P=0.007) and inflammatory activity (r(s)=0.68; P=0.0001) and TBR correlated with K-trans (r(s)=0.53; P<0.0001). In multivariable mixed linear regression modeling, TBR remained independently associated with K-trans (beta[SE], 2.68[0.47]; P<0.0001). Conclusions-Plaque regions with active inflammation, as determined by macrophage content and major histocompatibility complex class II expression, showed increased FDG uptake, which correlated with increased K-trans and microvascularization. The correlation between K-trans and TBR was moderate, direct, highly significant, and independent of clinical symptoms and plaque luminal severity. C1 [Taqueti, Viviany R.; Di Carli, Marcelo F.; Sukhova, Galina K.; Folco, Eduardo J.; Kwong, Raymond Y.; Ozaki, C. Keith; Belkin, Michael; Libby, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Heart & Vasc Ctr, Boston, MA 02115 USA. [Taqueti, Viviany R.; Di Carli, Marcelo F.; Jerosch-Herold, Michael; Kwong, Raymond Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Radiol, Noninvas Cardiovasc Imaging Program,Nucl Med & Mo, Boston, MA 02115 USA. [Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02115 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Div Nucl Med, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Div Cardiothorac Imaging, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Cardiothorac Imaging, Ann Arbor, MI 48109 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Libby, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Heart & Vasc Ctr, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu RI Murthy, Venkatesh/B-3448-2013 OI Murthy, Venkatesh/0000-0002-7901-1321 FU Donald W. Reynolds Foundation FX This research was supported by the Donald W. Reynolds Foundation. NR 28 TC 19 Z9 19 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD NOV PY 2014 VL 7 IS 6 BP 920 EP + DI 10.1161/CIRCIMAGING.114.002113 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AU0CA UT WOS:000345289500012 PM 25170063 ER PT J AU Jhund, PS Claggett, BL Voors, AA Zile, MR Packer, M Pieske, BM Kraigher-Krainer, E Shah, AM Prescott, MF Shi, V Lefkowitz, M McMurray, JJV Solomon, SD AF Jhund, Pardeep S. Claggett, Brian L. Voors, Adriaan A. Zile, Michael R. Packer, Milton Pieske, Burkert M. Kraigher-Krainer, Elisabeth Shah, Amil M. Prescott, Margaret F. Shi, Victor Lefkowitz, Marty McMurray, John J. V. Solomon, Scott D. CA PARAMOUNT Investigators TI Elevation in High-Sensitivity Troponin T in Heart Failure and Preserved Ejection Fraction and Influence of Treatment With the Angiotensin Receptor Neprilysin Inhibitor LCZ696 SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; neprilysin; troponin T ID SYSTOLIC FUNCTION; NATRIURETIC PEPTIDE; PREVALENCE; TRIAL; HYPERTROPHY; ASSOCIATION; RELAXATION; BIOMARKERS; DEATH; RISK AB Background-Elevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction, but less is known about the association in heart failure with preserved ejection fraction. Methods and Results-We examined the prevalence of elevated high-sensitivity troponin T (hs-TnT) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan. We assessed the association between hs-TnT and cardiac structure and function, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks. Elevated hs-TnT in the myocardial injury range (>0.014 mu g/L) was found in 55% of patients and was associated with older age, history of diabetes mellitus, higher N-terminal pro-brain natriuretic peptide, lower estimated glomerular filtration rate, and larger left atrial size, left ventricular volume, and mass. LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks (12% reduction; P=0.05) and at 36 weeks (14% reduction; P=0.03) compared with valsartan. Conclusions-Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure, function, and elevated baseline N-terminal pro-brain natriuretic peptide. Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction. C1 [Jhund, Pardeep S.; Claggett, Brian L.; Shah, Amil M.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Jhund, Pardeep S.; McMurray, John J. V.] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Zile, Michael R.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC USA. [Packer, Milton] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Pieske, Burkert M.; Kraigher-Krainer, Elisabeth] Med Univ Graz, Dept Cardiol, Graz, Austria. [Prescott, Margaret F.; Shi, Victor; Lefkowitz, Marty] Novartis Pharmaceut, E Hanover, NJ USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; mcmurray, john/0000-0002-6317-3975; Jhund, Pardeep/0000-0003-4306-5317 FU Novartis Pharmaceuticals, East Hanover, NJ FX The PARAMOUNT trial was funded by Novartis Pharmaceuticals, East Hanover, NJ. NR 28 TC 21 Z9 23 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2014 VL 7 IS 6 BP 953 EP U129 DI 10.1161/CIRCHEARTFAILURE.114.001427 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU0BS UT WOS:000345288800013 PM 25277997 ER PT J AU Oluleye, OW Rector, TS Win, S McMurray, JJV Zile, MR Komajda, M McKelvie, RS Massie, B Carson, PE Anand, IS AF Oluleye, Oludamilola W. Rector, Thomas S. Win, Sithu McMurray, John J. V. Zile, Michael R. Komajda, Michel McKelvie, Robert S. Massie, Barry Carson, Peter E. Anand, Inder S. TI History of Atrial Fibrillation as a Risk Factor in Patients With Heart Failure and Preserved Ejection Fraction SO CIRCULATION-HEART FAILURE LA English DT Article DE atrial fibrillation; heart failure; preserved ejection fraction; prognosis; stroke ID VENTRICULAR SYSTOLIC DYSFUNCTION; ACC/AHA/ESC 2006 GUIDELINES; EUROPEAN-SOCIETY; TASK-FORCE; MANAGEMENT; STROKE; ASSOCIATION; MORTALITY; INSIGHTS; MORBIDITY AB Background-Atrial fibrillation (AFib) is common in heart failure (HF) with preserved ejection fraction (HFpEF). Current AFib stroke risk prediction models include the presence of HF but do not specifically include HFpEF as a risk factor. Whether a history of AFib should be used to identify patients with HFpEF who are at risk has not been established. Methods and Results-Baseline characteristics and outcomes of patients with HFpEF in the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial were analyzed in relation to AFib. At baseline, 1209 (29.3%) had a history of AFib. Of these 557 (13.5%) had history of AFib alone, whereas 670 (16.2%) had both a history and AFib on ECG; 2901 (70.3%) had neither. There were no significant differences in the risk of stroke between the 2 groups with a history of AFib who did or did not have AFib present on baseline ECG. During a median follow-up of 53 months, a fatal or nonfatal stroke occurred in 6.5% (79/1209) patients with history of AFib compared with 3.9% (114/2901) with no AFib. Having a history of AFib was independently associated with higher risk of stroke (hazard ratio, 2.2; 95% confidence interval, 1.6-3.2; P<0.0001) compared with those with no history of AFib. Conclusions-In patients with HFpEF, a history of AFib was common and independently associated with increased risk of stroke, regardless of whether AFib was present on ECG. Patients with HFpEF and a history of AFib should be considered at risk. Further studies are needed to determine whether this risk can be safely reduced. C1 [Oluleye, Oludamilola W.; Rector, Thomas S.; Win, Sithu; Anand, Inder S.] VA Med Ctr, Dept Med, Minneapolis, MN 55417 USA. [Oluleye, Oludamilola W.; Rector, Thomas S.; Win, Sithu; Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. [McMurray, John J. V.] British Heart Fdn, Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Zile, Michael R.] Med Univ S Carolina, Dept Med, RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Inst Cardiol, Paris, France. [McKelvie, Robert S.] McMaster Univ, Dept Med, Populat Hlth Res Inst, Hamilton, ON, Canada. [Massie, Barry] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA USA. [Carson, Peter E.] Washington VAMC, Dept Med, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. RP Anand, IS (reprint author), VA Med Ctr, One Vet Dr, Minneapolis, MN 55417 USA. EM anand001@umn.edu OI mcmurray, john/0000-0002-6317-3975 FU Bristol-Myers Squibb FX Bristol-Myers Squibb sponsored the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-PRESERVE). Dr Rector was supported by resources and facilities of the Minneapolis VA Healthcare System. The views expressed herein do not necessarily represent the views of the Department of Veterans Affairs or the US Government. NR 22 TC 11 Z9 11 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2014 VL 7 IS 6 BP 960 EP 966 DI 10.1161/CIRCHEARTFAILURE.114.001523 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU0BS UT WOS:000345288800014 PM 25225241 ER PT J AU Mane, M O'Neill, AC Tirumani, SH Shi, M Shinagare, AB Fisher, DC AF Mane, Mayuresh O'Neill, Ailbhe C. Tirumani, Sree Harsha Shi, Min Shinagare, Atul B. Fisher, David C. TI Thyroid lymphoma on a background of Hashimoto's thyroiditis: PET/CT appearances SO CLINICAL IMAGING LA English DT Article DE Thyroid; Lymphoma; PET/CT ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; STAGE IE; GLAND; PROGNOSIS AB Primary thyroid lymphoma is a rare thyroid tumor accounting for only 5% of all thyroid malignancies. It is more common in patients with a background history of chronic thyroiditis. PET/CT is helpful in the initial staging and for follow up to assess treatment response. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mane, Mayuresh; O'Neill, Ailbhe C.; Tirumani, Sree Harsha; Shinagare, Atul B.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shi, Min] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Fisher, David C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP O'Neill, AC (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM aoneill9@partners.org NR 14 TC 1 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD NOV-DEC PY 2014 VL 38 IS 6 BP 864 EP 867 DI 10.1016/j.clinimag.2014.03.004 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT3MR UT WOS:000344839400016 PM 24679651 ER PT J AU Keshaviah, A Edkins, K Hastings, ER Krishna, M Franko, DL Herzog, DB Thomas, JJ Murray, HB Eddy, KT AF Keshaviah, Aparna Edkins, Katherine Hastings, Elizabeth R. Krishna, Meera Franko, Debra L. Herzog, David B. Thomas, Jennifer J. Murray, Helen B. Eddy, Kamryn T. TI Re-examining premature mortality in anorexia nervosa: A meta-analysis redux SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID LONG-TERM MORTALITY; 10-YEAR FOLLOW-UP; EATING-DISORDERS; OUTCOME PREDICTORS; PROGNOSTIC-FACTORS; SURVIVAL; DENMARK; DEATH; INTERMEDIATE; SUICIDE AB Anorexia nervosa (AN) is reported to have the highest premature mortality of any psychiatric disorder, but recent meta-analyses may have inflated estimates. We sought to re-estimate mortality after methodological corrections and to identify predictors of mortality. We included 41 cohorts from 40 peer-reviewed studies published between 1966 and 2010. Methods included double data extraction, log-linear regression with an over-dispersed Poisson model, and all-cause and suicide-specific standardized mortality ratios (SMRs), with 95% Poisson confidence intervals. Participants with AN were 5.2 [3.7-7.5] times more likely to die prematurely from any cause, and 18.1 [11.5-28.7] times more likely to die by suicide than 15-34 year old females in the general population. Our estimates were 10% and 49% lower, respectively, than previously reported SMRs. Risk of premature mortality was highest in studies with older participants, although confounding by treatment was present. Gender, ascertainment, and diagnostic criteria also impacted risk. (C) 2014 Elsevier Inc. All rights reserved. C1 [Keshaviah, Aparna; Edkins, Katherine; Hastings, Elizabeth R.; Krishna, Meera; Franko, Debra L.; Herzog, David B.; Thomas, Jennifer J.; Murray, Helen B.; Eddy, Kamryn T.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Hastings, Elizabeth R.] Amundsen Grp, Burlington, MA USA. [Franko, Debra L.] Northeastern Univ, Boston, MA 02115 USA. [Herzog, David B.; Thomas, Jennifer J.; Eddy, Kamryn T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl,Suite 200, Boston, MA 02114 USA. EM keddy@mgh.harvard.edu NR 69 TC 21 Z9 21 U1 4 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV PY 2014 VL 55 IS 8 BP 1773 EP 1784 DI 10.1016/j.comppsych.2014.07.017 PG 12 WC Psychiatry SC Psychiatry GA AT5HS UT WOS:000344975200001 PM 25214371 ER PT J AU Farmer, AS Gros, DF McCabe, RE Antony, MM AF Farmer, Antonina S. Gros, Daniel F. McCabe, Randi E. Antony, Martin M. TI Clinical predictors of diagnostic status in individuals with social anxiety disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID NATIONAL COMORBIDITY SURVEY; NEGATIVE EVALUATION SCALE; STRESS SCALES; PSYCHOMETRIC PROPERTIES; SURVEY REPLICATION; MOOD DISORDERS; PHOBIA; DEPRESSION; FEAR; UNCERTAINTY AB Objective: In psychiatric patients, comorbidity tends to be the rule, rather than the exception. This is especially true for patients with social anxiety disorder (SAD), but research on the implications of diagnostic status has been limited This study aimed to examine the frequency of SAD as: (1) the only diagnosis, (2) a principal diagnosis with comorbid conditions, or (3) a comorbid condition when another diagnosis is principal in a treatment-seeking population. The study also sought to identify clinical features that distinguish people in these diagnostic groups. Method: Our sample included 684 adult participants presenting for treatment in a specialty clinic for anxiety disorders. We established diagnoses with semistructured clinical interviews, and participants completed self-report measures of social anxiety, associated transdiagnostic symptoms, general distress, and impairment due to psychological difficulties. We analyzed group differences and investigated predictors of principal SAD diagnosis. Results: Over half of participants reported symptoms that met criteria for a SAD diagnosis (51.8%). Of these, 8.8% had SAD only (no comorbid psychiatric diagnoses), 48.6% had multiple conditions with SAD as the principal diagnosis, and 42.7% had multiple conditions with SAD as an additional diagnosis. SAD-only was associated with less severe impairment and transdiagnostic symptoms. Among participants with comorbid conditions, greater fear of negative evaluation, behavioral avoidance, and coping with substances predicted a principal SAD diagnosis, whereas SAD as an additional diagnosis was more likely when participants presented with greater anxiety sensitivity, intolerance of uncertainty, and thought avoidance. Conclusions: Our fmdings suggest that principal diagnosis of SAD is common in a treatment-seeking population and is associated with more severe disorder-specific symptoms and less severe transdiagnostic features related to anxiety. Implications for assessment and treatment planning in clinical practice are discussed. (C) 2014 Elsevier Inc. All rights reserved. C1 [Farmer, Antonina S.; Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Farmer, Antonina S.; Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [McCabe, Randi E.] St Josephs Healthcare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. [McCabe, Randi E.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Antony, Martin M.] Ryerson Univ, Dept Psychol, Toronto, ON, Canada. RP Farmer, AS (reprint author), Randolph Macon Coll, Dept Psychol, Ashland, VA 23005 USA. EM antoninafarmer@rmc.edu FU Department of Veteran Affairs Clinical Sciences Research and Development Career Development Award [CX000845]; Ralph H. Johnson VAMC FX This study is supported by Department of Veteran Affairs Clinical Sciences Research and Development Career Development Award CX000845 (PI: Gros). This material is the result of work supported with resources and the use of facilities at the Ralph H. Johnson VAMC. 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 or the United States government. Submitted for publication to Comprehensive Psychiatry (May 2014). NR 44 TC 0 Z9 0 U1 9 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV PY 2014 VL 55 IS 8 BP 1906 EP 1913 DI 10.1016/j.comppsych.2014.07.019 PG 8 WC Psychiatry SC Psychiatry GA AT5HS UT WOS:000344975200016 PM 25236968 ER PT J AU Ogbechie, OA Paul, S Schalock, PC AF Ogbechie, Oluwatobi A. Paul, Suchismita Schalock, Peter C. TI A Technique for Identifying Vicryl Suture Hypersensitivity SO DERMATITIS LA English DT Editorial Material C1 [Ogbechie, Oluwatobi A.; Paul, Suchismita; Schalock, Peter C.] Harvard Univ, Sch Med, Boston, MA USA. [Schalock, Peter C.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR 622,55 Fruit St, Boston, MA 02114 USA. EM schalock.prof@gmail.com NR 5 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1710-3568 EI 2162-5220 J9 DERMATITIS JI Dermatitis PD NOV-DEC PY 2014 VL 25 IS 6 BP 370 EP 371 DI 10.1097/DER.0000000000000085 PG 2 WC Dermatology SC Dermatology GA AT7QC UT WOS:000345131600007 PM 25384227 ER PT J AU Schuman-Olivier, Z Greene, MC Bergman, BG Kelly, JF AF Schuman-Olivier, Zev Greene, M. Claire Bergman, Brandon G. Kelly, John F. TI Is residential treatment effective for opioid use disorders? A longitudinal comparison of treatment outcomes among opioid dependent, opioid misusing, and non-opioid using emerging adults with substance use disorder SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opioid dependence; Emerging adult; 12-Step residential; Office-based opioid treatment; Youth; Abstinence ID YOUNG-ADULTS; DRUG-USE; PSYCHOMETRIC VALIDATION; BUPRENORPHINE TREATMENT; DEPRESSIVE SYMPTOMS; ADDICTION TREATMENT; QUESTIONNAIRE LDQ; MINNESOTA MODEL; SELF-EFFICACY; ADOLESCENTS AB Background: Opioid misuse and dependence rates among emerging adults have increased substantially. While office-based opioid treatments (e.g., buprenorphine/naloxone) have shown overall efficacy, discontinuation rates among emerging adults are high. Abstinence-based residential treatment may serve as a viable alternative, but has seldom been investigated in this age group. Methods: Emerging adults attending 12-step-oriented residential treatment (N=292; 18-24 years, 74% male, 95% White) were classified into opioid dependent (OD; 25%), opioid misuse (OM; 20%), and no opiate use (NO; 55%) groups. Paired t-tests and ANOVAs tested baseline differences and whether groups differed in their during-treatment response. Longitudinal multilevel models tested whether groups differed on substance use outcomes and treatment utilization during the year following the index treatment episode. Results: Despite a more severe clinical profile at baseline among OD, all groups experienced similar during-treatment increases on therapeutic targets (e.g., abstinence self-efficacy), while OD showed a greater decline in psychiatric symptoms. During follow-up relative to OM, both NO and OD had significantly greater Percent Days Abstinent, and significantly less cannabis use. OD attended significantly more outpatient treatment sessions than OM or NO; 29% of OD was completely abstinent at 12-month follow-up. Conclusions: Findings here suggest that residential treatment may be helpful for emerging adults with opioid dependence. This benefit may be less prominent, though, among non-dependent opioid misusers. Randomized trials are needed to compare more directly the relative benefits of outpatient agonist-based treatment to abstinence-based, residential care in this vulnerable age-group, and to examine the feasibility of an integrated model. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Schuman-Olivier, Zev; Bergman, Brandon G.; Kelly, John F.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Schuman-Olivier, Zev; Greene, M. Claire; Bergman, Brandon G.; Kelly, John F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schuman-Olivier, Zev] Cambridge Hlth Alliance, Cambridge, MA USA. RP Schuman-Olivier, Z (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Outpatient Addict Serv,Cambridge Hlth Alliance, Cambridge, MA 02138 USA. EM zschuman@cha.harvard.edu OI Schuman-Olivier, Zev/0000-0001-9216-2039 FU National Institute of Alcohol Abuse and Alcoholism [R21AA018185-02] FX This research was supported by grant funding from the National Institute of Alcohol Abuse and Alcoholism (R21AA018185-02) and by anonymous donations to the Hazelden Foundation. This work is solely the responsibility of the authors and the funding agencies had no role in the conception or execution of this work nor in the report presented here. NR 50 TC 1 Z9 1 U1 3 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2014 VL 144 BP 178 EP 185 DI 10.1016/j.drugalcdep.2014.09.009 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AT8SE UT WOS:000345201500021 PM 25267606 ER PT J AU Dubin, RF Beatty, AL Teerlink, JR Schiller, NB Alokozai, D Johansen, KL AF Dubin, Ruth F. Beatty, Alexis L. Teerlink, John R. Schiller, Nelson B. Alokozai, Dean Johansen, Kirsten L. TI Associations of Tissue Doppler Imaging with NT-proBNP and hs-TnT: A Pilot Study in End-Stage Renal Disease SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE Doppler tissue imaging; end-stage renal disease ID CARDIAC TROPONIN-T; VENTRICULAR DIASTOLIC FUNCTION; CHRONIC-HEMODIALYSIS PATIENTS; PRESERVED EJECTION FRACTION; C-REACTIVE PROTEIN; NATRIURETIC PEPTIDE; HEART-FAILURE; FILLING PRESSURES; ALL-CAUSE; DYSFUNCTION AB BackgroundDiastolic dysfunction is common and associated with higher mortality in the end-stage renal disease (ESRD) population. E/E, a measure derived from tissue Doppler imaging (TDI), is a correlate of left ventricular (LV) filling pressures. E/E may be viewed as a confirmatory marker of diastolic dysfunction, but it is not routinely used to quantify diastolic dysfunction. Whether E/E is associated with N-terminal brain natriuretic peptide (NT-proBNP) or high sensitivity troponin T (hs-TnT) in this population is not known. MethodsWe performed echocardiograms and serology prior to the 2nd or 3rd dialysis session of the week on 35 chronic hemodialysis patients. We compared TDI parameters (E/E and E alone), traditional categories of diastolic function (normal, impaired, pseudonormal or restrictive), and ejection fraction (EF) as potential predictors of the outcomes NT-proBNP and hs-TnT. ResultsHigher E/E was associated with higher NT-proBNP (rho 0.48, P=0.004) and hs-TnT (rho 0.37, P=0.03). EF did not have statistically significant associations with NT-proBNP (rho -0.2, P=0.4) or hs-TnT (rho -0.24, P=0.16). As compared to patients with normal diastolic function, those with impaired or pseudonormal filling patterns did not have significantly different levels of NT-proBNP (P=0.46); patients in traditional categories of worsened diastolic function actually had lower hs-TnT (P=0.02). The associations of E/E with higher NT-proBNP and hs-TnT persisted after multivariate adjustment for EF, LV mass, and volume status. ConclusionsTissue Doppler imaging may be more useful in evaluating cardiac function than traditional measures of diastolic dysfunction in the ESRD population. C1 [Dubin, Ruth F.; Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med Nephrol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Beatty, Alexis L.; Teerlink, John R.; Schiller, Nelson B.] Univ Calif San Francisco, Dept Med Cardiol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Alokozai, Dean] Cardiocore, San Francisco, CA USA. RP Dubin, RF (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM ruth.dubin@ucsf.edu FU University of California San Francisco Academic Senate, San Francisco, CA; Research Evaluation and Allocation Committee in the University of California San Francisco, School of Medicine Dean's Office, San Francisco, CA; National Institute of Diabetes and Digestive and Kidney Diseases [1K24-DK085153-02, 1K23-DK092354-01A1]; UCSF Clinical and Translational Science Institute [UL1 TR000004.4]; Roche Diagnostics Corporation, Indianapolis FX Funding for this project came from the following sources. 1. Individual Investigator Grant, University of California San Francisco Academic Senate, San Francisco, CA 2. Grant Huntington Fund provided by the Research Evaluation and Allocation Committee in the University of California San Francisco, School of Medicine Dean's Office, San Francisco, CA. 3. National Institute of Diabetes and Digestive and Kidney Diseases, 1K24-DK085153-02 4. National Institute of Diabetes and Digestive and Kidney Diseases, 1K23-DK092354-01A1 5. UCSF Clinical and Translational Science Institute Grant Number UL1 TR000004.4. Roche Diagnostics Corporation, Indianapolis, Indiana supplied reagents for the NT-proBNP and hs-TnT assays, but did not provide study funding. Conflict of Interest: Nelson Schiller is a consultant to Cardiocore for projects unrelated to the current manuscript. NR 28 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 EI 1540-8175 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD NOV PY 2014 VL 31 IS 10 BP 1205 EP 1212 DI 10.1111/echo.12552 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT3ST UT WOS:000344854600014 PM 24828699 ER PT J AU Akama-Garren, EH Bianchi, MT Leveroni, C Cole, AJ Cash, SS Westover, MB AF Akama-Garren, Elliot H. Bianchi, Matt T. Leveroni, Catherine Cole, Andrew J. Cash, Sydney S. Westover, M. Brandon TI Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: A decision analysis SO EPILEPSIA LA English DT Article DE Anterior temporal lobectomy; Verbal memory decline; Quality of life; Markov process ID QUALITY-OF-LIFE; VERBAL MEMORY; FOLLOW-UP; LOBECTOMY; SURGERY; DECLINE; PERFORMANCE; MORTALITY; SEIZURES; DEFICITS AB ObjectivesAnterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. MethodsWe constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. ResultsFor patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. SignificanceOur decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis. C1 [Akama-Garren, Elliot H.] MIT, Dept Biol, Cambridge, MA USA. [Bianchi, Matt T.; Leveroni, Catherine; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mwestover@partners.org FU NINDS NIH HHS [K23 NS090900] NR 40 TC 4 Z9 5 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD NOV PY 2014 VL 55 IS 11 BP 1844 EP 1853 DI 10.1111/epi.12790 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AT9DE UT WOS:000345227400027 PM 25244498 ER PT J AU Hermann, B Schachter, SC AF Hermann, Bruce Schachter, Steven C. TI Introduction to the "15th Anniversary Issue" of Epilepsy & Behavior SO EPILEPSY & BEHAVIOR LA English DT Editorial Material C1 [Hermann, Bruce] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53706 USA. [Schachter, Steven C.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. [Schachter, Steven C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schachter, Steven C.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Schachter, Steven C.] Consortia Improving Med Innovat & Technol, Minneapolis, MN USA. RP Hermann, B (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53706 USA. EM hermann@neurology.wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2014 VL 40 BP 1 EP 1 DI 10.1016/j.yebeh.2014.10.008 PG 1 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AT9FO UT WOS:000345233600001 PM 25458184 ER PT J AU Schachter, SC AF Schachter, Steven C. TI A brief history of Epilepsy & Behavior SO EPILEPSY & BEHAVIOR LA English DT Editorial Material C1 [Schachter, Steven C.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. [Schachter, Steven C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schachter, Steven C.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Schachter, Steven C.] Consortia Improving Med Innovat & Technol, Minneapolis, MN USA. RP Schachter, SC (reprint author), 165 Cambridge St,Suite 702, Boston, MA 02114 USA. EM sschacht@bidmc.harvard.edu NR 11 TC 2 Z9 2 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2014 VL 40 BP 4 EP 7 DI 10.1016/j.yebeh.2014.10.013 PG 4 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AT9FO UT WOS:000345233600003 ER PT J AU Kumbhani, DJ Steg, PG Cannon, CP Eagle, KA Smith, SC Goto, S Ohman, EM Elbez, Y Sritara, P Baumgartner, I Banerjee, S Creager, MA Bhatt, DL AF Kumbhani, Dharam J. Steg, Ph Gabriel Cannon, Christopher P. Eagle, Kim A. Smith, Sidney C., Jr. Goto, Shinya Ohman, E. Magnus Elbez, Yedid Sritara, Piyamitr Baumgartner, Iris Banerjee, Subhash Creager, Mark A. Bhatt, Deepak L. CA REACH Registry Investigators TI Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry SO EUROPEAN HEART JOURNAL LA English DT Article DE Statins; Peripheral vascular disease; Claudication; Morbidity; Registry ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENT RATES; LOWER-EXTREMITY; TASK-FORCE; NUTRITION EXAMINATION; PRACTICE GUIDELINES; NATIONAL-HEALTH; COMPETING RISK; FOLLOW-UP; MORTALITY AB Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an similar to 18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD. C1 [Kumbhani, Dharam J.; Banerjee, Subhash] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA. [Steg, Ph Gabriel; Elbez, Yedid] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Steg, Ph Gabriel; Elbez, Yedid] INSERM, U1148, Paris, France. [Steg, Ph Gabriel; Elbez, Yedid] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. [Steg, Ph Gabriel] Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6LY, England. [Cannon, Christopher P.; Creager, Mark A.; Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cannon, Christopher P.; Creager, Mark A.; Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Cannon, Christopher P.; Bhatt, Deepak L.] TIMI Study Grp, Boston, MA USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa 25911, Japan. [Ohman, E. Magnus] Duke Univ, Div Cardiol, Durham, NC USA. [Sritara, Piyamitr] Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Med, Bangkok 10400, Thailand. [Baumgartner, Iris] Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, Bern, Switzerland. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Kumbhani, DJ (reprint author), Univ Texas SW Med Ctr Dallas, Div Cardiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM dharam@post.harvard.edu NR 40 TC 33 Z9 38 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD NOV 1 PY 2014 VL 35 IS 41 SI SI BP 2864 EP 2872 DI 10.1093/eurheartj/ehu080 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AU1FS UT WOS:000345367100006 PM 24585266 ER PT J AU Ahasic, AM Zhai, R Su, L Zhao, Y Aronis, KN Thompson, BT Mantzoros, CS Christiani, DC AF Ahasic, Amy M. Zhai, Rihong Su, Li Zhao, Yang Aronis, Konstantinos N. Thompson, B. Taylor Mantzoros, Christos S. Christiani, David C. TI IGF1 and IGFBP3 in acute respiratory distress syndrome (vol 166, pg 121, 2012) SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Correction C1 [Ahasic, Amy M.] Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, New Haven, CT 06520 USA. [Ahasic, Amy M.; Zhai, Rihong; Su, Li; Zhao, Yang; Mantzoros, Christos S.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Aronis, Konstantinos N.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Ahasic, AM (reprint author), Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, 300 Cedar St,POB 208057, New Haven, CT 06520 USA. EM amy.ahasic@yale.edu RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 NR 1 TC 0 Z9 0 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 2014 VL 171 IS 5 BP X4 EP X4 DI 10.1530/EJE-11-0778e PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AT4YJ UT WOS:000344948400007 ER PT J AU Banks, CA Hadlock, TA AF Banks, Caroline A. Hadlock, Tessa A. TI Pediatric Facial Nerve Rehabilitation SO FACIAL PLASTIC SURGERY CLINICS OF NORTH AMERICA LA English DT Article DE Facial paralysis; Facial nerve palsy; Pediatric; Gracilis; Synkinesis; Bell palsy ID FREE-MUSCLE TRANSFER; PARALYZED FACE; GRACILIS TRANSFER; MOBIUS-SYNDROME; CHILDREN; PALSY; REANIMATION; MANAGEMENT; OUTCOMES; EYE AB Facial paralysis is a rare but severe condition in the pediatric population. Impaired facial movement has multiple causes and varied presentations, therefore individualized treatment plans are essential for optimal results. Advances in facial reanimation over the past 4 decades have given rise to new treatments designed to restore balance and function in pediatric patients with facial paralysis. This article provides a comprehensive review of pediatric facial rehabilitation and describes a zone-based approach to assessment and treatment of impaired facial movement. C1 [Banks, Caroline A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hadlock, Tessa A.] Harvard Univ, Sch Med, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hadlock, Tessa A.] Harvard Univ, Sch Med, Facial Nerve Ctr, Dept Otol & Laryngol,Massachusetts Eye & Ear Infi, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Harvard Univ, Sch Med, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 39 TC 2 Z9 2 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 1064-7406 J9 FACIAL PLAST SURG CL JI Facial Plast. Surg. Clin. N. Am. PD NOV PY 2014 VL 22 IS 4 BP 487 EP + DI 10.1016/j.fsc.2014.07.006 PG 17 WC Surgery SC Surgery GA AT8OS UT WOS:000345192900002 PM 25444723 ER PT J AU Goutaudier, N Sejourne, N Bui, E Cazenave, N Chabrol, H AF Goutaudier, N. Sejourne, N. Bui, E. Cazenave, N. Chabrol, H. TI Premature delivery: A traumatic birth ? Posttraumatic stress symptoms and associated features SO GYNECOLOGIE OBSTETRIQUE & FERTILITE LA French DT Article DE Posttraumatic stress disorder; Preterm birth; Postnatal depression; Trauma ID POSTNATAL-DEPRESSION-SCALE; PERCEIVED SOCIAL SUPPORT; PERINATAL DISSOCIATION; MULTIDIMENSIONAL SCALE; CHILDBIRTH PAIN; FRENCH VERSION; RISK-FACTORS; PREDICTORS; DISORDER; POSTPARTUM AB Objectives. - While researches focusing on posttraumatic stress disorder (PTSD) symptoms following childbirth tend to develop, few studies have been conducted on French samples. The aim of the current study was to explore the prevalence rate of women developing postpartum PTSD following preterm birth and highlighting associated features. Patients and method. - In the 4 weeks following the preterm infant's hospital discharge, a sample of 110 French women (mean age [SD] = 29.5 [4.3] years) who delivered prematurely completed questionnaires assessing PTSD symptoms (Impact of Event Scale-Revised) postpartum depressive symptomatology (Edinburgh Postnatal Depression Scale), quality of marital relationship (Dyadic Adjustment Scale) and partner support (Multidimensional Scale of Perceived Social Support). Sociodemographic and gynecologic data were also gathered. Results. - Thirty percent of our sample reported a score on the IES-R highlighting a probable posttraumatic stress disorder. Increased postpartum depressive symptoms (beta = 0.47, P < 0.05), having undergone a caesarian section (beta = 0.24, P < 0.05), and prior traumatic event (beta = 0.20, P < 0.05), were independently associated with the intensity of PTSD symptoms. Discussion and conclusion. - Given the traumatic impact of preterm birth on mothers, further studies focusing on the trauma of premature delivery are warranted. (C) 2014 Elsevier Masson SAS. All rights reserved. C1 [Goutaudier, N.; Sejourne, N.; Cazenave, N.; Chabrol, H.] Univ Toulouse II Le Mirail, Ctr Etud & Rech Pychopathol, URI Octogone, F-31058 Toulouse 9, France. [Bui, E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bui, E.] Harvard Univ, Sch Med, Boston, MA USA. RP Goutaudier, N (reprint author), Univ Toulouse II Le Mirail, Ctr Etud & Rech Pychopathol, URI Octogone, 5 Allees Antonio Machado, F-31058 Toulouse 9, France. EM nelly.goutaudier@gmail.com RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 51 TC 1 Z9 1 U1 5 U2 16 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1297-9589 EI 1769-6682 J9 GYNECOL OBSTET FERTI JI Gynecol. Obstet. Fertil. PD NOV PY 2014 VL 42 IS 11 BP 749 EP 754 DI 10.1016/j.gyobfe.2014.05.004 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AT9RU UT WOS:000345264700003 PM 24931321 ER PT J AU Schwartzenberg, S Passeri, JJ AF Schwartzenberg, Shmuel Passeri, Jonathan J. TI An intriguing finding in the right atrium SO HEART LA English DT Editorial Material C1 [Schwartzenberg, Shmuel; Passeri, Jonathan J.] Massachusetts Gen Hosp, Dept Internal Med, Div Cardiol, Boston, MA 02114 USA. RP Schwartzenberg, S (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Div Cardiol, 55 Fruit St 5E Yawkey Bldg, Boston, MA 02114 USA. EM sschwartzenberg@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD NOV PY 2014 VL 100 IS 21 BP 1695 EP + DI 10.1136/heartjnl-2014-306109 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT6CS UT WOS:000345027300011 PM 25306440 ER PT J AU Ojesina, A Murray, B Bjorge, L Woie, K Halle, M Lichtenstein, L Pedamulla, C Freeman, S Cherniack, A Lawrence, MS Cibulkis, K Carter, S Walline, H Carey, TE Vintermyr, OK Bertelsen, B Crum, C Getz, G Meyerson, M Salvesen, HB AF Ojesina, A. Murray, B. Bjorge, L. Woie, K. Halle, M. Lichtenstein, L. Pedamulla, C. Freeman, S. Cherniack, A. Lawrence, M. S. Cibulkis, K. Carter, S. Walline, H. Carey, T. E. Vintermyr, O. K. Bertelsen, B. Crum, C. Getz, G. Meyerson, M. Salvesen, H. B. TI RELATIONSHIPS BETWEEN SOMATIC GENOMIC ALTERATIONS, TUMOR STAGE AND PROGRESSION-FREE SURVIVAL IN CERVICAL CANCER SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Ojesina, A.; Pedamulla, C.; Cherniack, A.; Meyerson, M.] Broad Inst, Dana Farber Canc Inst, Boston, MA USA. [Murray, B.; Lichtenstein, L.; Freeman, S.; Lawrence, M. S.; Cibulkis, K.; Carter, S.] Harvard & MIT Broad Inst, Boston, MA USA. [Bjorge, L.; Woie, K.; Halle, M.; Vintermyr, O. K.; Bertelsen, B.; Salvesen, H. B.] Univ Bergen, Hauekland Univ Hosp, Bergen, Norway. [Walline, H.; Carey, T. E.] Univ Michigan, Canc Biol Program, Ann Arbor, MI 48109 USA. [Crum, C.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Getz, G.] Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. RI Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017 OI Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2014 VL 24 IS 9 SU 4 MA IGCSM-1118 BP 10 EP 11 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AT5EP UT WOS:000344966500009 ER PT J AU Mirza, M Berek, JS Vergote, I Wenham, RM Del Campo, JM Oza, AM Mahner, S Monk, BJ Fabbro, M Ledermann, JA Marth, C Bruchim, I Katsaros, D Lorusso, D Malander, S Dorum, A Agarwal, S Martell, RE Matulonis, U AF Mirza, M. Berek, J. S. Vergote, I. Wenham, R. M. Del Campo, J. M. Oza, A. M. Mahner, S. Monk, B. J. Fabbro, M. Ledermann, J. A. Marth, C. Bruchim, I. Katsaros, D. Lorusso, D. Malander, S. Dorum, A. Agarwal, S. Martell, R. E. Matulonis, U. TI ENGOT-OV16/NOVA: A PHASE 3 RANDOMIZED DOUBLE-BLIND TRIAL OF MAINTENANCE WITH PARP-INHIBITOR NIRAPARIB VERSUS PLACEBO IN PATIENTS WITH PLATINUM-SENSITIVE OVARIAN CANCER. SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Mirza, M.] Univ Copenhagen, NSGO, Copenhagen, Denmark. [Mirza, M.] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. [Berek, J. S.] Stanford Canc Inst, Stanford, CA USA. [Vergote, I.] BGOG, Leuven, Belgium. [Vergote, I.] UZ Leuven, Leuven, Belgium. [Wenham, R. M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Del Campo, J. M.] GEICO, Barcelona, Spain. [Del Campo, J. M.] Vall Hebron Inst Oncol, Barcelona, Spain. [Oza, A. M.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Mahner, S.] AGO, Hamburg, Germany. [Mahner, S.] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Monk, B. J.] Univ Arizona Ctr Phoenix, Phoenix, AZ USA. [Fabbro, M.] GINECO, Montpellier, France. [Fabbro, M.] ICM, Montpellier, France. [Ledermann, J. A.] NCRI, London, England. [Ledermann, J. A.] UCL, Inst Canc, London, England. [Marth, C.] AGO Austria, Innsbruck, Austria. [Marth, C.] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Bruchim, I.] ISGO, Tel Aviv, Israel. [Bruchim, I.] Tel Aviv Univ, Meir Med Ctr, IL-69978 Tel Aviv, Israel. [Katsaros, D.] MaNGO, Turin, Italy. [Katsaros, D.] Univ Turin, St Anna Hosp, Turin, Italy. [Lorusso, D.] MITO, Milan, Italy. [Lorusso, D.] Fdn IRCCS Natl Canc Inst Milan, Milan, Italy. [Malander, S.] NSGO, Lund, Sweden. [Malander, S.] Univ Lund Hosp, S-22185 Lund, Sweden. [Dorum, A.] NSGO, Oslo, Norway. [Dorum, A.] Oslo Radiumhosp, Oslo, Norway. [Agarwal, S.; Martell, R. E.] Tesaro Inc, Waltham, MA USA. [Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2014 VL 24 IS 9 SU 4 MA IGCSM-0215 BP 33 EP 34 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AT5EP UT WOS:000344966500027 ER PT J AU Menon, U Ryan, A Kalsi, J Gentry-Maharaj, A Dawnay, A Habib, M Apostolidou, S Singh, N Benjamin, E Burnell, M Davies, S Sharma, A Gunu, R Godfrey, K Lopes, A Oram, D Herod, J Williamson, K Seif, M Jenkins, H Mould, T Woolas, R Murdoch, J Dobbs, S Nazar, N Leeson, S Cruickshank, D Scott, I Fallowfield, L Widschwendter, M Reynolds, K Campbell, S Parmar, M Skates, SJ Jacobs, I AF Menon, U. Ryan, A. Kalsi, J. Gentry-Maharaj, A. Dawnay, A. Habib, M. Apostolidou, S. Singh, N. Benjamin, E. Burnell, M. Davies, S. Sharma, A. Gunu, R. Godfrey, K. Lopes, A. Oram, D. Herod, J. Williamson, K. Seif, M. Jenkins, H. Mould, T. Woolas, R. Murdoch, J. Dobbs, S. Nazar, N. Leeson, S. Cruickshank, D. Scott, I. Fallowfield, L. Widschwendter, M. Reynolds, K. Campbell, S. Parmar, M. Skates, S. J. Jacobs, I. TI SERIAL CA125 CAN DETECT OVARIAN CANCER IN THE ABSENCE OF ULTRASOUND ABNORMALITIES SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Menon, U.; Ryan, A.; Kalsi, J.; Gentry-Maharaj, A.; Habib, M.; Apostolidou, S.; Burnell, M.; Davies, S.; Sharma, A.; Gunu, R.; Widschwendter, M.; Jacobs, I.] UCL, Inst Womens Hlth, London, England. [Dawnay, A.; Mould, T.] Univ Coll London Hosp, London, England. [Singh, N.] Barts & London, Dept Pathol, London, England. [Benjamin, E.] Univ Coll London Hosp, Inst Canc, London, England. [Sharma, A.; Nazar, N.] Cardiff Univ, Coll Biomed & Life Sci, Sch Med, Cardiff CF10 3AX, S Glam, Wales. [Godfrey, K.; Lopes, A.] Queen Elizabeth Hosp, Northern Gynaecol Oncol Ctr, Gateshead, Tyne & Wear, England. [Lopes, A.] Royal Cornwall Hosp, Truro, Cornwall, England. [Oram, D.; Reynolds, K.] Barts & London, Gynaecol Oncol, London, England. [Herod, J.] Liverpool Womens Hosp, Liverpool, Merseyside, England. [Williamson, K.] City Hosp Nottingham, Nottingham, England. [Seif, M.] Univ Manchester, Inst Canc Sci, Manchester M13 9PL, Lancs, England. [Jenkins, H.; Scott, I.] Derby City Hosp, Derby, England. [Woolas, R.] Queen Alexandra Hosp, Portsmouth, Hants, England. [Murdoch, J.] St Michaels Hosp, Bristol, Avon, England. [Dobbs, S.] Belfast City Hosp, Belfast BT9 7AD, Antrim, North Ireland. [Leeson, S.] Llandudno Hosp, Llandudno, Gwynedd, Wales. [Cruickshank, D.] James Cook Univ Hosp, Middlesbrough, Cleveland, England. [Fallowfield, L.] Univ Sussex, Brighton & Sussex Med Sch, SHORE C, Falmer, England. [Campbell, S.] Create Hlth Clin, London, England. [Parmar, M.] UCL, MRC, Clin Trials Unit, London, England. [Skates, S. J.] Massachusetts Gen Hosp, MGH Biostat, Boston, MA 02114 USA. [Skates, S. J.] Harvard Univ, Sch Med, Boston, MA USA. [Jacobs, I.] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2014 VL 24 IS 9 SU 4 MA IGCSM-0003 BP 46 EP 47 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AT5EP UT WOS:000344966500036 ER PT J AU Lheureux, S Ledermann, J Kaye, S Gourley, C Friedlander, M Bowtell, D De Greve, J DeFazio, A Frommer, R De Bono, JS Audeh, MW Kohn, E Alsop, K Scott, C Matulonis, U Kaufman, B Burger, B Robertson, J Ho, T Oza, A AF Lheureux, S. Ledermann, J. Kaye, S. Gourley, C. Friedlander, M. Bowtell, D. De Greve, J. DeFazio, A. Frommer, R. De Bono, J. S. Audeh, M. W. Kohn, E. Alsop, K. Scott, C. Matulonis, U. Kaufman, B. Burger, B. Robertson, J. Ho, T. Oza, A. TI A PILOT INTEGRATED ANALYSIS OF LONG-TERM BENEFIT OF OLAPARIB IN OVARIAN CANCER: RESULTS OF FEASIBILITY TESTING. SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Lheureux, S.; Oza, A.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Ledermann, J.] UCL Canc Inst, London, England. [Kaye, S.; De Bono, J. S.] Royal Marsden Hosp, Sutton, Surrey, England. [Gourley, C.] Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland. [Friedlander, M.] Prince Wales Hosp, Sydney, NSW, Australia. [Bowtell, D.; Alsop, K.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [De Greve, J.] Univ Hosp Brussels, Familial Canc Clin, Brussels, Belgium. [De Greve, J.] Univ Hosp Brussels, Brussels, Belgium. [DeFazio, A.] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia. [Frommer, R.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Audeh, M. W.] Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA. [Kohn, E.] NCI, NIH, Bethesda, MD 20892 USA. [Scott, C.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaufman, B.] Chaim Sheba Med Ctr, Breast Canc Unit, IL-52621 Tel Hashomer, Israel. [Burger, B.] AstraZeneca, Stat, Wilmington, NC USA. [Robertson, J.] AstraZeneca, Med Oncol, Macclesfield, Cheshire, England. [Ho, T.] AstraZeneca, Med Oncol, Wilmington, NC USA. RI De Greve, Jacques/J-4939-2012 OI De Greve, Jacques/0000-0002-2389-0742 NR 0 TC 0 Z9 0 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2014 VL 24 IS 9 SU 4 MA IGCSM-0468 BP 141 EP 142 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AT5EP UT WOS:000344966500119 ER PT J AU Menon, U Ryan, A Kalsi, J Gentry-Maharaj, A Dawnay, A Habib, M Apostolidou, S Singh, N Benjamin, E Burnell, M Davies, S Sharma, A Gunu, R Godfrey, K Lopes, A Oram, D Herod, J Williamson, K Seif, M Jenkins, H Mould, T Woolas, R Murdoch, J Dobbs, S Nazar, N Leeson, S Cruickshank, D Scott, I Fallowfield, L Widschwendter, M Reynolds, K Campbell, S Parmar, M Skates, SJ Jacobs, I AF Menon, U. Ryan, A. Kalsi, J. Gentry-Maharaj, A. Dawnay, A. Habib, M. Apostolidou, S. Singh, N. Benjamin, E. Burnell, M. Davies, S. Sharma, A. Gunu, R. Godfrey, K. Lopes, A. Oram, D. Herod, J. Williamson, K. Seif, M. Jenkins, H. Mould, T. Woolas, R. Murdoch, J. Dobbs, S. Nazar, N. Leeson, S. Cruickshank, D. Scott, I Fallowfield, L. Widschwendter, M. Reynolds, K. Campbell, S. Parmar, M. Skates, S. J. Jacobs, I. TI A TIME SERIES ALGORITHM DOUBLES SENSITIVITY OF POPULATION SCREENING FOR OVARIAN CANCER IN THE UNITED KINGDOM COLLABORATIVE TRIAL OF OVARIAN CANCER SCREENING (UKCTOCS) SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Meeting Abstract C1 [Menon, U.; Ryan, A.; Kalsi, J.; Gentry-Maharaj, A.; Habib, M.; Apostolidou, S.; Burnell, M.; Davies, S.; Sharma, A.; Gunu, R.; Widschwendter, M.; Jacobs, I.] UCL, Inst Womens Hlth, London, England. [Dawnay, A.; Mould, T.] Univ Coll London Hosp, London, England. [Singh, N.] Barts & London, Dept Pathol, London, England. [Benjamin, E.] Univ Coll London Hosp, Inst Canc, London, England. [Sharma, A.; Nazar, N.] Cardiff Univ, Sch Med, Coll Biomed & Life Sci, Cardiff CF10 3AX, S Glam, Wales. [Godfrey, K.; Lopes, A.] Queen Elizabeth Hosp, Northern Gynaecol Oncol Ctr, Gateshead, England. [Lopes, A.] Royal Cornwall Hosp, Truro, England. [Oram, D.; Reynolds, K.] Barts & London, Gynaecol Oncol, London, England. [Herod, J.] Liverpool Womens Hosp, Liverpool, Merseyside, England. [Williamson, K.] City Hosp Nottingham, Nottingham, England. [Seif, M.] Univ Manchester, Inst Canc Sci, Manchester M13 9PL, Lancs, England. [Jenkins, H.; Scott, I] Derby City Hosp, Derby, England. [Woolas, R.] Queen Alexandra Hosp, Portsmouth, Hants, England. [Murdoch, J.] St Michaels Hosp, Bristol, Avon, England. [Dobbs, S.] Belfast City Hosp, Belfast BT9 7AD, Antrim, North Ireland. [Leeson, S.] Llandudno Hosp, N Wales, PA USA. [Cruickshank, D.] James Cook Univ Hosp, Middlesbrough, Cleveland, England. [Fallowfield, L.] Univ Sussex, Brighton & Sussex Med Sch, SHORE C, Falmer, England. [Campbell, S.] Create Hlth Clin, London, England. [Parmar, M.] UCL, MRC, Clin Trials Unit, London, England. [Skates, S. J.] Massachusetts Gen Hosp, MGH Biostat, Boston, MA 02114 USA. [Skates, S. J.] Harvard Univ, Sch Med, Boston, MA USA. [Jacobs, I.] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X EI 1525-1438 J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV PY 2014 VL 24 IS 9 SU 4 MA IGCSM-1269 BP 1587 EP 1588 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AT5EP UT WOS:000344966502326 ER PT J AU Klauss, J Pinheiro, LCP Merlo, BLS Santos, GDC Fregni, F Nitsche, MA Nakamura-Palacios, EM AF Klauss, Jaisa Penido Pinheiro, Leon Cleres Silva Merlo, Bruna Lima Correia Santos, Gerson de Almeida Fregni, Felipe Nitsche, Michael A. Nakamura-Palacios, Ester Miyuki TI A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcoholics; dorsolateral prefrontal cortex; quality of life; relapses; tDCS ID DIRECT-CURRENT STIMULATION; NONINVASIVE BRAIN-STIMULATION; TRANSCRANIAL DC STIMULATION; MAJOR DEPRESSION; DRUG-ADDICTION; CLINICAL-TRIAL; DOUBLE-BLIND; PLACEBO; RELAPSE; ACAMPROSATE AB Preliminary small studies have shown that transcranial direct current stimulation (tDCS) reduces craving in alcoholic subjects. It is unclear whether tDCS also leads to changes in clinically meaningful outcomes for alcohol dependence in a properly powered phase II randomized clinical trial. We aimed to investigate whether repetitive tDCS changes the risk of alcohol use relapse in severe alcoholics from outpatient services. Thirty-five subjects were randomized to receive active bilateral [left cathodal/right anodal over the dorsolateral prefrontal cortex (dlPFC)] repetitive (five consecutive days) tDCS (2 mA, 35 cm(2), two times daily stimulation for 13 min with a 20-min interval) or sham-tDCS. There were two dropouts before treatment. From 33 alcoholic subjects, 17 (mean age 45.5 +/- 8.9 S. D., 16 males) were randomized to sham and 16 (44 +/- 7.8 S. D., 16 males) to real tDCS treatment. By the end of the six months of follow-up, two subjects treated with sham (11.8%) and eight treated with real tDCS (50%) were still alcohol-abstinent [p = 0.02, Long-rank (Mantel-Cox) Test, HR = 0.35 (95% CI, 0.14-0.85)]. No differences with regard to changes on scores of craving, frontal function, global mental status, depressive or anxiety symptoms were observed between groups. However, subjects from the tDCS group improved with regard to their overall perception of quality of life (p = 0.02), and increased their scores in the environment domain (p = 0.04) after treatment. Bilateral tDCS over dlPFC reduces relapse probability in severe alcoholic subjects and results in improved perception of quality of life. C1 [Klauss, Jaisa; Penido Pinheiro, Leon Cleres; Silva Merlo, Bruna Lima; Correia Santos, Gerson de Almeida; Nakamura-Palacios, Ester Miyuki] Univ Fed Esprito Santo, Program Postgrad Physiol Sci, Lab Cognit Sci & Neuropsychopharmacol, Vitoria 29047105, Essex, Spain. [Fregni, Felipe] Harvard Univ, Sch Med, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spauding Rehabil Hosp, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat,Dept N, Boston, MA 02215 USA. [Nitsche, Michael A.] Univ Gottingen, Dept Clin Neurophysiol, Univ Med Ctr, Lab Neuroplast, D-37073 Gottingen, Germany. RP Nakamura-Palacios, EM (reprint author), Univ Fed Esprito Santo, Ctr Ciencias Saude, Programa Posgrad Ciencias Fisiol, Av Marechal Campos 1468, Vitoria 29047105, Essex, Spain. EM emnpalacios@gmail.com FU CNPq; CAPES FX We want to thank the patients and families who agreed to participate in this study, Catarine Conti who helped to apply tDCS in some subjects, Acyoman Pernambuco who kindly helped in the admission of patients at the research centre and application of the WHOQOF and other graduate students who helped to collect part of the data. JK and LCPP were recipients of governmental (CNPq or CAPES) student fellowships. NR 51 TC 17 Z9 18 U1 0 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD NOV PY 2014 VL 17 IS 11 BP 1793 EP 1803 DI 10.1017/S1461145714000984 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AT5TQ UT WOS:000345005400008 PM 25008145 ER PT J AU Gewirtz, H AF Gewirtz, Henry TI How Close Is Close Enough? SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE myocardial blood flow; PET 82Rb; PET 82Rb flow models; PET 82Rb software ID MYOCARDIAL BLOOD-FLOW; CORONARY FLOW; RESERVE; RB-82; THRESHOLDS; PERFUSION; HUMANS C1 [Gewirtz, Henry] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, Boston, MA USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM hgewirtz@partners.org NR 11 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 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD NOV PY 2014 VL 7 IS 11 BP 1128 EP 1129 DI 10.1016/j.jcmg.2014.09.001 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AT9NS UT WOS:000345254500010 PM 25459594 ER PT J AU Mormino, EC Betensky, RA Hedden, T Schultz, AP Amariglio, RE Rentz, DM Johnson, KA Sperling, RA AF Mormino, Elizabeth C. Betensky, Rebecca A. Hedden, Trey Schultz, Aaron P. Amariglio, Rebecca E. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. TI Synergistic Effect of beta-Amyloid and Neurodegeneration on Cognitive Decline in Clinically Normal Individuals SO JAMA NEUROLOGY LA English DT Article ID PRECLINICAL ALZHEIMER-DISEASE; NORMAL OLDER INDIVIDUALS; BRAIN; DEMENTIA; DEPOSITION; MEMORY; IMPAIRMENT; BIOMARKERS; MILD; ATROPHY AB IMPORTANCE Assessing the ability of Alzheimer disease neuroimaging markers to predict short-term cognitive decline among clinically normal (CN) individuals is critical for upcoming secondary prevention trials using cognitive outcomes. OBJECTIVE To determine whether neuroimaging markers of beta-amyloid (A beta) and neurodegeneration (ND) are independently or synergistically associated with longitudinal cognitive decline in CN individuals. DESIGN, SETTING, AND PARTICIPANTS Academic medical center longitudinal natural history study among 166 CN individuals (median age, 74 years; 92 women). MAIN OUTCOMES AND MEASURES The A beta statuswas determined with Pittsburgh Compound B-positron emission tomography, while ND was assessed using 2 a priori measures, hippocampus volume (magnetic resonance imaging) and glucose metabolism (positron emission tomography with fludeoxyglucose F 18), extracted from Alzheimer disease-vulnerable regions. Based on imaging markers, CN individuals were categorized into the following preclinical Alzheimer disease stages: stage 0 (A beta(-)/ND-), stage 1 (A beta(+)/ND-), stage 2 (A beta(+)/ND+), and suspected non-Alzheimer disease pathology (A beta(-)/ND+). Cognition was assessed with a composite of neuropsychological tests administered annually. RESULTS The A beta(+) CN individuals were more likely to be classified as ND+: 59.6% of A beta(+) CN individuals were ND+, whereas 31.9% of A beta-CN individuals were ND+ (odds ratio, 3.14; 95% CI, 1.44-7.02; P = .004). In assessing longitudinal cognitive performance, practice effects were evident in CN individuals negative for both A beta and ND, whereas diminished practice effects were observed in CN individuals positive for either A beta or ND. Decline over time was observed only in CN individuals positive for both A beta and ND, and decline in this group was significantly greater than that in all other groups (P < .001 for all). A significant interaction term between A beta and ND confirmed that this decline was greater than the additive contributions of A beta and ND (P = .04). CONCLUSIONS AND RELEVANCE The co-occurrence of A beta and ND accelerates cognitive decline in CN individuals. Therefore, both factors are important to consider in upcoming secondary prevention trials targeting CN individuals at high risk for progression to the symptomatic stages of Alzheimer disease. C1 [Mormino, Elizabeth C.; Schultz, Aaron P.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Charlestown, MA 02129 USA. [Hedden, Trey; Schultz, Aaron P.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Hedden, Trey; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Charlestown, MA 02129 USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, Charlestown, MA 02129 USA. RP Mormino, EC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM bmormino@nmr.mgh.harvard.edu FU National Institutes of Health [F32AG044054, P01 AG036694] FX The study was supported primarily by grants F32AG044054 and P01 AG036694 from the National Institutes of Health. NR 53 TC 52 Z9 52 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD NOV PY 2014 VL 71 IS 11 BP 1379 EP 1385 DI 10.1001/jamaneurol.2014.2031 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AT7WN UT WOS:000345145300007 PM 25222039 ER PT J AU Naj, AC Jun, G Reitz, C Kunkle, BW Perry, W Park, YS Beecham, GW Rajbhandary, RA Hamilton-Nelson, KL Wang, LS Kauwe, JSK Huentelman, MJ Myers, AJ Bird, TD Boeve, BF Baldwin, CT Jarvik, GP Crane, PK Rogaeva, E Barmada, MM Demirci, FY Cruchaga, C Kramer, PL Ertekin-Taner, N Hardy, J Graff-Radford, NR Green, RC Larson, EB St George-Hyslop, PH Buxbaum, JD Evans, DA Schneider, JA Lunetta, KL Kamboh, MI Saykin, AJ Reiman, EM De Jager, PL Bennett, DA Morris, JC Montine, TJ Goate, AM Blacker, D Tsuang, DW Hakonarson, H Kukull, WA Foroud, TM Martin, ER Haines, JL Mayeux, RP Farrer, LA Schellenberg, GD Pericak-Vance, MA AF Naj, Adam C. Jun, Gyungah Reitz, Christiane Kunkle, Brian W. Perry, William Park, Yo Son Beecham, Gary W. Rajbhandary, Ruchita A. Hamilton-Nelson, Kara L. Wang, Li-San Kauwe, John S. K. Huentelman, Matthew J. Myers, Amanda J. Bird, Thomas D. Boeve, Bradley F. Baldwin, Clinton T. Jarvik, Gail P. Crane, Paul K. Rogaeva, Ekaterina Barmada, M. Michael Demirci, F. Yesim Cruchaga, Carlos Kramer, Patricia L. Ertekin-Taner, Nilufer Hardy, John Graff-Radford, Neill R. Green, Robert C. Larson, Eric B. St George-Hyslop, Peter H. Buxbaum, Joseph D. Evans, Denis A. Schneider, Julie A. Lunetta, Kathryn L. Kamboh, M. Ilyas Saykin, Andrew J. Reiman, Eric M. De Jager, Philip L. Bennett, David A. Morris, John C. Montine, Thomas J. Goate, Alison M. Blacker, Deborah Tsuang, Debby W. Hakonarson, Hakon Kukull, Walter A. Foroud, Tatiana M. Martin, Eden R. Haines, Jonathan L. Mayeux, Richard P. Farrer, Lindsay A. Schellenberg, Gerard D. Pericak-Vance, Margaret A. CA Alzheimer Dis Genetics Consortium TI Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease A Genome-Wide Association Study SO JAMA NEUROLOGY LA English DT Article ID COMMON VARIANTS; PREVALENCE; DEMENTIA; POPULATION; CD2AP; EPHA1; CD33 AB IMPORTANCE Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. OBJECTIVES To investigate the effects of known Alzheimer disease risk loci in modifying AAO and to estimate their cumulative effect on AAO variation using data from genome-wide association studies in the Alzheimer Disease Genetics Consortium. DESIGN, SETTING, AND PARTICIPANTS The Alzheimer Disease Genetics Consortium comprises 14 case-control, prospective, and family-based data sets with data on 9162 participants of white race/ethnicity with Alzheimer disease occurring after age 60 years who also had complete AAO information, gathered between 1989 and 2011 at multiple sites by participating studies. Data on genotyped or imputed single-nucleotide polymorphisms most significantly associated with risk at 10 confirmed LOAD loci were examined in linear modeling of AAO, and individual data set results were combined using a random-effects, inverse variance-weighted meta-analysis approach to determine whether they contribute to variation in AAO. Aggregate effects of all risk loci on AAO were examined in a burden analysis using genotype scores weighted by risk effect sizes. MAIN OUTCOMES AND MEASURES Age at disease onset abstracted from medical records among participants with LOAD diagnosed per standard criteria. RESULTS Analysis confirmed the association of APOE with earlier AAO (P = 3.3 x 10(-96)), with associations in CR1 (rs6701713, P = 7.2 x 10(-4)), BIN1 (rs7561528, P = 4.8 x 10(-4)), and PICALM (rs561655, P = 2.2 x 10(-3)) reaching statistical significance (P < .005). Risk alleles individually reduced AAO by 3 to 6 months. Burden analyses demonstrated that APOE contributes to 3.7% of the variation in AAO (R-2 = 0.256) over baseline (R-2 = 0.221), whereas the other 9 loci together contribute to 2.2% of the variation (R-2 = 0.242). CONCLUSIONS AND RELEVANCE We confirmed an association of APOE (OMIM 107741) variants with AAO among affected participants with LOAD and observed novel associations of CR1 (OMIM 120620), BIN1 (OMIM 601248), and PICALM (OMIM 603025) with AAO. In contrast to earlier hypothetical modeling, we show that the combined effects of Alzheimer disease risk variants on AAO are on the scale of, but do not exceed, the APOE effect. While the aggregate effects of risk loci on AAO may be significant, additional genetic contributions to AAO are individually likely to be small. C1 [Naj, Adam C.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kunkle, Brian W.; Perry, William; Beecham, Gary W.; Rajbhandary, Ruchita A.; Hamilton-Nelson, Kara L.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Jun, Gyungah; Baldwin, Clinton T.; Farrer, Lindsay A.] Boston Univ, Dept Med, Genet Program, Boston, MA 02215 USA. [Jun, Gyungah; Lunetta, Kathryn L.; Farrer, Lindsay A.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Dept Ophthalmol, Boston, MA 02215 USA. [Reitz, Christiane] Columbia Univ, Taub Inst Alzheimers Dis & Aging Brain, Dept Neurol, New York, NY USA. [Reitz, Christiane; Mayeux, Richard P.] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Reitz, Christiane; Mayeux, Richard P.] Columbia Univ, Dept Neurol, New York, NY USA. [Park, Yo Son; Beecham, Gary W.; Martin, Eden R.; Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA. [Wang, Li-San; Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Huentelman, Matthew J.; Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Myers, Amanda J.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.; Tsuang, Debby W.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Boeve, Bradley F.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA USA. [Rogaeva, Ekaterina; St George-Hyslop, Peter H.] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [Barmada, M. Michael; Demirci, F. Yesim; Kamboh, M. Ilyas] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Cruchaga, Carlos; Goate, Alison M.] Washington Univ, Sch Med, Hope Ctr Program Prot Aggregat & Neurodegenerat, St Louis, MO 63110 USA. [Kramer, Patricia L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Kramer, Patricia L.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Ertekin-Taner, Nilufer; Graff-Radford, Neill R.] Mayo Clin, Dept Neurosci, Jacksonville, FL USA. [Ertekin-Taner, Nilufer; Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL USA. [Hardy, John] UCL, Inst Neurol, London, England. [Green, Robert C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. [Green, Robert C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Partners Ctr Personalized Genet Med, Boston, MA 02115 USA. [Larson, Eric B.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [St George-Hyslop, Peter H.] Univ Cambridge, Dept Clin Neurosci, Cambridge Inst Med Res, Cambridge, England. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Dept Internal Med, Chicago, IL 60612 USA. [Schneider, Julie A.; Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. [Kamboh, M. Ilyas] Univ Pittsburgh, Alheimer Dis Res Ctr, Pittsburgh, PA USA. [Saykin, Andrew J.; Foroud, Tatiana M.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. [Saykin, Andrew J.] Indiana Univ, Dept Radiol & Imaging Sci, Indianapolis, IN 46204 USA. [Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA. [Reiman, Eric M.] Univ Arizona, Dept Psychiat, Phoenix, AZ USA. [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [De Jager, Philip L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Inst Neurosci,Dept Neurol & Psychiat,Program Tran, Boston, MA 02115 USA. [De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Morris, John C.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Morris, John C.] Washington Univ, Dept Neurol, St Louis, MO USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilit Ctr Human Genet Res, Nashville, TN 37235 USA. [Mayeux, Richard P.] Columbia Univ, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Farrer, Lindsay A.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Farrer, Lindsay A.] Boston Univ, Dept Neurol, Boston, MA 02215 USA. RP Pericak-Vance, MA (reprint author), Univ Miami, John P Hussman Inst Human Genom, 1501 NW 10th Ave,Biomed Res Bldg,Rm 318, Miami, FL 33136 USA. EM mpericak@med.miami.edu RI Hardy, John/C-2451-2009; Kowall, Neil/G-6364-2012; Sonnen, 37382016/H-3738-2016; Tsuang, Debby/L-7234-2016; OI Ferris, Steven/0000-0001-8641-6223; Buxbaum, Joseph/0000-0001-8898-8313; Kowall, Neil/0000-0002-6624-0213; Sonnen, 37382016/0000-0001-9267-8705; Tsuang, Debby/0000-0002-4716-1894; Stern, Robert/0000-0002-5008-077X; Farrer, Lindsay/0000-0001-5533-4225; Reisberg, Barry/0000-0002-9104-7423; Demirci, F. Yesim/0000-0001-6907-9843; Kukull, Walter/0000-0001-8761-9014; Cruchaga, Carlos/0000-0002-0276-2899; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460 FU National Institute on Aging [U01 AG032984, RC2 AG036528, U01 AG016976, U24 AG021886, U24 AG026395, R01AG041797, U24 AG026390, P30 AG019610, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193, 1RC2AG036502, 1R01AG035137, P30 AG013854, P50 AG005131, P50 AG023501, P01 AG019724, P30 AG028383, AG05144, R01 AG027944, P01 AG03991, AG05128, AG025688, UO1 AG06781]; National Institute of Neurological Disorders and Stroke [NS39764]; National Institute of Mental Health [MH60451]; GlaxoSmithKline; Kronos Science; Alzheimer's Foundation; Johnnie B. Byrd Sr Alzheimer's Institute; Medical Research Council; State of Arizona; National Health Service trusts; Newcastle University; Medical Research Council London Brain Bank for Neurodegenerative Diseases via the Medical Research Council; South West Dementia Brain Bank; Higher Education Funding Council for England; Alzheimer's Research Trust; BRACE; North Bristol National Health Service Trust Research and Innovation Department and Dementias and Neurodegeneration); Netherlands Brain Bank; Stichting MS Research; Brain Net Europe; Hersenstichting Nederland BreinbrekendWerk; International Parkinson Fonds; Internationale Stiching Alzheimer Onderzoek; Institut de Neuropatologia; Servei Anatomia Patologica; Universitat de Barcelona; Abbott; AstraZeneca; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; Innogenetics; Johnson Johnson; Eli Lilly and Company; Medpace, Inc; Merck and Co, Inc; Novartis AG; Pfizer; F. Hoffman-La Roche; ScheringPlough; Synarc, Inc; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Dana Foundation; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association [IIRG-05-14147, IIRG-08-89720]; Biomedical Laboratory Research Program; Office of Research and Development; US Department of Veterans Affairs Administration; Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of Health Research; National Institute on Aging. [P30 AG008017, R01 AG026916, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146, R01 NS059873, P50 AG016582, UL1RR02777, R01 AG031581, P30 AG010129, P50 AG016573, P50 AG016575, P50 AG016576, P50 AG016577, P50 AG016570]; The National Institute on Aging [AG010491, AG027944, AG021547, AG019757, P50 AG008671, P30 AG010124, P50 AG005133, AG030653, AG041718, P50 AG005142, P30 AG012300, P50 AG005136, P50 AG005681, AG034504, U01 AG024904, RC2 AG036535, K01 AG030514, P50 AG008702, R37 AG015473, P30 AG028377]; The National Institute on Aging. [UO1 HG004610, P30 AG10133, P50 AG005146, R01 AG020688, P50 AG005134, P50 AG016574, P50 AG005138, P01 AG002219, P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616] FX The National Institute on Aging supported this work through the following grants: U01 AG032984 and RC2 AG036528 (Alzheimer Disease Genetics Consortium); U01 AG016976 (National Alzheimer's Coordinating Center); U24 AG021886 (National Cell Repository for Alzheimer Disease); U24 AG026395, R01AG041797, and U24 AG026390 (National Institute on Aging-Late-Onset Alzheimer Disease); P30 AG019610 (Banner Sun Health Research Institute); P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, and R01AG33193 (Boston University); P50 AG008702 and R37 AG015473 (Columbia University); P30 AG028377 and AG05128 (Duke University); AG025688 (Emory University); UO1 AG06781 and UO1 HG004610 (Group Health Research Institute); P30 AG10133 (Indiana University); P50 AG005146 and R01 AG020688 (The Johns Hopkins University); P50 AG005134 (Massachusetts General Hospital); P50 AG016574 (Mayo Clinic); P50 AG005138 and P01 AG002219 (Mount Sinai School of Medicine); P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, and 1R01AG035137 (New York University); P30 AG013854 (Northwestern University); P30 AG008017 and R01 AG026916 (Oregon Health & Science University); P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, and R01 AG30146 (Rush University); R01 NS059873 (Translational Genomics Research Institute); P50 AG016582 and UL1RR02777 (University of Alabama at Birmingham); R01 AG031581 (University of Arizona); P30 AG010129 (University of California, Davis); P50 AG016573, P50 AG016575, P50 AG016576, and P50 AG016577 (University of California, Irvine); P50 AG016570 (University of California, Los Angeles); P50 AG005131 (University of California, San Diego); P50 AG023501 and P01 AG019724 (University of California, San Francisco); P30 AG028383 and AG05144 (University of Kentucky); R01 AG027944, AG010491, AG027944, AG021547, and AG019757 (University of Miami); P50 AG008671 (University of Michigan); P30 AG010124 (University of Pennsylvania); P50 AG005133, AG030653, and AG041718 (University of Pittsburgh); P50 AG005142 (University of Southern California); P30 AG012300 (University of Texas Southwestern); P50 AG005136 (University of Washington); R01 AG019085 (Vanderbilt University); and P50 AG005681 and P01 AG03991 (Washington University in St Louis). The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by grant NS39764 from the National Institute of Neurological Disorders and Stroke, by grant MH60451 from the National Institute of Mental Health, and by GlaxoSmithKline. Genotyping of the Translational Genomics Research Institute 2 cohort was supported by Kronos Science. The Translational Genomics Research Institute series was also funded by grant AG034504 from the National Institute on Aging (Dr Myers) and by the Alzheimer's Foundation, Johnnie B.; Byrd Sr Alzheimer's Institute, Medical Research Council, and State of Arizona and includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local National Health Service trusts, and Newcastle University), Medical Research Council London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources, including the Higher Education Funding Council for England, Alzheimer's Research Trust, and BRACE [Bristol Research Into Alzheimer's and Care of the Elderly], as well as North Bristol National Health Service Trust Research and Innovation Department and Dementias and Neurodegeneration), Netherlands Brain Bank (funding via numerous sources, including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland BreinbrekendWerk, International Parkinson Fonds, and Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, and Universitat de Barcelona. Funding for the Alzheimer's Disease Neuroimaging Initiative is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Company, Medpace, Inc, Merck and Co, Inc, Novartis AG, Pfizer, F. Hoffman-La Roche, ScheringPlough, Synarc, Inc, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, and The Dana Foundation, as well as by the National Institute of Biomedical Imaging and Bioengineering and by grants U01 AG024904, RC2 AG036535, and K01 AG030514 from the National Institute on Aging. Support was also by grants IIRG-05-14147 and IIRG-08-89720 from the Alzheimer's Association (Dr Pericak-Vance) and by the Biomedical Laboratory Research Program, Office of Research and Development, US Department of Veterans Affairs Administration. Dr St. George-Hyslop is supported by the Wellcome Trust, Howard Hughes Medical Institute, and Canadian Institute of Health Research. NR 24 TC 37 Z9 37 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD NOV PY 2014 VL 71 IS 11 BP 1394 EP 1404 DI 10.1001/jamaneurol.2014.1491 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AT7WN UT WOS:000345145300009 PM 25199842 ER PT J AU Mata, IF Leverenz, JB Weintraub, D Trojanowski, JQ Hurtig, HI Van Deerlin, VM Ritz, B Rausch, R Rhodes, SL Factor, SA Wood-Siverio, C Quinn, JF Chung, KA Peterson, AL Espay, AJ Revilla, FJ Devoto, J Hu, SC Cholerton, BA Wan, JY Montine, TJ Edwards, KL Zabetian, CP AF Mata, Ignacio F. Leverenz, James B. Weintraub, Daniel Trojanowski, John Q. Hurtig, Howard I. Van Deerlin, Vivianna M. Ritz, Beate Rausch, Rebecca Rhodes, Shannon L. Factor, Stewart A. Wood-Siverio, Cathy Quinn, Joseph F. Chung, Kathryn A. Peterson, Amie L. Espay, Alberto J. Revilla, Fredy J. Devoto, Johnna Hu, Shu-Ching Cholerton, Brenna A. Wan, Jia Y. Montine, Thomas J. Edwards, Karen L. Zabetian, Cyrus P. TI APOE, MAPT, and SNCA Genes and Cognitive Performance in Parkinson Disease SO JAMA NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; VERBAL FLUENCY; DEMENTIA; IMPAIRMENT; ASSOCIATION; DECLINE; RISK; METAANALYSIS; INCIDENT; SUBTYPES AB IMPORTANCE Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature. OBJECTIVE To determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD. DESIGN, SETTING, AND PARTICIPANTS We studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE epsilon 2/epsilon 3/epsilon 4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene. MAIN OUTCOMES AND MEASURES Nine variables derived from 7 psychometric tests. RESULTS The APOE epsilon 4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 x 10(-6); corrected P [P-c] = 6.0 x 10(-5)), Delayed Recall (P = .001; P-c = .009), and Recognition Discrimination Index (P =.004; P-c = .04); a semantic verbal fluency test (P = .002; P-c = .02); the Letter-Number Sequencing Test (P = 1 x 10(-5); P-c = 9 x 10(-5)); and Trail Making Test B minus Trail Making Test A (P = .002; P-c = .02). In a subset of 645 patients without dementia, the APOE epsilon 4 allele was associated with lower scores on the HVLT-R Total Recall (P =.005; P-c = .045) and the semantic verbal fluency (P = .005; P-c = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests. CONCLUSIONS AND RELEVANCE Our data indicate that the APOE epsilon 4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE epsilon 4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD. C1 [Mata, Ignacio F.; Leverenz, James B.; Hu, Shu-Ching; Cholerton, Brenna A.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Leverenz, James B.; Hu, Shu-Ching; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Mata, Ignacio F.; Leverenz, James B.; Hu, Shu-Ching; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [Leverenz, James B.; Cholerton, Brenna A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Weintraub, Daniel; Hurtig, Howard I.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Trojanowski, John Q.; Van Deerlin, Vivianna M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA. [Trojanowski, John Q.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. [Ritz, Beate; Rhodes, Shannon L.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Dept Environm Hlth Sci, Los Angeles, CA 90024 USA. [Ritz, Beate; Rausch, Rebecca] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Factor, Stewart A.; Wood-Siverio, Cathy] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie L.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. [Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH USA. [Revilla, Fredy J.] Cincinnati Vet Affairs Med Ctr, Dept Neurol, Cincinnati, OH USA. [Wan, Jia Y.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Zabetian, CP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu RI Ritz, Beate/E-3043-2015; OI Zabetian, Cyrus/0000-0002-7739-4306 FU Department of Veterans Affairs [1I01BX000531]; NIH [P50 NS062684, P50 NS053488, P50 NS038367, R01 NS065070]; Consolidated Anti-Aging Foundation; Jane and Lee Seidman Fund FX This study was supported by grant 1I01BX000531 from the Department of Veterans Affairs, grants P50 NS062684, P50 NS053488, P50 NS038367, and R01 NS065070 from the NIH, by the Consolidated Anti-Aging Foundation, and by the Jane and Lee Seidman Fund. NR 50 TC 31 Z9 34 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD NOV PY 2014 VL 71 IS 11 BP 1405 EP 1412 DI 10.1001/jamaneurol.2014.1455 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AT7WN UT WOS:000345145300010 PM 25178429 ER PT J AU Agrawal, PB Joshi, M Marinakis, NS Schmitz-Abe, K Ciarlini, PDSC Sargent, JC Markianos, K De Girolami, U Chad, DA Beggs, AH AF Agrawal, Pankaj B. Joshi, Mugdha Marinakis, Nicholas S. Schmitz-Abe, Klaus Ciarlini, Pedro D. S. C. Sargent, Jane C. Markianos, Kyriacos De Girolami, Umberto Chad, David A. Beggs, Alan H. TI Expanding the Phenotype Associated With the NEFL Mutation Neuromuscular Disease in a Family With Overlapping Myopathic and Neurogenic Findings SO JAMA NEUROLOGY LA English DT Article ID MARIE-TOOTH-DISEASE; NEMALINE ROD MYOPATHY; CONGENITAL MYOPATHIES; GENE; DIAGNOSIS; GENOME AB IMPORTANCE Newer sequencing technologies in combination with traditional gene mapping techniques, such as linkage analysis, can help identify the genetic basis of disease for patients with rare disorders of uncertain etiology. This approach may expand the phenotypic spectrum of disease associated with those genetic mutations. OBJECTIVE To elucidate the molecular cause of a neuromuscular disease among a family in which 4 members, a mother and her 3 sons, were affected. DESIGN, SETTING, AND PARTICIPANTS Two of 4 affected members manifested nemaline myopathy, a common subtype of congenitalmyopathy, while the other 2 had a nonspecific myopathy. Single-nucleotide polymorphism-based linkage analysis was performed on DNA samples from the 4 affected family members, and whole-genome sequencing was performed in the proband. Real-time quantitative reverse transcription-polymerase chain reaction, immunofluorescence, and Western blot analysis were performed on muscle biopsy specimens. MAIN OUTCOMES AND MEASURES Whole-genome sequencing and linkage analysis identified a variant in a gene that explains the phenotype. RESULTS We identified a novel neurofilament light polypeptide (NEFL) nonsense mutation in all affected members. NEFL mutations have been previously linked to Charcot-Marie-Tooth disease in humans. This led us to reevaluate the diagnosis, and we recognized that several of the findings, especially those related to the muscle biopsy specimens and electromyography, were consistent with a neurogenic disease. CONCLUSIONS AND RELEVANCE NEFL mutations are known to cause Charcot-Marie-Tooth disease in humans and motor neuron disease in mice. We report the identification of an NEFL mutation in a family clinically manifesting congenitalmyopathy. We also describe potential overlap between myopathic and neurogenic findings in this family. These findings expand the phenotypic spectrum of diseases associated with NEFL mutations. This study is an example of the power of genomic approaches to identify potentially pathogenic mutations in unsuspected genes responsible for heterogeneous neuromuscular diseases. C1 [Agrawal, Pankaj B.; Joshi, Mugdha; Marinakis, Nicholas S.; Schmitz-Abe, Klaus; Ciarlini, Pedro D. S. C.; Markianos, Kyriacos; Beggs, Alan H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet & Genom, Boston, MA USA. [Agrawal, Pankaj B.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. [Agrawal, Pankaj B.; Joshi, Mugdha; Marinakis, Nicholas S.; Schmitz-Abe, Klaus; Markianos, Kyriacos; Beggs, Alan H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Ciarlini, Pedro D. S. C.; De Girolami, Umberto] MIT, Broad Inst, Cambridge, MA 02139 USA. [Schmitz-Abe, Klaus] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Sargent, Jane C.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Agrawal, PB (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Gen, 300 Longwood Ave, Boston, MA 02115 USA. EM pagrawal@enders.tch.harvard.edu; beggs@enders.tch.harvard.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [K08 AR055072, R01 AR044345]; Muscular Dystrophy Association [MDA201302]; Jean-Pierre and Nancy Boespflug Myopathic Research Foundation FX This work was supported by grants K08 AR055072 (Dr Agrawal) and R01 AR044345 (Dr Beggs) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, by grant MDA201302 from the Muscular Dystrophy Association (Dr Beggs), and by the Jean-Pierre and Nancy Boespflug Myopathic Research Foundation. NR 28 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD NOV PY 2014 VL 71 IS 11 BP 1413 EP 1420 DI 10.1001/jamaneurol.2014.1432 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AT7WN UT WOS:000345145300011 PM 25264603 ER PT J AU Videnovic, A Breen, DP Barker, RA Zee, PC AF Videnovic, Aleksandar Breen, David P. Barker, Roger A. Zee, Phyllis C. TI The Central Clock in Patients With Parkinson Disease Reply SO JAMA NEUROLOGY LA English DT Letter ID RHYTHM; SLEEP C1 [Videnovic, Aleksandar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Breen, David P.; Barker, Roger A.] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England. [Zee, Phyllis C.] Northwestern Univ, Dept Neurol, Chicago, IL USA. RP Videnovic, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Clin Res Inst,Dept Neurol, 165 Cambridge St,Ste 600, Boston, MA 02114 USA. EM avidenovic@mgh.harvard.edu FU NINDS NIH HHS [K23 NS072283]; Parkinson's UK [J-0801] NR 5 TC 4 Z9 4 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD NOV PY 2014 VL 71 IS 11 BP 1456 EP 1457 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AT7WN UT WOS:000345145300020 PM 25383776 ER PT J AU Sun, JK Lin, MM Lammer, J Prager, S Sarangi, R Silva, PS Aiello, LP AF Sun, Jennifer K. Lin, Michael M. Lammer, Jan Prager, Sonja Sarangi, Rutuparna Silva, Paolo S. Aiello, Lloyd Paul TI Disorganization of the Retinal Inner Layers as a Predictor of Visual Acuity in Eyes With Center-Involved Diabetic Macular Edema SO JAMA OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; RETINOPATHY; THICKNESS AB IMPORTANCE Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME. OBJECTIVE To determine whether baseline or early change in the novel spectral domain-optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME. DESIGN, SETTING, AND PARTICIPANTS At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, >= 320 mu m for men and >= 305 mu m for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity. MAIN OUTCOMES AND MEASURES Visual acuity and SD-OCT-derived retinal morphology. RESULTS Greater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 mu m; P < .001). An increase in DRIL during 4 months was associated with VA worsening at 8 months (point estimate, 0.03; 95% CI, 0.02-0.05 per 100 mu m; P < .001). A multivariate model that included a 4-month change in VA, DRIL, and external limiting membrane disruption was predictive of an 8-month VA change (r = 0.80). Each approximately 300-mu m DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 mu m at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 mu m at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had VA improvement of at least 1 line. CONCLUSIONS AND RELEVANCE Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME. C1 [Sun, Jennifer K.; Lin, Michael M.; Lammer, Jan; Silva, Paolo S.; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, Jennifer K.; Silva, Paolo S.; Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Lammer, Jan; Prager, Sonja] Med Univ Vienna, Dept Ophthalmol & Optometry, Vienna, Austria. RP Sun, JK (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM jennifer.sun@joslin.harvard.edu OI Lin, Michael/0000-0001-8739-4329 FU Harvard Medical School Scholars in Medicine Office; Eleanor Chesterman Beatson Childcare Ambassador Program Foundation; Juvenile Diabetes Research Foundation International [JDRF 17-2011-359]; Massachusetts Lions Eye Research Fund FX This study was supported by the Harvard Medical School Scholars in Medicine Office (Mr Lin), by a grant from the Eleanor Chesterman Beatson Childcare Ambassador Program Foundation (Dr Sun), by grant JDRF 17-2011-359 from the Juvenile Diabetes Research Foundation International (Dr Sun), and by the Massachusetts Lions Eye Research Fund (Drs Sun and Aiello). NR 13 TC 21 Z9 21 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD NOV PY 2014 VL 132 IS 11 BP 1309 EP 1316 DI 10.1001/jamaophthalmol.2014.2350 PG 8 WC Ophthalmology SC Ophthalmology GA AT8WO UT WOS:000345210100009 PM 25058813 ER PT J AU Jakobiec, FA Rashid, A Letko, E AF Jakobiec, Frederick A. Rashid, Alia Letko, Erik TI Conjunctival Intralymphatic Small Cell Lymphocytostasis Associated With a Salmon Patch SO JAMA OPHTHALMOLOGY LA English DT Letter C1 [Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Rashid, Alia] Harvard Univ, Sch Med, Boston, MA USA. [Letko, Erik] Corneal Consultants Colorado, Littleton, CO USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Ste 328, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD NOV PY 2014 VL 132 IS 11 BP 1379 EP 1381 DI 10.1001/jamaophthalmol.2014.2821 PG 4 WC Ophthalmology SC Ophthalmology GA AT8WO UT WOS:000345210100028 PM 25103729 ER PT J AU Pietrzak, RH Naganawa, M Huang, YY Corsi-Travali, S Zheng, MQ Stein, MB Henry, S Lim, K Ropchan, J Lin, SF Carson, RE Neumeister, A AF Pietrzak, Robert H. Naganawa, Mika Huang, Yiyun Corsi-Travali, Stefani Zheng, Ming-Qiang Stein, Murray B. Henry, Shannan Lim, Keunpoong Ropchan, Jim Lin, Shu-fei Carson, Richard E. Neumeister, Alexander TI Association of In Vivo K-Opioid Receptor Availability and the Transdiagnostic Dimensional Expression of Trauma-Related Psychopathology SO JAMA PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; PLACEBO-CONTROLLED TRIAL; ADMINISTERED PTSD SCALE; CENTRAL-NERVOUS-SYSTEM; MAJOR DEPRESSION; PSYCHOLOGICAL DISTRESS; CORTISOL-LEVELS; ACTIVATION; RATS AB IMPORTANCE Exposure to trauma increases the risk for developing threat (ie, fear) symptoms, such as reexperiencing and hyperarousal symptoms, and loss (ie, dysphoria) symptoms, such as emotional numbing and depressive symptoms. While preclinical data have implicated the activated dynorphin/K-opioid receptor (KOR) system in relation to these symptoms, the role of the KOR system in mediating these phenotypes in humans is unknown. Elucidation of molecular targets implicated in threat and loss symptoms is important because it can help inform the development of novel, mechanism-based treatments for trauma-related psychopathology. OBJECTIVE To use the newly developed [C-11]LY2795050 radiotracer and high-resolution positron emission tomography to evaluate the relation between in vivo KOR availability in an amygdala-anterior cingulate cortex-ventral striatal neural circuit and the severity of threat and loss symptoms. We additionally evaluated the role of 24-hour urinary cortisol levels in mediating this association. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional positron emission tomography study under resting conditions was conducted at an academic medical center. Thirty-five individuals representing a broad transdiagnostic and dimensional spectrum of trauma-related psychopathology, ranging from nontrauma-exposed psychiatrically healthy adults to trauma-exposed adults with severe trauma-related psychopathology (ie, posttraumatic stress disorder, major depressive disorder, and/or generalized anxiety disorder). MAIN OUTCOMES AND MEASURES [C-11]LY2795050 volume of distribution values in amygdala-anterior cingulate cortex-ventral striatal neural circuit; composite measures of threat (ie, reexperiencing, avoidance, and hyperarousal symptoms) and loss (ie, emotional numbing, major depressive disorder, and generalized anxiety disorder symptoms) symptoms as assessed using the Clinician-Administered PTSD Scale, Hamilton Depression Rating Scale, and Hamilton Rating Scale for Anxiety; and 24-hour urinary cortisol levels. RESULTS [C-11]LY2795050 volume of distribution values in an amygdala-anterior cingulate cortex-ventral striatal neural circuit were negatively associated with severity of loss (r = -0.39; 95% CI, -0.08 to -0.66), but not threat (r = -0.03; 95% CI, -0.30 to 0.27), symptoms; this association was most pronounced for dysphoria symptoms (r = -0.45; 95% CI, -0.10 to -0.70). Path analysis revealed that lower [C-11]LY2795050 volume of distribution values in this circuit was directly associated with greater severity of loss symptoms and indirectly mediated by 24-hour urinary cortisol levels. CONCLUSIONS AND RELEVANCE Results of this study suggest that KOR availability in an amygdala-anterior cingulate cortex-ventral striatal neural circuit mediates the phenotypic expression of trauma-related loss (ie, dysphoria) symptoms. They further suggest that an activated corticotropin-releasing factor/hypothalamic-pituitary-adrenal axis system, as assessed by 24-hour urinary cortisol levels, may indirectly mediate this association. These results may help inform the development of more targeted, mechanism-based transdiagnostic treatments for loss (ie, dysphoric) symptoms. C1 [Pietrzak, Robert H.] US Dept Vet Affairs, VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT USA. [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Naganawa, Mika; Huang, Yiyun; Zheng, Ming-Qiang; Henry, Shannan; Lim, Keunpoong; Ropchan, Jim; Lin, Shu-fei; Carson, Richard E.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Corsi-Travali, Stefani; Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Corsi-Travali, Stefani; Neumeister, Alexander] NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. [Stein, Murray B.] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Stein, Murray B.] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Neumeister, Alexander] Steven & Alexandra Cohen Vet Ctr, New York, NY USA. RP Neumeister, A (reprint author), NYU, Sch Med, 1 Pk Ave,8th Floor 225, New York, NY 10016 USA. EM alexander.neumeister@nyumc.org RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 FU National Institutes of Health (NIH) [R21MH096105, R21MH085627, RO1MH096876, RO1MH102566]; National Center for Research Resources [UL1 RR024139]; National Center for Advancing Translational Science, components of the NIH; NIH Roadmap for Medical Research; Clinical Neurosciences Division of the US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder; Eli Lilly Inc [[11C]LY2795050] FX This project was supported by the National Institutes of Health (NIH) through the following grants: R21MH096105, R21MH085627, RO1MH096876, and RO1MH102566. This was also supported by Clinical and Translational Science Award grant UL1 RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the NIH, NIH Roadmap for Medical Research, and Clinical Neurosciences Division of the US Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. We acknowledge grant support from Eli Lilly Inc for support in the development of [11C]LY2795050. NR 67 TC 13 Z9 13 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD NOV PY 2014 VL 71 IS 11 BP 1262 EP 1270 DI 10.1001/jamapsychiatry.2014.1221 PG 9 WC Psychiatry SC Psychiatry GA AT5NH UT WOS:000344989100008 PM 25229257 ER PT J AU Anestis, MD Joiner, T Hanson, JE Gutierrez, PM AF Anestis, Michael D. Joiner, Thomas Hanson, Jetta E. Gutierrez, Peter M. TI The Modal Suicide Decedent Did Not Consume Alcohol Just Prior to the Time of Death: An Analysis With Implications for Understanding Suicidal Behavior SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE suicide decedents; blood alcohol content; meta-analysis ID DEPENDENCE; TRENDS; ABUSE AB We identified and analyzed a total of 92 studies, representing 167,894 suicide decedents, to determine if there is evidence to support what appears to be a widely held cultural, clinical, and scholarly view that many people who die by suicide had been drinking at the time of death. It was determined that, based on weighted averages, approximately 27% of suicide decedents had above-zero blood alcohol concentrations (BACs) at the time of death. We emphasize that it was not 27% who were intoxicated at the time of death; rather, 27% had above-zero BACs and 73% had BACs of 0.00%. Among studies of suicide decedents, BACs differed as a function of race (higher in non-White individuals). We conclude that the role of alcohol use at the time of death may be less than some assume, and this interpretation can inform clinical practice and theories of suicide. Important unanswered questions are posed which will help refine research in this area going forward. C1 [Anestis, Michael D.] Univ So Mississippi, Dept Psychol, Hattiesburg, MS 39406 USA. [Joiner, Thomas] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Joiner, Thomas; Hanson, Jetta E.] Mil Suicide Res Consortium, Tallahassee, FL USA. [Gutierrez, Peter M.] Denver VA Med Ctr, MIRECC, Denver, CO 80220 USA. [Gutierrez, Peter M.] Mil Suicide Res Consortium, Denver, CO USA. [Gutierrez, Peter M.] Univ Colorado, Sch Med, Dept Psychiat, Boulder, CO 80309 USA. RP Gutierrez, PM (reprint author), Denver VA Med Ctr, MIRECC, 1055 Clermont St, Denver, CO 80220 USA. EM peter.gutierrez@va.gov NR 17 TC 11 Z9 11 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X EI 1939-1846 J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2014 VL 123 IS 4 BP 835 EP 840 DI 10.1037/a0037480 PG 6 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA AT7ZM UT WOS:000345153400015 PM 25286371 ER PT J AU Kaplan, KA McQuaid, J Primich, C Rosenlicht, N AF Kaplan, Katherine A. McQuaid, John Primich, Charles Rosenlicht, Nicholas TI An Evidence-Based Review of Insomnia Treatment in Early Recovery SO JOURNAL OF ADDICTION MEDICINE LA English DT Review DE abstinence; cognitive behavioral therapy; insomnia; recovery; sleep ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; ALCOHOL DEPENDENCE; SLEEP DISTURBANCE; OLDER-ADULTS; PSYCHIATRIC-DISORDERS; DOUBLE-BLIND; NONPHARMACOLOGIC TREATMENT; COMPARATIVE METAANALYSIS; SUBSTANCE DEPENDENCE AB Accruing evidence indicates that insomnia is prevalent and persistent in early recovery from substance use disorders and may predict relapse. As such, insomnia treatment after abstinence represents an important area for intervention. This article reviews the literature on insomnia predicting new-onset alcohol and substance use disorders, along with evidence for insomnia predicting relapse in recovering populations. Pharmacological and psychological treatment options are presented, and cognitive-behavioral therapy for insomnia applied to recovering populations is described in detail. C1 [Kaplan, Katherine A.] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [McQuaid, John; Rosenlicht, Nicholas] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [McQuaid, John; Primich, Charles; Rosenlicht, Nicholas] San Francisco VA Med Ctr, San Francisco, CA USA. RP Rosenlicht, N (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. EM Nicholas.Rosenlicht@ucsf.edu NR 70 TC 2 Z9 2 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD NOV-DEC PY 2014 VL 8 IS 6 BP 389 EP 394 DI 10.1097/ADM.0000000000000052 PG 6 WC Substance Abuse SC Substance Abuse GA AT7LD UT WOS:000345117200001 PM 25369938 ER PT J AU Kaplan, KA McQuaid, J Batki, SL Rosenlicht, N AF Kaplan, Katherine A. McQuaid, John Batki, Steven L. Rosenlicht, Nicholas TI Behavioral Treatment of Insomnia in Early Recovery SO JOURNAL OF ADDICTION MEDICINE LA English DT Article ID ALCOHOL DEPENDENCE; GABAPENTIN; TRIAL AB This clinical case discussion focuses on a veteran with alcohol dependence in early partial remission and comorbid insomnia. The case illustrates the use of cognitive behavioral therapy for insomnia (CBT-I) to treat sleep disturbance. After the case presentation, expert clinicians provide commentary on the case. C1 [Kaplan, Katherine A.] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [McQuaid, John; Batki, Steven L.; Rosenlicht, Nicholas] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Rosenlicht, N (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr 116C, Dept Psychiat, 4150 Clement St, San Francisco, CA 94121 USA. EM Nicholas.Rosenlicht@ucsf.edu NR 14 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD NOV-DEC PY 2014 VL 8 IS 6 BP 395 EP 398 DI 10.1097/ADM.0000000000000058 PG 4 WC Substance Abuse SC Substance Abuse GA AT7LD UT WOS:000345117200002 PM 25369939 ER PT J AU Alexander, ES Martin, LJ Collins, MH Kottyan, LC Sucharew, H He, H Mukkada, VA Succop, PA Abonia, JP Foote, H Eby, MD Grotjan, TM Greenler, AJ Dellon, ES Demain, JG Furuta, GT Gurian, LE Harley, JB Hopp, RJ Kagalwalla, A Kaul, A Nadeau, KC Noel, RJ Putnam, PE von Tiehl, KF Rothenberg, ME AF Alexander, Eileen S. Martin, Lisa J. Collins, Margaret H. Kottyan, Leah C. Sucharew, Heidi He, Hua Mukkada, Vincent A. Succop, Paul A. Abonia, J. Pablo Foote, Heather Eby, Michael D. Grotjan, Tommie M. Greenler, Alexandria J. Dellon, Evan S. Demain, Jeffrey G. Furuta, Glenn T. Gurian, Larry E. Harley, John B. Hopp, Russell J. Kagalwalla, Amir Kaul, Ajay Nadeau, Kari C. Noel, Richard J. Putnam, Philip E. von Tiehl, Karl F. Rothenberg, Marc E. TI Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Eosinophilia; food allergy; medical genetics; twins; immune system diseases; heritability; gene-environment interaction; drug hypersensitivity; gastrointestinal diseases; skin diseases ID MISSING HERITABILITY; SEASONAL-VARIATION; MOLECULAR CHARACTERIZATION; PROVIDES INSIGHT; LINKAGE ANALYSIS; CROHNS-DISEASE; EARLY-LIFE; CHILDREN; ASSOCIATION; EXPRESSION AB Background: Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. Objective: To quantify the risk associated with genes and environment on familial clustering of EoE. Methods: Family history was obtained from a hospital-based cohort of 914 EoE probands (n = 2192 first-degree "Nuclear-Family" relatives) and an international registry of monozygotic and dizygotic twins/triplets (n = 63 EoE "Twins" probands). Frequencies, recurrence risk ratios (RRRs), heritability, and twin concordance were estimated. Environmental exposures were preliminarily examined. Results: Analysis of the Nuclear-Family-based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10 to 64, depending on the family relationship, and were higher in brothers (64.0; P = .04), fathers (42.9; P = .004), and males (50.7; P < .001) than in sisters, mothers, and females, respectively. The risk of EoE for other siblings was 2.4%. In the Nuclear-Family cohort, combined gene and common environment heritability was 72.0% 6 2.7% (P < .001). In the Twins cohort, genetic heritability was 14.5% +/- 4.0% (P < .001), and common family environment contributed 81.0% +/- 4% (P < .001) to phenotypic variance. Probandwise concordance in monozygotic co-twins was 57.9% +/- 9.5% compared with 36.4% +/- 9.3% in dizygotic co-twins (P = .11). Greater birth weight difference between twins (P = .01), breast-feeding (P = .15), and fall birth season (P = .02) were associated with twin discordance in disease status. Conclusions: EoE RRRs are increased 10- to 64-fold compared with the general population. EoE in relatives is 1.8% to 2.4%, depending on relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, the Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%). C1 [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; Mukkada, Vincent A.; Succop, Paul A.; Abonia, J. Pablo; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; Mukkada, Vincent A.; Succop, Paul A.; Abonia, J. Pablo; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; Mukkada, Vincent A.; Succop, Paul A.; Abonia, J. Pablo; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Univ Cincinnati, Coll Med, Dept Pathol, Cincinnati, OH USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; Mukkada, Vincent A.; Succop, Paul A.; Abonia, J. Pablo; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Univ Cincinnati, Coll Med, Dept Lab Med, Cincinnati, OH USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Div Rheumatol, Cincinnati, OH 45229 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol, Cincinnati, OH 45229 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Div Hepatol & Nutr, Cincinnati, OH 45229 USA. [Alexander, Eileen S.; Martin, Lisa J.; Collins, Margaret H.; Kottyan, Leah C.; Sucharew, Heidi; He, Hua; Mukkada, Vincent A.; Abonia, J. Pablo; Foote, Heather; Eby, Michael D.; Grotjan, Tommie M.; Greenler, Alexandria J.; Harley, John B.; Kaul, Ajay; Putnam, Philip E.; Rothenberg, Marc E.] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA. [Alexander, Eileen S.] Xavier Univ, Dept Hlth Serv Adm, Cincinnati, OH 45207 USA. [Dellon, Evan S.] Univ N Carolina, Sch Med, Esophageal Dis & Swallowing, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Demain, Jeffrey G.] Allergy Asthma & Immunol Ctr Alaska, Anchorage, AK USA. [Furuta, Glenn T.] Univ Colorado, Sch Med, Digest Hlth Inst, Gastrointestinal Eosinophil Dis Program,Childrens, Aurora, CO USA. [Gurian, Larry E.] Ferrell Duncan Clin & CoxHlth, Springfield, MO USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Hopp, Russell J.] Creighton Univ, Dept Pediat, Div Allergy & Immunol, Omaha, NE 68178 USA. [Kagalwalla, Amir] Ann & Robert H Lurie Childrens Hosp Chicago, Div Gastroenterol Hepatol & Nutr, Chicago, IL USA. [Kagalwalla, Amir] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Nadeau, Kari C.] Stanford Med Sch, Stanford, CA USA. [Nadeau, Kari C.] Stanford Med Ctr, Div Allergy & Immunol, Stanford, CA USA. [Nadeau, Kari C.] Lucille Packard Childrens Hosp, Stanford, CA USA. [Noel, Richard J.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Noel, Richard J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [von Tiehl, Karl F.] Huntington Mem Hosp, Pasadena, CA USA. RP Rothenberg, ME (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, MLC 7028,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM Rothenberg@cchmc.org RI Sucharew, Heidi/M-4338-2015; Martin, Lisa/E-2425-2016; OI Martin, Lisa/0000-0001-8702-9946; Kottyan, Leah/0000-0003-3979-2220; Abonia, Juan/0000-0003-3788-6485 FU Cincinnati Children's Division of Biostatistics and Epidemiology; University of Cincinnati Research Council; Campaign Urging Research for Eosinophilic Diseases (CURED); Food Allergy Research and Education (FARE); Buckeye Foundation; National Institutes of Health (NIH) [T32-ES10957]; NIEHS [P30-ES006096]; CTSA; NCATS; NCRR/NIH [UL1-RR026314-01]; UAB Section on Statistical Genetics [1R25GM093044-01]; [NIH-1K24DK100303] FX This study was supported in part by the: Frank C. Woodside, Dinsmore& Shohl Fellowship through Cincinnati Children's Division of Biostatistics and Epidemiology; University of Cincinnati Research Council; Campaign Urging Research for Eosinophilic Diseases (CURED); Food Allergy Research and Education (FARE); Buckeye Foundation; National Institutes of Health (NIH) grants: T32-ES10957 Molecular Epidemiology in Children's Environmental Health Fellowship 2011-2013; NIEHS P30-ES006096 Center for Environmental Genetics New Investigator Scholar and PI Mentee/Mentor; NIH 8 UL1-TR000077-04 Center for Clinical and Translational Science and Training, CTSA, NCATS Just in Time; CCTST REDCap UL1-RR026314-01 NCRR/NIH; 1R25GM093044-01 UAB Section on Statistical Genetics; NIH-1K24DK100303 (GTF). This work was completed in partial fulfillment of the Doctor of Philosophy degree in Epidemiology in the Department of Environmental Health, Division of Epidemiology and Biostatistics, University of Cincinnati College of Medicine. NR 72 TC 23 Z9 25 U1 3 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2014 VL 134 IS 5 BP 1084 EP + DI 10.1016/j.jaci.2014.07.021 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA AT4UN UT WOS:000344938900013 PM 25258143 ER PT J AU Clark, S Wei, WH Rudders, SA Camargo, CA AF Clark, Sunday Wei, Wenhui Rudders, Susan A. Camargo, Carlos A., Jr. TI Risk factors for severe anaphylaxis in patients receiving anaphylaxis treatment in US emergency departments and hospitals SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Anaphylaxis; severity; emergency department; hospitalization ID ALLERGY; MANAGEMENT; HOSPITALIZATIONS; EPIDEMIOLOGY; FATALITIES; COLLEGE; FOOD AB Background: Although reported risk factors for severe anaphylaxis include older age, presence of comorbid medical conditions, and concomitant medications, previous studies have used varying definitions for anaphylaxis and heterogeneous methodology. Objective: To describe risk factors for severe anaphylaxis among US patients treated in emergency departments (EDs) or hospitals for anaphylaxis. Methods: Individuals with an ED visit/hospitalization for anaphylaxis were identified from 2 MarketScan Research Databases using an expanded International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithm. Eligibility for the current study required continuous medical and prescription coverage for at least 1 year before and after the index date. Severe anaphylaxis was defined as a reaction requiring hospital admission. Results: Among 11,972 individuals, 2,622 (22%) had severe anaphylaxis. Unadjusted analysis showed that severe anaphylaxis was associated with older age and higher comorbidity burden. These patients were also less likely to have filled an epinephrine autoinjector (EAI) prescription or visited an allergist/immunologist, but more likely to have had an ED visit/hospitalization (any cause). On multivariable analysis, filling an EAI prescription (odds ratio [OR], 0.64; 95% CI, 0.53-0.78) or visiting an allergist/immunologist (OR, 0.78; 95% CI, 0.63-0.95) before the index event was associated with a lower risk of severe anaphylaxis, while any previous ED visit (OR, 1.18; 95% CI, 1.07-1.30) or hospitalization (OR, 1.55; 95% CI, 1.36-1.75) was associated with a higher risk of severe anaphylaxis. Conclusions: In this large cohort with an ED visit or hospitalization for anaphylaxis, 22% had severe anaphylaxis. Pre-index preventive anaphylaxis care (ie, EAI prescription fill and allergist/immunologist visit) was associated with a significantly lower risk, supporting the benefits of preventive anaphylaxis care in real-world practice. C1 [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY 10065 USA. [Wei, Wenhui] Sanofi US, Bridgewater, MA USA. [Rudders, Susan A.] Brown Univ, Alpert Sch Med, Rhode Isl Hosp, Dept Pediat, Providence, RI 02912 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Emergency Med, Boston, MA USA. RP Clark, S (reprint author), Weill Cornell Med Coll, Dept Emergency Med, 525 E 68th St,Box 179, New York, NY 10065 USA. EM sunday.clark@gmail.com NR 31 TC 16 Z9 16 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2014 VL 134 IS 5 BP 1125 EP 1130 DI 10.1016/j.jaci.2014.05.018 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AT4UN UT WOS:000344938900018 PM 24985399 ER PT J AU Greenblatt, EE Butler, JP Venegas, JG Winkler, T AF Greenblatt, Elliot E. Butler, James P. Venegas, Jose G. Winkler, Tilo TI Pendelluft in the bronchial tree SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE ventilation distribution; ventilation mechanics; gas exchange; asthma; computational modeling ID HIGH-FREQUENCY OSCILLATION; LUNG MODEL; VENTILATION; FLOW; BIFURCATION; BEHAVIOR AB Inhomogeneous inflation or deflation of the lungs can cause dynamic pressure differences between regions and lead to interregional airflows known as pendelluft. This work first uses analytical tools to clarify the theoretical limits of pendelluft at a single bifurcation. It then explores the global and regional pendelluft that may occur throughout the bronchial tree in a realistic example using an in silico model of bronchoconstriction. The theoretical limits of pendelluft volume exchanged at a local bifurcation driven by sinusoidal breathing range from 15.5% to 41.4% depending on the relative stiffness of the subtended regions. When nonsinusoidal flows are considered, pendelluft can be as high as 200% inlet tidal volume (V-in). At frequencies greater than 10 Hz, the inertia of the air in the airways becomes important, and the maximal local pendelluft is theoretically unbounded, even with sinusoidal breathing. In a single illustrative numerical simulation of bronchoconstriction with homogenous compliances, the overall magnitude of global pendelluft volume was <2% of the tidal volume. Despite the small overall magnitude, pendelluft volume exchange was concentrated in poorly ventilated regions of the lung, including local pendelluft at bifurcations of up to 13% V-in. This example suggests that pendelluft may be an important phenomena contributing to regional gas exchange, irreversible mixing, and aerosol deposition patterns inside poorly ventilated regions of the lung. The analytical results support the concept that pendelluft may be more prominent in diseases with significant heterogeneity in both resistance and compliance. C1 [Greenblatt, Elliot E.] MIT, Cambridge, MA 02139 USA. [Butler, James P.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA. [Butler, James P.] Harvard Univ, Sch Med, Dept Med, Div Sleep Med, Boston, MA USA. [Butler, James P.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Butler, James P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Greenblatt, Elliot E.; Venegas, Jose G.; Winkler, Tilo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenblatt, Elliot E.; Venegas, Jose G.; Winkler, Tilo] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Winkler, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM twinkler@mgh.harvard.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Heart, Lung, and Blood Institute of the National Institutes of Health grant [R01HL087281] FX This work was supported by National Heart, Lung, and Blood Institute of the National Institutes of Health grant R01HL087281. NR 22 TC 5 Z9 5 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV 1 PY 2014 VL 117 IS 9 BP 979 EP 988 DI 10.1152/japplphysiol.00466.2014 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA AT5PT UT WOS:000344995300006 PM 25170072 ER PT J AU Carter, EA Paul, K Bonab, AA Tompkins, RG Fischman, AJ AF Carter, Edward A. Paul, Kasie Bonab, Ali A. Tompkins, Ronald G. Fischman, Alan J. TI Effect of Exercise on Burn-Induced Changes in Tissue-Specific Glucose Metabolism SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID MUSCLE; MICE; IL-6 AB Exercise is a component of the clinical management for burn patients, to help reduce muscle wasting associated with prolonged hospitalization. In the present study the authors examined 2-deoxy-2-[18F] fluoro-D-glucose ((18)FDG) uptake in mice subjected to burn injury with and without exercise. Mice had their the dorsums shaven, were placed in molds, and the exposed area was immersed in 90 degrees C water for 9 seconds followed by resuscitation with saline (2 ml) to produce a 30% full-thickness burn injury. Twenty-four hours later, the mice were subjected to treadmill exercise for 1 hour. Before exercise, mice were injected with similar to 50 mu Ci (18)FDG. Mice were killed after running and a complete biodistribution was performed. Exercise produced a stimulation of (18)FDG update by skeletal muscle and heart, while reducing (18)FDG accumulation in brain. Burn injury had no significant effect on (18)FDG update by skeletal muscle, but did increase (18)FDG accumulation in heart, while reducing (18)FDG accumulation in brain. However, exercise combined with a burn injury produced a significant increase in (18)FDG uptake in the skeletal muscle compared with the burned mice, as great as that produced in the sham animals subjected to exercise. The combination of burn plus exercise appeared to prevent the stimulation of (18)FDG uptake by the heart produced by burn injury alone. Exercise treatment did not correct the changes in (18)FDG uptake in the brain produced by burn injury. Separately, exercise and burn injury significantly increased serum interleukin-6 levels, increases that were higher when exercise was combined with the burn injury. These findings suggest that exercise may exert some therapeutic effects in burn patients by tissue-specific modulation of glucose metabolism, and these changes may be related to interleukin-6. C1 [Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Paul, Kasie; Tompkins, Ronald G.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA. [Bonab, Ali A.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Dept Pediat, 51 Blossom St, Boston, MA 02114 USA. FU National Institutes of Health; Shriners Hospital FX This study was supported by National Institutes of Health and Shriners Hospital for Children Grants. NR 17 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2014 VL 35 IS 6 BP 470 EP 473 DI 10.1097/BCR.0000000000000036 PG 4 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AT8BO UT WOS:000345159000012 PM 24476988 ER PT J AU Carter, EA Hamrahi, V Paul, K Bonab, AA Jung, W Tompkins, RG Fischman, AJ AF Carter, Edward A. Hamrahi, Victoria Paul, Kasie Bonab, Ali A. Jung, Walter Tompkins, Ronald G. Fischman, Alan J. TI Single Hind Limb Burn Injury to Mice Alters Nuclear Factor-kappa B Expression and [F-18] 2-Fluoro-2-Deoxy-D-Glucose Uptake SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID TRANSGENIC MOUSE MODEL; BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; THERMAL-INJURY; ACTIVATION; METABOLISM; RATS AB Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([F-18] 2-fluoro-2-deoxy-D-glucose [(18)FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-kappa B activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on (18)FDG uptake by NF-kappa B activity in vivo, and blood flow was determined by laser Doppler techniques. Male NF-kappa B luciferase reporter mice (28-30 g) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90 degrees C water for 5 seconds. Sham-treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 mL, i.p.). The individual animals were placed in wire bottom cages with no food and free access to water. After 24 hours, the animals were imaged with laser Doppler for measuring blood flow in the hind limb. The animals were then unanesthetized with 50 mu Ci of FDG or luciferin (1.0 mg, i.v.) via tail vein. Five minutes after luciferin injection, NF-kappa B mice were studied by bioluminescence imaging with a charge-coupled device camera. One hour after (18)FDG injection, the animals were killed with carbon dioxide overdose, and (18)FDG biodistribution was measured. Tissues were also analyzed for NF-kappa B luciferase activity. The scalding procedure used here produced a full-thickness burn injury to the leg with sharp margins. (18)FDG uptake by the burned leg was lower than that in the contralateral limb. Similarly, luciferase activity and blood flow in the burned leg were lower than those in the contralateral leg. (18)FDG uptake by BAT and heart increased, whereas that by brain decreased. In conclusion, the present study suggests that burn injury to a single leg decreased (18)FDG uptake by skeletal muscle but increased (18)FDG uptake by BAT. The injury to the leg reduced NF-kappa B expression compared with the contralateral leg and the uninjured skeletal muscle of the sham but activated NF-kappa B expression in a number of other organs. These findings are consistent with the hypothesis that burn trauma to the extremities can produce marked systemic effects, including activation of NF-kappa B expression and activation of (18)FDG uptake by BAT. C1 [Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Hamrahi, Victoria; Paul, Kasie; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA. [Bonab, Ali A.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Pediat Gastrointestinal Unit, 114 16th St 114-3503, Charlestown, MA 02129 USA. FU National Institutes of Health; Shriners Hospital FX Supported by National Institutes of Health and Shriners Hospital for Children grants. NR 22 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 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2014 VL 35 IS 6 BP E373 EP E378 DI 10.1097/BCR.0000000000000035 PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA AT8BO UT WOS:000345159000001 PM 25100541 ER PT J AU Busch, K da Silva, SA Holton, M Rabacow, FM Khalili, N Ludvigsson, JF AF Busch, Katharina da Silva, Simone A. Holton, Michelle Rabacow, Fabiana M. Khalili, Named Ludvigsson, Jonas F. TI Sick leave and disability pension in inflammatory bowel disease: A systematic review SO JOURNAL OF CROHNS & COLITIS LA English DT Review DE Work outcomes; Crohn's disease; Ulcerative colitis; Review ID QUALITY-OF-LIFE; SEVERE CROHNS-DISEASE; ACTIVITY IMPAIRMENT QUESTIONNAIRE; PERMANENT WORK DISABILITY; REGIONAL PATIENT GROUP; ULCERATIVE-COLITIS; CERTOLIZUMAB PEGOL; CLINICAL-TRIAL; HEALTH; PRODUCTIVITY AB Background & aims: Inflammatory bowel disease has considerable effects on work-related outcomes and leads to high societal costs due to sick leave and disability pension. The aims of this study were to systematically review evidence on work-related outcomes that are relevant to productivity losses and to evaluate whether medical or surgical interventions have a positive impact on patients work ability. Methods: A systematic literature search in PubMed was conducted in June 2013. Abstracts were screened by two independent reviewers, and full-text articles describing the frequency of work-related outcomes were retrieved. Two independent reviewers extracted data according to the PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses. Findings were organized by study design (non-interventional/interventional). Non-interventional studies were structured according to whether they presented data in comparison to control groups or not and interventional studies were summarized according to type of intervention. Results: This review included 30 non-interventional (15 with comparison groups and 15 without comparison group) and 17 interventional studies (9 surgical and 8 medical). The majority of the studies reported a high burden of work:related outcomes among inflammatory bowel disease patients regardless of the methodology used. While biologic agents showed positive effect on work absenteeism and presenteeism in randomized clinical trials, the impact of surgical interventions needs further evaluation. Conclusions: Inflammatory bowel disease patients experience a high burden in work-related outcomes. Additional data on productivity losses and the long-term impact of interventions is needed to help inform decision-makers about treatment options and their benefits in reducing productivity losses in inflammatory bowel disease patients. (C) 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. C1 [Busch, Katharina] Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden. [da Silva, Simone A.; Rabacow, Fabiana M.] Univ Sao Paulo, Dept Prevent Med, Sao Paulo, Brazil. [Holton, Michelle] Lorimer Enterprises Inc, Red Deer, AB, Canada. [Khalili, Named] Massachusetts Gen Hosp, Digest Healthcare Ctr, Boston, MA 02114 USA. [Ludvigsson, Jonas F.] Orebro Univ Hosp, Dept Pediat, Orebro, Sweden. [Ludvigsson, Jonas F.] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17176 Stockholm, Sweden. RP Busch, K (reprint author), Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden. EM katharina.busch@ki.se FU American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; Karolinska Institutet Strategic Research Program in Epidemiology FX HK is supported by a career development award from the American Gastroenterological Association (AGA) and by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). JFL has received funding from the Karolinska Institutet Strategic Research Program in Epidemiology. NR 69 TC 7 Z9 7 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-9946 EI 1876-4479 J9 J CROHNS COLITIS JI J. Crohns Colitis PD NOV 1 PY 2014 VL 8 IS 11 BP 1362 EP 1377 DI 10.1016/j.crohns.2014.06.006 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AT8KL UT WOS:000345182200003 PM 25001582 ER PT J AU Mazurek, MO Handen, BL Wodka, EL Nowinski, L Butter, E Engelhardt, CR AF Mazurek, Micah O. Handen, Benjamin L. Wodka, Ericka L. Nowinski, Lisa Butter, Eric Engelhardt, Christopher R. TI Age at First Autism Spectrum Disorder Diagnosis: The Role of Birth Cohort, Demographic Factors, and Clinical Features SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE autism; autism spectrum disorder; diagnosis; early diagnosis; delayed diagnosis ID CHILDREN; SAMPLE; TIME AB Objective: This study sought to identify factors that may be associated with delays in autism spectrum disorder (ASD) diagnosis, including birth cohort, sociodemographic characteristics, and clinical features. Methods: Participants included 1716 children and adolescents with ASD enrolled in the Autism Speaks Autism Treatment Network (AS-ATN) between the years 2008 and 2011. Data were collected at enrollment using AS-ATN parent- and clinician-report forms and standardized measures of I.Q., ASD symptoms, adaptive function, and psychiatric symptoms. Results: Age at first ASD diagnosis was positively correlated with current age, suggesting a birth cohort effect. Sociodemographic and clinical features were also associated with age at diagnosis, even after controlling for current age. Hierarchical linear regression results showed that older current age, lower socioeconomic status (SES), higher I.Q. score, and lower levels of autism symptoms were associated with later age at initial diagnosis. There was also a significant interaction between current age and I.Q., with higher functioning children being diagnosed at younger ages than in previous years. Conclusions: Early diagnosis of ASD is critically important for improving access to interventions; however, many children experience diagnostic delays. In this sample, children from the most recent birth cohorts were diagnosed earlier, suggesting that early signs of ASD are being increasingly recognized. However, socioeconomic barriers to diagnosis still seem to exist. Children with less severe ASD symptoms and with higher I.Q. are also diagnosed at later ages. Efforts are still needed to reduce diagnostic disparities for families of low SES and to improve early recognition of more subtle symptoms. C1 [Mazurek, Micah O.; Engelhardt, Christopher R.] Univ Missouri, Dept Hlth Psychol, Columbia, MO 65211 USA. [Mazurek, Micah O.; Engelhardt, Christopher R.] Univ Missouri, Thompson Ctr Autism & Neurodev Disorders, Columbia, MO 65211 USA. [Handen, Benjamin L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Wodka, Ericka L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Wodka, Ericka L.] Kennedy Krieger Inst, Ctr Autism & Related Disorders, Baltimore, MD USA. [Nowinski, Lisa] MassGen Hosp Children, Lurie Ctr Autism, Boston, MA USA. [Nowinski, Lisa] Harvard Univ, Sch Med, Boston, MA USA. [Butter, Eric] Ohio State Univ, Nationwide Childrens Hosp, Dept Pediat, Columbus, OH 43210 USA. [Butter, Eric] Ohio State Univ, Nationwide Childrens Hosp, Dept Psychol, Columbus, OH 43210 USA. RP Mazurek, MO (reprint author), Univ Missouri, Dept Hlth Psychol, 205 Portland St, Columbia, MO 65211 USA. EM mazurekm@missouri.edu OI Mazurek, Micah/0000-0001-7715-6538 FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054] FX The authors acknowledge the members of the Autism Speaks Autism Treatment Network (AS-ATN) for use of the data. The data for the study were collected as part of the AS-Am Further support came from a cooperative agreement (UA3 MC 11054) from the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program to the Massachusetts General Hospital. The views expressed in this publication do not necessarily reflect the views of the AS-ATN. NR 38 TC 10 Z9 10 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X EI 1536-7312 J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD NOV-DEC PY 2014 VL 35 IS 9 BP 561 EP 569 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA AT7HN UT WOS:000345107400001 PM 25211371 ER PT J AU Letourneau, K Goodman, JH AF Letourneau, Katherine Goodman, Janice H. TI A Patient-Centered Approach to Addressing Physical Activity in Older Adults Motivational Interviewing SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID NURSE-PRACTITIONER; METAANALYSIS AB Regular physical activity reduces the burden of chronic diseases in older adults, but the majority of this population is relatively sedentary. Individuals considering a change in behavior, such as increasing exercise, often experience a mental state of ambivalence, which can lead to inaction. Ambivalence is resistant to traditional counseling methods used in medical settings, such as patient education. Motivational interviewing (MI) is a conversational style that has been shown to help overcome ambivalence by guiding patients to voice their personal reasons for change. Nurse practitioners are uniquely positioned to use MI with older adults to address ambivalence toward increasing physical activity. C1 [Letourneau, Katherine; Goodman, Janice H.] Massachusetts Gen Hosp, Inst Hlth Profess, Sch Nursing, Boston, MA 02129 USA. RP Letourneau, K (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Sch Nursing, 36 First Ave, Boston, MA 02129 USA. EM kjletourneau@gmail.com NR 14 TC 1 Z9 1 U1 2 U2 16 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 EI 1938-243X J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD NOV PY 2014 VL 40 IS 11 BP 27 EP 33 DI 10.3928/00989134-20140819-01 PG 7 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA AT9QY UT WOS:000345262500005 PM 25199152 ER PT J AU Baumert, TF Fauvelle, C Chen, DY Lauer, GM AF Baumert, Thomas F. Fauvelle, Catherine Chen, Diana Y. Lauer, Georg M. TI A prophylactic hepatitis C virus vaccine: A distant peak still worth climbing SO JOURNAL OF HEPATOLOGY LA English DT Article DE Hepatitis C; Vaccine; T cells; Antibodies ID T-CELL RESPONSES; CHRONIC VIRAL-INFECTION; HUMAN MONOCLONAL-ANTIBODIES; ADAPTIVE IMMUNE-RESPONSES; IN-VITRO PROLIFERATION; ACUTE HCV INFECTION; NEUTRALIZING ANTIBODIES; E2 GLYCOPROTEIN; PEPTIDE-VACCINE; LIVER-TRANSPLANTATION AB Hepatitis C virus (HCV) infects an estimated more than 150 million people and is a leading cause of liver disease worldwide. The development of direct-acting antivirals (DAAs) will markedly improve the outcome of antiviral treatment with cure of the majority of treated patients. However, several hurdles remain before HCV infection can be considered a menace of the past: High treatment costs will most likely result in absent or limited access in middle and low resource countries and will lead to selective use even in wealthier countries. The limited efficacy of current HCV screening programs leads to a majority of cases being undiagnosed or diagnosed at a late stage and DAAs will not cure virus-induced end-stage liver disease such as hepatocellular carcinoma. Certain patient subgroups may not respond or not be eligible for DAA-based treatment strategies. Finally, reinfection remains possible, making control of HCV infection in people with ongoing infection risk difficult. The unmet medical needs justify continued efforts to develop an effective vaccine, protecting from chronic HCV infection as a mean to impact the epidemic on a global scale. Recent progress in the understanding of virus-host interactions provides new perspectives for vaccine development, but many critical questions remain unanswered. In this review, we focus on what is known about the immune correlates of HCV control, highlight key mechanisms of viral evasion that pose challenges for vaccine development and suggest areas of further investigation that could enable a rational approach to vaccine design. Within this context we also discuss insights from recent HCV vaccination studies and what they suggest about the best way to go forward. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Baumert, Thomas F.; Chen, Diana Y.; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Baumert, Thomas F.; Chen, Diana Y.; Lauer, Georg M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Baumert, Thomas F.; Fauvelle, Catherine] Univ Strasbourg, Inst Rech Malad Virales & Hepat, Strasbourg, France. [Baumert, Thomas F.] Hop Univ Strasbourg, Pole Hepatodigestif, Inst Hosp Univ, Strasbourg, France. RP Baumert, TF (reprint author), Univ Strasbourg, INSERM, U1110, 3 Rue Koeberle, F-67000 Strasbourg, France. EM Thomas.Baumert@unistra.fr; glauer@mgh.harvard.edu FU National Institutes of Health (NIH) [U19 AI082630, U19 AI066345, R01 AI105035]; French Cancer Foundation [ARC IHU201301187]; French Research Agency [LABEX ANR-10-LAB-28]; European Commission (EU) [ERC-2008-AdG-233130-HEPCENT] FX G.M. Lauer is supported by the National Institutes of Health (NIH) Grant U19 AI082630, NIH Grant U19 AI066345 and NIH Grant R01 AI105035. T.F. Baumert is supported by the French Cancer Foundation (ARC IHU201301187), French Research Agency (LABEX ANR-10-LAB-28) and the European Commission (ERC-2008-AdG-233130-HEPCENT, EU FP7 HepaMab; INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net2012). NR 107 TC 25 Z9 26 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2014 VL 61 SU 1 BP S34 EP S44 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AT7KR UT WOS:000345115800005 PM 25443345 ER PT J AU Hoshida, Y Fuchs, BC Bardeesy, N Baumert, TF Chung, RT AF Hoshida, Yujin Fuchs, Bryan C. Bardeesy, Nabeel Baumert, Thomas F. Chung, Raymond T. TI Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma SO JOURNAL OF HEPATOLOGY LA English DT Article DE Hepatitis C virus; Hepatocellular carcinoma; Prevention; Carcinogenesis ID EPIDERMAL-GROWTH-FACTOR; NF-KAPPA-B; HCV CORE PROTEIN; LIVER-DISEASE PROGRESSION; GENE-EXPRESSION; INTERFERON THERAPY; SIGNALING PATHWAY; STELLATE CELLS; FUNCTIONAL POLYMORPHISM; NONSTRUCTURAL PROTEIN AB Hepatitis C virus (HCV) is one of the major aetiologic agents that causes hepatocellular carcinoma (HCC) by generating an inflammatory, fibrogenic, and carcinogenic tissue microenvironment in the liver. HCV-induced HCC is a rational target for cancer preventive intervention because of the clear-cut high-risk condition, cirrhosis, associated with high cancer incidence (1% to 7% per year). Studies have elucidated direct and indirect carcinogenic effects of HCV, which have in turn led to the identification of candidate HCC chemoprevention targets. Selective molecular targeted agents may enable personalized strategies for HCC chemoprevention. In addition, multiple experimental and epidemiological studies suggest the potential value of generic drugs or dietary supplements targeting inflammation, oxidant stress, or metabolic derangements as possible HCC chemopreventive agents. While the successful use of highly effective direct-acting antiviral agents will make important inroads into reducing long-term HCC risk, there will remain an important role for HCC chemoprevention even after viral cure, given the persistence of HCC risk in persons with advanced HCV fibrosis, as shown in recent studies. The successful development of cancer preventive therapies will be more challenging compared to cancer therapeutics because of the requirement for larger and longer clinical trials and the need for a safer toxicity profile given its use as a preventive agent. Molecular biomarkers to selectively identify high-risk population could help mitigate these challenges. Genome-wide, unbiased molecular characterization, high-throughput drug/gene screening, experimental model-based functional analysis, and systems-level in silico modelling are expected to complement each other to facilitate discovery of new HCC chemoprevention targets and therapies. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Hoshida, Yujin] Icahn Sch Med Mt Sinai, Hess Ctr Sci & Med, Dept Med, Div Liver Dis,Liver Canc Program,Tisch Canc Inst, New York, NY 10029 USA. [Fuchs, Bryan C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Cambridge, MA 02138 USA. [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Cambridge, MA 02138 USA. [Baumert, Thomas F.] Univ Strasbourg, INSERM, Inst Rech Malad Virales & Hepat, U1110, Strasbourg, France. [Baumert, Thomas F.] Hop Univ Strasbourg, Pole Hepatodigestif, Inst Hosp Univ, Strasbourg, France. [Baumert, Thomas F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Liver, Cambridge, MA 02138 USA. [Baumert, Thomas F.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div,Dept Med, Cambridge, MA 02138 USA. RP Hoshida, Y (reprint author), Icahn Sch Med Mt Sinai, Hess Ctr Sci & Med, Dept Med, Div Liver Dis,Liver Canc Program,Tisch Canc Inst, 1470 Madison Ave,Box 1123, New York, NY 10029 USA. EM yujin.hoshida@mssm.edu; rtchung@partners.org FU National Institute of Health [DK099558, CA140861, DK078772]; French Cancer Foundation [ARC IHU201301187]; French Research Agency [LABEX ANR-10-LAB-28]; European Commission [259744, ERC-2008-AdG-233130-HEPCENT] FX This research was supported by the National Institute of Health (DK099558 to Y.H., CA140861 to B.C.F., DK078772 to R.T.C.), the European Commission Framework Programme 7 (Heptromic, proposal number 259744 to Y.H.), the French Cancer Foundation (ARC IHU201301187 to T.F.B.), the French Research Agency (LABEX ANR-10-LAB-28 to T.F.B.), and the European Commission (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Superieur-FEDER-Hepato-Regio-Net 2012 to T.F.B.). NR 169 TC 19 Z9 19 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2014 VL 61 SU 1 BP S79 EP S90 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AT7KR UT WOS:000345115800009 PM 25443348 ER PT J AU Fagotti, A Ghezzi, F Boruta, DM Scambia, G Escobar, P Fader, AN Malzoni, M Fanfani, F AF Fagotti, Anna Ghezzi, Fabio Boruta, David M. Scambia, Giovanni Escobar, Pedro Fader, Amanda N. Malzoni, Mario Fanfani, Francesco TI Minilaparoscopic Radical Hysterectomy (mLPS-RH) vs Laparoendoscopic Single-Site Radical Hysterectomy (LESS-RH) in Early Stage Cervical Cancer: A Multicenter Retrospective Study SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Early-stage cervical cancer; Laparoendoscopic single-site surgery; Minilaparoscopic surgery; Radical hysterectomy ID SURGERY LESS; MULTIINSTITUTIONAL EXPERIENCE; PELVIC LYMPHADENECTOMY; ENDOMETRIAL CANCER; LAPAROSCOPY AB Study Objective: To compare the perioperative outcomes of laparoendoscopic single-site radical hysterectomy (LESS-RH) and minilaparoscopic radical hysterectomy (mLPS-RH). Design: Retrospective study (Canadian Task Force classification II-2). Setting: Seven institutions in Italy. Patients: Forty-six patents with early cervical cancer (FIGO stage IA2-IB1/IIA1) were included in the study. Nineteen patients (41.3%) underwent LESS-RH, and 27 (58.7%) underwent mLPS-RH. Pelvic lymph node dissection was performed in all patients. Interventions: In the LESS-RH group, all surgical procedures were performed through a single umbilical multichannel port. In the mLPS-RH group, the procedure was completed using a 5-mm umbilical optical trocar and 3 additional 3-mm ancillary trocars, placed suprapubically and in the left and right lower abdominal regions. Measurements and Main Results: There was no difference in clinicopathologic characteristics at the time of diagnosis between the LESS-RH and mLPS-RH groups. Median operative time was 270 minutes (range, 149-380 minutes) for LESS-RH, and was 180 minutes (range, 90-240 minutes) for mLPS-RH (p = .001). No further differences were detected between the 2 groups insofar as type of radical hysterectomy, number of lymph nodes removed, or perioperative outcomes. In the LESS-RH group, conversion to laparotomy was necessary in 1 patient (5.3%) because of external iliac vein injury, and in another patient, conversion to standard laparoscopy was required because of truncal obesity. In the mLPS-RH group, no conversions were observed; however, a repeat operation was performed to repair a ureteral injury. The percentage of patients discharged 1 day after surgery was significantly higher in the LESS-RH group (57.9%) compared with the mLPS-RH group (25.0%) (p = .03). After a median follow-up of 27 months (range, 9-73 months), only 1 patient, who had undergone mLPS-RH, experienced pelvic recurrence and died of the disease. Conclusions: Both LESS-RH and mLPS-RH are feasible ultra-minimally invasive approaches for performance of radical hysterectomy plus pelvic lymph node dissection. Further technical improvements are required to enable wider use of these techniques for more complex procedures. (C) 2014 AAGL. All rights reserved. C1 [Fagotti, Anna] Univ Perugia, St Maria Hosp, Div Minimally Invas Gynaecol Surg, I-05100 Terni, Italy. [Ghezzi, Fabio] Univ Insubria, Dept Obstet & Gynecol, Div Gynecol Oncol, Varese, Italy. [Boruta, David M.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. [Scambia, Giovanni; Fanfani, Francesco] Univ Cattolica Sacro Cuore, Dept Obstet & Gynaecol, I-00168 Rome, Italy. [Escobar, Pedro] HIMA San Pablo, Div Gynecol Oncol, Caguas, Puerto Rico. [Escobar, Pedro] Cleveland Clin, Div Gynecol Oncol, Cleveland, OH 44106 USA. [Fader, Amanda N.] Johns Hopkins Univ Hosp, Dept Gynecol & Obstet, Kelly Gynecol Oncol Serv, Baltimore, MD 21287 USA. [Malzoni, Mario] Malzoni Med Ctr, Adv Gynecol Endoscopy Ctr, Avellino, Italy. RP Fagotti, A (reprint author), Univ Perugia, St Maria Hosp, Div Minimally Invas Gynaecol Surg, Via Tristano di Joannuccio 1, I-05100 Terni, Italy. EM annafagotti@libero.it RI Fanfani, Francesco/Q-1154-2015; OI Fanfani, Francesco/0000-0003-1991-7284; Ghezzi, Fabio/0000-0003-3949-5410 NR 22 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 EI 1553-4669 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD NOV-DEC PY 2014 VL 21 IS 6 BP 1005 EP 1009 DI 10.1016/j.jmig.2014.04.008 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AT5JM UT WOS:000344979600015 PM 24768978 ER PT J AU McCunney, RJ Mundt, KA Colby, WD Dobie, R Kaliski, K Blais, M AF McCunney, Robert J. Mundt, Kenneth A. Colby, W. David Dobie, Robert Kaliski, Kenneth Blais, Mark TI Wind Turbines and Health A Critical Review of the Scientific Literature SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LOW-FREQUENCY NOISE; BONE-CONDUCTED SOUND; PSYCHOMETRIC PROPERTIES; TRANSPORTATION NOISE; ENVIRONMENTAL NOISE; PERSONALITY-TRAITS; SPIRAL GANGLION; LIFE ASSESSMENT; ANNOYANCE; SENSITIVITY AB Objective: This review examines the literature related to health effects of wind turbines. Methods: We reviewed literature related to sound measurements near turbines, epidemiological and experimental studies, and factors associated with annoyance. Results: (1) Infrasound sound near wind turbines does not exceed audibility thresholds. (2) Epidemiological studies have shown associations between living near wind turbines and annoyance. (3) Infrasound and low-frequency sound do not present unique health risks. (4) Annoyance seems more strongly related to individual characteristics than noise from turbines. Discussion: Further areas of inquiry include enhanced noise characterization, analysis of predicted noise values contrasted with measured levels postinstallation, longitudinal assessments of health pre- and postinstallation, experimental studies in which subjects are "blinded" to the presence or absence of infrasound, and enhanced measurement techniques to evaluate annoyance. C1 [McCunney, Robert J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Mundt, Kenneth A.] Environ Int, Dept Epidemiol, Amherst, MA USA. [Colby, W. David] Middlesex London Hlth Unit, Travel Immunizat Clin, London, ON, Canada. [Dobie, Robert] Dobie Associates, San Antonio, TX USA. [Kaliski, Kenneth] Resource Syst Grp, White River Jct, VT USA. [Blais, Mark] Massachusetts Gen Hosp, Psychol Evaluat & Res Lab, Boston, MA 02114 USA. RP McCunney, RJ (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave,16-771, Cambridge, MA 02139 USA. EM mccunney@mit.edu OI dobie, robert/0000-0003-3833-1772 NR 156 TC 6 Z9 6 U1 3 U2 42 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 2014 VL 56 IS 11 BP E108 EP E130 DI 10.1097/JOM.0000000000000313 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AT7DE UT WOS:000345096100001 PM 25376420 ER PT J AU Pace, CG Hwang, KG Papadaki, M Troulis, MJ AF Pace, Christopher G. Hwang, Kyung-Gyun Papadaki, Maria Troulis, Maria J. TI Interventional Sialoendoscopy for Treatment of Obstructive Sialadenitis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CHRONIC RECURRENT PAROTITIS; SHOCK-WAVE LITHOTRIPSY; SALIVARY-GLAND STONES; MANAGEMENT; CALCULI; SIALOLITHIASIS; DIAGNOSIS; SIALENDOSCOPY; STRICTURES; ENDOSCOPY AB Purpose: This follow-up study documents the overall success rate of interventional sialoendoscopy; it is a novel, less invasive treatment for obstructive sialadenitis. Patients and Methods: This was a retrospective follow-up study of 189 patients who underwent a sialoendoscopic procedure at Massachusetts General Hospital from 2004 through 2013. Included were patients who underwent sialoendoscopic treatment for symptoms and clinical findings consistent with obstructive sialadenitis. Four different interventional sialoendoscopic techniques were used: dilation of stricture and irrigation, stone retrieval by basket, stone fragmentation with lithotripsy or laser, and stone removal by endoscopic-assisted "cutdown" operation using the "modified McGurk" technique. The outcome assessed was whether the patient was asymptomatic at 6 months postoperatively. Results: Interventional endoscopic navigation was accomplished in 164 of 189 patients (87%). In 17 cases, the duct orifice was inaccessible owing to scarring, so the duct could not be navigated. Symptomatic relief was achieved in 148 of 164 patients (90%). Dilatation and lavage for sialadenitis without a stone was accomplished in 52 of 189 patients (28%). Sialoliths were retrieved or fragmented in 137 of 164 cases (84%). Conclusion: The results of this study show a high success rate in the treatment of obstructive sialadenitis using interventional sialoendoscopy. (C) 2014 American Association of Oral and Maxillofacial Surgeons C1 [Pace, Christopher G.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Pace, Christopher G.] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA 02114 USA. [Hwang, Kyung-Gyun] Hanyang Univ, Div Oral & Maxillofacial Surg, Dept Dent, Coll Med, Seoul 133791, South Korea. [Papadaki, Maria] Univ Hosp Heraklio, Iraklion, Greece. [Troulis, Maria J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Troulis, Maria J.] Massachusetts Gen Hosp, Residency Training Program, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Pace, CG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Warren Suite 1201,55 Fruit St, Boston, MA 02114 USA. EM drcpace@yahoo.com NR 36 TC 6 Z9 6 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2014 VL 72 IS 11 BP 2157 EP 2166 DI 10.1016/j.joms.2014.06.438 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AT9CE UT WOS:000345224800019 PM 25438275 ER PT J AU Friedlander, AH Liebeskind, DS Tran, HQ Mallya, SM AF Friedlander, Arthur H. Liebeskind, David S. Tran, Huy Q. Mallya, Sanjay M. TI What Are the Potential Implications of Identifying Intracranial Internal Carotid Artery Atherosclerotic Lesions on Cone-Beam Computed Tomography? A Systematic Review and Illustrative Case Studies SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; SMALL VESSEL DISEASE; RISK-FACTORS; INCIDENTAL FINDINGS; CORONARY; STROKE; CALCIFICATIONS; PREVALENCE; OUTCOMES; STENOSIS AB Purpose: A systematic literature review was performed to examine the clinical implications of intracranial internal carotid artery calcific atherosclerotic lesions (IICACALs) detected at cone-beam computed tomographic (CBCT) examinations. Materials and Methods: The PubMed database was queried in 2 separate searches using the linked search terms non-contrast enhanced cone beam computed tomography and calcified intracranial vascular lesions and non-contrast enhanced computed tomography and calcified intracranial vascular lesions. Reviewed were all English-language articles using CBCT or CT imaging that enrolled neurologically asymptomatic and symptomatic patients. Excluded were studies describing patients with hemorrhagic stroke. Illustrative cases describing incidentally detected IICACALs on CBCT scans are provided. Results: Three articles described identification of IICACALs on CBCT scans of almost 1,500 dental patients. Two of these fully addressed the subject, with 1 noting that IICACALs were benign and another urging patient referral for further workup. Five non-contrast-enhanced CT studies were evaluated in detail; all confirmed IICACALs as a substantive risk marker of advanced stenotic disease in the cerebral circulation, central brain atrophy, concomitant advanced atherosclerotic disease in the cardiovascular circulation, and an indicator of future ischemic events. Five CBCT examinations showing IICACALs in the cavernous and ophthalmic segments are presented. Conclusion: Few studies have denoted the importance of identifying IICACALs on CBCT scans. However, all non-contrast-enhanced CT studies emphasized the clinical significance of these lesions in relation to cerebral and cardiovascular disease. Therefore, IICACALs seen on CBCT and CT scans present the same risk and should prompt referral for further evaluation. (C) 2014 American Association of Oral and Maxillofacial Surgeons C1 [Friedlander, Arthur H.] Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Assoc, Los Angeles, CA USA. [Friedlander, Arthur H.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Qual Assurance Hosp Dent Serv, Ronald Reagan UCLA Med Ctr, Los Angeles, CA 90095 USA. [Friedlander, Arthur H.] Univ Calif Los Angeles, Sect Oral & Maxillofacial Surg, Sch Dent, Los Angeles, CA 90095 USA. [Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Clin Neurol, Los Angeles, CA 90095 USA. [Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Stroke Program, Los Angeles, CA 90095 USA. [Tran, Huy Q.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA. [Mallya, Sanjay M.] Univ Calif Los Angeles, Div Diagnost & Surg Sci, Sect Oral & Maxillofacial Radiol, Sch Dent, Los Angeles, CA 90095 USA. RP Mallya, SM (reprint author), Univ Calif Los Angeles, Residency Program, Sect Oral & Maxillofacial Radiol, Sch Dent, Los Angeles, CA 90095 USA. EM smallya@dentistry.ucla.edu NR 29 TC 6 Z9 6 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2014 VL 72 IS 11 BP 2167 EP 2177 DI 10.1016/j.joms.2014.06.437 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AT9CE UT WOS:000345224800020 PM 25438276 ER PT J AU Gaither, JR Goulet, JL Becker, WC Crystal, S Edelman, EJ Gordon, K Kerns, RD Rimland, D Skanderson, M Weisberg, DF Justice, AC Fiellin, DA AF Gaither, Julie R. Goulet, Joseph L. Becker, William C. Crystal, Stephen Edelman, E. Jennifer Gordon, Kirsha Kerns, Robert D. Rimland, David Skanderson, Melissa Weisberg, Daniel F. Justice, Amy C. Fiellin, David A. TI Guideline-Concordant Management of Opioid Therapy Among Human Immunodeficiency Virus (HIV)-Infected and Uninfected Veterans SO JOURNAL OF PAIN LA English DT Article DE Opioid analgesics; practice guideline; quality of health care; chronic pain; HIV ID CHRONIC NONCANCER PAIN; HIV-INFECTED PATIENTS; UNITED-STATES; CLINICAL GUIDELINES; HEALTH-CARE; PRESCRIBING PRACTICES; PRESCRIPTION OPIOIDS; AGING COHORT; QUALITY; ABUSE AB Whether patients receive guideline-concordant opioid therapy (OT) is largely unknown and may vary based on provider and patient characteristics. We assessed the extent to which human immunodeficiency virus (HIV)-infected and uninfected patients initiating long-term (>= 90 days) OT received care concordant with American Pain Society/American Academy of Pain Medicine and Department of Veterans Affairs/Department of Defense guidelines by measuring receipt of 17 indicators during the first 6 months of OT. Of 20,753 patients, HIV-infected patients (n = 6,604) were more likely than uninfected patients to receive a primary care provider visit within 1 month (52.0% vs 30.9%) and 6 months (90.7% vs 73.7%) and urine drug tests within 1 month (14.8% vs 11.5%) and 6 months (19.5% vs 15.4%; all P < .001). HIV-infected patients were also more likely to receive OT concurrent with sedatives (24.6% vs 19.6%) and a current substance use disorder (21.6% vs 17.2%). Among both patient groups, only modest changes in guideline concordance were observed over time: urine drug tests and OT concurrent with current substance use disorders increased, whereas sedative coprescriptions decreased (all Ps for trend <.001). Over a 10-year period, on average, patients received no more than 40% of recommended care. OT guideline-concordant care is rare in primary care, varies by patient/provider characteristics, and has undergone few changes over time. Perspective: The promulgation of OT clinical guidelines has not resulted in substantive changes over time in OT management, which falls well short of the standard recommended by leading medical societies. Strategies are needed to increase the provision of OT guideline-concordant care for all patients. (C) 2014 by the American Pain Society. Published by Elsevier Inc. All rights reserved C1 [Gaither, Julie R.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Edelman, E. Jennifer; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Publ Hlth, Yale Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Goulet, Joseph L.; Kerns, Robert D.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Becker, William C.; Edelman, E. Jennifer; Weisberg, Daniel F.; Justice, Amy C.; Fiellin, David A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. [Goulet, Joseph L.; Becker, William C.; Gordon, Kirsha; Kerns, Robert D.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Rimland, David] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA. [Rimland, David] Atlanta VA Med Ctr, Decatur, GA USA. [Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Gaither, JR (reprint author), Yale Univ, Sch Publ Hlth, POB 208034,60 Coll St, New Haven, CT 06520 USA. EM julie.gaither@yale.edu OI Gaither, Julie/0000-0001-6053-8505; Fiellin, David/0000-0002-4006-010X; Goulet, Joseph/0000-0002-0842-804X FU National Institute on Drug Abuse [F31DA035567]; National Institute on Alcohol Abuse and Alcoholism [U10AA013566, U01AA020790, U24AA020794]; National Institute of Mental Health [P30MH062294]; VA Health Services Research and Development Research Enhancement Award Program [REA 08-266]; Agency for Healthcare Research and Quality [U19HS21112] FX Research reported in this paper was supported by grants from the National Institute on Drug Abuse (grant no. F31DA035567), National Institute on Alcohol Abuse and Alcoholism (grant nos. U10AA013566, U01AA020790, and U24AA020794), National Institute of Mental Health (grant no. P30MH062294), VA Health Services Research and Development Research Enhancement Award Program (grant no. REA 08-266), and the Agency for Healthcare Research and Quality (grant no. U19HS21112). NR 54 TC 7 Z9 8 U1 2 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD NOV PY 2014 VL 15 IS 11 BP 1130 EP 1140 DI 10.1016/j.jpain.2014.08.004 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AT4LZ UT WOS:000344912200007 PM 25152300 ER PT J AU Krebs, EE Bergman, AA Coffing, JM Campbell, SR Frankel, RM Matthias, MS AF Krebs, Erin E. Bergman, Alicia A. Coffing, Jessica M. Campbell, Steffanie R. Frankel, Richard M. Matthias, Marianne S. TI Barriers to Guideline-Concordant Opioid Management in Primary Care-A Qualitative Study SO JOURNAL OF PAIN LA English DT Article DE Chronic pain; opioid analgesics; qualitative research; primary care; guidelines ID RISK REDUCTION STRATEGIES; CHRONIC NONCANCER PAIN; CLINICAL GUIDELINES; THERAPY; TIME; ADHERENCE; NETWORK; MISUSE AB Prior studies have demonstrated poor physician adherence to opioid management guidelines in primary care. The objectives of this qualitative study were to understand physicians' and patients' perspectives on recommended opioid management practices and to identify potential barriers to and facilitators of guideline-concordant opioid management in primary care. Individual semistructured interviews were conducted with 14 primary care physicians and 26 of their patients receiving long-term opioid therapy. Data were analyzed using a qualitative immersion/crystallization approach. We identified 3 major barriers to and 1 facilitator of use of recommended opioid management practices. Major barriers were inadequate time and resources available; relying on general impressions of risk for opioid misuse; and viewing opioid monitoring as a "law enforcement" activity. The third barrier was most apparent for physicians in the context of drug testing and for patients in the context of opioid agreements. Beliefs about the need to protect patients from opioid-related harm emerged as a major facilitator, especially among patients. We hypothesize that future interventions to improve opioid management in primary care will be more effective if they address identified barriers and use a patient-centered framework, in which prevention of opioid-related harm to patients is emphasized as the primary goal. Perspective: This article describes primary care perspectives on guideline-recommended opioid management practices. Barriers identified in this study may contribute to underuse of recommended opioid management practices. Consideration of barriers and facilitators to guideline-concordant care could improve effectiveness of future interventions aimed at improving opioid management in primary care. Published by Elsevier Inc. on behalf of the American Pain Society C1 [Krebs, Erin E.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Krebs, Erin E.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55417 USA. [Bergman, Alicia A.] VA Greater Los Angeles Syst, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Coffing, Jessica M.; Frankel, Richard M.; Matthias, Marianne S.] Roudebush VA Med Ctr, Ctr Hlth Informat & Commun, Indianapolis, IN USA. [Campbell, Steffanie R.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Frankel, Richard M.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Frankel, Richard M.; Matthias, Marianne S.] Regenstrief Inst Inc, Indianapolis, IN USA. [Matthias, Marianne S.] Indiana Univ Purdue Univ, Dept Commun Studies, Indianapolis, IN 46202 USA. RP Krebs, EE (reprint author), Univ Minnesota, Sch Med, Minneapolis VA Hlth Care Syst, Dept Med,Ctr Chron Dis Outcomes Res, Minneapolis VAMC 152,One Vet Dr, Minneapolis, MN 55417 USA. EM erin.krebs@va.gov FU U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Career Development Awards [CDA 07-215, CDA 10-034] FX This work was supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Career Development Awards to E.E.K. (CDA 07-215) and M.S.M. (CDA 10-034). NR 37 TC 13 Z9 13 U1 2 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD NOV PY 2014 VL 15 IS 11 BP 1148 EP 1155 DI 10.1016/j.jpain.2014.08.006 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AT4LZ UT WOS:000344912200009 PM 25179150 ER PT J AU Danilack, VA Stolzmann, KL Gagnon, DR Brown, R Tun, CG Morse, LR Garshick, E AF Danilack, Valery A. Stolzmann, Kelly L. Gagnon, David R. Brown, Robert Tun, Carlos G. Morse, Leslie R. Garshick, Eric TI Associations with chest illness and mortality in chronic spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Spinal cord injuries; Respiratory tract infections; Mortality ID RISK-FACTORS; TRENDS; STANDARDIZATION; POPULATION; SPIROMETRY; DISORDERS; SURVIVAL; SYMPTOMS; VETERANS; OUTCOMES AB Objective: Identify factors associated with chest illness and describe the relationship between chest illness and mortality in chronic spinal cord injury (SCI). Design: Cross-sectional survey assessing chest illness and a prospective assessment of mortality. Methods: Between 1994 and 2005, 430 persons with chronic SCI (mean +/- SD), 52.0 +/- 14.9 years old, and >= 4 years post SCI (20.5 +/- 12.5 years) underwent spirometry, completed a health questionnaire, and reported any chest illness resulting in time off work, indoors, or in bed in the preceding 3 years. Deaths through 2007 were identified. Outcome measures: Logistic regression assessing relationships with chest illness at baseline and Cox regression assessing the relationship between chest illness and mortality. Results: Chest illness was reported by 139 persons (32.3%). Personal characteristics associated with chest illness were current smoking (odds ratio = 2.15; 95% confidence interval = 1.25-3.70 per each pack per day increase), chronic obstructive pulmonary disease (COPD) (3.52; 1.79-6.92), and heart disease (2.18; 1.14-4.16). Adjusting for age, subjects reporting previous chest illness had a non-significantly increased hazard ratio (HR) for mortality (1.30; 0.88-1.91). In a multivariable model, independent predictors of mortality were greater age, SCI level and completeness of injury, diabetes, a lower %-predicted forced expiratory volume in 1 second, heart disease, and smoking history. Adjusting for these covariates, the effect of a previous chest illness on mortality was attenuated (HR = 1.15; 0.77-1.73). Conclusion: In chronic SCI, chest illness in the preceding 3 years was not an independent risk factor for mortality and was not associated with level and completeness of SCI, but was associated with current smoking, physician-diagnosed COPD, and heart disease history. C1 [Danilack, Valery A.; Stolzmann, Kelly L.; Gagnon, David R.; Tun, Carlos G.; Garshick, Eric] VA Boston Healthcare Syst, Boston, MA USA. [Danilack, Valery A.] Brown Univ, Dept Epidemiol, Providence, RI 02903 USA. [Danilack, Valery A.; Stolzmann, Kelly L.; Brown, Robert; Tun, Carlos G.; Morse, Leslie R.; Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Brown, Robert] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Morse, Leslie R.] Spaulding Rehabil Hosp, Spaulding Harvard SCI Model Syst, Boston, MA USA. [Garshick, Eric] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. RP Danilack, VA (reprint author), Brown Univ, Dept Epidemiol, 121 South Main St,Box GS-121-2, Providence, RI 02903 USA. EM valery_danilack@brown.edu RI Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU NIH/NICHD [RO1 HD42141]; VA Rehabilitation Research and Development [B6618R]; Massachusetts Veterans Epidemiology Research and Information Center, Department of Veterans Affairs, Cooperative Studies Program; Department of Education, National Institute on Disability and Rehabilitation Research Grant [H133N110010] FX The work was supported by NIH/NICHD RO1 HD42141, VA Rehabilitation Research and Development Merit Review Grant B6618R (Dr. Garshick), the Massachusetts Veterans Epidemiology Research and Information Center, Department of Veterans Affairs, Cooperative Studies Program, and the Department of Education, National Institute on Disability and Rehabilitation Research Grant H133N110010 (Dr. Morse). NR 29 TC 3 Z9 3 U1 2 U2 5 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD NOV PY 2014 VL 37 IS 6 BP 662 EP 669 DI 10.1179/2045772313Y.0000000144 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AT9AE UT WOS:000345219200002 PM 24090450 ER PT J AU Warms, CA Backus, D Rajan, S Bombardier, CH Schomer, KG Burns, SP AF Warms, Catherine A. Backus, Deborah Rajan, Suparna Bombardier, Charles H. Schomer, Katherine G. Burns, Stephen P. TI Adverse events in cardiovascular-related training programs in people with spinal cord injury: A systematic review SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Review DE Aerobic exercise; Functional electric stimulation; Locomotor training; Gait training; Treadmill training; Ergometry; Wheelchair exercise; Spinal cord injuries; Tetraplegia; Paraplegia ID FUNCTIONAL ELECTRICAL-STIMULATION; PARASTEP(R)1 AMBULATION SYSTEM; ARM CRANKING EXERCISE; PHYSICAL-ACTIVITY; PHYSIOLOGICAL-RESPONSES; WHEELCHAIR ERGOMETER; TETRAPLEGIC PATIENTS; CLINICAL-EVALUATION; BODY-COMPOSITION; INDIVIDUALS AB Context: There are anecdotal reports of adverse events (AEs) associated with exercise in people with spinal cord injury (SCI) and consequent concern by people with SCI and their providers about potential risks of exercise. Enumeration of specific events has never been performed and the extent of risk of exercise to people with SCI is not understood. Objective: To systematically review published evidence to identify and enumerate reports of adverse events or AEs associated with training in persons with SCI. Methods: Review was limited to peer-reviewed studies published in English from 1970 to 2011: (1) in adults with SCI, (2) evaluating training protocols consisting of repeated sessions over at least 4 weeks to maintain or improve cardiovascular health, (3) including volitional exercise modalities and functional electrical stimulation (FES)-enhanced exercise modalities, and (4) including a specific statement about AEs. Trained reviewers initially identified a total of 145 studies. After further screening, 38 studies were included in the review. Quality of evidence was evaluated using established procedures. Results: There were no serious AEs reported. There were no common AEs reported across most types of interventions, except for musculoskeletal AEs related to FES walking. There were few AEs in volitional exercise studies. Conclusion: There is no evidence to suggest that cardiovascular exercise done according to guidelines and established safety precautions is harmful. To improve the strength of these conclusions, future publications should include definition of AEs, information about pre-intervention screening, and statements of the nature and extent of AEs. C1 [Warms, Catherine A.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Warms, Catherine A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Backus, Deborah] Shepherd Ctr, Atlanta, GA USA. [Rajan, Suparna; Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bombardier, Charles H.; Schomer, Katherine G.; Burns, Stephen P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Warms, CA (reprint author), Univ Washington, Med Ctr, Seattle, WA 98195 USA. EM cwarms@u.washington.edu FU National Institute for Disability and Rehabilitation Research, Office of Special Education and Rehabilitative Services, US Department of Education, Washington, DC [H133A060070]; University of Washington Northwest Regional Spinal Cord Injury System [H133N060033] FX This work was funded in part by grants from the National Institute for Disability and Rehabilitation Research, Office of Special Education and Rehabilitative Services, US Department of Education, Washington, DC to the University of Washington Model Systems Knowledge Translation Center (H133A060070) and the University of Washington Northwest Regional Spinal Cord Injury System (H133N060033). NR 57 TC 0 Z9 0 U1 5 U2 19 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD NOV PY 2014 VL 37 IS 6 BP 672 EP 692 DI 10.1179/2045772313Y.0000000115 PG 21 WC Clinical Neurology SC Neurosciences & Neurology GA AT9AE UT WOS:000345219200004 PM 24090603 ER PT J AU Emmons, RR Cirnigliaro, CM Kirshblum, SC Bauman, WA AF Emmons, Racine R. Cirnigliaro, Christopher M. Kirshblum, Steven C. Bauman, William A. TI The relationship between the postprandial lipemic response and lipid composition in persons with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Postprandial lipemia; Lipid particle size; Spinal cord injury; Abdominal fat; Apolipoprotein B ID LOW-DENSITY-LIPOPROTEIN; VISCERAL FAT; REMNANT LIPOPROTEINS; APOLIPOPROTEIN B-48; METABOLIC SYNDROME; RISK-FACTORS; CORONARY; ULTRASONOGRAPHY; ATHEROSCLEROSIS; ATHEROGENESIS AB Objective: To determine the influence of lipid concentration, lipid particle size, and total abdominal fat (TAF) on postprandial lipemic response (PPLr) in persons with spinal cord injury (SCI). Methods: Thirty-five persons with SCI (17 paraplegia, 18 tetraplegia) and 18 able-bodied (AB) individuals participated. Following a 10-hour fast, blood was drawn for lipids, apolipoprotein (apo) A1 and B concentrations, and low-density (LSP) and high-density (HSP) lipoprotein particle sizes. A high-fat milkshake was consumed (similar to 1.3 g fat/kg). Blood was drawn at 2, 4, and 6 hours to determine PPLr, (triglyceride (TG) area under the curve). TAF and visceral (VF) fat were measured by ultrasonography; total body fat (TBF) by dual-energy X-ray absorptiometry. Differences between the groups were determined by independent sample t-tests. Pearson correlation coefficients determined the relationship among PPLr and lipids, and TAF. Results: There were no significant differences in fasting TG, low-density lipoprotein (LDL), apoB, TAF, or PPLr values between the groups. In SCI, PPLr significantly correlated with: apoB (r = 0.63, P < 0.01, LSP (r = 0.57, P < 0.01), and TAF (r = 0.36, P < 0.01). After controlling for age and duration of injury, PPLr significantly correlated with apoB (r = 0.66, P = 0.001), TBF (r = 0.45, P = 0.03), VF (r = 0.66, P = 0.02), and TAF (r = 0.56, P = 0.007). Conclusions: Although concentrations of LDL cholesterol and apoB were not different between SCI and AB groups, LSP, apoB, and TAF correlated with PPLr in persons with SCI. ApoB was associated with a greater PPLr in those with motor complete SCI, after controlling for age and duration of injury. C1 [Emmons, Racine R.] William Paterson Univ, Dept Kinesiol, Wayne, NJ 07470 USA. [Emmons, Racine R.; Cirnigliaro, Christopher M.; Bauman, William A.] James J Peters VA Med Ctr, Rehabil Res & Dev Natl Ctr Excellence Med Consequ, Dept Vet Affairs, Bronx, NY USA. [Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA. [Kirshblum, Steven C.] Rutgers New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ USA. [Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. RP Emmons, RR (reprint author), William Paterson Univ, Dept Kinesiol, 300 Pompton Rd, Wayne, NJ 07470 USA. EM emmonshindelongr@wpunj.edu FU Veteran Affairs Rehabilitation Research and Development Service [B4162C]; James J. Peters VA Medical Center FX This research was supported by the Veteran Affairs Rehabilitation Research and Development Service (#B4162C) and the James J. Peters VA Medical Center. NR 30 TC 0 Z9 0 U1 0 U2 3 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD NOV PY 2014 VL 37 IS 6 BP 765 EP 773 DI 10.1179/2045772314Y.0000000231 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AT9AE UT WOS:000345219200013 PM 24961488 ER PT J AU Yang, HQ Trbovich, M Harrow, J AF Yang, Huiqing Trbovich, Michelle Harrow, Jeffrey TI Secondary adrenal insufficiency after glucocorticosteroid administration in acute spinal cord injury: A case report SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Acute spinal cord injury; Steroid; Adrenal insufficiency; Cosyntropin stimulation test ID ORTHOSTATIC HYPOTENSION; ILL PATIENTS; METHYLPREDNISOLONE; STIMULATION; PREVALENCE; DIAGNOSIS; THERAPY; TESTS; MEN AB Context/background: A 61-year-old female with cervical stenosis underwent an elective cervical laminectomy with post-op worsening upper extremity weakness. Over the first 3 weeks post-op, she received two separate courses of intravenous steroids. Two days after cessation of steroids, she presented with non-specific symptoms of adrenal insufficiency (AI). Initial formal diagnostic tests of random cortisol level and 250 mu g cosyntropin challenge were non-diagnostic; however, symptoms resolved with the initiation of empiric treatment with hydrocortisone. Ten days later, repeat cosyntropin (adrenocortocotropic hormone stimulation) test confirmed the diagnosis of AI. Findings: AI is a potentially life-threatening complication of acute spinal cord injury (ASCI), especially in those receiving steroids acutely. Only three cases have been reported to date of AI occurring in ASCI after steroid treatment. The presenting symptoms can be non-specific (as in this patient) and easily confused with other common sequelae of ASCI such as orthostasis and diffuse weakness. The 250 mu g cosyntropin simulation test may not the most sensitive test to diagnose AI in ASCI. Conclusion: The non-specific presentations and variability of diagnosis criteria make diagnosis more difficult. One microgram cosyntropin simulation test may be more sensitive than higher dose. Clinicians should be aware that AI can be a potential life-threatening complication of ASCI post-steroid treatment. Prompt diagnosis and treatment can reverse symptoms and minimize mortality. C1 [Yang, Huiqing; Trbovich, Michelle; Harrow, Jeffrey] Univ Texas Hlth Sci Ctr San Antonio, Dept Phys Med & Rehabil, San Antonio, TX 78229 USA. [Trbovich, Michelle; Harrow, Jeffrey] Audie L Murphy Mem Vet Affairs Hosp, Spinal Cord Injury Serv, San Antonio, TX USA. RP Trbovich, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, Mail Code 7798,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Michelle.Trbovich@va.gov NR 28 TC 0 Z9 0 U1 1 U2 4 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD NOV PY 2014 VL 37 IS 6 BP 786 EP 790 DI 10.1179/2045772314Y.0000000223 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AT9AE UT WOS:000345219200016 PM 24969098 ER PT J AU Marshall, L Miller, JAL Guinan, JJ Shera, CA Reed, CM Perez, ZD Delhorne, LA Boege, P AF Marshall, Lynne Miller, Judi A. Lapsley Guinan, John J. Shera, Christopher A. Reed, Charlotte M. Perez, Zachary D. Delhorne, Lorraine A. Boege, Paul TI Otoacoustic-emission-based medial-olivocochlear reflex assays for humans SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID COCHLEAR MICROMECHANICAL PROPERTIES; CONTRALATERAL ACOUSTIC STIMULATION; INDUCED HEARING-LOSS; FINE-STRUCTURE; EFFERENT FEEDBACK; INNER-EAR; NOISE; SUSCEPTIBILITY; AMPLITUDE; REPEATABILITY AB Otoacoustic emission (OAE) tests of the medial-olivocochlear reflex (MOCR) in humans were assessed for viability as clinical assays. Two reflection-source OAEs [TEOAEs: transient-evoked otoacoustic emissions evoked by a 47 dB sound pressure level (SPL) chirp; and discrete-tone SFOAEs: stimulus-frequency otoacoustic emissions evoked by 40 dB SPL tones, and assessed with a 60 dB SPL suppressor] were compared in 27 normal-hearing adults. The MOCR elicitor was a 60 dB SPL contralateral broadband noise. An estimate of MOCR strength, MOCR%, was defined as the vector difference between OAEs measured with and without the elicitor, normalized by OAE magnitude (without elicitor). An MOCR was reliably detected in most ears. Within subjects, MOCR strength was correlated across frequency bands and across OAE type. The ratio of across-subject variability to within-subject variability ranged from 2 to 15, with wideband TEOAEs and averaged SFOAEs giving the highest ratios. MOCR strength in individual ears was reliably classified into low, normal, and high groups. SFOAEs using 1.5 to 2 kHz tones and TEOAEs in the 0.5 to 2.5 kHz band gave the best statistical results. TEOAEs had more clinical advantages. Both assays could be made faster for clinical applications, such as screening for individual susceptibility to acoustic trauma in a hearing-conservation program. C1 [Marshall, Lynne; Miller, Judi A. Lapsley] Naval Submarine Med Res Lab, Groton, CT 06349 USA. [Guinan, John J.; Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Reed, Charlotte M.; Perez, Zachary D.; Delhorne, Lorraine A.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Marshall, L (reprint author), Naval Submarine Med Res Lab, Box 900, Groton, CT 06349 USA. EM Lynne.Marshall@med.navy.mil FU ONR [N0001412WX20904]; NSMRL Work Unit [50 904] FX Thanks to Mike Katzenbach from Mimosa Acoustics for technical support, Linton Miller for useful discussions about the analyses, and Tim Villabona from MIT for assistance with data collection. Thanks to Kelly Watts from NSMRL for providing many helpful, constructive comments. The work was supported by ONR Grant/Agreement No. N0001412WX20904 "Susceptibility to Noise-Induced Hearing Loss using Otoacoustic Emissions," NSMRL Work Unit No. 50 904. L. M. is an employee of the U. S. Government. This work was prepared as part of her official duties. Title 17 U. S. C. 105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U. S. C. 101 defines a U. S. Government work as a work prepared by a military service member or employee of the U. S. Government as part of that person's official duties. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or the United States Government. NR 53 TC 6 Z9 6 U1 1 U2 8 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2014 VL 136 IS 5 BP 2697 EP 2713 DI 10.1121/1.4896745 PG 17 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AT5NG UT WOS:000344989000039 PM 25373970 ER PT J AU Boland, GW Duszak, R Larson, PA AF Boland, Giles W. Duszak, Richard, Jr. Larson, Paul A. TI IMAGING VALUE CHAIN Communication of Actionable Information SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Boland, Giles W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. [Larson, Paul A.] Radiol Associates Fox Valley, Neenah, WI 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 1 TC 2 Z9 2 U1 1 U2 2 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 NOV PY 2014 VL 11 IS 11 BP 1019 EP 1021 DI 10.1016/j.jacr.2014.08.003 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT3KW UT WOS:000344834800005 PM 25245789 ER PT J AU Ha, CS Hodgson, DC Advani, R Dabaja, BS Dhakal, S Flowers, CR Hoppe, BS Mendenhall, NP Metzger, ML Plastaras, JP Roberts, KB Shapiro, R Smith, S Terezakis, SA Winkfield, KM Younes, A Constine, LS AF Ha, Chul S. Hodgson, David C. Advani, Ranjana Dabaja, Bouthaina S. Dhakal, Sughosh Flowers, Christopher R. Hoppe, Bradford S. Mendenhall, Nancy P. Metzger, Monika L. Plastaras, John P. Roberts, Kenneth B. Shapiro, Ronald Smith, Sonali Terezakis, Stephanie A. Winkfield, Karen M. Younes, Anas Constine, Louis S. TI ACR Appropriateness Criteria Follow-up of Hodgkin Lymphoma SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; Hodgkin lymphoma; follow up; surveillance; recurrence; treatment sequela ID POSITRON-EMISSION-TOMOGRAPHY; COST-EFFECTIVENESS ANALYSIS; CHILDHOOD-CANCER SURVIVOR; CORONARY-ARTERY-DISEASE; LONG-TERM SURVIVORS; BREAST-CANCER; MEDIASTINAL IRRADIATION; LUNG-CANCER; 1ST-LINE THERAPY; PULMONARY-FUNCTION AB The main objectives of follow-up studies after completion of treatment for Hodgkin lymphoma are detection of recurrence for salvage therapy and monitoring for sequelae of treatment. The focus of the follow-up shifts, with time after treatment, from detection of recurrence to long-term sequelae. A majority of recurrence is detected by history and physical examination. The yield for routine imaging studies and blood tests is low. Although routine surveillance CT scan can detect recurrence not detected by history and physical examination, its benefit in ultimate survival and cost-effectiveness is not well defined. Although PET scan is a useful tool in assessing response to treatment, its routine use for follow-up is not recommended. Long-term sequelae of treatment include secondary malignancy, cardiovascular disease, pneumonitis, reproductive dysfunction, and hypothyroidism. Follow-up strategies for these sequelae need to be individualized, as their risks in general depend on the dose and volume of radiation to these organs, chemotherapy, age at treatment, and predisposing factors for each sequela. The ACR 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 in which evidence is either lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Ha, Chul S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, San Antonio, TX 78229 USA. [Hodgson, David C.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. [Advani, Ranjana] Stanford Sch Med, Stanford Canc Ctr, Stanford, CA USA. [Dabaja, Bouthaina S.; Younes, Anas] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Dhakal, Sughosh] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. [Flowers, Christopher R.] Emory Univ, Dept Hematol & Oncol, Atlanta, GA 30322 USA. [Hoppe, Bradford S.] Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. [Mendenhall, Nancy P.] Univ Florida, Dept Radiat Oncol, Gainesville, FL USA. [Metzger, Monika L.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Plastaras, John P.] Univ Penn Hlth Syst, Dept Radiat Oncol, Philadelphia, PA USA. [Roberts, Kenneth B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Shapiro, Ronald] Indiana Univ, Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA. [Smith, Sonali] Univ Chicago, Chicago, IL 60637 USA. [Terezakis, Stephanie A.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Dept Radiat Oncol, Baltimore, MD 21287 USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Advani, Ranjana; Flowers, Christopher R.; Metzger, Monika L.; Younes, Anas] Amer Soc Clin Oncol, Alexandria, VA USA. [Smith, Sonali] Amer Soc Hematol, Washington, DC USA. RP Ha, CS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, 7703 Floyd Curl Dr MC 7889, San Antonio, TX 78229 USA. EM hac@uthscsa.edu RI Flowers, Christopher/F-1953-2010; OI Flowers, Christopher/0000-0002-9524-3990; Terezakis, Stephanie/0000-0003-4933-6712; Hoppe, Bradford/0000-0002-2312-5418; Mendenhall, Nancy/0000-0003-2893-7703 NR 63 TC 3 Z9 3 U1 1 U2 2 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 NOV PY 2014 VL 11 IS 11 BP 1026 EP 1033 DI 10.1016/j.jacr.2014.07.038 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT3KW UT WOS:000344834800008 PM 25278496 ER PT J AU Sundt, TM AF Sundt, Thoralf M. TI Sound arguments, true premises, and valid conclusions SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. EM tsundt@mgh.harvard.edu NR 0 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 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2014 VL 148 IS 5 BP 2070 EP 2071 DI 10.1016/j.jtcvs.2014.09.056 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AT7QM UT WOS:000345132600067 PM 25444188 ER PT J AU Lynch, JM Buckley, EM Schwab, PJ McCarthy, AL Winters, ME Busch, DR Xiao, R Goff, DA Nicolson, SC Montenegro, LM Fuller, S Gaynor, JW Spray, TL Yodh, AG Naim, MY Licht, DJ AF Lynch, Jennifer M. Buckley, Erin M. Schwab, Peter J. McCarthy, Ann L. Winters, Madeline E. Busch, David R. Xiao, Rui Goff, Donna A. Nicolson, Susan C. Montenegro, Lisa M. Fuller, Stephanie Gaynor, J. William Spray, Thomas L. Yodh, Arjun G. Naim, Maryam Y. Licht, Daniel J. TI Time to surgery and preoperative cerebral hemodynamics predict postoperative white matter injury in neonates with hypoplastic left heart syndrome SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID PERIVENTRICULAR LEUKOMALACIA; NEURODEVELOPMENTAL OUTCOMES; NORWOOD PROCEDURE; PRETERM INFANTS; RISK-FACTORS; CHILDREN; DISEASE; QUANTIFICATION; SPECTROSCOPY; MATURATION AB Objective: Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately one half of HLHS survivors will exhibit neurobehavioral symptoms believed to be associated with this injury, although the exact timing of the injury is unknown. Methods: Neonates with HLHS were recruited for pre- and postoperative monitoring of cerebral oxygen saturation, cerebral oxygen extraction fraction, and cerebral blood flow using 2 noninvasive optical-based techniques: diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomic magnetic resonance imaging was performed before and approximately 1 week after surgery to quantify the extent and timing of the acquired white matter injury. The risk factors for developing new or worsened white matter injury were assessed using uni- and multivariate logistic regression. Results: A total of 37 neonates with HLHS were studied. On univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time to surgery (P = .0003). In a multivariate model, a longer time between birth and surgery, delayed sternal closure, and greater preoperative cerebral blood flow were predictors of postoperative white matter injury. Additionally, a longer time to surgery and greater preoperative cerebral blood flow on the morning of surgery correlated with lower cerebral oxygen saturation (P = .03 and P = .05, respectively) and greater oxygen extraction fraction (P = .05 for both). Conclusions: A longer time to surgery was associated with new postoperative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation might decrease the likelihood of acquiring postoperative white matter injury. C1 [Lynch, Jennifer M.; Buckley, Erin M.; Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. [Buckley, Erin M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Opt Div, Charlestown, MA USA. [Buckley, Erin M.; Schwab, Peter J.; McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Licht, Daniel J.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Xiao, Rui] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Goff, Donna A.] Loma Linda Univ, Childrens Hosp, Div Pediat Cardiol, Loma Linda, CA 92350 USA. [Nicolson, Susan C.; Montenegro, Lisa M.] Childrens Hosp Philadelphia, Div Cardiothorac Anesthesia, Philadelphia, PA 19104 USA. [Fuller, Stephanie; Gaynor, J. William; Spray, Thomas L.] Childrens Hosp Philadelphia, Div Cardiothorac Surg, Philadelphia, PA 19104 USA. [Naim, Maryam Y.] Hosp Philadelphia, Div Crit Care Med, Philadelphia, PA USA. RP Lynch, JM (reprint author), Univ Penn, Dept Phys & Astron, 209 South 33rd St, Philadelphia, PA 19104 USA. EM jenlynch@alumni.upenn.edu RI Busch, David/B-5543-2013 OI Busch, David/0000-0002-9488-944X FU National Institutes of Health [NS-072338, NS-60653, HL-007954, HL-007915, P41-EB015893]; Thrasher Research Foundation; June and Steve Wolfson Family foundation FX This study was supported by the National Institutes of Health (grants NS-072338, NS-60653, HL-007954, HL-007915, and P41-EB015893), the Thrasher Research Foundation, and the June and Steve Wolfson Family foundation. NR 31 TC 19 Z9 19 U1 0 U2 8 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 NOV PY 2014 VL 148 IS 5 BP 2181 EP 2188 DI 10.1016/j.jtcvs.2014.05.081 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AT7QM UT WOS:000345132600087 PM 25109755 ER PT J AU Ahroni, JH AF Ahroni, Jessie H. TI Developing a Wound and Skin Care Program SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING LA English DT Article DE program development; skin care; wound care AB The purpose of this article is to review the process used in a large Veterans Affairs facility to unite a group of diverse wound care specialists together into a coordinated program. Program development is an iterative, interactive process requiring continued recycling of efforts until projects are completed. The Program Development Cycle is presented as an example of intentional planning that has been divided into 4 phases: (1) identifying the agency culture, (2) engaging in targeted project development, (3) developing operational strategies, and (4) conducting follow-up analysis. Specific examples of developing a mission, program goals, and wound care champions are discussed. Discussion also incorporates suggestions for changing organizational culture, developing policies and procedures, using best practices and guidelines, creating a wound fair, and incorporating a skin bundle and the challenges of outcome assessment. C1 [Ahroni, Jessie H.] VA Puget Sound Hlth Care Syst, Wound & Skin Care Program, Seattle, WA 98108 USA. [Ahroni, Jessie H.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. RP Ahroni, JH (reprint author), VA Puget Sound Hlth Care Syst, Wound & Skin Care Program, Mail Stop S-118-NEO,1660 South Columbian Way, Seattle, WA 98108 USA. EM Jessie.Ahroni@VA.gov NR 16 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1071-5754 EI 1528-3976 J9 J WOUND OSTOMY CONT JI J. Wound Ostomy Cont. Nurs. PD NOV-DEC PY 2014 VL 41 IS 6 BP 549 EP 555 DI 10.1097/WON.0000000000000085 PG 7 WC Nursing SC Nursing GA AT7RF UT WOS:000345134400009 PM 25377104 ER PT J AU Rowlands, CJ Wu, J Uzel, SGM Klein, O Evans, CL So, PTC AF Rowlands, Christopher J. Wu, Jackie Uzel, Sebastien G. M. Klein, Oliver Evans, Conor L. So, Peter T. C. TI 3D-resolved targeting of photodynamic therapy using temporal focusing SO LASER PHYSICS LETTERS LA English DT Article DE temporal focusing; photodynamic therapy; cancer; ultrafast amplifier ID 2-PHOTON EXCITATION; MICROSCOPY AB A method for selectively inducing apoptosis in tumor nodules is presented, with close-to-cellular level resolution, using 3D-resolved widefield temporal focusing illumination. Treatment times on the order of seconds were achieved using Verteporfin as the photosensitizer, with doses of 30 mu g ml(-1) and below. Results were achieved on both 2D and 3D cell cultures, demonstrating that treatment was possible through approximately one hundred microns of dense tumor nodules. C1 [Rowlands, Christopher J.; Wu, Jackie; So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Uzel, Sebastien G. M.; So, Peter T. C.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Klein, Oliver; Evans, Conor L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Rowlands, CJ (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ptso@mit.edu OI /0000-0002-8261-2371 FU NIH [9P41EB015871-26A1, R01-EX017656, 5 R01 NS051320, 4R44EB012415-02]; NSF [CBET-0939511]; Singapore-MIT Alliance 2; BioSym IRG of Singapore-MIT Alliance Research and Technology Center; MIT SkolTech initiative; Wellcome Trust MIT Postdoctoral Research Fellowship; Wellcome Trust [093831/Z/10/Z]; NIH Director's New Innovator Award [DP2 OD007096]; National Science Foundation Science and Technology Center for Emergent Behaviors of Integrated Cellular Systems [CBET-0939511] FX PTCSO acknowledges support from NIH 9P41EB015871-26A1, R01-EX017656, 5 R01 NS051320, 4R44EB012415-02, NSF CBET-0939511, the Singapore-MIT Alliance 2, the BioSym IRG of Singapore-MIT Alliance Research and Technology Center and the MIT SkolTech initiative. CJR is grateful for a Wellcome Trust MIT Postdoctoral Research Fellowship to carry out this research; this work was supported by the Wellcome Trust 093831/Z/10/Z. CLE and OJK were supported by an NIH Director's New Innovator Award, grant number DP2 OD007096. Information on the New Innovator Award Program is at http://nihroadmap.nih.gov/newinnovator/. SGMU is funded by the National Science Foundation Science and Technology Center for Emergent Behaviors of Integrated Cellular Systems (CBET-0939511). NR 22 TC 1 Z9 1 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1612-2011 EI 1612-202X J9 LASER PHYS LETT JI Laser Phys. Lett. PD NOV PY 2014 VL 11 IS 11 AR 115605 DI 10.1088/1612-2011/11/11/115605 PG 7 WC Optics; Physics, Applied SC Optics; Physics GA AT9AX UT WOS:000345221100015 ER PT J AU Amin, SB Yip, WK Minvielle, S Broyl, A Li, Y Hanlon, B Swanson, D Shah, PK Moreau, P van der Holt, B van Duin, M Magrangeas, F Sonneveld, PP Anderson, KC Li, C Avet-Loiseau, H Munshi, NC AF Amin, S. B. Yip, W-K Minvielle, S. Broyl, A. Li, Y. Hanlon, B. Swanson, D. Shah, P. K. Moreau, P. van der Holt, B. van Duin, M. Magrangeas, F. Sonneveld, P. Pieter Anderson, K. C. Li, C. Avet-Loiseau, H. Munshi, N. C. TI Gene expression profile alone is inadequate in predicting complete response in multiple myeloma SO LEUKEMIA LA English DT Article ID LENALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; MOLECULAR CLASSIFICATION; INTERGROUPE FRANCOPHONE; THERAPEUTIC TARGETS; MICROARRAY DATA; BREAST-CANCER; FOLLOW-UP; CHEMOTHERAPY; BORTEZOMIB AB With advent of several treatment options in multiple myeloma (MM), a selection of effective regimen has become an important issue. Use of gene expression profile (GEP) is considered an important tool in predicting outcome; however, it is unclear whether such genomic analysis alone can adequately predict therapeutic response. We evaluated the ability of GEP to predict complete response (CR) in MM. GEP from pretreatment MM cells from 136 uniformly treated MM patients with response data on an IFM, France led study were analyzed. To evaluate variability in predictive power due to microarray platform or treatment types, additional data sets from three different studies (n = 511) were analyzed using same methods. We used several machine learning methods to derive a prediction model using training and test subsets of the original four data sets. Among all methods employed for GEP-based CR predictive capability, we got accuracy range of 56-78% in test data sets and no significant difference with regard to GEP platforms, treatment regimens or in newly diagnosed or relapsed patients. Importantly, permuted P-value showed no statistically significant CR predictive information in GEP data. This analysis suggests that GEP-based signature has limited power to predict CR in MM, highlighting the need to develop comprehensive predictive model using integrated genomics approach. C1 [Amin, S. B.; Munshi, N. C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Amin, S. B.; Munshi, N. C.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Dept Hematol Oncol, Boston, MA USA. [Amin, S. B.; Shah, P. K.; Li, C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Yip, W-K; Swanson, D.; Shah, P. K.; Li, C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Minvielle, S.; Moreau, P.; Magrangeas, F.; Sonneveld, P. Pieter; Avet-Loiseau, H.] Hop Nantes, Dept Hematol, Nantes, France. [Minvielle, S.; Moreau, P.; Magrangeas, F.; Sonneveld, P. Pieter; Avet-Loiseau, H.] Univ Nantes, Dept Hematol, INSERM, U892, Nantes, France. [Broyl, A.; van der Holt, B.; van Duin, M.] Erasmus Med Ctr & Univ, Dept Hematol, Rotterdam, Netherlands. [Broyl, A.; van der Holt, B.; van Duin, M.] Erasmus Med Ctr & Univ, HOVON Data Ctr, Rotterdam, Netherlands. [Li, Y.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Hanlon, B.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI richard, chrystelle/K-8595-2015; Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; OI Amin, Samir/0000-0002-3207-9505 FU Department of Veterans Affairs Merit Review Awards [I01-BX001584]; National Institutes of Health [RO1-124929, RO1-050947, P50-100007, PO1-78378, PO1-155258, R01GM077122] FX This work was supported in part by grants from the Department of Veterans Affairs Merit Review Awards I01-BX001584 and from the National Institutes of Health Grants RO1-124929 to NCM., RO1-050947 to KCA, and P50-100007 and PO1-78378 to NCM and KCA, PO1-155258 to NCM, KCA, HAL, SM, CL and PM and R01GM077122 to CL. KCA is an American Cancer Society Clinical Research Professor. NR 59 TC 13 Z9 13 U1 1 U2 5 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 NOV PY 2014 VL 28 IS 11 BP 2229 EP 2234 DI 10.1038/leu.2014.140 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA AT4UY UT WOS:000344940300013 PM 24732597 ER PT J AU Gordon, PM Dias, S Williams, DA AF Gordon, P. M. Dias, Stuart Williams, D. A. TI Cytokines secreted by bone marrow stromal cells protect c-KIT mutant AML cells from c-KIT inhibitor-induced apoptosis SO LEUKEMIA LA English DT Letter ID COLONY-STIMULATING FACTOR; ENZYME-IMMUNOASSAY; LEUKEMIA; MUTATION; AML1-ETO; LINE C1 Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Stem Cell Inst, Boston, MA USA. RP Gordon, PM (reprint author), Univ Minnesota, Div Pediat Hematol Oncol, Minneapolis, MN 55455 USA. EM gord0047@umn.edu FU NCI NIH HHS [5K08CA154782-02, 5R01CA113969-08, K08 CA154782, R01 CA113969]; NIDDK NIH HHS [5R01DK062757, R01 DK062757] NR 14 TC 2 Z9 2 U1 0 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 NOV PY 2014 VL 28 IS 11 BP 2257 EP 2260 DI 10.1038/leu.2014.212 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA AT4UY UT WOS:000344940300020 PM 25030047 ER PT J AU Hansen, DC Bassler, N Sorensen, TS Seco, J AF Hansen, David C. Bassler, Niels Sorensen, Thomas Sangild Seco, Joao TI The image quality of ion computed tomography at clinical imaging dose levels SO MEDICAL PHYSICS LA English DT Article DE proton computed tomography; ion computed tomography; stopping power estimation; range estimation ID MONTE-CARLO SIMULATIONS; STOPPING-POWER RATIOS; LARGE ENERGY LOSSES; STRAGGLING DISTRIBUTIONS; DENSITY RESOLUTION; PROTON RADIOGRAPHY; PARTICLE THERAPY; RECONSTRUCTION; CT; SYSTEM AB Purpose: Accurately predicting the range of radiotherapy ions in vivo is important for the precise delivery of dose in particle therapy. Range uncertainty is currently the single largest contribution to the dose margins used in planning and leads to a higher dose to normal tissue. The use of ion CT has been proposed as a method to improve the range uncertainty and thereby reduce dose to normal tissue of the patient. A wide variety of ions have been proposed and studied for this purpose, but no studies evaluate the image quality obtained with different ions in a consistent manner. However, imaging doses ion CT is a concern which may limit the obtainable image quality. In addition, the imaging doses reported have not been directly comparable with x-ray CT doses due to the different biological impacts of ion radiation. The purpose of this work is to develop a robust methodology for comparing the image quality of ion CT with respect to particle therapy, taking into account different reconstruction methods and ion species. Methods: A comparison of different ions and energies was made. Ion CT projections were simulated for five different scenarios: Protons at 230 and 330 MeV, helium ions at 230 MeV/u, and carbon ions at 430 MeV/u. Maps of the water equivalent stopping power were reconstructed using a weighted least squares method. The dose was evaluated via a quality factor weighted CT dose index called the CT dose equivalent index (CTDEI). Spatial resolution was measured by the modulation transfer function. This was done by a noise-robust fit to the edge spread function. Second, the image quality as a function of the number of scanning angles was evaluated for protons at 230 MeV. In the resolution study, the CTDEI was fixed to 10 mSv, similar to a typical x-ray CT scan. Finally, scans at a range of CTDEI's were done, to evaluate dose influence on reconstruction error. Results: All ions yielded accurate stopping power estimates, none of which were statistically different from the ground truth image. Resolution (as defined by the modulation transfer function = 10% point) was the best for the helium ions (18.21 line pairs/cm) and worst for the lower energy protons (9.37 line pairs/cm). The weighted quality factor for the different ions ranged from 1.23 for helium to 2.35 for carbon ions. For the angle study, a sharp increase in absolute error was observed below 45 distinct angles, giving the impression of a threshold, rather than smooth, limit to the number of angles. Conclusions: The method presented for comparing various ion CT modalities is feasible for practical use. While all studied ions would improve upon x-ray CT for particle range estimation, helium appears to give the best results and deserves further study for imaging. (C) 2014 American Association of Physicists in Medicine. C1 [Hansen, David C.] Aarhus Univ Hosp, Dept Expt Clin Oncol, DK-8000 Aarhus, Denmark. [Bassler, Niels] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus, Denmark. [Sorensen, Thomas Sangild] Aarhus Univ, Dept Comp Sci, DK-8000 Aarhus, Denmark. [Sorensen, Thomas Sangild] Aarhus Univ, Dept Clin Med, DK-8000 Aarhus, Denmark. [Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hansen, DC (reprint author), Aarhus Univ Hosp, Dept Expt Clin Oncol, DK-8000 Aarhus, Denmark. EM dch@oncology.au.dk OI Sorensen, Thomas Sangild/0000-0002-8482-7667 FU CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology; Danish Council for Strategic Research FX Bjarne Thomsen, Department of Physics and Astronomy, Aarhus University is thanked for providing cluster computing time. This project was supported by CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology, The Danish Council for Strategic Research (http://www.cirro.dk). NR 53 TC 3 Z9 3 U1 3 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2014 VL 41 IS 11 AR 111908 DI 10.1118/1.4897614 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5RO UT WOS:000344999800029 PM 25370641 ER PT J AU Li, XH Zhang, D Liu, B AF Li, Xinhua Zhang, Da Liu, Bob TI Radiation dose calculations for CT scans with tube current modulation using the approach to equilibrium function SO MEDICAL PHYSICS LA English DT Article DE computed tomography (CT); dosimetry; tube current modulation ID DOSIMETRY; EQUATIONS AB Purpose: The approach to equilibrium function has been used previously to calculate the radiation dose to a shift-invariant medium undergoing CT scans with constant tube current [Li, Zhang, and Liu, Med. Phys. 39, 5347-5352 (2012)]. The authors have adapted this method to CT scans with tube current modulation (TCM). Methods: For a scan with variable tube current, the scan range was divided into multiple subscan ranges, each with a nearly constant tube current. Then the dose calculation algorithm presented previously was applied. For a clinical CT scan series that presented tube current per slice, the authors adopted an efficient approach that computed the longitudinal dose distribution for one scan length equal to the slice thickness, which center was at z = 0. The cumulative dose at a specific point was a summation of the contributions from all slices and the overscan. Results: The dose calculations performed for a total of four constant and variable tube current distributions agreed with the published results of Dixon and Boone [Med. Phys. 40, 111920 (14pp.) (2013)]. For an abdomen/pelvis scan of an anthropomorphic phantom (model ATOM 701-B, CIRS, Inc., VA) on a GE Lightspeed Pro 16 scanner with 120 kV, N x T = 20 mm, pitch = 1.375, z axis current modulation (auto mA), and angular current modulation (smart mA), dose measurements were performed using two lines of optically stimulated luminescence dosimeters, one of which was placed near the phantom center and the other on the surface. Dose calculations were performed on the central and peripheral axes of a cylinder containing water, whose cross-sectional mass was about equal to that of the ATOM phantom in its abdominal region, and the results agreed with the measurements within 28.4%. Conclusions: The described method provides an effective approach that takes into account subject size, scan length, and constant or variable tube current to evaluate CT dose to a shift-invariant medium. For a clinical CT scan, dose calculations may be performed with a water-containing cylinder whose cross-sectional mass is equal to that of the subject. This method has the potential to substantially improve evaluations of patient dose from clinical CT scans, compared to CTDIvol, size-specific dose estimate (SSDE), or the dose evaluated for a TCM scan with a constant tube current equal to the average tube current of the TCM scan. (C) 2014 American Association of Physicists in Medicine. C1 [Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Webster Ctr Adv Res & Educ Radiat, Boston, MA 02114 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA. EM bliu7@mgh.harvard.edu NR 11 TC 1 Z9 1 U1 1 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2014 VL 41 IS 11 AR 111910 DI 10.1118/1.4898124 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5RO UT WOS:000344999800031 PM 25370643 ER PT J AU Moteabbed, M Schuemann, J Paganetti, H AF Moteabbed, M. Schuemann, J. Paganetti, H. TI Dosimetric feasibility of real-time MRI-guided proton therapy SO MEDICAL PHYSICS LA English DT Article DE MRI-guided; proton therapy ID ADAPTIVE RADIATION-THERAPY; CARLO DOSE CALCULATION; MAGNETIC-FIELD; TUMOR TRACKING; BEAM THERAPY; CLINICAL IMPLEMENTATION; PHOTON RADIOTHERAPY; MOTION; SYSTEM; ACCELERATOR AB Purpose: Magnetic resonance imaging (MRI) is a prime candidate for image-guided radiotherapy. This study was designed to assess the feasibility of real-time MRI-guided proton therapy by quantifying the dosimetric effects induced by the magnetic field in patients' plans and identifying the associated clinical consequences. Methods: Monte Carlo dose calculation was performed for nine patients of various treatment sites (lung, liver, prostate, brain, skull-base, and spine) and tissue homogeneities, in the presence of 0.5 and 1.5 T magnetic fields. Dose volume histogram (DVH) parameters such as D-95, D-5, and V-20 as well as equivalent uniform dose were compared for the target and organs at risk, before and after applying the magnetic field. The authors further assessed whether the plans affected by clinically relevant dose distortions could be corrected independent of the planning system. Results: By comparing the resulting dose distributions and analyzing the respective DVHs, it was determined that despite the observed lateral beam deflection, for magnetic fields of up to 0.5 T, neither was the target coverage jeopardized nor was the dose to the nearby organs increased in all cases except for prostate. However, for a 1.5 T magnetic field, the dose distortions were more pronounced and of clinical concern in all cases except for spine. In such circumstances, the target was severely underdosed, as indicated by a decrease in D-95 of up to 41% of the prescribed dose compared to the nominal situation (no magnetic field). Sites such as liver and spine were less affected due to higher tissue homogeneity, typically smaller beam range, and the choice of beam directions. Simulations revealed that small modifications to certain plan parameters such as beam isocenter (up to 19 mm) and gantry angle (up to 10 degrees) are sufficient to compensate for the magnetic field-induced dose disturbances. The authors' observations indicate that the degree of required corrections strongly depends on the beam range and direction relative to the magnetic field. This method was also applicable to more heterogeneous scenarios such as skull-base tumors. Conclusions: This study confirmed the dosimetric feasibility of real-time MRI-guided proton therapy and delivering a clinically acceptable dose to patients with various tumor locations within magnetic fields of up to 1.5 T. This work could serve as a guide and encouragement for further efforts toward clinical implementation of hybrid MRI-proton gantry systems. (C) 2014 American Association of Physicists in Medicine. C1 [Moteabbed, M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Moteabbed, M (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM mmoteabbed@partners.org FU Federal Share of Project Income Program at Massachusetts General Hospital [C06 CA059267] FX This work was supported by the Federal Share of Project Income Program at Massachusetts General Hospital on C06 CA059267. The authors would like to give special thanks to Dr. Joseph Perl and Dr. Jungwook Shin from the TOMS collaboration for their help and support with incorporating the magnetic field module in TOPAS. NR 52 TC 5 Z9 5 U1 6 U2 10 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2014 VL 41 IS 11 AR 111713 DI 10.1118/1.4897570 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5RO UT WOS:000344999800015 PM 25370627 ER PT J AU Yip, S Chen, AB Aerts, HJWL Berbeco, R AF Yip, Stephen Chen, Aileen B. Aerts, Hugo J. W. L. Berbeco, Ross TI Sensitivity study of voxel-based PET image comparison to image registration algorithms SO MEDICAL PHYSICS LA English DT Article DE PET; deformable registration algorithms; voxel-based comparison; therapeutic response assessment ID POSITRON-EMISSION-TOMOGRAPHY; NECK-CANCER; RADIATION-THERAPY; OPTICAL-FLOW; DEFORMABLE REGISTRATION; TUMOR HYPOXIA; CU-ATSM; FDG-PET; HEAD; RADIOTHERAPY AB Purpose: Accurate deformable registration is essential for voxel-based comparison of sequential positron emission tomography (PET) images for proper adaptation of treatment plan and treatment response assessment. The comparison may be sensitive to the method of deformable registration as the optimal algorithm is unknown. This study investigated the impact of registration algorithm choice on therapy response evaluation. Methods: Sixteen patients with 20 lung tumors underwent a pre- and post-treatment computed tomography (CT) and 4D FDG-PET scans before and after chemoradiotherapy. All CT images were coregistered using a rigid and ten deformable registration algorithms. The resulting transformations were then applied to the respective PET images. Moreover, the tumor region defined by a physician on the registered PET images was classified into progressor, stable-disease, and responder subvolumes. Particularly, voxels with standardized uptake value (SUV) decreases > 30% were classified as responder, while voxels with SUV increases > 30% were progressor. All other voxels were considered stable-disease. The agreement of the subvolumes resulting from difference registration algorithms was assessed by Dice similarity index (DSI). Coefficient of variation (CV) was computed to assess variability of DSI between individual tumors. Root mean square difference (RMSrigid) of the rigidly registered CT images was used to measure the degree of tumor deformation. RMSrigid and DSI were correlated by Spearman correlation coefficient (R) to investigate the effect of tumor deformation on DSI. Results: Median DSIrigid was found to be 72%, 66%, and 80%, for progressor, stable-disease, and responder, respectively. Median DSIdeformable was 63%-84%, 65%-81%, and 82%-89%. Variability of DSI was substantial and similar for both rigid and deformable algorithms with CV > 10% for all subvolumes. Tumor deformation had moderate to significant impact on DSI for progressor subvolume with R-rigid = -0.60 (p = 0.01) and R-deformable = -0.46 (p = 0.01-0.20) averaging over all deformable algorithms. For stable-disease subvolumes, the correlations were significant (p < 0.001) for all registration algorithms with Rrigid = -0.71 and R-deformable = -0.72. Progressor and stable-disease subvolumes resulting from rigid registration were in excellent agreement (DSI > 70%) for RMSrigid < 150 HU. However, tumor deformation was observed to have negligible effect on DSI for responder subvolumes with insignificant vertical bar R vertical bar < 0.26, p > 0.27. Conclusions: This study demonstrated that deformable algorithms cannot be arbitrarily chosen; different deformable algorithms can result in large differences of voxel-based PET image comparison. For low tumor deformation (RMSrigid < 150 HU), rigid and deformable algorithms yield similar results, suggesting deformable registration is not required for these cases. (C) 2014 American Association of Physicists in Medicine. C1 [Yip, Stephen; Chen, Aileen B.; Aerts, Hugo J. W. L.; Berbeco, Ross] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yip, Stephen; Chen, Aileen B.; Aerts, Hugo J. W. L.; Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Yip, S (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM syip@lroc.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 NR 64 TC 4 Z9 4 U1 0 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2014 VL 41 IS 11 AR 111714 DI 10.1118/1.4898125 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5RO UT WOS:000344999800016 PM 25370628 ER PT J AU Cirstea, D Santo, L Hideshima, T Eda, H Mishima, Y Nemani, N Mahindra, A Yee, A Gorgun, G Hu, YG Ohguchi, H Suzuki, R Cottini, F Guichard, SM Anderson, KC Raje, N AF Cirstea, Diana Santo, Loredana Hideshima, Teru Eda, Homare Mishima, Yuko Nemani, Neeharika Mahindra, Anuj Yee, Andrew Gorgun, Gullu Hu, Yiguo Ohguchi, Hiroto Suzuki, Rikio Cottini, Francesca Guichard, Sylvie M. Anderson, Kenneth C. Raje, Noopur TI Delineating the mTOR Kinase Pathway Using a Dual TORC1/2 Inhibitor, AZD8055, in Multiple Myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GROWTH-FACTOR-I; MAMMALIAN TARGET; ANTITUMOR-ACTIVITY; COMPLEX 2; RAPAMYCIN; RECEPTOR; FEEDBACK; CELLS AB Despite promising preclinical results with mTOR kinase inhibitors in multiple myeloma, resistance to these drugs may arise via feedback activation loops. This concern is especially true for insulin-like growth factor 1 receptor (IGF1R), because IGF1R signaling is downregulated by multiple AKT and mTOR feedback mechanisms. We have tested this hypothesis in multiple myeloma using the novel selective mTOR kinase inhibitor AZD8055. We evaluated p-mTOR S-2481 as the readout for mTORC2/Akt activity in multiple myeloma cells in the context of mTOR inhibition via AZD8055 or rapamycin. We next validated AZD8055 inhibition of mTORC1 and mTORC2 functions in multiple myeloma cells alone or in culture with bone marrow stroma cells and growth factors. Unlike rapamycin, AZD8055 resulted in apoptosis of multiple myeloma cells. AZD8055 treatment, however, induced upregulation of IGF1R phosphorylation in p-Akt S-473-expressing multiple myeloma cell lines. Furthermore, exposure of AZD8055-treated cells to IGF1 induced p-Akt S-473 and rescued multiple myeloma cells from apoptosis despite mTOR kinase inhibition and TORC2/Akt blockage. The addition of blocking IGF1R antibody resulted in reversing this effect and increased AZD8055-induced apoptosis. Our study suggests that combination treatment with AZD8055 and IGF1R-blocking agents is a promising strategy in multiple myeloma with potential IGF1R/Akt signaling-mediated survival. (C) 2014 AACR. C1 [Cirstea, Diana; Santo, Loredana; Eda, Homare; Mishima, Yuko; Nemani, Neeharika; Mahindra, Anuj; Yee, Andrew; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA. [Cirstea, Diana; Hideshima, Teru; Gorgun, Gullu; Hu, Yiguo; Ohguchi, Hiroto; Suzuki, Rikio; Cottini, Francesca; Anderson, Kenneth C.; Raje, Noopur] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Cirstea, Diana; Hideshima, Teru; Gorgun, Gullu; Hu, Yiguo; Ohguchi, Hiroto; Suzuki, Rikio; Cottini, Francesca; Anderson, Kenneth C.; Raje, Noopur] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA 02115 USA. [Guichard, Sylvie M.] AstraZeneca, Macclesfield, Cheshire, England. RP Raje, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU Leukemia and Lymphoma Society FX N. Raje is a recipient of the Leukemia and Lymphoma Society clinical scholar Award. NR 24 TC 8 Z9 8 U1 0 U2 2 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 NOV PY 2014 VL 13 IS 11 BP 2489 EP 2500 DI 10.1158/1535-7163.MCT-14-0147 PG 12 WC Oncology SC Oncology GA AT5BB UT WOS:000344957600002 PM 25172964 ER PT J AU Findlay, VJ Wang, C Nogueira, LM Hurst, K Quirk, D Ethier, SP O'Carroll, KFS Watson, DK Camp, ER AF Findlay, Victoria J. Wang, Cindy Nogueira, Lourdes M. Hurst, Katie Quirk, Daniel Ethier, Stephen P. O'Carroll, Kevin F. Staveley Watson, Dennis K. Camp, E. Ramsay TI SNAI2 Modulates Colorectal Cancer 5-Fluorouracil Sensitivity through miR145 Repression SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID EMBRYONIC STEM-CELLS; EPITHELIAL-MESENCHYMAL TRANSITIONS; TRANSCRIPTION FACTOR SNAIL; RECTAL-CANCER; COLON-CANCER; PANCREATIC-CANCER; TUMOR-REGRESSION; DRUG-RESISTANCE; GENE-EXPRESSION; C-MYC AB Epithelial-to-mesenchymal transition (EMT) has been associated with poor treatment outcomes in various malignancies and is inversely associated with miRNA145 expression. Therefore, we hypothesized that SNAI2 (Slug) may mediate 5-fluorouracil (5FU) chemotherapy resistance through inhibition of miR145 in colorectal cancer and thus represents a novel therapeutic target to enhance current colorectal cancer treatment strategies. Compared with parental DLD1 colon cancer cells, 5FU-resistant (5FUr) DLD1 cells demonstrated features of EMT, including >2-fold enhanced invasion (P < 0.001) and migration, suppressed E-cadherin expression, and 2-fold increased SNAI2 expression. DLD1 and HCT116 cells with stable expression of SNAI2 (DLD1/SNAI2; HCT116/SNAI2) also demonstrated EMT features such as the decreased E-cadherin as well as significantly decreased miR145 expression, as compared with control empty vector cells. On the basis of an miR145 luciferase promoter assay, we demonstrated that SNAI2 repressed activity of the miR145 promoter in the DLD1 and HCT116 cells. In addition, the ectopic expressing SNAI2 cell lines demonstrated decreased 5FU sensitivity, and, conversely, miR145 replacement significantly enhanced 5FU sensitivity. In the parental SW620 colon cancer cell line with high SNAI2 and low miR145 levels, inhibition of SNAI2 directly with short hairpin sequence for SNAI2 and miR145 replacement therapy both decreased vimentin expression and increased in vitro 5FU sensitivity. In pretreatment rectal cancer patient biopsy samples, low miR145 expression levels correlated with poor response to neoadjuvant 5FU-based chemoradiation. These results suggested that the SNAI2: miR145 pathway may represent a novel clinical therapeutic target in colorectal cancer and may serve as a response predictor to chemoradiation therapy. (C) 2014 AACR. C1 [Findlay, Victoria J.; Nogueira, Lourdes M.; Ethier, Stephen P.; Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Findlay, Victoria J.; Ethier, Stephen P.; O'Carroll, Kevin F. Staveley; Watson, Dennis K.; Camp, E. Ramsay] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Wang, Cindy; Hurst, Katie; Quirk, Daniel; O'Carroll, Kevin F. Staveley; Camp, E. Ramsay] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [O'Carroll, Kevin F. Staveley; Camp, E. Ramsay] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Biochem Mol Biol, Charleston, SC 29425 USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, 25 Courtenay Dr,Room 7018,MSC 295, Charleston, SC 29425 USA. EM findlay@musc.edu; campe@musc.edu FU NIH grant [5R 1K08CA142904]; Hollings Cancer Center Translational Research Award; American Cancer Society FX The study was supported by NIH grant 5R 1K08CA142904 (E.R. Camp), Hollings Cancer Center Translational Research Award (E.R. Camp), and American Cancer Society: Institutional Research Grant (E.R. Camp). NR 42 TC 2 Z9 3 U1 3 U2 7 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 NOV PY 2014 VL 13 IS 11 BP 2713 EP 2726 DI 10.1158/1535-7163.MCT-14-0207 PG 14 WC Oncology SC Oncology GA AT5BB UT WOS:000344957600021 PM 25249558 ER PT J AU Gridling, M Ficarro, SB Breitwieser, FP Song, LX Parapatics, K Colinge, J Haura, EB Marto, JA Superti-Furga, G Bennett, KL Rix, U AF Gridling, Manuela Ficarro, Scott B. Breitwieser, Florian P. Song, Lanxi Parapatics, Katja Colinge, Jacques Haura, Eric B. Marto, Jarrod A. Superti-Furga, Giulio Bennett, Keiryn L. Rix, Uwe TI Identification of Kinase Inhibitor Targets in the Lung Cancer Microenvironment by Chemical and Phosphoproteomics SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PHASE-II TRIAL; PROTEIN-KINASE; CELL-LINES; TUMOR-CELL; DASATINIB; PROTEOMICS; REVEALS; TBK1; SELECTIVITY; RESISTANCE AB A growing number of gene mutations, which are recognized as cancer drivers, can be successfully targeted with drugs. The redundant and dynamic nature of oncogenic signaling networks and complex interactions between cancer cells and the microenvironment, however, can cause drug resistance. While these challenges can be addressed by developing drug combinations or polypharmacology drugs, this benefits greatly from a detailed understanding of the proteome-wide target profiles. Using mass spectrometry-based chemical proteomics, we report the comprehensive characterization of the drug-protein interaction networks for the multikinase inhibitors dasatinib and sunitinib in primary lung cancer tissue specimens derived from patients. We observed in excess of 100 protein kinase targets plus various protein complexes involving, for instance, AMPK, TBK1 (sunitinib), and ILK (dasatinib). Importantly, comparison with lung cancer cell lines and mouse xenografts thereof showed that most targets were shared between cell lines and tissues. Several targets, however, were only present in tumor tissues. In xenografts, most of these proteins were of mouse origin suggesting that they originate from the tumor microenvironment. Furthermore, intersection with subsequent global phosphoproteomic analysis identified several activated signaling pathways. These included MAPK, immune, and integrin signaling, which were affected by these drugs in both cancer cells and the microenvironment. Thus, the combination of chemical and phosphoproteomics can generate a systems view of proteins, complexes, and signaling pathways that are simultaneously engaged by multitargeted drugs in cancer cells and the tumor microenvironment. This may allow for the design of novel anticancer therapies that concurrently target multiple tumor compartments. (C) 2014 AACR. C1 [Gridling, Manuela; Breitwieser, Florian P.; Parapatics, Katja; Colinge, Jacques; Superti-Furga, Giulio; Bennett, Keiryn L.; Rix, Uwe] Austrian Acad Sci CeMM, Res Ctr Mol Med, Vienna, Austria. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Song, Lanxi; Haura, Eric B.] H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL 33612 USA. [Rix, Uwe] H Lee Moffitt Canc Ctr & Res Inst, Dept Drug Discovery, Tampa, FL 33612 USA. RP Rix, U (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Chem Biol & Mol Med Program, Dept Drug Discovery, MRC 3046,12902 Magnolia Dr, Tampa, FL 33612 USA. EM Uwe.Rix@moffitt.org RI Superti-Furga, Giulio/F-4755-2015 OI Superti-Furga, Giulio/0000-0002-0570-1768 FU Moffitt Cancer Center NIH/NCI SPORE in Lung Cancer [P50-CA119997]; Moffitt Cancer Center; Austrian Federal Ministry for Science, Research, and Economy (Gen-Au BIN); Austrian Science Fund FWF [P 24321-B21]; Austrian Academy of Sciences; Austrian Federal Ministry for Science, Research and Economy (Gen-Au APP); Dana-Farber Strategic Research Initiative; NIH [P01NS047572, R21CA178860]; NCI [P30-CA076292] FX U. Rix and E.B. Haura received funds from the Moffitt Cancer Center NIH/NCI SPORE in Lung Cancer (P50-CA119997) and the Moffitt Cancer Center. K.L. Bennett and J. Colinge were funded by the Austrian Federal Ministry for Science, Research, and Economy (Gen-Au BIN). J. Colinge was furthermore supported by the Austrian Science Fund FWF (grant no. P 24321-B21). G. Superti-Furga was funded by the Austrian Academy of Sciences and G. Superti-Furga and K.L. Bennett were funded by the Austrian Federal Ministry for Science, Research and Economy (Gen-Au APP). J.A. Marto received funding from the Dana-Farber Strategic Research Initiative and the NIH (P01NS047572 and R21CA178860). The authors also wish to acknowledge the Moffitt Chemical Biology Core Facility, which is supported by the NCI as a Cancer Center Support Grant (P30-CA076292). NR 50 TC 7 Z9 7 U1 3 U2 12 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 NOV PY 2014 VL 13 IS 11 BP 2751 EP 2762 DI 10.1158/1535-7163.MCT-14-0152 PG 12 WC Oncology SC Oncology GA AT5BB UT WOS:000344957600024 PM 25189542 ER PT J AU Luchette, M Korideck, H Makrigiorgos, M Tillement, O Berbeco, R AF Luchette, Matthew Korideck, Houari Makrigiorgos, Mike Tillement, Olivier Berbeco, Ross TI Radiation dose enhancement of gadolinium-based AGuIX nanoparticles on HeLa cells SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Radiation oncology; Dose enhancement; Nanoparticles ID GOLD NANOPARTICLES; X-RAY; CONTRAST AGENT; CANCER-THERAPY; TUMOR; NANOTECHNOLOGY; GUIDANCE AB Radiation dose enhancement of high-Z nanoparticles is an active area of research in cancer therapeutics. When kV and MV energy photon beams interact with high-Z nanoparticles in a tumor, the release of secondary electrons can injure tumor cells, leading to a higher treatment efficacy than radiation alone. We present a study that characterizes the radiation dose enhancing effects of gadolinium-based AGuIX nanoparticles on HeLa cells. Our in vitro clonogenic survival assays showed an average dose enhancement of 1.54x for 220 kVp radiation and 1.15x for 6 MV radiation. The sensitivity enhancement ratio at 4 Gy (SER4Gy) was 1.54 for 220 kVp and 1.28 for 6 MV, indicating that these nanoparticles may be useful for clinical radiation therapy. From the Clinical Editor: This study characterized the radiation dose enhancing effects of gadolinium-based AGuIX nanoparticles on HeLa cells, showing clear effects at 220kV as well as 6MV, suggesting that after additional studies, these nanoparticles may be beneficial in human radiation therapy. (C) 2014 Elsevier Inc. All rights reserved. C1 [Luchette, Matthew; Korideck, Houari; Makrigiorgos, Mike; Berbeco, Ross] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Luchette, Matthew; Korideck, Houari; Makrigiorgos, Mike; Berbeco, Ross] Harvard Univ, Sch Med, Boston, MA USA. [Tillement, Olivier] Univ Lyon 1, CNRS, Inst Lumiere Matiere, F-69622 Villeurbanne, France. RP Luchette, M (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM mfluchet@gmail.com NR 26 TC 13 Z9 13 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD NOV PY 2014 VL 10 IS 8 BP 1751 EP 1755 DI 10.1016/j.nano.2014.06.004 PG 5 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA AT4UT UT WOS:000344939700017 PM 24941464 ER PT J AU Brewster, PWH Melrose, RJ Marquine, MJ Johnson, JK Napoles, A MacKay-Brandt, A Farias, S Reed, B Mungas, D AF Brewster, Paul W. H. Melrose, Rebecca J. Marquine, Maria J. Johnson, Julene K. Napoles, Anna MacKay-Brandt, Anna Farias, Sarah Reed, Bruce Mungas, Dan TI Life Experience and Demographic Influences on Cognitive Function in Older Adults SO NEUROPSYCHOLOGY LA English DT Article DE aging; cognitive change; individual differences; minority and diverse populations; recreational activity ID NEUROPSYCHOLOGICAL ASSESSMENT SCALES; ETHNICALLY DIVERSE ELDERS; PHYSICAL-ACTIVITY; SOCIOECONOMIC-STATUS; ALZHEIMERS-DISEASE; AFRICAN-AMERICAN; TEST-PERFORMANCE; READING LEVEL; LEISURE-TIME; DECLINE AB Objective: We examined the influence of a broad spectrum of life experiences on longitudinal cognitive trajectories in a demographically diverse sample of older adults. Method: Participants were 333 educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. Mixed-effects regression was used to measure baseline status in episodic memory, executive functioning, and semantic memory and change in a global cognition factor defined by change in these 3 domain-specific measures. We examined effects of life experience variables (literacy, childhood socioeconomic status, morphometric measures of physical development, life course physical and recreational activity) on longitudinal cognitive trajectories, covarying for age, apolipoprotein E (APOE) genotype and demographics (education, ethnicity, language). Results: Non-Latino Whites had higher baseline cognition, but life experience variables attenuated ethnic differences in cognitive scores. Age, literacy, childhood socioeconomic status, and physical activity significantly influenced baseline cognition. Age, APOE epsilon 4, and decline in intellectually and socially stimulating recreational activity from mid to late life were independently associated with increased late life cognitive decline. Higher literacy and late life recreational activity were associated with less decline. Literacy had similar effects for English and Spanish readers/speakers. Bilingual English and Spanish speakers did not differ from English Speakers in cognitive performance. Conclusions: Life experience variables, especially literacy level, were strongly related to baseline cognition and substantially attenuated effects of race/ethnicity and education. Cognitive change was best explained by age, APOE epsilon 4, literacy, and current recreational activities. Literacy had robust associations with baseline cognition and cognitive change in both English and Spanish speakers. C1 [Brewster, Paul W. H.] Univ Victoria, Dept Psychol, Victoria, BC, Canada. [Melrose, Rebecca J.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA. [Melrose, Rebecca J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Marquine, Maria J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Johnson, Julene K.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. [Johnson, Julene K.; Napoles, Anna] Univ Calif San Francisco, Ctr Aging Div Commun, Dept Med, San Francisco, CA 94143 USA. [MacKay-Brandt, Anna] Nathan S Kline Inst Psychiat Res, Dept Outpatient Res, Orangeburg, NY USA. [Farias, Sarah; Reed, Bruce; Mungas, Dan] Univ Calif Davis, Sch Med, Dept Neurol, Davis, CA USA. RP Brewster, PWH (reprint author), Univ Victoria, Dept Psychol, Victoria, BC, Canada. EM pbrew@uvic.ca FU National Institute on Aging (NIA) [R13 AG030995, R01 AG042526, P30 AG15272]; NIA [P30 AG15272, R01 AG10220, P30 AG10129, R01 AG021028, R01 AG031252, R01 AG031563]; NIA Resource Centers for Minority Aging Research grant [P30 AG043097]; VA Career Development Award; Canadian Institutes for Health Research; Research Training in Late-Life Neuropsychiatric Disorders [T32 MH02004]; Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN) [T32 DA031098] FX This work was developed as part of a conference supported by the National Institute on Aging (NIA; R13 AG030995, Dan Mungas, PI). Data collection for this research was supported by multiple grants from the NIA (R01 AG10220, Dan Mungas, PI; P30 AG10129 and R01 AG021028, C. DeCarli, PI; R01 AG031252 Sarah Tomaszewski Farias, PI; R01 AG031563 Bruce Reed, PI), and analysis and manuscript development was supported by a NIA Resource Centers for Minority Aging Research grant (P30 AG043097, L. Hinton, PI). Rebecca J. Melrose was supported by a VA Career Development Award. Paul W. H. Brewster was funded by a Doctoral Research Award from the Canadian Institutes for Health Research. Anna Napoles was supported by NIA grant P30 AG15272. Anna MacKay-Brandt was funded by T32 MH02004, Research Training in Late-Life Neuropsychiatric Disorders. Maria J. Marquine was funded by T32 DA031098, Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN). Julene K. Johnson was funded by the National Institute on Aging grants R01 AG042526 and P30 AG15272. NR 69 TC 12 Z9 12 U1 2 U2 19 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2014 VL 28 IS 6 SI SI BP 846 EP 858 DI 10.1037/neu0000098 PG 13 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA AT8BI UT WOS:000345158400005 PM 24933483 ER PT J AU Field, AE Camargo, CA AF Field, Alison E. Camargo, Carlos A. TI Response to "Are the Results Likely Biased Toward the Null?" SO OBESITY LA English DT Letter ID ADOLESCENTS; BIOMARKER C1 [Field, Alison E.] Boston Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA. [Field, Alison E.; Camargo, Carlos A.] Harvard Univ, Sch Med, Boston, MA USA. [Field, Alison E.; Camargo, Carlos A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Field, Alison E.; Camargo, Carlos A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Field, AE (reprint author), Boston Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA. EM Alison.Field@childrens.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD NOV PY 2014 VL 22 IS 11 BP 2327 EP 2327 DI 10.1002/oby.20864 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AT3QR UT WOS:000344849400008 PM 25137625 ER PT J AU Abraham, TM Massaro, JM Hoffmann, U Yanovski, JA Fox, CS AF Abraham, Tobin M. Massaro, Joseph M. Hoffmann, Udo Yanovski, Jack A. Fox, Caroline S. TI Metabolic Characterization of Adults with Binge Eating in the General Population: The Framingham Heart Study SO OBESITY LA English DT Article ID DIABETES-MELLITUS; OBESE-PATIENTS; ALL-CAUSE; DISORDER; WOMEN; FAT; PREVALENCE; MORTALITY; PATHOGENESIS; ADIPONECTIN AB ObjectiveTo describe the metabolic profile of individuals with objective binge eating (OBE) and to evaluate whether associations between OBE and metabolic risk factors are mediated by body mass index (BMI). MethodsParticipants from the Framingham Heart Study, Third Generation and Omni 2 cohorts (n=3,551, 53.1% women, mean age 46.4 years) were screened for binge eating. Multivariable-adjusted regression models to examine the associations of OBE with metabolic risk factors were used. ResultsThe prevalence of OBE was 4.8% in women and 4.9% in men. Compared to non-binge eating, OBE was associated with higher odds of hypertension (OR 1.85, 95% CI 1.32-2.60), hypertriglyceridemia (OR 1.42, 95% CI 1.01-2.01), low HDL (OR 1.70, 95% CI 1.18-2.44), insulin resistance (OR 3.18, 95% CI 2.25-4.50) and metabolic syndrome (OR 2.75, 95% CI 1.94-3.90). Fasting glucose was 7.2 mg dl(-1) higher in those with OBE (P=0.0001). Individuals with OBE had more visceral, subcutaneous and liver fat. Most of these associations were attenuated with adjustment for BMI, with the exception of fasting glucose. ConclusionsBinge eating is associated with a high burden of metabolic risk factors. Much of the associated risk appears to be mediated by BMI, with the exception of fasting glucose. C1 [Abraham, Tobin M.; Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA 02115 USA. [Abraham, Tobin M.; Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yanovski, Jack A.] NICHHD, Sect Growth & Obes, Bethesda, MD 20892 USA. [Abraham, Tobin M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Abraham, Tobin M.; Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, 75 Francis St, Boston, MA 02115 USA. EM foxca@nhlbi.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU National Heart, Lung and Blood Institute [N01-HC-25195]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; Division of Intramural Research, the National Heart, Lung, and Blood Institute FX The Framingham Heart Study of the National Heart, Lung and Blood Institute is supported by contract N01-HC-25195. Dr. Yanovski is supported by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, and Dr. Fox is supported by the Division of Intramural Research, the National Heart, Lung, and Blood Institute. NR 34 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD NOV PY 2014 VL 22 IS 11 BP 2441 EP 2449 DI 10.1002/oby.20867 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AT3QR UT WOS:000344849400023 PM 25136837 ER PT J AU Ginat, DT Freitag, SK AF Ginat, Daniel Thomas Freitag, Suzanne K. TI Traumatic Globe Rupture and Herniation Into the Maxillary Sinus SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material C1 [Ginat, Daniel Thomas] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ginat, DT (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM ginatd01@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2014 VL 30 IS 6 BP E168 EP E168 DI 10.1097/IOP.0000000000000283 PG 1 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AT7PJ UT WOS:000345129600014 PM 25275787 ER PT J AU Gupta, SR Steele, EA Solomon, AR AF Gupta, Seema R. Steele, Eric A. Solomon, Alvin R. TI Idiopathic Lymphoplasmacellular Mucositis-Dermatitis of the Eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Idiopathic lymphoplasmacellular mucositis-dermatitis is a rare mucosal or cutaneous disorder characterized clinically by papules or plaques with variable erosion and microscopically by dense dermal inflammatory cell infiltrates with numerous plasma cells. It has been described in the oral and upper aerodigestive tracts, male and female genitalia, and other mucosal surfaces. In this article, the authors describe a case of idiopathic lymphoplasmacellular mucositis-dermatitis occurring in the skin of the eyelid that was removed by excisional biopsy and has not recurred in the 19-month follow-up period. C1 [Gupta, Seema R.; Steele, Eric A.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA. [Steele, Eric A.; Solomon, Alvin R.] Portland VA Med Ctr, Operat Care Div, Portland, OR USA. [Solomon, Alvin R.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Solomon, Alvin R.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. RP Gupta, SR (reprint author), Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA. EM steeleer@ohsu.edu FU Research to Prevent Blindness to Casey Eye Institute FX Funded, in part, from an unrestricted grant from Research to Prevent Blindness to Casey Eye Institute. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2014 VL 30 IS 6 BP E149 EP E151 DI 10.1097/01.iop.0000440707.52043.87 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA AT7PJ UT WOS:000345129600006 PM 24836448 ER PT J AU Parker, SE Starr, JR Collett, BR Speltz, ML Werler, MM AF Parker, Samantha E. Starr, Jacqueline R. Collett, Brent R. Speltz, Matthew L. Werler, Martha M. TI Nausea and Vomiting during Pregnancy and Neurodevelopmental Outcomes in Offspring SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE nausea and vomiting; pregnancy; neurocognitive; psychosocial; childhood ID HEMIFACIAL MICROSOMIA; MORNING SICKNESS; CHILDREN; RISK; ASSOCIATION; SEVERITY; SYMPTOMS AB BackgroundNausea and vomiting during pregnancy (NVP) is the most common complication of pregnancy. NVP has been associated with improved fetal outcomes, but its association with childhood neurodevelopmental outcomes has rarely been studied. MethodsSubjects were children aged 5-12 years (n=560) who were controls in a previously conducted case-control study of prenatal risk factors for craniofacial malformations. Information on NVP, including trimester, duration, and treatment, was collected through a maternal interview conducted within 3 years of delivery. Neurocognition was assessed using the Peabody Picture Vocabulary Test (PPVT-III) and the Beery-Buktenica Test of Visual Motor Integration-Fifth Edition (VMI-5). Psychosocial outcomes, including internalising and externalising behaviour problems, were measured by maternal report, using the Child Behavior Checklist (CBCL), and teacher report, using the Teacher Report Form. Linear regression models were used to calculate adjusted mean (adjMD -3.04, 95% confidence interval (CI) -5.02, -1.06) differences (adjMD) and 95% confidence intervals [CI] on test scores for children exposed and unexposed to NVPin utero. Differences based on trimester, duration, and treatment were assessed. ResultsNVP was reported among 63% of women and was most common in early pregnancy. Children exposed to NVP performed worse on the VMI-5 [-3.04, 95% CI: -5.02, -1.06] but exhibited few other differences from unexposed children. Durations of NVP 4 months were associated with poorer scores on PPVT-III (adjMD -2.52), VMI-5 (adjMD -5.41), and CBCL [adjMD 3.38 (internalising) and adjMD 4.19 (externalising)]. ConclusionsOverall, there were few differences between children exposed and unexposed to NVP. NVP was associated with slightly worse visual motor performance, and prolonged NVP and NVP extending late into pregnancy were associated with poorer scores on several neurodevelopmental measures. C1 [Parker, Samantha E.; Werler, Martha M.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Starr, Jacqueline R.] Forsyth Inst, Cambridge, MA USA. [Collett, Brent R.; Speltz, Matthew L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Parker, SE (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM separker@bu.edu OI /0000-0002-7193-077X FU National Institutes of Health through the National Institute of Dental and Craniofacial Research [R01 DE 11939]; National Institutes of Health (NIH) [T32 HD052458] FX This study was supported by the National Institutes of Health through the National Institute of Dental and Craniofacial Research (R01 DE 11939). Funded by the National Institutes of Health (NIH). Samantha Parker was a pre-doctoral trainee supported by NIH T32 HD052458 (Boston University Reproductive, Perinatal and Pediatric Epidemiology training programme). NR 27 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD NOV PY 2014 VL 28 IS 6 BP 527 EP 535 DI 10.1111/ppe.12151 PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AT9EY UT WOS:000345231900010 PM 25327160 ER PT J AU Humphrey, KL Saksena, MA Freer, PE Smith, BL Rafferty, EA AF Humphrey, Kathryn L. Saksena, Mansi A. Freer, Phoebe E. Smith, Barbara L. Rafferty, Elizabeth A. TI To Do or Not to Do: Axillary Nodal Evaluation after ACOSOG Z0011 Trial SO RADIOGRAPHICS LA English DT Article ID CORE-NEEDLE-BIOPSY; BREAST-CANCER; LYMPH-NODES; CONTEMPORARY MANAGEMENT; AMERICAN-SOCIETY; METASTASIS; DISSECTION; ASPIRATION; ULTRASOUND; SURGEONS AB Methods of axillary evaluation in invasive breast cancer continue to evolve. The recent American College of Surgeons Oncology Group Z0011 Trial is a prospective, randomized, multicenter trial that compared the survival and locoregional recurrence rates after complete axillary lymph node dissection (ALND) versus sentinel node biopsy (SNB) alone in women with a positive sentinel node in an effort to avoid the complications associated with ALND. As the results of this trial are implemented clinically, affecting surgical management of axillary metastatic disease, radiologists may need to redefine their role in the preoperative assessment of the axilla. Before the Z0011 trial, breast imagers worked to identify axillary metastases preoperatively, allowing appropriate patients to proceed directly to ALND and avoiding the need for SNB. However, the Z0011 trial concluded that ALND may not be necessary in women with metastatic axillary disease who meet the trial criteria. In the Z0011 trial, after 6 years of median follow-up there was no difference in either locoregional recurrence or survival among the women who underwent SNB alone compared with those who underwent ALND, suggesting that ALND is unnecessary in a subset of women with a positive node at SNB. These results raise questions about how aggressively radiologists should pursue percutaneous sampling of axillary nodes, as some practitioners conclude that, in an otherwise eligible woman, positive results from imaging-guided percutaneous biopsy preclude a Z0011 trial-directed pathway. Debate about the best way to implement the results of the Z0011 trial into daily clinical practice exists. It is important for breast imagers to work closely with breast surgeons to provide the most appropriate treatment course for each patient. (C) RSNA, 2014 center dot radiographics.rsna.org C1 [Humphrey, Kathryn L.; Saksena, Mansi A.; Freer, Phoebe E.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02114 USA. [Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Saksena, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, 55 Fruit St,Wang ACC 2, Boston, MA 02114 USA. EM msaksena@partners.org OI Freer, Phoebe/0000-0001-6886-7100 NR 26 TC 10 Z9 10 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2014 VL 34 IS 7 BP 1807 EP 1816 DI 10.1148/rg.347130141 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5SH UT WOS:000345001600005 PM 25384280 ER PT J AU Tirumani, SH Kim, KW Nishino, M Howard, SA Krajewski, KM Jagannathan, JP Cleary, JM Ramaiya, NH Shinagare, AB AF Tirumani, Sree Harsha Kim, Kyung Won Nishino, Mizuki Howard, Stephanie A. Krajewski, Katherine M. Jagannathan, Jyothi P. Cleary, James M. Ramaiya, Nikhil H. Shinagare, Atul B. TI Update on the Role of Imaging in Management of Metastatic Colorectal Cancer SO RADIOGRAPHICS LA English DT Article ID MOLECULAR TARGETED THERAPY; TUMOR RESPONSE ASSESSMENT; RENAL-CELL CARCINOMA; LIVER METASTASES; COMPUTED-TOMOGRAPHY; NEOADJUVANT CHEMOTHERAPY; HEPATIC METASTASES; RADIOLOGISTS NEED; VERSION 1.1; FDG-PET/CT AB Evolution in the treatment of metastatic colorectal cancer (mCRC) has led to significant improvement in the survival of these patients. Surgery is useful in patients with resectable disease. Liver-directed therapies such as hepatic arterial infusion, transarterial radio-and chemoembolization, and percutaneous ablation are sometimes used by oncologists when the liver is the only site of metastatic disease. Unresectable mCRC is typically treated with systemic chemotherapy. First-line systemic chemotherapeutic regimens for mCRC are FOLFOX (combination of 5-fluorouracil/leucovorin [5-FU/LV] and oxaliplatin) and FOLFIRI (combination of 5-FU/LV and irinotecan) combined with molecular targeted drugs. Molecular targeted therapies that are effective in treating mCRC include antiangiogenic agents such as bevacizumab-an antibody against vascular endothelial growth factor-and antibodies directed against epidermal growth factor receptor (EGFR). EGFR-directed antibodies such as cetuximab and panitumumab have been shown to produce activity only in wild-type KRAS tumors. Imaging modalities such as multidetector computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT play a major role in the selection of appropriate treatment strategies. Assessment of treatment response in patients who undergo liver-directed and systemic therapy requires imaging at regular intervals. Recent studies have shown that alternative treatment response criteria may be more predictive of pathologic response in mCRC than conventional criteria such as Response Evaluation Criteria in Solid Tumors. Awareness of unusual response patterns, as well as of complications and toxicities, is helpful in guiding patient management. (C) RSNA, 2014 center dot radiographics.rsna.org C1 [Tirumani, Sree Harsha; Kim, Kyung Won; Nishino, Mizuki; Howard, Stephanie A.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Imaging, Boston, MA 02215 USA. [Cleary, James M.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Kim, Kyung Won; Nishino, Mizuki; Howard, Stephanie A.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02215 USA. RP Shinagare, AB (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org FU Radiological Society of North America; National Cancer Institute FX A.B.S.: Activities related to the present article: grant from the Radiological Society of North America. Activities not related to the present article: disclosed no relevant relationships. Other activities: disclosed no relevant relationships. M.N.: Activities related to the present article: grant from the National Cancer Institute. Activities not related to the present article: disclosed no relevant relationships. Other activities: disclosed no relevant relationships. NR 63 TC 8 Z9 9 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2014 VL 34 IS 7 BP 1908 EP 1928 DI 10.1148/rg.347130090 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT5SH UT WOS:000345001600017 PM 25384292 ER PT J AU Kiatpongsan, S Meng, L Eisenberg, JD Herring, M Avery, LL Kong, CY Pandharipande, PV AF Kiatpongsan, Sorapop Meng, Lesley Eisenberg, Jonathan D. Herring, Maurice Avery, Laura L. Kong, Chung Yin Pandharipande, Pari V. TI Imaging for Appendicitis: Should Radiation-induced Cancer Risks Affect Modality Selection? SO RADIOLOGY LA English DT Article ID DIAGNOSING ACUTE APPENDICITIS; CONTRAST-ENHANCED CT; ACUTE KIDNEY INJURY; SUSPECTED APPENDICITIS; COMPUTED-TOMOGRAPHY; DOSE-RESPONSE; US; MRI; ACCURACY; ADULTS AB Purpose: To compare life expectancy (LE) losses attributable to three imaging strategies for appendicitis in adults-computed tomography (CT), ultrasonography (US) followed by CT for negative or indeterminate US results, and magnetic resonance (MR) imaging-by using a decision-analytic model. Materials and Methods: In this model, for each imaging strategy, LE losses for 20-, 40-, and 65-year-old men and women were computed as a function of five key variables: baseline cohort LE, test performance, surgical mortality, risk of death from delayed diagnosis (missed appendicitis), and LE loss attributable to radiation-induced cancer death. Appendicitis prevalence, test performance, mortality rates from surgery and missed appendicitis, and radiation doses from CT were elicited from the published literature and institutional data. LE loss attributable to radiation exposure was projected by using a separate organ-specific model that accounted for anatomic coverage during a typical abdominopelvic CT examination. One-and two-way sensitivity analyses were performed to evaluate effects of model input variability on results. Results: Outcomes across imaging strategies differed minimally for example, for 20-year-old men, corresponding LE losses were 5.8 days (MR imaging), 6.8 days (combined US and CT), and 8.2 days (CT). This order was sensitive to differences in test performance but was insensitive to variation in radiation-induced cancer deaths. For example, in the same cohort, MR imaging sensitivity had to be 91% at minimum (if specificity were 100%), and MR imaging specificity had to be 62% at minimum (if sensitivity were 100%) to incur the least LE loss. Conversely, LE loss attributable to radiation exposure would need to decrease by 74-fold for combined US and CT, instead of MR imaging, to incur the least LE loss. Conclusion: The specific imaging strategy used to diagnose appendicitis minimally affects outcomes. Paradigm shifts to MR imaging owing to concerns over radiation should be considered only if MR imaging test performance is very high. (C) RSNA, 2014 C1 [Kiatpongsan, Sorapop; Meng, Lesley; Eisenberg, Jonathan D.; Herring, Maurice; Kong, Chung Yin; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kiatpongsan, Sorapop] Chulalongkorn Univ, Fac Med, Dept Obstet & Gynecol, Bangkok 10330, Thailand. [Avery, Laura L.; Kong, Chung Yin; Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM pari@mgh-ita.org FU National Institutes of Health [K07CA133097, K25CA133141] FX This research was supported by the National Institutes of Health (grants K07CA133097 and K25CA133141). NR 49 TC 3 Z9 3 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2014 VL 273 IS 2 BP 472 EP 482 DI 10.1148/radiol.14132629 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT6SS UT WOS:000345069800020 PM 24988435 ER PT J AU Levine, MS Yee, J AF Levine, Marc S. Yee, Judy TI History, Evolution, and Current Status of Radiologic Imaging Tests for Colorectal Cancer Screening SO RADIOLOGY LA English DT Article ID CONTRAST BARIUM ENEMA; COMPUTED-TOMOGRAPHIC COLONOGRAPHY; MAGNETIC-RESONANCE COLONOGRAPHY; LUMEN MR COLONOGRAPHY; AVERAGE-RISK PATIENTS; ROW CT COLONOGRAPHY; WORK-IN-PROGRESS; AIDED DETECTION; CONVENTIONAL COLONOSCOPY; COLONIC DISTENSION AB Colorectal cancer screening is thought to be an effective tool with which to reduce the mortality from colorectal cancer through early detection and removal of colonic adenomas and early colon cancers. In this article, we review the history, evolution, and current status of imaging tests of the colon-including single-contrast barium enema, double-contrast barium enema, computed tomographic (CT) colonography, and magnetic resonance (MR) colonography-for colorectal cancer screening. Despite its documented value in the detection of colonic polyps, the double-contrast barium enema has largely disappeared as a screening test because it is widely perceived as a labor-intensive, time-consuming, and technically demanding procedure. In the past decade, the barium enema has been supplanted by CT colonography as the major imaging test in colorectal cancer screening in the United States, with MR colonography emerging as another viable option in Europe. Although MR colonography does not require ionizing radiation, the radiation dose for CT colonography has decreased substantially, and regular screening with this technique has a high benefit-to-risk ratio. In recent years, CT colonography has been validated as an effective tool for use in colorectal cancer screening that is increasingly being disseminated. (C)RSNA, 2014 C1 [Levine, Marc S.] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Yee, Judy] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Levine, MS (reprint author), Hosp Univ Penn, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM marc.levine@uphs.upenn.edu NR 169 TC 4 Z9 4 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2014 VL 273 IS 2S BP S160 EP S180 DI 10.1148/radiol.14140531 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AT9UR UT WOS:000345272400010 PM 25340435 ER PT J AU Williams, RM Turner, AP Norvell, DC Henderson, AW Hakimi, KN Czerniecki, JM AF Williams, Rhonda M. Turner, Aaron P. Norvell, Daniel C. Henderson, Alison W. Hakimi, Kevin N. Czerniecki, Joseph M. TI The Role of Expectations in Pain After Dysvascular Lower Extremity Amputation SO REHABILITATION PSYCHOLOGY LA English DT Article DE expectations; satisfaction; amputation; pain ID LOWER-LIMB AMPUTATION; PATIENT EXPECTATIONS; PHANTOM PAIN; BACK-PAIN; SATISFACTION; ARTHROPLASTY; DISABILITY; SECONDARY; MODERATE; MILD AB Objective: The objective was to determine the relationship between pain expectations assessed prior to surgery and satisfaction with pain 4 and 12 months after major dysvascular lower extremity amputation. Research Method: The study included a prospective cohort of male (n = 19) veterans experiencing their first lower extremity amputation due to complications of diabetes mellitus or peripheral arterial disease. Measures included presurgical expectations of pain at 4 and 12 months postamputation, actual average pain and satisfaction with pain at 4 and 12 months postamputation, and agreement between expected and actual pain. Results: Sixty-eight percent of participants expected to experience no or minimal pain at 4 months; 95% expected to experience no or minimal pain at 12 months. Thirty-two percent and 58% of participants had more pain than they expected at 4 and 12 months, respectively. Participants whose pain expectations were met reported higher satisfaction with their actual level of pain at 12 months postamputation, even after adjusting for current pain levels. Conclusion: The results underscore the potential value of fostering realistic expectations about the degree to which amputation may impact average pain. C1 [Williams, Rhonda M.] VA Puget Sound Hlth Care Syst, Ctr Polytrauma Care, Rehabil Care Serv, Seattle, WA 98108 USA. [Williams, Rhonda M.; Turner, Aaron P.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Turner, Aaron P.; Hakimi, Kevin N.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. [Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA. [Henderson, Alison W.] VA Puget Sound Hlth Care Syst, VA Res Ctr Excellence Limb Loss Prevent & Prosthe, Seattle, WA 98108 USA. [Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, VA Res Ctr Excellence Limb Loss Prevent & Prosthe, Rehabil Care Serv, Seattle, WA 98108 USA. RP Williams, RM (reprint author), VA Puget Sound Hlth Care Syst, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. EM Rhonda.Williams1@va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 21 TC 2 Z9 2 U1 1 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD NOV PY 2014 VL 59 IS 4 BP 459 EP 463 DI 10.1037/rep0000014 PG 5 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA AT8BQ UT WOS:000345159200011 PM 25313581 ER PT J AU Vincenzi, B Stock, S Borba, CPC Cleary, SM Oppenheim, CE Petruzzi, LJ Fan, XD Copeland, PM Freudenreich, O Cather, C Henderson, DC AF Vincenzi, Brenda Stock, Shannon Borba, Christina P. C. Cleary, Sarah M. Oppenheim, Claire E. Petruzzi, Liana J. Fan, Xiaoduo Copeland, Paul M. Freudenreich, Oliver Cather, Corinne Henderson, David C. TI A randomized placebo-controlled pilot study of pravastatin as an adjunctive therapy in schizophrenia patients: Effect on inflammation, psychopathology, cognition and lipid metabolism SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Statins; Psychosis; Inflammation; C-reactive protein; Cognitive functioning; Glucose metabolism ID C-REACTIVE PROTEIN; DENSITY-LIPOPROTEIN CHOLESTEROL; STATIN THERAPY; SCALE; PLASMA; RISK; SEVERITY; EVENTS AB Objective: The aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder. Methods: Schizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40 mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6 weeks and 12 weeks. Results: Pravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptom score from baseline to week 6. However, this decrease failed to remain significant at 12 weeks. Interestingly, triglycerides, LDL-cholesterol, total cholesterol, LDL particle number, small LDL particle number, large very lowdensity lipoprotein (VLDL) particle number and C-reactive protein (CRP) followed a similar pattern at 6 and 12 weeks as psychopathology. Conclusions: These results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders. (C) 2014 Elsevier B. V. All rights reserved. C1 [Vincenzi, Brenda; Cleary, Sarah M.; Oppenheim, Claire E.; Petruzzi, Liana J.] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA. [Stock, Shannon] Coll Holy Cross, Dept Math & Comp Sci, Worcester, MA 01610 USA. [Borba, Christina P. C.; Freudenreich, Oliver; Cather, Corinne; Henderson, David C.] Harvard Univ, Schizophrenia Clin & Res Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Fan, Xiaoduo] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Worcester, MA USA. [Copeland, Paul M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Henderson, DC (reprint author), FreedomTrail Clin, 25 Staniford St, Boston, MA 02114 USA. EM bvincenzi@partners.org; sstock@holycross.edu; cborba@partners.org; sarah.m.cleary@gmail.com; coppenheim@partners.org; lpetruzzi@partners.org; xiaoduo.fan@umassmed.edu; pccopeland@partners.org; Freudenreich.Oliver@partners.org; ccather@partners.org; dchenderson@partners.org FU Stanley Medical Research Institute [09T-1296] FX This work was supported by The Stanley Medical Research Institute (Grant number 09T-1296). NR 44 TC 9 Z9 9 U1 2 U2 11 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 NOV PY 2014 VL 159 IS 2-3 BP 395 EP 403 DI 10.1016/j.schres.2014.08.021 PG 9 WC Psychiatry SC Psychiatry GA AT9DX UT WOS:000345229200023 PM 25261882 ER PT J AU Seidman, LJ Rosso, IM Thermenos, HW Makris, N Juelich, R Gabrieli, JDE Faraone, SV Tsuang, MT Whitfield-Gabrieli, S AF Seidman, Larry J. Rosso, Isabelle M. Thermenos, Heidi W. Makris, Nikos Juelich, Richard Gabrieli, John D. E. Faraone, Stephen V. Tsuang, Ming T. Whitfield-Gabrieli, Susan TI Medial temporal lobe default mode functioning and hippocampal structure as vulnerability indicators for schizophrenia: A MRI study of non-psychotic adolescent first-degree relatives SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Relatives; Genetics; MRI; Hippocampus; Parahippocampus; Default mode ID WORKING-MEMORY; GENETIC RISK; PREFRONTAL CORTEX; YOUNG-ADULTS; MORPHOMETRIC-ANALYSIS; BRAIN-FUNCTION; FAMILIAL RISK; NETWORK; VOLUMES; INDIVIDUALS AB Background: Clues to the etiology and pathophysiology of schizophrenia can be examined in their first-degree relatives because they are genetically related to an ill family member, and have few confounds like medications. Brain abnormalities observed in young relatives are neurobiological indicators of vulnerability to illness. We examined the hypothesis that the hippocampus and parahippocampus are structurally abnormal and are related to default mode network (DMN) function and cognitive abnormalities in relatives of probands. Methods: Subjects were 27 non-psychotic, first-degree relatives of individuals diagnosed with schizophrenia, and 48 normal controls, ages 13 to 28, undergoing high-resolution magnetic resonance imaging (MRI) at 1.5 T. After structural scan acquisition a subset of subjects performed 2-back working memory (WM) and 0-back tasks during functional MRI (fMRI) alternating with rest. fMRI data were analyzed using SPM-8. Volumes of total cerebrum, hippocampus, and parahippocampal gyrus were measured using semi-automated morphometry. Results: Compared to controls, relatives had significantly smaller left hippocampi, without volumetric reduction in the parahippocampus. Relatives showed significantly less suppression of DMN activity in the left parahippocampal gyrus. Left hippocampal and posterior parahippocampal volumes were inversely and significantly associated with DMN processing (smaller volumes, less suppression) in relatives. Task suppression in parahippocampal gyrus significantly correlated with WM performance within the relatives. Conclusion: Results support the hypothesis that the vulnerability to schizophrenia includes smaller hippocampi and DMN suppression deficits, and these are associated with poorer WM. Findings suggest a primary structural, neurodevelopmental, medial temporal lobe abnormality associated with altered DMN function independent of psychosis. (C) 2014 Elsevier B. V. All rights reserved. C1 [Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Med Sch,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Makris, Nikos; Juelich, Richard] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Boston, MA 02114 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Makris, Nikos] Harvard Univ, Martinos Ctr Biomed Imaging, MIT, Sch Med, Charlestown, MA 02129 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Makris, Nikos] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Faraone, Stephen V.; Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Rosso, Isabelle M.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. [Makris, Nikos] Harvard Univ, Ctr Morphometr Anal, Massachusetts Gen Hosp, Med Sch,Dept Neurol Serv, Boston, MA 02129 USA. [Makris, Nikos] Harvard Univ, Ctr Morphometr Anal, Massachusetts Gen Hosp, Med Sch,Dept Radiol Serv, Boston, MA 02129 USA. [Gabrieli, John D. E.; Whitfield-Gabrieli, Susan] Harvard MIT Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Poitras Ctr Affect Disorders Res, MIT, Cambridge, MA 02139 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, SUNY Genet Res Program, Syracuse, NY 13210 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Inst Behav Gen, La Jolla, CA 92093 USA. RP Seidman, LJ (reprint author), Beth Israel Deaconess Med Ctr, Commonwealth Res Ctr, Neuropsychol Lab, 75 Fenwood Rd, Boston, MA 02115 USA. EM lseidman@bidmc.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU Mental Illness and Neuroscience Discovery (MIND) Institute; NIMH [MH 43518, MH 65562, K01 MH069687]; Massachusetts Department of Mental Health Commonwealth Research Center [SCDMH82101008006]; National Alliance for Research on Schizophrenia and Depression (NARSAD); Poitras Center for Affective Disorders Research at Massachusetts Institute of Technology; National Center for Research Resources [P41RR14075]; [MH092840] FX Grant support: Mental Illness and Neuroscience Discovery (MIND) Institute (LJS); NIMH MH 43518 and MH 65562 (MTT, LJS); MH092840 (LJS, JG) and the Massachusetts Department of Mental Health Commonwealth Research Center - SCDMH82101008006 (LJS); National Alliance for Research on Schizophrenia and Depression (NARSAD; LJS, MTT); NIMH K01 MH069687 (IMR) and the Poitras Center for Affective Disorders Research at Massachusetts Institute of Technology (JG, SWG). This work was also supported in part by The National Center for Research Resources (P41RR14075). NR 80 TC 10 Z9 10 U1 2 U2 10 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 NOV PY 2014 VL 159 IS 2-3 BP 426 EP 434 DI 10.1016/j.schres.2014.09.011 PG 9 WC Psychiatry SC Psychiatry GA AT9DX UT WOS:000345229200028 PM 25308834 ER PT J AU Yoon, JH Westphal, AJ Minzenberg, MJ Niendam, T Ragland, JD Lesh, T Solomon, M Carter, CS AF Yoon, Jong H. Westphal, Andrew J. Minzenberg, Michael J. Niendam, Tara Ragland, J. Daniel Lesh, Tyler Solomon, Marjorie Carter, Cameron S. TI Task-evoked substantia nigra hyperactivity associated with prefrontal hypofunction, prefrontonigral disconnectivity and nigrostriatal connectivity predicting psychosis severity in medication naive first episode schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Psychosis; fMRI; Substantia nigra; Prefrontal cortex; Striatum; Dopamine; Basal ganglia ID CONTEXT-PROCESSING DEFICITS; PRESYNAPTIC DOPAMINE FUNCTION; DOUBLE-BLIND PET; FUNCTIONAL CONNECTIVITY; CORTEX DYSFUNCTION; BASAL GANGLIA; BRAIN; STRIATUM; SYMPTOMS; SPECIFICITY AB The widely cited prefrontal dysfunction - excess subcortical dopamine model of schizophrenia posits that prefrontal deficits give rise to cognitive impairments and the disinhibition of subcortical dopamine release underlying psychosis. While this has been one of the most influential schizophrenia models, only a handful of studies have provided evidence supporting it directly in patients with schizophrenia. We previously demonstrated task-evoked substantia nigra hyperactivity in the context of prefrontal hypofunction and prefrontonigral functional disconnectivity. In addition, nigrostriatal functional connectivity was identified as a potential marker of psychosis. Because patients in this prior study had chronic schizophrenia and were treated with antipsychotics, in the present study we tested whether these findings were confounded by illness chronicity and medication effects by seeking to reproduce these findings in an independent sample of antipsychotic naive, first episode (FE) patients. We compared event-related fMRI activations from 12 FE patients with 15 demographically matched healthy control subjects during cognitive testing. We found substantia nigra hyperactivity associated with prefrontal hypofunction and prefrontonigral functional disconnectivity, as well as the magnitude of nigrostriatal functional connectivity positively correlating with severity of psychosis. This study adds to the body of evidence supporting the prefrontal-dopamine model of schizophrenia and further validates nigrostriatal functional connectivity as a marker of psychosis. Published by Elsevier B.V. C1 [Yoon, Jong H.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Yoon, Jong H.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Westphal, Andrew J.; Niendam, Tara; Ragland, J. Daniel; Lesh, Tyler; Solomon, Marjorie; Carter, Cameron S.] Univ Calif Davis, Dept Psychiat, Davis, CA USA. [Minzenberg, Michael J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Minzenberg, Michael J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Solomon, Marjorie] Univ Calif Davis, MIND Inst, Davis, CA USA. [Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA USA. RP Yoon, JH (reprint author), VA Palo Alto Hlth Care Syst, 3801 Miranda Ave,Bldg 4,2nd Floor, Palo Alto, CA 94304 USA. RI Niendam, Tara/K-8475-2015 OI Niendam, Tara/0000-0003-2285-5002 FU NIH FX The funding source for this study was entirely derived from investigator initiated NIH grants. Therefore, the conduct of the study was solely directed by the authors of this manuscript. NR 45 TC 3 Z9 3 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 NOV PY 2014 VL 159 IS 2-3 BP 521 EP 526 DI 10.1016/j.schres.2014.09.022 PG 6 WC Psychiatry SC Psychiatry GA AT9DX UT WOS:000345229200042 PM 25266549 ER PT J AU Jackson, J Eaton, W Cascella, N Fasano, A Santora, D Sullivan, K Feldman, S Raley, H McMahon, RP Carpenter, WT Demyanovich, H Kelly, DL AF Jackson, Jessica Eaton, William Cascella, Nicola Fasano, Alessio Santora, Debby Sullivan, Kelli Feldman, Stephanie Raley, Heather McMahon, Robert P. Carpenter, William T., Jr. Demyanovich, Haley Kelly, Deanna L. TI Gluten sensitivity and relationship to psychiatric symptoms in people with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Gluten; Celiac disease; Schizophrenia; Gliadin; Gluten sensitivity ID DANISH NATIONAL REGISTERS; CELIAC-DISEASE; FREE DIET; AUTOIMMUNE-DISEASES; ANTIBODIES; DEPRESSION; ATAXIA; INDIVIDUALS; PREVALENCE; GLIADIN AB The relationship between gluten sensitivity and schizophrenia has been of increasing interest and novel mechanisms explaining this relationship continue to be described. Our study in 100 people with schizophrenia compared to 100 matched controls replicates a higher prevalence of gluten sensitivity and higher mean antigliadin IgG antibody levels schizophrenia (2.9 +/- 7.7 vs. 1.3 +/- 1.3, p = 0.046, controlled for age). Additionally, we examined symptoms within the schizophrenia group and found that while positive symptoms are significantly lower in people who have elevated antigliadin antibodies (AGA; 4.11 +/- 1.36 vs. 6.39 +/- 2.99, p = 0.020), no robust clinical profile differentiates between positive and negative antibody groups. Thus, identifying people in schizophrenia who may benefit from a gluten-free diet remains possible by blood test only. (C) 2014 Published by Elsevier B.V. C1 [Jackson, Jessica] Temple Univ, Sch Med, Philadelphia, PA 19140 USA. [Eaton, William] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Cascella, Nicola] Sheppard Pratt Hosp, Neuropsychiat Program, Baltimore, MD 21285 USA. [Fasano, Alessio] Massachusetts Gen Hosp Children, Boston, MA 02114 USA. [Fasano, Alessio] Massachusetts Gen Hosp East, Charlestown, MA 02129 USA. [Santora, Debby] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Sullivan, Kelli; Feldman, Stephanie; McMahon, Robert P.; Carpenter, William T., Jr.; Demyanovich, Haley; Kelly, Deanna L.] Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Sch Med, Catonsville, MD 21228 USA. [Raley, Heather] NIDA, Baltimore, MD 21223 USA. RP Kelly, DL (reprint author), Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. EM dkelly@mprc.umaryland.edu FU NIMH [R34MH100776] FX This study was supported in part by NIMH R34MH100776 (PIs Eaton and Kelly). The funding source had no role in the design, results and dissemination of the findings. NR 33 TC 9 Z9 9 U1 4 U2 22 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 NOV PY 2014 VL 159 IS 2-3 BP 539 EP 542 DI 10.1016/j.schres.2014.09.023 PG 4 WC Psychiatry SC Psychiatry GA AT9DX UT WOS:000345229200045 PM 25311778 ER PT J AU Abayomi, O Amato, D Bailey, C Bitanihirwe, B Bowen, L Burshtein, S Cullen, A Fuste, M Herrmann, AP Khodaie, B Kilian, S Lang, QA Manning, EE Massuda, R Nurjono, M Sadiq, S Sanchez-Gutierrez, T Sheinbaum, T Shivakumar, V Simon, N Spiteri-Staines, A Sirijit, S Toftdahl, NG Wadehra, S Wang, Y Wigton, R Wright, S Yagoda, S Zaytseva, Y O'Shea, A DeLisi, LE AF Abayomi, Olukayode Amato, Davide Bailey, Candace Bitanihirwe, Byron Bowen, Lynneice Burshtein, Shimon Cullen, Alexis Fuste, Montserrat Herrmann, Ana P. Khodaie, Babak Kilian, Sanja Lang, Qortni A. Manning, Elizabeth E. Massuda, Raffael Nurjono, Milawaty Sadiq, Sarosh Sanchez-Gutierrez, Teresa Sheinbaum, Tamara Shivakumar, Venkataram Simon, Nicholas Spiteri-Staines, Anneliese Sirijit, Suttajit Toftdahl, Nanna Gilliam Wadehra, Sunali Wang, Yi Wigton, Rebekah Wright, Susan Yagoda, Sergey Zaytseva, Yuliya O'Shea, Anne DeLisi, Lynn E. TI The 4th Schizophrenia International Research Society Conference, 5-9 April 2014, Florence, Italy: A summary of topics and trends SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Genetics; Gene-environment interaction; Brain imaging; Treatment; Meeting report; Conference ID ULTRA-HIGH-RISK; 1ST EPISODE PSYCHOSIS; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; DOPAMINE SYNTHESIS CAPACITY; 1ST-EPISODE PSYCHOSIS; UNTREATED PSYCHOSIS; PREFRONTAL CORTEX; CHILDHOOD TRAUMA; ANTIPSYCHOTIC MEDICATION AB The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. Published by Elsevier B.V. C1 [Abayomi, Olukayode] Ladoke Akintola Univ Technol, Teaching Hosp, Ogbomosho, Oyo, Nigeria. [Amato, Davide] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany. [Bailey, Candace] Univ Texas Med Branch, Sch Med, Galveston, TX 77550 USA. [Bitanihirwe, Byron] Univ Zurich, Lab Syst & Cell Biol Neurodegenerat, CH-8952 Zurich, Switzerland. [Bowen, Lynneice] Morehouse Sch Med, Atlanta, GA 30310 USA. [Burshtein, Shimon] Chaim Sheba Med Ctr, Ramat Gan, Israel. [Cullen, Alexis] David Goldberg Ctr, Inst Psychiat, Hlth Serv & Populat Res Dept, London SE5 8AF, England. [Fuste, Montserrat] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London SE5 8AF, England. [Herrmann, Ana P.] Univ Fed Rio Grande do Sul, Basic Hlth Sci Inst, Dept Pharmacol, BR-90050170 Porto Alegre, RS, Brazil. [Khodaie, Babak] Shefa Neurosci Res Ctr, Tehran, Iran. [Kilian, Sanja] Univ Stellenbosch, Dept Psychiat, Fac Med & Hlth Sci, Cape Town, South Africa. [Lang, Qortni A.] Howard Univ, Coll Med, Washington, DC 20059 USA. [Manning, Elizabeth E.] Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia. [Massuda, Raffael] Univ Fed Rio Grande do Sul, Lab Mol Psychiat, INCT Translat Med, Hosp Clin Porto Alegre, BR-90035903 Porto Alegre, RS, Brazil. [Nurjono, Milawaty] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore. [Sadiq, Sarosh] Govt Coll Univ, Lahore, Pakistan. [Sanchez-Gutierrez, Teresa] Univ Complutense, Child & Adolescent Psychiat Dept, Hosp Gen Univ Gregorio Maranon, IiSGM,CIBERSAM,Sch Med, Madrid 28009, Spain. [Sheinbaum, Tamara] Univ Autonoma Barcelona, Dept Psicol Clin Salut, E-08193 Barcelona, Spain. [Shivakumar, Venkataram] Natl Inst Mental Hlth & Neurosci NIMHANS, Bengaluru, India. [Simon, Nicholas] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. [Spiteri-Staines, Anneliese] Univ Melbourne, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia. [Sirijit, Suttajit] Chiang Mai Univ, Dept Psychiat, Fac Med, Chiang Mai 50200, Thailand. [Toftdahl, Nanna Gilliam] Mental Hlth Ctr Copenhagen, DK-2400 Copenhagen NV, Denmark. [Wadehra, Sunali] Wayne State Univ, Sch Med, Detroit, MI 48201 USA. [Wang, Yi] Chinese Acad Sci, Neuropsychol & Appl Cognit Neurosci Lab, Key Lab Mental Hlth, Inst Psychol, Beijing 100101, Peoples R China. [Wigton, Rebekah] Kings Coll London, Inst Psychiat, Cognit & Schizophrenia Imaging Lab, London SE5 8AF, England. [Wright, Susan] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat,Neuroimaging Res Program, Baltimore, MD 21228 USA. [Yagoda, Sergey] Stavropol State Med Univ, Dept Psychiat Psychotherapy & Med Psychol, Stavropol 355007, Russia. [Zaytseva, Yuliya] Charles Univ Prague, Moscow Res Inst Psychiat, Russian Federat Prague Psychiat Ctr, Fac Med 3, Prague, Czech Republic. [O'Shea, Anne] Harvard Univ, Sch Med, Brockton, MA 02301 USA. [DeLisi, Lynn E.] Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA 02301 USA. [DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP DeLisi, LE (reprint author), Harvard Univ, Dept Psychiat, Sch Med, 940 Belmont St, Brockton, MA 02301 USA. EM anne_o'shea@hms.harvard.edu; Lynn_DeLisi@hms.harvard.edu RI Cullen, Alexis/A-1286-2016; Herrmann, A./F-3694-2011; OI Cullen, Alexis/0000-0002-3178-3920; Herrmann, A./0000-0002-0330-0741; Zaytseva, Yuliya/0000-0002-6560-8127 FU NIMH [R13MH082446]; NIDA [R13DA036925]; Schizophrenia International Research Society FX A travel award program funded by NIMH (R13MH082446) and NIDA (R13DA036925) with additional funds from the Schizophrenia International Research Society provided partial coverage of expenses to students, some of whom took on the additional role of becoming rapporteurs for oral sessions. NR 159 TC 0 Z9 0 U1 5 U2 15 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 NOV PY 2014 VL 159 IS 2-3 BP E1 EP E22 DI 10.1016/j.schres.2014.08.032 PG 22 WC Psychiatry SC Psychiatry GA AT9DX UT WOS:000345229200001 PM 25306204 ER PT J AU Williams, ME AF Williams, Mark E. TI Hemoglobin A1c in the ESRD Population: Status Report SO SEMINARS IN DIALYSIS LA English DT Article ID MAINTENANCE HEMODIALYSIS-PATIENTS; CHRONIC KIDNEY-DISEASE; GLYCEMIC CONTROL; GLYCATED ALBUMIN; GLYCOSYLATED HEMOGLOBIN; DIABETES-MELLITUS; DIALYSIS PATIENTS; AVERAGE GLUCOSE; COMPLICATIONS TRIAL/EPIDEMIOLOGY; ERYTHROPOIETIN INJECTION C1 [Williams, Mark E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 49 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 EI 1525-139X J9 SEMIN DIALYSIS JI Semin. Dial. PD NOV-DEC PY 2014 VL 27 IS 6 SI SI BP 559 EP 562 DI 10.1111/sdi.12276 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA AT6CA UT WOS:000345025200013 PM 25040220 ER PT J AU Zhu, BL Nahmias, Y Yarmush, ML Murthy, SK AF Zhu, Beili Nahmias, Yaakov Yarmush, Martin L. Murthy, Shashi K. TI Microfluidic Isolation of CD34-Positive Skin Cells Enables Regeneration of Hair and Sebaceous Glands In Vivo SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Microfluidic devices; CD34-positive stem cells; Skin graft site; Nude mice ID FOLLICLE STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; DERMAL CELLS; PROLIFERATION; KERATINOCYTES; MULTIPOTENCY; POPULATIONS; ENRICHMENT; CULTURE; NICHE AB Skin stem cells resident in the bulge area of hair follicles and at the basal layer of the epidermis are multipotent and able to self-renew when transplanted into full-thickness defects in nude mice. Based on cell surface markers such as CD34 and the alpha 6-integrin, skin stem cells can be extracted from tissue-derived cell suspensions for engraftment using the gold standard cell separation technique of fluorescence-activated cell sorting (FACS). This paper describes an alternative separation method using microfluidic devices coated with degradable antibody-functionalized hydrogels. The microfluidic method allows direct injection of tissue digestate (no preprocessing tagging of cells is needed), is fast (45 minutes from injected sample to purified cells), and scalable. This method is used in this study to isolate CD34-positive (CD34(+)) cells from murine skin tissue digestate, and the functional capability of these cells is demonstrated by transplantation into nude mice using protocols developed by other groups for FACS-sorted cells. Specifically, the transplantation of microfluidic isolated CD34(+) cells along with dermal and epidermal cells was observed to generate significant levels of hair follicles and sebaceous glands consistent with those observed previously with FACS-sorted cells. C1 [Zhu, Beili; Murthy, Shashi K.] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. [Zhu, Beili; Murthy, Shashi K.] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA. [Nahmias, Yaakov; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Dept Surg, Boston, MA USA. [Nahmias, Yaakov; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA USA. [Nahmias, Yaakov] Hebrew Univ Jerusalem, Grass Ctr Bioengn, Jerusalem, Israel. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. RP Murthy, SK (reprint author), Northeastern Univ, Dept Chem Engn, 360 Huntington Ave,342 Snell Engn, Boston, MA 02115 USA. EM s.murthy@neu.edu OI Nahmias, Yaakov/0000-0002-6051-616X FU U.S. National Institutes of Health [R01-EB009327]; U.S.-Israel Binational Science Foundation [2013002] FX We thank Adam Hatch for assistance in synthesizing antibody-alginate solutions. This work was supported by the U.S. National Institutes of Health under Grant R01-EB009327 and by the U.S.-Israel Binational Science Foundation under Grant 2013002. NR 27 TC 4 Z9 6 U1 1 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD NOV PY 2014 VL 3 IS 11 BP 1354 EP 1362 DI 10.5966/sctm.2014-0098 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA AT6OA UT WOS:000345057500021 PM 25205844 ER PT J AU Peterson, JR Eboda, O Agarwal, S Ranganathan, K Buchman, SR Lee, M Wang, SC Mishina, Y Levi, B AF Peterson, Jonathan R. Eboda, Oluwatobi Agarwal, Shailesh Ranganathan, Kavitha Buchman, Steven R. Lee, Min Wang, Stewart C. Mishina, Yuji Levi, Benjamin TI Targeting of ALK2, a Receptor for Bone Morphogenetic Proteins, Using the Cre/lox System to Enhance Osseous Regeneration by Adipose-Derived Stem Cells SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE Mesenchymal stem cells; ALK2; Calvarial defect; Bone tissue engineering ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; IN-VITRO; OSTEOGENIC DIFFERENTIATION; STROMAL CELLS; FUSION; MOUSE AB Access to readily available autogenous tissue that regenerates bone would greatly improve clinical care. We believe the osteogenic phenotype caused by mutations in ALK2 can be harnessed in adipose-derived stem cells (ASCs) to improve bone tissue engineering. We set out to demonstrate that ALK2 may serve as a novel target to (a) improve in vitro ASC osteogenic differentiation and (b) enhance in vivo bone regeneration and calvarial healing. Transgenic mice were designed using the Cre/lox system to express constitutively active ALK2 (caALK2) with ubiquitously inducible Cre expression after tamoxifen exposure. ASCs from caALK2+/- and caALK2-/- (control) mice were exposed to tamoxifen and assessed for pro-osteogenic gene expression, bone morphogenetic protein (BMP) signaling, and osteogenic differentiation. Next, ASCs collected from these transgenic mice were analyzed in vivo using a calvarial defect model and analyzed by micro-computed tomography (micro-CT) and histology. ASCs from caALK2+/- mice had increased BMP signaling as demonstrated by upregulation of pSmad 1/5. ASCs from caALK2+/- mice had enhanced bone signaling and osteogenic differentiation compared with caALK2-/- mice (n =4, p<.05). Transcription of pro-osteogenic genes at day 7 was significantly higher in ASCs from caALK2-overexpressing mice (Alp, Runx2, Ocn, Opn) (n= 4,p <.05). Using micro-CT and histomorphometry, we found that bone formation was significantly higher in mice treated with caALK2-expressing ASCs in vivo. Using a novel transgenic mouse model, we show that expression of constitutively active ALK2 receptor results in significantly increased ASC osteogenic differentiation. Furthermore, we demonstrate that this increased ASC differentiation can be harnessed to improve calvarial healing. C1 [Peterson, Jonathan R.; Eboda, Oluwatobi; Agarwal, Shailesh; Ranganathan, Kavitha; Buchman, Steven R.; Wang, Stewart C.] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. [Lee, Min] Univ Calif Los Angeles, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA USA. [Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Levi, Benjamin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02108 USA. RP Levi, B (reprint author), Massachusetts Gen Hosp, Dept Surg, 21 Beacon St, Boston, MA 02108 USA. EM benlevimd@gmail.com FU NIH [1K08GM109105-01]; Plastic Surgery Foundation National Endowment Award FX We thank Amanda Fair and the Center for Molecular Imaging at the University of Michigan for assistance with micro-CT imaging and analysis. B.L. was supported by NIH Grant 1K08GM109105-01 and a Plastic Surgery Foundation National Endowment Award. NR 17 TC 3 Z9 3 U1 2 U2 13 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD NOV PY 2014 VL 3 IS 11 BP 1375 EP 1380 DI 10.5966/sctm.2014-0082 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA AT6OA UT WOS:000345057500023 PM 25232183 ER PT J AU Gunn, JS Marshall, JM Baker, S Dongol, S Charles, RC Ryan, ET AF Gunn, John S. Marshall, Joanna M. Baker, Stephen Dongol, Sabina Charles, Richelle C. Ryan, Edward T. TI Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence SO TRENDS IN MICROBIOLOGY LA English DT Review DE Salmonella; typhoid fever; chronic carrier; epidemiology; diagnostics ID ENTERICA SEROVAR TYPHI; INTESTINAL EPITHELIAL-CELLS; BIOFILM FORMATION; GLOBAL BURDEN; PATHOGENICITY ISLAND; NONTYPHI SALMONELLA; CONJUGATE VACCINE; ENDEMIC AREA; VI SEROLOGY; NESTED PCR AB Typhoid (enteric fever) remains a major cause of morbidity and mortality worldwide, causing over 21 million new infections annually, with the majority of deaths occurring in young children. Because typhoid fever-causing Salmonella have no known environmental reservoir, the chronic, asymptomatic carrier state is thought to be a key feature of continued maintenance of the bacterium within human populations. Despite the importance of this disease to public health, our understanding of the molecular mechanisms that catalyze carriage, as well as our ability to reliably identify and treat the Salmonella carrier state, have only recently begun to advance. C1 [Gunn, John S.; Marshall, Joanna M.] Ohio State Univ, Dept Microbial Infect & Immun, Ctr Microbial Interface Biol, Columbus, OH 43210 USA. [Baker, Stephen] Univ Oxford, Hosp Trop Dis, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam. [Baker, Stephen] Univ Oxford, Ctr Trop Med, Oxford, England. [Baker, Stephen] London Sch Hyg & Trop Med, London WC1, England. [Dongol, Sabina] Univ Oxford, Patan Acad Hlth Sci, Clin Res Unit, Kathmandu, Nepal. [Charles, Richelle C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Gunn, JS (reprint author), Ohio State Univ, Dept Microbial Infect & Immun, Ctr Microbial Interface Biol, Columbus, OH 43210 USA. EM john.gunn@osumc.edu OI Marshall, Joanna/0000-0002-5829-9688 FU National Institutes of Health, including the National Institute of Allergy and Infectious Diseases [AI100023, AI106878, AI058935, AI066208]; Career Development Award [K08 AI089721]; Wellcome Trust; Royal Society [100087/Z/121Z] FX This work was supported by grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI100023, AI106878, and AI058935 to E.T.R.; AI066208 to J.S.G.) and Career Development Award K08 AI089721 (to R.C.C.). S.B is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (100087/Z/121Z). NR 98 TC 13 Z9 14 U1 5 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD NOV PY 2014 VL 22 IS 11 BP 648 EP 655 DI 10.1016/j.tim.2014.06.007 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA AT9PM UT WOS:000345258900009 PM 25065707 ER PT J AU Bastian, LA Trentalange, M Murphy, TE Brandt, C Bean-Mayberry, B Maisel, NC Wright, SM Gaetano, VS Allore, H Skanderson, M Reyes-Harvey, E Yano, EM Rose, D Haskell, S AF Bastian, Lori A. Trentalange, Mark Murphy, Terrence E. Brandt, Cynthia Bean-Mayberry, Bevanne Maisel, Natalya C. Wright, Steven M. Gaetano, Vera S. Allore, Heather Skanderson, Melissa Reyes-Harvey, Evelyn Yano, Elizabeth M. Rose, Danielle Haskell, Sally TI Association between Women Veterans' Experiences with VA Outpatient Health Care and Designation as a Women's Health Provider in Primary Care Clinics SO WOMENS HEALTH ISSUES LA English DT Article ID QUALITY-OF-CARE; PATIENT SATISFACTION; MEDICAL-CARE; PREFERENCES; PERCEPTIONS; SERVICES; VHA AB Background: Women veterans comprise a small percentage of Department of Veterans Affairs (VA) health care users. Prior research on women veterans' experiences with primary care has focused on VA site differences and not individual provider characteristics. In 2010, the VA established policy requiring the provision of comprehensive women's health care by designated women's health providers (DWHPs). Little is known about the quality of health care delivered by DWHPs and women veterans' experience with care from these providers. Methods: Secondary data were obtained from the VA Survey of Healthcare Experience of Patients (SHEP) using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) patient-centered medical home (PCMH) survey from March 2012 through February 2013, a survey designed to measure patient experience with care and the DWHPs Assessment of Workforce Capacity that discerns between DWHPs versus non-DWHPs. Findings: Of the 28,994 surveys mailed to women veterans, 24,789 were seen by primary care providers and 8,151 women responded to the survey (response rate, 32%). A total of 3,147 providers were evaluated by the SHEP-CAHPS-PCMH survey (40%; n = 1,267 were DWHPs). In a multivariable model, patients seen by DWHPs (relative risk, 1.02; 95% CI, 1.01-1.04) reported higher overall experiences with care compared with patients seen by non-DWHPs. Conclusions: The main finding is that women veterans' overall experiences with outpatient health care are slightly better for those receiving care from DWHPs compared with those receiving care from non-DWHPs. Our findings have important policy implications for how to continue to improve women veterans' experiences. Our work provides support to increase access to DWHPs at VA primary care clinics. Published by Elsevier Inc. C1 [Bastian, Lori A.; Trentalange, Mark; Murphy, Terrence E.; Brandt, Cynthia; Gaetano, Vera S.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bastian, Lori A.; Allore, Heather] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Bean-Mayberry, Bevanne; Yano, Elizabeth M.; Rose, Danielle] VA Greater Los Angeles Healthcare Syst, Vet Hlth Adm Hlth Serv Res & Dev, Ctr Study Healthcare Innovat Implementat & Policy, Sepulveda, CA USA. [Maisel, Natalya C.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Wright, Steven M.] Dept Vet Affairs, Off Performance Measurement, Providence, RI USA. [Skanderson, Melissa] Dept Vet Affairs, Pittsburgh, PA USA. [Reyes-Harvey, Evelyn] Off Analyt & Business Intelligence, Off Performance Measurement, Durham, NC USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Haskell, Sally] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Womens Hlth Serv,Patient Care Serv,VA Cent Off, West Haven, CT 06516 USA. RP Bastian, LA (reprint author), VA Connecticut Healthcare Syst, 555 Willard Ave, Newington, CT 06011 USA. EM lori.bastian@va.gov OI Gaetano, Vera/0000-0002-0723-7671; Allore, Heather/0000-0001-7685-8175 FU NIA NIH HHS [P30 AG021342] NR 33 TC 8 Z9 8 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 2014 VL 24 IS 6 BP 605 EP 612 DI 10.1016/j.whi.2014.07.005 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA AT8BD UT WOS:000345157900005 PM 25442706 ER PT J AU Co, JPT Gusic, M AF Co, John Patrick T. Gusic, Maryellen TI Educational Scholarship in Academic Pediatrics: Reflecting on Our Past and Looking Forward to Our Future SO ACADEMIC PEDIATRICS LA English DT Editorial Material ID MEDICAL-EDUCATION C1 [Co, John Patrick T.] MassGen Hosp Children, Partners Off Grad Med Educ, Boston, MA USA. [Co, John Patrick T.] MassGen Hosp Children, Dept Pediat, Boston, MA USA. [Gusic, Maryellen] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. RP Co, JPT (reprint author), Partners Off Grad Med Educ, 7 Whittier Pl,Suite 108, Boston, MA 02114 USA. EM JCO@mgh.harvard.edu NR 5 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 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD NOV-DEC PY 2014 VL 14 IS 6 BP 547 EP 548 PG 2 WC Pediatrics SC Pediatrics GA AT5ES UT WOS:000344966800003 PM 25439150 ER PT J AU Sharifi, M Marshall, G Goldman, R Rifas-Shiman, SL Horan, CM Koziol, R Marshall, R Sequist, TD Taveras, EM AF Sharifi, Mona Marshall, Gareth Goldman, Roberta Rifas-Shiman, Sheryl L. Horan, Christine M. Koziol, Renata Marshall, Richard Sequist, Thomas D. Taveras, Elsie M. TI Exploring Innovative Approaches and Patient-Centered Outcomes From Positive Outliers in Childhood Obesity SO ACADEMIC PEDIATRICS LA English DT Article DE attitude to health; obesity; overweight; parents; positive deviance; qualitative ID WEIGHT-LOSS MAINTENANCE; BODY-MASS INDEX; CONTROL REGISTRY; DEVIANCE; OVERWEIGHT; CHILDREN; PARENTS; PERCEPTIONS; BEHAVIOR; HEALTH AB OBJECTIVE: New approaches for obesity prevention and management can be gleaned from positive outliers-that is, individuals who have succeeded in changing health behaviors and reducing their body mass index (BMI) in the context of adverse built and social environments. We explored perspectives and strategies of parents of positive outlier children living in high-risk neighborhoods. METHODS: We collected up to 5 years of height/weight data from the electronic health records of 22,443 Massachusetts children, ages 6 to 12 years, seen for well-child care. We identified children with any history of BMI in the 95th percentile or higher (n = 4007) and generated a BMI z-score slope for each child using a linear mixed effects model. We recruited parents for focus groups from the subsample of children with negative slopes who also lived in zip codes where >15% of children were obese. We analyzed focus group transcripts using an immersion/crystallization approach. RESULTS: We reached thematic saturation after 5 focus groups with 41 parents. Commonly cited outcomes that mattered most to parents and motivated change were child inactivity, above-average clothing sizes, exercise intolerance, and negative peer interactions; few reported BMI as a motivator. Convergent strategies among positive outlier families were family-level changes, parent modeling, consistency, household rules/limits, and creativity in overcoming resistance. Parents voiced preferences for obesity interventions that include tailored education and support that extend outside clinical settings and are delivered by both health care professionals and successful peers. CONCLUSIONS: Successful strategies learned from positive outlier families can be generalized and tested to accelerate progress in reducing childhood obesity. C1 [Sharifi, Mona; Marshall, Gareth; Horan, Christine M.; Taveras, Elsie M.] Massachusetts Gen Hosp, Div Gen Acad Pediat, Boston, MA 02114 USA. [Goldman, Roberta] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Goldman, Roberta] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rifas-Shiman, Sheryl L.; Koziol, Renata; Taveras, Elsie M.] Harvard Univ, Sch Med, Dept Populat Med, Obes Prevent Program,Harvard Pilgrim Hlth Care In, Boston, MA USA. [Marshall, Richard; Sequist, Thomas D.] Harvard Vanguard Med Associates, Boston, MA USA. [Sequist, Thomas D.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Sequist, Thomas D.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Sequist, Thomas D.] Partners Healthcare Syst, Boston, MA USA. RP Sharifi, M (reprint author), Massachusetts Gen Hosp Children, Dept Pediat, Div Gen Acad Pediat, 100 Cambridge St,15th Floor,Suite 1523, Boston, MA 02114 USA. EM msharifi@partners.org FU Harvard Catalyst Child Health [8 UL 1 TR000170-05]; Patient Centered Outcomes Research Institute FX Supported in part by Harvard Catalyst Child Health pilot grant 8 UL 1 TR000170-05 (PI: Taveras) and a grant from the Patient Centered Outcomes Research Institute (PI: Taveras). NR 35 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 1876-2859 EI 1876-2867 J9 ACAD PEDIATR JI Acad. Pediatr. PD NOV-DEC PY 2014 VL 14 IS 6 BP 646 EP 655 PG 10 WC Pediatrics SC Pediatrics GA AT5ES UT WOS:000344966800019 PM 25439163 ER PT J AU Zhang, T Li, Y Wu, LJ AF Zhang, Tao Li, Yang Wu, Lijie TI An alternative method for data analysis in serial femtosecond crystallography SO ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES LA English DT Article DE serial femtosecond crystallography; SFX; free-electron lasers; structure analysis ID PROTEIN NANOCRYSTALLOGRAPHY AB Serial femtosecond crystallography (SFX) [Chapman et al. (2011), Nature, 470, 73-77], based on the X-ray free-electron laser, is a new and powerful tool for structure analysis at atomic resolution. This study proposes an extrapolation method for diffraction data analysis on the basis of diffraction intensity distribution in reciprocal space. Results show that this new method can restore SFX simulation data to structure factors that are more consistent with the structures used in simulation. C1 [Zhang, Tao] Chinese Acad Sci, Inst Phys, CAS Key Lab Soft Matter Phys, Beijing 100190, Peoples R China. [Li, Yang] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Wu, Lijie] Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. RP Zhang, T (reprint author), Chinese Acad Sci, Inst Phys, CAS Key Lab Soft Matter Phys, 8,South 3rd St Zhong Guan Cun, Beijing 100190, Peoples R China. EM zhangtao@cryst.iphy.ac.cn; yang.li@childrens.harvard.edu FU National Natural Science Foundation of China [11204364] FX This work was supported by the National Natural Science Foundation of China (Grant No. 11204364). We thank Professor Haifu Fan for discussions. NR 11 TC 4 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0108-7673 EI 1600-5724 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD NOV PY 2014 VL 70 BP 670 EP 676 DI 10.1107/S2053273314016982 PN 6 PG 7 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA AT0AM UT WOS:000344599300015 ER PT J AU Kelly, JF Greene, MC Bergman, BG AF Kelly, John F. Greene, M. Claire Bergman, Brandon G. TI Do Drug-Dependent Patients Attending Alcoholics Anonymous Rather than Narcotics Anonymous Do As Well? A Prospective, Lagged, Matching Analysis SO ALCOHOL AND ALCOHOLISM LA English DT Article ID SUBSTANCE-USE DISORDERS; HEALTH-CARE; MUTUAL-HELP; SELF-HELP; UNTREATED REMISSIONS; QUESTIONNAIRE LDQ; CONTINUING CARE; REDUCE DEMAND; ABUSE; RECOVERY AB Aims: Alcoholics Anonymous (AA) is the most prevalent 12-step mutual-help organization (MHO), yet debate has persisted clinically regarding whether patients whose primary substance is not alcohol should be referred to AA. Narcotics Anonymous (NA) was created as a more specific fit to enhance recovery from drug addiction; however, compared with AA, NA meetings are not as ubiquitous. Little is known about the effects of a mismatch between individuals' primary substance and MHOs, and whether any incongruence might result in a lower likelihood of continuation and benefit. More research would inform clinical recommendations. Method: Young adults (N = 279, M age 20.4, SD 1.6, 27% female; 95% White) in a treatment effectiveness study completed assessments at intake, and 3, 6, and 12 months post-treatment. A matching variable was created for 'primary drug' patients (i.e. those reporting cannabis, opiates or stimulants as primary substance; n = 198/279), reflecting the proportion of total 12-step meetings attended that were AA. Hierarchical linear models (HLMs) tested this variable's effects on future 12-step participation and percent days abstinent (PDA). Results: The majority of meetings attended by both alcohol and drug patients was AA. Drug patients attending proportionately more AA than NA meetings (i.e. mismatched) were no different than those who were better matched to NA with respect to future 12-step participation or PDA. Conclusion: Drug patients may be at no greater risk of discontinuation or diminished recovery benefit from participation in AA relative to NA. Findings may boost clinical confidence in making AA referrals for drug patients when NA is less available. C1 [Kelly, John F.; Greene, M. Claire; Bergman, Brandon G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. RP Kelly, JF (reprint author), MGH Harvard Ctr Addict Med, Dept Psychiat, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@mgh.harvard.edu FU National Institute of Alcohol Abuse and Alcoholism [R21AA018185-02] FX This research was supported by grant funding from the National Institute of Alcohol Abuse and Alcoholism (R21AA018185-02) and by anonymous donations to the Hazelden Foundation. This work is solely the responsibility of the authors and the funding agencies had no role in the conception or execution of this work nor in the report presented here. NR 47 TC 2 Z9 2 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 EI 1464-3502 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV-DEC PY 2014 VL 49 IS 6 BP 645 EP 653 DI 10.1093/alcalc/agu066 PG 9 WC Substance Abuse SC Substance Abuse GA AT0BJ UT WOS:000344601500007 PM 25294352 ER PT J AU McGrath, ER Paikin, JS Motlagh, B Salehian, O Kapral, MK O'Donnell, MJ AF McGrath, Emer R. Paikin, Jeremy S. Motlagh, Bahareh Salehian, Omid Kapral, Moira K. O'Donnell, Martin J. TI Transesophageal echocardiography in patients with cryptogenic ischemic stroke: A systematic review SO AMERICAN HEART JOURNAL LA English DT Review ID PATENT FORAMEN OVALE; ATRIAL SEPTAL ANEURYSM; MEDICAL THERAPY; AORTIC-ARCH; HEALTH-CARE; CLOSURE; ATTACK; EMBOLISM; RISK AB Background The clinical utility of routine transesophageal echocardiography (TEE) for patients with unexplained ischemic stroke is controversial. We performed a systematic review to determine the frequency of detection of new cardiac findings in patients with cryptogenic ischemic stroke (IS) undergoing transesophageal echocardiography (TEE). Methods Systematic review and meta-analysis of cohort studies of consecutive patients with "cryptogenic" IS undergoing TEE after routine etiologic workup. Patients were categorized into 2 groups: A (<55 years) and B (55 years). Outcomes included proportion of patients with new TEE-detected cardiac findings and proportion of patients commenced on oral anticoagulation after TEE. Results Twenty-seven studies were included (n = 5,653). We identified significant heterogeneity among studies and report a range of prevalence rates and l(2) statistic as our primary analysis. Prevalence of individual cardiac findings on TEE varied significantly among studies; patent foramen ovale (A: 12.0%-57.8%, l(2) = 89.9%; B: 3.9%-43.5%, l(2) = 86.7%), atrial septal aneurysm (A: 0-48.9%, l(2) = 91.9%; B: 3.5%-25.0%, l(2) = 84.5%), left atrial thrombus (A: 0-10.9%, l(2) = 61.1%; B: 0-21.2%, l(2) = 91.7%), spontaneous echo contrast (A: 0-11.9%, l(2) = 57.2%; B: 0-21.3%, l(2) = 89.8%), and aortic atheroma (A: 0-9.6%, l(2) = 53.8%; B: 2.8%-44.4%, l(2) = 89.7%). Definitions of common findings were not provided for many studies. Five studies (n = 591) reported on the proportion of patients who were commenced on anticoagulant therapy after TEE (range 0-30.7%). Conclusions Routine TEE in patients with cryptogenic IS identifies cardiac findings in a large proportion. However, there is marked interstudy variation in the definition and prevalence of common findings. Transesophageal echocardiography detected findings prompted the introduction of anticoagulant therapy in up to one-third of patients. However, these were mostly not for established guideline-based indications based on randomized controlled trial evidence. It is unclear if routine use of TEE in patients with cryptogenic IS is indicated. C1 [McGrath, Emer R.; O'Donnell, Martin J.] Natl Univ Ireland, HRB Clin Res Facil, Galway, Ireland. [McGrath, Emer R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Paikin, Jeremy S.; Motlagh, Bahareh; Salehian, Omid] McMaster Univ, Dept Cardiol, Hamilton, ON, Canada. [Kapral, Moira K.] Univ Toronto, Dept Internal Med & Clin Epidemiol, Toronto, ON M5S 1A1, Canada. RP McGrath, ER (reprint author), Natl Univ Ireland, HRB Clin Res Facil, Univ Rd, Galway, Ireland. EM emcgrath2@partners.org OI O'Donnell, Martin/0000-0002-7347-7761; McGrath, Emer/0000-0002-3589-2964 NR 22 TC 12 Z9 12 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 2014 VL 168 IS 5 BP 706 EP 712 DI 10.1016/j.ahj.2014.07.025 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AS7KE UT WOS:000344434300013 PM 25440799 ER PT J AU Dossett, ML Davis, RB Lembo, AJ Yeh, GY AF Dossett, Michelle L. Davis, Roger B. Lembo, Anthony J. Yeh, Gloria Y. TI Complementary and Alternative Medicine Use by US Adults With Gastrointestinal Conditions: Results from the 2012 National Health Interview Survey SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CONTROLLED-TRIAL; DISEASE; WOMEN AB OBJECTIVES: Use of complementary and alternative medicine (CAM) has increased over the past two decades, and a growing body of evidence suggests that some CAM modalities may be useful in addressing gastrointestinal (GI) conditions. However, the overall pattern of CAM use for GI conditions remains unknown. We sought to elucidate the prevalence and patterns of CAM use among US adults with GI conditions. METHODS: We used the 2012 National Health Interview Survey (n = 34,525), a nationally representative survey of the civilian, noninstitutionalized US population, to estimate the prevalence of CAM use among adults with GI conditions (abdominal pain, acid reflux/heartburn, digestive allergy, liver condition, nausea and/or vomiting, stomach or intestinal illness, and ulcer). We also examined the reasons for CAM use, perceived helpfulness, and disclosure of use to health-care providers among individuals who specifically used CAM to address a GI condition. Prevalence estimates were weighted to reflect the complex sampling design of the survey. RESULTS: Of the 13,505 respondents with a GI condition in the past year, 42% (n = 5629) used CAM in the past year and 3% (n = 407) used at least one CAM modality to address a GI condition. The top three modalities among those using CAM to address GI conditions were herbs and supplements, mind body therapies, and manipulative therapies. Of those using CAM to address a GI condition, 47% used three or more CAM therapies, and over 80% felt that it was helpful in addressing a GI condition and was important in maintaining health and well-being. Respondents told their health-care providers about use of these therapies 70% of the time. CONCLUSIONS: CAM was used by 42% of respondents with a GI condition in the past year. A small proportion use CAM specifically to address their GI condition, but the majority who do find it helpful. The most commonly used modalities in this group are herbs and supplements, and mind body and manipulative therapies. C1 [Dossett, Michelle L.; Davis, Roger B.; Yeh, Gloria Y.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Dossett, Michelle L.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Davis, Roger B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lembo, Anthony J.] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. RP Dossett, ML (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,CO-215, Boston, MA 02215 USA. EM mdossett@bidmc.harvard.edu FU institutional National Research Service Award from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health [T32AT000051]; Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center; Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award) [1UL1 TR001102-01]; Harvard University FX Financial support: M.L.D. was supported by an institutional National Research Service Award #T32AT000051 from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health and by the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center. This work was conducted with support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award 1UL1 TR001102-01 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. NR 17 TC 10 Z9 10 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2014 VL 109 IS 11 BP 1705 EP 1711 DI 10.1038/ajg.2014.108 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UZ UT WOS:000344461300002 PM 25001257 ER PT J AU Liang, PS Dominitz, JA AF Liang, Peter S. Dominitz, Jason A. TI Bowel Preparation: Is Fair Good Enough? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID ADENOMA DETECTION RATE; SOCIETY TASK-FORCE; COLORECTAL-CANCER; COLONOSCOPY; QUALITY; RECOMMENDATIONS; PERFORMANCE; VALIDATION; ENDOSCOPY; IMPACT AB The effectiveness of colonoscopy in reducing colorectal cancer incidence and mortality has been shown to be associated with an endoscopist's adenoma detection rate, although the ability to detect adenomas depends, in part, on the quality of bowel preparation. Many endoscopists routinely recommend shorter examination intervals for colonoscopies with a fair or intermediate-quality bowel preparation, assuming that the preparation is insufficient for the purpose of colorectal cancer screening. In this issue, Clark et al. performed a systematic review and meta-analysis to assess the adequacy of a fair-quality bowel preparation, finding no difference in the adenoma detection rate of colonoscopies with an intermediate-quality bowel preparation relative to those with a high-quality preparation. Although this finding has potentially significant implications for patient care and healthcare costs, the limitations of the adenoma detection rate as a performance measure and variability in the application of bowel preparation ratings are important issues that must be considered. C1 [Liang, Peter S.; Dominitz, Jason A.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA 98108 USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,111 Gastro, Seattle, WA 98108 USA. EM jason.dominitz@va.gov OI Liang, Peter/0000-0002-4160-421X FU NIDDK NIH HHS [T32 DK007742] NR 18 TC 4 Z9 4 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2014 VL 109 IS 11 BP 1725 EP 1727 DI 10.1038/ajg.2014.328 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UZ UT WOS:000344461300005 PM 25373582 ER PT J AU Abbas, AM Almukhtar, RM Loftus, EV Lichtenstein, GR Khan, N AF Abbas, Ali M. Almukhtar, Rawaa M. Loftus, Edward V., Jr. Lichtenstein, Gary R. Khan, Nabeel TI Risk of Melanoma and Non-Melanoma Skin Cancer in Ulcerative Colitis Patients Treated With Thiopurines: A Nationwide Retrospective Cohort SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ORGAN TRANSPLANT RECIPIENTS; BASAL-CELL CARCINOMAS; RECEIVE THIOPURINES; CLAIMS DATA; DNA-DAMAGE; US WOMEN; AZATHIOPRINE; POPULATION; THERAPY AB OBJECTIVES: There are limited data on the risk of non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC) among thiopurine-treated patients with ulcerative colitis (UC). Our aim was to investigate the risk while on, by cumulative years, and after stopping thiopurine therapy. METHODS: Nationwide data were obtained from the Veterans Affairs (VA) health-care system during 2001-2011. We performed a retrospective cohort study evaluating patients with UC. Cox regression was used to investigate the association between thiopurines use and time to NMSC while adjusting for demographics, ultraviolet radiation exposure, and VA visiting frequency. A matched nested case-control study was conducted to investigate the association between thiopurine use and MSC. RESULTS: We included 14,527 patients with UC in the analysis, with a median follow-up of 8.1 years. A total of 3,346 (23%) patients used thiopurines for a median duration of 1.6 years. We identified 421 NMSC and 45 MSC cases. The adjusted hazard ratios of developing NMSC while on and after stopping thiopurines were 2.1 (P<0.0001) and 0.7 (P=0.07), respectively, as compared with unexposed patients. The incidence rate of NMSC among those who never used thiopurines was 3.7 compared with 5.8, 7.9, 8.3, 7.8, and 13.6 per 1,000 person-years for the 1st, 2nd, 3th, 4th, and 5th year of thiopurine use, respectively. No statistically significant association was observed between thiopurine use and MSC, odds ratio 0.8 (P=0.6). CONCLUSIONS: In this predominantly white male nationwide cohort, there was a twofold increase in the risk of NMSC while on thiopurines. The incidence rate of NMSC significantly increased with subsequent years of cumulative exposure to thiopurines. Stopping thiopurines reduced the risk of NMSC to pre-exposure levels irrespective of the prior exposure duration. C1 [Abbas, Ali M.; Khan, Nabeel] Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, New Orleans, LA USA. [Abbas, Ali M.] Univ Florida, Dept Med, Gainesville, FL 32610 USA. [Almukhtar, Rawaa M.] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, Dept Epidemiol, New Orleans, LA USA. [Loftus, Edward V., Jr.] Mayo Clin, Div Gastroenterol & Hepatol, Dept Internal Med, Rochester, MN USA. [Lichtenstein, Gary R.; Khan, Nabeel] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia VA Med Ctr,Div Gastroenterol, Philadelphia, PA 19104 USA. RP Abbas, AM (reprint author), Univ Florida, Dept Med, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM Ali.Abbas@medicine.ufl.edu RI Loftus, Edward/E-8304-2011 FU Department of Veterans Affairs, Veterans Health Administration - Office of Research & Development Health Services [VA Project No. 425] FX Financial support: This study was funded in full by the Department of Veterans Affairs, Veterans Health Administration - Office of Research & Development Health Services. Grant number (VA Project No. 425). NR 68 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2014 VL 109 IS 11 BP 1781 EP 1793 DI 10.1038/ajg.2014.298 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UZ UT WOS:000344461300012 PM 25244964 ER PT J AU Spiegel, BMR Hays, RD Bolus, R Melmed, GY Chang, L Whitman, C Khanna, PP Paz, SH Hays, T Reise, S Khanna, D AF Spiegel, Brennan M. R. Hays, Ron D. Bolus, Roger Melmed, Gil Y. Chang, Lin Whitman, Cynthia Khanna, Puja P. Paz, Sylvia H. Hays, Tonya Reise, Steve Khanna, Dinesh TI Development of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Gastrointestinal Symptom Scales SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID QUALITY-OF-LIFE; IRRITABLE-BOWEL-SYNDROME; VISCERAL SENSITIVITY INDEX; CLINICAL-PRACTICE; CHRONIC ILLNESS; VALIDATION; DISEASE; QUESTIONNAIRE; INSTRUMENT; GASTROENTEROLOGY AB OBJECTIVES: The National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS (R)) is a standardized set of patient-reported outcomes (PROs) that cover physical, mental, and social health. The aim of this study was to develop the NIH PROMIS gastrointestinal (GI) symptom measures. METHODS: We first conducted a systematic literature review to develop a broad conceptual model of GI symptoms. We complemented the review with 12 focus groups including 102 GI patients. We developed PROMIS items based on the literature and input from the focus groups followed by cognitive debriefing in 28 patients. We administered the items to diverse GI patients (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), systemic sclerosis (SSc), and other common GI disorders) and a census-based US general population (GP) control sample. We created scales based on confirmatory factor analyses and item response theory modeling, and evaluated the scales for reliability and validity. RESULTS: A total of 102 items were developed and administered to 865 patients with GI conditions and 1,177 GP participants. Factor analyses provided support for eight scales: gastroesophageal reflux (13 items), disrupted swallowing (7 items), diarrhea (5 items), bowel incontinence/soilage (4 items), nausea and vomiting (4 items), constipation (9 items), belly pain (6 items), and gas/bloat/flatulence (12 items). The scales correlated significantly with both generic and disease-targeted legacy instruments, and demonstrate evidence of reliability. CONCLUSIONS: Using the NIH PROMIS framework, we developed eight GI symptom scales that can now be used for clinical care and research across the full range of GI disorders. C1 [Spiegel, Brennan M. R.; Melmed, Gil Y.] Cedars Sinai Med Ctr, Dept Gastroenterol, Los Angeles, CA 90048 USA. [Spiegel, Brennan M. R.; Bolus, Roger; Whitman, Cynthia] Cedars Sinai Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Spiegel, Brennan M. R.] VA Greater Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA. [Spiegel, Brennan M. R.; Hays, Ron D.; Paz, Sylvia H.; Hays, Tonya] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Hays, Ron D.; Chang, Lin] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Chang, Lin] Univ Calif Los Angeles, David Geffen Sch Med, Gail & Gerald Oppenheimer Family Ctr Neurobiol St, Los Angeles, CA 90095 USA. [Khanna, Puja P.; Khanna, Dinesh] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Reise, Steve] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Spiegel, BMR (reprint author), Univ Michigan, Scleroderma Program, Div Rheumatol, Dept Internal Med, 300 North Ingalls St,Suite 7C27, Ann Arbor, MI 48109 USA. EM bspiegel@ucla.edu; khannad@med.umich.edu FU NIH/NIAMS [U01 AR057936A]; National Institutes of Health through the NIH Roadmap for Medical Research grant [AR052177]; Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training grant NIAMS [1 T32 AR053463]; ACR Research and Education Foundation Clinical Investigator Fellowship Award; NIAMS [K24 AR063120]; NIH/NIA [P30-AG028748, P30-AG021684]; NCMHD [2P20MD000182]; NIDDK [P50 DK64539] FX Financial support : This study was supported by NIH/NIAMS U01 AR057936A, the National Institutes of Health through the NIH Roadmap for Medical Research grant (AR052177). Puja P. Khanna was supported by Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training grant NIAMS 1 T32 AR053463 and ACR Research and Education Foundation Clinical Investigator Fellowship Award 2009-11. Dinesh Khanna was also supported by NIAMS K24 AR063120. Ron D. Hays was also supported by NIH/NIA grants P30-AG028748 and P30-AG021684, and NCMHD grant 2P20MD000182. Lin Chang was also supported by NIDDK P50 DK64539. NR 29 TC 17 Z9 17 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2014 VL 109 IS 11 BP 1804 EP 1814 DI 10.1038/ajg.2014.237 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UZ UT WOS:000344461300014 PM 25199473 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Therapy Without Diagnosis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID IRRITABLE-BOWEL-SYNDROME C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol Hepatol, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Div Gastroenterol Hepatol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2014 VL 109 IS 11 BP 1837 EP 1838 DI 10.1038/ajg.2014.291 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AS7UZ UT WOS:000344461300023 PM 25373591 ER PT J AU Whittle, J Schapira, MM Fletcher, KE Hayes, A Morzinski, J Laud, P Eastwood, D Ertl, K Patterson, L Mosack, KE AF Whittle, Jeff Schapira, Marilyn M. Fletcher, Kathlyn E. Hayes, Avery Morzinski, Jeffrey Laud, Purushottam Eastwood, Dan Ertl, Kristyn Patterson, Leslie Mosack, Katie E. TI A Randomized Trial of Peer-Delivered Self-Management Support for Hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; hypertension; patient participation; randomized clinical trial; self-help groups ID CHRONIC DISEASE; BLOOD-PRESSURE; CARE MANAGEMENT; HEART-DISEASE; PROGRAMS; EDUCATION; VETERANS; ORGANIZATIONS; INTERVENTIONS; QUESTIONNAIRE AB Peer-led interventions to improve chronic disease self-management can improve health outcomes but are not widely used. Therefore, we tested a peer-led hypertension self-management intervention delivered at regular meetings of community veterans' organizations. We randomized 58 organizational units ("posts") of veterans' organizations in southeast Wisconsin to peer-led vs. professionally delivered self-management education. Volunteer peer leaders at peer-led posts delivered monthly presentations regarding hypertension self-management during regular post meetings. Volunteer post representatives at seminar posts encouraged post members to attend 3 didactic seminars delivered by health professionals at a time separate from the post meeting. Volunteers in both groups encouraged members to self-monitor using blood pressure cuffs, weight scales, and pedometers. Our primary outcome was change in systolic blood pressure (SBP) at 12 months. We measured SBP in 404 participants at baseline and in 379 participants at 12 months. SBP decreased significantly (4.4mm Hg; P < 0.0001) overall; the decrease was similar in peer-led and seminar posts (3.5mm Hg vs. 5.4mm Hg; P = 0.24). Among participants with uncontrolled BP at baseline, SBP decreased by 10.1mm Hg from baseline to 12 months but was again similar in the 2 groups. This pattern was also seen at 6 months and with diastolic blood pressure. Our peer-led educational intervention was not more effective than didactic seminars for SBP control. Although peer-led educational programs have had important impacts in a number of studies, we did not find our intervention superior to a similar intervention delivered by healthcare professionals. ClinicalTrials.gov NCT00571038. C1 [Whittle, Jeff; Fletcher, Kathlyn E.; Hayes, Avery] Clement J Zablocki VA Med Ctr, Primary Care Div, Milwaukee, WI 53295 USA. [Whittle, Jeff; Fletcher, Kathlyn E.; Laud, Purushottam; Ertl, Kristyn] Med Coll Wisconsin, Ctr Patient Care Outcomes Res, Milwaukee, WI 53226 USA. [Whittle, Jeff; Fletcher, Kathlyn E.] Med Coll Wisconsin, Dept Med, Div Gen Internal Med, Milwaukee, WI 53226 USA. [Schapira, Marilyn M.] Univ Penn, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Philadelphia VA, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Morzinski, Jeffrey; Patterson, Leslie] Med Coll Wisconsin, Dept Family & Community Med, Milwaukee, WI 53226 USA. [Laud, Purushottam; Eastwood, Dan] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Mosack, Katie E.] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA. RP Whittle, J (reprint author), Clement J Zablocki VA Med Ctr, Primary Care Div, Milwaukee, WI 53295 USA. EM jeffrey.whittle@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development [IAB 06-086-2] FX This work was supported by a grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (Project IAB 06-086-2, Working with Veterans Service Organizations to Improve Blood Pressure). 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 or the United States government. This work was reviewed and approved by the Human Studies Subcommittee (IRB) of the Milwaukee VA Medical Center. Data from this article were presented in poster format at the National VA HSRD Meeting, Washington, DC, 17 February 2011. NR 37 TC 2 Z9 4 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 2014 VL 27 IS 11 BP 1416 EP 1423 DI 10.1093/ajh/hpu058 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AT0BF UT WOS:000344601100012 PM 24755206 ER PT J AU McKinley, L Moriarty, H Short, TH Hagle, M Ranum, A Valentine, S Safdar, N AF McKinley, Linda Moriarty, Helene Short, Thomas H. Hagle, Mary Ranum, Abigail Valentine, Susan Safdar, Nasia TI Regional differences in vancomycin-resistant Enterococcus colonization rates in critically ill veterans SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Health care-associated infection; Antibiotic-resistant organism ID STAPHYLOCOCCUS-AUREUS; INFECTIONS; PATHOGENS; PRESSURE AB Screening for vancomycin-resistant Enterococcus (VRE) has not been universally implemented within the Department of Veterans Affairs (VA). A prospective study was conducted to identify the admission prevalence rate of VRE in patients admitted to the intensive care unit in 2 VA facilities. Significant regional differences were found between the 2 facilities. Further studies are needed to account for regional differences in VRE admission prevalence, to optimize infection control interventions. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [McKinley, Linda; Valentine, Susan; Safdar, Nasia] William S Middleton Mem VA Hosp, Madison, WI USA. [Moriarty, Helene] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Moriarty, Helene] Villanova Univ, Coll Nursing, Villanova, PA 19085 USA. [Short, Thomas H.] John Carroll Univ, University Hts, OH USA. [Hagle, Mary; Ranum, Abigail; Valentine, Susan] Milwaukee VA Med Ctr, Milwaukee, WI USA. [Safdar, Nasia] Univ Wisconsin, Madison, WI USA. RP McKinley, L (reprint author), 2500 Overlook Terrace, Madison, WI 53705 USA. EM Linda.mckinley2@va.gov OI McKinley, Linda/0000-0002-6172-7700 FU Health Services Research and Development Service of the VA Office of Research and Development [NRI 03-068] FX This material is based on work supported by NRI 03-068 from the Health Services Research and Development Service of the VA Office of Research and Development. 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 or the United States Government. NR 8 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 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD NOV PY 2014 VL 42 IS 11 BP 1226 EP 1228 DI 10.1016/j.ajic.2014.07.030 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AT2FI UT WOS:000344747900019 PM 25444269 ER PT J AU Goldman, RH Batsis, M Hacker, MR Souter, I Petrozza, JC AF Goldman, Randi H. Batsis, Maria Hacker, Michele R. Souter, Irene Petrozza, John C. TI Outcomes after intrauterine insemination are independent of provider type SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS) CY MAR 19-23, 2014 CL Indian Wells, CA SP Pacific Coast Reprod Soc DE infertility; intrauterine insemination; pregnancy rate; provider type ID MOTILE SPERM COUNT; PREGNANCY RATES; CYCLES; AGE; IUI; DETERMINANTS; INFERTILITY; EXPERIENCE; EFFICACY; QUALITY AB OBJECTIVE: We sought to determine whether the success of intrauterine insemination (IUI) varies based on the type of health care provider performing the procedure. STUDY DESIGN: This was a retrospective cohort study set at an infertility clinic at an academic institution. The patients who comprised this study were 1575 women who underwent 3475 IUI cycles from late 2003 through early 2012. Cycles were stratified into 3 groups according to the type of provider who performed the procedure: attending physician, fellow physician, or registered nurse (RN). The primary outcome was live birth. Additional outcomes of interest included positive pregnancy test and clinical pregnancy. Repeated measures log binomial regression was used to estimate the risk ratios (RR) and 95% confidence intervals (CI) for the outcomes and to evaluate the effect of potential confounders. All tests were 2-sided, and P values < .05 were considered statistically significant. RESULTS: Of the 3475 IUI cycles, 2030 (58.4%) were gonadotropin stimulated, 929 (26.7%) were clomiphene citrate stimulated, and 516 (14.9%) were natural. The incidences of clinical pregnancy and live birth among all cycles were 11.8% and 8.8%, respectively. After adjusting for female age, male partner age, and cycle type, the incidence of live birth was similar for RNs compared with attending physicians (RR, 0.80; 95% CI, 0.58-1.1) and fellow physicians compared with attending physicians (RR, 0.84; 95% CI, 0.58-1.2). Similar results were seen for positive pregnancy test and clinical pregnancy. CONCLUSION: There was no significant difference in live birth following IUI cycles in which the procedure was performed by a fellow physician or RN compared with an attending physician. C1 [Batsis, Maria; Souter, Irene; Petrozza, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fertil Ctr, Boston, MA USA. [Goldman, Randi H.; Souter, Irene; Petrozza, John C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA USA. [Hacker, Michele R.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Hacker, Michele R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Goldman, RH (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 4E, Boston, MA 02114 USA. EM randihgoldman@gmail.com OI Hacker, Michele/0000-0003-0217-9991 FU NCATS NIH HHS [1UL1TR001102-01, UL1 TR000170, UL1 TR001102] NR 24 TC 1 Z9 1 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2014 VL 211 IS 5 AR 492.e1 DI 10.1016/j.ajog.2014.05.033 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AS7ZN UT WOS:000344470500013 PM 24881820 ER PT J AU Choksy, P Davis, HC Januzzi, J Thayer, J Harshfield, G Robinson, VJB Kapuku, GK AF Choksy, Pratik Davis, Harry C. Januzzi, James Thayer, Julian Harshfield, Gregory Robinson, Vincent J. B. Kapuku, Gaston K. TI Brain Natriuretic Hormone Predicts Stress-Induced Alterations in Diastolic Function SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Brain natriuretic hormone; Mental stress; Diastolic function ID SILENT-MYOCARDIAL-ISCHEMIA; CORONARY-ARTERY-DISEASE; LEFT-VENTRICULAR MASS; HEART-FAILURE; MENTAL STRESS; PEPTIDE LEVELS; ESSENTIAL-HYPERTENSION; CIRCULATING LEVELS; AFRICAN-AMERICANS; BODY-COMPOSITION AB Background: Mental stress (MS) reduces diastolic function (DF) and may lead to congestive heart failure with preserved systolic function. Whether brain natriuretic hormone (brain natriuretic peptide [ BNP]) mediates the relationship of MS with DF is unknown. Methods: One hundred sixty individuals aged 30 to 50 years underwent 2-hour protocol of 40-minute rest, videogame stressor and recovery. Hemodynamics, pro-BNP samples and DF indices were obtained throughout the protocol. Separate regression analyses were conducted using rest and stress E/A, E ' and E/E ' as dependent variables. Predictor variables were entered into the stepwise regression models in a hierarchical fashion. At the first level, age, sex, race, height, body mass index, pro-BNP and left ventricular mass (LVM) were permitted to enter the models. The second level consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The final level contained cross-product terms of race by SBP, DBP and HR. Results: E/A ratio was lower during stress compared to rest and recovery (P< 0.01). Resting E/A ratio was predicted by a regression model of age (-0.31), pro-BNP (0.16), HR (-0.40) and DBP (-0.23) with an R-2 = 0.33. Stress E/A ratio was predicted by age (-0.24), pro-BNP (0.08), HR (-0.38) and SBP (-0.21) with total R-2 = 0.22. Resting E ' model consisted of age (-0.22), pro-BNP (0.26), DBP (20.27) and LVM (-0.15) with an R-2 = 0.29. Stress E ' was predicted by age (-0.18), pro-BNP (0.35) and LVM (-0.18) with an R-2 = 0.18. Resting E/E ' was predicted by race (0.17, B. W) and DBP (0.24) with an R-2 = 0.10. Stress E/E ' consisted of pro-BNP (-0.36), height (-0.26) and HR (-0.21) with an R-2 = 0.15. Conclusions: pro-BNP predicts both resting and stress DF, suggesting that lower BNP during MS may be a marker of diastolic dysfunction in apparently healthy individuals. C1 [Davis, Harry C.; Harshfield, Gregory; Robinson, Vincent J. B.; Kapuku, Gaston K.] Georgia Regents Univ, Med Coll Georgia, Dept Pediat, Georgia Prevent Ctr,Inst Publ & Prevent Hlth, Augusta, GA 30912 USA. [Choksy, Pratik; Kapuku, Gaston K.] Med Coll Georgia, Dept Med Cardiol, Augusta, GA 30912 USA. [Januzzi, James] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Thayer, Julian] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. RP Kapuku, GK (reprint author), Georgia Regents Univ, Med Coll Georgia, Dept Pediat, MCG Annex HS 1640, Augusta, GA 30912 USA. EM gkapuku@gru.edu FU National Institutes of Health [HL076696]; Cardiovascular Discovery Institute/Georgia Regents University FX Supported by the National Institutes of Health Grant HL076696 and Cardiovascular Discovery Institute/Georgia Regents University. NR 40 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 2014 VL 348 IS 5 BP 366 EP 370 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AT0DX UT WOS:000344608400003 PM 24841419 ER PT J AU Poon, SJ Greenwood-Ericksen, MB AF Poon, Sabrina J. Greenwood-Ericksen, Margaret B. TI The Opioid Prescription Epidemic and the Role of Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID CHRONIC NONCANCER PAIN; UNITED-STATES; MONITORING PROGRAM; OVERDOSE DEATHS; MANAGEMENT; PHYSICIANS; TRENDS; ANALGESICS; GUIDELINES; EDUCATION C1 [Poon, Sabrina J.; Greenwood-Ericksen, Margaret B.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Poon, SJ (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. EM sjpoon@partners.org NR 64 TC 8 Z9 8 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 NOV PY 2014 VL 64 IS 5 BP 490 EP 495 DI 10.1016/j.annemergmed.2014.06.016 PG 6 WC Emergency Medicine SC Emergency Medicine GA AS7LX UT WOS:000344438600010 PM 25017821 ER PT J AU Konstantopoulos, WLM Dreifuss, JA McDermott, KA Parry, BA Howell, ML Mandler, RN Fitzmaurice, GM Bogenschutz, MP Weiss, RD AF Konstantopoulos, Wendy L. Macias Dreifuss, Jessica A. McDermott, Katherine A. Parry, Blair Alden Howell, Melissa L. Mandler, Raul N. Fitzmaurice, Garrett M. Bogenschutz, Michael P. Weiss, Roger D. TI Identifying Patients With Problematic Drug Use in the Emergency Department: Results of a Multisite Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID SUBSTANCE USE; BRIEF INTERVENTION; MARIJUANA USE; ILLICIT DRUG; PRIMARY-CARE; ALCOHOL; RISK; CONSEQUENCES; DRINKERS; SERVICES AB Study objective: Drug-related emergency department (ED) visits have steadily increased, with substance users relying heavily on the ED for medical care. The present study aims to identify clinical correlates of problematic drug use that would facilitate identification of ED patients in need of substance use treatment. Methods: Using previously validated tests, 15,224 adult ED patients across 6 academic institutions were prescreened for drug use as part of a large randomized prospective trial. Data for 3,240 participants who reported drug use in the past 30 days were included. Self-reported variables related to demographics, substance use, and ED visit were examined to determine their correlative value for problematic drug use. Results: Of the 3,240 patients, 2,084 (64.3%) met criteria for problematic drug use (Drug Abuse Screening Test score >= 3). Age greater than or equal to 30 years, tobacco smoking, daily or binge alcohol drinking, daily drug use, primary noncannabis drug use, resource-intense ED triage level, and perceived drug-relatedness of ED visit were highly correlated with problematic drug use. Among primary cannabis users, correlates of problematic drug use were age younger than 30 years, tobacco smoking, binge drinking, daily drug use, and perceived relatedness of the ED visit to drug use. Conclusion: Clinical correlates of drug use problems may assist the identification of ED patients who would benefit from comprehensive screening, intervention, and referral to treatment. A clinical decision rule is proposed. The correlation between problematic drug use and resource-intense ED triage levels suggests that ED-based efforts to reduce the unmet need for substance use treatment may help decrease overall health care costs. C1 [Konstantopoulos, Wendy L. Macias; Parry, Blair Alden; Howell, Melissa L.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Dreifuss, Jessica A.; Weiss, Roger D.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Konstantopoulos, Wendy L. Macias; Dreifuss, Jessica A.; Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA. [Dreifuss, Jessica A.] McLean Hosp, Behav Hlth Partial Program, Belmont, MA 02178 USA. [McDermott, Katherine A.; Weiss, Roger D.] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02178 USA. [Mandler, Raul N.] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. [Fitzmaurice, Garrett M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Bogenschutz, Michael P.] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. RP Konstantopoulos, WLM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM wmacias@mgh.harvard.edu OI Bogenschutz, Michael/0000-0003-4530-3470 FU National Institute on Drug Abuse through McLean Hospital [5U10DA015]; National Institute on Drug Abuse [U10 DA01583, K24 DA022288, U10 DA020036, U10 DA13720, U10 DA13035, U10 DA15831, U10 DA13732, U10 DA15833] 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). Dr. Macias Konstantopoulos reports receiving grants from the National Institute on Drug Abuse through McLean Hospital during the conduct of the study. Ms. Parry reports receiving salary support from grants from the National Institute on Drug Abuse (grant #5U10DA015) through McLean Hospital during the conduct of the study. Dr. Mandler, an employee of the National Institute on Drug Abuse, reviewed and approved the article as a part of his authorship role. His role in the project is through the National Institute on Drug Abuse Clinical Trials Network (U10-DA13720). The National Institute on Drug Abuse appointed members and coordinated meetings of the data and safety monitoring board. Dr. Bogenschutz reports receiving grants from the National Institute on Drug Abuse during the conduct of the study. Dr. Weiss reports receiving grants from the National Institute on Drug Abuse during the conduct of the study. This secondary analysis was completed with financial support from the National Institute on Drug Abuse, grants U10 DA01583, K24 DA022288, U10 DA020036, U10 DA13720, U10 DA13035, U10 DA15831, U10 DA13732, and U10 DA15833. NR 38 TC 9 Z9 9 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 NOV PY 2014 VL 64 IS 5 BP 516 EP 525 DI 10.1016/j.annemergmed.2014.05.012 PG 10 WC Emergency Medicine SC Emergency Medicine GA AS7LX UT WOS:000344438600014 ER PT J AU Choueiri, TK Fay, AP Gray, KP Callea, M Ho, TH Albiges, L Bellmunt, J Song, J Carvo, I Lampron, M Stanton, ML Hodi, FS McDermott, DF Atkins, MB Freeman, GJ Hirsch, MS Signoretti, S AF Choueiri, T. K. Fay, A. P. Gray, K. P. Callea, M. Ho, T. H. Albiges, L. Bellmunt, J. Song, J. Carvo, I. Lampron, M. Stanton, M. L. Hodi, F. S. McDermott, D. F. Atkins, M. B. Freeman, G. J. Hirsch, M. S. Signoretti, S. TI PD-L1 expression in nonclear-cell renal cell carcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE renal cell carcinoma; nonclear-cell renal cell carcinoma; benign kidney tumors; PD-L1; PD-1 inhibitors; immunotherapy ID PROGNOSTIC-FACTORS; MANAGEMENT; CANCER; B7-H1; SUNITINIB; SURVIVAL; FEATURES; THERAPY; DISEASE; SYSTEM AB Programmed death ligand-1 (PD-L1) expression in nonclear-cell RCC (non-ccRCC) and its association with clinical outcomes are unknown. In this study, we report that PD-L1 expression occurs in patients with non-ccRCC depending on histology subtype and tumour cell membrane versus immune cell scoring. In addition, we showed that patients with PD-L1-positive tumours appear to have worse clinical outcomes in non-ccRCC .Programmed death ligand-1 (PD-L1) expression in nonclear-cell RCC (non-ccRCC) and its association with clinical outcomes are unknown. Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 101 patients with non-ccRCC. PD-L1 expression was evaluated by immunohistochemistry in both tumor cell membrane and tumor-infiltrating mononuclear cells (TIMC). PD-L1 tumor positivity was defined as a parts per thousand yen5% tumor cell membrane staining. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrate and percentage of positive cells was used. Baseline clinico-pathological characteristics and outcome data [time to recurrence (TTR) and overall survival (OS)] were correlated with PD-L1 staining. Among 101 patients, 11 (10.9%) were considered PD-L1+ in tumor cells: 2/36 (5.6%) of chromophobe RCC, 5/50 (10%) of papillary RCC, 3/10 (30%) of Xp11.2 translocation RCC and 1/5 (20%) of collecting duct carcinoma. PD-L1 positivity (PD-L1+) in tumor cells was significantly associated with higher stage (P = 0.01) and grade (P = 0.03), as well as shorter OS (P < 0.001). On the other hand, PD-L1 positivity by TIMC was observed in 57 (56.4%) patients: 13/36 (36.1%) of chromophobe RCC, 30/50 (60%) of papillary RCC, 9/10 (90%) of Xp11.2 translocation RCC and 5/5 (100%) of collecting duct carcinoma. A trend toward shorter OS was observed in patients with PD-L1+ in TIMC (P = 0.08). PD-L1+ in both tumor cell membrane and TIMC cells were associated with shorter TTR (P = 0.02 and P = 0.03, respectively). In non-ccRCC, patients with PD-L1+ tumors appear to have worse clinical outcomes, although only PD-L1 positivity in tumor cells is associated with higher tumor stage and grade. C1 [Choueiri, T. K.; Fay, A. P.; Albiges, L.; Bellmunt, J.; Lampron, M.; Hodi, F. S.; Freeman, G. J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Choueiri, T. K.; Bellmunt, J.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. [Choueiri, T. K.; Bellmunt, J.; Hodi, F. S.; McDermott, D. F.; Freeman, G. J.; Hirsch, M. S.; Signoretti, S.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, K. P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Callea, M.; Song, J.; Carvo, I.; Hirsch, M. S.; Signoretti, S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ho, T. H.; Stanton, M. L.] Mayo Clin, Dept Med Oncol, Scottsdale, AZ USA. [Hodi, F. S.] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02215 USA. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Atkins, M. B.] Georgetown Lombardi Comprehens Canc Ctr, Dept Med Oncol, Washington, DC USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave DANA 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu FU DF/HCC Kidney Cancer [SPORE: P50 CA101942-01]; Trust Family; Loker Pinard Fund for Kidney Cancer Research; Michael Brigham Fund for Kidney Cancer Research FX This work was supported in part by DF/HCC Kidney Cancer (SPORE: P50 CA101942-01) to DFM, SS and TKC, and by the Trust Family, the Loker Pinard and the Michael Brigham Funds for Kidney Cancer Research to TKC. NR 31 TC 62 Z9 63 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2014 VL 25 IS 11 BP 2178 EP 2184 DI 10.1093/annonc/mdu445 PG 7 WC Oncology SC Oncology GA AT0SC UT WOS:000344644200011 PM 25193987 ER PT J AU Abramson, JS Feldman, T Kroll-Desrosiers, AR Muffly, LS Winer, E Flowers, CR Lansigan, F Nabhan, C Nastoupil, LJ Nath, R Goy, A Castillo, JJ Jagadeesh, D Woda, B Rosen, ST Smith, SM Evens, AM AF Abramson, J. S. Feldman, T. Kroll-Desrosiers, A. R. Muffly, L. S. Winer, E. Flowers, C. R. Lansigan, F. Nabhan, C. Nastoupil, L. J. Nath, R. Goy, A. Castillo, J. J. Jagadeesh, D. Woda, B. Rosen, S. T. Smith, S. M. Evens, A. M. TI Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy SO ANNALS OF ONCOLOGY LA English DT Article DE peripheral T-cell lymphoma; PTCL; anaplastic large-cell lymphoma; angioimmunoblastic T-cell lymphoma; stem-cell transplantation ID NON-HODGKIN-LYMPHOMA; HIGH-DOSE THERAPY; PROPENSITY-SCORE; TRANSPLANTATION; EXPERIENCE AB Peripheral T-cell lymphomas remain clinically challenging in the modern era with 3-year progression-free and overall survivals of 32% and 52% in this multicenter analysis. Favorable prognostic factors were stage I-II disease and complete response to upfront therapy. Consolidation with stem-cell transplant offered no clear benefit in first remission. Novel treatment approaches are needed.Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear. We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses. PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission. This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed. C1 [Abramson, J. S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [Feldman, T.; Goy, A.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Kroll-Desrosiers, A. R.; Nath, R.; Jagadeesh, D.; Woda, B.] Univ Massachusetts, Sch Med, Dept Hematol Oncol, Worcester, MA USA. [Muffly, L. S.; Nabhan, C.; Smith, S. M.] Univ Chicago, Dept Hematol Oncol, Chicago, IL 60637 USA. [Winer, E.] Rhode Isl Hosp, Dept Hematol Oncol, Providence, RI USA. [Flowers, C. R.; Nastoupil, L. J.] Emory Univ, Sch Med, Dept Hematol Oncol, Atlanta, GA USA. [Lansigan, F.] Dartmouth Hitchcock Med Ctr, Dept Hematol Oncol, Lebanon, NH 03766 USA. [Castillo, J. J.] Miriam Hosp, Dept Hematol Oncol, Providence, RI 02906 USA. [Rosen, S. T.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Evens, A. M.] Tufts Med Ctr, Dept Hematol Oncol, Boston, MA 02111 USA. RP Evens, AM (reprint author), Tufts Med Ctr, Div Hematol Oncol, 800 Washington St,245, Boston, MA 02111 USA. EM aevens@tuftsmedicalcenter.org RI Flowers, Christopher/F-1953-2010; OI Flowers, Christopher/0000-0002-9524-3990; Castillo, Jorge/0000-0001-9490-7532 NR 17 TC 19 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2014 VL 25 IS 11 BP 2211 EP 2217 DI 10.1093/annonc/mdu443 PG 7 WC Oncology SC Oncology GA AT0SC UT WOS:000344644200016 PM 25193992 ER PT J AU Chung, CH Lee, JW Slebos, RJ Howard, JD Perez, J Kang, H Fertig, EJ Considine, M Gilbert, J Murphy, BA Nallur, S Paranjape, T Jordan, RC Garcia, J Burtness, B Forastiere, AA Weidhaas, JB AF Chung, C. H. Lee, J. W. Slebos, R. J. Howard, J. D. Perez, J. Kang, H. Fertig, E. J. Considine, M. Gilbert, J. Murphy, B. A. Nallur, S. Paranjape, T. Jordan, R. C. Garcia, J. Burtness, B. Forastiere, A. A. Weidhaas, J. B. TI A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE KRAS-variant; cisplatin; cetuximab; p16 expression; head and neck squamous cell carcinoma ID HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; PLUS CETUXIMAB; SURVIVAL; TRIAL; RISK; SITE AB A germline mutation in the 3'-untranslated region of KRAS (rs61764370, KRAS-variant: TG/GG) which disrupts microRNA regulation has previously been associated with altered patient outcome and drug sensitivity in various cancers. Our study suggests this KRAS-variant is a potential predictive biomarker for poor platinum response in recurrent/metastatic head and neck squamous cell carcinoma patients.A germline mutation in the 3'-untranslated region of KRAS (rs61764370, KRAS-variant: TG/GG) has previously been associated with altered patient outcome and drug resistance/sensitivity in various cancers. We examined the prognostic and predictive significance of this variant in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We conducted a retrospective study of 103 HNSCCs collected from three completed clinical trials. KRAS-variant genotyping was conducted for these samples and 8 HNSCC cell lines. p16 expression was determined in a subset of 26 oropharynx tumors by immunohistochemistry. Microarray analysis was also utilized to elucidate differentially expressed genes between KRAS-variant and non-variant tumors. Drug sensitivity in cell lines was evaluated to confirm clinical findings. KRAS-variant status was determined in 95/103 (92%) of the HNSCC tumor samples and the allelic frequency of TG/GG was 32% (30/95). Three of the HNSCC cell lines (3/8) studied had the KRAS-variant. No association between KRAS-variant status and p16 expression was observed in the oropharynx subset (Fisher's exact test, P = 1.0). With respect to patient outcome, patients with the KRAS-variant had poor progression-free survival when treated with cisplatin (log-rank P = 0.002). Conversely, KRAS-variant patients appeared to experience some improvement in disease control when cetuximab was added to their platinum-based regimen (log-rank P = 0.04). The TG/GG rs61764370 KRAS-variant is a potential predictive biomarker for poor platinum response in R/M HNSCC patients. NCT00503997, NCT00425750, NCT00003809. C1 [Chung, C. H.; Howard, J. D.; Perez, J.; Kang, H.; Fertig, E. J.; Considine, M.; Forastiere, A. A.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Chung, C. H.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Lee, J. W.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Slebos, R. J.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37235 USA. [Gilbert, J.; Murphy, B. A.] Vanderbilt Univ, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Nallur, S.; Paranjape, T.; Weidhaas, J. B.] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA. [Burtness, B.] Yale Univ, Sch Med, Dept Internal Med, Sect Med Oncol, New Haven, CT 06510 USA. [Weidhaas, J. B.] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA. [Jordan, R. C.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Garcia, J.] Mayo Clin, Rochester, MN USA. RP Chung, CH (reprint author), Johns Hopkins Univ, Dept Oncol, 1650 Orleans St,CRB-1 Rm 344, Baltimore, MD 21231 USA. EM cchung11@jhmi.edu FU NIH NIDCR [R01 (DE017982)]; NIH [R01 CA157749-01A1]; Public Health Service from the National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA16116, CA27525, CA13650, CA9957]; Department of Health and Human Services FX The project was funded in part by NIH NIDCR R01 (DE017982) to CHC. The project was also funded in part by NIH R01 CA157749-01A1 to JBW. This study was coordinated in part by the Eastern Cooperative Oncology Group (Robert L. Comis) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA16116, CA27525, CA13650, CA9957 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 23 TC 7 Z9 7 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2014 VL 25 IS 11 BP 2230 EP 2236 DI 10.1093/annonc/mdu367 PG 7 WC Oncology SC Oncology GA AT0SC UT WOS:000344644200019 PM 25081901 ER PT J AU Abola, MV Prasad, V Jena, AB AF Abola, M. V. Prasad, V. Jena, A. B. TI Association between treatment toxicity and outcomes in oncology clinical trials SO ANNALS OF ONCOLOGY LA English DT Article DE treatment toxicity; clinical trials ID CHEMOTHERAPY-INDUCED NEUTROPENIA; CELL LUNG-CANCER; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS; PROGNOSTIC-FACTOR; POOLED ANALYSIS; SURVIVAL; EFFICACY; CARCINOMA AB Whether treatment toxicity predicts outcomes in oncology is unknown. We analyzed treatment toxicity and outcomes in phase III oncology RCTs and examined whether treatments with relatively greater toxicity had relatively greater progression-free or overall survival (PFS or OS). Across trials, treatments with relatively greater toxicity (compared to controls) had relatively greater PFS but not OS.Whether or not toxicity predicts clinical outcomes has long been a question regarding cancer treatments. While prior studies have focused on specific cancers, therapies, and toxicities, no comprehensive evidence exists on whether treatment toxicity predicts favorable outcomes. We abstracted treatment toxicity and clinical outcome data from a sample of phase III oncology randomized clinical trials (n = 99 trials). We investigated whether treatments with relatively greater toxicity compared with their controls had relatively higher, lower, or equivocal rates of clinical efficacy, measured by progression-free survival (PFS) and overall survival (OS). Several toxicities were assessed (all grades, grades III/IV, cutaneous rash, gastrointestinal toxicity, and myelosuppression). Toxicity and efficacy were greater among treatments than controls (e.g. 3.5 instances of all-grade toxicity per patient in treatment arms versus 2.8 instances in controls, P < 0.001; mean PFS of 9.1 months across treatment arms versus 7.1 months across controls, P < 0.001; mean OS of 18.6 months across treatment arms versus 16.9 months across controls, P < 0.001). Across trials, greater relative treatment toxicity was strongly associated with greater PFS in treatments versus controls (P < 0.001), but not OS (P = 0.44). Although higher relative rates of myelosuppression and cutaneous rash among treatments were not associated with greater treatment efficacy, greater relative gastrointestinal toxicity among treatments was associated with greater relative PFS compared with controls (P = 0.007). Across trials, treatments with relatively greater all-grade toxicity compared with controls are associated with relatively greater PFS but not OS. C1 [Abola, M. V.] Case Western Reserve Univ, Dept Family Med, Sch Med, Cleveland, OH 44106 USA. [Prasad, V.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Jena, A. B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, A. B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu RI Abola, Matthew/F-4869-2015; OI Abola, Matthew/0000-0001-8084-3515; Prasad, Vinay/0000-0002-6110-8221 FU Office of the Director, National Institutes of Health (NIH Early Independence Award) [1DP5OD017897-01] FX Support was provided by the Office of the Director, National Institutes of Health (NIH Early Independence Award, 1DP5OD017897-01, ABJ). NR 21 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2014 VL 25 IS 11 BP 2284 EP 2289 DI 10.1093/annonc/mdu444 PG 6 WC Oncology SC Oncology GA AT0SC UT WOS:000344644200027 PM 25193993 ER PT J AU Jacobs, JP O'Brien, SM Pasquali, SK Kim, S Gaynor, JW Tchervenkov, CI Karamlou, T Welke, KF Lacour-Gayet, F Mavroudis, C Mayer, JE Jonas, RA Edwards, FH Grover, FL Shahian, DM Jacobs, ML AF Jacobs, Jeffrey Phillip O'Brien, Sean M. Pasquali, Sara K. Kim, Sunghee Gaynor, J. William Tchervenkov, Christo Ivanov Karamlou, Tara Welke, Karl F. Lacour-Gayet, Francois Mavroudis, Constantine Mayer, John E., Jr. Jonas, Richard A. Edwards, Fred H. Grover, Frederick L. Shahian, David M. Jacobs, Marshall Lewis TI The Importance of Patient-Specific Preoperative Factors: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 25-29, 2014 CL Orlando, FL SP Soc Thorac Surg ID EMPIRICALLY BASED TOOL; OPERATIONS; OUTCOMES; DISEASE AB Background. The most common forms of risk adjustment for pediatric and congenital heart surgery used today are based mainly on the estimated risk of mortality of the primary procedure of the operation. The goals of this analysis were to assess the association of patient-specific preoperative factors with mortality and to determine which of these preoperative factors to include in future pediatric and congenital cardiac surgical risk models. Methods. All index cardiac operations in The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) during 2010 through 2012 were eligible for inclusion. Patients weighing less than 2.5 kg undergoing patent ductus arteriosus closure were excluded. Centers with more than 10% missing data and patients with missing data for discharge mortality or other key variables were excluded. Rates of discharge mortality for patients with or without specific preoperative factors were assessed across age groups and were compared using Fisher's exact test. Results. In all, 25,476 operations were included (overall discharge mortality 3.7%, n = 943). The prevalence of common preoperative factors and their associations with discharge mortality were determined. Associations of the following preoperative factors with discharge mortality were all highly significant (p < 0.0001) for neonates, infants, and children: mechanical circulatory support, renal dysfunction, shock, and mechanical ventilation. Conclusions. Current STS-CHSD risk adjustment is based on estimated risk of mortality of the primary procedure of the operation as well as age, weight, and prematurity. The inclusion of additional patient-specific preoperative factors in risk models for pediatric and congenital cardiac surgery could lead to increased precision in predicting risk of operative mortality and comparison of observed to expected outcomes. (C) 2014 by The Society of Thoracic Surgeons C1 Johns Hopkins All Childrens Heart Inst, St Petersburg, FL 33701 USA. Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. McGill Univ, Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. Univ Calif San Francisco, Benioff Childrens Hosp, Div Pediat Cardiac Surg, San Francisco, CA 94143 USA. Childrens Hosp Illinois, Peoria, IL USA. Royal Brompton Hosp, London SW3 6LY, England. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. Childrens Natl Med Ctr, Childrens Natl Heart Inst, Washington, DC 20010 USA. Univ Florida, Coll Med Jacksonville, Shands Jacksonville, Jacksonville, FL USA. Univ Colorado Denver, Sch Med, Aurora, CO USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Jacobs, JP (reprint author), Johns Hopkins All Childrens Heart Inst, Andrews Daicoff Cardiovasc Program, 601 Fifth St S,Ste 607, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com FU NHLBI NIH HHS [K08 HL103631, R01 HL122261, K08HL103631] NR 13 TC 14 Z9 15 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 NOV PY 2014 VL 98 IS 5 BP 1653 EP 1658 DI 10.1016/j.athoracsur.2014.07.029 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AT2EZ UT WOS:000344746600035 PM 25262395 ER PT J AU Gilpin, SE Ren, X Okamoto, T Guyette, JP Mou, HM Rajagopal, J Mathisen, DJ Vacanti, JP Ott, HC AF Gilpin, Sarah E. Ren, Xi Okamoto, Tatsuya Guyette, Jacques P. Mou, Hongmei Rajagopal, Jayaraj Mathisen, Douglas J. Vacanti, Joseph P. Ott, Harald C. TI Enhanced Lung Epithelial Specification of Human Induced Pluripotent Stem Cells on Decellularized Lung Matrix SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 25-29, 2014 CL Orlando, FL SP Soc Thorac Surg ID ANTERIOR FOREGUT ENDODERM; ENDOTHELIAL GROWTH-FACTOR; EXTRACELLULAR-MATRIX; DIRECTED DIFFERENTIATION; GENERATION; TRANSPLANTATION; MORPHOGENESIS; REGENERATION; PNEUMOCYTES; PROGENITORS AB Background. Whole-lung scaffolds can be created by perfusion decellularization of cadaveric donor lungs. The resulting matrices can then be recellularized to regenerate functional organs. This study evaluated the capacity of acellular lung scaffolds to support recellularization with lung progenitors derived from human induced pluripotent stem cells (iPSCs). Methods. Whole rat and human lungs were decellularized by constant-pressure perfusion with 0.1% sodium dodecyl sulfate solution. Resulting lung scaffolds were cryosectioned into slices or left intact. Human iPSCs were differentiated to definitive endoderm, anteriorized to a foregut fate, and then ventralized to a population expressing NK2 homeobox 1 (Nkx2.1). Cells were seeded onto slices and whole lungs, which were maintained under constant perfusion biomimetic culture. Lineage specification was assessed by quantitative polymerase chain reaction and immunofluorescent staining. Regenerated left lungs were transplanted in an orthotopic position. Results. Activin-A treatment, followed by transforming growth factor-beta inhibition, induced differentiation of human iPSCs to anterior foregut endoderm as confirmed by forkhead box protein A2 (FOXA2), SRY (Sex Determining Region Y)-Box 17 (SOX17), and SOX2 expression. Cells cultured on decellularized lung slices demonstrated proliferation and lineage commitment after 5 days. Cells expressing Nkx2.1 were identified at 40% to 60% efficiency. Within whole-lung scaffolds and under perfusion culture, cells further upregulated Nkx2.1 expression. After orthotopic transplantation, grafts were perfused and ventilated by host vasculature and airways. Conclusions. Decellularized lung matrix supports the culture and lineage commitment of human iPSC-derived lung progenitor cells. Whole-organ scaffolds and biomimetic culture enable coseeding of iPSC-derived endothelial and epithelial progenitors and enhance early lung fate. Orthotopic transplantation may enable further in vivo graft maturation. (C) 2014 by The Society of Thoracic Surgeons C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ott, HC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 185 Cambridge St,CPZN 4812, Boston, MA 02114 USA. EM hott@partners.org FU NHLBI NIH HHS [R01 HL108678, 5R01-HL-108678-03]; NIH HHS [DP2-OD008749-01, DP2 OD008749] NR 37 TC 15 Z9 15 U1 1 U2 16 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 NOV PY 2014 VL 98 IS 5 BP 1721 EP 1729 DI 10.1016/j.athoracsur.2014.05.080 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AT2EZ UT WOS:000344746600049 PM 25149047 ER PT J AU Donaldson, CW Oklu, R Watkins, MT Donaldson, MC Abtahian, F Schainfeld, RM Jaff, MR Weinberg, I AF Donaldson, Cameron W. Oklu, Rahmi Watkins, Michael T. Donaldson, Magruder C. Abtahian, Farhad Schainfeld, Robert M. Jaff, Michael R. Weinberg, Ido TI Popliteal Venous Aneurysms: Characteristics, Management Strategies, and Clinical Outcomes-A Modern Single-Center Series SO ANNALS OF VASCULAR SURGERY LA English DT Article AB Background: Popliteal vein aneurysm (PVA) may be an incidental finding on imaging, but often presents in the context of acute venous thromboembolism (VTE). The role of anticoagulation with or without surgical excision versus expectant management is ill defined. Methods: In this single-center, retrospective, cohort study, patient records from January 2002 to December 2013 were queried for terminology consistent with PVA. Demographic data and clinical outcomes were extracted via chart review. Results: A total of 21 patients with PVA were identified (57% male). Mean follow-up was 38 +/- 31 months. Mean PVA diameter was 2.5 +/- 1.1 cm; 67% were saccular (with the remainder being fusiform), 19% contained thrombus, 67% were left sided, and bilateral PVA was present in 24% of cases. At the time of PVA diagnosis, 14% had pulmonary embolism. Treatment consisted of observation only (62%), anticoagulation (19%), surgery (5%), or both anticoagulation and surgery (14%). There were no recurrences of VTE once treated, although there was 1 acute deep venous thrombosis in a patient who was managed conservatively. Two patients had recurrent PVA after surgery, and there were 2 surgical complications (transient foot drop and hematoma). Conclusions: PVA is associated with VTE. Based on our series, it is unclear if incidentally discovered PVA (without VTE) warrants treatment with anticoagulation and/or surgical repair. Further multicenter studies are needed to establish the indications for safety and durability of surgery. C1 [Donaldson, Cameron W.; Watkins, Michael T.; Abtahian, Farhad; Schainfeld, Robert M.; Jaff, Michael R.; Weinberg, Ido] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Donaldson, Cameron W.; Oklu, Rahmi; Watkins, Michael T.; Abtahian, Farhad; Schainfeld, Robert M.; Jaff, Michael R.; Weinberg, Ido] Harvard Univ, Sch Med, Boston, MA USA. [Oklu, Rahmi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Donaldson, Magruder C.] MetroWest Med Ctr, Div Vasc Surg, Framingham, MA USA. RP Weinberg, I (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 852G, Boston, MA 02114 USA. EM iweinberg@mgh.harvard.edu NR 17 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 0890-5096 EI 1615-5947 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD NOV PY 2014 VL 28 IS 8 BP 1816 EP 1822 DI 10.1016/j.avsg.2014.06.065 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AS8EZ UT WOS:000344484100004 PM 25011086 ER PT J AU Amoozgar, Z Wang, L Brandstoetter, T Wallis, SS Wilson, EM Goldberg, MS AF Amoozgar, Zohreh Wang, Lei Brandstoetter, Tania Wallis, Samuel S. Wilson, Erin M. Goldberg, Michael S. TI Dual-Layer Surface Coating of PLGA-Based Nanoparticles Provides Slow-Release Drug Delivery To Achieve Metronomic Therapy in a Paclitaxel-Resistant Murine Ovarian Cancer Model SO BIOMACROMOLECULES LA English DT Article ID DIFFERENT CARRIER SOLUTIONS; SOLID TUMORS; INTRAPERITONEAL CHEMOTHERAPY; TISSUE DISTRIBUTION; PHARMACOKINETICS; PENETRATION; PERITONEAL AB Development of drug resistance is a central challenge to the treatment of ovarian cancer. Metronomic chemotherapy decreases the extent of drug-free periods, thereby hindering development of drug resistance. Intraperitoneal chemotherapy allows for treatment of tumors confined within the peritoneum, but achieving sustained tumor-localized chemotherapy remains difficult. We hypothesized that modulating the surface properties of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles could enhance their drug retention ability and extend their release profile, thereby enabling metronomic, localized chemotherapy in vivo. Paclitaxel was encapsulated in particles coated with a layer of polydopamine and a subsequent layer of poly(ethylene glycol) (PEG). These particles achieved a 3.8-fold higher loading content compared to that of nanoparticles formulated from linear PLGA-PEG copolymers. In vitro release kinetic studies and in vivo drug distribution profiles demonstrate sustained release of paclitaxel. Although free drug conferred no survival advantage, low-dose intraperitoneal administration of paclitaxel-laden surface-coated nanoparticles to drug-resistant ovarian tumor-bearing mice resulted in significant survival benefits in the absence of any apparent systemic toxicity. C1 [Amoozgar, Zohreh; Wang, Lei; Brandstoetter, Tania; Wallis, Samuel S.; Wilson, Erin M.; Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Amoozgar, Zohreh; Wang, Lei; Brandstoetter, Tania; Wallis, Samuel S.; Wilson, Erin M.; Goldberg, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM Michael_Goldberg1@dfci.harvard.edu FU Aid for Cancer Research (ACR); Ovarian Cancer Research Fund (OCRF) FX The authors would like to thank Aid for Cancer Research (ACR) for its financial support of Dr. Amoozgar (ACR Fellow) and the Ovarian Cancer Research Fund (OCRF) for its support of both this work and Dr. Goldberg (Liz Tilberis Scholar). NR 34 TC 8 Z9 8 U1 2 U2 48 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 EI 1526-4602 J9 BIOMACROMOLECULES JI Biomacromolecules PD NOV PY 2014 VL 15 IS 11 BP 4187 EP 4194 DI 10.1021/bm5011933 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA AT1WI UT WOS:000344721400033 PM 25251833 ER PT J AU Chai, XL Friebel, TM Singer, CF Evans, DG Lynch, HT Isaacs, C Garber, JE Neuhausen, SL Matloff, E Eeles, R Tung, N Weitzel, JN Couch, FJ Hulick, PJ Ganz, PA Daly, MB Olopade, OI Tomlinson, G Blum, JL Domchek, SM Chen, JB Rebbeck, TR AF Chai, Xinglei Friebel, Tara M. Singer, Christian F. Evans, D. Gareth Lynch, Henry T. Isaacs, Claudine Garber, Judy E. Neuhausen, Susan L. Matloff, Ellen Eeles, Rosalind Tung, Nadine Weitzel, Jeffrey N. Couch, Fergus J. Hulick, Peter J. Ganz, Patricia A. Daly, Mary B. Olopade, Olufunmilayo I. Tomlinson, Gail Blum, Joanne L. Domchek, Susan M. Chen, Jinbo Rebbeck, Timothy R. TI Use of risk-reducing surgeries in a prospective cohort of 1,499 BRCA1 and BRCA2 mutation carriers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Risk reduction; BRCA1; BRCA2; Surgical prevention; Uptake ID BILATERAL SALPINGO-OOPHORECTOMY; OVARIAN-CANCER; PROPHYLACTIC OOPHORECTOMY; CLINICAL COHORT; WOMEN; MULTICENTER; PREDICTORS; MORTALITY; BREAST AB Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan-Meier analyses. Use of RRSO was 45 % for BRCA1 and 34 % for BRCA2 by age 40, and 86 % for BRCA1 and 71 % for BRCA2 by age 50. RRM usage was estimated to be 46 % by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO. C1 [Chai, Xinglei; Friebel, Tara M.; Chen, Jinbo; Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Friebel, Tara M.; Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Basser Ctr BRCA, Philadelphia, PA 19104 USA. [Friebel, Tara M.; Domchek, Susan M.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Singer, Christian F.] Med Univ Vienna, Div Special Gynecol, Vienna, Austria. [Evans, D. Gareth] Univ Manchester, St Marys Hosp, Dept Genom Med, MAHSC, Manchester M13 0JH, Lancs, England. [Lynch, Henry T.] Creighton Univ, Omaha, NE 68178 USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Matloff, Ellen] Yale Univ, New Haven, CT USA. [Eeles, Rosalind] Inst Canc Res, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Eeles, Rosalind] Inst Canc Res, Sutton, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Couch, Fergus J.] Mayo Clin, Coll Med, Rochester, MN USA. [Hulick, Peter J.] NorthShore Univ HealthSyst, Evanston, IL USA. [Hulick, Peter J.] Univ Chicago, Chicago, IL 60637 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Tomlinson, Gail] Univ Texas Dallas, SW Med Ctr, Dallas, TX USA. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Domchek, Susan M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Chen, JB (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, 2 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jinboche@mail.med.upenn.edu; rebbeck@mail.med.upenn.edu OI Eeles, Rosalind/0000-0002-3698-6241; Evans, Gareth/0000-0002-8482-5784 FU Public Health Service [R01-CA164305, R01-CA83855, R01-CA102776]; Basser Center for BRCA at the University of Pennsylvania; Komen Foundation for the Cure; Dana-Farber/Harvard Cancer Center SPORE in BC [P50 CA-089393]; Department of Defense [DAMD-17-96-I-6088, DAMD-17-94-J-4340, DAMD-17-97-I-7112]; Utah Cancer registry - Public Health Service [NO1-CN-6700]; Utah State Department of Health; Nebraska State Cancer and Smoking-Related Diseases Research Program [LB595]; Cancer Research UK [C5047/A7357]; NCI [P30 CA51008-12]; NIHR; Royal Marsden NHS Foundation Trust; National Cancer Institute of the National Institutes of Health [RC4CA153828]; [P30-CA51008-15]; [P30-CA-16042] FX The PROSE Consortium acknowledges the following centers and individuals who contributed to the present study: University of Vienna, Austria (Christian Singer); Beth Israel, Boston, MA (Nadine Tung); Baylor-Charles A. Sammons Cancer Center (Joanne L. Blum, Becky Althaus, Gabrielle Ethington, Estelle Brothers); City of Hope, Duarte, CA (Jeffrey Weitzel); Creighton University, Omaha, NE (Carrie Snyder, Henry T. Lynch, Patrice Watson); Dana-Farber Cancer Institute, Boston, MA (Katherine Corso, Kathryn Stoeckert, Judy E. Garber); NorthShore University HealthSystem, Evanston, IL (Peter J. Hulick, Christina Selkirk, Scott M. Weissman); Fox Chase Cancer Center, Philadelphia, PA (Mary B. Daly); Guy's Hospital and St. Thomas Foundation Trust, London, UK (Gabriella Pichert, Caroline Langman, Leena da Silva); Georgetown University, Washington, DC (Camille Jasper, Claudine Isaacs); University of California, Los Angeles (Patricia A. Ganz, Joyce L. Seldon); Mayo Clinic College of Medicine, Rochester, MN (Fergus Couch); Netherlands Cancer Institute, Amsterdam, Netherlands (Marc van Beurden, Laura van 't Veer); The Institute of Cancer Research & Royal Marsden NHS Foundation Trust, London & Sutton (Rosalind Eeles, Elizabeth Bancroft, Elizabeth Page, Lucia D'Mello, Susan Shanley, Audrey Ardern-Jones, Elena Castro, Anita Mitra, Kelly Kohut, Jennifer Wiggins, The Carrier Clinic Collaborators); St. Mary's Hospital, Manchester, UK (Gareth Evans, Fiona Lalloo); University of Texas-Southwestern, Dallas (n = 63, Gail Tomlinson); University of Chicago, Chicago, IL (Shelly Cummings, Olufunmilayo Olopade); University of Pennsylvania, Philadelphia, PA (Susan Domchek, Tara M Friebel, Timothy Rebbeck, Jill Stopfer, Jacquelyn Powers, Katherine Nathanson); University of Utah, Salt Lake City, UT and University of California, Irvine (Susan Neuhausen, Linda Steele); Women's College Hospital, Toronto, CA (Steven A. Narod); Yale University, New Haven, CT (Ellen T. Matloff, Karina L. Brierly). This study was supported by grants from the Public Health Service (R01-CA164305 to XLC and JBC, R01-CA83855 and R01-CA102776 to TRR), The Basser Center for BRCA at the University of Pennsylvania (to TRR, SMD), Komen Foundation for the Cure (SMD), the Dana-Farber/Harvard Cancer Center SPORE in BC P50 CA-089393 (to JEG), the Department of Defense (DAMD-17-96-I-6088 to AKG; DAMD-17-94-J-4340 and DAMD-17-97-I-7112 to HTL), P30-CA51008-15 (to Georgetown University), The Utah Cancer registry (funded by Public Health Service Grant NO1-CN-6700) and the Utah State Department of Health, the Nebraska State Cancer and Smoking-Related Diseases Research Program (LB595 to HTL), P30-CA-16042 (to PAG), Cancer Research UK Grant Number C5047/A7357 (to RE), and NCI P30 CA51008-12 (to CI). OIO is Doris Duke Distinguished Clinical Scientist. RE acknowledges The Support of the NIHR to The Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number RC4CA153828 (PI: J. Weitzel). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 29 TC 9 Z9 9 U1 1 U2 11 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 NOV PY 2014 VL 148 IS 2 BP 397 EP 406 DI 10.1007/s10549-014-3134-0 PG 10 WC Oncology SC Oncology GA AT2BR UT WOS:000344736500015 PM 25311111 ER PT J AU Beucke, JC Sepulcre, J Eldaief, MC Sebold, M Kathmann, N Kaufmann, C AF Beucke, Jan C. Sepulcre, Jorge Eldaief, Mark C. Sebold, Miriam Kathmann, Norbert Kaufmann, Christian TI Default mode network subsystem alterations in obsessive-compulsive disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID STATE FUNCTIONAL CONNECTIVITY; SCALE BRAIN NETWORKS; RESTING-STATE; SUBCORTICAL CIRCUITRY; PREFRONTAL CORTEX; CINGULATE CORTEX; DEPRESSION; SELF; INVENTORY; ATTENTION AB Background Although neurobiological models of obsessive-compulsive disorder (OCD) traditionally emphasise the central role of corticostriatal brain regions, studies of default mode network integrity have garnered increasing interest, but have produced conflicting results. Aims To resolve these discrepant findings by examining the integrity of default mode network subsystems in OCD. Method Comparison of seed-based resting-state functional connectivity of 11 default mode network components between 46 patients with OCD and 46 controls using functional magnetic resonance imaging. Results Significantly reduced connectivity within the dorsal medial prefrontal cortex self subsystem was identified in the OCD group, and remained significant after controlling for medication status and life-time history of affective disorders. Further, greater connectivity between the self subsystem and salience and attention networks was observed. Conclusions Results indicate that people with OCD show abnormalities in a neural system previously associated with self-referential, processing in healthy individuals, and suggest the need for examination of dynamic interactions between this default mode network subsystem and other large-scale networks in this disorder. C1 [Beucke, Jan C.; Sebold, Miriam; Kathmann, Norbert; Kaufmann, Christian] Humboldt Univ, Dept Psychol, D-12489 Berlin, Germany. [Beucke, Jan C.; Sepulcre, Jorge] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sepulcre, Jorge] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Eldaief, Mark C.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Sebold, Miriam] Charite, Emot Neurosci Grp, D-13353 Berlin, Germany. RP Beucke, JC (reprint author), Humboldt Univ, Dept Psychol, Rudower Chaussee 18, D-12489 Berlin, Germany. FU Federal Ministry of Education and Research of Germany [BMBF-01GW0724]; Evangelisches Studienwerk e V Villigst (Schwerte, Germany); Alzheimer's Association [NIRG-11-205690] FX This work was supported by a grant from the Federal Ministry of Education and Research of Germany (grant number BMBF-01GW0724 to N.K.). J C.B is supported by a PhD scholarship from Evangelisches Studienwerk e V Villigst (Schwerte, Germany), and is a ERP scholar of the German National Academic Foundation. I S. is supported by the Alzheimer's Association (grant number NIRG-11-205690) NR 40 TC 7 Z9 9 U1 3 U2 11 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD NOV PY 2014 VL 205 IS 5 BP 376 EP 382 DI 10.1192/bjp.bp.113.137380 PG 7 WC Psychiatry SC Psychiatry GA AT5HD UT WOS:000344973700007 PM 25257066 ER PT J AU Martin, NE D'Amico, AV AF Martin, Neil E. D'Amico, Anthony V. TI Progress and Controversies: Radiation Therapy for Prostate Cancer SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review DE prostate cancer; radiation therapy; intensity-modulated radiation therapy; hypofractionation; proton beam radiation; adjuvant radiation; salvage radiation ID ANDROGEN-DEPRIVATION THERAPY; PHASE-III TRIAL; QUALITY-OF-LIFE; EXTERNAL-BEAM RADIOTHERAPY; STEREOTACTIC BODY RADIOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; PATIENT-REPORTED OUTCOMES; DOSE-ESCALATION TRIAL; EARLY BREAST-CANCER; RADICAL PROSTATECTOMY AB Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a curative treatment and has been shown to prolong survival in selected populations. In this article, the authors review recent advances in prostate radiationtreatment techniques, photon versus proton radiation, modification of treatment fractionation, and brachytherapyall focusing on disease control and the impact on morbidity. Also discussed are refinements in the risk stratification of men with prostate cancer and how these are better for matching patients to appropriate treatment, particularly around combined androgen-deprivation therapy. Many of these advances have cost and treatment burden implications, which have significant repercussions given the prevalence of prostate cancer. The discussion includes approaches to improve value and future directions for research. CA Cancer J Clin 2014;64:389-407. (c) 2014 American Cancer Society. C1 [Martin, Neil E.; D'Amico, Anthony V.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Med Sch, Boston, MA 02115 USA. RP Martin, NE (reprint author), Dept Radiat Oncol, 75 Francis St,ASB-1 L2, Boston, MA 02115 USA. EM nmartin@lroc.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 152 TC 11 Z9 11 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD NOV-DEC PY 2014 VL 64 IS 6 BP 389 EP 407 DI 10.3322/caac.21250 PG 19 WC Oncology SC Oncology GA AT2QN UT WOS:000344779300005 PM 25234700 ER PT J AU Bianchi, G Anderson, KC AF Bianchi, Giada Anderson, Kenneth C. TI Understanding Biology to Tackle the Disease: Multiple Myeloma From Bench to Bedside, and Back SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review DE multiple myeloma; monoclonal gammopathy of undetermined significance; smoldering multiple myeloma; microenvironment; hematopoietic stem cell transplant; proteasome inhibitors; immunomodulatory agents; molecularly targeted therapies ID STEM-CELL TRANSPLANTATION; PROTEASOME INHIBITOR PS-341; LOW-DOSE DEXAMETHASONE; PHASE-III TRIAL; OVERCOMES BORTEZOMIB RESISTANCE; UNDETERMINED SIGNIFICANCE MGUS; MULTIPARAMETER FLOW-CYTOMETRY; INTERNATIONAL STAGING SYSTEM; BONE-MARROW MICROENVIRONMENT; RANDOMIZED CONTROLLED-TRIAL AB Multiple myeloma (MM) is a cancer of antibody-producing plasma cells. The pathognomonic laboratory finding is a monoclonal immunoglobulin or free light chain in the serum and/or urine in association with bone marrow infiltration by malignant plasma cells. MM develops from a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage termed smoldering multiple myeloma (SMM), which differs from active myeloma by the absence of disease-related end-organ damage. Unlike MGUS and SMM, active MM requires therapy. Over the past 6 decades, major advancements in the care of MM patients have occurred, in particular, the introduction of novel agents (ie, proteasome inhibitors, immunomodulatory agents) and the implementation of hematopoietic stem cell transplantation in suitable candidates. The effectiveness and good tolerability of novel agents allowed for their combined use in induction, consolidation, and maintenance therapy, resulting in deeper and more sustained clinical response and extended progression-free and overall survival. Previously a rapidly lethal cancer with few therapeutic options, MM is the hematologic cancer with the most novel US Food and Drug Administration-approved drugs in the past 15 years. These advances have resulted in more frequent long-term remissions, transforming MM into a chronic illness for many patients. CA Cancer J Clin 2014;64:422-444. (c) 2014 American Cancer Society. C1 [Bianchi, Giada; Anderson, Kenneth C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Bianchi, Giada; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut,Dept Med Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02114 USA. EM kenneth_anderson@dfci.harvard.edu NR 177 TC 9 Z9 10 U1 2 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-9235 EI 1542-4863 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD NOV-DEC PY 2014 VL 64 IS 6 BP 422 EP 444 DI 10.3322/caac.21252 PG 23 WC Oncology SC Oncology GA AT2QN UT WOS:000344779300007 PM 25266555 ER PT J AU Sheshadri, N Catanzaro, JM Bott, AJ Sun, Y Ullman, E Chen, EI Pan, JA Wu, S Crawford, HC Zhang, JH Zong, WX AF Sheshadri, Namratha Catanzaro, Joseph M. Bott, Alex J. Sun, Yu Ullman, Erica Chen, Emily I. Pan, Ji-An Wu, Song Crawford, Howard C. Zhang, Jianhua Zong, Wei-Xing TI SCCA1/SERPINB3 Promotes Oncogenesis and Epithelial-Mesenchymal Transition via the Unfolded Protein Response and IL6 Signaling SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ENDOPLASMIC-RETICULUM STRESS; NF-KAPPA-B; TUMOR-GROWTH; STEM-CELLS; ER STRESS; ANTIGEN 1; CANCER; EXPRESSION; APOPTOSIS AB The serine/cysteine protease inhibitor SCCA1 (SERPINB3) is upregulated in many advanced cancers with poor prognosis, but there is limited information about whether it makes functional contributions to malignancy. Here, we show that SCCA1 expression promoted oncogenic transformation and epithelial-mesenchymal transition (EMT) in mammary epithelial cells, and that SCCA1 silencing in breast cancer cells halted their proliferation. SCCA1 overexpression in neu(+) mammary tumors increased the unfolded protein response (UPR), IL6 expression, and inflammatory phenotypes. Mechanistically, SCCA1 induced a prolonged nonlethal increase in the UPR that was sufficient to activate NF-kappa B and expression of the protumorigenic cytokine IL6. Overall, our findings established that SCCA1 contributes to tumorigenesis by promoting EMT and a UPR-dependent induction of NF-kappa B and IL6 autocrine signaling that promotes a protumorigenic inflammation. (C) 2014 AACR. C1 [Sheshadri, Namratha; Catanzaro, Joseph M.; Bott, Alex J.; Sun, Yu; Ullman, Erica; Pan, Ji-An; Zong, Wei-Xing] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Chen, Emily I.] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. [Wu, Song] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Crawford, Howard C.] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA. [Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Zong, WX (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. EM weixing.zong@stonybrook.edu OI Bott, Alex/0000-0003-2273-8922 FU NIH [R01CA129536, R01GM97355]; Carol Baldwin Breast Cancer Research Foundation; NCI T32 training grant [T32CA009176]; VA merit award; [NIHR01-NS064090] FX This work was supported by grants from NIH (R01CA129536 and R01GM97355) and the Carol Baldwin Breast Cancer Research Foundation to WXZ. J.M. Catanzaro was supported by the NCI T32 training grant (T32CA009176). J. Zhang was supported by NIHR01-NS064090 and a VA merit award. NR 50 TC 13 Z9 13 U1 1 U2 4 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 NOV 1 PY 2014 VL 74 IS 21 BP 6318 EP 6329 DI 10.1158/0008-5472.CAN-14-0798 PG 12 WC Oncology SC Oncology GA AT2IF UT WOS:000344756800036 PM 25213322 ER PT J AU Chaumon, M Kveraga, K Barrett, LF Bar, M AF Chaumon, Maximilien Kveraga, Kestutis Barrett, Lisa Feldman Bar, Moshe TI Visual Predictions in the Orbitofrontal Cortex Rely on Associative Content SO CEREBRAL CORTEX LA English DT Article DE fMRI; perception; top-down ID MEDIAL PREFRONTAL CORTEX; TOP-DOWN FACILITATION; MACAQUE MONKEYS; RECOGNITION; NEURONS; OBJECT; PERCEPTION; NETWORKS; BEHAVIOR; BRAIN AB Predicting upcoming events from incomplete information is an essential brain function. The orbitofrontal cortex (OFC) plays a critical role in this process by facilitating recognition of sensory inputs via predictive feedback to sensory cortices. In the visual domain, the OFC is engaged by low spatial frequency (LSF) and magnocellular-biased inputs, but beyond this, we know little about the information content required to activate it. Is the OFC automatically engaged to analyze any LSF information for meaning? Or is it engaged only when LSF information matches preexisting memory associations? We tested these hypotheses and show that only LSF information that could be linked to memory associations engages the OFC. Specifically, LSF stimuli activated the OFC in 2 distinct medial and lateral regions only if they resembled known visual objects. More identifiable objects increased activity in the medial OFC, known for its function in affective responses. Furthermore, these objects also increased the connectivity of the lateral OFC with the ventral visual cortex, a crucial region for object identification. At the interface between sensory, memory, and affective processing, the OFC thus appears to be attuned to the associative content of visual information and to play a central role in visuo-affective prediction. C1 [Chaumon, Maximilien; Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Interdisciplinary Affect Sci Lab, Boston, MA 02115 USA. [Chaumon, Maximilien; Kveraga, Kestutis; Barrett, Lisa Feldman; Bar, Moshe] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Chaumon, Maximilien; Kveraga, Kestutis; Barrett, Lisa Feldman; Bar, Moshe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Chaumon, Maximilien] Humboldt Univ, Berlin Sch Mind & Brain, D-10117 Berlin, Germany. [Bar, Moshe] Bar Ilan Univ, Gonda Ctr Brain Res, Ramat Gan, Israel. RP Chaumon, M (reprint author), Berlin Sch Mind & Brain, Luisenstr 56, D-10117 Berlin, Germany. EM maximilien.chaumon@gmail.com FU National Institutes of Health [DP1OD003312]; National Institute of Mental Health [K01MH084011]; National Eye Institute [NEI 1R01EY019477-01]; Defense Advanced Research Projects Agency [N10AP20036]; National Science Foundation [NSF BCS-0842947] FX This work was supported by the National Institutes of Health (DP1OD003312 to L.F.B.), National Institute of Mental Health (K01MH084011 to K.K.), National Eye Institute (NEI 1R01EY019477-01 to M.B.), Defense Advanced Research Projects Agency (N10AP20036 to M.B.), and National Science Foundation (NSF BCS-0842947 to M.B.). NR 54 TC 19 Z9 22 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2014 VL 24 IS 11 BP 2899 EP 2907 DI 10.1093/cercor/bht146 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AT0SX UT WOS:000344646200008 PM 23771980 ER PT J AU Pullicino, PM Qian, M Sacco, RL Freudenberger, R Graham, S Teerlink, JR Mann, D Di Tullio, MR Ponikowski, P Lok, DJ Anker, SD Lip, GYH Estol, CJ Levin, B Mohr, JP Thompson, JLP Homma, S AF Pullicino, Patrick M. Qian, Min Sacco, Ralph L. Freudenberger, Ron Graham, Susan Teerlink, John R. Mann, Douglas Di Tullio, Marco R. Ponikowski, Piotr Lok, Dirk J. Anker, Stefan D. Lip, Gregory Y. H. Estol, Conrado J. Levin, Bruce Mohr, Jay P. Thompson, John L. P. Homma, Shunichi CA WARCEF Investigators TI Recurrent Stroke in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial SO CEREBROVASCULAR DISEASES LA English DT Article DE Heart failure; Stroke; Ejection fraction ID HEART-FAILURE; ATRIAL-FIBRILLATION; SINUS RHYTHM; ISCHEMIC-STROKE; RISK; PREVENTION; THERAPY AB Background and Purpose: WARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) <= 35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods: We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/ aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results: Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) < 15% and 70 of 2,079 (3.4%) with EF >= 15% had IIS. In the multiple regression analysis stroke at baseline (p < 0.001) and EF < 15% vs. >= 15% (p = 0.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF < 15% and 0.95/100PY in patients with EF >= 15% (p = 0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF < 15% decreasing to 2.62/100PY with EF < 30%. Conclusions: In a WARCEF exploratory analysis, prior stroke and EF < 15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF. (C) 2014 S. Karger AG, Basel C1 [Pullicino, Patrick M.] Univ Kent, Canterbury CT2 7PD, Kent, England. [Qian, Min; Di Tullio, Marco R.; Levin, Bruce; Mohr, Jay P.; Thompson, John L. P.; Homma, Shunichi] Columbia Univ, New York, NY USA. [Sacco, Ralph L.] Univ Miami, Miami, FL USA. [Freudenberger, Ron] LeHigh Valley Hosp, Allentown, PA USA. [Graham, Susan] SUNY Buffalo, Buffalo, NY 14260 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Mann, Douglas] Washington Univ, St Louis, MO USA. [Ponikowski, Piotr] Med Univ, Wroclaw, Poland. [Lok, Dirk J.] Hosp Deventer, Deventer, Netherlands. [Anker, Stefan D.] Charite, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Lip, Gregory Y. H.] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Estol, Conrado J.] Ctr Neurol Tratamiento & Rehabil, Buenos Aires, DF, Argentina. RP Pullicino, PM (reprint author), Univ Kent, KentHlth, Rutherford Bldg, Canterbury CT2 7PD, Kent, England. EM P.Pullicino@kent.ac.uk RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Beran, David/0000-0001-7229-3920; Mann, Douglas /0000-0002-2516-0145; Kohsaka, Shun/0000-0003-3779-2972 FU NINDS [U01-NS-043975, U01-NS-039143] FX NINDS U01-NS-043975 and U01-NS-039143. NR 14 TC 5 Z9 5 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD NOV PY 2014 VL 38 IS 3 BP 176 EP 181 DI 10.1159/000365502 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AT1ZJ UT WOS:000344729400004 PM 25300706 ER PT J AU Craig, J Burdon, K Gharahkhani, P Hewitt, A Mackey, D Mitchell, P Graham, S Goldberg, I White, A Wiggs, J Pasquale, L Landers, J Casson, R Ruddle, J Sharma, S Brown, M Zhou, T Souzeau, E Mills, R Macgregor, S AF Craig, Jamie Burdon, Kathryn Gharahkhani, Puya Hewitt, Alex Mackey, David Mitchell, Paul Graham, Stuart Goldberg, Ivan White, Andrew Wiggs, Janey Pasquale, Lou Landers, John Casson, Robert Ruddle, Jon Sharma, Shiwani Brown, Matthew Zhou, Tiger Souzeau, Emmanuelle Mills, Richard Macgregor, Stuart CA NEIGHBOUR Consortium TI GENOME WIDE ASSOCIATION STUDY IN THE AUSTRALIAN AND NEW ZEALAND REGISTRY OF ADVANCED GLAUCOMA IDENTIFIES COMMON SEQUENCE VARIANTS IN ABCA1, AFAP1 AND GMDS WHICH CONFER RISK OF PRIMARY OPEN-ANGLE GLAUCOMA, AND REPLICATE IN MULTIPLE INDEPENDENT COHORTS SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Meeting Abstract C1 [Craig, Jamie; Burdon, Kathryn; Landers, John; Sharma, Shiwani; Zhou, Tiger; Souzeau, Emmanuelle; Mills, Richard] Flinders Univ S Australia, Adelaide, SA 5001, Australia. [Burdon, Kathryn; Hewitt, Alex] Univ Tasmania, Menzies Ctr, Hobart, Tas, Australia. [Gharahkhani, Puya; Macgregor, Stuart] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Brown, Matthew] Univ QLD, Diamantina Inst, Brisbane, Qld, Australia. [Wiggs, Janey] Harvard Univ, Sch Med, Boston, MA USA. [Wiggs, Janey; NEIGHBOUR Consortium] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Mitchell, Paul; White, Andrew] Westmead Millennium Inst Med Res, Westmead, NSW, Australia. [Mackey, David] Lions Eye Inst, Perth, WA, Australia. [Hewitt, Alex; Ruddle, Jon] Ctr Eye Res Australia, Melbourne, Vic, Australia. [Graham, Stuart; Goldberg, Ivan] Macquarie Univ, Sydney, NSW 2109, Australia. [White, Andrew; Pasquale, Lou] Sydney Eye Hosp, Sydney, NSW, Australia. [Casson, Robert] Univ Adelaide, Adelaide, SA, Australia. EM jamie.craig@flinders.edu.au RI Macgregor, Stuart/C-6442-2009; Hewitt, Alex/D-1936-2013 OI Macgregor, Stuart/0000-0001-6731-8142; Hewitt, Alex/0000-0002-5123-5999 NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1442-6404 EI 1442-9071 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD NOV PY 2014 VL 42 SU 1 SI SI MA P0506 BP 27 EP 28 PG 2 WC Ophthalmology SC Ophthalmology GA AS8YJ UT WOS:000344530600031 ER PT J AU Domsic, RT Dezfulian, C Shoushtari, A Ivanco, D Kenny, E Kwoh, CK Medsger, TA Champion, HC AF Domsic, R. T. Dezfulian, C. Shoushtari, A. Ivanco, D. Kenny, E. Kwoh, C. K. Medsger, T. A., Jr. Champion, H. C. TI Endothelial dysfunction is present only in the microvasculature and microcirculation of early diffuse systemic sclerosis patients SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE scleroderma; systemic; diffuse; endothelium; vascular; laser speckle contrast analysis ID PULMONARY ARTERIAL-HYPERTENSION; RAYNAUDS-PHENOMENON SECONDARY; STIFFNESS PARAMETERS; BRACHIAL-ARTERY; WOMEN; COMPLICATIONS; VASODILATION; INVOLVEMENT; REACTIVITY; RELEVANCE AB Objective. To evaluate endothelial function and vascular stiffness in large, medium, small and microcirculatory blood vessels in very early diffuse systemic sclerosis (SSc). Methods. We studied consecutive early diffuse SSc patients, defined as <2 years from first SSc symptom who did not have a prior cardiovascular event. Age, gender and race-matched controls were recruited. All underwent assessment of aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT) brachial flow-mediated dilation (FMD), digital peripheral artery tonometer (EndoPAT) assessment and laser speckle contrast imaging (LSCI). Results. Fifteen early diffuse SSc and controls were evaluated. The average age was 49 years, 63% were female and 93% were Caucasian. There were no ferences in body mass index, hypertension, diabetes or hyperlipidaemia between controls and SSc patients. Mean SSc disease duration was 1.3 years. In the large central vessels, there was no difference in aortic PWV (p=0.71) or carotid IMT (p=0.92) between SSc patients and controls. Similarly, there was no difference in endothelial dysfunction with brachial artery FMD after ischaemia (p=0.55) and nitroglycerin administration (p=0.74). There were significantly lower values for digital EndoPAT measures (p=0.0001) in SSc patients. LSCI revealed a distinct pattern of microcirculatory abnormalities in response to ischaemia in SSc patients compared to controls. Imaging demonstrated a blunted microcirculatory hyperaemia of the hand with greater subsequent response to nitroglycerin. Conclusions. These findings suggest that the earliest endothelial changes occur in smaller arterioles and microvascular beds, but not in medium or macrovascular beds, in early diffuse SSc. C1 [Domsic, R. T.; Ivanco, D.; Kwoh, C. K.; Medsger, T. A., Jr.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Dept Med, Sch Med, Pittsburgh, PA 15261 USA. [Dezfulian, C.; Kenny, E.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15261 USA. [Dezfulian, C.; Shoushtari, A.] Univ Pittsburgh, Div Crit Care Med, Dept Crit Care Med, Pittsburgh, PA 15261 USA. [Champion, H. C.] Univ Pittsburgh, Vas Med Inst, Pittsburgh, PA 15261 USA. [Kwoh, C. K.] VA Pittsburgh Healthcare, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Champion, H. C.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Heart & Vasc Inst, Pittsburgh, PA 15261 USA. RP Domsic, RT (reprint author), Univ Pittsburgh, Div Rheumatol & Clin Immunol, Dept Med, S724 Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15261 USA. EM rtd4@pitt.edu FU National Institutes of Health (NIAMS grant) [P60-AR054731]; National Institutes of Health (NIAMS) [K23AR057485]; National Institutes of Health (NINDS grant) [K08 -NS069817] FX this work was supported by a grant from the National Institutes of Health (NIAMS grant P60-AR054731). R.T. Domsic is supported by a grant from the National Institutes of Health (NIAMS grant K23AR057485);; C. Dezfulian is supported by a grant from the National Institutes of Health (NINDS grant K08 -NS069817). NR 27 TC 6 Z9 6 U1 0 U2 3 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 2014 VL 32 IS 6 SU 86 BP S154 EP S160 PG 7 WC Rheumatology SC Rheumatology GA AT1WJ UT WOS:000344721500026 ER PT J AU Herrera, AF Jacobsen, ED AF Herrera, Alex F. Jacobsen, Eric D. TI Ibrutinib for the Treatment of Mantle Cell Lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID BRUTON TYROSINE KINASE; SINGLE-AGENT LENALIDOMIDE; PHASE-II; INHIBITOR IBRUTINIB; THERAPEUTIC TARGET; FOLLOW-UP; BORTEZOMIB; TRIAL; PCI-32765; MULTICENTER AB Ibrutinib (PCI-32765)-a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway-was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The drug was granted accelerated approval based on the findings of an international, multicenter, single-arm phase II study that enrolled patients with relapsed or refractory MCL. In the study, ibrutinib (560 mg daily) was well tolerated as a single agent and resulted in an overall response rate of 68% and an estimated median response duration of 17.5 months. Ibrutinib's response rate and duration of response compare favorably with those for other novel agents approved for the treatment of relapsed or refractory MCL, while being less toxic than most chemotherapy or chemoimmunotherapy regimens. Ibrutinib is currently being studied in combination with chemoimmunotherapy, monoclonal antibody therapy, and novel agents in both the initial and the relapsed/refractory treatment settings. We review the mechanism of action, preclinical and clinical development, and the role of ibrutinib in the context of other available treatments. (C) 2014 AACR. C1 [Herrera, Alex F.; Jacobsen, Eric D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Jacobsen, ED (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Eric_Jacobsen@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 34 TC 14 Z9 15 U1 1 U2 9 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 NOV 1 PY 2014 VL 20 IS 21 BP 5365 EP 5371 DI 10.1158/1078-0432.CCR-14-0010 PG 7 WC Oncology SC Oncology GA AT2IU UT WOS:000344759100005 PM 25361916 ER PT J AU Kharbanda, A Rajabi, H Jin, CN Tchaicha, J Kikuchi, E Wong, KK Kufe, D AF Kharbanda, Akriti Rajabi, Hasan Jin, Caining Tchaicha, Jeremy Kikuchi, Eiki Wong, Kwok-Kin Kufe, Donald TI Targeting the Oncogenic MUC1-C Protein Inhibits Mutant EGFR-Mediated Signaling and Survival in Non-Small Cell Lung Cancer Cells SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; ACQUIRED-RESISTANCE; BETA-CATENIN; ONCOPROTEIN FUNCTIONS; TRANSCRIPTION FACTOR; REGULATORY LOOP; ACTIVATION; GEFITINIB; MUTATION; BREAST AB Purpose: Non-small cell lung cancers (NSCLC) that express EGF receptor with activating mutations frequently develop resistance to EGFR kinase inhibitors. The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in NSCLC cells and confers a poor prognosis; however, the functional involvement of MUC1 in mutant EGFR signaling is not known. Experimental Design: Targeting the oncogenic MUC1 C-terminal subunit (MUC1-C) in NSCLC cells harboring mutant EGFR was studied for effects on signaling, growth, clonogenic survival, and tumorigenicity. Results: Stable silencing of MUC1-C in H1975/EGFR(L858R/T790M) cells resulted in downregulation of AKT signaling and inhibition of growth, colony formation, and tumorigenicity. Similar findings were obtained when MUC1-C was silenced in gefitinib-resistant PC9GR cells expressing EGFR(delE746_A750/T790M). The results further show that expression of a MUC1-C(CQC -> AQA) mutant, which blocks MUC1-C homodimerization, suppresses EGFR(T790M), AKT and MEK -> ERK activation, colony formation, and tumorigenicity. In concert with these results, treatment of H1975 and PC9GR cells with GO-203, a cell-penetrating peptide that blocks MUC1-C homodimerization, resulted in inhibition of EGFR, AKT, and MEK -> ERK signaling and in loss of survival. Combination studies of GO-203 and afatinib, an irreversible inhibitor of EGFR, further demonstrate that these agents are synergistic in inhibiting growth of NSCLC cells harboring the activating EGFR(T790M) or EGFR(delE746-A750) mutants. Conclusions: These findings indicate that targeting MUC1-C inhibits mutant EGFR signaling and survival, and thus represents a potential approach alone and in combination for the treatment of NSCLCs resistant to EGFR kinase inhibitors. (C) 2014 AACR. C1 [Kharbanda, Akriti; Rajabi, Hasan; Jin, Caining; Tchaicha, Jeremy; Kikuchi, Eiki; Wong, Kwok-Kin; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA. EM donald_kufe@dfci.harvard.edu FU National Cancer Institute of the NIH [CA166480, CA97098]; Lung Cancer Research Foundation FX This work was supported by the National Cancer Institute of the NIH under award numbers CA166480 (to K.-K. Wong and D. Kufe) and CA97098 (to D.W. Kufe), and by a grant from the Lung Cancer Research Foundation (to D. Kufe). NR 50 TC 18 Z9 19 U1 0 U2 4 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 NOV 1 PY 2014 VL 20 IS 21 BP 5423 EP 5434 DI 10.1158/1078-0432.CCR-13-3168 PG 12 WC Oncology SC Oncology GA AT2IU UT WOS:000344759100012 PM 25189483 ER PT J AU Weisberg, E Nonami, A Chen, Z Nelson, E Chen, YF Liu, FY Cho, HY Zhang, JM Sattler, M Mitsiades, C Wong, KK Liu, QS Gray, NS Griffin, JD AF Weisberg, Ellen Nonami, Atsushi Chen, Zhao Nelson, Erik Chen, Yongfei Liu, Feiyang Cho, HaeYeon Zhang, Jianming Sattler, Martin Mitsiades, Constantine Wong, Kwok-Kin Liu, Qingsong Gray, Nathanael S. Griffin, James D. TI Upregulation of IGF1R by Mutant RAS in Leukemia and Potentiation of RAS Signaling Inhibitors by Small-Molecule Inhibition of IGF1R SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; FACTOR-I RECEPTOR; ANCHORAGE-INDEPENDENT GROWTH; ACUTE MYELOGENOUS LEUKEMIA; INSULIN-RECEPTOR; ANTITUMOR-ACTIVITY; MEK INHIBITION; ONCOGENIC NRAS; HEMATOPOIETIC-CELLS; KINASE INHIBITOR AB Purpose: Activating mutations in the RAS oncogene occur frequently in human leukemias. Direct targeting of RAS has proven to be challenging, although targeting of downstream RAS mediators, such as MEK, is currently being tested clinically. Given the complexity of RAS signaling, it is likely that combinations of targeted agents will be more effective than single agents. Experimental Design: A chemical screen using RAS-dependent leukemia cells was developed to identify compounds with unanticipated activity in the presence of an MEK inhibitor and led to identification of inhibitors of IGF1R. Results were validated using cell-based proliferation, apoptosis, cell-cycle, and gene knockdown assays; immunoprecipitation and immunoblotting; and a noninvasive in vivo bioluminescence model of acute myeloid leukemia ( AML). Results: Mechanistically, IGF1R protein expression/activity was substantially increased in mutant RAS-expressing cells, and suppression of RAS led to decreases in IGF1R. Synergy between MEK and IGF1R inhibitors correlated with induction of apoptosis, inhibition of cell-cycle progression, and decreased phospho-S6 and phospho-4E-BP1. In vivo, NSG mice tail veins injected with OCI-AML3-luc+ cells showed significantly lower tumor burden following 1 week of daily oral administration of 50 mg/kg NVP-AEW541 ( IGF1R inhibitor) combined with 25 mg/kg AZD6244 ( MEK inhibitor), as compared with mice treated with either agent alone. Drug combination effects observed in cell-based assays were generalized to additional mutant RAS-positive neoplasms. Conclusions: The finding that downstream inhibitors of RAS signaling and IGF1R inhibitors have synergistic activity warrants further clinical investigation of IGF1R and RAS signaling inhibition as a potential treatment strategy for RAS-driven malignancies. (C) 2014 AACR. C1 [Weisberg, Ellen; Nonami, Atsushi; Chen, Zhao; Nelson, Erik; Sattler, Martin; Mitsiades, Constantine; Wong, Kwok-Kin; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Yongfei; Liu, Feiyang; Liu, Qingsong] Chinese Acad Sci, High Magnet Field Lab, Hefei, Anhui, Peoples R China. [Cho, HaeYeon; Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM ellen_weisberg@dfci.harvard.edu; james_griffin@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU NIH LINCS [HG006097] FX N.S. Gray is supported by NIH LINCS grant HG006097. NR 48 TC 4 Z9 4 U1 0 U2 5 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 NOV 1 PY 2014 VL 20 IS 21 BP 5483 EP 5495 DI 10.1158/1078-0432.CCR-14-0902 PG 13 WC Oncology SC Oncology GA AT2IU UT WOS:000344759100017 PM 25186968 ER PT J AU Gopal, DM Larson, MG Januzzi, JL Cheng, SS Ghorbani, A Wollert, KC Kempf, T D'Agostino, RB Polak, JF Ramachandran, VS Wang, TJ Ho, JE AF Gopal, Deepa M. Larson, Martin G. Januzzi, James L. Cheng, Susan Ghorbani, Anahita Wollert, Kai C. Kempf, Tibor D'Agostino, Ralph B. Polak, Joseph F. Ramachandran, Vasan S. Wang, Thomas J. Ho, Jennifer E. TI Biomarkers of Cardiovascular Stress and Subclinical Atherosclerosis in the Community SO CLINICAL CHEMISTRY LA English DT Article ID GROWTH-DIFFERENTIATION FACTOR-15; INTIMA-MEDIA THICKNESS; ACUTE CORONARY SYNDROME; CHRONIC KIDNEY-DISEASE; CAROTID-ARTERY INTIMA; MYOCARDIAL-INFARCTION; OLDER-ADULTS; RISK-FACTORS; INHIBITORY CYTOKINE-1; NATRIURETIC PEPTIDE AB BACKGROUND: Biomarkers of cardiovascular stress have been associated with incident cardiovascular outcomes. Their relations with measures of subclinical atherosclerosis, as assessed by carotid intima-media thickness, have not been well described. METHODS: We measured plasma growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin I (hsTnI) in 3111 Framingham Offspring participants who also underwent carotid ultrasonography during the sixth examination (1995-1998, mean age 58 years, 54% women). Carotid measurements included maximal internal carotid artery (ICA) intima-media thickness (IMT), plaque presence (defined as ICA IMT >1.5 mm), and mean common carotid artery IMT. We carried out multivariable regressions for carotid measurements vs biomarkers using linear and logistic models; P < 0.0056 was deemed statistically significant. RESULTS: Maximal ICA IMT was significantly associated with plasma GDF-15 [beta-estimate 0.04 per 1-U increase in log(GDF-15), SE 0.01, P < 0.0001]. Similarly, the odds of having carotid plaque increased 33% [odds ratio 1.33 per 1-U increase in log(GDF-15), 95% CI 1.20-1.48, P < 0.0001]. In contrast, there was no significant association of maximal ICA IMT or plaque presence with sST2 or hsTnI, and none of the 3 biomarkers was significantly associated with mean CCA IMT. GDF-15 was a stronger predictor of maximal ICA thickness and plaque presence compared with BNP and CRP when these conventional biomarkers were tested together. CONCLUSIONS: Increased GDF-15 concentrations are associated with subclinical atherosclerosis, including maximal ICA IMT and carotid plaque presence. Future studies investigating the role of GDF-15 for screening and management of patients with subclinical atherosclerosis are warranted. (C) 2014 American Association for Clinical Chemistry C1 [Gopal, Deepa M.; Cheng, Susan] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Div Cardiol, Boston, MA USA. [Larson, Martin G.; Cheng, Susan; D'Agostino, Ralph B.; Ramachandran, Vasan S.; Wang, Thomas J.; Ho, Jennifer E.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.; Cheng, Susan; D'Agostino, Ralph B.; Ramachandran, Vasan S.; Wang, Thomas J.; Ho, Jennifer E.] Boston Univ, Sch Med, Framingham, MA USA. [Larson, Martin G.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. [Ghorbani, Anahita] Mt Auburn Hosp, Dept Med, Boston, MA USA. [Wollert, Kai C.; Kempf, Tibor] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany. [Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA. [Ramachandran, Vasan S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Ho, Jennifer E.] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Wang, Thomas J.] Vanderbilt Univ, Div Med, Div Cardiovasc Med, Nashville, TN 37235 USA. RP Ho, JE (reprint author), Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, 88 East Newton St,C-818, Boston, MA 02118 USA. EM jennifer.ho@bmc.org OI Gopal, Deepa/0000-0003-3534-9360; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; NIH [R00-HL107642, K23-HL116780]; Ellison Foundation; Roche Diagnostics; German Ministry of Education and Research (BMBF, Bio-ChancePlus); National Heart, Lung, and Blood Institute; Boston University School of Medicine Department of Medicine Career Investment Award; Singulex; Critical Diagnostics FX Funded by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195); GDF assays were provided by Roche Diagnostics, Inc. J. Januzzi, Siemens, Thermo Fisher, Singulex, Roche, Critical Diagnostics, the De-Sanctis Clinical Scholar Endowment; S. Cheng, NIH grant R00-HL107642, the Ellison Foundation; K.C. Wollert, Roche Diagnostics, the German Ministry of Education and Research (BMBF, Bio-ChancePlus); R.B. D'Agostino, funded on the Framingham contract by National Heart, Lung, and Blood Institute; T.J. Wang, Singulex, Critical Diagnostics; J.E. Ho, NIH grant K23-HL116780, Boston University School of Medicine Department of Medicine Career Investment Award. NR 40 TC 8 Z9 9 U1 1 U2 7 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 NOV PY 2014 VL 60 IS 11 BP 1402 EP 1408 DI 10.1373/clinchem.2014.227116 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AT2QW UT WOS:000344780100012 PM 25237063 ER PT J AU Greenblatt, MB Torre, M Means, J Tanasijevic, M Pedulla, LV Bunnell, CA Conrad, MJ Jarolim, P AF Greenblatt, Matthew B. Torre, Matthew Means, Janet Tanasijevic, Milenko Pedulla, Lillian Vitale Bunnell, Craig A. Conrad, Michael J. Jarolim, Petr TI Use of Potassium Concentrations as a Quality-of-Service Metric for Phlebotomists Detects Systematic Preanalytical Biases and Facilitates Their Correction SO CLINICAL CHEMISTRY LA English DT Letter C1 [Greenblatt, Matthew B.; Torre, Matthew; Tanasijevic, Milenko; Conrad, Michael J.; Jarolim, Petr] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Torre, Matthew; Tanasijevic, Milenko; Jarolim, Petr] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Means, Janet; Pedulla, Lillian Vitale; Bunnell, Craig A.; Jarolim, Petr] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jarolim, P (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM pjarolim@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2014 VL 60 IS 11 BP 1453 EP 1455 DI 10.1373/clinchem.2014.227686 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AT2QW UT WOS:000344780100019 PM 25161146 ER PT J AU Lucas, GM Ross, MJ Stock, PG Shlipak, MG Wyatt, CM Gupta, SK Atta, MG Wools-Kaloustian, KK Pham, PA Bruggeman, LA Lennox, JL Ray, PE Kalayjian, RC AF Lucas, Gregory M. Ross, Michael J. Stock, Peter G. Shlipak, Michael G. Wyatt, Christina M. Gupta, Samir K. Atta, Mohamed G. Wools-Kaloustian, Kara K. Pham, Paul A. Bruggeman, Leslie A. Lennox, Jeffrey L. Ray, Patricio E. Kalayjian, Robert C. TI Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV-1; chronic kidney disease; clinical practice guideline; HIV-associated nephropathy; kidney transplantation ID GRADE; RECOMMENDATIONS; CONSENSUS; QUALITY AB It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. C1 [Lucas, Gregory M.; Atta, Mohamed G.; Pham, Paul A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Ross, Michael J.; Wyatt, Christina M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Stock, Peter G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gupta, Samir K.; Wools-Kaloustian, Kara K.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Bruggeman, Leslie A.; Kalayjian, Robert C.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. [Lennox, Jeffrey L.] Emory Univ, Sch Med, Atlanta, GA USA. [Ray, Patricio E.] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Lucas, GM (reprint author), Johns Hopkins Univ, Dept Med, 1830 E Monument St,4th Floor, Baltimore, MD 21287 USA. EM glucas@jhmi.edu FU Infectious Diseases Society of America; National Institutes of Health (NIH) [R01 DA026770, K24 DA035684, P30 AI094189, AI 036219, PO1 DK 056492, RO1 KD 078510, P30 AI050409, AI 69501]; Veterans Administration: VISN10 Geriatric Research Educational and Clinical Centers; Veterans Administration: Louis Stokes Cleveland Veterans Administration Medical Center FX Support for this guideline was provided by the Infectious Diseases Society of America. The following authors were supported by the National Institutes of Health (NIH): G. M. L. (grant numbers R01 DA026770, K24 DA035684, and P30 AI094189); L. A. B (AI 036219); M. J. R., C. M. W., and M. G. A. (PO1 DK 056492); M. A. R (RO1 KD 078510); J. L. L (P30 AI050409); R. C. K. (AI 69501, AI 036219). Support was also received from the Veterans Administration: VISN10 Geriatric Research Educational and Clinical Centers, Louis Stokes Cleveland Veterans Administration Medical Center. NR 8 TC 3 Z9 4 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2014 VL 59 IS 9 BP 1203 EP 1207 DI 10.1093/cid/ciu730 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TG UT WOS:000344647100003 ER PT J AU Manian, FA AF Manian, Farrin A. TI The Role of Postoperative Factors in Surgical Site Infections: Time to Take Notice SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE postoperative; surgery; wound infection ID RESISTANT STAPHYLOCOCCUS-AUREUS; TOTAL HIP-ARTHROPLASTY; RISK-FACTORS; ANTIMICROBIAL PROPHYLAXIS; NOSOCOMIAL INFECTION; WOUND INFECTIONS; CARDIAC-SURGERY; MRSA; COLONIZATION; PATHOGENS AB Surgical site infections (SSIs) continue to occur, in many instances despite high compliance with best practice measures primarily revolving around pre- and intraoperative periods. Postoperative factors have traditionally been considered to play a relatively minor role in the causation of SSIs. An increasing body of evidence, however, suggests that many SSIs occur as a result of pathogens gaining access to surgical wounds either hematogenously, through drains, or through slowly healing wounds due to systemic anticoagulation or other factors, particularly in the setting of high compliance with standard perioperative antibiotic prophylaxis. Evidence also supports frequent acquisition of methicillin-resistant Staphylococcus aureus (MRSA) during the postoperative period. These findings, coupled with lack of clear efficacy of various pre- and intraoperative interventions such as MRSA decolonization and use of vancomycin for prophylaxis against this organism, should force us to consider the important role that postoperative factors may play in the causation of SSIs in the current era. C1 [Manian, Farrin A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Manian, FA (reprint author), Massachusetts Gen Hosp, 50 Staniford,503-B, Boston, MA 02114 USA. EM fmanian@mgh.harvard.edu NR 40 TC 7 Z9 7 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2014 VL 59 IS 9 BP 1272 EP 1276 DI 10.1093/cid/ciu552 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TG UT WOS:000344647100013 PM 25028464 ER PT J AU Besson, GJ Lalama, CM Bosch, RJ Gandhi, RT Bedison, MA Aga, E Riddler, SA McMahon, DK Hong, FY Mellors, JW AF Besson, Guillaume J. Lalama, Christina M. Bosch, Ronald J. Gandhi, Rajesh T. Bedison, Margaret A. Aga, Evgenia Riddler, Sharon A. McMahon, Deborah K. Hong, Feiyu Mellors, John W. TI HIV-1 DNA Decay Dynamics in Blood During More Than a Decade of Suppressive Antiretroviral Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV-1 persistence; antiretroviral therapy; HIV-1 DNA decay; immune activation ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; RALTEGRAVIR INTENSIFICATION; IMMUNE ACTIVATION; HIV-1-INFECTED PATIENTS; VIRAL REPLICATION; PCR ASSAY; IN-VIVO; VIREMIA; HAART AB Background. Human immunodeficiency virus type 1 (HIV-1) DNA dynamics during long-term antiretroviral therapy (ART) are not defined. Methods. Bloodmononuclear cells obtained during 7-12 years of effective ART were assayed for total HIV-1 DNA and 2-long terminal repeat (LTR) circles by quantitative polymerase chain reaction (qPCR). Slopes of HIV-1 DNA were estimated by participant-specific linear regressions. Plasma was assayed for residual viremia (HIV-1 RNA) by qPCR. Results. Thirty participants were studied. HIV-1 DNA decreased significantly from years 0-1 and 1-4 of ART with median decay slopes of -0.86 (interquartile range, -1.05, -0.59) and -0.11 (-0.17, -0.06) log(10)(copies/10(6) CD4+ T-cells)/year, respectively (P < .001). Decay was not significant for years 4-7 (-0.02 [-0.06, 0.02]; P =.09) or after year 7 of ART (-0.006 [-0.030, 0.015]; P = .17). All participants had detectable HIV-1 DNA after 10 years (median 439 copies/10(6) CD4+ T-cells; range: 7-2074). Pre-ART HIV-1 DNA levels were positively associated with pre-ART HIV-1 RNA levels (Spearman = 0.71, P < .001) and with HIV-1 DNA at years 4, 7, and 10 on ART (Spearman >= 0.75, P <.001). No associations were found (P = .25) between HIV-1 DNA slopes or levels and % activated CD8+ T-cells (average during years 1-4) or residual viremia (n = 18). 2-LTR circles were detected pre-ART in 20/29 and in 8/30 participants at last follow-up. Conclusions. Decay of HIV-1 DNA in blood is rapid in the first year after ART initiation (86% decline), slows during years 1-4 (23% decline/year), and subsequently plateaus. HIV-1 DNA decay is not associated with the levels of CD8+ T-cell activation or persistent viremia. The determinants of stable HIV-1 DNA persistence require further elucidation. C1 [Besson, Guillaume J.; Bedison, Margaret A.; Riddler, Sharon A.; McMahon, Deborah K.; Hong, Feiyu; Mellors, John W.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Lalama, Christina M.; Bosch, Ronald J.; Aga, Evgenia] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Gandhi, Rajesh T.] Harvard Univ, Sch Med, Ragon Inst, Boston, MA USA. RP Mellors, JW (reprint author), Univ Pittsburgh, Sch Med, S818 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM jwm1@pitt.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [U01AI068636]; National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR); AIDS Clinical Trials Group [AI068636]; Statistical and Data Management Center [UM1 AI068634, AAI38855]; Clinical Trials Unit at the University of Pittsburgh [AI069494] FX This project was funded by an award (U01AI068636) to the AIDS Clinical Trials Group from the National Institute of Allergy and Infectious Diseases (NIAID) and supported by the National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the National Institutes of Health. This work was also supported by grants from the AIDS Clinical Trials Group to the Pittsburgh Virology Specialty Laboratory (AI068636), the Statistical and Data Management Center (UM1 AI068634; AAI38855), and the Clinical Trials Unit at the University of Pittsburgh (AI069494). NR 42 TC 35 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2014 VL 59 IS 9 BP 1312 EP 1321 DI 10.1093/cid/ciu585 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TG UT WOS:000344647100018 PM 25073894 ER PT J AU Lucas, GM Ross, MJ Stock, PG Shlipak, MG Wyatt, CM Gupta, SK Atta, MG Wools-Kaloustian, KK Pham, PA Bruggeman, LA Lennox, JL Ray, PE Kalayjian, RC AF Lucas, Gregory M. Ross, Michael J. Stock, Peter G. Shlipak, Michael G. Wyatt, Christina M. Gupta, Samir K. Atta, Mohamed G. Wools-Kaloustian, Kara K. Pham, Paul A. Bruggeman, Leslie A. Lennox, Jeffrey L. Ray, Patricio E. Kalayjian, Robert C. TI Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV-1; chronic kidney disease; clinical practice guideline; HIV-associated nephropathy; kidney transplantation ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; TENOFOVIR DISOPROXIL FUMARATE; HEPATITIS-C VIRUS; AMBULATORY PERITONEAL-DIALYSIS; SOLID-ORGAN TRANSPLANTATION; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; SERVICES TASK-FORCE AB It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. C1 [Lucas, Gregory M.; Atta, Mohamed G.; Pham, Paul A.] Johns Hopkins Sch Med, Baltimore, MD USA. [Ross, Michael J.; Wyatt, Christina M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Stock, Peter G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gupta, Samir K.; Wools-Kaloustian, Kara K.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Bruggeman, Leslie A.; Kalayjian, Robert C.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. [Lennox, Jeffrey L.] Emory Univ, Sch Med, Atlanta, GA USA. [Ray, Patricio E.] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Lucas, GM (reprint author), Johns Hopkins Univ, Dept Med, 1830 E Monument St,4th Floor, Baltimore, MD 21287 USA. EM glucas@jhmi.edu FU Infectious Diseases Society of America; National Institutes of Health (NIH) [R01 DA026770, K24 DA035684, P30 AI094189, AI 036219, PO1 DK 056492, RO1 KD 078510, P30 AI050409, AI 69501]; Veterans Administration: VISN10 Geriatric Research Educational and Clinical Centers; Veterans Administration: Louis Stokes Cleveland Veterans Administration Medical Center FX Support for this guideline was provided by the Infectious Diseases Society of America. The following authors were supported by the National Institutes of Health (NIH): G. M. L. (grant numbers R01 DA026770, K24 DA035684, and P30 AI094189); L. A. B (AI 036219); M. J. R., C. M. W., and M. G. A. (PO1 DK 056492); M. A. R (RO1 KD 078510); J. L. L (P30 AI050409); R. C. K. (AI 69501, AI 036219). Support was also received from the Veterans Administration: VISN10 Geriatric Research Educational and Clinical Centers, Louis Stokes Cleveland Veterans Administration Medical Center. NR 439 TC 47 Z9 49 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2014 VL 59 IS 9 BP E96 EP E138 DI 10.1093/cid/ciu617 PG 43 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TG UT WOS:000344647100001 PM 25234519 ER PT J AU Keusch, GT Denno, DM Black, RE Duggan, C Guerrant, RL Lavery, JV Nataro, JP Rosenberg, IH Ryan, ET Tarr, PI Ward, H Bhutta, ZA Coovadia, H Lima, A Ramakrishna, B Zaidi, AKM Burgess, DCH Brewer, T AF Keusch, Gerald T. Denno, Donna M. Black, Robert E. Duggan, Christopher Guerrant, Richard L. Lavery, James V. Nataro, James P. Rosenberg, Irwin H. Ryan, Edward T. Tarr, Phillip I. Ward, Honorine Bhutta, Zulfiqar A. Coovadia, Hoosen Lima, Aldo Ramakrishna, Balakrishnan Zaidi, Anita K. M. Burgess, Deborah C. Hay Brewer, Thomas TI Environmental Enteric Dysfunction: Pathogenesis, Diagnosis, and Clinical Consequences SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE biomarkers; developing countries; enteropathy; malabsorption; stunting ID INTESTINAL BARRIER FUNCTION; PEACE CORPS VOLUNTEERS; GAMBIAN CHILDREN; SUBCLINICAL MALABSORPTION; TROPICAL ENTEROPATHY; NUTRITIONAL-STATUS; DEVELOPING-WORLD; GIARDIA-LAMBLIA; EAST PAKISTAN; PERMEABILITY AB Stunting is common in young children in developing countries, and is associated with increased morbidity, developmental delays, and mortality. Its complex pathogenesis likely involves poor intrauterine and postnatal nutrition, exposure to microbes, and the metabolic consequences of repeated infections. Acquired enteropathy affecting both gut structure and function likely plays a significant role in this outcome, especially in the first few months of life, and serve as a precursor to later interactions of infection and malnutrition. However, the lack of validated clinical diagnostic criteria has limited the ability to study its role, identify causative factors, and determine cost-effective interventions. This review addresses these issues through a historical approach, and provides recommendations to define and validate a working clinical diagnosis and to guide critical research in this area to effectively proceed. Prevention of early gut functional changes and inflammation may preclude or mitigate the later adverse vicious cycle of malnutrition and infection. C1 [Keusch, Gerald T.] Boston Univ, Boston, MA 02118 USA. [Denno, Donna M.] Univ Washington, Seattle, WA 98195 USA. [Black, Robert E.] Johns Hopkins Univ, Baltimore, MD USA. [Duggan, Christopher] Boston Childrens Hosp, Boston, MA USA. [Guerrant, Richard L.; Nataro, James P.] Univ Virginia, Charlottesville, VA USA. [Lavery, James V.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Rosenberg, Irwin H.; Ward, Honorine] Tufts Univ, Boston, MA 02111 USA. [Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarr, Phillip I.] Washington Univ, St Louis, MO 63130 USA. [Bhutta, Zulfiqar A.; Zaidi, Anita K. M.] Aga Khan Univ, Karachi, Pakistan. [Coovadia, Hoosen] Univ Witwatersrand, Johannesburg, South Africa. [Lima, Aldo] Univ Fed Ceara, Fortaleza, Ceara, Brazil. [Ramakrishna, Balakrishnan] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Zaidi, Anita K. M.; Burgess, Deborah C. Hay; Brewer, Thomas] Bill & Melinda Gates Fdn, Seattle, WA USA. RP Keusch, GT (reprint author), Boston Univ, Med Campus,620 Albany St, Boston, MA 02118 USA. EM keusch@bu.edu FU Bill & Melinda Gates Foundation FX The Working Group was funded by the Bill & Melinda Gates Foundation. NR 40 TC 37 Z9 37 U1 3 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2014 VL 59 SU 4 BP S207 EP S212 DI 10.1093/cid/ciu485 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TJ UT WOS:000344647400002 PM 25305288 ER PT J AU Nguyen, HM Labreche, MJ Graber, CJ AF Nguyen, Hien M. Labreche, Matthew J. Graber, Christopher J. TI Making Sense of Cephalosporin and Amoxicillin/Clavulanate Susceptibility Testing for Uropathogens SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID UNCOMPLICATED CYSTITIS; ORAL CEPHALOSPORINS; ENTEROBACTERIACEAE; WOMEN C1 [Nguyen, Hien M.; Labreche, Matthew J.] Kaiser Permanente Northwest, Portland, OR USA. [Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. [Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Nguyen, HM (reprint author), Kaiser Permanente Northwest, 9900 SE Sunnyside Rd, Clackamas, OR 97015 USA. EM hien.m.nguyen@kp.org NR 8 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2014 VL 59 IS 9 DI 10.1093/cid/ciu574 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AT0TG UT WOS:000344647100026 ER PT J AU Magidson, JF Pierce, CM Weisberg, RB AF Magidson, Jessica F. Pierce, Chester M. Weisberg, Risa B. TI Implementing Cognitive Behavioral Therapy in Specialty Medical Settings SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE cognitive behavioral therapy; medical settings; behavioral medicine ID RANDOMIZED CONTROLLED-TRIAL; ACUTE STRESS DISORDER; DEPRESSION CBT-AD; MENTAL-HEALTH; UNITED-STATES; PSYCHOLOGICAL INTERVENTIONS; CANCER-PATIENTS; PRIMARY-CARE; METAANALYSIS; ADHERENCE AB This article is an introduction to the second issue of a two-part special series on integrating cognitive behavioral therapy (CBT) into medical settings. The first issue focused on integrating CBT into primary care, and this issue focuses on implementing CBT in other specialty medical settings, including cancer treatment, HI V care, and specialized pediatric medical clinics. Models for treatment delivery to improve ease of implementation are also discussed, including telehealth and home-delivered treatment. The six articles in this series provide examples of how to transport CBT techniques that are largely designed for implementation in outpatient mental health settings to specialized medical settings, and discuss unique considerations and recommendations for implementation. C1 [Magidson, Jessica F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Behav Med Serv,Dept Psychiat, Boston, MA 02114 USA. [Pierce, Chester M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Behav Med Serv,Div Global Psychiat, Boston, MA 02114 USA. [Weisberg, Risa B.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Weisberg, Risa B.] Brown Univ, Alpert Med Sch, Dept Family Med, Providence, RI 02912 USA. [Weisberg, Risa B.] VA Boston Healthcare Syst, Boston, MA USA. RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jmagidson@partners.org NR 28 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 EI 1878-187X J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2014 VL 21 IS 4 BP 367 EP 371 PG 5 WC Psychology, Clinical SC Psychology GA AS8PR UT WOS:000344510900001 ER PT J AU Magidson, JF Seitz-Brown, CJ Safren, SA Daughters, SB AF Magidson, Jessica F. Seitz-Brown, C. J. Safren, Steven A. Daughters, Stacey B. TI Implementing Behavioral Activation and Life-Steps for Depression and HIV Medication Adherence in a Community Health Center SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE depression; HIV medication adherence; behavioral activation; CBT; community health center ID RANDOMIZED CONTROLLED-TRIAL; ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; CBT-AD; HAART ADHERENCE; SUBSTANCE-ABUSE; MENTAL-HEALTH; DRUG-USERS; SYMPTOMS; SCALE AB Antiretroviral therapy to treat HIV/AIDS has substantially improved clinical outcomes among patients living with HIV/AIDS, but only in the presence of very consistent adherence. One of the most prevalent and impactful individual-level predictors of poor adherence is depressive symptoms, even at subthreshold levels. Evidence-based cognitive behavioral interventions exist to address improvements in depressive symptoms and adherence in this population, yet these techniques have largely been designed and tested as individual treatments for delivery in mental health settings. This presents a significant challenge when transporting these techniques to medical settings where other formats for delivery may be more appropriate (i.e., groups, less frequent visits), and few hands-on resources exist to guide this process. As such, primary aims of this study were to adapt and implement evidence-based cognitive behavioral techniques for depression (behavioral activation; BA) and HIV medication adherence (Life-Steps) that have potential for dissemination in an outpatient community health center. The intervention incorporated feedback from health center staff and utilized a modular, group format that did not rely on sequential session attendance. Feasibility was examined over 8 weeks (n = 13). Preliminary effects on depression, health-related quality of life, and medication adherence were examined, and exit interviews were conducted with a subset of participants (n = 4) to inform future modifications. Treatment descriptions and recommendations for effective clinical implementation based on patient and clinician feedback are provided along with case material of two individual patients and an example group session. Current efforts are an important next step for disseminating evidence-based techniques for depression and HIV medication adherence to community health center or AIDS service organization settings. C1 [Magidson, Jessica F.; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, College Pk, MD USA. [Magidson, Jessica F.; Seitz-Brown, C. J.] Univ Maryland, College Pk, MD 20742 USA. [Daughters, Stacey B.] Univ N Carolina, Chapel Hill, NC USA. RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jmagidson@partners.org FU NICHD NIH HHS [R25 HD045810]; NIDA NIH HHS [R01 DA022974, R36 DA034513]; NIMH NIH HHS [T32 MH093310, K24 MH094214] NR 46 TC 5 Z9 5 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 EI 1878-187X J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2014 VL 21 IS 4 BP 386 EP 403 PG 18 WC Psychology, Clinical SC Psychology GA AS8PR UT WOS:000344510900003 PM 25419102 ER PT J AU Peyrot, M Egede, LE Campos, C Cannon, AJ Funnell, MM Hsu, WC Ruggiero, L Siminerio, LM Stuckey, HL AF Peyrot, Mark Egede, Leonard E. Campos, Carlos Cannon, Anthony J. Funnell, Martha M. Hsu, William C. Ruggiero, Laurie Siminerio, Linda M. Stuckey, Heather L. TI Ethnic differences in psychological outcomes among people with diabetes: USA results from the second Diabetes Attitudes, Wishes, and Needs (DAWN2) study SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE DAWN2; Ethnic disparities; Psychological outcomes; Quality of life; Well-being ID QUALITY-OF-LIFE; DISEASE MANAGEMENT; AMERICAN PATIENTS; GLYCEMIC CONTROL; OLDER-ADULTS; HEALTH; DISPARITIES; SUPPORT; CARE; PERCEPTIONS AB Objective: To assess differences in psychological outcomes as well as risk and protective factors for these outcomes among several USA ethnic groups and identify correlates of these psychological outcomes among adults with diabetes in the second Diabetes Attitudes, Wishes and Needs (DAWN2*) study. Research design and methods: The core USA DAWN2 sample was supplemented by independent samples of specific ethnic minority groups, yielding a total of 447 White non-Hispanics, 241 African Americans, 194 Hispanics, and 173 Chinese Americans (n = 1055). Multivariate analysis examined ethnic differences in psychological outcomes and risk/protective factors (disease, demographic and socioeconomic factors, health status and healthcare access/utilization, subjective burden of diabetes and social support/burden). Separate analyses were performed on each group to determine whether risk/protective factors differed across ethnic groups. Main outcome measures: Psychological outcomes include well-being, quality of life, impact of diabetes on life domains, diabetes distress, and diabetes empowerment. Results: Ethnic minorities tended to have better psychological outcomes than White non-Hispanics, although their diabetes distress was higher. Levels of most risk and protective factors differed significantly across ethnic groups; adjustment for these factors reduced ethnic group differences in psychological outcomes. Health status and modifiable diabetes-specific risk/protective factors (healthcare access/utilization, subjective diabetes burden, social support/burden) had strong associations with psychological outcomes, especially diabetes distress and empowerment. Numerous interactions between ethnicity and other correlates of psychological outcomes suggest that ethnic groups are differentially sensitive to various risk/protective factors. Potential limitations are the sample sizes and representativeness. Conclusions: Ethnic groups differ in their psychological outcomes. The risk/protective factors for psychological outcomes differ across ethnic groups and different ethnic groups are more/less sensitive to their influence. These findings can aid the development of strategies to overcome the most prominent and influential psychosocial barriers to optimal diabetes care within each ethnic group. C1 [Peyrot, Mark] Loyola Univ Maryland, Baltimore, MD 21210 USA. [Egede, Leonard E.] Med Univ S Carolina, Charleston, SC 29425 USA. [Campos, Carlos] Inst Publ Hlth & Educ Res, New Braunfels, TX USA. [Cannon, Anthony J.] Sleep & Wellness Med Associates, Hamilton, NJ USA. [Funnell, Martha M.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Hsu, William C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Joslin Hlth Solut Int, Boston, MA 02115 USA. [Ruggiero, Laurie] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA. [Siminerio, Linda M.] Univ Pittsburgh, Inst Diabet, Pittsburgh, PA USA. [Stuckey, Heather L.] Penn State Univ, Coll Med, Hershey, PA USA. RP Peyrot, M (reprint author), Loyola Univ Maryland, 4501 N Charles St, Baltimore, MD 21210 USA. EM mark.peyrot@gmail.com FU Novo Nordisk A/S, Bagsvaerd, Denmark FX This study was funded by Novo Nordisk A/S, Bagsvaerd, Denmark. NR 44 TC 6 Z9 6 U1 1 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 EI 1473-4877 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD NOV PY 2014 VL 30 IS 11 BP 2241 EP 2254 DI 10.1185/03007995.2014.947023 PG 14 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA AT0DD UT WOS:000344606300011 PM 25079662 ER PT J AU Loewy, R Fulford, D Pearson, R Hua, J Schlosser, D Stuart, B Wolkowitz, O Epel, E Mathalon, D Vinogradov, S AF Loewy, Rachel Fulford, Daniel Pearson, Rahel Hua, Jessica Schlosser, Danielle Stuart, Barbara Wolkowitz, Owen Epel, Elissa Mathalon, Daniel Vinogradov, Sophia TI Mechanisms of psychosis risk: childhood trauma and cortisol dysregulation SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Loewy, Rachel; Fulford, Daniel; Pearson, Rahel; Hua, Jessica; Schlosser, Danielle; Stuart, Barbara; Wolkowitz, Owen; Epel, Elissa; Mathalon, Daniel; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mathalon, Daniel; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 9 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 NOV PY 2014 VL 8 SU 1 SI SI BP 57 EP 57 PG 1 WC Psychiatry SC Psychiatry GA AT2SM UT WOS:000344785700210 ER PT J AU Schlosser, D Vergani, S Kim, D Campellone, T Vinogradov, S AF Schlosser, Danielle Vergani, Silvia Kim, Daniel Campellone, Tim Vinogradov, Sophia TI PRIME: A neuroscience-informed mobile app intervention to treat reward processing impairments and improve quality of life in recent onset schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Schlosser, Danielle; Kim, Daniel; Campellone, Tim; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Vergani, Silvia] IDEO, Palo Alto, CA USA. [Campellone, Tim] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 5 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 NOV PY 2014 VL 8 SU 1 SI SI MA C94 BP 157 EP 157 PG 1 WC Psychiatry SC Psychiatry GA AT2SM UT WOS:000344785700583 ER PT J AU Adabag, S Rector, TS Anand, IS McMurray, JJ Zile, M Komajda, M McKelvie, RS Massie, B Carson, PE AF Adabag, Selcuk Rector, Thomas S. Anand, Inder S. McMurray, John J. Zile, Michael Komajda, Michel McKelvie, Robert S. Massie, Barry Carson, Peter E. TI A prediction model for sudden cardiac death in patients with heart failure and preserved ejection fraction SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Death; sudden; Heart failure; Risk factors; Prognosis ID ACUTE MYOCARDIAL-INFARCTION; BRAIN NATRIURETIC PEPTIDE; POPULATION; SURVIVAL; RISK; IRBESARTAN; METAANALYSIS; DYSFUNCTION; COMMUNITY; LESSONS AB AimsSudden cardiac death (SCD) accounts for approximate to 25% of all deaths in heart failure with preserved ejection fraction (HFpEF). However, strategies to identify HFpEF patients at a higher risk of SCD have not been developed. Methods and resultsWe studied 4128 patients with HFpEF enrolled in the Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. All SCDs were adjudicated by a clinical endpoint committee. Cumulative incidences of SCD were estimated counting other deaths as competing risks. Cox regression analysis was used to generate a risk model for SCD. During a mean follow-up of 4.1 years, 231 (5.6%) patients died suddenly and 650 (15.7%) died non-suddenly. A multivariable model in 3480 patients including age, gender, history of diabetes and myocardial infarction, LBBB on ECG, and the natural logarithm of NT-proBNP identified a subgroup of 837 (24%) patients with 10% cumulative incidence of SCD over 5 years, accounting for other deaths as competing risk (Harrell's C index 0.75). The 5-year cumulative incidences of SCD in the higher and lower risk groups were 11% and 4%, respectively. In the higher risk group, 32% of deaths were SCD compared with 26% in the entire I-PRESERVE cohort. ConclusionsA multivariable prediction model identified patients with HFpEF who have a 10% risk of SCD over 5 years, similar to the risk of SCD in the Sudden Cardiac Death in Heart Failure (SCD-Heft) trial. This model may be useful for selecting patients with HFpEF for SCD prevention trials. C1 [Adabag, Selcuk; Rector, Thomas S.; Anand, Inder S.] Vet Affairs Hlth Care Syst, Minneapolis, MN USA. [Adabag, Selcuk; Rector, Thomas S.; Anand, Inder S.] Univ Minnesota, Minneapolis, MN 55455 USA. [McMurray, John J.] British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Zile, Michael] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael] Med Univ S Carolina, Charleston, SC 29425 USA. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [McKelvie, Robert S.] Populat Hlth Res Inst, Hamilton, ON, Canada. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [Massie, Barry] San Francisco VA Med Ctr, San Francisco, CA USA. [Massie, Barry] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carson, Peter E.] Washington Vet Affairs Med Ctr, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. RP Anand, IS (reprint author), VA Med Ctr, One Vet Dr, Minneapolis, MN 55417 USA. EM anand001@umn.edu OI Adabag, Selcuk/0000-0003-2154-8596; mcmurray, john/0000-0002-6317-3975 FU Bristol-Myers Squibb; Veterans Health Administration Health Services Research & Development Center of Innovation Grant [HFP-98-001]; Center for Epidemiology and Clinical Research at the Minneapolis VA Medical Center FX Bristol-Myers Squibb sponsored the I-PRESERVE Trial. T. S. R. was supported by Veterans Health Administration Health Services Research & Development Center of Innovation Grant HFP-98-001 and the Center for Epidemiology and Clinical Research at the Minneapolis VA Medical Center. The views expressed herein do not necessarily represent the views of the Department of Veterans Affairs. NR 38 TC 11 Z9 11 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD NOV PY 2014 VL 16 IS 11 BP 1175 EP 1182 DI 10.1002/ejhf.172 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AT0JB UT WOS:000344621500005 PM 25302657 ER PT J AU Wu, MF Wang, SB Driscoll, SJ Cha, TD Wood, KB Li, GA AF Wu, Minfei Wang, Shaobai Driscoll, Sean J. Cha, Thomas D. Wood, Kirkham B. Li, Guoan TI Dynamic motion characteristics of the lower lumbar spine: implication to lumbar pathology and surgical treatment SO EUROPEAN SPINE JOURNAL LA English DT Article DE Lumbar spine; Dynamic lumbar flexion-extension; Weight-lifting activity; In vivo kinematics ID IMAGE MATCHING METHOD; LOW-BACK-PAIN; IN-VIVO; FLEXION-EXTENSION; DEGENERATIVE SPONDYLOLISTHESIS; BIOMECHANICAL EVALUATION; DISC DEGENERATION; ADJACENT LEVELS; AXIAL ROTATION; JOINT MOTION AB Many studies have reported on the segmental motion range of the lumbar spine using various in vitro and in vivo experimental designs. However, the in vivo weightbearing dynamic motion characteristics of the L4-5 and L5-S1 motion segments are still not clearly described in literature. This study investigated in vivo motion of the lumbar spine during a weight-lifting activity. Ten asymptomatic subjects (M/F: 5/5; age: 40-60 years) were recruited. The lumbar segment of each subject was MRI-scanned to construct 3D models of the L2-S1 vertebrae. The lumbar spine was then imaged using a dual fluoroscopic imaging system as the subject performed a weight-lifting activity from a lumbar flexion position (45A degrees) to maximal extension position. The 3D vertebral models and the fluoroscopic images were used to reproduce the in vivo vertebral positions along the motion path. The relative translations and rotations of each motion segment were analyzed. All vertebral motion segments, L2-3, L3-4, L4-5 and L5-S1, rotated similarly during the lifting motion. L4-5 showed the largest anterior-posterior (AP) translation with 2.9 +/- A 1.5 mm and was significantly larger than L5-S1 (p < 0.05). L5-S1 showed the largest proximal-distal (PD) translation with 2.8 +/- A 0.9 mm and was significantly larger than all other motion segments (p < 0.05). The lower lumbar motion segments L4-5 and L5-S1 showed larger AP and PD translations, respectively, than the higher vertebral motion segments during the weight-lifting motion. The data provide insight into the physiological motion characteristics of the lumbar spine and potential mechanical mechanisms of lumbar disease development. C1 [Wu, Minfei; Wang, Shaobai; Driscoll, Sean J.; Cha, Thomas D.; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02138 USA. [Wu, Minfei] Jilin Univ, Dept Orthopaed Surg, China Japan Union Hosp, Changchun 130023, Jilin, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02138 USA. EM gli1@mgh.harvard.edu FU NIAMS NIH HHS [R21AR057989] NR 58 TC 18 Z9 19 U1 5 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 EI 1432-0932 J9 EUR SPINE J JI Eur. Spine J. PD NOV PY 2014 VL 23 IS 11 BP 2350 EP 2358 DI 10.1007/s00586-014-3316-9 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AS6RC UT WOS:000344389100013 PM 24777671 ER PT J AU Rathkopf, DE Smith, MR de Bono, JS Logothetis, CJ Shore, ND de Souza, P Fizazi, K Mulders, PFA Mainwaring, P Hainsworth, JD Beer, TM North, S Fradet, Y Van Poppel, H Carles, J Flaig, TW Efstathiou, E Yu, EY Higano, CS Taplin, ME Griffin, TW Todd, MB Yu, MK Park, YC Kheoh, T Small, EJ Scher, HI Molina, A Ryan, CJ Saad, F AF Rathkopf, Dana E. Smith, Matthew R. de Bono, Johann S. Logothetis, Christopher J. Shore, Neal D. de Souza, Paul Fizazi, Karim Mulders, Peter F. A. Mainwaring, Paul Hainsworth, John D. Beer, Tomasz M. North, Scott Fradet, Yves Van Poppel, Hendrik Carles, Joan Flaig, Thomas W. Efstathiou, Eleni Yu, Evan Y. Higano, Celestia S. Taplin, Mary-Ellen Griffin, Thomas W. Todd, Mary B. Yu, Margaret K. Park, Youn C. Kheoh, Thian Small, Eric J. Scher, Howard I. Molina, Arturo Ryan, Charles J. Saad, Fred TI Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302) SO EUROPEAN UROLOGY LA English DT Article DE Abiraterone acetate; Chemotherapy-naive; Efficacy; Metastatic castration-resistant; prostate cancer; Safety ID MITOXANTRONE PLUS PREDNISONE; DOCETAXEL CHEMOTHERAPY; INCREASED SURVIVAL; TRIAL; THERAPY; PLACEBO; PHASE-3; LIFE; MEN AB Background: Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy. Objective: Report the prespecified third interim analysis (IA) of efficacy and safety outcomes in study COU-AA-302. Design, setting, and participants: Study COU-AA-302, a double-blind placebo-controlled study, enrolled patients with mCRPC from April 2009 to June 2010. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1). Intervention: Patients were randomised 1: 1 to abiraterone 1000 mg plus prednisone 5 mg twice daily by mouth versus prednisone. Outcome measurements and statistical analysis: Co-primary end points were radiographic progression-free survival (rPFS) and overall survival (OS). Median times to event outcomes were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox model, and treatment comparison used the log-rank test. The O'Brien-Fleming Lan-DeMets a-spending function was used for OS. Adverse events were summarised descriptively. Results and limitations: With a median follow-up duration of 27.1 mo, improvement in rPFS was statistically significant with abiraterone treatment versus prednisone (median: 16.5 vs 8.2 mo; HR: 0.52 [95% CI, 0.45-0.61]; p < 0.0001). Abiraterone improved OS (median: 35.3 vs 30.1 mo; HR: 0.79 [95% CI, 0.66-0.95]; p = 0.0151) but did not reach the prespecified statistical efficacy boundary (alpha-level: 0.0035). A post hoc multivariate analysis for OS using known prognostic factors supported the primary results (HR: 0.74 [95% CI, 0.61-0.89]; p = 0.0017), and all clinically relevant secondary end points and patient-reported outcomes improved. While the post hoc nature of the long-term safety analysis is a limitation, the safety profile with longer treatment exposure was consistent with prior reports. Conclusions: The updated IA of study COU-AA-302 in patients with mCRPC without prior chemotherapy confirms that abiraterone delays disease progression, pain, and functional deterioration and has clinical benefit with a favourable safety profile, including in patients treated for >= 24 mo. Trial registration: Study COU-AA-302, ClinicalTrials.gov number, NCT00887198. Patient summary: The updated results of this ongoing study showed that disease progression was delayed in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone, and there was a continued trend in prolongation of life compared with patients treated with prednisone alone. Treatment with abiraterone acetate and prednisone was well tolerated by patients who were treated for > 2 yr. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Rathkopf, Dana E.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Rathkopf, Dana E.; Scher, Howard I.] Weill Cornell Med Coll, New York, NY USA. [Smith, Matthew R.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [de Bono, Johann S.] Inst Canc Res, Sutton, Surrey, England. [de Bono, Johann S.] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Logothetis, Christopher J.; Efstathiou, Eleni] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Shore, Neal D.] Carolina Urol Res Ctr, Atlantic Urol Clin, Myrtle Beach, SC USA. [de Souza, Paul] Univ Western Sydney, Sch Med, Penrith, NSW 1797, Australia. [Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Villejuif, France. [Mulders, Peter F. A.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Mainwaring, Paul] Hematol & Oncol Clin Australia, Brisbane, Qld, Australia. [Hainsworth, John D.] Sarah Cannon Res Inst, Nashville, TN USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [North, Scott] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Fradet, Yves] Univ Laval, Quebec City, PQ, Canada. [Van Poppel, Hendrik] Univ Hosp Leuven, Leuven, Belgium. [Carles, Joan] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, E-08193 Barcelona, Spain. [Flaig, Thomas W.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Flaig, Thomas W.] Univ Colorado, Sch Med, Aurora, CO USA. [Yu, Evan Y.; Higano, Celestia S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Taplin, Mary-Ellen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Griffin, Thomas W.; Yu, Margaret K.; Kheoh, Thian] Janssen Res & Dev, Los Angeles, CA USA. [Todd, Mary B.; Park, Youn C.] Janssen Res & Dev, Raritan, NJ USA. [Small, Eric J.; Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Molina, Arturo] Janssen Res & Dev, Menlo Pk, CA USA. [Saad, Fred] Univ Montreal, CRCHUM, Montreal, PQ, Canada. RP Rathkopf, DE (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM rathkopd@mskcc.org RI Mulders, Peter/H-8076-2014; OI Rathkopf, Dana/0000-0002-4503-7582 FU Janssen Global Services, LLC; Janssen Research & Development, Raritan, NJ, USA FX All aspects of the study, including design and conduct, data collection, management, and analysis, were sponsored by Janssen Research & Development (formerly Ortho Biotech Oncology Research and Development, unit of Cougar Biotechnology), Raritan, NJ, USA, and conducted on behalf of the Study 302 Investigators. Writing assistance was funded by Janssen Global Services, LLC. NR 30 TC 78 Z9 81 U1 1 U2 9 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 NOV PY 2014 VL 66 IS 5 BP 815 EP 825 DI 10.1016/j.eururo.2014.02.056 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AT1KY UT WOS:000344693500014 PM 24647231 ER PT J AU Voskoboynik, M Staffurth, J Malik, Z Sweeney, C Chowdhury, S AF Voskoboynik, Mark Staffurth, John Malik, Zafar Sweeney, Christopher Chowdhury, Simon TI 'Charting a new course for prostate cancer' - currying favor for docetaxel in hormone-sensitive metastatic prostate cancer SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Editorial Material DE CHAARTED; docetaxel; hormone sensitive; metastatic prostate cancer; Sweeney ID MITOXANTRONE PLUS PREDNISONE; INCREASED SURVIVAL; OPEN-LABEL; CHEMOTHERAPY; ABIRATERONE; ENZALUTAMIDE; PHASE-3; TRIAL C1 [Voskoboynik, Mark; Chowdhury, Simon] Guys Hosp, Dept Med Oncol, London SE1 9RT, England. [Voskoboynik, Mark; Chowdhury, Simon] Sarah Cannon Res Inst UK, London, England. [Staffurth, John] Cardiff Univ, Inst Canc & Genet, Velindre Canc Ctr, Cardiff, S Glam, Wales. [Malik, Zafar] Clatterbridge Canc Ctr, Bebington, Wirral, England. [Sweeney, Christopher] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sweeney, Christopher] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Chowdhury, S (reprint author), Guys Hosp, Dept Med Oncol, London SE1 9RT, England. EM Simon.Chowdhury@gstt.nhs.uk NR 14 TC 5 Z9 5 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD NOV PY 2014 VL 14 IS 11 BP 1253 EP 1256 DI 10.1586/14737140.2014.971112 PG 4 WC Oncology SC Oncology GA AT2NA UT WOS:000344770200002 PM 25353342 ER PT J AU Robert, MC Arafat, SN Ciolino, JB AF Robert, Marie-Claude Arafat, Samer N. Ciolino, Joseph B. TI Collagen Cross-Linking of the Boston Keratoprosthesis Donor Carrier to Prevent Corneal Melting in High-Risk Patients SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Review DE Corneal collagen cross-linking; Keratoprosthesis; Keratolysis; Aniridia ID STEVENS-JOHNSON-SYNDROME; INFECTIOUS KERATITIS; I KERATOPROSTHESIS; TYPE-1 KERATOPROSTHESIS; PROGRESSIVE KERATOCONUS; ULTRAVIOLET; RIBOFLAVIN; MEMBRANE; EFFICACY; MULTICENTER AB Objective:To examine the clinical relevance and pathophysiology of Boston keratoprosthesis (B-KPro)-related corneal keratolysis (cornea melt) and to describe a novel method of preventing corneal melt using ex vivo crosslinked cornea tissue carrier.Methods:A review of B-KPro literature was performed to highlight cases of corneal melt. Studies examining the effect of corneal collagen cross-linking (CXL) on the biomechanical properties of corneal tissue are summarized. The use of crosslinked corneal tissue as a carrier to the B-KPro is illustrated with a case.Results:Corneal melting after B-KPro is a relatively rare event, occurring in 3% of eyes during the first 3 years of postoperative follow-up. The risk of post-KPro corneal melting is heightened in eyes with chronic ocular surface inflammation such as eyes with Stevens-Johnson syndrome and mucous membrane pemphigoid. This chronic inflammation results in high tear levels of matrix metalloproteinases, the enzymes responsible for collagenolysis and corneal melt. Crosslinked corneal tissue has been shown to have stiffer biomechanical properties and to be more resistant to degradation by collagenolytic enzymes. We have previously optimized the technique for ex vivo corneal CXL and are currently studying its impact on the prevention of corneal melting after B-KPro surgery in high-risk eyes. Crosslinked carrier tissue was used in a 52-year-old man with familial aniridia and severe post-KPro corneal melt. The patient maintained his visual acuity and showed no evidence of corneal thinning or melt in the first postoperative year.Conclusion:Collagen crosslinking was previously shown to halt the enzymatic degradation of corneal buttons ex vivo. This study demonstrates the safety and potential benefit of using crosslinked corneal grafts as carriers for the B-KPro, especially in eyes at higher risk of postoperative melt. C1 [Robert, Marie-Claude; Arafat, Samer N.; Ciolino, Joseph B.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Ciolino, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM joseph_ciolino@meei.harvard.edu FU NEI [1K08EY019686-01]; Massachusetts Lions Eye Research Fund; New England Cornea Transplant Fund; KPro Fund; Career Development Award from Research to Prevent Blindness, Inc. FX Supported by NEI 1K08EY019686-01 (J.B.C.), Massachusetts Lions Eye Research Fund (J.B.C.), New England Cornea Transplant Fund (J.B.C.), KPro Fund (J.B.C.), and by a Career Development Award from Research to Prevent Blindness, Inc. (J.B.C.). NR 51 TC 3 Z9 3 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1542-2321 EI 1542-233X J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2014 VL 40 IS 6 SI SI BP 376 EP 381 DI 10.1097/ICL.0000000000000081 PG 6 WC Ophthalmology SC Ophthalmology GA AT4TW UT WOS:000344936400010 PM 25320957 ER PT J AU Kim, E Kinney, WH Ovrutsky, AR Vo, D Bai, XY Honda, JR Marx, G Peck, E Lindberg, L Falkinham, JO May, RM Chan, ED AF Kim, Eun Kinney, William H. Ovrutsky, Alida R. Vo, Danthy Bai, Xiyuan Honda, Jennifer R. Marx, Grace Peck, Emily Lindberg, Leslie Falkinham, Joseph O., III May, Rhea M. Chan, Edward D. TI A surface with a biomimetic micropattern reduces colonization of Mycobacterium abscessus SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE nontuberculous mycobacteria; biofilm; bioengineered surfaces; bacterial colonization ID ENGINEERED ANTIFOULING MICROTOPOGRAPHIES; BIOFILM FORMATION; AVIUM-COMPLEX; NONTUBERCULOUS MYCOBACTERIA; PULMONARY-DISEASE; CELL ATTACHMENT; LUNG-DISEASE; INFECTION; SUSCEPTIBILITY; CONTAMINATION AB Nontuberculous mycobacteria (NTM) are ubiquitous organisms found in soil, water, and biofilms. Engineered surface topography has been proposed as a method to reduce microbial biofilm formation. The Sharklet((R)) micropattern silicone surface has been shown to reduce biofilm formation of pyogenic bacteria. We hypothesized that this micropattern surface will also reduce colonization by Mycobacterium abscessus, a human pathogen. Smooth and micropattern silicone samples were incubated with 1x10(6)M.abscessusmL(-1) for 2 and 4days. After processing to optimize recovery of adhered mycobacteria, there was a 75% and 50% reduction in the number of viable M.abscessus recovered from the micropattern surfaces compared to the smooth surfaces at 2 and 4days after inoculation, respectively. Ziehl-Neelsen staining after measures to remove the adherent microorganisms revealed fewer residual M.abscessus on the micropattern samples as compared to smooth samples, validating the quantitative culture results. Microscopic observation of 2, 4, and 8day M.abscessus cultures on micropattern samples showed that the organisms preferentially colonized within the channels between the rectangular features. In summary, a micropattern surface reduces the colonization of a pathogenic NTM. It remains to be seen whether this micropattern can reduce infections in humans. C1 [Kim, Eun; Kinney, William H.; Ovrutsky, Alida R.; Vo, Danthy; Bai, Xiyuan; Honda, Jennifer R.; Peck, Emily; Chan, Edward D.] Natl Jewish Hlth, Dept Med & Acad Affairs, Denver, CO 80206 USA. [Bai, Xiyuan; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Marx, Grace] Univ Colorado Denver, Div Infect Dis, Aurora, CO USA. [Lindberg, Leslie; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Falkinham, Joseph O., III] Virginia Tech, Dept Biol Sci, Blacksburg, VA USA. [May, Rhea M.] Sharklet Technol, Aurora, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org NR 35 TC 4 Z9 4 U1 4 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV PY 2014 VL 360 IS 1 BP 17 EP 22 DI 10.1111/1574-6968.12587 PG 6 WC Microbiology SC Microbiology GA AT4OJ UT WOS:000344919000004 PM 25155501 ER EF