FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hashimoto, DA Gomez, ED Beyer-Berjot, L Khajuria, A Williams, NN Darzi, A Aggarwal, R AF Hashimoto, Daniel A. Gomez, Ernest D. Beyer-Berjot, Laura Khajuria, Ankur Williams, Noel N. Darzi, Ara Aggarwal, Rajesh TI A Randomized Controlled Trial to Assess the Effects of Competition on the Development of Laparescopic Surgical Skills SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE surgical education; virtual reality simulation; student education; competitive training; minimally invasive ID TECHNICAL SKILLS; OPERATING-ROOM; PERFORMANCE; SIMULATION; RESIDENTS; AUDIENCE; SURGERY AB BACKGROUND: Serious games have demonstrated efficacy in improving participation in surgical training activities, but studies have not yet demonstrated the effect of serious gaming on performance. This study investigated whether competitive training (CT) affects laparoscopic surgical performance. METHODS: A total of 20 novices were recruited, and 18 (2 dropouts) were randomized into control or CT groups to perform 10 virtual reality laparoscopic cholecystectomies (LCs). Competitiveness of each participant was assessed. The CT group members were informed they were competing to outperform one another for a prize; performance ranking was shown before each session. The control group did not compete. Performance was assessed on time, movements, and instrument path length. Quality of performance was assessed with a global rating scale score. RESULTS: There were no significant intergroup differences in baseline skill or measured competitiveness. Time and global rating scale score, at final LC, were not significantly different between groups; however, the CT group was significantly more dexterous than control and had significantly lower variance in number of movements and instrument path length at the final LC (p = 0.019). Contentiousness was inversely related to time in the CT group. CONCLUSION: This was the first randomized controlled trial to investigate if CT can enhance performance in laparoscopic surgery. CT may lead to improved dexterity in laparoscopic surgery but yields otherwise similar performance to that of standard training in novices. Competition may have different effects on novices vs experienced surgeons, and subsequent research should investigate CT in experienced surgeons as well. ((C) 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.) C1 [Hashimoto, Daniel A.; Gomez, Ernest D.; Williams, Noel N.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hashimoto, Daniel A.; Khajuria, Ankur; Darzi, Ara] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Biosurg & Surg Technol, London, England. [Beyer-Berjot, Laura] Univ Aix Marseille 2, Ctr Surg Teaching & Res CERC, Marseille, France. [Aggarwal, Rajesh] McGill Univ, Dept Surg, Fac Med, Montreal, PQ H3A 2T5, Canada. [Aggarwal, Rajesh] McGill Univ, Fac Med, Amold & Blema Steinberg Med Simulat Ctr, Montreal, PQ, Canada. RP Hashimoto, DA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM dahashimoto@partners.org FU National Center for Research Resources; National Center for Advancing Translational Sciences; National Institutes of Health [TL1TR000138] FX Rajesh Aggarwal is a consultant for Applied Medical. Daniel Hashimoto and Ernest Gomez were partly supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant TL1TR000138. NR 23 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD NOV-DEC PY 2015 VL 72 IS 6 BP 1077 EP 1084 DI 10.1016/j.jsurg.2015.06.005 PG 8 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA CY2LM UT WOS:000366240200003 PM 26169566 ER PT J AU Schmidt, TL Beliveau, BJ Uca, YO Theilmann, M Da Cruz, F Wu, CT Shih, WM AF Schmidt, Thorsten L. Beliveau, Brian J. Uca, Yavuz O. Theilmann, Mark Da Cruz, Felipe Wu, Chao-Ting Shih, William M. TI Scalable amplification of strand subsets from chip-synthesized oligonucleotide libraries SO NATURE COMMUNICATIONS LA English DT Article ID OLIGOPAINT FISH PROBES; IN-SITU SYNTHESIS; GENE SYNTHESIS; NANOSCALE SHAPES; FOLDING DNA; GENOME; VISUALIZATION; CHROMOSOMES; MICROCHIPS; PRECISE AB Synthetic oligonucleotides are the main cost factor for studies in DNA nanotechnology, genetics and synthetic biology, which all require thousands of these at high quality. Inexpensive chip-synthesized oligonucleotide libraries can contain hundreds of thousands of distinct sequences, however only at sub-femtomole quantities per strand. Here we present a selective oligonucleotide amplification method, based on three rounds of rolling-circle amplification, that produces nanomole amounts of single-stranded oligonucleotides per millilitre reaction. In a multistep one-pot procedure, subsets of hundreds or thousands of single-stranded DNAs with different lengths can selectively be amplified and purified together. These oligonucleotides are used to fold several DNA nanostructures and as primary fluorescence in situ hybridization probes. The amplification cost is lower than other reported methods (typically around US$ 20 per nanomole total oligonucleotides produced) and is dominated by the use of commercial enzymes. C1 [Schmidt, Thorsten L.; Theilmann, Mark; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Schmidt, Thorsten L.; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Schmidt, Thorsten L.; Da Cruz, Felipe; Shih, William M.] Wyss Inst Biol Inspired Engn Harvard, Boston, MA 02115 USA. [Schmidt, Thorsten L.; Uca, Yavuz O.] Tech Univ Dresden, Cfaed, D-01062 Dresden, Germany. [Beliveau, Brian J.; Wu, Chao-Ting] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Shih, WM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM william_shih@dfci.harvard.edu RI Schmidt, Thorsten/C-9874-2009 OI Schmidt, Thorsten/0000-0002-6798-5241 FU Feodor Lynen fellowship of the Alexander-von-Humboldt foundation; NIH [1DP2OD004641]; ARO MURI [W911NF-12-1-0420]; NSF [CCF-1317291]; Center for Advancing Electronics Dresden (cfaed); Wyss Institute at Harvard; NIH/NIGMS [RO1GM61936, 5DP1GM106412]; Harvard Medical School (HMS) FX This work was supported by a Feodor Lynen fellowship of the Alexander-von-Humboldt foundation to T.L.S. by NIH grant 1DP2OD004641, ARO MURI grant W911NF-12-1-0420 and NSF grant CCF-1317291 to W.M.S., by the Center for Advancing Electronics Dresden (cfaed) and by the Wyss Institute at Harvard. B.J.B. and C.-T.W. were supported by awards from NIH/NIGMS (RO1GM61936 and 5DP1GM106412) and Harvard Medical School (HMS) to C.-T.W. We thank Y. Ke, X. Lin and R. Jungmann for sequences of the DNA nanostructures; S. Kosuri and F. Vigneault for fruitful discussions, and S. Perrault, Y. Ke and R. Jungmann for help with TEM and AFM image acquisition. NR 29 TC 1 Z9 1 U1 9 U2 16 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 2015 VL 6 AR 8634 DI 10.1038/ncomms9634 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CY3HB UT WOS:000366298700001 PM 26567534 ER PT J AU Signore, S Sorrentino, A Borghetti, G Cannata, A Meo, M Zhou, Y Kannappan, R Pasqualini, F O'Malley, H Sundman, M Tsigkas, N Zhang, E Arranto, C Mangiaracina, C Isobe, K Sena, BF Kim, J Goichberg, P Nahrendorf, M Isom, LL Leri, A Anversa, P Rota, M AF Signore, Sergio Sorrentino, Andrea Borghetti, Giulia Cannata, Antonio Meo, Marianna Zhou, Yu Kannappan, Ramaswamy Pasqualini, Francesco O'Malley, Heather Sundman, Mark Tsigkas, Nikolaos Zhang, Eric Arranto, Christian Mangiaracina, Chiara Isobe, Kazuya Sena, Brena F. Kim, Junghyun Goichberg, Polina Nahrendorf, Matthias Isom, Lori L. Leri, Annarosa Anversa, Piero Rota, Marcello TI Late Na+ current and protracted electrical recovery are critical determinants of the aging myopathy SO NATURE COMMUNICATIONS LA English DT Article ID LATE SODIUM CURRENT; RAT VENTRICULAR MYOCYTES; CHRONIC HEART-FAILURE; ACTION-POTENTIAL PROLONGATION; AGE-ASSOCIATED CHANGES; CARDIAC STEM-CELL; LONG QT SYNDROME; DIASTOLIC DYSFUNCTION; EJECTION FRACTION; HYPERTROPHIC CARDIOMYOPATHY AB The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na+ current (I-NaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca2+ cycling and contractility. These alterations increase force development and passive tension. Inhibition of I-NaL shortens the AP and corrects dynamics of Ca2+ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, I-NaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly. C1 [Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia; Cannata, Antonio; Meo, Marianna; Zhou, Yu; Kannappan, Ramaswamy; Pasqualini, Francesco; Sundman, Mark; Tsigkas, Nikolaos; Zhang, Eric; Arranto, Christian; Mangiaracina, Chiara; Isobe, Kazuya; Kim, Junghyun; Goichberg, Polina; Leri, Annarosa; Anversa, Piero; Rota, Marcello] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia; Cannata, Antonio; Meo, Marianna; Zhou, Yu; Kannappan, Ramaswamy; Pasqualini, Francesco; Sundman, Mark; Tsigkas, Nikolaos; Zhang, Eric; Arranto, Christian; Mangiaracina, Chiara; Isobe, Kazuya; Kim, Junghyun; Goichberg, Polina; Leri, Annarosa; Anversa, Piero; Rota, Marcello] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Signore, Sergio; Sorrentino, Andrea; Borghetti, Giulia; Cannata, Antonio; Meo, Marianna; Zhou, Yu; Kannappan, Ramaswamy; Pasqualini, Francesco; Sundman, Mark; Tsigkas, Nikolaos; Zhang, Eric; Arranto, Christian; Mangiaracina, Chiara; Isobe, Kazuya; Kim, Junghyun; Goichberg, Polina; Leri, Annarosa; Anversa, Piero; Rota, Marcello] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [O'Malley, Heather; Isom, Lori L.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Sena, Brena F.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Rota, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesia, 20 Shattuck St, Boston, MA 02115 USA. EM mrota1@partners.org OI Pasqualini, Francesco/0000-0001-7038-3121; Cannata, Antonio/0000-0001-7609-6297 FU National Institute of Health [R01 HL114346, P01 AG043353, P01 HL092868, R01 AG037495, R01 HL111183, R01 AG037490, R01 HL105532, R01 AG044455, R37 HL081737, R01 NS076752] FX We thank Dr Hugues Abriel and members of his laboratory at the University of Bern for providing the rabbit polyclonal Nav1.5 antibody, Ms Cuiqi Li and Dr Nicola Alesi at the Brigham and Women's Hospital for histological and technical assistance, respectively. This work was supported by the National Institute of Health grants R01 HL114346, P01 AG043353, P01 HL092868, R01 AG037495, R01 HL111183, R01 AG037490, R01 HL105532, R01 AG044455, R37 HL081737 and R01 NS076752. NR 70 TC 7 Z9 7 U1 2 U2 2 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 2015 VL 6 AR 8803 DI 10.1038/ncomms9803 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CY3FY UT WOS:000366295400001 PM 26541940 ER PT J AU Wickstrom, M Dyberg, C Milosevic, J Einvik, C Calero, R Sveinbjornsson, B Sanden, E Darabi, A Siesjo, P Kool, M Kogner, P Baryawno, N Johnsen, JI AF Wickstrom, Malin Dyberg, Cecilia Milosevic, Jelena Einvik, Christer Calero, Raul Sveinbjornsson, Baldur Sanden, Emma Darabi, Anna Siesjo, Peter Kool, Marcel Kogner, Per Baryawno, Ninib Johnsen, John Inge TI Wnt/beta-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance SO NATURE COMMUNICATIONS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; TUMOR-GROWTH; THERAPEUTIC TARGETS; MALIGNANT GLIOMA; TEMOZOLOMIDE; CELLS; METHYLTRANSFERASE; GLIOBLASTOMA; MECHANISMS; RESISTANCE AB The DNA repair enzyme O6-methylguanine- DNA methyltransferase (MGMT) is commonly overexpressed in cancers and is implicated in the development of chemoresistance. The use of drugs inhibiting MGMT has been hindered by their haematologic toxicity and inefficiency. As a different strategy to inhibit MGMT we investigated cellular regulators of MGMT expression in multiple cancers. Here we show a significant correlation between Wnt signalling and MGMT expression in cancers with different origin and confirm the findings by bioinformatic analysis and immunofluorescence. We demonstrate Wnt-dependent MGMT gene expression and cellular co-localization between active beta-catenin and MGMT. Pharmacological or genetic inhibition of Wnt activity downregulates MGMT expression and restores chemosensitivity of DNA-alkylating drugs in mouse models. These findings have potential therapeutic implications for chemoresistant cancers, especially of brain tumours where the use of temozolomide is frequently used in treatment. C1 [Wickstrom, Malin; Dyberg, Cecilia; Milosevic, Jelena; Calero, Raul; Sveinbjornsson, Baldur; Kogner, Per; Johnsen, John Inge] Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, S-17176 Stockholm, Sweden. [Einvik, Christer] Univ Hosp North Norway, Dept Pediat, N-9038 Tromso, Norway. [Sveinbjornsson, Baldur] Univ Tromso, Dept Med Biol, N-9037 Tromso, Norway. [Sanden, Emma; Darabi, Anna; Siesjo, Peter] Lund Univ, Div Neurosurg, Glioma Immunotherapy Grp, Dept Clin Sci Lund, S-22185 Lund, Sweden. [Kool, Marcel] German Canc Res Ctr, DKFZ, Div Pediat Neurooncol, D-69120 Heidelberg, Germany. [Baryawno, Ninib] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Baryawno, Ninib] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Baryawno, Ninib] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Baryawno, Ninib] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Baryawno, N (reprint author), Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, S-17176 Stockholm, Sweden. EM baryawno.ninib@mgh.harvard.edu; John.Inge.Johnsen@ki.se RI Calero, Raul/F-7867-2016 OI Calero, Raul/0000-0003-1525-1921 FU Swedish Children's Cancer Foundation; Swedish Research Council; Swedish Cancer Society; Swedish Foundation for Strategic Research; Marta and Gunnar V. Philipson Foundation; Mary Beve Foundation; Damman Foundation; Erna and Olav Aakres Foundation for Cancer Research FX Confocal microscopy was performed at the University of Tromso, Norway Advanced Microscopy Core Facility. This work was supported by grants from The Swedish Children's Cancer Foundation, The Swedish Research Council, The Swedish Cancer Society, The Swedish Foundation for Strategic Research (www.nnbcr.com), Marta and Gunnar V. Philipson Foundation, The Mary Beve Foundation, Damman Foundation, and Erna and Olav Aakres Foundation for Cancer Research. NR 36 TC 3 Z9 3 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD NOV PY 2015 VL 6 AR 8904 DI 10.1038/ncomms9904 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CY4LF UT WOS:000366378900006 PM 26603103 ER PT J AU Tsu, AP Burish, MJ GodLove, J Ganguly, K AF Tsu, Adelyn P. Burish, Mark J. GodLove, Jason Ganguly, Karunesh TI Cortical neuroprosthetics from a clinical perspective SO NEUROBIOLOGY OF DISEASE LA English DT Review ID BRAIN-COMPUTER INTERFACES; AMYOTROPHIC-LATERAL-SCLEROSIS; ELECTROCORTICOGRAPHIC SPECTRAL-ANALYSIS; HUMAN SENSORIMOTOR CORTEX; MOTOR CORTEX; MACHINE INTERFACES; NEURAL PROSTHETICS; COGNITIVE CONTROL; ARM MOVEMENTS; STIMULATION AB Recent pilot clinical studies have demonstrated that subjects with severe disorders of movement and communication can exert direct neural control over assistive devices using invasive Brain-Machine Interface (BMI) technology, also referred to as 'cortical neuroprosthetics'. These important proof-of-principle studies have generated great interest among those with disability and clinicians who provide general medical, neurological and/or rehabilitative care. Taking into account the perspective of providers who may be unfamiliar with the field, we first review the clinical goals and fundamentals of invasive BMI technology, and then briefly summarize the vast body of basic science research demonstrating its feasibility. We emphasize recent translational progress in the target clinical populations and discuss translational challenges and future directions. Published by Elsevier Inc. C1 [Tsu, Adelyn P.; GodLove, Jason; Ganguly, Karunesh] San Francisco VA Med Ctr, Neurol & Rehabil Serv, San Francisco, CA USA. [Burish, Mark J.; GodLove, Jason; Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Ganguly, Karunesh] Univ Calif San Francisco, Ctr Neural Engn & Prosthet, San Francisco, CA 94143 USA. [Ganguly, Karunesh] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ganguly, K (reprint author), 1700 Owens St, San Francisco, CA 94158 USA. EM karunesh.ganguly@ucsf.edu FU Office of Academic Affairs at the Department of Veterans Affairs; Doris Duke Charitable Foundation [2013101]; UCSF Department of Neurology; NCIRE; Burroughs Wellcome Fund [1000985] FX This work was supported by a fellowship award to Adelyn Tsu from the Office of Academic Affairs at the Department of Veterans Affairs. This work was also supported by Grant 2013101 from the Doris Duke Charitable Foundation and start-up funds from the UCSF Department of Neurology and NCIRE. Karunesh Ganguly, M.D., Ph.D., also holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund (1000985). NR 109 TC 0 Z9 0 U1 5 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2015 VL 83 BP 154 EP 160 DI 10.1016/j.nbd.2015.07.015 PG 7 WC Neurosciences SC Neurosciences & Neurology GA CY2HS UT WOS:000366230000015 PM 26253606 ER PT J AU Piotrowska, Z Sequist, LV AF Piotrowska, Zofia Sequist, Lecia V. TI Continued EGFR Inhibition With Postprogression Chemotherapy: Where Do We Stand? SO ONCOLOGIST LA English DT Editorial Material ID CELL LUNG-CANCER; ACQUIRED-RESISTANCE; ERLOTINIB C1 [Piotrowska, Zofia; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Piotrowska, Z (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM zpiotrowska@partners.org NR 15 TC 0 Z9 0 U1 0 U2 0 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 2015 VL 20 IS 11 BP 1230 EP 1232 DI 10.1634/theoncologist.2015-0370 PG 3 WC Oncology SC Oncology GA CX9RS UT WOS:000366043600002 PM 26500230 ER PT J AU Hall, T Lee, SI Boruta, DM Goodman, A AF Hall, Tracilyn Lee, Susanna I. Boruta, David M. Goodman, Annekathryn TI Medical Device Safety and Surgical Dissemination of Unrecognized Uterine Malignancy: Morcellation in Minimally Invasive Gynecologic Surgery SO ONCOLOGIST LA English DT Article DE Morcellation; Power morcellation; Uterine sarcoma; Peritoneal dissemination ID PORT-SITE METASTASES; ENDOMETRIAL CANCER; OVARIAN-CANCER; SUPRACERVICAL HYSTERECTOMY; LAPAROSCOPIC HYSTERECTOMY; POWER MORCELLATION; TUMOR MORCELLATION; COLORECTAL-CANCER; ABDOMINAL-WALL; LEIOMYOSARCOMA AB There is a risk of dissemination of uterine malignancies during minimally invasive hysterectomies when morcellation is used. Although the technique of uterine power morcellation allows timely removal of large benign tumors through small laparoscopic incisions, there are concerns about iatrogenic spread of cancers and reduced survival for women with preoperatively unrecognized malignancies. This review examines the literature on intraperitoneal spread and implantation of mechanically disrupted malignant tissue, discusses the current diagnostic tools for preoperative assessment of uterine tumors, and summarizes the current recommendations of the Society of Gynecologic Oncologists, the American College of Obstetricians and Gynecologists, and the American Association of Gynecologic Laparoscopists. Recommendations include informed consent of the risk of disseminating an otherwise contained malignancy, appropriate preoperative evaluation for malignancy, and development of alternatives to intracorporeal morcellation. C1 [Hall, Tracilyn; Boruta, David M.; Goodman, Annekathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA USA. [Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Hall, T (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM trhall@mgh.harvard.edu NR 66 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 2015 VL 20 IS 11 BP 1274 EP 1282 DI 10.1634/theoncologist.2015-0061 PG 9 WC Oncology SC Oncology GA CX9RS UT WOS:000366043600010 PM 26382742 ER PT J AU Canellos, G DeVita, V AF Canellos, George DeVita, Vincent TI Gianni Bonadonna: A Personal Remembrance In Memoriam SO ONCOLOGIST LA English DT Biographical-Item C1 [Canellos, George] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [DeVita, Vincent] Yale Univ, Yale Canc Ctr, New Haven, CT USA. RP Canellos, G (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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 2015 VL 20 IS 11 BP 1348 EP 1349 DI 10.1634/theoncologist.2015-0367 PG 2 WC Oncology SC Oncology GA CX9RS UT WOS:000366043600022 PM 26854300 ER PT J AU Austin, JH Mieure, K Weber, L McCarthy, B AF Austin, Jennifer H. Mieure, Katherine Weber, Lynn McCarthy, Bryan, Jr. TI National characteristics of residency program interview processes SO PHARMACOTHERAPY LA English DT Meeting Abstract CT American-College-of-Clinical-Pharmacy Global Conference on Clinical Pharmacy CY OCT 17-21, 2015 CL San Francisco, CA SP Amer Coll Clin Pharm C1 [Austin, Jennifer H.; McCarthy, Bryan, Jr.] Univ Chicago Med, Chicago, IL USA. [Mieure, Katherine] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. [Weber, Lynn] Hennepin Cty Med Ctr, Minneapolis, MN 55415 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2015 VL 35 IS 11 MA 175 BP E217 EP E217 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CX9SG UT WOS:000366045000131 ER PT J AU Koffarnus, RL Darin, KM Hedges, A Man, B Nelson, C Peron, E Tran, T Holder, R AF Koffarnus, Robin L. Darin, Kristin M. Hedges, Ashley Man, Bernice Nelson, Cory Peron, Emily Tran Tran Holder, Renee TI An introduction to the Global Health PRN and its members SO PHARMACOTHERAPY LA English DT Meeting Abstract CT American-College-of-Clinical-Pharmacy Global Conference on Clinical Pharmacy CY OCT 17-21, 2015 CL San Francisco, CA SP Amer Coll Clin Pharm C1 [Koffarnus, Robin L.] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dallas, TX USA. [Darin, Kristin M.] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA. [Darin, Kristin M.] Northwestern Univ, Ctr Global Hlth, Feinberg Sch Med, Chicago, IL 60611 USA. [Hedges, Ashley] US Dept Vet Affairs, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Man, Bernice] Chicago State Univ, Coll Pharm, Chicago, IL USA. [Peron, Emily] Virginia Commonwealth Univ, Sch Pharm, Richmond, VA USA. [Tran Tran; Holder, Renee] Roseman Univ Hlth Sci, Coll Pharm, Henderson, NV 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 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2015 VL 35 IS 11 MA 320 BP E254 EP E254 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CX9SG UT WOS:000366045000248 ER PT J AU Lichvar, A Hedges, A Benedict, N Donihi, AC AF Lichvar, Alicia Hedges, Ashley Benedict, Neal Donihi, Amy C. TI Combination of a flipped classroom and a virtual patient case to enhance active learning in the classroom SO PHARMACOTHERAPY LA English DT Meeting Abstract CT American-College-of-Clinical-Pharmacy Global Conference on Clinical Pharmacy CY OCT 17-21, 2015 CL San Francisco, CA SP Amer Coll Clin Pharm C1 [Lichvar, Alicia] Univ Pittsburgh, Med Ctr, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Hedges, Ashley] US Dept Vet Affairs, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Benedict, Neal; Donihi, Amy C.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. RI 向飞, 郭/A-1604-2016 NR 0 TC 0 Z9 0 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2015 VL 35 IS 11 MA 39 BP E184 EP E184 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CX9SG UT WOS:000366045000036 ER PT J AU Schell, R Abramcyzk, A Fominaya, C Friedman, R Castle, S AF Schell, Ryan Abramcyzk, Anthony Fominaya, Cory Friedman, Robert Castle, Sharon TI Outcomes associated with a multidisciplinary pain oversight committee to facilitate appropriate management of chronic opioid therapy in Veterans SO PHARMACOTHERAPY LA English DT Meeting Abstract CT American-College-of-Clinical-Pharmacy Global Conference on Clinical Pharmacy CY OCT 17-21, 2015 CL San Francisco, CA SP Amer Coll Clin Pharm C1 [Schell, Ryan; Abramcyzk, Anthony; Fominaya, Cory; Castle, Sharon] Ralph H Johnson VA Med Ctr, Serv Pharm, Charleston, SC USA. [Friedman, Robert] Ralph H Johnson VA Med Ctr, Dept Anesthesiol, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2015 VL 35 IS 11 MA 410 BP E280 EP E281 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CX9SG UT WOS:000366045000335 ER PT J AU Tyburczy, ME Dies, KA Glass, J Camposano, S Chekaluk, Y Thorner, AR Lin, L Krueger, D Franz, DN Thiele, EA Sahin, M Kwiatkowski, DJ AF Tyburczy, Magdalena E. Dies, Kira A. Glass, Jennifer Camposano, Susana Chekaluk, Yvonne Thorner, Aaron R. Lin, Ling Krueger, Darcy Franz, David N. Thiele, Elizabeth A. Sahin, Mustafa Kwiatkowski, David J. TI Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing SO PLOS GENETICS LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; GENOTYPE-PHENOTYPE CORRELATIONS; TRUNCATING MUTATIONS; GERMLINE MUTATIONS; SOMATIC MOSAICISM; LEVEL MOSAICISM; GENE; DISEASE; FREQUENCY; MISSENSE AB Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor gene syndrome due to germline mutations in either TSC1 or TSC2. 10-15% of TSC individuals have no mutation identified (NMI) after thorough conventional molecular diagnostic assessment. 53 TSC subjects who were NMI were studied using next generation sequencing to search for mutations in these genes. Blood/saliva DNA including parental samples were available from all subjects, and skin tumor biopsy DNA was available from six subjects. We identified mutations in 45 of 53 subjects (85%). Mosaicism was observed in the majority (26 of 45, 58%), and intronic mutations were also unusually common, seen in 18 of 45 subjects (40%). Seventeen (38%) mutations were seen at an allele frequency < 5%, five at an allele frequency < 1%, and two were identified in skin tumor biopsies only, and were not seen at appreciable frequency in blood or saliva DNA. These findings illuminate the extent of mosaicism in TSC, indicate the importance of full gene coverage and next generation sequencing for mutation detection, show that analysis of TSC-related tumors can increase the mutation detection rate, indicate that it is not likely that a third TSC gene exists, and enable provision of genetic counseling to the substantial population of TSC individuals who are currently NMI. C1 [Tyburczy, Magdalena E.; Chekaluk, Yvonne; Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Dies, Kira A.; Sahin, Mustafa] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Glass, Jennifer] Cincinnati Childrens Hosp Med Ctr, Dept Human Genet, Cincinnati, OH 45229 USA. [Camposano, Susana; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Thorner, Aaron R.; Lin, Ling] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Krueger, Darcy; Franz, David N.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. RP Tyburczy, ME (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu FU National Institute of Health National Cancer Institute [1P01CA120964]; European Commission [602391-2]; FY Tuberous Sclerosis Alliance Postdoctoral Fellowship Award (MET); Developmental Synaptopathies Consortium which is a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) [U54NS092090]; NCATS; NINDS; NIMH; NICHD FX This work was supported by the National Institute of Health National Cancer Institute 1P01CA120964 (DJK); the European Commission 602391-2 (DJK), and FY2011 Tuberous Sclerosis Alliance Postdoctoral Fellowship Award (MET), http://www.tsalliance.org/; Developmental Synaptopathies Consortium (U54NS092090), which is a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and funded through collaboration between NCATS, NINDS, NIMH and NICHD (KAD, MS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 22 Z9 23 U1 3 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2015 VL 11 IS 11 AR e1005637 DI 10.1371/journal.pgen.1005637 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA CY1PF UT WOS:000366179000020 PM 26540169 ER PT J AU Fricchione, GL Crernens, MC Siberski, JR AF Fricchione, Gregory L. Crernens, M. Cornelia Siberski, John R. TI Edwin H. "Ned" Cassem, SJ, MA, Ph.L., MD, BD, FAPM (1935-2015) SO PSYCHOSOMATICS LA English DT Biographical-Item C1 [Fricchione, Gregory L.; Crernens, M. Cornelia] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Siberski, John R.] Campion Ctr, Weston, MA USA. RP Fricchione, GL (reprint author), Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. EM Fricchione.Gregory@mgh.harvard.edu NR 1 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2015 VL 56 IS 6 BP 628 EP 629 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CY3NB UT WOS:000366315400004 PM 26674481 ER PT J AU Golkari, S Teunis, T Ring, D Vranceanu, AM AF Golkari, Sina Teunis, Teun Ring, David Vranceanu, Ana-Maria TI Changes in Depression, Health Anxiety, and Pain Catastrophizing Between Enrollment and 1 Month After a Radius Fracture SO PSYCHOSOMATICS LA English DT Article ID MAJOR DEPRESSION; RECOVERY; SCALE; DIMENSIONS AB Objectives: To test the difference in symptoms of (1) depression, (2) health anxiety, and (3) catastrophic thinking between 1 and 6 weeks after injury to the radius. Patients and Methods: In total, 69 adult patients with a minimally displaced radial head or distal radius fracture were prospectively enrolled. After diagnosis, we recorded demographic variables, 11-point ordinal numerical pain score, and agreement with "no pain, no gain"; Disabilities of the Arms, Shoulder, and Hand (DASH) questionnaire; Center for Epidemiologic Studies Depression Scale; the Whiteley Index; and the Pain Catastrophizing Scale. In total, 55 patients (80%) returned after 1 month to reevaluate pain, Disabilities of the Arms, Shoulder, and Hand, Center for Epidemiologic Studies Depression, Whiteley Index, and Pain Catastrophizing Scale scores. Results: Center for Epidemiologic Studies Depression scores decreased by an average of 5 +/- 9 points (p < 0.001), and Pain Catastrophizing Scale scores decreased by 2 6 points (p = 0.0041). In multivariable analysis, decrease in Center for Epidemiologic Studies Depression was associated with not having an additional pain condition, more days elapsed between injury and final evaluation, and stronger agreement with "no pain, no gain" (adjusted R-2 = 0.26, p = 0.0006). An increase in Whiteley scores was associated with fewer years of education (R = 0.34, p = 0.012). Changes in Pain Catastrophizing Scale scores were associated with marital status (single 1.7 4.3 vs married 4.6 +/- 6.0 vs separated 0.55 +/- 6.2, p = 0.040). Conclusions: Symptoms of depression and catastrophic thinking, but not health anxiety, improved during recovery after injury. If psychologic measures are used as a screening tool to predict outcome after treatment, one should account for a patient's disease phase. C1 [Golkari, Sina; Teunis, Teun; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. EM dring@mgh.harvard.edu NR 15 TC 2 Z9 2 U1 3 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 2015 VL 56 IS 6 BP 652 EP 657 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA CY3NB UT WOS:000366315400008 PM 26002224 ER PT J AU Raschle, T Lin, CX Jungmann, R Shih, WM Wagner, G AF Raschle, Thomas Lin, Chenxiang Jungmann, Ralf Shih, William M. Wagner, Gerhard TI Controlled Co-reconstitution of Multiple Membrane Proteins in Lipid Bilayer Nanodiscs Using DNA as a Scaffold SO ACS CHEMICAL BIOLOGY LA English DT Article ID BACTERIORHODOPSIN; RECONSTITUTION; MODULATION; COMPLEXES; RHODOPSIN; DYNAMICS; CHANNEL; VDAC; GPCR AB Nanodiscs constitute a tool for the solubilization of membrane proteins in a lipid bilayer, thus offering a near native membrane environment. Many membrane proteins interact with other membrane proteins; however, the co-reconstitution, of multiple membrane proteins in a single nanodisc is a random process that is adversely affected by several factors, including protein aggregation. Here, we present an approach for the controlled co-reconstitution of multiple membrane proteins in a single nanodisc. The temporary attachment of designated oligonucleotides to individual membrane proteins enables the formation of stable; detergent-solubilized membrane protein complexes by base-pairing of complementary oligonucleotide sequences, thus facilitating the insertion of the membrane protein complex into nanodiscs with defined stoichiometry and composition. As a proof of principle nanodiscs containing a heterodimeric and heterotrimeric membrane protein complex were reconstituted using a fluorescently labeled voltage-gated anion channel (VDAC) as a model system. C1 [Raschle, Thomas; Lin, Chenxiang; Jungmann, Ralf; Shih, William M.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lin, Chenxiang; Jungmann, Ralf; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Lin, Chenxiang; Jungmann, Ralf; Shih, William M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. RP Raschle, T (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM traschle@creoptix.com; gerhard_wagner@hms.harvard.edu OI Lin, Chenxiang/0000-0001-7041-1946 FU National Institutes of Health [GM075879, PO1 GM62580] FX This research was supported by National Institutes of Health grants GM075879 (to G.W.). We thank the Nikon Imaging Center at Harvard Medical School and the molecular electron microscopy facility (National Institutes of Health grant PO1 GM62580) for the use of their microscopes. We would like to thank M. Chambers and T. Walz (Harvard Medical School) for help with electron microscopy. NR 35 TC 3 Z9 3 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD NOV PY 2015 VL 10 IS 11 BP 2448 EP 2454 DI 10.1021/acschembio.5b00627 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CX1NK UT WOS:000365462700004 PM 26356202 ER PT J AU Rehani, B Hirsch, JA Dillon, WP Gonzalez, RG Lev, MH Schaefer, PW AF Rehani, B. Hirsch, J. A. Dillon, W. P. Gonzalez, R. G. Lev, M. H. Schaefer, P. W. TI Multiple Procedure Payment Reduction: Health Policy Update SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article AB Multiple Procedure Payment Reduction currently applies to multiple diagnostic imaging services administered to the same patient during the same day and entails a 50% decrease in the technical component and a 25% decrease in the professional component reimbursement. This might change with time due to further legislation, so it is important to be up-to-date on these health policy developments. C1 [Rehani, B.; Dillon, W. P.] Univ Calif San Francisco, Dept Neuroradiol, San Francisco, CA 94110 USA. [Rehani, B.; Dillon, W. P.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94110 USA. [Hirsch, J. A.; Gonzalez, R. G.; Lev, M. H.; Schaefer, P. W.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Hirsch, J. A.; Gonzalez, R. G.; Lev, M. H.; Schaefer, P. W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rehani, B (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Neuroradiol, 1001 Poterero Ave,SFGH 5, San Francisco, CA 94110 USA. EM bhavya.rehani@ucsf.edu NR 4 TC 0 Z9 0 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 2015 VL 36 IS 11 BP 2007 EP 2009 DI 10.3174/ajnr.A4523 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CW4TK UT WOS:000364984800003 PM 26381559 ER PT J AU Schneider, A Henderson, JT Harper, CC Hsu, A Saraiya, M Sawaya, GF AF Schneider, Allison Henderson, Jillian T. Harper, Cynthia C. Hsu, Amy Saraiya, Mona Sawaya, George F. TI Obstetrician-gynecologists' beliefs about performing less cervical cancer screening: the pendulum swings SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID NEOPLASIA C1 [Schneider, Allison] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Henderson, Jillian T.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Harper, Cynthia C.; Sawaya, George F.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Hsu, Amy] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Saraiya, Mona] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Sawaya, George F.] Univ Calif San Francisco, Ctr Healthcare Value, San Francisco, CA 94143 USA. RP Schneider, A (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. EM George.sawaya@ucsf.edu FU NCI NIH HHS [R01 CA169093]; NICHD NIH HHS [K01 HD054495, K01HD054495] NR 5 TC 0 Z9 0 U1 0 U2 1 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 2015 VL 213 IS 5 BP 744 EP 745 DI 10.1016/j.ajog.2015.07.003 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX5SS UT WOS:000365763400046 PM 26184779 ER PT J AU Wang, AL Patil, SU Long, AA Banerji, A AF Wang, Alberta L. Patil, Sarita U. Long, Aidan A. Banerji, Aleena TI Risk-stratification protocol for carboplatin and oxaliplatin hypersensitivity: repeat skin testing to identify drug allergy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID RAPID DESENSITIZATION; EXPERIENCE; CHEMOTHERAPY; PREDICT AB Background: Hypersensitivity reactions (HSRs) to platinum-based chemotherapies are increasingly being recognized. The authors developed a novel risk-stratification protocol that was used successfully in a small number of patients with carboplatin-induced HSRs. Objective: To describe the utility of this protocol in a large number of patients with carboplatin-or oxaliplatin-induced HSRs. Methods: A 5-year retrospective review of patients referred to Massachusetts General Hospital with carboplatin-or oxaliplatin-induced HSR was performed. Patients were managed using a risk-stratification protocol using 3 repeat skin tests (STs) with intervening desensitizations. If the repeat ST result remained negative 3 times, patients received subsequent infusions without desensitization. Results: From 2008 to 2012, 142 patients (92 treated with carboplatin, 50 treated with oxaliplatin) completed 574 desensitizations. Most patients were women (84.5%, mean +/- SD 58.1 +/- 9.3 years). Patients with carboplatin-induced HSRs were classified as having positive (n = 32, 34.8%), negative (n = 38, 41.3%), or converted (n = 22, 23.9%) ST reactions when the initial negative ST reaction converted to positive at repeat ST. Of those with oxaliplatin-induced HSRs, 22 (44%) had positive, 25 (50%) had negative, and 3 (6%) had converted ST reactions. Of the patients with negative ST reactions, 17 with carboplatin-induced HSRs and 16 with oxaliplatin-induced HSRs safely completed 59 and 95 outpatient infusions, respectively, without desensitizations. For carboplatin and oxaliplatin, ST conversion was associated with an interval of at least 6 months from the HSR to the initial ST (carboplatin, P = .002; oxaliplatin, P = .045). Conclusion: This risk-stratification protocol for presumed carboplatin-and oxaliplatin-induced HSRs safely identifies false-negative ST reactions and nonallergic patients who can receive infusions without desensitizations. This leads to fewer unnecessary desensitizations and improved patient care. (C) 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Wang, Alberta L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Patil, Sarita U.; Long, Aidan A.; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Wang, AL (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 1 Jimmy Fund Way,SM 638, Boston, MA 02115 USA. EM awang14@partners.org NR 21 TC 3 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 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2015 VL 115 IS 5 BP 422 EP 428 DI 10.1016/j.anai.2015.07.017 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA CX3PP UT WOS:000365611700011 PM 26298407 ER PT J AU Regan, M Pagani, O Francis, P Fleming, G Walley, B Kammler, R Dell'Orto, P Russo, L Szoke, J Doimi, F Villani, L Pizzolitto, S Ohlschlegel, C Sessa, F Camara, VP Peralto, JLR MacGrogan, G Colleoni, M Goldhirsch, A Price, KN Coates, AS Gelber, RD Viale, G AF Regan, Meredith M. Pagani, Olivia Francis, Prudence A. Fleming, Gini F. Walley, Barbara A. Kammler, Roswitha Dell'Orto, Patrizia Russo, Leila Szoke, Janos Doimi, Franco Villani, Laura Pizzolitto, Stefano Oehlschlegel, Christian Sessa, Fausto Peg Camara, Vicente Rodriguez Peralto, Jose Luis MacGrogan, Gaetan Colleoni, Marco Goldhirsch, Aron Price, Karen N. Coates, Alan S. Gelber, Richard D. Viale, Giuseppe CA SOFT TEXT Investigators Int Breast TI Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Estrogen receptor; Exemestane; Ki-67; Ovarian function suppression; Progesterone receptor; Tamoxifen ID INTERNATIONAL EXPERT CONSENSUS; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; OVARIAN SUPPRESSION; TAMOXIFEN; EXPRESSION; HIGHLIGHTS; BIOMARKERS; EXEMESTANE AB The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2-) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2- early breast cancer. C1 [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr,Dept Biostat &, Boston, MA 02215 USA. [Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Inst Oncol Southern Switzerland, Lugano Viganello, Switzerland. [Francis, Prudence A.] Univ Melbourne, St Vincents Hosp, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Francis, Prudence A.] Univ Newcastle, ANZBCTG, Callaghan, NSW 2308, Australia. [Fleming, Gini F.] Univ Chicago, Med Ctr & Alliance Clin Trials Oncol, Chicago, IL 60637 USA. [Walley, Barbara A.] Baker Canc Ctr, Calgary, AB, Canada. [Walley, Barbara A.] NCIC Clin Trials Grp, Calgary, AB, Canada. [Kammler, Roswitha] Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. [Kammler, Roswitha] Cent Pathol Off, Bern, Switzerland. [Dell'Orto, Patrizia; Russo, Leila] European Inst Oncol, Dept Pathol, Int Breast Canc Study Grp Cent Pathol Off, Milan, Italy. [Szoke, Janos] Natl Inst Oncol, Dept Pathol, Budapest, Hungary. [Doimi, Franco] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Villani, Laura] Salvatore Maugeri Fdn, Div Pathol, Pavia, Italy. [Pizzolitto, Stefano] Univ Udine, Azienda Osped, Struttura Operat Complesa Anat Patol, I-33100 Udine, Italy. [Oehlschlegel, Christian] Swiss Grp Clin Canc Res SAKK, Kantonsspital St Gallen, St Gallen, Switzerland. [Sessa, Fausto] Univ Insubria, Osped Circolo, Varese, Italy. [Sessa, Fausto] Fdn Macchi, Varese, Italy. [Peg Camara, Vicente] Vall Hebron Univ Hosp, Dept Pathol, SOLTI Grp, Barcelona, Spain. [Rodriguez Peralto, Jose Luis] Univ Complutense Madrid, Hosp Univ Octubre I 12 12, Dept Pathol, SOLTI Grp, Madrid, Spain. [MacGrogan, Gaetan] Inst Bergonie, Lab Anatomopathol, Bordeaux, France. [MacGrogan, Gaetan] EORTC, Brussels, Belgium. [Colleoni, Marco] European Inst Oncol, Div Med Senol, Milan, Italy. [Goldhirsch, Aron] European Inst Oncol, Program Breast Hlth, Milan, Italy. [Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Int Breast Canc Study Grp Stat Ctr, Boston, MA USA. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Gelber, Richard D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr, Boston, MA 02215 USA. [Gelber, Richard D.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Viale, Giuseppe] Univ Milan, European Inst Oncol, Int Breast Canc Study Grp Cent Pathol Off, Milan, Italy. RP Regan, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Int Breast Canc Study Grp Stat Ctr,Dept Biostat &, 450 Brookline Ave,Mailstop CLS 11007, Boston, MA 02215 USA. EM mregan@jimmy.harvard.edu; olivia.pagani@ibcsg.org; prue.francis@petermac.org; gfleming@medicine.bsd.uchicago.edu; Barbara.Walley@albertahealthservices.ca; Rosita.Kammler@ibcsg.org; patrizia.dellorto@ieo.it; leila.russo@ieo.it; szoke.j@oncol.hu; fdoimi@inen.sld.pe; laura.villani@fsm.it; pizzolitto.stefano@aoud.sanita.fvg.it; christian.oehlschlegel@kssg.ch; fausto.sessa@ospedale.varese.it; vpeg@vhebron.net; jrperalto@salud.madrid.org; g.macgrogan@bordeaux.unicancer.fr; marco.colleoni@ieo.it; aron.goldhirsch@ibcsg.org; price@jimmy.harvard.edu; alan.coates@ibcsg.org; gelber@jimmy.harvard.edu; giuseppe.viale@ieo.it FU Pfizer; International Breast Cancer Study Group; US National Cancer Institute; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); US National Cancer Institute (NCI) [US NIH CA75362]; Susan G. Komen for the Cure Promise Grant [KG080081]; Breast Cancer Research Foundation; NHMRC [351161, 510788]; US NIH [CA32102, U10-CA180821, CA21115, CA16116, U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974, CA077202, CCSRI 015469, 021039]; CRUK [CRUKE/03/022, CRUKE/03/023, A15955]; NIHR RM/ICR Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre FX We thank many pathologists who submitted tumor blocks and slides, and the patients, physicians, nurses and data managers who participated in the TEXT and SOFT clinical trials. We thank Stefania Andrighetto and Elvira Bianca Benini of the IBCSG Central Pathology Office and Wilbur Helfer of the IBCSG Coordinating Center. TEXT and SOFT received financial support for trial conduct from Pfizer, the International Breast Cancer Study Group, and the US National Cancer Institute. Pfizer and Ipsen provided drug supply. Support for the coordinating group, IBCSG: Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), Cancer Research Switzerland/Oncosuisse, the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK), US National Cancer Institute (NCI) (US NIH CA75362), Susan G. Komen for the Cure Promise Grant (KG080081), Breast Cancer Research Foundation. Grant support of cooperative groups: Australia and New Zealand Breast Cancer Trials Group (NHMRC 351161 and 510788); SWOG (US NIH CA32102); Alliance/CALGB (US NIH U10-CA180821); ECOG-ACRIN (US NIH CA21115 and CA16116); NSABP/NRG (US NIH U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974); NCIC-CTG (US NIH CA077202 and CCSRI 015469 and 021039); ICR-CTSU on behalf of the National Cancer Research Institute (NCRI) Breast Clinical Studies Group United Kingdom (NCRI-BCSG-ICR-CTSU Partnership) was supported by CRUK, CRUKE/03/022, CRUKE/03/023, A15955, NIHR RM/ICR Biomedical Research Centre, and by NIHR Cambridge Biomedical Research Centre. NR 19 TC 4 Z9 4 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2015 VL 154 IS 2 BP 275 EP 286 DI 10.1007/s10549-015-3612-z PG 12 WC Oncology SC Oncology GA CW7OL UT WOS:000365188600006 PM 26493064 ER PT J AU Blackwell, K Burris, H Gomez, P Henry, NL Isakoff, S Campana, F Gao, L Jiang, J Mace, S Tolaney, SM AF Blackwell, Kimberly Burris, Howard Gomez, Patricia Henry, N. Lynn Isakoff, Steven Campana, Frank Gao, Lei Jiang, Jason Mace, Sandrine Tolaney, Sara M. TI Phase I/II dose-escalation study of PI3K inhibitors pilaralisib or voxtalisib in combination with letrozole in patients with hormone-receptor-positive and HER2-negative metastatic breast cancer refractory to a non-steroidal aromatase inhibitor SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE HER2-negative; Hormone-receptor-positive metastatic breast cancer; PI3K; Pilaralisib; Voxtalisib ID ADVANCED SOLID TUMORS; I SAFETY; PI3K/MTOR INHIBITOR; ENDOCRINE THERAPY; SAR245409 XL765; ESTROGEN; PATHWAY; RESISTANCE; MUTATIONS; XL147 AB This phase I/II dose-escalation study evaluated the efficacy, safety, and pharmacokinetics of pilaralisib (SAR245408), a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, or voxtalisib (SAR245409), a PI3K and mammalian target of rapamycin inhibitor, in combination with letrozole in hormone-receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, non-steroidal aromatase inhibitor-refractory, recurrent or metastatic breast cancer. Maximum tolerated doses (MTDs) were determined using a 3 + 3 design in phase I. Efficacy was evaluated at the MTDs in phase II. Twenty-one patients were enrolled in phase I; MTDs were determined to be pilaralisib tablets 400 mg once daily (QD) or voxtalisib capsules 50 mg twice daily in combination with letrozole tablets 2.5 mg QD. Fifty-one patients were enrolled in phase II; one patient had a partial response in the pilaralisib arm. Rates of progression-free survival at 6 months were 17 and 8 % in the pilaralisib and voxtalisib arms, respectively. The most frequently reported treatment-related grade a parts per thousand yen 3 adverse events were aspartate aminotransferase increased (5 %) and rash (5 %) in the pilaralisib arm, and alanine aminotransferase increased (11 %) and rash (9 %) in the voxtalisib arm. Pilaralisib and voxtalisib did not interact pharmacokinetically with letrozole. Pilaralisib had a greater pharmacodynamic impact than voxtalisib, as demonstrated by its impact on glucose homeostasis. There was no association between molecular alterations in the PI3K pathway and efficacy. In summary, pilaralisib or voxtalisib, in combination with letrozole, was associated with an acceptable safety profile and limited efficacy in endocrine therapy-resistant HR+ , HER2-negative metastatic breast cancer. C1 [Blackwell, Kimberly] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Burris, Howard] Sarah Cannon Res Inst, Nashville, TN USA. [Henry, N. Lynn] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Isakoff, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Campana, Frank; Gao, Lei] Sanofi, Cambridge, MA USA. [Jiang, Jason] Sanofi, Bridgewater, NJ USA. [Mace, Sandrine] Sanofi, Vitry Sur Seine, France. [Tolaney, Sara M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blackwell, K (reprint author), Duke Univ, Med Ctr, 2301 Erwin Rd, Durham, NC 27710 USA. EM black034@mc.duke.edu FU Sanofi FX This study was funded by Sanofi. The authors received editorial support from Simone Blagg of MediTech Media, funded by Sanofi. NR 37 TC 2 Z9 2 U1 0 U2 1 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 2015 VL 154 IS 2 BP 287 EP 297 DI 10.1007/s10549-015-3615-9 PG 11 WC Oncology SC Oncology GA CW7OL UT WOS:000365188600007 PM 26497877 ER PT J AU Stagl, JM Lechner, SC Carver, CS Bouchard, LC Gudenkauf, LM Jutagir, DR Diaz, A Yu, QL Blomberg, BB Ironson, G Gluck, S Antoni, MH AF Stagl, Jamie M. Lechner, Suzanne C. Carver, Charles S. Bouchard, Laura C. Gudenkauf, Lisa M. Jutagir, Devika R. Diaz, Alain Yu, Qilu Blomberg, Bonnie B. Ironson, Gail Glueck, Stefan Antoni, Michael H. TI A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast neoplasm; Survival; Recurrence; Cognitive therapy; Behavior therapy; Breast cancer ID DEPRESSIVE SYMPTOMS; INTERVENTION; WOMEN; DISTRESS; QUALITY; MODELS; SKILLS; LIFE AB U Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes. C1 [Stagl, Jamie M.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA. [Lechner, Suzanne C.; Antoni, Michael H.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Lechner, Suzanne C.; Carver, Charles S.; Blomberg, Bonnie B.; Antoni, Michael H.] Univ Miami, Miller Sch Med, Sylvester Canc Ctr, Miami, FL 33136 USA. [Carver, Charles S.; Bouchard, Laura C.; Gudenkauf, Lisa M.; Jutagir, Devika R.; Ironson, Gail; Antoni, Michael H.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Diaz, Alain; Blomberg, Bonnie B.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Yu, Qilu] Westat Corp, Rockville, MD 20850 USA. [Glueck, Stefan] Celgene Corp, Summit, NJ 07901 USA. RP Stagl, JM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, 55 Fruit St,Yawkey Suite 10B, Boston, MA 02114 USA. EM jstagl@mgh.harvard.edu OI Jacobs, Jamie M./0000-0001-9740-624X; carver, charles/0000-0002-3688-8545 FU Federal funds from the National Cancer Institute (NCI), National Institutes of Health [HHSN261200800001E]; NCI [R01-CA-064710]; NCI Network of Biobehavioral Pathways in Cancer [HHSN261200800001E] FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute (NCI), National Institutes of Health, under Contract No. HHSN261200800001E and NCI grant R01-CA-064710. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The NCI Network of Biobehavioral Pathways in Cancer (under Contract No. HHSN261200800001E) was involved in the design of the study, provided funding for data collection, provided statistical support for data analysis and interpretation through Westat, reviewed and approved the manuscript and the decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 29 TC 5 Z9 5 U1 1 U2 6 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 2015 VL 154 IS 2 BP 319 EP 328 DI 10.1007/s10549-015-3626-6 PG 10 WC Oncology SC Oncology GA CW7OL UT WOS:000365188600010 PM 26518021 ER PT J AU Waks, AG Tolaney, SM Galar, A Arnaout, A Porter, JB Marty, FM Winer, EP Hammond, SP Baden, LR AF Waks, Adrienne G. Tolaney, Sara M. Galar, Alicia Arnaout, Amal Porter, Julie B. Marty, Francisco M. Winer, Eric P. Hammond, Sarah P. Baden, Lindsey R. TI Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Pneumocystis jiroveci; Breast cancer; Adjuvant chemotherapy; Corticosteroids ID HUMAN-IMMUNODEFICIENCY-VIRUS; BETA-D-GLUCAN; CARINII-PNEUMONIA; IMMUNOCOMPROMISED PATIENTS; CORTICOSTEROID-THERAPY; DOSE-DENSE; LYMPHOPENIA; DIAGNOSIS; BLOOD; LYMPHOMA AB Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been recognized as a significant complication of early-stage breast cancer treatment. However, we have observed an increase in PCP incidence among patients receiving chemotherapy for early-stage breast cancer. Herein we identify risk factors for and calculate incidence of PCP in this population. We identified all cases of PCP at Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH) from 1/1/2000 to 12/31/2013 in patients with stage I-III breast cancer treated with an adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non-metastatic breast cancer patients were identified. All patients with PCP were diagnosed after receipt of either three or four cycles of AC chemotherapy on a dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg prednisone equivalents/day as nausea prophylaxis for a median 64 days. The overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3-1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC. There was one death from PCP. Women receiving dose-dense AC chemotherapy for early-stage breast cancer are at risk for PCP. Administering the same chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense schedule appears to have created a novel infectious vulnerability. Replacing dexamethasone with alternative anti-emetics may mitigate this risk. C1 [Waks, Adrienne G.; Tolaney, Sara M.; Arnaout, Amal; Marty, Francisco M.; Winer, Eric P.; Hammond, Sarah P.; Baden, Lindsey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Waks, Adrienne G.; Tolaney, Sara M.; Galar, Alicia; Marty, Francisco M.; Winer, Eric P.; Hammond, Sarah P.; Baden, Lindsey R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Waks, Adrienne G.; Tolaney, Sara M.; Marty, Francisco M.; Winer, Eric P.; Hammond, Sarah P.; Baden, Lindsey R.] Harvard Univ, Sch Med, Boston, MA USA. [Porter, Julie B.] Stanford Hlth Care, Stanford, CA USA. [Baden, Lindsey R.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Baden, LR (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM lbaden@bwh.harvard.edu NR 30 TC 1 Z9 1 U1 0 U2 1 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 2015 VL 154 IS 2 BP 359 EP 367 DI 10.1007/s10549-015-3573-2 PG 9 WC Oncology SC Oncology GA CW7OL UT WOS:000365188600014 PM 26420402 ER PT J AU Moskos, MM Hughes, KS AF Moskos, Margo M. Hughes, Kevin S. TI Doing "nothing" for DCIS: a case report SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article C1 [Moskos, Margo M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Hughes, Kevin S.] Harvard Univ, Sch Med, Boston, MA USA. [Hughes, Kevin S.] Bermuda Canc Genet & Risk Assessment Clin, Hamilton, Bermuda. RP Hughes, KS (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. EM MMOSKOS@mgh.harvard.edu; kshughes@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 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 2015 VL 154 IS 2 BP 435 EP 437 DI 10.1007/s10549-015-3620-z PG 3 WC Oncology SC Oncology GA CW7OL UT WOS:000365188600021 PM 26498020 ER PT J AU Rosenberg, SM Moskowitz, CS Ford, JS Henderson, TO Frazier, AL Diller, LR Hudson, MM Stanton, AL Chou, JF Smith, S Leisenring, WM Mertens, AC Cox, CL Nathan, PC Krull, KR Robison, LL Oeffinger, KC AF Rosenberg, Shoshana M. Moskowitz, Chaya S. Ford, Jennifer S. Henderson, Tara O. Frazier, A. Lindsay Diller, Lisa R. Hudson, Melissa M. Stanton, Annette L. Chou, Joanne F. Smith, Stephanie Leisenring, Wendy M. Mertens, Ann C. Cox, Cheryl L. Nathan, Paul C. Krull, Kevin R. Robison, Leslie L. Oeffinger, Kevin C. TI Health Care Utilization, Lifestyle, and Emotional Factors and Mammography Practices in the Childhood Cancer Survivor Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BRIEF SYMPTOM INVENTORY-18; YOUNG-ADULT CANCER; BODY-MASS INDEX; BREAST-CANCER; CHEST RADIATION; SCREENING MAMMOGRAPHY; HODGKINS-DISEASE; FAMILY-HISTORY; OVARIAN-CANCER; FOLLOW-UP AB Background: Women with a history of chest radiotherapy have an increased risk of breast cancer; however, many do not undergo annual recommended screening mammography. We sought to characterize the relationship between mammography and potentially modifiable factors, with the goal of identifying targets for intervention to improve utilization. Methods: Of 625 female participants sampled from the Childhood Cancer Survivor Study, who were treated with chest radiotherapy, 551 responded to a survey about breast cancer screening practices. We used multivariate Poisson regression to assess several lifestyle and emotional factors, health care practices, and perceived breast cancer risk, in relation to reporting a screening mammogram within the last two years. Results: Women who had a Papanicolaou test [prevalence ratio (PR): 1.77; 95% confidence interval (CI) 1.26-2.49], and who perceived their breast cancer risk as higher than the average woman were more likely to have had a mammogram (PR, 1.26; 95% CI, 1.09-1.46). We detected an attenuated effect of echocardiogram screening [PR, 0.70; 95% CI (0.52-0.95)] on having a mammogram among older women compared with younger women. Smoking, obesity, physical activity, coping, and symptoms of depression and somatization were not associated with mammographic screening. Conclusion: Our findings suggest that compliance with routine and risk-based screening can be an important indicator of mammography in childhood cancer survivors. In addition, there is a need to ensure women understand their increased breast cancer risk, as a means to encouraging them to follow breast surveillance guidelines. Impact: Screening encounters could be used to promote mammography compliance in this population. (C) 2015 AACR. C1 [Rosenberg, Shoshana M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rosenberg, Shoshana M.; Frazier, A. Lindsay; Diller, Lisa R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moskowitz, Chaya S.; Ford, Jennifer S.; Chou, Joanne F.; Smith, Stephanie; Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Henderson, Tara O.] Univ Chicago, Chicago, IL 60637 USA. [Hudson, Melissa M.; Cox, Cheryl L.; Krull, Kevin R.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Stanton, Annette L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Mertens, Ann C.] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Nathan, Paul C.] Univ Toronto, Hosp Sick Children, Toronto, ON M5S 1A1, Canada. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 300 East 66th St, New York, NY 10065 USA. EM oeffingk@mskcc.org FU NCI [U24CA55727, R21CA106972, K05CA160724, R01CA134722, R01CA136783]; Memorial Sloan Kettering Cancer Center Core Grant [P30 CA008748, R25CA057711, R25CA92203]; Cancer Center Support CORE Grant [P30 CA21765]; American Lebanese Syrian Associated Charities; Harvard Clinical and Translational Science Center; National Center for Research Resources; National Center for Advancing Translational Sciences, NIH [8UL1TR000170-05]; Harvard University FX This work was supported by grants from the NCI: U24CA55727 (PI: G.T. Armstrong); R21CA106972, K05CA160724, and R01CA134722 (PI: K.C. Oeffinger); R01CA136783 (PI: C.S. Moskowitz) and Memorial Sloan Kettering Cancer Center Core Grant P30 CA008748 (PI: C. Thompson); R25CA057711 and R25CA92203 (to S.M. Rosenberg); Cancer Center Support CORE Grant P30 CA21765 to St. Jude Children's Research Hospital, and by the American Lebanese Syrian Associated Charities. This work was also conducted with support from The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health care centers). NR 55 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2015 VL 24 IS 11 BP 1699 EP 1706 DI 10.1158/1055-9965.EPI-14-1377 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CX3KV UT WOS:000365598600008 PM 26304504 ER PT J AU Szulkin, R Karlsson, R Whitington, T Aly, M Gronberg, H Eeles, RA Easton, DF Kote-Jarai, Z Al Olama, AA Benlloch, S Muir, K Giles, GG Southey, MC FitzGerald, LM Henderson, BE Schumacher, FR Haiman, CA Sipeky, C Tammela, TLJ Nordestgaard, BG Key, TJ Travis, RC Neal, DE Donovan, JL Hamdy, FC Pharoah, PDP Pashayan, N Khaw, KT Stanford, JL Thibodeau, SN McDonnell, SK Schaid, DJ Maier, C Vogel, W Luedeke, M Herkommer, K Kibel, AS Cybulski, C Lubinski, J Kluzniak, W Cannon-Albright, L Brenner, H Herrmann, V Holleczek, B Park, JY Sellers, TA Lim, HY Slavov, C Kaneva, RP Mitev, VI Spurdle, A Teixeira, MR Paulo, P Maia, S Pandha, H Michael, A Kierzek, A Batra, J Clements, JA Albanes, D Andriole, GL Berndt, SI Chanock, S Gapstur, SM Giovannucci, EL Hunter, DJ Kraft, P Le Marchand, L Ma, J Mondul, AM Penney, KL Stampfer, MJ Stevens, VL Weinstein, SJ Trichopoulou, A Bueno-De-Mesquita, BH Tjonneland, A Cox, DG Maehle, L Schleutker, J Lindstrom, S Wiklund, F AF Szulkin, Robert Karlsson, Robert Whitington, Thomas Aly, Markus Gronberg, Henrik Eeles, Rosalind A. Easton, Douglas F. Kote-Jarai, Zsofia Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Giles, Graham G. Southey, Melissa C. FitzGerald, Liesel M. Henderson, Brian E. Schumacher, Fredrick R. Haiman, Christopher A. Sipeky, Csilla Tammela, Teuvo L. J. Nordestgaard, Borge G. Key, Timothy J. Travis, Ruth C. Neal, David E. Donovan, Jenny L. Hamdy, Freddie C. Pharoah, Paul D. P. Pashayan, Nora Khaw, Kay-Tee Stanford, Janet L. Thibodeau, Stephen N. McDonnell, Shannon K. Schaid, Daniel J. Maier, Christiane Vogel, Walther Luedeke, Manuel Herkommer, Kathleen Kibel, Adam S. Cybulski, Cezary Lubinski, Jan Kluzniak, Wojciech Cannon-Albright, Lisa Brenner, Hermann Herrmann, Volker Holleczek, Bernd Park, Jong Y. Sellers, Thomas A. Lim, Hui-Yi Slavov, Chavdar Kaneva, Radka P. Mitev, Vanio I. Spurdle, Amanda Teixeira, Manuel R. Paulo, Paula Maia, Sofia Pandha, Hardev Michael, Agnieszka Kierzek, Andrzej Batra, Jyotsna Clements, Judith A. Albanes, Demetrius Andriole, Gerald L. Berndt, Sonja I. Chanock, Stephen Gapstur, Susan M. Giovannucci, Edward L. Hunter, David J. Kraft, Peter Le Marchand, Loic Ma, Jing Mondul, Alison M. Penney, Kathryn L. Stampfer, Meir J. Stevens, Victoria L. Weinstein, Stephanie J. Trichopoulou, Antonia Bueno-de-Mesquita, Bas H. Tjonneland, Anne Cox, David G. Maehle, Lovise Schleutker, Johanna Lindstroem, Sara Wiklund, Fredrik CA PRACTICAL Consortium Australian Prostate Canc BioResour BPC3 Consortium TI Genome-Wide Association Study of Prostate Cancer-Specific Survival SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SUSCEPTIBILITY LOCI; METAANALYSIS; COHORT AB Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. (C) 2015 AACR. C1 [Szulkin, Robert; Karlsson, Robert; Whitington, Thomas; Aly, Markus; Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Szulkin, Robert] Karolinska Inst, Stockholm Cty Council, Acad Primary Healthcare Ctr, SE-17177 Stockholm, Sweden. [Eeles, Rosalind A.; Kote-Jarai, Zsofia] Inst Canc Res, London SW3 6JB, England. [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England. [Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England. [Easton, Douglas F.; Al Olama, Ali Amin; Benlloch, Sara] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England. [Muir, Kenneth] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Giles, Graham G.; FitzGerald, Liesel M.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [Henderson, Brian E.; Schumacher, Fredrick R.; Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Sipeky, Csilla; Schleutker, Johanna] Univ Turku, Inst Biomed, Dept Med Biochem & Genet, Turku, Finland. [Tammela, Teuvo L. J.] Tampere Univ Hosp, Dept Urol, Tampere, Finland. [Tammela, Teuvo L. J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Fac Med & Hlth Sci, Copenhagen, Denmark. [Key, Timothy J.; Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol, Oxford, England. [Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge CB2 2QQ, England. [Neal, David E.] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge, England. [Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England. [Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. [Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford OX3 9DU, England. [Pharoah, Paul D. P.; Pashayan, Nora] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Pashayan, Nora] UCL, Dept Appl Hlth Res, London, England. [Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.] Mayo Clin, Rochester, MN USA. [Maier, Christiane; Luedeke, Manuel] Univ Hosp Ulm, Dept Urol, Ulm, Germany. [Vogel, Walther] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany. [Herkommer, Kathleen] Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-80290 Munich, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02115 USA. [Cybulski, Cezary; Lubinski, Jan; Kluzniak, Wojciech] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Cannon-Albright, Lisa] Vet Affairs Med Ctr, George E Wahlen Dept, Salt Lake City, UT 84148 USA. [Brenner, Hermann; Herrmann, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Holleczek, Bernd] Saarland Canc Registry, Saarbrucken, Germany. [Park, Jong Y.; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA. [Lim, Hui-Yi] Univ S Florida, H Lee Moffitt Canc Ctr, Biostat Program, Tampa, FL 33682 USA. [Slavov, Chavdar] Med Univ Sofia, Dept Urol, Sofia, Bulgaria. [Slavov, Chavdar] Med Univ Sofia, Alexandrovska Univ Hosp, Sofia, Bulgaria. [Kaneva, Radka P.; Mitev, Vanio I.] Med Univ, Mol Med Ctr, Dept Med Chem & Biochem, Sofia, Bulgaria. [Spurdle, Amanda] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia. [Teixeira, Manuel R.; Paulo, Paula; Maia, Sofia] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Oporto, Portugal. [Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej] Univ Surrey, Surrey, England. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr Qld, Brisbane, Qld 4001, Australia. [Batra, Jyotsna; Clements, Judith A.] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia. [Australian Prostate Canc BioResour] Australian Prostate Canc BioResource, Brisbane, Qld, Australia. [Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen; Mondul, Alison M.; Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, St Louis, MO USA. [Chanock, Stephen] Frederick Natl Lab Canc Res, Core Genotyping Facil, Gaithersburg, MD USA. [Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward L.; Ma, Jing] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hunter, David J.; Kraft, Peter; Lindstroem, Sara] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Ma, Jing; Penney, Kathryn L.] Brigham & Womens Hosp, Channing Lab, Dept Epidemiol, Boston, MA 02115 USA. [Ma, Jing; Penney, Kathryn L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece. [Trichopoulou, Antonia] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Trichopoulou, Antonia] Acad Athens, Bureau Epidemiol Res, Athens, Greece. [Bueno-de-Mesquita, Bas H.] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands. [Bueno-de-Mesquita, Bas H.] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Bueno-de-Mesquita, Bas H.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Bueno-de-Mesquita, Bas H.] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia. [Tjonneland, Anne] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Cox, David G.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Cox, David G.] Ctr Leon Berard, INSERM, Canc Res Ctr Lyon, UMR1052, F-69373 Lyon, France. [Maehle, Lovise] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Med Genet, Inherited Canc Res Grp, Oslo, Norway. [Schleutker, Johanna] Univ Tampere, BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna] FimLab Labs, Tampere, Finland. RP Szulkin, R (reprint author), Karolinska Inst, Box 281, SE-17177 Stockholm, Sweden. EM robert.szulkin@ki.se RI Teixeira, Manuel/E-4885-2011; Paulo, Paula/F-1441-2016; Batra, Jyotsna/B-4130-2011; Cox, David/A-2023-2009; Brenner, Hermann/B-4627-2017; OI albright, lisa/0000-0003-2602-3668; Teixeira, Manuel/0000-0002-4896-5982; Paulo, Paula/0000-0001-8387-2127; Giles, Graham/0000-0003-4946-9099; Clements, Judith/0000-0001-6026-1964; Karlsson, Robert/0000-0002-8949-2587; Cox, David/0000-0002-2152-9259; Brenner, Hermann/0000-0002-6129-1572; Eeles, Rosalind/0000-0002-3698-6241; Mondul, Alison/0000-0002-8843-1416 FU Swedish Cancer Society [2012/823]; Swedish Research Council [2014/2269] FX F. Wiklund was recipient of the Swedish Cancer Society grant 2012/823 and Swedish Research Council grant 2014/2269. NR 8 TC 7 Z9 7 U1 5 U2 9 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 2015 VL 24 IS 11 BP 1796 EP 1800 DI 10.1158/1055-9965.EPI-15-0543 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CX3KV UT WOS:000365598600020 PM 26307654 ER PT J AU Shimada, YJ Yamashita, T Koretsune, Y Kimura, T Abe, K Sasaki, S Mercuri, M Ruff, CT Giugliano, RP AF Shimada, Yuichi J. Yamashita, Takeshi Koretsune, Yukihiro Kimura, Tetsuya Abe, Kenji Sasaki, Shunichi Mercuri, Michele Ruff, Christian T. Giugliano, Robert P. TI Effects of Regional Differences in Asia on Efficacy and Safety of Edoxaban Compared With Warfarin - Insights From the ENGAGE AF-TIMI 48 Trial SO CIRCULATION JOURNAL LA English DT Article DE Atrial fibrillation; East Asia; Edoxaban; Japan; Warfarin ID NONVALVULAR ATRIAL-FIBRILLATION; ORAL ANTICOAGULANTS; JAPANESE; REGISTRY; STROKE; RISK AB Background: In 21,105 patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial, edoxaban was non-inferior to warfarin in preventing thromboembolic events while reducing bleeding. We compared results in Japan with the rest of East Asia (EA), including China, Korea, and Taiwan. Methods and Results: We compared baseline characteristics, time-in-therapeutic range (TTR) for warfarin, and outcomes (efficacy: stroke or systemic embolic events [SEE], safety: major bleeding). Interaction P values were used to assess for effect modification of treatment (higher-dose edoxaban [HDE, 60 mg/30 mg] vs. warfarin; lower-dose edoxaban [LDE, 30 mg/15 mg] vs. warfarin) by region with adjustments for baseline characteristics. Fewer patients in Japan (n=1,010) were female, taking aspirin or amiodarone, naive to warfarin (P<0.001 for each), had a history of stroke or transient ischemic attack (P=0.02), and more patients needed dose reduction (P<0.001) compared with EA (n= 933). The mean TTR was higher in Japan (70% vs. 56%, P<0.001). Evidence for statistical interactions was observed for HDE vs. warfarin by region for stroke/SEE (adjusted P-int=0.052) and major bleeding (adjusted P-int=0.048) with greater relative efficacy and safety with HDE in EA compared with Japan. No interactions were observed for LDE vs. warfarin after adjustment. Conclusions: HDE had a greater relative efficacy and safety in EA compared with Japan that was only partially explained by differences in baseline characteristics and TTR. C1 [Shimada, Yuichi J.; Ruff, Christian T.; Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ruff, Christian T.; Giugliano, Robert P.] TIMI Study Grp, Boston, MA USA. [Yamashita, Takeshi] Cardiovasc Inst, Div Cardiol, Tokyo, Japan. [Koretsune, Yukihiro] Osaka Natl Hosp, Natl Hosp Org, Osaka, Japan. [Kimura, Tetsuya] Daiichi Sankyo Co Ltd, Clin Planning Dept, Tokyo, Japan. [Abe, Kenji] Daiichi Sankyo Co Ltd, Clin Data & Biostat Dept, Tokyo, Japan. [Sasaki, Shunichi; Mercuri, Michele] Daiichi Sankyo Pharma Dev, Clin Dev Dept, Edison, NJ USA. RP Shimada, YJ (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St,PBB 1, Boston, MA 02445 USA. EM yshimada@partners.org OI Shimada, Yuichi/0000-0002-3494-307X FU Daiichi Sankyo; Boehringer Ingelheim; Tanabe-Mitsubishi; Merck Co; Johnson Johnson; Sanofi-Aventis; AstraZeneca; Brigham and Women's Hospital from Daiichi Sankyo FX Y.J.S. was reimbursed by Daiichi Sankyo, Inc for attending a conference. T.Y. has received honoraria from Daiichi Sankyo, Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Eisai, Tanabe-Mitsubishi, and Ono Pharmaceutical and grants from Daiichi Sankyo, Boehringer Ingelheim, and Tanabe-Mitsubishi. Y.K. has received honoraria from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. T.K. and K.A. are employees of Daiichi Sankyo Co, Ltd, Tokyo, Japan. M.M. and S.S. report being employees of Daiichi Sankyo. M.M. also reports holding a pending patent related to the clinical properties of edoxaban. C.T.R. served as a consultant and received honoraria from Daiichi Sankyo, Boehringer Ingelheim, and Bayer, and reports grants (through the Brigham and Women's Hospital) from Daiichi Sankyo. R.P.G. has received honoraria for consulting and/or CME lectures from Bristol-Myers Squibb, Janssen, Portola, Pfizer, Daiichi Sankyo, Merck & Co, and Sanofi-Aventis; and grant support through his institution from Daiichi Sankyo, Merck & Co, Johnson & Johnson, Sanofi-Aventis and AstraZeneca. NR 20 TC 7 Z9 7 U1 2 U2 2 PU JAPANESE CIRCULATION SOC PI TOYKO PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO, 100-0011, JAPAN SN 1346-9843 EI 1347-4820 J9 CIRC J JI Circ. J. PD NOV PY 2015 VL 79 IS 12 BP 2560 EP + DI 10.1253/circj.CJ-15-0574 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX5SP UT WOS:000365763100013 PM 26460886 ER PT J AU Sogg, S Friedman, KE AF Sogg, Stephanie Friedman, Kelli E. TI Getting Off on the Right Foot: The Many Roles of the Psychosocial Evaluation in the Bariatric Surgery Practice SO EUROPEAN EATING DISORDERS REVIEW LA English DT Review DE outcome; treatment; weight loss surgery; psychosocial; assessment ID WEIGHT-LOSS SURGERY; LAPAROSCOPIC GASTRIC BYPASS; INFORMED-CONSENT; HEALTH-STATUS; CANDIDATES; OBESITY; PREDICTORS; EXPECTATIONS; DISORDERS; OUTCOMES AB A thorough and specialized pre-operative psychosocial assessment is an important part of a comprehensive bariatric treatment protocol. Over time, the presurgical psychosocial evaluation has evolved from a cut-and-dried process of recommending whether a patient should or should not undergo surgery to a more nuanced and multifaceted process that serves multiple functions. In this article, we review the many ways in which the pre-operative psychosocial evaluation can enhance patient outcomes and adjustment and even the functioning of the interdisciplinary bariatric surgery team. Copyright (c) 2015 John Wiley & Sons, Ltd and Eating Disorders Association. C1 [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Friedman, Kelli E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27708 USA. [Friedman, Kelli E.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27708 USA. RP Sogg, S (reprint author), Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. EM ssogg@partners.org NR 39 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1072-4133 EI 1099-0968 J9 EUR EAT DISORD REV JI Eur. Eat. Disord. Rev. PD NOV PY 2015 VL 23 IS 6 SI SI BP 451 EP 456 DI 10.1002/erv.2395 PG 6 WC Psychology, Clinical SC Psychology GA CX5PC UT WOS:000365753200005 PM 26294256 ER PT J AU Albiges, L Fay, AP Xie, WL Krajewski, K McDermott, DF Heng, DYC Dariane, C DeVelasco, G Lester, R Escudier, B Choueiri, TK AF Albiges, Laurence Fay, Andre P. Xie, Wanling Krajewski, Katherine McDermott, David F. Heng, Daniel Y. C. Dariane, Charles DeVelasco, Guillermo Lester, Renee Escudier, Bernard Choueiri, Toni K. TI Efficacy of targeted therapies after PD-1/PD-L1 blockade in metastatic renal cell carcinoma SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Renal cell carcinoma; Targeted therapy; PD-1; PD-L1; VEGFR; mTOR ID TYROSINE KINASE INHIBITOR; ANTI-PD-L1 ANTIBODY; CANCER-PATIENTS; PHASE-3 TRIAL; SUNITINIB; SAFETY; EVEROLIMUS; SORAFENIB; SURVIVAL; REVERSAL AB Background: Monoclonal antibodies that target the programmed death-1 (PD-1)/programmed death-ligand 1(PD-L1) pathway have shown antitumour activity in metastatic renal cell carcinoma (mRCC) and are currently being developed in first-line (in combination) and in previously treated patients. The efficacy targeted therapy (TT) after PD-1/PD-L1 blockade is still unknown. Methods: Medical records of mRCC patients treated with investigational PD-1 or PD-L1 inhibitors at 4 academic institutions were reviewed. Patients who received subsequent treatment with TT were selected to collect outcome measures of subsequent TT. Results: Of 99 patients who received PD-1/PD-L1 blockade as part of clinical trials, 56 patients have received subsequent therapy: 44 patients received vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors and 12 received mammalian target of rapamycin (mTOR) inhibitors as first subsequent TT. Median follow up, from the start of subsequent TT was 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 blockade was administered as second-line, third-line or beyond third-line in 9 (16%), 24 (43%) and 23 patients (41%) respectively. Median time to treatment failure on subsequent TT was 6.6 months (range: 0.2+, 23.0). 1-year and 2 year overall survival from the initiation of subsequent TT was 58% (95% confidence interval (CI): 41-72%) and 36% (95% CI: 18-54%), respectively. Conclusion: Both VEGF/VEGFR and mTOR inhibitors demonstrate antitumour activity following PD-1/PD-L1 blockade. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Albiges, Laurence; Fay, Andre P.; Xie, Wanling; Krajewski, Katherine; DeVelasco, Guillermo; Lester, Renee; Choueiri, Toni K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Kidney Canc Ctr, Boston, MA 02215 USA. [Albiges, Laurence; Dariane, Charles; Escudier, Bernard] Univ Paris 11, Gustave Roussy Canc Campus, Dept Canc Med, Villejuif, France. [McDermott, David F.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Heng, Daniel Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada. [Heng, Daniel Y. C.] Univ Calgary, Calgary, AB, Canada. [McDermott, David F.; Choueiri, Toni K.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Boston, MA USA. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, 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; Michael Brigham; Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute for TKC; Unicancer - Fondation de France FX This work was supported by the DF/HCC Kidney Cancer SPORE P50 CA101942-01 to TKC, DFM. Funded in part by the Trust Family, Michael Brigham and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute for TKC. Funded by Unicancer - Fondation de France for LA. NR 23 TC 9 Z9 9 U1 2 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 2015 VL 51 IS 17 BP 2580 EP 2586 DI 10.1016/j.ejca.2015.08.017 PG 7 WC Oncology SC Oncology GA CX3UC UT WOS:000365623900012 PM 26346135 ER PT J AU Alfares, AA Kelly, MA McDermott, G Funke, BH Lebo, MS Baxter, SB Shen, J McLaughlin, HM Clark, EH Babb, LJ Cox, SW DePalma, SR Ho, CY Seidman, JG Seidman, CE Rehm, HL AF Alfares, Ahmed A. Kelly, Melissa A. McDermott, Gregory Funke, Birgit H. Lebo, Matthew S. Baxter, Samantha B. Shen, Jun McLaughlin, Heather M. Clark, Eugene H. Babb, Larry J. Cox, Stephanie W. DePalma, Steven R. Ho, Carolyn Y. Seidman, J. G. Seidman, Christine E. Rehm, Heidi L. TI Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity SO GENETICS IN MEDICINE LA English DT Article DE cardiomyopathy; genes; genetics; genetics testing; hypertrophy ID COST-EFFECTIVENESS MODEL; FABRY-DISEASE; PREVALENCE; VARIANTS; POPULATION; MUTATIONS; PHENOTYPE; ADULTS; HEART AB Purpose: Hypertrophic cardiomyopathy (HCM) is caused primarily by pathogenic variants in genes encoding sarcomere proteins. We report genetic testing results for HCM in 2,912 unrelated individuals with nonsyndromic presentations from a broad referral population over 10 years. Methods: Genetic testing was performed by Sanger sequencing for 10 genes from 2004 to 2007, by HCM CardioChip for 11 genes from 2007 to 2011 and by next-generation sequencing for 18, 46, or 51 genes from 2011 onward. Results: The detection rate is similar to 32% among unselected probands, with inconclusive results in an additional 15%. Detection rates were not significantly different between adult and pediatric probands but were higher in females compared with males. An expanded gene panel encompassing more than 50 genes identified only a very small number of additional pathogenic variants beyond those identifiable in our original panels, which examined 11 genes. Familial genetic testing in at-risk family members eliminated the need for longitudinal cardiac evaluations in 691 individuals. Based on the projected costs derived from Medicare fee schedules for the recommended clinical evaluations of HCM family members by the American College of Cardiology Foundation/American Heart Association, our data indicate that genetic testing resulted in a minimum cost savings of about $0.7 million. Conclusion: Clinical HCM genetic testing provides a definitive molecular diagnosis for many patients and provides cost savings to families. Expanded gene panels have not substantively increased the clinical sensitivity of HCM testing, suggesting major additional causes of HCM still remain to be identified. C1 [Alfares, Ahmed A.; Kelly, Melissa A.; McDermott, Gregory; Funke, Birgit H.; Lebo, Matthew S.; Baxter, Samantha B.; Shen, Jun; McLaughlin, Heather M.; Clark, Eugene H.; Babb, Larry J.; Cox, Stephanie W.; Rehm, Heidi L.] Partners Healthcare Personalized Med, Lab Mol Med, Boston, MA 02115 USA. [Alfares, Ahmed A.] Qassim Univ, Dept Pediat, Buraydah, Saudi Arabia. [Funke, Birgit H.; Lebo, Matthew S.; Shen, Jun; McLaughlin, Heather M.; Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Funke, Birgit H.; Lebo, Matthew S.; Shen, Jun; McLaughlin, Heather M.; Rehm, Heidi L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Funke, Birgit H.; Lebo, Matthew S.; Shen, Jun; McLaughlin, Heather M.; Rehm, Heidi L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [DePalma, Steven R.; Seidman, Christine E.] Howard Hughes Med Inst, Boston, MA 02115 USA. [DePalma, Steven R.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Ho, Carolyn Y.; Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Rehm, HL (reprint author), Partners Healthcare Personalized Med, Lab Mol Med, Boston, MA 02115 USA. EM hrehm@partners.org OI Shen, Jun/0000-0001-8362-7535; Lebo, Matthew/0000-0002-9733-5207 NR 32 TC 29 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD NOV PY 2015 VL 17 IS 11 BP 880 EP 888 DI 10.1038/gim.2014.205 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CX8TL UT WOS:000365977000007 PM 25611685 ER PT J AU Oishi, SM Marshall, N Hamilton, AB Yano, EM Lerner, B Scheuner, MT AF Oishi, Sabine M. Marshall, Nell Hamilton, Alison B. Yano, Elizabeth M. Lerner, Barbara Scheuner, Maren T. TI Assessing multilevel determinants of adoption and implementation of genomic medicine: an organizational mixed-methods approach SO GENETICS IN MEDICINE LA English DT Article DE genomic medicine; health services; implementation; organization; translation ID KEY INFORMANT TECHNIQUE; HEALTH-CARE; VETERANS; CONTINUUM; DELIVERY; PERSPECTIVE; PERFORMANCE; INTEGRATION; CHALLENGES; SERVICES AB Purpose: Adoption and implementation of evidence-based genetic and genomic medicine have been slow. We describe a methodology for identifying the influence of organizational factors on adoption and implementation of these services in health-care organizations. Methods: We illustrate a three-component, mixed-methods health services research approach, including expert panels, qualitative interviews with key informants, and quantitative surveys completed by key informants. Results: This research approach yielded a baseline assessment of existing genetic health-care models in the Veterans Health Administration and identified organizational barriers to and facilitators of adoption. In aggregate, the panel and key informant strategies created a communication network of relevant organizational stakeholders and a detailed foundation of organizational knowledge from which to design tools and models for implementation-level genetic/genomic translation. Conclusion: Expert panel and key informant strategies can be used to create a backdrop of stakeholder involvement and baseline organizational knowledge within which to plan translation research and to inform strategic planning and policies for adoption and implementation of genetic services in health-care organizations. C1 [Oishi, Sabine M.; Marshall, Nell; Hamilton, Alison B.; Yano, Elizabeth M.; Scheuner, Maren T.] Vet Affairs Greater Los Angeles Healthcare Syst, Vett Affairs Hlth Serv Res & Dev Ctr, Study Healthcare Innovat Implementat & Policy, Los Angeles, CA 90073 USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Lerner, Barbara] Vet Affairs Boston Healthcare Syst, Vet Affairs Hlth Serv Res & Dev Ctr Healthcare Or, Boston, MA USA. [Scheuner, Maren T.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Med Genet, Los Angeles, CA USA. [Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Oishi, SM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Vett Affairs Hlth Serv Res & Dev Ctr, Study Healthcare Innovat Implementat & Policy, Los Angeles, CA 90073 USA. EM sabine.oishi@va.gov FU VHA Health Services Research & Development (HSRD) Service [IBD 09-101, DNA 08-128]; National Institute of Mental Health [R25 MH080916-01A2]; VA HSRD QUERI; VA HSR&D Senior Research Career Scientist Award [05-195]; VA Greater Los Angeles HSR&D Center of Innovation [CIN 13-417]; VA HSRD Service FX The VHA Health Services Research & Development (HSR&D) Service (grants IBD 09-101 and DNA 08-128) funded the research presented in this article. At the time of the study, A.B.H. was an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work, Washington University, St Louis, Missouri, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and VA HSR&D QUERI. E.M.Y.'s effort was supported by a VA HSR&D Senior Research Career Scientist Award (no. 05-195). This work was further supported by the VA Greater Los Angeles HSR&D Center of Innovation (CIN 13-417). S.M.O. 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. All authors are employed by the Department of Veterans Affairs. A.B.H., E.M.Y, B.L., and M.T.S. receive research funding from the VA HSR&D Service. The views expressed within are solely those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the US government. NR 40 TC 0 Z9 0 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD NOV PY 2015 VL 17 IS 11 BP 919 EP 926 DI 10.1038/gim.2015.7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA CX8TL UT WOS:000365977000012 PM 25741861 ER PT J AU Krause, DS Scadden, DT AF Krause, Daniela S. Scadden, David T. TI A hostel for the hostile: the bone marrow niche in hematologic neoplasms SO HAEMATOLOGICA LA English DT Review ID HEMATOPOIETIC STEM-CELL; ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MICROVASCULAR ENDOTHELIAL-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; MESENCHYMAL STROMAL CELLS; CXCR4 ANTAGONIST AMD3100; IN-VIVO MODEL; PROGENITOR CELLS AB Our understanding of the biology of the normal hematopoietic stem cell niche has increased steadily due to improved murine models and sophisticated imaging tools. Less well understood, but of growing interest, is the interaction between cells in the bone marrow during the initiation, maintenance and treatment of hematologic neoplasms. This review summarizes the emerging concepts of the normal and leukemic hematopoietic bone marrow niche. Furthermore, it reviews current models of how the microenvironment of the bone marrow may contribute to or be modified by leukemogenesis. Finally, it provides the rationale for a "two-pronged" approach, directly targeting cancer cells themselves while also targeting the bone microenvironment to make it inhospitable to malignant cells and, ultimately, eradicating cancer stem-like cells. C1 [Krause, Daniela S.] Inst Tumor Biol & Expt Therapy, Frankfurt, Germany. [Scadden, David T.] Harvard Univ, Ctr Regenerat Med, Dept Stem Cell & Regenerat Biol, Boston, MA USA. [Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA USA. [Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Krause, DS (reprint author), Inst Tumor Biol & Expt Therapy, Georg Speyer Haus, Frankfurt, Germany. EM Krause@gsh.uni-frankfurt.de; dscadden@mgh.harvard.edu FU LOEWE Center for Cell and Gene Therapy Frankfurt (CGT); Georg-Speyer-Haus; German Federal Ministry of Health (BMG); Ministry of Higher Education, Research and the Arts of the State of Hessen (HMWK); HMWK [III L 4-518/17.004]; [U54 CA163191] FX This work was supported in part by the LOEWE Center for Cell and Gene Therapy Frankfurt (CGT) and institutional funds of the Georg-Speyer-Haus to D.S.K. The Georg-Speyer-Haus is funded jointly by the German Federal Ministry of Health (BMG) and the Ministry of Higher Education, Research and the Arts of the State of Hessen (HMWK). The LOEWE Center for Cell and Gene Therapy Frankfurt is funded by HMWK, reference number: III L 4-518/17.004 (2010). Grants U54 CA163191 suppported D.T.S. NR 134 TC 13 Z9 13 U1 1 U2 9 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD NOV PY 2015 VL 100 IS 11 BP 1376 EP 1387 DI 10.3324/heamatol.2014.113852 PG 12 WC Hematology SC Hematology GA CX5YC UT WOS:000365777400016 PM 26521296 ER PT J AU Chowdhury, F Kuchta, A Khan, AI Faruque, ASG Calderwood, SB Ryan, ET Qadri, F AF Chowdhury, Fahima Kuchta, Alison Khan, Ashraful Islam Faruque, A. S. G. Calderwood, Stephen B. Ryan, Edward T. Qadri, Firdausi TI The increased severity in patients presenting to hospital with diarrhea in Dhaka, Bangladesh since the emergence of the hybrid strain of Vibrio cholerae O1 is not unique to cholera patients SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Cholera; Vibrio cholerae; Hybrid; Watery diarrhea; Severity ID COLONIZATION FACTORS; COAGGLUTINATION TEST; IMMUNE-RESPONSES; CELL RESPONSES; MALNUTRITION; DISEASE; VIBRIO-CHOLERAE-01; SURVEILLANCE; PREVALENCE; ABSORPTION AB Background: A hybrid strain of Vibrio cholerae O1 El Tor that expresses a classical cholera toxin (CT) emerged in 2001. This hybrid variant rapidly replaced the previous El Tor strain around the world. The global emergence of this variant coincided with anecdotal reports that cholera patients were presenting with more severe dehydration and disease in many locations. Methods: A comparison was made of the severity of disease before and after the emergence of the hybrid strain in cholera patients attending an icddr, b hospital in Dhaka, Bangladesh. Results: It was found that cholera patients presented with more severe dehydration and severe disease in the later period. However, this was also true for all non-cholera patients as well. In addition, in sub-analyses of patients who presented with rotavirus and enterotoxigenic Escherichia coli (ETEC), similar results were found. Comparing the two periods for differences in patient characteristics, nutritional status, vaccination status, and income, no plausible cause for patients presenting with more severe disease was identified in the later period. Conclusions: As a shift in severity for both cholera and non-cholera was observed, these results indicate that the altered El Tor strain cannot fully explain the difference in cholera severity before and after 2001. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. C1 [Chowdhury, Fahima; Kuchta, Alison; Khan, Ashraful Islam; Faruque, A. S. G.; Qadri, Firdausi] Int Ctr Diarrheal Dis Res Icddr B, Dhaka, Bangladesh. [Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Qadri, F (reprint author), Int Ctr Diarrheal Dis Res Icddr B, Dhaka, Bangladesh. EM fqadri@icddrb.org FU governments of Australia, Bangladesh, Canada, Sweden; Swedish Agency for Research and Economic Cooperation [INT-ICDDR, B-HN-01-AV]; Fogarty/Ellison Fellowship in Global Health - Fogarty International Center at the National Institutes of Health [D43 TW005572]; [U01 AI058935]; [RO3 AI063079]; [AI106878] FX This research was supported by core grants to the icddr, b. icddr, b is thankful to the governments of Australia, Bangladesh, Canada, Sweden, and the UK for providing core/unrestricted support. Additionally, the study was supported by the following grants: U01 AI058935 (S.B.C. and E.T.R), RO3 AI063079 (F.Q.), AI106878 (E.T.R.), and the Swedish Agency for Research and Economic Cooperation (F.Q. and A.M.S.) (Sida-SAREC, grant INT-ICDDR, B-HN-01-AV). F.C. was a previous recipient of a Fogarty/Ellison Fellowship in Global Health awarded by the Fogarty International Center at the National Institutes of Health (D43 TW005572). NR 44 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 1201-9712 EI 1878-3511 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD NOV PY 2015 VL 40 BP 9 EP 14 DI 10.1016/j.ijid.2015.09.007 PG 6 WC Infectious Diseases SC Infectious Diseases GA CX3UL UT WOS:000365624800002 PM 26409202 ER PT J AU Folmer, RL Theodoroff, SM AF Folmer, Robert L. Theodoroff, Sarah M. TI Assessment of Blinding in a Tinnitus Treatment Trial Reply SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Letter C1 [Folmer, Robert L.; Theodoroff, Sarah M.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Folmer, Robert L.; Theodoroff, Sarah M.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Folmer, RL (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM Robert.Folmer@va.gov NR 3 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 2168-6181 EI 2168-619X J9 JAMA OTOLARYNGOL JI JAMA Otolaryngol-Head Neck Surg. PD NOV PY 2015 VL 141 IS 11 BP 1031 EP 1032 DI 10.1001/jamaoto.2015.2422 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CX1PZ UT WOS:000365469400021 PM 26583514 ER PT J AU Anderson, RE Wilcox, S Miller, ES AF Anderson, R. Eleanor Wilcox, Susan Miller, Emily S. TI A RARE BUT LETHAL CAUSE OF CHEST PAIN SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID ESOPHAGEAL PERFORATIONS; SPONTANEOUS RUPTURE; BOERHAAVES-SYNDROME; PRIMARY REPAIR; MANAGEMENT; EXPERIENCE C1 [Anderson, R. Eleanor; Wilcox, Susan; Miller, Emily S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Anderson, R. Eleanor] Brigham & Womens Hosp, Boston, MA 02115 USA. [Anderson, R. Eleanor; Wilcox, Susan; Miller, Emily S.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. RP Miller, ES (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2015 VL 49 IS 5 BP 698 EP 702 PG 5 WC Emergency Medicine SC Emergency Medicine GA CX0SN UT WOS:000365407100026 PM 26281817 ER PT J AU Wilcox, SR AF Wilcox, Susan R. TI A RARE BUT LETHAL CAUSE OF CHEST PAIN REPLY SO JOURNAL OF EMERGENCY MEDICINE LA English DT Letter ID RHABDOMYOLYSIS C1 [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 EI 1090-1280 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2015 VL 49 IS 5 BP 709 EP 709 DI 10.1016/j.jemermed.2015.01.008 PG 1 WC Emergency Medicine SC Emergency Medicine GA CX0SN UT WOS:000365407100030 PM 25797937 ER PT J AU Guillemette, L Lacroix, M Allard, C Patenaude, J Battista, MC Doyon, M Moreau, J Menard, J Ardilouze, JL Perron, P Cote, AM Hivert, MF AF Guillemette, Laetitia Lacroix, Marilyn Allard, Catherine Patenaude, Julie Battista, Marie-Claude Doyon, Myriam Moreau, Julie Menard, Julie Ardilouze, Jean-Luc Perron, Patrice Cote, Anne-Marie Hivert, Marie-France TI Preeclampsia is associated with an increased pro-inflammatory profile in newborns SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE Preeclampsia; Gestational hypertension; TNF alpha; Umbilical cord ID NECROSIS-FACTOR-ALPHA; SERUM-LEVELS; TNF-ALPHA; INTERLEUKIN-6; PREGNANCY; DIAGNOSIS; PLASMA AB Hypertensive disorders of pregnancy (HDP) lead to high rates of maternal and fetal morbidity. Existing studies on inflammatory marker TNF alpha. in HDP offspring are inconsistent. We performed a population-based cohort study of 636 pregnancies, including normotensive (NT) women and women with preeclampsia (PE) or gestational hypertension (GH). TNF alpha was measured in maternal blood in the first and second trimesters and in cord blood at the time of delivery. Cord blood TNF alpha was higher in off-spring delivered of women with PE (6.53 [4.94-8.38]pg/mL) versus those delivered of NT women (5.13 [4.11-6.72]pg/mL; p = 0.01), independent of confounders. Maternal TNF alpha levels were not different among groups (p > 0.1) in either the first or second trimester. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Guillemette, Laetitia; Lacroix, Marilyn; Patenaude, Julie; Battista, Marie-Claude; Ardilouze, Jean-Luc; Perron, Patrice; Cote, Anne-Marie; Hivert, Marie-France] Univ Sherbrooke, Fac Med & Sci Sante, Dept Med, Sherbrooke, PQ J1H 5N4, Canada. [Allard, Catherine] Univ Sherbrooke, Fac Sci, Dept Math, Sherbrooke, PQ J1K 2R1, Canada. [Doyon, Myriam; Moreau, Julie; Menard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Cote, Anne-Marie; Hivert, Marie-France] Univ Sherbrooke, Ctr Hosp, Ctr Rech, Sherbrooke, PQ J1H 5N4, Canada. [Hivert, Marie-France] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02215 USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, 133 Brookline Ave, Boston, MA 02215 USA. EM marie-france_hivert@harvardpilgrim.org FU Fonds de la recherche du Quebec en sante (FRQ-S) operating grant; Diabete Quebec internship award; FRQ-S Master's training award; Diabete Quebec grant; Canadian Diabetes Association operating grant; Canadian Diabetes Association; Maud Menten Award from the Institute of Genetics-Canadian Institute of Health Research; FRQ-S FX The study was supported by a Fonds de la recherche du Quebec en sante (FRQ-S) operating grant (to M.F.H.), a Diabete Quebec internship award and a FRQ-S Master's training award (to L.G.), a Diabete Quebec grant (to P.P.), and by a Canadian Diabetes Association operating grant (to JLA). M.F.H. is an FRQ-S research scholar and was awarded a Clinical Scientist Award by the Canadian Diabetes Association and the Maud Menten Award from the Institute of Genetics-Canadian Institute of Health Research. JLA is a FRQ-S junior 2 research scholar. Clinical assessments were performed at the Centre de Recherche du CHUS, which is a FRQ-S-supported research center. NR 13 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD NOV PY 2015 VL 112 BP 111 EP 114 DI 10.1016/j.jri.2015.09.003 PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA CX0EU UT WOS:000365370500019 PM 26454417 ER PT J AU Cawthon, PM Blackwell, TL Cauley, J Kado, DM Barrett-Connor, E Lee, CG Hoffman, AR Nevitt, M Stefanick, ML Lane, NE Ensrud, KE Cummings, SR Orwoll, ES AF Cawthon, Peggy M. Blackwell, Terri L. Cauley, Jane Kado, Deborah M. Barrett-Connor, Elizabeth Lee, Christine G. Hoffman, Andrew R. Nevitt, Michael Stefanick, Marcia L. Lane, Nancy E. Ensrud, Kristine E. Cummings, Steven R. Orwoll, Eric S. TI Evaluation of the Usefulness of Consensus Definitions of Sarcopenia in Older Men: Results from the Observational Osteoporotic Fractures in Men Cohort Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE sarcopenia; falls; fractures; mortality; functional limitation ID SKELETAL-MUSCLE MASS; CLINICALLY RELEVANT WEAKNESS; LOWER-EXTREMITY FUNCTION; LOW LEAN MASS; PHYSICAL PERFORMANCE; GRIP STRENGTH; CARDIOVASCULAR HEALTH; MORTALITY RISK; GAIT SPEED; FAT MASS AB ObjectiveTo evaluate the associations between definitions of sarcopenia and clinical outcomes and the ability of the definitions to discriminate those with a high likelihood of having these outcomes from those with a low likelihood. DesignOsteoporotic Fractures in Men Study. SettingSix clinical centers. ParticipantsCommunity-dwelling men aged 65 and older (N = 5,934). MeasurementsSarcopenia definitions from the International Working Group, European Working Group on Sarcopenia in Older Persons, Foundation for the National Institutes of Health Sarcopenia Project, Baumgartner, and Newman were evaluated. Recurrent falls were defined as two or more self-reported falls in the year after baseline (n = 694, 11.9%). Incident hip fractures (n = 207, 3.5%) and deaths (n = 2,003, 34.1%) were confirmed according to central review of medical records over 9.8 years. Self-reported functional limitations were assessed at baseline and 4.6 years later. Logistic regression or proportional hazards models were used to estimate associations between sarcopenia and falls, hip fractures, and death. The discriminative ability of the sarcopenia definitions (vs reference models) for these outcomes was evaluated using area under the receiver operating characteristic curve or C-statistics. Referent models included age alone for falls, functional limitations and mortality, and age and bone mineral density for hip fractures. ResultsThe association between sarcopenia according to the various definitions and risk of falls, functional limitations, and hip fractures was variable; all definitions were associated with greater risk of death, but none of the definitions materially changed discrimination based on the AUC and C-statistic when compared with reference models (change 1% in all models). ConclusionSarcopenia definitions as currently constructed did not consistently improve prediction of clinical outcomes in relatively healthy older men. C1 [Cawthon, Peggy M.; Blackwell, Terri L.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94158 USA. [Cauley, Jane] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Kado, Deborah M.; Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Lee, Christine G.] Portland VA Med Ctr, Portland, OR USA. [Hoffman, Andrew R.; Stefanick, Marcia L.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Nevitt, Michael] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Lane, Nancy E.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Minneapolis Vet Affairs Hlth Syst, Minneapolis, MN USA. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. RP Cawthon, PM (reprint author), Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94158 USA. EM pcawthon@sfcc-cpmc.net RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institutes of Health; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Center for Advancing Translational Sciences; NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128]; VA Clinical Science Research and Development Career Development Award [5IK2CW000729-02] FX MrOS is supported by National Institutes of Health funding. The National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, and NIH Roadmap for Medical Research provide support under grants U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. CGL receives support from a VA Clinical Science Research and Development Career Development Award, Project number 5IK2CW000729-02. NR 44 TC 14 Z9 14 U1 2 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 2015 VL 63 IS 11 BP 2247 EP 2259 DI 10.1111/jgs.13788 PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CX4NV UT WOS:000365678500002 PM 26502831 ER PT J AU Rodriguez, JC Dzierzewski, JM Fung, CH Jouldjian, S Josephson, KR Mitchell, MN Song, YS Martin, JL Alessi, CA AF Rodriguez, Juan C. Dzierzewski, Joseph M. Fung, Constance H. Jouldjian, Stella Josephson, Karen R. Mitchell, Michael N. Song, Yeonsu Martin, Jennifer L. Alessi, Cathy A. TI Association Between Pain and Functional Independence in Older Adults During and After Admission to Rehabilitation After an Acute Illness or Injury SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pain; aged; rehabilitation; functional independence ID QUALITY-OF-LIFE; HIP FRACTURE; POSTOPERATIVE PAIN; PERSISTENT PAIN; INPATIENT REHABILITATION; MEDICAL COMPLICATIONS; STROKE; RECOVERY; SURGERY; PEOPLE AB ObjectivesTo investigate the association between pain and functional independence in older adults during and after admission to rehabilitation after an acute illness or injury. DesignProspective, observational cohort study. SettingOne community and one Veterans Affairs rehabilitation center. ParticipantsIndividuals aged 65 and older admitted for rehabilitation after an acute illness or injury (postacute rehabilitation) (N=245; mean age 80.6, 72% male)). MeasurementsPain was assessed using the Geriatric Pain Measure (GPM, score 0-100). Functional independence was measured using the motor component of the Functional Independence Measure (mFIM, score 13-91). Both scores were obtained at admission; discharge; and 3-, 6-, and 9-month follow-up. In bivariate analyses, discharge GPM and persistent pain (lasting >3months) were evaluated as predictors of mFIM score at 9months. Applying a multilevel modeling (MLM) approach, individual deviations in GPM scores were used to predict variations in mFIM. ResultsAt admission, 210 participants (87.9%) reported pain (16.3% mild (GPM<30); 49.3% moderate (GPM: 30-69); 22.1% severe (GPM>70)); 21.3% reported persistent pain after discharge. The bivariate analyses did not find statistically significant associations between discharge GPM or persistent pain and mFIM score at 9months, but in the MLM analysis, deviations in GPM were significant predictors of deviations in mFIM score, suggesting that, when individuals experienced above-average levels of pain (GPM > their personal mean GPM), they also experienced worse functional independence (mFIM160 kDa. High molecular weight species are by far the most prevalent and appear to be built from similar to 7 kDa A beta species. The similar to 7 kDa A beta species resist denaturation by chaotropic agents and have a higher A beta 42/A beta 40 ratio than monomers, and are unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1. Discussion: Further analysis of brain-derived similar to 7 kDa Ab species, the mechanism by which they assemble and the structures they form should reveal therapeutic and diagnostic opportunities. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Mc Donald, Jessica M.; O'Malley, Tiernan T.; Liu, Wen; Mably, Alexandra J.; Walsh, Dominic M.] Brigham & Womens Hosp, Ctr Neurol Dis, Lab Neurodegenerat Res, Boston, MA 02115 USA. [Mc Donald, Jessica M.; O'Malley, Tiernan T.; Liu, Wen; Mably, Alexandra J.; Walsh, Dominic M.] Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. [O'Malley, Tiernan T.] Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin 2, Ireland. [Brinkmalm, Gunnar; Portelius, Erik] Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Wittbold, William M., III] Wyatt Technol Corp, Woburn, MA USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Charlestown, MA USA. [Frosch, Matthew P.] Harvard Univ, Sch Med, Massachusetts Gen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Walsh, DM (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Lab Neurodegenerat Res, 75 Francis St, Boston, MA 02115 USA. EM dwalsh3@partners.org FU National Institutes of Health [AG027443, AG046275]; BrightFocus Foundation; Medical Research Council, UK (MRC CFAS) [G0900582]; Massachusetts Alzheimer's Disease Research Center [AG05134] FX This work was supported by grants to DMW from the National Institutes of Health (AG027443 and AG046275), BrightFocus Foundation, the Medical Research Council, UK (MRC CFAS, grant number G0900582), and to the Massachusetts Alzheimer's Disease Research Center (AG05134). We thank Drs. H. Vinters, T. Revesz, M. Farrell, N. Cairns, and J. Cleary for providing human brain tissue. Drs. D. Schenk, P. Seubert, and G. Basi kindly provided 3D6, 266, 2G3, and 21F12. Dr. D. Holtzman provided HJ2 and HJ7.4 and Dr. D. Selkoe provided pre-beta and Z31. Pro-biodrug provided antibody 07/1 and synthetic A beta pE3-40. We are grateful to K. Fitch for technical assistance and to Dr. J. Champagne for use of the Eclipse DualTec AF4. NR 67 TC 8 Z9 8 U1 3 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 2015 VL 11 IS 11 BP 1286 EP 1305 DI 10.1016/j.jalz.2015.01.005 PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA CW7FH UT WOS:000365162900004 PM 25846299 ER PT J AU Barnes, J Dickerson, BC Frost, C Jiskoot, LC Wolk, D van der Flier, WM AF Barnes, Josephine Dickerson, Bradford C. Frost, Chris Jiskoot, Lize C. Wolk, David van der Flier, Wiesje M. TI Alzheimer's disease first symptoms are age dependent: Evidence from the NACC dataset SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Clinical neurology history; First symptoms; Cognition; Behavior; Neuropsychology; Age ID POSTERIOR CORTICAL ATROPHY; UNIFORM DATA SET; EARLY-ONSET DEMENTIA; NEUROPSYCHIATRIC SYMPTOMS; CLINICAL CHARACTERISTICS; BEHAVIORAL SYMPTOMS; NATIONAL INSTITUTE; BRAIN ATROPHY; DIAGNOSIS; PATTERN AB Introduction: Determining the relationship between age and Alzheimer's disease (AD) presentation is important to improve understanding and provide better patient services. Methods: We used AD patient data (N = 7815) from the National Alzheimer Coordinating Center database and multinomial logistic regression to investigate presentation age and first cognitive/behavioral symptoms. Results: The odds of having a nonmemory first cognitive symptom (including impairment in judgment and problem solving, language, and visuospatial function) increased with younger age (P < .001, all tests). Compared with apathy/withdrawal, the odds of having depression and "other" behavioral symptoms increased with younger age (P<.02, both tests), whereas the odds of having psychosis and no behavioral symptom increased with older age (P<.001, both tests). Discussion: There is considerable heterogeneity in the first cognitive/behavioral symptoms experienced by AD patients. Proportions of these symptoms change with age with patients experiencing increasing nonmemory cognitive symptoms and more behavioral symptoms at younger ages. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Barnes, Josephine] UCL, Inst Neurol, Natl Hosp Neurol & Neurosurg, Dept Neurodegenerat Dis,Dementia Res Ctr, London, England. [Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Frontotemporal Dementia Unit, Boston, MA USA. [Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Ctr, Boston, MA USA. [Frost, Chris] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England. [Jiskoot, Lize C.; van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Neurol, Amsterdam, Netherlands. [Jiskoot, Lize C.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Wolk, David] Univ Penn, Penn Memory Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. RP Barnes, J (reprint author), UCL, Inst Neurol, Natl Hosp Neurol & Neurosurg, Dept Neurodegenerat Dis,Dementia Res Ctr, London, England. EM j.barnes@ucl.ac.uk FU NIA [U01 AG016976]; Wolfson Foundation; Alzheimer's Research UK; Brain Research Trust; NIHR Queen Square Dementia BRU; NIH [P50 AG05134]; Alzheimer Nederland; Stichting VUmc fonds FX The authors would like to thank Dr Manja Lehmann (Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology) for her helpful review of the manuscript and those associated with NACC database for their help in conducting this research. The NACC database is funded by NIA Grant U01 AG016976. J Barnes is an Alzheimer's Research UK Senior Research Fellow based at the Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology. The Dementia Research Centre is an Alzheimer's Research UK Co-ordinating Centre, is supported by the Wolfson Foundation, and has also received equipment funded by Alzheimer's Research UK and Brain Research Trust. Part of this work was supported by the NIHR Queen Square Dementia BRU. B Dickerson is supported in part by a grant from the NIH, P50 AG05134. W van der Flier works at the VUmc Alzheimer center, which is supported by Alzheimer Nederland and Stichting VUmc fonds. NR 54 TC 6 Z9 6 U1 5 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 2015 VL 11 IS 11 BP 1349 EP 1357 DI 10.1016/j.jalz.2014.12.007 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CW7FH UT WOS:000365162900009 PM 25916562 ER PT J AU Genkinger, JM Kitahara, CM Bernstein, L de Gonzalez, AB Brotzman, M Elena, JW Giles, GG Hartge, P Singh, PN Stolzenberg-Solomon, RZ Weiderpass, E Adami, HO Anderson, KE Beane-Freeman, LE Buring, JE Fraser, GE Fuchs, CS Gapstur, SM Gaziano, JM Helzlsouer, KJ Lacey, JV Linet, MS Liu, JJ Park, Y Peters, U Purdue, MP Robien, K Schairer, C Sesso, HD Visvanathan, K White, E Wolk, A Wolpin, BM Zeleniuch-Jacquotte, A Jacobs, EJ AF Genkinger, J. M. Kitahara, C. M. Bernstein, L. de Gonzalez, A. Berrington Brotzman, M. Elena, J. W. Giles, G. G. Hartge, P. Singh, P. N. Stolzenberg-Solomon, R. Z. Weiderpass, E. Adami, H. -O. Anderson, K. E. Beane-Freeman, L. E. Buring, J. E. Fraser, G. E. Fuchs, C. S. Gapstur, S. M. Gaziano, J. M. Helzlsouer, K. J. Lacey, J. V., Jr. Linet, M. S. Liu, J. J. Park, Y. Peters, U. Purdue, M. P. Robien, K. Schairer, C. Sesso, H. D. Visvanathan, K. White, E. Wolk, A. Wolpin, B. M. Zeleniuch-Jacquotte, A. Jacobs, E. J. TI Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies SO ANNALS OF ONCOLOGY LA English DT Review DE central adiposity; BMI; pancreatic cancer; pooled analysis ID BODY-MASS INDEX; LONGITUDINAL FOLLOW-UP; WAIST CIRCUMFERENCE; CARDIOVASCULAR-DISEASE; ABDOMINAL ADIPOSITY; INSULIN-RESISTANCE; PHYSICAL-ACTIVITY; BREAST-CANCER; RISK-FACTORS; HEALTH AB positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. Design: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity ( e. g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood ( ages 18- 21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later ( n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios ( HRs) and 95% confidence intervals ( CIs) were calculated using Cox proportional hazards regression models. Results: Higher waist-to-hip ratio ( HR = 1.09, 95% CI 1.02- 1.17 per 0.1 increment) and waist circumference ( HR = 1.07, 95% CI 1.00- 1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality ( HR = 1.18, 95% CI 1.11- 1.25 per 5 kg/ m2), with increased risk observed in both overweight and obese individuals ( compared with BMI of 21.0 to < 23 kg/ m(2), HR = 1.36, 95% CI 1.20- 1.55 for BMI 25.0 < 27.5 kg/ m2, HR = 1.48, 95% CI 1.20- 1.84 for BMI 27.5 to < 30 kg/ m2, HR = 1.43, 95% CI 1.11- 1.85 for BMI = 30 kg/ m2). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality ( HR = 1.05, 95% CI 1.01- 1.10 per 5 kg/ m2). Conclusions: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life. C1 [Genkinger, J. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Genkinger, J. M.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Kitahara, C. M.; de Gonzalez, A. Berrington; Hartge, P.; Stolzenberg-Solomon, R. Z.; Beane-Freeman, L. E.; Linet, M. S.; Liu, J. J.; Park, Y.; Purdue, M. P.; Schairer, C.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. [Bernstein, L.] City Hope Natl Med Ctr, Div Canc Etiol, Duarte, CA 91010 USA. [Brotzman, M.] WESTAT Corp, Rockville, MD 20850 USA. [Elena, J. W.] NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD 20892 USA. [Giles, G. G.] Univ Melbourne, Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, G. G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia. [Singh, P. N.; Fraser, G. E.] Loma Linda Univ, Sch Med, Dept Epidemiol Biostat & Populat Med, Loma Linda, CA USA. [Singh, P. N.; Fraser, G. E.] Loma Linda Univ, Ctr Hlth Res, Loma Linda, CA USA. [Weiderpass, E.] Univ Tromso, Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Weiderpass, E.] Canc Registry Norway, Dept Res, Oslo, Norway. [Weiderpass, E.; Adami, H. -O.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Weiderpass, E.] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland. [Adami, H. -O.; Buring, J. E.; Sesso, H. D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Anderson, K. E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Anderson, K. E.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Buring, J. E.; Sesso, H. D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, J. E.; Fuchs, C. S.; Sesso, H. D.; Wolpin, B. M.] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, C. S.; Wolpin, B. M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gapstur, S. M.; Jacobs, E. J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Gaziano, J. M.; Sesso, H. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Helzlsouer, K. J.] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Helzlsouer, K. J.; Visvanathan, K.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Park, Y.] Washington Univ, Div Publ Hlth Sci, Sch Med, St Louis, MO 63130 USA. [Peters, U.; White, E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Peters, U.; White, E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Robien, K.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA. [Visvanathan, K.] Johns Hopkins Sch Med, Sidney Kimmel Canc Ctr, Dept Med Oncol, Baltimore, MD USA. [Wolk, A.] Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-10401 Stockholm, Sweden. [Zeleniuch-Jacquotte, A.] NYU, Dept Populat Hlth, New York, NY USA. [Zeleniuch-Jacquotte, A.] NYU, Perlmutter Canc Ctr, New York, NY USA. RP Genkinger, JM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, 722 W 168th St,Rm 803, New York, NY 10032 USA. EM jg3081@columbia.edu RI Purdue, Mark/C-9228-2016; Weiderpass, Elisabete/M-4029-2016; Beane Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; OI Purdue, Mark/0000-0003-1177-3108; Weiderpass, Elisabete/0000-0003-2237-0128; Beane Freeman, Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU Intramural NIH HHS; NCI NIH HHS [CA105069, CA 016087, CA 34944, CA 40360, CA 77398, CA 97193, CA047988, K05 CA154337, P01 CA055075, P01 CA87969, P30 CA015704, R01 CA 098661, R01 CA105069, R01 CA124908, R01 CA39742, R01 CA49449, R01-CA14703, UM1 CA167552, UM1 CA182913, UM1 CA182934, UM1 CA186107, Z99CA999999]; NHLBI NIH HHS [HL 26490, HL 34595, HL043851, HL080467, R01- HL26210]; NIA NIH HHS [5U01AG018033, U01 AG18033]; NIEHS NIH HHS [ES 000260, Z01 ES049030-11]; PHS HHS [Z01 P010119] NR 62 TC 5 Z9 5 U1 1 U2 6 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 2015 VL 26 IS 11 BP 2257 EP 2266 DI 10.1093/annonc/mdv355 PG 10 WC Oncology SC Oncology GA CW7DW UT WOS:000365159200006 PM 26347100 ER PT J AU Graf, SA Stevenson, PA Holmberg, LA Till, BG Press, OW Chauncey, TR Smith, SD Philip, M Orozco, JJ Shustov, AR Green, DJ Libby, EN Bensinger, WI Pagel, JM Maloney, DG Zhou, Y Cassaday, RD Gopal, AK AF Graf, S. A. Stevenson, P. A. Holmberg, L. A. Till, B. G. Press, O. W. Chauncey, T. R. Smith, S. D. Philip, M. Orozco, J. J. Shustov, A. R. Green, D. J. Libby, E. N., III Bensinger, W. I. Pagel, J. M. Maloney, D. G. Zhou, Y. Cassaday, R. D. Gopal, A. K. TI Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma SO ANNALS OF ONCOLOGY LA English DT Article DE mantle lymphoma; autologous transplantation; rituximab; maintenance ID PROGRESSION-FREE SURVIVAL; NON-HODGKIN-LYMPHOMA; HIGH-DOSE THERAPY; HEMATOLOGIC MALIGNANCIES; ONSET NEUTROPENIA; RESPONSE CRITERIA; IMMUNOCHEMOTHERAPY; IMMUNOTHERAPY; CONSOLIDATION; MULTICENTER AB Background: High-dose therapy and autologous stem cell transplantation ( ASCT) improves outcomes for patients with mantle cell lymphoma ( MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab ( MR) after ASCT for MCL improves progression- free survival ( PFS). The maturation of these data and any benefit of MR on overall survival ( OS) remain to be defined. Patients and methods: In this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT ( n = 50) or did not ( n = 107). MR was treated as a time- dependent covariate to account for variation in timing of its initiation. Results: MR was associated with an improved PFS [ hazard ratio ( HR) 0.44; confidence interval ( CI) ( 0.24- 0.80), P = 0.007] and overall survival ( OS; HR 0.46; CI 0.23- 0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow- up of similar to 5 years. Grade 4 neutropenia was increased ( 34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed. Conclusions: These data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials. C1 [Graf, S. A.; Stevenson, P. A.; Holmberg, L. A.; Till, B. G.; Press, O. W.; Chauncey, T. R.; Smith, S. D.; Philip, M.; Orozco, J. J.; Shustov, A. R.; Green, D. J.; Libby, E. N., III; Bensinger, W. I.; Pagel, J. M.; Maloney, D. G.; Zhou, Y.; Cassaday, R. D.; Gopal, A. K.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Graf, S. A.; Chauncey, T. R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Graf, S. A.; Holmberg, L. A.; Till, B. G.; Press, O. W.; Chauncey, T. R.; Smith, S. D.; Philip, M.; Orozco, J. J.; Shustov, A. R.; Green, D. J.; Libby, E. N., III; Bensinger, W. I.; Pagel, J. M.; Maloney, D. G.; Cassaday, R. D.; Gopal, A. K.] Univ Washington, Dept Med, Seattle, WA 98109 USA. [Stevenson, P. A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Y.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Gopal, AK (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, 825 Eastlake Ave East,Mailstop G3-200, Seattle, WA 98109 USA. EM agopal@uw.edu FU NCI [P01 CA44991, K12 CA076930, K24 CA184039]; Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center Support Grant [P30 CA015704]; Frank and Betty Vandermeer, Don and Debbie Hunkins; Mary Aileen Wright Memorial Fund; David and Patricia Giuliani Family Foundation; Clinical Research of the Leukemia and Lymphoma Society; NIH [5T32 HL007093] FX This work was supported by research funding from NCI P01 CA44991, K12 CA076930, K24 CA184039, and Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Cancer Center Support Grant P30 CA015704, and gifts from Frank and Betty Vandermeer, Don and Debbie Hunkins, the Mary Aileen Wright Memorial Fund, and The David and Patricia Giuliani Family Foundation. A.K.G. is a Scholar in Clinical Research of the Leukemia and Lymphoma Society. SAG is supported by NIH 5T32 HL007093. NR 24 TC 4 Z9 5 U1 1 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 2015 VL 26 IS 11 BP 2323 EP 2328 DI 10.1093/annonc/mdv364 PG 6 WC Oncology SC Oncology GA CW7DW UT WOS:000365159200016 PM 26347113 ER PT J AU Musolino, PL Gong, Y Snyder, JMT Jimenez, S Lok, J Lo, EH Moser, AB Grabowski, EF Frosch, MP Eichler, FS AF Musolino, Patricia L. Gong, Yi Snyder, Juliet M. T. Jimenez, Sandra Lok, Josephine Lo, Eng H. Moser, Ann B. Grabowski, Eric F. Frosch, Matthew P. Eichler, Florian S. TI Brain endothelial dysfunction in cerebral adrenoleukodystrophy SO BRAIN LA English DT Article DE genetics; neurodegeneration; demyelination; leukodystrophy; neuroinflammation; blood-brain barrier ID X-LINKED ADRENOLEUKODYSTROPHY; CENTRAL-NERVOUS-SYSTEM; APPEARING WHITE-MATTER; CNS MYELOID CELLS; MULTIPLE-SCLEROSIS; IN-VITRO; C-MYC; LESION PROGRESSION; BARRIER DISRUPTION; TIGHT JUNCTIONS AB X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. C1 [Musolino, Patricia L.; Gong, Yi; Snyder, Juliet M. T.; Jimenez, Sandra; Frosch, Matthew P.; Eichler, Florian S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Musolino, Patricia L.; Gong, Yi; Eichler, Florian S.] Massachusetts Gen Hosp, Ctr Rare Neurol Dis, Boston, MA 02114 USA. [Lok, Josephine; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. [Lok, Josephine; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Moser, Ann B.] Kennedy Krieger Inst, Hugo W Moser Res Inst, Baltimore, MD USA. [Grabowski, Eric F.] Massachusetts Gen Hosp, Dept Paediat Haematol Oncol, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Eichler, FS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WAC 708, Boston, MA 02114 USA. EM feichler@partners.org FU Leblang Charitable Foundation; National Institute of Neurological Disease and Stroke (NINDS) [R25NS065743, K12NS066225] FX This study was supported by the Leblang Charitable Foundation and the National Institute of Neurological Disease and Stroke (NINDS) grants R25NS065743 and K12NS066225. NR 67 TC 3 Z9 3 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD NOV 1 PY 2015 VL 138 DI 10.1093/brain/awv250 PN 11 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CW6VF UT WOS:000365135700018 PM 26377633 ER PT J AU Krop, IE AF Krop, Ian E. TI OPTIMAL MANAGEMENT OF HER-2+ABC SO BREAST LA English DT Meeting Abstract C1 [Krop, Ian E.] Harvard Univ, Sch Med, 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 2015 VL 24 SU 3 MA IN04 BP S22 EP S23 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CW6AL UT WOS:000365078900005 ER PT J AU Mayer, EL Burstein, HJ AF Mayer, Erica L. Burstein, Harold J. TI Adjuvant endocrine therapy for postmenopausal women: Type and duration SO BREAST LA English DT Article DE Postmenopausal breast cancer; Tamoxifen; Aromatase inhibitors; Estrogen receptor; Late recurrence ID POSITIVE BREAST-CANCER; RECURRENCE SCORE; DISTANT RECURRENCE; RANDOMIZED-TRIAL; TAMOXIFEN; RISK; ANASTROZOLE; LETROZOLE AB Postmenopausal women with ER positive breast cancers benefit from adjuvant endocrine therapy. Most such patients should consider aromatase inhibitor therapy at some point in their treatment course as there are modest additional risk reductions over tamoxifen therapy, alone. Longer durations of therapy - beyond five years of tamoxifen - with either ongoing tamoxifen or an AI also improve cancer outcomes. Markers of risk for early recurrence are the same as those for late recurrence. Decisions regarding the optimal type and duration of therapy reflect patient preferences in light of well described side effects of tamoxifen and AI therapy, tolerability of treatment, and established clinical, pathological and genomic markers of risk. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Mayer, Erica L.; Burstein, Harold J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM hburstein@partners.org FU Eisai; Myriad; Pfizer FX Erica L Mayer has received research funding from Eisai, Myriad, and Pfizer. Harold J. Burstein has no potential conflicts of interest to declare. NR 14 TC 1 Z9 1 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 2015 VL 24 SU 2 BP S126 EP S128 DI 10.1016/j.breast.2015.07.028 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CW5NA UT WOS:000365041000027 PM 26279133 ER PT J AU Regan, MM AF Regan, Meredith M. TI Predicting benefit of endocrine therapy for early breast cancer SO BREAST LA English DT Article DE Adjuvant therapy; Aromatase inhibitor; Postmenopausal; Premenopausal; Tamoxifen ID INTERNATIONAL EXPERT CONSENSUS; 1-98 RANDOMIZED-TRIAL; OVARIAN SUPPRESSION; WOMEN; HIGHLIGHTS; TAMOXIFEN; RISK AB Adjuvant endocrine therapy is a mainstay of treatment for patients with endocrine-responsive early breast cancer. Questions remain concerning which patients should receive what type of endocrine therapy and for how long. Several factors have been considered as potential indicators to predict benefit of endocrine therapy, including patient factors, clinico-pathological factors and multigene assays. To date, factors associated with risk of recurrence have been the most widely adopted to influence treatment selection. The International Breast Cancer Study Group (IBCSG)-led adjuvant endocrine therapy trials BIG 1-98, for postmenopausal women, and SOFT and TEXT, for premenopausal women, can shed light on the role for risk of recurrence in identifying who should receive which type of adjuvant endocrine therapy and for how long. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Boston, MA USA. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM mregan@jimmy.harvard.edu FU US National Cancer Institute grant [CA075362]; International Breast Cancer Study Group; Novartis; Pfizer; Breast Cancer Research Foundation; Susan G. Komen for the Cure [KG080081]; US National Cancer Institute FX The IBCSG Statistical Center is partially supported by US National Cancer Institute grant CA075362. Pathology material collection and translational research in the BIG 1-98, TEXT and SOFT trials were supported by the International Breast Cancer Study Group, Novartis, Pfizer, Breast Cancer Research Foundation, Susan G. Komen for the Cure (KG080081), and the US National Cancer Institute. NR 10 TC 0 Z9 0 U1 1 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 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD NOV PY 2015 VL 24 SU 2 BP S129 EP S131 DI 10.1016/j.breast.2015.07.029 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CW5NA UT WOS:000365041000028 PM 26255197 ER PT J AU Rosenberg, SM Partridge, AH AF Rosenberg, Shoshana M. Partridge, Ann H. TI Management of breast cancer in very young women SO BREAST LA English DT Article DE Breast cancer; Young women; Age; Premenopausal ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; ADJUVANT ENDOCRINE THERAPY; CARCINOMA IN-SITU; CLINICAL-PRACTICE; RANDOMIZED-TRIAL; FERTILITY PRESERVATION; OVARIAN SUPPRESSION; AMERICAN SOCIETY; HORMONAL-THERAPY; CHEMOTHERAPY AB Breast cancer is the leading cause of cancer-related deaths in women age 40 and younger in developed countries, and although generally improving, survival rates for young women with breast cancer remain lower than for older women. Young women are more likely to develop more aggressive subtypes of breast cancer (more triple negative and more Human Epidermal Growth Factor Receptor 2 [HER2]positive disease) and present with more advanced stage disease. Previous research has demonstrated that young age is an independent risk factor for disease recurrence and death, although recent data suggest this may not be the case in certain tumor molecular subtypes. Recent preliminary evidence suggests potential unique biologic features of breast cancer that occurs in young women although this has yet to have been translated into treatment differences. There are clearly host differences that affect the management of breast cancer for young patients including generally being premenopausal at diagnosis, and fertility, genetics, and social/emotional issues in particular should be considered early in the course of their care. Despite an increased risk of local recurrence, young age alone is not a contraindication to breast conserving therapy given the equivalent survival seen in this population with either mastectomy or breast conservation. However, many young women in recent years are choosing bilateral mastectomy, even without a known hereditary predisposition to the disease. For those who need chemotherapy, multi-agent chemotherapy and biologic therapy targeting the tumor similar to the treatment in older women is the standard approach. Select young women will do well with hormone therapy only. Recent data from the TEXT and SOFT trials evaluating the optimal endocrine therapy for the first 5 years, and the ATTom and ATLAS trials demonstrating benefit from extended duration of tamoxifen (10 vs. 5 years), have further defined options for adjuvant endocrine therapy for young women with early breast cancer. Attention to adherence with endocrine therapy may be particularly important to improve outcomes in this population who are at increased risk of non-adherence compared to older women. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Rosenberg, Shoshana M.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Rosenberg, Shoshana M.; Partridge, Ann H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu FU Pink Agenda FX Dr. Rosenberg receives funding from The Pink Agenda, a 501(c)(3) non-profit organization. NR 51 TC 5 Z9 5 U1 0 U2 6 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 2015 VL 24 SU 2 BP S154 EP S158 DI 10.1016/j.breast.2015.07.036 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CW5NA UT WOS:000365041000033 PM 26255745 ER PT J AU Stover, DG Winer, EP AF Stover, Daniel G. Winer, Eric P. TI Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer SO BREAST LA English DT Article DE Breast cancer; Triple-negative; Chemotherapy; Adjuvant; BRCA; Precision cancer medicine ID PATHOLOGICAL COMPLETE RESPONSE; NEOADJUVANT CISPLATIN; MOLECULAR PORTRAITS; INTRINSIC SUBTYPES; RANDOMIZED-TRIALS; PHASE-3 TRIAL; THERAPY; CYCLOPHOSPHAMIDE; DOXORUBICIN; PACLITAXEL AB Cytotoxic chemotherapy remains the systemic therapy of choice for triple-negative breast cancer (TNBC), a poor-prognosis subtype of breast cancer. Growing data focusing on TNBC provides an opportunity to assess if we can tailor adjuvant chemotherapy based on patient and tumor characteristics. The standard of care for moderate-to-high risk TNBC remains a sequential anthracycline-taxane combination, with the potential for shorter and less toxic regimens in stage I disease. Platinums are promising in the neoadjuvant and metastatic settings but we await long-term outcome data before incorporation into standard regimens in the adjuvant setting. Specific subgroups within TNBC, such as BRCA mutation carriers, require special attention, and the role of platinums in these patients warrants further consideration. There is hope that in the future, further subdividing TNBC by gene expression profile, mutation, immune infiltrate, and others will reveal novel susceptibilities. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Stover, Daniel G.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Eric_Winer@dfci.harvard.edu OI Stover, Daniel/0000-0001-9003-8165 NR 38 TC 6 Z9 6 U1 0 U2 10 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 2015 VL 24 SU 2 BP S132 EP S135 DI 10.1016/j.breast.2015.07.032 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CW5NA UT WOS:000365041000029 PM 26255198 ER PT J AU Konstantinopoulos, PA Ceccaldi, R Shapiro, GI D'Andrea, AD AF Konstantinopoulos, Panagiotis A. Ceccaldi, Raphael Shapiro, Geoffrey I. D'Andrea, Alan D. TI Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer SO CANCER DISCOVERY LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; ADP-RIBOSE POLYMERASE; DNA-REPAIR PATHWAYS; CHROMOSOMAL TRANSLOCATION FORMATION; PEGYLATED LIPOSOMAL DOXORUBICIN; OLAPARIB MAINTENANCE THERAPY; MOUSE MAMMARY-TUMORS; 5' END RESECTION AB Approximately 50% of epithelial ovarian cancers (EOC) exhibit defective DNA repair via homologous recombination (HR) due to genetic and epigenetic alterations of HR pathway genes. Defective HR is an important therapeutic target in EOC as exemplified by the efficacy of platinum analogues in this disease, as well as the advent of PARP inhibitors, which exhibit synthetic lethality when applied to HR-deficient cells. Here, we describe the genotypic and phenotypic characteristics of HR-deficient EOCs, discuss current and emerging approaches for targeting these tumors, and present challenges associated with these approaches, focusing on development and overcoming resistance. Significance: Defective DNA repair via HR is a pivotal vulnerability of EOC, particularly of the high-grade serous histologic subtype. Targeting defective HR offers the unique opportunity of exploiting molecular differences between tumor and normal cells, thereby inducing cancer-specific synthetic lethality; the promise and challenges of these approaches in ovarian cancer are discussed in this review. (C)2015 AACR. C1 [Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Med Gynecol Oncol Program, Boston, MA 02115 USA. [Konstantinopoulos, Panagiotis A.; Ceccaldi, Raphael; Shapiro, Geoffrey I.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr DNA Damage & Repair, Boston, MA 02115 USA. [Ceccaldi, Raphael; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Early Drug Dev Ctr, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM panagiotis_konstantinopoulos@dfci.harvard.edu; alan_dandrea@dfci.harvard.edu FU Stand Up To Cancer-Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant [SU2C-AACR-DT16-15]; U.S. National Institutes of Health [P50CA168504]; Breast Cancer Research Foundation; Susan Smith Center for Women's Cancers, and the Department of Defense Ovarian Cancer Academy Award [W81XWH-10-1-0585] FX This research was supported by a Stand Up To Cancer-Ovarian Cancer Research Fund-Ovarian Cancer National Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant (grant number: SU2C-AACR-DT16-15). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. This work was also supported by grants from the U.S. National Institutes of Health (P50CA168504) and the Breast Cancer Research Foundation (to A.D. D'Andrea), the Susan Smith Center for Women's Cancers, and the Department of Defense Ovarian Cancer Academy Award (W81XWH-10-1-0585; to P.A. Konstantinopoulos). NR 178 TC 27 Z9 28 U1 1 U2 13 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 2015 VL 5 IS 11 BP 1137 EP 1154 DI 10.1158/2159-8290.CD-15-0714 PG 18 WC Oncology SC Oncology GA CX3KJ UT WOS:000365597400022 PM 26463832 ER PT J AU Brastianos, PK Carter, SL Santagata, S Cahill, DP Taylor-Weiner, A Jones, RT Van Allen, EM Lawrence, MS Horowitz, PM Cibulskis, K Ligon, KL Tabernero, J Seoane, J Martinez-Saez, E Curry, WT Dunn, IF Paek, SH Park, SH McKenna, A Chevalier, A Rosenberg, M Barker, FG Gill, CM Van Hummelen, P Thorner, AR Johnson, BE Hoang, MP Choueiri, TK Signoretti, S Sougnez, C Rabin, MS Lin, NU Winer, EP Stemmer-Rachamimov, A Meyerson, M Garraway, L Gabriel, S Lander, ES Beroukhim, R Batchelor, TT Baselga, J Louis, DN Getz, G Hahn, WC AF Brastianos, Priscilla K. Carter, Scott L. Santagata, Sandro Cahill, Daniel P. Taylor-Weiner, Amaro Jones, Robert T. Van Allen, Eliezer M. Lawrence, Michael S. Horowitz, Peleg M. Cibulskis, Kristian Ligon, Keith L. Tabernero, Josep Seoane, Joan Martinez-Saez, Elena Curry, William T. Dunn, Ian F. Paek, Sun Ha Park, Sung-Hye McKenna, Aaron Chevalier, Aaron Rosenberg, Mara Barker, Frederick G., II Gill, Corey M. Van Hummelen, Paul Thorner, Aaron R. Johnson, Bruce E. Hoang, Mai P. Choueiri, Toni K. Signoretti, Sabina Sougnez, Carrie Rabin, Michael S. Lin, Nancy U. Winer, Eric P. Stemmer-Rachamimov, Anat Meyerson, Matthew Garraway, Levi Gabriel, Stacey Lander, Eric S. Beroukhim, Rameen Batchelor, Tracy T. Baselga, Jose Louis, David N. Getz, Gad Hahn, William C. TI Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets SO CANCER DISCOVERY LA English DT Article ID BREAST-CANCER METASTASIS; GROWTH-FACTOR RECEPTOR; DEPENDENT KINASE 4/6; CELL LUNG-CANCER; ANTITUMOR-ACTIVITY; SINGLE METASTASES; PANCREATIC-CANCER; RANDOMIZED-TRIAL; PROSTATE-CANCER; PTEN LOSS AB Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing of 86 matched brain metastases, primary tumors, and normal tissue. In all clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases. SIGNIFICANCE: Decisions for individualized therapies in patients with brain metastasis are often made from primary-tumor biopsies. We demonstrate that clinically actionable alterations present in brain metastases are frequently not detected in primary biopsies, suggesting that sequencing of primary biopsies alone may miss a substantial number of opportunities for targeted therapy. (C)2015 AACR. C1 [Brastianos, Priscilla K.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Brastianos, Priscilla K.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brastianos, Priscilla K.; Getz, Gad] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA USA. [Brastianos, Priscilla K.; Jones, Robert T.; Van Allen, Eliezer M.; Ligon, Keith L.; Van Hummelen, Paul; Thorner, Aaron R.; Johnson, Bruce E.; Choueiri, Toni K.; Rabin, Michael S.; Lin, Nancy U.; Winer, Eric P.; Meyerson, Matthew; Garraway, Levi; Beroukhim, Rameen; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Brastianos, Priscilla K.; Carter, Scott L.; Taylor-Weiner, Amaro; Van Allen, Eliezer M.; Lawrence, Michael S.; Cibulskis, Kristian; McKenna, Aaron; Chevalier, Aaron; Rosenberg, Mara; Sougnez, Carrie; Meyerson, Matthew; Garraway, Levi; Gabriel, Stacey; Lander, Eric S.; Beroukhim, Rameen; Getz, Gad; Hahn, William C.] Broad Inst, Boston, MA USA. [Carter, Scott L.; Garraway, Levi] Dana Farber Canc Inst, Joint Ctr Canc Precis Med, Boston, MA 02115 USA. [Santagata, Sandro; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Santagata, Sandro; Ligon, Keith L.; Signoretti, Sabina; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Cahill, Daniel P.; Curry, William T.; Barker, Frederick G., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Jones, Robert T.; Van Hummelen, Paul; Thorner, Aaron R.; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Horowitz, Peleg M.; Dunn, Ian F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA. [Tabernero, Josep; Seoane, Joan] Vall dHebron Univ, Dept Med Oncol, Barcelona, Spain. [Tabernero, Josep; Seoane, Joan] Vall dHebron Univ, Dept Pathol, Barcelona, Spain. [Martinez-Saez, Elena] Vall dHebron Univ Hosp & Inst Oncol VHIO, Barcelona, Spain. [Park, Sung-Hye; McKenna, Aaron] Seoul Natl Univ, Coll Med, Dept Neurosurg, Seoul, South Korea. [Paek, Sun Ha; Park, Sung-Hye] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. [Hoang, Mai P.; Stemmer-Rachamimov, Anat; Louis, David N.; Getz, Gad] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Baselga, Jose] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. RP Brastianos, PK (reprint author), Massachusetts Gen Hosp, Div Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM pbrastianos@partners.org; carter.scott@jimmyharvard.edu; gadgetz@broadinstitute.org; william_hahn@dfci.harvard.edu OI Brastianos, Priscilla/0000-0003-4470-8425; Cahill, Daniel/0000-0003-2552-6546; Horowitz, Peleg/0000-0002-5177-1783 FU NIH (National Human Genome Research Institutes of Health Large-Scale Sequencing and Analysis Center) [U54 HG003067]; National Cancer Institute (TCGA Genome Characterization Center) [5U24CA143687]; Brain Science Foundation; Susan G. Komen for the Cure; Terri Brodeur Breast Cancer Foundation; Conquer Cancer Foundation; American Brain Tumor Association; Breast Cancer Research Foundation; Mary Kay Foundation; Novartis; [U54CA143798] FX This work was supported by a grant from the NIH (National Human Genome Research Institutes of Health Large-Scale Sequencing and Analysis Center) U54 HG003067 (to E.S. Lander) to the Broad Institute; the National Cancer Institute (TCGA Genome Characterization Center) 5U24CA143687 (to M. Meyerson and S. Gabriel) to the Broad Institute; the Brain Science Foundation (to P.K. Brastianos); Susan G. Komen for the Cure (to P.K. Brastianos); Terri Brodeur Breast Cancer Foundation (to P.K. Brastianos); Conquer Cancer Foundation (to P.K. Brastianos); the American Brain Tumor Association (to P.K. Brastianos); the Breast Cancer Research Foundation (to P.K. Brastianos); U54CA143798 (to R. Beroukhim and P.K. Brastianos); and the Mary Kay Foundation (to P.K. Brastianos and W.C. Hahn). W.C. Hahn and R. Beroukhim are supported by Novartis. G. Getz is the Paul C. Zamecnick, MD, Chair in Oncology at MGH. N.U. Lin and E.P. Winer are supported by the Breast Cancer Research Foundation. NR 52 TC 61 Z9 62 U1 7 U2 20 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 2015 VL 5 IS 11 BP 1164 EP 1177 DI 10.1158/2159-8290.CD-15-0369 PG 14 WC Oncology SC Oncology GA CX3KJ UT WOS:000365597400024 PM 26410082 ER PT J AU Newcomb, ME Bedoya, CA Blashill, AJ Lerner, JA O'Cleirigh, C Pinkston, MM Safren, SA AF Newcomb, Michael E. Bedoya, C. Andres Blashill, Aaron J. Lerner, Jonathan A. O'Cleirigh, Conall Pinkston, Megan M. Safren, Steven A. TI Description and Demonstration of Cognitive Behavioral Therapy to Enhance Antiretroviral Therapy Adherence and Treat Depression in HIV-Infected Adults SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE cognitive behavioral therapy; depression; HIV/AIDS; medication adherence ID RANDOMIZED CONTROLLED-TRIAL; CBT-AD; DRUG-RESISTANCE; HEALTH-PROBLEMS; UNITED-STATES; METAANALYSIS; RISK; MEN; SEX; DISORDERS AB There are an estimated 1.1 million individuals living with HIV/AIDS in the United States. In addition to the various medical comorbidities of HIV infection, depression is one of the most frequently co-occurring psychiatric conditions among HIV-infected individuals. Furthermore, depression has been found to be associated with nonadherence to antiretroviral therapy (ART), as well as HIV disease progression. Cognitive behavioral therapy (CBT) has repeatedly been found to effectively treat depression in adult populations, and CBT for adherence and depression (CBT-AD) is an effective treatment for improving depressive symptoms and medication adherence in the context of various chronic health conditions, including diabetes and HIV-infection. This paper provides a description of the CBT-AD approach to treat depression and ART adherence in HIV-infected adults, which we have developed and tested in our clinic, and for which detailed therapist and client guides exist. To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment, including Life-Steps for medication adherence, orientation to CBT-AD and psychoeducation, and suggestions for adaptation of core CBT modules for HIV-infected adults. Discussion of video demonstrations highlights differences in patient presentations and course of treatment between HIV-infected adults receiving CBT-AD and HIV-uninfected adults receiving traditional CBT for depression. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting. C1 [Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O'Cleirigh, Conall; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Newcomb, Michael E.; Bedoya, C. Andres; Blashill, Aaron J.; Lerner, Jonathan A.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Newcomb, Michael E.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Pinkston, Megan M.] Miriam Hosp, Providence, RI USA. [Pinkston, Megan M.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Newcomb, ME (reprint author), Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, 625 N Michigan Ave,Suite 2700, Chicago, IL 60611 USA. EM newcomb@northwestern.edu FU National Institute of Mental Health [R01MH084757, K24MH094214, K23MH096647] FX Funding for creation of the video role-plays came from a grant from the National Institute of Mental Health (R01MH084757; PI: Safren). During the preparation of this manuscript, Steven A. Safren was supported by a career development award from the National Institute of Mental Health (K24MH094214; PI: Safren), and Aaron J. Blashill was supported by a career development award from the National Institute of Mental Health (K23MH096647; PI: Blashill). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health. We acknowledge the important contributions of all study therapists on the trial from which this manuscript was based (in alphabetical order): C. Andres Bedoya, Aaron J. Blashill, Adam Gonzalez, Mark L. Hatzenbuehler, Ellen S. Hendriksen, Laura E. Knouse, Allison K. Labbe, Jonathan A. Lerner, Michael E. Newcomb, Megan M. Pinkston, Christina Psaros, Kelly Smith, and Lara Traeger. NR 28 TC 2 Z9 2 U1 5 U2 8 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 2015 VL 22 IS 4 BP 430 EP 438 DI 10.1016/j.cbpra.2014.02.001 PG 9 WC Psychology, Clinical SC Psychology GA CW8JP UT WOS:000365246000003 PM 26688659 ER PT J AU Shipherd, JC Fordiani, JM AF Shipherd, Jillian C. Fordiani, Joanne M. TI The Application of Mindfulness in Coping With Intrusive Thoughts SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE mindfulness; training; intrusive thoughts; Acceptance and Commitment Therapy; meditation ID POSTTRAUMATIC-STRESS-DISORDER; TRANSDIAGNOSTIC TREATMENT; EMOTIONAL DISORDERS; GENERALIZED ANXIETY; UNIFIED PROTOCOL; COGNITIVE MODEL; PAIN TOLERANCE; PANIC DISORDER; ACCEPTANCE; SUPPRESSION AB Across a variety of disorders, clients present with clinically significant intrusive thoughts. These thoughts can be problematic in their own right, with many clients reporting difficulty focusing on other therapeutic interventions due to problems with attention and increased distress that often accompany the experience of intrusive thoughts. Thus, cognitive-behavioral therapists can find value in learning thought management strategies that can be used with a variety of clients. Despite the increase in attention within the scientific literature and popular media on mindfulness-based interventions, many clinicians are unaware that it is possible to bring these skills into therapy as an adjunct to ongoing cognitive behavioral therapy (CBT). Thus, we provide an overview of how to teach brief mindfulness skills (5-10 minute trainings). Video segments will teach how to introduce these skills to clients, as well as highlight three skills that have been found to be particularly useful for coping with intrusive thoughts: observation of thoughts; nonjudgment of thoughts; and being larger than your thoughts. The benefits and challenges of using these skills will also be discussed. C1 [Shipherd, Jillian C.; Fordiani, Joanne M.] Natl Ctr PTSD Womens Hlth Sci Div, VA Boston Healthcare Syst, Boston, MA USA. [Shipherd, Jillian C.] MA Boston Univ, Sch Med, US Dept Vet Affairs, Boston, MA USA. [Fordiani, Joanne M.] MA Boston VA Res Inst Inc, Boston, MA USA. RP Shipherd, JC (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM Jillian.Shipherd@va.gov FU Department of Defense [W81XWH-09-1-0535] FX This research was funded by the Department of Defense (USAMRU-E; award W81XWH-09-1-0535; PI: Shipherd). The results described herein do not represent the views of Department of Defense or the Department of Veterans Affairs. NR 45 TC 1 Z9 1 U1 6 U2 18 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 2015 VL 22 IS 4 BP 439 EP 446 DI 10.1016/j.cbpra.2014.06.001 PG 8 WC Psychology, Clinical SC Psychology GA CW8JP UT WOS:000365246000004 ER PT J AU Blount, T Fredman, SJ Pukay-Martin, ND Macdonald, A Monson, CM AF Blount, Tabatha Fredman, Steffany J. Pukay-Martin, Nicole D. Macdonald, Alexandra Monson, Candice M. TI Cognitive-Behavioral Conjoint Therapy for PTSD: Application to an Operation Enduring Freedom Veteran SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article DE PTSD; CBCT for PTSD; couple; combat; veteran ID POSTTRAUMATIC-STRESS-DISORDER; RELATIONSHIP SATISFACTION; PSYCHOLOGICAL DISTRESS; CAREGIVER BURDEN; INITIAL FINDINGS; PARTNERS; SOLDIERS; SCALE; METAANALYSIS; VERSION AB There is increasing recognition that combat-related posttraumatic stress disorder (PTSD) affects the service member or veteran who experienced the trauma, his or her partner, and their relationship more broadly. Reactions by partners and other loved ones can also serve as impediments to, or facilitators of recovery in the wake of trauma exposure. In this article, we highlight research findings related to the association between PTSD symptoms and intimate relationship functioning in service members and veterans from the current conflicts and describe the application of cognitive-behavioral conjoint therapy for PTSD (CBCT for PTSD; Monson & Fredman, 2012), a disorder-specific couple therapy designed to simultaneously decrease PTSD symptoms and enhance intimate relationship functioning, to a veteran with combat-related PTSD and his wife. We conclude by discussing the powoful role that partners can play in helping individuals with combat-related PTSD recover from the disorder through improved communication, decreased couple-level avoidance, and modification of cognitions held by either member of the couple that can maintain PTSD symptoms and/or relationship distress. C1 [Blount, Tabatha] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Fredman, Steffany J.] Penn State Univ, University Pk, PA 16802 USA. [Pukay-Martin, Nicole D.] Cincinnati Vet Affairs Med Ctr, Ft Thomas Div, Cincinnati, OH USA. [Macdonald, Alexandra] VA Boston Healthcare Syst, Boston, MA USA. [Monson, Candice M.] Ryerson Univ, Toronto, ON, Canada. RP Blount, T (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7550 IH 10 West,Suite 1325, San Antonio, TX 78229 USA. EM blountt@uthscsa.edu NR 32 TC 1 Z9 1 U1 1 U2 3 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 2015 VL 22 IS 4 BP 458 EP 467 PG 10 WC Psychology, Clinical SC Psychology GA CW8JP UT WOS:000365246000007 ER PT J AU Szaflarski, JP Aurora, K Rawal, P Szaflarski, M Allendorfer, JB DeWolfe, J Pati, S Thomas, A Hoef, LLV Dworetzky, BA AF Szaflarski, Jerzy P. Aurora, Kanika Rawal, Pawan Szaflarski, M. Allendorfer, Jane B. DeWolfe, Jennifer Pati, Sandipan Thomas, Ashley Hoef, Lawrence L. Ver Dworetzky, Barbara A. TI Personalities of patients with nonepileptic psychogenic status SO EPILEPSY & BEHAVIOR LA English DT Article DE Psychogenic nonepileptic seizures (PNES); Nonepileptic psychogenic status (NEPS); Personality Assessment Inventory (PAI); Depression; Anxiety ID QUALITY-OF-LIFE; ASSESSMENT INVENTORY; PSEUDOEPILEPTIC SEIZURES; EPILEPTIC SEIZURES; MONITORING UNIT; PSEUDOSEIZURES; DISORDERS; DIAGNOSIS; SEMIOLOGY; PROFILE AB The purposes of this study were to determine whether personalities of patients with nonepileptic psychogenic status (NEPS) are different from those of patients with typical intermittent psychogenic nonepileptic seizures (iPNES) using the Personality Assessment Inventory (PAI) and to compare their PAI profiles with the population norms. We hypothesized that patients with NEPS have more psychopathology compared with patients with iPNES and that, as a group, patients with PNES (iPNES + NEPS) would have more psychopathology compared with healthy individuals. We first compared the PAI profiles of patients with iPNES and NEPS and then the profiles of patients with NEPS, iPNES, and PNES with population norms in order to assess which PAI specific scales differed between groups in order to better characterize the psychopathology of PNES. All patients admitted for diagnostic evaluation to the epilepsy monitoring unit (EMU) were prospectively approached for participation. All patient/family interviews were conducted by an epileptologist, and the diagnosis of iPNES or NEPS was confirmed in all cases through video/EEG and/or family interview. The population norms for PAI were obtained from the manual. Of the 224 approached patients, 130 completed the PAI, and included 43 iPNES and 11 with NEPS. There were no significant differences between the two groups in regard to demographic or PAI profiles. Comparison with population norms revealed the presence of abnormal personality profiles on all scales in patients with iPNES, NEPS, or PNES. We conclude that while the occurrence of NEPS is relatively common in patients with PNES, the demographic characteristics and personality profiles of patients with NEPS are not different from those of patients with iPNES. We also confirmed the presence of significant psychopathology in the group with PNES when compared with population norms. (C) 2015 Elsevier Inc. All rights reserved. C1 [Szaflarski, Jerzy P.; Aurora, Kanika; Rawal, Pawan; Allendorfer, Jane B.; DeWolfe, Jennifer; Pati, Sandipan; Thomas, Ashley; Hoef, Lawrence L. Ver] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Szaflarski, M.] Univ Alabama Birmingham, Dept Sociol, Birmingham, AL 35294 USA. [Szaflarski, Jerzy P.; DeWolfe, Jennifer; Hoef, Lawrence L. Ver] Univ Alabama Birmingham, UAB Epilepsy Ctr, Birmingham, AL 35294 USA. [Szaflarski, Jerzy P.; DeWolfe, Jennifer; Hoef, Lawrence L. Ver] Birmingham VA Med Ctr, Birmingham, AL USA. [Szaflarski, Jerzy P.] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, Cincinnati, OH USA. [Dworetzky, Barbara A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Szaflarski, JP (reprint author), Univ Alabama Birmingham, Dept Neurol, 1719 6th Ave South,CIRC 312, Birmingham, AL 35294 USA. EM szaflaj@uab.edu OI Dworetzky, Barbara/0000-0002-3364-2347; Szaflarski, Magdalena/0000-0002-6228-1405 NR 51 TC 0 Z9 0 U1 1 U2 4 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 2015 VL 52 BP 143 EP 148 DI 10.1016/j.yebeh.2015.09.001 PN A PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA CW4UH UT WOS:000364990000025 PM 26414344 ER PT J AU Woo, J Cohen, SA Grim, JE AF Woo, Janghee Cohen, Stacey A. Grim, Jonathan E. TI Targeted therapy in gastroesophageal cancers: past, present and future SO GASTROENTEROLOGY REPORT LA English DT Review DE esophageal cancer; gastric cancer; targeted therapy; molecular oncology ID ADVANCED GASTRIC-CANCER; PHASE-II TRIAL; ARBEITSGEMEINSCHAFT INTERNISTISCHE ONKOLOGIE; ADVANCED ESOPHAGEAL CANCER; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; METASTATIC BREAST-CANCER; JUNCTION ADENOCARCINOMA; DOUBLE-BLIND; OPEN-LABEL AB Gastroesophageal cancer is a significant global problem that frequently presents at an incurable stage and has very poor survival with standard chemotherapy approaches. This review will examine the epidemiology and molecular biology of gastroesophageal cancer and will focus on the key deregulated signaling pathways that have been targeted in the clinic. A comprehensive overview of clinical data highlighting successes and failures with targeted agents will be presented. Most notably, HER2-targeted therapy with the monoclonal antibody trastuzumab has proven beneficial in first-line therapy and has been incorporated into standard practice. Targeting the VEGF pathway has also proven beneficial, and the VEGFR-targeted monoclonal antibody ramucirumab is now approved for second-line therapy. In contrast to these positive results, agents targeting the EGFR and MET pathways have been evaluated extensively in gastroesophageal cancer but have repeatedly failed to show benefit. An increased understanding of the molecular predictors of response to targeted therapies is sorely needed. In the future, improved molecular pathology approaches should subdivide this heterogeneous disease entity to allow individualization of cancer therapy based on integrated and global identification of deregulated signaling pathways. Better patient selection, rational combinations of targeted therapies and incorporation of emerging immunotherapeutic approaches should further improve the treatment of this deadly disease. C1 [Woo, Janghee; Cohen, Stacey A.; Grim, Jonathan E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Woo, Janghee; Cohen, Stacey A.; Grim, Jonathan E.] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. [Grim, Jonathan E.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med, Seattle, WA 98108 USA. RP Grim, JE (reprint author), VA Puget Sound Hlth Care Syst, Hosp & Specialty Med, 1660 S Columbian Way S-111 ONC, Seattle, WA 98108 USA. EM jgrim@fhcrc.org FU NCI NIH HHS [T32 CA009515] NR 150 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND EI 2052-0034 J9 GASTROENTEROL REP JI Gastroenterol. Rep. PD NOV PY 2015 VL 3 IS 4 SI SI BP 316 EP 329 DI 10.1093/gastro/gov052 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW9FX UT WOS:000365305300006 PM 26510453 ER PT J AU Li, R Faden, DL Fakhry, C Langelier, C Jiao, YC Wang, YX Wilkerson, MD Pedamallu, CS Old, M Lang, J Loyo, M Ahn, SM Tan, M Gooi, Z Chan, J Richmon, J Wood, LD Hruban, RH Bishop, J Westra, WH Chung, CH Califano, J Gourin, CG Bettegowda, C Meyerson, M Papadopoulos, N Kinzler, KW Vogelstein, B DeRisi, JL Koch, WM Agrawal, N AF Li, Ryan Faden, Daniel L. Fakhry, Carole Langelier, Chaz Jiao, Yuchen Wang, Yuxuan Wilkerson, Matthew D. Pedamallu, Chandra Sekhar Old, Matthew Lang, James Loyo, Myriam Ahn, Sun Mi Tan, Marietta Gooi, Zhen Chan, Jason Richmon, Jeremy Wood, Laura D. Hruban, Ralph H. Bishop, Justin Westra, William H. Chung, Christine H. Califano, Joseph Gourin, Christine G. Bettegowda, Chetan Meyerson, Matthew Papadopoulos, Nickolas Kinzler, Kenneth W. Vogelstein, Bert DeRisi, Joseph L. Koch, Wayne M. Agrawal, Nishant TI Clinical, genomic, and metagenomic characterization of oral tongue squamous cell carcinoma in patients who do not smoke SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE head and neck cancer; oral tongue; squamous cell carcinoma; next-generation sequencing; nonsmokers ID EPSTEIN-BARR-VIRUS; HUMAN-PAPILLOMAVIRUS; NASOPHARYNGEAL CARCINOMA; HODGKINS-DISEASE; NEVER-DRINKERS; MUTATIONS; CANCER; HEAD; ALIGNMENT; DRINKING AB Background. Evidence suggests the incidence of oral tongue squamous cell carcinoma is increasing in young patients, many who have no history of tobacco use. Methods. We clinically reviewed 89 patients with oral tongue cancer. Exomic sequencing of tumor DNA from 6 nonsmokers was performed and compared to previously sequenced cases. RNA from 20 tumors was evaluated by massively parallel sequencing to search for potentially oncogenic viruses. Results. Non-smokers (53 of 89) were younger than smokers (36 of 89; mean, 50.4 vs 61.9 years; p < .001), and seemed more likely to be women (58.5% vs 38.9%; p = .069). Nonsmokers had fewer TP53 mutations (p = .02) than smokers. No tumor-associated viruses were detected. Conclusion. The young age of nonsmoking patients with oral tongue cancer and fewer TP53 mutations suggest a viral role in this disease. Our efforts to identify such a virus were unsuccessful. Further studies are warranted to elucidate the drivers of carcinogenesis in these patients. (C) 2014 Wiley Periodicals, Inc. C1 [Li, Ryan; Fakhry, Carole; Loyo, Myriam; Ahn, Sun Mi; Tan, Marietta; Gooi, Zhen; Chan, Jason; Richmon, Jeremy; Gourin, Christine G.; Koch, Wayne M.; Agrawal, Nishant] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Fakhry, Carole; Califano, Joseph] Greater Baltimore Med Ctr, Milton J Dance Head & Neck Ctr, Baltimore, MD USA. [Faden, Daniel L.] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA USA. [Langelier, Chaz] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Jiao, Yuchen; Wang, Yuxuan; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Agrawal, Nishant] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr, Baltimore, MD USA. [Jiao, Yuchen; Wang, Yuxuan; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Agrawal, Nishant] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA. [Wilkerson, Matthew D.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Wilkerson, Matthew D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Pedamallu, Chandra Sekhar; Meyerson, Matthew] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA. [Pedamallu, Chandra Sekhar; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Old, Matthew; Lang, James] Ohio State Univ, Dept Otolaryngol Head & Neck Surg, Columbus, OH 43210 USA. [Wood, Laura D.; Hruban, Ralph H.; Bishop, Justin; Westra, William H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Chung, Christine H.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Bettegowda, Chetan] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [DeRisi, Joseph L.] Howard Hughes Med Inst, Chevy Chase, MD USA. [DeRisi, Joseph L.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Agrawal, N (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,6th Floor, Baltimore, MD 21287 USA. EM nagrawal@jhmi.edu OI Chan, Jason/0000-0002-9480-4637 FU National Institutes of Health [RC2DE020957]; Virginia and D.K. Ludwig Fund for Cancer Research; Burroughs Wellcoma Award for Medical Scientists; Johns Hopkins Hospital Clinician Scientist Award; Johns Hopkins Head and Neck SPORE NIH/NIDCR [5P50DE019032] FX Contract grant sponsor: This work was supported by the National Institutes of Health grant RC2DE020957 and the Virginia and D.K. Ludwig Fund for Cancer Research, and the Burroughs Wellcoma Award for Medical Scientists, Johns Hopkins Hospital Clinician Scientist Award. This work was also supported by the Johns Hopkins Head and Neck SPORE NIH/NIDCR Grant 5P50DE019032. The manuscript/analysis of this article is based on a web database application provided by Research Information Technology Systems (RITS)-https://www.rits.onc.jhmi.edu/. NR 44 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1043-3074 EI 1097-0347 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD NOV PY 2015 VL 37 IS 11 BP 1642 EP 1649 DI 10.1002/hed.23807 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CX0SD UT WOS:000365406100021 PM 24954188 ER PT J AU Reisman, J Martineau, N Kairuki, A Mponzi, V Meda, AR Isangula, KG Thomas, E Plotkin, M Chan, GJ Davids, L Msemo, G Azayo, M Nelson, BD AF Reisman, Jonathan Martineau, Narra Kairuki, Allan Mponzi, Victor Meda, Amunga R. Isangula, Kahabi G. Thomas, Erica Plotkin, Marya Chan, Grace J. Davids, Leila Msemo, Georgina Azayo, Mary Nelson, Brett D. TI Validation of a novel tool for assessing newborn resuscitation skills among birth attendants trained by the Helping Babies Breathe program SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Birth asphyxia; Inter-rater reliability; Intrapartum-related complications; Low-income countries; Neonatal resuscitation; Newborn care; Objective structured clinical examination ID COMMUNICATION-SKILLS; CLINICAL COMPETENCE; EDUCATIONAL-IMPACT; VARIABILITY; EXAMINERS; AGREEMENT AB Objective: To validate a simplified objective structured clinical examination (OSCE) tool for evaluating the competency of birth attendants in low-resource countries who have been trained in neonatal resuscitation by the Helping Babies Breathe (HBB) program. Methods: A prospective cross-sectional study of the OSCE tool was conducted among trained birth attendants working at dispensaries, health centers, or hospitals in five regions of Tanzania between October 1, 2013, and May 1, 2014. A 13-item checklist was used to assess clinical competency in a simulated newborn resuscitation scenario. The OSCE tool was simultaneously administered by HBB trainers and experienced external evaluators. Paired results were compared using the Cohen kappa value to measure inter-rater reliability. Participant performance was rated by health cadre, region, and facility type. Results: Inter-rater reliability was moderate (kappa = 0.41-0.60) or substantial (kappa = 0.61-0.80) for eight of the OSCE items; agreement was fair (kappa = 0.21-0.41) for the remaining five items. The best OSCE performances were recorded among nurses and providers from facilities with high annual birth volumes. Conclusion: The simplified OSCE tool could facilitate efficient implementation of national-level HBB programs. Limitations in inter-rater reliability might be improved through additional training. (C) 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Reisman, Jonathan; Martineau, Narra; Kairuki, Allan; Meda, Amunga R.; Isangula, Kahabi G.; Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Reisman, Jonathan; Nelson, Brett D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. [Mponzi, Victor; Thomas, Erica; Plotkin, Marya] Jhpiego, Dar Es Salaam, Tanzania. [Meda, Amunga R.] Muhimbili Natl Hosp, Dar Es Salaam, Tanzania. [Isangula, Kahabi G.] Triangle Solut, Dar Es Salaam, Tanzania. [Chan, Grace J.] Boston Childrens Hosp, Div Med Crit Care, Boston, MA USA. [Davids, Leila] Childrens Investment Fund Fdn, London, England. [Msemo, Georgina; Azayo, Mary] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania. RP Reisman, J (reprint author), Harvard Univ, Sch Med, Dept Pediat, 55 Fruit St,Bulfinch 015, Boston, MA 02114 USA. EM reisman.jonathan@gmail.com OI Isangula, Kahabi/0000-0001-5409-0097; Nelson, Brett/0000-0002-5049-1798 FU Children's Investment Fund Foundation (London, UK) FX The present study was funded by the Children's Investment Fund Foundation (London, UK). NR 21 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 EI 1879-3479 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD NOV PY 2015 VL 131 IS 2 BP 196 EP 200 DI 10.1016/j.ijgo.2015.05.019 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CW3HN UT WOS:000364882700019 PM 26283225 ER PT J AU Natarajan, A Chavez, J Ahn, R Nelson, BD Eckardt, M Dulo, L Achieng, E Oguttu, M Tester, K Burke, TF AF Natarajan, Abirami Chavez, Jean Ahn, Roy Nelson, Brett D. Eckardt, Melody Dulo, Liddy Achieng, Emmaculate Oguttu, Monica Tester, Kristina Burke, Thomas F. TI Provider experiences with uterine balloon tamponade for uncontrolled postpartum hemorrhage in health facilities in Kenya SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Feasibility studies; Kenya; Maternal mortality; Postpartum hemorrhage; Uterine balloon tamponade ID MANAGEMENT; COUNTRIES AB Objective: To understand provider perceptions and experiences following training in the use of a condom-catheter uterine balloon tamponade (UBT) as second-line treatment for uncontrolled postpartum hemorrhage (PPH) in health facilities in Kenya. Methods: As part of a qualitative study, interviews of facility-based providers who had managed PPH following comprehensive PPH training were conducted between February and April 2014. Facilities were purposively sampled to represent a range of experience with UBT, facility size, and geography. Interviews continued until thematic saturation was achieved. Interview transcripts were analyzed for themes. Results: Overall, 68 providers from 29 facilities were interviewed, of whom 31 reported experience with UBT placement (25 midwives, 2 clinical officers, 4 medical officers). Qualitative analysis revealed several major themes. Providers used UBT appropriately within the PPH algorithm, although the timing and clinical severity of patients varied. UBT was most commonly used when bleeding was unresponsive to uterotonics, hysterectomy was unavailable, and referral times long. Providers reported that bleeding was arrested following UBT use in all except one patient, who had a suspected coagulopathy. Most providers described UBT as technically easy to use, although three described initial balloon displacement. Conclusion: UBT has been readily accepted by providers at all levels of training and is being incorporated into the existing PPH management algorithm in Kenya. (C) 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Eckardt, Melody; Tester, Kristina; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Dulo, Liddy; Achieng, Emmaculate; Oguttu, Monica] Kenya Med & Educ Trust, Kisumu, Kenya. RP Natarajan, A (reprint author), Zero Emerson Pl Suite 104, Boston, MA 02114 USA. EM abirami_natarajan@hms.harvard.edu OI Eckardt, Melody/0000-0001-9066-9856; Nelson, Brett/0000-0002-5049-1798 FU Saving Lives at Birth (Washington, DC, USA); IZUMI Foundation (Boston, MA, USA); Ujenzi Charitable Trust (Boston, MA, USA); Harvard Medical School (Boston, MA, USA) FX Funding was provided by Saving Lives at Birth (Washington, DC, USA), the IZUMI Foundation (Boston, MA, USA), Ujenzi Charitable Trust (Boston, MA, USA), and Harvard Medical School (Boston, MA, USA). NR 14 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 EI 1879-3479 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD NOV PY 2015 VL 131 IS 2 BP 201 EP 204 DI 10.1016/j.ijgo.2015.05.020 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CW3HN UT WOS:000364882700020 PM 26277599 ER PT J AU Liberthson, RR AF Liberthson, Richard R. TI Management Implications for Anomalous Aortic Origin of Coronary Arteries SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE anomalous coronary artery; best practices; echocardiography ID SUDDEN-DEATH; HIGH-RISK; SINUS; VALSALVA C1 [Liberthson, Richard R.] Massachusetts Gen Hosp, Congenital Heart Program, Boston, MA 02114 USA. RP Liberthson, RR (reprint author), Massachusetts Gen Hosp, Congenital Heart Program, 55 Fruit St, Boston, MA 02114 USA. EM RLIBERTHSON@mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 8 IS 11 BP 1250 EP 1251 DI 10.1016/j.jcmg.2015.05.009 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CW7AS UT WOS:000365150900002 PM 26563853 ER PT J AU Ferencik, M Liu, T Mayrhofer, T Puchner, SB Lu, MT Maurovich-Horvat, P Pope, JH Truong, QA Udelson, JE Peacock, WF White, CS Woodard, PK Fleg, JL Nagurney, JT Januzzi, JL Hoffmann, U AF Ferencik, Maros Liu, Ting Mayrhofer, Thomas Puchner, Stefan B. Lu, Michael T. Maurovich-Horvat, Pal Pope, J. Hector Truong, Quynh A. Udelson, James E. Peacock, W. Frank White, Charles S. Woodard, Pamela K. Fleg, Jerome L. Nagurney, John T. Januzzi, James L. Hoffmann, Udo TI hs-Troponin I Followed by CT Angiography Improves Acute Coronary Syndrome Risk Stratification Accuracy and Work-Up in Acute Chest Pain Patients Results From ROMICAT II Trial SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE acute coronary syndrome; coronary computed tomography angiography; coronary plaque; emergency department; highly sensitive troponin; risk stratification ID SENSITIVITY CARDIAC TROPONIN; ACUTE MYOCARDIAL-INFARCTION; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; EARLY-DIAGNOSIS; EMERGENCY-DEPARTMENT; SERIAL CHANGES; ASSAY; RULE; RECLASSIFICATION; ASSOCIATION AB OBJECTIVES This study compared diagnostic accuracy of conventional troponin/traditional coronary artery disease (CAD) assessment and highly sensitive troponin (hsTn) I/advanced CAD assessment for acute coronary syndrome (ACS) during the index hospitalization. BACKGROUND hsTnI and advanced assessment of CAD using coronary computed tomography angiography (CTA) are promising candidates to improve the accuracy of emergency department evaluation of patients with suspected ACS. METHODS We performed an observational cohort study in patients with suspected ACS enrolled in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia using Computer Assisted Tomography) trial and randomized to coronary CTA who also had hsTnI measurement at the time of the emergency department presentation. We assessed coronary CTA for traditional (no CAD, nonobstructive CAD, >= 50% stenosis) and advanced features of CAD (>= 50% stenosis, high-risk plaque features: positive remodeling, low <30-Hounsfield units plaque, napkin-ring sign, spotty calcium). RESULTS Of 160 patients (mean age: 53 +/- 8 years, 40% women) 10.6% were diagnosed with ACS. The ACS rate in patients with hsTnI below the limit of detection (n = 9, 5.6%), intermediate (n = 139, 86.9%), and above the 99th percentile (n = 12, 7.5%) was 0%, 8.6%, and 58.3%, respectively. Absence of >= 50% stenosis and high-risk plaque ruled out ACS in patients with intermediate hsTnI (n = 87, 54.4%; ACS rate 0%), whereas patients with both >= 50% stenosis and high-risk plaque were at high risk (n = 13, 8.1%; ACS rate 69.2%) and patients with either >= 50% stenosis or high-risk plaque were at intermediate risk for ACS (n = 39, 24.4%; ACS rate 7.7%). hsTnI/advanced coronary CTA assessment significantly improved the diagnostic accuracy for ACS as compared to conventional troponin/traditional coronary CTA (area under the curve 0.84, 95% confidence interval [CI]: 0.80 to .88 vs. 0.74, 95% CI: 0.70 to 0.78; p < 0.001). CONCLUSIONS hsTnI at the time of presentation followed by early advanced coronary CTA assessment improves the risk stratification and diagnostic accuracy for ACS as compared to conventional troponin and traditional coronary CTA assessment. (C) 2015 by the American College of Cardiology Foundation. C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Ferencik, Maros; Liu, Ting; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferencik, Maros; Liu, Ting; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Truong, Quynh A.; Nagurney, John T.; Januzzi, James L.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Ferencik, Maros; Liu, Ting; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Liu, Ting] China Med Univ, Dept Radiol, Affiliated Hosp 1, Shenyang 110001, Peoples R China. [Puchner, Stefan B.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Maurovich-Horvat, Pal] Semmelweis Univ, Heart & Vasc Ctr, TA SE Lendulet Cardiovasc Imaging Res Grp, H-1085 Budapest, Hungary. [Pope, J. Hector] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. [Truong, Quynh A.] New York Presbyterian Hosp, Dalio Inst Cardiovasc Imaging, New York, NY USA. [Truong, Quynh A.] Weill Cornell Med Coll, New York, NY USA. [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [White, Charles S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Woodard, Pamela K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Januzzi, James L.; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA. EM ferencik@ohsu.edu FU National Institutes of Health, ACRIN [NIH U01HL092040, U01HL092022]; American Heart Association [13FTF16450001]; NIH/NHLBI [K23HL098370, L30HL093896]; St. Jude Medical; American College of Radiology Imaging Network; Duke Clinical Research; Abbott; Alere; Banyan; Cardiorentis; Portola; Roche; Medicines Company; Siemens; Thermo Fisher; Singulex; NIH [U01HL092022, U01HL092040]; Siemens Medical Solutions; Heart Flow Inc.; Alere/Biosite; Brahms Ltd/Thermo-Fisher; Nanosphere FX The ROMICAT II trial is supported by the National Institutes of Health grant numbers NIH U01HL092040 and U01HL092022, ACRIN. The content of this paper is solely the responsibility of the authors and does not necessarily reflect the views of the National Institutes of Health or the Department of Health and Human Services. Dr. Ferencik has received a research grant from the American Heart Association Fellow to Faculty Award 13FTF16450001. Dr. Truong has received research grants from NIH/NHLBI K23HL098370 and L30HL093896, St. Jude Medical, American College of Radiology Imaging Network, and Duke Clinical Research. Dr. Peacock has received research grants from Abbott, Alere, Banyan, Cardiorentis, Portola, Roche, and The Medicines Company; has ownership of Comprehensive Research Associates LLC and Emergencies in Medicine LLC; is a consultant with and on advisory boards for BG Medicine, Beckman, Boehringer-Ingelheim, Instrument Labs, Prevencio, The Medicines Company, ZS Pharma, Alere, Cardiorentis, and Janssen. Dr. Nagumey has received research grants from Alere/Biosite, Brahms Ltd/Thermo-Fisher, Nanosphere; is a consultant for and on advisory board at CardioDx. Dr. Januzzi received research grants from Siemens, Thermo Fisher, and Singulex; is a consultant with and on advisory board of Critical Diagnostics, Sphingotec, and Roche. Dr. Hoffmann received research grants from NIH U01HL092040, U01HL092022, Siemens Medical Solutions, Heart Flow Inc.; and is a consultant for and on advisory board of Heart Flow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Ferencik and Liu contributed equally to this work. NR 26 TC 7 Z9 7 U1 0 U2 0 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 2015 VL 8 IS 11 BP 1272 EP 1281 DI 10.1016/j.jcmg.2015.06.016 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CW7AS UT WOS:000365150900007 PM 26476506 ER PT J AU Gerami, P Yelamos, O Lee, CY Obregon, R Yazdan, P Sholl, LM Guitart, GE Njauw, CN Tsao, HS AF Gerami, Pedram Yelamos, Oriol Lee, Christina Y. Obregon, Roxana Yazdan, Pedram Sholl, Lauren M. Guitart, Gerta E. Njauw, Ching-Ni Tsao, Hensin TI Multiple Cutaneous Melanomas and Clinically Atypical Moles in a Patient With a Novel Germline BAP1 Mutation SO JAMA DERMATOLOGY LA English DT Article ID MELANOCYTIC TUMORS; SPITZ TUMORS; EXPRESSION; PREDISPOSE AB IMPORTANCE Several kindreds having germline BAP1 mutations with a propensity for uveal and cutaneous melanomas and other internal malignancies have been described in an autosomal dominant tumor predisposition syndrome. However, clinically atypical moles have not been previously recognized as a component of this syndrome, to our knowledge. We describe the first kindred to date with a germline mutation in BAP1 associated with multiple cutaneous melanomas and classic dysplastic nevus syndrome. OBSERVATIONS We describe a 53-year-old man who was initially seen in 2003 with dysplastic nevus syndrome, multiple atypical melanocytic proliferations showing loss of immunostaining for BAP1, and 7 cutaneous melanomas. Germline testing was performed in the proband, his 16-year-old son, and his 13-year-old daughter, revealing a germline mutation in the BAP1 gene (c.592G>T, p.Glu198X) in the proband and in his 16-year-old son. CDKN2A and CDK4 genes were wild type. No members of this kindred reported a history of uveal melanoma. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of a patient with multiple melanomas, dysplastic nevus syndrome, and an inactivating germline BAP1 mutation. The coexistence of dysplastic nevus syndrome and a BAP1 germline mutation extends the spectrum of the BAP1 tumor predisposition syndrome and may confer a greater risk for cutaneous melanomas. C1 [Gerami, Pedram; Yelamos, Oriol; Lee, Christina Y.; Obregon, Roxana; Yazdan, Pedram; Sholl, Lauren M.; Guitart, Gerta E.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Gerami, Pedram] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. [Njauw, Ching-Ni; Tsao, Hensin] Harvard Univ, Wellman Ctr Photomed, Boston, MA 02115 USA. [Njauw, Ching-Ni; Tsao, Hensin] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Njauw, Ching-Ni; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gerami, P (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St,Ste 1600, Chicago, IL 60611 USA. EM pgerami@nmff.org FU IDP Foundation; National Institutes of Health [K24 CA149202] FX This study was supported in part by the IDP Foundation (Dr Gerami) and by grant K24 CA149202 from the National Institutes of Health (Dr Tsao). NR 13 TC 5 Z9 5 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 2015 VL 151 IS 11 BP 1235 EP 1239 DI 10.1001/jamadermatol.2015.1701 PG 5 WC Dermatology SC Dermatology GA CW9GD UT WOS:000365305900017 PM 26154183 ER PT J AU Gerami, P Tsao, HS AF Gerami, Pedram Tsao, Hensin TI Concerns About Presence of a Wild-Type BAP1 Allele in Absence of Nuclear Protein Expression Reply SO JAMA DERMATOLOGY LA English DT Letter C1 [Gerami, Pedram] Northwestern Univ, Dept Dermatol, Feinberg Sch Med, Chicago, IL 60611 USA. [Gerami, Pedram] Northwestern Univ, Robert H Lurie Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Tsao, Hensin] Harvard Univ, Wellman Ctr Photomed, Boston, MA 02115 USA. [Tsao, Hensin] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Gerami, P (reprint author), Northwestern Univ, Dept Dermatol, Feinberg Sch Med, Robert H Lurie Canc Ctr, 676 N St Clair St,Ste 1600, Chicago, IL 60611 USA. EM Pedram.Gerami@nmff.org NR 4 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 2015 VL 151 IS 11 BP 1266 EP 1266 PG 1 WC Dermatology SC Dermatology GA CW9GD UT WOS:000365305900031 PM 26559348 ER PT J AU Gill, CM Bredella, MA DeSilva, JM AF Gill, Corey M. Bredella, Miriam A. DeSilva, Jeremy M. TI Skeletal development of hallucal tarsometatarsal joint curvature and angulation in extant apes and modern humans SO JOURNAL OF HUMAN EVOLUTION LA English DT Article DE Medial cuneiform; Hallux mobility; Bipedal locomotion; Arboreality; Australopithecus; Homo ID HUMAN FOOT; AUSTRALOPITHECUS-AFARENSIS; HUMAN-EVOLUTION; EARLY HOMINIDS; BONES; ONTOGENY; BIPEDALISM; LOCOMOTION; MORPHOLOGY; PRIMATES AB The medial cuneiform, namely the curvature and angulation of its distal facet with metatarsal 1, is crucial as a stabilizer in bipedal locomotion and an axis upon which the great toe medially deviates during arboreal locomotion in extant apes. Previous work has shown that facet curvature and angulation in adult dry-bone specimens can distinguish African apes from Homo, and can even distinguish among species of Gorilla. This study provides the first ontogenetic assessment of medial cuneiform curvature and angulation in juvenile (n = 68) and adult specimens (n = 102) using computed tomography in humans and extant ape specimens, including Pongo. Our data find that modern human juveniles initially have a convex and slightly medially oriented osseous surface of the developing medial cuneiform distal facet that flattens and becomes more distally oriented with age. The same pattern (though of a different magnitude) occurs developmentally in the chimpanzee medial cuneiform, but not in Gorilla or Pongo, whose medial cuneiform facet angulation remains unchanged ontogenetically. These data suggest that the medial cuneiform ossifies in a distinguishable pattern between Pongo, Gorilla, Pan, and Homo, which may in part be due to subtle differences in the loading environment at the hallucal tarsometatarsal joint a finding that has important implications for interpreting fossil medial cuneiforms. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Gill, Corey M.; Bredella, Miriam A.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Dept Radiol, Boston, MA 02214 USA. [Gill, Corey M.; Bredella, Miriam A.] Harvard Univ, Sch Med, Boston, MA 02214 USA. [Gill, Corey M.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02214 USA. [Gill, Corey M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02214 USA. [Gill, Corey M.; DeSilva, Jeremy M.] Boston Univ, Dept Anthropol, Boston, MA 02214 USA. [DeSilva, Jeremy M.] Dartmouth Coll, Dept Anthropol, Hanover, NH 03755 USA. RP DeSilva, JM (reprint author), Boston Univ, Dept Anthropol, Boston, MA 02214 USA. EM cmgill@mgh.harvard.edu; mbredella@mgh.harvard.edu; jeremy.m.desilva@dartmouth.edu FU Leakey Foundation; Boston University FX This work is dedicated to the life and memory of Helga W. Luhrs. We thank J. Chupasko and the Museum of Comparative Zoology at Harvard University and E. Westwig and the American Museum of Natural History for the loaning of all extant ape specimens. A cast of A.L. 333-28 was provided by Z. Alemseged. OH 8 was examined thanks to P. Msemwa, A. Kwekason, and the Tanzania Commission for Science and Technology. We thank B. Zipfel and the University of the Witwatersrand fossil access advisory panel for access to the medial cuneiform of StW 573. We further thank M. Asaro, C. Hatley, and M. Verlicco for the assistance in the CT scanning of all specimens and T. Kivell and M. Hamrick for advice on ossification of foot bones. We are grateful to M. Cartmill at Boston University for review of the data. This research was funded in part by the Leakey Foundation and by Boston University. This manuscript benefitted from helpful advice offered by the associate editor and four anonymous reviewers. NR 56 TC 0 Z9 0 U1 7 U2 16 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0047-2484 J9 J HUM EVOL JI J. Hum. Evol. PD NOV PY 2015 VL 88 BP 137 EP 145 DI 10.1016/j.jhevol.2015.07.003 PG 9 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA CX0FP UT WOS:000365372600012 PM 26319411 ER PT J AU Seo, MJ Lee, YJ Hwang, JH Kim, KJ Lee, BY AF Seo, Min-Jung Lee, Yeon-Joo Hwang, Ji-Hyun Kim, Kui-Jin Lee, Boo-Yong TI The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Quercetin; Obesity; Obesity-induced inflammation; MAPK signaling; Adipogenesis ID NF-KAPPA-B; HUMAN ADIPOCYTE DIFFERENTIATION; ACTIVATED PROTEIN-KINASE; GENE-EXPRESSION; ADIPOSE-TISSUE; 3T3-L1 PREADIPOCYTES; MOLECULAR-MECHANISMS; INSULIN-RESISTANCE; NITRIC-OXIDE; PPAR-GAMMA AB Quercetin is a flavonoid found in fruits, vegetables, leaves and grains. It has inhibitory, antiviral, antiasthma, anticancer and antiinflammatory effects. Research has suggested that obesity is linked to metabolic disorders. In this study, we examined the inhibitory effect of quercetin on lipid accumulation and obesity-induced inflammation using 3T3-L1, RAW264.7, zebrafish and mouse models. Quercetin suppressed protein levels of the key adipogenic factors C/EBP beta, C/EBP alpha, PPAR gamma and FABP4 and the TG-synthesis enzymes lipin1, DGAT1 and LPAAT theta. Activation of m-TOR and p70S6K, which are related to insulin and adipogenesis, was down-regulated during adipogenesis in 3T3-L1 cells. Recent research suggested that MAPK signaling factors were involved in adipogenesis and inflammation and that the adipokines MCP-1 and TNF-alpha attracted macrophages into adipose tissue. Our data showed that quercetin inhibited the MAPK signaling factors ERK1/2, JNK and p38MAPK and MCP-1 and TNF-alpha in adipocytes and macrophages. Quercetin also inhibited secretion of the inflammatory cytokines IL-1 beta and IL-6 and stimulated that of IL-10, an antiinflammatory cytokine. In this study, we confirmed the inhibitory effects of quercetin in adipogenesis and inflammation using a mouse model. In mice, quercetin reduced body weight (almost 40%) and suppressed expression of adipogenic, lipogenic and inflammation-related cytokines. Our data demonstrated that quercetin inhibits lipid accumulation and obesity-induced inflammation in the cell and animal models. Our study suggested that quercetin may represent a potential therapeutic agent for other metabolic disorders by regulating obesity and obesity-induced inflammation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Seo, Min-Jung; Lee, Yeon-Joo; Hwang, Ji-Hyun; Lee, Boo-Yong] CHA Univ, Dept Food Sci & Biotechnol, Songnam 463400, Kyonggi, South Korea. [Kim, Kui-Jin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Lee, BY (reprint author), CHA Univ, Coll Life Sci, Dept Food Sci & Biotechnol, 335 Pangyo Ro, Songnam 463400, Kyonggi Do, South Korea. EM bylee@cha.ac.kr FU Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [2013R1A1A2064024] FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (No. 2013R1A1A2064024). NR 55 TC 14 Z9 14 U1 5 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD NOV PY 2015 VL 26 IS 11 BP 1308 EP 1316 DI 10.1016/j.jnutbio.2015.06.005 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA CW4RK UT WOS:000364979600021 PM 26277481 ER PT J AU Baker, JF Von Feldt, JM Mostoufi-Moab, S Kim, W Taratuta, E Leonard, MB AF Baker, Joshua F. Von Feldt, Joan Marie Mostoufi-Moab, Sogol Kim, Woojin Taratuta, Elena Leonard, Mary B. TI Insulin-like Growth Factor 1 and Adiponectin and Associations with Muscle Deficits, Disease Characteristics, and Treatments in Rheumatoid Arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ADIPONECTIN; RHEUMATOID ARTHRITIS; CACHEXIA; LEAN MASS ID CHRONIC KIDNEY-DISEASE; ANOREXIA-NERVOSA; HEART-FAILURE; PLASMA ADIPONECTIN; BODY-COMPOSITION; IGFBP-3 LEVELS; FACTOR-I; CACHEXIA; MASS; FAT AB Objective. Rheumatoid arthritis (RA) is associated with low muscle mass and density. The objective of our study was to evaluate associations between 2 serum biomarkers [insulin-like growth factor 1 (IGF-1) and adiponectin] and skeletal muscle in RA. Methods. Whole-body dual energy X-ray absorptiometry measures of the appendicular lean mass index (ALMI; kg/m(2)) and total fat mass index (kg/m(2)), as well as the peripheral quantitative computed tomography measures of the lower leg muscle and fat cross-sectional area (CSA; cm(2)) and muscle density (an index of fat infiltration) were obtained from 50 participants with RA, ages 18-70 years. Multivariable linear regression analyses evaluated associations between body composition and levels of adiponectin and IGF-1, adjusted for age, sex, and adiposity. Results. Greater age was associated with higher adiponectin (p = 0.06) and lower IGF-1 (p = 0.004). Eight subjects had IGF-1 levels below the reference range for their age and sex. These subjects had significantly lower ALMI and muscle CSA in multivariable models. Lower IGF-1 levels were associated with greater clinical disease activity and severity, as well as low ALMI, muscle CSA, and muscle density (defined as 1 SD below normative mean). After adjusting for age and sex, greater adiponectin levels were associated with lower BMI (p = 0.02) as well as lower ALMI, and lower muscle CSA, independent of adiposity (p < 0.05). Only greater Health Assessment Questionnaire scores were significantly associated with lower adiponectin levels. Conclusion. Low IGF-1 and greater adiponectin levels are associated with lower muscle mass in RA. Lower IGF-1 levels were seen in subjects with greater disease activity and severity. C1 [Baker, Joshua F.; Von Feldt, Joan Marie] Philadelphia Vet Affairs VA Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Baker, Joshua F.; Von Feldt, Joan Marie] Univ Penn, Perelman Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Baker, Joshua F.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mostoufi-Moab, Sogol] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Kim, Woojin; Taratuta, Elena] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. [Leonard, Mary B.] Stanford Univ, Dept Pediat & Med, Stanford, CA 94305 USA. RP Baker, JF (reprint author), Hosp Univ Penn, Dept Med, Div Rheumatol, 8 Penn Tower Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu FU University of Pennsylvania Clinical and Translational Research Center [UL1 RR024134]; VA Clinical Science Research and Development Career Development Award [IK2 CX000955]; K24 award [K24 DK076808]; US National Institutes of Health [R01 DK064966] FX Supported by the University of Pennsylvania Clinical and Translational Research Center (UL1 RR024134). Dr. Baker is supported by a VA Clinical Science Research and Development Career Development Award (IK2 CX000955). Dr. Leonard is supported by a K24 award (K24 DK076808). Also supported by US National Institutes of Health grant R01 DK064966. NR 43 TC 0 Z9 0 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2015 VL 42 IS 11 BP 2038 EP 2045 DI 10.3899/jrheum.150280 PG 8 WC Rheumatology SC Rheumatology GA CW8AS UT WOS:000365221400007 PM 26329340 ER PT J AU Hall, BL Huffman, KM Hamilton, BH Paruch, JL Zhou, L Richards, KE Cohen, ME Ko, CY AF Hall, Bruce Lee Huffman, Kristopher M. Hamilton, Barton H. Paruch, Jennifer L. Zhou, Lynn Richards, Karen E. Cohen, Mark E. Ko, Clifford Y. TI Profiling Individual Surgeon Performance Using Information from a High-Quality Clinical Registry: Opportunities and Limitations SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID HOSPITAL QUALITY; RELIABILITY; RISK AB BACKGROUND: There is increasing interest in profiling the quality of individual medical providers. Valid assessment of individuals should highlight improvement opportunities, but must be considered in the context of limitations. STUDY DESIGN: High quality clinical data from the American College of Surgeons NSQIP, gathered in accordance with strict policies and specifications, was used to construct individual surgeon-level assessments. There were 39,976 cases evaluated, performed by 197 surgeons across 9 hospitals. Both 2-level (cases by surgeon) and 3-level (cases by surgeon by hospital) risk-adjusted, hierarchical regression analyses were performed. Outcomes were 30-day postoperative morbidity, surgical site infection, and mortality. Surgeon performance was compared in both absolute and relative terms. "Signal-to-noise" reliability was calculated for surgeons and models. Projected case requirements for reliability levels were generated. RESULTS: Surgeon performances could be distinguished to different degrees: morbidity distinguished best, mortality least. Outliers could be identified for morbidity and infection, but not mortality. Reliability was also highest for morbidity and lowest for mortality. Even models with high overall reliability did not assess all providers reliably. Incorporating institutional effects had predictable effects: penalizing providers at "good" institutions, benefiting providers at "poor" institutions. CONCLUSIONS: Individual surgeon profiles can, at times, be distinguished with moderate or good reliability, but to different degrees in different models. Absolute and relative comparisons are feasible. Incorporating institutional level effects in individual provider modeling presents an interesting policy dilemma, appearing to benefit providers at "poor-performing" institutions, but penalizing those at "high-performing" ones. No portrayal of individual medical provider quality should be accepted without consideration of modeling rationale and, critically, reliability. (C) 2015 by the American College of Surgeons) C1 [Hall, Bruce Lee] Washington Univ, Dept Surg, St Louis, MO 63144 USA. [Hall, Bruce Lee] Washington Univ, Ctr Hlth Policy, St Louis, MO 63144 USA. [Hall, Bruce Lee] St Louis Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce Lee] BJC Healthcare, St Louis, MO USA. [Hall, Bruce Lee; Hamilton, Barton H.] Washington Univ, Olin Business Sch, St Louis, MO 63144 USA. [Hall, Bruce Lee; Huffman, Kristopher M.; Paruch, Jennifer L.; Zhou, Lynn; Richards, Karen E.; Cohen, Mark E.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA. [Paruch, Jennifer L.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hall, BL (reprint author), Washington Univ, Ctr Clin Excellence, BJC Healthcare, BJC Learning Inst, Mailstop 92-92-241,8300 Eager Rd, St Louis, MO 63144 USA. EM hallb@wustl.edu RI Hamilton, Barton/P-5187-2015 NR 20 TC 6 Z9 6 U1 0 U2 2 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 2015 VL 221 IS 5 BP 901 EP 913 DI 10.1016/j.jamcollsurg.2015.07.454 PG 13 WC Surgery SC Surgery GA CW9VK UT WOS:000365346100006 PM 26363711 ER PT J AU Fallon, JM Goodney, PP Stone, DH Patel, VI Nolan, BW Kalish, JA Zhao, YY Hamdan, AD AF Fallon, John M. Goodney, Philip P. Stone, David H. Patel, Virendra I. Nolan, Brian W. Kalish, Jeffrey A. Zhao, Yuanyuan Hamdan, Allen D. CA Vascular Study Grp New England TI Outcomes of lower extremity revascularization among the hemodialysis-dependent SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID STAGE RENAL-DISEASE; CRITICAL LIMB ISCHEMIA; INFRAINGUINAL BYPASS-SURGERY; PERIPHERAL ARTERIAL-DISEASE; CRITICAL LEG ISCHEMIA; REALISTIC EXPECTATIONS; ANGIOPLASTY; PREDICTION; DIALYSIS; REGISTRY AB Objective: Optimal patient selection for lower extremity revascularization remains a clinical challenge among the hemodialysis-dependent (HD). The purpose of this study was to examine contemporary real world open and endovascular outcomes of HD patients to better facilitate patient selection for intervention. Methods: A regional multicenter registry was queried between 2003 and 2013 for HD patients (N =689) undergoing open surgical bypass (n =295) or endovascular intervention (n =394) for lower extremity revascularization. Patient demographics and comorbidities were recorded. The primary outcome was overall survival. Secondary outcomes included graft patency, freedom from major adverse limb events, and amputation-free survival (AFS). Multivariate analysis was performed to identify independent risk factors for death and amputation. Results: Among the 689 HD patients undergoing lower extremity revascularization, 66% were male, and 83% were white. Ninety percent of revascularizations were performed for critical limb ischemia and 8% for claudication. Overall survival at 1, 2, and 5 years survival remained low at 60%, 43%, and 21%, respectively. Overall 1- and 2-year AFS was 40% and 17%. Mortality accounted for the primary mode of failure for both open bypass (78%) and endovascular interventions (80%) at two years. Survival, AFS, and freedom from major adverse limb event outcomes did not differ significantly between revascularization techniques. At 2 years, endovascular patency was higher than open bypass (76% vs 26%; 95% confidence interval [CI], 0.28-0.71; P =.02). Multivariate analysis identified age >= 80 years (hazard ratio [HR], 1.9; 95% CI, 1.4-2.5; P <.01), indication of rest pain or tissue loss (HR, 1.8; 95% CI, 1.3-2.6; P <.01), preoperative wheelchair/bedridden status (HR, 1.5; 95% CI, 1.1-2.1; P <.01), coronary artery disease (HR, 1.5; 95% CI, 1.2-1.9; P <.01), and chronic obstructive pulmonary disease (HR, 1.4; 95% CI, 1.1-1.8; P <.01) as independent predictors of death. The presence of three or more risk factors resulted in predicted 1-year mortality of 64%. Conclusions: Overall survival and AFS among HD patients remains poor, irrespective of revascularization strategy. Mortality remains the primary driver for these findings and justifies a prudent approach to patient selection. Focus for improved results should emphasize predictors of survival to better identify those most likely to benefit from revascularization. C1 [Fallon, John M.; Goodney, Philip P.; Stone, David H.; Nolan, Brian W.; Zhao, Yuanyuan] Dartmouth Hitchcock Med Ctr, Div Vasc Surg, Lebanon, NH 03756 USA. [Patel, Virendra I.] Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. [Kalish, Jeffrey A.] Boston Univ, Med Ctr, Div Vasc Surg, Boston, MA USA. [Hamdan, Allen D.] Beth Israel Deaconess Med Ctr, Div Vasc Surg, Boston, MA 02215 USA. RP Fallon, JM (reprint author), Dartmouth Hitchcock Med Ctr, Dept Surg, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM john.m.fallon@hitchcock.org FU NHLBI NIH HHS [K08 HL105676] NR 31 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2015 VL 62 IS 5 BP 1183 EP + DI 10.1016/j.jvs.2015.06.203 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CW8IF UT WOS:000365242000012 PM 26254454 ER PT J AU Kwolek, CJ Jaff, MR Leal, JI Hopkins, LN Shah, RM Hanover, TM Macdonald, S Cambria, RP AF Kwolek, Christopher J. Jaff, Michael R. Leal, J. Ignacio Hopkins, L. Nelson Shah, Rasesh M. Hanover, Todd M. Macdonald, Sumaira Cambria, Richard P. TI Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CAROTID REVASCULARIZATION ENDARTERECTOMY; HIGH-RISK PATIENTS; TRANSCERVICAL ACCESS; CEREBRAL PROTECTION; STENOSIS; NEUROPROTECTION; ANGIOPLASTY; OUTCOMES; STROKE; SYSTEM AB Objective: This report presents the 30-day results of the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) multicenter trial and evaluates the safety and efficacy of ENROUTE Transcarotid NPS (Silk Road Medical Inc, Sunnyvale, Calif), a novel transcarotid neuroprotection system that provides direct surgical common carotid access and cerebral embolic protection via high-rate flow reversal during carotid artery stenting (CAS). Methods: A prospective, single-arm, multicenter clinical trial was performed to evaluate the use of the ENROUTE Transcarotid NPS during CAS procedures performed in patients considered to be at high risk for complications from carotid endarterectomy. Symptomatic patients with >= 50% stenosis and asymptomatic patients with >= 70% stenosis were eligible to be treated with any U.S. Food and Drug Administration-approved carotid artery stent. The primary end point was the composite of all stroke, myocardial infarction (MI), and death at 30 days postprocedure as defined in the Food and Drug Administration-approved study protocol. Secondary end points included cranial nerve injury; 30-day stroke, death, stroke/death, and MI; acute device, technical, and procedural success; and access site complications. All major adverse events were adjudicated by an independent clinical events committee. Results: Between November 2012 and July 2014, 208 patients were enrolled at 18 sites. Sixty-seven patients were enrolled as lead-in cases, and 141 were enrolled in the pivotal phase. In the pivotal cohort, 26% were symptomatic and 75% were asymptomatic. Acute device and technical success were 99% (140 of 141). By hierarchical analysis, the all-stroke rate in the pivotal group was 1.4% (2 of 141), stroke and death was 2.8% (4 of 141), and stroke, death and MI was 3.5% (5 of 141). One patient (0.7%) experienced postoperative hoarseness from potential Xth cranial nerve injury, which completely resolved at the 6-month follow-up visit. Conclusions: The results of the ROADSTER trial demonstrate that the use of the ENROUTE Transcarotid NPS is safe and effective at preventing stroke during CAS. The overall stroke rate of 1.4% is the lowest reported to date for any prospective, multicenter clinical trial of CAS. C1 [Kwolek, Christopher J.; Cambria, Richard P.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Med, Boston, MA 02114 USA. [Kwolek, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Leal, J. Ignacio] Complejo Hosp Toledo, Vasc Surg Sect, Toledo, Spain. [Hopkins, L. Nelson] SUNY Buffalo, Dept Neurosurg, Buffalo, NY 14260 USA. [Hopkins, L. Nelson] Jacobs Inst, Buffalo, NY USA. [Shah, Rasesh M.] Eastern Virginia Med Sch, Dept Surg, Norfolk, VA 23501 USA. [Hanover, Todd M.] Greenville Hosp Syst, Acad Dept Surg, Greenville, SC USA. [Macdonald, Sumaira] Silk Rd Med Inc, Sunnyvale, CA USA. RP Kwolek, CJ (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, WAC 442,15 Parkman St, Boston, MA 02114 USA. EM ckwolek@partners.org NR 28 TC 9 Z9 9 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2015 VL 62 IS 5 BP 1227 EP + DI 10.1016/j.jvs.2015.04.460 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CW8IF UT WOS:000365242000017 PM 26506270 ER PT J AU Mohebali, J Patel, VI Romero, JM Hannon, KM Jaff, MR Cambria, RP LaMuraglia, GM AF Mohebali, Jahan Patel, Virendra I. Romero, Javier M. Hannon, Kathleen M. Jaff, Michael R. Cambria, Richard P. LaMuraglia, Glenn M. TI Acoustic shadowing impairs accurate characterization of stenosis in carotid ultrasound examinations SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID LUMINAL DIAMETER MEASUREMENTS; ARTERY STENOSIS; CT ANGIOGRAPHY; VASCULAR CALCIFICATION; ENDARTERECTOMY TRIAL; VELOCITY CRITERIA; DISEASE; RISK; AREA; INFLAMMATION AB Objective: Duplex ultrasonography (DUS) has been the mainstay for diagnosing carotid artery stenosis and is often the sole diagnostic modality used prior to intervention. Highly calcified plaque, however, results in an acoustic shadow (AcS) that obscures the vessel lumen and inhibits the sonographer's ability to obtain Doppler velocity measurements. It is unknown whether DUS can accurately determine the degree of carotid stenosis in these settings. Methods: From July 2012 to December 2013, all patients with AcS on DUS measuring >= 5 mm in the longitudinal axis were cross-referenced with multidetector computed tomographic angiography (MD-CTA) images of the neck to define the study population. After standardizing the MD-CTA windows, percent stenosis was determined by cross-sectional area reduction using two separate previously described methods based on North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) criteria. DUS waveform parameters in the internal carotid artery near the AcS were then compared with these MD-CTA measurements to determine the accuracy of DUS in characterizing the severity of carotid stenosis. Results: During this period, 8517 DUS studies were performed at the Massachusetts General Hospital, 550 of which had AcS, for an incidence of 6.45%. There were 92 lesions with a concomitant MD-CTA; however, seven were excluded because of poor study quality, because >= 6 months had elapsed between DUS and MD-CTA, or because the patient had undergone carotid reconstruction between studies. Of the 85 remaining lesions, DUS characterized 17 as severe (peak systolic velocity [PSV] > 250 cm/s), 31 as moderate (PSV=151-250 cm/s), and 37 as mild (PSV <= 150 cm/s) stenoses using PSV criteria. PSV weakly correlated with CTA-NASCET (r =0.361; P =.004) and CTA-ECST (r =0.306; P =.004) percent stenosis. Using PSV > 250 cm/s as the predictor of > 70% stenosis, and a >= 70% cutoff by both CTA-ECST and CTA-NASCET methods as the reference measure, DUS sensitivity ranged from 22.7% to 32.5%, specificity from 89.4% to 91.1%, positive predictive value from 88.2% to 76.4%, and negative predictive value from 25% to 60.2%. A subgroup analysis of lesions identified as non-severe by DUS revealed that waveforms with lower deceleration were associated with severe stenosis on CTA. Conclusions: In the presence of AcS, DUS alone is inadequate to accurately determine the degree of carotid stenosis with sensitivity, specificity, and negative predictive values far below that needed for clinical decision-making. MD-CTA may be necessary for improved characterization of plaque in these AcS lesions. Further studies are needed to determine DUS parameters that may identify patients who should undergo further evaluation with MD-CTA to characterize the true severity of the stenosis. C1 [Mohebali, Jahan; Patel, Virendra I.; Cambria, Richard P.; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Patel, Virendra I.; Jaff, Michael R.; Cambria, Richard P.; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. [Romero, Javier M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hannon, Kathleen M.; Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hannon, Kathleen M.; Jaff, Michael R.] Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiovasc Med, Vasc Ctr, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Surg, Boston, MA 02114 USA. EM glamuraglia@mgh.harvard.edu NR 35 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2015 VL 62 IS 5 BP 1236 EP 1244 DI 10.1016/j.jvs.2015.06.137 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA CW8IF UT WOS:000365242000019 PM 26506272 ER PT J AU Katzman, SM Strotmeyer, ES Nalls, MA Zhao, YQ Mooney, S Schork, N Newman, AB Harris, TB Yaffe, K Cummings, SR Liu, YM Tranah, GJ AF Katzman, Shana M. Strotmeyer, Elsa S. Nalls, Michael A. Zhao, Yiqiang Mooney, Sean Schork, Nik Newman, Anne B. Harris, Tamara B. Yaffe, Kristine Cummings, Steven R. Liu, Yongmei Tranah, Gregory J. CA Hlth Aging Body Composition Study TI Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve Function in the Elderly SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Sensory; Genetics; Epidemiology; Functional Performance ID AMYLOID PRECURSOR PROTEIN; CYCLIC VOMITING SYNDROME; ALZHEIMERS-DISEASE; BODY-COMPOSITION; CALORIE RESTRICTION; MUTATIONAL ANALYSIS; ENERGY-EXPENDITURE; DIABETES-MELLITUS; POLG MUTATIONS; RETT-SYNDROME AB Background. Mitochondrial dysfunction is a prominent hallmark of many sensory neuropathies. The purpose of this study was to assess the influence of mitochondrial DNA sequence variation on peripheral nerve function in the population-based Health, Aging, and Body Composition Study. Methods. We investigated the role of common mitochondrial DNA variation ( n = 1,580) and complete mitochondrial DNA sequences ( n = 138) on peroneal motor nerve conduction velocity and amplitude, average vibration detection threshold, and monofilament sensitivity. Results. Nominal associations among common mitochondrial DNA variants and haplogroups were identified but were not statistically significant after adjustment for multiple comparisons. Sequence-based approaches were used to identify aggregate variant associations across the 16S rRNA ( weighted- sum, p = 2E-05 and variable threshold, p = 9E-06) for nerve conduction velocity. Several of these rare 16S variants occurred at or near sites with earlier disease associations and are also in close proximity to the peptidyl transferase center, which is the catalytic center of the 16S rRNA Conclusions. These results suggest that sequence variation related to mitochondrial protein synthesis/ assembly is associated with peripheral nerve function and may provide insight into targets for intervention or new clinical strategies to preserve nerve function in late life. C1 [Katzman, Shana M.] Univ Calif San Francisco, Dept Innovat Technol & Alliances, San Francisco, CA 94143 USA. [Strotmeyer, Elsa S.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Zhao, Yiqiang] China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100094, Peoples R China. [Mooney, Sean] Buck Inst Res Aging, Dept Bioinformat, Novato, CA USA. [Schork, Nik] J Craig Venter Inst, Dept Human Biol, La Jolla, CA USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, Dept Geriatr Psychiat, San Francisco, CA USA. [Cummings, Steven R.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. RP Tranah, GJ (reprint author), UCSF, San Francisco Coordinating Ctr, Calif Pacific Med Ctr, Res Inst, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM gtranah@sfcc-cpmc.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050, R01-AG032098, R03-AG032498]; NINR [R01-NR012459, Z01A6000932]; National Institutes of Health [HHSN268200782096C]; NLM [LM009722]; NIH, National Institute on Aging FX This research was supported by National Institute on Aging (NIA) contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grants R01-AG028050, R01-AG032098, and R03-AG032498; NINR grant R01-NR012459 and Z01A6000932. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. Y.Z. was supported by NLM grant LM009722. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 85 TC 1 Z9 1 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2015 VL 70 IS 11 BP 1400 EP 1408 DI 10.1093/gerona/glu175 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CW1QF UT WOS:000364765700014 PM 25394619 ER PT J AU Tranah, GJ Yaffe, K Katzman, SM Lam, ET Pawlikowska, L Kwok, PY Schork, NJ Manini, TM Kritchevsky, S Thomas, F Newman, AB Harris, TB Coleman, AL Gorin, MB Helzner, EP Rowbotham, MC Browner, WS Cummings, SR AF Tranah, Gregory J. Yaffe, Kristine Katzman, Shana M. Lam, Ernest T. Pawlikowska, Ludmila Kwok, Pui-Yan Schork, Nicholas J. Manini, Todd M. Kritchevsky, Stephen Thomas, Fridtjof Newman, Anne B. Harris, Tamara B. Coleman, Anne L. Gorin, Michael B. Helzner, Elizabeth P. Rowbotham, Michael C. Browner, Warren S. Cummings, Steven R. CA Hlth Aging Body Composition TI Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Mitochondrial DNA; Heteroplasmy; Cognition; Vision; Hearing; Mobility ID HEREDITARY OPTIC NEUROPATHY; COMPLEX-I DEFICIENCY; SKELETAL-MUSCLE; CLONAL EXPANSION; MTDNA MUTATIONS; ND3 GENE; DISEASE; CELLS; SELECTION; DYSFUNCTION AB Background. Mitochondrial DNA ( mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease. Methods. We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study. Results. Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m. 10158T> C with Modified Mini-Mental State Examination score ( p =.009); m. 11778G> A with contrast sensitivity ( p =.02); m. 7445A> G with high-frequency hearing ( p =.047); and m. 5703G> A with 400 m walking speed ( p =.007). Conclusions. These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments. C1 [Tranah, Gregory J.; Rowbotham, Michael C.; Browner, Warren S.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Katzman, Shana M.] LA Eye Ctr & Clin, Los Angeles, CA USA. [Lam, Ernest T.] BioNano Genom Inc, San Diego, CA USA. [Pawlikowska, Ludmila] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Pawlikowska, Ludmila; Kwok, Pui-Yan] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Schork, Nicholas J.] J Craig Venter Inst, San Francisco, CA USA. [Schork, Nicholas J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Kritchevsky, Stephen] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Coleman, Anne L.; Gorin, Michael B.] Jules Stein Eye Inst, Los Angeles, CA 90024 USA. [Coleman, Anne L.; Gorin, Michael B.] Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. [Helzner, Elizabeth P.] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. RP Tranah, GJ (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, Mission Hall Global Hlth & Clin Sci Bldg,550 16th, San Francisco, CA 94143 USA. EM gtranah@sfcc-cpmc.net FU NIH, National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health [R01-AG028050, R03-AG032498, R01-NR012459, Z01A6000932, R01-HL121023]; Research and Education Leadership Committee of the CPMC Foundation FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging, Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; National Institutes of Health grants R01-AG028050, R03-AG032498, R01-NR012459, Z01A6000932, R01-HL121023, and a grant from the Research and Education Leadership Committee of the CPMC Foundation. NR 53 TC 3 Z9 3 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2015 VL 70 IS 11 BP 1418 EP 1424 DI 10.1093/gerona/glv097 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CW1QF UT WOS:000364765700016 PM 26328603 ER PT J AU Zhu, CW Cosentino, S Ornstein, K Gu, Y Scarmeas, N Andrews, H Stern, Y AF Zhu, Carolyn W. Cosentino, Stephanie Ornstein, Katherine Gu, Yian Scarmeas, Nikolaos Andrews, Howard Stern, Yaakov TI Medicare Utilization and Expenditures Around Incident Dementia in a Multiethnic Cohort SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Incident dementia; Medicare; Health care use; Health care expenditures; Longitudinal follow-up ID IDENTIFYING ALZHEIMERS-DISEASE; DIAGNOSIS; CLAIMS; CARE; TRAJECTORIES; POPULATION; ASSOCIATION; ACCURACY; SERVICES; MODELS AB Few studies have examined patterns of health care utilization and costs during the period around incident dementia. Participants were drawn from the Washington Heights-Inwood Columbia Aging Project, a multiethnic, population-based, prospective study of cognitive aging of Medicare beneficiaries in a geographically defined area of northern Manhattan. Medicare utilization and expenditure were examined in individuals with clinically diagnosed dementia from 2 years before until 2 years after the initial diagnosis. A sample of non-demented individuals who were matched on socio-demographic and clinical characteristics at study enrollment was used as controls. Multivariable regression analysis estimated effects on Medicare utilization and expenditures associated with incident dementia. During the 2 years before incident dementia, rates of inpatient admissions and outpatient visits were similar between dementia patients and non-demented controls, but use of home health and skilled nursing care and durable medical equipment were already higher in dementia patients. Results showed a small but significant excess increase associated with incident dementia in inpatient admissions but not in other areas of care. In the 2 years before incident dementia, total Medicare expenditures were already higher in dementia patients than in non-demented controls. But we found no excess increases in Medicare expenditures associated with incident dementia. Demand for medical care already is increasing and costs are higher at the time of incident dementia. There was a small but significant excess risk of inpatient admission associated with incident dementia. C1 [Zhu, Carolyn W.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, Bronx, NY 10468 USA. [Zhu, Carolyn W.] James J Peters VA Med Ctr, Bronx, NY USA. [Cosentino, Stephanie; Gu, Yian; Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, Cognit Neurosci Div, New York, NY 10027 USA. [Cosentino, Stephanie; Gu, Yian; Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Ornstein, Katherine] Icahn Sch Med Mt Sinai, Div Gen Internal Med, Samuel Bronfman Dept Med, New York, NY 10029 USA. [Andrews, Howard] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY USA. RP Zhu, CW (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu FU National Institute on Aging [AG07370, AG037212]; Department of Veterans Affairs, Veterans Health Administration FX This research was supported by grants from the National Institute on Aging (AG07370, AG037212). C.W.Z. was also supported by the Department of Veterans Affairs, Veterans Health Administration. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 33 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 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2015 VL 70 IS 11 BP 1448 EP 1453 DI 10.1093/gerona/glv124 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA CW1QF UT WOS:000364765700020 PM 26311543 ER PT J AU de la Puente, P Weisberg, E Muz, B Nonami, A Luderer, M Stone, RM Melo, JV Griffin, JD Azab, AK AF de la Puente, Pilar Weisberg, Ellen Muz, Barbara Nonami, Atsushi Luderer, Micah Stone, Richard M. Melo, Junia V. Griffin, James D. Azab, Abdel Kareem TI Identification of ILK as a novel therapeutic target for acute and chronic myeloid leukemia SO LEUKEMIA RESEARCH LA English DT Article DE Chronic myelogenous leukemia; Acute myeloid leukemia; ILK inhibitor; Compound 22; Targeted therapies ID INTEGRIN-LINKED KINASE; PROTEIN-KINASE; BCR-ABL; CHROMOSOME; ADHESION AB Current treatment options as well as clinical efficacy are limited for chronic myelogenous leukemia (CML), Ph+ acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). In response to the pressing need for more efficacious treatment approaches and strategies to override drug resistance in advanced stage CML, Ph+ ALL, and AML, we investigated the effects of inhibition of ILK as a potentially novel and effective approach to treatment of these challenging malignancies. Using the small molecule ILK inhibitor, Cpd22, and ILK knockdown, we investigated the importance of ILK in the growth and viability of leukemia. Our results suggest that the ILK inhibition may be an effective treatment for CML, Ph+ ALL, and AML as a single therapy, with ILK expression levels positively correlating with the efficacy of ILK inhibition. The identification of ILK as a novel target for leukemia therapy warrants further investigation as a therapeutic approach that could be of potential clinical benefit in both acute and chronic myeloid leukemias. (C) 2015 Elsevier Ltd. All rights reserved. C1 [de la Puente, Pilar; Muz, Barbara; Luderer, Micah; Azab, Abdel Kareem] Washington Univ, Sch Med, Dept Radiat Oncol, Div Canc Biol, St Louis, MO 63108 USA. [Weisberg, Ellen; Nonami, Atsushi; Stone, Richard M.; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Melo, Junia V.] Univ Adelaide, Adelaide, SA, Australia. RP Azab, AK (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, Div Canc Biol, 4511 Forest Pk Ave,Room 3103, St Louis, MO 63108 USA. EM aazab@radonc.wustl.edu NR 18 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 EI 1873-5835 J9 LEUKEMIA RES JI Leuk. Res. PD NOV PY 2015 VL 39 IS 11 BP 1299 EP 1308 DI 10.1016/j.leukres.2015.09.005 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA CW9RE UT WOS:000365335100025 ER PT J AU Shukla, SA Rooney, MS Rajasagi, M Tiao, G Dixon, PM Lawrence, MS Stevens, J Lane, WJ Dellagatta, JL Steelman, S Sougnez, C Cibulskis, K Kiezun, A Hacohen, N Brusic, V Wu, CJ Getz, G AF Shukla, Sachet A. Rooney, Michael S. Rajasagi, Mohini Tiao, Grace Dixon, Philip M. Lawrence, Michael S. Stevens, Jonathan Lane, William J. Dellagatta, Jamie L. Steelman, Scott Sougnez, Carrie Cibulskis, Kristian Kiezun, Adam Hacohen, Nir Brusic, Vladimir Wu, Catherine J. Getz, Gad TI Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes SO NATURE BIOTECHNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR TYPES; T-CELLS; MOLECULES; DISCOVERY; SEQUENCE; RNA; IMMUNOTHERAPY; LANDSCAPE AB Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole-exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations are enriched for likely functional mutations, including putative loss-of-function events. Recurrence of mutations suggested that these 'hotspot' sites were positively selected. Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes, supporting immune evasion by altered HLA function as a contributory mechanism in cancer. C1 [Shukla, Sachet A.; Rajasagi, Mohini; Brusic, Vladimir; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Shukla, Sachet A.; Rooney, Michael S.; Tiao, Grace; Lawrence, Michael S.; Steelman, Scott; Sougnez, Carrie; Cibulskis, Kristian; Kiezun, Adam; Hacohen, Nir; Wu, Catherine J.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA USA. [Shukla, Sachet A.; Dixon, Philip M.] Iowa State Univ, Dept Stat, Ames, IA USA. [Rooney, Michael S.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Rajasagi, Mohini; Brusic, Vladimir; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Stevens, Jonathan; Lane, William J.; Dellagatta, Jamie L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Lane, William J.] Harvard Univ, Sch Med, Boston, MA USA. [Hacohen, Nir; Wu, Catherine J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Getz, Gad] Dept Pathol, Boston, MA USA. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. EM cwu@partners.org; gadgetz@broadinstitute.org FU Blavatnik Family Foundation; American Association for Cancer Research (AACR) (SU2C Innovative Research Grant); National Heart, Lung, and Blood Institute (NHLBI) [1RO1HL103532-01]; National Cancer Institute (NCI) [1R01CA155010-01A1] FX C.J.W. is a Scholar of the Leukemia and Lymphoma Society and acknowledges support from the Blavatnik Family Foundation, American Association for Cancer Research (AACR) (SU2C Innovative Research Grant), National Heart, Lung, and Blood Institute (NHLBI) (1RO1HL103532-01) and National Cancer Institute (NCI) (1R01CA155010-01A1). This work has made extensive use of data generated by TCGA, a project of the National Cancer Institute and National Human Genome Research Institute. We thank E. Hodis for providing access to the melanoma data. We would also like to thank C. McCowan (Broad Technology Labs), T. Shea (Broad Technology Labs), S. Young (Broad Technology Labs) and M. Weiand (Pacific Biosciences) for their help in setting up, performing and analyzing data using Pacific Biosciences RSII instruments. We are grateful to E. Fritsch for critical reading of the manuscript and providing valuable feedback. NR 47 TC 37 Z9 37 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2015 VL 33 IS 11 BP 1152 EP U71 DI 10.1038/nbt.3344 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CW3TY UT WOS:000364916000020 PM 26372948 ER PT J AU Rotem, A Ram, O Shoresh, N Sperling, RA Goren, A Weitz, DA Bernstein, BE AF Rotem, Assaf Ram, Oren Shoresh, Noam Sperling, Ralph A. Goren, Alon Weitz, David A. Bernstein, Bradley E. TI Single-cell ChIP-seq reveals cell subpopulations defined by chromatin state SO NATURE BIOTECHNOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; RNA-SEQ; GENOME; PLURIPOTENT; EXPRESSION; HETEROGENEITY; DYNAMICS; CANCER; IMMUNOPRECIPITATION; DIFFERENTIATION AB Chromatin profiling provides a versatile means to investigate functional genomic elements and their regulation. However, current methods yield ensemble profiles that are insensitive to cell-to-cell variation. Here we combine microfluidics, DNA barcoding and sequencing to collect chromatin data at single-cell resolution. We demonstrate the utility of the technology by assaying thousands of individual cells and using the data to deconvolute a mixture of ES cells, fibroblasts and hematopoietic progenitors into high-quality chromatin state maps for each cell type. The data from each single cell are sparse, comprising on the order of 1,000 unique reads. However, by assaying thousands of ES cells, we identify a spectrum of subpopulations defined by differences in chromatin signatures of pluripotency and differentiation priming. We corroborate these findings by comparison to orthogonal single-cell gene expression data. Our method for single-cell analysis reveals aspects of epigenetic heterogeneity not captured by transcriptional analysis alone. C1 [Rotem, Assaf; Sperling, Ralph A.; Weitz, David A.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Rotem, Assaf; Sperling, Ralph A.; Weitz, David A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Rotem, Assaf; Ram, Oren; Shoresh, Noam; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Epigen Program, Cambridge, MA 02142 USA. [Ram, Oren; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ram, Oren; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ram, Oren; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA USA. [Goren, Alon] Broad Inst MIT & Harvard, Broad Technol Labs, Cambridge, MA USA. RP Bernstein, BE (reprint author), Broad Inst MIT & Harvard, Epigen Program, Cambridge, MA 02142 USA. EM Weitz@seas.harvard.edu; Bernstein.Bradley@mgh.harvard.edu FU Howard Hughes Medical Institute; National Human Genome Research Institute's Centers of Excellence in Genome Sciences [P50HG006193]; ENCODE Project [U54HG006991]; National Heart, Lung, and Blood Institute [U01HL100395]; National Science Foundation [DMR-1310266]; Harvard Materials Research Science and Engineering Center [DMR-1420570]; Defense Advanced Research Projects Agency [HR0011-11-C-0093] FX We thank A. Regev, N. Yosef, E. Shema, I. Tirosh, H. Zhang, S. Gillespie and J. Xing for their valuable comments and critiques of this work. We also thank G. Kelsey for sharing single-cell data for comparisons. This research was supported by funds from Howard Hughes Medical Institute, the National Human Genome Research Institute's Centers of Excellence in Genome Sciences (P50HG006193), ENCODE Project (U54HG006991), the National Heart, Lung, and Blood Institute (U01HL100395), the National Science Foundation (DMR-1310266), the Harvard Materials Research Science and Engineering Center (DMR-1420570) and the Defense Advanced Research Projects Agency (HR0011-11-C-0093). NR 44 TC 64 Z9 66 U1 17 U2 61 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2015 VL 33 IS 11 BP 1165 EP U91 DI 10.1038/nbt.3383 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CW3TY UT WOS:000364916000024 PM 26458175 ER PT J AU Choi, J Lee, S Mallard, W Clement, K Tagliazucchi, GM Lim, H Choi, IY Ferrari, F Tsankov, AM Pop, R Lee, G Rinn, JL Meissner, A Park, PJ Hochedlinger, K AF Choi, Jiho Lee, Soohyun Mallard, William Clement, Kendell Tagliazucchi, Guidantonio Malagoli Lim, Hotae Choi, In Young Ferrari, Francesco Tsankov, Alexander M. Pop, Ramona Lee, Gabsang Rinn, John L. Meissner, Alexander Park, Peter J. Hochedlinger, Konrad TI A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs SO NATURE BIOTECHNOLOGY LA English DT Article ID PLURIPOTENT STEM-CELLS; GENE-EXPRESSION SIGNATURES; HISTONE DEACETYLASE SIRT6; AUTISM SPECTRUM DISORDER; GENERATION; METABOLISM; HIF1-ALPHA; INDUCTION; MICE AB The equivalence of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) remains controversial. Here we use genetically matched hESC and hiPSC lines to assess the contribution of cellular origin (hESC vs. hiPSC), the Sendai virus (SeV) reprogramming method and genetic background to transcriptional and DNA methylation patterns while controlling for cell line clonality and sex. We find that transcriptional and epigenetic variation originating from genetic background dominates over variation due to cellular origin or SeV infection. Moreover, the 49 differentially expressed genes we detect between genetically matched hESCs and hiPSCs neither predict functional outcome nor distinguish an independently derived, larger set of unmatched hESC and hiPSC lines. We conclude that hESCs and hiPSCs are molecularly and functionally equivalent and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional and epigenetic comparisons of pluripotent cell lines, explaining some of the previously observed differences between genetically unmatched hESCs and hiPSCs. C1 [Choi, Jiho; Hochedlinger, Konrad] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Canc, Boston, MA 02114 USA. [Choi, Jiho; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Choi, Jiho; Clement, Kendell; Tsankov, Alexander M.; Pop, Ramona; Meissner, Alexander; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA USA. [Choi, Jiho; Hochedlinger, Konrad] Howard Hughes Med Inst, Chevy Chase, MD USA. [Lee, Soohyun; Tagliazucchi, Guidantonio Malagoli; Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02114 USA. [Mallard, William; Clement, Kendell; Tsankov, Alexander M.; Pop, Ramona; Rinn, John L.; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA USA. [Mallard, William; Clement, Kendell; Tsankov, Alexander M.; Pop, Ramona; Rinn, John L.; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Tagliazucchi, Guidantonio Malagoli] Univ Modena & Reggio Emilia, Dept Life Sci, Ctr Genome Res, Modena, Italy. [Lim, Hotae; Choi, In Young; Lee, Gabsang] Johns Hopkins Univ, Sch Med, Dept Neurol, Inst Cell Engn,Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. [Rinn, John L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Park, PJ (reprint author), Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA 02114 USA. EM peter_park@harvard.edu; khochedlinger@helix.mgh.harvard.edu RI Ferrari, Francesco/H-5007-2012 OI Ferrari, Francesco/0000-0002-9811-3753 FU New York Stem Cell Foundation; Maryland Stem Cell Research Fund (TEDCO); US National Institutes of Health (NIH) grant [P01GM099117]; Howard Hughes Medical Institute (HHMI); MGH startup funds; Gerald and Darlene Jordan Endowed Chair for Regenerative Medicine; NIH [P01GM099117]; Vranos Family Graduate Research Fellowship in Developmental & Regenerative Biology FX We thank members of the Hochedlinger and Park laboratories for productive discussions and a critical reading of the manuscript. We also thank M. Stadtfeld for his helpful discussions and D. Melton for his generous donation of HUES2 and HUES3 lines. We are grateful to K. Folz-Donahue, M. Weglarz and L. Prickett at the Massachusetts General Hospital (MGH)/Harvard Stem Cell Institute (HSCI) flow cytometry core for their constant assistance and support. We are also thankful to the members of the Tufts Genomics Core for performing RNA-seq. Work in the Lee laboratory was supported by grants from the Robertson Investigator Award of the New York Stem Cell Foundation and from the Maryland Stem Cell Research Fund (TEDCO). A. M. and J.L.R. are supported by US National Institutes of Health (NIH) grant P01GM099117. A. M. is a New York Stem Cell Foundation Robertson Investigator. Parts of this work were supported by the Howard Hughes Medical Institute (HHMI), MGH startup funds, the Gerald and Darlene Jordan Endowed Chair for Regenerative Medicine (to K.H.) and a pilot grant from the NIH (P01GM099117 to K.H.). J.C. was supported by the Vranos Family Graduate Research Fellowship in Developmental & Regenerative Biology. NR 55 TC 32 Z9 34 U1 6 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2015 VL 33 IS 11 BP 1173 EP U102 DI 10.1038/nbt.3388 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA CW3TY UT WOS:000364916000025 PM 26501951 ER PT J AU Goel, S Winer, EP AF Goel, Shorn Winer, Eric P. TI A Paradigm Shift From a Dogma of the Cytotoxic Era SO ONCOLOGY-NEW YORK LA English DT Article ID METASTATIC BREAST-CANCER; LAPATINIB GW572016; TRASTUZUMAB; PERTUZUMAB; COMBINATION; CELLS; INHIBITOR; SURVIVAL; THERAPY C1 [Goel, Shorn; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goel, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU Genentech FX The authors' institution has received research funding from Genentech. Neither Dr. Goel nor Dr. Winer has any significant personal financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article. NR 14 TC 0 Z9 0 U1 1 U2 1 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 2015 VL 29 IS 11 BP 797 EP + PG 3 WC Oncology SC Oncology GA CW6ZJ UT WOS:000365147100001 PM 26573058 ER PT J AU Dizon, DS AF Dizon, Don S. TI Don Dizon, MD, on sexual health after a cancer diagnosis, and the disappointments of precision medicine SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Oncol Sexual Hlth Clin, Boston, MA 02114 USA. RP Dizon, DS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Oncol Sexual Hlth Clin, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 2015 VL 29 IS 11 BP 865 EP 866 PG 2 WC Oncology SC Oncology GA CW6ZJ UT WOS:000365147100010 PM 26573065 ER PT J AU Jolly, S Soni, P Gaffney, DK Biagioli, M Elshaikh, MA Jhingran, A Kidd, E Lee, LJ Li, LN Moore, DH Rao, GG Wahl, AO Williams, NL Yashar, CM Small, W AF Jolly, Shruti Soni, Payal Gaffney, David K. Biagioli, Matthew Elshaikh, Mohamed A. Jhingran, Anuja Kidd, Elizabeth Lee, Larissa J. Li, Linna Moore, David H. Rao, Gautam G. Wahl, Andrew O. Williams, Ned L. Yashar, Catheryn M. Small, William, Jr. TI ACR Appropriateness Criteria (R) Adjuvant Therapy in Vulvar Cancer SO ONCOLOGY-NEW YORK LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GYNECOLOGIC-ONCOLOGY-GROUP; LYMPH-NODE METASTASES; RADIATION-THERAPY; INGUINOFEMORAL LYMPHADENECTOMY; RADICAL VULVECTOMY; PROGNOSTIC-FACTORS; RECURRENCE; CHEMORADIATION; RADIOTHERAPY AB These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy. C1 [Jolly, Shruti; Soni, Payal] Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA. [Gaffney, David K.] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Biagioli, Matthew] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Elshaikh, Mohamed A.] Henry Ford Hlth Syst, Detroit, MI USA. [Jhingran, Anuja] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kidd, Elizabeth] Stanford Canc Ctr, Stanford, CA USA. [Lee, Larissa J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, Larissa J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Li, Linna] Bryn Mawr Hosp, Bryn Mawr, PA USA. [Moore, David H.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Moore, David H.] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA. [Rao, Gautam G.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Rao, Gautam G.] Amer Soc Clin Oncol, Alexandria, VA USA. [Wahl, Andrew O.] Univ Nebraska Med Ctr, Omaha, NE USA. [Williams, Ned L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Yashar, Catheryn M.] Univ Calif San Diego, San Diego, CA 92103 USA. [Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL USA. RP Jolly, S (reprint author), Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA. NR 34 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 29 IS 11 BP 867 EP + PG 8 WC Oncology SC Oncology GA CW6ZJ UT WOS:000365147100011 PM 26568534 ER PT J AU Wu, PIK Meleger, A Witkower, A Mondale, T Borg-Stein, J AF Wu, Peter I-Kung Meleger, Alec Witkower, Alan Mondale, Timothy Borg-Stein, Joanne TI Nonpharmacologic Options for Treating Acute and Chronic Pain SO PM&R LA English DT Article ID LOW-BACK-PAIN; RANDOMIZED-CONTROLLED-TRIAL; PLATELET-RICH PLASMA; OF-THE-LITERATURE; CHRONIC NECK PAIN; INTRAARTICULAR HYALURONIC-ACID; COGNITIVE-BEHAVIORAL THERAPY; CHRONIC MUSCULOSKELETAL PAIN; EPIDURAL STEROID INJECTIONS; INTERNAL DISC DISRUPTION AB This article provides a broad overview of the clinical nonpharmacologic treatment options for managing acute and chronic pain. Physical therapy and modalities, interventional techniques, emerging regenerative medicine, and cognitive behavioral paradigms of treatment are presented. Recommendations are evidence-based and are a practical resource for the musculoskeletal pain and sports medicine practitioner. C1 [Wu, Peter I-Kung] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Charlestown, MA USA. [Wu, Peter I-Kung] Harvard Univ, Dept PM&R, Charlestown, MA USA. [Meleger, Alec] Harvard Univ, Sch Med, Newton Wellesley Hosp Spine Ctr, Spaulding Rehabil Hosp, Newton, MA USA. [Meleger, Alec] Harvard Univ, Sch Med, Dept PM&R, Newton, MA USA. [Witkower, Alan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Newton Wellesley Hosp,Dept Psychiat, Newton, MA USA. [Mondale, Timothy] Newton Wellesley Hosp, Newton, MA USA. [Borg-Stein, Joanne] Harvard Univ, Sch Med, Dept PM&R, Spaulding Rehabil Hosp,Newton Wellesley Spine Ctr, Wellesley, MA 02481 USA. RP Borg-Stein, J (reprint author), Harvard Univ, Sch Med, Dept PM&R, Spaulding Rehabil Hosp,Newton Wellesley Spine Ctr, Wellesley, MA 02481 USA. EM jborgstein@partners.org NR 238 TC 1 Z9 1 U1 6 U2 10 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 2015 VL 7 IS 11 SU S BP S278 EP S294 DI 10.1016/j.pmrj.2015.09.008 PG 17 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA CW5ZC UT WOS:000365074900007 PM 26568507 ER PT J AU Robinson, DG Gallego, JA John, M Petrides, G Hassoun, Y Zhang, JP Lopez, L Braga, RJ Sevy, SM Addington, J Kellner, CH Tohen, M Naraine, M Bennett, N Greenberg, J Lencz, T Correll, CU Kane, JM Malhotra, AK AF Robinson, Delbert G. Gallego, Juan A. John, Majnu Petrides, Georgios Hassoun, Youssef Zhang, Jian-Ping Lopez, Leonardo Braga, Raphael J. Sevy, Serge M. Addington, Jean Kellner, Charles H. Tohen, Mauricio Naraine, Melissa Bennett, Natasha Greenberg, Jessica Lencz, Todd Correll, Christoph U. Kane, John M. Malhotra, Anil K. TI A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes SO SCHIZOPHRENIA BULLETIN LA English DT Article DE clinical trial; treatment response; negative symptoms; akathisia; metabolic side effects ID CARDIOMETABOLIC RISK; COMPARATIVE EFFICACY; ANTIPSYCHOTIC-DRUGS; RAISE-ETP; OLANZAPINE; PSYCHOSIS; TOLERABILITY; QUETIAPINE; TRIAL; SCALE AB Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30mg/d) or risperidone (1-6mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications. C1 [Robinson, Delbert G.; Gallego, Juan A.; John, Majnu; Petrides, Georgios; Zhang, Jian-Ping; Lencz, Todd; Correll, Christoph U.; Kane, John M.; Malhotra, Anil K.] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Robinson, Delbert G.; Gallego, Juan A.; John, Majnu; Petrides, Georgios; Hassoun, Youssef; Zhang, Jian-Ping; Lopez, Leonardo; Braga, Raphael J.; Naraine, Melissa; Bennett, Natasha; Greenberg, Jessica; Lencz, Todd; Correll, Christoph U.; Kane, John M.; Malhotra, Anil K.] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA. [Robinson, Delbert G.; Gallego, Juan A.; Petrides, Georgios; Hassoun, Youssef; Zhang, Jian-Ping; Lopez, Leonardo; Braga, Raphael J.; Lencz, Todd; Correll, Christoph U.; Kane, John M.; Malhotra, Anil K.] Hofstra North Shore LIJ Sch Med, Dept Psychiat, Hempstead, NY USA. [Robinson, Delbert G.; Petrides, Georgios; Lencz, Todd; Correll, Christoph U.; Kane, John M.; Malhotra, Anil K.] Hofstra North Shore LIJ Sch Med, Dept Mol Med, Hempstead, NY USA. [John, Majnu] Hofstra Univ, Dept Math, Hempstead, NY 11550 USA. [Sevy, Serge M.] James J Peters VA Med Ctr, Bronx, NY USA. [Addington, Jean] Univ Calgary, Hotchkiss Brain Inst, Dept Psychiat, Calgary, AB, Canada. [Kellner, Charles H.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Tohen, Mauricio] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Albuquerque, NM 87131 USA. [Correll, Christoph U.; Kane, John M.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. RP Robinson, DG (reprint author), Zucker Hillside Hosp, Res Dept, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM drobinso@nshs.edu RI Zhang, Jianping/L-9805-2016; Lencz, Todd/J-3418-2014 OI Zhang, Jianping/0000-0001-6363-6362; Lencz, Todd/0000-0001-8586-338X FU National Institutes of Health [R01 MH060004, K23MH100264, P30MH090590, P50MH080173]; Brain & Behavior Research Foundation; Bristol-Meyers Squibb; Janssen; Otsuka; St. Jude Medical; Astra Zeneca; Proteus; Ai-Cure; Corcept Therapeutics; Amgen; Genomind, Inc.; Bristol-Myers Squibb; Janssen/JJ; Novo Nordisk A/S; Takeda FX This work was supported by the National Institutes of Health (R01 MH060004 to D.G.R., K23MH100264 to J.A.G., P30MH090590 to J.M.K. and P50MH080173 to A.K.M.) and by a NARSAD Young Investigator Grant to J.A.G. from the Brain & Behavior Research Foundation. Medication supplies were donated by Bristol-Myers Squibb and by Janssen Pharmaceuticals. D.G.R. has received grants from Bristol-Meyers Squibb, Janssen, and Otsuka. G.P. has received research support from St. Jude Medical, Astra Zeneca, Proteus, Ai-Cure, Corcept Therapeutics, and Amgen. J.-P.Z. has received grant support from Genomind, Inc. L.L. has received grant funding from Janssen. C.U.C. has received grant support from Bristol-Myers Squibb, Janssen/J&J, Novo Nordisk A/S, Otsuka, and Takeda. NR 25 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2015 VL 41 IS 6 BP 1227 EP 1236 DI 10.1093/schbul/sbv125 PG 10 WC Psychiatry SC Psychiatry GA CW1TR UT WOS:000364774900008 PM 26338693 ER PT J AU Qiao, Q Wu, H AF Qiao Qi Wu Hao TI Supramolecular organizing centers (SMOCs) as signaling machines in innate immune activation SO SCIENCE CHINA-LIFE SCIENCES LA English DT Review DE innate immunity; caspase-recruitment domain; pyrin domain; supramolecular organizing centers; filament ID NF-KAPPA-B; TOLL-LIKE RECEPTORS; RIG-I; DOMAIN; INFLAMMASOMES; COMPLEX; DEATH; TRANSDUCTION; MUTATIONS; MECHANISM AB Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving into the structural basis of signal transduction by innate immune receptors, our lab has recently helped to establish the new paradigm in which innate immune receptors transduce ligand-binding signals through formation of higher-order assemblies containing intracellular adapters, signaling enzymes and their substrates. These large signalosome assemblies may be visible under light microscopy as punctate structures in the A mu m scale, connecting to the underlying molecular structures in the nm scale. They drive proximity-induced enzyme activation, and provide a mechanism for signaling amplification by nucleated polymerization. These supramolecular signaling complexes also open new questions on their cellular organization and mode of regulation, pose challenges to our methodology, and afford valuable implications in drug discovery against these medically important pathways. C1 [Qiao Qi; Wu Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Qiao Qi; Wu Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Wu, H (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM wu@crystal.harvard.edu FU NIAID NIH HHS [R01 AI045937] NR 48 TC 2 Z9 2 U1 1 U2 3 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 EI 1869-1889 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD NOV PY 2015 VL 58 IS 11 BP 1067 EP 1072 DI 10.1007/s11427-015-4951-z PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CW6TF UT WOS:000365130000004 PM 26511517 ER PT J AU Tapias, LF Ott, HC Mathisen, DJ AF Tapias, Luis F. Ott, Harald C. Mathisen, Douglas J. TI Complications Following Carinal Resections and Sleeve Resections SO THORACIC SURGERY CLINICS LA English DT Article DE Carinal resection; Sleeve resection; Bronchopleural fistula; Airway anastomosis; Airway stenosis ID CELL LUNG-CANCER; POSTPNEUMONECTOMY PULMONARY-EDEMA; LONG-TERM SURVIVAL; INHALED NITRIC-OXIDE; ANASTOMOTIC COMPLICATIONS; PROGNOSTIC-FACTORS; BRONCHOPLASTIC PROCEDURES; PERSONAL-EXPERIENCE; INDUCTION THERAPY; LOBECTOMY AB Pulmonary resections with concomitant circumferential airway resection and resection and reconstruction of carina and main stem bronchi remain challenging operations in thoracic surgery. Anastomotic complications range from mucosal sloughing and formation of granulation tissue, anastomotic ischemia promoting scar formation and stricture, to anastonnotic breakdown leading to bronchopleural or bronchovascular fistulae or complete dehiscence. Careful attention to patient selection and technical detail results in acceptable morbidity and mortality as well as good long-term survival. In this article, we focus on the technical details of the procedures, how to avoid complications and most importantly how to manage complications when they occur. C1 [Tapias, Luis F.; Ott, Harald C.; Mathisen, Douglas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, 55 Fruit St,Blake 15, Boston, MA 02114 USA. EM dmathisen@mgh.harvard.edu NR 56 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD NOV PY 2015 VL 25 IS 4 BP 435 EP + DI 10.1016/j.thorsurg.2015.07.003 PG 14 WC Respiratory System; Surgery SC Respiratory System; Surgery GA CX0HL UT WOS:000365377400007 PM 26515944 ER PT J AU Sihag, S Wright, CD AF Sihag, Smita Wright, Cameron D. TI Prevention and Management of Complications Following Tracheal Resection SO THORACIC SURGERY CLINICS LA English DT Article DE Outcomes; Complications; Tracheal resection ID ANASTOMOTIC COMPLICATIONS; SURGICAL-TREATMENT; STENOSIS; LARYNGOTRACHEAL; RECONSTRUCTION; AIRWAY; LARYNGEAL; THERAPY AB Careful patient selection and preparation are paramount to optimize outcomes following tracheal resection. Risk factors for postoperative anastomotic complications include age less than 17 years, reoperation, laryngeal involvement, diabetes, increased length of resection, and need for preoperative tracheostomy. Major complications involve the anastomosis and are associated with an increased risk of mortality. Complications range from granulation tissue formation to stricture to separation, and successful management typically requires reoperation, T-tube stenting, or tracheostomy. Other complications to consider include vocal cord edema, recurrent laryngeal nerve injury, esophageal injury, wound infection, swallowing dysfunction, aspiration pneumonia, and fistula to the esophagus or innominate artery. C1 [Sihag, Smita; Wright, Cameron D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM cdwright@partners.org NR 28 TC 0 Z9 0 U1 2 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 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD NOV PY 2015 VL 25 IS 4 BP 499 EP + DI 10.1016/j.thorsurg.2015.07.011 PG 11 WC Respiratory System; Surgery SC Respiratory System; Surgery GA CX0HL UT WOS:000365377400012 PM 26515949 ER PT J AU Auchincloss, HG Donahue, DM AF Auchincloss, Hugh G. Donahue, Dean M. TI Prevention and Management of Nerve Injuries in Thoracic Surgery SO THORACIC SURGERY CLINICS LA English DT Article DE Peripheral nerves; Anatomy; Physiology; Thoracic surgery; Complications; Peripheral nerve injury ID TUMORS AB Nerve injuries can cause substantial morbidity after thoracic surgical procedures. These injuries are preventable, provided that the surgeon has a thorough understanding of the anatomy and follows important surgical principles. When nerve injuries occur, it is important to recognize the options available in the immediate and postoperative settings, including expectant management, immediate nerve reconstruction, or auxiliary procedures. This article covers the basic anatomy and physiology of nerves and nerve injuries, an overview of techniques in nerve reconstruction, and a guide to the nerves most commonly involved in thoracic operative procedures. C1 [Auchincloss, Hugh G.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. [Donahue, Dean M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, Boston, MA 02114 USA. RP Donahue, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM ddonahue@partners.org NR 10 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1547-4127 J9 THORAC SURG CLIN JI Thorac. Surg. Clin. PD NOV PY 2015 VL 25 IS 4 BP 509 EP + DI 10.1016/j.thorsurg.2015.07.012 PG 8 WC Respiratory System; Surgery SC Respiratory System; Surgery GA CX0HL UT WOS:000365377400013 PM 26515950 ER PT J AU Kozin, ED Remenschneider, AK Shah, P Reardon, E Lee, DJ AF Kozin, Elliott D. Remenschneider, Aaron K. Shah, Parth Reardon, Edward Lee, Daniel J. TI In reference to: Endoscopic transcanal removal of symptomatic external auditory canal exostoses Response SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Letter C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Kozin, ED (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RI Kozin, Elliott/J-1225-2014 OI Kozin, Elliott/0000-0002-0305-0682 NR 3 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 EI 1532-818X J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2015 VL 36 IS 6 BP 844 EP 845 DI 10.1016/j.amjoto.2015.07.002 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA CW2DS UT WOS:000364801900027 PM 26372197 ER PT J AU Mejaddam, AY Kaafarani, HMA Ramly, EP Avery, LL Yeh, DD King, DR de Moya, MA Velmahos, GC AF Mejaddam, Ali Y. Kaafarani, Haytham M. A. Ramly, Elie P. Avery, Laura L. Yeh, Dante D. King, David R. de Moya, Marc A. Velmahos, George C. TI The clinical significance of isolated loss of lordosis on cervical spine computed tomography in blunt trauma patients: a prospective evaluation of 1,007 patients SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Cervical spine; Trauma; Loss of lordosis; Computed tomography ID OBTUNDED PATIENTS; NECK PAIN; INJURIES; METAANALYSIS; IDENTIFICATION; ASSOCIATION; CLEARANCE AB BACKGROUND: A negative computed tomographic (CT) scan may be used to rule out cervical spine (c-spine) injury after trauma. Loss of lordosis (LOL) is frequently found as the only CT abnormality. We investigated whether LOL should preclude c-spine clearance. METHODS: All adult trauma patients with isolated LOL at our Level I trauma center (February 1, 2011 to May 31, 2012) were prospectively evaluated. The primary outcome was clinically significant injury on magnetic resonance imaging (MRI), flexion-extension views, and/or repeat physical examination. RESULTS: Of 3,333 patients (40 +/- 17 years, 60% men) with a c-spine CT, 1,007 (30%) had isolated LOL. Among 841 patients with a Glasgow Coma Scale score of 15, no abnormalities were found on MRI, flexion-extension views, and/or repeat examinations, and all collars were removed. Among 166 patients with Glasgow Coma Scale less than 15, 3 (.3%) had minor abnormal MRI findings but no clinically significant injury. CONCLUSION: Isolated LOL on c-spine CT is not associated with a clinically significant injury and should not preclude c-spine clearance. (C) 2015 Elsevier Inc. All rights reserved. C1 [Mejaddam, Ali Y.; Kaafarani, Haytham M. A.; Ramly, Elie P.; Yeh, Dante D.; King, David R.; de Moya, Marc A.; Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI King, David/0000-0003-1028-1478 NR 17 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2015 VL 210 IS 5 BP 822 EP 826 DI 10.1016/j.amjsurg.2015.04.008 PG 5 WC Surgery SC Surgery GA CW6DC UT WOS:000365086700005 PM 26145386 ER PT J AU Amri, R Bordeianou, LG Sylla, P Berger, DL AF Amri, Ramzi Bordeianou, Liliana G. Sylla, Patricia Berger, David L. TI Does active smoking induce hematogenous metastatic spread in colon cancer? SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Colon cancer; Current smoking; Active smoking; Baseline metastasis; Hematogenous metastasis; Mortality ID CIGARETTE-SMOKING; COLORECTAL-CANCER AB BACKGROUND: No consensus exists on the influence of active smoking on the baseline staging of colon cancer patients. METHODS: A cohort of colon cancer patients treated surgically at Massachusetts General Hospital (2004 to 2011) was reviewed. RESULTS: Of 1,071 patients, 563 reported ever smoking, among which 128 (12%) patients were current smokers. Ex-smokers and never smokers had similar rates of nodal (relative risk [RR] .9, P = .19) and metastatic disease (RR .96, P = .72), leading to comparable colon cancer-related mortality (RR 1.01, P = .95). Current smokers had similar rates of lymph node disease (RR 1.01, P = .88), but had significantly higher stage-adjusted odds of metastatic disease at presentation (odds ratio 2.57, 95% confidence interval 1.36 to 4.98, P = .005), in addition to higher stage-adjusted all-cause mortality (hazard ratio 1.44, P = .017). CONCLUSIONS: Active smoking was a stage-independent risk factor for baseline hematogenous metastasis and mortality. As this link was not present in former smokers, a potential healthcare benefit may be achieved in terms of baseline colon cancer presentation and outcomes through smoking cessation. (C) 2015 Elsevier Inc. All rights reserved. C1 [Berger, David L.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berger, DL (reprint author), Harvard Univ, Sch Med, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM dberger@mgh.harvard.edu OI Amri, Ramzi/0000-0001-7416-6650 NR 6 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2015 VL 210 IS 5 BP 930 EP 932 DI 10.1016/j.amjsurg.2015.03.034 PG 3 WC Surgery SC Surgery GA CW6DC UT WOS:000365086700021 PM 26251219 ER PT J AU Naing, A Infante, JR Papadopoulos, K Autio, K Ott, P Wong, D Falchook, GS Patel, MR Pant, S Oft, M AF Naing, A. Infante, J. R. Papadopoulos, K. Autio, K. Ott, P. Wong, D. Falchook, G. S. Patel, M. R. Pant, S. Oft, M. TI PEGylated human IL-10 (AM0010) in advanced solid tumors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Meeting of the European-Society-for-Medical-Oncology (ESMO) CY NOV 20-21, 2015 CL Lausanne, SWITZERLAND SP European Soc Med Oncol, Bristol Myers Squibb, MSD, Merck, Pfizer, Roche, Celldex Therapeut C1 [Naing, A.] Univ Texas Houston, MD Anderson Canc Ctr, Invest Canc Therapeut, Houston, TX 77030 USA. [Infante, J. R.] PLLC, Sarah Cannon Res Inst Tennessee Oncol, Drug Dev, Nashville, TN USA. [Papadopoulos, K.] START Ctr Canc Care, Clin Trials, San Antonio, TX USA. Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, New York, NY 10021 USA. [Ott, P.] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. [Wong, D.] Univ Calif Los Angeles, Med, Hematol & Oncol, Los Angeles, CA USA. [Falchook, G. S.] HealthONE, Sarah Cannon Res Inst, Drug Dev, Denver, CO USA. [Patel, M. R.] Florida Canc Specialists, Cattlemen Off, Tampa, FL USA. [Pant, S.] Univ Oklahoma, Stephenson Canc Ctr, Oklahoma City, OK USA. [Oft, M.] ARMO BioSci, Clin Res, Redwood City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2015 VL 26 SU 8 MA 3PD BP 1 EP 2 PG 2 WC Oncology SC Oncology GA CW7EH UT WOS:000365160300004 ER PT J AU Ohkawa, S Okusaka, T Kudo, M Hatano, E Fujii, H Masumoto, A Furuse, J Wada, Y Ishii, H Obi, S Arai, K Kawazoe, S Yokosuka, O Ikeda, M Ukai, K Morita, S Asou, H Abada, PB Yang, L Zhu, AX AF Ohkawa, Shinichi Okusaka, Takuji Kudo, Masatoshi Hatano, Etsuro Fujii, Hirofumi Masumoto, Akihide Furuse, Junji Wada, Yoshiyuki Ishii, Hiroshi Obi, Shuntaro Arai, Kuniaki Kawazoe, Seiji Yokosuka, Osamu Ikeda, Masafumi Ukai, Katsuaki Morita, Sojiro Asou, Hiroya Abada, Paolo B. Yang, Ling Zhu, Andrew X. TI Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Japanese subgroup analysis of the phase III REACH trial SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Japanese-Society-of-Medical-Oncology (JSMO) CY JUL 16-18, 2015 CL Sapporo, JAPAN SP Japanese Soc Med Oncol C1 [Ohkawa, Shinichi] Kanagawa Canc Ctr, Div Hepatobiliary & Pancreat Oncol, Kanagawa, Japan. [Okusaka, Takuji] Natl Canc Ctr Hosp, Chiba, Japan. [Kudo, Masatoshi] Kinki Univ Hosp, Osaka, Japan. [Hatano, Etsuro] Kyoto Univ Hosp, Kyoto, Japan. [Fujii, Hirofumi] Jichi Med Univ Hosp, Shimotsuke, Tochigi, Japan. [Masumoto, Akihide] Aso Corp Iizuka Hosp, Tokyo, Japan. [Furuse, Junji] Kyorin Univ Hosp, Kyoto, Japan. [Wada, Yoshiyuki] Natl Hosp Org Kyushu Med Ctr, Fukuoka, Japan. [Ishii, Hiroshi] Japanese Fdn Canc Res, Canc Inst Hosp, Fukuoka, Japan. [Obi, Shuntaro] Kyoundo Hosp, Sasaki Inst, Fukuoka, Japan. [Arai, Kuniaki] Kanazawa Univ Hosp, Kanazawa, Ishikawa, Japan. [Kawazoe, Seiji] Saga Ken Med Ctr Koseikan, Saga, Japan. [Yokosuka, Osamu] Chiba Univ Hosp, Chiba, Japan. [Ikeda, Masafumi] Natl Canc Ctr Hosp East, Chiba, Japan. [Ukai, Katsuaki] Sendai Med Ctr, Sendai, Miyagi, Japan. [Morita, Sojiro] Kochi Hlth Sci Ctr, Kochi, Japan. [Asou, Hiroya] Eli Lilly & Co, Kobe, Hyogo, Japan. [Abada, Paolo B.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Yang, Ling] Eli Lilly & Co, Bridgewater, NJ USA. [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2015 VL 26 SU 7 MA O2-8-1 BP 94 EP 94 PG 1 WC Oncology SC Oncology GA CW7ED UT WOS:000365159900228 ER PT J AU Mulligan, SP Brown, JR Hillmen, P O'Brien, S Barrientos, JC Reddy, NM Coutre, S Jaeger, U James, DF Byrd, JC AF Mulligan, Stephen P. Brown, Jennifer R. Hillmen, Peter O'Brien, Susan Barrientos, Jacqueline C. Reddy, Nishitha M. Coutre, Steven Jaeger, Ulrich James, Danelle F. Byrd, John C. TI Efficacy and safety in genetic and clinical subgroups: Phase III RESONATE (TM) trial of ibrutinib vs ofatumumab in CLL/SLL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Japanese-Society-of-Medical-Oncology (JSMO) CY JUL 16-18, 2015 CL Sapporo, JAPAN SP Japanese Soc Med Oncol C1 [Mulligan, Stephen P.] Royal N Shore Hosp, St Leonards, NSW, Australia. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA USA. [Hillmen, Peter] Leeds Teaching Hosp, St James Inst Oncol, Leeds, W Yorkshire, England. [O'Brien, Susan] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Reddy, Nishitha M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Coutre, Steven] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Jaeger, Ulrich] Med Univ Vienna, Vienna, Austria. [James, Danelle F.] Pharmacyclics Inc, Sunnyvale, CA USA. [Byrd, John C.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 2015 VL 26 SU 7 MA O2-11-2 BP 96 EP 96 PG 1 WC Oncology SC Oncology GA CW7ED UT WOS:000365159900237 ER PT J AU Neale, B AF Neale, Benjamin TI Leveraging genome-wide association analysis to estimate genetic correlation SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 45th Annual Meeting of the Behavior-Genetics-Association CY JUN 20, 2015 CL San Diego, CA SP Behav Genet Assoc C1 [Neale, Benjamin] Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 2015 VL 45 IS 6 SI SI BP 675 EP 675 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA CW4RI UT WOS:000364978800124 ER PT J AU Zhang, NQ Wu, HJ Zhang, WW Wang, J Wu, H Zheng, XQ AF Zhang, Naiqian Wu, Hua-Jun Zhang, Weiwei Wang, Jun Wu, Hao Zheng, Xiaoqi TI Predicting tumor purity from methylation microarray data SO BIOINFORMATICS LA English DT Article ID GENERATION SEQUENCING DATA; DNA METHYLATION; COPY NUMBER; CANCER; DECONVOLUTION; METHYLOME; SAMPLES; GENOME; ARRAYS AB Motivation: In cancer genomics research, one important problem is that the solid tissue sample obtained from clinical settings is always a mixture of cancer and normal cells. The sample mixture brings complication in data analysis and results in biased findings if not correctly accounted for. Estimating tumor purity is of great interest, and a number of methods have been developed using gene expression, copy number variation or point mutation data. Results: We discover that in cancer samples, the distributions of data from Illumina Infinium 450 k methylation microarray are highly correlated with tumor purities. We develop a simple but effective method to estimate purities from the microarray data. Analyses of the Cancer Genome Atlas lung cancer data demonstrate favorable performance of the proposed method. C1 [Zhang, Naiqian; Zhang, Weiwei; Wang, Jun; Zheng, Xiaoqi] Shanghai Normal Univ, Dept Math, Shanghai 200234, Peoples R China. [Wu, Hua-Jun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Wu, Hua-Jun] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Wu, Hao] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. RP Wu, H (reprint author), Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. EM hao.wu@emory.edu; xqzheng@shnu.edu.cn FU National Natural Science Foundations of China [31100953, 11171224] FX This work was supported by the National Natural Science Foundations of China (31100953 to X.Z.; 11171224 to J.W.). NR 19 TC 6 Z9 6 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2015 VL 31 IS 21 BP 3401 EP 3405 DI 10.1093/bioinformatics/btv370 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA CW6UT UT WOS:000365134400001 PM 26112293 ER PT J AU Zvolensky, MJ Farris, SG Kotov, R Schechter, CB Bromet, E Gonzalez, A Vujanovic, A Pietrzakf', RH Crane, M Kaplan, J Moline, J Southwick, SM Feder, A Udasin, I Reissman, DB Luft, BJ AF Zvolensky, Michael J. Farris, Samantha G. Kotov, Roman Schechter, Clyde B. Bromet, Evelyn Gonzalez, Adam Vujanovic, Anka Pietrzakf', Robert H. Crane, Michael Kaplan, Julia Moline, Jacqueline Southwick, Steven M. Feder, Adriana Udasin, Iris Reissman, Dori B. Luft, Benjamin J. TI Posttraumatic stress symptoms and smoking among World Trade Center disaster responders: A longitudinal investigation SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID HEALTH REGISTRY ENROLLEES; RECRUITED DAILY SMOKERS; PTSD CHECKLIST PCL; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; NEW-YORK; PSYCHOMETRIC PROPERTIES; TERRORIST ATTACKS; NEGATIVE AFFECT; CENTER RESCUE AB Purpose: The current longitudinal study examined posttraumatic stress disorder (PTSD) symptom severity in relation to smoking abstinence and reduction over time among responders to the World Trade Center (WTC) disaster. Method: Participants were 763 police and 1881 non-traditional (e.g., construction workers) WTC responders who reported being smokers at an initial examination obtained between July 2002 and July 2011 at the WTC Health Program (WTC-HP). WTC responders were reassessed, on average, 2.5 years later. Results: For police WTC responders, higher levels of WTC-related PTSD symptoms at the initial visit were associated with a decreased likelihood of smoking abstinence (OR = 0.98, p = .002) and with decreased smoking reduction (beta = .06, p = .012) at the follow-up visit. WTC-related PTSD symptom severity was not related to likelihood of smoking abstinence or change in number of cigarettes smoked among non-traditional responders. Post hoc analyses suggested that for police, hyperarousal PTSD symptoms were predictive of decreased abstinence likelihood at the follow-up visit (OR = 0.56, p = .006). Discussion: The present fmdings suggest that PTSD symptoms may be differentially related to smoking behavior among police and non-traditional WTC responders in a naturalistic, longitudinal investigation. Future work may benefit from exploring further which aspects of PTSD (as compared to each other and to common variance) explain smoking maintenance. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zvolensky, Michael J.; Farris, Samantha G.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Zvolensky, Michael J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. [Kotov, Roman; Bromet, Evelyn; Gonzalez, Adam] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. [Schechter, Clyde B.] Albert Einstein Coll Med, Dept Family & Social Med, Bronx, NY 10467 USA. [Vujanovic, Anka] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Pietrzakf', Robert H.; Southwick, Steven M.] US Dept Vet Affairs, VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA. [Pietrzakf', Robert H.; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Crane, Michael; Kaplan, Julia] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Moline, Jacqueline] North Shore LIJ Hlth Syst, Dept Populat Hlth, Great Neck, NY USA. [Feder, Adriana] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Udasin, Iris] Rutgers Robert Wood Johnson Med Sch, Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA. [Reissman, Dori B.] NIOSH, WTC Hlth Program, Washington, DC USA. [Luft, Benjamin J.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. RP Zvolensky, MJ (reprint author), Univ Houston, 126 Heyne Bldg,Suite 104, Houston, TX 77204 USA. EM mjzvolen@central.uh.edu NR 54 TC 0 Z9 0 U1 5 U2 9 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 2015 VL 63 BP 46 EP 54 DI 10.1016/j.comppsych.2015.08.006 PG 9 WC Psychiatry SC Psychiatry GA CW6YA UT WOS:000365143100007 PM 26555491 ER PT J AU Maughan, BC Bachhuber, MA Mitra, N Starrels, JL AF Maughan, Brandon C. Bachhuber, Marcus A. Mitra, Nandita Starrels, Joanna L. TI Prescription monitoring programs and emergency department visits involving opioids, 2004-2011 SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Prescription drug monitoring programs; Prescription drug abuse; Opioids; Emergency departments ID FATAL HEROIN OVERDOSE; DRUG OVERDOSE; UNITED-STATES; IMPACT; DEATHS; POLICY; RISK; ANALGESICS; PROVIDERS; CLINICIAN AB Objective: To determine the association between prescription drug monitoring program (PDMP) implementation and emergency department (ED) visits involving opioid analgesics. Methods: Rates of ED visits involving opioid analgesics per 100,000 residents were estimated from the Drug Abuse Warning Network dataset for 11 geographically diverse metropolitan areas in the United States on a quarterly basis from 2004 to 2011. Generalized estimating equations assessed whether implementation of a prescriber-accessible PDMP was associated with a difference in ED visits involving opioid analgesics. Models were adjusted for calendar quarter, metropolitan area, metropolitan area-specific linear time trends, and unemployment rate. Results: Rates of ED visits involving opioid analgesics increased in all metropolitan areas. PDMP implementation was not associated with a difference in ED visits involving opioid analgesics (mean difference of 0.8 visits [95% CI: -3.7 to 5.2] per 100,000 residents per quarter). Conclusions: During 2004-2011, PDMP implementation was not associated with a change in opioid-related morbidity, as measured by emergency department visits involving opioid analgesics. Urgent investigation is needed to determine the optimal PDMP structure and capabilities to improve opioid analgesic safety. Published by Elsevier Ireland Ltd. C1 [Maughan, Brandon C.; Bachhuber, Marcus A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Maughan, Brandon C.; Bachhuber, Marcus A.; Mitra, Nandita] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Maughan, Brandon C.; Bachhuber, Marcus A.] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Starrels, Joanna L.] Montefiore Med Ctr, Albert Einstein Coll Med, Div Gen Internal Med, Bronx, NY 10467 USA. RP Maughan, BC (reprint author), Univ Penn, 1303-A Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM bmaughan@gmail.com; marcus.bachhuber@gmail.com; nanditam@mail.med.upenn.edu; jostarre@montefiore.org OI Bachhuber, Marcus/0000-0002-5610-8382 FU NIH [K23DA027719]; Leonard Davis Institute of Health Economics; United States Department of Veterans Affairs; Robert Wood Johnson Foundation Clinical Scholars Program at the University of Pennsylvania FX This study was funded by NIH K23DA027719 (Dr. Starrels). Drs. Maughan and Bachhuber received additional support from the Leonard Davis Institute of Health Economics, the United States Department of Veterans Affairs, and the Robert Wood Johnson Foundation Clinical Scholars Program at the University of Pennsylvania. The funding bodies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. NR 66 TC 0 Z9 0 U1 4 U2 6 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 2015 VL 156 BP 282 EP 288 DI 10.1016/j.drugalcdep.2015.09.024 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA CW5SN UT WOS:000365057000038 PM 26454836 ER PT J AU Goessling, W Sadler, KC AF Goessling, Wolfram Sadler, Kirsten C. TI Zebrafish: An Important Tool for Liver Disease Research SO GASTROENTEROLOGY LA English DT Review DE Development; Technology; Liver Cancer; Toxicology; Regeneration ID FISH BRACHYDANIO-RERIO; B-VIRUS X; ENDOPLASMIC-RETICULUM FUNCTION; DIFFERENT DEVELOPMENTAL-STAGES; CHRONIC ETHANOL EXPOSURE; TROUT SALMO-GAIRDNERI; DANIO-RERIO; HEPATIC STEATOSIS; FATTY LIVER; HEPATOCELLULAR-CARCINOMA AB As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin-or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. C1 [Goessling, Wolfram] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Broad Inst MIT & Harvard, Boston, MA USA. [Sadler, Kirsten C.] Icahn Sch Med Mt Sinai, Dept Med, Div Liver Dis, New York, NY 10029 USA. [Sadler, Kirsten C.] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Sadler, Kirsten C.] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA. RP Sadler, KC (reprint author), New York Univ, Biol Program, Abu Dhabi Saadiyat Campus,POB 129188, Abu Dhabi, U Arab Emirates. EM kirsten.edepli@nyu.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU National Institutes of Health [5R01DK080789, 5R01AA018886, R01DK090311] FX Supported by grants from the National Institutes of Health (5R01DK080789 and 5R01AA018886 to K.C.S and R01DK090311 to W.G.). W.G. is a Pew Scholar in the Biomedical Sciences. NR 147 TC 3 Z9 4 U1 6 U2 27 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2015 VL 149 IS 6 BP 1361 EP 1377 DI 10.1053/j.gastro.2015.08.034 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6GN UT WOS:000365095800024 PM 26319012 ER PT J AU Nguyen, T Duan, ZG Naik, AD Kramer, JR El-Serag, HB AF Theresa Nguyen Duan, Zhigang Naik, Aanand D. Kramer, Jennifer R. El-Serag, Hashem B. TI Statin Use Reduces Risk of Esophageal Adenocarcinoma in US Veterans With Barrett's Esophagus: A Nested Case-Control Study SO GASTROENTEROLOGY LA English DT Article DE Chemoprevention; Drug; Esophageal Cancer; Pharmacoepidemiology; Statin ID PROLIFERATION; PROGRESSION; APOPTOSIS; MARKERS; GROWTH; CELLS AB BACKGROUND & AIMS: Statins have been reported to protect against esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). However, there are few data from adequately powered cohort studies of subjects with BE. METHODS: We conducted a nested case-control study of a cohort of BE patients identified from national Veteran Affairs (VA) outpatient files, diagnosed with BE from 2004 through 2009. New cases of EAC recorded after BE diagnosis were identified during a follow-up period that ended in 2011 and verified using electronic medical records. We selected patients with BE without EAC (controls) using incidence density sampling; 3 controls were matched to each case based on birth year and date of BE diagnosis. Our analysis included only male patients with at least 1 VA visit per year of follow up. We identified prescriptions for statins and non-statin lipid lowering medications filled after BE diagnosis and up to 90 days before EAC diagnosis for cases and controls (during the corresponding time period); we examined the association between statin use and EAC in conditional logistic regression models. RESULTS: We compared 311 EAC cases to 856 controls. Cases were less likely to use any statins than controls (40.2% vs 54.0%; P < .01). Significantly lower proportions of cases used statins for 6-18 months (10.0% cases vs 17.1% controls) and >18 months (19.3% vs 24.0%, respectively; P < .01). Simvastatin was the most commonly prescribed statin (accounting for 86.9% of statin use); the defined daily dose of simvastatin was lower in cases than in controls (21-40 mg/day, 9.3% vs 14.5%, respectively; and >40 mg/day, 8.4% vs 12.6%, respectively; P < .01). In multivariate analysis, statin use was inversely associated with development of EAC (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.47-0.91). This protective association was strongest for patients with advanced-stage EAC: in a stratified analysis, comparison of 189 cases with stage 0-1 EAC to 520 controls produced an adjusted OR of 0.85 (95% CI, 0.54-1.33). Among patients with late-stage EAC (stages 2-4, n = 106) and 291 controls, the adjusted OR was 0.44 (95% CI, 0.25-0.79). We found no association between EAC and non-statin lipid-lowering medications. CONCLUSIONS: In a case-control study of US veterans, statin use among those with BE appeared to decrease the risk of EAC. This protective effect was strongest against advanced-stage EAC, and increased with statin dose. C1 [Theresa Nguyen; Duan, Zhigang; El-Serag, Hashem B.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Theresa Nguyen; Naik, Aanand D.; Kramer, Jennifer R.; El-Serag, Hashem B.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), MEDVAMC 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.edu FU National Institutes of Health [NCI R01 116845]; Texas Digestive Disease Center NIH [DK58338]; resources of the Michael E. DeBakey VA Medical Center Section of Health Services Research and Development Center of Innovation in Quality, Effectiveness, and Safety, Houston, Texas [CIN 13-413]; National Institute of Diabetes and Digestive and Kidney Diseases [K24-04-107] FX This work was funded in part by National Institutes of Health grant NCI R01 116845, Texas Digestive Disease Center NIH grant DK58338, and resources of the Michael E. DeBakey VA Medical Center Section of Health Services Research and Development Center of Innovation in Quality, Effectiveness, and Safety (CIN 13-413), Houston, Texas. Dr El-Serag is also supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K24-04-107. The opinions expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, the US Government or Baylor College of Medicine. NR 22 TC 3 Z9 3 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2015 VL 149 IS 6 BP 1392 EP 1398 DI 10.1053/j.gastro.2015.07.009 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6GN UT WOS:000365095800027 PM 26208896 ER PT J AU Kelsen, JR Dawany, N Moran, CJ Petersen, BS Sarmady, M Sasson, A Pauly-Hubbard, H Martinez, A Maurer, K Soong, J Rappaport, E Franke, A Keller, A Winter, HS Mamula, P Piccoli, D Artis, D Sonnenberg, GF Daly, M Sullivan, KE Baldassano, RN Devoto, M AF Kelsen, Judith R. Dawany, Noor Moran, Christopher J. Petersen, Britt-Sabina Sarmady, Mahdi Sasson, Ariella Pauly-Hubbard, Helen Martinez, Alejandro Maurer, Kelly Soong, Joanne Rappaport, Eric Franke, Andre Keller, Andreas Winter, Harland S. Mamula, Petar Piccoli, David Artis, David Sonnenberg, Gregory F. Daly, Mark Sullivan, Kathleen E. Baldassano, Robert N. Devoto, Marcella TI Exome Sequencing Analysis Reveals Variants in Primary Immunodeficiency Genes in Patients With Very Early Onset Inflammatory Bowel Disease SO GASTROENTEROLOGY LA English DT Article DE IBD; Inherited Defects; Common Variable Immune; Deficiency; CVID; Innate and Adaptive Immunity ID COMMON VARIABLE IMMUNODEFICIENCY; INTERLEUKIN-10 RECEPTOR; IL-10-DEFICIENT MICE; COMMENSAL BACTERIA; IL-10 DEFICIENCY; CROHNS-DISEASE; T-CELLS; COLITIS; SUSCEPTIBILITY; ENTEROCOLITIS AB BACKGROUND & AIMS: Very early onset inflammatory bowel disease (VEO-IBD), IBD diagnosed at 5 years of age or younger, frequently presents with a different and more severe phenotype than older-onset IBD. We investigated whether patients with VEO-IBD carry rare or novel variants in genes associated with immunodeficiencies that might contribute to disease development. METHODS: Patients with VEO-IBD and parents (when available) were recruited from the Children's Hospital of Philadelphia from March 2013 through July 2014. We analyzed DNA from 125 patients with VEO-IBD (age, 3 wk to 4 y) and 19 parents, 4 of whom also had IBD. Exome capture was performed by Agilent SureSelect V4, and sequencing was performed using the Illumina HiSeq platform. Alignment to human genome GRCh37 was achieved followed by postprocessing and variant calling. After functional annotation, candidate variants were analyzed for change in protein function, minor allele frequency less than 0.1%, and scaled combined annotation-dependent depletion scores of 10 or less. We focused on genes associated with primary immunodeficiencies and related pathways. An additional 210 exome samples from patients with pediatric IBD (n = 45) or adult-onset Crohn's disease (n = 20) and healthy individuals (controls, n = 145) were obtained from the University of Kiel, Germany, and used as control groups. RESULTS: Four hundred genes and regions associated with primary immunodeficiency, covering approximately 6500 coding exons totaling more than 1 Mbp of coding sequence, were selected from the whole-exome data. Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19. CONCLUSIONS: In an exome sequence analysis of patients with VEO-IBD and their parents, we identified variants in genes that regulate B- and T-cell functions and could contribute to pathogenesis. Our analysis could lead to the identification of previously unidentified IBD-associated variants. C1 [Kelsen, Judith R.; Pauly-Hubbard, Helen; Martinez, Alejandro; Mamula, Petar; Piccoli, David; Baldassano, Robert N.] Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Dawany, Noor; Sarmady, Mahdi; Sasson, Ariella] Childrens Hosp Philadelphia, Dept Biomed Hlth Informat, Philadelphia, PA 19104 USA. [Maurer, Kelly; Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Div Immunol & Allergy, Philadelphia, PA 19104 USA. [Rappaport, Eric] Childrens Hosp Philadelphia, Nucl Acid Polymerase Chain React Core, Philadelphia, PA 19104 USA. [Devoto, Marcella] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Moran, Christopher J.; Winter, Harland S.] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA USA. [Petersen, Britt-Sabina; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Soong, Joanne; Artis, David; Sonnenberg, Gregory F.] Weill Cornell Med Coll, Dept Microbiol & Immunol, Div Gastroenterol & Hepatol, Joan & Sanford I Weill Dept Med, New York, NY USA. [Soong, Joanne; Artis, David; Sonnenberg, Gregory F.] Weill Cornell Med Coll, Jill Roberts Inst Res Inflammatory Bowel Dis, New York, NY USA. [Keller, Andreas] Univ Saarland, Dept Clin Bioinformat, D-66123 Saarbrucken, Germany. [Daly, Mark] Massachusetts Gen Hosp, Human Genet Res Dept Med, Analyt & Translat Unit Ctr, Boston, MA 02114 USA. [Daly, Mark] MIT & Harvard, Broad Inst, Boston, MA USA. [Devoto, Marcella] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Dept Pediat, Philadelphia, PA 19104 USA. [Devoto, Marcella] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy. RP Kelsen, JR (reprint author), Childrens Hosp Philadelphia, Div Pediat Gastroenterol, 7NW,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM Kelsen@email.chop.edu RI Franke, Andre/B-2151-2010; Petersen, Britt-Sabina/I-1671-2012; OI Franke, Andre/0000-0003-1530-5811; Petersen, Britt-Sabina/0000-0001-9022-9017; , Andreas/0000-0002-5361-0895 FU NIDDK NIH HHS [K23 DK100461] NR 53 TC 6 Z9 6 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2015 VL 149 IS 6 BP 1415 EP 1424 DI 10.1053/j.gastro.2015.07.006 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6GN UT WOS:000365095800030 PM 26193622 ER PT J AU Guindalini, RSC Win, AK Gulden, C Lindor, NM Newcomb, PA Haile, RW Raymond, V Stoffel, E Hall, M Llor, X Ukaegbu, CI Solomon, I Weitzel, J Kalady, M Blanco, A Terdiman, J Shuttlesworth, GA Lynch, PM Hampel, H Lynch, HT Jenkins, MA Olopade, OI Kupfer, SS AF Guindalini, Rodrigo Santa Cruz Win, Aung Ko Gulden, Cassandra Lindor, Noralane M. Newcomb, Polly A. Haile, Robert W. Raymond, Victoria Stoffel, Elena Hall, Michael Llor, Xavier Ukaegbu, Chinedu I. Solomon, Ilana Weitzel, Jeffrey Kalady, Matthew Blanco, Amie Terdiman, Jonathan Shuttlesworth, Gladis A. Lynch, Patrick M. Hampel, Heather Lynch, Henry T. Jenkins, Mark A. Olopade, Olufunmilayo I. Kupfer, Sonia S. TI Mutation Spectrum and Risk of Colorectal Cancer in African American Families with Lynch Syndrome SO GASTROENTEROLOGY LA English DT Article DE African Descent; Colon Cancer; DNA Repair; Hereditary Non-Polyposis Colorectal Cancer ID AFFECTED 1ST-DEGREE RELATIVES; REVISED BETHESDA GUIDELINES; MISMATCH-REPAIR GENES; COLON-CANCER; MICROSATELLITE INSTABILITY; EUROPEAN AMERICANS; GERMLINE MUTATIONS; ETHNIC-DIFFERENCES; RACIAL-DIFFERENCES; OVARIAN-CANCER AB BACKGROUND & AIMS: African Americans (AAs) have the highest incidence of and mortality resulting from colorectal cancer (CRC) in the United States. Few data are available on genetic and nongenetic risk factors for CRC among AAs. Little is known about cancer risks and mutations in mismatch repair (MMR) genes in AAs with the most common inherited CRC condition, Lynch syndrome. We aimed to characterize phenotype, mutation spectrum, and risk of CRC in AAs with Lynch syndrome. METHODS: We performed a retrospective study of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers. We analyzed data on personal and family histories of cancer. Modified segregation analysis conditioned on ascertainment criteria was used to estimate age-and sex-specific CRC cumulative risk, studying members of the mutation-carrying families. RESULTS: We identified 51 AA families with deleterious mutations that disrupt function of the MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 individual, and 11 have not been previously reported. In the 920 members of the 51 families with deleterious mutations, the cumulative risks of CRC at 80 years of age were estimated to be 36.2% (95% confidence interval [ CI], 10.5%-83.9%) for men and 29.7% (95% CI, 8.31%-76.1%) for women. CRC risk was significantly higher among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5). CONCLUSIONS: We estimate the cumulative risk for CRC in AAs with MMR gene mutations to be similar to that of individuals of European descent with Lynch syndrome. Twothirds of mutations were found in MLH1, some of which were found in multiple individuals and some that have not been previously reported. Differences in mutation spectrum are likely to reflect the genetic diversity of this population. C1 [Guindalini, Rodrigo Santa Cruz; Gulden, Cassandra; Olopade, Olufunmilayo I.; Kupfer, Sonia S.] Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA. [Win, Aung Ko; Jenkins, Mark A.] Univ Melbourne, Ctr Epidemiol & Biostat, Parkville, Vic 3052, Australia. [Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA. [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Haile, Robert W.] Stanford Univ, Div Oncol, Dept Med, Stanford, CA 94305 USA. [Raymond, Victoria; Stoffel, Elena] Univ Michigan, Ann Arbor, MI 48109 USA. [Hall, Michael] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Llor, Xavier] Univ Illinois, Chicago, IL USA. [Ukaegbu, Chinedu I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Solomon, Ilana; Weitzel, Jeffrey] City Hope Natl Med Ctr, Duarte, CA USA. [Kalady, Matthew] Cleveland Clin, Cleveland, OH 44106 USA. [Blanco, Amie; Terdiman, Jonathan] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shuttlesworth, Gladis A.; Lynch, Patrick M.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hampel, Heather] Ohio State Univ, Columbus, OH 43210 USA. [Lynch, Henry T.] Creighton Univ, Sch Med, Omaha, NE 68178 USA. RP Kupfer, SS (reprint author), 900 East 57th St,MB 9, Chicago, IL 60637 USA. EM skupfer@medicine.bsd.uchicago.edu RI Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Win, Aung Ko/0000-0002-2794-5261 FU National Institutes of Health/National Cancer Institute [K08 CA142892, CA167551]; Ralph and Marion Falk Medical Research Trust; City of Hope Clinical Cancer Genetics Community Research Network; Hereditary Cancer Research Registry; National Cancer Institute [RC4CA153828]; Office of the Director, National Institutes of Health FX This work was supported by two grants awarded to S.S.K. by the National Institutes of Health/National Cancer Institute: K08 CA142892 and UMI grant CA167551, and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. Collaborating centers include University of Southern California Consortium, Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, and Seattle Colorectal Cancer Family Registry. A.K.W. is an Australian National Health and Medical Research Council (NHMRC) Early Career Fellow. M.A.J. is NHMRC Senior Research Fellow. O.I.O. is an ACS Clinical Research Professor and is supported by grants from the Ralph and Marion Falk Medical Research Trust. This work was also supported by City of Hope Clinical Cancer Genetics Community Research Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (J.W.) from the National Cancer Institute and the Office of the Director, National Institutes of Health. NR 53 TC 3 Z9 3 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2015 VL 149 IS 6 BP 1446 EP 1453 DI 10.1053/j.gastro.2015.07.052 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6GN UT WOS:000365095800033 PM 26248088 ER PT J AU Beste, LA Leipertz, SL Green, PK Dominitz, JA Ross, D Ioannou, GN AF Beste, Lauren A. Leipertz, Steven L. Green, Pamela K. Dominitz, Jason A. Ross, David Ioannou, George N. TI Trends in Burden of Cirrhosis and Hepatocellular Carcinoma by Underlying Liver Disease in US Veterans, 2001-2013 SO GASTROENTEROLOGY LA English DT Article DE Diabetes; Hepatitis B Virus; NASH; Obesity ID CHRONIC HEPATITIS-C; SUSTAINED VIROLOGICAL RESPONSE; ALL-CAUSE MORTALITY; UNITED-STATES; VIRUS-INFECTION; VIRAL-HEPATITIS; PREVALENCE; AFFAIRS; SURVEILLANCE; PROGRESSION AB BACKGROUND & AIMS: Cirrhosis and hepatocellular carcinoma (HCC) are predicted to increase in the United States but the accuracy of prior forecasts and the contributions from various liver disease etiologies remain unclear. We aimed to determine the burden of cirrhosis and HCC according to underlying cause from 2001 to 2013. METHODS: We developed a national retrospective cohort of Veterans Affairs (VA) patients with the diagnosis of cirrhosis (n 129,998) or HCC (n = 21,326) from 2001 to 2013. We used laboratory results, International Classification of Diseases, ninth edition (ICD-9) codes, and body mass index to identify underlying etiologies. RESULTS: In 2013, VA provided care to 5,720,614 individuals, of whom 60,553 (1.06%) had cirrhosis and 7,670 (0.13%) had HCC. Hepatitis C virus (HCV) was present in an increasing proportion of cirrhosis and HCC between 2001 and 2013, reaching 48% of cirrhosis cases and deaths and 67% of HCC cases and deaths by 2013. Cirrhosis prevalence nearly doubled from 2001 to 2013 (664 to 1058 per 100,000 enrollees), driven by HCV and nonalcoholic fatty liver disease (NAFLD). Cirrhosis incidence ranged from 159 to 193 per 100,000 patient-years. Deaths in patients with cirrhosis increased from 83 to 126 per 100,000 patient-years, largely driven by HCV. HCC incidence was 2.5-fold increased from 17 to 45 per 100,000 patient-years. HCC mortality tripled from 13 to 37 per 100,000 patient-years, driven overwhelmingly by HCV, with much smaller contributions from NAFLD and alcoholic liver disease. CONCLUSIONS: Cirrhosis prevalence and mortality and HCC incidence and mortality increased from 2001 to 2013, driven by HCV, with a smaller contribution from NAFLD. If current trends continue, cirrhosis prevalence will peak in 2021. Health care systems will need to accommodate rising numbers of patients with cirrhosis and HCC. C1 [Beste, Lauren A.; Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, Primary Care Serv, Seattle, WA 98108 USA. [Beste, Lauren A.; Leipertz, Steven L.; Green, Pamela K.; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Beste, Lauren A.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Dominitz, Jason A.; Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Ross, David] US Dept Vet Affairs, HIV HCV & Publ Hlth Pathogens Programs, Off Publ Hlth Clin Publ Hlth, Washington, DC USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, S-111-Gastro,1660 South Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Merit Review grant, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs [I01CX000320]; HIV, Hepatitis, and Public Health Pathogens Program of the Office of Public Health, Department of Veterans Affairs FX This study was supported by Merit Review grant I01CX000320, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs (G.N.I.) and by the HIV, Hepatitis, and Public Health Pathogens Program of the Office of Public Health, Department of Veterans Affairs (L.A.B.). The sponsors had no role in study design or collection, analysis or interpretation of the data. NR 35 TC 21 Z9 22 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2015 VL 149 IS 6 BP 1471 EP + DI 10.1053/j.gastro.2015.07.056 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6GN UT WOS:000365095800036 PM 26255044 ER PT J AU Springer, S Wang, YX Dal Molin, M Masica, DL Jiao, YC Kinde, I Blackford, A Raman, SP Wolfgang, CL Tomita, T Niknafs, N Douville, C Ptak, J Dobbyn, L Allen, PJ Klimstra, DS Schattner, MA Schmidt, CM Yip-Schneider, M Cummings, OW Brand, RE Zeh, HJ Singhi, AD Scarpa, A Salvia, R Malleo, G Zamboni, G Falconi, M Jang, JY Kim, SW Kwon, W Hong, SM Song, KB Kim, SC Swan, N Murphy, J Geoghegan, J Brugge, W Fernandez-Del Castillo, C Mino-Kenudson, M Schulick, R Edil, BH Adsay, V Paulino, J van Hooft, J Yachida, S Nara, S Hiraoka, N Yamao, K Hijioka, S van der Merwe, S Goggins, M Canto, MI Ahuja, N Hirose, K Makary, M Weiss, MJ Cameron, J Pittman, M Eshleman, JR Diaz, LA Papadopoulos, N Kinzler, KW Karchin, R Hruban, RH Vogelstein, B Lennon, AM AF Springer, Simeon Wang, Yuxuan Dal Molin, Marco Masica, David L. Jiao, Yuchen Kinde, Isaac Blackford, Amanda Raman, Siva P. Wolfgang, Christopher L. Tomita, Tyler Niknafs, Noushin Douville, Christopher Ptak, Janine Dobbyn, Lisa Allen, Peter J. Klimstra, David S. Schattner, Mark A. Schmidt, C. Max Yip-Schneider, Michele Cummings, Oscar W. Brand, Randall E. Zeh, Herbert J. Singhi, Aatur D. Scarpa, Aldo Salvia, Roberto Malleo, Giuseppe Zamboni, Giuseppe Falconi, Massimo Jang, Jin-Young Kim, Sun-Whe Kwon, Wooil Hong, Seung-Mo Song, Ki-Byung Kim, Song Cheol Swan, Niall Murphy, Jean Geoghegan, Justin Brugge, William Fernandez-Del Castillo, Carlos Mino-Kenudson, Mari Schulick, Richard Edil, Barish H. Adsay, Volkan Paulino, Jorge van Hooft, Jeanin Yachida, Shinichi Nara, Satoshi Hiraoka, Nobuyoshi Yamao, Kenji Hijioka, Susuma van der Merwe, Schalk Goggins, Michael Canto, Marcia Irene Ahuja, Nita Hirose, Kenzo Makary, Martin Weiss, Matthew J. Cameron, John Pittman, Meredith Eshleman, James R. Diaz, Luis A., Jr. Papadopoulos, Nickolas Kinzler, Kenneth W. Karchin, Rachel Hruban, Ralph H. Vogelstein, Bert Lennon, Anne Marie TI A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts SO GASTROENTEROLOGY LA English DT Article DE Molecular; IPMN; Diagnosis; Pancreatic Cyst ID PAPILLARY MUCINOUS NEOPLASMS; CLINICOPATHOLOGICAL FEATURES; UPDATED EXPERIENCE; PREVALENCE; MUTATIONS; CANCER; GENES; DNA AB BACKGROUND & AIMS: The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. METHODS: We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. RESULTS: We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. CONCLUSIONS: We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery. C1 [Springer, Simeon; Wang, Yuxuan; Jiao, Yuchen; Kinde, Isaac; Ptak, Janine; Dobbyn, Lisa; Eshleman, James R.; Diaz, Luis A., Jr.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Hruban, Ralph H.; Vogelstein, Bert] Johns Hopkins Univ, Ludwig Ctr, Baltimore, MD USA. [Springer, Simeon; Wang, Yuxuan; Jiao, Yuchen; Kinde, Isaac; Ptak, Janine; Dobbyn, Lisa; Eshleman, James R.; Diaz, Luis A., Jr.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Hruban, Ralph H.; Vogelstein, Bert] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA. [Springer, Simeon; Wang, Yuxuan; Dal Molin, Marco; Masica, David L.; Jiao, Yuchen; Kinde, Isaac; Wolfgang, Christopher L.; Ptak, Janine; Dobbyn, Lisa; Goggins, Michael; Pittman, Meredith; Eshleman, James R.; Diaz, Luis A., Jr.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Karchin, Rachel; Hruban, Ralph H.; Vogelstein, Bert; Lennon, Anne Marie] Johns Hopkins Univ, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA. [Dal Molin, Marco; Pittman, Meredith; Hruban, Ralph H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Masica, David L.; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Karchin, Rachel] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Masica, David L.; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Karchin, Rachel] Johns Hopkins Univ, Johns Hopkins Med Inst, Baltimore, MD USA. [Masica, David L.; Tomita, Tyler; Niknafs, Noushin; Douville, Christopher; Karchin, Rachel] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD USA. [Blackford, Amanda] Johns Hopkins Univ, Dept Biostat & Bioinformat, Baltimore, MD USA. [Raman, Siva P.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Wolfgang, Christopher L.; Ahuja, Nita; Hirose, Kenzo; Makary, Martin; Weiss, Matthew J.; Cameron, John; Diaz, Luis A., Jr.; Lennon, Anne Marie] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA. [Wolfgang, Christopher L.; Goggins, Michael; Karchin, Rachel; Hruban, Ralph H.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Allen, Peter J.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Schattner, Mark A.] Mem Sloan Kettering Canc Ctr, Dept Gastroenterol, New York, NY 10021 USA. [Schmidt, C. Max] Indiana Univ, Dept Surg, Bloomington, IN USA. [Yip-Schneider, Michele; Cummings, Oscar W.] Indiana Univ, Dept Pathol, Bloomington, IN USA. [Brand, Randall E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Zeh, Herbert J.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Singhi, Aatur D.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Scarpa, Aldo] Univ & Hosp Trust Verona, ARC Net Res Ctr, Dept Pathol & Diagnost, Verona, Italy. [Scarpa, Aldo; Zamboni, Giuseppe] Univ & Hosp Trust Verona, Dept Pathol Gen Surg B, Verona, Italy. [Salvia, Roberto; Malleo, Giuseppe] Univ & Hosp Trust Verona, Dept Surg, Verona, Italy. [Zamboni, Giuseppe] Osped Sacro Cuore Don Calabraia, Dept Pathol, Negrar, Italy. [Falconi, Massimo] IRCCS San Raffaele Sci Inst, Dept Surg, Div Pancreat Surg, Milan, Italy. [Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Jang, Jin-Young; Kim, Sun-Whe; Kwon, Wooil] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Hong, Seung-Mo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea. [Song, Ki-Byung; Kim, Song Cheol] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Hepatobiliary & Pancreas Surg, Seoul, South Korea. [Swan, Niall; Murphy, Jean] St Vincents Univ Hosp, Dept Histopathol, Dublin 4, Ireland. [Geoghegan, Justin] St Vincents Univ Hosp, Dept Surg, Dublin 4, Ireland. [Brugge, William] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Fernandez-Del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Histopathol, Boston, MA 02114 USA. [Schulick, Richard; Edil, Barish H.] Univ Colorado, Dept Surg, Boulder, CO 80309 USA. [Adsay, Volkan] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Paulino, Jorge] Hosp Curry Cabral, Ctr Hepatobiliopancreat & Transplantacao, Dept Pathol, Lisbon, Portugal. [van Hooft, Jeanin] Amsterdam Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands. [Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Surg Pathol & Canc, Tokyo, Japan. [Yachida, Shinichi; Nara, Satoshi; Hiraoka, Nobuyoshi] Natl Canc Ctr, Tokyo, Japan. [Hijioka, Susuma] Aichi Canc Ctr Hosp, Dept Gastroenterol, Nagoya, Aichi 464, Japan. [van der Merwe, Schalk] Univ Hosp KU Leuven, Dept Hepatol, Leuven, Belgium. [Goggins, Michael; Canto, Marcia Irene; Lennon, Anne Marie] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Lennon, AM (reprint author), Johns Hopkins Med Inst, Ludwig Ctr, 1800 Orleans St, Baltimore, MD 21287 USA. EM amlennon@jhmi.edu RI Giuseppe, Zamboni/A-5991-2016; scarpa, aldo/K-6832-2016; OI Giuseppe, Zamboni/0000-0001-7428-4673; scarpa, aldo/0000-0003-1678-739X; Falconi, Massimo/0000-0001-9654-7243 FU Lustgarten Foundation for Pancreatic Cancer Research; Sol Goldman Center for Pancreatic Cancer Research; Virginia and D. K. Ludwig Fund for Cancer Research; Michael Rolfe Foundation; National Institutes of Health [P50 CA62924]; Associazione Italiana Ricerca Cancro Italian Ministry of Research (FIRB) and Health [12182, RBAP10AHJB, J33G13000210001] FX This work supported by The Lustgarten Foundation for Pancreatic Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, The Virginia and D. K. Ludwig Fund for Cancer Research, Susan Wojcicki and Dennis Troper, The Michael Rolfe Foundation, National Institutes of Health grant P50 CA62924, Associazione Italiana Ricerca Cancro (12182) Italian Ministry of Research (FIRB RBAP10AHJB) and Health (FIMP J33G13000210001). NR 24 TC 34 Z9 35 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2015 VL 149 IS 6 BP 1501 EP 1510 DI 10.1053/j.gastro.2015.07.041 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW6GN UT WOS:000365095800039 PM 26253305 ER PT J AU Michmizos, KP Rossi, S Castelli, E Cappa, P Krebs, HI AF Michmizos, Konstantinos P. Rossi, Stefano Castelli, Enrico Cappa, Paolo Krebs, Hermano Igo TI Robot-Aided Neurorehabilitation: A Pediatric Robot for Ankle Rehabilitation SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Ankle; assist-as-needed; cerebral palsy; robotic training; sensorimotor therapy ID MOTOR SKILL ACQUISITION; REACTION-TIME; PARKINSONS-DISEASE; STROKE REHABILITATION; CEREBRAL-PALSY; GAIT PATTERNS; SPASTIC HEMIPLEGIA; ASSISTED THERAPY; CHILDREN; RECOVERY AB This paper presents the pediAnklebot, an impedance-controlled low-friction, backdriveable robotic device developed at the Massachusetts Institute of Technology that trains the ankle of neurologically impaired children of ages 6-10 years old. The design attempts to overcome the known limitations of the lower extremity robotics and the unknown difficulties of what constitutes an appropriate therapeutic interaction with children. The robot's pilot clinical evaluation is on-going and it incorporates our recent findings on the ankle sensorimotor control in neurologically intact subjects, namely the speed-accuracy tradeoff, the deviation from an ideally smooth ankle trajectory, and the reaction time. We used these concepts to develop the kinematic and kinetic performance metrics that guided the ankle therapy in a similar fashion that we have done for our upper extremity devices. Here we report on the use of the device in at least nine training sessions for three neurologically impaired children. Results demonstrated a statistically significant improvement in the performance metrics assessing explicit and implicit motor learning. Based on these initial results, we are confident that the device will become an effective tool that harnesses plasticity to guide habilitation during childhood. C1 [Michmizos, Konstantinos P.; Krebs, Hermano Igo] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Michmizos, Konstantinos P.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Michmizos, Konstantinos P.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Rossi, Stefano] Univ Tuscia, Dept Econ & Management Ind Engn, I-01100 Viterbo, Italy. [Castelli, Enrico] Bambino Gesu Pediat Hosp, Pediat Neurorehabil Div, I-00050 Rome, Italy. [Castelli, Enrico] Bambino Gesu Pediat Hosp, Dept Neurosci & Neurorehabil, I-00050 Rome, Italy. [Cappa, Paolo] Univ Roma La Sapienza, Dept Mech & Aerosp Engn, I-00184 Rome, Italy. [Cappa, Paolo] NYU, Dept Mech & Aerosp Engn, Brooklyn, NY 11201 USA. [Cappa, Paolo] Bambino Gesu Pediat Hosp, I-00050 Rome, Italy. [Krebs, Hermano Igo] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Krebs, Hermano Igo] Fujita Hlth Univ, Dept Phys Med & Rehabil, Nagoya, Aichi 4701192, Japan. [Krebs, Hermano Igo] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. RP Michmizos, KP (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. EM konmic@mit.edu; hikrebs@mit.edu OI ROSSI, Stefano/0000-0003-0006-7013 FU Cerebral Palsy International Research Foundation (CPIRF); Niarchos Foundation; National Institute of Health (NIH) [R01HD069776-02]; Italian Institute of Technology (IIT)-Project Seed ("ITINERE-Interactive Technology: an Instrumented Novel Exoskeleton for Rehabilitation"); Italian Health Ministry; Foundation for Education and European Culture FX This work was supported in part by a grant from the Cerebral Palsy International Research Foundation (CPIRF), the Niarchos Foundation, the National Institute of Health (NIH) under Grant R01HD069776-02, a grant from the Italian Institute of Technology (IIT)-Project Seed ("ITINERE-Interactive Technology: an Instrumented Novel Exoskeleton for Rehabilitation" 2009), and by a grant from the Italian Health Ministry (Grant "Pilot study on a novel typology of medical devices: robotic exoskeletons for knee rehabilitation" 2009) to P. Cappa. The work of K. P. Michmizos was supported in part by the Foundation for Education and European Culture. NR 66 TC 1 Z9 1 U1 6 U2 30 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD NOV PY 2015 VL 23 IS 6 BP 1056 EP 1067 DI 10.1109/TNSRE.2015.2410773 PG 12 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA CW2XB UT WOS:000364855300015 PM 25769168 ER PT J AU Wainger, BJ Cudkowicz, ME AF Wainger, Brian J. Cudkowicz, Merit E. TI Cortical Hyperexcitability in Amyotrophic Lateral Sclerosis C9orf72 Repeats SO JAMA NEUROLOGY LA English DT Editorial Material ID SPINAL MOTONEURONS; EXCITABILITY; STIMULATION; SURVIVAL; LESSONS; DISEASE; MODEL C1 [Wainger, Brian J.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Wainger, Brian J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. RP Wainger, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St,Room 2007, Charlestown, MA 02129 USA. EM bwainger@partners.org NR 18 TC 1 Z9 1 U1 2 U2 4 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 2015 VL 72 IS 11 BP 1235 EP 1236 DI 10.1001/jamaneurol.2015.2197 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CW1ZO UT WOS:000364790900004 PM 26348624 ER PT J AU Tereshchenko, LG Josephson, ME AF Tereshchenko, Larisa G. Josephson, Mark E. TI Frequency content and characteristics of ventricular conduction SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Vectorcardiogram; Frequency content ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; LATE POTENTIALS; BODY-SURFACE; ELECTROCARDIOGRAM; TACHYCARDIA; COMPONENTS; OCCLUSION; ISCHEMIA AB The spectrum of frequencies producing the QRS complex has not been fully explored. In this manuscript we review previous studies of QRS frequency content, and discuss our novel method of the conjoint analysis of the ECG signal in six dimensions: in the domain of three space dimensions, in time domain, and in frequency domain. Orbital frequency of QRS loop is introduced as a six-dimensional characteristic of ventricular conduction, which helped to reveal inapparent ventricular conduction, and to characterize electrophysiological substrate. In this paper, we review our novel method in the historical context. (C) 2015 Elsevier Inc. All rights reserved. C1 [Tereshchenko, Larisa G.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA. [Josephson, Mark E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc Med, Boston, MA 02215 USA. RP Tereshchenko, LG (reprint author), 3181 SW Sam Jackson Pk Rd,UHN62, Portland, OR 97239 USA. EM tereshch@ohsu.edu OI Tereshchenko, Larisa/0000-0002-6976-1313 FU National Institutes of Health [1R01HL118277] FX This research was supported in part by the National Institutes of Health #1R01HL118277. NR 36 TC 1 Z9 1 U1 2 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2015 VL 48 IS 6 BP 933 EP 937 DI 10.1016/j.jelectrocard.2015.08.034 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW3MQ UT WOS:000364896800003 PM 26364232 ER PT J AU Fidler, R Bond, R Finlay, D Guldenring, D Gallagher, A Pelter, M Drew, B Hu, X AF Fidler, Richard Bond, Raymond Finlay, Dewar Guldenring, Daniel Gallagher, Anthony Pelter, Michele Drew, Barbara Hu, Xiao TI Human factors approach to evaluate the user interface of physiologic monitoring SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Central station; Bedside monitoring; human factors in monitoring; Usability; User interface; User experience AB Background: As technology infiltrates more of our personal and professional lives, user expectations for intuitive design have driven many consumer products, while medical equipment continues to have high training requirements. Not much is known about the usability and user experience associated with hospital monitoring equipment. This pilot project aimed to better understand and describe the user interface interaction and user experience with physiologic monitoring technology. Design: This was a prospective, descriptive, mixed-methods quality improvement project to analyze perceptions and task analyses of physiologic monitors. Methods: Following a survey of practice patterns and perceived abilities to accomplish key tasks, 10 voluntary experienced physician and nurse subjects were asked to perform a series of tasks in 7 domains of monitor operations on GE Monitoring equipment in a single institution. For each task analysis, data were collected on time to complete the task, the number of button pushes or clicks required to accomplish the task, economy of motion, and observed errors. Results: Although 60% of the participants reported incorporating monitoring data into patient care, 80% of participants preferred to receive monitoring data at the point of care (bedside). Average perceived central station usability is 5.3 out of 10 (ten is easiest). Conclusions: High variability exists in monitoring station interaction performance among those participating in this project. Alarms were almost universally silenced without cognitive recognition of the alarm state. Education related to monitoring operations appeared largely absent in this sample. Most users perceived the interface to not be intuitive, complaining of multiple layers and steps for data retrieval. These clinicians report real-time monitoring helpful for abrupt changes in condition like arrhythmias; however, reviewing alarms is not prioritized as valuable due to frequent false alarms. Participants requested exporting monitoring data to electronic medical records. Much research is needed to develop best practices for display of real-time information, organization and filtering of meaningful data, and simplified ways to find information. Published by Elsevier Inc. C1 [Fidler, Richard; Pelter, Michele; Drew, Barbara; Hu, Xiao] Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Fidler, Richard] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Bond, Raymond; Finlay, Dewar; Guldenring, Daniel; Gallagher, Anthony] Univ Ulster, Ulster, Ireland. RP Fidler, R (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Anesthesiol 129, San Francisco, CA 94121 USA. EM richard.fidler@ucsf.edu OI Fidler, Richard/0000-0003-4358-7887; Bond, Raymond/0000-0002-1078-2232 NR 7 TC 0 Z9 0 U1 4 U2 15 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2015 VL 48 IS 6 BP 982 EP 987 DI 10.1016/j.jelectrocard.2015.08.032 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW3MQ UT WOS:000364896800011 PM 26375330 ER PT J AU Hertz, DL Kidwell, KM Thibert, JN Gersch, C Regan, MM Skaar, TC Henry, NL Hayes, DF Van Poznak, CH Rae, JM AF Hertz, Daniel L. Kidwell, Kelley M. Thibert, Jacklyn N. Gersch, Christina Regan, Meredith M. Skaar, Todd C. Henry, N. Lynn Hayes, Daniel F. Van Poznak, Catherine H. Rae, James M. TI Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses SO MOLECULAR ONCOLOGY LA English DT Article DE Germline genome; Somatic genome; Formalin-fixed paraffin embedded; FFPE; Cancer; Pharmacogenetics ID DRUG-METABOLIZING-ENZYMES; PERIPHERAL-BLOOD; CANCER; TISSUE; SAMPLES; GERMLINE; ACCURACY; ARRAY AB Background: Cancer pharmacogenetic studies use archival tumor samples as a DNA source when germline DNA is unavailable. Genotyping DNA from formalin-fixed paraffin embedded tumors (FFPE-T) may be inaccurate due to FFPE storage, genetic aberrations, and/or insufficient DNA extraction. Our objective was to assess the extent and source of genotyping inaccuracy from FFPE-T DNA and demonstrate analytical validity of FFPE-T genotyping of candidate single nucleotide polymorphisms (SNPs) for pharmacogenetic analyses. Methods: Cancer pharmacogenetics SNPs were genotyped by Sequenom MassARRAYs in DNA harvested from matched FFPE-T, FFPE lymph node (FFPE-LN), and whole blood leukocyte samples obtained from breast cancer patients. No- and discordant-call rates were calculated for each tissue type and SNP. Analytical validity was defined as any SNP with <5% discordance between FFPE-T and blood and <10% discordance plus no-calls. Results: Matched samples from 114 patients were genotyped for 247 SNPs. No-call rate in FFPE-T was greater than FFPE-LN and blood (4.3% vs. 3.0% vs. 0.5%, p < 0.001). Discordant-call rate between FFPE-T and blood was very low, but greater than that between FFPE-LN and blood (1.1% vs. 0.3%, p < 0.001). Samples with heterozygous genotypes were more likely to be no- or discordantly-called in either tissue (p <0.001). Analytical validity of FFPE-T genotyping was demonstrated for 218 (88%) SNPs. Conclusions: No- and discordant-call rates were below concerning thresholds, confirming that most SNPs can be accurately genotyped from FFPE-T on our Sequenom platform. FFPE-T is a viable DNA source for prospective retrospective pharmacogenetic analyses of clinical trial cohorts. (c) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Hertz, Daniel L.] Univ Michigan, Coll Pharm, Dept Clin Pharm, Ann Arbor, MI 48109 USA. [Kidwell, Kelley M.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Thibert, Jacklyn N.; Gersch, Christina; Henry, N. Lynn; Hayes, Daniel F.; Van Poznak, Catherine H.; Rae, James M.] Univ Michigan Hlth Syst, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Skaar, Todd C.] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA. [Henry, N. Lynn; Hayes, Daniel F.; Van Poznak, Catherine H.] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. RP Hertz, DL (reprint author), Univ Michigan, Coll Pharm, Dept Clin Pharm, 428 Church St,Room 3054, Ann Arbor, MI 48109 USA. EM DLHertz@med.umich.edu; kidwell@umich.edu; jthibert@med.umich.edu; clgersch@med.umich.edu; mregan@jimmy.harvard.edu; tskaar@iu.edu; norahh@med.umich.edu; hayesdf@med.umich.edu; cvanpoz@med.umich.edu; jimmyrae@med.umich.edu OI Hertz, Daniel/0000-0003-0501-1035 FU Breast Cancer Research Foundation (BCRF) [N003173]; National Institute of General Medical Sciences [1RO1GM099143]; National Institute of Dental and Craniofacial Research [5K23DE020197]; MICHR Clinical and Translational Science Award [UL1RR024986]; Fashion Foot-wear Charitable Foundation of New York/QVC Presents Shoes on Sale(TM); National Institutes of Health through the University of Michigan's Cancer Center Support Grant [P30 CA046592] FX This research was supported by the Breast Cancer Research Foundation (BCRF) (N003173 to JMR and DFH), National Institute of General Medical Sciences (1RO1GM099143 to JMR), National Institute of Dental and Craniofacial Research (5K23DE020197 to CVP), the MICHR Clinical and Translational Science Award (UL1RR024986), a grant from the Fashion Foot-wear Charitable Foundation of New York/QVC Presents Shoes on Sale (TM) (DFH), and the National Institutes of Health through the University of Michigan's Cancer Center Support Grant (P30 CA046592) by the use of the following Cancer Center Core: University of Michigan DNA Sequencing Core. NR 34 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD NOV PY 2015 VL 9 IS 9 BP 1868 EP 1876 DI 10.1016/j.molonc.2015.07.002 PG 9 WC Oncology SC Oncology GA CW3LB UT WOS:000364892700011 PM 26276228 ER PT J AU Carr, AR Paholpak, P Daianu, M Fong, SS Mather, M Jimenez, EE Thompson, P Mendez, ME AF Carr, Andrew R. Paholpak, Pongsatorn Daianu, Madelaine Fong, Sylvia S. Mather, Michelle Jimenez, Elvira E. Thompson, Paul Mendez, Mario E. TI An investigation of care-based vs. rule-based morality in frontotemporal dementia, Alzheimer's disease, and healthy controls SO NEUROPSYCHOLOGIA LA English DT Article DE Morality; Dementia; Brain; Neuropsychology; Neuroimaging; Frontotemporal ID MILD COGNITIVE IMPAIRMENT; ACQUIRED SOCIOPATHY; BEHAVIORAL VARIANT; EXECUTIVE CONTROL; DECISION-MAKING; NEURAL BASIS; MIND; EMPATHY; NETWORKS; CORTEX AB Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules. Published by Elsevier Ltd. C1 [Carr, Andrew R.; Paholpak, Pongsatorn; Fong, Sylvia S.; Mather, Michelle; Jimenez, Elvira E.; Mendez, Mario E.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Carr, Andrew R.; Paholpak, Pongsatorn; Mather, Michelle; Jimenez, Elvira E.; Mendez, Mario E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Jimenez, Elvira E.; Mendez, Mario E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Jimenez, Elvira E.; Mendez, Mario E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Carr, Andrew R.; Paholpak, Pongsatorn; Daianu, Madelaine; Fong, Sylvia S.; Mather, Michelle; Jimenez, Elvira E.; Thompson, Paul; Mendez, Mario E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. [Paholpak, Pongsatorn] Khon Kaen Univ, Dept Psychiat, Khon Khaen, Thailand. [Daianu, Madelaine; Thompson, Paul] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. RP Carr, AR (reprint author), West Angeles VA Healthcare Ctr, Neurobehav Serv 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM andrew.carr@va.gov FU National Institute of Aging [5R01AG034499-05]; V.A. Geriatrics Research, Education, and Clinical Care fellowship (ARC) FX This work was supported by the National Institute of Aging (Grant number 5R01AG034499-05) and a V.A. Geriatrics Research, Education, and Clinical Care fellowship (ARC). NR 59 TC 2 Z9 2 U1 1 U2 12 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 2015 VL 78 BP 73 EP 79 DI 10.1016/j.neuropsychologia.2015.09.033 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA CW5RH UT WOS:000365053800008 PM 26432341 ER PT J AU Jahn, J Spielau, M Brandsch, C Stangl, GI Delank, KS Bahr, I Berreis, T Wrann, CD Kielstein, H AF Jahn, Janine Spielau, Marco Brandsch, Corinna Stangl, Gabriele I. Delank, Karl-Stefan Baehr, Ina Berreis, Tobias Wrann, Christiane D. Kielstein, Heike TI Decreased NK cell functions in obesity can be reactivated by fat mass reduction SO OBESITY LA English DT Article ID NATURAL-KILLER-CELLS; LEPTIN CONCENTRATIONS; ENERGY RESTRICTION; CYTOTOXIC ACTIVITY; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; WEIGHT-LOSS; EXERCISE; CANCER; WOMEN AB ObjectiveNatural killer (NK) cells are the first defense against malignant cells, and their functions are severely impaired in individuals with obesity. However, it is not known whether functions can be re-activated after weight loss. The alterations of NK cell functions after fat mass reduction were investigated. MethodsThirty-two healthy adults with obesity were divided into control and experimental groups. Participants of the experimental group performed a 3-month program of exercise training and nutrition. Anthropometric, physiological, and metabolic parameters and plasma adipocytokines were determined. Peripheral blood mononuclear cells were analyzed by means of flow cytometry and Western blot assay for various NK cell-specific functional parameters and leptin signaling components. NK cell-mediated cytotoxicity assay with leptin stimulation was performed. ResultsMale participants significantly decreased their body fat mass (P<0.05) and increased physical fitness (P<0.05). Plasma leptin levels were significantly reduced (P<0.05) and intracellular interferon gamma (IFN-) expression in CD56(dim) NK cells was significantly increased (P<0.001) 3 months after study end. Stimulation of NK-92 cells with different leptin dosages revealed a significant dose-dependent decrease of specific tumor cell lysis. ConclusionsThe present study demonstrates a reactivation of NK cell functionality after body fat mass reduction in persons with obesity. C1 [Jahn, Janine; Baehr, Ina; Berreis, Tobias; Kielstein, Heike] Univ Halle Wittenberg, Fac Med, Dept Anat & Cell Biol, D-06108 Halle, Saale, Germany. [Spielau, Marco] Univ Halle Wittenberg, Inst Performance Diagnost & Hlth Promot, D-06108 Halle, Saale, Germany. [Brandsch, Corinna; Stangl, Gabriele I.] Univ Halle Wittenberg, Inst Agr & Nutr Sci, D-06108 Halle, Saale, Germany. [Delank, Karl-Stefan] Univ Halle Wittenberg, Fac Med, Dept Orthopaed Surg & Traumatol, D-06108 Halle, Saale, Germany. [Wrann, Christiane D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wrann, Christiane D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Kielstein, H (reprint author), Univ Halle Wittenberg, Fac Med, Dept Anat & Cell Biol, D-06108 Halle, Saale, Germany. EM heike.kielstein@medizin.uni-halle.de FU Dr. Werner Jackstadt Foundation FX Institutional grant and Dr. Werner Jackstadt Foundation. NR 40 TC 5 Z9 5 U1 0 U2 3 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 2015 VL 23 IS 11 BP 2233 EP 2241 DI 10.1002/oby.21229 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA CV9SG UT WOS:000364626300013 PM 26390898 ER PT J AU Davis, KD Kucyi, A Moayedi, M AF Davis, Karen D. Kucyi, Aaron Moayedi, Massieh TI The pain switch: an "ouch" detector SO PAIN LA English DT Review ID PHYSICAL PAIN; NEUROMATRIX; FMRI C1 [Davis, Karen D.] Toronto Western Res Inst, Div Brain Imaging & Behav Syst, Toronto, ON, Canada. [Davis, Karen D.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [Davis, Karen D.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Kucyi, Aaron] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Kucyi, Aaron] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Moayedi, Massieh] UCL, Dept Neurosci Physiol & Pharmacol, London, England. RP Davis, KD (reprint author), Toronto Western Hosp, Toronto Western Res Inst, 399 Bathurst St,Room MP14-306, Toronto, ON M5T 2S8, Canada. EM kdavis@uhnres.utoronto.ca FU Canadian Institutes of Health Research operating grant FX K. D. Davis is funded by a Canadian Institutes of Health Research operating grant. NR 16 TC 2 Z9 2 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD NOV PY 2015 VL 156 IS 11 BP 2164 EP 2166 DI 10.1097/j.pain.0000000000000303 PG 3 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA CV2TS UT WOS:000364110700009 PM 26197345 ER PT J AU Mercado, R Foynes, MM Carpenter, SL Iverson, KM AF Mercado, Rowena Foynes, Melissa Ming Carpenter, S. Louisa Iverson, Katherine M. TI Sexual Intimate Partner Violence as a Form of MST: An Initial Investigation SO PSYCHOLOGICAL SERVICES LA English DT Article DE betrayal trauma theory; depression; physical health; posttraumatic stress disorder; sexual abuse ID WOMENS MENTAL-HEALTH; QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS; MILITARY SERVICE; FEMALE VETERANS; TRAUMA; ASSAULT; CONSEQUENCES; PREVALENCE; HARASSMENT AB Military sexual trauma (MST) is known to impact women's health, but little is known about the occurrence of MST perpetrated by a past or current intimate partner. This study identified the occurrence of intimate partner violence (IPV)-related MST in a sample of female veterans. We also examined the associations between MST history (no MST history, IPV-related MST, and MST by a nonintimate partner) and mental and physical health symptoms. Participants were 369 female veteran patients of Department of Veteran Affairs (VA) facilities in the New England region of the United States who completed a larger 2012 mail survey that included validated assessments of MST, posttraumatic stress disorder (PTSD Checklist) and depressive symptoms (CES-D), and general physical and mental health functioning (Short Form-36). Approximately half (49%) of the women in this sample reported a history of MST, of which 27 (15%) were categorized as IPV-related MST. Few differences in health measures were observed among women with IPV-related MST compared with women who experienced MST by a nonintimate partner or women with no MST history. However, women who experienced IPV-related MST had similarly severe health symptoms as women who reported MST by a nonintimate partner and more severe PTSD symptoms than women without a history of MST. Some women veterans have experienced MST at the hands of an intimate partner and face health impacts. This topic warrants additional attention in clinical and research efforts. C1 [Mercado, Rowena] VA Boston Healthcare Syst, Harvard South Shore Psychiat Residency Program, Boston, MA USA. [Mercado, Rowena] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Foynes, Melissa Ming; Carpenter, S. Louisa; Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Foynes, Melissa Ming; Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,116B-3, Boston, MA 02130 USA. EM katherine.iverson@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services of the VA Office of Research and Development; Dr. Iverson's Career Development Award [CDA-2 10-029]; Dr. Iverson's Presidential Early Career Award for Scientists and Engineers [USA 14-275] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services of the VA Office of Research and Development as part of Dr. Iverson's Career Development Award (CDA-2 10-029). This work was also supported by Dr. Iverson's Presidential Early Career Award for Scientists and Engineers (USA 14-275). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 57 TC 0 Z9 0 U1 1 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD NOV PY 2015 VL 12 IS 4 SI SI BP 348 EP 356 DI 10.1037/ser0000056 PG 9 WC Psychology, Clinical SC Psychology GA CV3MJ UT WOS:000364163000003 PM 26524276 ER PT J AU Voller, E Polusny, MA Noorbaloochi, S Street, A Grill, J Murdoch, M AF Voller, Emily Polusny, Melissa A. Noorbaloochi, Siamak Street, Amy Grill, Joseph Murdoch, Maureen TI Self-Efficacy, Male Rape Myth Acceptance, and Devaluation of Emotions in Sexual Trauma Sequelae: Findings From a Sample of Male Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE sexual trauma; adjustment; self-efficacy; rape myths; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; HELP-SEEKING; RISK-FACTORS; WOMEN; MASCULINITY; ASSAULT; ABUSE; PTSD; PREVALENCE AB Sexual trauma is an understudied but regrettably significant problem among male Veterans. As in women, sexual trauma often results in serious mental health consequences for men. Therefore, to guide potential future interventions in this important group, we investigated associations among self-efficacy, male rape myth acceptance, devaluation of emotions, and psychiatric symptom severity after male sexual victimization. We collected data from 1,872 Gulf War era Veterans who applied for posttraumatic stress disorder (PTSD) disability benefits using standard mailed survey methods. The survey asked about history of childhood sexual abuse, sexual assault during the time of Gulf War I, and past-year sexual assault as well as Veterans' perceived self-efficacy, male rape myth acceptance, devaluation of emotions, PTSD, and depression symptoms. Structural equation modeling revealed that self-efficacy partially mediated the association between participants' sexual trauma history and psychiatric symptoms. Greater male rape myth acceptance and greater devaluation of emotions were directly associated with lower self-efficacy, but these beliefs did not moderate associations between sexual trauma and self-efficacy. In this population, sexual trauma, male rape myth acceptance, and devaluation of emotions were associated with lowered self-efficacy, which in turn was associated with more severe psychiatric symptoms. Implications for specific, trauma-focused treatment are discussed. C1 [Voller, Emily; Polusny, Melissa A.] Minneapolis VA Hlth Care Syst, Dept Psychiat, Minneapolis, MN 55417 USA. [Voller, Emily; Polusny, Melissa A.] Minneapolis VA Hlth Care Syst, Dept Psychol, Minneapolis, MN 55417 USA. [Polusny, Melissa A.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, VA Hlth Serv Res & Dev HSR&D Serv Ctr Excellence, Minneapolis, MN 55417 USA. [Polusny, Melissa A.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Noorbaloochi, Siamak; Grill, Joseph; Murdoch, Maureen] Minneapolis VA Hlth Care Syst, VA HSR&D Serv Ctr Excellence, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. [Noorbaloochi, Siamak; Murdoch, Maureen] Univ Minnesota, Sch Med, Dept Internal Med, Minneapolis, MN 55455 USA. [Street, Amy] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Street, Amy] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Murdoch, Maureen] Minneapolis VA Hlth Care Syst, Gen Internal Med Sect, Minneapolis, MN 55417 USA. RP Voller, E (reprint author), Minneapolis VA Hlth Care Syst, One Vet Dr,116A6, Minneapolis, MN 55417 USA. EM Emily.Voller2@va.gov FU VA HSRD [GWI-04-352] FX This study was funded by VA HSR&D (GWI-04-352). NR 55 TC 1 Z9 1 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD NOV PY 2015 VL 12 IS 4 SI SI BP 420 EP 427 DI 10.1037/ser0000046 PG 8 WC Psychology, Clinical SC Psychology GA CV3MJ UT WOS:000364163000011 PM 26524284 ER PT J AU Lim, SY Lu, N Choi, HK AF Lim, Sian Yik Lu, Na Choi, Hyon K. TI Septic arthritis in gout patients: a population-based cohort study SO RHEUMATOLOGY LA English DT Article DE gout; septic arthritis; infection; epidemiology; population-based cohort study ID RHEUMATOID-ARTHRITIS; RISK; HEALTH AB Objective. To evaluate the association of incident gout with the risk of incident septic arthritis in a general population context. Methods. We investigated the association of incident gout with the risk of incident septic arthritis using the Health Improvement Network, a computerized medical record database from general practices in the UK. We conducted a cohort analysis of the risk of an incident septic arthritis diagnosis among adults with incident gout compared with up to five non-gout individuals matched by age, sex, date of study entry and enrolment year. We performed Cox proportional hazard regression models to adjust for lifestyle variables, physician visits, comorbidities and medication use. Results. We identified 72 073 incident gout patients and 358 342 matched non-gout patients. The incidence rates of a septic arthritis diagnosis were 0.24 cases and 0.09 cases per 1000 person-years in the gout and comparison cohorts, respectively. Matched univariate and multivariate hazard ratios of a septic arthritis diagnosis were 2.82 (95% CI 2.15, 3.71) and 2.60 (95% CI 1.93, 3.51), respectively. The association persisted among subgroups stratified by sex, age group (<75 and >= 75) and socio-economic deprivation level. Conclusion. This general population-based study suggests that gout is associated with an increased likelihood of septic arthritis. C1 [Lim, Sian Yik; Lu, Na; Choi, Hyon K.] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lu, Na; Choi, Hyon K.] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. RP Lim, SY (reprint author), Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM sylim@partners.org NR 18 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2015 VL 54 IS 11 BP 2095 EP 2099 DI 10.1093/rheumatology/kev236 PG 5 WC Rheumatology SC Rheumatology GA CW1OO UT WOS:000364760700024 PM 26170377 ER PT J AU Refaai, MA Goldstein, JN Lee, ML Durn, BL Milling, TJ Sarode, R Kovaleski, K AF Refaai, Majed A. Goldstein, Joshua N. Lee, Martin L. Durn, Billie L. Milling, Truman J., Jr. Sarode, Ravi Kovaleski, Kevin TI Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal SO TRANSFUSION LA English DT Article ID CIRCULATORY OVERLOAD; HEART-FAILURE; WARFARIN; OUTCOMES; PATIENT; SAFETY AB BACKGROUND Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion-related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT). STUDY DESIGN AND METHODS Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four-factor prothrombin complex concentrate (4F-PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA-treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F-PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis. RESULTS A total of 388 patients (4F-PCC, n=191; plasma, n=197) were enrolled. Volume overload occurred in 34 (9%) patients (4F-PCC, n=9; plasma, n=25). In univariate analyses, use of plasma (vs. 4F-PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F-PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F-PCC) was an independent volume overload predictor. CONCLUSIONS After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F-PCC in patients requiring urgent VKA reversal. C1 [Refaai, Majed A.] Univ Rochester Med, Rochester, NY USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Durn, Billie L.; Kovaleski, Kevin] CSL Behring, King Of Prussia, PA 19406 USA. [Milling, Truman J., Jr.] Univ Ctr Brackenridge, Dell Childrens Med Ctr, Seton UT Southwestern Clin Res Inst Austin, Austin, TX USA. [Sarode, Ravi] UT Southwestern Med Ctr, Dallas, TX USA. RP Kovaleski, K (reprint author), CSL Behring, 1020 First Ave,POB 61501, King Of Prussia, PA 19406 USA. EM Kevin.Kovaleski@cslbehring.com RI Goldstein, Joshua/H-8953-2016 FU CSL Behring FX The study was sponsored by CSL Behring. The sponsor was responsible for data collection, management, and analysis of the data according to a predefined statistical analysis plan. Preparation and review of the manuscript as well as decision to submit the manuscript for publication was performed by a publication steering committee that included academic medical experts and representatives of the sponsor. NR 22 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD NOV PY 2015 VL 55 IS 11 BP 2722 EP 2729 DI 10.1111/trf.13191 PG 8 WC Hematology SC Hematology GA CW3EZ UT WOS:000364876100028 PM 26135740 ER PT J AU Barkai, U Avni, Y Ludwig, B Colton, CC Weir, GC Zimermann, B Maimon, S Steffen, A Goldman, T de Vos, P Borenstein, SR Rotem, A AF Barkai, Uriel Avni, Yuval Ludwig, Barbara Colton, Clark C. Weir, Gordon C. Zimermann, Baruch Maimon, Shiri Steffen, Anja Goldman, Tali de Vos, Paul Borenstein, Stefan R. Rotem, Avi TI Composite membrane protecting implanted islets from allogenic and xenogeneic host immune system SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Barkai, Uriel; Avni, Yuval; Zimermann, Baruch; Maimon, Shiri; Goldman, Tali; Rotem, Avi] Beta O2 Technol, Rosh Haayin, Israel. [Ludwig, Barbara; Steffen, Anja; Borenstein, Stefan R.] Paul Langerhans Inst, Clin Carl Gustav Carus TU, Dresden, Germany. [Colton, Clark C.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [de Vos, Paul] Univ Med Ctr Groningen, Dept Pathol, NL-9713 AV Groningen, Netherlands. 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 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2015 VL 22 SU 1 SI SI MA 580 BP S92 EP S92 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100216 ER PT J AU Carrico, R Fridell, J Odorico, J Yeh, H Tyler, K Niederhaus, S AF Carrico, Robert Fridell, Jonathan Odorico, Jon Yeh, Heidi Tyler, Kristina Niederhaus, Silke TI Why are pancreas transplant volumes in the United States declining? SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Carrico, Robert; Tyler, Kristina] United Network Organ Sharing, Res, Richmond, VA USA. [Fridell, Jonathan] Indiana Univ, Surg, Indianapolis, IN 46204 USA. [Odorico, Jon] Univ Wisconsin, Surg, Madison, WI USA. [Yeh, Heidi] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Niederhaus, Silke] Univ Maryland, Surg, Baltimore, MD 21201 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 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2015 VL 22 SU 1 SI SI MA 265 BP S17 EP S17 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100038 ER PT J AU Colton, C Evron, Y Ludwig, B Weir, GC Zimmerman, B Maimon, S Neufield, T Shalev, N Goldman, T Leon, A Yavriyants, K Shabtay, N Rozenshtein, T DiIenno, AR Stefan, A Vardi, P Bloch, K de Vos, P Bornstein, SR Barkai, U Rotem, A AF Colton, Clark Evron, Y. Ludwig, B. Weir, G. C. Zimmerman, B. Maimon, S. Neufield, T. Shalev, N. Goldman, T. Leon, A. Yavriyants, K. Shabtay, N. Rozenshtein, T. DiIenno, A. R. Stefan, A. Vardi, P. Bloch, K. de Vos, P. Bornstein, S. R. Barkai, U. Rotem, A. TI Enhanced oxygen supply to islets encapsulated at high density leads to long-term normoglycenia in diabetic rats and facilitates development of smaller devices SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Colton, Clark; DiIenno, A. R.; Barkai, U.; Rotem, A.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Evron, Y.; Zimmerman, B.; Maimon, S.; Neufield, T.; Shalev, N.; Goldman, T.; Leon, A.; Yavriyants, K.; Shabtay, N.; Rozenshtein, T.] Beta O2 Technol, Rosh Haain, Israel. [Ludwig, B.; Stefan, A.; Bornstein, S. R.] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Med 3, D-01062 Dresden, Germany. [Weir, G. C.] Joslin Diabet Ctr, Div Res, Sect Islet Trasnplantat & Cell Biol, Boston, MA 02215 USA. [Vardi, P.; Bloch, K.] Tel Aviv Univ, Sackler Sch Med, Feisenstein Med Res Ctr, Petah Tiqwa, Israel. [de Vos, P.] Univ Med Ctr Groningen, Dept Pathol & Lab Med, NL-9713 AV Groningen, Netherlands. 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 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2015 VL 22 SU 1 SI SI MA 535 BP S78 EP S79 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100185 ER PT J AU Salama, A Conchon, S Perota, A Martinet, B Judor, JP Evanno, G Bernardet, SLB Le Berre, L Hervouet, J Minault, D Concordet, JP Dugast, E Vanhove, B Abadie, J Gaide, N Lagutina, I Duchi, R Lazzari, G Floch, R Duvaux, O Toutain, PL Maillasson, M Sachs, DH Gauthier, O Brouard, S Cozzi, E Blancho, G Perreault, H Bach, JM Galli, C Soulillou, JP AF Salama, Apolline Conchon, Sophie Perota, Andrea Martinet, Bernard Judor, Jean-Paul Evanno, Gwenaelle Bernardet, Stephanie Le-Bas Le Berre, Ludmilla Hervouet, Jeremy Minault, David Concordet, Jean-Paul Dugast, Emilie Vanhove, Bernard Abadie, Jerome Gaide, Nicolas Lagutina, Irina Duchi, Roberto Lazzari, Giovanna Floch, Robert Duvaux, Odile Toutain, Pierre-Louis Maillasson, Mike Sachs, David H. Gauthier, Olivier Brouard, Sophie Cozzi, Emanuele Blancho, Gilles Perreault, Helene Bach, Jean-Marie Galli, Cesare Soulillou, Jean-Paul TI Immune phenotype and IgG characteristics of Neu5Gc and alpha-1-3-gal double knock-out pigs SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Salama, Apolline; Conchon, Sophie; Martinet, Bernard; Judor, Jean-Paul; Evanno, Gwenaelle; Bernardet, Stephanie Le-Bas; Le Berre, Ludmilla; Hervouet, Jeremy; Minault, David; Dugast, Emilie; Vanhove, Bernard; Brouard, Sophie; Blancho, Gilles; Soulillou, Jean-Paul] Univ Nantes, CHU Nantes, ITUN, UMR 1064,INSERM, Nantes, France. [Salama, Apolline] Soc Accelerat Transfert Technol Ouest Valorisat, Rennes, France. [Perota, Andrea; Lagutina, Irina; Duchi, Roberto; Lazzari, Giovanna; Soulillou, Jean-Paul] Avantea, Lab Reprod Technol, Cremona, Italy. [Evanno, Gwenaelle; Floch, Robert; Duvaux, Odile] Xenothera, Nantes, France. [Concordet, Jean-Paul] CNRS, INSERM, U565, MNHN,USM503, Paris, France. [Abadie, Jerome; Gaide, Nicolas] ONIRIS Nantes Atlantic Coll Vet Med & Food Sci, AMaROC, Nantes, France. [Toutain, Pierre-Louis] Ecole Natl Vet Toulouse, INRA ENVT, UMR 1331, Toulouse, France. [Maillasson, Mike] Univ Nantes, INSERM, CRCNA, Plateforme IMPACT Biogenouest,UMR 892, Nantes, France. [Sachs, David H.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Gauthier, Olivier] ONIRIS, Ctr Rech & Invest Preclin, Nantes, France. [Cozzi, Emanuele] Padua Hosp, Padua, Italy. [Cozzi, Emanuele] Consortium Res Organ Transplantat, Padua, Italy. [Perreault, Helene] Univ Manitoba, Dept Chem, Winnipeg, MB R3T 2N2, Canada. [Bach, Jean-Marie] Univ Nantes, IECM, ONIRIS, EA4644,USC1383,INRA,ONIRIS, Nantes, France. [Galli, Cesare] Univ Bologna, Dept Vet Med Sci, Bologna, Italy. RI Toutain, Pierre-Louis/G-4540-2011; concordet, jean-paul/C-3417-2015 OI Toutain, Pierre-Louis/0000-0002-8846-8892; NR 0 TC 0 Z9 0 U1 2 U2 6 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 PY 2015 VL 22 SU 1 SI SI MA 348 BP S38 EP S38 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100086 ER PT J AU Schuetz, C Yi, P Markmann, JF AF Schuetz, Christian Yi, Peng Markmann, James F. TI The insulin receptor antagonist s961 induces minimal proliferation of pancreatic beta cells in non-human primates SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Schuetz, Christian; Markmann, James F.] Massachusetts Gen Hosp, Transplant Surg, Boston, MA 02114 USA. [Yi, Peng] Joslin Diabet Ctr, Islet Cell & Regenerat Biol Sect, Boston, MA 02215 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2015 VL 22 SU 1 SI SI MA 919 BP S180 EP S180 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100438 ER PT J AU Tena, A Sachs, DH Mallard, C Yang, YG Tasaki, M Farkash, E Colvin, RB Leonard, DA Hawley, R AF Tena, Aseda Sachs, David H. Mallard, Christopher Yang, Yong-Guang Tasaki, Masayuki Farkash, Evan Colvin, Robert B. Leonard, David A. Hawley, Robert TI Prolonged survival of porcine skin on baboons following administration of porcine cells expressing human CD47 SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Tena, Aseda; Sachs, David H.; Mallard, Christopher; Tasaki, Masayuki; Leonard, David A.; Hawley, Robert] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Yang, Yong-Guang; Farkash, Evan] Columbia Univ, Columbia Ctr Translat Immunol, New York, NY USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 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 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2015 VL 22 SU 1 SI SI MA 376 BP S45 EP S45 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100107 ER PT J AU Wang, LJ Kin, T O'Gorman, D Shapiro, AMJ Naziruddin, B Takita, M Levy, MF Posselt, A Szot, G Savari, O Barbaro, B McGarrigle, J Yeh, CC Oberholzer, J Lei, J Chen, T Markmann, JF Kim, JI Alvarez, A Linetsky, E Ricordi, C Balamurugan, AN Loganathan, G Wilhelm, JJ Hering, BJ Bottino, R Trucco, M Liu, CY Min, Z Li, YJ Naji, A Fernandez, LA Ziemelis, M Danobeitia, JS Millis, JM Wikowski, P AF Wang, Ling-Jia Kin, Tatsuya O'Gorman, Doug Shapiro, A. M. James Naziruddin, Bashoo Takita, Morihito Levy, Marlon F. Posselt, Andrew Szot, Gregory Savari, Omid Barbaro, Barbara McGarrigle, James Yeh, Chun Chieh Oberholzer, Jose Lei, Ji Chen, Tao Markmann, James F. Kim, James I. Alvarez, Alejandro Linetsky, Elina Ricordi, Camillo Balamurugan, A. N. Loganathan, Gopalakrishnan Wilhelm, Joshua J. Hering, Bernard. J. Bottino, Rita Trucco, Massimo Liu, Chengyang Min, Zaw Li, Yanjing Naji, Ali Fernandez, Luis A. Ziemelis, Marty Danobeitia, Juan S. Millis, J. Michael Wikowski, Piotr TI North america islet donor score in donor pancreas selection for successful islet isolation for transplantation - a multicenter study SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT IPITA/IXA/CTS Joint Congress CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP IPITA, IXA, CTS C1 [Wang, Ling-Jia; Savari, Omid; Millis, J. Michael; Wikowski, Piotr] Univ Chicago, Dept Surg, Sect Transplantat, Chicago, IL 60637 USA. [Wang, Ling-Jia; Barbaro, Barbara; McGarrigle, James; Yeh, Chun Chieh; Oberholzer, Jose] Univ Illinois, UIC Cell Isolat Program, Chicago, IL USA. [Kin, Tatsuya; O'Gorman, Doug; Shapiro, A. M. James] Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada. [Kin, Tatsuya; O'Gorman, Doug; Shapiro, A. M. James] Alberta Hlth Serv, Edmonton, AB, Canada. [Naziruddin, Bashoo; Takita, Morihito; Levy, Marlon F.] Baylor Simmons Transplant Inst, Dallas, TX USA. [Posselt, Andrew; Szot, Gregory] Univ Calif San Francisco, UCSF Transplantat Surg, San Francisco, CA 94143 USA. [Lei, Ji; Chen, Tao; Markmann, James F.; Kim, James I.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. [Alvarez, Alejandro; Linetsky, Elina; Ricordi, Camillo] Univ Miami, Miller Sch Med, cGMP Cell Proc Facil, Diabet Res Inst, Miami, FL 33136 USA. [Balamurugan, A. N.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Hering, Bernard. J.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA. [Bottino, Rita; Trucco, Massimo] Allegheny Hlth Network, Inst Cellular Therapeut, Pittsburgh, PA USA. [Liu, Chengyang; Min, Zaw; Li, Yanjing; Naji, Ali] Univ Penn, Perelman Sch Med, Div Transplantat, Philadelphia, PA 19104 USA. [Fernandez, Luis A.; Ziemelis, Marty; Danobeitia, Juan S.] Univ Wisconsin, Div Organ Transplantat, Madison, WI 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 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2015 VL 22 SU 1 SI SI MA 1043 BP S190 EP S191 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CV9FY UT WOS:000364594100466 ER PT J AU Bergthold, G Bandopadhayay, P Hoshida, Y Ramkissoon, S Ramkissoon, L Rich, B Maire, CL Paolella, BR Schumacher, SE Tabak, B Ferrer-Luna, R Ozek, M Sav, A Santagata, S Wen, PY Goumnerova, LC Ligon, AH Stiles, C Segal, R Golub, T Grill, J Ligon, KL Chan, JA Kieran, MW Beroukhim, R AF Bergthold, Guillaume Bandopadhayay, Pratiti Hoshida, Yujin Ramkissoon, Shakti Ramkissoon, Lori Rich, Benjamin Maire, Cecile L. Paolella, Brenton R. Schumacher, Steven E. Tabak, Barbara Ferrer-Luna, Ruben Ozek, Memet Sav, Aydin Santagata, Sandro Wen, Patrick Yung Goumnerova, Liliana C. Ligon, Azra H. Stiles, Charles Segal, Rosalind Golub, Todd Grill, Jacques Ligon, Keith L. Chan, Jennifer A. Kieran, Mark W. Beroukhim, Rameen TI Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype SO NEURO-ONCOLOGY LA English DT Article DE BRAF duplication; BRAF mutation; expression; heterogeneity; pediatric low-grade glioma ID GENE-EXPRESSION; PILOCYTIC ASTROCYTOMAS; OPTIC PATHWAY; CANCER; DUPLICATION; RECURRENT; PHOSPHORYLATION; CLASSIFICATION; HETEROGENEITY; ACTIVATION AB Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity. We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain. Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. "Not otherwise specified" (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs. Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related. C1 [Bergthold, Guillaume; Bandopadhayay, Pratiti; Paolella, Brenton R.; Schumacher, Steven E.; Tabak, Barbara; Ferrer-Luna, Ruben; Stiles, Charles; Segal, Rosalind; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,SM 1022C, Boston, MA 02215 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave,SM 1022C, Boston, MA 02215 USA. [Kieran, Mark W.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02215 USA. [Bergthold, Guillaume; Bandopadhayay, Pratiti; Paolella, Brenton R.; Schumacher, Steven E.; Tabak, Barbara; Ferrer-Luna, Ruben; Goumnerova, Liliana C.; Stiles, Charles; Segal, Rosalind; Kieran, Mark W.; Beroukhim, Rameen] Harvard Univ, Sch Med, Boston, MA USA. [Bergthold, Guillaume; Bandopadhayay, Pratiti; Paolella, Brenton R.; Schumacher, Steven E.; Tabak, Barbara; Ferrer-Luna, Ruben; Golub, Todd; Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Bandopadhayay, Pratiti; Goumnerova, Liliana C.; Kieran, Mark W.] Dana Farber Canc Inst, Dana Farber Boston Childrens Canc & Blood Disorde, Pediat Neurooncol Program, Boston, MA 02115 USA. [Bandopadhayay, Pratiti; Goumnerova, Liliana C.; Kieran, Mark W.] Boston Childrens Hosp, Boston, MA USA. [Hoshida, Yujin] Icahn Sch Med Mt Sinai, Dept Med, Div Liver Dis, Liver Canc Program,Tisch Canc Inst, New York, NY 10029 USA. [Ramkissoon, Shakti; Santagata, Sandro; Wen, Patrick Yung; Ligon, Azra H.; Ligon, Keith L.; Chan, Jennifer A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ramkissoon, Lori; Rich, Benjamin; Maire, Cecile L.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Ozek, Memet] Acibadem Univ, Med Ctr, Dept Neurosurg, Istanbul, Turkey. [Sav, Aydin] Acibadem Univ, Med Ctr, Dept Pathol, Istanbul, Turkey. [Goumnerova, Liliana C.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Grill, Jacques] Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. RP Beroukhim, R (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,SM 1022C, Boston, MA 02215 USA.; Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave,SM 1022C, Boston, MA 02215 USA.; Kieran, MW (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02215 USA. EM mark_kieran@dfci.harvard.edu; rameen_beroukhim@dfci.harvard.edu OI sav, aydin/0000-0002-7326-7801 FU NCI NIH HHS [F32 CA180653, P01 CA142536, P01CA142536, P50 CA165962]; NIDDK NIH HHS [R01 DK099558]; NINDS NIH HHS [K08 NS087118] NR 46 TC 5 Z9 5 U1 0 U2 6 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 2015 VL 17 IS 11 BP 1486 EP 1496 DI 10.1093/neuonc/nov045 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA CW1WZ UT WOS:000364783900008 PM 25825052 ER PT J AU Geyer, BC Kaji, AH Katz, ED Jones, AE Bebarta, VS AF Geyer, Brian C. Kaji, Amy H. Katz, Eric D. Jones, Alan E. Bebarta, Vikhyat S. TI A National Evaluation of the Scholarly Activity Requirement in Residency Programs: A Survey of Emergency Medicine Program Directors SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID PROJECT REQUIREMENT AB Objectives: The Review Committee for Emergency Medicine (RC-EM) requirement for scholarly activity, which programs may define as an original research project or some other form of scholarly activity, applies to all EM residents. The objectives of this study were to: 1) describe the percentage of residency programs that require an original research project to meet the RC-EM requirement for scholarly activity, 2) describe specific challenges and resources for residents completing the RC-EM scholarly activity requirement, and 3) identify associations between the interpretation of the requirement and early career outcomes. Methods: This was a cross-sectional online survey of program or research directors from all U.S. allopathic EM residency programs. Respondents were queried about key demographics and domains relating to research curriculum, resources, expectations, outcomes, challenges, and future opportunities. Data were analyzed using descriptive statistics. Results: The overall response rate was 113 of 156 (72%) EM residency programs. Respondents were more likely to represent university-based programs, but otherwise did not differ from nonrespondents across key demographic criteria. An original research project was required by 39% of responding programs, with a minimum deliverable in 93% of these programs. Program directors listed data collection and study design as the principle challenges residents face while completing their scholarly activities. Faculty mentorship, biostatistical support, and travel support were common resources reportedly available to residents. Comparison of programs with an original research requirement to those without revealed many differences in outcomes. Programs with a research requirement were more likely to have residents with oral or poster presentations (46% vs. 25%, mean difference = 21%, 95% confidence interval [CI] = 16% to 28%), published manuscripts (25% vs. 18%, mean difference = 7%, 95% CI = 2% to 10%), entering fellowship training after residency (27% vs. 20%, mean difference = 7%, 95% CI = 4% to 10%), and using a biostatistician (64% vs. 28%, median difference = 26%, 95% CI = 24% to 28%). There were no statistically significant differences in other evaluations of resources or outcome measures, including resident choice of academic career after leaving residency. Conclusions: There is no consistent interpretation and implementation of the RC-EM requirement for scholarly activity among EM residency programs. Residency programs requiring an original research project were more likely to have residents with accepted oral or poster presentations, published manuscripts, and entering fellowships after residency training. C1 [Geyer, Brian C.] Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Geyer, Brian C.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kaji, Amy H.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. [Katz, Eric D.] Maricopa Cty Gen Hosp, Dept Emergency Med, Phoenix, AZ USA. [Jones, Alan E.] Univ Mississippi, Med Ctr, Dept Emergency Med, Jackson, MS 39216 USA. [Bebarta, Vikhyat S.] San Antonio Mil Med Ctr, Dept Emergency Med, San Antonio, TX USA. RP Geyer, BC (reprint author), Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. EM briancgeyer@gmail.com RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2015 VL 22 IS 11 BP 1337 EP 1344 DI 10.1111/acem.12802 PG 8 WC Emergency Medicine SC Emergency Medicine GA CW1VG UT WOS:000364779300012 PM 26473482 ER PT J AU Sullivan, AF Camargo, CA AF Sullivan, Ashley F. Camargo, Carlos A., Jr. TI The National Emergency Department Inventory-USA SO ACADEMIC EMERGENCY MEDICINE LA English DT Letter C1 [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Sullivan, AF (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM ccamargo@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2015 VL 22 IS 11 BP 1360 EP 1360 DI 10.1111/acem.12807 PG 1 WC Emergency Medicine SC Emergency Medicine GA CW1VG UT WOS:000364779300019 PM 26469194 ER PT J AU Doll, JA Hellkamp, A Thomas, L Ho, PM Kontos, MC Whooley, MA Boyden, TF Peterson, ED Wang, TY AF Doll, Jacob A. Hellkamp, Anne Thomas, Laine Ho, P. Michael Kontos, Michael C. Whooley, Mary A. Boyden, Thomas F. Peterson, Eric D. Wang, Tracy Y. TI Effectiveness of cardiac rehabilitation among older patients after acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID AMERICAN-HEART-ASSOCIATION; SCIENTIFIC STATEMENT; TRIAL RAMIT; PREVENTION; CARDIOLOGY; EXERCISE; DISEASE; UPDATE; ADULTS AB Background Guidelines recommend cardiac rehabilitation after acute myocardial infarction, yet little is known about the impact of cardiac rehabilitation on medication adherence and clinical outcomes among contemporary older adults. The optimal number of cardiac rehabilitation sessions is not clear. Methods We linked patients 65 years or older enrolled in the Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) from January 2007 to December 2010 to Medicare longitudinal claims data to obtain 1 year follow-up. Results A total of 11,862 patients participated in cardiac rehabilitation after acute myocardial infarction, attending a median number of 26 sessions. Patients attending >= 26 sessions were more likely to be male, had lesser prevalence of comorbid conditions and prior revascularization, and were more likely to present with ST-segment elevation myocardial infarction, compared with patients attending 1 to 25 sessions. Among patients with Medicare Part D prescription coverage, increasing number of cardiac rehabilitation sessions was associated with improvement in adherence to secondary prevention medications such as P2Y(12) inhibitors and beta-blockers. Each 5-session increase in participation was associated with lower mortality (adjusted hazard ratio [HR] 0.87, 95% CI 0.83-0.92) and lower overall risk of major adverse cardiac event (adjusted HR 0.69, 95% CI 0.65-0.73) and death/readmission (adjusted HR 0.79, 95% CI 0.76-0.83). Conclusions In this older patient population, number of cardiac rehabilitation sessions attended was associated with improved medication adherence and lower downstream cardiovascular risk in a dose-response relationship. This provides support for the continued use of cardiac rehabilitation for older adults and encourages efforts to maximize attendance. C1 [Doll, Jacob A.; Hellkamp, Anne; Thomas, Laine; Peterson, Eric D.; Wang, Tracy Y.] Duke Clin Res Inst, Durham, NC USA. [Doll, Jacob A.; Peterson, Eric D.; Wang, Tracy Y.] Duke Univ, Dept Med, Durham, NC 27705 USA. [Ho, P. Michael] VA Eastern Colorado Hlth Care Syst, Aurora, CO USA. [Ho, P. Michael] Univ Colorado, Sch Med, Aurora, CO USA. [Kontos, Michael C.] Virginia Commonwealth Univ, Richmond, VA USA. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Whooley, Mary A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Boyden, Thomas F.] Spectrum Hlth, Grand Rapids, MI USA. RP Doll, JA (reprint author), Duke Univ, 2400 Pratt St, Durham, NC 27705 USA. EM jacob.doll@duke.edu OI Hellkamp, Anne/0000-0003-0919-4502 FU Eli Lilly; Daiichi Sankyo; Gilead Science; GlaxoSmith Kline; Astra Zeneca; Boston Scientific; American College of Cardiology Foundation's National Cardiovascular Data Registry; Society of Chest Pain Centers; American College of Emergency Physicians; Society of Hospital Medicine FX Dr Kontos has received consulting honoraria from Provencio, Astellas, Ikaria, and Wellpoint. Dr Wang has received research grants to the Duke Clinical Research Institute from Eli Lilly, Daiichi Sankyo, Gilead Science, GlaxoSmith Kline, Astra Zeneca, and Boston Scientific, as well as consulting honoraria from Astra Zeneca. Other authors report no relevant conflicts.; This research was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry. The views expressed in this manuscript represent those of the author(s) and do not necessarily represent the official views of the National Cardiovascular Data Registry or its associated professional societies identified at www.ncdr.com.; ACTION Registry-GWTG is an initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from the Society of Chest Pain Centers, the American College of Emergency Physicians, and the Society of Hospital Medicine. NR 25 TC 4 Z9 4 U1 1 U2 10 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 2015 VL 170 IS 5 BP 855 EP 864 DI 10.1016/j.ahj.2015.08.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV7EG UT WOS:000364434600004 PM 26542492 ER PT J AU Cohen, MG Matthews, R Maini, B Dixon, S Vetrovec, G Wohns, D Palacios, I Popma, J Ohman, EM Schreiber, T O'Neill, WW AF Cohen, Mauricio G. Matthews, Ray Maini, Brij Dixon, Simon Vetrovec, George Wohns, David Palacios, Igor Popma, Jeffrey Ohman, E. Magnus Schreiber, Theodore O'Neill, William W. TI Percutaneous left ventricular assist device for high-risk percutaneous coronary interventions: Real-world versus clinical trial experience SO AMERICAN HEART JOURNAL LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; ASSOCIATION TASK-FORCE; HEART-ASSOCIATION; PRACTICE GUIDELINES; MANAGEMENT; CARDIOLOGY; OUTCOMES; DISEASE; CATHETERIZATION; SUPPORT AB Background High-risk percutaneous coronary intervention (PCI) supported by percutaneous left ventricular assist devices offers a treatment option for patients with severe symptoms, complex and extensive coronary artery disease, and multiple comorbidities. The extrapolation from clinical trial to real-world practice has inherent uncertainties. We compared the characteristics, procedures, and outcomes of high-risk PCI supported by a microaxial pump (Impella 2.5) in a multicenter registry versus the randomized PROTECT II trial (NCT00562016). Methods The USpella registry is an observational multicenter voluntary registry of Impella technology. A total of 637 patients treated between June 2007 and September 2013 were included. Of them, 339 patients would have met enrollment criteria for the PROTECT II trial. These were compared with 216 patients treated in the Impella arm of PROTECT II. Results Compared to the clinical trial, registry patients were older (70 +/- 11.5 vs 67.5 +/- 11.0 years); more likely to have chronic kidney disease (30% vs 22.7%), prior myocardial infarction (69.3% vs 56.5%), or prior bypass surgery (39.4% vs. 30.2%); and had similar prevalence of diabetes, peripheral vascular disease, and prior stroke. Registry patients had more extensive coronary artery disease (2.2 vs 1.8 diseased vessels) and had a similar Society of Thoracic Surgeons predicted risk of mortality. At hospital discharge, registry patients experienced a similar reduction in New York Heart Association class III to IV symptoms compared to trial patients. Registry patients had a trend toward lower in-hospital mortality (2.7% vs 4.6, P =.27). Conclusions USpella provides a real-world and contemporary estimation of the type of procedures and outcomes of high-risk patients undergoing PCI supported by Impella 2.5. Despite the higher risk of registry patients, clinical outcomes appeared to be favorable and consistent compared with the randomized trial. C1 [Cohen, Mauricio G.] Univ Miami Hosp, Miami, FL 33136 USA. [Matthews, Ray] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Maini, Brij] Pinnacle Hlth Syst, Harrisburg, PA USA. [Dixon, Simon] William Beaumont Univ Hosp, Royal Oak, MI USA. [Vetrovec, George] Virginia Commonwealth Univ, Pauley Heart Ctr, Richmond, VA USA. [Wohns, David] Spectrum Hlth, Grand Rapids, MI USA. [Palacios, Igor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Popma, Jeffrey] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Ohman, E. Magnus] Duke Clin Res Inst, Durham, NC USA. [Schreiber, Theodore] Harper Univ Hosp, Detroit, MI USA. [O'Neill, William W.] Henry Ford Hosp, Detroit, MI 48202 USA. RP Cohen, MG (reprint author), Univ Miami Hosp, 1400 NW 12th Ave,Suite 1179, Miami, FL 33136 USA. EM mgcohen@med.miami.edu OI Cohen, Mauricio/0000-0003-2038-6070 FU Abiomed FX Simon Dixon: Institutional research support from Abiomed.; Jeffrey Popma: Institutional research support from Abiomed. NR 17 TC 10 Z9 11 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 2015 VL 170 IS 5 BP 872 EP 879 DI 10.1016/j.ahj.2015.08.009 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV7EG UT WOS:000364434600006 PM 26542494 ER PT J AU Lochhead, P Nishihara, R Qian, ZR Mima, K Cao, Y Sukawa, Y Kim, SA Inamura, K Zhang, XH Wu, K Giovannucci, E Meyerhardt, JA Chan, AT Fuchs, CS Ogino, S AF Lochhead, Paul Nishihara, Reiko Qian, Zhi Rong Mima, Kosuke Cao, Yin Sukawa, Yasutaka Kim, Sun A. Inamura, Kentaro Zhang, Xuehong Wu, Kana Giovannucci, Edward Meyerhardt, Jeffrey A. Chan, Andrew T. Fuchs, Charles S. Ogino, Shuji TI Postdiagnostic intake of one-carbon nutrients and alcohol in relation to colorectal cancer survival SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE alcohol; colorectal carcinoma; micronutrients; public health; survivorship ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; RANDOMIZED CLINICAL-TRIAL; FOLIC-ACID FORTIFICATION; III COLON-CANCER; MICROSATELLITE INSTABILITY; CARDIOVASCULAR-DISEASE; PROSPECTIVE COHORT; DIETARY-FOLATE; BRAF MUTATION; FOLLOW-UP AB Background: Observational data have suggested that intakes of nutrients involved in one-carbon metabolism are inversely associated with risk of colorectal carcinoma and adenomas. In contrast, results from some preclinical studies and cardiovascular and chemoprevention trials have raised concerns that high folate intake may promote carcinogenesis by facilitating the progression of established neoplasia. Objective: We tested the hypothesis that higher total folate intake (including food folate and folic acid from fortified foods and supplements) or other one-carbon nutrient intakes might be associated with poorer survival after a diagnosis of colorectal cancer. Design: We used rectal and colon cancer cases within the following 2 US prospective cohort studies: the Nurses' Health Study and the Health Professionals Follow-Up Study. Biennial questionnaires were used to gather information on medical history and lifestyle factors, including smoking and alcohol consumption. B-vitamin and methionine intakes were derived from food-frequency questionnaires. Data on tumor molecular characteristics (including microsatellite instability, CpG island methylator phenotype, KRAS, BRAF, and PIK3CA mutations, and long interspersed nucleotide element 1 methylation level) were available for a subset of cases. We assessed colorectal cancer-specific mortality according to postdiagnostic intakes of one-carbon nutrients with the use of multivariable Cox proportional hazards regression models. Results: In 1550 stage I-III colorectal cancer cases with a median follow-up of 14.9 y, we documented 641 deaths including 176 colorectal cancer-specific deaths. No statistically significant associations were observed between postdiagnostic intakes of folate or other one-carbon nutrients and colorectal cancer-specific mortality (multivariate P-trend >= 0.21). In an exploratory molecular pathologic epidemiology survival analysis, there was no significant interaction between one-carbon nutrients or alcohol and any of the tumor molecular biomarkers examined. Conclusions: Higher postdiagnostic intakes of one-carbon nutrients are not associated with the prognosis in stage colorectal cancer. Our findings do not support the hypothesis that higher folate intake after colorectal cancer diagnosis might increase risk of cancer-related death. C1 [Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Aberdeen, Scotland. [Lochhead, Paul; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Lochhead, Paul; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Lochhead, Paul; Nishihara, Reiko; Qian, Zhi Rong; Mima, Kosuke; Sukawa, Yasutaka; Kim, Sun A.; Inamura, Kentaro; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lochhead, Paul; Nishihara, Reiko; Qian, Zhi Rong; Mima, Kosuke; Sukawa, Yasutaka; Kim, Sun A.; Inamura, Kentaro; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nishihara, Reiko; Cao, Yin; Zhang, Xuehong; Giovannucci, Edward] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nishihara, Reiko; Cao, Yin; Zhang, Xuehong; Wu, Kana; Giovannucci, Edward] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, Edward; Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM plochhead@mgh.harvard.edu; shuji_ogino@dfci.harvard.edu FU US NIH [K07 CA190673, R01 CA137178, R01 CA176272, K24 DK098311, P50 CA127003, R01 CA151993, R35 CA197735, P01 CA87969, P01 CA55075, UM1 CA186107, UM1 CA167552]; Paula and Russell Agrusa Fund for Colorectal Cancer Research; Friends of the Dana-Farber Cancer Institute; Scottish Government Chief Scientist Office; Frank Knox Memorial Fellowship from Harvard University FX Supported by the US NIH [research grants K07 CA190673 to RN; R01 CA137178, R01 CA176272, and K24 DK098311 (to ATC); P50 CA127003 (to CSF); and R01 CA151993 and R35 CA197735 (to SO)], and by the Paula and Russell Agrusa Fund for Colorectal Cancer Research (to CSF) and the Friends of the Dana-Farber Cancer Institute (to SO). PL was supported by a personal fellowship from the Scottish Government Chief Scientist Office and by a Frank Knox Memorial Fellowship from Harvard University. The Nurses Health Study and Health Professionals Follow-Up study were supported by US NIH research grants P01 CA87969, P01 CA55075, UM1 CA186107, and UM1 CA167552. NR 50 TC 2 Z9 2 U1 1 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2015 VL 102 IS 5 BP 1134 EP 1141 DI 10.3945/ajcn.115.115162 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CV4YV UT WOS:000364273300022 PM 26423386 ER PT J AU Curhan, SG Stankovic, KM Eavey, RD Wang, ML Stampfer, MJ Curhan, GC AF Curhan, Sharon G. Stankovic, Konstantina M. Eavey, Roland D. Wang, Molin Stampfer, Meir J. Curhan, Gary C. TI Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self-reported hearing loss in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE aging; carotenoids; epidemiology; hearing loss; vitamins ID NUTRITION EXAMINATION SURVEY; RADICAL SCAVENGERS; ASCORBIC-ACID; INNER-EAR; CARDIOVASCULAR-DISEASE; CONTROLLED-TRIAL; NATIONAL-HEALTH; IMPULSE NOISE; UNITED-STATES; OLDER-ADULTS AB Background: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. Objective: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. Design: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. Results: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of beta-carotene and beta-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for beta-carotene and 0.90(95% CI: 0.84, 0.96; P-trend <0.001) for beta-cryptoxanthin. In comparison with women with folate intake 200-399 mu g/d, very low folate intake (<200 mu g/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake >= 1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. Conclusion: Higher intakes of beta-carotene, beta-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk. C1 [Curhan, Sharon G.; Wang, Molin; Stampfer, Meir J.; Curhan, Gary C.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Renal Div, Boston, MA 02115 USA. [Eavey, Roland D.] Vanderbilt Univ, Sch Med, Vanderbilt Bill Wilkerson Ctr Otolaryngol & Commu, Nashville, TN 37235 USA. [Wang, Molin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wang, Molin; Stampfer, Meir J.; Curhan, Gary C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Stankovic, Konstantina M.] Harvard Univ, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Boston, MA 02115 USA. [Stankovic, Konstantina M.] MIT, Boston, MA USA. [Curhan, Sharon G.; Curhan, Gary C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Curhan, SG (reprint author), Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM scurhan@partners.org FU NIH [DC010811, UM1 CA176726]; Vanderbilt University School of Medicine FX Supported by grants DC010811 and UM1 CA176726 from the NIH and the Vanderbilt University School of Medicine. NR 64 TC 5 Z9 5 U1 0 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2015 VL 102 IS 5 BP 1167 EP 1175 DI 10.3945/ajcn.115.109314 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CV4YV UT WOS:000364273300025 PM 26354537 ER PT J AU Fretts, AM Follis, JL Nettleton, JA Lemaitre, RN Ngwa, JS Wojczynski, MK Kalafati, IP Varga, TV Frazier-Wood, AC Houston, DK Lahti, J Ericson, U van den Hooven, EH Mikkila, V Kiefte-de Jong, JC Mozaffarian, D Rice, K Renstrom, F North, KE McKeown, NM Feitosa, MF Kanoni, S Smith, CE Garcia, ME Tiainen, AM Sonestedt, E Manichaikul, A Van Rooij, FJA Dimitriou, M Raitakari, O Pankow, JS Djousse, L Province, MA Hu, FB Lai, CQ Keller, MF Perala, MM Rotter, JI Hofman, A Graff, M Kahonen, M Mukamal, K Johansson, I Ordovas, JM Liu, YM Mannisto, S Uitterlinden, AG Deloukas, P Seppala, I Psaty, BM Cupples, LA Borecki, IB Franks, PW Arnett, DK Nalls, MA Eriksson, JG Orho-Melander, M Franco, OH Lehtimaki, T Dedoussis, GV Meigs, JB Siscovick, DS AF Fretts, Amanda M. Follis, Jack L. Nettleton, Jennifer A. Lemaitre, Rozenn N. Ngwa, Julius S. Wojczynski, Mary K. Kalafati, Ioanna Panagiota Varga, Tibor V. Frazier-Wood, Alexis C. Houston, Denise K. Lahti, Jari Ericson, Ulrika van den Hooven, Edith H. Mikkilae, Vera Kiefte-de Jong, Jessica C. Mozaffarian, Dariush Rice, Kenneth Renstroem, Frida North, Kari E. McKeown, Nicola M. Feitosa, Mary F. Kanoni, Stavroula Smith, Caren E. Garcia, Melissa E. Tiainen, Anna-Maija Sonestedt, Emily Manichaikul, Ani van Rooij, Frank J. A. Dimitriou, Maria Raitakari, Olli Pankow, James S. Djousse, Luc Province, Michael A. Hu, Frank B. Lai, Chao-Qiang Keller, Margaux F. Peraelae, Mia-Maria Rotter, Jerome I. Hofman, Albert Graff, Misa Kaehoenen, Mika Mukamal, Kenneth Johansson, Ingegerd Ordovas, Jose M. Liu, Yongmei Maennistoe, Satu Uitterlinden, Andre G. Deloukas, Panos Seppaelae, Ilkka Psaty, Bruce M. Cupples, L. Adrienne Borecki, Ingrid B. Franks, Paul W. Arnett, Donna K. Nalls, Mike A. Eriksson, Johan G. Orho-Melander, Marju Franco, Oscar H. Lehtimaeki, Terho Dedoussis, George V. Meigs, James B. Siscovick, David S. TI Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE gene-diet interaction; glucose; insulin; meat intake; diet; meta-analysis ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; DIABETES-MELLITUS; SUSCEPTIBILITY LOCI; CHARGE CONSORTIUM; UNPROCESSED RED; OLDER-ADULTS; TYPE-2; WOMEN AB Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined l) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-1n-pmon (95% CI: 0.035, 0.063-1n-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. C1 [Fretts, Amanda M.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lemaitre, Rozenn N.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Fretts, Amanda M.; Lemaitre, Rozenn N.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Frazier-Wood, Alexis C.] Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, USDA ARS, Houston, TX 77030 USA. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Follis, Jack L.] Univ St Thomas, Dept Math Comp Sci & Cooperat Engn, Houston, TX 77006 USA. [Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Wojczynski, Mary K.; Feitosa, Mary F.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Gen, Dept Genet, St Louis, MO USA. [Kalafati, Ioanna Panagiota; Dimitriou, Maria; Dedoussis, George V.] Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece. [Varga, Tibor V.; Renstroem, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Ericson, Ulrika; Sonestedt, Emily; Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Renstroem, Frida] Umea Univ, Dept Biobank Res, Umea, Sweden. [Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Houston, Denise K.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27103 USA. [Lahti, Jari] Univ Helsinki, Inst Behav Sci, Helsinki, Finland. [Mikkilae, Vera] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [van den Hooven, Edith H.; Kiefte-de Jong, Jessica C.; van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Mikkilae, Vera; Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Djousse, Luc] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [North, Kari E.; Graff, Misa] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [McKeown, Nicola M.] Tufts Univ, Nutr Epidemiol Program, Boston, MA 02111 USA. [McKeown, Nicola M.; Lai, Chao-Qiang; Ordovas, Jose M.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Smith, Caren E.; Lai, Chao-Qiang; Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Boston, MA 02111 USA. [Kanoni, Stavroula; Deloukas, Panos] Barts, William Harvey Res Inst, London, England. [Kanoni, Stavroula] Queen Mary Univ London, London Sch Med & Dent, London, England. [Garcia, Melissa E.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Keller, Margaux F.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Tiainen, Anna-Maija; Peraelae, Mia-Maria; Maennistoe, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [van Rooij, Frank J. A.] Netherlands Genom Initiat, Leiden, Netherlands. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Keller, Margaux F.] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Seppaelae, Ilkka; Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Seppaelae, Ilkka; Lehtimaeki, Terho] Univ Tampere, Fimlab Labs, FIN-33101 Tampere, Finland. [Kaehoenen, Mika; Seppaelae, Ilkka; Lehtimaeki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Kaehoenen, Mika] Univ Tampere, Tampere Univ Hosp, FIN-33101 Tampere, Finland. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Ordovas, Jose M.] Cardiovasc Res Ctr, Dept Epidemiol & Populat Genet, Madrid, Spain. [Ordovas, Jose M.] IMDEA Food Inst, Madrid, Spain. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Gen Practice Unit, Helsinki, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Diabet Res Unit, Boston, MA 02114 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Siscovick, David S.] New York Acad Med, New York, NY USA. RP Fretts, AM (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. EM amfretts@uw.edu RI Sonestedt, Emily/I-3814-2016; Deloukas, Panos/B-2922-2013; Feitosa, Mary/K-8044-2012; Djousse, Luc/F-5033-2017; OI Sonestedt, Emily/0000-0002-0747-4562; Deloukas, Panos/0000-0001-9251-070X; Feitosa, Mary/0000-0002-0933-2410; Djousse, Luc/0000-0002-9902-3047; Mannisto, Satu/0000-0002-8668-3046; Kiefte-de Jong, Jessica/0000-0002-8136-0918; Lahti, Jari/0000-0002-4310-5297 FU National Heart, Lung, and Blood Institute (NHLBI) [R01HL105756]; Institute of Translational Health Sciences [5KL2TR000421-08]; NHLBI [T32HL007902] FX Infrastructure for the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium is supported in part by National Heart, Lung, and Blood Institute (NHLBI) grant R01HL105756. This meta-analysis was supported by the Institute of Translational Health Sciences (5KL2TR000421-08) and NHLBI (T32HL007902). Sources of support for the participating cohorts are provided in Supplemental Table 12. Funders had no role in the design, implementation, analysis, and interpretation of the data for the studies. NR 65 TC 6 Z9 6 U1 5 U2 23 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2015 VL 102 IS 5 BP 1266 EP 1278 DI 10.3945/ajcn.114.101238 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA CV4YV UT WOS:000364273300036 PM 26354543 ER PT J AU Mangiavini, L Merceron, C Araldi, E Khatri, R Gerard-O'Riley, R Wilson, TL Sandusky, G Abadie, J Lyons, KM Giaccia, AJ Schipani, E AF Mangiavini, Laura Merceron, Christophe Araldi, Elisa Khatri, Richa Gerard-O'Riley, Rita Wilson, Tremika L. Sandusky, George Abadie, Jerome Lyons, Karen M. Giaccia, Amato J. Schipani, Ernestina TI Fibrosis and Hypoxia-Inducible Factor-1 alpha-Dependent Tumors of the Soft Tissue on Loss of Von Hippel-Lindau in Mesenchymal Progenitors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOCHONDRAL BONE-DEVELOPMENT; LIMB BUD MESENCHYME; GROWTH-FACTOR; SUPPRESSOR PROTEIN; E-CADHERIN; PROMOTES FIBROGENESIS; SKELETAL DEVELOPMENT; SIGNALING PATHWAY; GENE-EXPRESSION; CRE RECOMBINASE AB The hypoxia-inducible factor (Hif)-1 alpha (Hif-1 alpha) and Hif-2 alpha (Epas1) have a critical role in both normal development and cancer. von Hippel Lindau (Vhl) protein, encoded by a tumor suppressor gene, is an E3 ubiquitin Ligase that targets Hif-1a and Epas1 to the proteasome for degradation. To better understand the role of Vhl in the biology of mesenchymal cells, we analyzed mutant mice lacking Vhl in mesenchymal progenitors that give rise to the soft tissues that form and surround synovial joints. Loss of Vhl in mesenchymat progenitors of the limb bud caused severe fibrosis of the synovial joints and formation of aggressive masses with histologic features of mesenchymal tumors. Hif-1 alpha and its downstream target connective tissue growth factor were necessary for the development of these tumors, which conversely still developed in the absence of Epas1, but at lower frequency. Human tumors of the soft tissue are a very complex and heterogeneous group of neoplasias. Our novel findings in genetically altered mice suggest that activation of the HIF signaling pathway could be an important pathogenetic event in the development and progression of at least a subset of these tumors. C1 [Mangiavini, Laura; Merceron, Christophe; Wilson, Tremika L.; Schipani, Ernestina] Univ Michigan, Sch Med, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. [Mangiavini, Laura; Merceron, Christophe; Wilson, Tremika L.; Schipani, Ernestina] Univ Michigan, Sch Med, Dept Med, Div Endocrinol, Ann Arbor, MI 48109 USA. [Mangiavini, Laura; Merceron, Christophe; Gerard-O'Riley, Rita; Wilson, Tremika L.; Schipani, Ernestina] Indiana Univ, Sch Med, Dept Med, Div Endocrinol, Indianapolis, IN USA. [Sandusky, George] Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. [Mangiavini, Laura; Araldi, Elisa; Khatri, Richa; Wilson, Tremika L.; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Mangiavini, Laura] Milano Bicocca Univ, Dept Orthopaed & Traumatol, Milan, Italy. [Merceron, Christophe] INSERM, Ctr Osteoarticular & Dent Tissue Engn, UMRS LIOAD 791, Grp STEP Skeletal Tissue Engn & Physiopathol, Nantes, France. [Merceron, Christophe] Univ Nantes Angers le Mans LUNAM, Fac Dent Surg, Nantes, France. [Abadie, Jerome] Univ Nantes Angers le Mans LUNAM, Oniris Anim Canc, Models Comparat Oncol Res AMaROC, Nantes, France. [Lyons, Karen M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. [Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Ctr Clin Sci Res, Div Radiat & Canc Biol, Stanford, CA 94305 USA. RP Schipani, E (reprint author), Univ Michigan, Sch Med, A Alfred Taubman Biomed Sci Res Bldg, Ann Arbor, MI 48109 USA. EM klyons@mednet.ucla.edu; giaccia@stanford.edu; eschipan@med.umich.edu RI Mangiavini, Laura/K-6340-2016 OI Mangiavini, Laura/0000-0003-1892-1249 FU NIH [RO1 AR065403]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program registered under the Research Executive Agency [300388] FX Supported by NIH grant RO1 AR065403 (E.S. and A.J.G.) and grant FP7/2007-2013 from the People Program (Marie Curie Actions) of the European Union's Seventh Framework Program registered under the Research Executive Agency grant agreement 300388 (CM.). NR 69 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2015 VL 185 IS 11 BP 3090 EP 3101 DI 10.1016/j.ajpath.2015.07.008 PG 12 WC Pathology SC Pathology GA CV7FY UT WOS:000364439000020 PM 26348575 ER PT J AU Sever, S Reiser, J AF Sever, Sanja Reiser, Jochen TI CD2AP, Dendrin, and Cathepsin L in the Kidney SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Letter ID PODOCYTES; DISEASE C1 [Sever, Sanja] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Reiser, Jochen] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. RP Sever, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. EM ssever@partners.org; jochen_reiser@rush.edu FU NIDDK NIH HHS [R01 DK093773] NR 6 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2015 VL 185 IS 11 BP 3129 EP 3130 DI 10.1016/j.ajpath.2015.06.022 PG 2 WC Pathology SC Pathology GA CV7FY UT WOS:000364439000025 PM 26506476 ER PT J AU Chami, HA Gottlieb, DJ Redline, S Punjabi, NM AF Chami, Hassan A. Gottlieb, Daniel J. Redline, Susan Punjabi, Naresh M. TI Association between Glucose Metabolism and Sleep-disordered Breathing during REM Sleep SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE sleep apnea; REM sleep; insulin resistance; glucose intolerance; epidemiology ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; HEART HEALTH; INTERMITTENT HYPOXIA; APNEA SYNDROME; MEN; GENDER; INDIVIDUALS; SENSITIVITY; HOMEOSTASIS AB Rationale: Sleep-disordered breathing (SDB) has been associated with impaired glucose metabolism. It is possible that the association between SDB and glucose metabolism is distinct for non-REM versus REM sleep because of differences in sleep-state-dependent sympathetic activation and/or degree of hypoxemia. Objectives: To characterize the association between REM-related SDB, glucose intolerance, and insulin resistance in a community-based sample. Methods: Across-sectional analysis that included 3,310 participants from the Sleep Heart Health Study was undertaken (53% female; mean age, 66.1 yr). Full montage home-polysomnography and fasting glucose were available on all participants. SDB severity during REM and non-REM sleep was quantified using the apnea-hypopnea index in REM (AHI(REM)) and non-REM sleep (AHI(NREM)), respectively. Fasting and 2-hour post-challenge glucose levels were assessed during a glucose tolerance test (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA-IR) was calculated (n = 1,543). Linear regression was used to assess the associations of AHIREM and AHINREM with fasting and post-prandial glucose levels and HOMA-IR. Measurements and Main Results: AHIREM and AHINREM were associated with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that adjusted for age, sex, race, and site. However, with additional adjustment for body mass index, waist circumference, and sleep duration, AHIREM was only associated with HOMA-IR (beta = 0.04; 95% CI, 0.1-0.07; P = 0.01), whereas AHINREM was only associated with fasting (beta = 0.93; 95% CI, 0.14-1.72; P = 0.02) and post-prandial glucose levels (beta = 3.0; 95% CI, 0.5-5.5; P = 0.02). Conclusions: AHIREM is associated with insulin resistance but not with fasting glycemia or glucose intolerance. C1 [Chami, Hassan A.] Amer Univ Beirut, Dept Med, Beirut, Lebanon. [Chami, Hassan A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Gottlieb, Daniel J.; Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gottlieb, Daniel J.; Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Chami, HA (reprint author), Amer Univ Beirut, Internal Med, Beirut, Lebanon. EM hchami@aub.edu.lb FU NHLBI cooperative agreements [U01HL53940, U01HL53941, U01HL53938, U01HL53916, U01HL53934, U01HL53931, U01HL53937, U01HL64360, U01HL63463, U01HL63429]; Sleep Heart Health Study FX Supported by NHLBI cooperative agreements U01HL53940 (University of Washington), U01HL53941 (Boston University), U01HL53938 (University of Arizona), U01HL53916 (University of California, Davis), U01HL53934 (University of Minnesota), U01HL53931 (New York University), U01HL53937 and U01HL64360 (Johns Hopkins University), U01HL63463 (Case Western Reserve University), and U01HL63429 (Missouri Breaks Research), which supported the Sleep Heart Health Study. NR 54 TC 6 Z9 6 U1 2 U2 4 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 2015 VL 192 IS 9 BP 1118 EP 1126 DI 10.1164/rccm.201501-0046OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CV5TG UT WOS:000364333500017 PM 26200994 ER PT J AU Schwartz, BS Rosen, J Han, PV Hynes, NA Hagmann, SH Rao, SR Jentes, ES Ryan, ET LaRocque, RC AF Schwartz, Brian S. Rosen, Jessica Han, Pauline V. Hynes, Noreen A. Hagmann, Stefan H. Rao, Sowmya R. Jentes, Emily S. Ryan, Edward T. LaRocque, Regina C. CA Global TravEpiNet Consortium TI Immunocompromised Travelers: Demographic Characteristics, Travel Destinations, and Pretravel Health Care from the US Global TravEpiNet Consortium SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NECROSIS-FACTOR; TRANSPLANT RECIPIENTS; INTERNATIONAL TRAVEL; INFLUENZA VACCINE; HIV-INFECTION; MORBIDITY; RESPONSES AB An increasing number of immunocompromised individuals are pursuing international travel, and a better understanding of their international travel patterns and pretravel health care is needed. We evaluated the clinical features, itineraries, and pretravel health care of 486 immunocompromised international travelers seen at Global TravEpiNet sites from January 2009 to June 2012. We used bivariate analyses and logistic regressions using random intercept models to compare demographic and travel characteristics, vaccines administered, and medications prescribed for immunocompromised travelers versus 30,702 immunocompetent travelers. Immunocompromised travelers pursued itineraries that were largely similar to those of immunocompetent travelers, with nearly one-third of such travelers visiting countries with low human development indices. Biological agents, including tumor necrosis factor blockers, were commonly used immunosuppressive medications among immunocompromised travelers. A strong collaboration between travel-medicine specialists, primary care doctors, and specialist physicians is needed to prepare immunocompromised people for international travel. Incorporating routine questioning and planning regarding travel into the primary care visits of immunocompromised people may be useful. C1 [Schwartz, Brian S.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA. [Rosen, Jessica] Georgetown Univ, Div Infect Dis & Travel Med, Washington, DC USA. [Han, Pauline V.; Jentes, Emily S.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA. [Hynes, Noreen A.] Johns Hopkins Sch Med, Johns Hopkins Travel & Trop Med, Div Infect Dis, Baltimore, MD USA. Bronx Lebanon Hosp Ctr, Div Pediat Infect Dis, Bronx, NY 10456 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. Bedford Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [LaRocque, Regina C.] Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Hagmann, Stefan H.] Bronx Lebanon Hosp Ctr, Pediat, Bronx, NY 10456 USA. [Ryan, Edward T.; LaRocque, Regina C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Travelers Advice & Immunizat Ctr, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM brian.schwartz@ucsf.edu; jessicarosen@hotmail.com; pauline.han@gmail.com; nhynes1@jhmi.edu; shagmann@bronxleb.org; srrao@partners.org; efj8@cdc.gov; etryan@partners.org; rclarocque@partners.org FU U.S. Centers for Disease Control and Prevention [U19CI000514, U01CK000175] FX This work was supported by U.S. Centers for Disease Control and Prevention Grants U19CI000514 and U01CK000175. NR 30 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2015 VL 93 IS 5 BP 1110 EP 1116 DI 10.4269/ajtmh.15-0185 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA CV7FJ UT WOS:000364437500040 PM 26304922 ER PT J AU Almeida, RC Capelli, J Teles, RP AF Almeida, Rhita C. Capelli, Jonas, Jr. Teles, Ricardo P. TI Levels of gingival crevicular fluid matrix metalloproteinases in periodontally compromised teeth under orthodontic forces SO ANGLE ORTHODONTIST LA English DT Article DE Gingival crevicular fluid; Matrix metalloproteinases; Orthodontics; Tooth movement; Periodontal disease ID PROGRESSIVE CHRONIC PERIODONTITIS; ALKALINE-PHOSPHATASE ACTIVITY; TOOTH MOVEMENT; TISSUE INHIBITORS; TIMP-1; MMP-8; COLLAGENASE; BIOMARKERS; CHEMOKINES; MARKERS AB Objective: To examine levels of matrix metalloproteinases (MMPs)-1, -2, -3, -7, -8, -12, and -13 in the gingival crevicular fluid (GCF) of periodontally compromised teeth at different time points during orthodontic movement. Materials and Methods: Ten controlled periodontitis subjects were submitted to orthodontic treatment. One dental arch was subjected to orthodontic movement, and teeth in the opposite arch were used as controls. GCF samples were collected from the lingual sites of two movement and two control incisors 1 week before orthodontic activation (-7 d), immediately after orthodontic activation, and after 1 hour, 24 hours, and 7, 14, and 21 days. Multiplexed bead immunoassay was used to measure MMPs in GCF. Data were analyzed using Friedman and Wilcoxon statistical tests. Results: The only significant change found over time was in the levels of MMP-1 in the movement group (P < .05). When the two groups were compared after activation, the only statistically significant difference found was in levels of MMP-12 24 hours after activation (P < .05). Conclusions: Our findings suggested that the orthodontic movement of periodontally compromised teeth without active pockets did not result in significant changes in the GCF levels of MMPs. C1 [Almeida, Rhita C.; Capelli, Jonas, Jr.] Univ Estado Rio De Janeiro, Dept Orthodont, Rio De Janeiro, Brazil. [Teles, Ricardo P.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA. RP Almeida, RC (reprint author), Secretaria Posgrad & Pesquisa, Fac Odontol, Av 28 Setembro,157 Vila Isabel, BR-20551030 Rio De Janeiro, RJ, Brazil. EM rhita.almeida@gmail.com NR 26 TC 0 Z9 0 U1 1 U2 7 PU E H ANGLE EDUCATION RESEARCH FOUNDATION, INC PI NEWTON N PA 1615 BEACON ST, NEWTON N, MA 02468-1507 USA SN 0003-3219 EI 1945-7103 J9 ANGLE ORTHOD JI Angle Orthod. PD NOV PY 2015 VL 85 IS 6 BP 1009 EP 1014 DI 10.2319/101714-744.1 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CV6BW UT WOS:000364356700016 PM 25751014 ER PT J AU Gabayan, GZ Derose, SF Chiu, VY Yiu, SC Sarkisian, CA Jones, JP Sun, BC AF Gabayan, Gelareh Z. Derose, Stephen F. Chiu, Vicki Y. Yiu, Sau C. Sarkisian, Catherine A. Jones, Jason P. Sun, Benjamin C. TI Emergency Department Crowding and Outcomes After Emergency Department Discharge SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; CHEST-PAIN; ASSOCIATION; PERFORMANCE; PREDICTORS; PNEUMONIA; DELAYS; DEATH; CARE AB Study objective: We assess whether a panel of emergency department (ED) crowding measures, including 2 reported by the Centers for Medicare & Medicaid Services (CMS), is associated with inpatient admission and death within 7 days of ED discharge. Methods: We conducted a retrospective cohort study of ED discharges, using data from an integrated health system for 2008 to 2010. We assessed patient transit-level (n=3) and ED system-level (n=6) measures of crowding, using multivariable logistic regression models. The outcome measures were inpatient admission or death within 7 days of ED discharge. We defined a clinically important association by assessing the relative risk ratio and 95% confidence interval (Cl) difference and also compared risks at the 99th percentile and median value of each measure. Results: The study cohort contained a total of 625,096 visits to 12 EDs. There were 16,957 (2.7%) admissions and 328 (0.05%) deaths within 7 days. Only 2 measures, both of which were patient transit measures, were associated with the outcome. Compared with a median evaluation time of 2.2 hours, the evaluation time of 10.8 hours (99th percentile) was associated with a relative risk of 3.9 (95% Cl 3.7 to 4.1) of an admission. Compared with a median ED length of stay (a CMS measure) of 2.8 hours, the 99th percentile ED length of stay of 11.6 hours was associated with a relative risk of 3.5 (95% Cl 3.3 to 3.7) of admission. No system measure of ED crowding was associated with outcomes. Conclusion: Our findings suggest that ED length of stay is a proxy for unmeasured differences in case mix and challenge the validity of the CMS metric as a safety measure for discharged patients. C1 [Gabayan, Gelareh Z.; Sarkisian, Catherine A.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.; Sarkisian, Catherine A.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA. [Derose, Stephen F.; Chiu, Vicki Y.; Yiu, Sau C.; Jones, Jason P.] Kasier Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Gabayan, GZ (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. EM gelareh@gabayan.com FU Agency for Healthcare Research and Quality (AHRQ) [R03 HS18994]; Kaiser Permanente of Southern California; National Institutes of Health (NIH)/National Center for Research Resources (NCRR)/National Center for Advancing Translational Sciences (NCATS) University of California, Los Angeles (UCLA) Clinical and Translational Science Institute (CTSI) [KL2TR000122] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: This research was supported by the Agency for Healthcare Research and Quality (AHRQ) (R03 HS18994 to Dr. Sun) and Kaiser Permanente of Southern California. Dr. Gabayan receives support from the National Institutes of Health (NIH)/National Center for Research Resources (NCRR)/National Center for Advancing Translational Sciences (NCATS) University of California, Los Angeles (UCLA) Clinical and Translational Science Institute (CTSI) (grant KL2TR000122). NR 25 TC 3 Z9 3 U1 1 U2 4 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 2015 VL 66 IS 5 BP 483 EP 492 DI 10.1016/j.annemergmed.2015.04.009 PG 10 WC Emergency Medicine SC Emergency Medicine GA CV9QO UT WOS:000364621900010 PM 26003004 ER PT J AU Aebi, M Landolt, MA Mueller-Pfeiffer, C Schnyder, U Maier, T Mohler-Kuo, M AF Aebi, Marcel Landolt, Markus A. Mueller-Pfeiffer, Christoph Schnyder, Ulrich Maier, Thomas Mohler-Kuo, Meichun TI Testing the "Sexually Abused-Abuser Hypothesis" in Adolescents: A Population-Based Study SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE Sexual victimization; Sexual abuse; Sexual coercion; Juvenile sex offender ID SOCIAL-LEARNING THEORY; DIFFICULTIES QUESTIONNAIRE; INTERNET PORNOGRAPHY; COERCIVE BEHAVIOR; SEX OFFENDERS; CHILDHOOD; VICTIMIZATION; METAANALYSIS; AGGRESSION; CONSEQUENCES AB A long-standing belief in the literature on sex offenders is that sexually victimized youths are at increased risk of becoming sex offenders themselves. The present study tested the link between past sexual abuse, either with or without contact, and sexually offending behavior in a representative sample of male and female adolescents while controlling for other types of abuse, mental health problems, substance use, and non-sexual violent behaviors. Self-reported data were collected from a nationally representative sample of 6,628 students attending 9th grade public school in Switzerland (3,434 males, 3,194 females, mean age = 15.50 years, SD = 0.66 years). Exposure to contact and non-contact types of sexual abuse was assessed using the Child Sexual Abuse Questionnaire and sexually offending behavior by the presence of any of three behaviors indicating sexual coercion. Two-hundred-forty-five males (7.1 %) and 40 females (1.2 %) reported having sexually coerced another person. After controlling for non-sexual abuse, low parent education, urban versus rural living, mental health problems, substance use, and non-sexual violent behavior, male adolescents who were victims of contact sexual abuse and non-contact sexual abuse were significantly more likely to report coercive sexual behaviors. Females who experienced contact or non-contact sexual abuse were also found at increased risk of committing sexual coercion after controlling for covariates. The present findings demonstrate a strong relationship between past sexual abuse, with and without physical contact, and sexual-offending behavior in male and female adolescents. Reducing exposure to non-contact sexual abuse (like Internet-based sexual exploitation) should become a new area of sexual violence prevention in youths. C1 [Aebi, Marcel] Univ Zurich, Univ Clin Child & Adolescent Psychiat, CH-8032 Zurich, Switzerland. [Landolt, Markus A.] Univ Childrens Hosp Zurich, Dept Psychosomat & Psychiat, Zurich, Switzerland. [Landolt, Markus A.] Univ Zurich, Dept Child & Adolescent Hlth Psychol, Inst Psychol, CH-8032 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph; Schnyder, Ulrich] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph; Maier, Thomas] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen North, Wil, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [Mohler-Kuo, Meichun] Univ Zurich, Inst Social & Prevent Med, CH-8032 Zurich, Switzerland. RP Aebi, M (reprint author), Univ Zurich, Univ Clin Child & Adolescent Psychiat, Neptunstr 60, CH-8032 Zurich, Switzerland. EM marcel.aebi@uzh.ch OI Aebi, Marcel/0000-0001-7901-9801; Landolt, Markus/0000-0003-0760-5558 FU UBS OPTIMUS FOUNDATION FX The authors are grateful to all the students who participated in the study. We also thank Ursula Meidert from the Institute of Social and Preventive Medicine, University of Zurich, who helped with data collection. The data presented in this article were assessed in the context of the Optimus Study. The Optimus Study was initiated and funded by the UBS OPTIMUS FOUNDATION (http://www.optimusstudy.org). NR 52 TC 4 Z9 4 U1 11 U2 39 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 EI 1573-2800 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD NOV PY 2015 VL 44 IS 8 BP 2189 EP 2199 DI 10.1007/s10508-014-0440-x PG 11 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA CV8DV UT WOS:000364509800010 PM 25981223 ER PT J AU Hodi, FS Postow, MA Chesney, J Pavlik, AC Robert, C Grossman, K McDermott, D Linette, G Meyer, N Giguere, JK Agarwala, SS Shaheen, M Ernstoff, MS Minor, D Salama, AK Taylor, M Ott, PA Horak, C Gagnier, P Wolchok, JD AF Hodi, F. Stephen Postow, Michael A. Chesney, Jason Pavlik, Anna C. Robert, Caroline Grossman, Kenneth McDermott, David Linette, Gerald Meyer, Nicolas Giguere, Jeffrey K. Agarwala, Sanjiv S. Shaheen, Montaser Ernstoff, Marc S. Minor, David Salama, April K. Taylor, Matthew Ott, Patrick A. Horak, Christine Gagnier, Paul Wolchok, Jedd D. TI CLINICAL RESPONSE, PROGRESSION-FREE SURVIVAL (PFS) AND SAFETY IN PATIENTS (PTS) WITH ADVANCED MELANOMA (MEL) RECEIVING NIVOLUMAB (NIVO) COMBINED WITH IPILIMUMAB (IPI) VERSUS IPI MONOTHERAPY IN CHECKMATE 069 STUDY SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Hodi, F. Stephen] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hodi, F. Stephen; Ott, Patrick A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Postow, Michael A.; Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Postow, Michael A.] Weill Cornell Med Coll, New York, NY USA. [Chesney, Jason] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Pavlik, Anna C.] NYU, Perlmutter Canc Ctr, New York, NY USA. [Robert, Caroline] Canc Inst Gustave Roussy, Villejuif, France. [Robert, Caroline] Univ Paris 11, Villejuif Paris Sud, France. [Grossman, Kenneth] Huntsman Canc Inst, Salt Lake City, UT USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Linette, Gerald] Washington Univ, St Louis, MO USA. [Meyer, Nicolas] Inst Univ Canc, Toulouse, France. [Giguere, Jeffrey K.] Greenville Hlth Syst, Greenville, SC USA. [Agarwala, Sanjiv S.] St Lukes Canc Ctr, Bethlehem, PA USA. [Shaheen, Montaser] Univ New Mexico, New Mexico, NM USA. [Ernstoff, Marc S.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Minor, David] Calif Pacific Ctr Melanoma Res, San Francisco, CA USA. [Salama, April K.] Duke Univ, Med Ctr, Durham, NC USA. [Taylor, Matthew] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Horak, Christine] Bristol Myers Squibb Co, Princeton, NJ USA. [Gagnier, Paul] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 163 BP 109 EP 109 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800142 ER PT J AU Calvo, E Lopez-Martin, J Bendell, J Eder, JP Taylor, M Ott, PA Pietanza, MC Horn, L Jager, D de Braud, F Morse, MA Ascierto, PA Le, DT Amin, A Evans, J Simon, JS Lin, CS Christensen, O Antonia, SJ AF Calvo, Emiliano Lopez-Martin, Jose Bendell, Johanna Eder, Joseph P. Taylor, Matthew Ott, Patrick A. Pietanza, M. Catherine Horn, Leora Jaeger, Dirk de Braud, Filippo Morse, Michael A. Ascierto, Paolo A. Le, Dung T. Amin, Asim Evans, Jeff Simon, Jason S. Lin, Chen-Sheng Christensen, Olaf Antonia, Scott J. TI NIVOLUMAB (NIVO) MONOTHERAPY OR IN COMBINATION WITH IPILIMUMAB (IPI) FOR TREATMENT OF RECURRENT SMALL CELL LUNG CANCER (SCLC) SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Calvo, Emiliano] START Madrid, Ctr Integral Oncol Clara Campa, Madrid, Spain. [Lopez-Martin, Jose] Hosp Univ 12 Octubre, Madrid, Spain. [Bendell, Johanna] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Eder, Joseph P.] Yale Canc Ctr, New Haven, CT USA. [Taylor, Matthew] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Ott, Patrick A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pietanza, M. Catherine] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Horn, Leora] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Jaeger, Dirk] Univ Heidelberg Hosp, Heidelberg, Germany. [de Braud, Filippo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Morse, Michael A.] Duke Univ, Med Ctr, Durham, NC USA. [Ascierto, Paolo A.] Ist Nazl Tumori Fdn G Pascale, Naples, Italy. [Le, Dung T.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Amin, Asim] Levine Canc Inst, Charlotte, NC USA. [Evans, Jeff] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Simon, Jason S.; Lin, Chen-Sheng; Christensen, Olaf] Bristol Myers Squibb Co, Princeton, NJ USA. [Antonia, Scott J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 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 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 187 BP 118 EP 118 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800165 ER PT J AU Choueri, TK Fishman, MN Escudier, B McDermott, DF Kluger, H Stadler, WM Perez-Gracia, JL McNeel, D Curti, B Harrison, MR Plimack, ER Appleman, L Fong, L Drake, CG Young, TC Chasalow, SD Ross-Macdonald, P Simon, JS Walker, D Sznol, M AF Choueri, Toni K. Fishman, Mayer N. Escudier, Bernard McDermott, David F. Kluger, Harriet Stadler, Walter M. Perez-Gracia, Jose L. McNeel, Douglas Curti, Brendan Harrison, Michael R. Plimack, Elizabeth R. Appleman, Leonard Fong, Lawrence Drake, Charles G. Young, Tina C. Chasalow, Scott D. Ross-Macdonald, Petra Simon, Jason S. Walker, Dana Sznol, Mario TI IMMUNOMODULATORY ACTIVITY OF NIVOLUMAB IN METASTATIC RENAL CELL CARCINOMA (MRCC): ASSOCIATION OF BIOMARKERS WITH CLINICAL OUTCOMES SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Choueri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fishman, Mayer N.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Escudier, Bernard] Inst Gustave Roussy, Villejuif, France. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kluger, Harriet; Sznol, Mario] Yale Canc Ctr, New Haven, CT USA. [Stadler, Walter M.] Univ Chicago, Med, Chicago, IL 60637 USA. [Perez-Gracia, Jose L.] Univ Navarra Clin, Pamplona, Spain. [McNeel, Douglas] Univ Wisconsin, Dept Med, Madison, WI USA. [Curti, Brendan] Providence Portland Med Ctr, Providence Canc Ctr, Portland, OR USA. [Harrison, Michael R.] Duke Univ, Med Ctr, Durham, NC USA. [Plimack, Elizabeth R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Appleman, Leonard] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Fong, Lawrence] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Drake, Charles G.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Young, Tina C.; Chasalow, Scott D.; Ross-Macdonald, Petra; Simon, Jason S.; Walker, Dana] Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 189 BP 119 EP 119 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800167 ER PT J AU Larkin, J Chiarion-Sileni, V Gonzalez, R Grob, JJ Cowey, CL Lao, CD Wagstaff, J Hogg, D Hill, A Carlino, MS Wolter, P Lebbe, C Schachter, J Thomas, L Hassal, JC Lorigan, P Walker, D Jiang, J Hodi, FS Wolchok, JD AF Larkin, James Chiarion-Sileni, Vanna Gonzalez, Rene Grob, Jean-Jacques Cowey, C. Lance Lao, Christopher D. Wagstaff, John Hogg, David Hill, Andrew Carlino, Matteo S. Wolter, Pascal Lebbe, Celeste Schachter, Jacob Thomas, Luc Hassal, Jessica C. Lorigan, Paul Walker, Dana Jiang, Joel Hodi, F. Stephen Wolchok, Jedd D. TI EFFICACY AND SAFETY IN KEY PATIENT SUBGROUPS OF NIVOLUMAB (NIVO) ALONE OR COMBINED WITH IPILIMUMAB (IPI) VERSUS IPI ALONE IN TREATMENT-NAIVE PATIENTS WITH ADVANCED MELANOMA (MEL) (CHECKMATE 067) SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England. [Chiarion-Sileni, Vanna] IOV IRCCS, Melanoma Oncol Unit, Padua, Italy. [Gonzalez, Rene] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Grob, Jean-Jacques] Aix Marseille Univ, Hop La Timone, APHM, Marseille, France. [Cowey, C. Lance] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Lao, Christopher D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wagstaff, John] Singleton Hosp, South West Wales Canc Inst, Swansea SA2 8QA, W Glam, Wales. [Hogg, David] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Hill, Andrew] Tasman Oncol Res, South Port Gold Coast, Qld, Australia. [Carlino, Matteo S.] Melanoma Inst Australia, Sydney, NSW, Australia. [Carlino, Matteo S.] Univ Sydney, Sydney, NSW 2006, Australia. [Wolter, Pascal] UZ Leuven, Leuven, Belgium. [Lebbe, Celeste] Univ Paris Diderot, Hop St Louis, Paris, France. [Schachter, Jacob] Inst Oncol, Tel Hashomer, Israel. [Thomas, Luc] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [Hassal, Jessica C.] German Canc Res Ctr Univ Hosp, Heidelberg, Germany. [Lorigan, Paul] Christie NHS Fdn Trust, Manchester, Lancs, England. [Walker, Dana] Bristol Myers Squibb Co, Princeton, NJ USA. [Jiang, Joel] Bristol Myers Squibb Co, Hopewell, NJ USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 204 BP 126 EP 126 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800180 ER PT J AU Rechamp, K Spigel, DR Rizvi, N Poddubskaya, E West, H Eberhardt, W Baas, P Antonia, SJ Pluzanski, A Vokes, EE Holgado, E Waterhouse, D Reddy, N Gainor, J Frontera, OA Horn, L Paz-Ares, L Zhu, J Lynch, M Brahmer, J AF Rechamp, Karen Spigel, David R. Rizvi, Naiyer Poddubskaya, Elena West, Howard Eberhardt, Wilfried Baas, Paul Antonia, Scott J. Pluzanski, Adam Vokes, Everett E. Holgado, Esther Waterhouse, David Reddy, Neal Gainor, Justin Frontera, Osvaldo Aren Horn, Leora Paz-Ares, Luis Zhu, Jin Lynch, Mark Brahmer, Julie TI PHASE 3, RANDOMIZED TRIAL (CHECKMATE 017) OF NIVOLUMAB (NIVO) VS DOCETAXEL IN ADVANCED SQUAMOUS (SQ) CELL NON-SMALL CELL LUNG CANCER (NSCLC) SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Rechamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Spigel, David R.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Rizvi, Naiyer] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Poddubskaya, Elena] NN Blokhin Russian Canc Res Ctr, Moscow, Russia. [West, Howard] Swedish Canc Inst, Seattle, WA USA. [Eberhardt, Wilfried] Univ Duisburg Essen, Ruhrlandklin, West German Canc Ctr, Univ Hosp Essen, Essen, Germany. [Baas, Paul] Netherlands Canc Inst, Amsterdam, Netherlands. [Antonia, Scott J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Pluzanski, Adam] Inst Marii Sklodowskiej Curie, Ctr Onkol, Warsaw, Poland. [Vokes, Everett E.] Univ Chicago, Med & Biol Sci, Chicago, IL 60637 USA. [Holgado, Esther] Hosp Madrid, Norte Sanchinarro, Spain. [Waterhouse, David] Oncol Hematol Care, Cincinnati, OH USA. [Reddy, Neal] Duke Univ, Med Ctr, Durham, NC USA. [Gainor, Justin] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Frontera, Osvaldo Aren] Ctr Int Estudios Clin, Santiago, Chile. [Horn, Leora] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Paz-Ares, Luis] Hosp Univ Virgen Del Rocio, Seville, Spain. [Zhu, Jin; Lynch, Mark] Bristol Myers Squibb Co, Princeton, NJ USA. [Brahmer, Julie] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 214 BP 130 EP 130 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800190 ER PT J AU Davis, I Stockler, M Martin, A Hague, W Coskinas, X Yip, S Dazo, C Long, A Lawrence, N Chan, H McDermott, R Chowdhury, S Marchesin, V Deignan, O Parulekar, W Suris, AM Sweeney, C AF Davis, Ian Stockler, Martin Martin, Andrew Hague, Wendy Coskinas, Xanthi Yip, Sonia Dazo, Carlo Long, Anne Lawrence, Nicky Chan, Howard McDermott, Ray Chowdhury, Simon Marchesin, Vittorio Deignan, Olwyn Parulekar, Wendy Suris, Alexander Montenegro Sweeney, Christopher CA ANZUP TI RANDOMISED PHASE 3 TRIAL OF ENZALUTAMIDE IN FIRST LINE ANDROGEN DEPRIVATION THERAPY FOR METASTATIC PROSTATE CANCER: THE ANZUP ENZAMET TRIAL (ANZUP 1304) SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Davis, Ian] Monash Univ, Eastern Hlth Clin Sch, Melbourne, Vic 3004, Australia. [Stockler, Martin; Martin, Andrew; Hague, Wendy; Coskinas, Xanthi; Yip, Sonia; Dazo, Carlo; Long, Anne; Lawrence, Nicky; Chan, Howard] NHMRC Clin Trials Grp, Camperdown, NSW, Australia. [Yip, Sonia] Sydney Catalyst Translat Canc Res Ctr, Sydney, NSW, Australia. [McDermott, Ray; Marchesin, Vittorio; Deignan, Olwyn] All Ireland Cooperat Oncol Res Grp ICORG, Dublin, Ireland. [Chowdhury, Simon] Guys & St Thomas NHS Trust, Kings Coll, London, England. [Parulekar, Wendy; Suris, Alexander Montenegro] NCIC, Clin Trials Grp, Kingston, ON, Canada. [Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA. [ANZUP] Australian & New Zealand Urogenital & Prostate Ca, Sydney, NSW, Australia. RI Stockler, Martin/N-3859-2016 OI Stockler, Martin/0000-0003-3793-8724 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 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 269 BP 148 EP 148 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800240 ER PT J AU Williams, SG Davis, ID Sweeney, C Stockler, MR Martin, A Hague, W Coskinas, X Long, A Yip, S Tu, E Chan, H Lawrence, N McDermott, R Hughes, S Marchesin, V Deignan, O Nguyen, PL AF Williams, Scott G. Davis, Ian D. Sweeney, Christopher Stockler, Martin R. Martin, Andrew Hague, Wendy Coskinas, Xanthi Long, Anne Yip, Sonia Tu, Emily Chan, Howard Lawrence, Nicky McDermott, Ray Hughes, Simon Marchesin, Vittorio Deignan, Olwyn Nguyen, Paul L. TI RANDOMISED PHASE 3 TRIAL OF ENZALUTAMIDE IN ANDROGEN DEPRIVATION THERAPY WITH RADIATION THERAPY FOR HIGH RISK, CLINICALLY LOCALISED, PROSTATE CANCER: ENZARAD (ANZUP 1303) SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Williams, Scott G.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Davis, Ian D.] Monash Univ, Eastern Hlth Clin Sch, Melbourne, Vic 3004, Australia. [Sweeney, Christopher; Nguyen, Paul L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stockler, Martin R.; Martin, Andrew; Hague, Wendy; Coskinas, Xanthi; Long, Anne; Yip, Sonia; Tu, Emily; Chan, Howard; Lawrence, Nicky] NHMRC Clin Trials Grp, Camperdown, NSW, Australia. [Yip, Sonia] Sydney Catalyst Translat Canc Res Ctr, Sydney, NSW, Australia. [McDermott, Ray; Marchesin, Vittorio; Deignan, Olwyn] All Ireland Cooperat Oncol Res Grp ICORG, Dublin, Ireland. [Hughes, Simon] Guys & St Thomas NHS Fdn Trust, London, England. RI Stockler, Martin/N-3859-2016 OI Stockler, Martin/0000-0003-3793-8724 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 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 273 BP 149 EP 149 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800243 ER PT J AU Brose, M Schlumberger, M Tahara, M Wirth, L Robinson, B Elisei, R Newbold, K Kiyota, N Hoff, AO Dutcus, C Song, J Hughes, B Sherman, S Taylor, MH AF Brose, Marcia Schlumberger, Martin Tahara, Makoto Wirth, Lori Robinson, Bruce Elisei, Rossella Newbold, Kate Kiyota, Naomi Hoff, Ana O. Dutcus, Corina Song, James Hughes, Brett Sherman, Steven Taylor, Matthew Hiram TI EFFECT OF AGE AND LENVATINIB TREATMENT ON OVERALL SURVIVAL FOR PATIENTS WITH I-131- REFRACTORY DIFFERENTIATED THYROID CANCER IN SELECT SO Asia-Pacific Journal of Clinical Oncology LA English DT Meeting Abstract C1 [Brose, Marcia] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Abramsom Canc Ctr, Philadelphia, PA 19104 USA. [Schlumberger, Martin] Gustave Roussy, Ctr Reference Tumeurs Refractaires Thyroide, Dept Nucl Med & Endocrine Oncol, Villejuif, France. [Schlumberger, Martin] Univ Paris 11, Villejuif, France. [Tahara, Makoto] Natl Canc Ctr Hosp East, Div Head & Neck Med Oncol, Kashiwa, Chiba, Japan. [Wirth, Lori] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Robinson, Bruce] Univ Sydney, Kolling Inst Med Res, Dept Med, Northern Clin Sch, Sydney, NSW 2006, Australia. [Elisei, Rossella] Univ Pisa, Dipartimento Med Clin & Sperimentale, Pisa, Italy. [Newbold, Kate] Royal Marsden NHS Fdn Trust, London, England. [Kiyota, Naomi] Kobe Univ Hosp, Dept Med Oncol & Hematol, Kobe, Hyogo, Japan. [Hoff, Ana O.] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Sao Paulo, Brazil. [Dutcus, Corina] Eisai Inc, Oncol Prod Creat Unit, Woodcliff Lake, NJ USA. [Song, James] Eisai Inc, Woodcliff Lake, NJ USA. [Hughes, Brett] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Sherman, Steven] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Div Internal Med, Houston, TX 77030 USA. [Taylor, Matthew Hiram] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. RI Kiyota, Naomi/K-3226-2016 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 EI 1743-7563 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2015 VL 11 SU 4 SI SI MA 363 BP 173 EP 173 PG 1 WC Oncology SC Oncology GA CV5OQ UT WOS:000364320800312 ER PT J AU Abramovitch, A Reese, H Woods, DW Peterson, A Deckersbach, T Piacentini, J Scahill, L Wilhelm, S AF Abramovitch, Amitai Reese, Hannah Woods, Douglas W. Peterson, Alan Deckersbach, Thilo Piacentini, John Scahill, Lawrence Wilhelm, Sabine TI Psychometric Properties of a Self-Report Instrument for the Assessment of Tic Severity in Adults With Tic Disorders SO BEHAVIOR THERAPY LA English DT Article DE Tourette's disorder; Tourette's syndrome; chronic tic disorder; persistent tic disorder; adults; questionnaire ID OBSESSIVE COMPULSIVE SCALE; LA-TOURETTE-SYNDROME; CONTROLLED-TRIAL; CHILDREN; ADOLESCENTS; RELIABILITY; EXPRESSION; SYMPTOMS; VALIDITY; THERAPY AB The gold-standard measure of tic severity in tic disorders (TD), the Yale Global Tic Severity Scale (YGTSS), is a semistructured clinician-administered interview that can be time consuming and requires highly trained interviewers. Moreover, the YGTSS does not provide information regarding frequency and intensity of specific tics because all motor and all vocal tics are rated as a group. The aim of the present study is to describe and test the Adult Tic Questionnaire (ATQ), a measure for the assessment of tic severity in adults, and to report its preliminary psychometric properties. The ATQ is a brief self-report questionnaire that provides information regarding frequency, intensity, and severity of 27 specific tics. In addition, the ATQ produces total frequency, intensity, and severity scores for vocal and motor tics, as well as a global total tic severity score. Results showed that the ATQ demonstrated very good internal consistency and temporal stability. The total, vocal, and motor tic severity scales of the ATQ showed strong correlation with corresponding subscales of the YGTSS, indicating strong convergent validity. Weak correlations with measures of severity of obsessive-compulsive disorder and attention deficit/hyperactivity disorder, indicated strong discriminant validity. The ATQ, a promising measure for the assessment of tic severity in adults with TD, may be a valuable supplement to the current recommended assessment battery for TD. Furthermore, the ATQ enables clinicians and researchers to track changes in the frequency and intensity of specific tics, which is important given their complex and dynamic nature. C1 [Abramovitch, Amitai; Reese, Hannah; Deckersbach, Thilo; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abramovitch, Amitai] Texas State Univ, San Marcos, TX USA. [Abramovitch, Amitai; Reese, Hannah; Deckersbach, Thilo; Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Reese, Hannah] Bowdoin Coll, Brunswick, ME 04011 USA. [Woods, Douglas W.] Texas A&M Univ, College Stn, TX 77843 USA. [Peterson, Alan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Piacentini, John] Univ Calif Los Angeles, Los Angeles, CA USA. [Scahill, Lawrence] Yale Univ, New Haven, CT 06520 USA. [Scahill, Lawrence] Emory Univ, Atlanta, GA 30322 USA. RP Abramovitch, A (reprint author), Texas State Univ, Undergrad Acad Ctr, Dept Psychol, San Marcos, TX 78666 USA. EM abramovitch@txstate.edu FU National Institute of Mental Health (NIMH) [5R01MH069877, R01MH069874, RO1MH069875] FX This work was supported by grants from the National Institute of Mental Health (NIMH) to Drs. Wilhelm (5R01MH069877), Scahill (R01MH069874), and Peterson (RO1MH069875) with subcontracts to Drs. Piacentini and Woods. NR 33 TC 0 Z9 0 U1 4 U2 8 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD NOV PY 2015 VL 46 IS 6 BP 786 EP 796 PG 11 WC Psychology, Clinical SC Psychology GA CW2CD UT WOS:000364797800006 PM 26520221 ER PT J AU Liu, VM Vander Heiden, MG AF Liu, Vivian M. Vander Heiden, Matthew G. TI The Role of Pyruvate Kinase M2 in Cancer Metabolism SO BRAIN PATHOLOGY LA English DT Article DE cancer metabolism; glycolysis; pyruvate kinase M2 ID TUMOR-CELLS; ALLOSTERIC REGULATION; GENE-TRANSCRIPTION; ISOFORM; PKM2; GROWTH; PROLIFERATION; TUMORIGENESIS; MECHANISM; REVEALS AB The M2 isoform of pyruvate kinase is expressed preferentially in cancer cells over other pyruvate kinase isoforms. PKM2 is unique in its ability to be regulated allosterically by nutrients and growth signaling pathways, allowing cells to adapt their metabolic program to match physiological needs in different environments. Here, we discuss the role of pyruvate kinase M2 in glioma and in cancer metabolism. C1 [Liu, Vivian M.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Liu, Vivian M.] Harvard Univ, Sch Med, Harvard MIT Hlth Sci & Technol Div, Boston, MA USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave 76-561, Cambridge, MA 02139 USA. EM mvh@mit.edu OI , /0000-0002-9118-6204 FU Koch Institute at MIT; NCI; Burroughs Wellcome Fund; MIT UROP program FX The authors wish to thank William Israelsen and Aaron Hosios for the helpful comments on the manuscript. VML was supported by the MIT UROP program and MGVH acknowledges support from the Burroughs Wellcome Fund, the Koch Institute at MIT, and the NCI. MGVH is a consultant and advisory board member for Agios Pharmaceuticals. NR 39 TC 4 Z9 4 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1015-6305 EI 1750-3639 J9 BRAIN PATHOL JI Brain Pathol. PD NOV PY 2015 VL 25 IS 6 BP 781 EP 783 DI 10.1111/bpa.12311 PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CV5MB UT WOS:000364313700013 PM 26526946 ER PT J AU Bhatt, AB DeFaria, D AF Bhatt, Ami B. DeFaria, Doreen TI Pregnancy and Adult Congenital Heart Disease SO CARDIOLOGY CLINICS LA English DT Article DE Adult congenital heart disease; Pregnancy; Heart failure; Obstetrics; Obstetric anesthesia; Congenital heart disease; Arrhythmia; Preconception counseling ID SYSTEMIC RIGHT VENTRICLE; GREAT-ARTERIES; CORRECTED TRANSPOSITION; FONTAN REPAIR; SEPTAL-DEFECT; WOMEN; OUTCOMES; COMPLICATIONS; COARCTATION; PREDICTORS AB Most women with known congenital heart disease can have successful pregnancy, labor, and delivery. Preconception assessment is essential in understanding anatomy, repairs, and current physiology, all of which can influence risk in pregnancy. With that foundation, a multidisciplinary cardio-obstetric team can predict and prepare for complications that may occur with superimposed hemodynamic changes of pregnancy. Individuals with Eisenmenger syndrome, pulmonary hypertension, cyanosis, significant left heart obstruction, ventricular dysfunction, or prior major cardiac event are at the highest risk for complications. C1 [Bhatt, Ami B.; DeFaria, Doreen] Massachusetts Gen Hosp, Ctr Heart, Adult Congenital Heart Dis Program, Boston, MA 02114 USA. [Bhatt, Ami B.; DeFaria, Doreen] Massachusetts Gen Hosp, Ctr Heart, Cardiovasc Dis & Pregnancy Serv, Boston, MA 02114 USA. RP Bhatt, AB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Adult Congenital Heart Dis Program, 55 Fruit St,Yawkey 5700, Boston, MA 02114 USA. EM abhatt@mgh.harvard.edu NR 38 TC 5 Z9 5 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 0733-8651 EI 1558-2264 J9 CARDIOL CLIN JI Cardiol. Clin. PD NOV PY 2015 VL 33 IS 4 BP 611 EP + DI 10.1016/j.ccl.2015.07.008 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW1DG UT WOS:000364729200011 PM 26471824 ER PT J AU Renaud, L Harris, LG Mani, SK Kasiganesan, H Chou, JC Baicu, CF Van Laer, A Akerman, AW Stroud, RE Jones, JA Zile, MR Menick, DR AF Renaud, Ludivine Harris, Lillianne G. Mani, Santhosh K. Kasiganesan, Harinath Chou, James C. Baicu, Catalin F. Van Laer, An Akerman, Adam W. Stroud, Robert E. Jones, Jeffrey A. Zile, Michael R. Menick, Donald R. TI HDACs Regulate miR-133a Expression in Pressure Overload-Induced Cardiac Fibrosis SO CIRCULATION-HEART FAILURE LA English DT Article DE microRNA; epigenomics; heart ventricles; histone deacetylase; hypertrophy ID PRESERVED EJECTION FRACTION; TISSUE GROWTH-FACTOR; HEART-FAILURE; GENE-EXPRESSION; CLASS-I; HISTONE; HYPERTROPHY; MICRORNAS; PROLIFERATION; DISEASE AB Background-MICRORNAS (miRNAs) and histone deacetylases (HDACs) serve a significant role in the pathogenesis of a variety of cardiovascular diseases. The transcriptional regulation of miRNAs is poorly understood in cardiac hypertrophy. We investigated whether the expression of miR-133a is epigenetically regulated by class I and IIb HDACs during hypertrophic remodeling. Methods and Results-Transverse aortic constriction (TAC) was performed in CD1 mice to induce pressure overload hypertrophy. Mice were treated with class I and IIb HDAC inhibitor (HDACi) via drinking water for 2 and 4 weeks post TAC. miRNA expression was determined by real-time polymerase chain reaction. Echocardiography was performed at baseline and post TAC end points for structural and functional assessment. Chromatin immunoprecipitation was used to identify HDACs and transcription factors associated with miR-133a promoter. miR-133a expression was downregulated by 0.7- and 0.5-fold at 2 and 4 weeks post TAC, respectively, when compared with vehicle control (P<0.05). HDAC inhibition prevented this significant decrease 2 weeks post TAC and maintained miR-133a expression near vehicle control levels, which coincided with (1) a decrease in connective tissue growth factor expression, (2) a reduction in cardiac fibrosis and left atrium diameter (marker of end-diastolic pressure), suggesting an improvement in diastolic function. Chromatin immunoprecipitation analysis revealed that HDAC1 and HDAC2 are present on the miR-133a enhancer regions. Conclusions-The results reveal that HDACs play a role in the regulation of pressure overload-induced miR-133a downregulation. This work is the first to provide insight into an epigenetic-miRNA regulatory pathway in pressure overload-induced cardiac fibrosis. C1 [Renaud, Ludivine; Harris, Lillianne G.; Mani, Santhosh K.; Kasiganesan, Harinath; Baicu, Catalin F.; Van Laer, An; Zile, Michael R.; Menick, Donald R.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Akerman, Adam W.; Stroud, Robert E.; Jones, Jeffrey A.] Med Univ S Carolina, Dept Cardiothorac Surg Res, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Chou, James C.] Med Univ S Carolina, Coll Pharm, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Jones, Jeffrey A.; Zile, Michael R.; Menick, Donald R.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Menick, DR (reprint author), Gazes Cardiac Res Inst, 114 Doughty St,MSC 773, Charleston, SC 29425 USA. EM menickd@musc.edu FU National Institutes of Health through the Heart, Lung, and Blood Institute [R01HL094545, R56HL123478, R01HL123478, UL1TR000062]; United States Department of Veterans Affairs Merit Reviews through the Biomedical Laboratory Research and Development, and Clinical Sciences Research and Development Programs [I01 BX002327, I01 BX000904, 5101 CX000415-02, 5101 BX000487-04]; [T32HL07260] FX This work was supported in part by the National Institutes of Health (R01HL094545 [Dr Menick], R56HL123478 [Dr Zile], R01HL123478 [Dr Zile], and UL1TR000062 [Dr Menick]) through the Heart, Lung, and Blood Institute, by Postdoctoral Fellowship (T32HL07260 [Dr Harris]), and by United States Department of Veterans Affairs Merit Reviews (I01 BX002327 [Dr Menick], I01 BX000904 [Dr Jones], 5101 CX000415-02 and 5101 BX000487-04 [Dr Zile]) through the Biomedical Laboratory Research and Development, and Clinical Sciences Research and Development Programs. NR 58 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2015 VL 8 IS 6 BP 1094 EP 1104 DI 10.1161/CIRCHEARTFAILURE.114.001781 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW1SQ UT WOS:000364772000011 PM 26371176 ER PT J AU Teerlink, JR Malik, FI Kass, DA AF Teerlink, John R. Malik, Fady I. Kass, David A. TI Letter by Teerlink et al Regarding Article, "Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity" SO CIRCULATION-HEART FAILURE LA English DT Letter ID SYSTOLIC HEART-FAILURE C1 [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Malik, Fady I.] Cytokinetics Inc, San Francisco, CA USA. [Kass, David A.] Johns Hopkins Univ, Inst Med, Baltimore, MD USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01 HL114910] NR 6 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD NOV PY 2015 VL 8 IS 6 BP 1141 EP 1141 DI 10.1161/CIRCHEARTFAILURE.115.002492 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW1SQ UT WOS:000364772000017 PM 26578671 ER PT J AU George, RE AF George, Rani E. TI Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID ACTIVATING MUTATIONS; ALK KINASE; NEUROBLASTOMA; RECEPTOR; CANCER AB Bellini and colleagues demonstrate the importance of next-generation sequencing to uncover subclonal anaplastic lymphoma kinase (ALK) mutations in neuroblastoma. Although the significance of these subclonal aberrations is not yet understood, deep sequencing could identify patients whose tumors may respond to ALK inhibitors. (C)2015 AACR. C1 [George, Rani E.] Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02215 USA. [George, Rani E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 640E,450 Brookline Ave, Boston, MA 02215 USA. EM rani_george@dfci.harvard.edu FU NCI NIH HHS [R01CA148688, R01 CA148688] NR 12 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2015 VL 21 IS 21 BP 4747 EP 4749 DI 10.1158/1078-0432.CCR-15-1397 PG 3 WC Oncology SC Oncology GA CV7WW UT WOS:000364488100002 PM 26362998 ER PT J AU Laubach, JP Moreau, P San-Miguel, JF Richardson, PG AF Laubach, Jacob P. Moreau, Philippe San-Miguel, Jesus F. Richardson, Paul G. TI Panobinostat for the Treatment of Multiple Myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID PAN-DEACETYLASE INHIBITOR; LENALIDOMIDE PLUS DEXAMETHASONE; SINGLE-AGENT CARFILZOMIB; LOW-DOSE DEXAMETHASONE; HISTONE DEACETYLASES; BORTEZOMIB; COMBINATION; PHASE-2; LBH589; CANCER AB Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received >= 2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression- free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P < 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. (C)2015 AACR. C1 [Laubach, Jacob P.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Moreau, Philippe] Nantes Univ Hosp, Nantes, France. [San-Miguel, Jesus F.] Univ Navarra Clin, CIMA, IDISNA, Pamplona, Spain. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM paul_richardson@dfci.harvard.edu RI richard, chrystelle/K-8595-2015 FU Novartis Pharmaceuticals Corporation, East Hanover, New Jersey FX Editorial assistance was provided by Julie Shilane, PhD, and funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. NR 40 TC 27 Z9 27 U1 2 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 2015 VL 21 IS 21 BP 4767 EP 4773 DI 10.1158/1078-0432.CCR-15-0530 PG 7 WC Oncology SC Oncology GA CV7WW UT WOS:000364488100006 PM 26362997 ER PT J AU Karnitz, LM Zou, L AF Karnitz, Larry M. Zou, Lee TI Molecular Pathways: Targeting ATR in Cancer Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION REPAIR; SELECTIVE CHK1 INHIBITOR; ATAXIA-TELANGIECTASIA; GENOMIC INSTABILITY; IN-VIVO; SYNTHETIC LETHALITY; LUNG ADENOCARCINOMA; REPLICATION STRESS; PROTEIN-KINASE AB The human ATR gene encodes a kinase that is activated by DNA damage and replication stress as a central transducer of a checkpoint signaling pathway. Once activated, ATR phosphorylates multiple substrates, including the kinase Chk1, to regulate cell-cycle progression, replication fork stability, and DNA repair. These events promote cell survival during replication stress and in cells with DNA damage. Accordingly, there has been the tantalizing possibility that ATR inhibitors would be therapeutically useful, especially if they were more effective in tumor versus normal cells. Indeed, multiple studies have demonstrated that alterations that promote tumorigenesis, such as defects in the ATM-p53 pathway, constitutive oncogene activation, and acquisition of the alternative lengthening of telomeres pathway, render tumor cells sensitive to ATR inhibitor monotherapy and/or increase the synergy between ATR inhibitors and genotoxic chemotherapies. Now, nearly two decades after the discovery of ATR, two highly selective and potent ATR inhibitors, AZD6738 and VX-970, are in early-phase clinical trials either as monotherapies or paired with a variety of genotoxic chemotherapies. These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies. (C) 2015 AACR. C1 [Karnitz, Larry M.] Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA. [Karnitz, Larry M.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02115 USA. RP Karnitz, LM (reprint author), Mayo Clin, 200 First St SW,Gonda 19-300, Rochester, MN 55905 USA. EM Karnitz.larry@mayo.edu FU NIH [P50CA136393, GM076388] FX Research reported in this publication was supported in part by the NIH under award numbers P50CA136393 (to L.M. Karnitz) and GM076388 (to L. Zou). L. Zou is a Jim & Ann Orr Massachusetts General Hospital Research Scholar. NR 66 TC 13 Z9 13 U1 7 U2 22 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 2015 VL 21 IS 21 BP 4780 EP 4785 DI 10.1158/1078-0432.CCR-15-0479 PG 6 WC Oncology SC Oncology GA CV7WW UT WOS:000364488100008 PM 26362996 ER PT J AU Cai, C Chen, QB Han, ZD Zhang, YQ He, HC Chen, JH Chen, YR Yang, SB Wu, YD Zeng, YR Qin, GQ Liang, YX Dai, QS Jiang, FN Wu, SL Zeng, GH Zhong, WD Wu, CL AF Cai, Chao Chen, Qing-Biao Han, Zhao-Dong Zhang, Yan-Qiong He, Hui-Chan Chen, Jia-Hong Chen, Yan-Ru Yang, Sheng-Bang Wu, Yong-Ding Zeng, Yan-Ru Qin, Guo-Qiang Liang, Yu-Xiang Dai, Qi-Shan Jiang, Fu-Neng Wu, Shu-lin Zeng, Guo-Hua Zhong, Wei-De Wu, Chin-Lee TI miR-195 Inhibits Tumor Progression by Targeting RPS6KB1 in Human Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID P70 S6 KINASE; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; BREAST-CANCER; CELL-CYCLE; MICRORNAS; PATHWAY; BIOGENESIS; TRANSITION; RESISTANCE AB Purpose: To investigate the involvement of hsa-miRNA-195-5p (miR-195) in progression andprognosis ofhuman prostate cancer. Experimental Design: qRT-PCR was performed to detect miR-195 expression in both prostate cancer cell lines and clinical tissue samples. Its clinical significance was statistically analyzed. The roles of miR-195 and its candidate target gene, ribosomal protein S6 kinase, 70 kDa, polypeptide 1 (RPS6KB1) in prostate cancer progression were confirmed on the basis of both in vitro and in vivo systems. Results: miR-195 downregulation in prostate cancer tissues was significantly associated with high Gleason score (P = 0.001), positive metastasis failure (P < 0.001), and biochemical recurrence (BCR, P < 0.001). Survival analysis identified miR-195 as an independent prognostic factor for BCR-free survival of prostate cancer patients (P = 0.022). Then, we confirmed the tumor suppressive role of miR-195 through prostate cancer cell invasion, migration, and apoptosis assays in vitro, along with tumor xeno-graft growth, angiogenesis, and invasion in vivo according to both gain-of-function and loss-of-function experiments. In addition, RPS6KB1 was identified as a novel direct target of miR-195 through proteomic expression profiling combined with bioinformatic target prediction and luciferase reporter assay. Moreover, the reexpression and knockdown of RPS6KB1 could respectively rescue and imitate the effects induced by miR-195. Importantly, RPS6KB1 expression was closely correlated with aggressive progression and poor prognosis in prostate cancer patients as opposed to miR-195. Furthermore, we identified MMP-9, VEGF, BAD, and E-cadherin as the downstream effectors of miR-195-RPS6KB1 axis. Conclusion: The newly identified miR-195-RPS6KB1 axis partially illustrates the molecular mechanism of prostate cancer progression and represents a novel potential therapeutic target for prostate cancer treatment. (C) 2015 AACR. C1 [Cai, Chao; He, Hui-Chan; Zeng, Guo-Hua; Zhong, Wei-De] Guangzhou Med Univ, Affiliated Hosp 1, Minimally Invas Surg Ctr, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. [Cai, Chao; He, Hui-Chan; Zeng, Guo-Hua; Zhong, Wei-De] Guangdong Key Lab Urol, Guangzhou, Guangdong, Peoples R China. [Chen, Qing-Biao; Zeng, Yan-Ru; Zhong, Wei-De] Southern Med Univ, Guangdong Prov Inst Nephrol, Guangzhou, Guangdong, Peoples R China. [Han, Zhao-Dong; He, Hui-Chan; Chen, Jia-Hong; Chen, Yan-Ru; Yang, Sheng-Bang; Wu, Yong-Ding; Zeng, Yan-Ru; Liang, Yu-Xiang; Dai, Qi-Shan; Jiang, Fu-Neng; Zhong, Wei-De] Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Urol, Guangdong Key Lab Clin Mol Med & Diagnost, Guangzhou 510180, Guangdong, Peoples R China. [Zhang, Yan-Qiong] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China. [Qin, Guo-Qiang] Cent Hosp Panyu Dist, Guangzhou, Guangdong, Peoples R China. [Wu, Shu-lin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Shu-lin; Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Zhong, WD (reprint author), Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. EM zhongwd2009@live.cn; cwu2@partners.org FU National Natural Science Foundation of China [81170699, 81272813, 81200550, 81470983]; Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics; Guangzhou Municipal Science and Technology Project [201501010135]; NIH/NCI [P01 CA120964]; Beijing Nova program [Z1511000003150126] FX This work was supported by grants from the National Natural Science Foundation of China (81170699, 81272813, 81200550, 81470983), the Projects of Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, the Guangzhou Municipal Science and Technology Project (201501010135), NIH/NCI P01 CA120964, and Beijing Nova program (Z1511000003150126). NR 42 TC 9 Z9 9 U1 2 U2 12 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 2015 VL 21 IS 21 BP 4922 EP 4934 DI 10.1158/1078-0432.CCR-15-0217 PG 13 WC Oncology SC Oncology GA CV7WW UT WOS:000364488100021 PM 26080838 ER PT J AU Vathipadiekal, V Wang, V Wei, W Waldron, L Drapkin, R Gillette, M Skates, S Birrer, M AF Vathipadiekal, Vinod Wang, Victoria Wei, Wei Waldron, Levi Drapkin, Ronny Gillette, Michael Skates, Steven Birrer, Michael TI Creation of a Human Secretome: A Novel Composite Library of Human Secreted Proteins: Validation Using Ovarian Cancer Gene Expression Data and a Virtual Secretome Array SO CLINICAL CANCER RESEARCH LA English DT Article ID MICROARRAY ANALYSIS; CARCINOMA; BIOMARKER; IDENTIFICATION; TRANSMEMBRANE; SUBTRACTION; STATISTICS; DISCOVERY; SURVIVAL; ANTIGEN AB Purpose: To generate a comprehensive "Secretome" of proteins potentially found in the blood and derive a virtual Affymetrix array. To validate the utility of this database for the discovery of novel serum-based biomarkers using ovarian cancer transcriptomic data. Experimental Design: The secretome was constructed by aggregating the data from databases of known secreted proteins, transmembrane or membrane proteins, signal peptides, G-protein coupled receptors, or proteins existing in the extracellular region, and the virtual array was generated by mapping them to Affymetrix probeset identifiers. Whole-genome microarray data from ovarian cancer, normal ovarian surface epithelium, and fallopian tube epithelium were used to identify transcripts upregulated in ovarian cancer. Results: We established the secretome from eight public databases and a virtual array consisting of 16,521 Affymetrix U133 Plus 2.0 probesets. Using ovarian cancer transcriptomic data, we identified candidate blood-based biomarkers for ovarian cancer and performed bioinformatic validation by demonstrating rediscovery of known biomarkers including CA125 and HE4. Two novel top biomarkers (FGF18 and GPR172A) were validated in serum samples from an independent patient cohort. Conclusions: We present the secretome, comprising the most comprehensive resource available for protein products that are potentially found in the blood. The associated virtual array can be used to translate gene-expression data into cancer biomarker discovery. A list of blood-based biomarkers for ovarian cancer detection is reported and includes CA125 and HE4. FGF18 and GPR172A were identified and validated by ELISA as being differentially expressed in the serum of ovarian cancer patients compared with controls. (C) 2015 AACR. C1 [Vathipadiekal, Vinod; Wei, Wei; Gillette, Michael; Birrer, Michael] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vathipadiekal, Vinod; Wang, Victoria; Wei, Wei; Waldron, Levi; Skates, Steven; Birrer, Michael] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Victoria; Waldron, Levi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Waldron, Levi] CUNY, New York, NY 10021 USA. [Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gillette, Michael] Broad Inst MIT & Harvard, Cambridge, MA USA. [Skates, Steven] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. RP Birrer, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM MBIRRER@mgh.harvard.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Waldron, Levi/0000-0003-2725-0694 NR 35 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2015 VL 21 IS 21 BP 4960 EP 4969 DI 10.1158/1078-0432.CCR-14-3173 PG 10 WC Oncology SC Oncology GA CV7WW UT WOS:000364488100024 PM 25944803 ER PT J AU Safa, K Chandran, S Wojciechowski, D AF Safa, Kassem Chandran, Sindhu Wojciechowski, David TI Pharmacologic Targeting of Regulatory T Cells for Solid Organ Transplantation: Current and Future Prospects SO DRUGS LA English DT Article ID RENAL-ALLOGRAFT RECIPIENTS; HUMANIZED MOUSE MODEL; IN-VIVO; KIDNEY-TRANSPLANTATION; CALCINEURIN INHIBITORS; INDUCTION THERAPY; CYCLOSPORINE-A; MAINTENANCE IMMUNOSUPPRESSION; ANTITHYMOCYTE GLOBULIN; ALEMTUZUMAB INDUCTION AB The last three decades have witnessed significant advances in the development of immunosuppressive medications used in kidney transplantation leading to a remarkable gain in short-term graft function and outcomes. Despite these major breakthroughs, improvements in long-term outcomes lag behind due to a stalemate between drug-related nephrotoxicity and chronic rejection typically due to donor-specific antibodies. Regulatory T cells (Tregs) have been shown to modulate the alloimmune response and can exert suppressive activity preventing allograft rejection in kidney transplantation. Currently available immunosuppressive agents impact Tregs in the alloimmune milieu with some of these interactions being deleterious to the allograft while others may be beneficial. Variable effects are seen with common antibody induction agents such that basiliximab, an IL-2 receptor blocker, decreases Tregs while lymphocyte depleting agents such as antithymocyte globulin increase Tregs. Calcineurin inhibitors, a mainstay of maintenance immunosuppression since the mid-1980s, seem to suppress Tregs while mammalian targets of rapamycin (less commonly used in maintenance regimens) expand Tregs. The purpose of this review is to provide an overview of Treg biology in transplantation, identify in more detail the interactions between commonly used immunosuppressive agents and Tregs in kidney transplantation and lastly describe future directions in the use of Tregs themselves as therapy for tolerance induction. C1 [Safa, Kassem; Wojciechowski, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02114 USA. [Safa, Kassem; Wojciechowski, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Ctr, Boston, MA USA. [Chandran, Sindhu] Univ Calif San Francisco, Med Ctr, Dept Med, Div Nephrol, San Francisco, CA USA. RP Wojciechowski, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, 55 Fruit St, Boston, MA 02114 USA. EM dwojciechowski@mgh.harvard.edu FU BMS; Novartis; Oxford Immunotec; Qiagen FX K. Safa has no conflicts to report. S. Chandran has received grant support from BMS. D. Wojciechowski has received grant support from Novartis, BMS, Oxford Immunotec and Qiagen. NR 111 TC 2 Z9 2 U1 0 U2 4 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0012-6667 EI 1179-1950 J9 DRUGS JI Drugs PD NOV PY 2015 VL 75 IS 16 BP 1843 EP 1852 DI 10.1007/s40265-015-0487-6 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA CV6ZL UT WOS:000364421000002 PM 26493288 ER PT J AU Billings, CJ Penman, TM McMillan, GP Ellis, EM AF Billings, Curtis J. Penman, Tina M. McMillan, Garnett P. Ellis, Emily M. TI Electrophysiology and Perception of Speech in Noise in Older Listeners: Effects of Hearing Impairment and Age SO EAR AND HEARING LA English DT Article DE Background noise; Cortical auditory evoked potentials; Event-related potentials; N1; Perception in noise; Prediction; Psychometric function; Signals in noise; Signal-to-noise ratio ID AUDITORY-EVOKED POTENTIALS; SOUNDS VERTICAL-BAR; EVENT-RELATED POTENTIALS; BROAD-BAND NOISE; MASKING; RECOGNITION; INTENSITY; FREQUENCY; AMPLITUDE; SIGNALS AB Objectives: Speech perception in background noise is difficult for many individuals, and there is considerable performance variability across listeners. The combination of physiological and behavioral measures may help to understand sources of this variability for individuals and groups and prove useful clinically with hard-to-test populations. The purpose of this study was threefold: (1) determine the effect of signal-to-noise ratio (SNR) and signal level on cortical auditory evoked potentials (CAEPs) and sentence-level perception in older normal-hearing (ONH) and older hearing-impaired (OHI) individuals, (2) determine the effects of hearing impairment and age on CAEPs and perception, and (3) explore how well CAEPs correlate with and predict speech perception in noise. Design: Two groups of older participants (15 ONH and 15 OHI) were tested using speech-in-noise stimuli to measure CAEPs and sentence-level perception of speech. The syllable /ba/, used to evoke CAEPs, and sentences were presented in speech-spectrum background noise at four signal levels (50, 60, 70, and 80 dB SPL) and up to seven SNRs (-10, -5, 0, 5, 15, 25, and 35 dB). These data were compared between groups to reveal the hearing impairment effect and then combined with previously published data for 15 young normal-hearing individuals to determine the aging effect. Results: Robust effects of SNR were found for perception and CAEPs. Small but significant effects of signal level were found for perception, primarily at poor SNRs and high signal levels, and in some limited instances for CAEPs. Significant effects of age were seen for both CAEPs and perception, while hearing impairment effects were only found with perception measures. CAEPs correlate well with perception and can predict SNR50s to within 2 dB for ONH. However, prediction error is much larger for OHI and varies widely (from 6 to 12 dB) depending on the model that was used for prediction. Conclusions: When background noise is present, SNR dominates both perception-in-noise testing and cortical electrophysiological testing, with smaller and sometimes significant contributions from signal level. A mismatch between behavioral and electrophysiological results was found (hearing impairment effects were primarily only seen for behavioral data), illustrating the possible contributions of higher order cognitive processes on behavior. It is interesting that the hearing impairment effect size was more than five times larger than the aging effect size for CAEPs and perception. Sentence-level perception can be predicted well in normal-hearing individuals; however, additional research is needed to explore improved prediction methods for older individuals with hearing impairment. C1 [Billings, Curtis J.; Penman, Tina M.; McMillan, Garnett P.; Ellis, Emily M.] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Billings, Curtis J.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Billings, CJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM curtis.billings2@va.gov FU National Institute on Deafness and Other Communication Disorders [R03DC10914]; United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service [C4844C, C8006W] FX This work was supported by grant R03DC10914 from the National Institute on Deafness and Other Communication Disorders and career development awards (C4844C and C8006W) from the United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service. The contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. government. NR 38 TC 8 Z9 8 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD NOV-DEC PY 2015 VL 36 IS 6 BP 710 EP 722 DI 10.1097/AUD.0000000000000191 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA CV6VW UT WOS:000364410900009 PM 26502191 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI Searching for answers! SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE Empyema; Pleural infection; Lung C1 [Mathisen, Douglas J.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 1 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 1010-7940 EI 1873-734X J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD NOV PY 2015 VL 48 IS 5 BP 653 EP 654 DI 10.1093/ejcts/ezv290 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CW1PG UT WOS:000364762900005 PM 26345983 ER PT J AU Danis, E Yamauchi, T Echanique, K Haladyna, J Kalkur, R Riedel, S Zhu, N Xie, HF Bernt, KM Orkin, SH Armstrong, SA Neff, T AF Danis, Etienne Yamauchi, Taylor Echanique, Kristen Haladyna, Jessica Kalkur, Roshni Riedel, Simone Zhu, Nan Xie, Huafeng Bernt, Kathrin M. Orkin, Stuart H. Armstrong, Scott A. Neff, Tobias TI Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; METHYLTRANSFERASE GENE EZH2; ACUTE MYELOID-LEUKEMIA; REPRESSIVE COMPLEX 2; HEMATOPOIETIC STEM; CELL; PROGENITOR; DISORDERS; MUTATIONS; MLL-AF9 AB Polycomb repressive complex 2 (PRC2) is a chromatin regulator with central roles in development and cancer. The canonical function of PRC2 is the trimethylation of histone 3 on lysine residue 27. This epigenetic modification is associated with gene silencing. Both tumor suppressor and oncogenic functions have been reported for PRC2, depending on cellular context. In leukemia mediated by the leukemogenic fusion MLL-AF9, complete ablation of canonical PRC2 function by genetic inactivation of the core component embryonic ectoderm development (Eed) or by combined pharmacologic inhibition of the PRC2 methyltransferases EZH2 and EZH1 has a strong anti-leukemic effect, and this effect has been linked to derepression of the PRC2 target locus Cdkn2a. We asked whether inactivation of Cdkn2a is sufficient to restore leukemic activity of Eed-inactivated MLL-AF9 leukemia cells, using combined genetic inactivation of Cdkn2a and Eed. We found that Cdkn2a inactivation partially rescues in vitro and in vivo growth of Eed-inactivated MLL-AF9 cells. However, the growth of Eed-null Cdkn2a-null MLL-AF9 cells in the absence of Cdkn2a remained severely compromised in vitro and in vivo, compared with that of their Eed-floxed Cdkn2a-null counterparts. RNA sequencing analysis revealed that several genes previously implicated in inefficient growth of MLL-AF9-transformed cells, including Gata2, Egr1, and Cdkn2b were de-repressed as a consequence of Eed inactivation. Furthermore, we found that direct binding targets of MLL fusion proteins are negatively enriched in Eed-inactivated Cdkn2a-null MLL-AF9-transformed cells. Our data indicate that interference with PRC2 function affects MLL-AF9-mediated leukemogenesis by both Cdkn2a-dependent and Cdkn2a-independent mechanisms. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Danis, Etienne; Yamauchi, Taylor; Echanique, Kristen; Haladyna, Jessica; Kalkur, Roshni; Riedel, Simone; Bernt, Kathrin M.; Neff, Tobias] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO USA. [Danis, Etienne; Yamauchi, Taylor; Echanique, Kristen; Haladyna, Jessica; Kalkur, Roshni; Riedel, Simone; Bernt, Kathrin M.; Neff, Tobias] Univ Colorado Denver, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Dept Pediat, Aurora, CO 80045 USA. [Zhu, Nan; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Zuckerman Res Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Zhu, Nan; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA. [Zhu, Nan; Armstrong, Scott A.] Zuckerman Res Ctr, New York, NY USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Xie, Huafeng; Orkin, Stuart H.] Boston Childrens Hosp, Boston, MA USA. [Xie, Huafeng; Orkin, Stuart H.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Xie, Huafeng; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Neff, T (reprint author), Univ Colorado Denver, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Ctr Canc & Blood Disorders, Childrens Hosp Colorado,Dept Pediat, Anschutz Med Campus,Res Complex 1,North Tower, Aurora, CO 80045 USA. EM Tobias.Neff@ucdenver.edu RI Bernt, Kathrin/L-1826-2016; OI Bernt, Kathrin/0000-0002-5400-0482; Neff, Tobias/0000-0002-0188-8393 FU Children's Hospital Colorado Research Institute, Aurora, CO; National Heart, Lung, and Blood Institute, Bethesda, MD [K08HL102264]; NCI [K08CA154777]; National Cancer Institute, Bethesda, MD [P30CA046934]; Cancer League Colorado, Englewood, CO FX This work was supported by startup funds from Children's Hospital Colorado Research Institute, Aurora, CO (Tobias Neff), as well as National Heart, Lung, and Blood Institute, Bethesda, MD K08HL102264 (Kathrin Maria Bernt), NCI K08CA154777 (Tobias Neff), National Cancer Institute, Bethesda, MD P30CA046934 (Shared Resource of the University of Colorado Cancer Center) and the Cancer League Colorado, Englewood, CO (Tobias Neff). NR 24 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2015 VL 43 IS 11 BP 930 EP 935 DI 10.1016/j.exphem.2015.06.005 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA CV9OV UT WOS:000364617400002 PM 26118502 ER PT J AU Blackwell, TK Steinbaugh, MJ Hourihan, JM Ewald, CY Isik, M AF Blackwell, T. Keith Steinbaugh, Michael J. Hourihan, John M. Ewald, Collin Y. Isik, Meltem TI SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Aging; C. elegans; Detoxification; Metabolism; Proteasome; SKN-1/Nrf; Stress response ID LIFE-SPAN EXTENSION; RESTRICTION-INDUCED LONGEVITY; ENDOPLASMIC-RETICULUM STRESS; GLYCOGEN-SYNTHASE KINASE-3; UNFOLDED PROTEIN RESPONSE; BZIP TRANSCRIPTION FACTOR; DNA-BINDING DOMAIN; OXIDATIVE STRESS; C-ELEGANS; DIETARY-RESTRICTION AB The mammalian Nrf/CNC proteins (Nrf1, Nrf2, Nrf3, p45 NF-E2) perform a wide range of cellular protective and maintenance functions. The most thoroughly described of these proteins, Nrf2, is best known as a regulator of antioxidant and xenobiotic defense, but more recently has been implicated in additional functions that include proteostasis and metabolic regulation. In the nematode Caenorhabditis elegans, which offers many advantages for genetic analyses, the Nrf/CNC proteins are represented by their ortholog SKN-1. Although SKN-1 has diverged in aspects of how it binds DNA, it exhibits remarkable functional conservation with Nrf/CNC proteins in other species and regulates many of the same target gene families. C. elegans may therefore have considerable predictive value as a discovery model for understanding how mammalian Nrf/CNC proteins function and are regulated in vivo. Work in C elegans indicates that SKN-1 regulation is surprisingly complex and is influenced by numerous growth, nutrient, and metabolic signals. SKN-1 is also involved in a wide range of homeostatic functions that extend well beyond the canonical Nrf2 function in responses to acute stress. Importantly, SKN-1 plays a central role in diverse genetic and pharmacologic interventions that promote C. elegans longevity, suggesting that mechanisms regulated by SKN-1 may be of conserved importance in aging. These C. elegans studies predict that mammalian Nrf/CNC protein functions and regulation may be similarly complex and that the proteins and processes that they regulate are likely to have a major influence on mammalian life- and healthspan. C1 [Blackwell, T. Keith; Steinbaugh, Michael J.; Hourihan, John M.; Ewald, Collin Y.; Isik, Meltem] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Blackwell, T. Keith; Steinbaugh, Michael J.; Hourihan, John M.; Ewald, Collin Y.; Isik, Meltem] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Blackwell, T. Keith; Steinbaugh, Michael J.; Hourihan, John M.; Ewald, Collin Y.; Isik, Meltem] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu OI Steinbaugh, Michael/0000-0002-2403-2221; Ewald, Collin/0000-0003-1166-4171 FU NIH [R01GM062891, R01GM094398, R21AG043949]; MJS [T32DK007260]; Swiss National Science [P300P3_154633]; AFAR fellowship; Diabetes Research Center [P30DK036836] FX The work was supported by funding from the NIH to TKB (R01GM062891, R01GM094398, and R21AG043949) and MJS (T32DK007260), Swiss National Science funding to CYE (P300P3_154633), an AFAR fellowship to MI, and a Diabetes Research Center award to the Joslin Diabetes Center (P30DK036836). NR 158 TC 21 Z9 22 U1 5 U2 22 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 2015 VL 88 BP 290 EP 301 DI 10.1016/j.freeradbiomed.2015.06.008 PN B PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CV0TN UT WOS:000363966300019 PM 26232625 ER PT J AU Beach, SR Walker, J Celano, CM Mastromauro, CA Sharpe, M Huffman, JC AF Beach, Scott R. Walker, Jane Celano, Christopher M. Mastromauro, Carol A. Sharpe, Michael Huffman, Jeff C. TI Implementing collaborative care programs for psychiatric disorders in medical settings: a practical guide SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Collaborative care; Depression; Integrated care; Population health; Psychosomatic medicine ID RANDOMIZED-CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; MAJOR DEPRESSIVE DISORDER; MANAGEMENT RESEARCH TRIAL; ANXIETY DISORDERS; COMPLEX INTERVENTION; OUTCOMES; CANCER; IMPACT; METAANALYSIS AB Objective: Collaborative care is a systematic, team-based approach to the management of depression and other psychiatric disorders in medical settings. Collaborative care has been found to be effective and cost-effective, but there is little information to guide its implementation in clinical care. The objective of this article is to provide a practical guide to the implementation of collaborative care programs in real-world settings. Methods: Based on our experience delivering collaborative care programs, we provide (a) specific, stepwise recommendations for the successful implementation of collaborative care in outpatient settings and (b) an examination of the additional benefits and challenges of collaborative care programs that begin during hospitalization. Results: The implementation of collaborative care requires senior buy-in, an effective team, clear treatment components, engaged clinicians, procedures to ensure quality and adequate infrastructure. Beginning these programs with hospitalized patients may offer additional advantages but also requires additional flexibility to adapt to the inpatient setting. Conclusion: A systematic approach to the development and implementation of collaborative care programs may allow clinicians to effectively and efficiently treat psychiatric illness in medical populations in both inpatient and outpatient settings. (c) 2015 Elsevier Inc. All rights reserved. C1 [Beach, Scott R.; Celano, Christopher M.; Mastromauro, Carol A.; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Beach, Scott R.; Celano, Christopher M.; Huffman, Jeff C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Walker, Jane; Sharpe, Michael] Univ Oxford, Dept Psychiat, Psychol Med Res, Oxford OX1 2JD, England. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Blake 11, Boston, MA 02114 USA. EM jhuffman@partners.org FU UK National institute for Health Research Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford NHS Foundation Trust; NIH [R01HL113272]; Cancer Research UK; American Heart Association [10GRNT3450015, 0735530T] FX JW is supported by the UK National institute for Health Research Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford NHS Foundation Trust (the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health). JH time for manuscript conception and editing was supported by NIH grant R01HL113272 (the views expressed are not necessarily those of the NIH or NHLBI). The SMaRT oncology trials 1, 2 and 3 were funded by Cancer Research UK. SUCCEED and MOSAIC studies were funded by American Heart Association grants 10GRNT3450015 and 0735530T. NR 55 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2015 VL 37 IS 6 BP 522 EP 527 DI 10.1016/j.genhosppsych.2015.06.015 PG 6 WC Psychiatry SC Psychiatry GA CV8AK UT WOS:000364498700005 PM 26190822 ER PT J AU Petrik, ML Gutierrez, PM Berlin, JS Saunders, SM AF Petrik, Megan L. Gutierrez, Peter M. Berlin, Jon S. Saunders, Stephen M. TI Barriers and facilitators of suicide risk assessment in emergency departments: a qualitative study of provider perspectives SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Suicide; Suicide risk assessment; Emergency department; Qualitative methods; Health care providers ID SELF-INFLICTED INJURY; HEALTH-CARE; IDEATION; HARM; INSTRUMENT; PREVENTION; MANAGEMENT; MORTALITY; ATTITUDES; ACCIDENT AB Objective: To understand emergency department (ED) providers' perspectives regarding the barriers and facilitators of suicide risk assessment and to use these perspectives to inform recommendations for best practices in ED suicide risk assessment. Methods: Ninety-two ED providers from two hospital systems in a Midwestern state responded to open-ended questions via an online survey that assessed their perspectives on the barriers and facilitators to assess suicide risk as well as their preferred assessment methods. Responses were analyzed using an inductive thematic analysis approach. Results: Qualitative analysis yielded six themes that impact suicide risk assessment. Time, privacy, collaboration and consultation with other professionals and integration of a standard screening protocol in routine care exemplified environmental and systemic themes. Patient engagement/participation in assessment and providers' approach to communicating with patients and other providers also impacted the effectiveness of suicide risk assessment efforts. Conclusion: The findings inform feasible suicide risk assessment practices in EDs. Appropriately utilizing a collaborative, multidisciplinary approach to assess suicide-related concerns appears to be a promising approach to ameliorate the burden placed on ED providers and facilitate optimal patient care. Recommendations for clinical care, education, quality improvement and research are offered. Published by Elsevier Inc. C1 [Petrik, Megan L.; Gutierrez, Peter M.] Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Ctr, Denver, CO 80220 USA. [Petrik, Megan L.; Gutierrez, Peter M.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. [Berlin, Jon S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Saunders, Stephen M.] Marquette Univ, Dept Psychol, Milwaukee, WI 53233 USA. RP Petrik, ML (reprint author), Denver VA Med Ctr, Rocky Mt Mental Illness Res Educ & Clin Ctr, Denver, CO 80220 USA. FU Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs FX The authors thank Stephen Hargarten, M.D., M.P.H., and Ed de St. Aubin, Ph.D., for consultation throughout the study as well as Renae Delucia and Brett Adams for their assistance in qualitative analysis. A portion of the writing of this manuscript was supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs. NR 37 TC 3 Z9 3 U1 0 U2 4 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 2015 VL 37 IS 6 BP 581 EP 586 DI 10.1016/j.genhosppsych.2015.06.018 PG 6 WC Psychiatry SC Psychiatry GA CV8AK UT WOS:000364498700015 PM 26208868 ER PT J AU Elvers, I Turner-Maier, J Swofford, R Koltookian, M Johnson, J Stewart, C Zhang, CZ Schumacher, SE Beroukhim, R Rosenberg, M Thomas, R Mauceli, E Getz, G Di Palma, F Modiano, JF Breen, M Lindblad-Toh, K Alfoldi, J AF Elvers, Ingegerd Turner-Maier, Jason Swofford, Ross Koltookian, Michele Johnson, Jeremy Stewart, Chip Zhang, Cheng-Zhong Schumacher, Steven E. Beroukhim, Rameen Rosenberg, Mara Thomas, Rachael Mauceli, Evan Getz, Gad Di Palma, Federica Modiano, Jaime F. Breen, Matthew Lindblad-Toh, Kerstin Alfoeldi, Jessica TI Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background SO GENOME RESEARCH LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKIN-LYMPHOMA; NF-KAPPA-B; TUMOR-SUPPRESSOR; COMPULSIVE DISORDER; KINASE INHIBITOR; CANINE LYMPHOMA; GERMINAL-CENTER; HUMAN CANCERS; GENOME AB Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T-cell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B- and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive, and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options. C1 [Elvers, Ingegerd; Turner-Maier, Jason; Swofford, Ross; Koltookian, Michele; Johnson, Jeremy; Stewart, Chip; Zhang, Cheng-Zhong; Schumacher, Steven E.; Beroukhim, Rameen; Rosenberg, Mara; Mauceli, Evan; Getz, Gad; Di Palma, Federica; Lindblad-Toh, Kerstin; Alfoeldi, Jessica] Broad Inst, Cambridge, MA 02142 USA. [Elvers, Ingegerd; Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, SE-75123 Uppsala, Sweden. [Zhang, Cheng-Zhong; Schumacher, Steven E.; Beroukhim, Rameen] Dana Farber Canc Inst, Boston, MA 02215 USA. [Thomas, Rachael; Breen, Matthew] N Carolina State Univ, Raleigh, NC 27695 USA. [Getz, Gad] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Modiano, Jaime F.] Univ Minnesota, Coll Vet Med, Anim Canc Care & Res Program, Minneapolis, MN 55455 USA. [Modiano, Jaime F.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Breen, Matthew] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA. RP Elvers, I (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM ielvers@broadinstitute.org; kersli@broadinstitute.org OI Modiano, Jaime/0000-0001-6398-7648 FU National Institutes of Health [U54 HG003067-08]; European Research Council (ERC); American Kennel Club (AKC) Canine Health Foundation; Golden Retriever Foundation; Morris Animal Foundation; Swedish Medical Research Council; ESF; ERC FX We thank all dogs and their owners for their help and support, Leslie Gaffney for help with illustrations, the Broad Institute Genomics platform for sequencing, and the Breen laboratory and Dr. Daisuke Ito for immunophenotyping. Funding is gratefully acknowledged from the National Institutes of Health (U54 HG003067-08, awarded to the Broad Institute), the European Research Council (ERC), the American Kennel Club (AKC) Canine Health Foundation, the Golden Retriever Foundation, and the Morris Animal Foundation. I.E. is supported by a postdoctoral fellowship from the Swedish Medical Research Council. K.L.-T. is the recipient of a EURYI award from the ESF and an ERC Consolidator Award from the ERC. J.F.M. is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota. NR 90 TC 3 Z9 3 U1 2 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2015 VL 25 IS 11 BP 1634 EP 1645 DI 10.1101/gr.194449.115 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CV6BL UT WOS:000364355600005 PM 26377837 ER PT J AU Brooks, AN Duff, MO May, G Yang, L Bolisetty, M Landolin, J Wan, K Sandler, J Booth, BW Celniker, SE Graveley, BR Brenner, SE AF Brooks, Angela N. Duff, Michael O. May, Gemma Yang, Li Bolisetty, Mohan Landolin, Jane Wan, Ken Sandler, Jeremy Booth, Benjamin W. Celniker, Susan E. Graveley, Brenton R. Brenner, Steven E. TI Regulation of alternative splicing in Drosophila by 56 RNA binding proteins SO GENOME RESEARCH LA English DT Article ID EXON JUNCTION COMPLEX; GENOME-WIDE ANALYSIS; SEQ DATA; GENE; REVEALS; MELANOGASTER; TRANSLATION; NETWORK; MAP; TRANSCRIPTS AB Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs. C1 [Brooks, Angela N.; Brenner, Steven E.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. [Brooks, Angela N.] Broad Inst, Cambridge, MA 02142 USA. [Brooks, Angela N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Duff, Michael O.; May, Gemma; Yang, Li; Bolisetty, Mohan; Graveley, Brenton R.] Univ Connecticut, Ctr Hlth, Inst Syst Genom, Dept Genet & Genome Sci, Farmington, CT 06030 USA. [Landolin, Jane; Wan, Ken; Sandler, Jeremy; Booth, Benjamin W.; Celniker, Susan E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Genome Dynam, Berkeley, CA 94720 USA. [Brenner, Steven E.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. RP Graveley, BR (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. EM graveley@uchc.edu; brenner@compbio.berkeley.edu RI Brenner, Steven/A-8729-2008; OI Brenner, Steven/0000-0001-7559-6185; Graveley, Brenton/0000-0001-5777-5892 FU National Science Foundation Graduate Research Fellowship; Damon Runyon Cancer Research Foundation [DRG-2138-12]; National Human Genome Research Institute modENCODE Project under Department of Energy [U01 HG004271, DE-AC02-05CH11231] FX We thank Kasper Hansen and Sandrine Dudoit for helpful suggestions in the early design of this work; J.B. Brown for useful conversations regarding the CAGE data; and Courtney French, Nils Gehlenborg, and members of the modENCODE Drosophila Transcriptome Group for helpful suggestions. A.N.B. was supported by a National Science Foundation Graduate Research Fellowship and was a Merck Fellow of the Damon Runyon Cancer Research Foundation (DRG-2138-12). This work was funded by an award from the National Human Genome Research Institute modENCODE Project (U01 HG004271) to S.E.C. (Principal Investigator) and B.R.G. (Coprincipal Investigator) under Department of Energy contract no. DE-AC02-05CH11231. NR 58 TC 5 Z9 5 U1 2 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2015 VL 25 IS 11 BP 1771 EP 1780 DI 10.1101/gr.192518.115 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA CV6BL UT WOS:000364355600017 PM 26294686 ER PT J AU Klein, E Brown, T Sample, M Truitt, AR Goering, S AF Klein, Eran Brown, Tim Sample, Matthew Truitt, Anjali R. Goering, Sara TI Engineering the Brain: Ethical Issues and the Introduction of Neural Devices SO HASTINGS CENTER REPORT LA English DT Article ID MIND; STIMULATION; EMBODIMENT; DISABILITY; PAIN AB Neural engineering technologies such as implanted deep brain stimulators and brain-computer interfaces represent exciting and potentially transformative tools for improving human health and well-being. Yet their current use and future prospects raise a variety of ethical and philosophical concerns. Devices that alter brain function invite us to think deeply about a range of ethical concernsidentity, normality, authority, responsibility, privacy, and justice. If a device is stimulating my brain while I decide upon an action, am I still the author of the action? Does a device make the interiority of my experience accessible to others? Will the device change the way I think of myself and others think of me? Such fundamental questions arise even when a device is designed for only a relatively circumscribed purpose, such as restoring functioning via a smart prosthetic.We are part of a National Science Foundation-funded Engineering Research Center tasked with investigating philosophical and social implications of neural engineering research and technologies. Neural devices already in clinical use, such as deep brain stimulators for Parkinson's disease or essential tremor, have spurred healthy debate about such implications. Devices currently under developmentsuch as the BrainGate System of implanted brain sensors coupled to robotics in persons with paralysis, exoskeletons for augmented movement, transcranial do-it-yourself stimulators, closed-loop brain stimulating systems, or even brain-to-brain interfacingpromise to extend and deepen these debates. At our center, brain-computer interfaces are the principal focus of work. Even acknowledging that the clinical translation of neural devices and seamless integration by end users may still largely reside in the future, the potential these devices hold calls for careful early analysis. The launching of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative in April 2013 provides further impetus for this work. C1 [Klein, Eran; Brown, Tim; Sample, Matthew; Goering, Sara] Univ Washington, Philosophy, Seattle, WA 98195 USA. [Klein, Eran] Univ Washington, Ctr Sensorimotor Neural Engn, Seattle, WA 98195 USA. [Klein, Eran] Portland VA Med Ctr, Portland, OR USA. [Brown, Tim; Sample, Matthew] Ctr Sensorimotor Neural Engn, Seattle, WA USA. [Truitt, Anjali R.] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA. [Goering, Sara] Ctr Sensorimotor Neural Engn, Eth Thrust, Seattle, WA USA. RP Klein, E (reprint author), Univ Washington, Philosophy, Seattle, WA 98195 USA. OI Sample, Matthew/0000-0001-5290-1458; Truitt, Anjali/0000-0003-1509-0072 FU National Science Foundation [EEC-1028725] FX This work was supported by a grant from the National Science Foundation (award # EEC-1028725). The views are those of the authors and do not necessarily reflect those of the NSF. NR 57 TC 3 Z9 3 U1 6 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 EI 1552-146X J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD NOV-DEC PY 2015 VL 45 IS 6 BP 26 EP 35 DI 10.1002/hast.515 PG 10 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA CW1YD UT WOS:000364787000012 PM 26556144 ER PT J AU Mueller, S Wang, DH Fox, MD Pan, RQ Lu, J Li, KC Sun, W Buckner, RL Liu, HS AF Mueller, Sophia Wang, Danhong Fox, Michael D. Pan, Ruiqi Lu, Jie Li, Kuncheng Sun, Wei Buckner, Randy L. Liu, Hesheng TI Reliability correction for functional connectivity: Theory and implementation SO HUMAN BRAIN MAPPING LA English DT Article DE attenuation correction; default network; functional connectivity MRI; medial temporal lobe; reliability ID DEFAULT-MODE NETWORK; INDEPENDENT COMPONENT ANALYSIS; MONKEY RETROSPLENIAL CORTEX; RESTING-STATE CONNECTIVITY; SURFACE-BASED ANALYSIS; HUMAN BRAIN; MACAQUE MONKEY; ALZHEIMERS-DISEASE; MOTION ARTIFACT; BOLD SIGNAL AB Network properties can be estimated using functional connectivity MRI (fcMRI). However, regional variation of the fMRI signal causes systematic biases in network estimates including correlation attenuation in regions of low measurement reliability. Here we computed the spatial distribution of fcMRI reliability using longitudinal fcMRI datasets and demonstrated how pre-estimated reliability maps can correct for correlation attenuation. As a test case of reliability-based attenuation correction we estimated properties of the default network, where reliability was significantly lower than average in the medial temporal lobe and higher in the posterior medial cortex, heterogeneity that impacts estimation of the network. Accounting for this bias using attenuation correction revealed that the medial temporal lobe's contribution to the default network is typically underestimated. To render this approach useful to a greater number of datasets, we demonstrate that test-retest reliability maps derived from repeated runs within a single scanning session can be used as a surrogate for multi-session reliability mapping. Using data segments with different scan lengths between 1 and 30 min, we found that test-retest reliability of connectivity estimates increases with scan length while the spatial distribution of reliability is relatively stable even at short scan lengths. Finally, analyses of tertiary data revealed that reliability distribution is influenced by age, neuropsychiatric status and scanner type, suggesting that reliability correction may be especially important when studying between-group differences. Collectively, these results illustrate that reliability-based attenuation correction is an easily implemented strategy that mitigates certain features of fMRI signal nonuniformity. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Mueller, Sophia; Wang, Danhong; Fox, Michael D.; Pan, Ruiqi; Buckner, Randy L.; Liu, Hesheng] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Mueller, Sophia; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Mueller, Sophia; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Mueller, Sophia] Univ Munich, Inst Clin Radiol, Munich, Germany. [Fox, Michael D.] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol, Boston, MA 02215 USA. [Fox, Michael D.] Harvard Univ, Sch Med, Boston, MA USA. [Fox, Michael D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Pan, Ruiqi; Lu, Jie; Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China. [Sun, Wei] Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 100053, Peoples R China. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Liu, HS (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Suite 2301,149 13th St, Charlestown, MA 02129 USA. EM bmusunnyw@outlook.com; Hesheng@nmr.mgh.harvard.edu FU German Research Foundation [MU 3222/2-1]; NIH [1K25NS069805, R01NS091604, P50MH106435, K23NS083741]; NARSAD Young Investigator Grant; AAN/American Brain Foundation FX Contract grant sponsor: German Research Foundation (to S.M.); Contract grant number: MU 3222/2-1; Contract grant sponsor: NIH (to H.L.); Contract grant numbers: 1K25NS069805, R01NS091604, and P50MH106435; Contract grant sponsor: NARSAD Young Investigator Grant; Contract grant sponsor: NIH (to M.D.F.); Contract grant number: K23NS083741; Contract grant sponsor: AAN/American Brain Foundation. NR 86 TC 7 Z9 8 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2015 VL 36 IS 11 BP 4664 EP 4680 DI 10.1002/hbm.22947 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CV4EQ UT WOS:000364219500031 PM 26493163 ER PT J AU Barnett, ML Hsu, J McWilliams, JM AF Barnett, Michael L. Hsu, John McWilliams, J. Michael TI Patient Characteristics and Differences in Hospital Readmission Rates SO JAMA INTERNAL MEDICINE LA English DT Article ID ADMINISTRATIVE CLAIMS MEASURE; MEDICARE BENEFICIARIES; RISK; CARE; PERFORMANCE; MORTALITY; PROGRAM; MODELS AB IMPORTANCE Medicare penalizes hospitals with higher than expected readmission rates by up to 3% of annual inpatient payments. Expected rates are adjusted only for patients' age, sex, discharge diagnosis, and recent diagnoses. OBJECTIVE To assess the extent to which a comprehensive set of patient characteristics accounts for differences in hospital readmission rates. DESIGN, SETTING, AND PARTICIPANTS Using survey data from the nationally representative Health and Retirement Study (HRS) and linked Medicare claims for HRS participants enrolled in Medicare who were hospitalized from 2009 to 2012 (n = 8067 admissions), we assessed 29 patient characteristics from survey data and claims as potential predictors of 30-day readmission when added to standard Medicare adjustments of hospital readmission rates. We then compared the distribution of these characteristics between participants admitted to hospitals with higher vs lower hospital-wide readmission rates reported by Medicare. Finally, we estimated differences in the probability of readmission between these groups of participants before vs after adjusting for the additional patient characteristics. MAIN OUTCOMES AND MEASURES All-cause readmission within 30 days of discharge. RESULTS Of the additional 29 patient characteristics assessed, 22 significantly predicted readmission beyond standard adjustments, and 17 of these were distributed differently between hospitals in the highest vs lowest quintiles of publicly reported hospital-wide readmission rates (P <= .04 for all comparisons). Almost all of these differences (16 of 17) indicated that participants admitted to hospitals in the highest quintile of readmission rates were more likely to have characteristics that were associated with a higher probability of readmission. The difference in the probability of readmission between participants admitted to hospitals in the highest vs lowest quintile of hospital-wide readmission rates was reduced by 48% from 4.41 percentage points with standard adjustments used by Medicare to 2.29 percentage points after adjustment for all patient characteristics assessed (reduction in difference: -2.12; 95% CI, -3.33 to -0.67; P = .003). CONCLUSIONS AND RELEVANCE Patient characteristics not included in Medicare's current risk-adjustment methods explained much of the difference in readmission risk between patients admitted to hospitals with higher vs lower readmission rates. Hospitals with high readmission rates may be penalized to a large extent based on the patients they serve. C1 [Barnett, Michael L.; Hsu, John; McWilliams, J. Michael] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Barnett, Michael L.; McWilliams, J. Michael] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Care Policy, Boston, MA 02114 USA. RP McWilliams, JM (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM mcwilliams@hcp.med.harvard.edu FU National Institute on Aging [P01 AG032952]; Health Resources and Services Administration (HRSA) [T32-HP10251] FX This study was supported by grants from the National Institute on Aging (P01 AG032952) and Health Resources and Services Administration (HRSA) (T32-HP10251). NR 39 TC 36 Z9 36 U1 3 U2 15 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 2015 VL 175 IS 11 BP 1803 EP 1812 DI 10.1001/jamainternmed.2015.4660 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CV7BO UT WOS:000364427200016 PM 26368317 ER PT J AU Lehman, CD Wellman, RD Buist, DSM Kerlikowske, K Tosteson, ANA Miglioretti, DL AF Lehman, Constance D. Wellman, Robert D. Buist, Diana S. M. Kerlikowske, Karla Tosteson, Anna N. A. Miglioretti, Diana L. CA Breast Canc Surveillance TI Diagnostic Accuracy of Digital Screening Mammography With and Without Computer-Aided Detection SO JAMA Internal Medicine LA English DT Article ID BREAST-CANCER DIAGNOSIS; ASSISTED DETECTION; DETECTION SYSTEMS; RECALL RATES; PERFORMANCE; IMPACT; POPULATION; PROGRAM AB IMPORTANCE After the US Food and Drug Administration (FDA) approved computer-aided detection (CAD) for mammography in 1998, and the Centers for Medicare and Medicaid Services (CMS) provided increased payment in 2002, CAD technology disseminated rapidly. Despite sparse evidence that CAD improves accuracy of mammographic interpretations and costs over $400 million a year, CAD is currently used for most screening mammograms in the United States. OBJECTIVE To measure performance of digital screening mammography with and without CAD in US community practice. DESIGN, SETTING, AND PARTICIPANTS We compared the accuracy of digital screening mammography interpreted with (n = 495 818) vs without (n = 129 807) CAD from 2003 through 2009 in 323 973 women. Mammograms were interpreted by 271 radiologists from 66 facilities in the Breast Cancer Surveillance Consortium. Linkage with tumor registries identified 3159 breast cancers in 323 973 women within 1 year of the screening. MAIN OUTCOMES AND MEASURES Mammography performance (sensitivity, specificity, and screen-detected and interval cancers per 1000 women) was modeled using logistic regression with radiologist-specific random effects to account for correlation among examinations interpreted by the same radiologist, adjusting for patient age, race/ethnicity, time since prior mammogram, examination year, and registry. Conditional logistic regression was used to compare performance among 107 radiologists who interpreted mammograms both with and without CAD. RESULTS Screening performance was not improved with CAD on anymetric assessed. Mammography sensitivity was 85.3% (95% CI, 83.6%-86.9%) with and 87.3% (95% CI, 84.5%-89.7%) without CAD. Specificity was 91.6% (95% CI, 91.0%-92.2%) with and 91.4% (95% CI, 90.6%-92.0%) without CAD. There was no difference in cancer detection rate (4.1 in 1000 women screened with and without CAD). Computer-aided detection did not improve intraradiologist performance. Sensitivity was significantly decreased for mammograms interpreted with vs without CAD in the subset of radiologists who interpreted both with and without CAD (odds ratio, 0.53; 95% CI, 0.29-0.97). CONCLUSIONS AND RELEVANCE Computer-aided detection does not improve diagnostic accuracy of mammography. These results suggest that insurers pay more for CAD with no established benefit to women. C1 [Lehman, Constance D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wellman, Robert D.; Buist, Diana S. M.; Miglioretti, Diana L.] Grp Hlth Res Inst, Seattle, WA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tosteson, Anna N. A.] Dartmouth Coll, Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Miglioretti, Diana L.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. RP Lehman, CD (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Dept Radiol, 55 Fruit St,WAC 240, Boston, MA 02114 USA. EM clehman@mgh.harvard.edu FU National Cancer Institute (NCI) [PO1CA154292]; NCI [HHSN261201100031C, P01CA154292]; PROSPR [U54CA163303]; several state public health departments and cancer registries throughout the United States FX This original research was supported by the National Cancer Institute (NCI) (PO1CA154292). Data collection was further supported by the NCI-funded Breast Cancer Surveillance Consortium (BCSC) (HHSN261201100031C, P01CA154292), and PROSPR U54CA163303. The collection of cancer and vital status data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see the NCI website, BCSC Cancer Registry Acknowledgement: http://breastscreening.cancer.gov/work/acknowledgement.html. NR 41 TC 8 Z9 8 U1 4 U2 12 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 2015 VL 175 IS 11 BP 1828 EP 1837 DI 10.1001/jamainternmed.2015.5231 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CV7BO UT WOS:000364427200020 PM 26414882 ER PT J AU Elmariah, SB AF Elmariah, Sarina B. TI Careful Considerations Concerning Psychogenic Itch SO JAMA Internal Medicine LA English DT Letter ID CHRONIC PRURITUS C1 [Elmariah, Sarina B.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Elmariah, SB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, 149 Thirteenth St, Charlestown, MA 02129 USA. EM sbelmariah@mgh.harvard.edu NR 5 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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD NOV PY 2015 VL 175 IS 11 BP 1861 EP 1861 DI 10.1001/jamainternmed.2015.4677 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CV7BO UT WOS:000364427200033 PM 26524738 ER PT J AU Swenson, ER AF Swenson, Erik R. TI The True Environmental Cost of Chlorofluorocarbon-Based Inhalers SO JAMA Internal Medicine LA English DT Letter ID BAN C1 [Swenson, Erik R.] Univ Washington, VA Puget Sound Hlth Care Syst, Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu NR 3 TC 0 Z9 0 U1 1 U2 1 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 2015 VL 175 IS 11 BP 1867 EP 1867 DI 10.1001/jamainternmed.2015.5237 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CV7BO UT WOS:000364427200044 PM 26524749 ER PT J AU Reddy, A Werner, R AF Reddy, Ashok Werner, Rachel TI US Department of Veterans Affairs Primary Care Provider Turnover and Patient Satisfaction Reply SO JAMA Internal Medicine LA English DT Letter C1 [Reddy, Ashok] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Reddy, Ashok] Univ Washington, Med Ctr Scholarship Patient Care Qual & Safety, Seattle, WA 98195 USA. [Werner, Rachel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Werner, Rachel] Philadelphia VA Med Ctr, VISN Ctr Evaluat PACT 4, Philadelphia, PA USA. RP Reddy, A (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,Ste BB1240,POB 356526, Seattle, WA 98195 USA. EM reddya@uw.edu NR 2 TC 0 Z9 0 U1 1 U2 1 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 2015 VL 175 IS 11 BP 1870 EP 1871 DI 10.1001/jamainternmed.2015.5411 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CV7BO UT WOS:000364427200049 PM 26524754 ER PT J AU Greenzang, KA Kesselheim, JC AF Greenzang, Katie A. Kesselheim, Jennifer C. TI Responsibility for Patient Care in Graduate Medical Education Yours, Mine, or Ours? SO JAMA Pediatrics LA English DT Editorial Material ID PROFESSIONALISM C1 [Greenzang, Katie A.; Kesselheim, Jennifer C.] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Greenzang, KA (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM katie.greenzang@childrens.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD NOV PY 2015 VL 169 IS 11 BP 987 EP 988 DI 10.1001/jamapediatrics.2015.1825 PG 2 WC Pediatrics SC Pediatrics GA CV7CM UT WOS:000364430000004 PM 26390139 ER PT J AU Primack, BA Soneji, S Stoolmiller, M Fine, MJ Sargent, JD AF Primack, Brian A. Soneji, Samir Stoolmiller, Michael Fine, Michael J. Sargent, James D. TI Progression to Traditional Cigarette Smoking After Electronic Cigarette Use Among US Adolescents and Young Adults SO JAMA PEDIATRICS LA English DT Article ID TOBACCO PRODUCT USE; UNITED-STATES; FOLLOW-UP; FUTURE SMOKING; CESSATION; ASSOCIATION; SMOKERS; RISK; REDUCTION; IMPACT AB IMPORTANCE Electronic cigarettes (e-cigarettes) may help smokers reduce the use of traditional combustible cigarettes. However, adolescents and young adults who have never smoked traditional cigarettes are now using e-cigarettes, and these individuals may be at risk for subsequent progression to traditional cigarette smoking. OBJECTIVE To determine whether baseline use of e-cigarettes among nonsmoking and nonsusceptible adolescents and young adults is associated with subsequent progression along an established trajectory to traditional cigarette smoking. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, a national US sample of 694 participants aged 16 to 26 years who were never cigarette smokers and were attitudinally nonsusceptible to smoking cigarettes completed baseline surveys from October 1, 2012, to May 1, 2014, regarding smoking in 2012-2013. They were reassessed 1 year later. Analysis was conducted from July 1, 2014, to March 1, 2015. Multinomial logistic regression was used to assess the independent association between baseline e-cigarette use and cigarette smoking, controlling for sex, age, race/ethnicity, maternal educational level, sensation-seeking tendency, parental cigarette smoking, and cigarette smoking among friends. Sensitivity analyses were performed, with varying approaches to missing data and recanting. EXPOSURES Use of e-cigarettes at baseline. MAIN OUTCOMES AND MEASURES Progression to cigarette smoking, defined using 3 specific states along a trajectory: nonsusceptible nonsmokers, susceptible nonsmokers, and smokers. Individuals who could not rule out smoking in the future were defined as susceptible. RESULTS Among the 694 respondents, 374 (53.9%) were female and 531 (76.5%) were non-Hispanic white. At baseline, 16 participants (2.3%) used e-cigarettes. Over the 1-year follow-up, 11 of 16 e-cigarette users and 128 of 678 of those who had not used e-cigarettes (18.9%) progressed toward cigarette smoking. In the primary fully adjusted models, baseline e-cigarette use was independently associated with progression to smoking (adjusted odds ratio [AOR], 8.3; 95% CI, 1.2-58.6) and to susceptibility among nonsmokers (AOR, 8.5; 95% CI, 1.3-57.2). Sensitivity analyses showed consistent results in the level of significance and slightly larger magnitude of AORs. CONCLUSIONS AND RELEVANCE In this national sample of US adolescents and young adults, use of e-cigarettes at baseline was associated with progression to traditional cigarette smoking. These findings support regulations to limit sales and decrease the appeal of e-cigarettes to adolescents and young adults. C1 [Primack, Brian A.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Ctr Res Media Technol & Hlth, Pittsburgh, PA 15213 USA. [Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15261 USA. [Soneji, Samir; Sargent, James D.] Dartmouth Coll, Geisel Sch Med, Norris Cotton Canc Ctr, Hanover, NH USA. [Soneji, Samir; Sargent, James D.] Dartmouth Coll, Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Stoolmiller, Michael] Univ Oregon, Coll Educ, Oregon Social Learning Ctr, Eugene, OR 97403 USA. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ & Res Promot, Pittsburgh, PA USA. [Sargent, James D.] Dartmouth Coll, Geisel Sch Med, Dept Pediat, Hanover, NH USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, 230 McKee Pl,Ste 600, Pittsburgh, PA 15213 USA. FU National Cancer Institute [R01-CA077026, R01-CA140150, R21-CA185767]; National Center for Advancing Translational Sciences [KL2-TR001088] FX This study was supported by grant R01-CA077026 for the survey from the National Cancer Institute (Dr Sargent), grants R01-CA140150 and R21-CA185767 from the National Cancer Institute (Dr Primack), and grant KL2-TR001088 from the National Center for Advancing Translational Sciences (Dr Soneji). NR 41 TC 65 Z9 65 U1 2 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD NOV PY 2015 VL 169 IS 11 BP 1018 EP 1023 DI 10.1001/jamapediatrics.2015.1742 PG 6 WC Pediatrics SC Pediatrics GA CV7CM UT WOS:000364430000011 PM 26348249 ER PT J AU Fava, M AF Fava, Maurizio TI Implications of a Biosignature Study of the Placebo Response in Major Depressive Disorder SO JAMA Psychiatry LA English DT Editorial Material ID CLINICAL-TRIALS C1 [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Div Clin Res, MGH Res Inst, Dept Psychiat,CTNI, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM mfava@mgh.harvard.edu FU Abbott Laboratories; Adamed Co; Advanced Meeting Partners; Affectis Pharmaceuticals AG; Alkermes Inc; Amarin Pharma Inc; American Cyanamid; American Psychiatric Association; American Society of Clinical Psychopharmacology; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Avanir Pharmaceuticals; AXSOME Therapeutics; Bayer AG; Belvoir Media Group; Best Practice Project Management Inc; BioMarin Pharmaceuticals Inc; BioResearch; Biovail Corp; Boehringer Ingelheim GmbH; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon Inc; Cerecor; Clintara LLC; CME Institute/Physicians Postgraduate Press Inc; CNS Response Inc; Compellis Pharmaceuticals; Covance; Covidien; Cypress Pharmaceutical Inc; DiagnoSearch Life Sciences Ltd; Dinippon Sumitomo Pharma Co Inc; Dov Pharmaceuticals Inc; Edgemont Pharmaceuticals Inc; Eisai Inc; Eli Lilly and Co; EnVivo Pharmaceuticals Inc; ePharmaSolutions; EPIX Pharmaceuticals Inc; Euthymics Bioscience Inc; Fabre-Kramer Pharmaceuticals Inc; Forest Pharmaceuticals Inc; Forum Pharmaceuticals; Ganeden Biotech Inc; GenOmind LLC; GlaxoSmithKline; Grunenthal GmbH; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenis; Imedex LLC; Janssen Pharmaceutica; Jazz Pharmaceuticals Inc; Jed Foundation; Johnson and Johnson Pharmaceutical Research Development LLC; Knoll Pharmaceuticals Corp; Labopharm Inc; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc; MedAvante Inc; Merck Co Inc; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; MSI Methylation Sciences Inc; National Alliance for Research on Schizophrenia Depression; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; Naurex Inc; Nestle Health Sciences; Neuralstem Inc; Neuronetics Inc; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics Inc; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab LLC; Pfizer Inc; Pharmacia and Upjohn; Pharmaceutical Research Associates Inc; PharmaStar; Pharmavite LLC; PharmoRx Therapeutics; Photothera; Precision Human Biolaboratory; Prexa Pharmaceuticals Inc; PPD; Puretech Ventures; PsychoGenics; Psylin Neurosciences Inc; RCT Logic LLC; Reckitt Benckiser; Rexahn Pharmaceuticals Inc; Ridge Diagnostics Inc; Roche; Sanofi US LLC; Sepracor Inc; Servier Laboratories; Schering-Plough Corp; Shire; Solvay Pharmaceuticals Inc; Somaxon Pharmaceuticals Inc; Somerset Pharmaceuticals Inc; Stanley Medical Research Institute; Sunovion Pharmaceuticals; Supernus Pharmaceuticals Inc; Synthelabo; Takeda Pharmaceutical Co Ltd; Tal Medical Inc; Tetragenex Pharmaceuticals Inc; TransForm Pharmaceuticals Inc; Transcept Pharmaceuticals Inc; United BioSource Corp; Vanda Pharmaceuticals Inc; Wyeth-Ayerst Laboratories FX Dr Fava has received research support from, has served on the advisory board for, has served as a consultant for, and/or has been involved with speaking/publishing for Abbott Laboratories; Adamed Co; Advanced Meeting Partners; Affectis Pharmaceuticals AG; Alkermes Inc; Amarin Pharma Inc; American Cyanamid; American Psychiatric Association; American Society of Clinical Psychopharmacology; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Avanir Pharmaceuticals; AXSOME Therapeutics; Bayer AG; Belvoir Media Group; Best Practice Project Management Inc; BioMarin Pharmaceuticals Inc; BioResearch; Biovail Corp; Boehringer Ingelheim GmbH; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon Inc; Cerecor; Clintara LLC; CME Institute/Physicians Postgraduate Press Inc; CNS Response Inc; Compellis Pharmaceuticals; Covance; Covidien; Cypress Pharmaceutical Inc; DiagnoSearch Life Sciences Ltd; Dinippon Sumitomo Pharma Co Inc; Dov Pharmaceuticals Inc; Edgemont Pharmaceuticals Inc; Eisai Inc; Eli Lilly and Co; EnVivo Pharmaceuticals Inc; ePharmaSolutions; EPIX Pharmaceuticals Inc; Euthymics Bioscience Inc; Fabre-Kramer Pharmaceuticals Inc; Forest Pharmaceuticals Inc; Forum Pharmaceuticals; Ganeden Biotech Inc; GenOmind LLC; GlaxoSmithKline; Grunenthal GmbH; Harvard Clinical Research Institute; Hoffman-LaRoche; Icon Clinical Research; i3 Innovus/Ingenis; Imedex LLC; Janssen Pharmaceutica; Jazz Pharmaceuticals Inc; Jed Foundation; Johnson and Johnson Pharmaceutical Research Development LLC; Knoll Pharmaceuticals Corp; Labopharm Inc; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Lundbeck Inc; MedAvante Inc; Merck Co Inc; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; MSI Methylation Sciences Inc; National Alliance for Research on Schizophrenia Depression; National Center for Complementary and Alternative Medicine; National Institute on Drug Abuse; Naurex Inc; Nestle Health Sciences; Neuralstem Inc; Neuronetics Inc; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics Inc; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab LLC; Pfizer Inc; Pharmacia and Upjohn; Pharmaceutical Research Associates Inc; PharmaStar; Pharmavite LLC; PharmoRx Therapeutics; Photothera; Precision Human Biolaboratory; Prexa Pharmaceuticals Inc; PPD; Puretech Ventures; PsychoGenics; Psylin Neurosciences Inc; RCT Logic LLC, formerly Clinical Trials Solutions LLC; Reckitt Benckiser; Rexahn Pharmaceuticals Inc; Ridge Diagnostics Inc; Roche; Sanofi US LLC; Sepracor Inc; Servier Laboratories; Schering-Plough Corp; Shire; Solvay Pharmaceuticals Inc; Somaxon Pharmaceuticals Inc; Somerset Pharmaceuticals Inc; Stanley Medical Research Institute; Sunovion Pharmaceuticals; Supernus Pharmaceuticals Inc; Synthelabo; Takeda Pharmaceutical Co Ltd; Tal Medical Inc; Tetragenex Pharmaceuticals Inc; TransForm Pharmaceuticals Inc; Transcept Pharmaceuticals Inc; United BioSource Corp; Vanda Pharmaceuticals Inc; and Wyeth-Ayerst Laboratories. He has equity holdings in Compellis and PsyBrain Inc and royalty/other income from patents for sequential parallel comparison design licensed by Massachusetts General Hospital to Pharmaceutical Product Development LLC PPD and a patent application for a combination of ketamine plus scopolamine in major depressive disorder licensed by Massachusetts General Hospital to Biohaven. NR 7 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 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD NOV PY 2015 VL 72 IS 11 BP 1073 EP 1074 DI 10.1001/jamapsychiatry.2015.1727 PG 2 WC Psychiatry SC Psychiatry GA CV6YG UT WOS:000364417600004 PM 26421499 ER PT J AU Pecina, M Bohnert, ASB Sikora, M Avery, ET Langenecker, SA Mickey, BJ Zubieta, JK AF Pecina, Marta Bohnert, Amy S. B. Sikora, Magdalena Avery, Erich T. Langenecker, Scott A. Mickey, Brian J. Zubieta, Jon-Kar TI Association Between Placebo-Activated Neural Systems and Antidepressant Responses Neurochemistry of Placebo Effects in Major Depression SO JAMA Psychiatry LA English DT Article ID TRICYCLIC ANTIDEPRESSANT; OPIOID RECEPTORS; FUNCTIONAL NEUROANATOMY; NEUROPATHIC ALLODYNIA; PSYCHIATRIC-DISORDERS; EMOTION PERCEPTION; ANALGESIA; REWARD; PAIN; TRIALS AB IMPORTANCE High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. OBJECTIVE To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD). DESIGN, SETTING, AND PARTICIPANTS In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the mu-opioid receptor-selective radiotracer [C-11]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. MAIN OUTCOMES AND MEASURES Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of mu-opioid receptor binding. RESULTS Higher baseline mu-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced mu-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala (nucleus accumbens: r = 0.6; P < .001). Placebo-induced endogenous opioid release in these regions was associated with better antidepressant treatment response, predicting 43% of the variance in symptom improvement at the end of the antidepressant trial. CONCLUSIONS AND RELEVANCE These data demonstrate that placebo-induced activation of the mu-opioid system is implicated in the formation of placebo antidepressant effects in patients with MDD and also participate in antidepressant responses, conferring illness resiliency, during open administration. C1 [Pecina, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Mickey, Brian J.; Zubieta, Jon-Kar] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Bohnert, Amy S. B.] US Dept Vet Affairs, Ann Arbor, MI USA. [Langenecker, Scott A.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Zubieta, Jon-Kar] Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI USA. RP Zubieta, JK (reprint author), Univ Michigan, Sch Med, Dept Psychiat, 205 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM zubieta@umich.edu RI Mickey, Brian/J-1756-2014 OI Mickey, Brian/0000-0002-7847-7680 FU National Institutes of Health [R01 MH086858]; Phil F. Jenkins Foundation; Michigan Institute for Clinical & Health Research grant [CTSA UL1RR024986] FX This work was supported by National Institutes of Health grant R01 MH086858 (Dr Zubieta), the Phil F. Jenkins Foundation, and a Michigan Institute for Clinical & Health Research grant (CTSA UL1RR024986). NR 59 TC 9 Z9 10 U1 1 U2 10 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 2015 VL 72 IS 11 BP 1087 EP 1094 DI 10.1001/jamapsychiatry.2015.1335 PG 8 WC Psychiatry SC Psychiatry GA CV6YG UT WOS:000364417600007 PM 26421634 ER PT J AU Magruder, K Serpi, T Kimerling, R Kilbourne, AM Collins, JF Cypel, Y Frayne, SM Furey, J Huang, GD Gleason, T Reinhard, MJ Spiro, A Kang, H AF Magruder, Kathryn Serpi, Tracey Kimerling, Rachel Kilbourne, Amy M. Collins, Joseph F. Cypel, Yasmin Frayne, Susan M. Furey, Joan Huang, Grant D. Gleason, Theresa Reinhard, Matthew J. Spiro, Avron Kang, Han TI Prevalence of Posttraumatic Stress Disorder in Vietnam-Era Women Veterans The Health of Vietnam-Era Women's Study (HealthVIEWS) SO JAMA Psychiatry LA English DT Article ID DIAGNOSTIC INTERVIEW CIDI; MORTALITY; MILITARY; TRAUMA; PTSD; EXPOSURE; SERVICE AB IMPORTANCE Many Vietnam-era women veterans served in or near war zones and may have experienced stressful or traumatic events during their service. Although posttraumatic stress disorder (PTSD) is well studied among men who served in Vietnam, no major epidemiologic investigation of PTSD among women has been performed. OBJECTIVES To assess (1) the onset and prevalence of lifetime and current PTSD for women who served during the Vietnam era, stratified by wartime location (Vietnam, near Vietnam, or the United States), and (2) the extent to which wartime location was associated with PTSD, with adjustment for demographics, service characteristics, and wartime exposures. DESIGN, SETTING, AND PARTICIPANTS Survey of 8742 women who were active-duty military personnel in the US Armed Forces at any time from July 4, 1965, through March 28, 1973, and alive as of survey receipt as part of Department of Veterans Affairs Cooperative Study 579, HealthVIEWS. Data were obtained from mailed and telephone surveys from May 16, 2011, through August 5, 2012, and analyzed from June 26, 2013, through July 30, 2015. MAIN OUTCOMES AND MEASURES Lifetime and current PTSD as measured by the PTSD module of the Composite International Diagnostic Interview, version 3.0; onset of PTSD; and wartime experiences as measured by the Women's Wartime Exposure Scale-Revised. RESULTS Among the 4219 women (48.3%) who completed the survey and a telephone interview, the weighted prevalence (95% CI) of lifetime PTSD was 20.1% (18.3%-21.8%), 11.5%(9.1%-13.9%), and 14.1%(12.4%-15.8%) for the Vietnam, near-Vietnam, and US cohorts, respectively. The weighted prevalence (95% CI) of current PTSD was 15.9% (14.3%-17.5%), 8.1% (6.0%-10.2%), and 9.1% (7.7%-10.5%) for the 3 cohorts, respectively. Few cases of PTSD among the Vietnam or near-Vietnam cohorts were attributable to premilitary onset (weighted prevalence, 2.9%[95% CI, 2.2%-3.7%] and 2.9% [95% CI, 1.7%-4.2%], respectively). Unadjusted models for lifetime and current PTSD indicated that women who served in Vietnam were more likely to meet PTSD criteria than women who mainly served in the United States (odds ratio [OR] for lifetime PTSD, 1.53 [95% CI, 1.28-1.83]; OR for current PTSD, 1.89 [95% CI, 1.53-2.33]). When we adjusted for wartime exposures, serving in Vietnam or near Vietnam did not increase the odds of having current PTSD (adjusted ORs, 1.05 [95% CI, 0.75-1.46] and 0.77 [95% CI, 0.52-1.14], respectively). CONCLUSIONS AND RELEVANCE The prevalence of PTSD for the Vietnam cohort was higher than previously documented. Vietnam service significantly increased the odds of PTSD relative to US service; this effect appears to be associated with wartime exposures, especially sexual discrimination or harassment and job performance pressures. Results suggest long-lasting mental health effects of Vietnam-era service among women veterans. C1 [Magruder, Kathryn] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. [Magruder, Kathryn] Med Univ S Carolina, Dept Psychiat, Charleston, SC USA. [Serpi, Tracey; Collins, Joseph F.] VA Maryland Hlth Care Syst, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Kimerling, Rachel; Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Kilbourne, Amy M.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA. [Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. [Cypel, Yasmin; Kang, Han] US Dept Vet Affairs, Off Publ Hlth, Post Deployment Strateg Healthcare Grp, Washington, DC USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. [Furey, Joan] Vietnam Vet, Sayville, NY USA. [Huang, Grant D.] VA Off Res & Dev, Cooperat Studies Program Cent Off, Washington, DC USA. [Gleason, Theresa] VA Off Res & Dev, Clin Sci Res & Dev, Washington, DC USA. [Reinhard, Matthew J.] War Related Illness & Injury Ctr, Washington, DC USA. [Reinhard, Matthew J.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Spiro, Avron] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Spiro, Avron] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Spiro, Avron] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Magruder, K (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, 109 Bee St, Charleston, SC 29401 USA. EM magrudkm@musc.edu FU Department of Veterans Affairs (VA), Veterans Health Administration, VA Office of Research and Development, Cooperative Studies Program FX This study was supported by the Department of Veterans Affairs (VA), Veterans Health Administration, VA Office of Research and Development, Cooperative Studies Program. NR 30 TC 4 Z9 4 U1 3 U2 6 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 2015 VL 72 IS 11 BP 1127 EP 1134 DI 10.1001/jamapsychiatry.2015.1786 PG 8 WC Psychiatry SC Psychiatry GA CV6YG UT WOS:000364417600012 PM 26445103 ER PT J AU Blumenthal, KG Youngster, I Rabideau, DJ Parker, RA Manning, KS Walensky, RP Nelson, SB AF Blumenthal, Kimberly G. Youngster, Ilan Rabideau, Dustin J. Parker, Robert A. Manning, Karen S. Walensky, Rochelle P. Nelson, Sandra B. TI Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergy; antibiotic; drug; eosinophilia; hypersensitivity; drug rash with eosinophilia and systemic symptoms syndrome; vancomycin; metronidazole; outpatient parenteral antimicrobial therapy ID ACUTE INTERSTITIAL NEPHRITIS; TOXIC EPIDERMAL NECROLYSIS; ADVERSE DRUG-REACTIONS; DRESS SYNDROME; SYSTEMIC SYMPTOMS; PERSISTENT EOSINOPHILIA; DIFFERENTIAL-DIAGNOSIS; ANTIMICROBIAL THERAPY; PRACTICE GUIDELINES; RENAL-FAILURE AB Background: Although drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. Objective: We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). Methods: We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least 1 differential blood count. We used multivariate Cox proportional hazards models with time-varying antibiotic treatment indicators to assess the effect of demographic data and antibiotic exposures on eosinophilia and subsequent HSRs, including documented rash, renal injury, and liver injury. Possible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome cases were identified and manually validated. Results: Of 824 patients (60% male; median age, 60 years; median therapy duration, 41 days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of 726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin, rifampin, and linezolid was associated with a higher hazard of having eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n = 13). Patients with eosinophilia were significantly more likely to have rash (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P < .0001) and renal injury (HR, 2.13; 95% CI, 1.36-3.33; P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92-3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4 (57%) were receiving vancomycin. Conclusions: Drug-induced eosinophilia is common with parenteral antibiotics. Although most patients with eosinophilia do not have an HSR, eosinophilia increases the hazard rate of having rash and renal injury. DRESS syndrome was more common than previously described. C1 [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Youngster, Ilan; Manning, Karen S.; Walensky, Rochelle P.; Nelson, Sandra B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Parker, Robert A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Parker, Robert A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Rabideau, Dustin J.; Parker, Robert A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Blumenthal, Kimberly G.; Youngster, Ilan; Parker, Robert A.; Walensky, Rochelle P.; Nelson, Sandra B.] Harvard Univ, Sch Med, Boston, MA USA. [Youngster, Ilan] Boston Childrens Hosp, Dept Pediat, Div Infect Dis, Boston, MA USA. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Rheumatol Allergy & Immunol, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM kblumenthal1@partners.org OI Youngster, Ilan/0000-0001-5233-1213 FU National Institutes of Health (NIH) [T32 HL116275]; National Center for Research Resources; National Center for Advancing Translational Sciences; NIH Award [8UL1TR000170-05]; Harvard University FX K.G.B. is supported by the National Institutes of Health (NIH) (grant no. T32 HL116275). I.Y. received career support from Harvard Catalyst, Harvard Clinical and Translational Science Center, funded by the National Center for Research Resources and the National Center for Advancing Translational Sciences; NIH Award 8UL1TR000170-05; and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, the NIH, Harvard University, its affiliated academic health care centers, or its corporate contributors. NR 41 TC 3 Z9 3 U1 1 U2 3 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 2015 VL 136 IS 5 BP 1288 EP + DI 10.1016/j.jaci.2015.04.005 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA CW1YE UT WOS:000364787200018 PM 25981739 ER PT J AU Melanson, EL Gavin, KM Shea, KL Wolfe, P Wierman, ME Schwartz, RS Kohrt, WM AF Melanson, Edward L. Gavin, Kathleen M. Shea, Karen L. Wolfe, Pamela Wierman, Margaret E. Schwartz, Robert S. Kohrt, Wendy M. TI Regulation of energy expenditure by estradiol in premenopausal women SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE estradiol; premenopausal women; room calorimetry; resistance exercise; gonadotropin releasing hormone ID EARLY POSTMENOPAUSAL WOMEN; BODY-FAT DISTRIBUTION; GNRH AGONIST THERAPY; REPLACEMENT THERAPY; MENSTRUAL-CYCLE; ADIPOSE-TISSUE; MENOPAUSAL TRANSITION; HORMONE-THERAPY; SKELETAL-MUSCLE; METABOLIC-RATE AB Suppressing sex hormones in women for 1 wk reduces resting energy expenditure (REE). The effects of more chronic suppression on REE and other components of total energy expenditure (TEE), and whether the reduction in REE is specifically due to loss of estradiol (E-2), are not known. We compared the effects of 5 mo of sex hormone suppression (gonadotropin releasing hormone agonist therapy, GnRH(AG)) with placebo (PL) or E-2 add-back therapy on REE and the components of TEE. Premenopausal women received GnRH(AG) (leuprolide acetate 3.75 mg/mo) and were randomized to receive transdermal therapy that was either E-2 (0.075 mg/d; n = 24; means +/- SD, aged = 37 +/- 8 yr, BMI = 27.3 +/- 6.2 kg/m(2)) or placebo (n = 21; aged = 34 +/- 9 yr, BMI = 26.8 +/- 6.2 kg/m(2)). REE was measured by using a metabolic cart, and TEE, sleep EE (SEE), exercise EE (ExEE, 2 X 30 min bench stepping), non-Ex EE (NExEE), and the thermic effect of feeding (TEF) were measured by using whole room indirect calorimetry. REE decreased in GnRH(AG) + PL [mean (95% CI), -54 (-98, -15) kcal/d], but not GnRH(AG) + E-2 [+ 6 (-33, +45) kcal/d] (difference in between-group changes, P = 0.05). TEE decreased in GnRH(AG) + PL [-128 (-214, -41) kcal/d] and GnRH(AG) + E-2 [-96 (-159, -32) kcal/d], with no significant difference in between-group changes (P = 0.55). SEE decreased similarly in both GnRH(AG) + PL [-0.07 (-0.12, -0.03) kcal/min] and GnRH(AG) + E-2 [-0.07 (-0.12, -0.02) kcal/min]. ExEE decreased in GnRH(AG) + PL [-0.46 (-0.79, -0.13) kcal/min], but not GnRH(AG) + E-2 [- 0.30 (-0.65, +0.06) kcal/min]. There were no changes in TEF or NExEE in either group. In summary, chronic pharmacologic suppression of sex hormones reduced REE and this was prevented by E-2 therapy. C1 [Melanson, Edward L.; Wierman, Margaret E.] Univ Colorado, Div Endocrinol Metab & Diabet, Sch Med, Aurora, CO 80045 USA. [Melanson, Edward L.; Gavin, Kathleen M.; Shea, Karen L.; Wolfe, Pamela; Schwartz, Robert S.; Kohrt, Wendy M.] Univ Colorado, Div Geriatr Med, Sch Med, Aurora, CO 80045 USA. [Melanson, Edward L.; Gavin, Kathleen M.; Shea, Karen L.; Wierman, Margaret E.; Schwartz, Robert S.; Kohrt, Wendy M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Melanson, EL (reprint author), Univ Colorado, MS 8106,12801 East 17th Ave,RC1 South RM 7103, Aurora, CO 80045 USA. EM ed.melanson@ucdenver.edu FU National Institutes of Health [R01 AG-018198, P30 DK-048520, UL1 TR-001082, T32 AG000279, F32 AG046957] FX This work was supported by National Institutes of Health Grants R01 AG-018198; P30 DK-048520; and UL1 TR-001082, T32 AG000279, and F32 AG046957. NR 44 TC 1 Z9 1 U1 0 U2 1 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 2015 VL 119 IS 9 BP 975 EP 981 DI 10.1152/japplphysiol.00473.2015 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA CV7TO UT WOS:000364478200004 PM 26338457 ER PT J AU Hickerson, WL Ryan, CM Conlon, KM Harrington, DT Foster, K Schwartz, S Iyer, N Jeschke, M Haller, HL Faucher, LD Arnoldo, BD Jeng, JC AF Hickerson, William L. Ryan, Colleen M. Conlon, Kathe M. Harrington, David T. Foster, Kevin Schwartz, Suzanne Iyer, Narayan Jeschke, Marc Haller, Herbert L. Faucher, Lee D. Arnoldo, Brett D. Jeng, James C. TI What's in a Name? Recent Key Projects of the Committee on Organization and Delivery of Burn Care SO Journal of Burn Care & Research LA English DT Article ID PLAN AB The Committee for the Organization and Delivery of Burn Care (ODBC) was charged by President Palmieri and the American Burn Association (ABA) Board of Directors with presenting a plenary session at the 45th Meeting of the ABA in Palm Springs, CA, in 2013. The objective of the plenary session was to inform the membership about the wide range of the activities performed by the ODBC committee. The hope was that this session would encourage active involvement within the ABA as a means to improve the delivery of future burn care. Selected current activities were summarized by key leaders of each project and highlighted in the plenary session. The history of the committee, current projects in disaster management, regionalization, best practice guidelines, federal partnerships, product development, new technologies, electronic medical records, and manpower issues in the burn workforce were summarized. The ODBC committee is a keystone committee of the ABA. It is tasked by the ABA leadership with addressing and leading progress in many areas that constitute current challenges in the delivery of burn care. C1 [Hickerson, William L.] Univ Tennessee, Ctr Hlth Sci, Reg Med Ctr, Firefighters Reg Burn Ctr, Memphis, TN 38163 USA. [Ryan, Colleen M.] Harvard Univ, Sch Med, Shriners Hosp Children Boston, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Conlon, Kathe M.] St Barnabas Hosp, Burn Ctr, Livingston, NJ USA. [Harrington, David T.] Rhode Isl Hosp, Providence, RI USA. [Foster, Kevin] Maricopa Cty Gen Hosp, Arizona Burn Ctr, Phoenix, AZ USA. [Schwartz, Suzanne] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Iyer, Narayan] US Dept HHS, Div CBRN Countermeasures, Biomed Adv Res & Dev Author, Washington, DC USA. Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, Toronto, ON, Canada. [Haller, Herbert L.] Unfallkrankenhaus Linz, Linz, Austria. [Faucher, Lee D.; Arnoldo, Brett D.] Univ Wisconsin, Med Ctr, Madison, WI 53706 USA. [Jeng, James C.] George Washington Univ, Medstar Washington Hosp Ctr, Washington, DC USA. RP Hickerson, WL (reprint author), Univ Tennessee, Ctr Hlth Sci, Reg Med Ctr, Firefighters Reg Burn Ctr, Memphis, TN 38163 USA. EM whicker1@uthsc.edu FU American Burn Association FX This study was supported by the American Burn Association. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2015 VL 36 IS 6 BP 619 EP 625 DI 10.1097/BCR.0000000000000189 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA CV5UZ UT WOS:000364338000007 PM 25423435 ER PT J AU Chen, NC Ring, D AF Chen, Neal C. Ring, David TI Terrible Triad Injuries of the Elbow SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Review DE Terrible; triad; elbow; fracture; instability ID RADIAL HEAD PROSTHESIS; MEDIAL COLLATERAL LIGAMENT; CORONOID FRACTURES; FIXATION; RECONSTRUCTION; INSTABILITY; STABILITY; REPLACEMENT; DISLOCATION; ARTHROPLASTY AB The treatment of terrible triad injuries of the elbow continues to evolve. Radial head fixation and arthroplasty, coronoid process fixation, and repair of the lateral collateral ligament continue to be the mainstays of treatment. In the elbow with persistent instability after repair of these elements, application of a static external fixation, hinged external fixation, ulnohumeral joint pinning, or an internal hinge may be needed. In patients who undergo treatment after the acute injury period, the coronoid may require reconstruction using radial head autograft, iliac crest autograft, olecranon autograft, or allograft. (Copyright (C) 2015 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Chen, Neal C.; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM dring@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879 FU Skeletal Dynamics; Biomet; Acumed FX D.R. reports receiving grants from Skeletal Dynamics; royalties from Wright Medical; personal fees from Biomet, Acumed, universities and hospitals, and lawers; stock options from Illuminos; speaking honoraria from other universities and hospitals; and personal fees from being a deputy editor for Journal of Hand Surgery and Clinical Orthopaedics and Related Research. NR 32 TC 2 Z9 2 U1 2 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 EI 1531-6564 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 2015 VL 40 IS 11 BP 2297 EP 2303 DI 10.1016/j.jhsa.2015.04.039 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CW2EO UT WOS:000364804100031 PM 26440743 ER PT J AU Platt, MY Fathi, AT Borger, DR Brunner, AM Hassejian, RP Balaj, L Lum, A Yip, S Dias-Santagata, D Zheng, ZL Le, LP Graubert, TA Iafrate, AJ Nardi, V AF Platt, Mia Y. Fathi, Amir T. Borger, Darrell R. Brunner, Andrew M. Hassejian, Robert P. Balaj, Leonora Lum, Amy Yip, Stephen Dias-Santagata, Dora Zheng, Zongli Le, Long P. Graubert, Timothy A. Iafrate, A. John Nardi, Valentina TI Detection of Dual IDH1 and IDH2 Mutations by Targeted Next-Generation Sequencing in Acute Myeloid Leukemia and Myelodysplastic Syndromes SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MUTANT IDH1; IN-VIVO; DIFFERENTIATION; LEUKEMOGENESIS; INHIBITORS; EVOLUTION; CELLS; TET2; AML AB Studies in myeloid neoplasms have described recurrent IDH1 and IDH2 mutations as primarily mutually exclusive. Over a 6-month period of clinical testing with a targeted next-generation sequencing assay, we evaluated 92 patients with acute myeloid Leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia and identified a subset of 21 patients (23%) who harbored mutations in either IDH1 or IDH2. Of the 21 patients with IDH mutations, 4 (19%) were found to have single nucleotide variants in both IDH1 and IDH2. An additional patient included in the study was found to have two different IDH2 mutations. The mutations were typically present at different variant allelic frequencies, with one predominating over the other, consistent with the presence of multiple subclones in a single patient. In one case, the variant allelic frequencies in both IDH1 and IDH2 were equally low in the setting of a high percentage of blasts, suggesting that the IDH mutations were unlikely to be present in the founding clone. Given these data, we conclude that dual IDH1/2 mutations likely were previously underestimated, a finding that may carry important treatment implications. C1 [Platt, Mia Y.; Borger, Darrell R.; Hassejian, Robert P.; Dias-Santagata, Dora; Zheng, Zongli; Le, Long P.; Iafrate, A. John; Nardi, Valentina] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fathi, Amir T.; Brunner, Andrew M.; Graubert, Timothy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Balaj, Leonora] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Platt, Mia Y.; Fathi, Amir T.; Borger, Darrell R.; Brunner, Andrew M.; Hassejian, Robert P.; Balaj, Leonora; Dias-Santagata, Dora; Zheng, Zongli; Le, Long P.; Graubert, Timothy A.; Iafrate, A. John; Nardi, Valentina] Harvard Univ, Sch Med, Boston, MA USA. [Lum, Amy; Yip, Stephen] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. RP Nardi, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ 245, Boston, MA 02114 USA. EM vnardi@partners.org RI Zheng, Zongli/B-2917-2011 OI Zheng, Zongli/0000-0003-4849-4903 FU NCI NIH HHS [T32 CA 71345-18, T32 CA071345] NR 35 TC 1 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 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2015 VL 17 IS 6 BP 661 EP 668 DI 10.1016/j.jmoldx.2015.06.004 PG 8 WC Pathology SC Pathology GA CU8YM UT WOS:000363830000005 PM 26331834 ER PT J AU Wang, WX Corrigan-Cummins, M Barber, EA Saleh, LM Zingone, A Ghafoor, A Costello, R Zhang, Y Kurlander, RJ Korde, N Roccaro, AM Ghobrial, IM Landgren, O Calvo, KR AF Wang, Weixin Corrigan-Cummins, Meghan Barber, Emily A. Saleh, Layla M. Zingone, Adriana Ghafoor, Azam Costello, Rene Zhang, Yong Kurlander, Roger J. Korde, Neha Roccaro, Aldo M. Ghobrial, Irene M. Landgren, Ola Calvo, Katherine R. TI Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID UNDETERMINED SIGNIFICANCE MGUS; SMOLDERING MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; MICRORNA EXPRESSION; GENE-EXPRESSION; CIRCULATING MICRORNAS; 14Q32 TRANSLOCATIONS; DOWN-REGULATION; HUMAN LEUKEMIA; PLASMA-CELLS AB The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant Levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeLoma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeLoma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression. C1 [Wang, Weixin; Corrigan-Cummins, Meghan; Barber, Emily A.; Saleh, Layla M.; Ghafoor, Azam; Kurlander, Roger J.; Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Zingone, Adriana; Costello, Rene; Zhang, Yong; Korde, Neha; Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Calvo, KR (reprint author), NIH, Hematol Sect, Dept Lab Med, Ctr Clin, 10 Ctr Dr,Bldg 10-2C306, Bethesda, MD 20892 USA. EM calvok@cc.nih.gov OI Roccaro, Aldo/0000-0002-1872-5128 FU Intramural NIH HHS NR 56 TC 3 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2015 VL 17 IS 6 BP 669 EP 678 DI 10.1016/j.jmoldx.2015.06.006 PG 10 WC Pathology SC Pathology GA CU8YM UT WOS:000363830000006 PM 26433312 ER PT J AU Platt, M Fathi, AT Borger, DR Brunner, AM Hasserjian, RP Balaj, L Lum, A Yip, S Dias-Santagata, D Zheng, Z Le, LP Graubert, TA Iafrate, AJ Nardi, V AF Platt, M. Fathi, A. T. Borger, D. R. Brunner, A. M. Hasserjian, R. P. Balaj, L. Lum, A. Yip, S. Dias-Santagata, D. Zheng, Z. Le, L. P. Graubert, T. A. Iafrate, A. J. Nardi, V. TI Detection of Dual IDH1 and IDH2 Mutations by Targeted Next-Generation Sequencing in Acute Myeloid Leukemia and Myelodysplastic Syndromes SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology (AMP) CY NOV 05-07, 2015 CL Austin, TX SP Assoc Mol Pathol C1 [Platt, M.; Fathi, A. T.; Borger, D. R.; Brunner, A. M.; Hasserjian, R. P.; Balaj, L.; Dias-Santagata, D.; Zheng, Z.; Le, L. P.; Graubert, T. A.; Iafrate, A. J.; Nardi, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lum, A.; Yip, S.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. 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 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2015 VL 17 IS 6 MA H18 BP 769 EP 769 PG 1 WC Pathology SC Pathology GA CU8YM UT WOS:000363830000084 ER PT J AU Church, A Calicchio, ML Dubuc, AM Dela Cruz, F Tannenbaum, S Kung, A Glade-Bender, J Pinto, A Dillon, D Gomez-Fernandez, C Nardi, V Skalova, A Perez-Atayde, A Janeway, KA Harris, MH AF Church, A. Calicchio, M. L. Dubuc, A. M. Dela Cruz, F. Tannenbaum, S. Kung, A. Glade-Bender, J. Pinto, A. Dillon, D. Gomez-Fernandez, C. Nardi, V. Skalova, A. Perez-Atayde, A. Janeway, K. A. Harris, M. H. TI A Novel EML4-NTRK3 Translocation in Infantile Fibrosarcoma and Congenital Mesoblastic Nephroma Requires a New Approach to Conventional Diagnostic Algorithms SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology (AMP) CY NOV 05-07, 2015 CL Austin, TX SP Assoc Mol Pathol C1 [Church, A.; Calicchio, M. L.; Perez-Atayde, A.; Harris, M. H.] Boston Childrens Hosp, Boston, MA USA. [Dubuc, A. M.; Pinto, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dela Cruz, F.; Tannenbaum, S.; Kung, A.] Columbia Univ, New York, NY USA. [Glade-Bender, J.] Columbia Univ, New York, NY USA. [Dillon, D.] Dillon, Boston, MA USA. [Gomez-Fernandez, C.] Univ Miami, Miami, FL USA. [Nardi, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skalova, A.] Charles Univ Prague, Prague, Czech Republic. [Janeway, K. A.] Dana Farber Canc Inst, Boston, MA 02115 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 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2015 VL 17 IS 6 MA ST16 BP 816 EP 816 PG 1 WC Pathology SC Pathology GA CU8YM UT WOS:000363830000276 ER PT J AU Song, C Fontana, R Makrigiorgos, G AF Song, C. Fontana, R. Makrigiorgos, G. TI Multiplexed Minority Mutation Detection in Gene Panels Using Nuclease-Assisted Minor-Allele Enrichment (NaME) SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology (AMP) CY NOV 05-07, 2015 CL Austin, TX SP Assoc Mol Pathol C1 [Song, C.; Fontana, R.; Makrigiorgos, G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 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 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2015 VL 17 IS 6 MA TT14 BP 847 EP 847 PG 1 WC Pathology SC Pathology GA CU8YM UT WOS:000363830000402 ER PT J AU Biederman, J Feinberg, L Chan, J Adeyemo, BO Woodworth, KY Panis, W McGrath, N Bhatnagar, S Spencer, TJ Uchida, M Kenworthy, T Grossman, R Zafonte, R Faraone, SV AF Biederman, Joseph Feinberg, Leah Chan, James Adeyemo, Bamidele O. Woodworth, K. Yvonne Panis, Walter McGrath, Neal Bhatnagar, Saurabha Spencer, Thomas J. Uchida, Mai Kenworthy, Tara Grossman, Rebecca Zafonte, Ross Faraone, Stephen V. TI Mild Traumatic Brain Injury and Attention-Deficit Hyperactivity Disorder in Young Student Athletes SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Traumatic brain injury; mild; attention-deficit hyperactivity disorder; student athlete ID PROFESSIONAL FOOTBALL PLAYERS; DEFICIT/HYPERACTIVITY DISORDER; RECURRENT CONCUSSION; LEAGUE PLAYER; HEAD-INJURY; ADOLESCENTS; CHILDREN; IMPACT; ENCEPHALOPATHY; RECOVERY AB A recent meta-analysis documented a significant statistical association between mild traumatic brain injury (mTBI) and attention deficit hyperactivity disorder (ADHD) (Adeyemo et al., 2014), but the direction of this effect was unclear. In this study, we hypothesized that ADHD would be an antecedent risk factor for mTBI. Participants were student athletes ages 12 to 25 who had sustained a mTBI and Controls of similar age and sex selected from studies of youth with and without ADHD. Subjects were assessed for symptoms of ADHD, concussion severity, and cognitive function. mTBI subjects had a significantly higher rate of ADHD than Controls, and in all cases the age of onset of ADHD was before mTBI onset. mTBI+ADHD subjects also had more severe concussion symptoms (fatigue and poor concentration) than mTBI-ADHD subjects. These results support ADHD as an antecedent risk factor for mTBI in student athletes and that its presence complicates the course of mTBI. C1 [Biederman, Joseph; Feinberg, Leah; Chan, James; Woodworth, K. Yvonne; Spencer, Thomas J.; Uchida, Mai; Kenworthy, Tara; Grossman, Rebecca] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA. [Biederman, Joseph; Adeyemo, Bamidele O.; Bhatnagar, Saurabha; Spencer, Thomas J.; Uchida, Mai; Zafonte, Ross] Harvard Univ, Sch Med, Boston, MA USA. [Adeyemo, Bamidele O.] Emory Univ, Sch Med, Dept Phys Med & Rehabil, Atlanta, GA USA. [Panis, Walter; Bhatnagar, Saurabha; Zafonte, Ross] Massachusetts Gen Hosp, Spaulding Rehabil Hospital, Dept Phys Med & Rehabil, Charlestown, MA USA. [McGrath, Neal] Sports Concuss New England, Brookline, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. [Faraone, Stephen V.] Univ Bergen, KG Jebsen Ctr Res Neuropsychiat Disorders, Bergen, Norway. RP Biederman, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM jbiederman@partners.org RI Meijer, Anna/K-5118-2016 FU NIH [R01MH050657, R01HD036317]; Pediatric Psychopharmacology Research Council Fund FX This work was supported by NIH grants (J.B., grant numbers R01MH050657, R01HD036317) and by the Pediatric Psychopharmacology Research Council Fund. The authors thank Elana Kagan for her contributions to the early stages of coordinating this study. NR 44 TC 2 Z9 2 U1 6 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2015 VL 203 IS 11 BP 813 EP 819 DI 10.1097/NMD.0000000000000375 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CV7UW UT WOS:000364482100001 PM 26461480 ER PT J AU Jalal, B Hinton, DE AF Jalal, Baland Hinton, Devon E. TI Sleep Paralysis Among Egyptian College Students Association With Anxiety Symptoms (PTSD, Trait Anxiety, Pathological Worry) SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Sleep paralysis; PTSD; anxiety; worry; hypnopompic/hypnogogic hallucinations ID POSTTRAUMATIC-STRESS-DISORDER; GENERAL-POPULATION; CAMBODIAN REFUGEES; PANIC DISORDER; PREVALENCE; RATES; SYMPTOMATOLOGY; QUESTIONNAIRE; VALIDATION; DIAGNOSIS AB Among Egyptian college students in Cairo (n = 100), this study examined the relationship between sleep paralysis (SP) and anxiety symptoms, viz., posttraumatic stress disorder (PTSD), trait anxiety, and pathological worry. SP rates were high; 43% of participants reported at least one lifetime episode of SP, and 24% of those who reported at least one lifetime episode had experienced four or more episodes during the previous year. Fourteen percent of men had experienced SP as compared to 86% of women. As hypothesized, relative to non-SP experiencers, participants who had SP reported higher symptoms of PTSD, trait anxiety, and pathological worry. Also, as hypothesized, the experiencing of hypnogogic/hypnopompic hallucinations during SP, even after controlling for negative affect, was highly correlated with symptoms of PTSD and trait anxiety. The study also investigated possible mechanisms by examining the relationship of hallucinations to anxiety variables. C1 [Jalal, Baland] Univ Calif San Diego, Ctr Brain & Cognit, La Jolla, CA 92093 USA. [Hinton, Devon E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Jalal, B (reprint author), Univ Calif San Diego, Ctr Brain & Cognit, 0109 Mandler Hall,9500 Gilman Dr, La Jolla, CA 92093 USA. EM bjalal@ucsd.edu NR 42 TC 1 Z9 1 U1 6 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2015 VL 203 IS 11 BP 871 EP 875 DI 10.1097/NMD.0000000000000382 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CV7UW UT WOS:000364482100009 PM 26488914 ER PT J AU Mahmood, U AF Mahmood, Umar TI 2015 SNMMI Highlights Lecture: Oncology, Part I SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material AB From the News line Editor: The Highlights Lecture, presented at the closing session of each SNMMI Annual Meeting, was originated and delivered for more than 30 years by Henry N. Wagner, Jr., MD. Beginning in 2010, the duties of summarizing selected significant presentations at the meeting were divided annually among 4 distinguished nuclear and molecular medicine subject matter experts. The 2015 Highlights Lectures were delivered on June 10 at the SNMMI Annual Meeting in Baltimore, MD. Umar Mahmood, MD, PhD, a professor of radiology at Massachusetts General Hospital (Boston, MA), spoke on oncology highlights from the meeting's sessions. Because of its length, the oncology presentation will be divided between 2 Newsline issues. Note that in the following summary, numerals in brackets represent abstract numbers as published in The Journal of Nuclear Medicine [2015;56:suppl 3). C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2015 VL 56 IS 11 BP 9N EP 16N PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6BQ UT WOS:000364356100001 PM 26626870 ER PT J AU Dubroff, JG Doot, RK Falcone, M Schnoll, RA Ray, R Tyndale, RF Brody, AL Hou, C Schmitz, A Lerman, C AF Dubroff, Jacob G. Doot, Robert K. Falcone, Mary Schnoll, Robert A. Ray, Riju Tyndale, Rachel F. Brody, Arthur L. Hou, Catherine Schmitz, Alexander Lerman, Caryn TI Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; nicotine; addiction; 2-F-18-FA-85380; nicotine metabolite ratio; alpha 4 beta 2*nAChR ID ACETYLCHOLINE-RECEPTORS; SMOKING-CESSATION; HUMAN-BRAIN; CIGARETTE-SMOKING; TRANSDERMAL NICOTINE; TOBACCO SMOKING; IN-VIVO; RATIO; ABSTINENCE; DEPENDENCE AB The nicotine metabolite ratio (NMR), a stable measure of hepatic nicotine metabolism via the CYP2A6 pathway and total nicotine clearance, is a predictive biomarker of response to nicotine replacement therapy, with increased quit rates in slower metabolizers. Nicotine binds directly to nicotinic acetylcholine receptors (nAChRs) to exert its psychoactive effects. This study examined the relationship between NMR and nAChR (alpha 4 beta 2* subtype) availability using PET imaging of the radiotracer 2-F-18-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-F-18-FA-85380, or 2-F-18-FA). Methods: Twenty-four smokers-12 slow metabolizers (NMR < 0.26) and 12 normal metabolizers (NMR >= 0.26) underwent 2-F-18-FA-PET brain imaging after overnight nicotine abstinence (18 h before scanning), using a validated bolus-plus-infusion protocol. Availability of nAChRs was compared between NMR groups in a priori volumes of interest, with total distribution volume (V-T/f(P)) being the measure of nAChR availability. Cravings to smoke were assessed before and after the scans. Results: Thalamic nAChR alpha 4 beta 2* availability was significantly reduced in slow nicotine metabolizers (P = 0.04). Slow metabolizers exhibited greater reductions in cravings after scanning than normal metabolizers; however, craving was unrelated to nAChR availability. Conclusion: The rate of nicotine metabolism is associated with thalamic nAChR availability. Additional studies could examine whether altered nAChR availability underlies the differences in treatment response between slow and normal metabolizers of nicotine. C1 [Dubroff, Jacob G.; Doot, Robert K.; Hou, Catherine; Schmitz, Alexander] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Falcone, Mary; Schnoll, Robert A.; Lerman, Caryn] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Ray, Riju] GlaxoSmithKline, Global Med Affairs, Brussels, Belgium. [Tyndale, Rachel F.] Univ Toronto, CAMH, Dept Pharmacol & Toxicol, Toronto, ON, Canada. [Tyndale, Rachel F.] Univ Toronto, Dept Psychiat, CAMH, Toronto, ON, Canada. [Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Brody, Arthur L.] Vet Adm Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Dubroff, JG (reprint author), Hosp Univ Penn, Div Nucl Med & Clin Mol Imaging, Dept Radiol, 3400 Spruce St,110 Donner Bldg, Philadelphia, PA 19104 USA. EM jacob.dubroff@uphs.upenn.edu FU Pharmacogenetics Research Network (PNAT) [U01-DA20830]; Abramson Cancer Center at the University of Pennsylvania; Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania (NIH), a McCabe Pilot Award (University of Pennsylvania); Commonwealth of Pennsylvania (Pennsylvania Department of Health); National Institute on Drug Abuse [R01 DA20872]; Department of Veterans Affairs Office of Research and Development (CSR&D Merit Review Award) [I01 CX000412]; Tobacco-Related Disease Research Program [23XT-0002] FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported by a grant from the Pharmacogenetics Research Network (PNAT, U01-DA20830), the Abramson Cancer Center at the University of Pennsylvania, the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania (NIH), a McCabe Pilot Award (University of Pennsylvania), and the Commonwealth of Pennsylvania (the Pennsylvania Department of Health disclaims responsibility for analyses, interpretations, or conclusions). Additional support was provided by Pfizer, the National Center for Research Resources, and the National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR000003). Arthur Brody is supported by grants from the National Institute on Drug Abuse (R01 DA20872), the Department of Veterans Affairs Office of Research and Development (CSR&D Merit Review Award I01 CX000412), and the Tobacco-Related Disease Research Program (23XT-0002). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. No other potential conflict of interest relevant to this article was reported. NR 48 TC 3 Z9 3 U1 3 U2 7 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2015 VL 56 IS 11 BP 1724 EP 1729 DI 10.2967/jnumed.115.155002 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6BQ UT WOS:000364356100019 PM 26272810 ER PT J AU Jacobson, O Weiss, ID Wang, L Wang, Z Yang, XY Dewhurst, A Ma, Y Zhu, GZ Niu, G Kiesewetter, DO Vasdev, N Liang, SH Chen, XY AF Jacobson, Orit Weiss, Ido D. Wang, Lu Wang, Zhe Yang, Xiangyu Dewhurst, Andrew Ma, Ying Zhu, Guizhi Niu, Gang Kiesewetter, Dale O. Vasdev, Neil Liang, Steven H. Chen, Xiaoyuan TI F-18-Labeled Single-Stranded DNA Aptamer for PET Imaging of Protein Tyrosine Kinase-7 Expression SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PTK7; PET imaging; F-18; click chemistry; ssDNA aptamer ID CELL POLARITY; PTK7; CANCER; REGULATOR; CARCINOMA; LEUKEMIA; FAMILY; PROBES; GENES; ROLES AB Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase superfamily initially identified as colon carcinoma kinase-4, is highly expressed in various human malignancies. Its expression was found to correlate with aggressive biologic behaviors such as increased cell proliferation, invasiveness, and migration. Despite the importance and unmet need of imaging PTK7 in vivo, there is currently no clinically relevant method to visualize tumoral PTK7 expression noninvasively such as PET or SPEC. This study aimed to develop a specific, selective, and high-affinity PET radioligand based on single-stranded DNA aptamer to address this challenge. Methods: Sgc8, a 41-oligonucleotide that targets to PTK7, was labeled with F-18 using a 2-step radiochemical synthesis, which featured a direct 1-step radio-fluorination on the distinctive spirocyclic hypervalent iodine(III) precursor to give F-18-fluorobenzyl azide followed by copper-mediated click conjugation with Sgc8-allcyne. F-18-Sgc8 was evaluated in vitro and in vivo in 2 cell lines, HCT116 and U87MG, which express high and low amounts of PTK7, respectively. Results: Sgc8 was labeled efficiently with F-18 in an isolated radiochemical yield of 62% 2%, non decay-corrected based on F-18-fluorobenzyl azide. F-18-Tr-Sgc8 was found to possess high-affinity binding to both cell lines, with binding affinity values of 2.7 +/- 0.6 nM for HCT116 and 16.9 +/- 2.1 nM for U87MG. In vivo PET imaging clearly visualized PTK7 expression in HCT116 xenografted mice, with tumor uptake of 0.76 +/- 0.09 percentage injected dose per gram (%ID/g) at 30 min after injection for the subcutaneous tumor model and greater than 1.5 %ID/g for the liver metastasis model. U87MG xenograft tumors had much lower tracer accumulation (0.13 +/- 0.06 %ID/g at 30 min after injection), which was consistent with the lower expression of PTK7 in this tumor model. The labeled aptamer was rapidly cleared from the blood through the kidneys and bladder to give high tumor-to-blood and tumor-to-muscle ratios of 7.29 +/- 1.51 and 10.25 +/- 2.08, respectively. Conclusion: The F-18-radiolabeling methodology shown here is a robust procedure for labeling aptamers and similar chemical moieties and can be applied to many different targets. Quantification of PTK7 using F-18-Tr-Sgc8 may be suitable for clinical translation and might help in the future to select and monitor appropriate therapies. C1 [Jacobson, Orit; Wang, Zhe; Yang, Xiangyu; Dewhurst, Andrew; Ma, Ying; Zhu, Guizhi; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. [Weiss, Ido D.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Wang, Lu; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Wang, Lu; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Chen, XY (reprint author), NIH, 35A Convent Dr,GD937, Bethesda, MD 20892 USA. EM Liang.Steven@mgh.harvard.edu; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported by the intramural research program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). No other potential conflict of interest relevant to this article was reported. NR 26 TC 6 Z9 6 U1 16 U2 33 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2015 VL 56 IS 11 BP 1780 EP 1785 DI 10.2967/jnumed.115.160960 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6BQ UT WOS:000364356100027 PM 26315836 ER PT J AU Stewart, KR Stewart, GL Lampman, M Wakefield, B Rosenthal, G Solimeo, SL AF Stewart, Kenda R. Stewart, Greg L. Lampman, Michelle Wakefield, Bonnie Rosenthal, Gary Solimeo, Samantha L. TI Implications of the Patient-Centered Medical Home for Nursing Practice SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID CARE STAFF PERSPECTIVES; HEALTH-CARE; PROFESSIONAL BOUNDARIES; IMPLEMENTATION; DELEGATION; TEAMWORK; VETERANS; NURSES AB OBJECTIVE: The experiences of RNs and licensed practical nurses (LPNs) implementing a patient-centered medical home (PCMH) in the Department of Veterans Affairs (VA) primary care clinics were examined to understand model implications for nursing practice and professional identity. BACKGROUND: National implementation of the PCMH model, called patient-aligned care teams (PACTs) in VA, emphasizes areas of nursing expertise, yet little is known about the effect of medical homes on the day-to-day work of nurses. METHODS: As part of a formative evaluation to identify barriers and facilitators to PACT implementation, we interviewed 18 nurses implementing PACT. RESULTS: Challenges to nurse's organizational and professional roles were experienced differently by RNs and LPNs in the following areas: (1) diversified modes of care and expanded clinical duties, (2) division of labor among PACT nurses, and (3) interprofessional status in the team. CONCLUSIONS: Healthcare managers implementing PCMH should consider its inherent cultural and practice transformations. C1 [Stewart, Kenda R.; Stewart, Greg L.; Lampman, Michelle; Wakefield, Bonnie; Rosenthal, Gary; Solimeo, Samantha L.] VISN 23 Patient Aligned Care Team Demonstrat Lab, US Dept Vet Affairs, Iowa City, IA USA. [Stewart, Greg L.; Lampman, Michelle; Wakefield, Bonnie; Rosenthal, Gary; Solimeo, Samantha L.] Ctr Comprehens Access & Delivery Res & Evaluat, US Dept Vet Affairs, Iowa City, IA USA. [Stewart, Greg L.] Iowa City VA Hlth Care Syst, Vet Rural Hlth Resource Ctr Cent Reg, US Dept Vet Affairs, Iowa City, IA 52246 USA. [Stewart, Greg L.] Univ Iowa, Tippie Coll Business, Iowa City, IA USA. [Rosenthal, Gary; Solimeo, Samantha L.] Univ Iowa Carver, Div Gen Internal Med, Coll Med, Iowa City, IA USA. RP Stewart, KR (reprint author), Iowa City VA Hlth Care Syst, 601 Hwy 6 W, Iowa City, IA 52246 USA. EM kenda.stewart@va.gov FU VISN 23 PACT Demonstration Laboratory; Office of Patient Care Services, Department of Veterans Affairs; Center for Comprehensive Access and Delivery Research and Evaluation, Department of Veterans Affairs, Iowa City VA Health Care System, Iowa City [CIN 13-412] FX This work was supported by VISN 23 PACT Demonstration Laboratory, supported by the Office of Patient Care Services, Department of Veterans Affairs. Additional support was provided by the Center for Comprehensive Access and Delivery Research and Evaluation (grant CIN 13-412), Department of Veterans Affairs, Iowa City VA Health Care System, Iowa City. NR 27 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2015 VL 45 IS 11 BP 569 EP 574 DI 10.1097/NNA.0000000000000265 PG 6 WC Nursing SC Nursing GA CV5SO UT WOS:000364331600011 PM 26492149 ER PT J AU Chow, C Pincus, DB Comer, JS AF Chow, Candice Pincus, Donna B. Comer, Jonathan S. TI Pediatric Food Allergies and Psychosocial Functioning: Examining the Potential Moderating Roles of Maternal Distress and Overprotection SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE food allergies; pediatric; psychosocial functioning; quality of life ID QUALITY-OF-LIFE; ANXIETY STRESS SCALES; PSYCHOMETRIC PROPERTIES; ANAPHYLACTIC REACTIONS; CHILDREN; CHILDHOOD; PARENTS; IMPACT; YOUTH; QUESTIONNAIRE AB ObjectivesaEuro integral Identify factors associated with maternal perceptions of health-related quality of life (QoL) among youth with food allergies (FA), and identify maternal factors that may moderate relationships between FA-related challenges and child QoL.aEuro integral MethodsaEuro integral In all, 533 mothers of children with FA completed measures assessing characteristics of their child's FA, maternal perceptions of child QoL, maternal psychological distress, and maternal overprotection.aEuro integral ResultsaEuro integral FA severity, maternal psychological distress, and overprotection were significantly associated with maternal reports of poorer child functioning and/or poorer QoL among youth with FA. Hierarchical linear regression analyses showed an FA severity by maternal distress interaction in the prediction of child FA-related anxiety; children of higher stress mothers showed a stronger link between auto-injector use and anxiety than children of lower stress mothers.aEuro integral ConclusionsaEuro integral When identifying youth with FA who are at risk for low QoL, it is important to assess history of FA-related challenges, parental psychological distress, and overprotection. C1 [Chow, Candice] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Psychosocial Oncol, Cambridge, MA 02138 USA. [Pincus, Donna B.] Boston Univ, Ctr Anxiety & Related Disorders, Dept Psychol, Boston, MA 02215 USA. [Comer, Jonathan S.] Florida Int Univ, Mental Hlth Intervent & Technol MINT Program, Miami, FL 33199 USA. RP Chow, C (reprint author), Dana Farber Canc Inst, Div Pediat Psychosocial Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM candice_chow@dfci.harvard.edu FU Clara Mayo Memorial Fellowship; John and Geraldine Weil Foundation; Center for Anxiety and Related Disorders at Boston University; NIH [K23 MH090247] FX Funding for this work was provided by the Clara Mayo Memorial Fellowship, the John and Geraldine Weil Foundation, the Center for Anxiety and Related Disorders at Boston University, and by NIH (K23 MH090247). NR 41 TC 1 Z9 1 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 EI 1465-735X J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD NOV-DEC PY 2015 VL 40 IS 10 BP 1065 EP 1074 DI 10.1093/jpepsy/jsv058 PG 10 WC Psychology, Developmental SC Psychology GA CW1SM UT WOS:000364771600009 PM 26089553 ER PT J AU Iverson, KM Vogt, D Dichter, ME Carpenter, SL Kimerling, R Street, AE Gerber, MR AF Iverson, Katherine M. Vogt, Dawne Dichter, Melissa E. Carpenter, S. Louisa Kimerling, Rachel Street, Amy E. Gerber, Megan R. TI Intimate Partner Violence and Current Mental Health Needs Among Female Veterans SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Comorbidity; Domestic Violence; Mental Health; Patient Care Team; Screening ID WOMEN VETERANS; DOMESTIC VIOLENCE; SCREENING TOOL; VHA PATIENTS; SERVICES; TRAUMA AB Background: The Veterans Health Administration (VHA) recommends screening female patients for intimate partner violence (IPV), yet few studies inform IPV screening efforts among this population. This study examined the proportion of women who experienced IPV within the past year and the associations between IPV and depression, post-traumatic stress disorder (PTSD), alcohol dependence, mental health multimorbidity (ie, 2 or 3 of these conditions), and military sexual trauma (MST) among female veterans. Methods: A cross-sectional mail survey of 160 female VHA patients with an intimate partner within the past year was conducted in 2012 in New England. Self-reported IPV was assessed using the Hurt, Insult, Threaten, Scream screening tool. The survey also included validated screening measures of depression (Center for Epidemiologic Studies Depression Scale), PTSD (PTSD Checklist-Civilian), alcohol misuse (10-item Alcohol Use Disorders Identification Test), and MST. Results: Approximately 37% of women reported IPV within the past year on the Hurt, Insult, Threaten, Scream tool. Odds ratios for the associations between reporting IPV and mental health outcomes ranged between 2.75 and 3.67. With the exception of alcohol dependence, IPV remained strongly associated with mental health conditions when adjusting for MST. Conclusions: These findings can increase provider knowledge of the strong connection between past-year IPV and mental health conditions among female veterans. This may encourage IPV screening and facilitate appropriate referrals, treatment conceptualization, and planning within the VHA and other health care settings. C1 [Iverson, Katherine M.; Vogt, Dawne; Carpenter, S. Louisa; Street, Amy E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Iverson, Katherine M.; Vogt, Dawne; Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Gerber, Megan R.] VA Boston Healthcare Syst, Womens Hlth Ctr, Boston, MA USA. [Gerber, Megan R.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Iverson, KM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA. EM katherine.iverson@va.gov OI Gerber, Megan/0000-0002-8444-5554 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of HSR&D Career Development Awards [CDA 10-029, CDA 10-202]; Presidential Early Career Award for Scientists and Engineers [USA 14-275] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of HSR&D Career Development Awards (CDA 10-029 to KMI, and CDA 10-202 to MED) and a Presidential Early Career Award for Scientists and Engineers (USA 14-275 to KMI). NR 24 TC 3 Z9 4 U1 1 U2 5 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD NOV-DEC PY 2015 VL 28 IS 6 BP 772 EP 776 DI 10.3122/jabfm.2015.06.150154 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA CW3CK UT WOS:000364869400013 PM 26546653 ER PT J AU Harvey, HB Alkasab, TK Pandharipande, V Halpern, EE Prabhakar, AM Oklu, R Rosenthal, DI Hirsch, JA Gazelle, GS Brink, JA AF Harvey, H. Benjamin Alkasab, Tank K. Pandharipande, V. Halpern, Elkan E. Prabhakar, Anand M. Oklu, Rahmi Rosenthal, Daniel I. Hirsch, Joshua A. Gazelle, G. Scott Brink, James A. TI Non-Research-Related Physician-Industry Relationships of Radiologists in the United States SO Journal of the American College of Radiology LA English DT Article DE Conflict of interest; industry interaction; financial relationship; Sunshine Act; ethics; regulation ID ACADEMIC MEDICAL-CENTERS; PAYMENT SUNSHINE ACT; DRUG COMPANIES; TRANSPARENCY AB Purpose: To evaluate non-research-related, physician-industry financial relationships in the United States, in 2013, as reported pursuant to the Physician Payments Sunshine Act (a provision of the Affordable Care Act). Methods: In September 2014, CMS released the first five months (August 2013 to December 2013) of data disclosing physician-3 industry financial relationships. The frequency and value of non-research-related transfers in radiology were calculated and compared with those for 19 other specialties. Subanalyses of the frequency and value of such transfers in radiology were performed, based on state of licensure, radiologic subspecialty, nature of payment, manufacturer identity, and drug or device involved. Results: A total of 7.4% (2,654 of 35,768) of radiologists from the United States had reportable non-research-related financial relationship(s) with industry during the 5-month period, the second-lowest level among the medical specialties evaluated. The average value of non-research-related transfers of value to radiologists, excluding royalties and licenses, was low ($438.71; SD: $2,912.15; median: $43.85), with <4% of radiologists receiving >$10 per month. Of all categories, that of food and beverage had the most transfers of value (86.0%; 5,655 of 6,577); royalties and licensure were associated with the greatest average value ($27,072.34; SD: $67,524.92). Although high-value relationships were rare, 57.8% (26 of 45) of radiologists who received a value >$1,000 per month held leadership positions in imaging enterprises. Conclusions: Less than 4% of radiologists have non-research-related financial relationships with industry that are valued at >$10 per month, suggesting that meaningful, deleterious effects of such relationships on radiology practice, if present, are infrequent. C1 [Harvey, H. Benjamin; Alkasab, Tank K.; Pandharipande, V.; Prabhakar, Anand M.; Oklu, Rahmi; Rosenthal, Daniel I.; Hirsch, Joshua A.; Gazelle, G. Scott; Brink, James A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Harvey, H. Benjamin; Alkasab, Tank K.; Pandharipande, V.; Halpern, Elkan E.; Prabhakar, Anand M.; Oklu, Rahmi; Rosenthal, Daniel I.; Hirsch, Joshua A.; Gazelle, G. Scott; Brink, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Pandharipande, V.; Halpern, Elkan E.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA 02114 USA. EM hbharvey@partners.org NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2015 VL 12 IS 11 BP 1142 EP 1150 DI 10.1016/j.jacr.2015.04.017 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV4UV UT WOS:000364262900008 PM 26243797 ER PT J AU Kidwai, AS Abujudeh, HH AF Kidwai, Arif S. Abujudeh, Hani H. TI Radiologist Productivity Increases With Real-Time Monitoring: The Hawthorne Effect SO Journal of the American College of Radiology LA English DT Editorial Material C1 [Kidwai, Arif S.] Profound Radiol LLC, Jacksonville, FL 32256 USA. [Abujudeh, Hani H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kidwai, AS (reprint author), Profound Radiol LLC, 10348 Cypress Lakes Dr, Jacksonville, FL 32256 USA. EM kidwai@profoundradiology.com NR 7 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2015 VL 12 IS 11 BP 1151 EP 1154 DI 10.1016/j.jacr.2015.03.041 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV4UV UT WOS:000364262900009 PM 26208406 ER PT J AU Tuite, MJ Kransdorf, MJ Beaman, FD Adler, RS Amini, B Appel, M Bernard, SA Dempsey, ME Fries, IB Greenspan, BS Khurana, B Mosher, TJ Walker, EA Ward, RJ Wessell, DE Weissman, BN AF Tuite, Michael J. Kransdorf, Mark J. Beaman, Francesca D. Adler, Ronald S. Amini, Behrang Appel, Marc Bernard, Stephanie A. Dempsey, Molly E. Fries, Ian Blair Greenspan, Bennett S. Khurana, Bharti Mosher, Timothy J. Walker, Eric A. Ward, Robert J. Wessell, Daniel E. Weissman, Barbara N. TI ACR Appropriateness Criteria Acute Trauma to the Knee SO Journal of the American College of Radiology LA English DT Article DE Appropriateness criteria; knee injury; diagnostic imaging; radiograph; CT; MRI ID LATERAL PATELLAR DISLOCATION; TIBIAL PLATEAU FRACTURES; VIRTUAL NONCALCIUM TECHNIQUE; ANTERIOR CRUCIATE LIGAMENT; CLINICAL DECISION RULES; BONE-MARROW LESIONS; MENISCAL TEARS; COMPUTED-TOMOGRAPHY; IMAGING FINDINGS; LOCKED KNEE AB More than 500,000 visits to the emergency room occur annually in the United States, for acute knee trauma. Many of these are twisting injuries in young patients who can walk and bear weight, and emergent radiographs are not required. Several clinical decision rules have been devised that can considerably reduce the number of radiographs ordered without missing a clinically significant fracture. Although a fracture is seen on only 5% of emergency department knee radiographs, 86% of knee fractures result from blunt trauma. In patients with a fall or twisting injury who have focal tenderness, effusion, or inability to bear weight, radiographs should be the first imaging study obtained. If the radiograph shows no fracture, MRI is best for evaluating for a suspected meniscus or ligament tear, or the injuries from a reduced patellar dislocation. Patients with a knee dislocation should undergo radiographs and an MRI, as well as an angiographic study such as a fluoroscopic, CT, or MR angiogram. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures, by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Tuite, Michael J.] Univ Wisconsin Hosp, Madison, WI 53792 USA. [Kransdorf, Mark J.] Mayo Clin, Phoenix, AZ USA. [Beaman, Francesca D.] Univ Kentucky, Lexington, KY USA. [Adler, Ronald S.] NYU, Ctr Musculoskeletal Care, New York, NY USA. [Amini, Behrang] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Appel, Marc] James J Peters VA Med Ctr, Bronx, NY USA. [Appel, Marc] Amer Acad Orthopaed Surg, Rosemont, IL USA. [Bernard, Stephanie A.; Mosher, Timothy J.; Walker, Eric A.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Dempsey, Molly E.] Texas Scottish Rite Hosp Crippled Children, Dallas, TX USA. [Fries, Ian Blair] Chartered, Bone Spine & Hand Surg, Brick, NJ USA. [Greenspan, Bennett S.] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Khurana, Bharti; Weissman, Barbara N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ward, Robert J.] Tufts Med Ctr, Boston, MA USA. [Wessell, Daniel E.] Mayo Clin, Jacksonville, FL 32224 USA. RP Tuite, MJ (reprint author), Univ Wisconsin Hosp, Clin Sci Ctr E3 311, Dept Radiol, 600 Highland Ave, Madison, WI 53792 USA. EM mtuite@uwhealth.org FU Medical Metrics; Kensey Nash Corporation; Johnson and Johnson FX Timothy J. Mosher, MD, reported being a paid consultant for Medical Metrics and for Kensey Nash Corporation, and a stockholder with Johnson and Johnson. NR 69 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2015 VL 12 IS 11 BP 1164 EP 1172 DI 10.1016/j.jacr.2015.08.014 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV4UV UT WOS:000364262900012 PM 26541130 ER PT J AU Mehrotra, P Flynn, AW Jansen, K Tan, TC Mak, G Julien, HM Zeng, X Picard, MH Passeri, JJ Hung, J AF Mehrotra, Praveen Flynn, Aidan W. Jansen, Katrijn Tan, Timothy C. Mak, Gary Julien, Howard M. Zeng, Xin Picard, Michael H. Passeri, Jonathan J. Hung, Judy TI Differential Left Ventricular Outflow Tract Remodeling and Dynamics in Aortic Stenosis SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Left ventricular outflow tract; Aortic stenosis; Three-dimensional echocardiography; Dynamics; Stiffness ID PRESERVED EJECTION FRACTION; 3-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY; VALVE AREA; LOW-FLOW; CONTINUITY EQUATION; COMPUTED-TOMOGRAPHY; GEOMETRY; CT; CLASSIFICATION; ECCENTRICITY AB Background: Left ventricular outflow tract (LVOT) geometry is variable and often elliptical, which can affect aortic valve area calculation in patients with aortic stenosis (AS). Specific differences in LVOT geometry and dynamics between patients with AS and normal control subjects have not been described. The aim of this study was to test the hypothesis that differences in LVOT geometry in patients with AS might relate to variable LVOT remodeling and stiffness relative to normal control subjects. Methods: In 54 patients with severe AS and 33 control subjects without AS, LVOT geometry, dynamics, remodeling, and stiffness were assessed by three-dimensional transesophageal echocardiography. LVOT stiffness was measured by calculating the distensibility coefficient, defined as the percentage change in LVOT area relative to change in left ventricular pressure. LVOT remodeling was assessed by measuring the posterior LVOT wall thickness. Multivariate linear regression analysis was used to determine independent associations with peak systolic LVOT ellipticity. LVOT area by three-dimensional transesophageal echocardiographic planimetry was compared with areas obtained assuming circular or elliptical geometry. Results: At end-diastole, LVOT geometry was similar between patients with AS and normal control subjects. In patients with AS, however, the percentage change in cross-sectional area (7.5% vs 14.7%, P < .001) from end-diastole to peak systole was lower compared with normal control subjects, while peak systolic ellipticity index was higher in patients with AS (1.18 vs 1.08, P < .001). Compared with control subjects, patients with AS had lower distensibility coefficients (4.7 +/- 1.9 x 10(4) vs 12.5 +/- 5.3 x 10(4) mm Hg-1, P < .001) and higher posterior LVOT wall thickness (3.5 +/- 0.8 vs 2.3 +/- 0.5 mm, P < .001). In multivariate analysis, posterior LVOT wall thickness and distensibility coefficient were independently associated with peak systolic LVOT ellipticity index. LVOT area underestimation by transthoracic echocardiography was higher in patients with AS when assuming circular geometry (20% vs 12%, P = .001). Conclusions: The LVOT is less distensible and undergoes remodeling in severe AS. These changes lead to greater peak systolic ellipticity and greater LVOT cross-sectional area underestimation relative to normal control subjects. These findings have important implications for the assessment of AS severity. C1 [Mehrotra, Praveen; Flynn, Aidan W.; Jansen, Katrijn; Tan, Timothy C.; Mak, Gary; Zeng, Xin; Picard, Michael H.; Passeri, Jonathan J.; Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. [Mehrotra, Praveen; Flynn, Aidan W.; Jansen, Katrijn; Tan, Timothy C.; Mak, Gary; Zeng, Xin; Picard, Michael H.; Passeri, Jonathan J.; Hung, Judy] Harvard Univ, Sch Med, Boston, MA USA. [Julien, Howard M.] Thomas Jefferson Univ Hosp, Div Cardiol, Philadelphia, PA 19107 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 23 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 2015 VL 28 IS 11 BP 1259 EP 1266 DI 10.1016/j.echo.2015.07.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV7DY UT WOS:000364433800001 PM 26307374 ER PT J AU Koh, WJ Greer, BE Abu-Rustum, NR Apte, SM Campos, SM Cho, KR Chu, C Cohn, D Crispens, MA Dizon, DS Dorigo, O Eifel, PJ Fisher, CM Frederick, P Gaffney, DK George, S Han, E Higgins, S Huh, WK Lurain, JR Mariani, A Mutch, D Fader, AN Remmenga, SW Reynolds, RK Tillmanns, T Valea, FA Yashar, CM McMillian, NR Scavone, JL AF Koh, Wui-Jin Greer, Benjamin E. Abu-Rustum, Nadeem R. Apte, Sachin M. Campos, Susana M. Cho, Kathleen R. Chu, Christina Cohn, David Crispens, Marta Ann Dizon, Don S. Dorigo, Oliver Eifel, Patricia J. Fisher, Christine M. Frederick, Peter Gaffney, David K. George, Suzanne Han, Ernest Higgins, Susan Huh, Warner K. Lurain, John R., III Mariani, Andrea Mutch, David Fader, Amanda Nickles Remmenga, Steven W. Reynolds, R. Kevin Tillmanns, Todd Valea, Fidel A. Yashar, Catheryn M. McMillian, Nicole R. Scavone, Jillian L. TI Uterine Sarcoma, Version 1.2016 Featured Updates to the NCCN Guidelines SO Journal of the National Comprehensive Cancer Network LA English DT Article ID SOFT-TISSUE SARCOMA; ENDOMETRIAL STROMAL SARCOMA; PHASE-II TRIAL; GYNECOLOGIC-ONCOLOGY-GROUP; GRADE UNDIFFERENTIATED SARCOMAS; GEMCITABINE PLUS DOCETAXEL; OF-THE-LITERATURE; PROGNOSTIC-FACTORS; CENTER EXPERIENCE; HORMONAL-THERAPY AB The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes. (J Natl Compr Canc Netw 2015;13:1321-1331) C1 [Koh, Wui-Jin] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Greer, Benjamin E.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Abu-Rustum, Nadeem R.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Apte, Sachin M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Campos, Susana M.; George, Suzanne] Dana Farber Brigham Womens Canc Ctr, Boston, MA USA. [Cho, Kathleen R.; Reynolds, R. Kevin] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chu, Christina] Fox Chase Canc Ctr, Philadelphia, PA USA. [Cohn, David] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Cohn, David] Solove Res Inst, Columbus, OH USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Dorigo, Oliver] Stanford Canc Inst, Stanford, CA USA. [Eifel, Patricia J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fisher, Christine M.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Frederick, Peter] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gaffney, David K.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Han, Ernest] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Higgins, Susan] Yale Univ, Ctr Canc, Smilow Canc Hosp, New Haven, CT 06520 USA. [Huh, Warner K.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Lurain, John R., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Mutch, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Mutch, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Fader, Amanda Nickles] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Remmenga, Steven W.] Nebraska Med Ctr, Fred & Pamela Buffet Canc Ctr, Omaha, NE USA. [Tillmanns, Todd] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Valea, Fidel A.] Duke Canc Inst, Durham, NC USA. [Yashar, Catheryn M.] UC San Diego Moores Canc Ctr, San Diego, CA USA. [McMillian, Nicole R.; Scavone, Jillian L.] Natl Comprehens Canc Network, Washington, DC USA. RP Koh, WJ (reprint author), Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. FU Eisai; Bristol-Myers Squibb; Genentech BioOncology; Merck; Novartis Oncology; Novocure; Boehringer Ingelheim Pharmaceuticals, Inc. FX Supported by an educational grant from Eisai; a contribution from Exelixis Inc.; educational grants from Bristol-Myers Squibb, Genentech BioOncology, Merck, Novartis Oncology, Novocure; and by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc. NR 68 TC 4 Z9 7 U1 2 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2015 VL 13 IS 11 BP 1321 EP 1331 PG 11 WC Oncology SC Oncology GA CV5AL UT WOS:000364277500005 PM 26553763 ER PT J AU Kurzrock, R Colevas, AD Olszanski, A Akerley, W Arteaga, CL Carson, WE Clark, JW DiPersio, JF Ettinger, DS Morgan, RJ Schwartzberg, LS Venook, AP Gocke, CD Tait, J Stewart, FM AF Kurzrock, Razelle Colevas, A. Dimitrios Olszanski, Anthony Akerley, Wallace Arteaga, Carlos L. Carson, William E., III Clark, Jeffrey W. DiPersio, John F. Ettinger, David S. Morgan, Robert J., Jr. Schwartzberg, Lee S. Venook, Alan P. Gocke, Christopher D. Tait, Jonathan Stewart, F. Marc TI NCCN Oncology Research Program's Investigator Steering Committee and NCCN Best Practices Committee Molecular Profiling Surveys SO Journal of the National Comprehensive Cancer Network LA English DT Article ID LUNG-CANCER; CLINICAL-TRIALS; MEDICINE; PERSPECTIVES; THERAPY AB Background: With advances such as next-generation sequencing (NGS) increasing understanding of the basis of cancer and its response to treatment, NCCN believes it is important to understand how molecular profiling/diagnostic testing is being performed and used at NCCN Member Institutions and their community affiliates. Methods: The NCCN Oncology Research Program's Investigator Steering Committee and the NCCN Best Practices Committee gathered baseline information on the use of cancer-related molecular testing at NCCN Member Institutions and community members of the NCCN Affiliate Research Consortium through 2 separate surveys distributed in December 2013 and September 2014, respectively. Results: A total of 24 NCCN Member Institutions and 8 affiliate sites provided quantitative and qualitative data. In the context of these surveys, "molecular profiling/diagnostics" was defined as a panel of at least 10 genes examined as a diagnostic DNA test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Conclusions: Results indicated that molecular profiling/diagnostics are used at 100% of survey respondents' institutions to make patient care decisions. However, challenges relating to reimbursement, lack of data regarding actionable targets and targeted therapies, and access to drugs on or off clinical trials were cited as barriers to integration of molecular profiling into patient care. Frameworks for using molecular diagnostic results based on levels of evidence, alongside continued research into the predictive value of biomarkers and targeted therapies, are recommended to advance understanding of the role of genomic biomarkers. Greater evidence and consensus regarding the clinical and cost-effectiveness of molecular profiling may lead to broader insurance coverage and increased integration into patient care. (J Natl Compr Canc Netw 2015; 13: 1337-1346) C1 [Kurzrock, Razelle] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Colevas, A. Dimitrios] Stanford Canc Inst, Stanford, CA USA. [Olszanski, Anthony] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Arteaga, Carlos L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Carson, William E., III] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Carson, William E., III] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [Clark, Jeffrey W.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [DiPersio, John F.; Tait, Jonathan] Washington Univ, St Louis, MO USA. [Ettinger, David S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Morgan, Robert J., Jr.] City Hope Comprehens Canc Ctr, Los Angeles, CA USA. [Schwartzberg, Lee S.] West Clin, Memphis, TN USA. [Venook, Alan P.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Gocke, Christopher D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Stewart, F. Marc] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. RP Kurzrock, R (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr,MC 0658, La Jolla, CA 92093 USA. EM rkurzrock@ucsd.edu FU Sequenom; Merck; Serono; Genentech; Pfizer; Foundation Medicine, Inc.; Sequenom and Guardant Inc. FX Dr. Kurzrock has consultant fees from Sequenom and an ownership interest in RScueRx Inc. Dr. Kurzrock receives research funding from Merck, Serono, Genentech, Pfizer, Foundation Medicine, Inc., Sequenom and Guardant Inc. Dr. Olszanski participated in advisory boards for Takeda Oncology, Bristol-Myers Squibb, Merck & Co., Inc., and Celgene Corporation. Dr. Ettinger has served on a data safety monitoring board for ARIAD Pharmaceuticals, Inc. and as a consultant for Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., Golden Biotechnology Corp., Helsinn Therapeutics (U.S.), Inc., Eli Lilly and Company, Genentech, and Sandoz, Inc. Dr. Schwartzberg has a consulting agreement with Caris Life Sciences. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. NR 21 TC 3 Z9 3 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2015 VL 13 IS 11 BP 1337 EP 1346 PG 10 WC Oncology SC Oncology GA CV5AL UT WOS:000364277500006 PM 26553764 ER PT J AU Fossati, N Nguyen, DP Trinh, QD Sammon, J Sood, A Larcher, A Guazzoni, G Montorsi, F Briganti, A Menon, M Abdollah, F AF Fossati, Nicola Nguyen, Daniel P. Trinh, Quoc-Dien Sammon, Jesse Sood, Akshay Larcher, Alessandro Guazzoni, Giorgio Montorsi, Francesco Briganti, Alberto Menon, Mani Abdollah, Firas TI The Impact of Insurance Status on Tumor Characteristics and Treatment Selection in Contemporary Patients With Prostate Cancer SO Journal of the National Comprehensive Cancer Network LA English DT Article ID AFFORDABLE CARE ACT; RADICAL PROSTATECTOMY; ASSOCIATION; DISPARITIES; DIAGNOSIS; STAGE; RECURRENCE; GUIDELINE; SURVIVAL; DATABASE AB Background: Approximately 15% of the US population does not have health insurance. The objective of this study was to evaluate the impact of insurance status on tumor characteristics and treatment selection in patients with prostate cancer. Materials and Methods: We identified 20,393 patients younger than 65 years with prostate cancer in the 2010-2011 SEER database. Multivariable logistic regression analysis tested the relationship between insurance status and 2 end points: (1) presenting with low-risk prostate cancer at diagnosis and (2) receiving local treatment of the prostate. Locally weighted scatterplot smoothing methods were used to graphically explore the interaction among insurance status, use of local treatment, and baseline risk of cancer recurrence. The latter was defined using the Stephenson nomogram and CAPRA score. Results: Overall, 18,993 patients (93%) were insured, 849 (4.2%) had Medicaid coverage, and 551 (2.7%) were uninsured. At multivariable analysis, Medicaid coverage (odds ratio [OR], 0.67; 95% CI, 0.57, 0.80; P < .0001) and uninsured status (OR, 0.57; 95% CI, 0.46, 0.71; P < .0001) were independent predictors of a lower probability of presenting with low-risk disease. Likewise, Medicaid coverage (OR, 0.72; 95% CI, 0.60, 0.86; P = .0003) and uninsured status (OR, 0.45; 95% CI, 0.37, 0.55; P < .0001) were independent predictors of a lower probability of receiving local treatment. In uninsured patients, treatment disparities became more pronounced as the baseline cancer recurrence risk increased (10% in low-risk patients vs 20% in high-risk patients). Conclusions: Medicaid beneficiaries and uninsured patients are diagnosed with higher-risk disease and are undertreated. The latter is more accentuated for patients with high-risk prostate cancer. This may seriously compromise the survival of these individuals. (J Natl Compr Canc Netw 2015;13:1351-1358) C1 [Fossati, Nicola] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Fossati, Nicola; Larcher, Alessandro; Montorsi, Francesco; Briganti, Alberto] IRCCS Osped San Raffaele, URI, Div Oncol, Unit Urol, Milan, Italy. [Nguyen, Daniel P.] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA. [Trinh, Quoc-Dien] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sammon, Jesse; Sood, Akshay; Menon, Mani; Abdollah, Firas] Henry Ford Hosp, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Sammon, Jesse; Sood, Akshay; Menon, Mani; Abdollah, Firas] Henry Ford Hosp, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Guazzoni, Giorgio] Humanitas Univ, Clin & Res Hosp, Ist Clin Humanitas IRCCS, Dept Urol, Milan, Italy. RP Fossati, N (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 East 63rd St, New York, NY 10065 USA. EM nicola.fossati@gmail.com OI Fossati, Nicola/0000-0002-6816-3725; Larcher, Alessandro/0000-0002-5005-589X NR 29 TC 3 Z9 3 U1 1 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2015 VL 13 IS 11 BP 1351 EP 1358 PG 8 WC Oncology SC Oncology GA CV5AL UT WOS:000364277500007 PM 26553765 ER PT J AU Anderson, KC Alsina, M Atanackovic, D Biermann, JS Chandler, JC Costello, C Djulbegovic, B Fung, HC Gasparetto, C Godby, K Hofmeister, C Holmberg, L Holstein, S Huff, CA Kassim, A Krishnan, AY Kumar, SK Liedtke, M Lunning, M Raje, N Singhal, S Smith, C Somlo, G Stockerl-Goldstein, K Treon, SP Weber, D Yahalom, J Shead, DA Kumar, R AF Anderson, Kenneth C. Alsina, Melissa Atanackovic, Djordje Biermann, J. Sybil Chandler, Jason C. Costello, Caitlin Djulbegovic, Benjamin Fung, Henry C. Gasparetto, Cristina Godby, Kelly Hofmeister, Craig Holmberg, Leona Holstein, Sarah Huff, Carol Ann Kassim, Adetola Krishnan, Amrita Y. Kumar, Shaji K. Liedtke, Michaela Lunning, Matthew Raje, Noopur Singhal, Seema Smith, Clayton Somlo, George Stockerl-Goldstein, Keith Treon, Steven P. Weber, Donna Yahalom, Joachim Shead, Dorothy A. Kumar, Rashmi TI Multiple Myeloma, Version 2.2016 SO Journal of the National Comprehensive Cancer Network LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; THALIDOMIDE PLUS DEXAMETHASONE; DONOR LYMPHOCYTE INFUSIONS; NEWLY-DIAGNOSED MYELOMA; TERM-FOLLOW-UP; RANDOMIZED CONTROLLED-TRIAL; POSITRON-EMISSION-TOMOGRAPHY; BONE-MARROW-TRANSPLANTATION; NATIONAL-CANCER-INSTITUTE AB Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM. (J Natl Compr Canc Netw 2015;13:1398-1435) C1 [Anderson, Kenneth C.; Treon, Steven P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Alsina, Melissa; Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Atanackovic, Djordje] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Biermann, J. Sybil] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chandler, Jason C.] St Jude Childrens Res Hosp, Memphis, TN USA. [Chandler, Jason C.] Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. [Costello, Caitlin] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Fung, Henry C.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Gasparetto, Cristina] Duke Canc Inst, Durham, NC 27710 USA. [Godby, Kelly] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Hofmeister, Craig] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Holmberg, Leona] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Holmberg, Leona] Seattle Canc Care Alliance, Seattle, WA USA. [Holstein, Sarah] Roswell Pk Canc Inst, Buffalo, NY USA. [Huff, Carol Ann] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Kassim, Adetola] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Krishnan, Amrita Y.; Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Kumar, Shaji K.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Liedtke, Michaela] Stanford Canc Inst, Stanford, CA USA. [Lunning, Matthew] Nebraska Med Ctr, Fred & Pamela Buffet Canc Ctr, Omaha, NE USA. [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Singhal, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Smith, Clayton] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Stockerl-Goldstein, Keith] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Weber, Donna] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. RP Anderson, KC (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. RI Hofmeister, Craig/E-3256-2011; Djulbegovic, Benjamin/I-3661-2012 OI Hofmeister, Craig/0000-0003-4816-1607; Djulbegovic, Benjamin/0000-0003-0671-1447 FU NCI NIH HHS [R01 CA174951] NR 203 TC 7 Z9 9 U1 0 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2015 VL 13 IS 11 BP 1398 EP 1435 PG 38 WC Oncology SC Oncology GA CV5AL UT WOS:000364277500010 PM 26553768 ER PT J AU Deforche, L Roose, E Vandenbulcke, A Vandeputte, N Feys, HB Springer, TA Mi, LZ Muia, J Sadler, JE Soejima, K Rottensteiner, H Deckmyn, H De Meyer, SF Vanhoorelbeke, K AF Deforche, L. Roose, E. Vandenbulcke, A. Vandeputte, N. Feys, H. B. Springer, T. A. Mi, L. Z. Muia, J. Sadler, J. E. Soejima, K. Rottensteiner, H. Deckmyn, H. De Meyer, S. F. Vanhoorelbeke, K. TI Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS-13 SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ADAMTS-13 protein; human; allosteric regulation; autoantibodies; protein conformation; von Willebrand factor ID VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; CRYSTAL-STRUCTURES; ENDOTHELIAL-CELLS; CATALYTIC DOMAIN; INDUCED CLEAVAGE; SHEAR-STRESS; VWF; PROTEIN; FLOW AB Background: Recently, conformational activation of ADAMTS-13 was identified. This mechanism showed the evolution from a condensed conformation, in which the proximal MDTCS and distal T2-CUB2 domains are in close contact with each other, to an activated, open structure due to binding with von Willebrand factor (VWF). Objectives: Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS-13. Methods: The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined with ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through rapid automatic detection and alignment of repeats (RADAR) analysis, tested with ELISA using deletion variants and visualized using electron microscopy. Results: Eleven activating anti-ADAMTS-13 antibodies, directed against the T5-CUB2 domains, were identified in the FRETS-VWF73 assay. RADAR analysis identified three linker regions in the distal domains. Interestingly, identification of an antibody recognizing a cryptic epitope in the metalloprotease domain confirmed the contribution of these linker regions to conformational activation of the enzyme. The proof of flexibility around both the T2 and metalloprotease domains, as shown by by electron microscopy, further supported this contribution. In addition, cryptic epitope exposure was identified in the distal domains, because activating anti-T2-CUB2 antibodies increased the binding to folded VWF up to similar to 3-fold. Conclusion: Conformational activation of ADAMTS-13 leads to cryptic epitope/exosite exposure in both proximal and distal domains, subsequently inducing increased activity. Furthermore, three linker regions in the distal domains are responsible for flexibility and enable the interaction between the proximal and the T8-CUB2 domains. C1 [Deforche, L.; Roose, E.; Vandenbulcke, A.; Vandeputte, N.; Deckmyn, H.; De Meyer, S. F.; Vanhoorelbeke, K.] KU Leuven Kulak, IRF Life Sci, Lab Thrombosis Res, B-8500 Kortrijk, Belgium. [Feys, H. B.] Belgian Red Cross Flanders, Transfus Res Ctr, Ghent, Belgium. [Springer, T. A.; Mi, L. Z.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA USA. [Springer, T. A.; Mi, L. Z.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Muia, J.; Sadler, J. E.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Muia, J.; Sadler, J. E.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [Soejima, K.] Chemoserotherapeut Res Inst, Kikuchi, Kumamoto, Japan. [Rottensteiner, H.] Baxter Innovat GmbH, Vienna, Austria. RP Vanhoorelbeke, K (reprint author), KU Leuven Kulak, IRF Life Sci, Lab Thrombosis Res, Etienne Sabbelaan 53, B-8500 Kortrijk, Belgium. EM karen.vanhoorelbeke@kuleuven-kulak.be RI Mi, Li-Zhi/B-1371-2016; Deckmyn, Hans/L-9434-2015; OI Mi, Li-Zhi/0000-0001-9907-5245; Deckmyn, Hans/0000-0003-3952-5501; Vanhoorelbeke, Karen/0000-0003-2288-8277; Muia, Joshua/0000-0001-5011-2420 FU Agency for Innovation by Science and Technology (IWT, ) Flanders, Belgium [IWT-SB/111507]; 'Fonds voor Wetenschappelijk Onderzoek' (FWO, ) Flanders, Belgium [G.0548.11]; National Institutes of Health [R01 HL72917, R01 HL89746, U54 HL112303, T32 HL007088] FX This work was funded by a PhD grant from the Agency for Innovation by Science and Technology (IWT, ) Flanders, Belgium (IWT-SB/111507, awarded to L. Deforche), and a grant from the 'Fonds voor Wetenschappelijk Onderzoek' (FWO, ) Flanders, Belgium (G.0548.11, awarded to K. Vanhoorelbeke). This work was also supported by National Institutes of Health grants (grants.nih.gov/) R01 HL72917, R01 HL89746, U54 HL112303 and T32 HL007088 (awarded to J. E. Sadler). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank I. Pareyn for the development of the mAbs. NR 44 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD NOV PY 2015 VL 13 IS 11 BP 2063 EP 2075 DI 10.1111/jth.13149 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CW1VB UT WOS:000364778700015 PM 26391536 ER PT J AU Wojak, JC Abruzzo, TA Bello, JA Blackham, KA Hirsch, JA Jayaraman, MV Dariushnia, SR Meyers, PM Midia, M Russell, EJ Walker, TG Nikolic, B AF Wojak, Joan C. Abruzzo, Todd A. Bello, Jacqueline A. Blackham, Kristine Ann Hirsch, Joshua A. Jayaraman, Mahesh V. Dariushnia, Sean R. Meyers, Philip M. Midia, Mehran Russell, Eric J. Walker, T. Gregory Nikolic, Boris TI Quality Improvement Guidelines for Adult Diagnostic Cervicocerebral Angiography: Update Cooperative Study between the Society of Interventional Radiology (SIR), American Society of Neuroradiology (ASNR), and Society of NeuroInterventional Surgery (SNIS) SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; INTERNAL CAROTID-ARTERY; BALLOON TEST OCCLUSION; ACUTE ISCHEMIC-STROKE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; MAGNETIC-RESONANCE ANGIOGRAPHY; MULTIDETECTOR CT ANGIOGRAPHY; 3D ROTATIONAL ANGIOGRAPHY; CEREBRAL ARTERIOVENOUS-MALFORMATIONS; SUBARACHNOID HEMORRHAGE C1 [Wojak, Joan C.] Our Lady Lourdes Reg Med Ctr, Dept Radiol, Lafayette, LA USA. [Abruzzo, Todd A.] Univ Cincinnati, Dept Neurosurg, Cincinnati, OH USA. [Bello, Jacqueline A.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Radiol, Bronx, NY 10467 USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. [Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA. [Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Dept Neurol Surg, New York, NY 10032 USA. [Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Inst Neurol, New York, NY 10032 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Jayaraman, Mahesh V.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Diagnost Imaging & Neurosurg, Providence, RI 02903 USA. [Dariushnia, Sean R.] Emory Univ, Sch Med, Dept Radiol Intervent Radiol & Image Guided Med, Atlanta, GA USA. [Russell, Eric J.] Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. [Blackham, Kristine Ann] Univ Basel Hosp, Dept Radiol, CH-4031 Basel, Switzerland. [Midia, Mehran] McMaster Med Ctr, Dept Diagnost Imaging, Burlington, ON, Canada. RP Wojak, JC (reprint author), SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM woji@msn.com NR 208 TC 1 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2015 VL 26 IS 11 BP 1596 EP 1608 DI 10.1016/j.jvir.2015.07.002 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CV9PQ UT WOS:000364619500002 PM 26372000 ER PT J AU Marcia, S Hirsch, JA Chandra, RV Marras, M Piras, E Anselmetti, GC Muto, M Saba, L AF Marcia, Stefano Hirsch, Joshua A. Chandra, Ronil V. Marras, Mariangela Piras, Emanuele Anselmetti, Giovanni Carlo Muto, Mario Saba, Luca TI Midterm Clinical and Radiologic Outcomes after Percutaneous Interspinous Spacer Treatment for Neurogenic Intermittent Claudication SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID LUMBAR SPINAL STENOSIS; 2-YEAR FOLLOW-UP; QUALITY-OF-LIFE; X-STOP DEVICE; DEGENERATIVE SPONDYLOLISTHESIS; PROCESS DECOMPRESSION; SURGERY; SYSTEM AB Purpose: To evaluate the midterm clinical and radiologic outcome of percutaneous interspinous process spacer (IPS) treatment, for neurogenic intermittent claudication (NIC) in patients who fail conservative treatment. Methods: Consecutive patients with NIC, lumbar spinal stenosis confirmed on magnetic resonance imaging, failure of conservative management for at least 6 months, and treatment with percutaneous IPS were included. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores were recorded at baseline, 1 month, 1 year and 3 years after treatment. Spinal canal and foraminal cross-sectional areas were calculated from multidetector computed tomography at baseline and 1 year. Results: There were 80 patients treated with 94 IPS devices; 83% of patients received a single [PS; 78% of IPS devices were placed at L4-L5. An [PS dislocation was the single periprocedural major complication. VAS score of 8.1 +/- 2 before treatment was reduced to 4.4 +/- 2 at 1 month after treatment (P = .0001); ODI score of 23.3 +/- 10 before treatment was reduced to 11.7 +/- 8.5 at 1 month after treatment (P = .0001). These significant reductions were durable at 1-year and 3-year follow-up evaluations (P < .01). Spinal canal and foraminal cross-sectional area increased by 15% at 1 year (P = .0001). Conclusions: Patients with MC who failed conservative treatment and were treated with percutaneous [PS achieved significant gains in pain relief and reduced disability that remained durable at 3-year clinical follow-up evaluation., This outcome was accompanied by significant increases in spinal canal and foraminal cross-sectional areas at the treated level. C1 [Marcia, Stefano; Piras, Emanuele] SS Trinita Hosp, Dept Radiol, Cagliari, Italy. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendovasc Program,Dept Radiol, Boston, MA USA. [Chandra, Ronil V.] Monash Univ, Monash Hlth, Neurovasc Surg Serv, Melbourne, Vic 3004, Australia. [Chandra, Ronil V.] Monash Univ, Monash Hlth, Serv Neuroradiol, Melbourne, Vic 3004, Australia. [Anselmetti, Giovanni Carlo] Villa Maria Hosp, Intervent Radiol, Turin, Italy. [Muto, Mario] Osped Cardarelli, Dept Neuroradiol, Naples, Italy. [Marras, Mariangela] Osped Microcitem, Dept Radiol, Cagliari, Italy. [Saba, Luca] AOU, Dept Radiol, I-09045 Cagliari, Italy. RP Saba, L (reprint author), AOU, Dept Radiol, Cagliari Polo Monserrato Ss 554 Monserrato, I-09045 Cagliari, Italy. EM lucasaba@tiscali.it NR 24 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 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2015 VL 26 IS 11 BP 1687 EP 1693 DI 10.1016/j.jvir.2015.05.011 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA CV9PQ UT WOS:000364619500015 PM 26119203 ER PT J AU Adams, SA Choi, SK Eberth, JM Friedman, DB Yip, MP Tucker-Seeley, RD Wigfall, LT Hebert, JR AF Adams, Swann Arp Choi, Seul Ki Eberth, Jan M. Friedman, Daniela B. Yip, Mei Po Tucker-Seeley, Reginald D. Wigfall, Lisa T. Hebert, James R. TI Is Availability of Mammography Services at Federally Qualified Health Centers Associated with Breast Cancer Mortality-to-Incidence Ratios? An Ecological Analysis SO JOURNAL OF WOMENS HEALTH LA English DT Article ID FARMERS MARKET; UNITED-STATES; CARE ACCESS; FOLLOW-UP; STAGE; DISPARITIES; DIAGNOSIS; INTERVENTION; PARTNERSHIPS; WOMEN AB Objective: Mammography is the most effective method to detect breast cancer in its earliest stages, reducing the risk of breast cancer death. We investigated the relationship between accessibility of mammography services at Federally Qualified Health Centers (FQHCs) and mortality-to-incidence ratio (MIR) of breast cancer in each county in the United States. Methods: County-level breast cancer mortality and incidence rates in 2006-2010 were used to estimate MIRs. We compared breast cancer MIRs based on the density and availability of FQHC delivery sites with or without mammography services both in the county and in the neighboring counties. Results: The relationship between breast cancer MIRs and access to mammography services at FQHCs differed by race and county of residence. Breast cancer MIRs were lower in counties with mammography facilities or FQHC delivery sites than in counties without a mammography facility or FQHC delivery site. This trend was stronger in urban counties (p=0.01) and among whites (p=0.008). Counties with a high density of mammography facilities had lower breast cancer MIRs than other counties, specifically in urban counties (p=0.01) and among whites (p=0.01). Breast cancer MIR for blacks was the lowest in counties having mammography facilities; and was highest in counties without a mammography facility within the county or the neighboring counties (p=0.03). Conclusions: Mammography services provided at FQHCs may have a positive impact on breast cancer MIRs. Expansion of services provided at the FQHCs and placement of FQHCs in additional underserved areas might help to reduce cancer disparities in the United States. C1 [Adams, Swann Arp; Choi, Seul Ki; Eberth, Jan M.; Friedman, Daniela B.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Canc Prevent & Control Program, Columbia, SC 29208 USA. [Adams, Swann Arp; Eberth, Jan M.; Hebert, James R.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Choi, Seul Ki; Friedman, Daniela B.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Wigfall, Lisa T.] Univ S Carolina, Arnold Sch Publ Hlth, Inst Partnerships Eliminate Hlth Dispar, Columbia, SC 29208 USA. [Adams, Swann Arp] Univ S Carolina, Coll Nursing, Columbia, SC 29208 USA. [Yip, Mei Po] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [Tucker-Seeley, Reginald D.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Tucker-Seeley, Reginald D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Adams, SA (reprint author), Univ S Carolina, Canc Prevent & Control Program, 915 Greene St,Rm 244, Columbia, SC 29208 USA. EM swann.adams@sc.edu RI Eberth, Jan/A-1335-2014 OI Eberth, Jan/0000-0001-9500-4212 FU Centers for Disease Control and Prevention (Prevention Research Centers) [U48/DP001936, U48/DP005000-01S2]; National Cancer Institute (NCI); NCI [R01 CA 124397]; Established Investigator Award in Cancer Prevention and Control from the Cancer Training Branch of the NCI [K05 CA136975]; Cancer Network Program Center grant from the NCI [1U54 CA153461-01]; NCI K01 Career Development Grant [1K01CA169041-01] FX This publication was supported by Cooperative Agreement Number U48/DP001936 and U48/DP005000-01S2 from the Centers for Disease Control and Prevention (Prevention Research Centers) and the National Cancer Institute (NCI) (PIs: Dr. Hebert, Dr. Friedman). Dr. Yip was partially supported by the NCI (R01 CA 124397; PI: S-P Tu). This work also was partially supported by an Established Investigator Award in Cancer Prevention and Control from the Cancer Training Branch of the NCI to Dr. Hebert (K05 CA136975), a Cancer Network Program Center grant from the NCI [(1U54 CA153461-01 Hebert, JR (PI)], and an NCI K01 Career Development Grant to Dr. Tucker-Seeley (1K01CA169041-01). NR 49 TC 2 Z9 2 U1 5 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD NOV 1 PY 2015 VL 24 IS 11 BP 916 EP 923 DI 10.1089/jwh.2014.5114 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA CV6SI UT WOS:000364400300010 PM 26208105 ER PT J AU Motzer, RJ Hutson, TE Glen, H Michaelson, MD Molina, A Eisen, T Jassem, J Zolnierek, J Maroto, JP Mellado, B Melichar, B Tomasek, J Kremer, A Kim, HJ Wood, K Dutcus, C Larkin, J AF Motzer, Robert J. Hutson, Thomas E. Glen, Hilary Michaelson, M. Dror Molina, Ana Eisen, Timothy Jassem, Jacek Zolnierek, Jakub Pablo Maroto, Jose Mellado, Begona Melichar, Bohuslav Tomasek, Jiri Kremer, Alton Kim, Han-Joo Wood, Karen Dutcus, Corina Larkin, James TI Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial SO LANCET ONCOLOGY LA English DT Article ID ANTITUMOR ACTIVITIES; INTERFERON-ALPHA; III TRIAL; BEVACIZUMAB; INHIBITOR; GROWTH; E7080; TEMSIROLIMUS; SORAFENIB; TARGETS AB Background Currently, metastatic renal cell carcinoma is treated with sequential single agents targeting VEGF or mTOR. Here, we aimed to assess lenvatinib, everolimus, or their combination as second-line treatment in patients with metastatic renal cell carcinoma. Methods We did a randomised, phase 2, open-label, multicentre trial at 37 centres in five countries and enrolled patients with advanced or metastatic, clear-cell, renal cell carcinoma. We included patients who had received treatment with a VEGF-targeted therapy and progressed on or within 9 months of stopping that agent. Patients were randomised via an interactive voice response system in a 1:1:1 ratio to either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively) administered orally in continuous 28-day cycles until disease progression or unacceptable toxic effects. The randomisation procedure dynamically minimised imbalances between treatment groups for the stratification factors haemoglobin and corrected serum calcium. The primary objective was progression-free survival in the intention-to-treat population. This study is closed to enrolment but patients' treatment and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT01136733. Findings Between March 16, 2012, and June 19, 2013, 153 patients were randomly allocated to receive either the combination of lenvatinib plus everolimus (n=51), single-agent lenvatinib (n=52), or single-agent everolimus (n=50). Lenvatinib plus everolimus significantly prolonged progression-free survival compared with everolimus alone (median 14.6 months [95% CI 5.9-20.1] vs 5.5 months [3.5-7.1]; hazard ratio [HR] 0.40, 95% CI 0.24-0.68; p=0.0005), but not compared with lenvatinib alone (7.4 months [95% CI 5.6-10.2]; HR 0.66, 95% CI 0.30-1.10; p=0.12). Single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone (HR 0.61, 95% CI 0.38-0.98; p=0.048). Grade 3 and 4 events occurred in fewer patients allocated single-agent everolimus (25 [50%]) compared with those assigned lenvatinib alone (41 [79%]) or lenvatinib plus everolimus (36 [71%]). The most common grade 3 or 4 treatment-emergent adverse event in patients allocated lenvatinib plus everolimus was diarrhoea (ten [20%]), in those assigned single-agent lenvatinib it was proteinuria (ten [19%]), and in those assigned single-agent everolimus it was anaemia (six [12%]). Two deaths were deemed related to study drug, one cerebral haemorrhage in the lenvatinib plus everolimus group and one myocardial infarction with single-agent lenvatinib. Interpretation Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma. C1 [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hutson, Thomas E.] Texas Oncol, Dallas, TX USA. [Glen, Hilary] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Molina, Ana] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. [Eisen, Timothy] Addenbrookes Hosp, Cambridge Biomed Res Ctr, Cambridge, England. [Jassem, Jacek] Med Univ Gdansk, Gdansk, Poland. [Zolnierek, Jakub] Inst Warszawie, Ctr Onkol, Warsaw, Poland. [Pablo Maroto, Jose] Dept Med Oncol, Barcelona, Spain. [Mellado, Begona] Hosp Clin Barcelona, IDIBAPS, Dept Med Oncol, Translat Genom & Targeted Therapeut Solid Tumors, Barcelona, Spain. [Melichar, Bohuslav] Univ Palackeho, Fak Nemocnice, Lekarska Fak, Onkol Klin, Olomouc, Czech Republic. [Tomasek, Jiri] Masaryk Univ, Masaryk Mem Canc Inst, Brno, Czech Republic. [Kremer, Alton; Kim, Han-Joo; Dutcus, Corina] Eisai Inc, Woodcliff Lake, NJ USA. [Wood, Karen] Eisai Ltd, Hatfield, Herts, England. [Larkin, James] Royal Marsden Hosp NHS Fdn Trust, London, England. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. EM motzerr@mskcc.org OI Michaelson, Dror/0000-0001-9249-6338 FU Eisai FX This study was funded by Eisai. We thank patients and their families and all investigators and their teams who took part in the study. Investigators and sites involved in the study are listed in the appendix. We also thank Min Ren (Eisai Inc) for his contribution to this report. Editorial assistance was provided by Suhaida A Selamat and Brian Falcone (Oxford PharmaGenesis), funded by Eisai. NR 24 TC 72 Z9 75 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2015 VL 16 IS 15 BP 1473 EP 1482 DI 10.1016/S1470-2045(15)00290-9 PG 10 WC Oncology SC Oncology GA CV7RE UT WOS:000364470900030 PM 26482279 ER PT J AU Kroger, NM Deeg, JH Olavarria, E Niederwieser, D Bacigalupo, A Barbui, T Rambaldi, A Mesa, R Tefferi, A Griesshammer, M Gupta, V Harrison, C Alchalby, H Vannucchi, AM Cervantes, F Robin, M Ditschkowski, M Fauble, V McLornan, D Ballen, K Popat, UR Passamonti, F Rondelli, D Barosi, G AF Kroeger, N. M. Deeg, J. H. Olavarria, E. Niederwieser, D. Bacigalupo, A. Barbui, T. Rambaldi, A. Mesa, R. Tefferi, A. Griesshammer, M. Gupta, V. Harrison, C. Alchalby, H. Vannucchi, A. M. Cervantes, F. Robin, M. Ditschkowski, M. Fauble, V. McLornan, D. Ballen, K. Popat, U. R. Passamonti, F. Rondelli, D. Barosi, G. TI Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group SO LEUKEMIA LA English DT Review ID BONE-MARROW-TRANSPLANTATION; PROGNOSTIC SCORING SYSTEM; PRETRANSPLANTATION SERUM FERRITIN; AGNOGENIC MYELOID METAPLASIA; REDUCED-INTENSITY; MYELOPROLIFERATIVE NEOPLASMS; LEUKEMIC TRANSFORMATION; EUROPEAN GROUP; IRON OVERLOAD; ESSENTIAL THROMBOCYTHEMIA AB The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age < 70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age < 65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) 42%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2-or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted. C1 [Kroeger, N. M.; Alchalby, H.] Univ Hamburg Hosp, Dept Stem Cell Transplantat, Hamburg, Germany. [Deeg, J. H.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Clin Res Div, Seattle, WA 98195 USA. [Olavarria, E.] Hosp Navarra, Dept Hematol, Navarra Hlth Serv, Pamplona, Spain. [Niederwieser, D.] Univ Leipzig, Dept Haematol Clin Oncol & Hemostasiol, D-04109 Leipzig, Germany. [Bacigalupo, A.] Osped San Martino Genova, Genoa, Italy. [Barbui, T.] Osped Papa Giovanni XXIII, Res Fdn, Bergamo, Italy. [Rambaldi, A.] Osped Papa Giovanni XXIII, Hematol & Bone Marrow Transplant Unit, Bergamo, Italy. [Mesa, R.] Mayo Clin, Div Hematol & Oncol, Scottsdale, AZ USA. [Tefferi, A.] Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA. [Griesshammer, M.] Johannes Wesling Teaching Hosp, Acad Dept Hematol & Oncol, Minden, Germany. [Gupta, V.] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Harrison, C.; McLornan, D.] Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England. [Vannucchi, A. M.] Univ Florence, Dept Expt & Clin Med, Florence, Italy. [Cervantes, F.] Univ Barcelona, IDIBAPS, Hosp Clin, Barcelona, Spain. [Robin, M.] St Louis Hosp, Dept Hematol & Bone Marrow Transplantat, Paris, France. [Ditschkowski, M.] Univ Hosp Essen, Ctr Comprehens Canc, WTZ, Dept Bone Marrow Transplantat, Essen, Germany. [Fauble, V.] Mayo Clin, Ctr Canc, Scottsdale, AZ USA. [McLornan, D.] Kings Coll Hosp London, Dept Haematol Med, London, England. [Ballen, K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Popat, U. R.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Passamonti, F.] Osped Circolo Varese, Univ Hosp, Dept Med, Div Hematol, Varese, Italy. [Passamonti, F.] Fdn Macchi, Varese, Italy. [Rondelli, D.] Univ Illinois, Hosp & Hlth Sci Syst, Chicago, IL USA. [Rondelli, D.] Univ Illinois, Ctr Canc, Chicago, IL USA. [Barosi, G.] IRCCS Policlin S Matteo Fdn, Ctr Study Myelofibrosis, Pavia, Italy. RP Barosi, G (reprint author), Fdn IRCCS Policlin S Matteo Fdn, Ctr Study Myelofibrosis, Viale Golgi 19, I-27100 Pavia, Italy. EM barosig@smatteo.pv.it OI Passamonti, Francesco/0000-0001-8068-5289 FU Sanofi; Novartis; Incyte; Gilead; Genentech; Biosciences; CTI Pharma; Otsuka FX NMK declares speakers' bureau and research funding from Sanofi and Novartis; FC declares consulting and speakers' bureau from Novartis, AOP and Baxter; DM declares honoraria, speakers' bureau and research funding from Novartis; AR declares consulting from Piere Fabre Pharma, and Travels from Piere Fabre Pharma and Novartis; EO declares travel expenses for Novartis, Bristol Meyers Squibb and Sanofi; CH declares honoraria and speakers' bureau from Novartis, Sanofi and Shire. GB declares consulting from Celgene; DN declares speakers' bureau and travels from Novartis; TB declares consulting, speakers' bureau from Novartis and Shire; RM declares honoraria and consulting from Novartis, and funding from Incyte, Gilead, Genentech; VG declares honoraria, consulting, and research funding from Novartis and Incyte; AMV declares consulting and speakers' bureau from Novartis; MD declares consulting from MSD Sharp and Dohme, and research funding from Biosciences; URP declares research funding from CTI Pharma and Otsuka; DR declares consulting from Incyte, and speakers' bureau from Sanofi. The remaining authors declare no conflict of interest. NR 67 TC 26 Z9 27 U1 0 U2 9 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 2015 VL 29 IS 11 BP 2126 EP 2133 DI 10.1038/leu.2015.233 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA CV8IR UT WOS:000364527400002 PM 26293647 ER PT J AU Morelli, E Leone, E Cantafio, MEG Di Martino, MT Amodio, N Biamonte, L Gulla, A Foresta, U Pitari, MR Botta, C Rossi, M Neri, A Munshi, NC Anderson, KC Tagliaferri, P Tassone, P AF Morelli, E. Leone, E. Cantafio, M. E. Gallo Di Martino, M. T. Amodio, N. Biamonte, L. Gulla, A. Foresta, U. Pitari, M. R. Botta, C. Rossi, M. Neri, A. Munshi, N. C. Anderson, K. C. Tagliaferri, P. Tassone, P. TI Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo SO LEUKEMIA LA English DT Article ID ANTITUMOR-ACTIVITY; TUMOR-SUPPRESSOR; C-MYC; DOWN-REGULATION; CELL-DEATH; EXPRESSION; INHIBITION; MICRORNAS; PATHOGENESIS; APOPTOSIS AB Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-MM activity of miR-125b-5p was mediated via direct downregulation of IRF4 and its downstream effector BLIMP-1. Moreover, inhibition of IRF4 translated into downregulation of c-Myc, caspase-10 and cFlip, relevant IRF4-downstream effectors. Finally, in vivo intra-tumor or systemic delivery of formulated miR-125b-5p mimics against human MM xenografts in severe combined immunodeficient/non-obese diabetic mice induced significant anti-tumor activity and prolonged survival. Taken together, our findings provide evidence that miR-125b, differently from other hematologic malignancies, has tumor-suppressor activity in MM. Furthermore, our data provide proof-of-concept that synthetic miR-125b-5p mimics are promising anti-MM agents to be validated in early clinical trials. C1 [Morelli, E.; Leone, E.; Cantafio, M. E. Gallo; Di Martino, M. T.; Amodio, N.; Biamonte, L.; Gulla, A.; Foresta, U.; Pitari, M. R.; Botta, C.; Rossi, M.; Tagliaferri, P.; Tassone, P.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy. [Neri, A.] Univ Milan, Dept Med Sci, IRCCS Policlin Fdn, Hematol 1, Milan, Italy. [Munshi, N. C.; Anderson, K. C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Munshi, N. C.] VA Boston Healthcare Syst, Boston, MA USA. [Tassone, P.] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA. RP Tassone, P (reprint author), Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Med Oncol, Viale Europa, I-88100 Catanzaro, Italy. EM tassone@unicz.it RI Amodio, Nicola/K-7335-2016; OI Amodio, Nicola/0000-0002-1345-4410; neri, antonino/0000-0001-9047-5912; ROSSI, Marco/0000-0002-7258-475X; Botta, Cirino/0000-0002-1522-4504 FU funds of Italian Association for Cancer Research (AIRC), PI [9980]; NIH [PO1-155258, RO1-124929, P50-100007, PO1-78378]; VA merit grant [IO1-24467]; 'Fondazione Umberto Veronesi' post-doctoral fellowship FX This work has been supported by funds of Italian Association for Cancer Research (AIRC), PI: PT. 'Special Program Molecular Clinical Oncology-5 per mille' n. 9980, 2010/15. This work has also been supported by a grant from NIH PO1-155258, RO1-124929, P50-100007, PO1-78378 and VA merit grant IO1-24467. Nicola Amodio was supported by a 'Fondazione Umberto Veronesi' post-doctoral fellowship. NR 51 TC 18 Z9 18 U1 2 U2 6 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 2015 VL 29 IS 11 BP 2173 EP 2183 DI 10.1038/leu.2015.124 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA CV8IR UT WOS:000364527400007 PM 25987254 ER PT J AU Jagannathan, S Abdel-Malek, MAY Malek, E Vad, N Latif, T Anderson, K Driscoll, JJ AF Jagannathan, S. Abdel-Malek, M. A. Y. Malek, E. Vad, N. Latif, T. Anderson, K. C. Driscoll, J. J. TI Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib SO LEUKEMIA LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; STEM-LIKE CELLS; MULTIPLE-MYELOMA; ER STRESS; DIABETIC-PATIENTS; DRUG-RESISTANCE; SIDE POPULATION; DOWN-REGULATION; GASTRIC-CANCER AB Although the therapeutic benefit of proteasome inhibition in multiple myeloma remains unchallenged, drug resistance inevitably emerges through mechanisms that remain elusive. Bortezomib provokes unwanted protein accumulation and the endoplasmic reticulum stress to activate the unfolded protein response (UPR) and autophagy as compensatory mechanisms that restore protein homeostasis. High-throughput screens to detect pharmacologics that modulated autophagy to enhance the anti-myeloma effect of bortezomib revealed metformin, a widely used antidiabetic agent with proven efficacy and limited adverse effects. Metformin co-treatment with bortezomib suppressed induction of the critical UPR effector glucose-regulated protein 78 (GRP78) to impair autophagosome formation and enhance apoptosis. Gene expression profiling of newly diagnosed myeloma patient tumors further correlated the hyperexpression of GRP78-encoding HSPA5 with reduced clinical response to bortezomib. The effect of bortezomib was enhanced with metformin co-treatment using myeloma patient tumor cells and the chemoresistant, stem cell-like side population that may contribute to disease recurrence. The relevance of the findings was confirmed in vivo as shown by metformin co-treatment with bortezomib that delayed the growth of myeloma xenotransplants. Taken together, our results suggest that metformin suppresses GRP78, a key driver of bortezomib-induced autophagy, and support the pharmacologic repositioning of metformin to enhance the anti-myeloma benefit of bortezomib. C1 [Jagannathan, S.; Abdel-Malek, M. A. Y.; Malek, E.; Vad, N.; Driscoll, J. J.] Univ Cincinnati, Coll Med, Vontz Ctr Mol Studies, Div Hematol & Oncol, Cincinnati, OH 45267 USA. [Jagannathan, S.; Abdel-Malek, M. A. Y.; Malek, E.; Vad, N.; Latif, T.; Driscoll, J. J.] Univ Cincinnati, Coll Med, Div Hematol & Oncol, Cincinnati, OH 45267 USA. [Latif, T.; Driscoll, J. J.] Univ Cincinnati, Inst Canc, Cincinnati, OH 45267 USA. [Anderson, K. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Driscoll, J. J.] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45267 USA. RP Driscoll, JJ (reprint author), Univ Cincinnati, Coll Med, Vontz Ctr Mol Studies, Div Hematol & Oncol, 3125 Eden Ave, Cincinnati, OH 45267 USA. EM driscojs@uc.edu FU UC Hematology and Oncology Translational Studies Award; Egyptian Cultural and Educational Bureau Award in the Egyptian-US Joint Program FX JJD is a recipient of the UC Hematology and Oncology Translational Studies Award and a mentor in the Egyptian-US Joint Supervision Program. MAYAM is a recipient of the Egyptian Cultural and Educational Bureau Award in the Egyptian-US Joint Program. NR 49 TC 15 Z9 15 U1 2 U2 8 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 2015 VL 29 IS 11 BP 2184 EP 2191 DI 10.1038/leu.2015.157 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA CV8IR UT WOS:000364527400008 PM 26108695 ER PT J AU Wedeh, G Cerny-Reiterer, S Eisenwort, G Herrmann, H Blatt, K Hadzijusufovic, E Sadovnik, I Muullauer, L Schwaab, J Hoffmann, T Bradner, JE Radia, D Sperr, WR Hoermann, G Reiter, A Horny, HP Zuber, J Arock, M Valent, P AF Wedeh, G. Cerny-Reiterer, S. Eisenwort, G. Herrmann, H. Blatt, K. Hadzijusufovic, E. Sadovnik, I. Muellauer, L. Schwaab, J. Hoffmann, T. Bradner, J. E. Radia, D. Sperr, W. R. Hoermann, G. Reiter, A. Horny, H-P Zuber, J. Arock, M. Valent, P. TI Identification of bromodomain-containing protein-4 as a novel marker and epigenetic target in mast cell leukemia SO LEUKEMIA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITORS; PROTOONCOGENE C-KIT; OF-THE-ART; SYSTEMIC MASTOCYTOSIS; DEPENDENT ACTIVATION; RESPONSE CRITERIA; GROWTH; MUTATION; BRD4 AB Advanced systemic mastocytosis (SM) is a life-threatening neoplasm characterized by uncontrolled growth and accumulation of neoplastic mast cells (MCs) in various organs and a poor survival. So far, no curative treatment concept has been developed for these patients. We identified the epigenetic reader bromodomain-containing protein-4 (BRD4) as novel drug target in aggressive SM (ASM) and MC leukemia (MCL). As assessed by immunohistochemistry and PCR, neoplastic MCs expressed substantial amounts of BRD4 in ASM and MCL. The human MCL lines HMC-1 and ROSA also expressed BRD4, and their proliferation was blocked by a BRD4-specific short hairpin RNA. Correspondingly, the BRD4-targeting drug JQ1 induced dose-dependent growth inhibition and apoptosis in HMC-1 and ROSA cells, regardless of the presence or absence of KIT D816V. In addition, JQ1 suppressed the proliferation of primary neoplastic MCs obtained from patients with ASM or MCL (IC50: 100-500 nM). In drug combination experiments, midostaurin (PKC412) and all-trans retinoic acid were found to cooperate with JQ1 in producing synergistic effects on survival in HMC-1 and ROSA cells. Taken together, we have identified BRD4 as a promising drug target in advanced SM. Whether JQ1 or other BET-bromodomain inhibitors are effective in vivo in patients with advanced SM remains to be elucidated. C1 [Wedeh, G.; Cerny-Reiterer, S.; Eisenwort, G.; Blatt, K.; Hadzijusufovic, E.; Sadovnik, I.; Sperr, W. R.; Valent, P.] Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, A-1090 Vienna, Austria. [Wedeh, G.; Arock, M.] Ecole Normale Super, LBPA, CNRS, UMR8113, Cachan, France. [Cerny-Reiterer, S.; Eisenwort, G.; Herrmann, H.; Hadzijusufovic, E.; Sperr, W. R.; Valent, P.] Med Univ Vienna, Ludwig Boltzmann Cluster Oncol, A-1090 Vienna, Austria. [Herrmann, H.] Med Univ Vienna, Dept Radiotherapy, A-1090 Vienna, Austria. [Muellauer, L.] Med Univ Vienna, Dept Pathol, A-1090 Vienna, Austria. [Schwaab, J.; Reiter, A.] Heidelberg Univ, Div Hematol, Med Dept 3, Mannheim, Germany. [Hoffmann, T.; Zuber, J.] Res Inst Mol Pathol IMP, Vienna, Austria. [Bradner, J. E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Radia, D.] Guys Hosp, Div Clin Haematol, London SE1 9RT, England. [Hoermann, G.] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria. [Horny, H-P] Univ Munich, Inst Pathol, D-80539 Munich, Germany. RP Valent, P (reprint author), Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM peter.valent@meduniwien.ac.at RI Hadzijusufovic, Emir/B-8109-2016; Hoermann, Gregor/B-8832-2016 OI Hadzijusufovic, Emir/0000-0001-7409-4204; Hoermann, Gregor/0000-0002-7374-4380 FU Austrian Science Fund, SFB [F4611, F4704-B20, F4710-B20] FX We thank Daniela Berger and Gabriele Stefanzl for excellent technical assistance, and Gunther Hofbauer and Andreas Spittler (both at the Cell Sorting Core Unit of the Medical University of Vienna) for excellent technical support and advice. This study was supported by Austrian Science Fund, SFB Grant Nos. F4611, F4704-B20 and F4710-B20. NR 50 TC 4 Z9 4 U1 2 U2 10 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 2015 VL 29 IS 11 BP 2230 EP 2237 DI 10.1038/leu.2015.138 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA CV8IR UT WOS:000364527400013 PM 26055303 ER PT J AU Shahwan, KT Kimball, AB AF Shahwan, Kathryn T. Kimball, Alexa B. TI Psoriasis and Cardiovascular Disease SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Psoriasis; Psoriatic arthritis; Metabolic syndrome; Cardiovascular disease; Cerebrovascular disease ID MYOCARDIAL-INFARCTION RISK; FACTOR INHIBITOR THERAPY; CORONARY-ARTERY-DISEASE; DANISH NATIONWIDE COHORT; CHRONIC PLAQUE PSORIASIS; POPULATION-BASED COHORT; INTIMA-MEDIA THICKNESS; EPICARDIAL FAT TISSUE; SUBCLINICAL ATHEROSCLEROSIS; VASCULAR INFLAMMATION AB Psoriasis, a chronic inflammatory skin disease, has been linked to the metabolic syndrome and various manifestations of cardiovascular disease. Together, psoriasis and the metabolic syndrome constitute a proinflammatory state, and psoriasis shares many pathogenic features with the development of atherosclerotic plaques. Measures of early endothelial dysfunction and subclinical atherosclerosis, as well as corresponding serum biomarkers, may be useful tools to predict which patients are at greatest risk. Regular screening of patients with psoriasis for metabolic and cardiovascular risk factors is of utmost importance, and treatment goals should include management of modifiable risk factors and reduction in systemic inflammation. C1 [Shahwan, Kathryn T.; Kimball, Alexa B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Unit Res Trials & Outcomes Skin CURTIS,Dept, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Unit Res Trials & Outcomes Skin CURTIS,Dept, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Janssen FX A.B. Kimball has been a consultant and investigator for Amgen, Abbvie, Janssen, Novartis, Celgene and Pfizer, has been a consultant for Eli Lilly, and receives fellowship funding from Janssen. K.T. Shahwan receives fellowship funding from Janssen. NR 142 TC 6 Z9 6 U1 1 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2015 VL 99 IS 6 BP 1227 EP + DI 10.1016/j.mcna.2015.08.001 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA CW1CP UT WOS:000364727500007 PM 26476250 ER PT J AU Guan, F Peeler, C Bronk, L Geng, CR Taleei, R Randeniya, S Ge, SP Mirkovic, D Grosshans, D Mohan, R Titt, U AF Guan, Fada Peeler, Christopher Bronk, Lawrence Geng, Changran Taleei, Reza Randeniya, Sharmalee Ge, Shuaiping Mirkovic, Dragan Grosshans, David Mohan, Radhe Titt, Uwe TI Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the GEANT4 Monte Carlo code SO MEDICAL PHYSICS LA English DT Article DE GEANT4; Monte Carlo; proton therapy; LET; LET spectrum; step limit ID RELATIVE BIOLOGICAL EFFECTIVENESS; LINEAR-ENERGY-TRANSFER; NUCLEOTIDE EXCISION-REPAIR; EFFECTIVENESS RBE VALUES; HEAVY-ION RADIOTHERAPY; DNA-DAMAGE SITES; BEAM THERAPY; MODEL; SIMULATION; RADIATION AB Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the GEANT4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from GEANT4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LETt and dose-averaged LET, LETd) using GEANT4 for different tracking step size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LETt and LETd of protons with six different step limits ranging from 1 to 500 mu m in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LETt but significant for LETd. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in GEANT4 can result in incorrect LETd calculation results in the dose plateau region for small step limits. The erroneous LETd results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in GEANT4. The incorrect LETd values lead to substantial differences in the calculated RBE. Conclusions: When the GEANT4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 mu m, the authors recommend the use of LETt in the dose plateau region and LETd around the Bragg peak. For a large step limit, i.e., 500 mu m, LETd is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LETd and LETt becomes positive. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License. C1 [Guan, Fada; Peeler, Christopher; Taleei, Reza; Randeniya, Sharmalee; Ge, Shuaiping; Mirkovic, Dragan; Mohan, Radhe; Titt, Uwe] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Bronk, Lawrence; Grosshans, David] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Geng, Changran] Nanjing Univ Aeronaut & Astronaut, Dept Nucl Sci & Engn, Nanjing 210016, Jiangsu, Peoples R China. [Geng, Changran] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Geng, Changran] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grosshans, David] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. RP Titt, U (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM UTitt@mdanderson.org OI GUAN, FADA/0000-0001-8477-7391; Peeler, Christopher/0000-0003-3418-076X FU National Cancer Institute [U19 CA021239-35, R21 CA187484-01] FX This work was partly supported by National Cancer Institute Grant Nos. U19 CA021239-35 and R21 CA187484-01. The authors would like to thank Dr. Michel Maire and Dr. Sebastien Incerti from the National Institute of Nuclear and Particle Physics, France (IN2P3) for discussing the energy deposition fluctuation algorithms in GEANT4 simulations and GEANT4-DNA physics. The authors thank Dr. Leslie Braby from Texas A&M University for discussing the application of physics quantities in biological effectiveness of radiations. The authors thank Dr. Makoto Asai and Dr. Joseph Perl from SLAC National Accelerator Laboratory for discussing GEANT4 particle tracking algorithms. The authors also appreciate Dr. Gabriel Sawakuchi for discussing in LET calculations. NR 56 TC 4 Z9 5 U1 2 U2 6 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 2015 VL 42 IS 11 BP 6234 EP 6247 DI 10.1118/1.4932217 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6SY UT WOS:000364402100012 PM 26520716 ER PT J AU Li, XH Shi, JQ Zhang, D Singh, S Padole, A Otrakji, A Ka, MK Xu, XG Liu, B AF Li, Xinhua Shi, Jim Q. Zhang, Da Singh, Sarabjeet Padole, Atul Otrakji, Alexi Ka, Mannudeep K. Xu, X. George Liu, Bob TI A new technique to characterize CT scanner bow-tie filter attenuation and applications in human cadaver dosimetry simulations SO MEDICAL PHYSICS LA English DT Article DE CT; bow-tie filter; linear array x-ray detector; in vitro dose; Monte Carlo simulation ID DOSE INDEX AB Purpose: To present a noninvasive technique for directly measuring the CT bow-tie filter attenuation with a linear array x-ray detector. Methods: A scintillator based x-ray detector of 384 pixels, 307 mm active length, and fast data acquisition (model X-Scan 0.8c4-307, Detection Technology, FI-91100 Ii, Finland) was used to simultaneously detect radiation levels across a scan field-of-view. The sampling time was as short as 0.24 ms. To measure the body bow-tie attenuation on a GE Lightspeed Pro 16 CT scanner, the x-ray tube was parked at the 12 o'clock position, and the detector was centered in the scan field at the isocenter height. Two radiation exposures were made with and without the bow-tie in the beam path. Each readout signal was corrected for the detector background offset and signal-level related nonlinear gain, and the ratio of the two exposures gave the bow-tie attenuation. The results were used in the GEANT4 based simulations of the point doses measured using six thimble chambers placed in a human cadaver with abdomen/pelvis CT scans at 100 or 120 kV, helical pitch at 1.375, constant or variable tube current, and distinct x-ray tube starting angles. Results: Absolute attenuation was measured with the body bow-tie scanned at 80-140 kV. For 24 doses measured in six organs of the cadaver, the median or maximum difference between the simulation results and the measurements on the CT scanner was 8.9% or 25.9%, respectively. Conclusions: The described method allows fast and accurate bow-tie filter characterization. (C) 2015 American Association of Physicists in Medicine. C1 [Li, Xinhua; Shi, Jim Q.; Zhang, Da; Singh, Sarabjeet; Padole, Atul; Otrakji, Alexi; Ka, Mannudeep K.; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Xu, X. George] Rensselaer Polytech Inst, Nucl Engn Program, Troy, NY 12180 USA. RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM bliu7@mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering [R01EB015478] FX This research is sponsored in part by the National Institute of Biomedical Imaging and Bioengineering (No. R01EB015478). The authors are grateful to Thomas Long and Tomi Falt from Detection Technology (Billerica, MA) for lending an X-Scan 0.8c4-307 detector that was used in this study, Dr. Baorui Ren from Hologic, Inc. (Bedford, MA) for assistance and enlightening discussions, and Dr. Tianyu Liu, Yiming Gao, and Dr. Peter F. Caracappa from Rensselaer Polytechnic Institute (Troy, NY) for invaluable comments. This work used the High Performance Clusters of the Partners Cooperation for Monte Carlo calculations, and the authors thank the Enterprise Research IS group at Partners Healthcare for their in-depth support. NR 18 TC 2 Z9 2 U1 0 U2 0 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 2015 VL 42 IS 11 BP 6274 EP 6282 DI 10.1118/1.4932364 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6SY UT WOS:000364402100016 PM 26520720 ER PT J AU Titt, U Sell, M Unkelbach, J Bangert, M Mirkovic, D Oelfke, U Mohan, R AF Titt, Uwe Sell, Martin Unkelbach, Jan Bangert, Mark Mirkovic, Dragan Oelfke, Uwe Mohan, Radhe TI Degradation of proton depth dose distributions attributable to microstructures in lung-equivalent material SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; measurements; proton therapy; lung tissue; dose degradation ID MULTIPLE COULOMB; BRAGG PEAK; THERAPY AB Purpose: The purpose of the work reported here was to investigate the influence of sub-millimeter size heterogeneities on the degradation of the distal edges of proton beams and to validate Monte Carlo (MC) methods' ability to correctly predict such degradation. Methods: A custom-designed high-resolution plastic phantom approximating highly heterogeneous, lung-like structures was employed in measurements and in Monte Carlo simulations to evaluate the degradation of proton Bragg curves penetrating heterogeneous media. Results: Significant differences in distal falloff widths and in peak dose values were observed in the measured and the Monte Carlo simulated curves compared to pristine proton Bragg curves. Furthermore, differences between simulations of beams penetrating CT images of the phantom did not agree well with the corresponding experimental differences. The distal falloff widths in CT image-based geometries were underestimated by up to 0.2 cm in water (corresponding to 0.8-1.4 cm in lung tissue), and the peak dose values of pristine proton beams were overestimated by as much as similar to 35% compared to measured curves or depth-dose curves simulated on the basis of true geometry. The authors demonstrate that these discrepancies were caused by the limited spatial resolution of CT images that served as a basis for dose calculations and lead to underestimation of the impact of the fine structure of tissue heterogeneities. A convolution model was successfully applied to mitigate the underestimation. Conclusions: The results of this study justify further development of models to better represent heterogeneity effects in soft-tissue geometries, such as lung, and to correct systematic underestimation of the degradation of the distal edge of proton doses. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License. C1 [Titt, Uwe; Sell, Martin; Mirkovic, Dragan; Mohan, Radhe] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Sell, Martin; Bangert, Mark; Oelfke, Uwe] German Canc Res Ctr, Dept Med Phys, D-69120 Heidelberg, Germany. [Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Oelfke, Uwe] Inst Canc Res, Dept Phys, London SW7 3RP, England. RP Titt, U (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM utitt@mdanderson.org FU National Cancer Institute [P01CA021239]; University of Texas MD Anderson Cancer Center in Houston; German Cancer Research Center in Heidelberg (Sister Institutions Network Fund) FX This project was supported by No. P01CA021239 from the National Cancer Institute and by a grant from The University of Texas MD Anderson Cancer Center in Houston and the German Cancer Research Center in Heidelberg (Sister Institutions Network Fund). The 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, The University of Texas MD Anderson Cancer Center, or the German Cancer Research Center. The authors would also like to thank Von Hagens Plastination (Gubener Plastinate GmbH, Guben, Germany) for kindly providing a sample of plastinated lung tissue for experimental comparisons to their lung-like phantom. NR 8 TC 1 Z9 1 U1 1 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 2015 VL 42 IS 11 BP 6425 EP 6432 DI 10.1118/1.4932625 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6SY UT WOS:000364402100028 PM 26520732 ER PT J AU Herraiz, JL Sitek, A AF Herraiz, J. L. Sitek, A. TI Sensitivity estimation in time-of-flight list-mode positron emission tomography SO MEDICAL PHYSICS LA English DT Article DE positron emission tomography; normalization; time-of-flight; Bayesian statistics; list-mode data ID ATTENUATION CORRECTION; SCATTER CORRECTION; PET-MRI; TOF-PET; 3D PET; RECONSTRUCTION; QUANTIFICATION; CHALLENGES; RISK; CT AB Purpose: An accurate quantification of the images in positron emission tomography (PET) requires knowing the actual sensitivity at each voxel, which represents the probability that a positron emitted in that voxel is finally detected as a coincidence of two gamma rays in a pair of detectors in the PET scanner. This sensitivity depends on the characteristics of the acquisition, as it is affected by the attenuation of the annihilation gamma rays in the body, and possible variations of the sensitivity of the scanner detectors. In this work, the authors propose a new approach to handle time-of-flight (TOF) list-mode PET data, which allows performing either or both, a self-attenuation correction, and self-normalization correction based on emission data only. Methods: The authors derive the theory using a fully Bayesian statistical model of complete data. The authors perform an initial evaluation of algorithms derived from that theory and proposed in this work using numerical 2D list-mode simulations with different TOF resolutions and total number of detected coincidences. Effects of randoms and scatter are not simulated. Results: The authors found that proposed algorithms successfully correct for unknown attenuation and scanner normalization for simulated 2D list-mode TOF-PET data. Conclusions: A new method is presented that can be used for corrections for attenuation and normalization (sensitivity) using TOF list-mode data. (C) 2015 American Association of Physicists in Medicine. C1 [Herraiz, J. L.] MIT, Madrid MIT M Vis Consortium, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Herraiz, J. L.] Univ Complutense Madrid, Dept Fis Atom Mol & Nucl, Grp Fis Nucl, CEI Moncloa, E-28040 Madrid, Spain. [Sitek, A.] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. [Sitek, A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Herraiz, JL (reprint author), MIT, Madrid MIT M Vis Consortium, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM sarkadiu@gmail.com RI LOPEZ HERRAIZ, JOAQUIN/E-9234-2010 OI LOPEZ HERRAIZ, JOAQUIN/0000-0001-7208-8863 FU Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid (Spain); European Union; National Institutes of Health [R21HL106474, R01CA165221, R01HL110241, S10 RR031551] FX This work was supported in part by Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid (Spain) through the Madrid-MIT M+Vision Consortium, the Seventh Framework Programme of the European Union, and National Institutes of Health Nos. R21HL106474, R01CA165221, R01HL110241, and S10 RR031551. NR 39 TC 1 Z9 1 U1 1 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 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD NOV PY 2015 VL 42 IS 11 BP 6690 EP 6702 DI 10.1118/1.4934374 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV6SY UT WOS:000364402100055 PM 26520759 ER PT J AU Dichter, ME Wagner, C True, G AF Dichter, Melissa E. Wagner, Clara True, Gala TI Timing of Intimate Partner Violence in Relationship to Military Service Among Women Veterans SO MILITARY MEDICINE LA English DT Article ID HEALTH AB Women U.S. military veterans report higher rates of lifetime intimate partner violence (IPV) compared with women who have never served in the military. However, we know little about the timing of IPV exposure relative to military service. To begin to understand the relationship between military service and IPV experience, we conducted surveys with 249 women military veterans seeking care at a Veterans Affairs medical center about experiences of physical, psychological, and sexual IPV before, during, and after military service. Additionally, we examined the association between deployment and IPV experience during and after military service. Findings indicated that women experienced IPV during each time period (before/during/after military service), with significant overlap of experiencing IPV during more than one time period and one-third (34.6%) experiencing IPV during all three time periods. Compared to those who were not deployed, women who had been deployed reported increased odds of experiencing psychological, but not physical or sexual, IPV during (but not after) military service. Implications of study findings for theory, research, and practice are discussed. C1 [Dichter, Melissa E.; Wagner, Clara; True, Gala] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [True, Gala] Univ Penn, Philadelphia, PA 19104 USA. RP Dichter, ME (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave,Bldg 4100 Annex, Philadelphia, PA 19104 USA. FU U.S. Department of Veterans Affairs, Health Services Research and Development Service [10-202]; U.S. Department of Veterans Affairs, Center for Evaluation of Patient Aligned Care Teams [12-005] FX Dr. Dichter is a Career Development Awardee, supported by the U.S. Department of Veterans Affairs, Health Services Research and Development Service (CDA #10-202). This work was additionally supported by U.S. Department of Veterans Affairs, Center for Evaluation of Patient Aligned Care Teams ("IPV Assessment and Response with the PACT Model: Needs, Barriers, and Opportunities," CEPACT #12-005, Principal Investigator: Dichter). NR 15 TC 0 Z9 0 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 2015 VL 180 IS 11 BP 1124 EP 1127 DI 10.7205/MILMED-D-14-00582 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CV9UT UT WOS:000364633400007 PM 26540701 ER PT J AU Siddiquee, Z Smith, RN Stone, JR AF Siddiquee, Zakir Smith, R. Neal Stone, James R. TI An elevated IgG4 response in chronic infectious aortitis is associated with aortic atherosclerosis SO MODERN PATHOLOGY LA English DT Article ID IGG4-RELATED SYSTEMIC-DISEASE; LYMPHOPLASMACYTIC AORTITIS; CONSENSUS STATEMENT; SURGICAL PATHOLOGY; PERIAORTITIS; ANEURYSMS AB Recently, it was shown that infectious bacterial aortitis can stimulate an elevated IgG4(+) plasma cell response in the vessel wall, which could mimic IgG4 aortitis/periaortitis. However, the factors that are associated with an elevated IgG4(+) plasma cell response in infectious aortitis are unclear. To ascertain these factors, 17 cases of infectious aortitis and 6 cases of non-infectious severe abdominal aortic atherosclerosis were assessed for the magnitude of IgG4(+) plasma cell response. The degree of IgG4(+) plasma cell infiltration was determined by immunohistochemistry. Infectious cases were subcharacterized as chronic (>3 weeks duration) or acute (< 3 weeks duration) based on the duration of symptoms, and as involving either the ascending aorta or the distal aorta, ie, the descending thoracic and/or abdominal aorta. There was a 5-16-fold greater degree of IgG4(+) plasma cell infiltration in the chronic distal infectious aortitis group compared with the other three infectious aortitis groups (P<0.0007), and compared with non-infectious severe abdominal aortic atherosclerosis (P<0.0008). This resulted in a greater IgG4/IgG ratio in the chronic distal infectious aortitis group compared with the acute ascending and acute distal infectious aortitis groups (P<0.03). The degree of IgG4(+) plasma cell infiltration in chronic distal infectious aortitis overlaps with that seen in the aortitis and periaortitis of IgG4-related disease. In the chronic infectious aortitis cases, the degree of IgG4(+) plasma cell infiltration was more intense in patients with moderate to severe aortic atherosclerosis compared with those patients with less aortic atherosclerosis (P=0.007). These findings indicate that an elevated IgG4(+) plasma cell response occurs in the descending thoracic and abdominal aorta in the setting of chronic bacterial infectious aortitis and pre-existing atherosclerosis. This inflammatory response to chronic infection in atherosclerosis-laden aortas may have implications for the development of IgG4-rich inflammatory atherosclerotic aortic aneurysms. C1 [Siddiquee, Zakir; Smith, R. Neal; Stone, James R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Simches Res Bldg Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org NR 18 TC 0 Z9 0 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 2015 VL 28 IS 11 BP 1428 EP 1434 DI 10.1038/modpathol.2015.105 PG 7 WC Pathology SC Pathology GA CV4YZ UT WOS:000364273700003 PM 26336884 ER PT J AU Mirkovic, J Sholl, LM Garcia, E Lindeman, N MacConaill, L Hirsch, M Dal Cin, P Gorman, M Barletta, JA Nucci, MR Glenn, MW Howitt, BE AF Mirkovic, Jelena Sholl, Lynette M. Garcia, Elizabeth Lindeman, Neal MacConaill, Laura Hirsch, Michelle Dal Cin, Paola Gorman, Melissa Barletta, Justine A. Nucci, Marisa R. Glenn, McCluggage W. Howitt, Brooke E. TI Targeted genomic profiling reveals recurrent KRAS mutations and gain of chromosome 1q in mesonephric carcinomas of the female genital tract SO MODERN PATHOLOGY LA English DT Article ID PROBABLE WOLFFIAN ORIGIN; CELL LUNG-CANCER; UTERINE CERVIX; MICROSATELLITE INSTABILITY; ENDOMETRIAL CARCINOMAS; MEK INHIBITION; GLANDULAR LESIONS; CD10 EXPRESSION; SEQUENCING DATA; ADENOCARCINOMA AB Mesonephric carcinoma is a rare form of gynecologic cancer derived from mesonephric remnants usually located in the lateral wall of the uterine cervix. An analogous tumor occurs in the adnexa, female adnexal tumor of probable Wolffian origin. The pathogenesis and molecular events in mesonephric carcinoma are not known. The aim of this study was to examine the molecular alterations in mesonephric carcinoma to identify driver mutations and therapeutically targetable mutations. This study consisted of 19 tumors from 17 patients: 18 mesonephric carcinomas (15 primary tumors and three metastatic tumors) and 1 female adnexal tumor of probable Wolffian origin. In two patients, both primary and metastatic tumors were available. Genomic DNA was isolated and targeted next-generation sequencing was performed to detect mutations, copy number variations, and structural variants by surveying full exonic regions of 300 cancer genes and 113 selected intronic regions across 35 genes. Fluorescence in situ hybridization (FISH) for 1p and 1q was performed in two cases. Eighty-one percent (13/16) of mesonephric carcinomas had either a KRAS (n=12) or NRAS (n=1) mutation. Mutations in chromatin remodeling genes (ARID1A, ARID1B, or SMARCA4) were present in 62% of mesonephric carcinomas. All mesonephric carcinomas lacked mutations in PIK3CA and PTEN. The most common copy number alteration was 1q gain, found in 12 (75%) mesonephric carcinomas; this was confirmed by FISH in two cases. Mesonephric carcinoma is characterized by molecular alterations that differ from those of more common variants of cervical and endometrial adenocarcinoma, which harbor KRAS/NRAS mutations in 7% and 25% of cases, respectively. KRAS/NRAS mutations are common in mesonephric carcinoma and are often accompanied by gain of 1q and mutations in chromatin remodeling genes. Targeting inhibitors of the RAS/MAPK pathway may be useful in the treatment of mesonephric carcinoma. C1 [Mirkovic, Jelena; Sholl, Lynette M.; Lindeman, Neal; Hirsch, Michelle; Dal Cin, Paola; Gorman, Melissa; Barletta, Justine A.; Nucci, Marisa R.; Howitt, Brooke E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mirkovic, Jelena; Sholl, Lynette M.; Lindeman, Neal; MacConaill, Laura; Hirsch, Michelle; Dal Cin, Paola; Barletta, Justine A.; Nucci, Marisa R.; Howitt, Brooke E.] Harvard Univ, Sch Med, Boston, MA USA. [Sholl, Lynette M.; Garcia, Elizabeth; Lindeman, Neal; MacConaill, Laura; Dal Cin, Paola] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, Boston, MA 02115 USA. [MacConaill, Laura] Dana Farber Canc Inst, Boston, MA 02115 USA. [Glenn, McCluggage W.] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland. RP Howitt, BE (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM bhowitt@partners.org FU Department of Pathology, Brigham and Women's Hospital FX This work was funded by the Department of Pathology, Brigham and Women's Hospital. We thank the staff at the Center for Advanced Molecular Diagnostics for their assistance with this project. NR 43 TC 3 Z9 4 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 2015 VL 28 IS 11 BP 1504 EP 1514 DI 10.1038/modpathol.2015.103 PG 11 WC Pathology SC Pathology GA CV4YZ UT WOS:000364273700010 PM 26336887 ER PT J AU Kunjachan, S Detappe, A Kumar, R Ireland, T Cameron, L Biancur, DE Motto-Ros, V Sancey, L Sridhar, S Makrigiorgos, GM Berbeco, RI AF Kunjachan, Sijumon Detappe, Alexandre Kumar, Rajiv Ireland, Thomas Cameron, Lisa Biancur, Douglas E. Motto-Ros, Vincent Sancey, Lucie Sridhar, Srinivas Makrigiorgos, G. Mike Berbeco, Ross I. TI Nanoparticle Mediated Tumor Vascular Disruption: A Novel Strategy in Radiation Therapy SO NANO LETTERS LA English DT Article DE Gold nanoparticles; image-guided radiation therapy; endothelial radiation damage; tumor vascular disruption ID COATED GOLD NANOPARTICLES; CELLULAR UPTAKE; CANCER-TREATMENT; DRUG-DELIVERY; RADIOTHERAPY; RADIOSENSITIZATION; SIZE; ENHANCEMENT; CELLS; MICE AB More than 50% of all cancer patients receive radiation therapy. The clinical delivery of curative radiation dose is strictly restricted by the proximal healthy tissues. We propose a dual-targeting strategy using vessel-targeted-radio-sensitizing gold nanoparticles and conformal-image guided radiation therapy to specifically amplify damage in the tumor neoendothelium. The resulting tumor vascular disruption substantially improved the therapeutic outcome and subsidized the radiation/nanoparticle toxicity, extending its utility to intransigent or nonresectable tumors that barely respond to standard therapies. C1 [Kunjachan, Sijumon; Detappe, Alexandre; Kumar, Rajiv; Biancur, Douglas E.; Sridhar, Srinivas; Makrigiorgos, G. Mike; Berbeco, Ross I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Kunjachan, Sijumon; Detappe, Alexandre; Kumar, Rajiv; Biancur, Douglas E.; Sridhar, Srinivas; Makrigiorgos, G. Mike; Berbeco, Ross I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Detappe, Alexandre; Motto-Ros, Vincent; Sancey, Lucie] Univ Lyon 1, CNRS, Inst Lumiere Mat, F-69007 Lyon, France. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Nanomed Sci & Technol Ctr, Boston, MA 02115 USA. [Kumar, Rajiv; Sridhar, Srinivas] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Ireland, Thomas] Boston Univ, LA ICP MS, Boston, MA 02215 USA. [Ireland, Thomas] Boston Univ, ICP ES Labs, Boston, MA 02215 USA. [Cameron, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Kunjachan, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM sijumon@gmail.com; rberbeco@lroc.harvard.edu OI Kunjachan, Sijumon /0000-0002-5359-9219; Detappe, Alexandre/0000-0001-9364-1621 FU JCRT Foundation; National Cancer Institute (NCI) [R03 CA164645, R21 CA188833] FX We acknowledge the efforts by Dr. Houari Korideck for assistance with the SARRP irradiations at Dana-Farber Cancer Institute, and the histology core facility at Brigham and Women's Hospital and Harvard Medical School, and the TEM imaging core facility at Harvard Medical School. This project was supported, in part, by a grant from the JCRT Foundation and by award numbers R03 CA164645 and R21 CA188833 from the National Cancer Institute (NCI). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or NIH. NR 58 TC 15 Z9 15 U1 5 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 EI 1530-6992 J9 NANO LETT JI Nano Lett. PD NOV PY 2015 VL 15 IS 11 BP 7488 EP 7496 DI 10.1021/acs.nanolett.5b03073 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA CW1BU UT WOS:000364725400047 PM 26418302 ER PT J AU Goedeke, L Rotllan, N Canfran-Duque, A Aranda, JF Ramirez, CM Araldi, E Lin, CS Anderson, NN Wagschal, A de Cabo, R Horton, JD Lasuncion, MA Naar, AM Suarez, Y Fernandez-Hernando, C AF Goedeke, Leigh Rotllan, Noemi Canfran-Duque, Alberto Aranda, Juan. F. Ramirez, Cristina M. Araldi, Elisa Lin, Chin-Sheng Anderson, Norma N. Wagschal, Alexandre de Cabo, Rafael Horton, Jay D. Lasuncion, Miguel A. Naeaer, Anders M. Suarez, Yajaira Fernandez-Hernando, Carlos TI MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels SO NATURE MEDICINE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; LEUCINE ZIPPER PROTEIN; CHOLESTEROL HOMEOSTASIS; LIPID-METABOLISM; TRANSCRIPTION FACTOR; NONHUMAN-PRIMATES; MESSENGER-RNAS; TARGET GENES; HUMAN GENOME; MICE AB The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL cholesterol (LDL-C). Whereas the transcriptional regulation of LDLR is well characterized, the post-transcriptional mechanisms that govern LDLR expression are just beginning to emerge. Here we develop a high-throughput genome-wide screening assay to systematically identify microRNAs (miRNAs) that regulate LDLR activity in human hepatic cells. From this screen we identified and characterized miR-148a as a negative regulator of LDLR expression and activity and defined a sterol regulatory element binding protein 1 (SREBP1)-mediated pathway through which miR-148a regulates LDL-C uptake. In mice, inhibition of miR-148a increased hepatic LDLR expression and decreased plasma LDL-C. Moreover, we found that miR-148a regulates hepatic expression of ATP-binding cassette, subfamily A, member 1 (ABCA1) and circulating high-density lipoprotein cholesterol (HDL-C) levels in vivo. These studies uncover a role for miR-148a as a key regulator of hepatic LDL-C clearance through direct modulation of LDLR expression and demonstrate the therapeutic potential of inhibiting miR-148a to ameliorate an elevated LDL-C/HDL-C ratio, a prominent risk factor for cardiovascular disease. C1 [Goedeke, Leigh; Rotllan, Noemi; Canfran-Duque, Alberto; Aranda, Juan. F.; Ramirez, Cristina M.; Araldi, Elisa; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06520 USA. [Goedeke, Leigh; Rotllan, Noemi; Canfran-Duque, Alberto; Aranda, Juan. F.; Ramirez, Cristina M.; Araldi, Elisa; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Comparat Med Sect, Integrat Cell Signaling & Neurobiol Metab Program, New Haven, CT 06510 USA. [Goedeke, Leigh; Aranda, Juan. F.; Araldi, Elisa; Lin, Chin-Sheng; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY USA. [Goedeke, Leigh; Araldi, Elisa; Lin, Chin-Sheng; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. [Anderson, Norma N.; Horton, Jay D.] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA. [Anderson, Norma N.; Horton, Jay D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Wagschal, Alexandre; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. [Wagschal, Alexandre; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Lasuncion, Miguel A.] Hosp Univ Ramon y Cajal, Serv Bioquim Invest, Inst Ramon y Cajal Invest Sanitaria, Madrid, Spain. [Lasuncion, Miguel A.] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Madrid, Spain. RP Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06520 USA. EM carlos.fernandez@yale.edu RI Lasuncion, Miguel A./K-6167-2014; de Cabo, Rafael/J-5230-2016; OI Lasuncion, Miguel A./0000-0003-0299-9391; de Cabo, Rafael/0000-0002-3354-2442; Ramirez, Cristina M/0000-0003-2589-0786; , rafael/0000-0003-2830-5693 FU US National Institutes of Health (NIH) [R01HL107953, R01HL107953-04S1, R01HL106063, R01HL105945, 1F31AG043318, P30KD034989]; American Heart Association [15SDG23000025]; Howard Hughes Medical Institute International Student Research Fellowship; Foundation Leducq Transatlantic Network of Excellence in Cardiovascular Research; Ministerio de Industria y Comercio, Spain [SAF2011-29951]; NIH, National Institute of Aging; NIH [R01DK 094184, U24 DK059635]; Laura and Isaac Perlmutter Cancer Center (NIH, National Cancer Institute grant) [P30CA16087]; New York State Stem Cell Science (NYSTEM) [C026719] FX We thank C. Yun, J. Recio, S. Katz and R. DasGupta at the New York University (NYU) RNAi Core for their advice and assistance with the miRNA screen, K. Harry and members of the Yale University Liver Center for primary mouse hepatocyte isolation, members of the Iwakiri laboratory for reagents and advice on primary hepatocyte culture, the Yale University School of Medicine Mouse Metabolic Phenotyping Center (MMPC) for liver toxicity measurements, P. Tontonoz (UCLA) for generously providing the LDLR-GFP plasmid, the Nonhuman Primate Core of the National Institute on Aging for providing liver samples and E. Fisher (NYU School of Medicine) for kindly providing the human hepatocellular carcinoma cell line (Huh7) and mouse hepatic cell line (Hepal-6). This work was supported through grants by the US National Institutes of Health (NIH; grants R01HL107953, R01HL107953-04S1 and R01HL106063 (C.F.-H.); grant R01HL105945 (Y.S.); grant 1F31AG043318 (L.G.); grant P30KD034989 (Yale University Liver Center), the American Heart Association (grant 15SDG23000025 (C.M.R.)), the Howard Hughes Medical Institute International Student Research Fellowship (E.A.), the Foundation Leducq Transatlantic Network of Excellence in Cardiovascular Research (C.F.-H.) and the Ministerio de Industria y Comercio, Spain (grant SAF2011-29951 (M.A.L.)). Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CIBERobn) is an initiative of Instituto de Salud Carlos III (ISCIII), Spain. R.d.C. is supported by the Intramural Research Program of the NIH, National Institute of Aging. A.M.N. and A.W. are supported by NIH grant R01DK 094184. The NYU RNAi core is supported by the Laura and Isaac Perlmutter Cancer Center (NIH, National Cancer Institute grant P30CA16087) and the New York State Stem Cell Science (NYSTEM) contract C026719. The Yale University School of Medicine MMPC is supported by NIH grant U24 DK059635. NR 60 TC 25 Z9 25 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD NOV PY 2015 VL 21 IS 11 BP 1280 EP 1289 DI 10.1038/nm.3949 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CV9QH UT WOS:000364621200012 PM 26437365 ER PT J AU Wagschal, A Najafi-Shoushtari, SH Wang, L Goedeke, L Sinha, S deLemos, AS Black, JC Ramirez, CM Li, YX Tewhey, R Hatoum, I Shah, N Lu, Y Kristo, F Psychogios, N Vrbanac, V Lu, YC Hla, T de Cabo, R Tsang, JS Schadt, E Sabeti, PC Kathiresan, S Cohen, DE Whetstine, J Chung, RT Fernandez-Hernando, C Kaplan, LM Bernards, A Gerszten, RE Naar, AM AF Wagschal, Alexandre Najafi-Shoushtari, S. Hani Wang, Lifeng Goedeke, Leigh Sinha, Sumita deLemos, Andrew S. Black, Josh C. Ramirez, Cristina M. Li, Yingxia Tewhey, Ryan Hatoum, Ida Shah, Naisha Lu, Yong Kristo, Fjoralba Psychogios, Nikolaos Vrbanac, Vladimir Lu, Yi-Chien Hla, Timothy de Cabo, Rafael Tsang, John S. Schadt, Eric Sabeti, Pardis C. Kathiresan, Sekar Cohen, David E. Whetstine, Johnathan Chung, Raymond T. Fernandez-Hernando, Carlos Kaplan, Lee M. Bernards, Andre Gerszten, Robert E. Naeaer, Anders M. TI Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis SO NATURE MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS; HDL; MICE; HYPERCHOLESTEROLEMIA; TRANSPORTERS; METABOLISM; MECHANISMS; RECEPTOR; BINDING AB Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet-fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders. C1 [Wagschal, Alexandre; Najafi-Shoushtari, S. Hani; Wang, Lifeng; Black, Josh C.; Kristo, Fjoralba; Whetstine, Johnathan; Bernards, Andre; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Wagschal, Alexandre; Najafi-Shoushtari, S. Hani; Wang, Lifeng; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Goedeke, Leigh; Ramirez, Cristina M.; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Dept Pathol, Comparat Med Sect, New Haven, CT 06510 USA. [Sinha, Sumita; Psychogios, Nikolaos; Kathiresan, Sekar; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. [deLemos, Andrew S.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Liver, Boston, MA USA. [deLemos, Andrew S.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div, Boston, MA USA. [Black, Josh C.; Kathiresan, Sekar; Whetstine, Johnathan; Chung, Raymond T.; Kaplan, Lee M.; Bernards, Andre; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA USA. [Li, Yingxia; Cohen, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gastroenterol, Boston, MA 02115 USA. [Tewhey, Ryan; Sabeti, Pardis C.; Kathiresan, Sekar] MIT, Broad Inst, Cambridge, MA 02139 USA. [Tewhey, Ryan; Sabeti, Pardis C.; Kathiresan, Sekar] Harvard, Cambridge, MA USA. [Tewhey, Ryan; Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Hatoum, Ida; Kaplan, Lee M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Obes Metab & Nutr Inst, Boston, MA USA. [Hatoum, Ida; Kaplan, Lee M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. [Shah, Naisha; Lu, Yong; Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. [Vrbanac, Vladimir] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Lu, Yi-Chien; Hla, Timothy] Cornell Univ, Weill Cornell Med Coll, Dept Pathol & Lab Med, Ctr Vasc Biol, New York, NY 10021 USA. [de Cabo, Rafael] NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Schadt, Eric] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Kathiresan, Sekar; Bernards, Andre] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Naar, AM (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. EM naar@helix.mgh.harvard.edu RI Black, Joshua/Q-2484-2015; de Cabo, Rafael/J-5230-2016; Hla, Timothy/G-5873-2012; OI de Cabo, Rafael/0000-0002-3354-2442; Kristo, Fjoralba/0000-0002-8045-9756; Hla, Timothy/0000-0001-8355-4065; Ramirez, Cristina M/0000-0003-2589-0786; , rafael/0000-0003-2830-5693 FU US National Institutes of Health (NIH) [R21DK084459, R01DK094184, R37DK048873, R01DK056626, K24DK078772, R01HL107953, R01HL106063]; Massachusetts General Hospital (MGH); American Heart Association; Fondation Leducq Transatlantic Network of Excellence in Cardiovascular Research Award; NIH [R01HL49094]; US National Institute of Allergy and Infectious Diseases; American Heart Association SDG Grant [15SDG23000025]; MGH Executive Committee on Research; Neural Imaging Center as part of a National Institutes on Neurological Disorders and Stroke P30 Core Center grant [NS072030]; Harvard Digestive Diseases Center [P30 DK034854] FX This work was supported by the following grants: US National Institutes of Health (NIH) grants R21DK084459 and R01DK094184 (A.M.N); R37DK048873 and R01DK056626 to D.E.C.; K24DK078772 to R.T.C.; and R01HL107953 and R01HL106063 to C.F.-H. A.M.N. was supported by a scholar award from the Massachusetts General Hospital (MGH). R.E.G. was supported by an Established Investigator Award from the American Heart Association. C.F.-H. was supported by a Fondation Leducq Transatlantic Network of Excellence in Cardiovascular Research Award. T.H. acknowledges the support of NIH grant R01HL49094 and a Fondation Leducq Transatlantic Network of Excellence in Cardiovascular Research Award. N.S. and J.S.T. were supported by the Intramural Research Program of the US National Institute of Allergy and Infectious Diseases. C.M.R. was supported by the American Heart Association SDG Grant 15SD G23000025. A.W. was supported bye fellowship from the MGH Executive Committee on Research. We thank C. Molony of Merck Research Laboratories for help with genotyping data quality assessment. We thank the Harvard Medical School Neurobiology Department and the Neurobiology Imaging Facility for consultation and instrument availability that supported this work. This facility is supported in part by the Neural Imaging Center as part of a National Institutes on Neurological Disorders and Stroke P30 Core Center grant no. NS072030, and by the Harvard Digestive Diseases Center (P30 DK034854). NR 31 TC 30 Z9 30 U1 5 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD NOV PY 2015 VL 21 IS 11 BP 1290 EP 1297 DI 10.1038/nm.3980 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CV9QH UT WOS:000364621200013 PM 26501192 ER PT J AU Spisak, S Lawrenson, K Fu, YF Csabai, I Cottman, RT Seo, JH Haiman, C Han, Y Lenci, R Li, QY Tisza, V Szallasi, Z Herbert, ZT Chabot, M Pomerantz, M Solymosi, N Gayther, SA Joung, JK Freedman, ML AF Spisak, Sandor Lawrenson, Kate Fu, Yanfang Csabai, Istvan Cottman, Rebecca T. Seo, Ji-Heui Haiman, Christopher Han, Ying Lenci, Romina Li, Qiyuan Tisza, Viktoria Szallasi, Zoltan Herbert, Zachery T. Chabot, Matthew Pomerantz, Mark Solymosi, Norbert Gayther, Simon A. Joung, J. Keith Freedman, Matthew L. CA GAME-ON ELLIPSE Consortium TI CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants SO NATURE MEDICINE LA English DT Article ID OFF-TARGET CLEAVAGE; PROSTATE-CANCER; ENGINEERED NUCLEASES; WIDE ASSOCIATION; GENE-EXPRESSION; DISEASE; TALENS; DNA; CRISPR-CAS9; TRAITS AB The vast majority of disease-associated single-nucleotide polymorphisms (SNPs) mapped by genome-wide association studies (GWASs) are located in the non-protein-coding genome, but establishing the functional and mechanistic roles of these sequence variants has proven challenging. Here we describe a general pipeline in which candidate functional SNPs are first evaluated by fine mapping, epigenomic profiling, and epigenome editing, and then interrogated for causal function by using genome editing to create isogenic cell lines followed by phenotypic characterization. To validate this approach, we analyzed the 6q22.1 prostate cancer risk locus and identified rs339331 as the top-scoring SNP. Epigenome editing confirmed that the rs339331 region possessed regulatory potential. By using transcription activator-like effector nuclease (TALEN)-mediated genome editing, we created a panel of isogenic 22Rv1 prostate cancer cell lines representing all three genotypes (TT, TC, CC) at rs339331. Introduction of the 'T' risk allele increased transcription of the regulatory factor 6 (RFX6) gene, increased homeobox B13 (HOXB13) binding at the rs339331 region, and increased deposition of the enhancer-associated H3K4me2 histone mark at the rs339331 region compared to lines homozygous for the 'C' protective allele. The cell lines also differed in cellular morphology and adhesion, and pathway analysis of differentially expressed genes suggested an influence of androgens. In summary, we have developed and validated a widely accessible approach that can be used to establish functional causality for noncoding sequence variants identified by GWASs. C1 [Spisak, Sandor; Seo, Ji-Heui; Lenci, Romina; Li, Qiyuan; Tisza, Viktoria; Chabot, Matthew; Pomerantz, Mark; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Spisak, Sandor; Seo, Ji-Heui; Lenci, Romina; Li, Qiyuan; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Lawrenson, Kate; Haiman, Christopher; Han, Ying; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Fu, Yanfang; Cottman, Rebecca T.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Fu, Yanfang; Cottman, Rebecca T.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Fu, Yanfang; Cottman, Rebecca T.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Fu, Yanfang; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Csabai, Istvan] Eotvos Lorand Univ, Dept Phys Complex Syst, Budapest, Hungary. [Cottman, Rebecca T.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. [Haiman, Christopher] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen, Peoples R China. [Tisza, Viktoria; Szallasi, Zoltan] Boston Childrens Hosp, CHIP, Boston, MA USA. [Szallasi, Zoltan] Tech Univ Denmark, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Szallasi, Zoltan] Semmelweis Univ, Dept Pathol 2, H-1085 Budapest, Hungary. [Herbert, Zachery T.] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. [Solymosi, Norbert] Szent Istvan Univ, Dept Anim Hyg, Budapest, Hungary. [Gayther, Simon A.] Cedars Sinai Med Ctr, Ctr Canc Prevent & Translat Genom, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Freedman, Matthew L.] Eli & Edythe L Broad Inst, Cambridge, MA USA. RP Gayther, SA (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. EM simon.gayther@cshs.org; jjoung@mgh.harvard.edu; freedman@broadinstitute.org OI Szallasi, Zoltan/0000-0001-5395-7509; Csabai, Istvan/0000-0001-9232-9898 FU US National Institutes of Health (NIH) [R01 GM107427]; NIH [DP1 GM105378]; Jim and Ann Orr Massachusetts General Hospital Research Scholar Award; Prostate Cancer Foundation; US NIH [R01CA193910]; H.L. Snyder Medical Foundation; US National Cancer Institute GAME-ON Post-GWAS Initiative [U19CA148112, U19CA148537]; National Cancer Institute [1K99CA184415-01]; Hungarian National Research, Development and Innovation Office [KMR-12-1-2012-0216]; Hungarian National Research Fund [OTKA103244]; Breast Cancer Research Foundation; Szechenyi Progam, Hungary [KTIA_NAP_13-2014-0021]; Program Project Development Grant from the Ovarian Cancer Research Fund FX M.L.F. and J.K.J. were supported by US National Institutes of Health (NIH) grant no. R01 GM107427; J.K.J. was supported by a NIH Director's Pioneer Award (DP1 GM105378) and The Jim and Ann Orr Massachusetts General Hospital Research Scholar Award; M.L.F. is supported by the Prostate Cancer Foundation (Challenge Award), the US NIH grant no. R01CA193910, and the H.L. Snyder Medical Foundation. The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19CA148112 and U19CA148537). K.L. is supported by a K99/R00 grant from the National Cancer Institute (grant no. 1K99CA184415-01). I.C. is supported by grants from the Hungarian National Research, Development and Innovation Office (KMR-12-1-2012-0216) and the Hungarian National Research Fund (OTKA103244). Z.S. is supported by the Breast Cancer Research Foundation and the Szechenyi Progam, Hungary (KTIA_NAP_13-2014-0021). This project was also supported by a Program Project Development Grant from the Ovarian Cancer Research Fund (K.L. and SAG). We thank the Dana-Farber Cancer Institute Molecular Biology Core Facility for Sanger sequencing and Illumina high-throughput sequencing. We thank C. Nicolet at the University of Southern California Epigenome Center Core for RNA-seq services and M. Li at the University of Southern California Norris Medical Library Bioinformatics Center, who provided assistance with the analysis of RNA-seq data. NR 25 TC 11 Z9 11 U1 3 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD NOV PY 2015 VL 21 IS 11 BP 1357 EP 1363 DI 10.1038/nm.3975 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA CV9QH UT WOS:000364621200022 PM 26398868 ER PT J AU Kiani, S Chavez, A Tuttle, M Hal, RN Chari, R Ter-Ovanesyan, D Qian, J Pruitt, BW Beal, J Vora, S Buchthal, J Kowal, EJK Ebrahimkhani, MR Collins, JJ Weiss, R Church, G AF Kiani, Samira Chavez, Alejandro Tuttle, Marcelle Hal, Richard N. Chari, Raj Ter-Ovanesyan, Dmitry Qian, Jason Pruitt, Benjamin W. Beal, Jacob Vora, Suhani Buchthal, Joanna Kowal, Emma J. K. Ebrahimkhani, Mohammad R. Collins, James J. Weiss, Ron Church, George TI Cas9 gRNA engineering for genome editing, activation and repression SO NATURE METHODS LA English DT Article ID HUMAN-CELLS; CRISPR; RNA; CIRCUITS; SYSTEMS AB We demonstrate that by altering the length of Cas9-associated guide RNA (gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein. C1 [Kiani, Samira; Hal, Richard N.; Vora, Suhani; Ebrahimkhani, Mohammad R.; Weiss, Ron] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Kiani, Samira; Hal, Richard N.; Collins, James J.; Weiss, Ron] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA. [Chavez, Alejandro; Tuttle, Marcelle; Ter-Ovanesyan, Dmitry; Qian, Jason; Pruitt, Benjamin W.; Vora, Suhani; Buchthal, Joanna; Kowal, Emma J. K.; Collins, James J.; Church, George] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA USA. [Chavez, Alejandro] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chavez, Alejandro; Chari, Raj; Ter-Ovanesyan, Dmitry; Qian, Jason; Vora, Suhani; Church, George] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Beal, Jacob] Raytheon BBN Technol, Cambridge, MA USA. [Ebrahimkhani, Mohammad R.; Weiss, Ron] MIT, Ctr Emergent Behav Integrated Cellular Syst EBICS, Cambridge, MA 02139 USA. [Collins, James J.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Collins, James J.] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Weiss, R (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rweiss@mit.edu; gchurch@genetics.med.harvard.edu OI Pruitt, Benjamin/0000-0001-7532-7081; Beal, Jacob/0000-0002-1663-5102; Kowal, Emma/0000-0002-8992-7608 FU US National Institutes of Health National Human Genome Research Institute [P50 HG005550]; US Department of Energy [DE-FG02-02ER63445]; Wyss Institute for Biologically Inspired Engineering; US Army Research Office (DARPA) [W911NF-11-2-0054]; National Science Foundation (Emerging Frontiers in Research and Innovation Award in Engineering New Technologies Based on Multicellutar and Inter-kingdom Signaling); US National Institutes of Health [5R01CA155320-04, P50 GM098792]; National Cancer Institute [5T32CA009216-34]; National Science Foundation Graduate Research Fellowship Program; Department of Biological Engineering at MIT; Department of Genetics at Harvard Medical School; Canadian Institutes of Health Research; Defense Threat Reduction Agency [HDTRA1-14-1-0006] FX We thank K. Esvelt, J. Scheiman, J. Huh, J. Aach, M.K. Cromer, S. Hague, M. Tung and all the other members of the Church, Collins and Weiss labs for their assistance and insightful discussions. We also thank P. Mali at University of California San Diego (UCSD; San Diego, California, USA) for the HEK293T cells. The dSaCas9 plasmid was a generous gift from F.A. Ran, W.X. Yan and F. Zhang (Broad Institute-MIT, Boston, Massachusetts, USA). This work was supported by US National Institutes of Health National Human Genome Research Institute grant P50 HG005550, US Department of Energy grant DE-FG02-02ER63445, the Wyss Institute for Biologically Inspired Engineering, the US Army Research Office (DARPA W911NF-11-2-0054), the National Science Foundation (Emerging Frontiers in Research and Innovation Award in Engineering New Technologies Based on Multicellutar and Inter-kingdom Signaling) and US National Institutes of Health grants 5R01CA155320-04 and P50 GM098792. A.C. acknowledges funding by the National Cancer Institute (grant 5T32CA009216-34). S.V. acknowledges funding by the National Science Foundation Graduate Research Fellowship Program, the Department of Biological Engineering at MIT and the Department of Genetics at Harvard Medical School. R.C. was funded by a Banting postdoctoral fellowship from the Canadian Institutes of Health Research. J.J.C. acknowledges funding from Defense Threat Reduction Agency grant HDTRA1-14-1-0006. NR 17 TC 36 Z9 37 U1 9 U2 49 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD NOV PY 2015 VL 12 IS 11 BP 1051 EP 1054 DI 10.1038/NMETH.3580 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CV8BG UT WOS:000364500900019 PM 26344044 ER PT J AU Thaler, NS Sayegh, P Arentoft, A Thames, AD Castellon, SA Hinkin, CH AF Thaler, Nicholas S. Sayegh, Philip Arentoft, Alyssa Thames, April D. Castellon, Steven A. Hinkin, Charlie H. TI Increased Neurocognitive Intra-Individual Variability Is Associated With Declines in Medication Adherence in HIV-Infected Adults SO NEUROPSYCHOLOGY LA English DT Article DE HIV; intra-individual variability; medication adherence; longitudinal ID ANTIRETROVIRAL THERAPY; RESPONSE VARIABILITY; PERFORMANCE; DISORDERS; INDIVIDUALS; DISPERSION; DISEASE; TASK; ERA AB Objective: There is cross-sectional evidence that neurocognitive intra-individual variability (IIV), or dispersion, is elevated in human immunodeficiency virus (HIV) disease and is associated with declines in activities of daily living, including medication adherence. Methods: This longitudinal study extends this literature by examining whether increased neurocognitive IIV in HIV-positive persons over time predicts declines in medication adherence above and beyond changes in mean level of performance over a 6-month observation. Results: After controlling for drug use, declines in mean performance, and changes in depressive symptoms, results confirmed that increases in IIV were associated with overall poorer antiretroviral medication adherence. HIV-positive individuals with the greatest increases in dispersion demonstrated marked reductions in adherence by the third month that exceeded what was observed in less variable individuals. Conclusions: Our results indicate that increases in dispersion are associated with poorer declines in medication adherence in HIV disease, which may have implications for the early detection and remediation of suboptimal antiretroviral adherence. C1 [Thaler, Nicholas S.; Sayegh, Philip; Arentoft, Alyssa; Thames, April D.; Castellon, Steven A.; Hinkin, Charlie H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Castellon, Steven A.; Hinkin, Charlie H.] VA Greater Los Angeles Healthcare Syst, Dept Psychol, Los Angeles, CA USA. RP Thaler, NS (reprint author), 760 Westwood Plaza C8-735, Los Angeles, CA 90024 USA. EM nthaler@mednet.ucla.edu OI Arentoft, Alyssa/0000-0002-4235-4638 FU National Institutes of Health [R01 DA13799]; National Institutes of Health Ruth L. Kirschstein National Research Service award [T32 MH19535] FX This work was supported by National Institutes of Health Grant R01 DA13799 and the National Institutes of Health Ruth L. Kirschstein National Research Service award T32 MH19535. NR 29 TC 3 Z9 3 U1 0 U2 2 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 2015 VL 29 IS 6 BP 919 EP 925 DI 10.1037/neu0000191 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA CV9FF UT WOS:000364592100011 PM 25730729 ER PT J AU Choi, CJ Bauza, A Yoon, MK Sobel, RK Freitag, SK AF Choi, Catherine J. Bauza, Alain Yoon, Michael K. Sobel, Rachel K. Freitag, Suzanne K. TI Full-Thickness Skin Graft as an Independent or Adjunctive Technique for Repair of Cicatricial Lower Eyelid Ectropion Secondary to Actinic Skin Changes SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ELASTOSIS; EXPRESSION; PROTEINS AB Purpose: To retrospectively review and describe full-thickness skin graft repair of lower eyelid cicatricial ectropion secondary to actinic skin. Methods: A retrospective, noncomparative chart review of all patients who underwent lower eyelid ectropion repair with placement of a full-thickness skin graft between June 2004 and March 2014 was conducted with IRB approval. The etiology of lower eyelid ectropion, demographics including age, gender, ethnicity, laterality, graft donor site, additional surgical procedures, graft viability, surgical success rate, complications, and clinical exam findings were summarized. Results: Twenty-nine eyelids in 24 patients underwent skin grafting for repair of cicatricial ectropion secondary to actinic skin changes. Ninety six percent of patients were male and 96% were Caucasian. Donor sites for skin grafts included upper eyelid (9, 31%), supraclavicular skin (9, 31%), postauricular skin (7, 24%), inner brachial skin (2, 7%), axilla (1, 3.5%), and preauricular skin (1, 3.5%). Twenty-four of 29 eyelids in the series underwent 1 or more additional procedures at the time of full-thickness skin grafting, including lateral tarsal strip (9 eyelids, 37.5%), punctoplasty (8, 33%), canthoplasty (7, 29%), excision of keratinized conjunctiva (2, 8%), transverse tarsotomy (1, 4%), ipsilateral external dacryocystorhinostomy (3, 12.5%), and lesion removal (1, 4%). There was 100% viability of the skin grafts. Overall surgical success rate was 76%, with asymptomatic recurrence rate of 17% and symptomatic recurrence rate of 7%. Conclusion: Repair of cicatricial lower eyelid ectropion secondary to actinic skin changes may be accomplished with full-thickness skin grafting, and is often performed in conjunction with additional procedures to fully address anatomic abnormalities. C1 [Choi, Catherine J.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Bauza, Alain] Boston Univ, Boston Med Ctr, Dept Ophthalmol, Boston, MA 02215 USA. [Yoon, Michael K.; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Surg Serv,Dept Ophthalmol, Boston, MA USA. [Sobel, Rachel K.] Boston Univ, Boston Med Ctr, Dept Ophthalmol, Ophthalm Plast & Reconstruct Surg Serv, Boston, MA 02215 USA. RP Freitag, SK (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM Suzanne_Freitag@meei.harvard.edu NR 16 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2015 VL 31 IS 6 BP 474 EP 477 DI 10.1097/IOP.0000000000000524 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA CW2IJ UT WOS:000364814700012 PM 26164158 ER PT J AU Nouizi, F Kwong, TC Cho, J Lin, YT Sampathkumaran, U Gulsen, G AF Nouizi, Farouk Kwong, Tiffany C. Cho, Jaedu Lin, Yuting Sampathkumaran, Uma Gulsen, Gultekin TI Implementation of a new scanning method for high-resolution fluorescence tomography using thermo-sensitive fluorescent agents SO OPTICS LETTERS LA English DT Article AB Conventional fluorescence tomography provides images of the distribution of fluorescent agents within highly scattering media, but suffers from poor spatial resolution. Previously, we introduced a new method termed "temperature-modulated fluorescence tomography" (TM-FT) that generates fluorescence images with high spatial resolution. TM-FT first uses focused ultrasound to locate the distribution of temperature-sensitive fluorescence probes. Afterward, this a priori information is utilized to improve the performance of the inverse solver for conventional fluorescence tomography and reveal quantitatively accurate fluorophore concentration maps. However, the disadvantage of this novel method is the long data acquisition time as the ultrasound beam was scanned in a step-and-shoot mode. In this Letter, we present a new, fast scanning method that reduces the imaging time 40 fold. By continuously scanning the ultrasound beam over a 50 mm by 25 mm field-of-view, high-resolution fluorescence images are obtained in less than 29 min, which is critical for in vivo small animal imaging. (C) 2015 Optical Society of America C1 [Nouizi, Farouk; Kwong, Tiffany C.; Cho, Jaedu; Lin, Yuting; Gulsen, Gultekin] Univ Calif Irvine, Dept Biomed Engn, Dept Radiol Sci, Tu & Yuen Ctr Funct Oncoimaging, Irvine, CA 92697 USA. [Sampathkumaran, Uma] InnoSense LLC, Torrance, CA 90505 USA. [Lin, Yuting] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lin, Yuting] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nouizi, F (reprint author), Univ Calif Irvine, Dept Biomed Engn, Dept Radiol Sci, Tu & Yuen Ctr Funct Oncoimaging, Irvine, CA 92697 USA. EM fnouizi@uci.edu FU Fulbright Commission; National Institutes of Health (NIH) [F31CA17191501A1, P30CA062203, R01EB008716, R21CA191389, R21EB013387, SBIRHHSN261201300068C] FX Fulbright Commission (Visiting Scholar); National Institutes of Health (NIH) (F31CA17191501A1, P30CA062203, R01EB008716, R21CA191389, R21EB013387, SBIRHHSN261201300068C). NR 12 TC 2 Z9 2 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD NOV 1 PY 2015 VL 40 IS 21 BP 4991 EP 4994 DI 10.1364/OL.40.004991 PG 4 WC Optics SC Optics GA CV7QH UT WOS:000364468600043 PM 26512501 ER PT J AU Han, JK Stringer, SP Rosenfeld, RM Archer, SM Baker, DP Brown, SM Edelstein, DR Gray, ST Lian, TS Ross, EJ Seiden, AM Setzen, M Tollefson, TT Ward, PD Welch, KC Wise, SK Nnacheta, LC AF Han, Joseph K. Stringer, Scott P. Rosenfeld, Richard M. Archer, Sanford M. Baker, Dole P. Brown, Seth M. Edelstein, David R. Gray, Stacey T. Lian, Timothy S. Ross, Erin J. Seiden, Allen M. Setzen, Michael Tollefson, Travis T. Ward, P. Daniel Welch, Kevin C. Wise, Sarah K. Nnacheta, Lorraine C. TI Clinical Consensus Statement: Septoplasty with or without Inferior Turbinate Reduction SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE septoplasty; turbinoplasty; septorhinoplasty; nasal; nose; nasal septum; turbinates; turbinate surgery; septal surgery; septum surgery; Delphi method ID NASAL SEPTAL PERFORATION; EVALUATION NOSE SCALE; ENDOSCOPIC SEPTOPLASTY; RADIOFREQUENCY TREATMENT; OBSTRUCTION; HYPERTROPHY; SURGERY; DEVIATION; TRIAL; ANTIBIOTICS AB Objective To develop a clinical consensus statement on septoplasty with or without inferior turbinate reduction. Methods An expert panel of otolaryngologists with no relevant conflicts of interest was assembled to represent general otolaryngology and relevant subspecialty societies. A working definition of septoplasty with or without inferior turbinate reduction and the scope of pertinent otolaryngologic practice were first established. Patients 18 years and older were defined as the targeted population of interest. A modified Delphi method was then used to distill expert opinion into clinical statements that met a standardized definition of consensus. Results The group defined nasal septoplasty as a surgical procedure designed to correct a deviated nasal septum for the purpose of improving nasal function, form, or both. After 2 iterative Delphi method surveys, 20 statements met the standardized definition of consensus, while 13 statements did not. The clinical statements were grouped into 8 categories for presentation and discussion: (1) definition and diagnosis, (2) imaging studies, (3) medical management prior to septoplasty, (4) perioperative management, (5) surgical considerations, (6) adjuvant procedures, (7) postoperative care, and (8) outcomes. Conclusion This clinical consensus statement was developed by and for otolaryngologists and is intended to promote appropriate and, when possible, evidence-based care for patients undergoing septoplasty with or without inferior turbinate reduction. A complete definition of septoplasty with or without inferior turbinate reduction was first developed, and additional statements were subsequently produced and evaluated addressing diagnosis, medical management prior to septoplasty, and surgical considerations, as well as the appropriate role of perioperative, postoperative, and adjuvant procedures, in addition to outcomes. Additionally, a series of clinical statements were developed, such as Computed tomography scan may not accurately demonstrate the degree of septal deviation, Septoplasty can assist delivery of intranasal medications to the nasal cavity, Endoscopy can be used to improve visualization of posterior-based septal deviation during septoplasty, and Quilting sutures can obviate the need for nasal packing after septoplasty. It is anticipated that the application of these principles will result in decreased variations in the care of septoplasty patients and an increase in the quality of care. C1 [Han, Joseph K.] Eastern Virginia Med Sch, Norfolk, VA 23507 USA. [Stringer, Scott P.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Rosenfeld, Richard M.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Archer, Sanford M.] Univ Kentucky, Lexington, KY USA. [Baker, Dole P.] Anderson ENT & Facial Plast, Anderson, SC USA. [Brown, Seth M.] Univ Connecticut, Farmington, CT USA. [Edelstein, David R.] Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. [Edelstein, David R.] New York Head & Neck Inst, New York, NY USA. [Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lian, Timothy S.] Louisiana State Univ, Shreveport, LA 71105 USA. [Ross, Erin J.] Beachwood Family Hlth Ctr, Beachwood, OH USA. [Seiden, Allen M.] Univ Cincinnati, Cincinnati, OH USA. [Setzen, Michael] NYU, Sch Med, Great Neck, NY USA. [Tollefson, Travis T.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Ward, P. Daniel] Univ Utah, Salt Lake City, UT USA. [Welch, Kevin C.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Wise, Sarah K.] Emory Univ, Atlanta, GA 30322 USA. [Nnacheta, Lorraine C.] Amer Acad Otolaryngol Head & Neck Surg Fdn, Alexandria, VA USA. RP Han, JK (reprint author), Eastern Virginia Med Sch, Dept OTO HNS, 600 Gresham Dr,Ste 1100, Norfolk, VA 23507 USA. EM hanjk@evms.edu OI Tollefson, Travis/0000-0002-8658-8647 FU American Academy of Otolaryngology-Head and Neck Surgery Foundation FX Sponsorships: American Academy of Otolaryngology-Head and Neck Surgery Foundation. NR 54 TC 2 Z9 2 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2015 VL 153 IS 5 BP 708 EP 720 DI 10.1177/0194599815606435 PG 13 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CV6MF UT WOS:000364383600005 PM 26527752 ER PT J AU Noij, KS Kozin, ED Sethi, R Shah, PV Kaplan, AB Herrmann, B Remenschneider, A Lee, DJ AF Noij, Kimberley S. Kozin, Elliott D. Sethi, Rosh Shah, Parth V. Kaplan, Alyson B. Herrmann, Barbara Remenschneider, Aaron Lee, Daniel J. TI Systematic Review of Nontumor Pediatric Auditory Brainstem Implant Outcomes SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review DE auditory brainstem implant; nontumor; pediatric; children; deafness; hearing loss; systematic review; review ID UNSUCCESSFUL COCHLEAR IMPLANTATION; NERVE DEFICIENCY; MICROVASCULAR DECOMPRESSION; NEUROFIBROMATOSIS TYPE-2; PREOPERATIVE EVALUATION; VESTIBULAR SCHWANNOMA; TRIGEMINAL NEURALGIA; CHILDREN; EXPERIENCE; APLASIA AB Objective The auditory brainstem implant (ABI) was initially developed for patients with deafness as a result of neurofibromatosis type 2. ABI indications have recently extended to children with congenital deafness who are not cochlear implant candidates. Few multi-institutional outcome data exist. Herein, we aim to provide a systematic review of outcomes following implantation of the ABI in pediatric patients with nontumor diagnosis, with a focus on audiometric outcomes. Data Sources PubMed, Embase, and Cochrane. Review Methods A systematic review of literature was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations. Variables assessed included age at implantation, diagnosis, medical history, cochlear implant history, radiographic findings, ABI device implanted, surgical approach, complications, side effects, and auditory outcomes. Results The initial search identified 304 articles; 21 met inclusion criteria for a total of 162 children. The majority of these patients had cochlear nerve aplasia (63.6%, 103 of 162). Cerebrospinal fluid leak occurred in up to 8.5% of cases. Audiometric outcomes improved over time. After 5 years, almost 50% of patients reached Categories of Auditory Performance scores >4; however, patients with nonauditory disabilities did not demonstrate a similar increase in scores. Conclusion ABI surgery is a reasonable option for the habilitation of deaf children who are not cochlear implant candidates. Although improvement in Categories of Auditory Performance scores was seen across studies, pediatric ABI users with nonauditory disabilities have inferior audiometric outcomes. C1 [Noij, Kimberley S.; Kozin, Elliott D.; Sethi, Rosh; Shah, Parth V.; Kaplan, Alyson B.; Herrmann, Barbara; Remenschneider, Aaron; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Noij, Kimberley S.; Kozin, Elliott D.; Sethi, Rosh; Shah, Parth V.; Kaplan, Alyson B.; Remenschneider, Aaron; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Herrmann, Barbara] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Lee@meei.harvard.edu NR 47 TC 5 Z9 5 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2015 VL 153 IS 5 BP 739 EP 750 DI 10.1177/0194599815596929 PG 12 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CV6MF UT WOS:000364383600008 PM 26227469 ER PT J AU Willson, TJ Shams, A Lospinoso, J Weitzel, E McMains, K AF Willson, Thomas J. Shams, Alexandra Lospinoso, Joshua Weitzel, Erik McMains, Kevin TI Searching for Cedar: Geographic Variation in Single Aeroallergen Shows Dose Response in Internet Search Activity SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE aeroallergen; allergen; mountain cedar; juniper; Google; Internet AB Objective To assess the effect of a single aeroallergen on Internet search activity in 3 distinct geographic regions over time. Study Design A retrospective time series analysis. Setting Tertiary academic medical center. Methods Mountain Cedar pollen counts spanning the periods from 2011 to 2014 were collected for San Antonio, Dallas-Ft Worth, and Houston metro regions (Texas). Google search data for the corresponding period and regions were also obtained for the search terms pollen and mountain cedar. Data were analyzed through time series plots and autoregressive integrated moving average. Results Seasonal maximum pollen counts were greatest in San Antonio, ranging from 5413 to 9982 grains per cubic centimeter. In San Antonio, there was a strong, positive, and statistically significant effect of mountain cedar pollen count on search activity for both pollen (P = .001) and mountain cedar (P < .001) when evaluated by autoregressive integrated moving average. Conclusions Environmental levels of a single allergenmountain cedar pollenshow a geographic and temporal relationship between Internet searches and mountain cedar pollen, based on Google Trends. These data are useful to understand patients' perceptions of the health risk presented by mountain cedar pollen. In turn, this information affords practitioners the opportunity to offer targeted patient education in a geographically unique region, as well as adjust surveillance of related pathologies. C1 [Willson, Thomas J.; Weitzel, Erik] San Antonio Mil Med Ctr, Dept Otolaryngol Head & Neck Surg, San Antonio, TX 78234 USA. [Willson, Thomas J.; Shams, Alexandra; Weitzel, Erik; McMains, Kevin] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Lospinoso, Joshua] Portia Stat Consulting LLC, San Antonio, TX USA. [McMains, Kevin] South Texas Vet Hlth Care Syst, ENT Sect, San Antonio, TX USA. RP Willson, TJ (reprint author), San Antonio Mil Med Ctr, Dept Otolaryngol Head & Neck Surg, 3551 Roger Brooke Dr, San Antonio, TX 78234 USA. EM S10twillson@gmail.com NR 8 TC 0 Z9 0 U1 2 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2015 VL 153 IS 5 BP 770 EP 774 DI 10.1177/0194599815601650 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CV6MF UT WOS:000364383600011 PM 26340925 ER PT J AU McMains, KC Peel, J Weitzel, EK Der-Torossian, H Couch, M AF McMains, Kevin Christopher Peel, Jennifer Weitzel, Erik K. Der-Torossian, Hirak Couch, Marion TI Perception of Shame in Otolaryngology-Head and Neck Surgery Training SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE education; otolaryngology; faculty; teaching; environment of learning ID MEDICAL-STUDENTS; PATIENT SAFETY; EXPERIENCES; GUILT AB Objective This survey was developed to assess the prevalence and effects of the perception of shame in otolaryngology-head and neck surgery residency training in the United States. Study Design Survey. Setting US otolaryngology training programs. Subjects Faculty and trainees in US otolaryngology training programs. Methods A 14-item survey to assess the prevalence of the experience of shame and the attitudes toward use of shame in otolaryngology residency training was sent to all otolaryngology-head and neck surgery program directors for distribution among their respective faculty and resident cohorts. Results A total of 267 responses were received (women, 24.7%; men, 75.3%): 42.7% of respondents were trainees; 7.0% of trainees thought that shame was a necessary/effective tool, compared with 11.4% of faculty; 50% of respondents felt that they had been personally shamed during residency; and 69.9% of respondents had witnessed another trainee being shamed during residency training. Trainees were most commonly shamed in the operating room (78.4%). Otolaryngology faculty members did the shaming 95.1% of the time. Although shaming prompted internal reflection/self-improvement in 57.4% of trainees, it also caused loss of self-confidence in 52.5%. Trainees who had been shamed were more likely to view shame as an appropriate educational tool (P < .05). Conclusion Half of respondents have felt shamed during their residency training, and a majority has witnessed a colleague being shamed. Understanding the negative impact that shaming behaviors have on the learning environment and on the performance of the individual within it is an important first step in creating an environment maximally conducive to learning, professional development, and patient safety. C1 [McMains, Kevin Christopher; Weitzel, Erik K.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Peel, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Der-Torossian, Hirak] Univ Vermont, Coll Med, Burlington, VT USA. [Couch, Marion] Indiana Univ, Dept Otolaryngol Head & Neck Surg, Indianapolis, IN USA. RP McMains, KC (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Dr, San Antonio, TX 78229 USA. EM kevin.mcmains@va.gov NR 17 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2015 VL 153 IS 5 BP 786 EP 790 DI 10.1177/0194599815598288 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CV6MF UT WOS:000364383600014 PM 26243025 ER PT J AU Goyal, N Deschler, DG AF Goyal, Neerav Deschler, Daniel G. TI Minimally Invasive Removal of Mandibular Hardware after Free Flap Reconstruction SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE free flap reconstruction; hardware removal; infection; surgical technique; reconstruction; fistula; minimally invasive; fibula; mandible ID VASCULARIZED BONE-GRAFTS; FIXATION; PLATE C1 [Goyal, Neerav; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Goyal, Neerav] Penn State Milton S Hershey Med Ctr, Div Otolaryngol Head & Neck Surg, Hershey, PA 17033 USA. RP Goyal, N (reprint author), Penn State Milton S Hershey Med Ctr, Div Otolaryngol Head & Neck Surg, Surg, 500 Univ Dr,MC H091, Hershey, PA 17033 USA. EM ngoyal@psualum.com OI Goyal, Neerav/0000-0001-7783-1097 NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2015 VL 153 IS 5 BP 888 EP 890 DI 10.1177/0194599815604329 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA CV6MF UT WOS:000364383600030 PM 26378185 ER PT J AU Byrne, T Fargo, JD Montgomery, AE Roberts, CB Culhane, DP Kane, V AF Byrne, Thomas Fargo, Jamison D. Montgomery, Ann Elizabeth Roberts, Christopher B. Culhane, Dennis P. Kane, Vincent TI Screening for Homelessness in the Veterans Health Administration: Monitoring Housing Stability through Repeat Screening SO PUBLIC HEALTH REPORTS LA English DT Article ID SERVICE USE; COSTS; RISK; CARE AB Objective. This study examined veterans' responses to the Veterans Health Administration's (VHA's) universal screen for homelessness and risk of homelessness during the first 12 months of implementation. Methods. We calculated the baseline annual frequency of homelessness and risk of homelessness among all veterans who completed an initial screen during the study period. We measured changes in housing status among veterans who initially screened positive and then completed a follow-up screen, assessed factors associated with such changes, and identified distinct risk profiles of veterans who completed a follow-up screen. Results. More than 4 million veterans completed an initial screen; 1.8% (n=77,621) screened positive for homelessness or risk of homelessness. Of those who initially screened positive for either homelessness or risk of homelessness and who completed a second screen during the study period, 85.0% (n=15,060) resolved their housing instability prior to their second screen. Age, sex, race, VHA eligibility, and screening location were all associated with changes in housing stability. We identified four distinct risk profiles for veterans with ongoing housing instability. Conclusion. To address homelessness among veterans, efforts should include increased and targeted engagement of veterans experiencing persistent housing instability. C1 [Byrne, Thomas] Boston Univ, Sch Social Work, Boston, MA 02155 USA. [Byrne, Thomas; Fargo, Jamison D.; Montgomery, Ann Elizabeth; Roberts, Christopher B.; Culhane, Dennis P.; Kane, Vincent] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Byrne, T (reprint author), Boston Univ, Sch Social Work, 264 Bay State Rd, Boston, MA 02155 USA. EM tbyrne@bu.edu NR 23 TC 0 Z9 0 U1 3 U2 6 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 2015 VL 130 IS 6 BP 684 EP 692 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CV8CI UT WOS:000364503700017 PM 26556940 ER PT J AU Hess, DR AF Hess, Dean R. TI Recruitment Maneuvers and PEEP Titration SO RESPIRATORY CARE LA English DT Article DE ARDS; mechanical ventilation; PEEP; recruitment maneuver ID ACUTE RESPIRATORY-DISTRESS; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; ELECTRICAL-IMPEDANCE TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; TIDAL VOLUME VENTILATION; CONVENTIONAL MECHANICAL VENTILATION; HIGH-FREQUENCY OSCILLATION; CARBON-DIOXIDE GRADIENT; CARE-UNIT PATIENTS AB The injurious effects of alveolar overdistention are well accepted, and there is little debate regarding the importance of pressure and volume limitation during mechanical ventilation. The role of recruitment maneuvers is more controversial. Alveolar recruitment is desirable if it can be achieved, but the potential for recruitment is variable among patients with ARDS. A stepwise recruitment maneuver, similar to an incremental PEEP titration, is favored over sustained inflation recruitment maneuvers. Many approaches to PEEP titration have been proposed, and the best method to choose the most appropriate level for an individual patient is unclear. A PEEP level should be selected that balances alveolar recruitment against overdistention. The easiest approach to select PEEP might be according to the severity of the disease: 5-10 cm H2O PEEP in mild ARDS, 10-15 cm H2O PEEP in moderate ARDS, and 15-20 cm H2O PEEP in severe ARDS. Recruitment maneuvers and PEEP should be used within the context of lung protection and not just as a means of improving oxygenation. C1 [Hess, Dean R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hess, Dean R.] Northwestern Univ, 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@mgh.harvard.edu NR 111 TC 2 Z9 2 U1 1 U2 5 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 2015 VL 60 IS 11 BP 1688 EP 1704 DI 10.4187/respcare.04409 PG 17 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CV6FH UT WOS:000364365600019 PM 26493593 ER PT J AU Kacmarek, RM Villar, J Blanch, L AF Kacmarek, Robert M. Villar, Jesus Blanch, Lluis TI Why Use Anything But a Standard Spontaneous Breathing Trial to Determine Readiness for Ventilator Discontinuation? SO Respiratory Care LA English DT Editorial Material ID PROPORTIONAL ASSIST VENTILATION; PRESSURE SUPPORT VENTILATION; MECHANICAL VENTILATION; ASYNCHRONY; DURATION C1 [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol, Dept Resp Care, Boston, MA USA. [Villar, Jesus; Blanch, Lluis] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. [Blanch, Lluis] Univ Autonoma Barcelona, Inst Invest Innovac Parc Tauli, Corp Sanitaria Univ Parc Tauli, Sabadell, Spain. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St, Boston, MA 01460 USA. EM rkacmarek@partners.org NR 20 TC 2 Z9 2 U1 0 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD NOV PY 2015 VL 60 IS 11 BP 1705 EP 1707 DI 10.4187/respcare.04535 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CV6FH UT WOS:000364365600020 PM 26493594 ER PT J AU Iezzoni, LI Chen, Y McLain, ABJ AF Iezzoni, L. I. Chen, Y. McLain, A. B. J. TI Current pregnancy among women with spinal cord injury: findings from the US national spinal cord injury database SO SPINAL CORD LA English DT Article ID PHYSICAL-DISABILITIES; OBSTETRIC MANAGEMENT; OUTCOMES; SCALE AB Study design: Cross-sectional study Objectives: To examine the prevalence of pregnancy and associations with sociodemographic and clinical factors among women with spinal cord injury (SCI) Setting: US National Spinal Cord Injury Database, an SCI registry that interviews participants 1, 5 and then every 5 years post injury. Data include SCI clinical details, functional impairments, participation measures, depressive symptoms and life satisfaction. Women aged 18-49 are asked about hospitalizations in the last year relating to pregnancy or its complications. Data represent 1907 women, who completed 3054 interviews. Methods: We used generalized estimating equations to examine bivariable associations between pregnancy and clinical and psychosocial variables and to perform multivariable regressions predicting pregnancy. Results: Across all women, 2.0% reported pregnancy during the prior 12 months. This annual prevalence differed significantly by the years elapsed since injury; the highest rate occurred 15 years post injury (3.7%). Bivariable analyses found that younger age at injury was significantly associated with current pregnancy (P<0.0001). Compared with nonpregnant women, those reporting current pregancy were significantly more likely to be married or partnered, have sport-related SCI, have higher motor scores and have more positive psychosocial status scores. Multivariable analyses found significant associations between current pregnancy and age, marital status, motor score and mobility and occupation scale scores. Conclusion: Current pregnancy rates among reproductive-aged women with SCI are similar to rates of other US women with chronic mobility impairments. More information is needed about pregnancy experiences and outcomes to inform both women with SCI seeking childbearing and clinicians providing their care. C1 [Iezzoni, L. I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Iezzoni, L. I.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y.; McLain, A. B. J.] Univ Alabama Birmingham, Sch Med, Dept Phys Med & Rehabil, Birmingham, AL USA. RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA. EM liezzoni@mgh.harvard.edu FU US National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [R21 HD068756-02]; National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, US Department of Education, Washington DC [H133A110002] FX US National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, grant no. R21 HD068756-02 and National Institute on Disability and Rehabilitation Research, Office of Special Education and Rehabilitation Services, US Department of Education, Washington DC (grant no. H133A110002). NR 18 TC 2 Z9 2 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD NOV PY 2015 VL 53 IS 11 BP 821 EP 826 DI 10.1038/sc.2015.88 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CW2GC UT WOS:000364808100011 PM 25987000 ER PT J AU Cipriani, NA Nagar, S Kaplan, SP White, MG Antic, T Sadow, PM Aschebrook-Kilfoy, B Angelos, P Kaplan, EL Grogan, RH AF Cipriani, Nicole A. Nagar, Sapna Kaplan, Sharone P. White, Michael G. Antic, Tatjana Sadow, Peter M. Aschebrook-Kilfoy, Briseis Angelos, Peter Kaplan, Edwin L. Grogan, Raymon H. TI Follicular Thyroid Carcinoma: How Have Histologic Diagnoses Changed in the Last Half-Century and What Are the Prognostic Implications? SO THYROID LA English DT Article ID OBSERVER VARIATION; PATTERNED LESIONS; PAPILLARY; CANCER; SURVIVAL; VARIANT; GLAND; INTEROBSERVER; RECURRENCE; FEATURES AB Background: Follicular thyroid carcinoma (FTC) comprises 10% of differentiated thyroid cancers. Diagnostic controversy and interobserver variability render the practical diagnosis of FTC difficult. Overall survival rates vary (46-97%). The aims of this study were to review FTC histologically at the authors' tertiary care institution and to evaluate long-term survival and recurrence. Methods: Diagnostic slides from 66 FTC cases (1965-2007) were reviewed by three pathologists from two institutions (blinded to clinical outcomes), and consensus was obtained. Patient demographics, tumor characteristics, and treatment, survival, and recurrence data were collected. Thyroid cancer-specific and recurrence-free survival were calculated by original and reclassified diagnoses. Results: Forty-seven cases (71%) were reclassified: 24 (36%) to papillary thyroid carcinoma (PTC), 18 (27%) to follicular adenoma (FA), and five (8%) to poorly differentiated carcinoma (PDC). Nineteen (29%) maintained a diagnosis of FTC. The extent of surgical resection and rates of radioiodine treatment did not differ by reclassification diagnosis. Pre-review FTC-specific survival was 83.5% and 75.1% at 10 and 20 years, respectively. Following contemporary reclassification, FTC-specific survival was 77% and 33.7% at 10 and 20 years, respectively. There were no cancer-specific deaths in the FA or PTC groups. Conclusions: Over the past 50 years, changes in our understanding of the pathogenesis, histology, and behavior of thyroid carcinoma may partially account for the changes in histologic diagnosis. Elimination of PTC and FA contaminants led to decrease in survival following reclassification. Variability in histologic interpretation contributes to diagnostic challenges in follicular lesions. Histologic review of thyroid tumors for research studies is crucial, especially given the ever-changing diagnostic criteria. C1 [Cipriani, Nicole A.; Antic, Tatjana] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Kaplan, Sharone P.; White, Michael G.; Angelos, Peter; Kaplan, Edwin L.; Grogan, Raymon H.] Univ Chicago, Dept Surg, Endocrine Surg Res Program, Chicago, IL 60637 USA. [Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Nagar, Sapna] Oakland Univ, Dept Surg, William Beaumont Sch Med, Royal Oak, MI USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cipriani, NA (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave,MC 6101, Chicago, IL 60637 USA. EM Nicole.Cipriani@uchospitals.edu FU University of Chicago Department of Surgery Endocrine Surgery Research Program; Department of Pathology FX Funding provided by internal resources from the University of Chicago Department of Surgery Endocrine Surgery Research Program and the Department of Pathology. NR 30 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD NOV 1 PY 2015 VL 25 IS 11 BP 1209 EP 1216 DI 10.1089/thy.2015.0297 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV5SQ UT WOS:000364331800006 PM 26440366 ER PT J AU Pisciolaro, RL Duailibi, MT Novo, NF Juliano, Y Pallos, D Yelick, PC Vacanti, JP Ferreira, LM Duailibi, SE AF Pisciolaro, Ricardo Luiz Duailibi, Monica Talarico Novo, Neil Ferreira Juliano, Yara Pallos, Debora Yelick, Pamela Crotty Vacanti, Joseph Phillip Ferreira, Lydia Masako Duailibi, Silvio Eduardo TI Tooth Tissue Engineering: The Importance of Blood Products as a Supplement in Tissue Culture Medium for Human Pulp Dental Stem Cells SO TISSUE ENGINEERING PART A LA English DT Article ID PLATELET-RICH PLASMA; AUTOLOGOUS SERUM; EXPANSION; DIFFERENTIATION; BIOLOGY; GROWTH; TEETH; BONE AB One of the goals in using cells for tissue engineering (TE) and cell therapy consists of optimizing the medium for cell culture. The present study compares three different blood product supplements for improved cell proliferation and protection against DNA damage in cultured human dental pulp stem cells for tooth TE applications. Human cells from dental pulp were first characterized as adult stem cells (ectomesenchymal mixed origin) by flow cytometry. Next, four different cell culture conditions were tested: I, supplement-free; II, supplemented with fetal bovine serum; III, allogeneic human serum; and IV, autologous human serum. Cultured cells were then characterized for cell proliferation, mineralized nodule formation, and colony-forming units (CFU) capability. After 28 days in culture, the comet assay was performed to assess possible damage in cellular DNA. Our results revealed that Protocol IV achieved higher cell proliferation than Protocol I (p=0.0112). Protocols II and III resulted in higher cell proliferation than Protocol I, but no statistical differences were found relative to Protocol IV. The comet assay revealed less cell damage in cells cultured using Protocol IV as compared to Protocols II and III. The damage percentage observed on Protocol II was significantly higher than all other protocols. CFUs capability was highest using Protocol IV (p=0.0018) and III, respectively, and the highest degree of mineralization was observed using Protocol IV as compared to Protocols II and III. Protocol IV resulted in significantly improved cell proliferation, and no cell damage was observed. These results demonstrate that human blood product supplements can be used as feasible supplements for culturing adult human dental stem cells. C1 [Pisciolaro, Ricardo Luiz; Duailibi, Monica Talarico; Duailibi, Silvio Eduardo] Univ Fed Sao Paulo, Ctr Cellular & Mol Therapy, CTCMol, BR-04044010 Sao Paulo, Brazil. [Pisciolaro, Ricardo Luiz; Duailibi, Monica Talarico; Novo, Neil Ferreira; Juliano, Yara; Ferreira, Lydia Masako; Duailibi, Silvio Eduardo] Univ Fed Sao Paulo, Dept Surg, Translat Surg, BR-04044010 Sao Paulo, Brazil. [Duailibi, Monica Talarico; Duailibi, Silvio Eduardo] BIOFABRIS, Natl Inst Sci & Technol, Biofabricat Inst, Campinas, SP, Brazil. [Novo, Neil Ferreira; Juliano, Yara] Univ Santo Amaro, Dept Hlth Sci, Sao Paulo, Brazil. [Juliano, Yara; Pallos, Debora] Univ Santo Amaro, Dept Dent, Sao Paulo, Brazil. [Yelick, Pamela Crotty] Tufts Univ, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA. [Vacanti, Joseph Phillip] Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. [Vacanti, Joseph Phillip] Harvard Univ, Sch Med, Boston, MA USA. RP Duailibi, MT (reprint author), Univ Fed Sao Paulo, Ctr Cellular & Mol Therapy, Rua Mirassol 207, BR-04044010 Sao Paulo, Brazil. EM monica@duailibiodonto.com.br FU UNIFESP; Surgery Plastic Department; FAPESP [07/58856-7, 07/51227-4, 07/59488-1]; CAPES; CNPq [310049/2011-3, 310048/2011-7, 133745/2012-0]; Instituto Nacional de Ciencia e Tecnologia (INCT)-Biofabrication [CNPq 5736661/2008-1, FAPESP 08/57860-3]; NIH/NIDCR/NIBIB [DE016132, TW007665] FX The authors would like to thank Dr. Esper Georges Kallas who provided technical support of the LIM 60, Medical Investigation Laboratories (Kallas' Lab), University of Sao Paulo. The authors thank the Brazilian sponsors UNIFESP, Surgery Plastic Department, FAPESP (07/58856-7; 07/51227-4; 07/59488-1), and CAPES for the RLP's scholarship, CNPq (310049/2011-3; 310048/2011-7; 133745/2012-0), Instituto Nacional de Ciencia e Tecnologia (INCT)-Biofabrication (CNPq 5736661/2008-1 and FAPESP 08/57860-3), and NIH/NIDCR/NIBIB for their continued support [DE016132, TW007665 (PCY)]. NR 38 TC 1 Z9 1 U1 2 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD NOV 1 PY 2015 VL 21 IS 21-22 BP 2639 EP 2648 DI 10.1089/ten.tea.2014.0617 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CV7UI UT WOS:000364480600001 PM 26414682 ER PT J AU Kim, IL Pfeifer, CG Fisher, MB Saxena, V Meloni, GR Kwon, MY Kim, M Steinberg, DR Mauck, RL Burdick, JA AF Kim, Iris L. Pfeifer, Christian G. Fisher, Matthew B. Saxena, Vishal Meloni, Gregory R. Kwon, Mi Y. Kim, Minwook Steinberg, David R. Mauck, Robert L. Burdick, Jason A. TI Fibrous Scaffolds with Varied Fiber Chemistry and Growth Factor Delivery Promote Repair in a Porcine Cartilage Defect Model SO TISSUE ENGINEERING PART A LA English DT Article ID ARTICULAR-CARTILAGE; HYALURONIC-ACID; MECHANICAL-PROPERTIES; MSC CHONDROGENESIS; SUBCHONDRAL BONE; DRUG-DELIVERY; ANIMAL-MODELS; REGENERATION; TISSUE; NANOFIBERS AB Current clinically approved methods for cartilage repair are generally based on either endogenous cell recruitment (e.g., microfracture) or chondrocyte delivery (e.g., autologous chondrocyte implantation). However, both methods culminate in repair tissue with inferior mechanical properties and the addition of biomaterials to these clinical interventions may improve their efficacy. To this end, the objective of this study was to investigate the ability of multipolymer acellular fibrous scaffolds to improve cartilage repair when combined with microfracture in a large animal (i.e., minipig) model. Composite scaffolds were formulated from a combination of hyaluronic acid (HA) fibers and poly(-caprolactone) (PCL) fibers, either with or without transforming growth factor-3 (TGF3). After 12 weeks in vivo, material choice and TGF3 delivery had a significant impact on outcomes; specifically, PCL scaffolds without TGF3 had inferior gross appearance and reduced mechanical properties, whereas HA scaffolds that released TGF3 resulted in improved histological scores and increased type 2 collagen content. Importantly, analysis of the overall dataset revealed that histology, but not gross appearance, was a better predictor of mechanical properties. This study highlights the importance of scaffold properties on in vivo cartilage repair as well as the need for numerous quantitative outcome measures to fully evaluate treatment methods. C1 [Kim, Iris L.; Kwon, Mi Y.; Mauck, Robert L.; Burdick, Jason A.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Kim, Iris L.; Pfeifer, Christian G.; Fisher, Matthew B.; Saxena, Vishal; Meloni, Gregory R.; Kim, Minwook; Steinberg, David R.; Mauck, Robert L.; Burdick, Jason A.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA. [Pfeifer, Christian G.; Fisher, Matthew B.; Saxena, Vishal; Meloni, Gregory R.; Kim, Minwook; Steinberg, David R.; Mauck, Robert L.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Burdick, JA (reprint author), Univ Penn, Dept Bioengn, 240 Skirkanich Hall,210 S 33rd St, Philadelphia, PA 19104 USA. EM burdick2@seas.upenn.edu RI Fisher, Matthew/M-5809-2016 OI Fisher, Matthew/0000-0002-3212-0870 FU National Science Foundation; National Institutes of Health [R01 EB008722]; Department of Veterans Affairs [I01 RX000700] FX This work was supported by a graduate research fellowship from the National Science Foundation (I.L.K.) and grants from the National Institutes of Health (R01 EB008722) and the Department of Veterans Affairs (I01 RX000700). The authors also acknowledge Dr. Nicole Belkin and Dr. Andrew Milby for assistance with surgeries and Dr. Ross Marklein for assistance with principal component analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. NR 47 TC 4 Z9 4 U1 3 U2 18 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD NOV 1 PY 2015 VL 21 IS 21-22 BP 2680 EP 2690 DI 10.1089/ten.tea.2015.0150 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CV7UI UT WOS:000364480600005 PM 26401910 ER PT J AU Struzyna, LA Wolf, JA Mietus, CJ Adewole, DO Chen, HI Smith, DH Cullen, DK AF Struzyna, Laura A. Wolf, John A. Mietus, Constance J. Adewole, Dayo O. Chen, H. Isaac Smith, Douglas H. Cullen, D. Kacy TI Rebuilding Brain Circuitry with Living Micro-Tissue Engineered Neural Networks SO TISSUE ENGINEERING PART A LA English DT Article ID SPINAL-CORD-INJURY; STEM-CELL TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; IN-VITRO; GUIDANCE CHANNELS; AXON REGENERATION; NEURITE EXTENSION; FUNCTIONAL RECOVERY; CHONDROITINASE ABC; NEURONAL GROWTH AB Prominent neuropathology following trauma, stroke, and various neurodegenerative diseases includes neuronal degeneration as well as loss of long-distance axonal connections. While cell replacement and axonal pathfinding strategies are often explored independently, there is no strategy capable of simultaneously replacing lost neurons and re-establishing long-distance axonal connections in the central nervous system. Accordingly, we have created micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of long integrated axonal tracts spanning discrete neuronal populations. These living micro-TENNs reconstitute the architecture of long-distance axonal tracts, and thus may serve as an effective substrate for targeted neurosurgical reconstruction of damaged pathways in the brain. Cerebral cortical neurons or dorsal root ganglia neurons were precisely delivered into the tubular constructs, and properties of the hydrogel exterior and extracellular matrix internal column (180-500m diameter) were optimized for robust neuronal survival and to promote axonal extensions across the 2.0cm tube length. The very small diameter permits minimally invasive delivery into the brain. In this study, preformed micro-TENNs were stereotaxically injected into naive rats to bridge deep thalamic structures with the cerebral cortex to assess construct survival and integration. We found that micro-TENN neurons survived at least 1 month and maintained their long axonal architecture along the cortical-thalamic axis. Notably, we also found neurite penetration from micro-TENN neurons into the host cortex, with evidence of synapse formation. These micro-TENNs represent a new strategy to facilitate nervous system repair by recapitulating features of neural pathways to restore or modulate damaged brain circuitry. C1 [Struzyna, Laura A.; Wolf, John A.; Mietus, Constance J.; Adewole, Dayo O.; Chen, H. Isaac; Smith, Douglas H.; Cullen, D. Kacy] Univ Penn, Dept Neurosurg, Ctr Brain Injury & Repair, Perelman Sch Med, Philadelphia, PA 19104 USA. [Struzyna, Laura A.; Wolf, John A.; Adewole, Dayo O.; Chen, H. Isaac; Cullen, D. Kacy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Struzyna, Laura A.; Adewole, Dayo O.] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. RP Cullen, DK (reprint author), Univ Penn, Dept Neurosurg, 105E Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM dkacy@mail.med.upenn.edu FU U.S. Army Medical Research and Materiel Command through the Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034]; Congressionally Directed Medical Research Program [W81XWH-10-1-0941]; Joint Warfighter Medical Research Program [W81XWH-13207004]; Department of Veterans Affairs through a RRD Merit Review [B1097-I]; National Institutes of Health/NINDS [T32-NS043126]; Penn Medicine Neuroscience Center; Graduate Research Fellowship through the National Science Foundation [DGE-1321851] FX Financial support was provided by the U.S. Army Medical Research and Materiel Command through the Armed Forces Institute of Regenerative Medicine (#W81XWH-08-2-0034), the Congressionally Directed Medical Research Program (#W81XWH-10-1-0941), and the Joint Warfighter Medical Research Program (#W81XWH-13207004); the Department of Veterans Affairs through a RR&D Merit Review (#B1097-I); the National Institutes of Health/NINDS (T32-NS043126); Penn Medicine Neuroscience Center; and a Graduate Research Fellowship through the National Science Foundation (DGE-1321851). The authors would like to thank Andrew Jaye, Joseph Morand, and Ariana Barkley for technical assistance in these studies, and Dr. James Harris for assistance with figure preparation. NR 71 TC 3 Z9 4 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD NOV 1 PY 2015 VL 21 IS 21-22 BP 2744 EP 2756 DI 10.1089/ten.tea.2014.0557 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA CV7UI UT WOS:000364480600011 PM 26414439 ER PT J AU Allard, CB Gelpi-Hammerschmidt, F Harshman, LC Choueiri, TK Faiena, I Modi, P Chung, BI Tinay, I Singer, EA Chang, SL AF Allard, Christopher B. Gelpi-Hammerschmidt, Francisco Harshman, Lauren C. Choueiri, Toni K. Faiena, Izak Modi, Parth Chung, Benjamin I. Tinay, Ilker Singer, Eric A. Chang, Steven L. TI Contemporary rends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE High-dose interleukin-2; Immunotherapy; Renal cell carcinoma; Kidney cancer; Therapy trends; Toxicity ID PHASE-III TRIAL; INTERFERON-ALPHA; DOUBLE-BLIND; CANCER; STATISTICS; SURVIVAL; ANTIBODY; MELANOMA; SAFETY AB Background: Targeted therapies (TTs) have revolutionized metastatic renal cell carcinoma (mRCC) treatment in the past decade, largely replacing immunotherapy including high-dose interleukin-2 (HD IL-2) therapy. We evaluated trends in HD IL-2 use for mRCC in the IT era. Methods: Our cohort comprised a weighted estimate of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the Premier Hospital Database. We assessed temporal trends in HD IL-2 use including patient. disease, and hospital characteristics stratified by era (pre-TT uptake: 2004-2006, uptake: 2007-2009, and post-TT uptake: 2010-2012) and fitted multivariable regression models to identify predictors of treatment toxicity and tolerability. Results: An estimated 2,351 patients received HD IL-2 therapy for mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008. HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy were men, white, younger than 60 years, had lung metastases, and were otherwise healthy. Vasopressors, intensive care unit admission, and hemodialysis were necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with toxicities in multivariable analyses included being unmarried, male sex, and multiple metastatic sites. African Americans and patients with single-site metastases were less likely to receive multiple treatment cycles. Conclusions: HD IL-2 therapy is used infrequently for mRCC in the United States, and its application has diminished with the uptake of TT. Patients are being increasingly treated in teaching hospitals, suggesting a centralization of care and possible barriers to access. A recent slight increase in HD IL-2 therapy use likely reflects recognition of the inability of TT to effect a complete response. (C) 2015 Elsevier Inc. All rights reserved. C1 [Allard, Christopher B.; Gelpi-Hammerschmidt, Francisco; Tinay, Ilker; Chang, Steven L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. [Allard, Christopher B.; Gelpi-Hammerschmidt, Francisco] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Harshman, Lauren C.; Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA. [Faiena, Izak; Modi, Parth; Singer, Eric A.] Rutgers Inst New Jersey, Sect Urol Oncol, New Brunswick, NJ USA. [Faiena, Izak; Modi, Parth; Singer, Eric A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Chung, Benjamin I.] Stanford Sch Med, Dept Urol, Palo Alto, CA USA. [Tinay, Ilker] Marmara Univ, Dept Urol, Sch Med, Istanbul, Turkey. RP Allard, CB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol, Boston, MA 02115 USA. EM Callard@mgh.harvard.edu FU Grant from the National Cancer Institute, USA [P30CA072720]; Kidney SPORE [5P50CA101942-09] FX This work was supported by a Grant from the National Cancer Institute, USA (P30CA072720) and Kidney SPORE (5P50CA101942-09). NR 28 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 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV PY 2015 VL 33 IS 11 AR 496.e11 DI 10.1016/j.urolonc.2015.06.014 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA CV6TS UT WOS:000364404400013 PM 26210683 ER PT J AU Lee, T Ul Haq, N AF Lee, Timmy Ul Haq, Naveed TI New Developments in Our Understanding of Neointimal Hyperplasia SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Neointimal hyperplasia; Vascular remodeling; Arteriovenous accesses; Novel therapies; Cannulation ID CHRONIC KIDNEY-DISEASE; HEMODIALYSIS VASCULAR ACCESS; ARTERIOVENOUS-FISTULA MODEL; RANDOMIZED CONTROLLED-TRIAL; INDUCED ARTERIAL ENLARGEMENT; INHIBIT INTIMAL HYPERPLASIA; ENDOTHELIAL-CELL IMPLANTS; SHEAR-STRESS; VENOUS STENOSIS; GRAFT PATENCY AB The vascular access remains the lifeline for the hemodialysis patient. The most common etiology of vascular access dysfunction is venous stenosis at the vein-artery anastomosis in arteriovenous fistula and at the vein-graft anastomosis in arteriovenous grafts (AVG). This stenotic lesion is typically characterized on histology as aggressive venous neointimal hyperplasia in both arteriovenous fistula and AVG. In recent years, we have advanced our knowledge and understanding of neointimal hyperplasia in vascular access and begun testing several novel therapies. This article will (1) review recent developments in our understanding of the pathophysiology of neointimal hyperplasia development in AVG and fistula failure, (2) discuss atypical factors leading to neointimal hyperplasia development, (3) highlight key novel therapies that have been evaluated in clinical trials, and (4) discuss future opportunities and challenges to improve our understanding of vascular access dysfunction and translate this knowledge into novel and innovative therapies. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Lee, Timmy] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. King Faisal Specialist Hosp & Res Ctr, Dept Med, Nephrol Sect, Riyadh, Saudi Arabia. RP Lee, T (reprint author), Univ Alabama Birmingham, Dept Med, Div Nephrol, Zeigler Res Bldg 524,1720 2nd Ave South, Birmingham, AL 35294 USA. EM txlee@uab.edu FU American Society of Nephrology Carl W. Gottschalk Research Scholar Grant; University of Alabama at Birmingham Nephrology Research Training Center Anderson Innovation Award FX The author has research funding from an American Society of Nephrology Carl W. Gottschalk Research Scholar Grant and University of Alabama at Birmingham Nephrology Research Training Center Anderson Innovation Award. NR 76 TC 1 Z9 1 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 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD NOV PY 2015 VL 22 IS 6 BP 431 EP 437 DI 10.1053/j.ackd.2015.06.010 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CV4UQ UT WOS:000364262400005 PM 26524947 ER PT J AU White, BA Baron, JM Dighe, AS Camargo, CA Brown, DFM AF White, Benjamin A. Baron, Jason M. Dighe, Anand S. Camargo, Carlos A., Jr. Brown, David F. M. TI Applying Lean methodologies reduces ED laboratory turnaround times SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT THROUGHPUT; MODEL AB Background: Increasing the value of health care delivery is a national priority, and providers face growing pressure to reduce cost while improving quality. Ample opportunity exists to increase efficiency and quality simultaneously through the application of systems engineering science. Objective: We examined the hypothesis that Lean-based reorganization of laboratory process flow would improve laboratory turnaround times (TAT) and reduce waste in the system. Methods: This study was a prospective, before-after analysis of laboratory process improvement in a teaching hospital emergency department (ED). The intervention included a reorganization of laboratory sample flow based in systems engineering science and Lean methodologies, with no additional resources. The primary outcome was the median TAT from sample collection to result for 6 tests previously performed in an ED kiosk. Results: After the intervention, median laboratory TAT decreased across most tests. The greatest d ecreases were found in "reflex tests" performed after an initial screening test: troponin T TAT was reduced by 33 minutes (86 to 53 minutes; 99% confidence interval, 30-35 minutes) and urine sedimentation TAT by 88 minutes (117 to 29 minutes; 99% confidence interval, 87-90 minutes). In addition, troponin I TAT was reduced by 12 minutes, urinalysis by 9 minutes, and urine human chorionic gonadotropin by 10 minutes. Microbiology rapid testing TAT, a "control," did not change. Conclusions: In this study, Lean-based reorganization of laboratory process flow significantly increased process efficiency. Broader application of systems engineering science might further improve health care quality and capacity while reducing waste and cost. (C) 2015 Elsevier Inc. All rights reserved. C1 [White, Benjamin A.; Camargo, Carlos A., Jr.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Baron, Jason M.; Dighe, Anand S.] Massachusetts Gen Hosp, Dept Lab Med, Boston, MA 02114 USA. RP White, BA (reprint author), Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM bwhite3@partners.org FU National Institutes of Health Loan Repayment Program grant FX This research was supported by a National Institutes of Health Loan Repayment Program grant awarded to Benjamin A White. NR 26 TC 1 Z9 1 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2015 VL 33 IS 11 BP 1572 EP 1576 DI 10.1016/j.ajem.2015.06.013 PG 5 WC Emergency Medicine SC Emergency Medicine GA CU9KH UT WOS:000363862900006 PM 26145581 ER PT J AU Prabhakar, AM Le, TQ Abujudeh, HH Raja, AS AF Prabhakar, Anand M. Le, Thang Q. Abujudeh, Hani H. Raja, Ali S. TI Incidental findings and recommendations are common on ED CT angiography to evaluate for aortic dissection SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID FLEISCHNER-SOCIETY; GUIDELINES; MANAGEMENT; NODULES AB Purpose: The aim of this study was to assess the outcomes, incidental findings, recommendations, and adherence to recommendations on computed tomography angiography (CTA) studies obtained in the emergency department (ED) to evaluate for aortic dissection. Methods: The institutional database of ED patients was retrospectively reviewed to identify CTA examinations for dissection during 2014. The radiology report and electronic medical records were reviewed to assess outcomes, radiology report incidental findings, and recommendations, as well as adherence to these recommendations. Results: There were 370 dissection CTAs performed during the 12-month study period. The average age of the patients was 63 years (range, 15-97 years). Eighty-seven patients (23.5%) had clinically significant aortic pathology including 46 patients (12.4%) with dissection and 19 (5.1%) which were new. Three hundred twenty-nine (88.9%) of patients had at least 1 incidental finding. One hundred six (28.6%) of patients had recommendations on the radiology report, and 44.3% of these were for pulmonary nodules. Thirty recommendations (28.3%) were acted upon, most commonly related to pulmonary nodule. Conclusion: Computed tomography angiography is useful in detecting aortic pathology. However, emergency physicians should be aware of the potential for clinically significant incidental findings and recommendations. Adherence to recommendations was limited, and future research could investigate mechanisms to improve compliance. (C) 2015 Elsevier Inc. All rights reserved. C1 [Prabhakar, Anand M.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiovasc Imaging, Dept Radiol,Sch Med, Boston, MA 02114 USA. [Prabhakar, Anand M.; Abujudeh, Hani H.] Harvard Univ, Massachusetts Gen Hosp, Div Emergency Imaging, Dept Radiol,Sch Med, Boston, MA 02114 USA. [Le, Thang Q.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Raja, Ali S.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Sch Med, Boston, MA 02114 USA. RP Prabhakar, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiovasc Imaging, Dept Radiol,Sch Med, 55 Fruit St,Gray 2, Boston, MA 02114 USA. EM aprabhakar@mgh.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2015 VL 33 IS 11 BP 1639 EP 1641 DI 10.1016/j.ajem.2015.07.078 PG 3 WC Emergency Medicine SC Emergency Medicine GA CU9KH UT WOS:000363862900019 PM 26324008 ER PT J AU Jubelt, LE Volpp, KG Gatto, DE Friedman, JY Shea, JA AF Jubelt, Lindsay E. Volpp, Kevin G. Gatto, Dana E. Friedman, Joelle Y. Shea, Judy A. TI A Qualitative Evaluation of Patient-Perceived Benefits and Barriers to Participation in a Telephone Care Management Program SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Patient-Centered Care; Patient Care Management; Care Coordination; Disease Management; Chronic Disease; Health Behavior; Prevention Research AB Purpose. To examine why high-risk individuals targeted for a telephone care management program participated at low rates. Design. Study design consisted of qualitative, semistructured interviews. Setting. The setting was a large national insurer's telephone-based care management program. The program employed registered nurses to provide individually tailored education and counseling about health and health care. Subjects. Study subjects comprised members of a national insurer who were recruited to participate in a care management program but had either dropped out of the program after a short period of initial engagement or had never participated despite recruitment efforts. Measures. Interview content was divided into four categories: knowledge of the case management program, bathers to program participation, perceptions of benefits of the program, and suggestions for program improvement. Analysis. Investigators conducted a directed content analysis. Results. The most commonly cited barriers to participation were a lack of perceived need and a sense of distrust toward the program and its staff The most commonly cited benefits were psychosocial support and goal setting. Conclusion. Care management programs may benefit from changes to how insurance plan members are selected for the program and from adjusting program content to address perceived needs among members. C1 [Jubelt, Lindsay E.] Univ Penn, Robert Wood Johnson Fdn Clin Scholars, Philadelphia, PA 19104 USA. [Jubelt, Lindsay E.; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Jubelt, Lindsay E.; Volpp, Kevin G.; Gatto, Dana E.; Friedman, Joelle Y.] Univ Penn, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Jubelt, Lindsay E.] NYU, Dept Populat Hlth, Sch Med, New York, NY 10016 USA. [Volpp, Kevin G.; Gatto, Dana E.; Friedman, Joelle Y.; Shea, Judy A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. RP Jubelt, LE (reprint author), NYU, Dept Populat Hlth, Sch Med, 227 East 30th St,Floor 6, New York, NY 10016 USA. EM lindsay.jubelt@nyumc.org NR 8 TC 1 Z9 1 U1 1 U2 3 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD NOV-DEC PY 2015 VL 30 IS 2 BP 117 EP 119 DI 10.4278/ajhp.131203-ARB-610 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CV0AM UT WOS:000363909000009 PM 25615709 ER PT J AU Becker, NV Asch, DA Kullgren, JT Bellamy, SL Sen, AP Volpp, KG AF Becker, Nora V. Asch, David A. Kullgren, Jeffrey T. Bellamy, Scarlett L. Sen, Aditi P. Volpp, Kevin G. TI Stages of Change and Patient Activation Measure Scores in the Context of Incentive-Based Health Interventions SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Behavioral Economics; Health Incentives; Motivation; Stage of Change; Patient Activation; Prevention Research ID BEHAVIORS; OUTCOMES AB Purpose. To determine if two widely used behavioral change measures-Stages of Change (SoC) and Patient Activation Measure (PAM)-correlate with each other; are affected by financial incentives, or predict positive outcomes in the context of incentive-based health interventions. Design. Secondary analysis of two randomized controlled trials of incentives. for weight loss and for improved diabetes self-monitoring. Setting. Philadelphia, Pennsylvania; Newark, New Jersey. Subjects. A total of 132 obese and 75 diabetic adults enrolled in one of two trials. Measures. SoC and PAM scores; weight loss and usage rate of diabetes self-monitoring equipment. Analysis. Multiple regression; Kruskal-Wallis test. Results. We found no association between baseline SoC and PAM sews in either study (p = .30 and p = .89). Regression models showed no association between baseline PAM score and SoC and subsequent outcomes for either study (weight loss study: PAM: p = .14, SoC: p = .1; diabetes study: PAM: p = .45, SoC: p = .61). Change in PAM score and SoC among participants in the intervention groups did not differ by study arm or among participants with better outcomes. Conclusion. PAM score and SoC may not effectively predict success or monitor progress among individuals enrolled in incentive-based interventions. C1 [Becker, Nora V.; Sen, Aditi P.] Univ Penn, Wharton Sch, Dept Hlth Care Management & Econ, Philadelphia, PA 19104 USA. [Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Dept Med, Perelman Sch Med, Philadelphia, PA USA. [Kullgren, Jeffrey T.] Univ Michigan, Inst Healthcare Policy & Innovat, VA Ctr Clin Management Res, VA Ann Arbor Healthcare Syst,Dept Internal Med,Sc, Ann Arbor, MI 48109 USA. [Bellamy, Scarlett L.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Becker, NV (reprint author), Univ Penn, Wharton Sch, Dept Hlth Care Management & Econ, 3641 Locust Walk,Suite 402, Philadelphia, PA 19104 USA. EM norab@wharton.upenn.edu NR 7 TC 0 Z9 0 U1 2 U2 7 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD NOV-DEC PY 2015 VL 30 IS 2 BP 133 EP 135 DI 10.4278/ajhp.141001-QUAN-489 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CV0AM UT WOS:000363909000012 PM 26517587 ER PT J AU Gvilia, I Suntsova, N Kumar, S McGinty, D Szymusiak, R AF Gvilia, Irma Suntsova, Natalia Kumar, Sunil McGinty, Dennis Szymusiak, Ronald TI Suppression of preoptic sleep-regulatory neuronal activity during corticotropin-releasing factor-induced sleep disturbance SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE CRF; sleep homeostasis; stress; preoptic hypothalamus ID STRESSOR-INDUCED ALTERATIONS; REDUCES SPONTANEOUS WAKING; C-FOS; HOMEOSTATIC REGULATION; GALANINERGIC NEURONS; DISCHARGE PATTERNS; AREA NEURONS; HORMONE CRH; RAT; NUCLEUS AB Corticotropin releasing factor (CRF) is implicated in sleep and arousal regulation. Exogenous CRF causes sleep suppression that is associated with activation of at least two important arousal systems: pontine noradrenergic and hypothalamic orexin/hypocretin neurons. It is not known whether CRF also impacts sleep-promoting neuronal systems. We hypothesized that CRF-mediated changes in wake and sleep involve decreased activity of hypothalamic sleep-regulatory neurons localized in the preoptic area. To test this hypothesis, we examined the effects of intracerebroventricular administration of CRF on sleep-wake measures and c-Fos expression in GABAergic neurons in the median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) in different experimental conditions. Administration of CRF (0.1 nmol) during baseline rest phase led to delayed sleep onset and decreases in total amount and mean duration of non-rapid eye movement (NREM) sleep. Administration of CRF during acute sleep deprivation (SD) resulted in suppression of recovery sleep and decreased c-Fos expression in MnPN/VLPO GABAergic neurons. Compared with vehicle controls, intracerebroventricular CRF potentiated disturbances of both NREM and REM sleep in rats exposed to a species-specific psychological stressor, the dirty cage of a male conspecific. The number of MnPN/VLPO GABAergic neurons expressing c-Fos was reduced in the CRF-treated group of dirty cage-exposed rats. These findings confirm the involvement of CRF in wake-sleep cycle regulation and suggest that increased CRF signaling in the brain 1) negatively affects homeostatic responses to sleep loss, 2) exacerbates stress-induced disturbances of sleep, and 3) suppresses the activity of sleep-regulatory neurons of the MnPN and VLPO. C1 [Gvilia, Irma; Kumar, Sunil; McGinty, Dennis; Szymusiak, Ronald] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91344 USA. [Gvilia, Irma; Szymusiak, Ronald] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Suntsova, Natalia; McGinty, Dennis] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Gvilia, Irma] Ilia State Univ, Tbilisi, Rep of Georgia. RP Gvilia, I (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91344 USA. EM igvilia@ucla.edu FU Department of Veterans Affairs FX This study was supported by the Department of Veterans Affairs. The authors thank Keng-Tee Chow for her excellent technical assistance. NR 45 TC 0 Z9 0 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV 1 PY 2015 VL 309 IS 9 BP R1092 EP R1100 DI 10.1152/ajpregu.00176.2015 PG 9 WC Physiology SC Physiology GA CV5OI UT WOS:000364320000010 PM 26333784 ER PT J AU Kanayama, G DeLuca, J Meehan, WP Hudson, JI Isaacs, S Baggish, A Weiner, R Micheli, L Pope, HG AF Kanayama, Gen DeLuca, James Meehan, William P., III Hudson, James I. Isaacs, Stephanie Baggish, Aaron Weiner, Rory Micheli, Lyle Pope, Harrison G., Jr. TI Ruptured Tendons in Anabolic-Androgenic Steroid Users: A Cross-Sectional Cohort Study SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE anabolic-androgenic steroids; weightlifting; bodybuilding; tendon rupture; men ID PERFORMANCE-ENHANCING DRUGS; ACHILLES-TENDON; RISK-FACTORS; RAT TENDON; TRICEPS; ABUSE; EXERCISE; HORMONE; WEIGHTLIFTERS; CONSEQUENCES AB Background: Accumulating case reports have described tendon rupture in men who use anabolic-androgenic steroids (AAS). However, no controlled study has assessed the history of tendon rupture in a large cohort of AAS users and comparison nonusers. Hypothesis: Men reporting long-term AAS abuse would report an elevated lifetime incidence of tendon rupture compared with non-AAS-using bodybuilders. Study Design: Cohort study; Level of evidence, 3. Methods: Medical histories were obtained from 142 experienced male bodybuilders aged 35 to 55 years recruited in the course of 2 studies. Of these men, 88 reported at least 2 years of cumulative lifetime AAS use, and 54 reported no history of AAS use. In men reporting a history of tendon rupture, the circumstances of the injury, prodromal symptoms, concomitant drug or alcohol use, and details of current and lifetime AAS use (if applicable) were recorded. Surgical records were obtained for most participants. Results: Nineteen (22%) of the AAS users, but only 3 (6%) of the nonusers, reported at least 1 lifetime tendon rupture. The hazard ratio for a first ruptured tendon in AAS users versus nonusers was 9.0 (95% CI, 2.5-32.3; P < .001). Several men reported 2 or more independent lifetime tendon ruptures. Interestingly, upper-body tendon ruptures occurred exclusively in the AAS group (15 [17%] AAS users vs 0 nonusers; risk difference, 0.17 [95% CI, 0.09-0.25]; P < .001 [hazard ratio not estimable]), whereas there was no significant difference between users and nonusers in risk for lower-body ruptures (6 [7%] AAS users, 3 [6%] nonusers; hazard ratio, 3.1 [95% CI, 0.7-13.8]; P = .13). Of 31 individual tendon ruptures assessed, only 6 (19%) occurred while weightlifting, with the majority occurring during other sports activities. Eight (26%) ruptures followed prodromal symptoms of nonspecific pain in the region. Virtually all ruptures were treated surgically, with complete or near-complete ultimate restoration of function. Conclusion: AAS abusers, compared with otherwise similar bodybuilders, showed a markedly increased risk of tendon ruptures, particularly upper-body tendon rupture. C1 [Kanayama, Gen; Hudson, James I.; Pope, Harrison G., Jr.] McLean Hosp, Biol Psychiat Lab, Belmont, MA 02478 USA. [Kanayama, Gen; Hudson, James I.; Pope, Harrison G., Jr.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [DeLuca, James; Isaacs, Stephanie; Baggish, Aaron; Weiner, Rory] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meehan, William P., III; Micheli, Lyle] Boston Childrens Hosp, Div Sports Med, Boston, MA USA. [Meehan, William P., III; Micheli, Lyle] Harvard Univ, Sch Med, Boston, MA USA. RP Pope, HG (reprint author), McLean Hosp, Biol Psychiat Lab, Belmont, MA 02478 USA. EM hpope@mclean.harvard.edu FU United States National Institutes on Drug Abuse (NIDA) [R01 DA029141] FX One or more of the authors has declared the following potential conflict of interest or source of funding: This research was supported in part by grant R01 DA029141 from the United States National Institutes on Drug Abuse (NIDA) to G.K., J.I.H., A.B., R.W., H.G.P., J.D., and S.I. NIDA had no further role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 55 TC 3 Z9 3 U1 0 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 EI 1552-3365 J9 AM J SPORT MED JI Am. J. Sports Med. PD NOV PY 2015 VL 43 IS 11 BP 2638 EP 2644 DI 10.1177/0363546515602010 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CV3XF UT WOS:000364199100003 PM 26362436 ER PT J AU Lohr, KM Clauser, A Hess, BJ Gelber, AC Valeriano-Marcet, J Lipner, RS Haist, SA Hawley, JL Zirkle, S Bolster, MB AF Lohr, Kristine M. Clauser, Amanda Hess, Brian J. Gelber, Allan C. Valeriano-Marcet, Joanne Lipner, Rebecca S. Haist, Steven A. Hawley, Janine L. Zirkle, Sarah Bolster, Marcy B. CA Amer Coll Rheumatology Comm Rheuma TI Performance on the Adult Rheumatology In-Training Examination and Relationship to Outcomes on the Rheumatology Certification Examination SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID RESIDENT PERFORMANCE; INTERNAL-MEDICINE; SCORES; BOARD; USMLE AB Objective. The American College of Rheumatology (ACR) Adult Rheumatology In-Training Examination (ITE) is a feedback tool designed to identify strengths and weaknesses in the content knowledge of individual fellows-in-training and the training program curricula. We determined whether scores on the ACR ITE, as well as scores on other major standardized medical examinations and competency-based ratings, could be used to predict performance on the American Board of Internal Medicine (ABIM) Rheumatology Certification Examination. Methods. Between 2008 and 2012, 629 second-year fellows took the ACR ITE. Bivariate correlation analyses of assessment scores and multiple linear regression analyses were used to determine whether ABIM Rheumatology Certification Examination scores could be predicted on the basis of ACR ITE scores, United States Medical Licensing Examination scores, ABIM Internal Medicine Certification Examination scores, fellowship directors' ratings of overall clinical competency, and demographic variables. Logistic regression was used to evaluate whether these assessments were predictive of a passing outcome on the Rheumatology Certification Examination. Results. In the initial linear model, the strongest predictors of the Rheumatology Certification Examination score were the second-year fellows' ACR ITE scores (beta=0.438) and ABIM Internal Medicine Certification Examination scores (beta=0.273). Using a stepwise model, the strongest predictors of higher scores on the Rheumatology Certification Examination were second-year fellows' ACR ITE scores (beta=0.449) and ABIM Internal Medicine Certification Examination scores (beta=0.276). Based on the findings of logistic regression analysis, ACR ITE performance was predictive of a pass/fail outcome on the Rheumatology Certification Examination (odds ratio 1.016 [95% confidence interval 1.011-1.021]). Conclusion. The predictive value of the ACR ITE score with regard to predicting performance on the Rheumatology Certification Examination supports use of the Adult Rheumatology ITE as a valid feedback tool during fellowship training. C1 [Lohr, Kristine M.] Univ Kentucky, Coll Med, Lexington, KY 40536 USA. [Clauser, Amanda; Haist, Steven A.; Hawley, Janine L.] Natl Board Med Examiners, Philadelphia, PA USA. [Hess, Brian J.] Hess Consulting, Montreal, PQ, Canada. [Gelber, Allan C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Valeriano-Marcet, Joanne] Univ S Florida, Morsani Coll Med, Tampa, FL USA. [Lipner, Rebecca S.] Amer Board Internal Med, Philadelphia, PA USA. [Zirkle, Sarah] Amer Coll Rheumatol, Atlanta, GA 30329 USA. [Bolster, Marcy B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lohr, KM (reprint author), Univ Kentucky, Div Rheumatol, Kentucky Clin J503,740 South Limestone St, Lexington, KY 40536 USA. EM kristinelohr@uky.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD NOV PY 2015 VL 67 IS 11 BP 3082 EP 3090 DI 10.1002/art.39281 PG 9 WC Rheumatology SC Rheumatology GA CU9RC UT WOS:000363881400034 PM 26215276 ER PT J AU Heisler, JM O'Connor, JC AF Heisler, Jillian M. O'Connor, Jason C. TI Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Neuroinflammation; Recognition memory; Novel object recognition; Kynurenine; Indoleamine 2,3-dioxygenase; Kynurenine monooxygenase; Neuropsychiatric symptom; Perirhinal cortex; Mouse; Behavior ID DEPRESSIVE-LIKE BEHAVIOR; OBJECT RECOGNITION; NMDA RECEPTOR; RESIDUAL SYMPTOMS; PREFRONTAL CORTEX; LIPOPOLYSACCHARIDE; BRAIN; RATS; MICE; HIPPOCAMPUS AB Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proin-flammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (ID01), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of ID01, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. C1 [Heisler, Jillian M.; O'Connor, Jason C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Heisler, Jillian M.; O'Connor, Jason C.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, Sch Med, San Antonio, TX 78229 USA. [O'Connor, Jason C.] Audie L Murphy VA Hosp, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP O'Connor, JC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl,216b Med Bldg, San Antonio, TX 78229 USA. EM HeislerJ@uthscsa.edu; oconnorj@uthscsa.edu FU National Institute of Mental Health [R01-MH090127, P30-MH089868]; Norman Hackerman Advanced Research Program; National Center for Advancing Translational Sciences [UL1TR001120]; NCRR-NIH [U42-RR024244]; trans-NIH Knock-Out Mouse Project (KOMP) [5U01HG004080] FX This research was supported by Grant Nos. R01-MH090127 and P30-MH089868 from the National Institute of Mental Health, the Norman Hackerman Advanced Research Program and Award Number UL1TR001120 from the National Center for Advancing Translational Sciences. The Kmo mouse model used for this research project was obtained from the KOMP Repository www.komp.org, a NCRR-NIH supported mouse strain repository (U42-RR024244). ES cells from which this mouse was generated were created by the CSD consortium from funds provided by the trans-NIH Knock-Out Mouse Project (KOMP) (Grant # 5U01HG004080). Email product inquiries to service@komp.org. NR 44 TC 9 Z9 10 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD NOV PY 2015 VL 50 BP 115 EP 124 DI 10.1016/j.bbi.2015.06.022 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CV4UK UT WOS:000364261800014 PM 26130057 ER PT J AU Opp, MR George, A Ringgold, KM Hansen, KM Bullock, KM Banks, WA AF Opp, Mark R. George, Amrita Ringgold, Kristyn M. Hansen, Kim M. Bullock, Kristin M. Banks, William A. TI Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-alpha in aging SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Sleep; Aging; Sepsis; Tumor necrosis factor-alpha; Blood-brain barrier ID TNF-ALPHA; INFLAMMATORY MARKERS; ENDOTHELIAL-CELLS; YOUNG-ADULTS; RAT-BRAIN; PERMEABILITY; MICE; LIPOPOLYSACCHARIDE; DEPRIVATION; CYTOKINES AB The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis factor-alpha (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood-brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism's responses to those insults occurs with aging. Published by Elsevier Inc. C1 [Opp, Mark R.; George, Amrita; Ringgold, Kristyn M.] Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA. [Hansen, Kim M.; Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. [Hansen, Kim M.; Bullock, Kristin M.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Banks, WA (reprint author), VAPSHCS, WAB, Rm 810A,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU VA; [R01 AG041287] FX Supported by R01 AG041287 (MRO) and VA (WAB). NR 63 TC 1 Z9 1 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD NOV PY 2015 VL 50 BP 259 EP 265 DI 10.1016/j.bbi.2015.07.023 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA CV4UK UT WOS:000364261800028 PM 26218294 ER PT J AU Brueckmann, B Sasaki, N Grobara, P Li, MK Woo, T de Bie, J Maktabi, M Lee, J Kwo, J Pino, R Sabouri, AS McGovern, F Staehr-Rye, AK Eikermann, M AF Brueckmann, B. Sasaki, N. Grobara, P. Li, M. K. Woo, T. de Bie, J. Maktabi, M. Lee, J. Kwo, J. Pino, R. Sabouri, A. S. McGovern, F. Staehr-Rye, A. K. Eikermann, M. TI Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE neostigmine/glycopyrrolate; neuromuscular blockade; neuromuscular blocking agents; randomized-controlled trial; rocuronium; sugammadex ID BLOCKING-AGENTS; RESPIRATORY COMPLICATIONS; CONTROLLED-TRIAL; NEOSTIGMINE REVERSAL; ROCURONIUM; SURGERY; PARALYSIS; DURATION; RISK; CURARIZATION AB Background: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. Methods: Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio <0.9, using TOF-Watch (R) SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance. Results: Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch (R) SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P<0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs 18.6 min respectively; P=0.02). Conclusions: After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room. C1 [Brueckmann, B.; Sasaki, N.; Kwo, J.; Pino, R.; Sabouri, A. S.; Staehr-Rye, A. K.; Eikermann, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Grobara, P.] MSD, Biostat & Res Decis Sci, Oss, Netherlands. [Li, M. K.; Woo, T.; de Bie, J.] Merck Sharp & Dohme Corp, Clin Res, Whitehouse Stn, NJ USA. [Maktabi, M.; Lee, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trauma,Emergency Surg,Surg Crit Care, Boston, MA USA. [Kwo, J.; Pino, R.; McGovern, F.; Eikermann, M.] Harvard Univ, Sch Med, Boston, MA USA. [McGovern, F.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Staehr-Rye, A. K.] Univ Copenhagen, Herlev Hosp, Dept Anesthesiol, DK-2730 Herlev, Denmark. [Eikermann, M.] Essen Duisburg Univ, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org FU Merck Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA FX Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA provided financial support to the study. NR 36 TC 19 Z9 19 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 EI 1471-6771 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD NOV PY 2015 VL 115 IS 5 BP 743 EP 751 DI 10.1093/bja/aev104 PG 9 WC Anesthesiology SC Anesthesiology GA CV0IP UT WOS:000363934700014 PM 25935840 ER PT J AU Diefenbach, CS Li, HL Hong, FX Gordon, LI Fisher, RI Bartlett, NL Crump, M Gascoyne, RD Wagner, H Stiff, PJ Cheson, BD Stewart, DA Kahl, BS Friedberg, JW Blum, KA Habermann, TM Tuscano, JM Hoppe, RT Horning, SJ Advani, RH AF Diefenbach, Catherine S. Li, Hailun Hong, Fangxin Gordon, Leo I. Fisher, Richard I. Bartlett, Nancy L. Crump, Michael Gascoyne, Randy D. Wagner, Henry, Jr. Stiff, Patrick J. Cheson, Bruce D. Stewart, Douglas A. Kahl, Brad S. Friedberg, Jonathan W. Blum, Kristie A. Habermann, Thomas M. Tuscano, Joseph M. Hoppe, Richard T. Horning, Sandra J. Advani, Ranjana H. TI Evaluation of the International Prognostic Score (IPS-7) and a Simpler Prognostic Score (IPS-3) for advanced Hodgkin lymphoma in the modern era SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Hodgkin lymphoma; International Prognostic Score; prognostic score; ABVD; Stanford V ID TUMOR-ASSOCIATED MACROPHAGES; RESPONSE ASSESSMENT; RADIATION-THERAPY; INTERGROUP TRIAL; STANFORD V; R-CHOP; CHEMOTHERAPY; ABVD; INTENSITY; SURVIVAL AB The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P=0.0001) and OS (P<0.0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned. C1 [Diefenbach, Catherine S.] NYU, New York, NY 10016 USA. [Li, Hailun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hong, Fangxin] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Gordon, Leo I.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Fisher, Richard I.] Washington Univ, Sch Med, St Louis, MO USA. [Bartlett, Nancy L.] Princess Margaret Canc Ctr, Toronto, ON, Canada. [Crump, Michael] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Gascoyne, Randy D.] Penn State Canc Inst, Hershey, PA USA. [Wagner, Henry, Jr.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Stiff, Patrick J.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Cheson, Bruce D.] Tom Baker Canc Clin, Calgary, AB, Canada. [Stewart, Douglas A.] Univ Wisconsin, Madison, WI USA. [Kahl, Brad S.] Univ Rochester, Rochester, NY USA. [Friedberg, Jonathan W.] Ohio State Univ, Columbus, OH 43210 USA. [Blum, Kristie A.] Mayo Clin, Rochester, MN USA. [Tuscano, Joseph M.] Calif State Univ Sacramento, Davis Canc Ctr, Sacramento, CA 95819 USA. [Hoppe, Richard T.; Advani, Ranjana H.] Stanford Univ, Stanford, CA 94305 USA. [Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA. RP Diefenbach, CS (reprint author), NYU, Perlmutter Canc Ctr, 240 East 38th St,19th Floor, New York, NY 10016 USA. EM catherine.diefenbach@nyumc.org OI Diefenbach, Catherine/0000-0003-1116-3246 FU American Cancer Society [MRSG-14-052-01-LIB]; ECOG-ACRIN Cancer Research Group; Public Health Service [CA21115, CA180820, CA180794, CA23318, CA66636, CA17145, CA13650, CA180790, CA21076, CA180799, CA180816, CA11083, CA27525, CA32102, CA46282, CA77440, CA77597, CA77658, CA31946, CA33601, CA77202]; National Cancer Institute; National Institutes of Health; Department of Health and Human Services FX Supported in part by research funding from the American Cancer Society (MRSG-14-052-01-LIB) CD. This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service CA21115, CA180820, CA180794, CA23318, CA66636, CA17145, CA13650, CA180790, CA21076, CA180799, CA180816, CA11083, CA27525, CA32102, CA46282, CA77440, CA77597, CA77658, CA31946, CA33601, CA77202 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Presented in part: 9th International Hodgkin Lymphoma Symposium, Cologne 2013; American Society of Hematology Annual Meeting, 2013. NR 36 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2015 VL 171 IS 4 BP 530 EP 538 DI 10.1111/bjh.13634 PG 9 WC Hematology SC Hematology GA CV0NL UT WOS:000363947300012 PM 26343802 ER PT J AU Song, C Castellanos-Rizaldos, E Bejar, R Ebert, BL Makrigiorgos, GM AF Song, Chen Castellanos-Rizaldos, Elena Bejar, Rafael Ebert, Benjamin L. Makrigiorgos, G. Mike TI DMSO Increases Mutation Scanning Detection Sensitivity of High-Resolution Melting in Clinical Samples SO CLINICAL CHEMISTRY LA English DT Article ID POLYMERASE-CHAIN-REACTION; COLD-PCR; DNA-SEQUENCES; AMPLIFICATION; TEMPERATURE; ENRICHMENT; CANCER; RENATURATION; SPECIFICITY; IMPROVES AB BACKGROUND: Mutation seanning provides the simplest, lowest-cost method for identifying DNA variations on single PCR amplicons, and it may be performed before sequencing to avoid screening of noninformative wild-type samples. High-resolution melting (HRM) is the most commonly used method for mutation scanning. With PCR-HRM, however, mutations less abundant than approximately 3%-10% that can still be clinically significant may often be missed. Therefore, enhancing HRM detection sensitivity is important for mutation scanning and its clinical application. METHODS: We used serial dilution of cell lines containing the TP53 exon 8 mutation to demonstrate the improvement in detection sensitivity for conventional-PCR-HRM in the presence of DMSO. We also conducted coamplification at lower denaturation temperature (COLD)-PCR with an extra step for cross-hybridization, followed by preferential denaturation and amplification at optimized critical temperature (full-COLD-PCR), to further enrich low-level mutations before HRM with or without DMSO, and we used droplet-digital PCR to derive the optimal conditions for mutation enrichment. Both conventional PCR-HRM and full-COLD-PCR-HRM with and without DMSO were used for mutation scanning of TP53 exon 8 in cancer samples containing known mutations and myelodysplastic syndrome samples with unknown mutations. Mutations in other genes were also examined. RESULTS: The detection sensitivity of PCR-HRM scanning increases 2- to 5-fold in the presence of DMSO, depending on mutation type and sequence context, and can typically detect mutation abundance of approximately 1%. When mutation enrichment is applied during amplification with full-COLD-PCR followed by HRM in the presence of DMSO, mutations with 0.2%-0.3% abundance in TP53 exon 8 can be detected. CONCLUSIONS: DMSO improves HRM mutation scanning sensitivity with saturating dyes. When full-COLD-PCR is used, followed by DMSO-HRM, the overall improvement is about 20-fold compared with conventional PCR-HRM. (C) 2015 American Association for Clinical Chemistry C1 [Song, Chen; Castellanos-Rizaldos, Elena; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Bejar, Rafael] UCSD, Div Hematol & Oncol, Moores Canc Ctr, La Jolla, CA USA. [Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Radiat Therapy, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu RI Song, Chen/H-6615-2015 OI Song, Chen/0000-0002-4439-4377 FU National Cancer Institute grant [R21CA-175542] FX G.M. Makrigiorgos, National Cancer Institute grant R21CA-175542. NR 37 TC 1 Z9 1 U1 5 U2 8 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 2015 VL 61 IS 11 BP 1354 EP 1362 DI 10.1373/clinchem.2015.245357 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CV2UH UT WOS:000364112200008 PM 26432802 ER PT J AU Huang, JQ Lohr, JM Nilsson, M Segersvard, R Matsson, H Verbeke, C Heuchel, R Kere, J Iafrate, AJ Zheng, ZL Ye, WM AF Huang, Jiaqi Lohr, Johannes-Matthias Nilsson, Magnus Segersvard, Ralf Matsson, Hans Verbeke, Caroline Heuchel, Rainer Kere, Juha Iafrate, A. John Zheng, Zongli Ye, Weimin TI Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma SO CLINICAL CHEMISTRY LA English DT Article ID K-RAS MUTATIONS; CIGARETTE-SMOKING; SIGNALING PATHWAYS; TGF-BETA; CANCER; CARCINOMAS; P53; TRANSVERSIONS; FREQUENCY; PROGNOSIS AB BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Variant profiling is crucial for developing personalized treatment and elucidating the etiology of this disease. METHODS: Patients with PDAC undergoing surgery from 2007 to 2012 (n = 73) were followed from diagnosis until death or the end of the study. We applied an anchored multiplex PCR (AMP)-based next-generation sequencing (NGS) method to a panel of 65 selected genes and assessed analytical performance by sequencing a quantitative multiplex DNA reference standard. In clinical PDAC samples, detection of low-level KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations was validated by allele-specific PCR and digital PCR. We compared overall survival of patients according to KRAS mutation status by log-rank test and applied logistic regression to evaluate the association between smoking and tumor variant types. RESULTS: The AMP-based NGS method could detect variants with allele frequencies as low as 1% given sufficient sequencing depth (>1500X). Low-frequency KRAS G12 mutations (allele frequency 1%-5%) were all confirmed by allele-specific PCR and digital PCR. The most prevalent genetic alterations were in KRAS (78% of patients), TP53 (tumor protein p53) (25%), and SMAD4 (SMAD family member 4) (8%). Overall survival in T3-stage PDAC patients differed among KRAS mutation subtypes (P = 0.019). Transversion variants were more common in ever-smokers than in never-smokers (odds ratio 5.7; 95% CI 1.2-27.8). CONCLUSIONS: The AMP-based NGS method is applicable for profiling tumor-variants. Using this approach, we demonstrated that in PDAC patients, KRAS mutant sub. type G12V is associated with poorer survival, and that transversion variants are more common among smokers. (C) 2015 American Association for Clinical Chemistry C1 [Huang, Jiaqi; Zheng, Zongli; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Verbeke, Caroline] Karolinska Inst, Div Pathol, Dept Lab Med, Stockholm, Sweden. [Lohr, Johannes-Matthias; Nilsson, Magnus; Segersvard, Ralf; Heuchel, Rainer] Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden. [Lohr, Johannes-Matthias; Nilsson, Magnus; Segersvard, Ralf; Heuchel, Rainer] Karolinska Univ Hosp, Div Surg, CLINTEC, Stockholm, Sweden. [Verbeke, Caroline] Karolinska Univ Hosp, Clin Pathol Cytol, Stockholm, Sweden. [Matsson, Hans; Kere, Juha] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden. [Matsson, Hans; Kere, Juha] Karolinska Inst, Ctr Innovat Med CIMED, Huddinge, Sweden. [Iafrate, A. John; Zheng, Zongli] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zheng, ZL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM zhengzongli@gmail.com; weimin.ye@ki.se RI Kere, Juha/A-9179-2008; Zheng, Zongli/B-2917-2011; OI Kere, Juha/0000-0003-1974-0271; Zheng, Zongli/0000-0003-4849-4903; Lohr, Matthias/0000-0002-7647-198X FU Robert Lundbergs Memory Foundation [2014lund40761, 2015lund45331]; Karolinska Institutet (KID); ALF [20130022]; MolDiagPaCa from the Sixth framework programme of European Union [018771]; Swedish Research Council [2012-2279, 2012-368]; Cancerfonden [2013-798] FX J. Huang, the Robert Lundbergs Memory Foundation (2014lund40761, 2015lund45331) and a scholarship from Karolinska Institutet (KID); J.-M. Lohr, ALF (20130022) and MolDiagPaCa from the Sixth framework programme of European Union (018771); M. Nilsson, MolDiagPaCa from the Sixth framework programme of European Union (018771); J. Kere, Swedish Research Council (2012-2279); Z. Zheng, Swedish Research Council (2012-368); W. Ye, Cancerfonden (2013-798). NR 40 TC 5 Z9 5 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2015 VL 61 IS 11 BP 1408 EP 1416 DI 10.1373/clinchem.2015.238543 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA CV2UH UT WOS:000364112200014 PM 26378065 ER PT J AU Willey, A Anderson, RR Sakamoto, FH AF Willey, Andrea Anderson, R. Rox Sakamoto, Fernanda H. TI Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A One-Year Follow-up Study SO DERMATOLOGIC SURGERY LA English DT Article ID 5-AMINOLEVULINIC ACID; BLUE-LIGHT; TRIAL; GEL AB BACKGROUNDThe efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AK) is lower on the distal extremities compared with head and neck areas. A recent pilot study demonstrated increased efficacy of ALA PDT when the skin is warmed during ALA incubation. Prolonged clearance rates on the heated extremity were noted in 3 subjects that were evaluated after the study ended. The aim of this study was to evaluate the longevity of clearance rates after temperature-modulated PDT for the treatment of AKs on the extremities.MATERIALS AND METHODSA total of 18 subjects (20 pairs of extremities) with at least 10 AKs on the upper or lower extremities were enrolled in the single-center study. Twenty percent ALA was applied to both extremities and heated during the 1-hour incubation period, followed by exposure to 10 J/cm(2) 417-nm blue light. Lesions were photographed, counted, and templated at baseline, 1 week, and 3, 6, 9, and 12 months after treatment.RESULTSA total of 17 subjects completed the 1-year study. The total number of lesions counted at baseline was 724 Grade 1 and 2 AKs (median 15 on each extremity). The lesion count at 3 and 12 months was 70 (9.6%) and 72 (9.9%), respectively. Grade 3 AKs did not resolve with treatment. The median baseline temperature of the treated extremities was 31.6 degrees C. The median maximum temperature during the 1-hour incubation period was 41.2 degrees C. The median clearance at 3 months was 90% and the same was maintained at 12 months. No new AK lesions formed in the treated areas within the 12-month follow-up period.CONCLUSIONWarming the skin after application of ALA is well tolerated, does not increase side effects, and increases the long-term efficacy of PDT for the treatment of AKs. The authors suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice. C1 [Willey, Andrea] Surg & Aesthet Dermatol Sacramento, Sacramento, CA USA. [Willey, Andrea] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. [Anderson, R. Rox; Sakamoto, Fernanda H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Anderson, R. Rox; Sakamoto, Fernanda H.] Harvard Univ, Sch Med, Boston, MA USA. RP Willey, A (reprint author), 2277 Fair Oaks Blvd,Suite 402, Sacramento, CA 95825 USA. EM andrea.willey@mac.com FU DUSA Pharmaceuticals, Inc. FX Dr. A. Willey received a research grant, equipment loan, and study drug from DUSA Pharmaceuticals, Inc. to perform this study. Dr. A. Willey is a member of the scientific advisory board for DUSA Pharmaceuticals. The remaining authors have indicated no significant interest with commercial supporters. NR 15 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 2015 VL 41 IS 11 BP 1290 EP 1295 DI 10.1097/DSS.0000000000000512 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA CV3ZD UT WOS:000364204300011 PM 26445287 ER PT J AU Hwang, YC Hayashi, T Fujimoto, WY Kahn, SE Leonetti, DL McNeely, MJ Boyko, EJ AF Hwang, You-Cheol Hayashi, Tomoshige Fujimoto, Wilfred Y. Kahn, Steven E. Leonetti, Donna L. McNeely, Marguerite J. Boyko, Edward J. TI Differential Association Between HDL Subclasses and the Development of Type 2 Diabetes in a Prospective Study of Japanese Americans SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; LIPOPROTEIN CHOLESTEROL LEVELS; APOLIPOPROTEIN-A-I; VISCERAL ADIPOSITY; INSULIN-RESISTANCE; RISK-FACTORS; GLUCOSE; MELLITUS; SUBFRACTIONS; METAANALYSIS AB OBJECTIVE Recent studies have suggested that HDL cholesterol is inversely associated with the development of type 2 diabetes. However, little is known about the association between different HDL subclasses and the risk for future type 2 diabetes. RESEARCH DESIGN AND METHODS The study enrolled 406 Japanese Americans (51% male) without diabetes, aged 34-75 years. Oral glucose tolerance tests were performed to determine type 2 diabetes status at baseline, 2.5 years, 5 years, and 10 years after enrollment. HDL2, HDL3, total HDL cholesterol, and visceral adipose tissue (VAT) area by computed tomography were measured at baseline. RESULTS In univariate analysis, total HDL and HDL2 cholesterol were inversely associated with the incidence of type 2 diabetes, but HDL3 cholesterol was not. In multivariate analysis, total HDL cholesterol (odds ratio per 1-SD increment, 0.72 [95% CI 0.52-0.995], P = 0.047) and HDL2 cholesterol (odds ratio per 1-SD increment, 0.64 [95% CI 0.44-0.93], P = 0.018) were inversely associated with the risk for type 2 diabetes independent of age, sex, BM!, waist circumference, family history of diabetes, lifestyle factors, systolic blood pressure, lipid-lowering medication use, triglyceride level, HOMA-insulin resistance, and 2-h glucose; however, HDL3 cholesterol was not associated with diabetes risk. The association between diabetes risk and total HDL and HDL2 cholesterol became insignificant after adjustment for VAT area. CONCLUSIONS Subjects with higher HDL2 cholesterol were at lower risk for incident type 2 diabetes, but this association was confounded by and not independent of VAT. Higher HDL3 cholesterol was not associated with diabetes risk. C1 [Hwang, You-Cheol; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Hwang, You-Cheol] Kyung Hee Univ, Sch Med, Hosp Gangdong, Dept Med,Div Endocrinol & Metab, Seoul, South Korea. [Hayashi, Tomoshige] Osaka City Univ, Grad Sch Med, Dept Prevent Med & Environm Hlth, Osaka 558, Japan. [Fujimoto, Wilfred Y.; Kahn, Steven E.; McNeely, Marguerite J.; Boyko, Edward J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Hosp & Specialty Med Serv, Seattle, WA USA. [Leonetti, Donna L.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. EM eboyko@uw.edu OI Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-17047, DK-35816]; National Institutes of Health Clinical Center [RR-00037]; VA Puget Sound Health Care System FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grants DK-17047 and DK-35816 to the Diabetes Research Center Clinical Nutrition Research Unit for facilities and services, and by National Institutes of Health Clinical Center grant RR-00037 to the General Clinical Research Center at the University of Washington. The VA Puget Sound Health Care System provided support to S.E.K. and E.J.B. for their involvement in this research. NR 32 TC 2 Z9 2 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2015 VL 38 IS 11 BP 2100 EP 2105 DI 10.2337/dc15-0625 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV5WQ UT WOS:000364342500029 PM 26384391 ER PT J AU Mosenzon, O Wei, C Davidson, J Scirica, BM Yanuv, I Rozenberg, A Hirshberg, B Cahn, A Stahre, C Strojek, K Bhatt, DL Raz, I AF Mosenzon, Ofri Wei, Cheryl Davidson, Jaime Scirica, Benjamin M. Yanuv, Ilan Rozenberg, Aliza Hirshberg, Boaz Cahn, Avivit Stahre, Christina Strojek, Krzysztof Bhatt, Deepak L. Raz, Itamar TI Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial SO DIABETES CARE LA English DT Article ID BONE-MINERAL DENSITY; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; DEPENDENT INSULINOTROPIC PEPTIDE; INCREASED RISK; POSTMENOPAUSAL WOMEN; HIP-FRACTURES; OLDER WOMEN; MELLITUS; ROSIGLITAZONE; GLUCOSE AB OBJECTIVE Patients with type 2 diabetes have an increased risk of bone fractures, the predisposing factors for which are unknown. Treatment with thiazolidinediones (TZDs) further increases the incidence of osteoporotic fractures. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, fractures were considered an adverse event of special interest, and information regarding fractures was collected. RESEARCH DESIGN AND METHODS We compared the incidence of fractures among the 8,280 patients who were assigned to treatment with saxagliptin with that in the 8,212 patients who were assigned to placebo. We further analyzed the participants' baseline characteristics and fracture risk. RESULTS During a median follow-up of 2.1 years, 241 patients (2.9%) in the saxagliptin group and 240 (2.9%) in the placebo group experienced a fracture (hazard ratio [HR] 1.00 [95% CI 0.83-1.19]). Event rates for fractures were the same in both treatment arms: 14.7 per 1,000 patient-years in the entire population and 14.0 in the on-treatment population (first event only). Fracture risk was similar in patients treated with saxagliptin or placebo across different subgroups defined by race, cardiovascular risk, and renal function. A multivariable Cox regression analysis showed that risk of fracture was associated with female sex (P < 0.0001), longer diabetes duration (P < 0.0001), older age (P = 0.002), major hypoglycemic events (P = 0.01), noncompliance with study drug (P = 0.01), and treatment with TZDs (P = 0.03). CONCLUSIONS In a large population of older patients with type 2 diabetes, treatment with saxagliptin was not associated with an increased risk of fractures. The association between longer diabetes duration and increased risk of bone fracture is an intriguing finding. C1 [Mosenzon, Ofri; Yanuv, Ilan; Rozenberg, Aliza; Cahn, Avivit; Raz, Itamar] Hadassah Hebrew Univ Hosp, Diabet Unit, Jerusalem, Israel. [Wei, Cheryl] AstraZeneca, Gaithersburg, MD USA. [Davidson, Jaime] Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA. [Scirica, Benjamin M.; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Hirshberg, Boaz] AstraZeneca Res & Dev, Wilmington, DE USA. [Stahre, Christina] AstraZeneca, Molndal, Sweden. [Strojek, Krzysztof] Med Univ Silesia, Dept Internal Dis,Diabetol & Cardiometabol Dis, Sch Med Div Dent Zabrze, Katowice, Poland. RP Raz, I (reprint author), Hadassah Hebrew Univ Hosp, Diabet Unit, Jerusalem, Israel. FU AstraZeneca; Bristol-Myers Squibb FX The SAVOR-TIMI 53 trial was funded by AstraZeneca and Bristol-Myers Squibb. NR 38 TC 10 Z9 11 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2015 VL 38 IS 11 BP 2142 EP 2150 DI 10.2337/dc15-1068 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CV5WQ UT WOS:000364342500035 PM 26358285 ER PT J AU Struck, AF Cole, AJ Cash, SS Westover, MB AF Struck, Aaron F. Cole, Andrew J. Cash, Sydney S. Westover, M. Brandon TI The number of seizures needed in the EMU SO EPILEPSIA LA English DT Article DE Epilepsy monitoring unit; Epilepsy surgery; Bayesian inference; Survival analysis ID TEMPORAL-LOBE EPILEPSY; CLINICAL-TRIALS; LOBECTOMY AB ObjectiveThe purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU). MethodsPatient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission. ResultsMultifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p<0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p=0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%. SignificanceThese results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery. C1 [Struck, Aaron F.; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Struck, AF (reprint author), 55 Fruit St,Wang 7, Boston, MA 02114 USA. EM astruck@mgh.harvard.edu OI Cole, Andrew/0000-0002-0828-826X FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [K23 NS090900]; Rappaport Foundation; Andrew David Heitman Neuroendovascular Research Fund; NIH-NINDS [RO1 NS062092, K24 NS088568] FX Dr. Westover was supported by grants from National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS; K23 NS090900), The Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Fund. Dr. Cash received funding from NIH-NINDS (RO1 NS062092, K24 NS088568). Dr Cole reports no disclosures. Dr. Struck reports no disclosures. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 21 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 56 IS 11 BP 1753 EP 1759 DI 10.1111/epi.13090 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CU9RZ UT WOS:000363884100020 PM 26222350 ER PT J AU Van Eylen, L Boets, B Steyaert, J Wagemans, J Noens, I AF Van Eylen, Lien Boets, Bart Steyaert, Jean Wagemans, Johan Noens, Ilse TI Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Autism spectrum disorders; Executive functioning; Age; IQ; Gender; Symptom severity ID DEVELOPMENTAL DISORDERS; COMMUNICATION DEFICITS; INDIVIDUAL-DIFFERENCES; REPETITIVE BEHAVIORS; DIAGNOSTIC INTERVIEW; RESPONSE-INHIBITION; YOUNG-CHILDREN; REAL-WORLD; GENERATIVITY; FLEXIBILITY AB Impaired executive functioning (EF) has been proposed to underlie symptoms of autism spectrum disorders (ASD). However, insight in the EF profile of ASD individuals is hampered due to task impurity and inconsistent findings. To elucidate these inconsistencies, we investigated the influence of task and sample characteristics on EF in ASD, with an extended test battery designed to reduce task impurity. Additionally, we studied the relation between EF and ASD symptoms. EF (inhibition, cognitive flexibility, generativity, working memory and planning) was measured in open-ended versus structured assessment situations, while controlling for possible confounding EF and non-EF variables. The performance of 50 individuals with ASD was compared with that of 50 age, gender and IQ matched typically developing (TD) individuals. The effects of group (ASD versus TD), age (children versus adolescents) and gender were examined, as well as the correlation between age, IQ, ASD symptoms and EF. Individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in open-ended compared to structured settings. Group differences did not depend on gender and only occasionally on participants' age. This suggests that inconsistencies between studies largely result from differences in task characteristics and less from differences in the investigated sample features. However, age and IQ strongly correlated with EF, indicating that group differences in these factors should be controlled for when studying EF. Finally, EF correlated with both social and non-social ASD symptoms, but further research is needed to clarify the nature of this relationship. C1 [Van Eylen, Lien; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Unit, B-3000 Leuven, Belgium. [Van Eylen, Lien; Boets, Bart; Steyaert, Jean; Wagemans, Johan; Noens, Ilse] Katholieke Univ Leuven, Leuven Autism Res LAuRes, B-3000 Leuven, Belgium. [Boets, Bart; Steyaert, Jean] UPC KU Leuven, Dept Child Psychiat, Leuven, Belgium. [Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. [Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, B-3000 Leuven, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Van Eylen, L (reprint author), Katholieke Univ Leuven, Parenting & Special Educ Res Unit, Leopold Vanderkelenstr 32,Box 3765, B-3000 Leuven, Belgium. EM Lien.VanEylen@ppw.kuleuven.be FU Marguerite-Marie Delacroix; Research Council of KU Leuven [IDO/08/013] FX L. Van Eylen is a doctoral and B. Boets a post-doctoral research fellow of the Research Foundation Flanders (FWO). Additionally, the research was funded by a fellowship from the Marguerite-Marie Delacroix to L. Van Eylen and a grant from the Research Council of KU Leuven (IDO/08/013). We thank all participants, and all master students as well as B. Machilsen, A. Verhappen and V. Stevens for assistance in data collection and scoring. NR 82 TC 5 Z9 5 U1 8 U2 41 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 EI 1435-165X J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD NOV PY 2015 VL 24 IS 11 BP 1399 EP 1417 DI 10.1007/s00787-015-0689-1 PG 19 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CV0UJ UT WOS:000363968600011 PM 25697266 ER PT J AU Gonzalez, TA Lucas, RC Miller, TJ Gitajn, IL Zurakowski, D Kwon, JY AF Gonzalez, Tyler A. Lucas, Robert C. Miller, Timothy J. Gitajn, I. Leah Zurakowski, David Kwon, John Y. TI Posterior Facet Settling and Changes in Bohler's Angle in Operatively and Nonoperatively Treated Calcaneus Fractures SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE calcaneus fracture; Bohler's angle; foot and ankle; posterior facet settling; outcomes; intra-articular ID COMPUTED-TOMOGRAPHY; NONLOCKING PLATES; LOCKING PLATES; FIXATION; ALCOHOL; REDUCTION; CARTILAGE; REPAIR; MODEL; TRIAL AB Background: Patients with calcaneus fractures often exhibit settling of the posterior facet with a corresponding decrease in Bohler's angle (BA) following either operative or nonoperative treatment. Both injury BA and postoperative BA have been shown to be prognostic for outcomes; however, the demographic and surgeon-specific factors that may contribute to settling have not been critically examined in the literature. The purpose of this study was to identify these causative factors. Methods: 234 patients with intra-articular calcaneus fractures were analyzed. All patients had preoperative plain radiographs, at least 5 months of orthopedic follow-up, and computed tomography scanning performed. BA was measured on the injury radiographs for all patients. For operatively treated patients, BA was measured on the immediate postoperative radiographs and compared with the last available radiograph. For nonoperatively treated patients, BA was measured on the last available radiograph. All patients were fully weightbearing at the time of final follow-up but not on initial radiographs due to their recent injury. Demographic data including age, gender, energy of injury mechanism, tobacco use, diabetes, osteoporosis, rheumatoid arthritis, and substance/alcohol abuse were retrospectively collected. Fractures were classified using the Essex-Lopresti and Sanders classifications. Time to full weightbearing was documented, as were any reports of noncompliance with weightbearing restrictions. For patients treated operatively, type of fixation (calcaneal-specific perimeter plate, nonperimeter plate, screw fixation), use of locking screws, use of bone graft or graft substitutes, and the number of screws supporting the posterior facet were documented. Results: There was a statistically significant amount of settling within the operative and nonoperative groups, but there was no statistically significant difference in settling of BA between the groups. The average settling of BA for the operative and nonoperative group was 8 degrees. Age greater than 50 years, diabetes, and alcohol abuse were all statistically significant and independent predictors of BA settling irrespective of treatment. Conclusion: The amount of BA settling between the operative and nonoperative group was not significant and showed an average decrease of 8 degrees in each group. However, the amount of settling that we found, irrespective of treatment, increased with patient age, alcohol abuse, and diabetes. Level of Evidence: Level III, retrospective comparative study. C1 [Gonzalez, Tyler A.; Gitajn, I. Leah] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. [Lucas, Robert C.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Miller, Timothy J.] KSF Orthopaed Ctr PA, Orthopaed Surg, Houston, TX USA. [Zurakowski, David] Boston Childrens Hosp, Orthoped Ctr, Boston, MA USA. [Kwon, John Y.] Harvard Univ, Sch Med, Orthopaed Surg, Boston, MA USA. [Kwon, John Y.] Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Div Foot & Ankle Surg, Boston, MA 02215 USA. RP Gonzalez, TA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Combined Orthopaed Residency Program, 55 Fruit St,White 565, Boston, MA 02114 USA. EM tagonzalez@partners.org NR 43 TC 3 Z9 3 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD NOV PY 2015 VL 36 IS 11 BP 1297 EP 1309 DI 10.1177/1071100715592448 PG 13 WC Orthopedics SC Orthopedics GA CV3XZ UT WOS:000364201300006 PM 26109606 ER PT J AU Shin, EJ Topazian, M Goggins, MG Syngal, S Saltzman, JR Lee, JH Farrell, JJ Canto, MI AF Shin, Eun Ji Topazian, Mark Goggins, Michael G. Syngal, Sapna Saltzman, John R. Lee, Jeffrey H. Farrell, James J. Canto, Marcia I. TI Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL NEOPLASTIC POLYPS; COLONOSCOPIC MISS-RATE; TO-BACK COLONOSCOPIES; ENDOSCOPIC ULTRASOUND; CANCER; RATES; ENDOSONOGRAPHY; ULTRASONOGRAPHY; PREVALENCE; DIAGNOSIS AB Background: Studies comparing linear and radial EUS for the detection of pancreatic lesions in an asymptomatic population with increased risk for pancreatic cancer are lacking. Objectives: To compare pancreatic lesion detection rates between radial and linear EUS and to determine the incremental diagnostic yield of a second EUS examination. Design: Randomized controlled tandem study. Setting: Five academic centers in the United States. Patients: Asymptomatic high-risk individuals (HRIs) for pancreatic cancer undergoing screening EUS. Interventions: Linear and radial EUS performed in randomized order. Main Outcome Measurements: Pancreatic lesion detection rate by type of EUS, miss rate of 1 EUS examination, and incremental diagnostic yield of a second EUS examination (second-pass effect). Results: Two hundred seventy-eight HRIs were enrolled, mean age 56 years (43.2%), and 90% were familial pancreatic cancer relatives. Two hundred twenty-four HRIs underwent tandem radial and linear EUS. When we used per-patient analysis, the overall prevalence of any pancreatic lesion was 45%. Overall, 16 of 224 HRIs (7.1%) had lesions missed during the initial EUS that were detected by the second EUS examination. The per-patient lesion miss rate was significantly greater for radial followed by linear EUS (9.8%) than for linear followed by radial EUS (4.5%) (P = .03). When we used per-lesion analysis, 73 of 109 lesions (67%) were detected by radial EUS and 99 of 120 lesions (82%) were detected by linear EUS (P < .001) during the first examination. The overall miss rate for a pancreatic lesion after 1 EUS examination was 47 of 229 (25%). The miss rate was significantly lower for linear EUS compared with radial EUS (17.5% vs 33.0%, P = .007). Limitations: Most detected pancreatic lesions were not confirmed by pathology. Conclusion: Linear EUS detects more pancreatic lesions than radial EUS. There was a "second-pass effect" with additional lesions detected with a second EUS examination. This effect was significantly greater when linear EUS was used after an initial radial EUS examination. C1 [Shin, Eun Ji; Goggins, Michael G.; Canto, Marcia I.] Johns Hopkins Med Inst, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21205 USA. [Topazian, Mark] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna; Saltzman, John R.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Lee, Jeffrey H.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Farrell, James J.] Yale Univ, Sch Med, Sect Digest Dis, New Haven, CT USA. RP Canto, MI (reprint author), Johns Hopkins Univ, Div Gastroenterol, Sol Goldman Pancreat Canc Res Ctr, 600 N Wolfe St,Blalock Room 407, Baltimore, MD 21287 USA. EM mcanto@jhmi.edu OI Syngal, Sapna/0000-0001-5487-7471 FU National Cancer Institute Specialized Program in Research Excellence (SPORE) Clinical Intervention Supplement [2 P50 CA62924]; Lustgarten Foundation for Pancreatic Cancer Research; Michael Rolfe Foundation; Olympus Corporation; Cooke Medical; Karp Family H.H. & M. Metals, Inc. Fund for Cancer Research; ChiRhoClin FX All authors received research support for this study from National Cancer Institute Specialized Program in Research Excellence (SPORE) Clinical Intervention Supplement 2 P50 CA62924, The Lustgarten Foundation for Pancreatic Cancer Research, The Michael Rolfe Foundation, Olympus Corporation, Cooke Medical, Karp Family H.H. & M. Metals, Inc. Fund for Cancer Research, and ChiRhoClin. All authors disclosed no financial relationships relevant to this publication. NR 34 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2015 VL 82 IS 5 BP 812 EP 818 DI 10.1016/j.gie.2015.02.028 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV3NP UT WOS:000364166200006 PM 25930097 ER PT J AU Lemire, M Qu, CH Loo, LWM Zaidi, SHE Wang, H Berndt, SI Bezieau, S Brenner, H Campbell, PT Chan, AT Chang-Claude, J Du, MM Edlund, CK Gallinger, S Haile, RW Harrison, TA Hoffmeister, M Hopper, JL Hou, LF Hsu, L Jacobs, EJ Jenkins, MA Jeon, J Kury, S Li, L Lindor, NM Newcomb, PA Potter, JD Rennert, G Rudolph, A Schoen, RE Schumacher, FR Seminara, D Severi, G Slattery, ML White, E Woods, MO Cotterchio, M Le Marchand, L Casey, G Gruber, SB Peters, U Hudson, TJ AF Lemire, Mathieu Qu, Conghui Loo, Lenora W. M. Zaidi, Syed H. E. Wang, Hansong Berndt, Sonja I. Bezieau, Stephane Brenner, Hermann Campbell, Peter T. Chan, Andrew T. Chang-Claude, Jenny Du, Mengmeng Edlund, Christopher K. Gallinger, Steven Haile, Robert W. Harrison, Tabitha A. Hoffmeister, Michael Hopper, John L. Hou, Lifang Hsu, Li Jacobs, Eric J. Jenkins, Mark A. Jeon, Jihyoun Kuery, Sebastien Li, Li Lindor, Noralane M. Newcomb, Polly A. Potter, John D. Rennert, Gad Rudolph, Anja Schoen, Robert E. Schumacher, Fredrick R. Seminara, Daniela Severi, Gianluca Slattery, Martha L. White, Emily Woods, Michael O. Cotterchio, Michelle Le Marchand, Loic Casey, Graham Gruber, Stephen B. Peters, Ulrike Hudson, Thomas J. TI A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1 SO HUMAN GENETICS LA English DT Article ID SOCIETY-TASK-FORCE; SUSCEPTIBILITY LOCI; ER STRESS; METAANALYSIS; TUMORS; CELLS; SCAN; SURVEILLANCE; VARIANTS; 8Q24 AB Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 x 10(-10); odds ratio estimated by re-including all controls (OR) = 0.87, 95 % confidence interval (CI) 0.83-0.91; minor allele frequency (MAF) = 13 %]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95 % CI 0.77-0.97; MAF = 16 %). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 x 10(-8)). C1 [Lemire, Mathieu; Zaidi, Syed H. E.; Hudson, Thomas J.] Ontario Inst Canc Res, MaRS Ctr, Toronto, ON M5G 0A3, Canada. [Qu, Conghui; Harrison, Tabitha A.; Hsu, Li; Jeon, Jihyoun; Newcomb, Polly A.; Potter, John D.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Loo, Lenora W. M.; Wang, Hansong; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Berndt, Sonja I.] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. [Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France. [Bezieau, Stephane] Univ Nantes, Fac Med, EA 4273, Nantes, France. [Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Campbell, Peter T.; Jacobs, Eric J.] Amer Canc Soc, Atlanta, GA 30329 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, Heidelberg, Germany. [Edlund, Christopher K.; Schumacher, Fredrick R.; Casey, Graham; Gruber, Stephen B.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Gallinger, Steven] Samuel Lunenfeld Res Inst, Toronto, ON M5S 1X5, Canada. [Gallinger, Steven] Toronto Gen Hosp, Div Gen Surg, Toronto, ON M5G 2C4, Canada. Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA. Univ Melbourne, Ctr Biostat & Epidemiol, Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Evanston, IL USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. [Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Li, Li] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Li, Li] Case Western Reserve Univ, Swetland Ctr Environm Hlth, Cleveland, OH 44106 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Newcomb, Polly A.; Potter, John D.; White, Emily] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad] Natl Canc Control Ctr, Clalit Hlth Serv, Haifa, Israel. [Rennert, Gad] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Severi, Gianluca] Human Genet Fdn HuGeF, Turin, Italy. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Woods, Michael O.] Mem Univ Newfoundland, Discipline Genet, St John, NF A1B 3V6, Canada. [Cotterchio, Michelle] Univ Toronto, Canc Care Ontario, Toronto, ON, Canada. [Gruber, Stephen B.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Med, Los Angeles, CA USA. [Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. RP Lemire, M (reprint author), Ontario Inst Canc Res, MaRS Ctr, 661 Univ Ave,Suite 510, Toronto, ON M5G 0A3, Canada. EM mathieu.lemire@oicr.on.ca; cqu@fredhutch.org; lloo@cc.hawaii.edu; hassan.zaidi@oicr.on.ca; hwang@cc.hawaii.edu; berndts@mail.nih.gov; stephane.bezieau@univ-nantes.fr; h.brenner@dkfz.de; Peter.Campbell@cancer.org; achan@mgh.harvard.edu; j.chang-claude@dkfz.de; mdu@fredhutch.org; cedlund@usc.edu; Steven.Gallinger@uhn.on.ca; rhaile@stanford.edu; tharriso@fredhutch.org; m.hoffmeister@dkfz.de; j.hopper@unimelb.edu.au; l-hou@northwestern.edu; lih@fredhutch.org; Eric.Jacobs@cancer.org; m.jenkins@unimelb.edu.au; jhjeon@fredhutch.org; sebastien.kury@chu-nantes.fr; lxl62@cwru.edu; nlindor@mayo.edu; pnewcomb@fredhutch.org; jpotter@fredhutch.org; rennert@tx.technion.ac.il; a.rudolph@dkfz.de; rschoen@pitt.edu; fschumac@usc.edu; seminard@mail.nih.gov; Gianluca.Severi@cancervic.org.au; marty.slattery@hsc.utah.edu; ewhite@fredhutch.org; mwoods@mun.ca; michelle.cotterchio@cancercare.on.ca; loic@cc.hawaii.edu; gcasey@usc.edu; sgruber@usc.edu; upeters@fredhutch.org; tom.hudson@oicr.on.ca RI Jenkins, Mark/P-7803-2015; KURY, Sebastien/G-5971-2015; Gallinger, Steven/E-4575-2013; Brenner, Hermann/B-4627-2017; OI Jenkins, Mark/0000-0002-8964-6160; KURY, Sebastien/0000-0001-5497-0465; Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hoffmeister, Michael/0000-0002-8307-3197 FU American Cancer Society (ACS); Centers for Disease Control and Prevention National Program of Cancer Registries; National Cancer Institute Surveillance Epidemiology and End Results program FX CANCER PREVENTION STUDY II: CPS-II is supported by the American Cancer Society (ACS). We would like to thank the CPS-II participants and the CPS-II Study Management Group for their invaluable contributions to this research. The authors would also like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. NR 37 TC 5 Z9 5 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD NOV PY 2015 VL 134 IS 11-12 BP 1249 EP 1262 DI 10.1007/s00439-015-1598-6 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA CV0VZ UT WOS:000363973000008 PM 26404086 ER PT J AU Ananthakrishnan, AN Cagan, A Cai, TX Gainer, VS Shaw, SY Churchill, S Karlson, EW Murphy, SN Kohane, I Liao, KP Xavier, RJ AF Ananthakrishnan, Ashwin N. Cagan, Andrew Cai, Tianxi Gainer, Vivian S. Shaw, Stanley Y. Churchill, Susanne Karlson, Elizabeth W. Murphy, Shawn N. Kohane, Isaac Liao, Katherine P. Xavier, Ramnik J. TI Common Genetic Variants Influence Circulating Vitamin D Levels in Inflammatory Bowel Diseases SO INFLAMMATORY BOWEL DISEASES LA English DT Article ID ELECTRONIC MEDICAL-RECORDS; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; RHEUMATOID-ARTHRITIS; ULCERATIVE-COLITIS; HEALTH RECORDS; REDUCED RISK; PHENOME-WIDE; D-RECEPTOR; SUPPLEMENTATION C1 [Ananthakrishnan, Ashwin N.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Karlson, Elizabeth W.; Murphy, Shawn N.; Kohane, Isaac; Liao, Katherine P.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA. [Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Murphy, Shawn N.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Cagan, Andrew; Gainer, Vivian S.; Murphy, Shawn N.] Partners HealthCare, Res IS & Comp, Charlestown, MA USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Churchill, Susanne; Kohane, Isaac] I2b2 Natl Ctr Biomed Comp, Boston, MA USA. [Karlson, Elizabeth W.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kohane, Isaac] Childrens Hosp, Boston, MA 02115 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU NIH [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01 AR049880, P30 DK043351]; US National Institutes of Health [K23 DK097142]; Harold and Duval Bowen Fund FX Supported by NIH U54-LM008748. A. N. Ananthakrishnan is supported by funding from the US National Institutes of Health (K23 DK097142). K. P. Liao is supported by NIH K08 AR060257 and the Harold and Duval Bowen Fund. E. W. Karlson is supported by grants from the NIH (K24 AR052403, P60 AR047782, and R01 AR049880). Also supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. NR 46 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2015 VL 21 IS 11 BP 2507 EP 2514 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV0UZ UT WOS:000363970400003 PM 26241000 ER PT J AU Polytarchou, C Oikonomopoulos, A Mahurkar, S Touroutoglou, A Koukos, G Hommes, DW Iliopoulos, D AF Polytarchou, Christos Oikonomopoulos, Angelos Mahurkar, Swapna Touroutoglou, Alexandra Koukos, Georgios Hommes, Daniel W. Iliopoulos, Dimitrios TI Assessment of Circulating MicroRNAs for the Diagnosis and Disease Activity Evaluation in Patients with Ulcerative Colitis by Using the Nanostring Technology SO INFLAMMATORY BOWEL DISEASES LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; C-REACTIVE PROTEIN; CROHNS-DISEASE; CARDIOVASCULAR-DISEASE; POTENTIAL BIOMARKER; PREVALENCE; CANCER; EXPRESSION; THERAPY; UPDATE C1 [Polytarchou, Christos; Mahurkar, Swapna; Koukos, Georgios; Iliopoulos, Dimitrios] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Div Digest Dis, Los Angeles, CA 90095 USA. [Oikonomopoulos, Angelos; Hommes, Daniel W.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Inflammatory Bowel Dis, Div Digest Dis, Los Angeles, CA 90095 USA. [Touroutoglou, Alexandra] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Touroutoglou, Alexandra] Harvard Univ, Sch Med, Boston, MA USA. [Touroutoglou, Alexandra] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Iliopoulos, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Div Digest Dis, 650 Charles E Young Dr,CHS 44-133, Los Angeles, CA 90095 USA. EM diliopoulos@mednet.ucla.edu FU Broad Medical Research Program at CCFA; Leona M. and Harry B. Helmsley Charitable Trust FX Supported by the Broad Medical Research Program at CCFA (C.P.) and the Leona M. and Harry B. Helmsley Charitable Trust (to D.I.). NR 28 TC 10 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2015 VL 21 IS 11 BP 2533 EP 2539 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV0UZ UT WOS:000363970400005 PM 26313695 ER PT J AU Dave, M Mehta, K Luther, J Baruah, A Dietz, AB Faubion, WA AF Dave, Maneesh Mehta, Kathan Luther, Jay Baruah, Anushka Dietz, Allan B. Faubion, William A. TI Mesenchymal Stem Cell Therapy for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis SO INFLAMMATORY BOWEL DISEASES LA English DT Review ID COMPLEX PERIANAL FISTULA; MARROW STROMAL CELLS; UMBILICAL-CORD BLOOD; CROHNS-DISEASE; BONE-MARROW; ULCERATIVE-COLITIS; DENDRITIC CELLS; CLINICAL-TRIAL; LYMPHOCYTE-PROLIFERATION; ADIPOSE-TISSUE C1 [Dave, Maneesh] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Gastroenterol & Liver Dis, Cleveland, OH 44106 USA. [Mehta, Kathan] Univ Pittsburgh, Shadyside Hosp, Med Ctr, Div Internal Med, Pittsburgh, PA USA. [Luther, Jay] Massachusetts Gen Hosp, Div Gastroenterol & Hepatol, Boston, MA 02114 USA. [Baruah, Anushka] John H Stroger Jr Hosp Cook Cty, Div Internal Med, Chicago, IL USA. [Dietz, Allan B.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Faubion, William A.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. RP Dave, M (reprint author), Univ Hosp Case Med Ctr, Div Gastroenterol & Liver Dis, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM maneesh.dave@uhhospitals.org; faubion.william@mayo.edu OI Dietz, Allan/0000-0003-3410-9621 FU National Institutes of Health [R01 AI089714] FX W. A. Faubion's laboratory is supported by National Institutes of Health grants R01 AI089714. NR 87 TC 4 Z9 4 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2015 VL 21 IS 11 BP 2696 EP 2707 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CV0UZ UT WOS:000363970400025 PM 26230863 ER PT J AU Long, JA Watts, LT Li, W Shen, Q Muir, ER Huang, SL Boggs, RC Suri, A Duong, TQ AF Long, Justin A. Watts, Lora T. Li, Wei Shen, Qiang Muir, Eric R. Huang, Shiliang Boggs, Robert C. Suri, Abhinav Duong, Timothy Q. TI The effects of perturbed cerebral blood flow and cerebrovascular reactivity on structural MRI and behavioral readouts in mild traumatic brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE functional outcomes; hypercapnia; MRI: diffusion tensor imaging; TBI ID CONTROLLED CORTICAL IMPACT; PERFUSION; RATS; DIFFUSION; HYPERPERFUSION; HYPERCAPNIA; HYPOXIA; MICROCIRCULATION; MECHANISMS; ISOFLURANE AB This study investigated the effects of perturbed cerebral blood flow (CBF) and cerebrovascular reactivity (CR) on relaxation time constant (T-2), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and behavioral scores at 1 and 3 hours, 2, 7, and 14 days after traumatic brain injury (TBI) in rats. Open-skull TBI was induced over the left primary forelimb somatosensory cortex (N=8 and 3 sham). We found the abnormal areas of CBF and CR on days 0 and 2 were larger than those of the T-2, ADC, and FA abnormalities. In the impact core, CBF was reduced on day 0, increased to 2.5 times of.normal on day 2, and returned toward normal by day 14, whereas in the tissue surrounding the impact, hypoperfusion was observed on days 0 and 2. CR in the impact core was negative, most severe on day 2 but gradually returned toward normal. T-2, ADC, and FA abnormalities in the impact core were detected on day 0, peaked on day 2, and pseudonormalized by day 14. Lesion volumes peaked on day 2 and were temporally correlated with forelimb asymmetry and foot-fault scores. This study quantified the effects of perturbed CBF and CR on structural magnetic resonance imaging and behavioral readouts. C1 [Long, Justin A.; Watts, Lora T.; Li, Wei; Shen, Qiang; Muir, Eric R.; Huang, Shiliang; Boggs, Robert C.; Suri, Abhinav; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Watts, Lora T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Watts, Lora T.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Opthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu FU NIH/NINDS [R01 NS45879]; Mike Hogg Fund via the Clinical Translational Science Awards (CTSA) [UL1TR000149, TL1TR001119, KL2TR001118]; [KL2 TR001118] FX This work was supported in part by NIH/NINDS R01 NS45879 (TQD), a TL1 (JAL) and KL2 TR001118 and Mike Hogg Fund (LTW) via the Clinical Translational Science Awards (CTSA, parent grants UL1TR000149, TL1TR001119, and KL2TR001118). NR 39 TC 5 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 2015 VL 35 IS 11 BP 1852 EP 1861 DI 10.1038/jcbfm.2015.143 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA CV4TR UT WOS:000364259900018 PM 26104285 ER PT J AU Ladha, KS Wanderer, JP Nanji, KC AF Ladha, Karim S. Wanderer, Jonathan P. Nanji, Karen C. TI Age as a predictor of rescue opioid administration immediately after the emergence of general anesthesia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Acute pain management; Perioperative opioid use; Geriatric anesthesia ID POSTOPERATIVE PAIN; HIP-FRACTURE; MORPHINE REQUIREMENTS; ANALGESICS; DELIRIUM; IMPACT AB Background and objectives: While previous studies have shown that elderly patients require lower dosages of opioids, the literature suggests that pain is undertreated in the geriatric population, which may lead to postoperative pain and high rescue analgesia requirements. The purpose of this study is to determine whether elderly patients undergoing hip and knee arthroplasty require higher levels of postoperative rescue opioids than their younger counterparts early after emergence from anesthesia. Methods: Using a nonconcurrent retrospective cohort study design, patients who underwent hip or knee arthroplasty under general anesthesia at a tertiary academic hospital from 2007 to 2012 were identified. Demographic information and data regarding patients' anesthetic care were obtained from the institution's anesthesia information management system. To assess the presence of pain after the emergence of anesthesia, we used, as a proxy, opioid administration by the anesthesia provider after leaving the operating room and before the end of anesthesia care. Results: A total of 2731 patients met inclusion criteria, of which 487 (17.8%) received rescue opioids. Patients older than 80 years were less likely to receive opioids after leaving the operating room (odds ratio, 0.57; 95% confidence interval, 0.37-0.88; P =.01) and received 1.37 mg less of hydromotphone equivalent opioid compared to patients younger than the age of 50 years (95% confidence interval, 1.18-1.55; P<.001). The proportion of patients who received rescue opioids varied significantly between anesthesia providers from 0% to 38% (P <.001). Conclusions: While elderly patients received lower doses of opioids intraoperatively, they were less likely to require rescue analgesia. The variability among providers in rescue opioid administration after emergence presents an opportunity for further research. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ladha, Karim S.; Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Anesthesiol, Nashville, TN 37235 USA. [Wanderer, Jonathan P.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA. [Nanji, Karen C.] Harvard Univ, Sch Med, Boston, MA USA. RP Ladha, KS (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM karim.ladha@post.harvard.edu FU Foundation for Anesthesia Education and Research (FAER); Anesthesia Quality Institute (AQI) Health Services Research Mentored Research Training Grant (HSR-MRTG), Schaumburg, IL, USA FX Dr. Wanderer is supported by the Foundation for Anesthesia Education and Research (FAER) and Anesthesia Quality Institute (AQI) Health Services Research Mentored Research Training Grant (HSR-MRTG), Schaumburg, IL, USA. NR 25 TC 1 Z9 1 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 EI 1873-4529 J9 J CLIN ANESTH JI J. Clin. Anesth. PD NOV PY 2015 VL 27 IS 7 BP 537 EP 542 DI 10.1016/j.jclinane.2015.07.026 PG 6 WC Anesthesiology SC Anesthesiology GA CV2TI UT WOS:000364109700001 PM 26342632 ER PT J AU Pena, CG Nakada, Y Saatcioglu, HD Aloisio, GM Cuevas, I Zhang, S Miller, DS Lea, JS Wong, KK DeBerardinis, RJ Amelio, AL Brekken, RA Castrillon, DH AF Pena, Christopher G. Nakada, Yuji Saatcioglu, Hatice D. Aloisio, Gina M. Cuevas, Ileana Zhang, Song Miller, David S. Lea, Jayanthi S. Wong, Kwok-Kin DeBerardinis, Ralph J. Amelio, Antonio L. Brekken, Rolf A. Castrillon, Diego H. TI LKB1 loss promotes endometrial cancer progression via CCL2-dependent macrophage recruitment SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; ACTIVATED PROTEIN-KINASE; PEUTZ-JEGHERS-SYNDROME; MOTIF LIGAND 2; BREAST-CANCER; MONOCYTE RECRUITMENT; LUNG ADENOCARCINOMA; ENERGY SENSOR; CARCINOMA; EXPRESSION AB Endometrial cancer is the most common gynecologic malignancy and the fourth most common malignancy in women. For most patients in whom the disease is confined to the uterus, treatment results in successful remission; however, there are no curative treatments for tumors that have progressed beyond the uterus. The serine/threonine kinase LKB1 has been identified as a potent suppressor of uterine cancer, but the biological modes of action of LKB1 in this context remain incompletely understood. Here, we have shown that LKB1 suppresses tumor progression by altering gene expression in the tumor microenvironment. We determined that LKB1 inactivation results in abnormal, cell-autonomous production of the inflammatory cytokine chemokine (C-C motif) ligand 2 (CCL2) within tumors, which leads to increased recruitment of macrophages with prominent tumor-promoting activities. Inactivation of Ccl2 in an Lkb1-driven mouse model of endometrial cancer slowed tumor progression and increased survival. In human primary endometrial cancers, loss of LKB1 protein was strongly associated with increased CCL2 expression by tumor cells as well as increased macrophage density in the tumor microenvironment. These data demonstrate that CCL2 is a potent effector of LKB1 loss in endometrial cancer, creating potential avenues for therapeutic opportunities. C1 [Pena, Christopher G.; Nakada, Yuji; Saatcioglu, Hatice D.; Aloisio, Gina M.; Cuevas, Ileana; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Pena, Christopher G.; Nakada, Yuji; Saatcioglu, Hatice D.; Aloisio, Gina M.; Cuevas, Ileana; Zhang, Song; Miller, David S.; Lea, Jayanthi S.; DeBerardinis, Ralph J.; Brekken, Rolf A.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Zhang, Song] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Miller, David S.; Lea, Jayanthi S.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX 75390 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA. [Amelio, Antonio L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. RP Castrillon, DH (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM diego.castrillon@utsouthwestern.edu RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 FU David M. Crowley Foundation; NIH [R01CA137181, U01CA141576]; Cancer Prevention & Research Institute of Texas [RP100550] FX We thank the David M. Crowley Foundation for support and members of the Castrillon laboratory for critically reading the manuscript. We also thank Jae-Wook Jeong for providing tissue samples. This work was supported by grants to D.H. Castrillon from the NIH (R01CA137181) and the Cancer Prevention & Research Institute of Texas (RP100550) and by a grant from the NIH (U01CA141576) to D.H. Castrillon and K.K. Wong. NR 78 TC 4 Z9 8 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2015 VL 125 IS 11 BP 4063 EP 4076 DI 10.1172/JCI82152 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CV2TL UT WOS:000364110000012 PM 26413869 ER PT J AU Walter, JE Rosen, LB Csomos, K Rosenberg, JM Mathew, D Keszei, M Ujhazi, B Chen, K Lee, YN Tirosh, I Dobbs, K Al-Herz, W Cowan, MJ Puck, J Bleesing, JJ Grimley, MS Malech, H De Ravin, SS Gennery, AR Abraham, RS Joshi, AY Boyce, TG Butte, MJ Nadeau, KC Balboni, I Sullivan, KE Akhter, J Adeli, M El-Feky, RA El-Ghoneimy, DH Dbaibo, G Wakim, R Azzari, C Palma, P Cancrini, C Capuder, K Condino-Neto, A Costa-Carvalho, BT Oliveira, JB Roifman, C Buchbinder, D Kumanovics, A Franco, JL Niehues, T Schuetz, C Kuijpers, T Yee, C Chou, J Masaad, MJ Geha, R Uze, G Gelman, R Holland, SM Recher, M Utz, PJ Browne, SK Notarangelo, LD AF Walter, Jolan E. Rosen, Lindsey B. Csomos, Krisztian Rosenberg, Jacob M. Mathew, Divij Keszei, Marton Ujhazi, Boglarka Chen, Karin Lee, Yu Nee Tirosh, Irit Dobbs, Kerry Al-Herz, Waleed Cowan, Morton J. Puck, Jennifer Bleesing, Jack J. Grimley, Michael S. Malech, Harry De Ravin, Suk See Gennery, Andrew R. Abraham, Roshini S. Joshi, Avni Y. Boyce, Thomas G. Butte, Manish J. Nadeau, Kari C. Balboni, Imelda Sullivan, Kathleen E. Akhter, Javeed Adeli, Mehdi El-Feky, Reem A. El-Ghoneimy, Dalia H. Dbaibo, Ghassan Wakim, Rima Azzari, Chiara Palma, Paolo Cancrini, Caterina Capuder, Kelly Condino-Neto, Antonio Costa-Carvalho, Beatriz T. Oliveira, Joao Bosco Roifman, Chaim Buchbinder, David Kumanovics, Attila Luis Franco, Jose Niehues, Tim Schuetz, Catharina Kuijpers, Taco Yee, Christina Chou, Janet Masaad, Michel J. Geha, Raif Uze, Gulbu Gelman, Rebecca Holland, Steven M. Recher, Mike Utz, Paul J. Browne, Sarah K. Notarangelo, Luigi D. TI Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC MUCOCUTANEOUS CANDIDIASIS; IMMUNOGLOBULIN-SECRETING CELLS; ACTIVATING GENE-1 DEFICIENCY; MYASTHENIA-GRAVIS PATIENTS; SYNDROME TYPE-I; OMENN-SYNDROME; AUTOIMMUNE-DISEASE; GRANULOMATOUS-DISEASE AB Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/ autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-alpha or anti-IFN-omega antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1(5723C/5723C) mice, Le which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations. C1 [Walter, Jolan E.; Csomos, Krisztian; Ujhazi, Boglarka] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Allergy & Immunol, Boston, MA USA. [Walter, Jolan E.; Csomos, Krisztian; Ujhazi, Boglarka] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA. [Walter, Jolan E.; Lee, Yu Nee; Dobbs, Kerry; Capuder, Kelly; Yee, Christina; Chou, Janet; Masaad, Michel J.; Geha, Raif; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Rosen, Lindsey B.; Uze, Gulbu; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Rosenberg, Jacob M.; Utz, Paul J.] Stanford Univ, Dept Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA. [Mathew, Divij] Univ Colorado, Integrated Dept Immunol, Natl Jewish Hlth, Denver, CO 80202 USA. [Keszei, Marton] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Ujhazi, Boglarka] Univ Debrecen, Dept Biochem & Mol Biol, Debrecen, Hungary. [Chen, Karin] Univ Utah, Div Allergy Immunol & Rheumatol, Dept Pediat, Salt Lake City, UT USA. [Tirosh, Irit] Boston Childrens Hosp, Pediat Rheumatol, Boston, MA 02115 USA. [Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait, Kuwait. [Cowan, Morton J.; Puck, Jennifer] UCSF Benioff Childrens Hosp, Pediat Allergy Immunol & Blood & MarrowTransplant, San Francisco, CA USA. [Bleesing, Jack J.; Grimley, Michael S.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA. [Malech, Harry; De Ravin, Suk See] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA. [Gennery, Andrew R.] Newcastle Upon Tyne Hosp, Dept Pediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England. [Gennery, Andrew R.] Newcastle Upon Tyne Hosp, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. [Abraham, Roshini S.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Joshi, Avni Y.] Mayo Clin, Div Pediat Allergy Immunol, Dept Pediat & Adolescent Med, Rochester, MN USA. [Boyce, Thomas G.] Mayo Clin, Div Pediat Infect Dis, Dept Pediat, Rochester, MN USA. [Butte, Manish J.; Nadeau, Kari C.; Balboni, Imelda] Stanford Univ, Dept Pediat, Div Allergy, Immunol,Rheumatol, Stanford, CA 94305 USA. [Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Allergy & Immunol, Philadelphia, PA 19104 USA. [Akhter, Javeed] Advocate Childrens Hosp, Jeffrey Modell Fdn Immunol Referral Ctr, Oak Lawn, IL USA. [Adeli, Mehdi] Hamad Med Corp, Dept Pediat, Weill Cornell Med Coll, Doha, Qatar. [El-Feky, Reem A.; El-Ghoneimy, Dalia H.] Ain Shams Univ, Dept Pediat Allergy & Immunol, Childrens Hosp, Fac Med, Cairo, Egypt. [Dbaibo, Ghassan; Wakim, Rima] Amer Univ Beirut, Dept Pediat & Adolescent Med, Beirut, Lebanon. [Azzari, Chiara] Anna Meyer Childrens Univ Hosp, Florence, Italy. [Palma, Paolo; Cancrini, Caterina] IRCCS Bambino Gasu Childrens Hosp, Univ Dept Paediat, Rome, Italy. [Condino-Neto, Antonio] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Sao Paulo, Brazil. [Costa-Carvalho, Beatriz T.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Oliveira, Joao Bosco] Inst Med Integral, Recife, PE, Brazil. [Roifman, Chaim] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Buchbinder, David] UC Irvine, Pediat Hematol, CHOC Childrens Hosp, Orange, CA USA. [Kumanovics, Attila] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Luis Franco, Jose] Univ Antioquia, Grp Primary Immunodeficiencies, Dept Microbiol & Parasitol, Sch Med, Medellin, Colombia. [Niehues, Tim] Univ Dusseldorf, Ctr Child Hlth & Adolescence, Helios Klinikum Krefeld Acad Hosp, Dusseldorf, Germany. [Schuetz, Catharina] Univ Hosp Ulm, Dept Pediat & Adolescent Med, Ulm, Germany. [Kuijpers, Taco] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Recher, Mike] Univ Basel Hosp, Immunodeficiency Clin, Med Outpatient Unit, CH-4031 Basel, Switzerland. [Recher, Mike] Univ Basel Hosp, Immunodeficiency Lab, Dept Biomed, CH-4031 Basel, Switzerland. [Utz, Paul J.] Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA. [Notarangelo, Luigi D.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Notarangelo, LD (reprint author), Boston Childrens Hosp, Div Immunol, Karp Res Bldg,Room 10217,One Blackfan Circle, Boston, MA 02115 USA. EM jewalter@mgh.harvard.edu; Luigi.Notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016; Keszei, Marton/F-3295-2014; OI Notarangelo, Luigi/0000-0002-8335-0262; Keszei, Marton/0000-0002-1158-2179; Adeli, Mehdi/0000-0002-3051-3080; Malech, Harry/0000-0001-5874-5775; Palma, Paolo/0000-0002-3066-4719; cancrini, caterina/0000-0001-8410-9617; Butte, Manish/0000-0002-4490-5595 FU NIAID, NIH [5R01AI100887, U54AI082973, 5K08AI103035, T32GM007365]; Manton Foundation; Jeffrey Modell Foundation; Intramural Research Program of the NIAID, NIH FX This work was partly supported by grants from the NIAID, NIH (5R01AI100887 and U54AI082973, to L.D. Notarangelo; 5K08AI103035, to J.E. Walter; and T32GM007365, to P.J. Utz); the Manton Foundation (to L.D. Notarangelo); and the Jeffrey Modell Foundation (to L.D. Notarangelo). This research was also supported in part by the Intramural Research Program of the NIAID, NIH (to L.B. Rosen, S.M. Holland, and S.K. Browne). We acknowledge Quan-Zhen Li and Jinchun Zhou of the Genomics and Microarray Core Facility at the University of Texas Southwestern Medical Center for autoantibody profiling using autoantigen microarrays. NR 68 TC 16 Z9 16 U1 3 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2015 VL 125 IS 11 BP 4135 EP 4148 DI 10.1172/JCI80477 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CV2TL UT WOS:000364110000017 PM 26457731 ER PT J AU Lopez, L AF Lopez, Lenny TI Use of Interpreters by Physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Letter C1 [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Med Genet, Boston, MA 02114 USA. [Lopez, Lenny] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM llopez1@partners.org 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 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2015 VL 30 IS 11 BP 1590 EP 1590 DI 10.1007/s11606-015-3474-4 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CU7LT UT WOS:000363721100012 PM 26224153 ER PT J AU Park, JD Kim, E Werner, RM AF Park, James D. Kim, Edward Werner, Rachel M. TI Inpatient Hospital Charge Variability of US Hospitals SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hospital charges; variability ID UNINSURED ADULTS; UNITED-STATES; COST-SHIFT; HEALTH; DETERMINANTS; DISPARITIES; SERVICES; MARKET AB The range of hospital charges for similar diagnoses show tremendous variability across U.S. hospitals. This charge variability remains unexplained. We aimed to describe hospital charge variability in the U.S. and examine its relationship to local health factors. This was a descriptive study of the 2011 Medicare Inpatient Charge data summarizing inpatient hospital charges billed to Medicare. This data was evaluated using 29 county-level measures of health status, health behavior, clinical access and quality, built environment, and socioeconomic status in a clustered, multivariate linear regression. 2871 U.S. hospitals registered with Medicare and with at least ten discharges for diagnosis-related groups (DRGs) of six common inpatient conditions. Inpatient hospital charges were assessed. No community health measures were associated with hospital charges. The one notable exception associated with higher charges was higher rates of uninsured status ($344.84 higher charges for every one-percentage point increase in prevalence (p < 0.001)). One variable was associated with lower hospital charges: the percentage of children living in poverty [$309.30 lower charges for every one-percentage point increase in prevalence (p < 0.001)]. Overall, hospital charges lacked an association with population health measures, and their variability remains largely unexplained. However, the association of higher charges with uninsured status raises concerns about hospitals' price-setting strategies, such as price discrimination and cost-shifting strategies that expose vulnerable populations to great financial risks. C1 [Park, James D.] Rutgers Robert Wood Johnson Med Sch, Div Gen Internal Med, New Brunswick, NJ 08903 USA. [Kim, Edward] Coll New Jersey, Dept Comp Sci, Ewing, NJ USA. [Kim, Edward] Villanova Univ, Dept Comp Sci, Villanova, PA 19085 USA. [Werner, Rachel M.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. [Werner, Rachel M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Park, JD (reprint author), Rutgers Robert Wood Johnson Med Sch, Div Gen Internal Med, New Brunswick, NJ 08903 USA. EM james.d.park@rutgers.edu FU Robert Wood Johnson Foundation Health Hospital FX Funders: This analysis was awarded second place in the Robert Wood Johnson Foundation Health Hospital Price Transparency Challenge, which had no role in the conduct of the study. NR 26 TC 1 Z9 1 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2015 VL 30 IS 11 BP 1627 EP 1632 DI 10.1007/s11606-015-3352-0 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CU7LT UT WOS:000363721100017 PM 25931006 ER PT J AU Duru, OK Turk, N Ettner, SL Neugebauer, R Moin, T Li, JN Kimbro, L Chan, C Luchs, RH Keckhafer, AM Kirvan, A Ho, S Mangione, CM AF Duru, O. Kenrik Turk, Norman Ettner, Susan L. Neugebauer, Romain Moin, Tannaz Li, Jinnan Kimbro, Lindsay Chan, Charles Luchs, Robert H. Keckhafer, Abigail M. Kirvan, Anya Ho, Sam Mangione, Carol M. TI Adherence to Metformin, Statins, and ACE/ARBs Within the Diabetes Health Plan (DHP) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID MEDICATION ADHERENCE; PROGRAMS; SAVINGS AB Reducing patient cost-sharing and engaging patients in disease management activities have been shown to increase uptake of evidence-based care. To evaluate the effect of employer purchase of a disease-specific plan with reduced cost-sharing and disease management (the Diabetes Health Plan/DHP) on medication adherence among eligible employees and dependents. Employer-level "intent to treat" cohort study, including data from eligible employees and their dependents with diabetes, regardless of whether they were enrolled in the DHP. Employers that contracted with a large national health plan administrator in 2009, 2010, and/or 2011. Ten employers that purchased the DHP and 191 employers that did not (controls). Inverse probability weighting (IPW) estimation was used to adjust for inter-group differences. The DHP includes free or low-cost medications and physician visits. Enrollment strategies and specific benefit designs are determined by the employer and vary in practice. DHP participants are notified up front that they must engage in their own health care (e.g., receiving diabetes-related screening) in order to remain enrolled. Mean employee adherence to metformin, statins, and ACE/ARBs at the employer level at one year post-DHP implementation, as measured by the proportion of days covered (PDC). Baseline adherence to the three medications was similar across DHP and control employers, ranging from 64 to 69 %. In the first year after DHP implementation, predicted employer-level adherence for metformin (+4.9 percentage points, p = 0.017), statins (+4.8, p = 0.019), and ACE/ARBs (+4.4, p = 0.02) was higher with DHP purchase. Non-randomized, observational study. The Diabetes Health Plan, an innovative health plan that combines reduced cost-sharing and disease management with an up-front requirement of enrollee participation in his or her own health care, is associated with a modest improvement in medication adherence at 12 months. C1 [Duru, O. Kenrik; Turk, Norman; Ettner, Susan L.; Li, Jinnan; Kimbro, Lindsay; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ettner, Susan L.; Mangione, Carol M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Neugebauer, Romain] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Moin, Tannaz] VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Moin, Tannaz] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chan, Charles; Luchs, Robert H.; Keckhafer, Abigail M.; Kirvan, Anya; Ho, Sam] UnitedHealthcare, Minnetonka, MN USA. RP Duru, OK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM kduru@mednet.ucla.edu FU Centers for Disease Control and Prevention (Division of Diabetes Translation) [DP002722]; National Institute of Diabetes and Digestive and Kidney Diseases as part of the Natural Experiments for the Translation of Diabetes (NEXT-D) Study [DP002722]; VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship [TPM65-010]; VA Greater Los Angeles Healthcare System; UCLA Robert Wood Johnson Clinical Scholars Program; U.S. Department of Veterans Affairs [67799]; NIH/NCATS UCLA CTSI [UL1TR000124]; University of California, Los Angeles; Resource Center for Minority Aging Research; Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA [P30-AG021684]; NIH Career Development Award [K08-AG033360] FX This study was jointly funded by the Centers for Disease Control and Prevention (Division of Diabetes Translation) and the National Institute of Diabetes and Digestive and Kidney Diseases as part of the Natural Experiments for the Translation of Diabetes (NEXT-D) Study (Grant number DP002722).; Dr. Moin received support from the VA Office of Academic Affiliations through the VA Health Services Research and Development Advanced Fellowship Program (TPM65-010), VA Greater Los Angeles Healthcare System, from 2011 to 2014. Dr. Mangione is supported in part by the UCLA Robert Wood Johnson Clinical Scholars Program and the U.S. Department of Veterans Affairs (Grant #67799). Dr. Mangione also receives support from NIH/NCATS UCLA CTSI Grant Number UL1TR000124 and from the Barbara A. Levey, M.D., and Gerald S. Levey, M.D., Endowed Chair at the David Geffen School of Medicine at UCLA.; The efforts of Drs. Mangione, Duru, and Steers are supported in part by the University of California, Los Angeles, Resource Center for Minority Aging Research and the Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA Grant P30-AG021684. Dr. Duru is also supported by NIH Career Development Award K08-AG033360. NR 18 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2015 VL 30 IS 11 BP 1645 EP 1650 DI 10.1007/s11606-015-3284-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CU7LT UT WOS:000363721100020 PM 25944019 ER PT J AU Shih, SL Gerrard, P Goldstein, R Mix, J Ryan, CM Niewczyk, P Kazis, L Hefner, J Ackerly, DC Zafonte, R Schneider, JC AF Shih, Shirley L. Gerrard, Paul Goldstein, Richard Mix, Jacqueline Ryan, Colleen M. Niewczyk, Paulette Kazis, Lewis Hefner, Jaye Ackerly, D. Clay Zafonte, Ross Schneider, Jeffrey C. TI Functional Status Outperforms Comorbidities in Predicting Acute Care Readmissions in Medically Complex Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE functional status; care transitions; statistical modeling; risk assessment; outcomes ID PROFILING HOSPITAL PERFORMANCE; ACUTE MYOCARDIAL-INFARCTION; INPATIENT REHABILITATION; STROKE REHABILITATION; INDEPENDENCE MEASURE; RISK-FACTORS; ASSESSMENT SCALES; BODY-COMPOSITION; CANCER-PATIENTS; DISCHARGE AB To examine functional status versus medical comorbidities as predictors of acute care readmissions in medically complex patients. Retrospective database study. U.S. inpatient rehabilitation facilities. Subjects included 120,957 patients in the Uniform Data System for Medical Rehabilitation admitted to inpatient rehabilitation facilities under the medically complex impairment group code between 2002 and 2011. A Basic Model based on gender and functional status was developed using logistic regression to predict the odds of 3-, 7-, and 30-day readmission from inpatient rehabilitation facilities to acute care hospitals. Functional status was measured by the FIMA (R) motor score. The Basic Model was compared to six other predictive models-three Basic Plus Models that added a comorbidity measure to the Basic Model and three Gender-Comorbidity Models that included only gender and a comorbidity measure. The three comorbidity measures used were the Elixhauser index, Deyo-Charlson index, and Medicare comorbidity tier system. The c-statistic was the primary measure of model performance. We investigated 3-, 7-, and 30-day readmission to acute care hospitals from inpatient rehabilitation facilities. Basic Model c-statistics predicting 3-, 7-, and 30-day readmissions were 0.69, 0.64, and 0.65, respectively. The best-performing Basic Plus Model (Basic+Elixhauser) c-statistics were only 0.02 better than the Basic Model, and the best-performing Gender-Comorbidity Model (Gender+Elixhauser) c-statistics were more than 0.07 worse than the Basic Model. Readmission models based on functional status consistently outperform models based on medical comorbidities. There is opportunity to improve current national readmission risk models to more accurately predict readmissions by incorporating functional data. C1 [Shih, Shirley L.; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Shih, Shirley L.; Zafonte, Ross; Schneider, Jeffrey C.] Massachusetts Gen Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Shih, Shirley L.; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gerrard, Paul] New England Rehabil Hosp Portland, Portland, ME USA. [Mix, Jacqueline; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Ryan, Colleen M.] Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Childrenr Boston, Boston, MA USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Hefner, Jaye] Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. [Ackerly, D. Clay] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Ackerly, D. Clay] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Ackerly, D. Clay] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Schneider, JC (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. EM jcschneider@partners.org NR 63 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2015 VL 30 IS 11 BP 1688 EP 1695 DI 10.1007/s11606-015-3350-2 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CU7LT UT WOS:000363721100026 PM 25956826 ER PT J AU Morris, SE Block, SD AF Morris, Sue E. Block, Susan D. TI Adding Value to Palliative Care Services: The Development of an Institutional Bereavement Program SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; RISK-MANAGEMENT; HEALTH-CARE; GRIEF; COMMUNICATION; INTERVENTION; PERSPECTIVES; PHYSICIANS; CAREGIVERS; OUTCOMES AB Background: Although bereavement programs are a common element of palliative medicine and hospice programs, few health care institutions currently offer universal bereavement services to all their patients. The elevated risk of serious physical and mental health problems among the bereaved is a strong argument for the development of universal institution-based bereavement programs as an element of quality care for family members of all patients who die. Objective: We describe the development of the bereavement program at Dana-Farber Cancer Institute (DFCI) where we conceptualized bereavement services as a preventive model of care. Design: We identified education, guidance and support as the primary constructs of the program. The essential components include a formal acknowledgement of the death of the patient by the cancer center, information about grief and what to expect, individual visits to assess coping, and staff support and education. Subjects: One hundred and forty bereaved families completed a survey about the bereavement program. Results: The findings indicated that the formal letter of condolence and the bereavement guide had a positive impact on the grieving of the respondents. Contact from the patient's oncologist and nurse was especially well received. Conclusions: Bereavement programs can both help bereaved individuals adapt to their loss, and positively impact hospitals by enhancing the reputation of the hospital within the community and providing an avenue for identifying opportunities for improvement in care processes. We recommend that all hospitals implement basic bereavement programs for families of all deceased patients as the standard of care. C1 [Morris, Sue E.] Dana Farber Brigham & Womens Canc Ctr, Dept Psychosocial Oncol & Palliat Care, Dana Farber Canc Inst, Boston, MA USA. [Block, Susan D.] Harvard Univ, Brigham & Womens Hosp, Dept Psychosocial Oncol & Palliat Care,Med Sch, Dana Farber Canc Inst,Ctr Palliat Care,Ariadne La, Boston, MA 02115 USA. RP Morris, SE (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,2016A, Boston, MA 02215 USA. EM sue_morris@dfci.harvard.edu NR 31 TC 4 Z9 5 U1 3 U2 14 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD NOV 1 PY 2015 VL 18 IS 11 BP 915 EP 922 DI 10.1089/jpm.2015.0080 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CV0LK UT WOS:000363942000006 PM 26275079 ER PT J AU Deng, J Coy, D Zhang, W Sunkara, M Morris, AJ Wang, C Chaiswing, L St Clair, D Vore, M Jungsuwadee, P AF Deng, Jun Coy, Donna Zhang, Wei Sunkara, Manjula Morris, Andrew J. Wang, Chi Chaiswing, Luksana St Clair, Daret Vore, Mary Jungsuwadee, Paiboon TI Elevated Glutathione Is Not Sufficient to Protect against Doxorubicin-Induced Nuclear Damage in Heart in Multidrug Resistance-Associated Protein 1 (Mrp1/Abcc1) Null Mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACUTE CARDIAC TOXICITY; LIPID-PEROXIDATION; MRP1; CARDIOTOXICITY; CARDIOMYOPATHY; TRANSFERASE; EXPRESSION; CONJUGATE; ALDEHYDES; INJURY AB Cardiotoxicity is a major dose-limiting adverse effect of doxorubicin (DOX), mediated in part by overproduction of reactive oxygen species and oxidative stress. Abcc1 (Mrp1) mediates the efflux of reduced and oxidized glutathione (GSH, GSSG) and is also a major transporter that effluxes the GSH conjugate of 4-hydroxy-2-nonenal (HNE; GS-HNE), a toxic product of lipid peroxidation formed during oxidative stress. To assess the role of Mrp1 in protecting the heart from DOX-induced cardiac injury, wild-type (WT) and Mrp1 null (Mrp1(-/-)) C57BL/6 littermate mice were administered DOX (15 mg/kg) or saline (7.5 ml/kg) i.v., and heart ventricles were examined at 72 hours. Morphometric analysis by electron microscopy revealed extensive injuries in cytosol, mitochondria, and nuclei of DOX-treated mice in both genotypes. Significantly more severely injured nuclei were observed in Mrp1(-/-) versus WT mice (P = 0.031). GSH and the GSH/GSSG ratio were significantly increased in treatment-naive Mrp1(-/-) versus WT mice; GSH remained significantly higher in Mrp1(-/-) versus WT mice after saline and DOX treatment, with no changes in GSSG or GSH/GSSG. GS-HNE, measured by mass spectrometry, was lower in the hearts of treatment-naive Mrp1(-/-) versus WT mice (P < 0.05). DOX treatment decreased GS-HNE in WT but not Mrp1(-/-) mice, so that GS-HNE was modestly but significantly higher in Mrp1(-/-) versus WT hearts after DOX. Expression of enzymes mediating GSH synthesis and antioxidant proteins did not differ between genotypes. Thus, despite elevated GSH levels in Mrp1(-/-) hearts, DOX induced significantly more injury in the nuclei of Mrp1(-/-) versus WT hearts. C1 [Deng, Jun; Coy, Donna; Zhang, Wei; Chaiswing, Luksana; St Clair, Daret; Vore, Mary] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY 40536 USA. [Sunkara, Manjula; Morris, Andrew J.] Univ Kentucky, Div Cardiovasc Med, Lexington, KY 40536 USA. [Wang, Chi] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA. [Chaiswing, Luksana] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Dept Pathol & Lab Med, Madison, WI 53792 USA. [Chaiswing, Luksana] Univ Wisconsin, Sch Med, Madison, WI USA. [Jungsuwadee, Paiboon] Fairleigh Dickinson Univ, Sch Pharm, Florham Pk, NJ USA. RP Vore, M (reprint author), Univ Kentucky, Dept Toxicol & Canc Biol, 306 Hlth Sci Res Bldg, Lexington, KY 40536 USA. EM maryv@email.uky.edu; paiboon@fdu.edu FU Biostatistics and Bioinformatics Shared Resource of the University of Kentucky Markey Cancer Center [P30CA177558]; Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103527] FX The authors thank Dr. Terry D. Oberley, University of Wisconsin Medical School, Madison, Wisconsin, who died before publication of these studies, for his expert help; Dr. Ladislav Dory, University of North Texas, Denton, Texas, for a generous gift of rabbit anti-ECSOD pAb; and Dr. Luksana Chaiswing, who was at the University of Wisconsin Medical School during the experimental phase of this research, but moved to the University of Kentucky during the preparation of this manuscript. This research was supported by the Biostatistics and Bioinformatics Shared Resource of the University of Kentucky Markey Cancer Center [P30CA177558] and by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103527]. NR 36 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2015 VL 355 IS 2 BP 272 EP + DI 10.1124/jpet.115.225490 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CV3MT UT WOS:000364164000017 PM 26354996 ER PT J AU Pandey, SK Wheeler, TM Justice, SL Kim, A Younis, HS Gattis, D Jauvin, D Puymirat, J Swayze, EE Freier, SM Bennett, CF Thornton, CA MacLeod, AR AF Pandey, Sanjay K. Wheeler, Thurman M. Justice, Samantha L. Kim, Aneeza Younis, Husam S. Gattis, Danielle Jauvin, Dominic Puymirat, Jack Swayze, Eric E. Freier, Susan M. Bennett, C. Frank Thornton, Charles A. MacLeod, A. Robert TI Identification and Characterization of Modified Antisense Oligonucleotides Targeting DMPK in Mice and Nonhuman Primates for the Treatment of Myotonic Dystrophy Type 1 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SMALL-INTERFERING RNA; MOUSE MODEL; MUSCLEBLIND PROTEINS; MUSCULAR-DYSTROPHY; MESSENGER-RNA; CUG REPEATS; MUTANT RNA; CTG REPEAT; TOXICITY; PEPTIDE AB Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults. DM1 is caused by an expanded CTG repeat in the 3'-untranslated region of DMPK, the gene encoding dystrophiamyotonica protein kinase (DMPK). Antisense oligonucleotides (ASOs) containing 2',4'-constrained ethylmodified (cEt) residues exhibit a significantly increased RNA binding affinity and in vivo potency relative to those modified with other 2'-chemistries, which we speculated could translate to enhanced activity in extrahepatic tissues, such as muscle. Here, we describe the design and characterization of a cEt gapmer DMPK ASO (ISIS 486178), with potent activity in vitro and in vivo against mouse, monkey, and human DMPK. Systemic delivery of unformulated ISIS 486718 to wild-type mice decreased DMPK mRNA levels by up to 90% in liver and skeletal muscle. Similarly, treatment of either human DMPK transgenic mice or cynomolgus monkeys with ISIS 486178 led to up to 70% inhibition of DMPK in multiple skeletal muscles and similar to 50% in cardiac muscle in both species. Importantly, inhibition of DMPK was well tolerated and was not associated with any skeletal muscle or cardiac toxicity. Also interesting was the demonstration that the inhibition of DMPK mRNA levels in muscle was maintained for up to 16 and 13 weeks post-treatment in mice and monkeys, respectively. These results demonstrate that cEt-modified ASOs show potent activity in skeletal muscle, and that this attractive therapeutic approach warrants further clinical investigation to inhibit the gain-of-function toxic RNA underlying the pathogenesis of DM1. C1 [Pandey, Sanjay K.; Justice, Samantha L.; Kim, Aneeza; Younis, Husam S.; Gattis, Danielle; Swayze, Eric E.; Freier, Susan M.; Bennett, C. Frank; MacLeod, A. Robert] Isis Pharmaceut Inc, Carlsbad, CA 92010 USA. [Wheeler, Thurman M.; Thornton, Charles A.] Univ Rochester, Dept Neurol, Rochester, NY USA. [Wheeler, Thurman M.; Thornton, Charles A.] Univ Rochester, Ctr Neural Dev & Dis, Rochester, NY USA. [Wheeler, Thurman M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Jauvin, Dominic; Puymirat, Jack] Ctr Hosp Univ Quebec, Dept Human Genet, Quebec City, PQ, Canada. RP Pandey, SK (reprint author), Isis Pharmaceut Inc, 2855 Gazelle Court, Carlsbad, CA 92010 USA. EM spandey@isisph.com; rmacleod@isisph.com FU Isis Pharmaceuticals; National Institutes of Health [U01NS072323, U54NS48843, K08NS64293] FX Financial support for this project was provided by Isis Pharmaceuticals and by the National Institutes of Health [Grant U01NS072323, U54NS48843, and K08NS64293]. NR 54 TC 5 Z9 5 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2015 VL 355 IS 2 BP 329 EP + DI 10.1124/jpet.115.226969 PG 28 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CV3MT UT WOS:000364164000022 PM 26330536 ER PT J AU Shelton, RC Falola, M Li, L Zajecka, J Fava, M Papakostas, GI AF Shelton, Richard C. Falola, Michael Li, Li Zajecka, John Fava, Maurizio Papakostas, George I. TI The pro-inflammatory profile of depressed patients is (partly) related to obesity SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Depression; Inflammation; Cytokine; C-reactive protein; Leptin; Adiponectin ID CORONARY-HEART-DISEASE; MIDDLE-AGED WOMEN; MAJOR DEPRESSION; METABOLIC SYNDROME; TREATMENT RESPONSE; RISK-MARKERS; OLDER MEN; SYMPTOMS; METAANALYSIS; CYTOKINES AB Many people with major depressive disorder (MDD) show evidence of systemic inflammation, including elevations in inflammatory factors, but the cause is unclear. The purpose of this analysis was to determine if obesity might contribute to the pro-inflammatory state in MDD patients. Blood was obtained from 135 MDD patients and 50 controls. Serum was extracted and assayed for interleukin (IL) - 1 beta, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), C-reactive protein (CRP), leptin, and adiponectin using single- or multi-plex human immunoassay kits. The primary analysis contrasted IL-6, TNF alpha, and CRP between MDD and control groups with body mass index (BMI) as a covariate. The other analytes were compared in an exploratory fashion. IL-6 (but not TNF alpha or CRP) showed significant differences between MDD and controls even after covarying for BMI. Obese controls and obese MDD groups were significantly higher in IL-6 than both lean groups, but the two obese groups did not differ from each other. In the exploratory analyses, the IL-2 level showed robust and significant differences between MDD and controls even after covarying for BMI. Both lean and obese MDD were higher than lean and obese controls. Adiponectin levels were also lower in the MDD sample than controls. Prior findings of higher IL-6, and CRP in MDD patients may be explained, at least in part, based on obesity. High IL-2, however, was associated with depression and not obesity. The results have significant implications for the understanding of pathophysiology and, potentially treatment of MDD. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Shelton, Richard C.; Falola, Michael; Li, Li] Univ Alabama Birmingham, Dept Psychiat, Birmingham, AL 35294 USA. [Zajecka, John] Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Fava, Maurizio; Papakostas, George I.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fava, Maurizio; Papakostas, George I.] Massachusetts Gen Hosp, CTNI, Boston, MA 02114 USA. RP Shelton, RC (reprint author), Univ Alabama Birmingham, SC 1060,1720 2nd Ave South, Birmingham, AL 35294 USA. EM rshelton@uab.edu OI Shelton, Richard/0000-0002-3806-4208 FU NIH National Center for Research Resources [5UL1RR025777-03, 5KL2RR025776-03, 5TL1RR025775-03]; Brain & Behavior Research Foundation and Pamlab, Inc. FX Support for the sample collection and analysis was provided by the Brain & Behavior Research Foundation and Pamlab, Inc. Funding for the REDCAP database was provided by the NIH National Center for Research Resources as part of its Clinical and Translational Science Award Program (5UL1RR025777-03, 5KL2RR025776-03, 5TL1RR025775-03) NR 55 TC 4 Z9 4 U1 5 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2015 VL 70 BP 91 EP 97 DI 10.1016/j.psychires.2015.09.001 PG 7 WC Psychiatry SC Psychiatry GA CU8XG UT WOS:000363826800011 PM 26424427 ER PT J AU Mischoulon, D De Jong, ME Vitolo, OV Cusin, C Dording, CM Yeung, AS Durham, K Parkin, SR Fava, M Dougherty, DD AF Mischoulon, David De Jong, Marasha E. Vitolo, Ottavio V. Cusin, Cristina Dording, Christina M. Yeung, Albert S. Durham, Kelley Parkin, Susannah R. Fava, Maurizio Dougherty, Darin D. TI Efficacy and safety of a form of cranial electrical stimulation (CES) as an add-on intervention for treatment-resistant major depressive disorder: A three week double blind pilot study SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Cranial electrical stimulation; CES; Major depression; Treatment resistant depression ID ELECTROTHERAPY STIMULATION; ELECTROSLEEP THERAPY; CLINICAL-TRIAL; RATING-SCALE; ANXIETY AB We examined efficacy and safety of one specific cranial electrical stimulator (CES) device at a fixed setting in subjects with treatment-resistant major depressive disorder (MDD). Thirty subjects (57% female, mean age 48.1 +/- 12.3 years) with MDD and inadequate response to standard antidepressants were randomized to 3 weeks of treatment with CES (151500/15,000 Hz, symmetrical rectangular biphasic current of 1-4 mAmp, 40 V) or sham CES (device off) for 20 min, 5 days per week. The primary outcome measure was improvement in the 17-item Hamilton Depression Rating Scale (HAM-D-17). Adverse effects (AEs) were assessed using the Patient Related Inventory of Side Effects (PRISE). Completion rates were 88% for CES, 100% for sham. Both treatment groups demonstrated improvement of about 3-5 points in HAM-D-17 scores (p < 0.05 for both), and no significant differences were observed between groups. Remission rates were 12% for CES, and 15% for sham, a nonsignificant difference. CES was deemed safe, with good tolerability; poor concentration and malaise were the only distressing AEs that differed significantly between CES and sham (p = 0.019 and p = 0.043, respectively). Limitations include a small sample and lack of an active comparator therapy. Although both treatment groups improved significantly, this CES at the setting chosen did not separate from sham in this sample. Thus we cannot rule out that the benefit from this setting used in this particular form of CES was due to placebo effects. Since this form of CES has other settings, future studies should test these settings and compare it against other CES devices. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Mischoulon, David; De Jong, Marasha E.; Vitolo, Ottavio V.; Cusin, Cristina; Dording, Christina M.; Yeung, Albert S.; Durham, Kelley; Parkin, Susannah R.; Fava, Maurizio; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org FU Fisher Wallace, Inc. FX This work was supported by a grant from Fisher Wallace, Inc. Sponsors had no further role in the study design, collection, analysis and interpretation of data, writing of the report, and the decision to submit the paper for publication. NR 27 TC 0 Z9 0 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD NOV PY 2015 VL 70 BP 98 EP 105 DI 10.1016/j.psychires.2015.08.016 PG 8 WC Psychiatry SC Psychiatry GA CU8XG UT WOS:000363826800012 PM 26424428 ER PT J AU Ploumis, A Simpson, AK Cha, TD Herzog, JP Wood, KB AF Ploumis, Avraam Simpson, Andrew K. Cha, Thomas D. Herzog, Joshua P. Wood, Kirkham B. TI Coronal Spinal Balance in Adult Spine Deformity Patients With Long Spinal Fusions A Minimum 2- to 5-Year Follow-up Study SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article DE coronal; sagittal; balance; deformity; long fusion ID ADOLESCENT IDIOPATHIC SCOLIOSIS; PEDICLE SCREW FIXATION; ADJACENT SEGMENTS; LUMBAR CURVES; DECOMPENSATION; INSTRUMENTATION; POPULATION; PREVALENCE; PARAMETERS; LEVEL AB Study Design: This study was a retrospective one. Objective: The objective of the study was to analyze the causes, prevalence of, and risk factors for coronal decompensation in long adult lumbar spinal instrumentation and fusion (from thoracic or upper lumbar spine) to L5 or S1. Summary of Background Data: Coronal and sagittal decompensation after long fusions for spinal deformities can affect outcomes negatively. There is no study reporting the natural history of coronal spinal balance after long spinal fusions. Methods: A single-center retrospective review of data from 54 patients with spinal deformity was performed. Inclusion criteria were patients over 18 years with long fusions (>4 segments) to L5 or the pelvis who had full spine standing radiographs before surgery and up to 2-5 years postoperatively. Radiographic data included C7PL, magnitude of scoliotic curve, shoulder or pelvic asymmetry in the coronal plane, thoracic kyphosis, lumbar lordosis, and pelvic parameters (pelvic incidence, pelvic tilt, sacral slope). Coronal imbalance (CI) was considered if the C7PL was >4 cm lateral to the central sacral line, and sagittal imbalance (SI) was considered when the C7 plumbline was >4 cm anterior to the middle of the upper sacral plate. Paired t test, chi(2) test, and repeated measures regression analysis using demographic data (age, sex, body mass index), operative (previous fusion, posterior only or anteroposterior fusion, iliac fixation or not, decompression or not, osteotomy or not) and postoperative (complications, use of bracing) data, and radiographic parameters (including SI) were performed. Results: Patients showing CI equaled 11 (19.3%) preoperatively, remained 11 (19.3%) (4 of whom were new patients with CI) at 6 weeks postoperatively, and increased (P<0.001) to 18 (31.6%) (8 of them without initial CI) at 2-5 years follow-up. However, in terms of numeric distance of C7PL from the midsacrum, there was no statistically significant change (P>0.05) from preoperative to last follow-up. SI showed significant improvement (P<0.05) from preoperative to 6 weeks postoperative and no statistical significant change (P>0.05) from 6 weeks to 2-5 years postoperatively. Repeated measures regression analysis showed that the presence of osteoporosis and the combination of anterior approach surgery with a history of previous surgery were significant (P<0.05) factors predictive of changes in coronal balance. Conclusions: After surgical correction of spinal deformities, coronal spinal decompensation appears in an increased number of patients at last follow-up postoperatively but without significant differences in coronal plane C7PL during the postoperative period. Attention should be paid to patients with osteoporosis and those with a combination of previous same site posterior spine surgery and new anterior approach surgery for changes of coronal balance postoperatively. C1 [Ploumis, Avraam; Simpson, Andrew K.; Cha, Thomas D.; Herzog, Joshua P.; Wood, Kirkham B.] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed, Spine Serv, Boston, MA USA. RP Ploumis, A (reprint author), Univ Ioannina, Fac Med, Ioannina 45110, Greece. EM aploumis@cc.uoi.gr NR 27 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1536-0652 EI 1539-2465 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD NOV PY 2015 VL 28 IS 9 BP 341 EP 347 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA CV5DE UT WOS:000364286000008 PM 24077418 ER PT J AU Lee, HW Khan, SQ Faridi, MH Wei, CL Tardi, NJ Altintas, MM Elshabrawy, HA Mangos, S Quick, KL Sever, S Reiser, J Gupta, V AF Lee, Ha Won Khan, Samia Q. Faridi, Mohd Hafeez Wei, Changli Tardi, Nicholas J. Altintas, Mehmet M. Elshabrawy, Hatem A. Mangos, Steve Quick, Kevin L. Sever, Sanja Reiser, Jochen Gupta, Vineet TI A Podocyte-Based Automated Screening Assay Identifies Protective Small Molecules SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PUROMYCIN AMINONUCLEOSIDE NEPHROSIS; GLOMERULAR EPITHELIAL-CELLS; RHO-KINASE INHIBITOR; KIDNEY-DISEASE; ACTIN CYTOSKELETON; KNOCKOUT MICE; IN-VITRO; EXPRESSION; INJURY; GLOMERULOSCLEROSIS AB Podocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell-based high-throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high-content screening-based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quantitatively measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z' value >0.44, making it suitable for compound screening. On screening with >2100 pharmacologically active agents, we identified 24 small molecules that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an beta 1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active beta 1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS-induced podocyte foot process effacement and proteinuria. Analysis of the murine glomeruli showed that LPS administration reduced the levels of active integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside-induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte-based screening assays for identifying novel therapeutics for proteinuric kidney diseases. C1 [Lee, Ha Won; Khan, Samia Q.; Faridi, Mohd Hafeez; Wei, Changli; Tardi, Nicholas J.; Altintas, Mehmet M.; Elshabrawy, Hatem A.; Mangos, Steve; Reiser, Jochen; Gupta, Vineet] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60026 USA. [Quick, Kevin L.] PerkinElmer Life Sci, Cellular Imaging & Anal, Waltham, MA USA. [Sever, Sanja] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Nephrol, Charlestown, MA USA. RP Reiser, J (reprint author), Rush Univ, Med Ctr, Dept Med, Kellogg 1004, Chicago, IL 60026 USA. EM jochen_reiser@rush.edu; vineet_gupta@rush.edu OI Altintas, Mehmet/0000-0002-1871-6985 FU National Institutes of Health [DK073495, DK089394, DK101350, DK084195, HL109582]; Nephcure Foundation; Rush University Medical Center FX This work was supported, in part, by National Institutes of Health Grants DK073495 (to J.R.), DK089394 (to J.R.), DK101350 (to J.R.), DK084195 (to V.G.), and HL109582 (to V.G.); the Nephcure Foundation; and resources from the Rush University Medical Center. NR 54 TC 9 Z9 9 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2015 VL 26 IS 11 BP 2741 EP 2752 DI 10.1681/ASN.2014090859 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA CV0CR UT WOS:000363915500018 PM 25858967 ER PT J AU Chan, KE Newton-Cheh, C Gusella, JF Maddux, FW AF Chan, Kevin E. Newton-Cheh, Christopher Gusella, James F. Maddux, Franklin W. TI Heritability of Risk for Sudden Cardiac Arrest in ESRD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CARDIOVERTER-DEFIBRILLATOR RECIPIENTS; STAGE RENAL-DISEASE; MYOCARDIAL-INFARCTION; HEMODIALYSIS-PATIENTS; DEATH; MORTALITY; DIALYSIS; IMPLANTATION AB Patients on dialysis are 20 times more likely to have a cardiac arrest compared with the general population. We considered whether inherited factors associate with cardiac arrest among patients on dialysis. From a sample of 647,457 patients on chronic dialysis, we identified 5117 pairs of patients who came from the same family. These patients were each matched to a control subject from the same population. McNemar's tests were used to compare the risk of cardiac arrest between the familial related and unrelated pairs. Genetically related family members who did not cohabitate had an odds ratio of 1.88(95% confidence interval [95% Cl], 1.25 to 2.84) for cardiac arrest compared with their phenotypically matched unrelated controls. Genetically related family members who lived together in the same environment had an odds ratio of 1.66(95% Cl, 1.20 to 2.28). Spouses, who are genetically unrelated but live together in the same environment, had an odds ratio of 0.95(95% Cl, 0.60 to 1:59) for cardiac arrest. The risk of cardiac arrest in patients on dialysis may be attributable to inherited factors. Additional studies are needed to identify such candidate genes that modify cardiovascular risk in ESRD. C1 [Chan, Kevin E.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Chan, Kevin E.; Maddux, Franklin W.] Fresenius Med Care North Amer, Div Clin Res, Waltham, MA USA. RP Chan, KE (reprint author), Massachusetts Gen Hosp, Div Nephrol, Fresenius Med Care North Amer, Div Clin Res, 920 Winter St, Waltham, MA 02451 USA. EM kevin.chan@fmc-na.com NR 19 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2015 VL 26 IS 11 BP 2815 EP 2820 DI 10.1681/ASN.2014090881 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA CV0CR UT WOS:000363915500024 PM 25882830 ER PT J AU Murugan, VA Bhargavan-Chatfield, M Rehani, M Kalra, MK AF Murugan, Venkatesh A. Bhargavan-Chatfield, Mythreyi Rehani, Madan Kalra, Mannudeep K. TI American College of Radiology Dose Index Registry: A User's Guide for Cardiothoracic Radiologists Part 1 Dose Index Registry (DIR)-What it Means and Does for CT? SO JOURNAL OF THORACIC IMAGING LA English DT Review DE American College of Radiology; Dose Index Registry; history; logistics ID ACR; CAMPAIGN AB Computed tomography (CT) is an indispensable part of diagnostic imaging and contributes significantly to patient care. With increasing use of CT, there have been growing concerns regarding risks from radiation exposure. This has prompted efforts to introduce measures to optimize the radiation dose used in CT imaging. The Dose Index Registry (DIR) was launched by the American College of Radiology (ACR) in 2011. It provides a national database of radiation dose indices for various CT examinations performed at participating institutions. It affords an opportunity for institutions to compare and tailor their CT protocols against existing national averages. In this article, we review the history, mechanism, and major elements of the DIR. We also briefly discuss similar radiation dose registries in other countries. C1 [Murugan, Venkatesh A.; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Murugan, Venkatesh A.; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bhargavan-Chatfield, Mythreyi; Rehani, Madan] Amer Coll Radiol, Reston, VA USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. EM mkatra@mgh.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD NOV PY 2015 VL 30 IS 6 BP W66 EP W68 DI 10.1097/RTI.0000000000000184 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV5CB UT WOS:000364282900003 PM 26458238 ER PT J AU Murugan, VA Chatfield, MB Rehani, M Kalra, MK AF Murugan, Venkatesh A. Chatfield, Mythreyi B. Rehani, Madan Kalra, Mannudeep K. TI ACR DIR: A User's Guide for Cardiothoracic Radiologists Part 2: How to Interpret Your DIR Report SO JOURNAL OF THORACIC IMAGING LA English DT Review DE Dose Index Registry; interpreting report; scenarios AB In the initial installment of this 3-part article, we reviewed the role and logistics of the American College of Radiology (ACR) Dose Index Registry (DIR). In this second installment, we review the essential components of ACR DIR and describe how users can interpret their biannual dose reports by benchmarking them against regional or national levels. Understanding these reports can help participating institutions to identify specific protocols or practices that may benefit from changes in order to minimize patient dose while maintaining diagnostic quality examinations. C1 [Murugan, Venkatesh A.; Rehani, Madan; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Murugan, Venkatesh A.; Rehani, Madan; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chatfield, Mythreyi B.] Amer Coll Radiol, Reston, VA USA. RP Murugan, VA (reprint author), Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. EM varumuganmurugan@mgh.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0883-5993 EI 1536-0237 J9 J THORAC IMAG JI J. Thorac. Imaging PD NOV PY 2015 VL 30 IS 6 BP W69 EP W72 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CV5CB UT WOS:000364282900004 PM 25856412 ER PT J AU Yeh, DD Cropano, C Fagenholz, P King, DR Chang, YC Klein, EN DeMoya, M Kaafarani, H Velmahos, G AF Yeh, Daniel Dante Cropano, Catrina Fagenholz, Peter King, David R. Chang, Yuchiao Klein, Eric N. DeMoya, Marc Kaafarani, Haytham Velmahos, George TI Gangrenous cholecystitis: Deceiving ultrasounds, significant delay in surgical consult, and increased postoperative morbidity! SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Panamerican-Trauma-Society CY NOV 11-14, 2014 CL Panama City, PANAMA SP Panamerican Trauma Soc DE Gangrenous cholecystitis; surgical consult; ultrasound; acute cholecystitis ID LAPAROSCOPIC CHOLECYSTECTOMY; DIAGNOSIS AB BACKGROUND Gangrenous cholecystitis (GC) is difficult to diagnose preoperatively in the patient with suspected acute cholecystitis. We sought to characterize preoperative risk factors and post-operative complications. METHODS Pathology reports of all patients undergoing cholecystectomy for suspected acute cholecystitis from June 2010 to January 2014 and admitted through the emergency department were examined. Patients with GC were compared with those with acute/chronic cholecystitis (AC/CC). Data collected included demographics, preoperative signs and symptoms, radiologic studies, operative details, and clinical outcomes. RESULTS Thirty-eight cases of GC were identified and compared with 171 cases of AC/CC. Compared with AC/CC, GC patients were more likely to be older (57 years vs. 41 years, p < 0.001), of male sex (63% vs. 31%, p < 0.001), hypertensive (47% vs. 22%, p = 0.002), hyperlipidemic (29% vs. 14%, p = 0.026), and diabetic (24% vs. 8%, p = 0.006). GC patients were more likely to have a fever (29% vs. 12%, p = 0.007) and less likely to have nausea/vomiting (61% vs. 80%, p = 0.019) or an impacted gallstone on ultrasound (US) (8% vs. 26%, p = 0.017). Otherwise, there was no significant difference in clinical or US findings. Among GC patients, US findings were absent (8%, n = 3) or minimal (42%, n = 16). Median time from emergency department registration to US (3.3 hours vs. 2.8 hours, p = 0.28) was similar, but US to operation was longer (41.2 hours vs. 18.4 hours, p < 0.001), conversion to open cholecystectomy was more common (37% vs. 10%, p < 0.001), and hospital stay was longer (median, 4 days vs. 2 days, p < 0.0001). Delay in surgical consultation occurred in 16% of GC patients compared with 1% of AC patients (p < 0.001). CONCLUSION Demographic features may be predictive of GC. Absent or minimal US signs occur in 50%, and delay in surgical consultation is common. Postoperative morbidity is greater for patients with GC compared with those with AC/CC. LEVEL OF EVIDENCE Epidemiologic study, level III; therapeutic study, level IV. C1 [Yeh, Daniel Dante; Cropano, Catrina; Fagenholz, Peter; King, David R.; Klein, Eric N.; DeMoya, Marc; Kaafarani, Haytham; Velmahos, George] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, 165 Cambridge St 810, Boston, MA 02114 USA. EM Dyeh2@partners.org OI King, David/0000-0003-1028-1478 FU TEM Systems, Inc.; LFB Biotechnologies FX Ernest E. Moore, Editor: PI, research support and shared U.S. patents Haemonetics; PI, research support, TEM Systems, Inc. Ronald V. Maier, Associate editor: consultant, consulting fee, LFB Biotechnologies. Associate editors: David Hoyt and Steven Shackford have nothing to disclose. Editorial staff: Jennifer Crebs, Jo Fields, and Angela Sauaia have nothing to disclose. NR 9 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD NOV PY 2015 VL 79 IS 5 BP 812 EP 816 DI 10.1097/TA.0000000000000832 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CV3XX UT WOS:000364201100016 PM 26496106 ER PT J AU Levi, B Jayakumar, P Giladi, A Jupiter, JB Ring, DC Kowalske, K Gibran, NS Herndon, D Schneider, JC Ryan, CM AF Levi, Benjamin Jayakumar, Prakash Giladi, Avi Jupiter, Jesse B. Ring, David C. Kowalske, Karen Gibran, Nicole S. Herndon, David Schneider, Jeffrey C. Ryan, Colleen M. TI Risk factors for the development of heterotopic ossification in seriously burned adults: A National Institute on Disability, Independent Living and Rehabilitation Research burn model system database analysis SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Extremity trauma; burn injury; heterotopic ossification ID TOTAL HIP-ARTHROPLASTY; SPINAL-CORD INJURY; COX-2 INHIBITORS; SMOKE-INHALATION; PREVENTION; INDOMETHACIN; FRACTURES; INFLAMMATION; MULTICENTER; EXPERIENCE AB BACKGROUND Heterotopic ossification (HO) is a debilitating complication of burn injury; however, incidence and risk factors are poorly understood. In this study, we use a multicenter database of adults with burn injuries to identify and analyze clinical factors that predict HO formation. METHODS Data from six high-volume burn centers, in the Burn Injury Model System Database, were analyzed. Univariate logistic regression models were used for model selection. Cluster-adjusted multivariate logistic regression was then used to evaluate the relationship between clinical and demographic data and the development of HO. RESULTS Of 2,979 patients in the database with information on HO that addressed risk factors for development of HO, 98 (3.5%) developed HO. Of these 98 patients, 97 had arm burns, and 96 had arm grafts. When controlling for age and sex in a multivariate model, patients with greater than 30% total body surface area burn had 11.5 times higher odds of developing HO (p < 0.001), and those with arm burns that required skin grafting had 96.4 times higher odds of developing HO (p = 0.04). For each additional time a patient went to the operating room, odds of HO increased by 30% (odds ratio, 1.32; p < 0.001), and each additional ventilator day increased odds by 3.5% (odds ratio, 1.035; p < 0.001). Joint contracture, inhalation injury, and bone exposure did not significantly increase odds of HO. CONCLUSION Risk factors for HO development include greater than 30% total body surface area burn, arm burns, arm grafts, ventilator days, and number of trips to the operating room. Future studies can use these results to identify highest-risk patients to guide deployment of prophylactic and experimental treatments. LEVEL OF EVIDENCE Prognostic study, level III. C1 [Levi, Benjamin; Giladi, Avi] Univ Michigan, Ann Arbor, MI 48109 USA. [Jayakumar, Prakash; Jupiter, Jesse B.; Ring, David C.; Schneider, Jeffrey C.; Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kowalske, Karen] Spaulding Rehabil Hosp, Boston, MA USA. [Kowalske, Karen] Univ Texas Southwestern, Dallas, TX USA. [Gibran, Nicole S.] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. RP Ryan, CM (reprint author), 1150W Med Ctr Dr,MSRB2A Off 570A, Ann Arbor, MI 48109 USA. EM cryan@mgh.harvard.edu FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0035]; National Institute for Disability and Rehabilitation Research [H133A130023, H133A120034] FX The contents of this report were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this report do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. Jesse B. Jupiter, MD, David C. Ring, MD, PhD, Karen Kowalske, MD, Nicole S. Gibran, MD, David Herndon, MD, Jeffrey C. Schneider, MD, and Colleen M. Ryan, were funded by National Institute for Disability and Rehabilitation Research (H133A130023 and H133A120034). Drs. Schneider and Ryan served as co-senior authors for this paper. NR 47 TC 2 Z9 2 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD NOV PY 2015 VL 79 IS 5 BP 870 EP 876 DI 10.1097/TA.0000000000000838 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA CV3XX UT WOS:000364201100026 PM 26496115 ER PT J AU Louapre, C Lubetzki, C AF Louapre, Celine Lubetzki, Catherine TI Neurodegeneration in multiple sclerosis is a process separate from inflammation: Yes SO MULTIPLE SCLEROSIS JOURNAL LA English DT Editorial Material DE Multiple sclerosis; neurodegeneration; neuroinflammation; neuroprotection ID CORTICAL DEMYELINATION; SEX; PATHOLOGY; GRADIENT; ATROPHY C1 [Louapre, Celine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. Univ Paris 06, Sorbonne Univ, Hop La Pitie Salpetriere, ICM, Paris, France. RP Lubetzki, C (reprint author), Univ Paris 06, Sorbonne Univ, Hop La Pitie Salpetriere, ICM, Paris, France. EM catherine.lubetzki@psl.aphp.fr NR 19 TC 4 Z9 4 U1 2 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD NOV PY 2015 VL 21 IS 13 BP 1626 EP 1628 DI 10.1177/1352458515587598 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CV3LP UT WOS:000364161000003 PM 26515289 ER PT J AU Finucane, HK Bulik-Sullivan, B Gusev, A Trynka, G Reshef, Y Loh, PR Anttila, V Xu, H Zang, CZ Farh, K Ripke, S Day, FR Purcell, S Stahl, E Lindstrom, S Perry, JRB Okada, Y Raychaudhuri, S Daly, MJ Patterson, N Neale, BM Price, AL AF Finucane, Hilary K. Bulik-Sullivan, Brendan Gusev, Alexander Trynka, Gosia Reshef, Yakir Loh, Po-Ru Anttila, Verneri Xu, Han Zang, Chongzhi Farh, Kyle Ripke, Stephan Day, Felix R. Purcell, Shaun Stahl, Eli Lindstrom, Sara Perry, John R. B. Okada, Yukinori Raychaudhuri, Soumya Daly, Mark J. Patterson, Nick Neale, Benjamin M. Price, Alkes L. CA ReproGen Consortium Psychiat Genomics Consortium RACI Consortium TI Partitioning heritability by functional annotation using genome-wide association summary statistics SO NATURE GENETICS LA English DT Article ID BODY-MASS INDEX; GENETIC ARCHITECTURE; HUMAN HEIGHT; COMMON SNPS; CELL-TYPES; VARIANTS; LOCI; DISEASE; SUSCEPTIBILITY; PROPORTION AB Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior. C1 [Finucane, Hilary K.] MIT, Dept Math, Cambridge, MA 02139 USA. [Finucane, Hilary K.; Gusev, Alexander; Loh, Po-Ru; Lindstrom, Sara; Price, Alkes L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bulik-Sullivan, Brendan; Anttila, Verneri; Farh, Kyle; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bulik-Sullivan, Brendan; Anttila, Verneri; Farh, Kyle; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Bulik-Sullivan, Brendan; Anttila, Verneri; Ripke, Stephan; Daly, Mark J.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Trynka, Gosia; Purcell, Shaun; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA USA. [Trynka, Gosia; Purcell, Shaun; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Div Rheumatol, Brigham & Womens Hosp, Boston, MA USA. [Trynka, Gosia; Raychaudhuri, Soumya] Partners Ctr Personalized Genet Med, Boston, MA USA. [Trynka, Gosia; Anttila, Verneri; Raychaudhuri, Soumya; Daly, Mark J.; Patterson, Nick; Neale, Benjamin M.; Price, Alkes L.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Trynka, Gosia] Wellcome Trust Sanger Inst, Cambridge, England. [Reshef, Yakir] Harvard Univ, Dept Comp Sci, Cambridge, MA 02138 USA. [Xu, Han; Zang, Chongzhi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Xu, Han; Zang, Chongzhi] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Farh, Kyle] Broad Inst MIT & Harvard, Epigen Program, Cambridge, MA USA. [Day, Felix R.; Perry, John R. B.] Univ Cambridge, MRC, Epidemiol Unit, Sch Clin Med,Inst Metab Sci, Cambridge, England. [Purcell, Shaun; Stahl, Eli] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Okada, Yukinori] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan. [Okada, Yukinori] RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. RP Finucane, HK (reprint author), MIT, Dept Math, Cambridge, MA 02139 USA. EM hilaryf@mit.edu; bulik@broadinstitute.org; bneale@broadinstitute.org; aprice@hsph.harvard.edu RI Zang, Chongzhi/D-1445-2011; Hansen, Thomas Folkmann/O-5965-2014 OI Day, Felix/0000-0003-3789-7651; Gusev, Alexander/0000-0002-7980-4620; Hansen, Thomas Folkmann/0000-0001-6703-7762 FU US National Institutes of Health [R01 MH101244, R01 HG006399, R03 CA173785, R21 CA182821, F32 GM106584, U01 HG0070033]; Fannie and John Hertz Foundation; Wellcome Trust Sanger Institute [WT098051]; National Institute of General Medical Sciences [T32 GM007753]; Arthritis Foundation; Doris Duke Clinical Scientist Development Award; Wellcome Trust [076113] FX We thank B. Bernstein, M. Finucane, A. Forrest, E. Hodis, D. Kotliar, X.S. Liu, M. Kellis, M. O'Donovan, B. Pasaniuc, A. Sandelin, A. Sarkar, P. Sullivan, B. Vilhjalmsson, A. Veres and the anonymous reviewers for helpful discussions and/or comments. This research was funded by US National Institutes of Health grants R01 MH101244, R01 HG006399, R03 CA173785, R21 CA182821, F32 GM106584 and U01 HG0070033. H.K.F. was also supported by the Fannie and John Hertz Foundation. G.T. is supported by the Wellcome Trust Sanger Institute (WT098051). Y.R. was supported by award T32 GM007753 from the National Institute of General Medical Sciences. S. Raychaudhuri is supported by funding from the Arthritis Foundation and by a Doris Duke Clinical Scientist Development Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. 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 http://www.wtccc.org.uk/. Funding for the WTCCC project was provided by the Wellcome Trust under award 076113. NR 49 TC 67 Z9 67 U1 8 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2015 VL 47 IS 11 BP 1228 EP + DI 10.1038/ng.3404 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA CV1BN UT WOS:000363988200005 PM 26414678 ER PT J AU Bulik-Sullivan, B Finucane, HK Anttila, V Gusev, A Day, FR Loh, PR Duncan, L Perry, JRB Patterson, N Robinson, EB Daly, MJ Price, AL Neale, BM AF Bulik-Sullivan, Brendan Finucane, Hilary K. Anttila, Verneri Gusev, Alexander Day, Felix R. Loh, Po-Ru Duncan, Laramie Perry, John R. B. Patterson, Nick Robinson, Elise B. Daly, Mark J. Price, Alkes L. Neale, Benjamin M. CA ReproGen Consortium Psychiat Genomics Consortium Genetic Consortium Anorexia Nervos TI An atlas of genetic correlations across human diseases and traits SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; CARDIOVASCULAR-DISEASE; BIPOLAR DISORDER; COMMON VARIANTS; MENDELIAN RANDOMIZATION; ALZHEIMERS-DISEASE; EATING-DISORDERS; ADULT HEIGHT; DE-NOVO AB Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment. C1 [Bulik-Sullivan, Brendan; Anttila, Verneri; Loh, Po-Ru; Duncan, Laramie; Patterson, Nick; Robinson, Elise B.; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Bulik-Sullivan, Brendan; Anttila, Verneri; Duncan, Laramie; Robinson, Elise B.; Daly, Mark J.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Genet, Cambridge, MA USA. [Bulik-Sullivan, Brendan; Anttila, Verneri; Duncan, Laramie; Robinson, Elise B.; Daly, Mark J.; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bulik-Sullivan, Brendan; Anttila, Verneri; Duncan, Laramie; Robinson, Elise B.; Daly, Mark J.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA. [Finucane, Hilary K.] MIT, Dept Math, Cambridge, MA 02139 USA. [Gusev, Alexander; Loh, Po-Ru; Price, Alkes L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Gusev, Alexander; Price, Alkes L.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Day, Felix R.; Perry, John R. B.] Univ Cambridge, Sch Clin Med, Inst Metab Sci, Epidemiol Unit,MRC, Cambridge, England. RP Bulik-Sullivan, B (reprint author), Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. EM bulik@broadinstitute.org; hilaryf@mit.edu; aprice@hsph.harvard.edu; bneale@broadinstitute.org RI Visser, Jenny /F-8156-2011; Hansen, Thomas Folkmann/O-5965-2014 OI Day, Felix/0000-0003-3789-7651; Robinson, Elise/0000-0003-2314-2792; Gusev, Alexander/0000-0002-7980-4620; Hansen, Thomas Folkmann/0000-0001-6703-7762 FU US National Institutes of Health (NIH) [R01 MH101244, R01 HG006399, 1R01 MH101244-02, 5U01 MH094432-03, R03 CA173785]; Fannie and John Hertz Foundation; Wellcome Trust Case Control Consortium 3 project titled "A Genome-Wide Association Study of Anorexia Nervosa" [WT088827/Z/09]; LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant; INSERM; Institut Pasteur de Lille, Universit de Lille 2; Lille University Hospital; Medical Research Council, UK [503480]; Alzheimer's Research UK [503176]; Wellcome Trust [082604/2/07/Z]; German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) [01GI0102, 01GI0711]; US NIH/National Institute on Aging [R01 AG033193, AG081220, U01 AG032984, U24 AG021886, U01 AG016976]; AGES [N01-AG-12100]; National Heart, Lung, and Blood Institute (NHLBI) [R01 HL105756]; Icelandic Heart Association; Erasmus Medical Center; Alzheimer's Association [ADGC-10-196728]; Erasmus University; French National Foundation on Alzheimer's Disease and Related Disorders FX We would like to thank P. Sullivan, C. Bulik, S. Caldwell, C. Arabica and O. Andreassen for helpful comments. This work was supported by US National Institutes of Health (NIH) grants R01 MH101244 (A.L.P.), R01 HG006399 (N.P.), 1R01 MH101244-02 (B.M.N.), 5U01 MH094432-03 (B.M.N.) and R03 CA173785 (H.K.F.) and by the Fannie and John Hertz Foundation (H.K.F.). Data on anorexia nervosa were obtained by funding from the Wellcome Trust Case Control Consortium 3 project titled "A Genome-Wide Association Study of Anorexia Nervosa" (WT088827/Z/09). Data on glycemic traits were contributed by MAGIC investigators and were downloaded from http://www.magicinvestigators.org/. Data on coronary artery disease and myocardial infarction were contributed by CARDIoGRAMplusC4D investigators and were downloaded from http://www.cardiogramplusc4d.org/.; We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in the analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients and their families. The work with iSelect chips was funded by the French National Foundation on Alzheimer's Disease and Related Disorders. EADI was supported by a LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant, INSERM, Institut Pasteur de Lille, Universit de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council, UK (grant 503480), Alzheimer's Research UK (grant 503176), the Wellcome Trust (grant 082604/2/07/Z) and the German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grants 01GI0102 and 01GI0711, 01GI0420. CHARGE was partly supported by US NIH/National Institute on Aging grants R01 AG033193 and AG081220 and AGES contract N01-AG-12100, National Heart, Lung, and Blood Institute (NHLBI) grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by US NIH/National Institute on Aging grants U01 AG032984, U24 AG021886 and U01 AG016976 and Alzheimer's Association grant ADGC-10-196728. NR 61 TC 120 Z9 120 U1 24 U2 71 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2015 VL 47 IS 11 BP 1236 EP + DI 10.1038/ng.3406 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CV1BN UT WOS:000363988200006 PM 26414676 ER PT J AU Kato, N Loh, M Takeuchi, F Verweij, N Wang, X Zhang, WH Kelly, TN Saleheen, D Lehne, B Leach, IM Drong, AW Abbott, J Wahl, S Tan, ST Scott, WR Campanella, G Chadeau-Hyam, M Afzal, U Ahluwalia, TS Bonder, MJ Chen, P Dehghan, A Edwards, TL Esko, T Go, MJ Harris, SE Hartiala, J Kasela, S Kasturiratne, A Khor, CC Kleber, ME Li, HX Mok, ZY Nakatochi, M Sapari, NS Saxena, R Stewart, AFR Stolk, L Tabara, Y Teh, AL Wu, Y Wu, JY Zhang, Y Aits, I Alves, ADC Das, S Dorajoo, R Hopewell, JC Kim, YK Koivula, RW Luan, J Lyytikainen, LP Nguyen, QN Pereira, MA Postmus, I Raitakari, OT Bryan, MS Scott, RA Sorice, R Tragante, V Traglia, M White, J Yamamoto, K Zhang, YH Adair, LS Ahmed, A Akiyama, K Asif, R Aung, T Barroso, I Bjonnes, A Braun, TR Cai, H Chang, LC Chen, CH Cheng, CY Chong, YS Collins, R Courtney, R Davies, G Delgado, G Do, LD Doevendans, PA Gansevoort, RT Gao, YT Grammer, TB Grarup, N Grewal, J Gu, DF Wander, GS Hartikainen, AL Hazen, SL He, J Heng, CK Hixson, JE Hofman, A Hsu, C Huang, W Husemoen, LLN Hwang, JY Ichihara, S Igase, M Isono, M Justesen, JM Katsuy, T Kibriya, MG Kim, YJ Kishimoto, M Koh, WP Kohara, K Kumari, M Kwek, K Lee, NR Lee, J Liao, JM Lieb, W Liewald, DCM Matsubara, T Matsushita, Y Meitinger, T Mihailov, E Milani, L Mills, R Mononen, N Muller-Nurasyid, M Nabika, T Nakashima, E Ng, HK Nikus, K Nutile, T Ohkubo, T Ohnaka, K Parish, S Paternoster, L Peng, H Peters, A Pham, ST Pinidiyapathirage, MJ Rahman, M Rakugi, H Rolandsson, O Rozario, MA Ruggiero, D Sala, CF Sarju, R Shimokawa, K Snieder, H Sparso, T Spiering, W Starr, JM Stott, DJ Stram, DO Sugiyama, T Szymczak, S Tang, WHW Tong, L Trompet, S Turjanmaa, V Ueshima, H Uitterlinden, AG Umemura, S Vaarasmaki, M van Dam, RM van Gilst, WH van Veldhuisen, DJ Viikari, JS Waldenberger, M Wang, YQ Wang, AL Wilson, R Wong, TY Xiang, YB Yamaguchi, S Ye, XW Young, RD Young, TL Yuan, JM Zhou, XY Asselbergs, FW Ciullo, M Clarke, R Deloukas, P Franke, A Franks, PW Franks, S Friedlander, Y Gross, MD Guo, ZR Hansen, T Jarvelin, MR Jorgensen, T Jukema, JW Kahonen, M Kajio, H Kivimaki, M Lee, JY Lehtimaki, T Linneberg, A Miki, T Pedersen, O Samani, NJ Sorensen, TIA Takayanagi, R Toniolo, D Ahsan, H Allayee, H Chen, YT Danesh, J Deary, IJ Franco, OH Franke, L Heijman, BT Holbrook, JD Isaacs, A Kim, BJ Lin, X Liu, JJ Marz, W Metspalu, A Mohlke, KL Sanghera, DK Shu, XO van Meurs, JBJ Vithana, E Wickremasinghe, AR Wijmenga, C Wolffenbuttel, BHW Yokota, M Zheng, W Zhu, DL Vineis, P Kyrtopoulos, SA Kleinjans, JCS McCarthy, MI Soong, R Gieger, C Scott, J Teo, YY He, J Elliott, P Tai, ES van der Harst, P Kooner, JS Chambers, JC AF Kato, Norihiro Loh, Marie Takeuchi, Fumihiko Verweij, Niek Wang, Xu Zhang, Weihua Kelly, Tanika N. Saleheen, Danish Lehne, Benjamin Leach, Irene Mateo Drong, Alexander W. Abbott, James Wahl, Simone Tan, Sian-Tsung Scott, William R. Campanella, Gianluca Chadeau-Hyam, Marc Afzal, Uzma Ahluwalia, Tarunveer S. Bonder, Marc Jan Chen, Peng Dehghan, Abbas Edwards, Todd L. Esko, Tonu Go, Min Jin Harris, Sarah E. Hartiala, Jaana Kasela, Silva Kasturiratne, Anuradhani Khor, Chiea-Chuen Kleber, Marcus E. Li, Huaixing Mok, Zuan Yu Nakatochi, Masahiro Sapari, Nur Sabrina Saxena, Richa Stewart, Alexandre F. R. Stolk, Lisette Tabara, Yasuharu Teh, Ai Ling Wu, Ying Wu, Jer-Yuarn Zhang, Yi Aits, Imke Alves, Alexessander Da Silva Couto Das, Shikta Dorajoo, Rajkumar Hopewell, Jemma C. Kim, Yun Kyoung Koivula, Robert W. Luan, Jian'an Lyytikainen, Leo-Pekka Nguyen, Quang N. Pereira, Mark A. Postmus, Iris Raitakari, Olli T. Bryan, Molly Scannell Scott, Robert A. Sorice, Rossella Tragante, Vinicius Traglia, Michela White, Jon Yamamoto, Ken Zhang, Yonghong Adair, Linda S. Ahmed, Alauddin Akiyama, Koichi Asif, Rasheed Aung, Tin Barroso, Ines Bjonnes, Andrew Braun, Timothy R. Cai, Hui Chang, Li-Ching Chen, Chien-Hsiun Cheng, Ching-Yu Chong, Yap-Seng Collins, Rory Courtney, Regina Davies, Gail Delgado, Graciela Do, Loi D. Doevendans, Pieter A. Gansevoort, Ron T. Gao, Yu-Tang Grammer, Tanja B. Grarup, Niels Grewal, Jagvir Gu, Dongfeng Wander, Gurpreet S. Hartikainen, Anna-Liisa Hazen, Stanley L. He, Jing Heng, Chew-Kiat Hixson, James E. Hofman, Albert Hsu, Chris Huang, Wei Husemoen, Lise L. N. Hwang, Joo-Yeon Ichihara, Sahoko Igase, Michiya Isono, Masato Justesen, Johanne M. Katsuy, Tomohiro Kibriya, Muhammad G. Kim, Young Jin Kishimoto, Miyako Koh, Woon-Puay Kohara, Katsuhiko Kumari, Meena Kwek, Kenneth Lee, Nanette R. Lee, Jeannette Liao, Jiemin Lieb, Wolfgang Liewald, David C. M. Matsubara, Tatsuaki Matsushita, Yumi Meitinger, Thomas Mihailov, Evelin Milani, Lili Mills, Rebecca Mononen, Nina Mueller-Nurasyid, Martina Nabika, Toru Nakashima, Eitaro Ng, Hong Kiat Nikus, Kjell Nutile, Teresa Ohkubo, Takayoshi Ohnaka, Keizo Parish, Sarah Paternoster, Lavinia Peng, Hao Peters, Annette Pham, Son T. Pinidiyapathirage, Mohitha J. Rahman, Mahfuzar Rakugi, Hiromi Rolandsson, Olov Rozario, Michelle Ann Ruggiero, Daniela Sala, Cinzia F. Sarju, Ralhan Shimokawa, Kazuro Snieder, Harold Sparso, Thomas Spiering, Wilko Starr, John M. Stott, David J. Stram, Daniel O. Sugiyama, Takao Szymczak, Silke Tang, W. H. Wilson Tong, Lin Trompet, Stella Turjanmaa, Vaino Ueshima, Hirotsugu Uitterlinden, Andre G. Umemura, Satoshi Vaarasmaki, Marja van Dam, Rob M. van Gilst, Wiek H. van Veldhuisen, Dirk J. Viikari, Jorma S. Waldenberger, Melanie Wang, Yiqin Wang, Aili Wilson, Rory Wong, Tien-Yin Xiang, Yong-Bing Yamaguchi, Shuhei Ye, Xingwang Young, Robin D. Young, Terri L. Yuan, Jian-Min Zhou, Xueya Asselbergs, Folkert W. Ciullo, Marina Clarke, Robert Deloukas, Panos Franke, Andre Franks, Paul W. Franks, Steve Friedlander, Yechiel Gross, Myron D. Guo, Zhirong Hansen, Torben Jarvelin, Marjo-Riitta Jorgensen, Torben Jukema, J. Wouter Kahonen, Mika Kajio, Hiroshi Kivimaki, Mika Lee, Jong-Young Lehtimaki, Terho Linneberg, Allan Miki, Tetsuro Pedersen, Oluf Samani, Nilesh J. Sorensen, Thorkild I. A. Takayanagi, Ryoichi Toniolo, Daniela Ahsan, Habibul Allayee, Hooman Chen, Yuan-Tsong Danesh, John Deary, Ian J. Franco, Oscar H. Franke, Lude Heijman, Bastiaan T. Holbrook, Joanna D. Isaacs, Aaron Kim, Bong-Jo Lin, Xu Liu, Jianjun Maerz, Winfried Metspalu, Andres Mohlke, Karen L. Sanghera, Dharambir K. Shu, Xiao-Ou van Meurs, Joyce B. J. Vithana, Eranga Wickremasinghe, Ananda R. Wijmenga, Cisca Wolffenbuttel, Bruce H. W. Yokota, Mitsuhiro Zheng, Wei Zhu, Dingliang Vineis, Paolo Kyrtopoulos, Soterios A. Kleinjans, Jos C. S. McCarthy, Mark I. Soong, Richie Gieger, Christian Scott, James Teo, Yik-Ying He, Jiang Elliott, Paul Tai, E. Shyong van der Harst, Pim Kooner, Jaspal S. Chambers, John C. CA BIOS-consortium CARDIo GRAMplusCD LifeLines Cohort Study InterAct Consortium TI Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation SO NATURE GENETICS LA English DT Article ID PULMONARY ARTERIAL-HYPERTENSION; CENTRIC ARRAY; RISK-FACTORS; CARDIOVASCULAR-DISEASE; VARIANTS; REGIONS; KIDNEY; TISSUE; METAANALYSIS; INDIVIDUALS AB We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. C1 [Kato, Norihiro; Takeuchi, Fumihiko; Akiyama, Koichi; Isono, Masato; Shimokawa, Kazuro] Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan. [Loh, Marie; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Loh, Marie; Zhang, Weihua; Lehne, Benjamin; Scott, William R.; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Grewal, Jagvir; Vineis, Paolo; Elliott, Paul; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [Loh, Marie] ASTAR, Translat Lab Genet Med, Singapore, Singapore. [Verweij, Niek; Leach, Irene Mateo; van Gilst, Wiek H.; van Veldhuisen, Dirk J.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Wang, Xu; Chen, Peng; Khor, Chiea-Chuen; Cheng, Ching-Yu; Koh, Woon-Puay; Lee, Jeannette; van Dam, Rob M.; Liu, Jianjun; Teo, Yik-Ying; Tai, E. Shyong] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Wang, Xu; Chen, Peng; Khor, Chiea-Chuen; Cheng, Ching-Yu; Koh, Woon-Puay; Lee, Jeannette; van Dam, Rob M.; Liu, Jianjun; Teo, Yik-Ying; Tai, E. Shyong] Natl Univ Hlth Syst, Singapore, Singapore. [Zhang, Weihua; Tan, Sian-Tsung; Afzal, Uzma; Grewal, Jagvir; Mills, Rebecca; Kooner, Jaspal S.; Chambers, John C.] Ealing Hosp Natl Hlth Serv NHS Trust, Southall, Middx, England. [Kelly, Tanika N.; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Saleheen, Danish; Asif, Rasheed] Ctr Non Communicable Dis, Karachi, Pakistan. [Saleheen, Danish; Young, Robin D.; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England. [Saleheen, Danish] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Drong, Alexander W.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Abbott, James] Univ London Imperial Coll Sci Technol & Med, Bioinformat Support Serv, London, England. [Wahl, Simone; Waldenberger, Melanie; Wilson, Rory; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany. [Wahl, Simone; Peters, Annette; Waldenberger, Melanie; Wilson, Rory; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany. [Wahl, Simone] German Ctr Diabet Res DZD, Neuherberg, Germany. [Tan, Sian-Tsung; Scott, William R.; Scott, James; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Ahluwalia, Tarunveer S.; Grarup, Niels; Justesen, Johanne M.; Sparso, Thomas; Hansen, Torben; Pedersen, Oluf; Sorensen, Thorkild I. A.] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood COSP, Copenhagen, Denmark. [Ahluwalia, Tarunveer S.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Bonder, Marc Jan; Franke, Lude; Wijmenga, Cisca; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Isaacs, Aaron] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Edwards, Todd L.] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr,Ctr Human Genet Res, Nashville, TN USA. [Esko, Tonu; Kasela, Silva; Mihailov, Evelin; Milani, Lili; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Esko, Tonu] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Go, Min Jin; Kim, Yun Kyoung; Hwang, Joo-Yeon; Kim, Young Jin; Kim, Bong-Jo] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea. [Harris, Sarah E.] Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. [Harris, Sarah E.] Western Gen Hosp, Inst Genet & Mol Med, MRC, Edinburgh EH4 2XU, Midlothian, Scotland. [Harris, Sarah E.; Davies, Gail; Liewald, David C. M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Aging & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. [Kasturiratne, Anuradhani; Pinidiyapathirage, Mohitha J.; Wickremasinghe, Ananda R.] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka. [Khor, Chiea-Chuen; Dorajoo, Rajkumar; Liu, Jianjun; Teo, Yik-Ying] ASTAR, Genome Inst Singapore, Singapore, Singapore. [Khor, Chiea-Chuen; Cheng, Ching-Yu; Liao, Jiemin; Wong, Tien-Yin; Vithana, Eranga] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. [Khor, Chiea-Chuen] Natl Univ Singapore, Dept Paediat, Singapore 117548, Singapore. [Kleber, Marcus E.; Delgado, Graciela; Grammer, Tanja B.; Maerz, Winfried] Heidelberg Univ, Mannheim Med Fac, Med Clin V, Mannheim, Germany. [Li, Huaixing; Wang, Yiqin; Ye, Xingwang; Lin, Xu] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Mok, Zuan Yu; Sapari, Nur Sabrina; Ng, Hong Kiat; Rozario, Michelle Ann; Soong, Richie] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Nakatochi, Masahiro] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Nagoya, Aichi, Japan. [Saxena, Richa; Bjonnes, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Stewart, Alexandre F. R.] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. [Stewart, Alexandre F. R.] Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada. [Stolk, Lisette; Uitterlinden, Andre G.; van Meurs, Joyce B. J.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Tabara, Yasuharu] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan. [Teh, Ai Ling; Chong, Yap-Seng; Holbrook, Joanna D.] ASTAR, Singapore Inst Clin Sci, Singapore, Singapore. [Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Wu, Jer-Yuarn; Chang, Li-Ching; Chen, Chien-Hsiun; Chen, Yuan-Tsong] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Wu, Jer-Yuarn; Chen, Chien-Hsiun] China Med Univ, Sch Chinese Med, Taichung, Taiwan. [Zhang, Yi; Zhu, Dingliang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Ruijin Hosp, State Key Lab Med Genet, Shanghai 200030, Peoples R China. [Zhang, Yi; Zhu, Dingliang] Shanghai Res Inst Hypertens, Shanghai, Peoples R China. [Aits, Imke; Lieb, Wolfgang] Univ Kiel, Inst Epidemiol & Biobank Popgen, Kiel, Germany. [Alves, Alexessander Da Silva Couto; Das, Shikta; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC,Hlth Protect Agcy PHE,Ctr Environm & Hlth, London, England. [Hopewell, Jemma C.; Collins, Rory; Parish, Sarah; Clarke, Robert] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trials Support Unit, Oxford, England. [Koivula, Robert W.; Franks, Paul W.] Skane Univ, Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Luan, Jian'an; Scott, Robert A.] Univ Cambridge, Epidemiol Unit, MRC, Inst Metab Sci, Cambridge, England. [Lyytikainen, Leo-Pekka; Mononen, Nina; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lyytikainen, Leo-Pekka; Mononen, Nina; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland. [Nguyen, Quang N.; Do, Loi D.; Pham, Son T.] Bach Mai Hosp, Vietnam Natl Heart Inst, Hanoi, Vietnam. [Pereira, Mark A.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Postmus, Iris] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Postmus, Iris] Netherlands Consortium Hlth Ageing, Leiden, Netherlands. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Bryan, Molly Scannell; Kibriya, Muhammad G.; Tong, Lin; Ahsan, Habibul] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. [Sorice, Rossella; Nutile, Teresa; Ruggiero, Daniela; Ciullo, Marina] CNR, Inst Genet & Biophys Buzzati Traverso, I-80125 Naples, Italy. [Tragante, Vinicius; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands. [Traglia, Michela; Sala, Cinzia F.; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Traglia, Michela] Ist Ricovero & Cura Carattere Sci IRCCS Burlo Gar, Inst Maternal & Child Hlth, Trieste, Italy. [White, Jon] UCL, Genet Inst, Dept Genet Environm & Evolut, London, England. [Yamamoto, Ken] Kyushu Univ, Med Inst Bioregulat, Div Genom, Fukuoka 812, Japan. [Zhang, Yonghong; Peng, Hao; Wang, Aili; Guo, Zhirong] Soochow Univ, Coll Med, Sch Publ Hlth, Dept Epidemiol, Suzhou, Peoples R China. [Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Ahmed, Alauddin; Rahman, Mahfuzar] UChicago Res Bangladesh, Dhaka, Bangladesh. [Aung, Tin; Cheng, Ching-Yu; Liao, Jiemin; Wong, Tien-Yin; Vithana, Eranga; Teo, Yik-Ying] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Barroso, Ines] Wellcome Trust Sanger Inst, Metabol Dis Grp, Cambridge, England. [Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England. [Braun, Timothy R.; Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA. [Cai, Hui; Courtney, Regina; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr,Vanderbilt Genet Inst, Nashville, TN USA. [Cai, Hui; Courtney, Regina; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Cheng, Ching-Yu] Duke Natl Univ Singapore, Grad Sch Med, Off Clin Sci, Ctr Quantitat Med, Singapore, Singapore. [Chong, Yap-Seng] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Davies, Gail; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Gu, Dongfeng] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100730, Peoples R China. [Gu, Dongfeng] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China. [Gu, Dongfeng] Peking Union Med Coll, Beijing 100021, Peoples R China. [Wander, Gurpreet S.; Sarju, Ralhan] Hero DMC Heart Inst, Dayanand Med Coll & Hosp Unit, Ludhiana, Punjab, India. [Hartikainen, Anna-Liisa; Vaarasmaki, Marja] Oulu Univ Hosp, Dept Obstet & Gynecol, Oulu, Finland. [Hartikainen, Anna-Liisa; Vaarasmaki, Marja] Univ Oulu, Med Res Ctr, Oulu, Finland. [Hartikainen, Anna-Liisa; Vaarasmaki, Marja; Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. [Hazen, Stanley L.; Tang, W. H. Wilson] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Hazen, Stanley L.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA. [He, Jing] Vanderbilt Univ, Dept Biostat, Nashville, TN 37235 USA. [Heng, Chew-Kiat] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pediat, Singapore 117595, Singapore. [Hixson, James E.] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. [Hsu, Chris; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Huang, Wei] Chinese Natl Human Genom Ctr, Dept Genet, Shanghai, Peoples R China. [Husemoen, Lise L. N.; Jorgensen, Torben; Linneberg, Allan] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Ichihara, Sahoko] Mie Univ, Grad Sch Reg Innovat Studies, Tsu, Mie 514, Japan. [Igase, Michiya; Kohara, Katsuhiko; Miki, Tetsuro] Ehime Univ, Grad Sch Med, Dept Geriatr Med, Toon, Ehime, Japan. [Katsuy, Tomohiro; Tai, E. Shyong] Osaka Univ, Grad Sch Med, Dept Clin Gene Therapy, Suita, Osaka, Japan. [Katsuy, Tomohiro; Rakugi, Hiromi] Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Suita, Osaka, Japan. [Kishimoto, Miyako; Matsushita, Yumi; Kajio, Hiroshi] Natl Ctr Global Hlth & Med, Toyama, Japan. [Koh, Woon-Puay] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Kumari, Meena; Kivimaki, Mika] UCL, Dept Epidemiol & Publ Hlth, London, England. [Kwek, Kenneth] KK Womens & Childrens Hosp, Singapore, Singapore. [Lee, Nanette R.] Univ San Carlos, Off Populat Studies Fdn, Cebu, Philippines. [Lee, Nanette R.] Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines. [Matsubara, Tatsuaki] Aichi Gakuin Univ, Sch Dent, Dept Internal Med, Nagoya, Aichi 464, Japan. [Meitinger, Thomas] Helmholtz Zenntrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany. [Mueller-Nurasyid, Martina] Helmholtz Zenntrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Munich, Germany. [Mueller-Nurasyid, Martina; Peters, Annette] German Ctr Cardiovasc Res DZHK, Munich, Germany. [Nabika, Toru] Shimane Univ, Fac Med, Dept Funct Pathol, Izumo, Shimane, Japan. [Nakashima, Eitaro] Nagoya Univ, Grad Sch Med, Dept Internal Med, Div Endocrinol & Diabet, Nagoya, Aichi 4648601, Japan. [Nakashima, Eitaro] Chubu Rosai Hosp, Dept Endocrinol & Diabet, Nagoya, Aichi, Japan. [Nikus, Kjell] Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere, Finland. [Nikus, Kjell] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Ohkubo, Takayoshi] Teikyo Univ, Sch Med, Dept Hyg & Publ Hlth, Tokyo 173, Japan. [Ohnaka, Keizo] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Fukuoka, Japan. [Paternoster, Lavinia; Sorensen, Thorkild I. A.] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England. [Rahman, Mahfuzar] Bangladesh Rehabil Assistance Comm, Res & Evaluat Div, Dhaka, Bangladesh. [Rolandsson, Olov; Franks, Paul W.] Umea Univ, Sect Family Med, Dept Publ Hlth & Clin Med, Umea, Sweden. [Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Spiering, Wilko] Univ Med Ctr Utrecht, Dept Vasc Med, Utrecht, Netherlands. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Acad Sect Geriatr Med, Glasgow, Lanark, Scotland. [Sugiyama, Takao] Asahi Life Fdn, Inst Adult Dis, Tokyo, Japan. [Szymczak, Silke; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany. [Tang, W. H. Wilson] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA. [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Turjanmaa, Vaino; Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Turjanmaa, Vaino; Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Ueshima, Hirotsugu] Shiga Univ Med Sci, Dept Hlth Sci, Otsu, Shiga 52021, Japan. [Ueshima, Hirotsugu] Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Otsu, Shiga 52021, Japan. [Umemura, Satoshi] Yokohama City Univ, Grad Sch Med, Dept Med Sci & Cardiorenal Med, Yokohama, Kanagawa 232, Japan. [Viikari, Jorma S.] Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland. [Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland. [Yamaguchi, Shuhei] Shimane Univ, Fac Med, Dept Internal Med 3, Izumo, Shimane, Japan. [Young, Terri L.; Vithana, Eranga] Duke Natl Univ Singapore, Grad Sch Med, Neurosci & Behav Disorders NBD Program, Singapore, Singapore. [Young, Terri L.] Duke Univ, Med Ctr, Duke Eye Ctr, Durham, NC USA. [Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Canc Control & Populat Sci, Pittsburgh, PA USA. [Zhou, Xueya] Tsinghua Univ, Tsinghua Natl Lab Informat Sci & Technol, Dept Automat, Bioinformat Div,Minist Educ,Key Lab Bioinformat, Beijing 100084, Peoples R China. [Zhou, Xueya] Tsinghua Univ, Dept Automat, Ctr Synthet & Syst Biol, TNLIST,Minist Educ,Key Lab Bioinformat, Beijing 100084, Peoples R China. [Zhou, Xueya] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Asselbergs, Folkert W.; Jukema, J. Wouter; van der Harst, Pim] Netherlands Heart Inst, Interuniv Cardiol Inst Netherlands, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England. [Deloukas, Panos] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Deloukas, Panos] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Franks, Steve] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Inst Reprod & Dev Biol, London, England. [Friedlander, Yechiel] Hebrew Univ Jerusalem, Sch Publ Hlth, Jerusalem, Israel. [Gross, Myron D.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Fac Med, Ctr Life Course Epidemiol, Oulu, Finland. [Jukema, J. Wouter] ICIN, Utrecht, Netherlands. [Lee, Jong-Young] Minist Hlth & Welf, Seoul, South Korea. [Lee, Jong-Young] THERAGEN ETEX Bio Inst, Suwon, South Korea. [Linneberg, Allan] Rigshosp, Dept Clin Expt Res, DK-2100 Copenhagen, Denmark. [Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark. [Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh J.] Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark. [Takayanagi, Ryoichi] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Kyushu, Japan. [Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Danesh, John] Wellcome Trust Sanger Inst, Hinxton, England. [Heijman, Bastiaan T.] Leiden Univ, Med Ctr, Mol Epidemiol, Leiden, Netherlands. [Maerz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria. [Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria. [Maerz, Winfried] Synlab Acad, Synlab Serv, Mannheim, Germany. [Wolffenbuttel, Bruce H. W.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Yokota, Mitsuhiro] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan. [Kyrtopoulos, Soterios A.] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, GR-11635 Athens, Greece. [Kleinjans, Jos C. S.] Maastricht Univ, Dept Toxicogenom, Maastricht, Netherlands. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Soong, Richie] Natl Univ Singapore, Dept Pathol, Singapore 117548, Singapore. [Teo, Yik-Ying] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore. [Teo, Yik-Ying] Natl Univ Singapore, Inst Life Sci, Singapore 117548, Singapore. [Teo, Yik-Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Kooner, Jaspal S.; Chambers, John C.] Imperial Coll Healthcare NHS Trust, London, England. RP Chambers, JC (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. EM nokato@ri.ncgm.go.jp; jhe@tulane.edu; p.elliott@ic.ac.uk; e_shyong_tai@nuhs.edu.sg; p.van.der.harst@umcg.nl; j.kooner@ic.ac.uk; john.chambers@ic.ac.uk RI Campanella, Gianluca/G-2617-2010; Meitinger, Thomas/O-1318-2015; Verweij, Niek/A-4499-2017; Franke, Andre/B-2151-2010; Waldenberger, Melanie/B-5355-2014; Peters, Annette/A-6117-2011; Lyytikainen, Leo-Pekka/C-8544-2016; Nakatochi, Masahiro/Q-1247-2015; ruggiero, daniela/K-5638-2016; Grarup, Niels/K-2807-2015; Franke, Lude/P-7036-2016; Wijmenga, Cisca/D-2173-2009; Justesen, Johanne Marie/L-6023-2015; Deloukas, Panos/B-2922-2013; Lieb, Wolfgang/C-1990-2012 OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Rakugi, Hiromi/0000-0001-6508-4338; Jorgensen, Torben/0000-0001-9453-2830; Khor, Chiea Chuen/0000-0002-1128-4729; Tai, E Shyong/0000-0003-2929-8966; Bonder, Marc Jan/0000-0002-8431-3180; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Linneberg, Allan/0000-0002-0994-0184; Peters, Annette/0000-0001-6645-0985; Paternoster, Lavinia/0000-0003-2514-0889; Campanella, Gianluca/0000-0002-5411-6338; Abbott, James/0000-0001-7701-4249; Verweij, Niek/0000-0002-4303-7685; Pinidiyapathirage, Mohitha/0000-0003-2947-3015; NUTILE, TERESA/0000-0001-7062-8352; Gieger, Christian/0000-0001-6986-9554; Kumari, Meena/0000-0001-9716-1035; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Franke, Andre/0000-0003-1530-5811; Waldenberger, Melanie/0000-0003-0583-5093; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Nakatochi, Masahiro/0000-0002-1838-4837; ruggiero, daniela/0000-0003-3898-7827; Grarup, Niels/0000-0001-5526-1070; Franke, Lude/0000-0002-5159-8802; Justesen, Johanne Marie/0000-0002-0484-8522; Deloukas, Panos/0000-0001-9251-070X; FU Grants for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan [24390084, 21390099, 20390185, 22390186, 24591060, 25253059, 25461127]; Science and Technology Incubation Program in Advanced Regions, Japanese Science and Technology Agency; Japanese Atherosclerosis Prevention Fund; Takeda Medical Research Foundation; National Cardiovascular Research Grants; US National Institutes of Health (NIH) - National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082766]; National Human Genome Research Institute [NOT-HG-11-009]; VPR bridge grant from the University of Oklahoma Health Sciences Center; BBMRI-NL; Netherlands Organization for Scientific Research (NWO project) [184.021.007]; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japanese Society for the Promotion of Science; grants for Core Research for Evolutional Science and Technology (CREST) from the Japanese Science and Technology Agency; Program for the Promotion of Fundamental Studies in Health Sciences, National Institute of Biomedical Innovation Organization (NIBIO); KAKENHI on Priority Area 'Applied Genomics' from the Ministry of Education, Culture, Sports, Science and Technology of Japan; National Center for Global Health and Medicine; Okinaga Scholarship; Grants for International Health Research from the Ministry of Health, Labour and Welfare of Japan [17C-1, 20S-6]; National Center for Global Health and Medicine [22S-10, 25S-1]; Manpei Suzuki Diabetes Foundation; Italian Ministry of Universities (Interomics Flag project) [FIRB-RBNE08NKH7]; Assessorato Ricerca Regione Campania; Fondazione con il SUD [2011-PDR-13]; Fondazione Banco di Napoli; National Institutes of Health [DK078150, TW05596, HL085144, TW008288]; Novo Nordisk; Swedish Research Council; Pahlssons Foundation; Swedish Heart Lung Foundation; Skane Regional Health Authority; Estonian government [SF0180142s08]; Center of Excellence in Genomics (EXCEGEN); University of Tartu [SP1GVARENG]; Competitive Research Funding from Tampere University Hospital [9M048, 9N035]; Finnish Cultural Foundation; Finnish Foundation for Cardiovascular Research; Emil Aaltonen Foundation, Finland; Tampere Tuberculosis Foundation; US NIH [R01CA107431, P42ES10349, 2R01LM010098, NCI RO1CA55069, R35CA53890, R01CA80205, R01CA144034, RO1CA82729, UM1CA173640, R37CA70867]; National Heart, Lung, and Blood Institute [P01HL098055, P01HL076491, R01HL103866, P20HL113452, R01HL103931]; National Institute of Environmental Health Sciences [R01ES021801]; National Heart, Lung, and Blood Institute, US NIH [U01HL072507, R01HL087263, R01HL090682]; Velux Foundation; Danish Medical Research Council; Danish Agency for Science, Technology and Innovation; Aase and Ejner Danielsens Foundation; ALK-Abello (Horsholm, Denmark); Timber Merchant Vilhelm Bangs Foundation; MEKOS Laboratories Denmark; Research Centre for Prevention and Health; Capital Region of Denmark; Lundbeck Foundation; Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp); Novo Nordisk Foundation; Korean Centers for Disease Control and Prevention [4845-301, 4851-302, 4851-307]; Korean National Institute of Health, Republic of Korea [2012-N73002-00]; UK Medical Research Council; British Heart Foundation; Merck Co.; Roche Vitamins, Ltd.; University of Oxford; Centre National de Genotypage from Merck Co.; Oxford British Heart Foundation Centre of Research Excellence; British Heart Foundation [FS/14/55/30806, RG/07/008/23674]; GENDINOB project; Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme [NMRC/TCR/012-NUHS/2014]; Singapore Institute for Clinical Sciences, A*STAR, Singapore; Compagnia di San Paolo (Torino, Italy); Fondazione Cariplo, Italy; Ministry of Health, Ricerca Finalizzata; CCM; Telethon, Italy; Danish Research Council; Danish Centre for Health Technology Assessment; Research Foundation of Copenhagen County; Ministry of Internal Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical Association; Augustinus Foundation; Ib Henriksen Foundation; Becket Foundation; Danish Diabetes Association; European Union (Sixth Framework Programme of the European Community) [LSHM-CT-2006-037197]; Ministry of Education, Culture, Sports, Science and Technology of Japan [21390099, 20390185, 19659163, 16790336, 12204008, 15790293, 16590433, 17790381, 18390192, 18590265, 18590587, 18590811, 19590929, 19650188, 19790423, 17390186, 20390184, 21390223]; Ministry of Health, Labor and Welfare of Japan [H15-Longevity-005, H17-Longevity-003, H16-Kenko-001, H18-Longevity(kokusai), H11-Longevity-020, H17-Kenkou-007, H17-Pharmaco-common-003, H18-Junkankitou[Seishuu]-Ippan-012, H20-Junkankitou[Seishuu]-Ippan-009, 013]; Health and Labor Sciences Research Grants, Japan; Science and Technology Incubation Program in Advanced Regions; Japanese Science and Technology Agency; Japanese Society for the Promotion of Science [16.54041, 18.54042, 19.7152, 20.7198, 20.7477, 20.54043]; Health Science Research Grants and Medical Technology Evaluation Research Grants from the Ministry of Health, Labour and Welfare of Japan; Uehara Memorial Foundation; Biomedical Innovation Grants; Japanese Research Foundation for Clinical Pharmacology; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; German Federal Ministry of Education and Research (BMBF); Federal Ministry of Health; Munich Center of Health Sciences (MC Health), LMUinnovativ; German-Israeli Foundation for Scientific Research and Development; European Union [305280, 279143, 201668, 305739, LSHM-CT-2004-503485]; Helmholtz-Russia Joint Research Group (HRJRG) [310]; German Center for Diabetes Research (DZD); EU [602936]; BMBF e:Med project e:AtheroSysMed-Systems Medicine of Myocardial Infarction and Stroke; UK Biotechnology and Biological Sciences Research Council (BBSRC); Royal Society; Chief Scientist Office of the Scottish government; BBSRC; Age UK (The Disconnected Mind project); Netherlands Organization for Scientific Research (NWO) [175.010.2007.006, 184021007]; Economic Structure-Enhancing Fund (FES) of the Dutch government; Ministry of Economic Affairs; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; Northern Netherlands Collaboration of Provinces (SNN); province of Groningen, University Medical Center Groningen; University of Groningen; Dutch Kidney Foundation; Dutch Diabetes Research Foundation; NIHR Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust; Medical Research Council, UK [G0601966, G0700931, G0500539, G0600331, G0902037]; Wellcome Trust [084723/Z/08/Z]; NIHR [RP-PG-0407-10371]; Action on Hearing Loss [G51]; INTERREG IV Oberrhein Program (Genetic Mechanisms of Cardiovascular Diseases) [A28]; European Regional Development Fund (ERDF); Wissenschaftsoffensive TMO; Academy of Finland (Center of Excellence in Complex Disease Genetics) [104781, 120315, 129269]; University Hospital Oulu, Biocenter; University of Oulu, Finland [75617]; European Commission [QLG1-CT-2000-01643, 223004]; National Heart, Lung, and Blood Institute through the STAMPEED program [5R01HL087679-02, 1RL1MH083268-01]; US NIH/National Institute of Mental Health [5R01MH63706:02]; ENGAGE project; Academy of Finland [286284, 134309, 126925, 121584, 124282, 129378, 117787, 41071]; Biocentrum Helsinki; German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN); Ministry of Science, Commerce and Transportation of the state of Schleswig-Holstein; German Ministry of Education and Research [01EY1103]; Dutch Kidney Foundation [E033]; European Union project grant GENECURE [FP-6 LSHM CT 2006 037697]; Netherlands Organization for Health Research and Development (NWO-Groot grant) [175.010.2007.006]; Netherlands Organization for Health Research and Development (NWO VENI grant) [916.761.70]; Netherlands Organization for Health Research and Development (ZonMw grant) [90.700.441]; Dutch Interuniversity Cardiology Institute Netherlands (ICIN); Pfizer; Bristol-Myers-Squibb; Netherlands Heart Foundation [2001 D 032]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant) [050-060-810]; Erasmus Medical Center; Erasmus University; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); European Commission (DG XII); municipality of Rotterdam; Genetic Laboratory of the Department of Internal Medicine, Erasmus Medical Center; Biomedical Research Council of Singapore [08/1/35/19/550, 09/1/35/19/616]; NMRC, Singapore [STaR/0003/2008, CG/SERI/2010, NMRC/1270/2010, 0796/2003, IRG07nov013, IRG09nov014]; Genetic and Environmental Determinants of Type 2 Diabetes in Chinese Singaporeans, grant from the US NIH [R01DK080720]; NMRC of Singapore; Genome Institute of Singapore; A*STAR, Singapore; US NIH/National Cancer Institute [R35CA53890, R01CA80205, R01CA144034, RO1CA55069]; NUS-HUJ CREATE Programme of the National Research Foundation, Singapore [370062002]; Biomedical Research Council of Singapore (A*STAR, Singapore); Dutch government [NWO 184.021.007]; National Natural Science Foundation of China [81172761]; Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions; Yong Loo Lin School of Medicine; National University Health System; Life Sciences Institute of the National University of Singapore; National Research Foundation of Singapore [NRF-RF-2010-05]; Biomedical Research Council of Singapore (under the individual research grants scheme); Chinese National Key Program for Basic Research (973) [2004CB518603, 2006CB503804, 2009CB521905]; Chinese National High-Tech Program (863) [2009AA022703, 2006AA022179]; Ministry of Science and Technology, National Natural Science Foundation of China [30871361]; Academia Sinica Genomic Medicine Multicenter Study, Taiwan [40-05-GMM]; Stroke Association; National Institute on Aging [5RO1AG13196]; Agency for Health Care Policy Research [HS06516]; John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-Economic Status and Health; Social Insurance Institution of Finland; Kuopio, Tampere and Turku University Hospital Medical Funds [X51001]; Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research; Emil Aaltonen Foundation; Yrjo Jahnsson Foundation; [RR20649]; [ES10126]; [DK56350]; [HEALTH-F4-2007-201413] FX AASC. This work was supported by Grants for Scientific Research (24390084, 21390099 and 20390185) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a Science and Technology Incubation Program in Advanced Regions, Japanese Science and Technology Agency; the Japanese Atherosclerosis Prevention Fund; the Takeda Medical Research Foundation; and National Cardiovascular Research Grants.; AIDHS/SDS. This study was supported by US National Institutes of Health (NIH) grants R01DK082766 (D.K.S.) funded by the National Institute of Diabetes and Digestive and Kidney Diseases and NOT-HG-11-009 (D.K.S.) funded by the National Human Genome Research Institute (D.K.S.) and by a VPR bridge grant (D.K.S.) from the University of Oklahoma Health Sciences Center.; BIOS-consortium. The BIOS-consortium is funded by BBMRI-NL, a research infrastructure financed by the Netherlands Organization for Scientific Research (NWO project 184.021.007).; CAGE-Amagasaki. We acknowledge the outstanding contributions of the employees of the National Center for Global Health and Medicine who provided technical and infrastructural support for this work. Above all, we thank the participants who made this work possible and who gave it value. We also thank T. Ogihara, Y. Yamori, A. Fujioka, C. Makibayashi, S. Katsuya, K. Sugimoto, K. Kamide, R. Morishita and the many physicians of the participating hospitals and medical institutions in the Amagasaki Medical Association for their assistance in collecting the DNA samples and accompanying clinical information. This work was supported by Grants for Scientific Research (22390186, 24591060, 25253059 and 25461127) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.; CAGE-Fukuoka. This work was supported by Grants-in-Aid for the 21st Century Center of Excellence Program (Kyushu University) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Grants-in-Aid for Scientific Research (category A) from the Japanese Society for the Promotion of Science. We are grateful to all participants of this study. We also especially thank S. Kono for his management of the DNA samples and clinical information.; CAGE_GWAS1. The CAGE Network studies were supported by grants for Core Research for Evolutional Science and Technology (CREST) from the Japanese Science and Technology Agency; the Program for the Promotion of Fundamental Studies in Health Sciences, National Institute of Biomedical Innovation Organization (NIBIO); KAKENHI (Grant-in-Aid for Scientific Research) on Priority Area 'Applied Genomics' from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and a grant from the National Center for Global Health and Medicine. N.K. is a recipient of the Okinaga Scholarship and thanks S. Okinaga, H. Okinaga and other staff at Teikyo University, Japan, for their considerable support of doctoral work.; CAGE-KING. This study was supported in part by Grants-in-Aid for Scientific Research, including ones from categories A and B and the NEXT program of the Japanese Society for the Promotion of Science and by Grants-in-Aid on Priority Areas 'Comprehensive Genomics' and 'Applied Genomics', from the Ministry of Education, Culture, Sports, Science and Technology of Japan.; CAGE-Vietnam. The CAGE-Vietnam study was supported by Grants for International Health Research (17C-1 and 20S-6) from the Ministry of Health, Labour and Welfare of Japan, grants for the National Center for Global Health and Medicine (22S-10 and 25S-1) and the Manpei Suzuki Diabetes Foundation. We acknowledge the following investigators and institutions for their substantial contribution to the current study: T. Sasazuki, M. Noda, N. Kato, S. Kanagawa, T. Mizoue, H. Ohara and Y. Takahashi (Japanese investigators); T. Quy, N. Lan Viet, P. Thi Hong Hoa, N. Hoa Dieu Van, N. Thi Lam, L. Bach Mai, N. Quang Bay, P. Thi Phuong Thuy and B. Minh Duc (Vietnamese investigators); the National Center for Global Health and Medicine (Japan), Bach Mai Hospital (Vietnam), the Vietnam National Institute of Nutrition and the NCGM-BMH Medical Collaboration Center.; Cilento. We thank the populations of Cilento, Italy, for their participation in the study. This work was supported by grants from the Italian Ministry of Universities (FIRB-RBNE08NKH7, Interomics Flag project), the Assessorato Ricerca Regione Campania, the Fondazione con il SUD (2011-PDR-13) and the Fondazione Banco di Napoli to M.C.; CLHNS. We thank the Office of Population Studies Foundation research and data collection teams for the Cebu Longitudinal Health and Nutrition Survey. This work was supported by National Institutes of Health grants DK078150, TW05596, HL085144 and TW008288 and pilot funds from RR20649, ES10126 and DK56350.; DIABNORD. We are grateful to the study participants who dedicated their time and samples to these studies. We also thank the VHS, the Swedish Diabetes Registry and the Umea Medical Biobank staff for biomedical data and DNA extraction. We also thank M. Sterner, M. Juhas and P. Storm for their expert technical assistance with genotyping and genotype data preparation. The current study was funded by Novo Nordisk, the Swedish Research Council, Pahlssons Foundation, the Swedish Heart Lung Foundation and the Skane Regional Health Authority (all to P.W.F.).; EGCUT. EGCUT received targeted financing from the Estonian government (SF0180142s08), the Center of Excellence in Genomics (EXCEGEN) and the University of Tartu (SP1GVARENG). We acknowledge EGCUT technical personnel, especially V. Soo and S. Smit. Data analyses were carried out in part at the High-Performance Computing Center of the University of Tartu.; FINCAVAS. This work was supported by Competitive Research Funding from Tampere University Hospital (grants 9M048 and 9N035), the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, Finland, and the Tampere Tuberculosis Foundation. The authors thank the staff of the Department of Clinical Physiology for collecting the exercise test data.; GEMS. This work was partially supported by US NIH grants R01CA107431 and P42ES10349 to H. Ahsan. We would like to thank the study participants, as well as the staff of UChicago Research Bangladesh.; GeneBank. The Cleveland Clinic GeneBank study is supported by National Heart, Lung, and Blood Institute grants P01HL098055, P01HL076491, R01HL103866, P20HL113452 and R01HL103931. H. Allayee was supported by grant R01ES021801 from the National Institute of Environmental Health Sciences.; GenSalt. The Genetic Epidemiology Network of Salt Sensitivity is supported by research grants (U01HL072507, R01HL087263 and R01HL090682) from the National Heart, Lung, and Blood Institute, US NIH.; GLACIER-exome. We are indebted to the study participants who dedicated their time and samples to these studies. We thank J. Hutiainen and A. Agren (Umea Medical Biobank) for data organization and K. Enquist and T. Johansson (Vasterbottens County Council) for technical assistance with DNA extraction. We also thank M. Sterner, M. Juhas and P. Storm for their expert technical assistance with genotyping and genotype data preparation. The current study was funded by Novo Nordisk, the Swedish Research Council, Pahlssons Foundation, the Swedish Heart Lung Foundation and the Skane Regional Health Authority (all to P.W.F.).; GLACIER Metabochip. We are indebted to the study participants who dedicated their time and samples to these studies. We also thank the VIP and Umea Medical Biobank staff for biomedical data collection and preparation. We specifically thank J. Hutiainen, A. Agren and S. Nilsson (Umea Medical Biobank) for data organization, K. Enquist and T. Johansson (Vasterbottens County Council) for expert technical assistance with DNA preparation, and D. Hunter, P. Soule and H. Ranu (Harvard School of Public Health) for expert assistance with planning and undertaking genotyping of GLACIER samples. The current study was funded by Novo Nordisk, the Swedish Research Council, Pahlssons Foundation, the Swedish Heart Lung Foundation and the Skane Regional Health Authority (all to P.W.F.).; Health2006. The Health2006 study was financially supported by grants from the Velux Foundation; the Danish Medical Research Council, Danish Agency for Science, Technology and Innovation; the Aase and Ejner Danielsens Foundation; and ALK-Abello (Horsholm, Denmark), Timber Merchant Vilhelm Bangs Foundation, MEKOS Laboratories Denmark and Research Centre for Prevention and Health, the Capital Region of Denmark. This project was also funded by the Lundbeck Foundation and produced by the Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp; http://www.lucamp.org/). The Novo Nordisk Foundation Centre for Basic Metabolic Research is an independent Research Centre at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk/).; HEXA. This work was supported by grants from the Korean Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307) and an intramural grant from the Korean National Institute of Health (2012-N73002-00), Republic of Korea.; HPS. The Heart Protection Study (ISRCTN48489393) was funded by the UK Medical Research Council, the British Heart Foundation, Merck & Co., and Roche Vitamins, Ltd. Genotyping and analysis were supported by a grant to the University of Oxford and the Centre National de Genotypage from Merck & Co. and the Oxford British Heart Foundation Centre of Research Excellence. J.C.H. acknowledges support from the British Heart Foundation (FS/14/55/30806).; GOYA. This study was conducted as part of the activities of the Gene-Diet Interactions in Obesity project (GENDINOB; http://www.gendinob.dk/) and the Medical Research Council Centre for Causal Analyses in Translational Epidemiology (MRC CAiTE). We thank the staff of the Copenhagen City Heart Study for their skillful examination of the study subjects in the collection of baseline and follow-up data. T.S.A. was also funded by the GENDINOB project and acknowledges the same.; GUSTO. The GUSTO study group includes P. Agarwal, A. Biswas, C. Looi Bong, B.F.P. Broekman, S. Cai, J.K.Y. Chan, Y.H. Chan, C.Y.I. Chee, H.Y.H. Chen, Y.B. Cheung, A. Chia, A. Chinnadurai, C.K. Chng, M.F.-F. Chong, S. C. Chong, M.C. Chua, C.M. Ding, E.A. Finkelstein, D. Fok, M. Fortier, A.E.N. Goh, Y.T.D. Goh, J.J. Gooley, W.M. Han, M. Hanson, C.J. Henry, C.-Y. Hsu, H. Inskip, J. Kapur, K. Kwek, I.Y.-M. Lau, B.W. Lee, N. Lek, S. B. Lim, Y.-L. Low, I. Magiati, L. Mary Daniel, C. Ngo, K. Naiduvaje, W.W. Pang, A. Qiu, B.L. Quah, V.S. Rajadurai, M. Rauff, S. A. Rebello, J.L. Richmond, A. Rifkin-Graboi, L.P.-C. Shek, A. Sheppard, B. Shuter, L. Singh, W. Stunkel, L.L. Su, O.H. Teoh, H.P.S. van Bever, R.M. van Dam, I.B.Y. Wong, P.C. Wong and G.S.H. Yeo. This research is supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore-NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, A*STAR, Singapore.; INGI-VB. The research was supported by funds from Compagnia di San Paolo (Torino, Italy); Fondazione Cariplo, Italy, and the Ministry of Health, Ricerca Finalizzata 2008 and CCM 2010, and Telethon, Italy, to D.T. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank the inhabitants of Val Borbera who made this study possible, the local administrations, the Tortona and Genova archdioceses, and the ASL-22, Novi Ligure (Al), for support. We also thank C. Camaschella for the supervision of data collection and organization of the clinical data collection, F. Vigano for technical help, and C. Masciullo and M. Cocca for building the analysis platform.; Inter99. Inter99 was initiated by T.J. (principal investigator), K. Borch-Johnsen (co-principal investigator), H. Ibsen and T.F. Thomsen. The steering committee comprises the first two and C. Pisinger. The study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk, the Research Foundation of Copenhagen County, the Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation and the Danish Diabetes Association. This project was also funded by the Lundbeck Foundation and produced by LuCamp (http://www.lucamp.org/). The Novo Nordisk Foundation Centre for Basic Metabolic Research is an independent Research Centre at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk/).; InterAct. We are grateful to all participants who gave their time and effort to the study. We are also extremely grateful to all persons who contributed to the data collection across the study sites. This study was supported by funding from the European Union (integrated project LSHM-CT-2006-037197 in the Sixth Framework Programme of the European Community) and the Medical Research Council, UK.; This work was supported by Grants-in-Aid for Scientific Research (Priority Areas 'Medical Genome Science (Millennium Genome Project)' and 'Applied Genomics'), the Leading Project for Personalized Medicine and Scientific Research (20390185, 21390099, 19659163, 16790336, 12204008, 15790293, 16590433, 17790381, 17790381, 18390192, 18590265, 18590587, 18590811, 19590929, 19650188, 19790423, 17390186, 20390184 and 21390223) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid (H15-Longevity-005, H17-Longevity-003, H16-Kenko-001, H18-Longevity(kokusai), H11-Longevity-020, H17-Kenkou-007, H17-Pharmaco-common-003, H18-Junkankitou[Seishuu]-Ippan-012 and H20-Junkankitou[Seishuu]-Ippan-009, 013) from the Ministry of Health, Labor and Welfare of Japan, Health and Labor Sciences Research Grants, Japan; a Science and Technology Incubation Program in Advanced Regions, the Japanese Science and Technology Agency; Grants-in-Aid from Japanese Society for the Promotion of Science fellows (16.54041, 18.54042, 19.7152, 20.7198, 20.7477 and 20.54043); Health Science Research Grants and Medical Technology Evaluation Research Grants from the Ministry of Health, Labour and Welfare of Japan; the Japanese Atherosclerosis Prevention Fund; the Uehara Memorial Foundation; the Takeda Medical Research Foundation; National Cardiovascular Research Grants; Biomedical Innovation Grants; and the Japanese Research Foundation for Clinical Pharmacology.; KARE. This work was supported by grants from the Korean Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307) and an intramural grant from the Korean National Institute of Health (2012-N73002-00), Republic of Korea.; KORA. KORA was initiated and financed by the Helmholtz Zentrum Munchen-German Research Center for Environmental Health and supported by grants from the German Federal Ministry of Education and Research (BMBF), the Federal Ministry of Health and the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. This research was supported by a grant from the German-Israeli Foundation for Scientific Research and Development, by the European Union's Seventh Framework Programme (FP7-HEALTH-F5-2012) under grant agreement 305280 (MIMOmics), by Helmholtz-Russia Joint Research Group (HRJRG) 310 and by the German Center for Diabetes Research (DZD). We thank all members of the field staff who were involved in the planning and conduct of the MONICA/KORA Augsburg studies. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. C.G. is supported by EU-FP7-HEALTH grant 602936: CARTARDIS-Identification and Validation of Novel Pharmaceutical Drug Targets for Cardiovascular Disease and BMBF e:Med project e:AtheroSysMed-Systems Medicine of Myocardial Infarction and Stroke.; LBC1921. We thank the cohort participants and team members who contributed to these studies. Phenotype collection was supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC), the Royal Society and the Chief Scientist Office of the Scottish government. Genotyping was funded by the BBSRC. The work was undertaken by the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the BBSRC and Medical Research Council, UK, is gratefully acknowledged.; LBC1936. We thank the cohort participants and team members who contributed to these studies. Phenotype collection was supported by Age UK (The Disconnected Mind project). Genotyping was funded by the BBSRC. The work was undertaken by the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the BBSRC and Medical Research Council, UK, is gratefully acknowledged.; LifeLines. The LifeLines Cohort Study and the generation and management of GWAS genotype data for the LifeLines Cohort Study are supported by the Netherlands Organization for Scientific Research (NWO; grant 175.010.2007.006), the Economic Structure-Enhancing Fund (FES) of the Dutch government, the Ministry of Economic Affairs, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the Northern Netherlands Collaboration of Provinces (SNN), the province of Groningen, University Medical Center Groningen, the University of Groningen, the Dutch Kidney Foundation and the Dutch Diabetes Research Foundation. We thank B. Alizadeh, A. Boesjes, M. Bruinenberg, N. Festen, I. Nolte, L. Franke and M. Valimohammadi for their help in creating the GWAS database and R. Bieringa, J. Keers, R. Oostergo, R. Visser and J. Vonk for their work related to data collection and validation. The authors are grateful to the study participants, the staff of the LifeLines Cohort Study and Medical Biobank Northern Netherlands, and the participating general practitioners and pharmacists. LifeLines Scientific Protocol Preparation: R. de Boer, H. Hillege, M. van der Klauw, G. Navis, H. Ormel, D. Postma, J. Rosmalen, J. Slaets, R. Stolk and B. Wolffenbuttel; LifeLines GWAS Working Group: B. Alizadeh, M. Boezen, M. Bruinenberg, N. Festen, L. Franke, P. van der Harst, G. Navis, D. Postma, H. Snieder, C. Wijmenga and B. Wolffenbuttel.; LOLIPOP. The LOLIPOP study is supported by the NIHR Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust, the British Heart Foundation (SP/04/002), the Medical Research Council, UK (G0601966 and G0700931), the Wellcome Trust (084723/Z/08/Z), the NIHR (RP-PG-0407-10371), the European Union's Seventh Framework Programme (EpiMigrant, 279143) and Action on Hearing Loss (G51). We thank the participants and research staff who made the study possible.; LURIC. We extend our appreciation to the participants of the LURIC study; without their collaboration, this report would not have been written. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital, the University of Freiburg and the University of Ulm, Germany. LURIC has received funding from the Sixth Framework Programme (integrated project Bloodomics, grant LSHM-CT-2004-503485) and from the Seventh Framework Programme (Atheroremo, grant agreement 201668 and RiskyCAD, grant agreement 305739) of the European Union as well as from the INTERREG IV Oberrhein Program (project A28, Genetic Mechanisms of Cardiovascular Diseases) with support from the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO.; NFBC86. We thank P. Rantakallio (launch of NFBC1986 and initial data collection), S. Vaara (data collection), T. Ylitalo (administration), M. Koiranen (data management), and O. Tornwall and M. Jussila (DNA biobanking). Financial support was provided by the Academy of Finland (project grants 104781, 120315, 129269 Center of Excellence in Complex Disease Genetics), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Fifth Framework Programme award QLG1-CT-2000-01643), National Heart, Lung, and Blood Institute grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), the US NIH/National Institute of Mental Health (5R01MH63706:02), the ENGAGE project and grant agreement HEALTH-F4-2007-201413 and the Medical Research Council, UK (grants G0500539, G0600331 nad PrevMetSyn). DNA extraction, sample quality control, biobank upkeep and aliquotting were performed at the National Public Health Institute, Biomedicum Helsinki, Finland, and supported financially by the Academy of Finland and Biocentrum Helsinki. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.; POPGEN. The POPGEN study was supported by the German Ministry of Education and Research (BMBF) through the National Genome Research Network (NGFN) and the Ministry of Science, Commerce and Transportation of the state of Schleswig-Holstein. The project has also received infrastructure support through the DFG excellence cluster 'Inflammation at Interfaces'. The POPGEN 2.0 network is supported by a grant from the German Ministry of Education and Research (01EY1103).; PREVEND. PREVEND genetics is supported by the Dutch Kidney Foundation (grant E033), European Union project grant GENECURE (FP-6 LSHM CT 2006 037697), the US NIH (grant 2R01LM010098), the Netherlands Organization for Health Research and Development (NWO-Groot grant 175.010.2007.006, NWO VENI grant 916.761.70 and ZonMw grant 90.700.441) and the Dutch Interuniversity Cardiology Institute Netherlands (ICIN).; PROMIS. Genotyping in PROMIS was supported by the Wellcome Trust and Pfizer. Some core support to PROMIS was provided by the British Heart Foundation. The Cardiovascular Epidemiology Unit at the University of Cambridge is underpinned by the Medical Research Council, UK (G0800270), the British Heart Foundation (SP/09/002), the British Heart Foundation Cambridge Cardiovascular Centre of Excellence and the NIHR Cambridge Biomedical Research Centre.; PROSPER. The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers-Squibb. J.W.J. is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the Seventh Framework Programme of the European Commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810).; RHS. RHS was supported by a grant from the National Center for Global Health and Medicine.; Rotterdam Study. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of the Illumina 450K methylation array data (EWAS data) for the Rotterdam Study were executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus Medical Center, the Netherlands. The EWAS data were funded by the Genetic Laboratory of the Department of Internal Medicine, Erasmus Medical Center, and by the Netherlands Organization for Scientific Research (NWO; project 184021007) and were made available as a Rainbow Project (RP3; BIOS) of BBMRI-NL. We thank M. Verbiest, M. Jhamai, S. Higgins and M. Verkerk for their help in creating the methylation database.; SCES. SCES is funded by the Biomedical Research Council of Singapore (grant 08/1/35/19/550) and the NMRC, Singapore (grants STaR/0003/2008 and CG/SERI/2010). The National University Health System Tissue Repository and the Genome Institute of Singapore (A*STAR, Singapore) provided services for tissue archiving and genotyping, respectively.; SCHS. We would like to thank S.-H. Low of the National University of Singapore for supervising the field work of the Singapore Chinese Health Study and K. Arakawa for development of the cohort study database. The founding, long-standing principal investigator of the Singapore Chinese Health Study is M. C. Yu. Significant contributions to the GWAS substudy of SCHS were made by W.-P. Koh, J.-M. Yuan, R. Wang, Z. Chen, M. Seielstad, A. O. Odegaard, E. S. Tai, Y.-Y. Teo, J. Liu, B. Thyagarajan and R. Koratkar. Funding sources included Genetic and Environmental Determinants of Type 2 Diabetes in Chinese Singaporeans, grant R01DK080720 from the US NIH. Additional support came from the NMRC of Singapore under the individual research grants scheme, from the Genome Institute of Singapore, the NMRC of Singapore under its individual research grants and clinician scientist award scheme, and from A*STAR, Singapore. The Singapore Chinese Health Study primary cohort was supported by US NIH/National Cancer Institute grants RO1CA55069, R35CA53890, R01CA80205 and R01CA144034.; SCHS_MI. SCHS was supported by the US NIH (NCI RO1CA55069, R35CA53890, R01CA80205 and R01CA144034), the NUS-HUJ CREATE Programme of the National Research Foundation, Singapore (project 370062002) and a grant from the NMRC, Singapore (NMRC/1270/2010).; SiMES. SiMES is funded by the NMRC, Singapore (grants 0796/2003, IRG07nov013, IRG09nov014, STaR/0003/2008 and CG/SERI/2010) and the Biomedical Research Council of Singapore (grant 09/1/35/19/616). The Singapore Tissue Network and the Genome Institute of Singapore (A*STAR, Singapore) provided services for tissue archiving and genotyping, respectively. SINDI. SINDI is funded by the Biomedical Research Council of Singapore (A*STAR, Singapore) provided services for tissue archiving and genotyping, respectively.; SINDI. SINDI is funded by the Biomedical Research Council of Singapore (grant 08/1/35/19/550) and the NMRC, Singapore (grants STaR/0003/2008 and CG/SERI/2010). The National University Health System Tissue Repository and the Genome Institute of Singapore (A*STAR, Singapore) provided services for tissue archiving and genotyping, respectively.; SMART. This research was financially supported by BBMRI-NL, a research infrastructure financed by the Dutch government (NWO 184.021.007).; SMHS. The study was supported by grants RO1CA82729 and UM1CA173640 from the US NIH. The authors thank the participants and staff members of the SMHS research team for their important contributions.; SMSS. SMSS was supported by the National Natural Science Foundation of China (grant 81172761) and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.; SMHS. The study was supported by grants RO1CA82729 and UM1CA173640 from the US NIH. The authors thank the participants and staff members of the SMHS research team for their important contributions.; SMSS. SMSS was supported by the National Natural Science Foundation of China (grant 81172761) and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.; SP2. This project acknowledges the support of the Yong Loo Lin School of Medicine, the National University Health System and the Life Sciences Institute of the National University of Singapore. We also acknowledge the support of the National Research Foundation of Singapore (NRF-RF-2010-05), the Biomedical Research Council of Singapore (under the individual research grants scheme) and the NMRC, Singapore, under the individual research grant and the clinician scientist award schemes).; SRS. This work was supported by the Chinese National Key Program for Basic Research (973 grants: 2004CB518603, 2006CB503804 and 2009CB521905), the Chinese National High-Tech Program (863 grants: 2009AA022703 and 2006AA022179) and the Ministry of Science and Technology, National Natural Science Foundation of China (30871361).; SWHS. This research was supported by US NIH research grant R37CA70867. The authors thank the participants and staff members of SWHS for their important contributions.; TWSC. We gratefully acknowledge the members of the Translational Resource Center (TRC) (NSC102-2325-B-001-040) and the National Center for Genome Medicine (NSC102-2319-B-001-001) at Academia Sinica for their support in subject recruitment, genotyping and statistical analysis. The TWSC study was supported by the Academia Sinica Genomic Medicine Multicenter Study, Taiwan (40-05-GMM).; WHII. The WHII study is supported by grants from the Medical Research Council, UK (G0902037), the British Heart Foundation (RG/07/008/23674), the Stroke Association, the National Heart, Lung, and Blood Institute (5RO1HL036310), the National Institute on Aging (5RO1AG13196), the Agency for Health Care Policy Research (HS06516) and the John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-Economic Status and Health.; YFS. The Young Finns Study has been financially supported by the Academy of Finland through grants 286284 (T.L.), 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi) and 41071 (Skidi); the Social Insurance Institution of Finland; Kuopio, Tampere and Turku University Hospital Medical Funds (grant X51001 for T.L.); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation of Cardiovascular Research (T.L.); the Finnish Cultural Foundation; the Tampere Tuberculosis Foundation (T.L.); the Emil Aaltonen Foundation (T.L.); and the Yrjo Jahnsson Foundation (T.L.). NR 50 TC 35 Z9 35 U1 12 U2 44 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2015 VL 47 IS 11 BP 1282 EP + DI 10.1038/ng.3405 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA CV1BN UT WOS:000363988200012 PM 26390057 ER PT J AU Day, FR Ruth, KS Thompson, DJ Lunetta, KL Pervjakova, N Chasman, DI Stolk, L Finucane, HK Sulem, P Bulik-Sullivan, B Esko, T Johnson, AD Elks, CE Franceschini, N He, CY Altmaier, E Brody, JA Franke, LL Huffman, JE Keller, MF McArdle, PF Nutile, T Porcu, E Robino, A Rose, LM Schick, UM Smith, JA Teumer, A Traglia, M Vuckovic, D Yao, J Zhao, W Albrecht, E Amin, N Corre, T Hottenga, JJ Mangino, M Smith, AV Tanaka, T Abecasis, GR Andrulis, IL Anton-Culver, H Antoniou, AC Arndt, V Arnold, AM Barbieri, C Beckmann, MW Beeghly-Fadiel, A Benitez, J Bernstein, L Bielinski, SJ Blomqvist, C Boerwinkle, E Bogdanova, NV Bojesen, SE Bolla, MK Borresen-Dale, AL Boutin, TS Brauch, H Brenner, H Bruning, T Burwinkel, B Campbell, A Campbell, H Chanock, SJ Chapman, JR Chen, YDI Chenevix-Trench, G Couch, FJ Coviello, AD Cox, A Czene, K Darabi, H De Vivo, I Demerath, EW Dennis, J Devilee, P Dork, T Dos-Santos-Silva, I Dunning, AM Eicher, JD Fasching, PA Faul, JD Figueroa, J Flesch-Janys, D Gandin, I Garcia, ME Garcia-Closas, M Giles, GG Girotto, GG Goldberg, MS Gonzalez-Neira, A Goodarzi, MO Grove, ML Gudbjartsson, DF Guenel, P Guo, XQ Haiman, CA Hall, P Hamann, U Henderson, BE Hocking, LJ Hofman, A Homuth, G Hooning, MJ Hopper, JL Hu, FB Huang, JY Humphreys, K Hunter, DJ Jakubowska, A Jones, SE Kabisch, M Karasik, D Knight, JA Kolcic, I Kooperberg, C Kosma, VM Kriebel, J Kristensen, V Lambrechts, D Langenberg, C Li, JM Li, X Lindstrom, S Liu, YM Luan, JN Lubinski, J Magi, R Mannermaa, A Manz, J Margolin, S Marten, J Martin, NG Masciullo, C Meindl, A Michailidou, K Mihailov, E Milani, L Milne, RL Muller-Nurasyid, M Nalls, M Neale, BM Nevanlinna, H Neven, P Newman, AB Nordestgaard, BG Olson, JE Padmanabhan, S Peterlongo, P Peters, U Petersmann, A Peto, J Pharoah, PDP Pirastu, NN Pirie, A Pistis, G Polasek, O Porteous, D Psaty, BM Pylkas, K Radice, P Raffel, LJ Rivadeneira, F Rudan, I Rudolph, A Ruggiero, D Sala, CF Sanna, S Sawyer, EJ Schlessinger, D Schmidt, MK Schmidt, F Schmutzler, RK Schoemaker, MJ Scott, RA Seynaeve, CM Simard, J Sorice, R Southey, MC Stockl, D Strauch, K Swerdlow, A Taylor, KD Thorsteinsdottir, U Toland, AE Tomlinson, I Truong, T Tryggvadottir, L Turner, ST Vozzi, D Wang, Q Wellons, M Willemsen, G Wilson, JF Winqvist, R Wolffenbuttel, BBHR Wright, AF Yannoukakos, D Zemunik, T Zheng, W Zygmunt, M Bergmann, S Boomsma, DI Buring, JE Ferrucci, L Montgomery, GW Gudnason, V Spector, TD van Duijn, CM Alizadeh, BZ Ciullo, M Crisponi, L Easton, DF Gasparini, PP Gieger, C Harris, TB Hayward, C Kardia, SLR Kraft, P McKnight, B Metspalu, A Morrison, AC Reiner, AP Ridker, PM Rotter, JI Toniolo, D Uitterlinden, AG Ulivi, S Volzke, H Wareham, NJ Weir, DR Yerges-Armstrong, LM Price, AL Stefansson, K Visser, JA Ong, KK Chang-Claude, J Murabito, JM Perry, JRB Murray, A AF Day, Felix R. Ruth, Katherine S. Thompson, Deborah J. Lunetta, Kathryn L. Pervjakova, Natalia Chasman, Daniel I. Stolk, Lisette Finucane, Hilary K. Sulem, Patrick Bulik-Sullivan, Brendan Esko, Tonu Johnson, Andrew D. Elks, Cathy E. Franceschini, Nora He, Chunyan Altmaier, Elisabeth Brody, Jennifer A. Franke, Lude L. Huffman, Jennifer E. Keller, Margaux F. McArdle, Patrick F. Nutile, Teresa Porcu, Eleonora Robino, Antonietta Rose, Lynda M. Schick, Ursula M. Smith, Jennifer A. Teumer, Alexander Traglia, Michela Vuckovic, Dragana Yao, Jie Zhao, Wei Albrecht, Eva Amin, Najaf Corre, Tanguy Hottenga, Jouke-Jan Mangino, Massimo Smith, Albert V. Tanaka, Toshiko Abecasis, Goncalo R. Andrulis, Irene L. Anton-Culver, Hoda Antoniou, Antonis C. Arndt, Volker Arnold, Alice M. Barbieri, Caterina Beckmann, Matthias W. Beeghly-Fadiel, Alicia Benitez, Javier Bernstein, Leslie Bielinski, Suzette J. Blomqvist, Carl Boerwinkle, Eric Bogdanova, Natalia V. Bojesen, Stig E. Bolla, Manjeet K. Borresen-Dale, Anne-Lise Boutin, Thibaud S. Brauch, Hiltrud Brenner, Hermann Bruening, Thomas Burwinkel, Barbara Campbell, Archie Campbell, Harry Chanock, Stephen J. Chapman, J. Ross Chen, Yii-Der Ida Chenevix-Trench, Georgia Couch, Fergus J. Coviello, Andrea D. Cox, Angela Czene, Kamila Darabi, Hatef De Vivo, Immaculata Demerath, Ellen W. Dennis, Joe Devilee, Peter Doerk, Thilo dos-Santos-Silva, Isabel Dunning, Alison M. Eicher, John D. Fasching, Peter A. Faul, Jessica D. Figueroa, Jonine Flesch-Janys, Dieter Gandin, Ilaria Garcia, Melissa E. Garcia-Closas, Montserrat Giles, Graham G. Girotto, Giorgia G. Goldberg, Mark S. Gonzalez-Neira, Anna Goodarzi, Mark O. Grove, Megan L. Gudbjartsson, Daniel F. Guenel, Pascal Guo, Xiuqing Haiman, Christopher A. Hall, Per Hamann, Ute Henderson, Brian E. Hocking, Lynne J. Hofman, Albert Homuth, Georg Hooning, Maartje J. Hopper, John L. Hu, Frank B. Huang, Jinyan Humphreys, Keith Hunter, David J. Jakubowska, Anna Jones, Samuel E. Kabisch, Maria Karasik, David Knight, Julia A. Kolcic, Ivana Kooperberg, Charles Kosma, Veli-Matti Kriebel, Jennifer Kristensen, Vessela Lambrechts, Diether Langenberg, Claudia Li, Jingmei Li, Xin Lindstroem, Sara Liu, Yongmei Luan, Jian'an Lubinski, Jan Maegi, Reedik Mannermaa, Arto Manz, Judith Margolin, Sara Marten, Jonathan Martin, Nicholas G. Masciullo, Corrado Meindl, Alfons Michailidou, Kyriaki Mihailov, Evelin Milani, Lili Milne, Roger L. Mueller-Nurasyid, Martina Nalls, Michael Neale, Benjamin M. Nevanlinna, Heli Neven, Patrick Newman, Anne B. Nordestgaard, Borge G. Olson, Janet E. Padmanabhan, Sandosh Peterlongo, Paolo Peters, Ulrike Petersmann, Astrid Peto, Julian Pharoah, Paul D. P. Pirastu, Nicola N. Pirie, Ailith Pistis, Giorgio Polasek, Ozren Porteous, David Psaty, Bruce M. Pylkas, Katri Radice, Paolo Raffel, Leslie J. Rivadeneira, Fernando Rudan, Igor Rudolph, Anja Ruggiero, Daniela Sala, Cinzia F. Sanna, Serena Sawyer, Elinor J. Schlessinger, David Schmidt, Marjanka K. Schmidt, Frank Schmutzler, Rita K. Schoemaker, Minouk J. Scott, Robert A. Seynaeve, Caroline M. Simard, Jacques Sorice, Rossella Southey, Melissa C. Stoeckl, Doris Strauch, Konstantin Swerdlow, Anthony Taylor, Kent D. Thorsteinsdottir, Unnur Toland, Amanda E. Tomlinson, Ian Truong, Therese Tryggvadottir, Laufey Turner, Stephen T. Vozzi, Diego Wang, Qin Wellons, Melissa Willemsen, Gonneke Wilson, James F. Winqvist, Robert Wolffenbuttel, Bruce B. H. R. Wright, Alan F. Yannoukakos, Drakoulis Zemunik, Tatijana Zheng, Wei Zygmunt, Marek Bergmann, Sven Boomsma, Dorret I. Buring, Julie E. Ferrucci, Luigi Montgomery, Grant W. Gudnason, Vilmundur Spector, Tim D. van Duijn, Cornelia M. Alizadeh, Behrooz Z. Ciullo, Marina Crisponi, Laura Easton, Douglas F. Gasparini, Paolo P. Gieger, Christian Harris, Tamara B. Hayward, Caroline Kardia, Sharon L. R. Kraft, Peter McKnight, Barbara Metspalu, Andres Morrison, Alanna C. Reiner, Alex P. Ridker, Paul M. Rotter, Jerome I. Toniolo, Daniela Uitterlinden, Andre G. Ulivi, Sheila Voelzke, Henry Wareham, Nicholas J. Weir, David R. Yerges-Armstrong, Laura M. Price, Alkes L. Stefansson, Kari Visser, Jenny A. Ong, Ken K. Chang-Claude, Jenny Murabito, Joanne M. Perry, John R. B. Murray, Anna CA EPIC-InterAct Consortium LifeLines Cohort Study TI Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair SO NATURE GENETICS LA English DT Article ID PREMATURE OVARIAN FAILURE; BRCA2 MUTATION CARRIERS; BODY-MASS INDEX; NATURAL MENOPAUSE; HOMOLOGOUS RECOMBINATION; CHROMOSOMAL INSTABILITY; WIDE ASSOCIATION; BLOOD-PRESSURE; CELL-TYPES; LOCI AB Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in similar to 70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (similar to 6% increase in risk per year; P = 3 x 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms. C1 [Day, Felix R.; Elks, Cathy E.; Langenberg, Claudia; Luan, Jian'an; Scott, Robert A.; Wareham, Nicholas J.; Ong, Ken K.; Perry, John R. B.] Univ Cambridge, MRC, Epidemiol Unit, Sch Clin Med,Inst Metab Sci, Cambridge, England. [Ruth, Katherine S.; Jones, Samuel E.; Murray, Anna] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England. [Thompson, Deborah J.; Antoniou, Antonis C.; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Pharoah, Paul D. P.; Pirie, Ailith; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Lunetta, Kathryn L.; Johnson, Andrew D.; Huffman, Jennifer E.; Eicher, John D.; Murabito, Joanne M.] NHLBI, Framingham, MA USA. [Lunetta, Kathryn L.; Johnson, Andrew D.; Huffman, Jennifer E.; Eicher, John D.; Murabito, Joanne M.] Boston Univ, Framingham Heart Study, Framingham, MA USA. 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[Giles, Graham G.; Hopper, John L.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia. [Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Dept Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. [Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Gudbjartsson, Daniel F.] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland. [Guenel, Pascal; Truong, Therese] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France. [Guenel, Pascal; Truong, Therese] Univ Paris Sud, UMRS 1018, Villejuif, France. [Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hamann, Ute; Kabisch, Maria] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany. [Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland. [Homuth, Georg; Schmidt, Frank] Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Hooning, Maartje J.; Seynaeve, Caroline M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA. [Huang, Jinyan] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200030, Peoples R China. [Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Karasik, David] Hebrew SeniorLife Inst Aging Res, Boston, MA USA. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada. [Kolcic, Ivana; Polasek, Ozren; Zemunik, Tatijana] Univ Split, Fac Med, Split, Croatia. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Pathol & Forens Med, Inst Clin Med, Sch Med, Kuopio, Finland. [Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland. [Kriebel, Jennifer] German Ctr Diabet Res, Neuherberg, Germany. [Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA. [Margolin, Sara] Karolinska Inst, Dept Oncology Pathol, Stockholm, Sweden. [Martin, Nicholas G.; Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Meindl, Alfons] Tech Univ Munich, Div Obstet & Gynecol, D-80290 Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Munich, Germany. [Mueller-Nurasyid, Martina] German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany. [Nalls, Michael] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Neven, Patrick] Univ Hosp Leuven, Dept Oncol, Leuven, Belgium. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [Padmanabhan, Sandosh] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci,Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol IFOM, Milan, Italy. [Petersmann, Astrid] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Psaty, Bruce M.; Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Pylkas, Katri; Winqvist, Robert] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland. [Pylkas, Katri; Winqvist, Robert] Ctr NordLab, Northern Finland Lab, Lab Canc Genet & Tumor Biol, Oulu, Finland. [Radice, Paolo] Fdn IRCCS, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Raffel, Leslie J.] Cedars Sinai Med Ctr, Med Genet Res Ctr, Los Angeles, CA 90048 USA. [Raffel, Leslie J.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Clin & Translat Sci Inst, Los Angeles, CA 90048 USA. 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[Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Tomlinson, Ian] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England. [Tryggvadottir, Laufey] Icelandic Canc Registry, Reykjavik, Iceland. [Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA. [Wellons, Melissa] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA. [Wolffenbuttel, Bruce B. H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Wolffenbuttel, Bruce B. H. R.] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study & Biobank, Groningen, Netherlands. [Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Inst Radioisotopes & Radiodiagnost Prod, Mol Diagnost Lab, Athens, Greece. [Zygmunt, Marek] Univ Med Greifswald, Dept Gynecol & Obstet, Greifswald, Germany. [Alizadeh, Behrooz Z.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Kraft, Peter; Ong, Ken K.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Perry, JRB (reprint author), Univ Cambridge, MRC, Epidemiol Unit, Sch Clin Med,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England. EM john.perry@mrc-epid.cam.ac.uk RI Padmanabhan, Sandosh/S-3963-2016; Brenner, Hermann/B-4627-2017; Polasek, Ozren/B-6002-2011; Kolcic, Ivana/E-2713-2017; Gudnason, Vilmundur/K-6885-2015; Smith, Albert Vernon/K-5150-2015; Dork, Thilo/J-8620-2012; Johnson, Andrew/G-6520-2013; Franke, Lude/P-7036-2016; Schmidt, Frank, ZIK FunGene/B-6075-2009; Knight, Julia/A-6843-2012; Montgomery, Grant/B-7148-2008; Li, Jingmei/I-2904-2012; Bielinski, Suzette/A-2238-2009; Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Andrulis, Irene/E-7267-2013; ruggiero, daniela/K-5638-2016; mangino, massimo/F-5134-2011; OI Tryggvadottir, Laufey/0000-0001-8067-9030; NUTILE, TERESA/0000-0001-7062-8352; Dunning, Alison Margaret/0000-0001-6651-7166; Karasik, David/0000-0002-8826-0530; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; dos Santos Silva, Isabel/0000-0002-6596-8798; vozzi, diego/0000-0002-2902-8184; Cox, Angela/0000-0002-5138-1099; Girotto, Giorgia/0000-0003-4507-6589; Chapman, Ross/0000-0002-6477-4254; Yannoukakos, Drakoulis/0000-0001-7509-3510; Brenner, Hermann/0000-0002-6129-1572; Polasek, Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052; Day, Felix/0000-0003-3789-7651; Vuckovic, Dragana/0000-0001-9343-6142; Magi, Reedik/0000-0002-2964-6011; Schoemaker, Minouk/0000-0001-8403-2234; Murray, Anna/0000-0002-2351-2522; Hocking, Lynne J/0000-0002-2414-2826; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert Vernon/0000-0003-1942-5845; Franke, Lude/0000-0002-5159-8802; Montgomery, Grant/0000-0002-4140-8139; Li, Jingmei/0000-0001-8587-7511; Bielinski, Suzette/0000-0002-2905-5430; Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; ruggiero, daniela/0000-0003-3898-7827; mangino, massimo/0000-0002-2167-7470; Smith, Jennifer/0000-0002-3575-5468; Ewing, Ailith/0000-0002-2272-1277; Arndt, Volker/0000-0001-9320-8684; Bergmann, Sven/0000-0002-6785-9034 FU Cancer Research UK [10124, 11174, C12292/A11174, C1281/A12014, C1287/A 10710, C1287/A10118, C5047/A10692, C5047/A15007, C5047/A8384, C8197/A16565]; Chief Scientist Office [CZD/16/6/4]; Medical Research Council [MC_PC_U127561128, MC_U106179471, MC_U106179472, MC_UU_12015/1, MC_UU_12015/2]; NCATS NIH HHS [UL1 TR000124, UL1 TR001108, UL1TR000124]; NCI NIH HHS [1U19 CA148065, 1U19 CA148112, 1U19 CA148537, CA128978, CA164920, P30 CA015704, UM1 CA182910, UM1 CA182913]; NCRR NIH HHS [UL1RR025005]; NHGRI NIH HHS [HG005552, HG005581, HG006513, HG007022, HG007089, U01HG004402]; NHLBI NIH HHS [N01HC85086, 5RC2HL102419, HL043851, HL054457, HL054464, HL054481, HL080295, HL080467, HL087652, HL087660, HL105756, K01-HL116770, N01-HC-25195, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N02-HL-6-4278, R01 HL087660, R01 HL119443, R01HL087641, R01HL59367, U01-HL72515, U01-HL84756]; NIA NIH HHS [1R01AG032098-01A1, AG009740, AG023629, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-1-2109, N01-AG-5-0002, N01AG62101, N01AG62103, N01AG62106, R01AG29451, R21AG032598, RC2 AG036495, RC4 AG039029, U01AG009740]; NIDDK NIH HHS [DK063491, P30 DK063491, P30 DK072488, P30-DK072488, R01DK075787]; PHS HHS [HHSN268200625226C, HHSN268200782096C, HHSN268200800007C, HHSN268200960009C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201100046C, HHSN268201200036C, HHSN271201100004C, HHSN271201100005C, R01-088119]; Wellcome Trust [090532] NR 60 TC 22 Z9 23 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2015 VL 47 IS 11 BP 1294 EP + DI 10.1038/ng.3412 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CV1BN UT WOS:000363988200013 PM 26414677 ER PT J AU Stieglitz, E Taylor-Weiner, AN Chang, TY Gelston, LC Wang, YD Mazor, T Esquivel, E Yu, A Seepo, S Olsen, SR Rosenberg, M Archambeault, SL Abusin, G Beckman, K Brown, PA Briones, M Carcamo, B Cooper, T Dahl, GV Emanuel, PD Fluchel, MN Goyal, RK Hayashi, RJ Hitzler, J Hugge, C Liu, YL Messinger, YH Mahoney, DH Monteleone, P Nemecek, ER Roehrs, PA Schore, RJ Stine, KC Takemoto, CM Toretsky, JA Costello, JF Olshen, AB Stewart, C Li, YJ Ma, J Gerbing, RB Alonzo, TA Getz, G Gruber, TA Golub, TR Stegmaier, K Loh, ML AF Stieglitz, Elliot Taylor-Weiner, Amaro N. Chang, Tiffany Y. Gelston, Laura C. Wang, Yong-Dong Mazor, Tali Esquivel, Emilio Yu, Ariel Seepo, Sara Olsen, Scott R. Rosenberg, Mara Archambeault, Sophie L. Abusin, Ghada Beckman, Kyle Brown, Patrick A. Briones, Michael Carcamo, Benjamin Cooper, Todd Dahl, Gary V. Emanuel, Peter D. Fluchel, Mark N. Goyal, Rakesh K. Hayashi, Robert J. Hitzler, Johann Hugge, Christopher Liu, Y. Lucy Messinger, Yoav H. Mahoney, Donald H., Jr. Monteleone, Philip Nemecek, Eneida R. Roehrs, Philip A. Schore, Reuven J. Stine, Kimo C. Takemoto, Clifford M. Toretsky, Jeffrey A. Costello, Joseph F. Olshen, Adam B. Stewart, Chip Li, Yongjin Ma, Jing Gerbing, Robert B. Alonzo, Todd A. Getz, Gad Gruber, Tanja A. Golub, Todd R. Stegmaier, Kimberly Loh, Mignon L. TI The genomic landscape of juvenile myelomonocytic leukemia SO NATURE GENETICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; DNA-SEQUENCING DATA; GATA2 MUTATIONS; MONOMAC SYNDROME; RAS MUTATIONS; NF1 GENE; MYELOPROLIFERATIVE NEOPLASMS; MYELODYSPLASTIC SYNDROMES; NEUROFIBROMATOSIS TYPE-1; POINT MUTATIONS AB Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription. Notably, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome. C1 [Stieglitz, Elliot; Chang, Tiffany Y.; Gelston, Laura C.; Esquivel, Emilio; Yu, Ariel; Archambeault, Sophie L.; Beckman, Kyle; Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Taylor-Weiner, Amaro N.; Seepo, Sara; Rosenberg, Mara; Stewart, Chip; Getz, Gad; Golub, Todd R.; Stegmaier, Kimberly] Broad Inst MIT & Harvard, Cambridge, MA USA. [Wang, Yong-Dong; Li, Yongjin] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA. [Mazor, Tali] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Olsen, Scott R.] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. [Abusin, Ghada] Univ Iowa, Carver Coll Med, Stead Family Dept Pediat, Iowa City, IA USA. [Brown, Patrick A.; Takemoto, Clifford M.] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA. [Briones, Michael] Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorder Ctr, Atlanta, GA USA. [Carcamo, Benjamin] Texas Tech Univ, Dept Pediat, El Paso, TX USA. [Cooper, Todd] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA. [Dahl, Gary V.] Stanford Sch Med, Dept Pediat, Stanford, CA USA. [Emanuel, Peter D.] Univ Arkansas Med Sci, Winthrop P Rockefeller Canc Inst, Little Rock, AR 72205 USA. [Fluchel, Mark N.] Univ Utah, Dept Pediat Hematol Oncol, Salt Lake City, UT USA. [Goyal, Rakesh K.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15213 USA. [Hayashi, Robert J.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Hitzler, Johann] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Hugge, Christopher] SSM Cardinal Glennon Childrens Med Ctr, Pediat Hematol Oncol, St Louis, MO USA. [Messinger, Yoav H.] Childrens Hosp & Clin Minnesota, Div Pediat Hematol Oncol, Minneapolis, MN USA. [Mahoney, Donald H., Jr.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Monteleone, Philip] Pediat Specialists Lehigh Valley Hosp, Pediat Hematol Oncol, Bethlehem, PA USA. [Nemecek, Eneida R.] Oregon Hlth & Sci Univ, Pediat Bone Marrow Transplant Program, Portland, OR 97201 USA. [Roehrs, Philip A.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Schore, Reuven J.] Childrens Natl Med Ctr, Div Pediat Oncol, Washington, DC 20010 USA. [Stine, Kimo C.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Toretsky, Jeffrey A.] Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. [Toretsky, Jeffrey A.] Georgetown Univ, Dept Oncol, Washington, DC USA. [Olshen, Adam B.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Olshen, Adam B.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Ma, Jing; Gruber, Tanja A.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Gerbing, Robert B.] Childrens Oncol Grp, Dept Stat, Monrovia, CA USA. [Alonzo, Todd A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Getz, Gad; Golub, Todd R.; Stegmaier, Kimberly] Harvard Univ, Sch Med, Boston, MA USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Gruber, Tanja A.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Golub, Todd R.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Golub, Todd R.; Stegmaier, Kimberly] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Stieglitz, E (reprint author), Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA 94143 USA. EM elliot.stieglitz@ucsf.edu; mignon.loh@ucsf.edu RI Wang, Yong-Dong/K-3563-2013; LI, YONGJIN/E-1688-2011; OI YU, ARIEL/0000-0003-3941-2195 FU Carlos Slim Foundation in Mexico as part of the Slim Initiative for Genomic Medicine; St. Baldrick's Foundation; Alex's Lemonade Stand Foundation; Leukemia and Lymphoma Society [6059-09, 6466-15]; Leukemia and Lymphoma Society Scholar award; US National Institutes of Health, National Cancer Institute [T32CA128583, R01CA173085]; National Cancer Institute Cancer Center [5P30CA082103]; Children's Oncology Group (COG) Statistics and Data Center [1U10CA180899]; COG Chair's Grant [5U10CA098543]; US National Institutes of Health [P30CA82103]; Frank A. Campini Foundation; Hyundai Hope on Wheels; University of California San Francisco Dean's Commitment to the Center for Advanced Technologies facility FX This work was supported by the Carlos Slim Foundation in Mexico as part of the Slim Initiative for Genomic Medicine; the St. Baldrick's Foundation (E.S.); Alex's Lemonade Stand Foundation (E.S.); the Leukemia and Lymphoma Society (grants 6059-09 and 6466-15) (M.L.L.) and a Leukemia and Lymphoma Society Scholar award (K.S.)); US National Institutes of Health, National Cancer Institute grants T32CA128583 (E.S.) and R01CA173085 (M.L.L.), National Cancer Institute Cancer Center Support grant 5P30CA082103, Children's Oncology Group (COG) Statistics and Data Center grant 1U10CA180899 (T.A.A.), COG Chair's Grant 5U10CA098543 (T.A.A.) and US National Institutes of Health grant P30CA82103 (A.B.O.); the Frank A. Campini Foundation (E.S. and M.L.L.); Hyundai Hope on Wheels (M.L.L.); and a University of California San Francisco Dean's Commitment to the Center for Advanced Technologies facility. NR 79 TC 15 Z9 16 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2015 VL 47 IS 11 BP 1326 EP + DI 10.1038/ng.3400 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA CV1BN UT WOS:000363988200016 PM 26457647 ER PT J AU Pomerantz, MM Li, FG Takeda, DY Lenci, R Chonkar, A Chabot, M Cejas, P Vazquez, F Cook, J Shivdasani, RA Bowden, M Lis, R Hahn, WC Kantoff, PW Brown, M Loda, M Long, HW Freedman, ML AF Pomerantz, Mark M. Li, Fugen Takeda, David Y. Lenci, Romina Chonkar, Apurva Chabot, Matthew Cejas, Paloma Vazquez, Francisca Cook, Jennifer Shivdasani, Ramesh A. Bowden, Michaela Lis, Rosina Hahn, William C. Kantoff, Philip W. Brown, Myles Loda, Massimo Long, Henry W. Freedman, Matthew L. TI The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis SO NATURE GENETICS LA English DT Article ID TRANSCRIPTIONAL PROGRAM; CANCER; GENE; HOXB13; EXPRESSION; DIFFERENTIATION; MUTATIONS; ENHANCERS; ELEMENTS; FOXA1 AB Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells(1,2). The genome-wide map of these transcription factor binding sites has been termed the cistrome(3). Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13 colocalized at the reprogrammed AR binding sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR cistrome reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium toward transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis. C1 [Pomerantz, Mark M.; Takeda, David Y.; Lenci, Romina; Chonkar, Apurva; Chabot, Matthew; Cejas, Paloma; Cook, Jennifer; Shivdasani, Ramesh A.; Hahn, William C.; Kantoff, Philip W.; Brown, Myles; Loda, Massimo; Long, Henry W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pomerantz, Mark M.; Takeda, David Y.; Lenci, Romina; Chonkar, Apurva; Chabot, Matthew; Cejas, Paloma; Cook, Jennifer; Shivdasani, Ramesh A.; Bowden, Michaela; Lis, Rosina; Hahn, William C.; Kantoff, Philip W.; Brown, Myles; Loda, Massimo; Long, Henry W.; Freedman, Matthew L.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Fugen; Cejas, Paloma; Shivdasani, Ramesh A.; Brown, Myles; Long, Henry W.; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA. [Li, Fugen] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Takeda, David Y.; Vazquez, Francisca; Hahn, William C.; Loda, Massimo; Freedman, Matthew L.] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Bowden, Michaela; Lis, Rosina; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM freedman@broadinstitute.org OI Brown, Myles/0000-0002-8213-1658 FU Prostate Cancer Foundation; H.L. Snyder Medical Foundation; US National Institutes of Health (NIH) grant [R01CA193910]; Anna Fuller Fund (PS) [6241901, Infoed 2013-0369]; NIH GAME-ON U19 [U19CA148537]; Dana-Farber Prostate Cancer Specialized Program of Research Excellence (SPORE) [NIH P50CA90381-11]; NIH [U01CA176058] FX We thank Z. Herbert and the Molecular Biology Core Facility at the Dana-Farber Cancer Institute for their sequencing expertise. We acknowledge funding from the Prostate Cancer Foundation (Challenge Award), the H.L. Snyder Medical Foundation (M.L.F.), US National Institutes of Health (NIH) grant R01CA193910, the Anna Fuller Fund (PS#6241901; Infoed 2013-0369), the NIH GAME-ON U19 (grant U19CA148537), the Dana-Farber Prostate Cancer Specialized Program of Research Excellence (SPORE; NIH P50CA90381-11) and the NIH grant U01CA176058 (F.V. and W.C.H.). NR 36 TC 17 Z9 17 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2015 VL 47 IS 11 BP 1346 EP + DI 10.1038/ng.3419 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA CV1BN UT WOS:000363988200019 PM 26457646 ER PT J AU Sullivan, RJ Flaherty, KT AF Sullivan, Ryan J. Flaherty, Keith T. TI Anti-PD-1 therapies- a new first-line option in advanced melanoma SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID UNTREATED MELANOMA; IPILIMUMAB; PEMBROLIZUMAB; NIVOLUMAB; SAFETY; TRIAL C1 [Sullivan, Ryan J.; Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM kflaherty@mgh.harvard.edu NR 10 TC 2 Z9 2 U1 4 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD NOV PY 2015 VL 12 IS 11 DI 10.1038/nrclinonc.2015.170 PG 2 WC Oncology SC Oncology GA CV2RO UT WOS:000364105000001 ER PT J AU Esselen, KM Vitonis, A Einarsson, J Muto, MG Cohen, S AF Esselen, Katharine M. Vitonis, Allison Einarsson, Jon Muto, Michael G. Cohen, Sarah TI Health Care Disparities in Hysterectomy for Gynecologic Cancers Data From the 2012 National Inpatient Sample SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LAPAROSCOPIC RADICAL HYSTERECTOMY; ENDOMETRIAL CANCER; CERVICAL-CANCER; UNITED-STATES; ETHNIC DISPARITIES; RACIAL DISPARITIES; OUTCOMES; COST; SURGERY; LYMPHADENECTOMY AB OBJECTIVE:To examine hysterectomies in the United States performed for gynecologic malignancies and identify factors associated with the use of minimally invasive techniques.METHODS:This is a cross-sectional analysis of the 2012 National Inpatient Sample, the largest national all-payer database of hospital discharges. International Classification of Diseases, 9th Revision, Clinical Modification codes for any type of hysterectomy performed for gynecologic malignancy were used to abstract pertinent observations. Weighted multivariable logistic regression models were used to examine the associations between demographic and clinical factors and mode of hysterectomy by cancer diagnosis.RESULTS:In 2012, there were an estimated 46,450 hysterectomies for gynecologic malignancy in the United States. Of these, 28,285 (61%) were performed for uterine, 4,275 (9%) for cervical, 12,370 (27%) for ovarian cancer, and 1,520 (3%) for other gynecologic malignancies. Minimally invasive hysterectomy was used in 50% of uterine, 43% of cervical, and 8.5% of ovarian cancer cases. Black women had decreased odds of undergoing minimally invasive hysterectomy for uterine (adjusted odds ratio [OR] 0.50, 95% confidence interval [CI] 0.40-0.0.63, P<.001) and cervical (adjusted OR 0.56, 95% CI 0.33-0.96, P=.03) cancers. Those without insurance or with Medicaid had decreased odds of undergoing minimally invasive hysterectomy (P<.001) for uterine cancer. As compared with the Northeast, patients in the South (adjusted OR 0.72, 95% CI 0.53-0.98, P=.04) were less likely to undergo minimally invasive hysterectomy for uterine cancer, whereas those in the West more likely (adjusted OR 1.48, 95% CI 1.10-1.99, P=.009).CONCLUSION:Minimally invasive hysterectomy for gynecologic malignancies remained underused in 2012; there were striking racial disparities associated with use of minimally invasive hysterectomy for uterine and cervical cancers.LEVEL OF EVIDENCE:III C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gynecol Oncol,Dept Obstet & Gynecol,Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Minimally Invas Gynecol,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Esselen, KM (reprint author), Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM kesselen14@gmail.com NR 33 TC 2 Z9 2 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2015 VL 126 IS 5 BP 1029 EP 1039 DI 10.1097/AOG.0000000000001088 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CV0WI UT WOS:000363974000019 PM 26444112 ER PT J AU Bradbury, AR Patrick-Miller, L Schwartz, L Egleston, B Sands, CB Chung, WK Glendon, G McDonald, JA Moore, C Rauch, P Tuchman, L Andrulis, IL Buys, SS Frost, CJ Keegan, THM Knight, JA Terry, MB John, EM Daly, MB AF Bradbury, Angela R. Patrick-Miller, Linda Schwartz, Lisa Egleston, Brian Sands, Colleen Burke Chung, Wendy K. Glendon, Gord McDonald, Jasmine A. Moore, Cynthia Rauch, Paula Tuchman, Lisa Andrulis, Irene L. Buys, Saundra S. Frost, Caren J. Keegan, Theresa H. M. Knight, Julia A. Terry, Mary Beth John, Esther M. Daly, Mary B. TI Psychosocial Adjustment in School-age Girls With a Family History of Breast Cancer SO PEDIATRICS LA English DT Article ID PARENTAL CANCER; PSYCHOLOGICAL DISTRESS; ADOLESCENT HEALTH; PHYSICAL-ACTIVITY; ASSESSMENT DEVICE; DEPRESSION SCALE; HOSPITAL ANXIETY; RISK BEHAVIOR; GENETIC TEST; EVENT SCALE AB OBJECTIVE: Understanding how young girls respond to growing up with breast cancer family histories is critical given expansion of genetic testing and breast cancer messaging. We examined the impact of breast cancer family history on psychosocial adjustment and health behaviors among >800 girls in the multicenter LEGACY Girls Study. METHODS: Girls aged 6 to 13 years with a family history of breast cancer or familial BRCA1/2 mutation (BCFH+), peers without a family history (BCFH-), and their biological mothers completed assessments of psychosocial adjustment (maternal report for 6- to 13-year-olds, self-report for 10- to 13-year-olds), breast cancer-specific distress, perceived risk of breast cancer, and health behaviors (10- to 13-year-olds). RESULTS: BCFH+ girls had better general psychosocial adjustment than BCFH-peers by maternal report. Psychosocial adjustment and health behaviors did not differ significantly by self-report among 10- to 13-year-old girls. BCFH+ girls reported higher breast cancer-specific distress (P = .001) and were more likely to report themselves at increased breast cancer risk than BCFH-peers (38.4% vs 13.7%, P < .001), although many girls were unsure of their risk. In multivariable analyses, higher daughter anxiety was associated with higher maternal anxiety and poorer family communication. Higher daughter breast cancer-specific distress was associated with higher maternal breast cancer-specific distress. CONCLUSIONS: Although growing up in a family at risk for breast cancer does not negatively affect general psychosocial adjustment among preadolescent girls, those from breast cancer risk families experience greater breast cancer-specific distress. Interventions to address daughter and mother breast cancer concerns and responses to genetic or familial risk might improve psychosocial outcomes of teen daughters. C1 [Bradbury, Angela R.; Sands, Colleen Burke] Univ Penn, Perelman Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Bradbury, Angela R.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Patrick-Miller, Linda] Univ Chicago, Dept Med, Div Hematol Oncol, Chicago, IL 60637 USA. [Patrick-Miller, Linda] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA. [Schwartz, Lisa] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. [Schwartz, Lisa] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Egleston, Brian] Temple Univ Hlth Syst, Fox Chase Canc Ctr, Biostat & Bioinformat Facil, Philadelphia, PA USA. [Daly, Mary B.] Temple Univ Hlth Syst, Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. [Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Med, New York, NY USA. [Terry, Mary Beth] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [McDonald, Jasmine A.; Terry, Mary Beth] Columbia Univ, Med Ctr, Mailman Sch Publ Hlth, New York, NY USA. [Glendon, Gord; Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Moore, Cynthia; Rauch, Paula] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. [Tuchman, Lisa] Childrens Natl Med Ctr, Dept Adolescent Med, Washington, DC 20010 USA. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Lab Med, Toronto, ON, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Dept Med, Div Oncol, Salt Lake City, UT 84132 USA. [Frost, Caren J.] Univ Utah, Coll Social Work, Salt Lake City, UT USA. [Keegan, Theresa H. M.; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Keegan, Theresa H. M.; John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Keegan, Theresa H. M.; John, Esther M.] Stanford Canc Inst, Stanford, CA USA. RP Bradbury, AR (reprint author), Univ Penn, Perelman Sch Med, West Perelman Ctr 3, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM angela.bradbury@uphs.upenn.edu RI Knight, Julia/A-6843-2012; Andrulis, Irene/E-7267-2013 FU National Cancer Institute [R01 CA138819, R01 138822, R01 CA138638, R01 138844, P30CA042014, P30CA006927]; NCATS [UL1TR000003, UL1RR024134] FX Supported by grants from the National Cancer Institute (R01 CA138819, R01 138822, R01 CA138638, R01 138844 and Core grants: P30CA042014, P30CA006927) and UL1TR000003 (NCATS) and UL1RR024134 grants to the Clinical & Translational Research Center, The Children's Hospital of Philadelphia. The Stanford Cancer Institute (Developmental Cancer Research Award to Dr Keegan) and the Canadian Breast Cancer Foundation (Dr Andrulis). Dr Andrulis holds the Anne and Max Tanenbaum Chair in Molecular Medicine at Mount Sinai Hospital and the University of Toronto. NR 72 TC 2 Z9 2 U1 1 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2015 VL 136 IS 5 BP 927 EP 937 DI 10.1542/peds.2015-0498 PG 11 WC Pediatrics SC Pediatrics GA CV0US UT WOS:000363969600058 PM 26482668 ER PT J AU Ananth, P Melvin, P Feudtner, C Wolfe, J Berry, JG AF Ananth, Prasanna Melvin, Patrice Feudtner, Chris Wolfe, Joanne Berry, Jay G. TI Hospital Use in the Last Year of Life for Children With Life-Threatening Complex Chronic Conditions SO PEDIATRICS LA English DT Article ID STEM-CELL TRANSPLANTATION; SUPPORTIVE CARE SERVICES; MEDICAL COMPLEXITY; WASHINGTON-STATE; MECHANICAL VENTILATION; RETROSPECTIVE COHORT; PALLIATIVE CARE; NATIONAL TRENDS; UNITED-STATES; CORD BLOOD AB BACKGROUND AND OBJECTIVES: Although many adults experience resource-intensive and costly health care in the last year of life, less is known about these health care experiences in children with life-threatening complex chronic conditions (LT-CCCs). We assessed hospital resource use in children by type and number of LT-CCCs. METHODS: A retrospective analysis of 1252 children with LT-CCCs, ages 1 to 18 years, who died in 2012 within 40 US children's hospitals of the Pediatric Health Information System database. LT-CCCs were identified with International Classification of Diseases, 9th Revision, Clinical Modification codes. Using generalized linear models, we assessed hospital admissions, days, costs, and interventions (mechanical ventilation and surgeries) in the last year of life by type and number of LT-CCCs. RESULTS: In the last year of life, children with LT-CCCs experienced a median of 2 admissions (interquartile range [IQR] 1-5), 27 hospital days (IQR 7-84), and $142 562 (IQR $45 270-$410 087) in hospital costs. During the terminal admission, 76% (n = 946) were mechanically ventilated; 36% (n = 453) underwent surgery. Hospital use was greatest (P < .001) among children with hematologic/immunologic conditions (99 hospital days [IQR 51-146]; cost = $504 145 [IQR $250 147-$879 331]) and children with >= 3 LT-CCCs (75 hospital days [IQR 28-132]; cost = $ 341 222 [IQR $ 146 698-$686 585]). CONCLUSIONS: Hospital use for children with LT-CCCs in the last year of life varies significantly across the type and number of conditions. Children with hematologic/immunologic or multiple conditions have the greatest hospital use. This information may be useful for clinicians striving to improve care for children with LT-CCCs nearing the end of life. C1 [Ananth, Prasanna; Wolfe, Joanne] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Hematol Oncol, Boston, MA 02215 USA. [Melvin, Patrice] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, Boston, MA 02115 USA. [Berry, Jay G.] Harvard Univ, Sch Med, Dept Pediat, Div Gen Pediat,Boston Childrens Hosp, Boston, MA 02115 USA. [Melvin, Patrice] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Boston, MA USA. [Feudtner, Chris] Univ Penn, Dept Pediat, Perelman Sch Med, Pediat Adv Care Team,Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Ananth, P (reprint author), Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Hematol Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM prasanna.ananth@childrens.harvard.edu FU David A. Abraham Fellowship at Dana-Farber Cancer Institute; Eunice Kennedy Shriver National Institute for Child Health and Human Development [K23HD058092]; Agency for Healthcare Research and Quality [R21HS23092, R011HS018425]; National Institutes of Health (NIH) FX Dr Ananth was supported by the David A. Abraham Fellowship at Dana-Farber Cancer Institute. Dr Berry was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development (K23HD058092) and the Agency for Healthcare Research and Quality (R21HS23092). Dr Feudtner was supported by the Agency for Healthcare Research and Quality (R011HS018425). Funded by the National Institutes of Health (NIH). NR 46 TC 6 Z9 6 U1 2 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2015 VL 136 IS 5 BP 938 EP 946 DI 10.1542/peds.2015-0260 PG 9 WC Pediatrics SC Pediatrics GA CV0US UT WOS:000363969600059 PM 26438707 ER PT J AU Anderson, LE Chen, MHL Perrin, JM Van Cleave, J AF Anderson, L. Elizabeth Chen, Minghua L. Perrin, James M. Van Cleave, Jeanne TI Outpatient Visits and Medication Prescribing for US Children With Mental Health Conditions SO PEDIATRICS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; QUALITY-OF-CARE; UNITED-STATES; ADOLESCENT PSYCHIATRISTS; PRACTICE GUIDELINES; ETHNIC DISPARITIES; PEDIATRIC PRACTICE; INSURANCE STATUS; SERVICE USE; ACCESS AB OBJECTIVE: To compare the mental health care US children receive from primary care providers (PCPs) and other mental health care providers. METHODS: Using nationally representative data from the Medical Expenditure Panel Survey (MEPS) from 2008 to 2011, we determined whether children and youth aged 2 to 21 years with outpatient visits for mental health problems in the past year saw PCPs, psychiatrists, and/or psychologists/social workers for these conditions. We compared the proportion of children prescribed psychotropic medications by provider type. Using logistic regression, we examined associations of provider type seen and medication prescribing with race/ethnicity, household income, insurance status, geographical area, and language at home. RESULTS: One-third (34.8%) of children receiving outpatient care for mental health conditions saw PCPs only, 26.2% saw psychiatrists only, and 15.2% saw psychologists/social workers only. Nearly a quarter (23.8%) of children saw multiple providers. A greater proportion of children with attention-deficit/hyperactivity disorder (ADHD) versus children with anxiety/mood disorders saw a PCP only (41.8% vs 17.2%). PCPs prescribed medications to a higher percentage of children than did psychiatrists. Children seeing a PCP for ADHD were more likely to receive stimulants or alpha-agonists than children with ADHD seeing psychiatrists (73.7% vs 61.4%). We found only limited associations of sociodemographic characteristics with provider type or medication use. CONCLUSIONS: PCPs appear to be sole physician managers for care of 4 in 10 US children with ADHD, and one-third with mental health conditions overall. Efforts supporting mental health in primary care will reach a substantial portion of children receiving mental health services. C1 [Anderson, L. Elizabeth] Univ Tennessee, Coll Med, Memphis, TN USA. [Chen, Minghua L.] Ctr Child & Adolescent Hlth Res & Policy, Div Gen Pediat, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Perrin, James M.; Van Cleave, Jeanne] MassGen Hosp Children, Div Gen Acad Pediat, Boston, MA 02114 USA. [Perrin, James M.; Van Cleave, Jeanne] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Van Cleave, J (reprint author), MassGen Hosp Children, Div Gen Acad Pediat, 125 Nashua St 860, Boston, MA 02114 USA. EM jvancleave@partners.org FU American Pediatric Society/Society for Pediatric Research Student Research Program [T35 HD 7446]; National Institutes of Health [5K23MH083885-05]; National Institutes of Health (NIH) FX Ms Anderson received funding through the American Pediatric Society/Society for Pediatric Research Student Research Program (T35 HD 7446). Drs Van Cleave and Chen were supported by the National Institutes of Health (5K23MH083885-05). Funded by the National Institutes of Health (NIH). NR 46 TC 8 Z9 8 U1 3 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2015 VL 136 IS 5 BP E1178 EP E1185 DI 10.1542/peds.2015-0807 PG 8 WC Pediatrics SC Pediatrics GA CV0US UT WOS:000363969600002 PM 26459647 ER PT J AU Rouhani, SA Scott, J Greiner, A Albutt, K Hacker, MR Kuwert, P VanRooyen, M Bartels, S AF Rouhani, Shada A. Scott, Jennifer Greiner, Ashley Albutt, Katherine Hacker, Michele R. Kuwert, Philipp VanRooyen, Michael Bartels, Susan TI Stigma and Parenting Children Conceived From Sexual Violence SO PEDIATRICS LA English DT Article ID HIDDEN POPULATIONS; CONTROLLED-TRIAL; CHILDHOOD; ATTITUDES; SURVIVORS; CONGO; EXPERIENCES; DEPRESSION; TRAUMA; HEALTH AB BACKGROUND AND OBJECTIVES: Since armed conflict began in 1996, widespread sexual violence in eastern Democratic Republic of Congo has resulted in many sexual violence-related pregnancies (SVRPs). However, there are limited data on the relationships between mothers and their children from sexual violence. This study aimed to evaluate the nature and determinants of these maternal-child relationships. METHODS: Using respondent-driven sampling, 757 women raising children from SVRPs in South Kivu Province, Democratic Republic of Congo were interviewed. A parenting index was created from questions assessing the maternal-child relationship. The influences of social stigma, family and community acceptance, and maternal mental health on the parenting index were assessed in univariate and multivariable analyses. RESULTS: The majority of mothers reported positive attitudes toward their children from SVRPs. Prevalence of perceived family or community stigma toward the women or their children ranged from 31.8% to 42.9%, and prevalence of perceived family or community acceptance ranged from 45.2% to 73.5%. In multivariable analyses, stigma toward the child, as well as maternal anxiety and depression, were associated with lower parenting indexes, whereas acceptance of the mother or child and presence of a spouse were associated with higher parenting indexes (all P <= .01). CONCLUSIONS: In this study with a large sample size, stigma and mental health disorders negatively influenced parenting attitudes, whereas family and community acceptance were associated with adaptive parenting attitudes. Interventions to reduce stigmatization, augment acceptance, and improve maternal mental health may improve the long-term well-being of mothers and children from SVRPs. C1 [Rouhani, Shada A.; Scott, Jennifer; Greiner, Ashley; Albutt, Katherine; VanRooyen, Michael; Bartels, Susan] Harvard Humanitarian Initiat, Cambridge, MA USA. [Rouhani, Shada A.; Scott, Jennifer; Greiner, Ashley; Albutt, Katherine; Hacker, Michele R.; VanRooyen, Michael; Bartels, Susan] Harvard Univ, Sch Med, Boston, MA USA. [Scott, Jennifer] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Rouhani, Shada A.; Scott, Jennifer; VanRooyen, Michael] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02130 USA. [Hacker, Michele R.] Beth Israel Deaconess Med Ctr, Dept Obstetr & Gynecol, Boston, MA 02215 USA. [Greiner, Ashley; Bartels, Susan] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Albutt, Katherine] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hacker, Michele R.; VanRooyen, Michael] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Kuwert, Philipp] Univ Med Greifswald, HELIOS Hansehosp, Dept Psychiat, Stralsund, Germany. [Bartels, Susan] Queens Univ, Dept Emergency Med, Kingston, ON K7L 3N6, Canada. RP Rouhani, SA (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02130 USA. EM shada.rouhani@gmail.com FU Eleanor Miles Shore Foundation (GL Dept) [01025283]; Harvard Humanitarian Initiative; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [8UL1TR000170-05]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (Harvard University) FX The study was supported by the Eleanor Miles Shore Foundation (GL Dept ID 01025283) and Harvard Humanitarian Initiative. Analysis was supported by Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05 and financial contributions from Harvard University and affiliated academic health centers). NR 47 TC 0 Z9 0 U1 4 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD NOV PY 2015 VL 136 IS 5 BP E1195 EP E1203 DI 10.1542/peds.2014-3373 PG 9 WC Pediatrics SC Pediatrics GA CV0US UT WOS:000363969600004 PM 26438704 ER PT J AU Lopez, J Lopez, S Means, J Mohan, R Soni, A Milton, J Tufaro, AP May, JW Dorafshar, A AF Lopez, Joseph Lopez, Sandra Means, Jessica Mohan, Raja Soni, Ashwin Milton, Jacqueline Tufaro, Anthony P. May, James W., Jr. Dorafshar, Amir TI Financial Conflicts of Interest: An Association between Funding and Findings in Plastic Surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; ACELLULAR DERMAL MATRIX; PHARMACEUTICAL-INDUSTRY; LIFE SCIENCES; TRIALS; DISCLOSURE; BIAS; TRANSPARENCY; PUBLICATION; PHYSICIANS AB Background: Despite a growing interest in examining the effects of industry funding on research in plastic surgery, no study to date has comprehensively examined the effects of financial conflicts of interest on publication outcomes. The authors investigated the association between financial conflicts of interest and reported study findings in plastic surgery research. Methods: The authors reviewed all entries in Plastic and Reconstructive Surgery, Annals of Plastic Surgery, and Journal of Plastic, Reconstructive & Aesthetic Surgery from January 1, 2012, to December 31, 2012. All clinical and basic science articles were analyzed. The following article characteristics were extracted: self-reported financial conflicts of interest, sample size, level of evidence, study design, and prospectiveness. The findings reported in each abstract were blindly graded as not applicable, negative, or positive. Results: Of the 1650 abstracts that resulted from the authors' initial search, 568 fulfilled the inclusion criteria. The majority of the included articles covered breast (20.8 percent), experimental (19.7 percent), and general reconstruction (31.69 percent). Financial conflicts of interest were disclosed in only 17.6 percent of the articles. Of the total studies that met inclusion criteria, 66.2 percent were reviewed as having positive outcomes, and 33.8 percent were reviewed as having negative or not applicable results. Studies that disclosed a financial conflict of interest were 7.12 times more likely (p < 0.0001) to present a positive outcome over a negative outcome compared with studies with no financial conflict of interest. Conclusion: Investigators with a financial conflict of interest are significantly more likely to publish plastic surgery studies with a positive conclusion compared with investigators with no conflicts of interest. C1 Johns Hopkins Univ Hosp, Dept Plast & Reconstruct Surg, Baltimore, MD 21287 USA. Columbia Univ Coll Phys & Surg, New York, NY USA. Univ Washington, Med Ctr, Div Plast Surg, Seattle, WA 98195 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Lopez, J (reprint author), Univ Maryland, Med Ctr, Johns Hopkins Hosp, Dept Plast Surg, 1780 East Fayette St,Bloomberg 7th Floor, Baltimore, MD 21231 USA. EM jlopez37@jhmi.edu FU KLS Martin; De Puy Synthes FX Dr. May is a consultant for TEI Biosciences and an educational consultant for Johnson & Johnson/Mentor. Dr. Dorafshar receives royalties and research support from KLS Martin and research support from De Puy Synthes. The other authors have no financial information to disclose. NR 47 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 2015 VL 136 IS 5 BP 690E EP 697E DI 10.1097/PRS.0000000000001718 PG 8 WC Surgery SC Surgery GA CV2OY UT WOS:000364097300001 PM 26505726 ER PT J AU Kuehlewein, L Dansingani, KK De Carlo, TE Bonini, MA Iafe, NA Lenis, TL Freund, KB Waheed, NK Duker, JS Sadda, SR Sarraf, D AF Kuehlewein, Laura Dansingani, Kunal K. De Carlo, Talisa E. Bonini Filho, Marco A. Iafe, Nicholas A. Lenis, Tamara L. Freund, K. Bailey Waheed, Nadia K. Duker, Jay S. Sadda, Srinivas R. Sarraf, David TI OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TYPE 3 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; angiography; optical coherence tomography angiography ID RETINAL ANGIOMATOUS PROLIFERATION; CHOROIDAL NEOVASCULARIZATION; OCT ANGIOGRAPHY; CLINICOPATHOLOGICAL CORRELATION; MOTION CORRECTION; CLASSIFICATION; SPECTRUM; THERAPY AB Purpose: To characterize the vascular structure of Type 3 neovascularization secondary to age-related macular degeneration using optical coherence tomography angiography. Methods: Optical coherence tomography angiography cube scans (3 mm x 3 mm) were acquired in 29 eyes of 24 patients with Type 3 lesions secondary to age-related macular degeneration using the RTVue XR Avanti with AngioVue, Split-spectrum amplitude-decorrelation, and motion correction technology. Automated layer segmentation boundaries were adjusted to best visualize the neovascular complex on en face projection images. Results: A distinct neovascular complex could be identified in 10 (34%) eyes, all of which were active on optical coherence tomography imaging. In all 10 eyes, the neovascular complex appeared as a small tuft of bright, high-flow tiny vessels with curvilinear morphology located in the outer retinal layers with a feeder vessel communicating with the inner retinal circulation (i.e., deep retinal capillary plexus). The mean (SD) size of the neovascular complex measured 0.07 ( 0.07) mm(2). Conclusion: With optical coherence tomography angiography, it is possible to identify small intraretinal neovascular complexes communicating with the deep retinal capillary plexus in eyes with Type 3 neovascularization secondary to age-related macular degeneration. Qualitative and quantitative analyses of Type 3 neovascular complexes can be performed using optical coherence tomography angiography. C1 [Kuehlewein, Laura; Sadda, Srinivas R.] Doheny Eye Inst, Los Angeles, CA 90033 USA. [Kuehlewein, Laura; Iafe, Nicholas A.; Lenis, Tamara L.; Sadda, Srinivas R.; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Dansingani, Kunal K.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY USA. [Dansingani, Kunal K.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY USA. [Dansingani, Kunal K.] Moorfields Eye Hosp, London, England. [De Carlo, Talisa E.; Bonini Filho, Marco A.; Waheed, Nadia K.; Duker, Jay S.] Tufts Univ, New England Eye Ctr, Boston, MA 02111 USA. [De Carlo, Talisa E.; Bonini Filho, Marco A.; Waheed, Nadia K.; Duker, Jay S.] Tufts Univ, Tufts Med Ctr, Boston, MA 02111 USA. [De Carlo, Talisa E.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [De Carlo, Talisa E.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Bonini Filho, Marco A.] Minist Educ Brazil, CAPES Fdn, Brasilia, DF, Brazil. [Iafe, Nicholas A.; Lenis, Tamara L.; Sarraf, David] Stein Eye Inst, Los Angeles, CA USA. [Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Retinal Disorders & Ophthalm Genet Div, Stein Eye Inst, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu FU Macular Foundation, Inc, New York, NY; Carl Zeiss Meditech; Massachusetts Lions Clubs; Optovue; Allergan; Carl Zeiss Meditec; Genentech; Optos; Regeneron FX K. Bailey Freund is supported by the Macular Foundation, Inc, New York, NY. He is a consultant to Optovue, Genentech, Optos, ThromboGenics, Ohr Pharmaceutical, and Heidelberg Engineering (honorarium for each). N. K. Waheed was a consultant for Iconic therapeutics, served the speaker's bureau for Thrombogenics, and receives research support from Carl Zeiss Meditech. J. S. Duker is supported by the Massachusetts Lions Clubs. He is a consultant for and receives research support from Optovue and Carl Zeiss Meditech. S. R. Sadda is a coinventor of Doheny intellectual property related to optical coherence tomography that has been licensed by Topcon Medical Systems and is a member of the scientific advisory board for Heidelberg Engineering. He receives research support from and serves as a consultant for Allergan, Carl Zeiss Meditec, Genentech, and Optos. He also serves as a consultant for Alcon, Novartis, and Roche. D. Sarraf has research grants from Regeneron and Genentech, has served on an advisory board for Genentech, and has been loaned the Optovue machine with Split-spectrum amplitude-decorrelation capability from Optovue Inc. for research purposes. The other authors have no financial/conflicting interests to disclose. NR 23 TC 18 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD NOV PY 2015 VL 35 IS 11 BP 2229 EP 2235 PG 7 WC Ophthalmology SC Ophthalmology GA CV5LD UT WOS:000364311100009 PM 26502007 ER PT J AU Bonini, MA Adhi, M De Carlo, TE Ferrara, D Baumal, CR Witkin, AJ Reichel, E Kuehlewein, L Sadda, SR Sarraf, D Duker, JS Waheed, NK AF Bonini Filho, Marco A. Adhi, Mehreen De Carlo, Talisa E. Ferrara, Daniela Baumal, Caroline R. Witkin, Andre J. Reichel, Elias Kuehlewein, Laura Sadda, Srinivas R. Sarraf, David Duker, Jay S. Waheed, Nadia K. TI OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL ARTERY OCCLUSION SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE optical coherence tomography angiography; retinal artery occlusion ID FLUORESCEIN ANGIOGRAPHY AB Purpose:To describe the retinal microvasculature of the eyes with nonarteritic retinal artery occlusion (RAO) based on optical coherence tomography angiography. Methods:Cross-sectional, prospective, observational study performed from September 2014 through February 2015. En face projection of optical coherence tomography angiography images centered at the macula and optic disk of the eyes presenting with RAO were acquired using the RTVue XR Avanti with AngioVue software. Qualitative analysis of the morphology of the superficial and deep retinal capillary plexuses, and radial peripapillary capillaries was performed. Retinal vasculature images using optical coherence tomography angiography were correlated with fluorescein angiography images. Results:Seven patients (seven eyes) were enrolled in the study, including three eyes with central RAO and four eyes with branch RAO. Distinct differences in the distribution of zones of decreased vascular perfusion between the superficial and deep retinal capillary plexus corresponding to areas of delayed dye perfusion on fluorescein angiography were demonstrated in 6 of 7 (86.5%) eyes. Conclusion:This small series suggests that optical coherence tomography angiography imaging can accurately discern retinal capillary plexuses at different levels in the eyes with RAO and may be sensitive for more precisely characterizing the extent of macular ischemia and monitoring vascular flow changes during the course of the disease. C1 [Bonini Filho, Marco A.; Adhi, Mehreen; De Carlo, Talisa E.; Ferrara, Daniela; Baumal, Caroline R.; Witkin, Andre J.; Reichel, Elias; Duker, Jay S.; Waheed, Nadia K.] Tufts Univ, New England Eye Ctr, Boston, MA 02111 USA. [Bonini Filho, Marco A.; Adhi, Mehreen; De Carlo, Talisa E.; Ferrara, Daniela; Baumal, Caroline R.; Witkin, Andre J.; Reichel, Elias; Duker, Jay S.; Waheed, Nadia K.] Tufts Univ, Tufts Med Ctr, Boston, MA 02111 USA. [Bonini Filho, Marco A.] Minist Educ Brazil, CAPES Fdn, Brasilia, DF, Brazil. [De Carlo, Talisa E.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [De Carlo, Talisa E.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Kuehlewein, Laura; Sadda, Srinivas R.; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Kuehlewein, Laura; Sadda, Srinivas R.] Doheny Eye Inst, Los Angeles, CA 90033 USA. [Sarraf, David] Stein Eye Inst, Los Angeles, CA USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Waheed, NK (reprint author), New England Eye Ctr, Tufts Med Ctr, 260 Tremont St,Biewend Bldg,9-11th Floor, Boston, MA 02116 USA. EM nadiakwaheed@gmail.com FU Research to Prevent Blindness; Massachusetts Lions Club FX Supported in part by a Research to Prevent Blindness Unrestricted grant to the New England Eye Center/Department of Ophthalmology, Tufts University School of Medicine, and Massachusetts Lions Club. NR 12 TC 6 Z9 6 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD NOV PY 2015 VL 35 IS 11 BP 2339 EP 2346 PG 8 WC Ophthalmology SC Ophthalmology GA CV5LD UT WOS:000364311100022 PM 26457398 ER PT J AU Greene, MF AF Greene, Michael F. TI FDA drug labeling for pregnancy and lactation drug safety monitoring systems SO SEMINARS IN PERINATOLOGY LA English DT Review ID CONGENITAL ABNORMALITIES; THALIDOMIDE AB The product label required by the FDA for every drug approved for marketing in the US is a legal document that originates with the company that wants to market the drug, but it must be approved by the FDA. Despite the recognized limitations of registries, the FDA's new labeling rule, effective from July 1, 2015, has given the data available from post-marketing surveillance priority in the new label. For this information to be maximally useful to both providers and consumers, providers must refer as many exposed consumers as possible to the registries, preferably prior to knowledge of the outcomes of the pregnancies. Consumers need to cooperate with the registries to share their health information with as much detail as possible with the registries. It will take years to accumulate a meaningful quantity of information in many of the registries, but they promise to be our best hope for useful counseling information in the future. (C) 2015 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greene, MF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. EM Greene.Michael@mgh.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD NOV PY 2015 VL 39 IS 7 BP 520 EP 523 DI 10.1053/j.semperi.2015.08.004 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA CV4VY UT WOS:000364265800004 PM 26428020 ER PT J AU Mayer, KH Gangakhedkar, R Sivasubramanian, M Biello, KB Abuelezam, N Mane, S Risbud, A Anand, V Safren, S Mimiaga, MJ AF Mayer, Kenneth H. Gangakhedkar, Raman Sivasubramanian, Murugesan Biello, Katie B. Abuelezam, Nadia Mane, Sandeep Risbud, Arun Anand, Vivek Safren, Steven Mimiaga, Matthew J. TI Differing Identities but Comparably High HIV and Bacterial Sexually Transmitted Disease Burdens Among Married and Unmarried Men Who Have Sex With Men in Mumbai, India SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID KOTHI-IDENTIFIED MEN; RISK BEHAVIOR; CHENNAI; EPIDEMIC; POPULATIONS; PREVALENCE; PREVENTION; DEPRESSION; INFECTION; STRESS AB Background Although HIV incidence has declined in India, men and transgender women who have sex with men (MSM) continue to have high rates of HIV and sexually transmitted disease (STD). Indian MSM face substantial pressures to marry and have families, but the HIV/STD burden among married Indian MSM is not well characterized. Methods A diverse sample of Indian MSM were recruited through respondent-driven sampling. Independent variables that produced a P value of 0.10 or less were then added to a multivariable logistic regression model. Results Most of the 307 MSM (95 married and 212 unmarried) recruited into the study were younger than 30 years, and less than one-third had more than a high school education. Almost two-thirds of the married men had children, compared with 1.4% of the unmarried men (P < 0.001). The numbers of condomless anal sex acts did not differ by marriage status. Although unmarried MSM more often identified themselves as kothi (receptive role), their rates of HIV or bacterial STD were similar to married MSM, with 14.3% being HIV infected. The respondent-driven sampling-adjusted prevalence of any bacterial STD was 18.3% for married MSM and 20% for unmarried MSM (not significant). Participants reported high levels of psychological distress, with 27.4% of married and 20.1% of unmarried MSM reporting depressive symptoms (not significant). Conclusions Men who have sex with men in Mumbai had high rates of HIV, STD, and behavioral health concerns. Clinicians need to become more comfortable in eliciting sexual histories so that they can identify MSM who need HIV/STD treatment and/or prevention services. C1 [Mayer, Kenneth H.; Biello, Katie B.; Safren, Steven; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mayer, Kenneth H.; Biello, Katie B.; Safren, Steven; Mimiaga, Matthew J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Gangakhedkar, Raman; Risbud, Arun] Natl AIDS Res Inst, Pune, Maharashtra, India. [Sivasubramanian, Murugesan; Mane, Sandeep; Anand, Vivek] Humsafar Trust, Bombay, Maharashtra, India. [Biello, Katie B.; Abuelezam, Nadia; Mimiaga, Matthew J.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Safren, Steven; Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Mayer, KH (reprint author), Fenway Hlth, 1340 Boylston St,8th Floor, Boston, MA 02215 USA. EM kmayer@fenwayhealth.org FU Indo-US Joint Working Group on Prevention of Sexually Transmitted Diseases; HIV/AIDS through US National Institute of Mental Health [1 R21 MH085319-01]; Indian Council of Medical Research [Indo-U.S./65/2007-ECD-11] FX Funding; This project was supported by the Indo-US Joint Working Group on Prevention of Sexually Transmitted Diseases and HIV/AIDS through US National Institute of Mental Health (Grant No. 1 R21 MH085319-01 [Kenneth Mayer, Principal Investigator]) and Indian Council of Medical Research (Grant No. Indo-U.S./65/2007-ECD-11 [Raman Gangakhedkar, Principal Investigator]). NR 33 TC 0 Z9 0 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-5717 EI 1537-4521 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD NOV PY 2015 VL 42 IS 11 BP 629 EP 633 DI 10.1097/OLQ.0000000000000344 PG 5 WC Infectious Diseases SC Infectious Diseases GA CV2LY UT WOS:000364089400006 PM 26462187 ER PT J AU Singh, G Zhou, XH Lee, JY Yousuf, MA Ramke, M Ismail, AM Lee, JS Robinson, CM Seto, D Dyer, DW Jones, MS Rajaiya, J Chodosh, J AF Singh, Gurdeep Zhou, Xiaohong Lee, Jeong Yoon Yousuf, Mohammad A. Ramke, Mirja Ismail, Ashrafali M. Lee, Ji Sun Robinson, Christopher M. Seto, Donald Dyer, David W. Jones, Morris S. Rajaiya, Jaya Chodosh, James TI Recombination of the epsilon determinant and corneal tropism: Human adenovirus species D types 15, 29, 56, and 69 SO VIROLOGY LA English DT Article DE Adenovirus; Epidemic keratoconjunctivitis; Homologous recombination; Keratitis ID EPIDEMIC KERATOCONJUNCTIVITIS; COMPUTATIONAL ANALYSIS; MOLECULAR EVOLUTION; GENOME SEQUENCE; GENE-TRANSFER; RESTRICTED REPLICATION; CONJUNCTIVAL CELLS; CELLULAR RECEPTOR; SIALIC-ACID; INFECTION AB Viruses within human adenovirus species D (HAdV-D) infect epithelia at essentially every mucosal site. Hypervariable loops I and 2 of the hexon capsid protein contain epitopes that together form the epsilon determinant for serum neutralization. We report our analyses comparing HAdV-D15, 29, 56, and the recently identified type 69, each with highly similar hexons and the same serum neutralization profile, but otherwise disparate genomes. Of these, only HAdV-D type 56 is associated with epidemic keratoconjunctivitis (EKC), a severe infection of ocular surface epithelium and underlying corneal stroma. In the mouse adenovirus keratitis model, all four viruses induced inflammation. However, HAdV-D56 entry into human corneal epithelial cells and fibroblasts in vitro dramatically exceeded that of the other three viruses. We conclude that the hexon epsilon determinant is not a prime contributor to corneal tropism. (C) 2015 Elsevier Inc. All rights reserved. C1 [Singh, Gurdeep; Zhou, Xiaohong; Lee, Jeong Yoon; Yousuf, Mohammad A.; Ramke, Mirja; Ismail, Ashrafali M.; Lee, Ji Sun; Robinson, Christopher M.; Rajaiya, Jaya; Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA USA. [Seto, Donald] George Mason Univ, Sch Syst Biol, Bioinformat & Computat Biol Program, Manassas, VA USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. [Jones, Morris S.] US Navy, Div Infect Dis, San Diego Med Ctr, San Diego, CA 92152 USA. RP Rajaiya, J (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM jaya_rajaiya@meei.harvard.edu; james_chodosh@meei.harvard.edu OI Ashrafali, Mohamed Ismail/0000-0001-8694-7235 FU NIH [EY013124, EY021558, P30EY014104]; Research to Prevent Blindness, Inc., NY, NY; Falk Foundation; Massachusetts Lions Eye Research Fund FX We acknowledge Beth Benas for her technical support of select experiments. This work was supported by NIH Grants EY013124, EY021558, and P30EY014104, a Senior Scientific Investigator Award (to JC) from Research to Prevent Blindness, Inc., NY, NY, the Falk Foundation, and the Massachusetts Lions Eye Research Fund. NR 68 TC 2 Z9 2 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 2015 VL 485 BP 452 EP 459 DI 10.1016/j.virol.2015.08.018 PG 8 WC Virology SC Virology GA CV1DH UT WOS:000363993100047 PM 26343864 ER PT J AU Giess, CS Poole, PS Chikarmane, SA Sippo, DA Birdwell, RL AF Giess, Catherine S. Poole, Patricia S. Chikarmane, Sona A. Sippo, Dorothy A. Birdwell, Robyn L. TI Screening Breast MRI in Patients Previously Treated for Breast Cancer: Diagnostic Yield for Cancer and Abnormal Interpretation Rate SO ACADEMIC RADIOLOGY LA English DT Article DE Breast; breast cancer; screening; breast MRI ID SURGICAL ADJUVANT BREAST; PERSONAL HISTORY; HIGH-RISK; LOCOREGIONAL RECURRENCES; CONTRALATERAL BREAST; COST-EFFECTIVENESS; MUTATION CARRIERS; TUMOR RECURRENCE; MAMMOGRAPHY; WOMEN AB Rationale and Objectives: To determine the cancer detection rate and abnormal interpretation rate of screening breast magnetic resonance imaging (MRI) in previously treated breast cancer patients. Materials and Methods: Institutional review board-approved retrospective review of the breast MRI database from 2009 to 2011 identified a total of 3297 screening examinations. After excluding genetic mutation carriers, untested first-degree relatives of known mutation carriers, and patients with a history of chest irradiation, there were 1194(36.2%) examinations in 691 patients previously treated for breast cancer. MRI reports were reviewed to determine MRI findings and breast imaging reporting and data system (BI-RADS) assessments. The longitudinal medical record was reviewed to determine patient demographics and outcomes of imaging surveillance and biopsy. Results: Mean patient age at initial cancer diagnosis was 46.1 years, and mean patient age during the study interval was 52 years. Cancer detection rate was 10 per 1000(1%; 95% confidence interval [Cl], 0.5%-1.8%]; 12 of 1194 examinations). Overall 10.7% (128 of 1194) of examinations received an abnormal interpretation, including 5.4% (65 of 1194) BI-RADS 4 or 5 and 5.3% (63 of 1194) BI-RADS 3 assessments with a 9.4% positive predictive value (PPV1; 12 of 128 examinations) and a 17.9% PPV3 (12 malignancies per 67 biopsies). Conclusions: Screening breast MRI in women previously treated for breast cancer detected cancer in 1.0% of examinations, with a 10.7% abnormal interpretation rate, and a PPV for malignancy of 17.9%. C1 [Giess, Catherine S.; Poole, Patricia S.; Chikarmane, Sona A.; Sippo, Dorothy A.; Birdwell, Robyn L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Giess, CS (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM cgiess@partners.org NR 30 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2015 VL 22 IS 11 BP 1331 EP 1337 DI 10.1016/j.acra.2015.05.009 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU5WG UT WOS:000363602100002 PM 26142951 ER PT J AU Lee, SH Hayano, K Zhu, AX Sahani, DV Yoshida, H AF Lee, Sang Ho Hayano, Koichi Zhu, Andrew X. Sahani, Dushyant V. Yoshida, Hiroyuki TI Dynamic Contrast-Enhanced MRI Kinetic Parameters as Prognostic Biomarkers for Prediction of Survival of Patient with Advanced Hepatocellular Carcinoma: A Pilot Comparative Study SO ACADEMIC RADIOLOGY LA English DT Article DE Tracer kinetic modeling; hepatocellular carcinoma; antiangiogenic treatment; image biomarker; dynamic contrast-enhanced MRI ID DCE-MRI; BLOOD-FLOW; CAPILLARY-PERMEABILITY; PERFUSION PARAMETERS; HEPATIC METASTASES; TUMOR ANGIOGENESIS; TRACER KINETICS; MODEL; CT; DECONVOLUTION AB Rationale and Objectives: Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data analysis influences its use as a prognostic biomarker. Our aim was to find DCE-MRI parameters that predict 1-year survival (1 YS) and overall survival (OS) among patients with advanced hepatocellular carcinoma (HOC) treated with antiangiogenic monotherapy by conducting a proof-of-concept comparative study of five different kinetic models. Materials and Methods: Twenty patients with advanced HOC underwent DCE-MRI and subsequently received sunitinib. Pretreatment DCE-MRI data were analyzed retrospectively by using the Tofts-Kety (TK), extended TK, two compartment exchange, adiabatic approximation to the tissue homogeneity (AATH), and distributed parameter (DP) models. Arterial flow fraction (7), arterial blood flow (BFA,), permeability-surface area product (PS), fractional interstitial volume (v(1)), and other five parameters were calculated for each model. Individual parameters were evaluated for 1YS prediction using cross-validated Kaplan-Meier analysis, and for association with OS using univariate Cox regression analysis, with additional permutation testing. Results: For 1YS prediction, the TK model-derived 7 (P =.007) and vi (P =.029) and the AATH model-derived PS (P =.005) were significant; all these parameters were lower in the high-risk group. Increase in the AATH model-derived PS and the DP model-derived BFA was associated with significant increase in OS with hazard ratios of 0.766 (P =.023) and 0.809 (P =.025), respectively. Conclusions: The AATH model-derived PS was an effective prognostic biomarker for both 1 YS and OS. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, Boston, MA 02114 USA. [Lee, Sang Ho; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hayano, Koichi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Imaging Res 3D, 25 New Chardon St,Suite 4000, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu RI Lee, Sang Ho/B-9149-2017 OI Lee, Sang Ho/0000-0002-4634-4904 FU NCI NIH HHS [R21 CA187877, R21CA187877] NR 50 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2015 VL 22 IS 11 BP 1344 EP 1360 DI 10.1016/j.acra.2015.05.012 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU5WG UT WOS:000363602100004 PM 26211553 ER PT J AU Ryu, JH Hong, S Lee, H AF Ryu, Ji Hyun Hong, Seonld Lee, Haeshin TI Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini review SO ACTA BIOMATERIALIA LA English DT Review DE Chitosan; Catechol; Mussel; Adhesive; Biomedical ID TYRAMINE HYDROGEL SYSTEM; CROSS-LINKING; DRUG-DELIVERY; MUSSEL ADHESION; MECHANICAL-PROPERTIES; TISSUE ADHESIVES; REDOX-CAPACITOR; GENE DELIVERY; FUNCTIONALIZED CHITOSAN; POLY(ETHYLENE GLYCOL) AB The development of adhesive materials, such as cyanoacrylate derivatives, fibrin glues, and gelatin-based adhesives, has been an emerging topic in biomaterial science because of the many uses of these materials, including in wound healing patches, tissue sealants, and hemostatic materials. However, most bio-adhesives exhibit poor adhesion to tissue and related surfaces due to the presence of body fluid. For a decade, studies have aimed at addressing this issue by developing wet-resistant adhesives. Mussels demonstrate robust wet-resistant adhesion despite the ceaseless waves at seashores, and mussel adhesive proteins play a key role in this adhesion. Adhesive proteins located at the distal end (i.e., those that directly contact surfaces) are composed of nearly 60% of amino acids called 3,4-dihydroxy-L-phenylalanine (DOPA), lysine, and histidine, which contain side chains of catechol, primary amines, and secondary amines, respectively. Inspired by the abundant catecholamine in mussel adhesive proteins, researchers have developed various types of polymeric mimics, such as polyethylenimine-catechol, chitosan-catechol, and other related catecholic polymers. Among them, chitosan-catechol is a promising adhesive polymer for biomedical applications. The conjugation of catechol onto chitosan dramatically increases its solubility from zero to nearly 60 mg/mL (i.e., 6% w/v) in pH 7 aqueous solutions. The enhanced solubility maximizes the ability of catecholamine to behave similar to mussel adhesive proteins. Chitosan-catechol is biocompatible and exhibits excellent hemostatic ability and tissue adhesion, and thus, chitosan-catechol will be widely used in a variety of medical settings in the future. This review focuses on the various aspects of chitosan-catechol, including its (1) preparation methods, (2) physicochemical properties, and (3) current applications. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Ryu, Ji Hyun; Lee, Haeshin] Korea Adv Inst Sci & Technol, Dept Chem, Daejeon, South Korea. [Hong, Seonld] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lee, Haeshin] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Daejeon, South Korea. [Lee, Haeshin] Korea Adv Inst Sci & Technol, Ctr Nat Inspired Technol CNiT, Daejeon, South Korea. RP Lee, H (reprint author), Korea Adv Inst Sci & Technol, Dept Chem, Daejeon, South Korea. EM haeshin@kaist.ac.kr RI Lee, Haeshin/C-1720-2011 OI Lee, Haeshin/0000-0003-3961-9727 FU National Research Foundation of South Korea [2015021564, 20090083525]; World Premier Material (WPM) Development Program from the Ministry of Industry, Trade, and Natural Resources FX This study was supported by grants from the National Research Foundation of South Korea: the Mid-career Scientist Grant (2015021564) and SRC Program (Molecular-level Interface Research Center, 20090083525). This study is also supported in part by World Premier Material (WPM) Development Program from the Ministry of Industry, Trade, and Natural Resources. NR 120 TC 14 Z9 14 U1 59 U2 231 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD NOV PY 2015 VL 27 BP 101 EP 115 DI 10.1016/j.actbio.2015.08.043 PG 15 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA CU8VK UT WOS:000363822000010 PM 26318801 ER PT J AU Guirguis, J Chhatwal, J Dasarathy, J Rivas, J McMichael, D Nagy, LE McCullough, AJ Dasarathy, S AF Guirguis, John Chhatwal, Jagpreet Dasarathy, Jaividhya Rivas, John McMichael, David Nagy, Laura E. McCullough, Arthur J. Dasarathy, Srinivasan TI Clinical Impact of Alcohol-Related Cirrhosis in the Next Decade: Estimates Based on Current Epidemiological Trends in the United States SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Alcohol; Liver Disease; Cirrhosis; Hepatitis C; Healthcare Costs ID NONALCOHOLIC FATTY LIVER; C VIRUS-INFECTION; CHRONIC HEPATITIS-C; DISEASE; TRANSPLANTATION; PREVALENCE; BURDEN; VACCINATION; OBESITY AB BackgroundIdentifying changes in the epidemiology of liver disease is critical for establishing healthcare priorities and allocating resources to develop therapies. The projected contribution of different etiologies toward development of cirrhosis in the United States was estimated based on current publications on epidemiological data and advances in therapy. Given the heterogeneity of published reports and the different perceptions that are not always reconcilable, a critical overview rather than a formal meta-analysis of the existing data and projections for the next decade was performed. MethodsData from the World Health Organization Global Status Report on Alcohol and Health of 2014, Scientific Registry of Transplant Recipients from 1999 to 2012, National Institute on Alcohol Abuse and Alcoholism, and the Centers for Disease Control and Prevention were inquired to determine future changes in the epidemiology of liver disease. ResultsAlcohol consumption has increased over the past 60years. In 2010, transplant-related costs for liver recipients were the highest for hepatitis C (similar to$124million) followed by alcohol-related cirrhosis (similar to$86million). We anticipate a significant reduction in incidence cirrhosis due to causes other than alcohol because of the availability of high efficiency antiviral agents for hepatitis C, universal and effective vaccination for hepatitis B, relative stabilization of the obesity trends in the United States, and novel, potentially effective therapies for nonalcoholic steatohepatitis. The proportion of alcohol-related liver disease is therefore likely to increase in both the population as a whole and the liver transplant wait list. ConclusionsAlcohol-related cirrhosis and alcohol-related liver disorders will be the major cause of liver disease in the coming decades. There is an urgent need to allocate resources aimed toward understanding the pathogenesis of the disease and its complications so that effective therapies can be developed. C1 [Guirguis, John; Rivas, John; McMichael, David; McCullough, Arthur J.; Dasarathy, Srinivasan] Cleveland Clin, Dept Gastroenterol, Cleveland, OH 44195 USA. [Guirguis, John; Rivas, John; McMichael, David; McCullough, Arthur J.; Dasarathy, Srinivasan] Cleveland Clin, Dept Hepatol & Transplant Surg, Cleveland, OH 44195 USA. [Chhatwal, Jagpreet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hlth Serv Res, Boston, MA USA. [Dasarathy, Jaividhya] Metro Hlth Med Ctr, Dept Family Med, Cleveland, OH USA. [Nagy, Laura E.] Cleveland Clin Fdn, Dept Pathobiol, Lerner Res Inst, Cleveland, OH 44195 USA. RP Dasarathy, S (reprint author), Cleveland Clin, Lerner Res Inst, NE4 208, Cleveland, OH 44195 USA. EM dasaras@ccf.org FU NIAAA NIH HHS [U01 AA021893, R21 AA 022742, R21 AA022742, U01 AA021890, UOI AA 021890]; NIDDK NIH HHS [R01 DK083414, R0I DK 083414, U01 DK061732] NR 44 TC 3 Z9 3 U1 3 U2 9 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 2015 VL 39 IS 11 BP 2085 EP 2094 DI 10.1111/acer.12887 PG 10 WC Substance Abuse SC Substance Abuse GA CU6ZR UT WOS:000363684700004 PM 26500036 ER PT J AU Lam, DL Larson, DB Eisenberg, JD Forman, HP Lee, CI AF Lam, Diana L. Larson, David B. Eisenberg, Jonathan D. Forman, Howard P. Lee, Christoph I. TI Communicating Potential Radiation-Induced Cancer Risks From Medical Imaging Directly to Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE informed consent; patient-physician communication; radiation dose; radiation-induced cancer ID DIAGNOSTIC CT SCANS; INFORMED-CONSENT; EMERGENCY-DEPARTMENT; COMPUTED-TOMOGRAPHY; DOCTORS KNOWLEDGE; DECISION-MAKING; IONIZING-RADIATION; NUCLEAR-MEDICINE; PEDIATRIC CT; AWARENESS AB OBJECTIVE. Over the past decade, efforts have increasingly been made to decrease radiation dose from medical imaging. However, there remain varied opinions about whether, for whom, by whom, and how these potential risks should be discussed with patients. We aimed to provide a review of the literature regarding awareness and communication of potential radiation- induced cancer risks from medical imaging procedures in hopes of providing guidance for communicating these potential risks with patients. MATERIALS AND METHODS. We performed a systematic literature review on the topics of radiation dose and radiation-induced cancer risk awareness, informed consent regarding radiation dose, and communication of radiation-induced cancer risks with patients undergoing medical imaging. We included original research articles from North America and Europe published between 1995 and 2014. RESULTS. From more than 1200 identified references, a total of 22 original research articles met our inclusion criteria. Overall, we found that there is insufficient knowledge regarding radiation-induced cancer risks and the magnitude of radiation dose associated with CT examinations among patients and physicians. Moreover, there is minimal sharing of information before nonacute imaging studies between patients and physicians about potential long-term radiation risks. CONCLUSION. Despite growing concerns regarding medical radiation exposure, there is still limited awareness of radiation-induced cancer risks among patients and physicians. There is also no consensus regarding who should provide patients with relevant information, as well as in what specific situations and exactly what information should be communicated. Radiologists should prioritize development of consensus statements and novel educational initiatives with regard to radiation-induced cancer risk awareness and communication. C1 [Lam, Diana L.; Lee, Christoph I.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98109 USA. [Larson, David B.] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Eisenberg, Jonathan D.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Forman, Howard P.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Lee, Christoph I.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98109 USA. [Lee, Christoph I.] Fred Hutchinson Canc Res Ctr, Hutchinson Inst Canc Outcomes Res, Seattle, WA 98104 USA. RP Lee, CI (reprint author), Univ Washington, Sch Med, Dept Radiol, 825 Eastlake Ave East,G3-200, Seattle, WA 98109 USA. EM stophlee@uw.edu NR 51 TC 6 Z9 6 U1 1 U2 8 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 2015 VL 205 IS 5 BP 962 EP 970 DI 10.2214/AJR.15.15057 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU8SV UT WOS:000363814900023 PM 26295534 ER PT J AU McDonald, ES McCarthy, AM Akhtar, AL Synnestvedt, MB Schnall, M Conant, EF AF McDonald, Elizabeth S. McCarthy, Anne Marie Akhtar, Amana L. Synnestvedt, Marie B. Schnall, Mitchell Conant, Emily F. TI Baseline Screening Mammography: Performance of Full-Field Digital Mammography Versus Digital Breast Tomosynthesis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE baseline screening; digital breast tomosynthesis; full-field digital mammography; recall screening harms; screening mammography ID IMPLEMENTATION; COMBINATION; IMAGES AB OBJECTIVE. Baseline mammography studies have significantly higher recall rates than mammography studies with available comparison examinations. Digital breast tomosynthesis reduces recalls when compared with digital mammographic screening alone, but many sites operate in a hybrid environment. To maximize the effect of screening digital breast tomosynthesis with limited resources, choosing which patient populations will benefit most is critical. This study evaluates digital breast tomosynthesis in the baseline screening population. MATERIALS AND METHODS. Outcomes were compared for 10,728 women who underwent digital mammography screening, including 1204 (11.2%) baseline studies, and 15,571 women who underwent digital breast tomosynthesis screening, including 1859 (11.9%) baseline studies. Recall rates, cancer detection rates, and positive predictive values were calculated. Logistic regression estimated the odds ratios of recall for digital mammography versus digital breast tomosynthesis for patients undergoing baseline screening and previously screened patients, adjusted for age, race, and breast density. RESULTS. In the baseline subgroup, recall rates for digital mammography and digital breast tomosynthesis screening were 20.5% and 16.0%, respectively (p = 0.002); digital breast tomosynthesis screening in the baseline subgroup resulted in a 22% reduction in recall compared with digital mammography, or 45 fewer patients recalled per 1000 patients screened. Digital breast tomosynthesis screening in the previously screened patients resulted in recall reduction of 14.3% (p < 0.001; p for interaction = 0.21). The recall rate reduction for baseline screening was especially pronounced in women younger than 50 years (p = 0.005). DBT implementation resulted in an increase in cancer detection in the baseline subgroup of 40.5% versus an increase in the previously screened subgroup of 17.4%. DBT implementation resulted in an increase in PPV1 in the baseline subgroup of 85% versus 35.3% in the previously screened subgroup, although the p-interaction was not significant. CONCLUSION. If resources are limited, women younger than 50 years who are undergoing baseline screening or do not have prior available mammograms may benefit more from digital breast tomosynthesis than from digital mammography alone. C1 [McDonald, Elizabeth S.; Akhtar, Amana L.; Schnall, Mitchell; Conant, Emily F.] Univ Penn, Perelman Sch Med, Dept Radiol, Breast Imaging Div, Philadelphia, PA 19104 USA. [McCarthy, Anne Marie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Synnestvedt, Marie B.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP McDonald, ES (reprint author), Univ Penn, Perelman Sch Med, Dept Radiol, Breast Imaging Div, 3400 Spruce St,1 Silverstein, Philadelphia, PA 19104 USA. EM Elizabeth.mcdonald@uphs.upenn.edu FU National Cancer Institute at the National Institutes of Health: Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) Network [U54CA163313] FX Supported by grant U54CA163313 from the National Cancer Institute at the National Institutes of Health: Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) Network. NR 18 TC 8 Z9 8 U1 1 U2 7 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 2015 VL 205 IS 5 BP 1143 EP 1148 DI 10.2214/AJR.15.14406 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU8SV UT WOS:000363814900046 PM 26496565 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI "Off Label" Use of FDA-Approved Devices and Digital Breast Tomosynthesis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE breast; breast cancer screening; digital breast tomosynthesis; mammography ID ONE-VIEW; MAMMOGRAPHY; COMBINATION; READER AB OBJECTIVE. The purpose of this article is to clarify for radiologists the meaning of U.S. Food and Drug Administration (FDA) approval with respect to Digital Breast Tomosynthesis (DBT). CONCLUSION. DBT is a major improvement over 2D mammography in the detection of cancers (sensitivity) and the reduction in recalls resulting from screening (specificity). Most imaging systems that have been approved by the FDA are used "off label" for breast imaging. Although the FDA determines which claims a manufacturer can make for a device, physicians may use approved devices, such as DBT, off label to provide better patient care. C1 Harvard Univ, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Radiol,Breast Imaging Div,Avon Breast Ctr,Me, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Radiol,Breast Imaging Div,Avon Breast Ctr,Me, Ste 240,55 Fruit St, Boston, MA 02114 USA. EM dkopans@partners.org NR 15 TC 0 Z9 0 U1 0 U2 1 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 2015 VL 205 IS 5 BP 1149 EP 1151 DI 10.2214/AJR.15.14632 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU8SV UT WOS:000363814900047 PM 26496566 ER PT J AU Drapkin, ZA Lindgren, KA Lopez, MJ Stabio, ME AF Drapkin, Zachary A. Lindgren, Kristen A. Lopez, Michael J. Stabio, Maureen E. TI Development and assessment of a new 3D neuroanatomy teaching tool for MRI training SO ANATOMICAL SCIENCES EDUCATION LA English DT Article DE neuroanatomy education; medical education; brain; magnetic resonance imaging; three-dimensional; two-dimensional sections; brain imaging; computer-based instructions ID MEDICAL-EDUCATION; VIRTUAL-REALITY; COMPUTER-MODELS; ANATOMY; NEUROLOGY; TRACTOGRAPHY; INSTRUCTION; STUDENTS; SYSTEM AB A computerized three-dimensional (3D) neuroanatomy teaching tool was developed for training medical students to identify subcortical structures on a magnetic resonance imaging (MRI) series of the human brain. This program allows the user to transition rapidly between two-dimensional (2D) MRI slices, 3D object composites, and a combined model in which 3D objects are overlaid onto the 2D MRI slices, all while rotating the brain in any direction and advancing through coronal, sagittal, or axial planes. The efficacy of this tool was assessed by comparing scores from an MRI identification quiz and survey in two groups of first-year medical students. The first group was taught using this new 3D teaching tool, and the second group was taught the same content for the same amount of time but with traditional methods, including 2D images of brain MRI slices and 3D models from widely used textbooks and online sources. Students from the experimental group performed marginally better than the control group on overall test score (P=0.07) and significantly better on test scores extracted from questions involving C-shaped internal brain structures (P<0.01). Experimental participants also expressed higher confidence in their abilities to visualize the 3D structure of the brain (P=0.02) after using this tool. Furthermore, when surveyed, 100% of the students in the experimental group recommended this tool for future students. These results suggest that this neuroanatomy teaching tool is an effective way to train medical students to read an MRI of the brain and is particularly effective for teaching C-shaped internal brain structures. (c) 2015 American Association of Anatomists. C1 [Drapkin, Zachary A.] Univ Utah, Dept Surg, Div Emergency Med, Salt Lake City, UT USA. [Lindgren, Kristen A.] Massachusetts Gen Hosp, Dept Neurol, Div Child Neurol, Boston, MA 02114 USA. [Lindgren, Kristen A.] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Michael J.] Skidmore Coll, Dept Math & Comp Sci, Saratoga Springs, NY 12866 USA. [Stabio, Maureen E.] Univ Colorado, Dept Cell & Dev Biol, Sch Med, Aurora, CO 80045 USA. RP Stabio, ME (reprint author), Univ Colorado, Dept Cell & Dev Biol, Sch Med, Mail Stop F435,13001 E 17th Pl,Room N5209B, Aurora, CO 80045 USA. EM maureen.stabio@ucdenver.edu NR 37 TC 3 Z9 3 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1935-9772 EI 1935-9780 J9 ANAT SCI EDUC JI Anat. Sci. Educ. PD NOV-DEC PY 2015 VL 8 IS 6 BP 502 EP 509 DI 10.1002/ase.1509 PG 8 WC Education, Scientific Disciplines SC Education & Educational Research GA CU8DH UT WOS:000363770900002 PM 25573020 ER PT J AU Bateman, BT Butwick, AJ Huybrechts, KF AF Bateman, Brian T. Butwick, Alexander J. Huybrechts, Krista F. TI What Is the True Incidence of Postpartum Hemorrhage? Response SO ANESTHESIA AND ANALGESIA LA English DT Letter ID SAMPLE C1 [Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. [Butwick, Alexander J.] Stanford Univ, Med Ctr, Dept Anesthesia, Stanford, CA 94305 USA. [Huybrechts, Krista F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. EM bbateman@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2015 VL 121 IS 5 BP 1397 EP 1398 DI 10.1213/ANE.0000000000000847 PG 2 WC Anesthesiology SC Anesthesiology GA CU1QQ UT WOS:000363296800014 PM 26484466 ER PT J AU Marquie, M Normandin, MD Vanderburg, CR Costantino, IM Bien, EA Rycyna, LG Klunk, WE Mathis, CA Ikonomovic, MD Debnath, ML Vasdev, N Dickerson, BC Gomperts, SN Growdon, JH Johnson, KA Frosch, MP Hyman, BT Gomez-Isla, T AF Marquie, Marta Normandin, Marc D. Vanderburg, Charles R. Costantino, Isabel M. Bien, Elizabeth A. Rycyna, Lisa G. Klunk, William E. Mathis, Chester A. Ikonomovic, Milos D. Debnath, Manik L. Vasdev, Neil Dickerson, Bradford C. Gomperts, Stephen N. Growdon, John H. Johnson, Keith A. Frosch, Matthew P. Hyman, Bradley T. Gomez-Isla, Teresa TI Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue SO ANNALS OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; NEURITIC PLAQUES; MOUSE MODEL; DIAGNOSIS; CONSENSUS; CRITERIA; DEGENERATION; TAUOPATHIES; CONSORTIUM AB ObjectiveTo examine region- and substrate-specific autoradiographic and in vitro binding patterns of positron emission tomography tracer [F-18]-AV-1451 (previously known as T807), tailored to allow in vivo detection of paired helical filament-tau-containing lesions, and to determine whether there is off-target binding to other amyloid/non-amyloid proteins. MethodsWe applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography, and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau, frontotemporal lobar degeneration-transactive response DNA binding protein 43 (TDP-43), progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology. ResultsOur data suggest that [F-18]-AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer brains (eg, intraneuronal and extraneuronal tangles and dystrophic neurites), but does not seem to bind to a significant extent to neuronal and glial inclusions mainly composed of straight tau filaments in non-Alzheimer tauopathy brains or to lesions containing -amyloid, -synuclein, or TDP-43. [F-18]-AV-1451 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions was identified. InterpretationOur data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention. Ann Neurol 2015 Ann Neurol 2015;78:Ann Neurol 2015;78:679-696 C1 [Marquie, Marta; Vanderburg, Charles R.; Costantino, Isabel M.; Bien, Elizabeth A.; Rycyna, Lisa G.; Gomperts, Stephen N.; Frosch, Matthew P.; Hyman, Bradley T.; Gomez-Isla, Teresa] MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Marquie, Marta; Vanderburg, Charles R.; Costantino, Isabel M.; Bien, Elizabeth A.; Rycyna, Lisa G.; Dickerson, Bradford C.; Gomperts, Stephen N.; Growdon, John H.; Johnson, Keith A.; Frosch, Matthew P.; Hyman, Bradley T.; Gomez-Isla, Teresa] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Marquie, Marta] Autonomous Univ Barcelona, Med Doctoral Studies, Barcelona, Spain. [Normandin, Marc D.; Vasdev, Neil] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol, Ctr Adv Med Imaging Sci,Div Nucl Med & Mol Imagin, Boston, MA 02115 USA. [Vanderburg, Charles R.; Bien, Elizabeth A.; Rycyna, Lisa G.; Hyman, Bradley T.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA 02115 USA. [Klunk, William E.; Debnath, Manik L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Mathis, Chester A.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] Vet Adm Pittsburgh Clin Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Gomez-Isla, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC, Suite 715,15th Parkman St, Boston, MA 02114 USA. EM tgomezisla@mgh.harvard.edu OI Marquie, Marta/0000-0002-0660-0950 FU ASISA Foundation (Madrid, Spain); NIH National Institute of Neurological Disorders and Stroke [U01NS086659]; NIH National Institute of Mental Health [R01MH100350]; Harvard Neuro-Discovery Center (Boston, MA); NIH National Institute on Aging [AG025204, AG005133, AG014449, AG005134, AG036694] FX This study was supported by the ASISA Foundation (Madrid, Spain; M.M.); NIH National Institute of Neurological Disorders and Stroke (U01NS086659, M.D.N.); NIH National Institute of Mental Health (R01MH100350, M.D.N.); Harvard Neuro-Discovery Center (Boston, MA; C.R.V.); and NIH National Institute on Aging (AG005133, AG025204, W.E.K.; AG005133, AG025204, C.A.M.; AG025204, AG014449, M.D.I.; AG005134 and AG036694, T.G.-I.). NR 26 TC 69 Z9 70 U1 6 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2015 VL 78 IS 5 BP 787 EP 800 DI 10.1002/ana.24517 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CU7NP UT WOS:000363727900013 PM 26344059 ER PT J AU Grassi, CM Cruzat, A Taniguchi, EV Crnej, A Colby, KA Dohlman, CH Chodosh, J AF Grassi, Christina M. Cruzat, Andrea Taniguchi, Elise V. Crnej, Alja Colby, Kathryn A. Dohlman, Claes H. Chodosh, James TI Periprosthetic Tissue Loss in Patients With Idiopathic Vitreous Inflammation After the Boston Keratoprosthesis SO CORNEA LA English DT Article DE keratoprosthesis; anterior segment OCT; idiopathic vitritis ID OPTICAL COHERENCE TOMOGRAPHY; TYPE-1 KERATOPROSTHESIS; ANTERIOR SEGMENT; I KERATOPROSTHESIS; MANAGEMENT; INTERFACE; VITRITIS; IMPLANT; PLATE AB Purpose:Idiopathic vitritis is a poorly understood complication after Boston keratoprosthesis surgery with unclear etiology. We sought to determine whether an association exists between periprosthetic corneal tissue loss and the development of idiopathic vitritis in keratoprosthesis recipients.Methods:Thirteen Boston type I keratoprosthesis recipient eyes with a history of idiopathic vitritis and 34 type I keratoprosthesis recipient eyes with no history of idiopathic vitritis underwent anterior segment optical coherence tomography (AS-OCT) at a median time postoperatively of 2.4 years versus 1.9 years (range, 0.5-14.2 vs. 0.1-13.6 years), respectively. Areas of corneal graft tissue loss (gaps) around the keratoprosthesis stem were identified and analyzed by 2 masked observers. The difference in the presence, number, and size of gaps was compared between cases and controls.Results:A periprosthetic gap was identified more commonly in idiopathic vitritis cases than in controls on AS-OCT (11/13, 86% vs. 11/34, 33.3%, P < 0.001). The number of gaps between cases and controls was also significantly different (2.6 1.6 vs. 0.5 +/- 0.8, P < 0.001), but not the estimated gap area (0.056 +/- 0.049 mm(2) vs. 0.039 +/- 0.025 mm(2), P = 0.22).Conclusions:A significantly higher proportion of keratoprosthesis recipient eyes with idiopathic vitritis had corneal tissue loss around the keratoprosthesis stem than did controls. Tissue loss could serve as an entry point for debris or bacterial components, triggering idiopathic vitritis. Our study underscores the utility of AS-OCT imaging in the postoperative management of keratoprosthesis patients. C1 [Grassi, Christina M.; Cruzat, Andrea; Taniguchi, Elise V.; Crnej, Alja; Colby, Kathryn A.; Dohlman, Claes H.; Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Chodosh, J (reprint author), 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU Research to Prevent Blindness, New York, NY FX Supported by a Medical Student Eye Research Fellowship to C. M. Grassi. from Research to Prevent Blindness, New York, NY. The sponsor had no role in the design or conduct of this research. NR 25 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD NOV PY 2015 VL 34 IS 11 BP 1378 EP 1382 DI 10.1097/ICO.0000000000000557 PG 5 WC Ophthalmology SC Ophthalmology GA CU6HK UT WOS:000363632500009 PM 26226472 ER PT J AU Chen, HA Kleinberger, JW Takane, KK Salim, F Fiaschi-Taesch, N Pappas, K Parsons, R Jiang, J Zhang, Y Liu, HT Wang, P Bender, AS Frank, SJ Stewart, AF AF Chen, Hainan Kleinberger, Jeffrey W. Takane, Karen K. Salim, Fatimah Fiaschi-Taesch, Nathalie Pappas, Kyrie Parsons, Ramon Jiang, Jing Zhang, Yue Liu, Hongtao Wang, Peng Bender, Aaron S. Frank, Stuart J. Stewart, Andrew F. TI Augmented Stat5 Signaling Bypasses Multiple Impediments to Lactogen-Mediated Proliferation in Human beta-Cells SO DIABETES LA English DT Article ID GESTATIONAL DIABETES-MELLITUS; ISLET FUNCTION; PROLACTIN RECEPTORS; PLACENTAL LACTOGENS; INSULIN-SECRETION; GENE-EXPRESSION; CYCLIN D-1; IN-VIVO; PREGNANCY; MICE AB Pregnancy in rodents is associated with a two- to three-fold increase in beta-cell mass, which is attributable to large increases in beta-cell proliferation, complimented by increases in beta-cell size, survival, and function and mediated mainly by the lactogenic hormones prolactin (PRL) and placental lactogens. In humans, however, beta-cell mass does not increase as dramatically during pregnancy, and PRL fails to activate proliferation in human islets in vitro. To determine why, we explored the human PRL-prolactin receptor (hPRLR)-Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5)-cyclin-cdk signaling cascade in human beta-cells. Surprisingly, adult human beta-cells express little or no PRLR. As expected, restoration of the hPRLR in human beta-cells rescued JAK2-STAT5 signaling in response to PRL. However, rescuing hPRLR-STAT5 signaling nevertheless failed to confer proliferative ability on adult human beta-cells in response to PRL. Surprisingly, mouse (but not human) Stat5a overexpression led to upregulation of cyclins D1-3 and cdk4, as well as their nuclear translocation, all of which are associated with beta-cell cycle entry. Collectively, the findings show that human beta-cells fail to proliferate in response to PRL for multiple reasons, one of which is a paucity of functional PRL receptors, and that murine Stat5 overexpression is able to bypass these impediments. C1 [Chen, Hainan; Takane, Karen K.; Fiaschi-Taesch, Nathalie; Liu, Hongtao; Wang, Peng; Bender, Aaron S.; Stewart, Andrew F.] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY 10029 USA. [Kleinberger, Jeffrey W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Salim, Fatimah] Duquesne Univ, Sch Nursing, Pittsburgh, PA 15219 USA. [Pappas, Kyrie; Parsons, Ramon] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA. [Jiang, Jing; Zhang, Yue; Frank, Stuart J.] Univ Alabama Birmingham, Div Endocrinol Diabet & Metab, Birmingham, AL USA. [Frank, Stuart J.] Birmingham VA Med Ctr, Endocrinol Sect, Birmingham, AL USA. RP Chen, HA (reprint author), Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY 10029 USA. EM hainanchen2011@gmail.com; andrew.stewart@mssm.edu FU JDRF [1-2011-603]; National Institutes of Health [R-01 DK55023, R-01 DK58259, R-01 DK 46395, U-01 DK089538, UC4 DK104211]; James A. Haley Veterans' Hospital Merit Review FX This work was supported by JDRF grant 1-2011-603; National Institutes of Health grants R-01 DK55023, R-01 DK58259, R-01 DK 46395, U-01 DK089538, and UC4 DK104211; and a James A. Haley Veterans' Hospital Merit Review (to S.J.F.). NR 49 TC 9 Z9 9 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2015 VL 64 IS 11 BP 3784 EP 3797 DI 10.2337/db15-0083 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU8ZL UT WOS:000363832500018 PM 26159175 ER PT J AU Mishra, RK Tietjens, J Regan, M Whooley, MA Schiller, NB AF Mishra, Rakesh K. Tietjens, Jeremy Regan, Mathilda Whooley, Mary A. Schiller, Nelson B. TI The Prognostic Utility of Echo-Estimated Left Ventricular End-Diastolic Pressure-Volume Relationship in Stable Coronary Artery Disease: The Heart and Soul Study SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE coronary artery disease; diastolic function; echocardiography; heart failure; left ventricular end-diastolic pressure ID PRESERVED EJECTION FRACTION; LEFT ATRIAL VOLUME; DOPPLER-ECHOCARDIOGRAPHY; CARDIOVASCULAR EVENTS; NATRIURETIC PEPTIDE; AMBULATORY PATIENTS; NT-PROBNP; FAILURE; DYSFUNCTION; STIFFNESS AB Background: While changes in the left ventricular end-diastolic pressure-volume relationship (LV-EDPVR) can be estimated using echocardiography, their prognostic utility in stable coronary artery disease (CAD) is unknown. Methods: Using echo-estimated LV end-diastolic volume index and diastolic function category, the relative position of the LV-EDPVR was defined in 901 participants with stable CAD as: (1) left-shifted, (2) right-shifted, or (3) intermediate. We then evaluated the association of LV-EDPVR position relative to the intermediate category with time to hospitalization for heart failure (HF) or cardiovascular (CV) death using Cox proportional hazards models. Results: During 7.0 +/- 3.1 years of follow-up, there were 207 admissions for HF or CV deaths. Both leftward and rightward shifts of LV-EDPVR were associated with a significantly higher risk of HF or CV death (HR 1.73, 95% CI 1.15-2.62 and HR 6.75, 95% CI 4.02-11.31, respectively). In multivariable-adjusted models, these associations were attenuated but remained significant (HR 1.66, 95% CI 1.08-2.55 for left-shifted and HR 4.19, 95% CI 2.32-7.55 for right-shifted). The association of LV-EDPVR with HF or CV death was no longer significant after inclusion of N-terminal pro-brain natriuretic peptide level as a covariate. Conclusions: In stable CAD, echo-estimated leftward and rightward shifts in the LV-EDPVR are associated with HF and CV death. The loss of these associations after adjustment for N-terminal pro-brain natriuretic peptide level suggests that echo-estimated LV-EDPVR captures changes in LV filling pressure at any given LV end-diastolic volume. C1 [Mishra, Rakesh K.; Tietjens, Jeremy; Whooley, Mary A.; Schiller, Nelson B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mishra, Rakesh K.; Regan, Mathilda; Whooley, Mary A.; Schiller, Nelson B.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Mishra, RK (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111C, San Francisco, CA 94121 USA. EM rakesh.mishra@ucsf.edu NR 41 TC 0 Z9 0 U1 0 U2 0 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 2015 VL 32 IS 11 BP 1639 EP 1646 DI 10.1111/echo.12955 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU7SA UT WOS:000363740600005 PM 25959601 ER PT J AU Jung, DS Farmakiotis, D Jiang, Y Tarrand, JJ Kontoyiannis, DP AF Jung, Dong Sik Farmakiotis, Dimitrios Jiang, Ying Tarrand, Jeffrey J. Kontoyiannis, Dimitrios P. TI Uncommon Candida Species Fungemia among Cancer Patients, Houston, Texas, USA SO EMERGING INFECTIOUS DISEASES LA English DT Article ID MARROW TRANSPLANT RECIPIENTS; HEMATOLOGIC MALIGNANCIES; ANTIFUNGAL AGENTS; RISK-FACTORS; DECREASED SUSCEPTIBILITY; PROPHYLACTIC FLUCONAZOLE; ECHINOCANDIN RESISTANCE; GUILLIERMONDII FUNGEMIA; EPIDEMIOLOGY; CASPOFUNGIN AB Many uncommon Candida species that cause bloodstream infections (BSIs) are not well-characterized. We investigated the epidemiology, antifungal use, susceptibility patterns, and factors associated with all-cause death among cancer patients in whom uncommon Candida BSIs were diagnosed at a cancer treatment center during January 1998 September 2013. Of 1,395 Candida bloodstream isolates, 79 from 68 patients were uncommon Candida spp. The incidence density of uncommon Candida spp. BSIs and their proportion to all candidemia episodes substantively increased during the study period, and the rise was associated with increasing use of echinocandin antifungal drugs. Thirty-seven patients had breakthrough infections during therapy or prophylaxis with various systemic antifungal drugs for >= 7 consecutive days; 21 were receiving an echinocandin. C. kefyr (82%), and C. lusitaniae (21%) isolates frequently showed caspofungin MICs above the epidemiologic cutoff values. These findings support the need for institutional surveillance for uncommon Candida spp among cancer patients. C1 [Jung, Dong Sik] Dong A Univ, Coll Med, Busan, South Korea. [Jung, Dong Sik; Farmakiotis, Dimitrios; Jiang, Ying; Tarrand, Jeffrey J.; Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Farmakiotis, Dimitrios] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Farmakiotis, D (reprint author), T Boone Pickens Acad Tower,FCT12-5070, Houston, TX 77030 USA. EM dkontoyi@mdanderson.org FU Merck Co, Inc.; Astellas Pharma US; Pfizer FX Dong Sik Jung, MD; Dimitrios Farmakiotis, MD; Ying Jiang, MS; and Jeffrey J. Tarrand, MD, have disclosed no relevant financial relationships. Dimitrios P. Kontoyiannis, MD, ScD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Merck & Co, Inc., Astellas Pharma US; served as a speaker or a member of a speakers bureau for Merck & Co, Inc., Astellas Pharma US, Gilead Sciences, Inc.; received grants for clinical research from Merck & Co, Inc., Astellas Pharma US, Pfizer. NR 39 TC 5 Z9 5 U1 0 U2 1 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2015 VL 21 IS 11 BP 1942 EP 1950 DI 10.3201/eid2111.150404 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU5WA UT WOS:000363601500007 PM 26488845 ER PT J AU Quinn, LS Anderson, BG Conner, JD Wolden-Hanson, T AF Quinn, LeBris S. Anderson, Barbara G. Conner, Jennifer D. Wolden-Hanson, Tami TI Circulating irisin levels and muscle FNDC5 mRNA expression are independent of IL-15 levels in mice SO ENDOCRINE LA English DT Article DE Irisin; Interleukin-15; Muscle; Exercise; Cytokines; Myokines ID BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; PPAR-DELTA; EXERCISE; INTERLEUKIN-15; FAT; HUMANS; ASSOCIATION; ADIPOCYTES; RESISTANCE AB Interleukin-15 (IL-15) and irisin are exercise-induced myokines that exert favorable effects on energy expenditure and metabolism. IL-15 can induce PGC-1 alpha expression, which in turn induces expression of irisin and its precursor, FNDC5. Therefore, the present study tested the hypothesis that increases in circulating irisin levels and muscle FNDC5 mRNA expression are dependent on IL-15. Circulating irisin levels and gastrocnemius muscle FNDC5 mRNA expression were examined following acute exercise in control and IL-15-deleted (IL-15 KO) mice, following injection of IL-15 into IL-15 KO mice, and in transgenic mice with elevated circulating IL-15 levels (IL-15 Tg mice). Circulating IL-15 levels and muscle PGC-1 alpha and PPAR delta mRNA expressions were determined as positive controls. No effect of IL-15 deletion on post-exercise serum irisin levels or muscle FNDC5 mRNA expression was detected. While serum IL-15 levels and muscle PGC-1 alpha expression were elevated post-exercise in control mice, both serum irisin levels and muscle FNDC5 expression decreased shortly after exercise in both control and IL-15 KO mice. A single injection of recombinant IL-15 into IL-15 KO mice that significantly increased muscle PPAR delta and PGC-1 alpha mRNA expressions had no effect on circulating irisin release, but modestly induced muscle FNDC5 expression. Additionally, serum irisin and gastrocnemius muscle FNDC5 expression in IL-15 Tg mice were similar to those of control mice. Muscle FNDC5 mRNA expression and irisin release are not IL-15-dependent in mice. C1 [Quinn, LeBris S.; Anderson, Barbara G.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Quinn, LeBris S.; Wolden-Hanson, Tami] VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. [Quinn, LeBris S.; Anderson, Barbara G.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Quinn, LeBris S.; Conner, Jennifer D.] Seattle Inst Biomed & Clin Res, Seattle, WA 98108 USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, S-182 GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM quinnL@uw.edu FU Department of Veterans Affairs [BX001026] FX Supported by Merit Review #BX001026 from the Department of Veterans Affairs (LSQ), and use of resources and facilities at VA Puget Sound Health Care System. NR 34 TC 1 Z9 1 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD NOV PY 2015 VL 50 IS 2 BP 368 EP 377 DI 10.1007/s12020-015-0607-9 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU4HP UT WOS:000363488800015 PM 25920499 ER PT J AU Rubin, MR Goldfine, AB McMahon, DJ Donovan, DS Cremers, S Dworakowski, E Schaefer, EJ Shoelson, SE Silverberg, SJ AF Rubin, Mishaela R. Goldfine, Allison B. McMahon, Donald J. Donovan, Daniel S. Cremers, Serge Dworakowski, Elzbieta Schaefer, Ernst J. Shoelson, Steven E. Silverberg, Shonni J. TI Effects of the anti-inflammatory drug salsalate on bone turnover in type 2 diabetes mellitus SO ENDOCRINE LA English DT Editorial Material ID INSULIN-RESISTANCE; KAPPA-B; RECEPTOR ACTIVATOR; SERUM OSTEOCALCIN; FRACTURE RISK; INFLAMMATION; RESORPTION; MARKERS; BETA C1 [Rubin, Mishaela R.; McMahon, Donald J.; Cremers, Serge; Dworakowski, Elzbieta; Silverberg, Shonni J.] Columbia Univ Coll Phys & Surg, Dept Med, Metab Bone Dis Unit, New York, NY 10032 USA. [Goldfine, Allison B.; Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Donovan, Daniel S.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Schaefer, Ernst J.] Tufts Univ, Lipid Metab Lab, Boston, MA 02111 USA. RP Rubin, MR (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, Metab Bone Dis Unit, 630 W 168th St, New York, NY 10032 USA. EM mrr6@columbia.edu FU NHLBI NIH HHS [P50 HL083813]; NIDDK NIH HHS [K24 DK074457, P30 DK036836, P01 DK036836, RC4 DK090776, U01 DK74556, U01 DK074556] NR 18 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD NOV PY 2015 VL 50 IS 2 BP 504 EP 507 DI 10.1007/s12020-015-0535-8 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU4HP UT WOS:000363488800030 PM 25636441 ER PT J AU McAvoy, K Russo, C Kim, S Rankin, G Sahay, A AF McAvoy, Kathleen Russo, Craig Kim, Shannen Rankin, Genelle Sahay, Amar TI Fluoxetine induces input-specific hippocampal dendritic spine remodeling along the septotemporal axis in adulthood and middle age SO HIPPOCAMPUS LA English DT Article DE fluoxetine; dendritic spines; hippocampus; aging; neurogenesis; dematuration; dentate gyrus; CA1 ID DEPRESSIVE-LIKE BEHAVIOR; LONG-TERM POTENTIATION; CA1 PYRAMIDAL CELLS; DORSAL-VENTRAL AXIS; DENTATE GYRUS; STRUCTURAL PLASTICITY; ANTIDEPRESSANT TREATMENTS; SYNAPTIC PLASTICITY; DORSOVENTRAL AXIS; RAT HIPPOCAMPUS AB Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is known to induce structural rearrangements and changes in synaptic transmission in hippocampal circuitry. In the adult hippocampus, structural changes include neurogenesis, dendritic, and axonal plasticity of pyramidal and dentate granule neurons, and dedifferentiation of dentate granule neurons. However, much less is known about how chronic fluoxetine affects these processes along the septotemporal axis and during the aging process. Importantly, studies documenting the effects of fluoxetine on density and distribution of spines along different dendritic segments of dentate granule neurons and CA1 pyramidal neurons along the septotemporal axis of hippocampus in adulthood and during aging are conspicuously absent. Here, we use a transgenic mouse line in which mature dentate granule neurons and CA1 pyramidal neurons are genetically labeled with green fluorescent protein (GFP) to investigate the effects of chronic fluoxetine treatment (18 mg/kg/day) on input-specific spine remodeling and mossy fiber structural plasticity in the dorsal and ventral hippocampus in adulthood and middle age. In addition, we examine levels of adult hippocampal neurogenesis, maturation state of dentate granule neurons, neuronal activity, and glutamic acid decarboxylase-67 expression in response to chronic fluoxetine in adulthood and middle age. Our studies reveal that while chronic fluoxetine fails to augment adult hippocampal neurogenesis in middle age, the middle-aged hippocampus retains high sensitivity to changes in the dentate gyrus (DG) such as dematuration, hypoactivation, and increased glutamic acid decarboxylase 67 (GAD67) expression. Interestingly, the middle-aged hippocampus shows greater sensitivity to fluoxetine-induced input-specific synaptic remodeling than the hippocampus in adulthood with the stratum-oriens of CA1 exhibiting heightened structural plasticity. The input-specific changes and circuit-level modifications in middle-age were associated with modest enhancement in contextual fear memory precision, anxiety-like behavior and antidepressant-like behavioral responses. (c) 2015 Wiley Periodicals, Inc. C1 [McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA. [McAvoy, Kathleen; Russo, Craig; Kim, Shannen; Rankin, Genelle; Sahay, Amar] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sahay, A (reprint author), MGH, Ctr Regenerat Med, CPZN 4242,185 Cambridge St, Boston, MA 02114 USA. EM asahay@mgh.harvard.edu FU NIMH Biobehavioral Research Awards for Innovative New Scientists [1-R01MH104175]; Ellison Medical Foundation New Scholar in Aging; Whitehall Foundation; Harvard Stem Cell Institute Internship Program; Harvard College Research Program funds; Bennington College Field Work Term Grant FX Grant sponsor: NIMH Biobehavioral Research Awards for Innovative New Scientists; Grant number: 1-R01MH104175; Grant sponsors: Ellison Medical Foundation New Scholar in Aging and a Whitehall Foundation grant (to A.S.), Harvard Stem Cell Institute Internship Program (to C.R. and S.K.), Harvard College Research Program funds (to S.K.), and Bennington College Field Work Term Grant (to G.R.). NR 82 TC 7 Z9 8 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD NOV PY 2015 VL 25 IS 11 BP 1429 EP 1446 DI 10.1002/hipo.22464 PG 18 WC Neurosciences SC Neurosciences & Neurology GA CU6YW UT WOS:000363682300023 PM 25850664 ER PT J AU Hansson, S Rolfson, O Akesson, K Nemes, S Leonardsson, O Rogmark, C AF Hansson, Susanne Rolfson, Ola Akesson, Kristina Nemes, Szilard Leonardsson, Olof Rogmark, Cecilia TI Complications and patient-reported outcome after hip fracture. A consecutive annual cohort study of 664 patients SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Hip fracture; Fast-track; Complications; Patient-reported outcome; Function ID FEMORAL-NECK FRACTURES; QUALITY-OF-LIFE; NATIONAL REGISTRATION; FUNCTIONAL STATUS; CARE; MORTALITY; RECOVERY; TIME AB Introduction: The aim of every patient with hip fracture is to regain previous function but we know little about the outcome, especially patient-reported outcome. We wanted to investigate what factors influence the result one year after hip fracture, including fast-track for hip fracture patients, as well as investigating the patients' satisfaction with their rehabilitation and to what degree they regained their pre-fracture function. Methods: All patients (>20 years, non-pathological fracture, residents in the catchment area, n = 664) having surgery for hip fracture at our hospital during 2011 were included in a retrospective cohort study. From medical records, information was gathered about pre-fracture condition as well as fracture type, surgical details, length of stay and whether the patient entered the hospital through the fast-track system. Medical records were scrutinised for general complications up to six months and for local complications up to one year after surgery. A postal questionnaire was sent one year after surgery inquiring about health status, pain and satisfaction along with multiple-choice questions regarding mobility and rehabilitation. Variables were analysed with linear regression or the proportional odds model. Results: The most common general complications were new falls, pneumonia and new fractures. Deep infection was the most frequent local complication. The only significant effect of the fast-track system was shorter time to surgery (78 vs. 62% had surgery within 24 h, p < 0.001). A total of 29% reported to have regained their previous mobility and 30% considered the rehabilitation to be adequate. Mean value for pain VAS was 24 (SD 22) and for satisfaction 28 (SD 25). Absence of general and local complications correlated to satisfaction and hip pain. General complications correlated to loss of function. Higher age correlated to inadequate rehabilitation. Conclusion: General complications seem to be the major risk factor, being the only factor affecting functional outcome and together with local complications affecting pain and satisfaction. To avoid general complications, co-operation between orthopaedic surgeons and internists may be crucial in the aftercare of hip fracture patients. A majority did not receive adequate rehabilitation and efforts need to be made to improve the rehabilitation process. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Hansson, Susanne; Akesson, Kristina; Rogmark, Cecilia] Lund Univ, Dept Orthopaed, Skane Univ Hosp, Malmo, Sweden. [Rolfson, Ola; Nemes, Szilard; Rogmark, Cecilia] Registerctr VGR, Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Rolfson, Ola] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden. [Rolfson, Ola] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Leonardsson, Olof] Blekinge Hosp, Dept Orthopaed, Karlskrona, Sweden. RP Hansson, S (reprint author), Skane Univ Hosp, Dept Orthopaed, SE-20502 Malmo, Sweden. EM susanne.hansson@med.lu.se RI Hansson, Susanne/K-9183-2015; OI Hansson, Susanne/0000-0001-7679-9398; Rolfson, Ola/0000-0001-6534-1242 NR 25 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 EI 1879-0267 J9 INJURY JI Injury-Int. J. Care Inj. PD NOV PY 2015 VL 46 IS 11 BP 2206 EP 2211 DI 10.1016/j.injury.2015.07.024 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA CU9XY UT WOS:000363901600020 PM 26298023 ER PT J AU Parikh, VN Park, J Nikolic, I Channick, R Yu, PB De Marco, T Hsue, PY Chan, SY AF Parikh, Victoria N. Park, Joseph Nikolic, Ivana Channick, Richard Yu, Paul B. De Marco, Teresa Hsue, Priscilla Y. Chan, Stephen Y. TI Coordinated Modulation of Circulating miR-21 in HIV, HIV-Associated Pulmonary Arterial Hypertension, and HIV/Hepatitis C Virus Coinfection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE microRNA; HIV; HCV coinfection; HIV-PAH ID CD4(+) T-LYMPHOCYTES; MICRORNAS; EXPRESSION; BIOMARKERS; INFECTION; THERAPY; HYPOXIA; DISEASE; PATHOGENESIS; REPLICATION AB Dysregulation of microRNA-21 (miR-21) is independently associated with HIV infection, pulmonary arterial hypertension (PAH), and hepatitis C virus (HCV) infection. To assess the expression of miR-21 in these overlapping comorbidities, we measured plasma miR-21 in HIV with and without PAH and then stratified by concomitant HCV infection. MiR-21 was increased in HIV and HIV-PAH versus uninfected subjects, but it did not differ between these groups. HIV/HCV coinfection correlated with even higher miR-21 levels within the HIV-infected population. These data reveal specific regulation of plasma miR-21 in HIV, HIV/HCV coinfection, and PAH and suggest that miR-21 may integrate complex disease-specific signaling in the setting of HIV infection. C1 [Parikh, Victoria N.; De Marco, Teresa; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Parikh, Victoria N.; De Marco, Teresa; Hsue, Priscilla Y.] Univ Calif San Francisco, San Francisco Gen Hosp, Ctr Excellence Vasc Res, San Francisco, CA 94110 USA. [Park, Joseph; Nikolic, Ivana; Yu, Paul B.; Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Channick, Richard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulmonol, Boston, MA USA. [Channick, Richard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Network Med, Boston, MA 02115 USA. RP Hsue, PY (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, Room 5G1 Cardiol SFGH,1001 Potrero Ave, San Francisco, CA 94110 USA. EM phsue@medsfgh.ucsf.edu; sychan@partners.org FU NIH [K08HL096834, R01HL124021, K24AI112393, R01HL095130]; McArthur-Radovsky Fund; Lerner Fund; Harris Fund; Watkins Fund; American Heart Association [14GRNT19600012]; Pulmonary Hypertension Association; United Therapeutics FX Supported by NIH [grants K08HL096834; R01HL124021 (S.Y.C.) and K24AI112393; R01HL095130 (P.Y.H.)]; the McArthur-Radovsky, Lerner, Harris, and Watkins Funds; the American Heart Association (14GRNT19600012) (S.Y.C.); and the Pulmonary Hypertension Association (S.Y.C.).; P.Y.H. has received honoraria from Gilead. T.D. is a consultant for Gilead and Actelion and has research grants from United Therapeutics. The remaining authors have no funding or conflicts of interest to disclose. NR 43 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2015 VL 70 IS 3 BP 236 EP 241 DI 10.1097/QAI.0000000000000741 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU6ID UT WOS:000363634600003 PM 26473639 ER PT J AU Attia, EF McGinnis, KA Feemster, LC Akgun, KM Butt, AA Graber, CJ Fine, MJ Goetz, MB Rodriguez-Barradas, MC Pisani, MA Tindle, HA Brown, ST Soo Hoo, GW Rimland, D Gibert, CL Huang, L Freiberg, MS Hough, CL Crothers, K AF Attia, Engi F. McGinnis, Kathleen A. Feemster, Laura C. Akguen, Kathleen M. Butt, Adeel A. Graber, Christopher J. Fine, Michael J. Goetz, Matthew B. Rodriguez-Barradas, Maria C. Pisani, Margaret A. Tindle, Hilary A. Brown, Sheldon T. Soo Hoo, Guy W. Rimland, David Gibert, Cynthia L. Huang, Laurence Freiberg, Matthew S. Hough, Catherine L. Crothers, Kristina TI Association of COPD With Risk for Pulmonary Infections Requiring Hospitalization in HIV-Infected Veterans SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE COPD; pulmonary infection; pneumonia; HIV; comorbidities ID COMMUNITY-ACQUIRED PNEUMONIA; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY ERA; BACTERIAL PNEUMONIA; DISEASE; COHORT; ADULTS; TRENDS; COMORBIDITY; MORBIDITY AB Background:Pulmonary infections remain more common in HIV-infected (HIV+) compared with uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients.Methods:We analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort from 1996 to 2009. Using International Classification of Diseases, Ninth Revision codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB), and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within 2 years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRRs) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4(+) cell count, HIV viral load, smoking status, substance use, vaccinations, and calendar year at baseline.Results:Unadjusted incidence rates of CAP, TB, and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; P 0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB, and PCP (IRR: 1.94, 95% confidence interval [CI]: 1.64 to 2.30; IRR: 2.60, 95% CI: 1.70 to 3.97; and IRR: 1.48, 95% CI: 1.10 to 2.01, respectively).Conclusions:COPD is an independent risk factor for CAP, TB, and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections. C1 [Attia, Engi F.; Feemster, Laura C.; Hough, Catherine L.; Crothers, Kristina] Univ Washington, Dept Med, Seattle, WA USA. [McGinnis, Kathleen A.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Feemster, Laura C.] Vet Affairs Puget Sound Healthcare Syst, Vet Affairs Hlth Serv Res & Dev, Seattle, WA USA. [Akguen, Kathleen M.] Vet Affairs Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. [Akguen, Kathleen M.; Pisani, Margaret A.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. [Butt, Adeel A.] Hamad Med Corp, Doha, Qatar. [Graber, Christopher J.; Goetz, Matthew B.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Graber, Christopher J.; Goetz, Matthew B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Med, Pittsburgh, PA 15213 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Tindle, Hilary A.; Freiberg, Matthew S.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Tindle, Hilary A.; Freiberg, Matthew S.] Nashville Vet Affairs Med Ctr, Nashville, TN USA. [Brown, Sheldon T.] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Brown, Sheldon T.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Rimland, David] Atlanta Vet Affairs Med Ctr, Dept Med, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Gibert, Cynthia L.] Washington DC Vet Affairs Med Ctr, Dept Med, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Sch Med, Washington, DC USA. [Huang, Laurence] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Attia, EF (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Pulm & Crit Care, 325 Ninth Ave,Campus Box 359762, Seattle, WA 98104 USA. EM eattia@uw.edu OI Butt, Adeel/0000-0002-1118-1826; Attia, Engi/0000-0002-5044-9602; Goetz, Matthew/0000-0003-4542-992X; Crothers, Kristina/0000-0001-9702-0371 FU National Institutes of Health [R01 HL090342, F32 HL125031-01, K23 HL111116, K24 HL087713, U24-AA020794] FX Supported by the National Institutes of Health (R01 HL090342, F32 HL125031-01, K23 HL111116, K24 HL087713, and U24-AA020794). NR 53 TC 2 Z9 3 U1 2 U2 7 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 1 PY 2015 VL 70 IS 3 BP 280 EP 288 DI 10.1097/QAI.0000000000000751 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU6ID UT WOS:000363634600010 PM 26181820 ER PT J AU Byakwaga, H Hunt, PW Laker-Oketta, M Glidden, DV Huang, Y Bwana, BM Mocello, AR Bennett, J Walusansa, V Dollard, SC Bangsberg, DR Mbidde, EK Martin, JN AF Byakwaga, Helen Hunt, Peter W. Laker-Oketta, Miriam Glidden, David V. Huang, Yong Bwana, Bosco M. Mocello, A. Rain Bennett, John Walusansa, Victoria Dollard, Sheila C. Bangsberg, David R. Mbidde, Edward K. Martin, Jeffrey N. TI The Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE tryptophan; kynurenine; indoleamine 2; 3-dioxygenase-1; HIV; Kaposi sarcoma; plasma HIV RNA; Africa ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; PLASMACYTOID DENDRITIC CELLS; HIV-INFECTED PATIENTS; HERPESVIRUS TYPE 8; T-CELL; INDOLEAMINE 2,3-DIOXYGENASE; HUMAN-HERPESVIRUS-8 INFECTION; HOMOSEXUAL-MEN; GROWTH-FACTOR AB Background:Other than Kaposi sarcoma (KS)-associated herpesvirus and CD4(+) T-cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3-dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T-cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.Methods:In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography-tandem mass spectrometry.Results:We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, interquartile range: 90 to 190 nM/M) than KS cases (110, interquartile range: 90 to 150 nM/M) (P = 0.004). After adjustment for age, sex, CD4 count, and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% confidence interval: 27% to 77%) in the odds of KS compared with those with the lowest (first quartile) levels. KS was also independently associated with lower CD4(+) count, higher plasma HIV RNA, and men.Conclusions:Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers. C1 [Byakwaga, Helen; Bwana, Bosco M.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Byakwaga, Helen; Hunt, Peter W.; Laker-Oketta, Miriam; Glidden, David V.; Huang, Yong; Mocello, A. Rain; Bennett, John; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Laker-Oketta, Miriam; Mbidde, Edward K.] Infect Dis Inst, Kampala, Uganda. [Walusansa, Victoria] Uganda Canc Inst, Kampala, Uganda. [Dollard, Sheila C.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. [Mbidde, Edward K.] Uganda Virus Res Inst, Entebbe, Uganda. RP Byakwaga, H (reprint author), Mbarara Univ Sci & Technol, POB 1397, Mbarara, Uganda. EM hbyakwaga@gmail.com FU National Institutes of Health (NIH) [D43 CA153717, R01 CA119903, R01 MH054097, U01 CA066529, U01 AI069911, P30 AI027763] FX Supported by National Institutes of Health (NIH) grants D43 CA153717, R01 CA119903, R01 MH054097, U01 CA066529, U01 AI069911, and P30 AI027763. NR 58 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2015 VL 70 IS 3 BP 296 EP 303 DI 10.1097/QAI.0000000000000747 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU6ID UT WOS:000363634600012 PM 26181812 ER PT J AU Johnson, HM Bartels, CM Thorpe, CT Schumacher, JR Pandhi, N Smith, MA AF Johnson, Heather M. Bartels, Christie M. Thorpe, Carolyn T. Schumacher, Jessica R. Pandhi, Nancy Smith, Maureen A. TI Differential Diagnosis and Treatment Rates Between Systolic and Diastolic Hypertension in Young Adults: A Multidisciplinary Observational Study SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID AMERICAN-HEART-ASSOCIATION; HIGH BLOOD-PRESSURE; PRIMARY-CARE USE; UNITED-STATES; CARDIOVASCULAR-DISEASE; ADMINISTRATIVE DATA; POPULATION; EDUCATION; RISK; RECOMMENDATIONS AB Differential rates of diagnosis and treatment by hypertension (HTN) type may contribute to poor HTN control in young adults. The objective of this study was to compare rates of receiving a hypertension diagnosis and antihypertensive agent among young adults with (1) isolated systolic, (2) isolated diastolic, and (3) combined systolic/diastolic HTN. A retrospective analysis was conducted in patients aged 18 to 39 years (n=3003) with incident HTN. Kaplan-Meier survival and Cox proportional hazards analyses were performed. Only 56% with isolated systolic HTN received a diagnosis compared with 63% (systolic/diastolic); 32% with isolated systolic HTN received an initial antihypertensive compared with 52% (systolic/diastolic). Compared with patients with systolic/diastolic HTN, those with isolated systolic HTN had a 50% slower diagnosis rate (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.41-0.60) and those with isolated diastolic HTN had a 26% slower rate (HR, 0.74; CI, 0.60-0.92). Patients with isolated systolic HTN had 58% slower medication initiation (HR, 0.42; CI, 0.34-0.51) and those with isolated diastolic HTN had 31% slower rates (HR,0.69; CI, 0.55-0.86). Young adults with isolated systolic HTN have lower diagnosis and treatment rates. (C) 2015 Wiley Periodicals, Inc. C1 [Johnson, Heather M.; Bartels, Christie M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Johnson, Heather M.; Bartels, Christie M.; Schumacher, Jessica R.; Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Madison, WI USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Schumacher, Jessica R.; Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. RP Johnson, HM (reprint author), Div Cardiovasc Med, H4-512 CSC,MC 3248,600 Highland Ave, Madison, WI 53792 USA. EM hm2@medicine.wisc.edu OI Johnson, Heather/0000-0002-4916-3519 FU Clinical and Translational Science Award program through the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1TR000427]; National Heart, Lung, and Blood Institute of the NIH [K23HL112907]; University of Wisconsin (UW) Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH [K23AR062381]; National Institute on Aging of the NIH [K08AG029527]; UW Health Innovation Program; UW School of Medicine and Public Health from The Wisconsin Partnership Program FX This original research was supported by the Clinical and Translational Science Award program, previously through the National Center for Research Resources (NCRRUL1RR025011), and now by the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) under award number UL1TR000427. Heather Johnson is supported by the National Heart, Lung, and Blood Institute of the NIH (K23HL112907), and also by the University of Wisconsin (UW) Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health. Christie Bartels is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (K23AR062381). Nancy Pandhi is supported by the National Institute on Aging of the NIH (K08AG029527). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders did not play any role in the study design; in the collection, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to submit the article for publication. Additional funding for this project was provided by the UW Health Innovation Program and the UW School of Medicine and Public Health from The Wisconsin Partnership Program. H. Johnson, C. Bartels, and N. Pandhi have clinical appointments with the academic group practice that has a financial interest in delivering care to the general population from which study participants were drawn. For the remaining authors, none were declared. NR 41 TC 1 Z9 1 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD NOV PY 2015 VL 17 IS 11 BP 885 EP 894 DI 10.1111/jch.12596 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CU7BA UT WOS:000363688500011 PM 26073687 ER PT J AU Breu, AC Theisen-Toupal, J Feldman, LS AF Breu, Anthony C. Theisen-Toupal, Jesse Feldman, Leonard S. TI Serum and red blood cell folate testing on hospitalized patients SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID FOLIC-ACID INTAKE; FOOD FORTIFICATION; CLINICAL UTILITY; UNITED-STATES; ANEMIA; MACROCYTOSIS; DEFICIENCY; DIAGNOSIS; IMPACT; ERA C1 [Breu, Anthony C.] Vet Affairs Boston Healthcare Syst, Med Serv, West Roxbury, MA 02132 USA. [Breu, Anthony C.; Theisen-Toupal, Jesse] Harvard Univ, Sch Med, Boston, MA USA. [Theisen-Toupal, Jesse] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Feldman, Leonard S.] Johns Hopkins Univ Hosp, Div Gen Internal Med, Baltimore, MD 21287 USA. [Feldman, Leonard S.] Johns Hopkins Univ Hosp, Div Pediat, Baltimore, MD 21287 USA. [Feldman, Leonard S.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Breu, AC (reprint author), VA Boston Healthcare Syst, Med Serv 111,1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM anthony.breu@va.gov NR 24 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD NOV PY 2015 VL 10 IS 11 BP 753 EP 755 DI 10.1002/jhm.2385 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CU6YD UT WOS:000363680300009 PM 26463111 ER PT J AU Carrasco, E Calvo, MI Blazquez-Castro, A Vecchio, D Zamarron, A de Almeida, IJD Stockert, JC Hamblin, MR Juarranz, A Espada, J AF Carrasco, Elisa Calvo, Maria I. Blazquez-Castro, Alfonso Vecchio, Daniela Zamarron, Alicia Joyce Dias de Almeida, Irma Stockert, Juan C. Hamblin, Michael R. Juarranz, Angeles Espada, Jesus TI Photoactivation of ROS Production In Situ Transiently Activates Cell Proliferation in Mouse Skin and in the Hair Follicle Stem Cell Niche Promoting Hair Growth and Wound Healing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID REDOX REGULATION; NADPH-OXIDASE; FREE-RADICALS; ANTIOXIDANTS; PATHWAYS; DISEASE; CANCER; MODEL AB The role of reactive oxygen species (ROS) in the regulation of hair follicle (HF) cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and aging, but recent findings suggest that they can also have beneficial physiological functions in vivo in mammals. To test this hypothesis, we transiently switched on in situ ROS production in mouse skin. This process activated cell proliferation in the tissue and, interestingly, in the bulge region of the HF, a major reservoir of epidermal stem cells, promoting hair growth, as well as stimulating tissue repair after severe burn injury. We further show that these effects were associated with a transient Src kinase phosphorylation at Tyr416 and with a strong transcriptional activation of the prolactin family 2 subfamily c of growth factors. Our results point to potentially relevant modes of skin homeostasis regulation and demonstrate that a local and transient ROS production can regulate stem cell and tissue function in the whole organism. C1 [Carrasco, Elisa; Calvo, Maria I.; Blazquez-Castro, Alfonso; Joyce Dias de Almeida, Irma; Espada, Jesus] Univ Autonoma Madrid, Dept Bioquim, CSIC, Inst Invest Biomed Alberto Sols, E-28049 Madrid, Spain. [Carrasco, Elisa; Calvo, Maria I.; Blazquez-Castro, Alfonso; Zamarron, Alicia; Joyce Dias de Almeida, Irma; Stockert, Juan C.; Juarranz, Angeles; Espada, Jesus] Univ Autonoma Madrid, Fac Ciencias, Dept Biol, E-28049 Madrid, Spain. [Carrasco, Elisa; Vecchio, Daniela; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vecchio, Daniela; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Espada, J (reprint author), Univ Autonoma Madrid, Dept Bioquim, CSIC, Inst Invest Biomed Alberto Sols, Darwin 2, E-28049 Madrid, Spain. EM jespada@iib.uam.es RI Juarranz, Angeles/L-2446-2013; Blazquez-Castro, Alfonso/A-9716-2017; calvo sanchez, maria inmaculada/B-2842-2017; Carrasco, Elisa/G-7746-2015 OI Juarranz, Angeles/0000-0002-6574-2887; Blazquez-Castro, Alfonso/0000-0002-3270-7065; Carrasco, Elisa/0000-0002-0817-1627 FU Spanish MINECO [SAF11-23493, RTC-2014-2626-1, FIS PI12/01253, CAM S10/BMD-2359]; Comunidad Autonoma de Madrid grant SkinModel CAM [S10/BMD-2359]; US NIH [R01AI050875]; Spanish MCINN [CTQ2010-20870-C03-03]; Spanish MECD-FPU fellowship; Spanish UAM-FPI fellowship FX JE was supported by Spanish MINECO grants SAF11-23493 and RTC-2014-2626-1 and Comunidad Autonoma de Madrid grant SkinModel CAM S10/BMD-2359. DV and MRH were supported by US NIH grant R01AI050875. AJ was supported by Spanish MINECO grant FIS PI12/01253 and CAM S10/BMD-2359. JCS was supported by Spanish MCINN grant CTQ2010-20870-C03-03. EC and MIC were supported by Spanish MECD-FPU and UAM-FPI fellowships, respectively. We thank Dr Colin Jahoda for the kind review of this manuscript. We thank biocellavi.com for assistance in the preparation of figures. NR 33 TC 4 Z9 4 U1 5 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2015 VL 135 IS 11 BP 2611 EP 2622 DI 10.1038/jid.2015.248 PG 12 WC Dermatology SC Dermatology GA CV1DM UT WOS:000363993600012 PM 26134949 ER PT J AU Garibyan, L Cornelissen, L Sipprell, W Pruessner, J Elmariah, S Luo, T Lerner, EA Jung, Y Evans, C Zurakowski, D Berde, CB Anderson, RR AF Garibyan, Lilit Cornelissen, Laura Sipprell, William Pruessner, Joachim Elmariah, Sarina Luo, Tuan Lerner, Ethan A. Jung, Yookyung Evans, Conor Zurakowski, David Berde, Charles B. Anderson, R. Rox TI Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN SKIN; NOXIOUS HEAT; INDUCED ITCH; COLD INJURY; PAIN; FIBERS; MODEL; NOCICEPTORS; HUMANS AB Cryolipolysis is a noninvasive, skin cooling treatment for local fat reduction that causes prolonged hypoesthesia over the treated area. We tested the hypothesis that cryolipolysis can attenuate nociception of a range of sensory stimuli, including stimuli that evoke itch. The effects of cryolipolysis on sensory phenomena were evaluated by quantitative sensory testing (QST) in 11 healthy subjects over a period of 56 days. Mechanical and thermal pain thresholds were measured on treated and contralateral untreated (control) flanks. Itch duration was evaluated following histamine iontophoresis. Unmyelinated epidermal nerve fiber and myelinated dermal nerve fiber densities were quantified in skin biopsies from six subjects. Cryolipolysis produced a marked decrease in mechanical and thermal pain sensitivity. Hyposensitivity started between two to seven days after cryolipolysis and persisted for at least thirty-five days post treatment. Skin biopsies revealed that cryolipolysis decreased epidermal nerve fiber density, as well as dermal myelinated nerve fiber density, which persisted throughout the study. In conclusion, cryolipolysis causes significant and prolonged decreases in cutaneous sensitivity. Our data suggest that controlled skin cooling to specifically target cutaneous nerve fibers has the potential to be useful for prolonged relief of cutaneous pain and might have a use as a research tool to isolate and study cutaneous itchsensing nerves in human skin. C1 [Garibyan, Lilit; Sipprell, William; Pruessner, Joachim; Jung, Yookyung; Evans, Conor; Anderson, R. Rox] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Garibyan, Lilit; Sipprell, William; Pruessner, Joachim; Elmariah, Sarina; Luo, Tuan; Lerner, Ethan A.; Jung, Yookyung; Evans, Conor; Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Cornelissen, Laura; Zurakowski, David; Berde, Charles B.] Boston Childrens Hosp, Dept Anesthesiol Peroperat & Pain Med, Boston, MA USA. [Cornelissen, Laura; Zurakowski, David; Berde, Charles B.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. [Elmariah, Sarina; Luo, Tuan; Lerner, Ethan A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Garibyan, L (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St Thier 2, Boston, MA 02114 USA. EM lgaribyan@partners.org FU National Institutes of Health (NIH) FX L.G. was supported by a National Institutes of Health (NIH) T32 training grant. This was an investigator-initiated study supported by discretionary funds. NR 32 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2015 VL 135 IS 11 BP 2623 EP 2631 DI 10.1038/jid.2015.233 PG 9 WC Dermatology SC Dermatology GA CV1DM UT WOS:000363993600013 PM 26099028 ER PT J AU Horste, GMZ Derksen, A Stassart, R Szepanowski, F Thanos, M Stettner, M Boettcher, C Lehmann, HC Hartung, HP Kieseier, BC AF Horste, Gerd Meyer Zu Derksen, Angelika Stassart, Ruth Szepanowski, Fabian Thanos, Melissa Stettner, Mark Boettcher, Christina Lehmann, Helmar C. Hartung, Hans-Peter Kieseier, Bernd C. TI Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the Peripheral Nervous System SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ADAM10; Axonal outgrowth; Nerve conduction; Neuregulin; Remyelination ID ALPHA-SECRETASE; NEUREGULIN-1; BACE1; CELLS; NOTCH; GENE; REGENERATION; PROTEINS; IDENTITY; DISEASE AB The regulation of myelination and axonal outgrowth in the peripheral nervous system is controlled by a complex signaling network involving various signaling pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are membrane-anchored proteinases with both proteolytic and disintegrin characteristics that modulate the function of signaling molecules. One family member, ADAM17, is known to influence myelination by cleaving and thus regulating one of the key signals, neuregulin-1, which controls peripheral nervous system myelination. A similar function for ADAM10 had been suggested by previous in vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo and deleted ADAM10 in a cell type-specific manner in either neurons or Schwann cells. We found that ADAM10 is not required in either Schwann cells or neurons for normal myelination during development or for remyelination after injury. Instead, ADAM10 is required specifically in neurons for the outgrowth of myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration that is distinct from that of the related protein family member ADAM17 and that may have implications for targeting ADAM function in nervous system diseases. C1 [Horste, Gerd Meyer Zu; Derksen, Angelika; Szepanowski, Fabian; Stettner, Mark; Boettcher, Christina; Lehmann, Helmar C.; Hartung, Hans-Peter; Kieseier, Bernd C.] Univ Dusseldorf, Dept Neurol, Fac Med, D-40225 Dusseldorf, Germany. [Stassart, Ruth] Univ Gottingen, Dept Neuropathol, D-37073 Gottingen, Germany. [Stassart, Ruth] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany. [Thanos, Melissa] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Horste, GMZ (reprint author), Univ Dusseldorf, Dept Neurol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM gerd.mzh@uni-duesseldorf.de RI Lehmann, Helmar/G-4998-2016; Meyer zu Horste, Gerd/O-9549-2016 OI Meyer zu Horste, Gerd/0000-0002-4341-4719 FU Peripheral Nerve Society (PNS Baxter Fellowship); DFG [ME-4050/1-1, ME-4162/1-1]; Research Commission of the Heinrich-Heine University (FoKo) FX This study was funded in part by grants from the Peripheral Nerve Society (PNS Baxter Fellowship), the DFG (ME-4050/1-1), and the Research Commission of the Heinrich-Heine University (FoKo), all to Gerd Meyer zu Horste, as well as by the DFG grant ME-4162/1-1 to Melissa Thanos. NR 35 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2015 VL 74 IS 11 BP 1077 EP 1085 DI 10.1097/NEN.0000000000000253 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA CU7AZ UT WOS:000363688400005 ER PT J AU Skelton, F Hoffman, JM Reyes, M Burns, SP AF Skelton, Felicia Hoffman, Jeanne M. Reyes, Maria Burns, Stephen P. TI Examining health-care utilization in the first year following spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Health-care utilization; Spinal cord injury; Re-hospitalization ID REHOSPITALIZATION; OUTCOMES AB Objective: To identify factors associated with health-care utilization during the first year after inpatient rehabilitation (IR) in individuals with traumatic spinal cord injury (SCI). Design: Prospective cohort. Methods: One hundred and sixty-eight patients were prospectively enrolled and followed over 1 year after discharge from an SCI Model System IR program. Telephone follow-up occurred at 3, 6, 9, and 12 months. Participants were grouped into four impairment levels (C1-4 American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-C, C5-C8 AIS A-C, paraplegia AIS A-C, and all AIS D). Three domains of healthcare utilization were examined: hospital care, outpatient provider visits, and home services. Results: Health-care utilization in the first year following IR was high with 45% of subjects reporting rehospitalization. Twenty percent of patients were initially discharged to a skilled nursing facility (SNF), and an additional 10% required SNF care during this first year. Overall, those with C1-4 AIS A-C used the most services. Participants discharged home used less health care compared to those discharged elsewhere. SCI due to falls (vs. vehicular crashes) was associated with fewer in-home service visits. Age, sex, race, and education were unrelated to higher use. Conclusion: Those with greater neurological impairment or not discharged home after IR had higher health-care utilization, while age was not associated with utilization. Targeted efforts to reduce genitourinary and respiratory complications may reduce the need for hospital care in the first year after IR. C1 [Skelton, Felicia; Hoffman, Jeanne M.; Reyes, Maria] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Burns, Stephen P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Skelton, F (reprint author), Univ Washington, Dept Rehabil Med, 1959 NE Pacific St,Box 356490, Seattle, WA 98195 USA. EM felicia.skelton@gmail.com FU SCI model systems grant FX The study was done through a model systems center; the SCI model systems grant should be mentioned. NR 12 TC 1 Z9 1 U1 2 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 2015 VL 38 IS 6 BP 690 EP 695 DI 10.1179/2045772314Y.0069000000269 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CU8KC UT WOS:000363790300002 PM 25299152 ER PT J AU Lin, YS Boninger, ML Day, KA Koontz, AM AF Lin, Yen-Sheng Boninger, Michael L. Day, Kevin A. Koontz, Alicia M. TI Ultrasonographic measurement of the acromiohumeral distance in spinal cord injury: Reliability and effects of shoulder positioning SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Ultrasound; Reliability; Shoulder positioning; Subacromial space; Spinal cord injury; Wheelchair ID SUBACROMIAL SPACE WIDTH; GREATER TUBEROSITY DISTANCE; IMPINGEMENT SYNDROME; ROTATOR CUFF; SONOGRAPHIC EVALUATION; WHEELCHAIR PROPULSION; HUMERAL DISTANCE; PARAPLEGIA; ABNORMALITIES; ASSOCIATION AB Objective: To investigate the reliability of ultrasonographic measurement of acromiohumeral distance (AHD) and the effects of shoulder positioning on AHD among manual wheelchair users (MWUs) with spinal cord injury (SCI) and an able-bodied control group. Methods: Ten MWUs with SCI and 10 able-bodied subjects participated in this study. The ultrasonographic measurements of AHD from each subject were obtained by two raters during passive and active scapular plane arm elevation in neutral, 45 degrees, 90 degrees with and without resistance and in a weight relief raise position. The measurements were recorded again by each rater using the same procedures after a 30-minute time interval. All raters were blinded to each other's measurements. Setting: University Laboratories and Veteran Affairs Healthcare System. Results: Intra-rater (intraclass correlation coefficient, ICC > 0.83) and inter-rater (ICC > 0.78) reliability was excellent for both the MWUs with SCI and able-bodied groups across all arm positions except for the 45 degrees position in the control group for one of the raters (intra-rater: ICC < 0.40 and inter-rater: ICC < 0.60). AHD significantly reduced when the shoulder was in the 90 degrees arm elevated positions with or without resistance. Conclusion: Findings from our study demonstrated that ultrasonography is a reliable means to evaluate AHD in both able bodied and individuals with SCI, who are known to have significant shoulder pathology. This technique could be used to develop reference measures and to identify changes in AHD caused by interventions. C1 [Lin, Yen-Sheng; Boninger, Michael L.; Day, Kevin A.; Koontz, Alicia M.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Lin, Yen-Sheng; Boninger, Michael L.; Koontz, Alicia M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. [Boninger, Michael L.; Day, Kevin A.; Koontz, Alicia M.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15206 USA. [Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA. RP Koontz, AM (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave Suite 400, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X FU VA Rehabilitation R&D Center of Excellence, Department of Veterans Affairs [B6789C] FX VA Rehabilitation R&D Center of Excellence, Project B6789C, Department of Veterans Affairs. NR 42 TC 1 Z9 1 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1079-0268 EI 2045-7723 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD NOV PY 2015 VL 38 IS 6 BP 700 EP 708 DI 10.1179/2045772314Y.0000000205 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CU8KC UT WOS:000363790300004 PM 24968117 ER PT J AU Lyons, BL Korsten, MA Spungen, AM Radulovic, M Rosman, AS Hunt, K Galea, MD Kornfeld, SD Yen, C Bauman, WA AF Lyons, Brian L. Korsten, Mark A. Spungen, Ann M. Radulovic, Miroslav Rosman, Alan S. Hunt, Kristel Galea, Marinella D. Kornfeld, Stephen D. Yen, Christina Bauman, William A. TI Comparison between pulsed irrigation enhanced evacuation and polyethylene glycol-electrolyte lavage solution for bowel preparation prior to elective colonoscopy in veterans with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Polyethylene glycol; Bowel preparations; Paraplegia; Tetraplegia; Colonoscopy; Polyp detection ID ORAL SODIUM-PHOSPHATE; COLORECTAL-CANCER; CONTROLLED-TRIAL; SAFETY; GLYCOPYRROLATE; NEOSTIGMINE; IMPACTION; REGIMENS; EFFICACY AB Background: Poor preparation for elective colonoscopy is common in persons with spinal cord injury (SCI). This unsatisfactory outcome is likely due to long-standing difficulty with evacuation and decreased colonic motility. Our objective was to determine the most effective preparation for elective colonoscopy applying a novel and traditional approach to bowel cleansing. Methods: Twenty-four subjects with SCI were consented and scheduled to receive one of the two possible arms: pulsed irrigation enhanced evacuation (PIEE) or polyethylene glycol-electrolyte lavage solution (PEG; CoLyte (R)). The quality of the preparation was scored during the colonoscopy by applying the Ottawa scoring system. Results: Patients with SCI who received PIEE tended to have lower Ottawa scores and a higher percentage of acceptable preparations than did those who received PEG; however, the results were not statistically different. Conclusion: In this preliminary study in subjects with SCI, neither PIEE nor PEG produced acceptable bowel preparation for elective colonoscopy. Future studies should confirm our findings and consider studying alternative, more efficacious approaches to bowel cleansing prior to colonoscopic procedures in patients with SCI, which should provide better outcomes. C1 [Lyons, Brian L.; Korsten, Mark A.; Spungen, Ann M.; Radulovic, Miroslav; Galea, Marinella D.; Kornfeld, Stephen D.; Yen, Christina; Bauman, William A.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA. [Korsten, Mark A.; Radulovic, Miroslav; Rosman, Alan S.; Hunt, Kristel; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Korsten, Mark A.; Galea, Marinella D.; Kornfeld, Stephen D.; Bauman, William A.] James J Peters VA Med Ctr, Spinal Cord Injury Serv, Bronx, NY 10468 USA. [Korsten, Mark A.; Spungen, Ann M.; Radulovic, Miroslav; Rosman, Alan S.; Hunt, Kristel; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Spungen, Ann M.; Galea, Marinella D.; Kornfeld, Stephen D.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. RP Lyons, BL (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences SCI, Rm 7A-13,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM brian.lyons@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development Service [A6428R, B2468-C, B4162-C]; James J. Peters VA Medical Center FX This research was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (#A6428R, #B2468-C, #B4162-C) and the James J. Peters VA Medical Center. NR 24 TC 0 Z9 0 U1 0 U2 1 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 2015 VL 38 IS 6 BP 805 EP 811 DI 10.1179/2045772314Y.0000000256 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CU8KC UT WOS:000363790300014 PM 25096918 ER PT J AU Chen, JA Liu, LS Zhao, XD Yeung, AS AF Chen, Justin A. Liu, Lusha Zhao, Xudong Yeung, Albert S. TI Chinese International Students: An Emerging Mental Health Crisis SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 [Chen, Justin A.; Yeung, Albert S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02115 USA. [Yeung, Albert S.] South Cove Community Hlth Ctr, Boston, MA USA. [Zhao, Xudong] Shanghai East Hosp, Shanghai, Peoples R China. [Zhao, Xudong] Tongji Univ, Shanghai 200092, Peoples R China. RP Chen, JA (reprint author), Massachusetts Gen Hosp, Psychiat, MGH DCRP, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM jchen37@partners.org NR 5 TC 0 Z9 0 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2015 VL 54 IS 11 BP 879 EP 880 DI 10.1016/j.jaac.2015.06.022 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CU8ZA UT WOS:000363831400001 PM 26506576 ER PT J AU Wilens, TE Robertson, B Sikirica, V Harper, L Young, JL Bloomfield, R Lyne, A Rynkowski, G Cutler, AJ AF Wilens, Timothy E. Robertson, Brigitte Sikirica, Vanja Harper, Linda Young, Joel L. Bloomfield, Ralph Lyne, Andrew Rynkowski, Gail Cutler, Andrew J. TI A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; nonstimulants; guanfacine; GXR ID DEFICIT-HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; MIXED AMPHETAMINE SALTS; QUALITY-OF-LIFE; LISDEXAMFETAMINE DIMESYLATE; DOUBLE-BLIND; FUNCTIONAL OUTCOMES; PARALLEL-GROUP; YOUNG-ADULTS; ADDERALL-XR AB Objective: Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. Method: This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. Results: A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p < .001). More participants on GXR also showed significant improvement in CGI-S scores compared with placebo (50.6% versus 36.1%; p = .010). There was no statistically significant difference between treatments at week 13 in the 2 WFIRS-P domains. Most treatment-emergent adverse events were mild to moderate, with sedation-related events reported most commonly. Conclusion: GXR was associated with statistically significant improvements in ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. Clinical Trial Registration Information Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/;NCT01081132. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Robertson, Brigitte; Sikirica, Vanja; Bloomfield, Ralph; Lyne, Andrew; Rynkowski, Gail] Shire, Wayne, PA USA. [Robertson, Brigitte] Neurovance Inc, Cambridge, MA USA. [Sikirica, Vanja] GlaxoSmithKline, King Of Prussia, PA USA. [Bloomfield, Ralph] AstraZeneca, Cambridge, England. [Harper, Linda] CNS Healthcare, Orlando, FL USA. [Young, Joel L.] Rochester Ctr Behav Med, Rochester Hills, MI USA. [Cutler, Andrew J.] Florida Clin Res Ctr LLC, Bradenton, FL USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM twilens@partners.org FU Shire Development, LLC.; Shire FX Clinical research and writing/editorial support was funded by the sponsor, Shire Development, LLC. The initial draft of the manuscript was completed by the primary author, Dr. Wilens Shire provided funding to MedErgy for support in editing this manuscript Although the sponsor was involved in the design, collection, analysis, interpretation, and fact checking of information, the content of this manuscript, the ultimate interpretation, reviewing/editing of the manuscript, and the decision to submit it for publication in the Journal of the American Academy of Child and Adolescent Psychiatry were made by all authors. NR 57 TC 4 Z9 4 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2015 VL 54 IS 11 BP 916 EP 925 DI 10.1016/j.jaac.2015.08.016 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CU8ZA UT WOS:000363831400007 PM 26506582 ER PT J AU Veenstra-VanderWeele, J McGuire, K Shui, AM AF Veenstra-VanderWeele, Jeremy McGuire, Kelly Shui, Amy M. TI Clinical Correlates of Early Generalized Overgrowth in Autism Spectrum Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter ID CHILDREN C1 [Veenstra-VanderWeele, Jeremy] Columbia Univ, Sackler Inst Dev Psychobiol, New York State Psychiat Inst, New York, NY 10027 USA. [Veenstra-VanderWeele, Jeremy] New York Presbyterian Hosp, Ctr Autism & Developing Brain, New York, NY USA. [McGuire, Kelly] Columbia Univ, New York, NY USA. [McGuire, Kelly] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Shui, Amy M.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Veenstra-VanderWeele, J (reprint author), Columbia Univ, Sackler Inst Dev Psychobiol, New York State Psychiat Inst, New York, NY 10027 USA. EM veenstr@nyspi.columbia.edu NR 4 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 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2015 VL 54 IS 11 BP 957 EP 958 DI 10.1016/j.jaac.2015.07.016 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA CU8ZA UT WOS:000363831400013 ER PT J AU Yu, S Garvin, KL Healy, WL Pellegrini, VD Iorio, R AF Yu, Stephen Garvin, Kevin L. Healy, William L. Pellegrini, Vincent D., Jr. Iorio, Richard TI Preventing Hospital Readmissions and Limiting the Complications Associated With Total Joint Arthroplasty SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID TOTAL KNEE ARTHROPLASTY; ELECTIVE ORTHOPEDIC-SURGERY; PRIMARY TOTAL HIP; POSTOPERATIVE COMPLICATIONS; BARIATRIC SURGERY; SURGICAL OUTCOMES; GLYCEMIC CONTROL; UNITED-STATES; REPLACEMENT; RISK AB Total joint arthroplasty is a highly successful surgical procedure for patients with painful arthritic joints. The increasing prevalence of the procedure is generating significant expenditures in the American healthcare system. Healthcare payers, specifically the Center for Medicare and Medicaid Services, currently target total joint arthroplasty as an area for healthcare cost-savings initiatives, resulting in increased scrutiny surrounding orthopaedic care, health resource utilization, and hospital readmissions. Identifying the complications associated with total hip and total knee arthroplasty that result in readmissions will be critically important for predictive modeling and for decreasing the number of readmissions following total joint arthroplasty. Additionally, improving perioperative optimization, providing seamless episodic care, and intensifying posthospital coordination of care may result in a decreasing number of unnecessary hospital readmissions. Identified modifiable risk factors that significantly contribute to poor clinical outcome following total joint arthroplasty include morbid obesity; poorly controlled diabetes and nutritional deficiencies; Staphylococcus aureus colonization; tobacco use; venous thromboembolic disease; cardiovascular disease; neurocognitive, psychological, and behavioral problems; and physical deconditioning and fall risk. Both clinical practice and research will be enhanced if there is standardization of defined total joint arthroplasty complications and utilization of stratification schemes to identify high-risk patients. Subsequently, clinical intervention would be warranted to address modifiable risk factors before proceeding with total joint arthroplasty. C1 [Garvin, Kevin L.] Univ Nebraska Med Ctr, Omaha, NE USA. [Healy, William L.] Massachusetts Gen Hosp, Kaplan Joint Ctr, Newton Wellesley Hosp, Boston, MA 02114 USA. [Pellegrini, Vincent D., Jr.] Med Univ S Carolina, Charleston, SC 29425 USA. OI Iorio, Richard/0000-0001-8083-8687 NR 48 TC 9 Z9 9 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD NOV PY 2015 VL 23 IS 11 BP E60 EP E71 DI 10.5435/JAAOS-D-15-00044 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CU6HY UT WOS:000363634100001 PM 26498587 ER PT J AU Sharmeen, F Rosenthal, MH Wood, MJ Tirumani, SH Sweeney, C Howard, SA AF Sharmeen, Farhana Rosenthal, Michael H. Wood, Monica J. Tirumani, Sree Harsha Sweeney, Christopher Howard, Stephanie A. TI Relationship Between the Pathologic Subtype/Initial Stage and Microliths in Testicular Germ Cell Tumors SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE embryonal carcinoma; genitourinary ultrasound; microlithiasis; seminoma; testicular germ cell tumor; testicular sonography ID LYMPH-NODE DISSECTION; CANCER; CALCIFICATIONS; PREVALENCE AB Objectives-To investigate the relationship between microliths and germ cell tumor histologic subtypes and determine whether microliths correlate with tumor stage at diagnosis. Methods-A total of 1249 patients with testicular cancer seen between 1999 and 2013 were evaluated; 346 of 1249 patients (28%) with primary testicular tumors and sonographic imaging of unaffected testicular tissue formed the analytic cohort. Age, ethnicity, tumor histologic subtype, and stage at diagnosis were extracted from the medical record. Two examiners concurrently recorded the highest number of microliths per image of unaffected testicular tissue. Results-A total of 175 of 346 patients (51%) had 1 or more microliths; 69 of 346 (20%) had more than 5 microliths per image. The histologic percentage of seminomas positively correlated with the microlith count (r(s) = 0.12; P = .036); the histologic percentage of embryonal components negatively correlated with the microlith count (r(s) = 0.15; P = .007). A higher microlith count was associated with a lower stage at diagnosis (P = .0243). Subgroup analysis of pure seminomas suggested a trend toward a higher microlith count inpatients with lower-stage disease at diagnosis (P = .07). No association was found between the tumor stage at diagnosis and microlith count in patients with greater than 50% embryonal components of tumors (P = .55). No association was found between microliths and age, tumor size, and presence of lymphovascular/rete testis invasion (P = .120, .500, .629, and .155, respectively). Conclusions-Patients with testicular cancer who have microliths may be more likely to have a higher percentage of seminomas and a lower percentage of embryonal components in their primary tumors. Microliths also showed an association with earlier stages of disease at diagnosis. C1 [Sharmeen, Farhana; Rosenthal, Michael H.; Tirumani, Sree Harsha; Howard, Stephanie A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Sharmeen, Farhana; Rosenthal, Michael H.; Tirumani, Sree Harsha; Howard, Stephanie A.] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02215 USA. [Wood, Monica J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sweeney, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sweeney, Christopher] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Wood, MJ (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM monicajwood@post.harvard.edu NR 13 TC 1 Z9 1 U1 2 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 EI 1550-9613 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2015 VL 34 IS 11 BP 1977 EP 1982 DI 10.7863/ultra.14.09031 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA CU8VL UT WOS:000363822100007 PM 26396167 ER PT J AU Xu, YZ Chen, H Yeh, HD Wang, HG Leng, JJ Dong, JH AF Xu, Yinzhe Chen, Hao Yeh, Heidi Wang, Hongguang Leng, Jianjun Dong, Jiahong TI Living donor liver transplantation using dual grafts: Experience and lessons learned from cases worldwide SO LIVER TRANSPLANTATION LA English DT Review ID FOR-SIZE GRAFT; LOBE GRAFTS; HEPATECTOMY; MODULATION; ADULTS; SAFE; STEATOSIS; MORBIDITY; PRESSURE; SURGERY AB In living donor liver transplantation (LDLT), insufficient graft volume could result in small-for-size syndrome in recipients, whereas major liver donation predisposes the donor to a high risk of posthepatectomy liver failure. Dual graft LDLT is therefore introduced to obtain combined graft sufficiency. To date, 367 patients have been reported worldwide. We reviewed all the relevant literature, with a special focus on 43 case reports containing enough data to extract and analyze. A simple decision-making algorithm was developed. Dual graft LDLT is indicated when (1) a single donation is unacceptable due to graft-to-recipient size mismatch; (2) the future liver remnant is insufficient in the single donor after major resection; or (3) there is a significant underlying disorder or anatomical variation within the donor liver. The outcome of dual graft LDLT is reported to be comparable with that of single donor LDLT. Unilateral graft atrophy was found in 7 of the 43 patients, predominantly in the right-sided, heterotopic and initially smaller grafts. Technically, the heterotopic implantation and complex vascular reconstruction are the most demanding. Elaborate surgical planning and modification are needed. Ethical concerns about involving a second living donor need to be addressed. In conclusion, dual graft LDLT should be prudently performed in select cases by surgeons of proven expertise when single donation is unacceptable and a second living donor is available. The decision-making criteria need to be standardized. More surgical modification and clinical research are needed. Liver Transpl 21:1438-1448, 2015. (c) 2015 AASLD. C1 [Xu, Yinzhe; Chen, Hao; Wang, Hongguang; Leng, Jianjun; Dong, Jiahong] Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, Beijing 100853, Peoples R China. [Xu, Yinzhe; Yeh, Heidi] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dong, Jiahong] Tsinghua Univ, Med Ctr, Beijing Tsinghua Changgung Hosp, Beijing 100084, Peoples R China. RP Dong, JH (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, 28 Fuxing Rd, Beijing 100853, Peoples R China. EM dongjh301@163.com FU National Key Technology Research and Development Program of China [2012BAI06B01]; National Science and Technology Major Project for Infectious Diseases of China [2012ZX10002-017] FX The work is supported by the National Key Technology Research and Development Program of China (No. 2012BAI06B01) and the National Science and Technology Major Project for Infectious Diseases of China (No. 2012ZX10002-017). NR 52 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2015 VL 21 IS 11 BP 1438 EP 1448 DI 10.1002/lt.24315 PG 11 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA CU7CQ UT WOS:000363693800014 PM 26336078 ER PT J AU Chan, G White, CC Winn, PA Cimpean, M Replogle, JM Glick, LR Cuerdon, NE Ryan, KJ Johnson, KA Schneider, JA Bennett, DA Chibnik, LB Sperling, RA Bradshaw, EM De Jager, PL AF Chan, Gail White, Charles C. Winn, Phoebe A. Cimpean, Maria Replogle, Joseph M. Glick, Laura R. Cuerdon, Nicole E. Ryan, Katie J. Johnson, Keith A. Schneider, Julie A. Bennett, David A. Chibnik, Lori B. Sperling, Reisa A. Bradshaw, Elizabeth M. De Jager, Philip L. TI CD33 modulates TREM2: convergence of Alzheimer loci SO NATURE NEUROSCIENCE LA English DT Article ID DISEASE SUSCEPTIBILITY; COMMON VARIANTS; MOUSE MODELS; ASSOCIATION; MICROGLIA; PATHOLOGY; CD2AP; EPHA1 AB We used a protein quantitative trait analysis in monocytes from 226 individuals to evaluate cross-talk between Alzheimer loci. The NME8 locus influenced PTK2B and the CD33 risk allele led to greater TREM2 expression. There was also a decreased TREM1/TREM2 ratio with a TREM1 risk allele, decreased TREM2 expression with CD33 suppression and elevated cortical TREM2 mRNA expression with amyloid pathology. C1 [Chan, Gail; White, Charles C.; Winn, Phoebe A.; Cimpean, Maria; Replogle, Joseph M.; Glick, Laura R.; Cuerdon, Nicole E.; Ryan, Katie J.; Chibnik, Lori B.; Bradshaw, Elizabeth M.; De Jager, Philip L.] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA. [Chan, Gail; White, Charles C.; Winn, Phoebe A.; Cimpean, Maria; Replogle, Joseph M.; Glick, Laura R.; Cuerdon, Nicole E.; Ryan, Katie J.; Chibnik, Lori B.; Bradshaw, Elizabeth M.; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Inst Neurosci, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Chan, Gail; White, Charles C.; Winn, Phoebe A.; Cimpean, Maria; Replogle, Joseph M.; Glick, Laura R.; Cuerdon, Nicole E.; Ryan, Katie J.; Chibnik, Lori B.; Bradshaw, Elizabeth M.; De Jager, Philip L.] Brigham & Womens Hosp, Dept Psychiat, Inst Neurosci, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Chan, Gail; White, Charles C.; Winn, Phoebe A.; Cimpean, Maria; Replogle, Joseph M.; Glick, Laura R.; Cuerdon, Nicole E.; Ryan, Katie J.; Chibnik, Lori B.; Bradshaw, Elizabeth M.; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Chan, Gail; Replogle, Joseph M.; Ryan, Katie J.; Johnson, Keith A.; Chibnik, Lori B.; Sperling, Reisa A.; Bradshaw, Elizabeth M.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA USA. [Johnson, Keith A.; Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimers Res & Treatment, Boston, MA 02115 USA. [Johnson, Keith A.; Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Schneider, Julie A.; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. RP De Jager, PL (reprint author), Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. EM pdejager@rics.bwh.harvard.edu FU US National Institutes of Health [R01 AG036836, R01 AG048015, R01 AG043617, P01 AG036694, P30 AG10161, R01 AG15819, R01 AG17917, U01 AG46152] FX The authors are grateful to the participants of PGP, HABS, ROS and MAP for the time and specimens that they contributed. This work was supported by US National Institutes of Health grants R01 AG036836, R01 AG048015, R01 AG043617, P01 AG036694, P30 AG10161, R01 AG15819, R01 AG17917 and U01 AG46152. NR 20 TC 15 Z9 15 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2015 VL 18 IS 11 BP 1556 EP 1558 DI 10.1038/nn.4126 PG 3 WC Neurosciences SC Neurosciences & Neurology GA CU8YT UT WOS:000363830700008 PM 26414614 ER PT J AU Vinegoni, C Aguirre, AD Lee, S Weissleder, R AF Vinegoni, Claudio Aguirre, Aaron D. Lee, Sungon Weissleder, Ralph TI Imaging the beating heart in the mouse using intravital microscopy techniques SO NATURE PROTOCOLS LA English DT Article ID IN-VIVO; CARDIAC-FUNCTION; BLOOD-FLOW; MOTION; MODELS; CELLS; MICE AB Real-time microscopic imaging of moving organs at single-cell resolution represents a major challenge in studying complex biology in living systems. Motion of the tissue from the cardiac and respiratory cycles severely limits intravital microscopy by compromising ultimate spatial and temporal imaging resolution. However, significant recent advances have enabled single-cell resolution imaging to be achieved in vivo. In this protocol, we describe experimental procedures for intravital microscopy based on a combination of thoracic surgery, tissue stabilizers and acquisition gating methods, which enable imaging at the single-cell level in the beating heart in the mouse. Setup of the model is typically completed in 1 h, which allows 2 h or more of continuous cardiac imaging. This protocol can be readily adapted for the imaging of other moving organs, and it will therefore broadly facilitate in vivo high-resolution microscopy studies. C1 [Vinegoni, Claudio; Aguirre, Aaron D.; Lee, Sungon; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio; Aguirre, Aaron D.; Lee, Sungon; Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA USA. [Aguirre, Aaron D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lee, Sungon] Hanyang Univ, Sch Elect Engn, Ansan, South Korea. RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu FU US National Institutes of Health (NIH) [HHSN268201000044C, R01EB006432]; National Research Foundation of Korea - Korean Government (MSIP) [2012M3A6A3055694]; American Heart Association [14FTF20380185] FX The project was funded by US National Institutes of Health (NIH) Contracts HHSN268201000044C and R01EB006432. This work was also supported by the National Research Foundation of Korea funded by the Korean Government (MSIP) 2012M3A6A3055694. A.D.A. was funded by the American Heart Association 14FTF20380185. NR 25 TC 6 Z9 6 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD NOV PY 2015 VL 10 IS 11 BP 1802 EP 1819 DI 10.1038/nprot.2015.119 PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA CU4CC UT WOS:000363472700010 PM 26492138 ER PT J AU Bowtell, DD Bohm, S Ahmed, AA Aspuria, PJ Bast, RC Beral, V Berek, JS Birrer, MJ Blagden, S Bookman, MA Brenton, JD Chiappinelli, KB Martins, FC Coukos, G Drapkin, R Edmondson, R Fotopoulou, C Gabra, H Galon, J Gourley, C Heong, V Huntsman, DG Iwanicki, M Karlan, BY Kaye, A Lengyel, E Levine, DA Lu, KH McNeish, IA Menon, U Narod, SA Nelson, BH Nephew, KP Pharoah, P Powell, DJ Ramos, P Romero, IL Scott, CL Sood, AK Stronach, EA Balkwill, FR AF Bowtell, David D. Boehm, Steffen Ahmed, Ahmed A. Aspuria, Paul-Joseph Bast, Robert C., Jr. Beral, Valerie Berek, Jonathan S. Birrer, Michael J. Blagden, Sarah Bookman, Michael A. Brenton, James D. Chiappinelli, Katherine B. Martins, Filipe Correia Coukos, George Drapkin, Ronny Edmondson, Richard Fotopoulou, Christina Gabra, Hani Galon, Jerome Gourley, Charlie Heong, Valerie Huntsman, David G. Iwanicki, Marcin Karlan, Beth Y. Kaye, Allyson Lengyel, Ernst Levine, Douglas A. Lu, Karen H. McNeish, Iain A. Menon, Usha Narod, Steven A. Nelson, Brad H. Nephew, Kenneth P. Pharoah, Paul Powell, Daniel J., Jr. Ramos, Pilar Romero, Iris L. Scott, Clare L. Sood, Anil K. Stronach, Euan A. Balkwill, Frances R. TI Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer SO NATURE REVIEWS CANCER LA English DT Review ID BRCA MUTATION CARRIERS; TUBAL-INTRAEPITHELIAL-CARCINOMA; OLAPARIB MAINTENANCE THERAPY; SINGLE-THRESHOLD RULE; HUMAN BREAST-TUMORS; CELL LUNG-CANCER; FALLOPIAN-TUBE; T-CELLS; GERMLINE MUTATIONS; SOMATIC MUTATIONS AB High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. C1 [Bowtell, David D.] Peter MacCallum Canc Ctr, Canc Genom & Genet Program, Melbourne, Vic 8006, Australia. [Bowtell, David D.] Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW 2010, Australia. [Boehm, Steffen; Balkwill, Frances R.] Queen Mary Univ London, Barts Canc Inst, London EC1M6BQ, England. [Ahmed, Ahmed A.] John Radcliffe Hosp, Dept Obstet & Gynaecol, Oxford OX3 9DS, England. [Ahmed, Ahmed A.] John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Aspuria, Paul-Joseph; Karlan, Beth Y.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Bast, Robert C., Jr.; Lu, Karen H.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Beral, Valerie] Univ Oxford, Oxford OX3 7LF, England. [Berek, Jonathan S.] Stanford Univ, Stanford, CA 94305 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blagden, Sarah; Fotopoulou, Christina; Gabra, Hani; Stronach, Euan A.] Univ London Imperial Coll Sci Technol & Med, Ovarian Canc Action Res Ctr, London W12 0NN, England. [Bookman, Michael A.] Arizona Oncol, Tucson, AZ 85711 USA. [Brenton, James D.; Martins, Filipe Correia] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England. [Chiappinelli, Katherine B.] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD 21287 USA. [Coukos, George] Univ Lausanne Hosp, Lausanne, Switzerland. [Drapkin, Ronny] Univ Penn, Penn Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Edmondson, Richard] Univ Manchester, Manchester M13 9WL, Lancs, England. [Galon, Jerome] Univ Paris 06, Sorbonne Univ, UMRS1138,Lab Integrat Canc Immunol,INSERM, Cordeliers Res Ctr,Univ Paris Descartes,Sorbonne, F-75006 Paris, France. [Gourley, Charlie] Univ Edinburgh, Canc Res Ctr, Edinburgh EH4 2XR, Midlothian, Scotland. [Heong, Valerie; Scott, Clare L.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia. [Huntsman, David G.] Univ British Columbia, Dept Pathol & Lab Med, Fac Med, Vancouver, BC V6T 2B5, Canada. [Huntsman, David G.] Univ British Columbia, Dept Obstet & Gynecol, Fac Med, Vancouver, BC V6T 2B5, Canada. [Iwanicki, Marcin] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kaye, Allyson] Ovarian Canc Act, London NW1 0JK, England. [Lengyel, Ernst; Romero, Iris L.] Univ Chicago, Chicago, IL 60637 USA. [Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [McNeish, Iain A.] Univ Glasgow, Glasgow G61 1QH, Lanark, Scotland. [Menon, Usha] UCL, Womens Canc, Inst Womens Hlth, London WC1E 6BT, England. [Narod, Steven A.] Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada. [Nelson, Brad H.] British Columbia Canc Agcy, Victoria, BC V8R 6V5, Canada. [Nephew, Kenneth P.] Indiana Univ Sch Med, Bloomington, IN 47405 USA. [Nephew, Kenneth P.] Simon Canc Ctr, Bloomington, IN 47405 USA. [Pharoah, Paul] Univ Cambridge, Strangeways Res Lab, Cambridge CB1 8RN, England. [Powell, Daniel J., Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Ramos, Pilar] Translat Genom Res Inst Tgen, Phoenix, AZ 85004 USA. RP Bowtell, DD (reprint author), Peter MacCallum Canc Ctr, Canc Genom & Genet Program, Melbourne, Vic 8006, Australia. EM d.bowtell@petermac.org; f.balkwill@qmul.ac.uk RI Bast, Robert/E-6585-2011; Drapkin, Ronny/E-9944-2016; Bowtell, David/H-1007-2016; OI Bast, Robert/0000-0003-4621-8462; Drapkin, Ronny/0000-0002-6912-6977; Bowtell, David/0000-0001-9089-7525; Brenton, James/0000-0002-5738-6683; Balkwill, Frances/0000-0002-5587-9759 FU Chief Scientist Office [SCD/11, ETM/92]; Medical Research Council [G0501974, G0902418, MR/K02700X/1]; NCI NIH HHS [P30 CA016672, R01 CA111882, R01 CA168900, R01 CA182832] NR 184 TC 60 Z9 60 U1 5 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2015 VL 15 IS 11 BP 668 EP 679 DI 10.1038/nrc4019 PG 12 WC Oncology SC Oncology GA CU7BV UT WOS:000363691100007 PM 26493647 ER PT J AU Turley, SJ Cremasco, V Astarita, JL AF Turley, Shannon J. Cremasco, Viviana Astarita, Jillian L. TI Immunological hallmarks of stromal cells in the tumour microenvironment SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID FIBROBLAST ACTIVATION PROTEIN; PANCREATIC DUCTAL ADENOCARCINOMA; ENDOTHELIAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; CD8(+) T-CELLS; MACROPHAGE INFILTRATION; ANTITUMOR IMMUNITY; ANGIOGENIC SWITCH; BREAST-CANCER; MOUSE MODEL AB A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function. C1 [Turley, Shannon J.; Astarita, Jillian L.] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA. [Cremasco, Viviana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Cremasco, Viviana] Novartis Inst BioMed Res, Exploratory Immunooncol, Cambridge, MA 02139 USA. RP Turley, SJ (reprint author), Genentech Inc, Dept Canc Immunol, 1 DNA Way, San Francisco, CA 94080 USA. EM turley.shannon@gene.com NR 148 TC 39 Z9 39 U1 15 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 EI 1474-1741 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2015 VL 15 IS 11 BP 669 EP 682 DI 10.1038/nri3902 PG 14 WC Immunology SC Immunology GA CU7CG UT WOS:000363692400007 PM 26471778 ER PT J AU Lipsett, SC Pollock, NR Branda, JA Gordon, CD Gordon, CR Lantos, PM Nigrovic, LE AF Lipsett, Susan C. Pollock, Nira R. Branda, John A. Gordon, Caroline D. Gordon, Catherine R. Lantos, Paul M. Nigrovic, Lise E. TI THE POSITIVE PREDICTIVE VALUE OF LYME ELISA FOR THE DIAGNOSIS OF LYME DISEASE IN CHILDREN SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Lyme disease; Lyme ELISA; predictive value; pediatrics ID KNEE MONOARTHRITIS; CLINICAL-PRACTICE; ENDEMIC AREAS; MENINGITIS; VALIDATION; MODEL AB By using a Lyme enzyme-linked immunosorbent assay (ELISA), we demonstrated that high ELISA index values are strongly predictive of Lyme disease. In children with clinical presentations consistent with Lyme disease, ELISA index values 3.0 had a positive predictive value of 99.4% (95% confidence interval: 98.1-99.8%) for Lyme disease, making a supplemental Western immunoblot potentially unnecessary. C1 [Lipsett, Susan C.; Gordon, Caroline D.; Gordon, Catherine R.; Nigrovic, Lise E.] Boston Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Pollock, Nira R.] Boston Childrens Hosp, Infect Dis Diagnost Lab, Boston, MA 02115 USA. [Pollock, Nira R.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lantos, Paul M.] Duke Univ, Sch Med, Div Pediat Infect Dis, Durham, NC USA. [Lantos, Paul M.] Duke Univ, Sch Med, Div Pediat Infect Dis, Durham, NC USA. RP Nigrovic, LE (reprint author), Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM lise.nigrovic@childrens.harvard.edu OI Lipsett, Susan/0000-0002-4758-6905 FU Boston Children's Hospital Pilot Research Grant; National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) [KL2 TR001115]; Immunetics, Inc.; bioMerieux SA; Alere, Inc.; DiaSorin, Inc.; AdvanDx, Inc. FX This study was supported by a Boston Children's Hospital Pilot Research Grant (L.E.N.) and a National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) KL2 TR001115 (P.M.L.). Branda reports receiving investigator initiated research grants from Immunetics, Inc., bioMerieux SA, Alere, Inc., and DiaSorin, Inc. and he was also a paid consultant to AdvanDx, Inc. All the other authors have no conflicts of interest to disclose. NR 14 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2015 VL 34 IS 11 BP 1260 EP 1262 DI 10.1097/INF.0000000000000858 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA CU4WF UT WOS:000363530500022 PM 26222064 ER PT J AU Ercoli, LM Petersen, L Hunter, AM Castellon, SA Kwan, L Kahn-Mills, BA Embree, LM Cernin, PA Leuchter, AF Ganz, PA AF Ercoli, L. M. Petersen, L. Hunter, A. M. Castellon, S. A. Kwan, L. Kahn-Mills, B. A. Embree, L. M. Cernin, P. A. Leuchter, A. F. Ganz, P. A. TI Cognitive rehabilitation group intervention for breast cancer survivors: results of a randomized clinical trial SO PSYCHO-ONCOLOGY LA English DT Article ID CHEMOTHERAPY; COMPLAINTS; DYSFUNCTION; UPDATE; STATE AB PurposeWe conducted a randomized clinical trial evaluating the efficacy of a cognitive rehabilitation (CR) intervention compared with a wait list (WL) control condition on cognitive complaints, neuropsychological and brain functioning in breast cancer survivors (BCS). MethodsThe small group intervention of five sessions included psychoeducation and cognitive exercises. EligibilityDisease-free BCS with cognitive complaints, diagnosed with stage I, II or III breast cancer, completed primary treatment 18 months to 5 years earlier. Neurocognitive test data and cognitive complaints on the Patient's Assessment of Own Functioning Inventory (PAOFI) were assessed at baseline (T1), immediately post-intervention (T2), and 2 months later (T3). A subgroup of participants underwent resting state quantitative electroencephalography (qEEG) at all three assessment time points. ResultsForty-eight participants [mean age (SD) 53.8 (8.2)] completed T1 assessments, and 29 participants had analyzable qEEG data. The CR group improved significantly over time compared with the WL group on PAOFI total and memory scores (both p=.01) and on Rey Auditory Verbal Learning Test (RAVLT) total (trials I-V) (p=.02) and RAVLT delayed recall (p=.007) scores. On qEEG, the CR group showed a significant decrease in delta slow wave' power (p=.02) and an increase in the frontal distribution of alpha power (p=.04) from T1 to T2. ConclusionsBCS in the CR group showed immediate and sustained improvements in self-reported cognitive complaints and memory functioning on neurocognitive testing. Results of the qEEG substudy provide some support for neurophysiological changes underlying the intervention. Copyright (c) 2015 John Wiley & Sons, Ltd. C1 [Ercoli, L. M.; Hunter, A. M.; Castellon, S. A.; Embree, L. M.; Cernin, P. A.; Leuchter, A. F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Ercoli, L. M.; Hunter, A. M.; Castellon, S. A.; Kwan, L.; Leuchter, A. F.; Ganz, P. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Petersen, L.; Kahn-Mills, B. A.; Ganz, P. A.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Castellon, S. A.; Embree, L. M.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ganz, P. A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. RP Ercoli, LM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. EM lercoli@mednet.ucla.edu FU Breast Cancer Research Foundation; Jonsson Cancer Center Foundation FX Funding for this research was provided by the Breast Cancer Research Foundation and the Jonsson Cancer Center Foundation. We thank Elaiza Torralba for her assistance with the study as well as the breast cancer survivors who participated in the study. NR 37 TC 10 Z9 10 U1 5 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD NOV PY 2015 VL 24 IS 11 BP 1360 EP 1367 DI 10.1002/pon.3769 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA CU6TV UT WOS:000363667600003 PM 25759235 ER PT J AU Felsenfeld, AJ Levine, BS Rodriguez, M AF Felsenfeld, Arnold J. Levine, Barton S. Rodriguez, Mariano TI Pathophysiology of Calcium, Phosphorus, and Magnesium Dysregulation in Chronic Kidney Disease SO SEMINARS IN DIALYSIS LA English DT Article ID CHRONIC-RENAL-FAILURE; GROWTH-FACTOR 23; PARATHYROID-HORMONE SECRETION; LEFT-VENTRICULAR HYPERTROPHY; SERUM PHOSPHATE LEVELS; TRADE-OFF HYPOTHESIS; INTACT PTH LEVELS; FGF-RECEPTOR 1; HEMODIALYSIS-PATIENTS; VITAMIN-D AB Calcium, phosphorus, and magnesium homeostasis is altered in chronic kidney disease (CKD). Hypocalcemia, hyperphosphatemia, and hypermagnesemia are not seen until advanced CKD because adaptations develop. Increased parathyroid hormone (PTH) secretion maintains serum calcium normal by increasing calcium efflux from bone, renal calcium reabsorption, and phosphate excretion. Similarly, renal phosphate excretion in CKD is maintained by increased secretion of fibroblast growth factor 23 (FGF23) and PTH. However, the phosphaturic effect of FGF23 is reduced by downregulation of its cofactor Klotho necessary for binding FGF23 to FGF receptors. Intestinal phosphate absorption is diminished in CKD due in part to reduced levels of 1,25 dihydroxyvitamin D. Unlike calcium and phosphorus, magnesium is not regulated by a hormone, but fractional excretion of magnesium increases as CKD progresses. As 60-70% of magnesium is reabsorbed in the thick ascending limb of Henle, activation of the calcium-sensing receptor by magnesium may facilitate magnesium excretion in CKD. Modification of the TRPM6 channel in the distal tubule may also have a role. Besides abnormal bone morphology and vascular calcification, abnormalities in mineral homeostasis are associated with increased cardiovascular risk, increased mortality and progression of CKD. C1 [Felsenfeld, Arnold J.; Levine, Barton S.] Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. [Felsenfeld, Arnold J.; Levine, Barton S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rodriguez, Mariano] Univ Cordoba, Hosp Univ Reina Sofia, Serv Nephrol, IMIBIC, Cordoba, Spain. RP Rodriguez, M (reprint author), Univ Hosp, Serv Nefrol, Avd Menendez Pidal S-N, Cordoba 14004, Spain. EM marianorodriguezportillo@gmail.com NR 155 TC 6 Z9 7 U1 2 U2 8 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 2015 VL 28 IS 6 BP 564 EP 577 DI 10.1111/sdi.12411 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA CU8RO UT WOS:000363811000005 PM 26303319 ER PT J AU Denburg, MR Bhan, I AF Denburg, Michelle R. Bhan, Ishir TI Vitamin D-Binding Protein in Health and Chronic Kidney Disease SO SEMINARS IN DIALYSIS LA English DT Article ID MACROPHAGE-ACTIVATING FACTOR; BONE-MINERAL DENSITY; NORMAL RENAL-FUNCTION; GROUP-SPECIFIC COMPONENT; 25-HYDROXYVITAMIN D LEVELS; ACUTE LIVER-FAILURE; FREE GC-GLOBULIN; NEPHROTIC SYNDROME; D METABOLITES; HEMODIALYSIS-PATIENTS AB Vitamin D-binding protein (DBP) is a multifunctional protein that has attracted increasing interest in recent years, largely because of its potential role in modulating the activity of vitamin D. Nearly all circulating vitamin D (similar to 85-90%) circulates bound to DBP, with a smaller proportion bound to albumin, leaving <5% circulating freely. DBP may also play roles beyond vitamin D binding, with potential roles in the immune system and elsewhere. Numerous polymorphisms of DBP exist around the world, and recent studies have identified relevance of different DBP phenotypes in determining DBP concentration and vitamin D affinity. This review focuses on the known roles of DBP in health and kidney disease, and current views on the relevance of DBP polymorphisms. C1 [Denburg, Michelle R.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Denburg, Michelle R.] Univ Penn, Childrens Hosp Philadelphia, Dept Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bhan, Ishir] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Bhan, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 50 Stanford St, Boston, MA 02114 USA. EM ibhan@mgh.harvard.edu FU NIDDK NIH HHS [K23 DK093556] NR 116 TC 1 Z9 1 U1 0 U2 6 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 2015 VL 28 IS 6 BP 636 EP 644 DI 10.1111/sdi.12422 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CU8RO UT WOS:000363811000013 PM 26332676 ER PT J AU Cui, J Freed, R Liu, FY Irani, Z AF Cui, Jie Freed, Robert Liu, Fengyong Irani, Zubin TI Interrupting Rivaling Access-flow with Nonsurgical Image-guided ligation: the "IRANI" Procedure SO SEMINARS IN DIALYSIS LA English DT Article ID ARTERIOVENOUS-FISTULA; VASCULAR ACCESS; HEMODIALYSIS-PATIENTS; SALVAGE; PREDICTORS AB The presence of collateral veins is one of the most common causes of fistula failure to mature. The traditional approach to eliminate collateral vessel flow is coil embolization under fluoroscopy or surgical cut down and branch vessel ligation. However, both approaches are expensive and time consuming. Here, we described an image-guided nonsurgical method to ligate collateral veins. The collateral veins were ligated using Hawkins-Akins needle under ultrasound guidance. The average time for one ligation procedure was 17minutes. There was a significant increase of blood flow in the venous outflow postligation procedure. Four weeks postprocedure ultrasound demonstrated occlusion of the target vessels. This procedure was well tolerated without major complications. In summary, the novel procedure described here offers an image-guided nonsurgical approach for collateral vein occlusion. C1 [Cui, Jie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. [Freed, Robert; Irani, Zubin] Harvard Univ, Sch Med, Dept Radiol, Div Intervent Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Liu, Fengyong] Chinese Peoples Liberat Army Gen Hosp, Div Intervent Radiol, Beijing, Peoples R China. RP Irani, Z (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, 55 Fruits St, Boston, MA 02114 USA. EM zirani@mgh.harvard.edu FU American Society of Nephrology Ben J. Lipps Research Fellowship; American Society of Interventional Nephrology; Division of Interventional Radiology at Massachusetts General Hospital FX The authors thank Linda Romano RN and Ann Mini RN for their assistance with patient's care coordination. This study was supported by grants from the American Society of Nephrology Ben J. Lipps Research Fellowship (to J.C.), fellowship grant from American Society of Interventional Nephrology (to J.C.) and the Division of Interventional Radiology at Massachusetts General Hospital. NR 12 TC 1 Z9 1 U1 1 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 2015 VL 28 IS 6 BP E53 EP E57 DI 10.1111/sdi.12450 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA CU8RO UT WOS:000363811000001 PM 26507374 ER PT J AU Cordero-Coma, M Sobrin, L AF Cordero-Coma, Miguel Sobrin, Lucia TI Anti-tumor necrosis factor-a therapy in uveitis SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE uveitis; tumor necrosis factor-alpha; infliximab; adalimumab; etanercept; golimumab; certolizumab; serum levels of anti TNF-alpha drug; anti-drug antibodies; pharmacogenomics of anti TNF-alpha therapy ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; JUVENILE IDIOPATHIC ARTHRITIS; INFLAMMATORY-BOWEL-DISEASE; FACTOR-ALPHA THERAPY; REGULATORY T-CELLS; CHRONIC NONINFECTIOUS UVEITIS; RANDOMIZED CONTROLLED-TRIALS; TNF-TARGETED THERAPIES; RHEUMATOID-ARTHRITIS; BEHCETS-DISEASE AB Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-alpha) agent, infliximab, for the treatment of uveitis, several new anti TNF-alpha agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti TNF-alpha agents in ocular inflammation and the evidence for their efficacy. (C) 2015 Elsevier Inc. All rights reserved. C1 [Cordero-Coma, Miguel] Univ Hosp Leon, Dept Ophthalmol, Uveitis Unit, Leon, Spain. [Cordero-Coma, Miguel] Univ Leon, Inst Biomed IBIOMED, E-24071 Leon, Spain. [Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Uveitis & Retina Serv, Boston, MA 02114 USA. [Sobrin, Lucia] Harvard Univ, Sch Med, Ophthalmol, Boston, MA USA. RP Cordero-Coma, M (reprint author), Hosp Univ Leon, FEBOphth, C Altos de Nava S-N, Leon 24080, Spain. EM miguelcorderocoma@gmail.com OI Sobrin, Lucia/0000-0003-1575-0819 NR 154 TC 11 Z9 11 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 2015 VL 60 IS 6 BP 575 EP 589 DI 10.1016/j.survophthal.2015.06.004 PG 15 WC Ophthalmology SC Ophthalmology GA CU5WL UT WOS:000363602600006 PM 26164735 ER PT J AU Boyers, LN Karimkhani, C Riggs, J Dellavalle, RP AF Boyers, Lindsay N. Karimkhani, Chante Riggs, Jennifer Dellavalle, Robert P. TI US campus and university debit card policies regarding tobacco and electronic cigarettes SO TOBACCO CONTROL LA English DT Letter C1 [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Riggs, Jennifer] NYU, Langone Med Ctr, Dept Internal Med, New York, NY USA. [Dellavalle, Robert P.] US Dept Vet Affairs, Eastern Colorado Hlth Care Syst, Denver, CO USA. [Dellavalle, Robert P.] Univ Colorado, Sch Med, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dellavalle, RP (reprint author), Dept Veteran Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,Box 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu FU Centers for Disease Control and Prevention (CDC); National Institutes of Health (NIH) FX RPD is supported by grants from the Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) and is also chair of the Colorado Skin Cancer Prevention Task Force. LNB and RPD are employed by the US Department of Veterans Affairs. The CDC, NIH, and US Department of Veterans Affairs were not involved in the creation of this manuscript and its contents do not express their opinions. NR 9 TC 1 Z9 1 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 EI 1468-3318 J9 TOB CONTROL JI Tob. Control PD NOV PY 2015 VL 24 IS 6 BP 623 EP 624 DI 10.1136/tobaccocontrol-2014-051957 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU4BI UT WOS:000363470600025 PM 25552519 ER PT J AU Hoffmann, HJ Santos, AF Mayorga, C Nopp, A Eberlein, B Ferrer, M Rouzaire, P Ebo, DG Sabato, V Sanz, ML Pecaric-Petkovic, T Patil, SU Hausmann, OV Shreffler, WG Korosec, P Knol, EF AF Hoffmann, H. J. Santos, A. F. Mayorga, C. Nopp, A. Eberlein, B. Ferrer, M. Rouzaire, P. Ebo, D. G. Sabato, V. Sanz, M. L. Pecaric-Petkovic, T. Patil, S. U. Hausmann, O. V. Shreffler, W. G. Korosec, P. Knol, E. F. TI The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease SO ALLERGY LA English DT Review DE allergy diagnosis; allergy monitoring; basophil activation test; basophil granulocyte; CD63 ID FC-EPSILON-RI; HYMENOPTERA VENOM ALLERGY; PEANUT-SENSITIZED CHILDREN; AFFINITY IGE RECEPTOR; IN-VITRO DIAGNOSIS; SKIN PRICK TEST; CHRONIC URTICARIA; HISTAMINE-RELEASE; CD-SENS; FLOW-CYTOMETRY AB The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an exvivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases. C1 [Hoffmann, H. J.] Aarhus Univ, Dept Resp Dis & Allergy, Dept Clin Med, DK-8000 Aarhus C, Denmark. [Santos, A. F.] Kings Coll London, Dept Paediat Allergy, Div Asthma Allergy & Lung Biol, London, England. [Santos, A. F.] MRC & Asthma UK Ctr Allerg Mech Asthma, London, England. [Santos, A. F.] Coimbra Univ Hosp, Immunoallergol Dept, Coimbra, Portugal. [Mayorga, C.] UMA, IBIMA Reg Univ Hosp Malaga, Res Lab & Allergy Serv, Malaga, Spain. [Nopp, A.] Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Clin Immunol & Allergy Unit, Stockholm, Sweden. [Eberlein, B.] Tech Univ Munich, Dept Dermatol & Allergy Biederstein, D-80290 Munich, Germany. [Ferrer, M.; Sanz, M. L.] Univ Navarra Clin, Dept Allergy & Clin Immunol, Pamplona, Spain. [Rouzaire, P.] Univ Auvergne, Univ Hosp, Dept Immunol, Clermont Ferrand & ERTICa Res Grp, Clermont Ferrand, France. [Ebo, D. G.; Sabato, V.] Univ Antwerp, Dept Immunol Allergol Rheumatol, B-2020 Antwerp, Belgium. [Ebo, D. G.; Sabato, V.] Univ Antwerp Hosp, Antwerp, Belgium. [Pecaric-Petkovic, T.] Adverse Drug React Anal & Consulting ADR AC GmbH, Bern, Switzerland. [Patil, S. U.; Shreffler, W. G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Patil, S. U.; Shreffler, W. G.] Harvard Univ, Sch Med, Boston, MA USA. [Hausmann, O. V.] Univ Bern, Inselspital, Dept Rheumatol Immunol & Allergol, CH-3010 Bern, Switzerland. [Hausmann, O. V.] Loewenpraxis, Luzern, Switzerland. [Korosec, P.] Univ Clin Resp & Allerg Dis Golnik, Lab Clin Immunol & Mol Genet, Golnik, Slovenia. [Knol, E. F.] Univ Med Ctr Utrecht, Dept Immunol, Utrecht, Netherlands. [Knol, E. F.] Univ Med Ctr Utrecht, Dept Dermatol Allergol, Utrecht, Netherlands. RP Hoffmann, HJ (reprint author), Aarhus Univ, Dept Resp Dis & Allergy, Dept Clin Med, Norrebrogade 44, DK-8000 Aarhus C, Denmark. EM hjh@clin.au.dk RI EBO, Didier/H-4894-2016; Sabato, Vito/B-6479-2017; OI EBO, Didier/0000-0003-0672-7529; Sabato, Vito/0000-0002-1321-314X; Ferrer, Marta/0000-0001-8495-1302 FU BD Biosciences, Erembodegem, Belgium; Novartis, Basel, CH FX AFS, BE, SUP, WGS, OVH obtained research funding, and BE and OVH received speaker honoraria from Buhlmann Laboratories, Schoenenbuch, CH. BE received research funding from BD Biosciences, Erembodegem, Belgium. AN received research funding from Novartis, Basel, CH. HJH, CM, MF, PR, DE, VS, MLS, TPP, PK, and EFK have no conflict of interest to report. NR 137 TC 36 Z9 38 U1 5 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD NOV PY 2015 VL 70 IS 11 BP 1393 EP 1405 DI 10.1111/all.12698 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA CU2CJ UT WOS:000363329400004 PM 26198455 ER PT J AU Napadow, V Li, A Loggia, ML Kim, J Mawla, I Desbordes, G Schalock, PC Lerner, EA Tran, TN Ring, J Rosen, BR Kaptchuk, TJ Pfab, F AF Napadow, V. Li, A. Loggia, M. L. Kim, J. Mawla, I. Desbordes, G. Schalock, P. C. Lerner, E. A. Tran, T. N. Ring, J. Rosen, B. R. Kaptchuk, T. J. Pfab, F. TI The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients SO ALLERGY LA English DT Article DE atopic dermatitis; caudate; nocebo; placebo; pruritus ID HISTAMINE-INDUCED ITCH; INTRINSIC FUNCTIONAL CONNECTIVITY; I HYPERSENSITIVITY ITCH; SURFACE-BASED ANALYSIS; CROSSOVER TRIAL; NEURAL MECHANISMS; CHRONIC PRURITUS; PLACEBO; ACUPUNCTURE; PAIN AB BackgroundPsychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. MethodsWe collected functional MRI (fMRI) data from atopic dermatitis (AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen vs open-label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. ResultsNocebo saline produced greater itch than open saline control (P<0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dlPFC), and intraparietal sulcus (iPS) - brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dlPFC and caudate activation to nocebo-induced itch also demonstrated greater dlPFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen-evoked itch, suggesting increased generalized modulation of itch perception. ConclusionsOur study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients. C1 [Napadow, V.; Li, A.; Loggia, M. L.; Kim, J.; Mawla, I.; Desbordes, G.; Rosen, B. R.; Pfab, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, V.] Logan Univ, Dept Radiol, Chesterfield, MO USA. [Schalock, P. C.; Lerner, E. A.; Tran, T. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Ring, J.; Pfab, F.] Tech Univ Munich, Dept Dermatol & Allergy, D-80290 Munich, Germany. [Kaptchuk, T. J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies, Boston, MA 02215 USA. [Pfab, F.] Tech Univ Munich, Dept Prevent & Sports Med, D-80290 Munich, Germany. RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, 149 Thirteenth St 2301, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu FU NIH [VN: K01-AT002166, R01-AT004714, BRR: P01-AT002048, TK: K24-AT004095, EAL: R01-AR057744]; NCRR (Harvard Clinical and Translational Science Center) [P41RR14075, CRC 1 UL1 RR025758]; Shared Instrumentation Grant [1S10RR023043, S10RR023401]; German Acupuncture Society (DAGfA); German Research Foundation [pf 690/2-1]; Christine Kuhne Center of Allergy and Education (CK-Care) FX We would like to thank NIH for funding support (VN: K01-AT002166, R01-AT004714, BRR: P01-AT002048; TK: K24-AT004095; EAL: R01-AR057744), the NCRR (P41RR14075; CRC 1 UL1 RR025758, Harvard Clinical and Translational Science Center), and the Shared Instrumentation Grant (1S10RR023043 & S10RR023401). This study was also partly funded by a grant of the German Acupuncture Society (DAGfA), German Research Foundation (pf 690/2-1), and the Christine Kuhne Center of Allergy and Education (CK-Care). NR 44 TC 5 Z9 5 U1 4 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD NOV PY 2015 VL 70 IS 11 BP 1485 EP 1492 DI 10.1111/all.12727 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA CU2CJ UT WOS:000363329400014 PM 26280659 ER PT J AU Zeidan, AM Sekeres, MA Wang, XF Al Ali, N Garcia-Manero, G Steensma, DP Roboz, G Barnard, J Padron, E DeZern, A Maciejewski, JP List, AF Komrokji, RS AF Zeidan, Amer M. Sekeres, Mikkael A. Wang, Xiao-Feng Al Ali, Najla Garcia-Manero, Guillermo Steensma, David P. Roboz, Gail Barnard, John Padron, Eric DeZern, Amy Maciejewski, Jaroslaw P. List, Alan F. Komrokji, Rami S. CA MDS Clinical Res Consortium TI Comparing the prognostic value of risk stratifying models for patients with lower-risk myelodysplastic syndromes: Is one model better? SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID SCORING SYSTEM IPSS; STRATIFICATION; VALIDATION; MUTATIONS; THERAPY AB Some patients classified as having lower-risk (LR)-disease by the International Prognostic Scoring System (IPSS) fare more poorly than predicted. We examined the prognostic utility of IPSS, the MD Anderson LR-Prognostic System (LR-PSS), and the revised IPSS (IPSS-R) in a large cohort of patients classified as having IPSS LR-MDS in the MDS Clinical Research Consortium database. Actual overall survival (OS) was assessed in patients with IPSS LR-MDS (i.e. low and intermediate-1) using Kaplan-Meier methods. Harrell's c index (HCI) and Akaike information criteria (AIC) were used to compare the models. Median OS of 1,140 eligible patients was 47 months (95% CI, 44-52). Median follow-up was 62 months. HCI values indicating the discriminatory power of the models (higher is better) were better for LR-PSS (0.74, 95% CI, 0.70-0.78) than IPSS-R (0.64, 95% CI, 0.60-0.67) and IPSS (0.64, 95% CI, 0.60-0.68). Similarly, AIC values indicating the goodness of the fit were better for LR-PSS than IPSS-R and IPSS (8,110, 8,147, and 8,150, respectively, lower is better). LR-PSS assigned 25.1% and 37.4% of patients with IPSS LR-MDS into LR-PSS Category 3 and IPSS-R Categories Intermediate, respectively. Of 291 patients (25.5%) who survived 24 months from diagnosis, only 37.1% and 45% were classified as LR-PSS category 3 and IPSS-R categories Intermediate, respectively (P = 0.06). While both LR-PSS and IPSS-R distinguish groups with varied survival outcome among patients with IPSS LR-MDS, both tools fail to identify a significant subset with poor OS. Future studies should assess whether patients identified as at increased risk will benefit from earlier interventions with disease-modifying therapies. Am. J. Hematol. 90:1036-1040, 2015. (c) 2015 Wiley Periodicals, Inc. C1 [Zeidan, Amer M.] Yale Univ, Dept Internal Med, Sect Hematol, New Haven, CT 06520 USA. [Zeidan, Amer M.] Yale Comprehens Canc Ctr, New Haven, CT USA. [Sekeres, Mikkael A.; Wang, Xiao-Feng; Barnard, John; Maciejewski, Jaroslaw P.] Cleveland Clin, Dept Med, Leukemia Program, Cleveland, OH 44106 USA. [Al Ali, Najla; List, Alan F.; Komrokji, Rami S.] H Lee Moffitt Canc Ctr & Res Inst, Dept Malignant Hematol, Tampa, FL USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Roboz, Gail] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. [DeZern, Amy] Johns Hopkins Univ, Dept Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Zeidan, AM (reprint author), Yale Univ, Dept Internal Med, 333 Cedar St,POB 208028, New Haven, CT 06520 USA. EM amer.zeidan@yale.edu FU Evans Foundation; Aplastic Anemia and Myelodysplastic Syndromes Foundation (AAMDSF) FX Contract grant sponsors: Evans Foundation and the Aplastic Anemia and Myelodysplastic Syndromes Foundation (AAMDSF). NR 17 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2015 VL 90 IS 11 BP 1036 EP 1040 DI 10.1002/ajh.24173 PG 5 WC Hematology SC Hematology GA CU3YW UT WOS:000363463600015 PM 26284571 ER PT J AU Lavigne, J Sharr, C Ozonoff, A Prock, LA Baumer, N Brasington, C Cannon, S Crissman, B Davidson, E Florez, JC Kishnani, P Lombardo, A Lyerly, J McCannon, JB McDonough, ME Schwartz, A Berrier, KL Sparks, S Stock-Guild, K Toler, TL Vellody, K Voelz, L Skotko, BG AF Lavigne, Jenifer Sharr, Christianne Ozonoff, Al Prock, Lisa Albers Baumer, Nicole Brasington, Campbell Cannon, Sheila Crissman, Blythe Davidson, Emily Florez, Jose C. Kishnani, Priya Lombardo, Angela Lyerly, Jordan McCannon, Jessica B. McDonough, Mary Ellen Schwartz, Alison Berrier, Kathryn L. Sparks, Susan Stock-Guild, Kara Toler, Tomi L. Vellody, Kishore Voelz, Lauren Skotko, Brian G. TI National down syndrome patient database: Insights from the development of a multi-center registry study SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE down syndrome; patient database; registry; trisomy 21 ID CHILDREN; DISEASE AB The Down Syndrome Study Group (DSSG) was founded in 2012 as a voluntary, collaborative effort with the goal of supporting evidenced-based health care guidelines for individuals with Down syndrome (DS). Since then, 5 DS specialty clinics have collected prospective, longitudinal data on medical conditions that co-occur with DS. Data were entered by clinical staff or trained designees into the National Down Syndrome Patient Database, which we created using REDCap software. In our pilot year, we enrolled 663 participants across the U.S., ages 36 days to 70 years, from multiple racial and ethnic backgrounds. Here we report: (i) the demographic distribution of participants enrolled, (ii) a detailed account of our database infrastructure, and (iii) lessons learned during our pilot year to assist future researchers with similar goals for other patient populations. (c) 2015 Wiley Periodicals, Inc. C1 [Lavigne, Jenifer; Brasington, Campbell; Lyerly, Jordan; Sparks, Susan] Carolinas Healthcare Syst, Levine Childrens Hosp, Clin Genet, Dept Pediat, Charlotte, NC USA. [Sharr, Christianne; Florez, Jose C.; McCannon, Jessica B.; McDonough, Mary Ellen; Schwartz, Alison; Toler, Tomi L.; Skotko, Brian G.] Massachusetts Gen Hosp, Div Genet, Dept Pediat, Down Syndrome Program, Boston, MA 02114 USA. [Ozonoff, Al; Prock, Lisa Albers; Baumer, Nicole; Davidson, Emily; Florez, Jose C.; McCannon, Jessica B.; Schwartz, Alison; Skotko, Brian G.] Harvard Univ, Sch Med, Boston, MA USA. [Ozonoff, Al] Boston Childrens Hosp, Ctr Patient Safety & Qual Res, Program Patient Safety & Qual, Boston, MA USA. [Prock, Lisa Albers; Baumer, Nicole; Davidson, Emily; Lombardo, Angela; Stock-Guild, Kara; Voelz, Lauren] Boston Childrens Hosp, Div Dev Med, Dept Med, Down Syndrome Program, Boston, MA USA. [Cannon, Sheila; Vellody, Kishore] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Down Syndrome Ctr Western Penn, Pittsburgh, PA USA. [Crissman, Blythe; Kishnani, Priya; Berrier, Kathryn L.] Duke Univ, Med Ctr, Div Med Genet, Comprehens Down Syndrome Program, Durham, NC USA. RP Skotko, BG (reprint author), Massachusetts Gen Hosp, Div Genet, Dept Pediat, Down Syndrome Program, 185 Cambridge St,Room 2222, Boston, MA 02114 USA. EM bskotko@mgh.harvard.edu OI Berrier, Kathryn/0000-0003-3510-6836; Toler, Tomi/0000-0002-1637-8310 FU Hoffmann-La Roche, Inc. FX We do not believe that any of the authors have conflicts of interest as defined in the Guide for Authors, though we wanted to share the following about our connections to Down syndrome: Dr. Skotko serves in a non-paid capacity on the Board of Directors for the Band of Angels Foundation, a non-profit organization, and on the Medical and Scientific Advisory Board for the Massachusetts Down Syndrome Congress. He is a non-paid clinical adviser to the National Center for Prenatal and Postnatal Down Syndrome Diagnoses Resources. Dr. Skotko occasionally gets remunerated from Down syndrome non-profit organizations for speaking engagements about Down syndrome. He receives research support from Hoffmann-La Roche, Inc. He has a sister with Down syndrome. Dr. McCannon and Dr. Schwartz are co- investigators for research funded by Hoffmann-La Roche, Inc. Dr. Kishnani serves on the clinical advisory board for National Down Syndrome Society. She also serves on the board for DSConnect (TM), a contact registry for individuals with Down syndrome. She has received research support from Hoffmann-La Roche, Inc. Dr. Davidson and Dr. Baumer serve in a non-paid capacity on the Medical and Scientific Advisory Board for the Massachusetts Down Syndrome Congress. NR 15 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV PY 2015 VL 167 IS 11 BP 2520 EP 2526 DI 10.1002/ajmg.a.37267 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA CU1LB UT WOS:000363281900007 PM 26249752 ER PT J AU Li, P Boronat, S Geffrey, AL Barber, I Grottkau, BE Thiele, EA AF Li, Patrick Boronat, Susana Geffrey, Alexandra Lauryn Barber, Ignasi Grottkau, Brian Edward Thiele, Elizabeth Anne TI Rib and vertebral bone fibrous dysplasia in a child with tuberous sclerosis complex SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE tuberous sclerosis complex; pediatric; bone lesion; fibrous dysplasia; mTOR inhibitors AB Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems, primarily the skin, brain, heart, kidneys, lungs, and eyes. The skeletal system is commonly affected in patients with TSC, but these bone lesions are generally asymptomatic and have not been well characterized. We present clinically significant bone growth in two ribs and vertebrae in an 8-year-old male patient with TSC and discuss the effects of mammalian target of rapamycin (mTOR) inhibitors as a possible treatment for these osseous abnormalities. This report suggests that skeletal lesions may hold more clinical significance than previously assumed and that further research should be directed toward understanding bone involvement in TSC. (c) 2015 Wiley Periodicals, Inc. C1 [Li, Patrick; Boronat, Susana; Geffrey, Alexandra Lauryn; Thiele, Elizabeth Anne] Massachusetts Gen Hosp, Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA. [Boronat, Susana] Univ Autonoma Barcelona, Vall dHebron Hosp, Pediat Neurol, E-08193 Barcelona, Spain. [Barber, Ignasi] Univ Autonoma Barcelona, Vall dHebron Hosp, Pediat Radiol, E-08193 Barcelona, Spain. [Grottkau, Brian Edward] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Herscot Ctr Tuberous Sclerosis Complex, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for TSC, Massachusetts General Hospital FX Grant sponsor: Herscot Center for TSC, Massachusetts General Hospital. NR 8 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV PY 2015 VL 167 IS 11 BP 2755 EP 2757 DI 10.1002/ajmg.a.37235 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA CU1LB UT WOS:000363281900043 PM 26177838 ER PT J AU Karaca, E Yuregir, OO Bozdogan, ST Aslan, H Pehlivan, D Jhangiani, SN Akdemir, ZC Gambin, T Bayram, Y Atik, MM Erdin, S Muzny, D Gibbs, RA Lupski, JR AF Karaca, Ender Yuregir, Ozge O. Bozdogan, Sevcan T. Aslan, Huseyin Pehlivan, Davut Jhangiani, Shalini N. Akdemir, Zeynep C. Gambin, Tomasz Bayram, Yavuz Atik, Mehmed M. Erdin, Serkan Muzny, Donna Gibbs, Richard A. Lupski, James R. CA Baylor-Hopkins Ctr Mendelian TI Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Klippel-Feil syndrome; heterotaxy; notch signaling; somitogenesis; right-left axis determination ID VERTEBRAL SEGMENTATION DEFECTS; MUTATIONS; PROTEINS; PHENOTYPE; FAMILY; GDF6 AB Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in additionfrom a mechanistic standpointsuggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. (c) 2015 Wiley Periodicals, Inc. C1 [Karaca, Ender; Pehlivan, Davut; Jhangiani, Shalini N.; Akdemir, Zeynep C.; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M.; Muzny, Donna; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Yuregir, Ozge O.] Ankara Numune Training & Res Hosp, Dept Med Genet, Adana, Turkey. [Bozdogan, Sevcan T.] Mersin Univ, Dept Med Genet, Mersin, Turkey. [Aslan, Huseyin] Eskisehir Osmangazi Univ, Dept Med Genet, Fac Med, Eskisehir, Turkey. [Jhangiani, Shalini N.; Muzny, Donna; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Erdin, Serkan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Erdin, Serkan] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Lupski, JR (reprint author), Baylor Coll Med, Dept Mol & Human Genet, One Baylor Plaza,Room 604B, Houston, TX 77030 USA. EM jlupski@bcm.edu RI Erdin, Serkan/B-4988-2008; OI Erdin, Serkan/0000-0001-6587-2625; Gambin, Tomasz/0000-0002-0941-4571 FU US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) [U54HG006542] FX Grant sponsor: US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI); Grant number: U54HG006542. NR 17 TC 3 Z9 3 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV PY 2015 VL 167 IS 11 BP 2795 EP 2799 DI 10.1002/ajmg.a.37263 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA CU1LB UT WOS:000363281900049 PM 26238661 ER PT J AU Jones, GH Tefferi, A Steensma, D Kantarjian, H AF Jones, Gregory H. Tefferi, Ayalew Steensma, David Kantarjian, Hagop TI The Hippocratic Oath, the US Health Care System, and the Affordable Care Act in 2015 SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Jones, Gregory H.; Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Tefferi, Ayalew] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN USA. [Steensma, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kantarjian, H (reprint author), Univ Texas MD Anderson Canc Ctr, 1400 Holcombe, Houston, TX 77030 USA. EM hkantarjian@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 16 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD NOV PY 2015 VL 128 IS 11 BP 1162 EP 1164 DI 10.1016/j.amjmed.2015.06.036 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CU3VI UT WOS:000363453500025 PM 26184683 ER PT J AU Simon, HB AF Simon, Harvey B. TI Exercise and Health: Dose and Response, Considering Both Ends of the Curve SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Moderate exercise; Health; Strenuous exercise; Heart ID CORONARY-HEART-DISEASE; TIME PHYSICAL-ACTIVITY; LEISURE-TIME; ALL-CAUSE; CARDIOVASCULAR-DISEASE; PROSPECTIVE COHORT; VIGOROUS EXERCISE; AMERICAN-COLLEGE; LIFE EXPECTANCY; SPORTS-MEDICINE AB Over the past 60 years, an enormous body of data has demonstrated that exercise is good for health. Recently, however, there has been concern that repetitive intense exercise may have deleterious cardiovascular effects. To evaluate this possibility, I have reviewed the health response to exercise, with particular attention to the body's minimum daily requirement and to the maximum amount that is safe and effective. (C) 2015 Elsevier Inc. All rights reserved. C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. [Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Simon, HB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM hsimon@mgh.harvard.edu NR 46 TC 4 Z9 4 U1 2 U2 8 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 2015 VL 128 IS 11 BP 1171 EP 1177 DI 10.1016/j.amjmed.2015.05.012 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CU3VI UT WOS:000363453500028 PM 26031888 ER PT J AU Newell, KA Asare, A Sanz, I Wei, C Rosenberg, A Gao, Z Kanaparthi, S Asare, S Lim, N Stahly, M Howell, M Knechtle, S Kirk, A Marks, WH Kawai, T Spitzer, T Tolkoff-Rubin, N Sykes, M Sachs, DH Cosimi, AB Burlingham, WJ Phippard, D Turka, LA AF Newell, K. A. Asare, A. Sanz, I. Wei, C. Rosenberg, A. Gao, Z. Kanaparthi, S. Asare, S. Lim, N. Stahly, M. Howell, M. Knechtle, S. Kirk, A. Marks, W. H. Kawai, T. Spitzer, T. Tolkoff-Rubin, N. Sykes, M. Sachs, D. H. Cosimi, A. B. Burlingham, W. J. Phippard, D. Turka, L. A. TI Longitudinal Studies of a B Cell-Derived Signature of Tolerance in Renal Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID KIDNEY-TRANSPLANTATION; MAINTENANCE IMMUNOSUPPRESSION; OPERATIONAL TOLERANCE; BONE-MARROW; EXPRESSION; WITHDRAWAL; REJECTION; ALLOGRAFT; SURVIVAL; PROFILE AB Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transplant recipients and patients enrolled in two interventional tolerance trials using flow cytometry and gene expression profiling. Using a previously reported tolerant cohort as well as newly identified tolerant patients, we confirmed our previous finding that tolerance was associated with increased expression of B cell-associated genes relative to immunosuppressed patients. This was not accounted for merely by an increase in total B cell numbers, but was associated with the increased frequencies of transitional and naive B cells. Moreover, serial measurements of gene expression demonstrated that this pattern persisted over several years, although patients receiving immunosuppression also displayed an increase in the two most dominant tolerance-related B cell genes, IGKV1D-13 and IGLL-1, over time. Importantly, patients rendered tolerant via induction of transient mixed chimerism, and those weaned to minimal immunosuppression, showed similar increases in IGKV1D-13 as did spontaneously tolerant individuals. Collectively, these findings support the notion that alterations in B cells may be a common theme for tolerant kidney transplant recipients, and that it is a useful monitoring tool in prospective trials. C1 [Newell, K. A.; Sanz, I.; Wei, C.; Knechtle, S.; Kirk, A.] Emory Univ, Dept Surg, Atlanta, GA 30322 USA. [Asare, A.; Kanaparthi, S.; Asare, S.; Lim, N.; Stahly, M.; Howell, M.; Phippard, D.; Turka, L. A.] Immune Tolerance Network, Bethesda, MD 20814 USA. [Asare, A.; Gao, Z.; Kanaparthi, S.; Asare, S.; Lim, N.; Stahly, M.; Kawai, T.; Sachs, D. H.; Cosimi, A. B.; Turka, L. A.] Harvard Univ, Sch Med, Dept Surg, Ctr Transplantat Sci,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosenberg, A.] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA. [Marks, W. H.] Swedish Med Ctr, Seattle, WA USA. [Spitzer, T.; Tolkoff-Rubin, N.; Turka, L. A.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Sykes, M.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Sykes, M.] Columbia Univ Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. [Burlingham, W. J.] Univ Wisconsin, Dept Surg, Madison, WI USA. RP Turka, LA (reprint author), Immune Tolerance Network, Bethesda, MD 20814 USA. EM kanewel@emory.edu; lturka@partners.org FU National Institute of Allergy and Infectious Diseases FX This research was performed as a project of the Immune Tolerance Network (NIH N01 AI15416 and UM1 AI-109565), an international clinical research consortium headquartered at the Benaroya Research Institute and supported by the National Institute of Allergy and Infectious Diseases. We thank the many clinicians, staff, and particularly the patients, who participated in the clinical trials that made this study possible. NR 38 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2015 VL 15 IS 11 BP 2908 EP 2920 DI 10.1111/ajt.13480 PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA CU1FG UT WOS:000363264800014 PM 26461968 ER PT J AU Huprikar, S Danziger-Isakov, L Ahn, J Kotton, CN Kumar, D AF Huprikar, S. Danziger-Isakov, L. Ahn, J. Kotton, C. N. Kumar, D. TI Reply to: "Need to Consider Full Societal Impact of Hepatitis B Virus-Positive Donors" SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Letter C1 [Huprikar, S.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Danziger-Isakov, L.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Ahn, J.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. [Kotton, C. N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kumar, D.] Univ Toronto, Dept Med, Toronto, ON, Canada. RP Huprikar, S (reprint author), Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. EM shirish.huprikar@mssm.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2015 VL 15 IS 11 BP 3014 EP 3014 DI 10.1111/ajt.13451 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA CU1FG UT WOS:000363264800030 PM 26372834 ER PT J AU Rudolph, JL AF Rudolph, James L. TI Delirium After Hip Fracture: Still a Problem SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID INTENSIVE-CARE-UNIT; POSTOPERATIVE DELIRIUM; METAANALYSIS; RECOGNITION; RISK C1 [Rudolph, James L.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org NR 17 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2015 VL 121 IS 5 BP 1119 EP 1120 DI 10.1213/ANE.0000000000000960 PG 2 WC Anesthesiology SC Anesthesiology GA CU1QE UT WOS:000363295600002 PM 26484450 ER PT J AU Mhyre, JM Bateman, BT AF Mhyre, Jill M. Bateman, Brian T. TI Stemming the Tide of Obstetric Morbidity SO ANESTHESIOLOGY LA English DT Article ID SEVERE MATERNAL MORBIDITY; UNITED-STATES; MORTALITY; COMPLICATIONS; CARE; SAFETY C1 [Mhyre, Jill M.] Univ Arkansas Med Sci, Dept Anesthesiol, Little Rock, AR 72205 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM bbateman@partners.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health [K08HD075831] FX Dr. Bateman is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (grant No. K08HD075831). NR 25 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2015 VL 123 IS 5 BP 986 EP 989 DI 10.1097/ALN.0000000000000847 PG 4 WC Anesthesiology SC Anesthesiology GA CT7RG UT WOS:000363011600002 PM 26352382 ER PT J AU Pollak, KA Stephens, LS Posner, KL Rathmell, JP Fitzgibbon, DR Dutton, RP Michna, E Domino, KB AF Pollak, Kelly A. Stephens, Linda S. Posner, Karen L. Rathmell, James P. Fitzgibbon, Dermot R. Dutton, Richard P. Michna, Edward Domino, Karen B. TI Trends in Pain Medicine Liability SO ANESTHESIOLOGY LA English DT Article ID CHRONIC NONCANCER PAIN; CLOSED CLAIMS PROJECT; OPIOID THERAPY; UNITED-STATES; MEDICARE POPULATION; NONMALIGNANT PAIN; ACTING OPIOIDS; MANAGEMENT; COMPLICATIONS; SOCIETY AB Background: The authors examined changes in the frequency of pain medicine malpractice claims and associated treatment modalities and outcomes over time. Methods: The authors analyzed trends in pain medicine claims from 1980 to 2012 in the Anesthesia Closed Claims Project database by binary logistic regression on year of event. Pain procedures in claims from 2000 to 2012 were compared with the proportion of pain procedures reported to the National Anesthesia Clinical Outcomes Registry in 2010-2014. Results: Malpractice claims for pain medicine increased from 3% of 2,966 total malpractice claims in the Anesthesia Closed Claims Project database in 1980-1989 to 18% of 2,743 anesthesia claims in 2000-2012 (odds ratio [OR], 1.088 per year; 95% CI, 1.078 to 1.098; P < 0.001). Outcomes in pain claims became more severe over time, with increases in death and permanent disabling injury (OR, 1.094 per year; P < 0.001). Nonneurolytic cervical injections increased to 27% of pain claims in 2000-2012 (OR, 1.054; P < 0.001), whereas National Anesthesia Clinical Outcomes Registry demonstrates that lumbar injections are a more common procedure. Claims associated with medication management increased to 17% of pain claims in 2000-2012 (OR, 1.116 per year; P < 0.001). Conclusions: Pain medicine claims have increased over time and have increased in severity. Claims related to cervical procedures were out of proportion to the frequency with which they are performed. These liability findings suggest that pain specialists should aggressively continue the search for safer and more effective therapies. C1 [Pollak, Kelly A.; Stephens, Linda S.; Posner, Karen L.; Fitzgibbon, Dermot R.; Domino, Karen B.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA. [Dutton, Richard P.] Amer Soc Anesthesiologists, Anesthesia Qual Inst, Schaumburg, IL USA. [Dutton, Richard P.] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. [Michna, Edward] Harvard Univ, Sch Med, Brigham & Womens Hosp, Pain Management Ctr, Boston, MA USA. RP Domino, KB (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, 1959 NE Pacific St,Box 356540, Seattle, WA 98195 USA. EM kdomino@uw.edu FU ASA; Anesthesia Quality Institute (AQI), Schaumburg, Illinois FX Supported in part by the ASA and the Anesthesia Quality Institute (AQI), Schaumburg, Illinois. All opinions expressed are those of the authors and do not reflect the policy of the ASA or AQI. NR 47 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2015 VL 123 IS 5 BP 1133 EP 1141 DI 10.1097/ALN.0000000000000855 PG 9 WC Anesthesiology SC Anesthesiology GA CT7RG UT WOS:000363011600018 PM 26378399 ER PT J AU Wellman, TJ Winkler, T Melo, MFV AF Wellman, Tyler J. Winkler, Tilo Melo, Marcos F. Vidal TI Modeling of Tracer Transport Delays for Improved Quantification of Regional Pulmonary F-18-FDG Kinetics, Vascular Transit Times, and Perfusion SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Plasma input function; Tracer kinetics; Capillary transit times; Positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE LUNG INJURY; BLOOD-FLOW MEASUREMENTS; PET HUMAN BRAIN; INPUT FUNCTION; MECHANICAL VENTILATION; METABOLIC-ACTIVITY; VOLUME; SHEEP; INFLAMMATION AB F-18-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary F-18-FDG kinetics do not account for delays in F-18-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of F-18-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic F-18-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n = 6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. (NN)-N-13 bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of F-18-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0 to 13.6 s, averaging 6.4 +/- 2.9 s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on (NN)-N-13-PET (R-2 = 0.92, p < 0.001). By incorporating local vascular transports delays, this model of pulmonary F-18-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation. C1 [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU National Heart, Lung, and Blood Institute [R01-HL121228, R01-HL086827] FX This work was supported by grants R01-HL121228 and R01-HL086827 from the National Heart, Lung, and Blood Institute. The authors declare that they have no conflicts of interest. Two authors (T. Winkler and M. F. Vidal Melo) have a patent related to the computation of the image-derived input function used in the study. NR 45 TC 0 Z9 0 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2015 VL 43 IS 11 BP 2722 EP 2734 DI 10.1007/s10439-015-1327-2 PG 13 WC Engineering, Biomedical SC Engineering GA CU0WE UT WOS:000363238800011 PM 25940652 ER PT J AU Van Stan, JH Mehta, DD Zeitels, SM Burns, JA Barbu, AM Hillman, RE AF Van Stan, Jarrad H. Mehta, Daryush D. Zeitels, Steven M. Burns, James A. Barbu, Anca M. Hillman, Robert E. TI Average Ambulatory Measures of Sound Pressure Level, Fundamental Frequency, and Vocal Dose Do Not Differ Between Adult Females With Phonotraumatic Lesions and Matched Control Subjects SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE ambulatory voice monitoring; occupational voice use; vocal fold nodules; vocal fold polyps; vocal loading; voice disorders ID VOICE THERAPY; FOLD NODULES; TREATMENT OUTCOMES; TEACHERS; PHONATION; HYPERFUNCTION; DISORDERS; DYSPHONIA; VIBRATION; HYGIENE AB Objectives: Clinical management of phonotraumatic vocal fold lesions (nodules, polyps) is based largely on assumptions that abnormalities in habitual levels of sound pressure level (SPL), fundamental frequency (f0), and/or amount of voice use play a major role in lesion development and chronic persistence. This study used ambulatory voice monitoring to evaluate if significant differences in voice use exist between patients with phonotraumatic lesions and normal matched controls. Methods: Subjects were 70 adult females: 35 with vocal fold nodules or polyps and 35 age-, sex-, and occupation-matched normal individuals. Weeklong summary statistics of voice use were computed from anterior neck surface acceleration recorded using a smartphone-based ambulatory voice monitor. Results: Paired t tests and Kolmogorov-Smirnov tests resulted in no statistically significant differences between patients and matched controls regarding average measures of SPL, f0, vocal dose measures, and voicing/voice rest periods. Paired t tests comparing f0 variability between the groups resulted in statistically significant differences with moderate effect sizes. Conclusions: Individuals with phonotraumatic lesions did not exhibit differences in average ambulatory measures of vocal behavior when compared with matched controls. More refined characterizations of underlying phonatory mechanisms and other potentially contributing causes are warranted to better understand risk factors associated with phonotraumatic lesions. C1 [Van Stan, Jarrad H.; Mehta, Daryush D.; Zeitels, Steven M.; Burns, James A.; Barbu, Anca M.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Van Stan, Jarrad H.; Mehta, Daryush D.; Hillman, Robert E.] MGH Inst Hlth Profess, Boston, MA USA. [Mehta, Daryush D.; Zeitels, Steven M.; Burns, James A.; Barbu, Anca M.; Hillman, Robert E.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Hillman, RE (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq, Boston, MA 02114 USA. EM Hillman.Robert@MGH.HARVARD.EDU RI Emchi, Karma/Q-1952-2016 FU Voice Health Institute; National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders [R33 DC011588] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Voice Health Institute and the National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders under Grant R33 DC011588. The paper's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 70 TC 2 Z9 2 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-4894 EI 1943-572X J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 2015 VL 124 IS 11 BP 864 EP 874 DI 10.1177/0003489415589363 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA CT8KM UT WOS:000363065300004 PM 26024911 ER PT J AU Jackevicius, CA de Leon, NK Lu, LY Chang, DS Warner, AL Mody, FV AF Jackevicius, Cynthia A. de Leon, Noelle K. Lu, Lingyun Chang, Donald S. Warner, Alberta L. Mody, Freny Vaghaiwalla TI Impact of a Multidisciplinary Heart Failure Post-hospitalization Program on Heart Failure Readmission Rates SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE heart failure; hospitalization; readmission ID RANDOMIZED-TRIAL; DISCHARGE; CARE; INTERVENTION; METAANALYSIS; ADMISSIONS; MANAGEMENT; OUTCOMES; DISEASE; CLINICS AB Background: Specialized chronic heart failure (HF) clinics have demonstrated significant reductions in readmissions. Limited evidence is available regarding HF clinics in the immediate post-discharge period. Objective: To evaluate the effect of a multidisciplinary HF clinic on 90-day readmission rates and all-cause mortality in those recently discharged from a HF hospitalization. Methods: In this retrospective cohort study, patients discharged with a primary HF diagnosis who attended the HF postdischarge clinic in 2010-2012 were compared with controls from 2009. During 6 clinic visits, patients were seen by a physician assistant, clinical pharmacist specialist, and case manager, with care overseen by a cardiologist. The program focused on optimizing therapy, identifying HF etiology/precipitating factors, medication titration, education, and medication adherence. The primary outcome was 90-day HF readmission. A multivariate Cox proportional hazards model was used to compare outcomes. Results: Among the 277 patients (144 clinic, 133 control) in the study, 7.6% of patients in the clinic and 23.3% of patients in the control group were readmitted for HF within 90 days (aHR (adjusted hazard ratio) = 0.17; 95% CI = 0.07-0.41; P < 0.001; ARR (absolute risk reduction) = 15.7%; NNT (number needed to treat) = 7). Clinic patients had lower 90-day time-to-first HF readmission or all-cause mortality (9.0% vs 28.6%; aHR = 0.28; 95% CI = 0.06-0.31; P < 0.001; ARR = 19.6%; NNT = 6). Conclusions: The multidisciplinary HF posthospitalization outpatient program was associated with a significant reduction in 90-day HF readmissions in patients who were recently discharged from a HF hospitalization. C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Pomona, CA USA. [Jackevicius, Cynthia A.; Lu, Lingyun; Chang, Donald S.; Warner, Alberta L.; Mody, Freny Vaghaiwalla] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [de Leon, Noelle K.] Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. [de Leon, Noelle K.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. [Lu, Lingyun] Calif Northstate Univ, Coll Pharm, Elk Grove, CA USA. [Chang, Donald S.; Warner, Alberta L.; Mody, Freny Vaghaiwalla] Univ Calif Los Angeles, Los Angeles, CA USA. RP Jackevicius, CA (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Cynthia.jackevicius@va.gov FU Reginald Villacorta, MS FX We would like to acknowledge Reginald Villacorta, MS, who was a paid statistical consultant for the study. We would also like to acknowledge the following clinic providers: Jeffrey Garcia, PA-C, Maria Greco, RN, as well as the cardiology clinic nurse practitioners, cardiology fellows, clinic nurses, and clinic clerks. NR 19 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2015 VL 49 IS 11 BP 1189 EP 1196 DI 10.1177/1060028015599637 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CU0OW UT WOS:000363217800002 PM 26259774 ER PT J AU Marcum, ZA Perera, S Thorpe, JM Switzer, GE Gray, SL Castle, NG Strotmeyer, ES Simonsick, EM Bauer, DC Shorr, RI Studenski, SA Hanlon, JT AF Marcum, Zachary A. Perera, Subashan Thorpe, Joshua M. Switzer, Galen E. Gray, Shelly L. Castle, Nicholas G. Strotmeyer, Elsa S. Simonsick, Eleanor M. Bauer, Douglas C. Shorr, Ronald I. Studenski, Stephanie A. Hanlon, Joseph T. CA Hlth ABC Study USA TI Anticholinergic Use and Recurrent Falls in Community-Dwelling Older Adults: Findings From the Health ABC Study SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE cholinergic antagonist; accidental falls; older adults; pharmacoepidemiology ID BODY-COMPOSITION; PEOPLE; COHORT; ASSOCIATIONS; MEDICATIONS; BURDEN; ELDERS; RISK; CARE AB Background: Although it is generally accepted that anticholinergic use may lead to a fall, results from studies assessing the association between anticholinergic use and falls are mixed. In addition, direct evidence of an association between use of anticholinergic medications and recurrent falls among community-dwelling elders is not available. Objective: To assess the association between anticholinergic use across multiple anticholinergic subclasses, including over-the-counter medications, and recurrent falls. Methods: This was a longitudinal analysis of 2948 participants, with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Self-reported use of anticholinergic medication was identified at years 1, 2, 3, 5, and 6 as defined by the list from the 2015 American Geriatrics Society Beers Criteria. Dosage and duration were also examined. The main outcome was recurrent falls (2) in an ensuing 12-month period from each medication data collection. Results: Using multivariable generalized estimating equation models, controlling for demographic, health status/behaviors, and access-to-care factors, a 34% increase in likelihood of recurrent falls in anticholinergic users (adjusted odds ratio = 1.34; 95% CI = 0.93-1.93) was observed, but the results were not statistically significant; similar results were found with higher doses and longer duration of use. Conclusion: Increased point estimates suggest an association of anticholinergic use with recurrent falls, but the associations did not reach statistical significance. Future studies are needed for more definitive evidence and to examine other measures of anticholinergic burden and associations with more intermediate adverse effects such as cognitive function. C1 [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Seattle, WA 98102 USA. [Perera, Subashan; Thorpe, Joshua M.; Switzer, Galen E.; Castle, Nicholas G.; Strotmeyer, Elsa S.; Hanlon, Joseph T.] Univ Pittsburgh, Pittsburgh, PA USA. [Thorpe, Joshua M.; Switzer, Galen E.; Hanlon, Joseph T.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Simonsick, Eleanor M.; Studenski, Stephanie A.] NIA, Baltimore, MD 21224 USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shorr, Ronald I.] Vet Affairs Med Ctr, Gainesville, FL 32608 USA. RP Marcum, ZA (reprint author), Univ Washington, Sch Pharm, Dept Pharm, 1959 NE Pacific St,H375G,Box 357630, Seattle, WA 98102 USA. EM zmarcum@uw.edu OI Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging (NIA) [P30AG024827, T32 AG021885, K07AG033174, R01AG028050]; National Institutes of Health, NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Nursing research grant [R01NR012459] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was primarily supported by National Institute on Aging (NIA) grants and contracts (P30AG024827, T32 AG021885, K07AG033174, R01AG028050). This research was also supported in part by the Intramural Research program of the National Institutes of Health, NIA (N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106), and a National Institute of Nursing research grant (R01NR012459). NR 29 TC 2 Z9 2 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2015 VL 49 IS 11 BP 1214 EP 1221 DI 10.1177/1060028015596998 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CU0OW UT WOS:000363217800005 PM 26228936 ER PT J AU Kim, SC Schneeweiss, S Glynn, RJ Doherty, M Goldfine, AB Solomon, DH AF Kim, Seoyoung C. Schneeweiss, Sebastian Glynn, Robert J. Doherty, Michael Goldfine, Allison B. Solomon, Daniel H. TI Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: a population-based cohort study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ACTIVATED T-CELLS; RHEUMATOID-ARTHRITIS; IV CD26; PSORIATIC-ARTHRITIS; MULTIPLE-SCLEROSIS; CONTROLLED-TRIAL; SYNOVIAL-FLUID; VALIDATION; EXPRESSION AB Objective Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane glycoprotein that has a costimulatory function in the immune response. DPP4 inhibitors (DPP4i) are oral glucose-lowering drugs for type 2-diabetes mellitus (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis, multiple sclerosis and inflammatory bowel disease, associated with DPP4i in patients with T2DM. Methods Using US insurance claims data (2005-2012), we conducted a population-based cohort study that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and non-DPP4i (non-DPP4i plus metformin). RA and other AD were identified with >= 2 diagnoses and >= 1 dispensing for AD-specific immunomodulating drugs or steroids. Composite AD includes RA or other AD. Propensity score (PS)-stratified Cox proportional hazards models compared the risk of AD in DPP4i initiators versus non-DPP4i, controlling for potential confounders. Results After asymmetric trimming on the PS, 73 928 patients with T2DM starting DPP4i combination therapy and 163 062 starting non-DPP4i combination therapy were selected. Risks of incident RA and composite AD were lower in the DPP4i group versus non-DPP4i with the PS-stratified HR of 0.66 (95% Cl 0.44 to 0.99) for RA, 0.73 (0.51 to 1.03) for other AD and 0.68 (95% Cl 0.52 to 0.89) for composite AD. Conclusions In this large cohort of diabetic patients, those initiating DPP4i combination therapy appear to have a decreased risk of incident AD including RA compared with those initiating non-DPP4i combination therapy. These results may suggest possible pharmacological pathways for prevention or treatment of AD. C1 [Kim, Seoyoung C.; Schneeweiss, Sebastian; Glynn, Robert J.; Doherty, Michael; Solomon, Daniel H.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02120 USA. [Kim, Seoyoung C.; Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02120 USA. [Kim, Seoyoung C.; Schneeweiss, Sebastian] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kim, SC (reprint author), Brigham & Womens Hosp, Dept Med, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM skim62@partners.org RI Schneeweiss, Sebastian/C-2125-2013; OI Kim, Seoyoung/0000-0002-2517-3579 FU Pfizer; Pharmaceutical Research and Manufacturers of America (PhRMA) foundation; Novartis; AstraZeneca; Amgen; Lilly; CORRONA; Bristol Myers Squibb FX SCK receives research support from Pfizer and tuition support for the Pharmacoepidemiology Program at the Harvard School of Public Health partially funded by the Pharmaceutical Research and Manufacturers of America (PhRMA) foundation. SS is consultant to WHISCON, LLC and to Aetion, Inc. of which he also owns shares. He is principal investigator of investigator-initiated grants to the Brigham and Women's Hospital from Novartis, and Boehringer-Ingelheim unrelated to the topic of this study. RJG received research grants from AstraZeneca and Novartis. DHS receives research support from Amgen, Lilly, Pfizer, and CORRONA and serves in unpaid roles on studies sponsored by Pfizer, Novartis, Lilly and Bristol Myers Squibb. DHS also receives royalties from UpToDate. NR 57 TC 8 Z9 8 U1 0 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2015 VL 74 IS 11 BP 1968 EP 1975 DI 10.1136/annrheumdis-2014-205216 PG 8 WC Rheumatology SC Rheumatology GA CU2JC UT WOS:000363348800004 PM 24919467 ER PT J AU Schmidt-Lauber, C Bossaller, L Abujudeh, HH Vladimer, GI Christ, A Fitzgerald, KA Latz, E Gravallese, EM Marshak-Rothstein, A Kay, J AF Schmidt-Lauber, Christian Bossaller, Lukas Abujudeh, Hani H. Vladimer, Gregory I. Christ, Anette Fitzgerald, Katherine A. Latz, Eicke Gravallese, Ellen M. Marshak-Rothstein, Ann Kay, Jonathan TI Gadolinium-based compounds induce NLRP3-dependent IL-1 beta production and peritoneal inflammation SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; ALTERNATIVELY ACTIVATED MACROPHAGES; STAGE RENAL-DISEASE; CONTRAST AGENTS; NLRP3 INFLAMMASOME; DERMAL FIBROBLASTS; NALP3 INFLAMMASOME; POTENTIAL ROLE; TGF-BETA; SKIN AB Objective Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the precise mechanism by which fibrosis occurs in NSF is incompletely understood. Because other profibrotic agents, such as silica or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1 beta release with the subsequent development of fibrosis, we evaluated the effects of GBCAs on inflammasome activation. Methods Bone marrow derived macrophages from C57BL/6, Nlrp3(-/-) and Asc(-/-) mice were incubated with three Gd-containing compounds and IL-1 beta activation and secretion was detected by ELISA and western blot analysis. Inflammasome activation and regulation was investigated in IL-4- and interferon (IFN)gamma-polarised macrophages by ELISA, quantitative real time (qRT)-PCR and Nano String nCounter analysis. Furthermore, C57BL/6 and Nlrp3(-/-) mice were intraperitoneally injected with GBCA and recruitment of inflammatory cells to the peritoneum was analysed by fluorescence-activated cell sorting (FACS). Results Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL-1 beta secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo. Gd activated IL-4-polarised macrophages more effectively than IFN gamma-polarised macrophages, which preferentially expressed genes known to downregulate inflammasome activity. Conclusions These data suggest that Gd released from GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to fibrosis in an appropriate clinical setting. The preferential activation of IL-4-differentiated macrophages is consistent with the predominantly fibrotic presentation of NSF. C1 [Schmidt-Lauber, Christian; Gravallese, Ellen M.; Marshak-Rothstein, Ann; Kay, Jonathan] Univ Massachusetts, Sch Med, Div Rheumatol, Dept Med, Worcester, MA 01605 USA. [Bossaller, Lukas; Vladimer, Gregory I.; Christ, Anette; Fitzgerald, Katherine A.; Latz, Eicke] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, Worcester, MA 01605 USA. [Abujudeh, Hani H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abujudeh, Hani H.] Harvard Univ, Sch Med, Boston, MA USA. [Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany. [Latz, Eicke] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. RP Kay, J (reprint author), Univ Massachusetts, Sch Med, Div Rheumatol, Dept Med, Mem Campus,119 Belmont St, Worcester, MA 01605 USA. EM jonathan.kay@umassmemorial.org RI Latz, Eicke/H-3951-2014 OI Latz, Eicke/0000-0003-1488-5666 FU Alliance for Lupus Research; NIH [HL093262]; Biomedical Sciences Exchange Program (Hannover, Germany) FX This study was supported by a grant from the Alliance for Lupus Research (to AM-R) and NIH grant HL093262 (to EL) and by charitable contributions to the UMass Memorial Foundation from Lawrence J. and Beth A. Gornick, Peter W. and Sandra L. Burg, Jeffrey A. and Beth A. Kaiser, TorHoerman Law LLC and the Thomas and Diana Ryan Charitable Foundation, Inc. CS-L was supported by the Biomedical Sciences Exchange Program (Hannover, Germany). NR 56 TC 7 Z9 7 U1 0 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2015 VL 74 IS 11 BP 2062 EP 2069 DI 10.1136/annrheumdis-2013-204900 PG 8 WC Rheumatology SC Rheumatology GA CU2JC UT WOS:000363348800017 PM 24914072 ER PT J AU Chaudhari, SM Sluimer, JC Koch, M Theelen, TL Manthey, HD Busch, M Caballero-Franco, C Vogel, F Cochain, C Pelisek, J Daemen, MJ Lutz, MB Gorlach, A Kissler, S Hermanns, HM Zernecke, A AF Chaudhari, Sweena M. Sluimer, Judith C. Koch, Miriam Theelen, Thomas L. Manthey, Helga D. Busch, Martin Caballero-Franco, Celia Vogel, Frederick Cochain, Clement Pelisek, Jaroslav Daemen, Mat J. Lutz, Manfred B. Goerlach, Agnes Kissler, Stephan Hermanns, Heike M. Zernecke, Alma TI Deficiency of HIF1 alpha in Antigen-Presenting Cells Aggravates Atherosclerosis and Type 1 T-Helper Cell Responses in Mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE antigen-presenting cells; atherosclerosis; diet; high-fat; inflammation; leukocytes ID INDUCIBLE FACTOR 1-ALPHA; DENDRITIC CELLS; IN-VIVO; MURINE ATHEROSCLEROSIS; NEGATIVE REGULATOR; IMMUNE-RESPONSES; HYPOXIA; MACROPHAGES; ACTIVATION; LIPOPOLYSACCHARIDE AB Objective Although immune responses drive the pathogenesis of atherosclerosis, mechanisms that control antigen-presenting cell (APC)-mediated immune activation in atherosclerosis remain elusive. We here investigated the function of hypoxia-inducible factor (HIF)-1 in APCs in atherosclerosis. Approach and Results We found upregulated HIF1 expression in CD11c(+) APCs within atherosclerotic plaques of low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Conditional deletion of Hif1a in CD11c(+) APCs in high-fat diet-fed Ldlr(-/-) mice accelerated atherosclerotic plaque formation and increased lesional T-cell infiltrates, revealing a protective role of this transcription factor. HIF1 directly controls Signal Transducers and Activators of Transcription 3 (Stat3), and a reduced STAT3 expression was found in HIF1-deficient APCs and aortic tissue, together with an upregulated interleukin-12 expression and expansion of type 1 T-helper (Th1) cells. Overexpression of STAT3 in Hif1a-deficient APCs in bone marrow reversed enhanced atherosclerotic lesion formation and reduced Th1 cell expansion in chimeric Ldlr(-/-) mice. Notably, deletion of Hif1a in LysM(+) bone marrow cells in Ldlr(-/-) mice did not affect lesion formation or T-cell activation. In human atherosclerotic lesions, HIF1, STAT3, and interleukin-12 protein were found to colocalize with APCs. Conclusions Our findings identify HIF1 to antagonize APC activation and Th1 T cell polarization during atherogenesis in Ldlr(-/-) mice and to attenuate the progression of atherosclerosis. These data substantiate the critical role of APCs in controlling immune mechanisms that drive atherosclerotic lesion development. C1 [Chaudhari, Sweena M.; Koch, Miriam; Cochain, Clement; Zernecke, Alma] Univ Wurzburg, Univ Hosp Wurzburg, Inst Clin Biochem & Pathobiochem, D-97070 Wurzburg, Germany. [Manthey, Helga D.; Busch, Martin; Hermanns, Heike M.] Univ Wurzburg, Rudolf Virchow Ctr, D-97070 Wurzburg, Germany. [Lutz, Manfred B.] Univ Wurzburg, Inst Virol & Immunobiol, D-97070 Wurzburg, Germany. [Hermanns, Heike M.] Univ Wurzburg, Univ Hosp Wurzburg, Med Clin 2, Div Hepatol, D-97070 Wurzburg, Germany. [Sluimer, Judith C.; Theelen, Thomas L.] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht, Dept Pathol, Maastricht, Netherlands. [Caballero-Franco, Celia; Kissler, Stephan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Vogel, Frederick; Goerlach, Agnes] Tech Univ Munich, German Heart Ctr Munich, Expt & Mol Pediat Cardiol, Munich, Germany. [Pelisek, Jaroslav] Tech Univ Munich, Klinikum Rechts Isar, Dept Vasc & Endovasc Surg, D-80290 Munich, Germany. [Daemen, Mat J.] Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands. RP Zernecke, A (reprint author), Univ Klinikum Wurzburg, Inst Klin Biochem & Pathobiochem, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM alma.zernecke@uni-wuerzburg.de RI Sluimer, Judith/D-5277-2012; OI , /0000-0003-3062-7800 FU VENI fellowship of the Netherlands Organization of Scientific research [016.116.017]; Deutsche Forschungsgemeinschaft [ZE827/1-2, SFB688 TPA22]; Juvenile Diabetes Research Foundation [2-2010-383]; DRC from NIH [P30DK036836] FX This work was supported in part by the VENI fellowship of the Netherlands Organization of Scientific research (016.116.017) to J.C. Sluimer, the Deutsche Forschungsgemeinschaft (ZE827/1-2, SFB688 TPA22) to A. Zernecke, by a Career Development Award from Juvenile Diabetes Research Foundation (2-2010-383) to S. Kissler, and by DRC grant from NIH (P30DK036836) to the Joslin Diabetes Center. NR 46 TC 4 Z9 4 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2015 VL 35 IS 11 BP 2316 EP 2325 DI 10.1161/ATVBAHA.115.306171 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA CU1SV UT WOS:000363302500009 PM 26404487 ER PT J AU Siegel, MO Borkowska, AG Dubrovsky, L Roth, M Welti, R Roberts, AD Parenti, DM Simon, GL Sviridov, D Simmens, S Bukrinsky, M Fitzgerald, ML AF Siegel, Marc O. Borkowska, Alison G. Dubrovsky, Larisa Roth, Mary Welti, Ruth Roberts, Afsoon D. Parenti, David M. Simon, Gary L. Sviridov, Dmitri Simmens, Samuel Bukrinsky, Michael Fitzgerald, Michael L. TI HIV infection induces structural and functional changes in high density lipoproteins SO ATHEROSCLEROSIS LA English DT Article DE HIV; Anti-retroviral treatment; HDL; Proteomics; Lipidomics; Cholesterol efflux; PON; Atherosclerosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE CHOLESTEROL EFFLUX; SERUM PARAOXONASE-1 ACTIVITY; CARDIOVASCULAR RISK-FACTORS; ACUTE MYOCARDIAL-INFARCTION; HDL-CHOLESTEROL; ANTIRETROVIRAL THERAPY; GENERAL-POPULATION; ATHEROSCLEROSIS; DISEASE AB Background and aims: Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients. Methods and results: Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 +/- 0.01 U/mu l) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 +/- 0.01 U/mu l, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 +/- 0.01 U/mu l, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 +/- 0.01 U/mu l, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 +/- 0.01 U/mu l, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R-2 = 0.2611, p < 0.05; R-2 = 0.2722, p < 0.05; and R-2 = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R-2 = 0.26, p = 0.026). Conclusions: Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Siegel, Marc O.; Roberts, Afsoon D.; Parenti, David M.; Simon, Gary L.] George Washington Univ, SMHS, Dept Med, Div Infect Dis, Washington, DC 20037 USA. [Borkowska, Alison G.; Fitzgerald, Michael L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit,Dept Med, Boston, MA USA. [Dubrovsky, Larisa; Bukrinsky, Michael] George Washington Univ, SMHS, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. [Roth, Mary; Welti, Ruth] Kansas State Univ, Kansas Lipid Res Ctr, Manhattan, KS 66506 USA. [Sviridov, Dmitri] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia. [Simmens, Samuel] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Epidemiol & Biostat, Washington, DC 20037 USA. RP Bukrinsky, M (reprint author), George Washington Univ, SMHS, 2300 Eye St NW,Ross Hall 624, Washington, DC 20037 USA. EM mbukrins@gwu.edu; mfitzgerald@ccib.mgh.harvard.edu FU NIH [R01 HL093818, R01 HL101274, R01 HL112661]; District of Columbia Developmental Center for AIDS Research (DC DCFAR), an NIH [5P30 AI087714]; National Science Foundation [MCB 0455318, DBI 0521587]; EPSCoR Grant [EPS-0236913]; State of Kansas through Kansas Technology Enterprise Corporation; Kansas State University; National Institutes of Health [P20 RR16475] FX We wish to acknowledge the assistance of the clinical research coordinators in the Division of Infectious Diseases for their effort in the collection of these serum samples. We also wish to acknowledge Dr. Sylvia Silver at the George Washington University whose laboratory is responsible for maintaining the patient samples in the HIV Institute Biorepository. This study was supported by NIH grants R01 HL093818, R01 HL101274 and R01 HL112661, and by the District of Columbia Developmental Center for AIDS Research (DC DCFAR), an NIH-funded program (5P30 AI087714). DS is a fellow of the National Health and Medical Research Council of Australia. The Kansas Lipidomics Research Center was supported by National Science Foundation Grants MCB 0455318 and DBI 0521587, by EPSCoR Grant EPS-0236913 with matching support from the State of Kansas through Kansas Technology Enterprise Corporation and Kansas State University, and by National Institutes of Health Grant P20 RR16475. NR 48 TC 5 Z9 5 U1 0 U2 1 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 2015 VL 243 IS 1 BP 19 EP 29 DI 10.1016/j.atherosclerosis.2015.08.036 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CU1FQ UT WOS:000363266000003 PM 26343868 ER PT J AU Laugsand, LE Ix, JH Bartz, TM Djousse, L Kizer, JR Tracy, RP Dehghan, A Rexrode, K Lopez, OL Rimm, EB Siscovick, DS O'Donnell, CJ Newman, A Mukamal, KJ Jensen, MK AF Laugsand, Lars E. Ix, Joachim H. Bartz, Traci M. Djousse, Luc Kizer, Jorge R. Tracy, Russell P. Dehghan, Abbas Rexrode, Kathryn Lopez, Oscar L. Rimm, Eric B. Siscovick, David S. O'Donnell, Christopher J. Newman, Anne Mukamal, Kenneth J. Jensen, Majken K. TI Fetuin-A and risk of coronary heart disease: A Mendelian randomization analysis and a pooled analysis of AHSG genetic variants in 7 prospective studies SO ATHEROSCLEROSIS LA English DT Article DE Fetuin-A; Single nucleotide polymorphisms; Coronary heart disease; Mendelian randomization; Meta-analysis ID ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; INCIDENT DIABETES-MELLITUS; CARDIOVASCULAR HEALTH; OLDER-ADULTS; INSULIN-RECEPTOR; TYROSINE KINASE; ASSOCIATION; ATHEROSCLEROSIS; INHIBITOR; CALCIFICATION AB Background and aims: Fetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification). Methods: Genetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993. Results: Among Caucasians, both rs2248690 and rs4917 were associated with 12% lower fetuin-A concentrations per minor allele (P < 0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95% CI: 0.70-1.00) for rs2248690 and 0.97 (95% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048). Conclusion: Common variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Laugsand, Lars E.] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway. [Laugsand, Lars E.; Rimm, Eric B.; Jensen, Majken K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA. [Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Djousse, Luc] Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Djousse, Luc; Rexrode, Kathryn] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Biochem, Burlington, VT 05405 USA. [Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Kizer, Jorge R.; Rimm, Eric B.; Jensen, Majken K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Siscovick, David S.] Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David S.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Newman, Anne] UPMC, Univ Pittsburgh, Sch Hlth Sci, Pittsburgh, PA USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Jensen, MK (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RI Djousse, Luc/F-5033-2017; Newman, Anne B./C-6408-2013; OI Djousse, Luc/0000-0002-9902-3047; Newman, Anne B./0000-0002-0106-1150; Rexrode, Kathryn/0000-0003-3387-8429; Dehghan, Abbas/0000-0001-6403-016X FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL094555]; NHLBI CARe project (Broad Institute of Massachusetts Institute of Technology and Harvard) [N01HC65226]; NHLBI [HL080295]; National Institute on Aging (NIA) [R01AG023629]; Liaison Committee; National Institutes of Health, Bethesda, MD [HL35464, CA55075, CA87969, HL34594]; NIH [N01-AG-12100]; NIA Intramural Research Program; Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Netherlands Organization for Scientific Research (NWO) [916.12.154]; EUR Fellowship; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of Education, Culture and Science; Ministry of Health Welfare and Sports; European Commission; Municipality of Rotterdam; Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; National Institutes of Aging; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; Hjartavernd (the Icelandic Heart Association); Erasmus Medical Center; [HHSN268201200036C]; [HHSN268200800007C]; [N01HC55222]; [N01HC85079]; [N01HC85080]; [N01HC85081]; [N01HC85082]; [N01HC85083]; [NO1HC85086] FX The manuscript was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI) (R01 HL094555 to LD, J.R.K.J.H.I, and K.J.M) and genotyping was funded by the NHLBI CARe project (Broad Institute of Massachusetts Institute of Technology and Harvard, N01HC65226). The Cardiovascular Health Study was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and NO1HC85086, and by grant HL080295 from NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A complete list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm. Lars E. Laugsand received a research fellowship grant from the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology.; Replication studies; The HPFS CHD case-control study was supported by HL35464, and CA55075 from the National Institutes of Health, Bethesda, MD, with additional support for genotyping from Merck/Rosetta Research Laboratories, North Wales, PA. NHS: The NHS CHD case-control study was supported by CA87969 and HL34594 from the National Institutes of Health, Bethesda, MD, with additional support for genotyping from Merck/Rosetta Research Laboratories, North Wales, PA.; CHARGE cohorts: AGES study was funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). ARIC is supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. FHS was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (N02-HL-6-4278). Abbas Dehghan is supported by Netherlands Organization for Scientific Research (NWO) grant (veni, 916.12.154) and the EUR Fellowship. Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. Health ABC was funded by the National Institutes of Aging. This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). NR 38 TC 2 Z9 2 U1 1 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 2015 VL 243 IS 1 BP 44 EP 52 DI 10.1016/j.atherosclerosis.2015.08.031 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CU1FQ UT WOS:000363266000006 PM 26343871 ER PT J AU Torres, HA Chong, PP De Lima, M Friedman, MS Giralt, S Hammond, SP Kiel, PJ Masur, H McDonald, GB Wingard, JR Gambarin-Gelwan, M AF Torres, Harrys A. Chong, Pearlie P. De Lima, Marcos Friedman, Mark S. Giralt, Sergio Hammond, Sarah P. Kiel, Patrick J. Masur, Henry McDonald, George B. Wingard, John R. Gambarin-Gelwan, Maya TI Hepatitis C Virus Infection among Hematopoietic Cell Transplant Donors and Recipients: American Society for Blood and Marrow Transplantation Task Force Recommendations SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS; LIVER-TRANSPLANTATION; TRANSIENT ELASTOGRAPHY; PEGYLATED INTERFERON; ACUTE EXACERBATION; LIVING-DONOR; FOLLOW-UP; B-VIRUS; HCV C1 [Torres, Harrys A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Chong, Pearlie P.] Univ N Carolina, Chapel Hill, NC USA. [De Lima, Marcos] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [De Lima, Marcos] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Cleveland, OH 44106 USA. [Friedman, Mark S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Giralt, Sergio; Gambarin-Gelwan, Maya] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Hammond, Sarah P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hammond, Sarah P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kiel, Patrick J.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Masur, Henry] NIH, Ctr Clin, Bethesda, MD 20892 USA. [McDonald, George B.] Univ Washington, Seattle, WA 98195 USA. [McDonald, George B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. RP Torres, HA (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1460, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM htorres@mdanderson.org FU University of Texas MD Anderson Cancer Center; Gilead Sciences; Merck Co., Inc.; Vertex Pharmaceuticals; Ansun Biopharma; Hoffman-La Roche; Coley Pharmaceutical; GlaxoSmithKline; LabCorp Corporation; Conatus Pharmaceuticals; Bristol-Myers Squibb FX H.A.T. is a consultant for Janssen Pharmaceuticals, Inc., Gilead Sciences, Merck & Co., Inc., Vertex Pharmaceuticals, Novartis, Genentech, Astellas, Pfizer, and Theravance, Inc. and has received research grants from The University of Texas MD Anderson Cancer Center, Gilead Sciences, Merck & Co., Inc., and Vertex Pharmaceuticals. S.P.H. has received research grants from Merck & Co., Inc. and Ansun Biopharma. J.R.W. is a consultant for Ansun, Gilead Sciences, Merck & Co, and Astellas; speaker for Pfizer; and has received royalties from UpToDate Inc. M.G.G. is a consultant for Gilead Sciences, Bristol-Myers Squibb and has received research grants from Hoffman-La Roche, Coley Pharmaceutical, GlaxoSmithKline, LabCorp Corporation, Conatus Pharmaceuticals, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors have no conflicts of interest to declare. NR 69 TC 9 Z9 10 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2015 VL 21 IS 11 BP 1870 EP 1882 DI 10.1016/j.bbmt.2015.07.033 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CU2MI UT WOS:000363357200004 PM 26256943 ER PT J AU Deeg, HJ Bredeson, C Farnia, S Ballen, K Gupta, V Mesa, RA Popat, U Hari, P Saber, W Sefte, M Tamari, R Petersdorf, EW AF Deeg, H. Joachim Bredeson, Christopher Farnia, Stephanie Ballen, Karen Gupta, Vikas Mesa, Ruben A. Popat, Uday Hari, Parameswaran Saber, Wael Sefte, Matthew Tamari, Roni Petersdorf, Effie W. TI Hematopoietic Cell Transplantation as Curative Therapy for Patients with Myelofibrosis: Long-Term Success in all Age Groups SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Myeloproliferative neoplasms; Polycythemia vera; Essential thrombocythemia; Primary myelofibrosis; Hematopoietic cell transplantation ID PROGNOSTIC SCORING SYSTEM; ACUTE MYELOID-LEUKEMIA; MYELOPROLIFERATIVE NEOPLASMS; ESSENTIAL THROMBOCYTHEMIA; MARROW TRANSPLANTATION; POLYCYTHEMIA-VERA; AVAILABLE THERAPY; EUROPEAN GROUP; TRANSFORMATION; RUXOLITINIB AB Myeloproliferative neoplasms (MPN) are chronic marrow disorders with variable prognoses. Most patients with polycythemia vera, essential thrombocythemia, or even primary myelofibrosis (PMF) are successfully treated with conservative strategies for years or even decades, and recent data suggest that even in patients with high-risk disease, in particular those with PMF, life expectancy can be extended by treatment with janus kinase (JAK2) inhibitors. However, none of those modalities are curative, and after marrow failure develops, the disease "accelerates," or transforms to acute leukemia, the only option able to effectively treat and, in fact, cure MPN is allogeneic hematopoietic cell transplantation (HCT). Outcome is superior if HCT is performed before leukemic transformation occurs. Several reports document survival in unmaintained remission beyond 10 years. The most recent analyses show reduced regimen-related mortality (less than 10% or even 5% at day 100) and progressively improved survival with both HLA-identical sibling and unrelated donors. The development of low/reduced-intensity conditioning regimens has contributed to the improved success rate and has allowed successful HCT in patients in their seventh and even eighth decade of life. We propose, therefore, that HCT should be offered to fit patients in these age groups and should be covered by their respective insurance carriers. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Deeg, H. Joachim; Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Deeg, H. Joachim; Petersdorf, Effie W.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Bredeson, Christopher] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Farnia, Stephanie] Natl Marrow Donor Program, Minneapolis, MN USA. [Ballen, Karen] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Gupta, Vikas] Univ Toronto, Princess Margaret Canc Ctr, Med Oncol & Hematol, Toronto, ON, Canada. [Mesa, Ruben A.] Mayo Clin, Ctr Canc, Div Hematol & Med Oncol, Scottsdale, AZ USA. [Popat, Uday] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Hari, Parameswaran; Saber, Wael] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Sefte, Matthew] Univ Manitoba, Sect Hematol Oncol, Winnipeg, MB, Canada. [Tamari, Roni] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplantat Serv, New York, NY 10021 USA. [Tamari, Roni] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Deeg, HJ (reprint author), Fred Hutchinson Canc Res Ctr, D1-100,Box 19024, Seattle, WA 98109 USA. EM jdeeg@fredhutch.org OI Hari, Parameswaran/0000-0002-8800-297X FU NCI NIH HHS [U24 CA076518, R01 CA087948] NR 38 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2015 VL 21 IS 11 BP 1883 EP 1887 DI 10.1016/j.bbmt.2015.09.005 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CU2MI UT WOS:000363357200005 PM 26371371 ER PT J AU Koreth, J Kim, HT Lange, PB Bindra, B Reynolds, CG Chammas, MJ Armand, P Cutler, CS Ho, VT Glotzbecker, B Nikiforow, S Ritz, J Blazar, BR Soiffer, RJ Antin, JH Alyea, EP AF Koreth, John Kim, Haesook T. Lange, Paulina B. Bindra, Bhavjot Reynolds, Carol G. Chammas, Marie J. Armand, Philippe Cutler, Corey S. Ho, Vincent T. Glotzbecker, Brett Nikiforow, Sarah Ritz, Jerome Blazar, Bruce R. Soiffer, Robert J. Antin, Joseph H. Alyea, Edwin P., III TI A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE HLA mismatch; Proteasome inhibitor; Allogeneic; Myeloablative; Transplantation; T cell replete ID STEM-CELL TRANSPLANTATION; PROTEASOME INHIBITOR BORTEZOMIB; BUSULFAN PLUS CYCLOPHOSPHAMIDE; TOTAL-BODY IRRADIATION; MARROW-TRANSPLANTATION; INTRAVENOUS BUSULFAN; IDENTICAL SIBLINGS; ACUTE-LEUKEMIA; REMISSION; ACTIVATION AB Hematopoietic stem cell transplantation (HSCT) recipients lacking HLA-matched related donors have increased graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). Bortezomib added to reduced-intensity conditioning can offer benefit in T cell replete HLA-mismatched HSCT and may also benefit myeloablative conditioning (MAC) transplants. We conducted a phase II trial of short-course bortezomib plus standard tacrolimus/methotrexate after busulfan/fiudarabine MAC in 34 patients with predominantly myeloid malignancies. Fourteen (41%) received 8/8 HLA-matched unrelated donor (MUD) and 20 (59%) received 7/8 HLA-mismatched related/unrelated donor peripheral blood stem cell grafts. Median age was 49 years (range, 21 to 60), and median follow-up was 25 months (range, 11 to 36). The regimen was well tolerated. No dose modifications were required. Neutrophil and platelet engraftment occurred at a median of 14 (range, '10 to 33) and 17 (range, 10 to 54) days, respectively. Median 30-day donor chimerism was 99% (range, 90 to 100), and 100-day grades II to IV and III to IV acute GVHD incidence was 32% and 12% respectively. One-year chronic GVHD incidence was 50%. Two-year cumulative incidence of both NRM and relapse was 16%. Two-year progression-free and overall survival rates were 70% and 71%, respectively. Outcomes were comparable to an 8/8 MUD MAC cohort (n = 45). Immune reconstitution was robust. Bortezomib-based MAC HSCT is well tolerated, with HLA-mismatched outcomes comparable with 8/8 MUD MAC HSCT, and is suitable for randomized evaluation. (C) 2015 American Society for Blood and Marrow Transplantation. C1 [Koreth, John; Lange, Paulina B.; Bindra, Bhavjot; Reynolds, Carol G.; Chammas, Marie J.; Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Glotzbecker, Brett; Nikiforow, Sarah; Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.; Alyea, Edwin P., III] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Koreth, John; Lange, Paulina B.; Bindra, Bhavjot; Reynolds, Carol G.; Chammas, Marie J.; Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Glotzbecker, Brett; Nikiforow, Sarah; Ritz, Jerome; Soiffer, Robert J.; Antin, Joseph H.; Alyea, Edwin P., III] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kim, Haesook T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Blazar, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Div Blood & Marrow Transplantat, Minneapolis, MN USA. [Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. RP Koreth, J (reprint author), D2029 Dana Farber Canc Inst, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA. EM john_koreth@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU Millennium Pharmaceuticals Inc.; Otsuka Pharmaceuticals Inc.; Jock and Bunny Adams Education and Research Endowment; National Institutes of Health [CA183560, CA183559, P01CA142106] FX This study was supported in part by Millennium Pharmaceuticals Inc. and Otsuka Pharmaceuticals Inc., the Jock and Bunny Adams Education and Research Endowment, and by the National Institutes of Health (grants CA183560, CA183559, and P01CA142106). NR 21 TC 7 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2015 VL 21 IS 11 BP 1907 EP 1913 DI 10.1016/j.bbmt.2015.05.027 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA CU2MI UT WOS:000363357200008 PM 26055298 ER PT J AU Hughes, KS AF Hughes, Kevin S. TI DCIS does not need treatment . . . really? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Editorial Material ID CARCINOMA IN-SITU; BREAST-CONSERVING SURGERY; ONCOLOGY CONSENSUS GUIDELINE; LOCAL RECURRENCE; AMERICAN SOCIETY; RANDOMIZED-TRIAL; CANCER; RISK; RADIATION; RADIOTHERAPY C1 [Hughes, Kevin S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. [Hughes, Kevin S.] Bermuda Canc Genet & Risk Assessment Clin, Hamilton, Bermuda. RP Hughes, KS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Avon Comprehens Breast Evaluat Ctr, 55 Fruit St,Yawkey 7, Boston, MA 02114 USA. EM kshughes@partners.org NR 22 TC 2 Z9 2 U1 1 U2 5 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 2015 VL 154 IS 1 BP 1 EP 4 DI 10.1007/s10549-015-3606-x PG 4 WC Oncology SC Oncology GA CU4YP UT WOS:000363538100001 PM 26476724 ER PT J AU Sadek, BT Homayounfar, G Raad, RFA Niemierko, A Shenouda, MN Keruakous, AR Specht, MC Taghian, AG AF Sadek, Betro T. Homayounfar, Gelareh Raad, Rita F. Abi Niemierko, Andrzej Shenouda, Mina N. Keruakous, Amany R. Specht, Michelle C. Taghian, Alphonse G. TI Is a higher boost dose of radiation necessary after breast-conserving therapy for patients with breast cancer with final close or positive margins? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Higher radiation boost; Close/positive margins; Lumpectomy; Breast cancer ID ONCOLOGY CONSENSUS GUIDELINE; 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; SURGICAL MARGINS; LOCAL RECURRENCE; CONSERVATIVE TREATMENT; BRACHYTHERAPY BOOST; AMERICAN SOCIETY; STAGES I; SURGERY AB To determine rates of loco-regional recurrence (LRR), distant failure and overall survival for patients with breast cancer treated with breast-conserving therapy (BCT) with a close or positive surgical margin (C/PM) treated with standard dose boost radiation compared with a higher boost of radiation. We retrospectively studied 1476 patients with T1-T3 invasive breast cancer treated with BCT between 1992 and 2009. Median age was 57 years. Patients were divided into three groups: Group I included 1197 patients (81 %) with negative margins who received a standard boost (median 60 Gy) total dose to the lumpectomy cavity; Group II included 116 patients (8 %) with C/PM who received a standard boost (median 60 Gy); and Group III included 163 patients (11 %) with C/PM who received a higher boost (median 68 Gy). Biological subtypes (e.g., ER, PR, HER2/neu) were available for 858 patients (58 %) and were also assessed for any relationship to LRR rate. The Kaplan-Meier, Cox-regression, and log-rank tests were used to estimate rates of LRR and the significance of risk factors. Median follow-up was 8.6 years. The overall 5- and 10-year cumulative incidences of LRR were 2.1 % (95 % CI 0.8-2.1 %) and 4.5 % (95 % CI 3.4-6.0 %), respectively. The 5- and 10-year cumulative incidences of LRR for Group I (negative margins + standard boost) were 1.9 and 4.4 %; for Group II (C/PM + standard boost) were 3.9 and 7.0 %; and for Group III (C/PM + higher boost) were 2.9 and 3.8 %, respectively. No statistically significant differences in LRR rates were found among the three groups (p = 0.4). Similar results were obtained for distant failure (p = 0.3) and overall survival (p = 0.4). On multivariate analysis, tumor grade (p = 0.03), systemic-therapy (p = 0.005), node positivity (p = 0.05), young age (p = 0.001), and biological subtype (p = 0.04) were statistically significantly associated with higher LRR. Higher boost dose and margin positivity were not significant. Our data suggest that the 10-year risk of local recurrence for patients with close or positive margins receiving a standard boost was 7 % compared to 3.8 % for those receiving a higher boost; however, this difference was not significant. A higher boost dose did not significantly improve local control, nor did margins impact LRR risk in our cohort of patients. C1 [Sadek, Betro T.; Homayounfar, Gelareh; Raad, Rita F. Abi; Niemierko, Andrzej; Shenouda, Mina N.; Keruakous, Amany R.; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Niemierko, Andrzej] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stat Sect, Boston, MA 02114 USA. [Specht, Michelle C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3 Bldg,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 29 TC 2 Z9 2 U1 0 U2 1 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 2015 VL 154 IS 1 BP 71 EP 79 DI 10.1007/s10549-015-3579-9 PG 9 WC Oncology SC Oncology GA CU4YP UT WOS:000363538100009 PM 26420403 ER PT J AU Ozanne, EM Schneider, KH Soeteman, D Stout, N Schrag, D Fordis, M Punglia, RS AF Ozanne, Elissa M. Schneider, Katharine H. Soeteman, Djora Stout, Natasha Schrag, Deborah Fordis, Michael Punglia, Rinaa S. TI onlineDeCISion.org: a web-based decision aid for DCIS treatment SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Clinical decision support; Decision aid; Ductal carcinoma in situ ID CARCINOMA-IN-SITU; INVASIVE BREAST-CANCER; RANDOMIZED CONTROLLED-TRIAL; ADJUVANT BREAST; RISK PERCEPTION; WOMEN; MANAGEMENT; RADIOTHERAPY; DIAGNOSIS; EXPRESSION AB Women diagnosed with DCIS face complex treatment decisions and often do so with inaccurate and incomplete understanding of the risks and benefits involved. Our objective was to create a tool to guide these decisions for both providers and patients. We developed a web-based decision aid designed to provide clinicians with tailored information about a patient's recurrence risks and survival outcomes following different treatment strategies for DCIS. A theoretical framework, microsimulation model (Soeteman et al., J Natl Cancer 105:774-781, 2013) and best practices for web-based decision tools guided the development of the decision aid. The development process used semi-structured interviews and usability testing with key stakeholders, including a diverse group of multidisciplinary clinicians and a patient advocate. We developed onlineDeCISion.org to include the following features that were rated as important by the stakeholders: (1) descriptions of each of the standard treatment options available; (2) visual projections of the likelihood of time-specific (10-year and lifetime) breast-preservation, recurrence, and survival outcomes; and (3) side-by-side comparisons of down-stream effects of each treatment choice. All clinicians reviewing the decision aid in usability testing were interested in using it in their clinical practice. The decision aid is available in a web-based format and is planned to be publicly available. To improve treatment decision making in patients with DCIS, we have developed a web-based decision aid onlineDeCISion.org that conforms to best practices and that clinicians are interested in using in their clinics with patients to better inform treatment decisions. C1 [Ozanne, Elissa M.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03766 USA. [Schneider, Katharine H.] Baylor Coll Med, Houston, TX 77030 USA. [Soeteman, Djora] Harvard Univ, Ctr Hlth Decis Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Stout, Natasha] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Stout, Natasha] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Schrag, Deborah; Punglia, Rinaa S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fordis, Michael] Baylor Coll Med, Ctr Collaborat & Interact Technol, Houston, TX 77030 USA. [Fordis, Michael] Baylor Coll Med, John M Eisenberg Ctr Clin Decis & Commun Sci, Houston, TX 77030 USA. RP Ozanne, EM (reprint author), Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, 35 Centerra Pkwy, Lebanon, NH 03766 USA. EM elissa.m.ozanne@dartmouth.edu FU Agency for Healthcare Research and Quality (AHRQ) [HHSA290200500161] FX This work was supported by contract HHSA290200500161 from the Agency for Healthcare Research and Quality (AHRQ). The views expressed in this article are those of the authors, and no official endorsement by AHRQ or the U.S. Department of Health and Human Services is intended or should be inferred. NR 29 TC 2 Z9 2 U1 0 U2 3 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 2015 VL 154 IS 1 BP 181 EP 190 DI 10.1007/s10549-015-3605-y PG 10 WC Oncology SC Oncology GA CU4YP UT WOS:000363538100021 PM 26475704 ER PT J AU Syed, ZA Moayedi, J Mohamedi, M Tashter, J Anthony, T Celiker, C Khazen, G Melki, SA AF Syed, Zeba A. Moayedi, Javad Mohamedi, Mehdi Tashter, Jacob Anthony, Teresa Celiker, Celadet Khazen, Georges Melki, Samir A. TI Cataract surgery outcomes at a UK independent sector treatment centre SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ELECTRONIC MULTICENTER AUDIT; POSTERIOR CAPSULE RUPTURE; BENCHMARK STANDARDS; REFRACTIVE OUTCOMES; HEALTH-CARE; CASE-MIX; PROPHYLAXIS; CHOICE; RATES AB Background/Aims The goal of this study was to review cataract surgery outcomes at three independent surgery treatment centres established by the UK Specialist Hospitals (UKSH) and to compare these outcomes with recognised benchmarks. Methods All patients who underwent cataract surgery at UKSH between July 2005 and March 2013 were included. Complication rates were obtained using annual quality reports, logbooks kept in operating theatres and outpatient departments, and electronic medical records. Refractive outcomes and biometry results between December 2010 and March 2013 were obtained from electronic medical records. Results were compared with previously published benchmarks. Results This study reviewed 20 070 cataract surgeries. UKSH had lower rates of several operative complications compared with the Cataract National Dataset benchmark study. These included choroidal haemorrhage, hyphaema, intraocular lens complications, iris damage from phacoemulsification, nuclear fragment into the vitreous, phacoemulsification wound burn, posterior capsule rupture or vitreous loss or both, vitreous in anterior chamber, and zonular dialysis. UKSH had lower rates of postoperative complications including corneal decompensation, cystoid macular oedema, iris to wound, posterior capsule opacification with yttrium aluminium garnet indicated, raised intraocular pressure, retained soft lens matter, uveitis, vitreous to section, and wound leak. Biometry outcomes at UKSH were significantly better than recently published benchmarks from the National Healthcare Service. Conclusions This is the first large-scale retrospective study of cataract surgery outcomes in the UK independent sector. The results indicate comparable or lower rates for most complications as compared with data collected in a previously published study. C1 [Syed, Zeba A.; Melki, Samir A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Moayedi, Javad; Mohamedi, Mehdi; Tashter, Jacob; Anthony, Teresa; Celiker, Celadet; Melki, Samir A.] UK Specialist Hosp, London, England. [Khazen, Georges] Lebanese Amer Univ, Beirut, Lebanon. [Melki, Samir A.] Boston Eye Grp, Boston, MA USA. RP Melki, SA (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM samir_melki@meei.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD NOV PY 2015 VL 99 IS 11 BP 1460 EP 1465 DI 10.1136/bjophthalmol-2014-306586 PG 6 WC Ophthalmology SC Ophthalmology GA CU4BA UT WOS:000363469800004 PM 25926519 ER PT J AU Mountjoy, M Sundgot-Borgen, J Burke, L Carter, S Constantini, N Lebrun, C Meyer, N Sherman, R Steffen, K Budgett, R Ljungqvist, A Ackerman, K AF Mountjoy, Margo Sundgot-Borgen, Jorunn Burke, Louise Carter, Susan Constantini, Naama Lebrun, Constance Meyer, Nanna Sherman, Roberta Steffen, Kathrin Budgett, Richard Ljungqvist, Arne Ackerman, Kathryn TI The IOC relative energy deficiency in sport clinical assessment tool (RED-S CAT) SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Editorial Material C1 [Mountjoy, Margo] McMaster Univ, Dept Family Med, Michael G DeGroote Sch Med, Hamilton, ON L8S 4L8, Canada. [Sundgot-Borgen, Jorunn; Steffen, Kathrin] Norwegian Sch Sport Sci, Dept Sports Med, Oslo, Norway. [Burke, Louise] Australian Inst Sport, Dept Sports Nutr, Belconnen, ACT, Australia. [Carter, Susan] Univ Colorado, Sch Med, Univ No Colorado, Boulder, CO 80309 USA. [Constantini, Naama] Hadassah Hebrew Univ, Med Ctr, Dept Orthoped, Jerusalem, Israel. [Lebrun, Constance] Univ Alberta, Fac Med & Dent, Dept Family Med, Edmonton, AB, Canada. [Lebrun, Constance] Univ Alberta, Glen Sather Sports Med Clin, Edmonton, AB, Canada. [Meyer, Nanna] Univ Colorado, Dept Hlth Sci, Colorado Springs, CO 80907 USA. [Sherman, Roberta] Victory Program McCallum Pl, St Louis, MO USA. [Steffen, Kathrin; Budgett, Richard; Ljungqvist, Arne] IOC Med & Sci Dept, Lausanne, Switzerland. [Ackerman, Kathryn] Harvard Univ, Massachusetts Gen Hosp, Boston Childrens Hosp, Div Sports Med,Neuroendocrine Unit,Med Sch, Cambridge, MA 02138 USA. [Ackerman, Kathryn] Harvard Univ, Massachusetts Gen Hosp, Boston Childrens Hosp, Div Endocrinol,Neuroendocrine Unit,Med Sch, Cambridge, MA 02138 USA. RP Mountjoy, M (reprint author), McMaster Univ, Dept Family Med, Michael G DeGroote Sch Med, Hamilton, ON L8S 4L8, Canada. EM mmsportdoc@mcmaster.ca4444 NR 0 TC 2 Z9 2 U1 2 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD NOV PY 2015 VL 49 IS 21 BP 1354 EP 1354 DI 10.1136/bjsports-2015-094873 PG 1 WC Sport Sciences SC Sport Sciences GA CT9NP UT WOS:000363144200002 PM 26764434 ER PT J AU Traeger, L McDonnell, TM McCarty, CE Greer, JA El-Jawahri, A Temel, JS AF Traeger, Lara McDonnell, Theresa M. McCarty, Caitlin E. Greer, Joseph A. El-Jawahri, Areej Temel, Jennifer S. TI Nursing intervention to enhance outpatient chemotherapy symptom management: Patient-reported outcomes of a randomized controlled trial SO CANCER LA English DT Article DE chemotherapy; health services intervention; nursing; oncology; patient-reported outcomes ID CANCER-RELATED FATIGUE; DOUBLE-BLIND; ADJUVANT CHEMOTHERAPY; LUNG-CANCER; FOLLOW-UP; COLORECTAL-CANCER; BREAST-CANCER; METHYLPHENIDATE; WOMEN; CARE AB BACKGROUNDThe authors conducted a randomized controlled trial to evaluate a nurse practitioner (NP)-delivered symptom management intervention for patients initiating chemotherapy for nonmetastatic cancer. The aim was to reduce patient-reported symptom burden by facilitating patient-NP collaboration and the early management of symptoms. METHODSAt the time of the first chemotherapy visit, adult participants with nonmetastatic breast, colorectal, or lung cancer (120 participants) completed self-report measures and were then randomly assigned to standard care plus the intervention or standard care alone. Intervention participants received proactive telephone calls from their oncology team NP during the week after each of the first 2 chemotherapy administration visits. Measures were repeated at the second and third chemotherapy visits. Group differences were analyzed with regard to patient-reported symptoms (Memorial Symptom Assessment Scale-Short Form items), satisfaction with care (Family Caregiver Satisfaction-patient scale), and the likelihood of depression or anxiety symptoms (Patient Health Questionnaire-4). RESULTSAt the time of the first visit, 50.8% of participants reported 1 physical symptom, most commonly lack of energy (35.8%) and drowsiness (30.8%). The number of symptoms (gamma coefficient [] = 0.16; P<.001), symptom distress ( = 0.45; P<.001), and satisfaction with care ( = 0.24; P = .004) increased whereas the likelihood of anxiety symptoms decreased ( = -0.19; P = .02) and the likelihood of depression symptoms did not change ( = 0.01; P = .91). Outcomes did not differ by randomized group. Randomized group interacted with emetogenic potential in predicting symptom distress ( = 0.43; P = .03) and satisfaction with care ( = -0.45; P = .045). CONCLUSIONSThe intervention did not appear to reduce symptom burden compared with standard care. Early symptoms highlight the importance of continuing to examine strategies to improve symptom management during chemotherapy for nonmetastatic disease. Cancer 2015;121:3905-3913. (c) 2015 American Cancer Society. A proactive, telephone-based nursing intervention delivered by a patient's oncology nurse practitioner does not appear to improve patient-reported symptom burden in adults initiating chemotherapy for nonmetastatic cancer. Critical factors underlying null results will inform future symptom management trials. C1 [Traeger, Lara; McCarty, Caitlin E.; Greer, Joseph A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [McDonnell, Theresa M.; El-Jawahri, Areej; Temel, Jennifer S.] Massachusetts Gen Hosp, Hematol Oncol, Boston, MA 02114 USA. RP Traeger, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,Ste 701, Boston, MA 02114 USA. EM ltraeger@mgh.harvard.edu FU Massachusetts General Hospital Clinical Innovation Award; American Cancer Society [MRSG-PCSM-1410701] FX Supported by a Massachusetts General Hospital Clinical Innovation Award. Dr. Traeger was supported by the American Cancer Society (MRSG-PCSM-1410701). NR 31 TC 1 Z9 1 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2015 VL 121 IS 21 BP 3905 EP 3913 DI 10.1002/cncr.29585 PG 9 WC Oncology SC Oncology GA CU1EH UT WOS:000363262100022 PM 26194461 ER PT J AU Bendell, JC Rosen, LS Mayer, RJ Goldman, JW Infante, JR Benedetti, F Lin, DH Mizuguchi, H Zergebel, C Patel, MR AF Bendell, Johanna C. Rosen, Lee S. Mayer, Robert J. Goldman, Jonathan W. Infante, Jeffrey R. Benedetti, Fabio Lin, Donghu Mizuguchi, Hirokazu Zergebel, Christopher Patel, Manish R. TI Phase 1 study of oral TAS-102 in patients with refractory metastatic colorectal cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Antimetabolite; Metastatic colorectal cancer; Phase 1 study; Recommended dose; Safety; TAS-102 ID SOLID TUMORS; IRINOTECAN FOLFIRI; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL; FLUOROURACIL; LEUCOVORIN; CELLS; ANTIMETABOLITE; 5-FLUOROURACIL; MULTICENTER AB To evaluate safety of TAS-102 administered twice daily (bid) on days 1-5 and 8-12 of a 4-week cycle, confirm feasibility of the Japanese recommended dose (RD), 35 mg/m(2), in Western patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies, and describe preliminary antitumor activity. This open-label, dose-escalation phase 1 study was conducted at four US centers. Patients were enrolled into two sequential cohorts [30 (cohort 1) or 35 mg/m(2)/dose bid (cohort 2)]; dose-limiting toxicities (DLT) were evaluated during cycle 1 in dose-escalation cohorts. At RD, 15 additional patients were enrolled in an expansion cohort. Patients (N = 27) with refractory mCRC received TAS-102; 74 % had received a parts per thousand yen4 prior regimens. DLT was not observed in three patients in cohort 1, and was in one out of nine patients in cohort 2 (grade 3 febrile neutropenia). Therefore, RD was identified as 35 mg/m(2) bid. At RD, fatigue (63 %), gastrointestinal disturbances and nausea (46 %), vomiting (46 %), and diarrhea (42 %) were common but rarely grade 3/4. Grade 3/4 nausea, vomiting, and diarrhea occurred at 4 % each. Grade 3/4 toxicity was predominantly hematologic [neutropenia (71 %), anemia (25 %)]; febrile neutropenia was observed in two patients. Stable disease lasting a parts per thousand yen6 weeks was achieved by 16 evaluable patients (70 %); median progression-free survival and overall survival were 5.3 and 7.5 months, respectively. TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC. Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population. C1 [Bendell, Johanna C.; Infante, Jeffrey R.] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN 37203 USA. [Rosen, Lee S.; Goldman, Jonathan W.] Univ Calif Los Angeles, Los Angeles, CA 90404 USA. [Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Benedetti, Fabio; Mizuguchi, Hirokazu; Zergebel, Christopher] Taiho Oncol Inc, Princeton, NJ 08540 USA. [Lin, Donghu] Taiho Pharmaceut Beijing Co Ltd, Beijing 100004, Peoples R China. [Patel, Manish R.] Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL 34232 USA. RP Bendell, JC (reprint author), Tennessee Oncol PLLC, Sarah Cannon Res Inst, 250 25th Ave North,Suite 200, Nashville, TN 37203 USA. EM jbendell@tnonc.com FU Taiho Oncology Inc. FX The authors thank the patients and their families and study site personnel who participated in this study. This study was sponsored by Taiho Oncology Inc. Medical writing assistance was provided by Taiho Oncology Inc. Many thanks to Paul Bebeau, Gihan Atalla, Susan Darrah, and Hiroshi Ambe of Taiho, and John Ilgenfritz of United Biosources whose help was instrumental in the conduct of this study. NR 28 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2015 VL 76 IS 5 BP 925 EP 932 DI 10.1007/s00280-015-2850-4 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA CU0YR UT WOS:000363245800005 PM 26370544 ER PT J AU Sarma, A O'Donoghue, ML AF Sarma, Amy O'Donoghue, Michelle L. TI PHILO - Ensuring Trial Results Are Not Lost in Translation - SO CIRCULATION JOURNAL LA English DT Editorial Material ID ACUTE CORONARY SYNDROME; OUTCOMES PLATO TRIAL; PLATELET INHIBITION; CLOPIDOGREL; TICAGRELOR; PRASUGREL; JAPANESE; PHARMACODYNAMICS; PHARMACOKINETICS; THERAPY C1 [Sarma, Amy] Massachusetts Gen Hosp, Cardiovasc Div, Boston, MA 02114 USA. [O'Donoghue, Michelle L.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 1st Floor,350 Longwood Ave, Boston, MA 02115 USA. EM modonoghue@partners.org NR 15 TC 1 Z9 1 U1 0 U2 0 PU JAPANESE CIRCULATION SOC PI TOYKO PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO, 100-0011, JAPAN SN 1346-9843 EI 1347-4820 J9 CIRC J JI Circ. J. PD NOV PY 2015 VL 79 IS 11 BP 2326 EP 2328 DI 10.1253/circj.CJ-15-1035 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU1ML UT WOS:000363285900009 PM 26467081 ER PT J AU Shiota, S Singh, S Anshasi, A El-Serag, HB AF Shiota, Seiji Singh, Siddharth Anshasi, Ashraf El-Serag, Hashem B. TI Prevalence of Barrett's Esophagus in Asian Countries: A Systematic Review and Meta-analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review DE Barrett's Esophagus; Systematic Review; Meta-analysis; Prevalence; Risk Factors ID GASTROESOPHAGEAL-REFLUX DISEASE; HELICOBACTER-PYLORI INFECTION; RISK-FACTORS; EROSIVE ESOPHAGITIS; GENERAL-POPULATION; CHINESE POPULATION; KOREAN POPULATION; M CRITERIA; PRAGUE C; ENDOSCOPIC ESOPHAGITIS AB BACKGROUND & AIMS: The prevalence and risk factors of Barrett's esophagus (BE) in Asian countries are unclear. Studies report a wide range of BE prevalence in Asian countries. We conducted a systematic review and meta-analysis to examine the prevalence of BE and its temporal changes and risk factors in Asian countries. METHODS: Two investigators performed independent literature searches by using PubMed and EMBASE databases, and subsequent data abstraction for studies had to meet several set inclusion and exclusion criteria. Pooled BE prevalence was calculated by using a random-effect model. Estimates of relative risk for possible risk or protective factors were also calculated. RESULTS: A total of 51 studies (N [453,147), mainly from Eastern Asia, were included. The pooled prevalence of endoscopic BE was 7.8% (95% confidence interval, 5.0-12.1; 23 studies) and of histologically confirmed BE was 1.3% (95% confidence interval, 0.7-2.2; 28 studies). Most of histologic BE (82.1%) was short-segment BE (< 3 cm). There was a trend toward an increase in prevalence of BE over time from 1991 to 2014, especially in Eastern Asian countries. Within BE cohorts, pooled prevalence of low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma was 6.9%, 3.0%, and 2.0%, respectively. Reflux symptoms, male sex, hiatus hernia, and smoking were associated with a significantly increased risk of histologic BE in patients with BE compared with patients without BE. However, half of the patients with histologic BE did not have reflux symptoms. CONCLUSIONS: BE is not uncommon in Asian countries and seems to share similar risk factors and potential for neoplastic progression to those seen in Western countries. C1 [Shiota, Seiji; Anshasi, Ashraf; El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX USA. [Shiota, Seiji; Anshasi, Ashraf; El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. [Singh, Siddharth] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.edu FU National Institutes of Health [NCI R01 116845]; Texas Digestive Disease Center [NIH DK58338]; NIDDK [K24-04-107] FX Funded in part by National Institutes of Health grant NCI R01 116845 and the Texas Digestive Disease Center NIH DK58338. Dr El-Serag is also supported by NIDDK K24-04-107. This research was supported in part with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413) at the Michael E. DeBakey VA Medical Center, Houston, TX. The opinions expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, the US government, or Baylor College of Medicine. NR 90 TC 8 Z9 9 U1 0 U2 3 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 2015 VL 13 IS 11 BP 1907 EP 1918 DI 10.1016/j.cgh.2015.07.050 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT9VW UT WOS:000363165700013 PM 26260107 ER PT J AU Cadoni, S Falt, P Gallittu, P Liggi, M Mura, D Smajstrla, V Erriu, M Leung, FW AF Cadoni, Sergio Falt, Premysl Gallittu, Paolo Liggi, Mauro Mura, Donatella Smajstrla, Vit Erriu, Matteo Leung, Felix W. TI Water Exchange Is the Least Painful Colonoscope Insertion Technique and Increases Completion of Unsedated Colonoscopy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Medication-Free Colonoscopy; Pain; Discomfort; Bowel Preparation ID RANDOMIZED CONTROLLED-TRIAL; CARBON-DIOXIDE INSUFFLATION; ON-DEMAND SEDATION; AIR INSUFFLATION; AIDED COLONOSCOPY; PATIENT PAIN; IMMERSION AB BACKGROUND & AIMS: Unsedated colonoscopy is acceptable for diagnostic, surveillance, and screening indications worldwide. However, insertion of the colonoscope can be painful; it is not clear which technique is least painful and thereby increases the likelihood of colonoscopy completion. We performed a head-to-head comparison of air insufflation (AI), carbon dioxide (CO2) insufflation, water immersion (WI), and water exchange (WE) to determine which combination of insertion techniques produces the least amount of pain. METHODS: In a patient-blinded prospective trial, 624 subjects were assigned randomly to groups that underwent colonoscopy with AI-AI, CO2-CO2, WI-AI, WE-AI, WI-CO2, or WE-CO2 insertion and withdrawal techniques, including on-demand sedation, at the St. Barbara Hospital (Iglesias, Italy) or the Vitkovice Hospital (Ostrava, Czech Republic), from October 2013 through June 2014. The primary outcome was real-time maximum insertion pain (0 = none, 10 = worst), recorded by an unblinded nurse assistant. At discharge, a blinded observer recorded the recalled maximum insertion pain and patients' and investigators' guesses about method or gas used. RESULTS: Patients and investigators correctly guessed the method used for fewer than 44% of procedures, confirming adequate blinding. The correlation between real-time and recalled maximum insertion pain (r = 0.9; P < .0005) confirmed internal validation of the primary outcome. The WE group had the lowest scores: mean pain values were 5.2 for AI-AI (95% confidence interval [CI], 4.6-5.8), 4.9 for CO2-CO2 (95% CI, 4.3-5.4), 4.3 for WI-CO2 (95% CI, 3.8-4.9), 4.0 for WI-AI (95% CI, 3.5-4.5), 3.1 for WE-CO2 (95% CI, 2.7-3.4), and 3.1 for WE-AI (95% CI, 2.7-3.6) (P < .0005). The highest proportions of patients completing unsedated colonoscopy were in the WE groups. WE groups also had significantly better colon cleanliness, particularly in the transverse and right colon (P < .0005). One limitation of the study was that colonoscopists and assistants were not blinded to water-aided insertion methods. CONCLUSIONS: In a prospective study of colonoscopy insertion methods, CO2 insufflation did not reduce real-time maximum insertion pain. Compared with AI or CO2, WI and WE reduced insertion pain. The least painful technique was WE, which significantly increased completion of unsedated colonoscopy and bowel cleanliness without prolonging insertion time. C1 [Cadoni, Sergio; Gallittu, Paolo; Liggi, Mauro; Mura, Donatella] St Barbara Hosp, Digest Endoscopy Unit, Iglesias, Carbonia Iglesi, Italy. [Falt, Premysl; Smajstrla, Vit] Vitkovice Hosp, Ctr Digest Dis, Ostrava, Czech Republic. [Erriu, Matteo] Univ Cagliari, Dept Surg Sci, I-09124 Cagliari, Italy. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Cadoni, S (reprint author), St Barbara Hosp, Digest Endoscopy Unit, Via S Leonardo 1, I-09016 Iglesias, CI, Italy. EM cadonisergio@gmail.com NR 22 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2015 VL 13 IS 11 BP 1972 EP + DI 10.1016/j.cgh.2015.04.178 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT9VW UT WOS:000363165700023 PM 25956838 ER PT J AU Ho, SB Brau, N Cheung, R Liu, L Sanchez, C Sklar, M Phelps, TE Marcus, SG Wasil, MM Tisi, A Huynh, L Robinson, SK Gifford, AL Asch, SM Groesslk, EJ AF Ho, Samuel B. Braeu, Norbert Cheung, Ramsey Liu, Lin Sanchez, Courtney Sklar, Marisa Phelps, Tyler E. Marcus, Sonja G. Wasil, Michelene M. Tisi, Amelia Huynh, Lia Robinson, Shannon K. Gifford, Allen L. Asch, Steven M. Groesslk, Erik J. TI Integrated Care Increases Treatment and Improves Outcomes of Patients With Chronic Hepatitis C Virus Infection and Psychiatric Illness or Substance Abuse SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Care Integration; Hepatitis C; Substance Use Disorders; PTSD ID SUSTAINED VIROLOGICAL RESPONSE; ANTIVIRAL TREATMENT; COST-EFFECTIVENESS; PEGYLATED INTERFERON; UNITED-STATES; INVENTORY-II; VETERANS; MANAGEMENT; DEPRESSION; MODELS AB BACKGROUND & AIMS: Patients with hepatitis C virus (HCV) infection with psychiatric disorders and/or substance abuse face significant barriers to antiviral treatment. New strategies are needed to improve treatment rates and outcomes. We investigated whether an integrated care (IC) protocol, which includes multidisciplinary care coordination and patient case management, could increase the proportion of patients with chronic HCV infection who receive antiviral treatment (a combination of interferon-based and direct-acting antiviral agents) and achieve a sustained virologic response (SVR). METHODS: We performed a prospective randomized trial at 3 medical centers in the United States. Participants (n = 363 patients attending HCV clinics) had been screened and tested positive for depression, post-traumatic stress disorder, and/or substance use; they were assigned randomly to groups that received IC or usual care (controls) from March 2009 through February 2011. A midlevel mental health practitioner was placed at each HCV clinic to provide IC with brief mental health interventions and case management, according to formal protocol. The primary end point was SVR. RESULTS: Of the study participants, 63% were non-white, 51% were homeless in the past 5 years, 64% had psychiatric illness, 65% were substance abusers within 1 year before enrollment, 57% were at risk for post-traumatic stress disorder, 71% had active depression, 80% were infected with HCV genotype 1, and 23% had advanced fibrosis. Over a mean follow-up period of 28 months, a greater proportion of patients in the IC group began receiving antiviral therapy (31.9% vs 18.8% for controls; P = .005) and achieved a SVR (15.9% vs 7.7% of controls; odds ratio, 2.26; 95% confidence interval, 1.15-4.44; P=. 018). There were no differences in serious adverse events between groups. CONCLUSIONS: Integrated care increases the proportion of patients with HCV infection and psychiatric illness and/or substance abuse who begin antiviral therapy and achieve SVRs, without serious adverse events. C1 [Ho, Samuel B.] VA San Diego Healthcare Syst, Med Serv, Gastroenterol Sect, San Diego, CA 92161 USA. [Sanchez, Courtney; Sklar, Marisa; Wasil, Michelene M.] VA San Diego Healthcare Syst, Res Serv, San Diego, CA 92161 USA. [Robinson, Shannon K.] VA San Diego Healthcare Syst, Dept Psychiat, San Diego, CA 92161 USA. [Groesslk, Erik J.] VA San Diego Healthcare Syst, Div Hlth Serv Res & Dev, Res Serv, San Diego, CA 92161 USA. [Ho, Samuel B.] Univ Calif San Diego, Dept Med, Div Gastroenterol, San Diego, CA 92103 USA. [Liu, Lin] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Biostat, San Diego, CA 92103 USA. [Robinson, Shannon K.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Groesslk, Erik J.] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Behav Med, San Diego, CA 92103 USA. [Braeu, Norbert] James J Peters VA Med Ctr, Infect Dis Sect, Bronx, NY USA. [Marcus, Sonja G.; Tisi, Amelia] James J Peters VA Med Ctr, Res Serv, Bronx, NY USA. [Braeu, Norbert] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USA. [Braeu, Norbert] Icahn Sch Med Mt Sinai, Dept Med, Div Liver Dis, New York, NY 10029 USA. [Cheung, Ramsey; Phelps, Tyler E.; Groesslk, Erik J.] VA Palo Alto Healthcare Syst, Gastroenterol Sect, Med Serv, Palo Alto, CA USA. [Huynh, Lia; Asch, Steven M.] VA Palo Alto Healthcare Syst, Res Serv, Palo Alto, CA USA. [Cheung, Ramsey] Stanford Univ, Dept Med, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA. [Asch, Steven M.] Stanford Univ, Dept Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Gifford, Allen L.] Edith Nourse Rogers Mem Vet Hosp, Infect Dis Sect, Med Serv, Bedford, MA USA. [Gifford, Allen L.] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Gifford, Allen L.] Boston Univ, Dept Med, Boston, MA 02215 USA. RP Ho, SB (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM samuel.ho2@va.gov FU VA Health Services Research and Development grant [IIR-07-101-3] FX Supported by VA Health Services Research and Development grant IIR-07-101-3 (ClinicalTrials.gov # NCT00722423). NR 39 TC 7 Z9 7 U1 2 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 2015 VL 13 IS 11 BP 2005 EP + DI 10.1016/j.cgh.2015.02.022 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CT9VW UT WOS:000363165700028 PM 25724704 ER PT J AU Alabed, YZ Aghayev, A Sakellis, C Van den Abbeele, AD AF Alabed, Yazan Z. Aghayev, Ayaz Sakellis, Christopher Van den Abbeele, Annick D. TI Pancreatitis Secondary to Anti-Programmed Death Receptor 1 Immunotherapy Diagnosed by FDG PET/CT SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE FDG; PET; CT; immunotherapy; melanoma; pancreatitis; pembrolizumab; PD-1; immune-related adverse event ID CANCER-IMMUNOTHERAPY; B7 FAMILY; CELL; MEMBER; ACTIVATION; EXPRESSION; MELANOMA; B7-H1; PD-1 AB A 57-year-old man with metastatic melanoma developed colitis secondary to ipilimumab, a known immune-related adverse event (irAE). The patient then received pembrolizumab immunotherapy, an anti-programmed-death-receptor-1 (PD-1) antibody. Restaging FDG PET/CT study following 3 cycles of therapy demonstrated diffuse increased FDG uptake throughout the body of the pancreas associated with fat stranding in the peripancreatic region, suggestive of pembrolizumab-induced pancreatitis. Although the patient was clinically asymptomatic, diagnosis was biochemically confirmed with elevated amylase and lipase levels. In the era of immunotherapy, it will be critical to recognize irAEs early to allow prompt initiation of appropriate therapy and reduce the risk of long-term sequelae. C1 [Alabed, Yazan Z.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Alabed, YZ (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM yazan.alabed@gmail.com NR 16 TC 8 Z9 8 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD NOV PY 2015 VL 40 IS 11 BP e528 EP e529 DI 10.1097/RLU.0000000000000940 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CT8CQ UT WOS:000363043000013 PM 26284765 ER PT J AU Marathe, CS Feinle-Bisset, C Pilichiewicz, A Lange, K Jones, KL Rayner, CK Kahn, SE Horowitz, M AF Marathe, C. S. Feinle-Bisset, C. Pilichiewicz, A. Lange, K. Jones, K. L. Rayner, C. K. Kahn, S. E. Horowitz, M. TI The duodenal glucose load impacts the oral disposition index in healthy subjects SO DIABETIC MEDICINE LA English DT Article ID FUTURE; TOLERANCE; GLYCEMIA; HORMONES AB AimIn healthy subjects, the oral disposition index (ratio of insulin response to insulin sensitivity) is predictive of the development of Type2 diabetes. Gastric emptying, which exhibits a substantial interindividual variation, is a major determinant of postprandial glycaemia in health and diabetes. We sought to determine whether the rate of intraduodenal glucose delivery affects the disposition index in people without diabetes. MethodsNineteen Caucasian males received glucose infusions via an intraduodenal catheter at either 2kcal/min (ID2) or 4kcal/min (ID4) for 120min, on two separate days with measurements of blood glucose (G) and plasma insulin (I) at frequent intervals. The insulin response was estimated by the ratio of the change in insulin to that of change in glucose at 30min (I0-30/G(0-30)) and 60min (I0-60/G(0-60)). Insulin sensitivity was estimated as 1/fasting insulin. The oral disposition index (DI) was calculated as I0-30/G(0-30)x1/fasting insulin and I0-60/G(0-60)x1/fasting insulin. ResultsThe overall glycaemic response was comparable on both days, but the insulin response was much greater at ID4 when calculated at either 30 or 60min (P<0.05). DI was also greater (P<0.05) in response to ID4 than ID2. ConclusionsThe rate of duodenal glucose delivery has a major impact on insulin release and, thereby, DI. This suggests that the rate of gastric emptying, which determines duodenal glucose delivery, is a determinant of DI. C1 [Marathe, C. S.; Feinle-Bisset, C.; Pilichiewicz, A.; Lange, K.; Jones, K. L.; Rayner, C. K.; Horowitz, M.] Univ Adelaide, Discipline Med, Royal Adelaide Hosp, Adelaide, SA 5005, Australia. [Marathe, C. S.; Feinle-Bisset, C.; Lange, K.; Jones, K. L.; Rayner, C. K.; Horowitz, M.] Univ Adelaide, Ctr Res Excellence CRE Translating Nutr Sci Good, Adelaide, SA 5005, Australia. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. RP Marathe, CS (reprint author), Univ Adelaide, Discipline Med, Royal Adelaide Hosp, Adelaide, SA 5005, Australia. EM chinmaymarathe@gmail.com OI Kahn, Steven/0000-0001-7307-9002; Jones, Karen/0000-0002-1155-5816 FU National Health and Medical Research Council of Australia (NHMRC); United States Department of Veterans Affairs; NHMRC FX The study was supported by a project grant awarded by the National Health and Medical Research Council of Australia (NHMRC) and the United States Department of Veterans Affairs. CFB was supported by an NHMRC Senior Research Fellowship, and KJ by an NHMRC Career Development Fellowship. NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-3071 EI 1464-5491 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2015 VL 32 IS 11 BP 1500 EP 1503 DI 10.1111/dme.12802 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU1EW UT WOS:000363263800014 PM 25981372 ER PT J AU Liu, S Milne, L Yun, B Walsh, K AF Liu, Shan Milne, Leslie Yun, Brian Walsh, Kathleen TI The boarding experience from the patient perspective: the wait SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID QUALITY-OF-CARE; EMERGENCY-DEPARTMENT; CONCEPTUAL-MODEL; SATISFACTION; LENGTH; STAY AB Study objective We sought to better understand the experience of being a boarder patient. Methods We conducted a qualitative study between March and August 2012 to examine the experience of boarding in an urban, teaching hospital emergency department (ED). We included boarder patients and selected patients based on a convenience sample. Interviews were semistructured, consisting of eight main open-ended questions. Interviews were transcribed; codes were generated and then organised into categorises and subsequently into one theme. We concluded analysis when we achieved thematic saturation. Our institutional review board approved this study. Results Our final sample included 18 patients. The average age was 62.3 years. Patients characterised waiting as central to their experience as a boarder patient. One patient stated, "Well if you have to wait for a bed you have to wait for a bed, it's terrible." Three categories exemplified this waiting experience: (1) there was often lack of communication; (2) patients experienced frustration during this waiting period; and yet (3) patients often differentiated the experience of waiting from the care they were receiving. Conclusions Being a boarder patient was characterised as a waiting experience associated with poor communication and frustration. However, patients may still differentiate their feelings towards the wait from those towards the medical care they are receiving. Our data add more reason to eradicate the practice of ED boarding. C1 [Liu, Shan; Milne, Leslie; Walsh, Kathleen] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Yun, Brian] Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Boston, MA USA. RP Liu, S (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Zero Emerson 348, Boston, MA 02114 USA. EM sliu1@partners.org OI Yun, Brian/0000-0002-3842-420X NR 26 TC 1 Z9 1 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 EI 1472-0213 J9 EMERG MED J JI Emerg. Med. J. PD NOV PY 2015 VL 32 IS 11 BP 854 EP U101 DI 10.1136/emermed-2014-204107 PG 6 WC Emergency Medicine SC Emergency Medicine GA CU4CK UT WOS:000363473600006 PM 25637579 ER PT J AU Shah, RV Murthy, VL Abbasi, SA Eng, J Wu, CL Ouyang, P Kwong, RY Goldfine, A Bluemke, DA Lima, J Jerosch-Herold, M AF Shah, Ravi V. Murthy, Venkatesh L. Abbasi, Siddique A. Eng, John Wu, Colin Ouyang, Pamela Kwong, Raymond Y. Goldfine, Allison Bluemke, David A. Lima, Joao Jerosch-Herold, Michael TI Weight loss and progressive left ventricular remodelling: The Multi-Ethnic Study of Atherosclerosis (MESA) SO EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY LA English DT Article DE Obesity; cardiac magnetic resonance; weight loss ID INCIDENT CARDIOVASCULAR EVENTS; WHITE ADULT MEN; BARIATRIC SURGERY; OBESITY CARDIOMYOPATHY; INSULIN-RESISTANCE; RISK-FACTORS; MASS; GEOMETRY; DISEASE; IMPACT AB Aims Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR). Methods and results 2351 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent CMR at Exam 1 (2002) and Exam 5 (2011) were included. Primary outcomes were percentage change in LV mass (indexed to height) and LV mass-to-volume ratio (concentric LV remodelling). Multivariable linear regression was used to measure the association between outcomes and weight change. At median 9.4 years' follow-up, 639 individuals (27%) experienced >5% weight loss (median 6.9kg) and 511 (22%) had >5% weight gain (median 6.4kg). A >5% weight gain was associated with the greatest increase in LV mass (+5.4% median) and LV mass-to-volume ratio (+12.2% median). Adjusting for medications, hypertension/diabetes (and change in these risk factors), age, race and other risk factors, every 5% weight loss was associated with a 1.3% decrease in height-indexed LV mass and 1.3% decrease in LV mass-to-volume ratio (p<0.0001). There was no effect modification/confounding by age, race, gender or baseline BMI. Change in LV mass-to-volume ratio was roughly linear, specifically for modest degrees of weight loss (-10% to +10%). Change in LV mass was linear with weight loss, suggesting no threshold of weight loss is needed for LV mass regression. Conclusions In a large multi-ethnic population, weight loss is associated with beneficial effects on cardiac structure, independent of age, race, gender, BMI and obesity-related cardiometabolic risk. There is no threshold of weight loss required to produce these effects. C1 [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 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, Cardiothorac Imaging Div, Ann Arbor, MI 48109 USA. [Abbasi, Siddique A.; Kwong, Raymond Y.; Jerosch-Herold, Michael] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging, Boston, MA 02115 USA. [Eng, John; Wu, Colin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Ouyang, Pamela] Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA. [Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA. [Lima, Joao] Johns Hopkins Med Ctr, Dept Cardiol & Med, Baltimore, MD USA. RP Jerosch-Herold, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St,L1-RA050, Boston, MA 02115 USA. EM mjerosch-herold@partners.org RI Murthy, Venkatesh/B-3448-2013; OI Murthy, Venkatesh/0000-0002-7901-1321; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [NO1-HC-95159, NO1-HC-95160, NO1-HC-95161, NO1-HC-95162, NO1-HC-95163, NO1-HC-95164, NO1-HC-95165, NO1-HC-95166, NO1-HC-95167, NO1-HC-95168, N01-HC-95169]; American Heart Association Post-Doctoral Fellowship Award [11POST000002]; Heart Failure National Institutes of Health Clinical Research Network [U01-HL084877]; [R01-HL-65580] FX MESA is supported by contracts NO1-HC-95159 to N01-HC-95169 from the National Heart, Lung, and Blood Institute. Dr Shah was supported by an American Heart Association Post-Doctoral Fellowship Award (11POST000002) and a training grant from the Heart Failure National Institutes of Health Clinical Research Network (U01-HL084877). Dr Jerosch-Herold receives support through R01-HL-65580. All other authors have no financial disclosures relevant to the content of this manuscript. NR 31 TC 2 Z9 2 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2047-4873 EI 2047-4881 J9 EUR J PREV CARDIOL JI Eur. J. Prev. Cardiol. PD NOV PY 2015 VL 22 IS 11 BP 1408 EP 1418 DI 10.1177/2047487314541731 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT7LE UT WOS:000362995400005 PM 25009171 ER PT J AU Sammon, JD Abdollah, F D'Amico, A Gettman, M Haese, A Suardi, N Vickers, A Trinh, QD AF Sammon, Jesse D. Abdollah, Firas D'Amico, Anthony Gettman, Matthew Haese, Alexander Suardi, Nazareno Vickers, Andrew Trinh, Quoc-Dien TI Predicting Life Expectancy in Men Diagnosed with Prostate Cancer SO EUROPEAN UROLOGY LA English DT Review DE Prostate cancer; Life expectancy; Survival; Prediction ID RADICAL PROSTATECTOMY; SURVIVAL RATES; 10-YEAR RULE; ACCURACY; MORTALITY; RADIOTHERAPY; ONCOLOGISTS; COMORBIDITY; PHYSICIANS; CLINICIAN AB Context: The widespread use of prostate-specific antigen (PSA) screening has led to the detection of more indolent prostate cancer (PCa) in healthy men. PCa treatment and screening must therefore balance the potential for life gained against the potential for harm. Fundamental to this balance is physician awareness of a patient's estimated life expectancy (LE). Objective: To review the evidence on LE differences between men diagnosed with PCa and the general population. To examine clinician-and model-predicted LE and publicly available LE calculators. Evidence acquisition: A comprehensive search of the PubMed database between 1990 and September 2014 was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Free text protocols of the following search terms were used "life expectancy prostate cancer", "life expectancy non-cancer", "non-cancer mortality prostate", and "comorbidity-adjusted life expectancy". Two internet search engines were queried daily for 1 mo for the search term "life expectancy calculator", and the top 20 results were examined. Evidence synthesis: Of 992 articles and 32 websites screened, 17 articles and nine websites were selected for inclusion. Men with non-screening-detected PCa and distant disease at diagnosis were found to have shorter LE than age-matched peers, whereas men with localized PCa had prolonged LE. In general, clinician-predicted 10-yr LE was pessimistic and of limited accuracy; however, model-predicted LE provided only modest improvements in accuracy (c-index of models 0.65-0.84). Online LE calculators provide consistent LE estimates, but government life tables provide LE estimates near the mean for all calculators examined. Conclusions: The accuracy of clinician-predicted survival is limited, and while available statistical models offer improvement in discrimination, it is unclear whether they provide advantages over freely available government life tables. Patient summary: We examined differences in life expectancy between men diagnosed with prostate cancer and the general population, and ways of predicting life expectancy to help guide treatment decisions. We found that current models for predicting life expectancy specific to prostate cancer might not be any better than government life tables or simple rules of thumb. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Sammon, Jesse D.; Abdollah, Firas] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Sammon, Jesse D.; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [D'Amico, Anthony] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Gettman, Matthew] Mayo Clin, Dept Urol, Rochester, MN USA. [Haese, Alexander] Univ Hamburg Eppendorf, Dept Urol, Hamburg, Germany. [Suardi, Nazareno] Univ Vita Salute San Raffaele, Urol Res Inst, Dept Urol, Milan, Italy. [Vickers, Andrew] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Trinh, Quoc-Dien] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, Boston, MA 02115 USA. RP Sammon, JD (reprint author), Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM jsammon79@gmail.com OI Vickers, Andrew/0000-0003-1525-6503 FU Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital FX We would like to thank Akshay Sood for his invaluable assistance with the exploration of internet-based life expectancy calculators. Quoc-Dien Trinh is supported by the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital. NR 45 TC 17 Z9 17 U1 1 U2 8 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 2015 VL 68 IS 5 BP 756 EP 765 DI 10.1016/j.eururo.2015.03.020 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA CU4DC UT WOS:000363475800013 PM 25819724 ER PT J AU Sineshaw, HM Gray, PJ Efstathiou, JA Jemal, A AF Sineshaw, Helmneh M. Gray, Phillip J. Efstathiou, Jason A. Jemal, Ahmedin TI Declining Use of Radiotherapy for Adverse Features After Radical Prostatectomy: Results From the National Cancer Data Base SO EUROPEAN UROLOGY LA English DT Article DE Androgen deprivation therapy; Postoperative radiotherapy; Prostate cancer; Radical prostatectomy ID CLINICAL-PRACTICE GUIDELINES; RADIATION-THERAPY; ADJUVANT RADIOTHERAPY; FOLLOW-UP; POSTOPERATIVE RADIOTHERAPY; SALVAGE RADIOTHERAPY; TRIAL; RISK; SURVIVAL; EFFICACY AB Background: Patterns of postoperative radiotherapy (RT) use in prostate cancer (PCa) after the publication of major randomized trials have not been well characterized. Objective: To describe patterns of postoperative RT use after radical prostatectomy (RP) in patients with adverse pathologic features in the United States. Design, setting, and participants: Retrospective analysis of 97 270 patients with PCa diagnosed between 2005 and 2011 whose presentation and outcomes were recorded in the National Cancer Data Base. Outcome measurements and statistical analysis: Temporal changes in receipt of postoperative RT and factors associated with receipt of this treatment using the Cochran-Armitage trend test and multiple logistic regression, respectively. Results and limitations: Between 2005 and 2011, receipt of postoperative RT decreased steadily from 9.1% to 7.3% (p(trend) < 0.001). Use of RT with or without androgen deprivation therapy monotonically decreased with advancing age from 8.5% in patients aged 18-59 yr to 6.8% in patients aged 70-79 yr (p(trend) < 0.001). Receipt of RT was higher at community cancer programs compared with teaching/research centers (14% vs 7.3%; odds ratio [OR]: 2.16; p < 0.001), in those with pT3-4 disease and positive margins compared with those with pT3-4 and negative margins (17% vs 5.9%; OR: 2.89; p < 0.001), and in patients with a Gleason score of 8-10 compared with those with a Gleason score of 2-6 (17% vs 4.2%; OR: 3.50; p < 0.001). Limitations include lack of postprostatectomy prostate-specific antigen level. Conclusions: Postoperative RT use for localized PCa in patients with adverse pathologic features is declining in the United States. Patient summary: In this report, we show that use of postoperative radiotherapy in patients with prostate cancer with adverse pathologic features is declining. Patients treated at community cancer programs, those with locally advanced disease and positive margins, and those with a high Gleason score were more likely to receive postoperative radiotherapy. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Sineshaw, Helmneh M.; Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30303 USA. [Gray, Phillip J.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Sineshaw, HM (reprint author), Amer Canc Soc, 250 Williams St NW, Atlanta, GA 30303 USA. EM helmneh.sineshaw@cancer.org FU American Cancer Society Intramural Research Department; Prostate Cancer Foundation Young Investigator Award FX This work was supported by the American Cancer Society Intramural Research Department and a Prostate Cancer Foundation Young Investigator Award (J.A.E.). NR 29 TC 15 Z9 15 U1 1 U2 3 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 2015 VL 68 IS 5 BP 768 EP 774 DI 10.1016/j.eururo.2015.04.003 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CU4DC UT WOS:000363475800015 PM 25896124 ER PT J AU Tombal, B Borre, M Rathenborg, P Werbrouck, P Van Poppel, H Heidenreich, A Iversen, P Braeckman, J Heracek, J Baskin-Bey, E Ouatas, T Perabo, F Phung, D Baron, B Hirmand, M Smith, MR AF Tombal, Bertrand Borre, Michael Rathenborg, Per Werbrouck, Patrick Van Poppel, Hendrik Heidenreich, Axel Iversen, Peter Braeckman, Johan Heracek, Jiri Baskin-Bey, Edwina Ouatas, Taoufik Perabo, Frank Phung, De Baron, Benoit Hirmand, Mohammad Smith, Matthew R. TI Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naive Prostate Cancer: 1-and 2-Year Open-label Follow-up Results SO EUROPEAN UROLOGY LA English DT Article DE Androgen receptor; Enzalutamide; Hormone-naive prostate cancer; Prostate-specific antigen response ID ANDROGEN-DEPRIVATION THERAPY; BONE-MINERAL DENSITY; III EXTENSION TRIAL; QUALITY-OF-LIFE; BICALUTAMIDE MONOTHERAPY; BODY-COMPOSITION; 1-ARM CROSSOVER; 150 MG; CASTRATION; ANTIANDROGEN AB Background: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naive prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. Objective: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. Design, setting, and participants: Open-label, single-arm study in patients with HNPC and noncastrate testosterone (>= 230 ng/dl). Intervention: Oral enzalutamide 160 mg/d until disease progression or unacceptable toxicity. Outcome measurements and analysis: PSA response (>= 80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk). Results and limitations: The median (range) age was 73 (48-86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92-100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk. Conclusions: Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD. Patient summary: In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naive prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. (C) 2015 European Association of Urology. Published by Elsevier B.V. C1 [Tombal, Bertrand] Catholic Univ Louvain, Inst Rech Clin, B-1200 Brussels, Belgium. [Borre, Michael] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Rathenborg, Per] Herlev Hosp, DK-2730 Herlev, Denmark. [Werbrouck, Patrick] AZ Groeninge Kortrijk, Kortrijk, Belgium. [Van Poppel, Hendrik] UZ Leuven, Leuven, Belgium. [Heidenreich, Axel] Rhein Westfal TH Aachen, Klin & Poliklin Urol, Aachen, Germany. [Iversen, Peter] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. [Braeckman, Johan] UZ Brussel, Brussels, Belgium. [Heracek, Jiri] Univ Karlova Praze, Prague, Czech Republic. [Baskin-Bey, Edwina; Ouatas, Taoufik; Phung, De; Baron, Benoit] Astellas Pharma Global Dev, Leiden, Netherlands. [Perabo, Frank] Astellas Pharma Global Dev, Northbrook, IL USA. [Hirmand, Mohammad] Medivation Inc, San Francisco, CA USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tombal, B (reprint author), Catholic Univ Louvain, Clin Univ St Luc, Inst Rech Clin, Ave Hippocrate 10, B-1200 Brussels, Belgium. EM bertrand.tombal@uclouvain.be FU Astellas Pharma, Inc.; Medivation, Inc. FX Astellas Pharma, Inc. and Medivation, Inc. provided funding and played a role in study design and conduct; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. NR 30 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD NOV PY 2015 VL 68 IS 5 BP 787 EP 794 DI 10.1016/j.eururo.2015.01.027 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CU4DC UT WOS:000363475800019 PM 25687533 ER PT J AU Higano, CS Beer, TM Taplin, ME Efstathiou, E Hirmand, M Forer, D Scher, HI AF Higano, Celestia S. Beer, Tomasz M. Taplin, Mary-Ellen Efstathiou, Eleni Hirmand, Mohammad Forer, David Scher, Howard I. TI Long-term Safety and Antitumor Activity in the Phase 1-2 Study of Enzalutamide in Pre- and Post-docetaxel Castration-Resistant Prostate Cancer SO EUROPEAN UROLOGY LA English DT Article DE Androgen receptor inhibitor; Castration-resistant prostate cancer; Enzalutamide; Long-term follow-up; MDV3100; Tolerability ID CHEMOTHERAPY AB Background: Given that some patients with castration-resistant prostate cancer (CRPC) have shown extended responses to the androgen receptor inhibitor enzalutamide, long-term safety of this drug is of interest. Objective: To evaluate the long-term safety and antitumor activity of enzalutamide in CRPC patients. Design, setting, and participants: This phase 1-2 study evaluated enzalutamide in 140 CRPC patients with and without prior chemotherapy. Initial findings were published in 2010. We report updated results from an additional 17-mo follow-up for antitumor activity and >4 yr for safety. Intervention: Patients received 30-600 mg/d oral enzalutamide. During long-term dosing, all patients were switched first to the maximum tolerated dose of 240 mg/d and then to the phase 3 dose of 160 mg/d. Outcome measurements and statistical analysis: Safety was assessed regularly. The Kaplan-Meier method was used to estimate the distributions of time to prostate-specific antigen (PSA) progression and time to radiographic progression. Results and limitations: The safety profile of enzalutamide was consistent over time, with little change in the rates of commonly reported adverse events (AEs) or the incidence of grade 3/4 AEs. Fatigue of any grade was the most common dose-dependent AE, experienced by 70% of patients, with 14% of patients reporting grade 3/4 fatigue. The median time to PSA progression was not reached for chemotherapy-naive patients and was 45 wk for postchemotherapy patients; the corresponding median time to radiographic progression was 56 wk and 25 wk. Conclusions: Enzalutamide showed durable antitumor activity in chemotherapy-naive and postchemotherapy patients, and was well tolerated, even in patients treated for 4 yr. Patient summary: Enzalutamide was active against prostate cancer and was well tolerated, even for up to 4 yr of treatment, supporting its potential for long-term use in men with prostate cancer. Fatigue was the most common side effect, occurring at varying degrees of severity in most patients. (C) 2015 Published by Elsevier B.V. on behalf of European Association of Urology. C1 [Higano, Celestia S.] Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Efstathiou, Eleni] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hirmand, Mohammad; Forer, David] Medivation Inc, San Francisco, CA USA. [Scher, Howard I.] Weill Cornell Med Coll, Genitourinary Oncol Serv, Sidney Kimmel Ctr Prostate & Urol Canc, Mem Sloan Kettering Canc Ctr,Dept Med, New York, NY 10021 USA. RP Higano, CS (reprint author), Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Box 358081,825 Eastlake Ave E, Seattle, WA 98109 USA. EM thigano@u.washington.edu FU Medivation; Astellas Pharma FX The study was funded by Medivation. Writing assistance was funded by Astellas Pharma and Medivation. Medivation was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. NR 7 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD NOV PY 2015 VL 68 IS 5 BP 795 EP 801 DI 10.1016/j.eururo.2015.01.026 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CU4DC UT WOS:000363475800020 PM 25698064 ER PT J AU Gartrell, BA Coleman, R Efstathiou, E Fizazi, K Logothetis, CJ Smith, MR Sonpavde, G Sartor, O Saad, F AF Gartrell, Benjamin A. Coleman, Robert Efstathiou, Eleni Fizazi, Karim Logothetis, Christopher J. Smith, Matthew R. Sonpavde, Guru Sartor, Oliver Saad, Fred TI Metastatic Prostate Cancer and the Bone: Significance and Therapeutic Options SO EUROPEAN UROLOGY LA English DT Review DE Prostate cancer; Bone metastases; Bone-targeted agents; Skeletal-related events; Symptomatic skeletal events ID SKELETAL-RELATED EVENTS; PLACEBO-CONTROLLED TRIAL; ZOLEDRONIC ACID; SOLID TUMORS; RADIUM-223 DICHLORIDE; N-TELOPEPTIDE; FREE SURVIVAL; DOUBLE-BLIND; LUNG-CANCER; PHASE-II AB Context: Skeletal involvement is common in metastatic prostate cancer (PCa) and is associated with skeletal-related events (SREs). The interaction of PCa with the bone microenvironment contributes to self-perpetuating progression of cancer in bone. Bone-targeted agents (BTAs) are available for use in metastatic castration-resistant prostate cancer (mCRPC). Objective: To review the biology of bone metastases in PCa and to review the clinical trial data for BTAs in PCa. Evidence acquisition: A literature search was conducted in October 2014. Keywords included clinical trial, prostate cancer, denosumab, bisphosphonates, zoledronic acid, radium-223, bone turnover markers, skeletal-related events, and symptomatic skeletal events. Evidence synthesis: The biology of bone metastases in PCa is summarized. Data supporting the use of BTAs in PCa are reviewed, and issues related to the combination and sequencing of available agents are discussed. Conclusions: The osteoclast-targeted agents zoledronic acid and denosumab decrease SREs in mCRPC, and the a-emitting radiopharmaceutical agent radium-223 improves survival and decreases symptomatic skeletal events. Limited data are available to guide the sequence and combination of BTAs with disease-modifying agents, although data support the use of osteoclast-targeted drugs with chemotherapy, androgen-targeted agents, and radium-223. Zoledronic acid does not reduce SREs when started prior to castration resistance, although osteoclast-targeted agents do improve outcomes when used in patients with asymptomatic to minimally symptomatic chemotherapy-naive mCRPC. The optimal sequence of radium-223 with chemotherapy is uncertain, although data suggest the efficacy and tolerability of radium-223 is similar with either sequence. Clinical trials evaluating the combination of BTAs with other agents are under way. The optimization of sequence and combination strategies will guide the best use of available agents. Patient summary: The literature pertaining to bone metastases in prostate cancer (PCa) was reviewed, and the current understanding of the biology of PCa having spread to bone and the agents available to reduce skeletal complications was discussed. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Gartrell, Benjamin A.] Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10647 USA. [Coleman, Robert] Weston Pk Hosp, CR UK YCR Sheffield Canc Res Ctr, Acad Unit Clin Oncol, Sheffield, S Yorkshire, England. [Efstathiou, Eleni] David H Koch Ctr Appl Res Genitourinary Canc, Stanford Alexander Tissue Derivat Lab, Dept Genitourinary Med Oncol, Houston, TX USA. Univ Athens, Dept Clin Therapeut, Athens, Greece. [Fizazi, Karim] Univ Paris Sud, Inst Gustave Roussy, Dept Canc Med, Villejuif, France. [Logothetis, Christopher J.] David H Koch Ctr Appl Res Genitourinary Canc, Stanford Alexander Tissue Derivat Lab, Dept Genitourinary Med Oncol, Houston, TX USA. [Smith, Matthew R.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sonpavde, Guru] UAB Med Ctr, Dept Internal Med, Sect Med Oncol, Birmingham, AL USA. [Sartor, Oliver] Tulane Univ, Dept Med & Urol, New Orleans, LA 70118 USA. [Saad, Fred] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. RP Gartrell, BA (reprint author), Albert Einstein Coll Med, Med Oncol, Montefiore Med Ctr, 111 E 210th St,Hofheimer 100, Bronx, NY 10647 USA. EM bgartrel@montefiore.org FU Bayer; Sanofi; Medivation; Astellas; Onyx; Oliver Sartor; Janssen; Takeda; Oncogenex; BMS; Bavarian Nordic FX Benjamin A. Gartrell certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Benjamin A. Gartrell is on the advisory boards and receives honoraria from Dendreon, Astellas, and Bayer. Robert Coleman provides expert legal testimony on behalf of Novartis. Eleni Efstathiou is on the advisory boards and receives honoraria from Johnson & Johnson, Sanofi-Aventis, Bayer, Takeda, Astellas, and Astrazeneca. She also receives research funding from Bayer, Sanofi, Medivation, and Astellas. Karim Fizazi is on the advisory boards and receives honoraria from Amgen, Astellas, Bayer, BMS, Ipsen, Janssen, Takeda, Novartis, Orion, and Sanofi-Aventis. Matthew Snith is a consultant for Bayer and Amgen. Guru Sonpavde is on the advisory boards for Bayer, Sanofi, Genentech, and Merck, and he receives research support from Onyx and Bayer. Oliver Sartor is a consultant for Bayer, Sanofi, Oncogenex, Medivation, JNJ, and Bellicum. He receives clinical trial support from Sanofi, Bayer, Progenics, and JNJ. Fred Saad is a consultant for Amgen, Janssen, Astellas, Bayer, Sanofi, Takeda, Bavarian, and Nordic. His institution receives research funding from Janssen, Astellas, Bayer, Sanofi, Takeda, Oncogenex, BMS, and Bavarian Nordic. NR 51 TC 6 Z9 7 U1 3 U2 11 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 2015 VL 68 IS 5 BP 850 EP 858 DI 10.1016/j.eururo.2015.06.039 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA CU4DC UT WOS:000363475800031 PM 26153564 ER PT J AU Morgans, AK van Bommel, ACM Stowell, C Abrahm, JL Basch, E Bekelman, JE Berry, DL Bossi, A Davis, ID de Reijke, TM Denis, LJ Evans, SM Fleshner, NE George, DJ Kiefert, J Lin, DW Matthew, AG McDermott, R Payne, H Roos, IAG Schrag, D Steuber, T Tombal, B van Basten, JP van der Hoeven, JJM Penson, DF AF Morgans, Alicia K. van Bommel, Annelotte C. M. Stowell, Caleb Abrahm, Janet L. Basch, Ethan Bekelman, Justin E. Berry, Donna L. Bossi, Alberto Davis, Ian D. de Reijke, Theo M. Denis, Louis J. Evans, Sue M. Fleshner, Neil E. George, Daniel J. Kiefert, Jim Lin, Daniel W. Matthew, Andrew G. McDermott, Ray Payne, Heather Roos, Ian A. G. Schrag, Deborah Steuber, Thomas Tombal, Bertrand van Basten, Jean-Paul van der Hoeven, Jacobus J. M. Penson, David F. CA Int Consortium Hlth Outcomes TI Development of a Standardized Set of Patient-centered Outcomes for Advanced Prostate Cancer: An International Effort for a Unified Approach SO EUROPEAN UROLOGY LA English DT Article DE Outcome assessment (health care); Patient-centered care; Prostate cancer; Quality indicators; Health care; Palliative care ID QUALITY-OF-LIFE; SOCIOECONOMIC-STATUS; INDEX COMPOSITE; CLINICAL-TRIALS; CARE; MEN; RECOMMENDATIONS; COMORBIDITY; VALIDATION; INSTRUMENT AB Background: There are no universally monitored outcomes relevant to men with advanced prostate cancer, making it challenging to compare health outcomes between populations. Objective: We sought to develop a standard set of outcomes relevant to men with advanced prostate cancer to follow during routine clinical care. Design, setting, and participants: The International Consortium for Health Outcomes Measurement assembled a multidisciplinary working group to develop the set. Outcome measurements and statistical analysis: We used a modified Delphi method to achieve consensus regarding the outcomes, measures, and case mix factors included. Results and limitations: The 25 members of the multidisciplinary international working group represented academic and nonacademic centers, registries, and patients. Recognizing the heterogeneity of men with advanced prostate cancer, the group defined the scope as men with all stages of incurable prostate cancer (metastatic and biochemical recurrence ineligible for further curative therapy). Wedefined outcomes important to all men, such as overall survival, and measures specific to subgroups, such as time to metastasis. Measures gathered from clinical data include measures of disease control. We also identified patient-reported outcome measures (PROMs), such as degree of urinary, bowel, and erectile dysfunction, mood symptoms, and pain control. Conclusions: The international multidisciplinary group identified clinical data and PROMs that serve as a basis for international health outcome comparisons and quality-of-care assessments. The set will be revised annually. Patient summary: Our international group has recommended a standardized set of patient-centered outcomes to be followed during routine care for all men with advanced prostate cancer. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Morgans, Alicia K.; Penson, David F.] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. [van Bommel, Annelotte C. M.; Stowell, Caleb] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [van Bommel, Annelotte C. M.] Dutch Inst Clin Auditing, Leiden, Netherlands. [Abrahm, Janet L.; Berry, Donna L.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. [Basch, Ethan] Univ N Carolina, Chapel Hill, NC USA. [Bekelman, Justin E.] Univ Penn, Philadelphia, PA 19104 USA. [Bossi, Alberto] Gustave Roussy Canc Inst, Villejuif, France. [Davis, Ian D.] Monash Univ, Eastern Hlth Clin Sch, Melbourne, Vic 3004, Australia. [de Reijke, Theo M.] Acad Med Ctr Amsterdam, Amsterdam, Netherlands. [Denis, Louis J.] Oncol Ctr Antwerp, Antwerp, Belgium. [Denis, Louis J.] US TOO Belgium, Antwerp, Belgium. [Evans, Sue M.] Monash Univ, Melbourne, Vic 3004, Australia. [Fleshner, Neil E.; Matthew, Andrew G.] Univ Toronto, Toronto, ON, Canada. [George, Daniel J.] Duke Univ, Med Ctr, Durham, NC USA. [Kiefert, Jim] US TOO Int, Des Plaines, IL USA. [Lin, Daniel W.] Univ Washington, Seattle, WA 98195 USA. [McDermott, Ray] St Vincents Univ Hosp, Dublin 4, Ireland. [Payne, Heather] Univ Coll London Hosp, London, England. [Roos, Ian A. G.] Canc Act Victoria, Melbourne, Vic, Australia. [Steuber, Thomas] Univ Hosp Hamburg Eppendorf, Hamburg, Germany. [Tombal, Bertrand] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium. [van Basten, Jean-Paul] Canisius Wilhelmina Hosp, Nijmegen, Netherlands. [van der Hoeven, Jacobus J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Penson, David F.] VA Tennessee Valley Geriatr Res Educ & Clin Ctr G, Nashville, TN USA. RP Morgans, AK (reprint author), Vanderbilt Univ, Med Ctr, Div Hematol Oncol, 2220 Pierce Ave,777 Preston Res Bldg, Nashville, TN 37232 USA. EM alicia.morgans@vanderbilt.edu OI Evans, Sue/0000-0003-2962-8400 FU Movember Foundation FX This work was funded by the Movember Foundation. The sponsor played a role in manuscript review. NR 29 TC 3 Z9 4 U1 1 U2 7 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 2015 VL 68 IS 5 BP 891 EP 898 DI 10.1016/j.eururo.2015.06.007 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CU4DC UT WOS:000363475800036 PM 26129856 ER PT J AU Childs, EJ Chaffee, KG Gallinger, S Syngal, S Schwartz, AG Cote, ML Bondy, M Goggins, MG Hruban, RH Chanock, S Hoover, R Fuchs, C Rider, DN Amundadottir, L Stolzenberg-Solomon, R Wolpin, B Risch, HA Petersen, GM Klein, AP AF Childs, Erica J. Chaffee, Kari G. Gallinger, Steven Syngal, Sapna Schwartz, Ann G. Cote, Michele L. Bondy, Melissa Goggins, Michael G. Hruban, Ralph H. Chanock, Stephen Hoover, Robert Fuchs, Charles Rider, David N. Amundadottir, Laufey Stolzenberg-Solomon, Rachael Wolpin, Brian Risch, Harvey A. Petersen, Gloria M. Klein, Alison P. TI Examination of established cancer risk variants in putatively high-risk pancreatic cancer patients: A PACGENE study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 04-06, 2015 CL Baltimore, MD SP Int Genet Epidemiol Soc C1 [Childs, Erica J.] Johns Hopkins Sch Med, Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Chaffee, Kari G.; Rider, David N.; Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Schwartz, Ann G.; Cote, Michele L.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Detroit, MI USA. [Bondy, Melissa] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Goggins, Michael G.; Hruban, Ralph H.] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA. [Chanock, Stephen; Hoover, Robert; Amundadottir, Laufey] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Fuchs, Charles; Wolpin, Brian] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Fuchs, Charles; Wolpin, Brian] Harvard Univ, Sch Med, Boston, MA USA. [Stolzenberg-Solomon, Rachael] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Wolpin, Brian] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Klein, Alison P.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA. [Klein, Alison P.] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 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 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2015 VL 39 IS 7 MA 27 BP 538 EP 539 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CU2FZ UT WOS:000363340500031 ER PT J AU Childs, EJ Lau, B Blackford, A Parmigiani, G Klein, AP AF Childs, Erica J. Lau, Bryan Blackford, Amanda Parmigiani, Giovanni Klein, Alison P. TI Estimating penetrance in the context of competing mortality: Application to Familial Pancreatic cancer SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 04-06, 2015 CL Baltimore, MD SP Int Genet Epidemiol Soc C1 [Childs, Erica J.; Blackford, Amanda; Klein, Alison P.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 02115 USA. [Blackford, Amanda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA. [Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Klein, Alison P.] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2015 VL 39 IS 7 MA 26 BP 538 EP 538 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CU2FZ UT WOS:000363340500030 ER PT J AU Davis, LK Lee, SH Gamazon, ER Im, HK Yu, DM Williams, S Sullivan, PF Mathews, C Knowles, J Scharf, J Wray, N Cox, NJ AF Davis, Lea K. Lee, S. Hong Gamazon, Eric R. Im, Hae-Kyung Yu, Dongmei Williams, Stephanie Sullivan, Patrick F. Mathews, Carol Knowles, James Scharf, Jeremiah Wray, Naomi Cox, Nancy J. TI Characterizing an inverse axis between orthogonal sources of genetic risk SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 04-06, 2015 CL Baltimore, MD SP Int Genet Epidemiol Soc C1 [Davis, Lea K.; Im, Hae-Kyung] Univ Chicago, Chicago, IL 60637 USA. [Lee, S. Hong; Wray, Naomi] Univ Queensland, Brisbane, Qld 4072, Australia. [Gamazon, Eric R.; Cox, Nancy J.] Vanderbilt Univ, Nashville, TN USA. [Yu, Dongmei; Scharf, Jeremiah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Williams, Stephanie; Sullivan, Patrick F.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Mathews, Carol] Univ Florida, Gainesville, FL 32611 USA. [Knowles, James] Univ So Calif, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2015 VL 39 IS 7 MA 36 BP 542 EP 543 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CU2FZ UT WOS:000363340500040 ER PT J AU Do, R Won, HH Natarajan, P Dobbyn, A Lage, K Raychaudhuri, S Stahl, E AF Do, Ron Won, Hong-Hee Natarajan, Pradeep Dobbyn, Amanda Lage, Kasper Raychaudhuri, Soumya Stahl, Eli TI Different Genomic Subsets and Cell Types Contribute to the Polygenicity and Heritability for Coronary Artery Disease SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 04-06, 2015 CL Baltimore, MD SP Int Genet Epidemiol Soc C1 [Do, Ron] Icahn Sch Med Mt Sinai, Genet & Genom Sci, New York, NY 10029 USA. [Won, Hong-Hee; Natarajan, Pradeep] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dobbyn, Amanda] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, Dept Genet & Genom, New York, NY 10029 USA. [Lage, Kasper] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Harvard Univ, Sch Med, Boston, MA USA. [Stahl, Eli] Icahn Sch Med Mt Sinai, Div Psychiat Genom, New York, NY 10029 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 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2015 VL 39 IS 7 MA 41 BP 544 EP 545 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CU2FZ UT WOS:000363340500045 ER PT J AU Friedrichs, S Amos, CI Brennan, P Christiani, D Hung, RJ Risch, A Bruske, I Caporaso, N Landi, MT Rafnar, T Bickeboller, H AF Friedrichs, Stefanie Amos, Christopher I. Brennan, Paul Christiani, David Hung, Rayjean J. Risch, Angela Brueske, Irene Caporaso, Neil Landi, Maria T. Rafnar, Thorunn Bickeboeller, Heike TI Kernel-based Pathway Meta-Analysis in ILCCO / TRICL Genome-wide Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 04-06, 2015 CL Baltimore, MD SP Int Genet Epidemiol Soc C1 [Friedrichs, Stefanie; Bickeboeller, Heike] Univ Gottingen, Dept Genet Epidemiol, Univ Med Ctr, D-37073 Gottingen, Germany. [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Christiani, David] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Christiani, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hung, Rayjean J.] Mt Sinai Hosp, Prosserman Ctr Hlth Res, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Risch, Angela] Salzburg Univ, Div Mol Biol, A-5020 Salzburg, Austria. [Risch, Angela] Translat Lung Res Ctr Heidelberg TLRC H, Heidelberg, Germany. [Risch, Angela] DKFZ German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany. [Brueske, Irene] German Res Ctr Environm Hlth, Helmholtz Zentrum Geesthacht, Neuherberg, Germany. [Caporaso, Neil] Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Reykjavik, Iceland. RI Hung, Rayjean/A-7439-2013 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 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2015 VL 39 IS 7 MA 52 BP 549 EP 549 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CU2FZ UT WOS:000363340500056 ER PT J AU Warren, HR Surendran, P Drenos, F Young, R Cook, JP Manning, AK Grarup, N Sim, X Saleheen, D Asselbergs, FW Lindgren, CM Danesh, J Wain, LV Butterworth, AS Howson, JMM Munroe, PB AF Warren, Helen R. Surendran, Praveen Drenos, Fotios Young, Robin Cook, James P. Manning, Alisa K. Grarup, Niels Sim, Xueling Saleheen, Danish Asselbergs, Folkert W. Lindgren, Cecilia M. Danesh, John Wain, Louise V. Butterworth, Adam S. Howson, Joanna M. M. Munroe, Patricia B. CA CHARGE Consortium T2D-GENES Consortium GoT2DGenes Consortium ExomeBP Consortium CHD Exome Consortium TI Investigating the Association of Rare Genetic Variants with Blood Pressure traits SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 04-06, 2015 CL Baltimore, MD SP Int Genet Epidemiol Soc C1 [Warren, Helen R.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol, London, England. [Warren, Helen R.] Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Biomed Res Unit, London, England. [Surendran, Praveen; Young, Robin; Saleheen, Danish; Danesh, John; Butterworth, Adam S.; Howson, Joanna M. M.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge CB2 1TN, England. [Drenos, Fotios] Univ Bristol, Sch Social & Community Med, MRC, Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England. [Drenos, Fotios] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London WC1E 6BT, England. [Cook, James P.; Wain, Louise V.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Cook, James P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. [Manning, Alisa K.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Manning, Alisa K.; Lindgren, Cecilia M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Manning, Alisa K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Grarup, Niels] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-1168 Copenhagen, Denmark. [Sim, Xueling] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Sim, Xueling] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Sim, Xueling] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Saleheen, Danish] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands. [Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London WC1E 6BT, England. [Lindgren, Cecilia M.] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford OX1 2JD, England. [Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Danesh, John] Wellcome Trust Sanger Inst, London, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2015 VL 39 IS 7 MA 168 BP 591 EP 591 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA CU2FZ UT WOS:000363340500172 ER PT J AU Simon, RE Pearson, SD Hur, C Chung, RT AF Simon, Rachel E. Pearson, Steven D. Hur, Chin Chung, Raymond T. TI Tackling the hepatitis C cost problem: A test case for tomorrow's cures SO HEPATOLOGY LA English DT Editorial Material ID UNITED-STATES; VIRUS-INFECTION; SOFOSBUVIR; HCV; LEDIPASVIR; RIBAVIRIN C1 [Simon, Rachel E.; Hur, Chin; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Pearson, Steven D.] Inst Clin & Econ Review, Boston, MA USA. [Hur, Chin; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, GI Unit, Boston, MA 02114 USA. [Hur, Chin] Inst Technol Assessment, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org OI Hur, Chin/0000-0002-2819-7576 NR 10 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD NOV PY 2015 VL 62 IS 5 BP 1334 EP 1336 DI 10.1002/hep.28157 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU1EZ UT WOS:000363264100001 PM 26359645 ER PT J AU Khalili, M Lombardero, M Chung, RT Terrault, NA Ghany, MG Kim, WR Lau, D Lisker-Melman, M Sanyal, A Lok, AS AF Khalili, Mandana Lombardero, Manuel Chung, Raymond T. Terrault, Norah A. Ghany, Marc G. Kim, W. Ray Lau, Daryl Lisker-Melman, Mauricio Sanyal, Arun Lok, Anna S. CA HBRN TI Diabetes and prediabetes in patients with hepatitis B residing in North America SO HEPATOLOGY LA English DT Article ID METABOLIC SYNDROME INCREASES; IMPAIRED FASTING GLUCOSE; COUNTRY-OF-ORIGIN; BODY-MASS INDEX; VIRUS INFECTION; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; INSULIN-RESISTANCE; VIRAL-HEPATITIS; LIVER FIBROSIS AB Diabetes is associated with liver disease progression and increased hepatocellular carcinoma risk, but factors associated with diabetes in patients with chronic hepatitis B virus (HBV) infection in North America are unknown. We aimed to determine factors predictive of diabetes and impaired fasting glucose (IFG) in a large HBV-infected multiethnic cohort. Adults with chronic HBV not receiving antiviral therapy were enrolled from 21 centers in North America. Diabetes was defined by history/medication use or fasting glucose 126 mg/dL and IFG as fasting glucose 100-125 mg/dL. Of 882 patients included, 47.2% were female, 71.3% Asian, 83.7% foreign born, median age was 44 years, and median body mass index BMI 24.3 kg/m(2). In this cohort, 26.0% were hepatitis B envelope antigen (HBeAg) positive, 43.9% had HBV DNA 20,000 IU/mL, and 26.7% alanine aminotransferase (ALT) 2x upper limit of normal (40 U/L women, 60 U/L men). Overall, 12.5% had diabetes and 7.8% IFG. The combined prevalence of diabetes or IFG was highest among blacks (36.7%) and those either born in the United States/Canada or foreign born with migration >20 years ago (25.5%). Obesity (odds ratio [OR]: 2.13), hyperlipidemia (OR, 4.13), hypertension (OR, 3.67), high ALT level (OR, 1.86), and family history of diabetes (OR, 3.43) were associated with diabetes. Factors associated with IFG were obesity (OR, 4.13) and hypertension (OR, 3.27), but also HBeAg positivity (OR, 0.39). Recent migration was negatively associated with diabetes among non-Asians (OR, 0.30). Conclusions: Diabetes is more prevalent in HBV-infected North American adults than the general population and is associated with known metabolic risk factors and liver damage, as determined by ALT levels. Among the foreign born, longer duration of North America residence predicted diabetes risk in non-Asians. These results highlight the opportunities for interventions to prevent diabetes especially among at-risk ethnic groups with HBV. (Hepatology 2015;62:1364-1374) C1 [Khalili, Mandana; Terrault, Norah A.] Univ Calif San Francisco, San Francisco, CA 94110 USA. [Lombardero, Manuel] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ghany, Marc G.] NIH, Bethesda, MD USA. [Kim, W. Ray] Stanford Univ, Stanford, CA 94305 USA. [Lau, Daryl] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Lisker-Melman, Mauricio] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Sanyal, Arun] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Lok, Anna S.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Khalili, M (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, 1001 Potrero Ave,NH-3D, San Francisco, CA 94110 USA. EM Mandana.Khalili@ucsf.edu OI Cloonan, Yona/0000-0003-3893-3693; Wahed, Abdus/0000-0001-6911-7221 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK 082843, DK082863, DK082864, DK082866, DK082867, DK082871U01, DK082872, DK082874, DK082919, DK082923, DK082927, DK082943, U01 DK082944]; NIDDK [A-DK-3002-001]; NIDDK, National Institutes of Health (NIH); Immunology Center (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases) [P30DK50306]; Immunology Center (NIH Public Health Service Research) [M01-RR00040, UL1TR000058]; CTSA [UL1TR000004, UL1TR001111, UL1RR024986]; Gilead Sciences, Inc. FX The HBRN was funded by a U01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to the following investigators: Lewis R. Roberts, M.B., Ch.B., Ph.D. (DK 082843); Anna Suk-Fong Lok, M.D. (DK082863); Steven H. Belle, Ph.D., MScHyg (DK082864); Kyong-Mi Chang, M.D. (DK082866); Michael W. Fried, M.D. (DK082867); Adrian M. Di Bisceglie, M.D. (DK082871); William M. Lee, M.D. (U01 DK082872); Harry L.A. Janssen, M.D., Ph.D. (DK082874); Daryl T.-Y. Lau, M.D., M.P.H. (DK082919); Richard K. Sterling, M.D., M.Sc. (DK082923); Steven-Huy B. Han, M.D. (DK082927); Robert C. Carithers, M.D. (DK082943); Norah A. Terrault, M.D., M.P.H. (U01 DK082944); an interagency agreement with NIDDK: Lilia M. Ganova-Raeva, Ph.D. (A-DK-3002-001) and support from the intramural program, NIDDK, National Institutes of Health (NIH): Marc G. Ghany, M.D. Additional funding to support this study was provided to Kyong-Mi Chang, M.D., the Immunology Center (NIH/NIDDK Center of Molecular Studies in Digestive and Liver Diseases P30DK50306, NIH Public Health Service Research Grant M01-RR00040), Richard K. Sterling, M.D., M.Sc. (UL1TR000058, NCATS [National Center for Advancing Translational Sciences], NIH), Norah A. Terrault, M.D., M.P.H. (CTSA grant no: UL1TR000004), Michael W. Fried, M.D. (CTSA grant no.: UL1TR001111), and Anna Suk-Fong Lok (CTSA grant no.: UL1RR024986). Additional support was provided by Gilead Sciences, Inc., and Roche Molecular Systems by a CRADA through the NIDDK. NR 40 TC 8 Z9 8 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD NOV PY 2015 VL 62 IS 5 BP 1364 EP 1374 DI 10.1002/hep.28110 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU1EZ UT WOS:000363264100008 PM 26390278 ER PT J AU Chapko, MK Dufour, DR Hatia, RI Drobeniuc, J Ward, JW Teo, CG AF Chapko, Michael K. Dufour, D. Robert Hatia, Rikita I. Drobeniuc, Jan Ward, John W. Teo, Chong-Gee TI Cost-effectiveness of strategies for testing current hepatitis C virus infection SO HEPATOLOGY LA English DT Article ID POINT-OF-CARE; UNITED-STATES; HCV; ANTIBODY; POPULATIONS; MORTALITY; SETTINGS; OUTBREAK; SEROLOGY; OUTCOMES AB Six strategies for identifying hepatitis C virus (HCV) viremia, involving testing for HCV antibody (HCVAb) followed by a nucleic acid test (NAT) for HCV RNA when the antibody test is positive, are compared. Decision analysis was used to determine mean relative cost per person tested and outcomes of HCV viremia detection. Parameters included proportions of test population with HCVAb and viremia plus specificity, sensitivity, and cost of individual tests. For testing a population with an HCVAb seroprevalence of 3.25%, all strategies when adopting quantitative NAT vary little in cost (range, $29.50-$30.70) and are highly viremia specific (0.9997). Four of the strategies using venipuncture blood for HCVAb testing (whether laboratory conducted or employing a rapid, point-of-care assay) and for NAT (whether done by reflex or using separately drawn blood) achieve the highest viremia sensitivities (range, 0.9950-0.9954). Point-of-care HCVAb testing in fingerstick blood followed by NAT in venipuncture blood yields relatively lower viremia sensitivity (0.9301). The strategy that requires returning for NAT is even less viremia sensitive (<0.9000) because of follow-up loss. Strategies adopting qualitative rather than quantitative NAT are slightly cheaper (range, $28.90-$29.99), similarly viremia specific (0.9997), but less viremia sensitive (0.9456). Viremia sensitivity and specificity remain the same regardless of the proportion of HCVAb-seropositive persons in the cohort being tested. Conclusions: Strategies involving HCVAb testing in venipuncture blood, whether laboratory conducted or using a point-of-care assay, when followed by quantitative NAT done reflexively or in separately drawn blood, are comparably economical and suitably viremia sensitive. Less cost-effective is point-of-care HCVAb testing in fingerstick blood followed by NAT in venipuncture blood. Least cost-effective is the strategy requiring the tested person to return for NAT. (Hepatology 2015;62:1396-1404) C1 [Chapko, Michael K.] Vet Affairs Paget Sound Hlth Care Syst, Seattle, WA USA. [Chapko, Michael K.] Univ Washington, Seattle, WA 98195 USA. [Dufour, D. Robert] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Hatia, Rikita I.; Drobeniuc, Jan; Ward, John W.; Teo, Chong-Gee] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA. RP Chapko, MK (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev 152, 1660 S Columbian Way, Seattle, WA 98108 USA. EM michael.chapko@va.gov NR 27 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD NOV PY 2015 VL 62 IS 5 BP 1396 EP 1404 DI 10.1002/hep.27966 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU1EZ UT WOS:000363264100011 PM 26126725 ER PT J AU Darghouth, S Brody, L Alegria, M AF Darghouth, Sarah Brody, Leslie Alegria, Margarita TI Does Marriage Matter? Marital Status, Family Processes, and Psychological Distress Among Latino Men and Women SO HISPANIC JOURNAL OF BEHAVIORAL SCIENCES LA English DT Article DE family; gender; Latinos; marital status; marriage; psychological distress ID PSYCHIATRIC EPIDEMIOLOGY; SOCIAL SUPPORT; LONGITUDINAL ANALYSIS; DEPRESSIVE SYMPTOMS; MEXICAN-AMERICANS; MAJOR DEPRESSION; NATIONAL LATINO; ASIAN-AMERICAN; OLDER-ADULTS; LATER LIFE AB This study examined the association between marital status and psychological distress among Latinos in the United States, with attention to the impact of gender and family processes (family support, family cohesion, family cultural conflict, and family burden). Analyses were conducted using the National Latino and Asian American Study (NLAAS). The sample was a national randomized stratified probability sample (N = 2,554). For the entire sample, being separated, divorced, cohabitating, or single was associated with higher levels of psychological distress compared with being married. For women, being separated or divorced was associated with higher levels of psychological distress compared with being married, but for men, distress was not related to marital status. For both men and women, lower levels of support and higher levels of cultural conflict and burden in the family were related to higher psychological distress. Among divorced women, family variables impacted the relationship between marital status and psychological distress. C1 [Darghouth, Sarah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Brody, Leslie] Boston Univ, Psychol, Boston, MA 02215 USA. [Alegria, Margarita] Boston Univ, Dept Med, Dispar Res Unit, Boston, MA 02215 USA. [Alegria, Margarita] Massachusetts Gen Hosp, Dispar Res Unit, Dept Med, Boston, MA 02114 USA. RP Darghouth, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St WAC 815, Boston, MA 02114 USA. EM sdarghouth@mgh.harvard.edu FU NIH - National Institute of Mental Health [U01 MH62209]; Substance Abuse and Mental Health Services Administration Center for Mental Health Services (SAMHSA/CMHS); Office of Behavioral and Social Sciences Research (OBSSR) FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The NLAAS was supported by NIH Research Grant # U01 MH62209 funded by the National Institute of Mental Health as well as the Substance Abuse and Mental Health Services Administration Center for Mental Health Services (SAMHSA/CMHS) and the Office of Behavioral and Social Sciences Research (OBSSR). NR 48 TC 0 Z9 0 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0739-9863 EI 1552-6364 J9 HISPANIC J BEHAV SCI JI Hisp. J. Behav. Sci. PD NOV PY 2015 VL 37 IS 4 BP 482 EP 502 DI 10.1177/0739986315606947 PG 21 WC Psychology, Multidisciplinary SC Psychology GA CU1KX UT WOS:000363281400002 ER PT J AU Drain, PK Kleene, JM Coleman, SM Losina, E Katz, JN Giddy, J Ross, D Freedberg, KA Bassett, I AF Drain, P. K. Kleene, J. M. Coleman, S. M. Losina, E. Katz, J. N. Giddy, J. Ross, D. Freedberg, K. A. Bassett, I. V. TI Prevalence of cryptococcal antigenuria at initial HIV diagnosis in KwaZulu-Natal SO HIV MEDICINE LA English DT Article DE CD4 count; cryptococcal urine antigen; cryptococcosis; cryptococcus; diagnosis; HIV; AIDS; South Africa ID SOUTH-AFRICA; ANTIGENEMIA; MENINGITIS; SERUM; CARE; THERAPY; UGANDA; ADULTS AB ObjectivesThe World Health Organization (WHO) recommends screening HIV-infected people for cryptococcal antigens to identify cryptococcosis, a major cause of AIDS-related deaths. As the burden of cryptococcosis is unknown in South Africa's KwaZulu-Natal province, we assessed the cryptococcal antigenuria prevalence among newly diagnosed HIV-infected adults there. MethodsWe conducted a cross-sectional study of newly diagnosed HIV-infected adults who received voluntary HIV testing in an out-patient clinic. Participants provided a urine specimen in a sterile container, and we performed testing with a WHO-endorsed rapid cryptococcal antigen lateral flow assay (Immy Inc., Norman, OK, USA) per the manufacturer's specifications. We assessed cryptococcal antigenuria prevalence among participants with CD4 counts<200cells/L, and stratified results by CD4 count categories. ResultsAmong 432 participants, the mean (standard deviation) age was 36.1 +/- 9.9 years and 172 (40%) were female. The overall estimated prevalence of cryptococcal antigenuria was 9.0% [95% confidence interval (CI) 6.5-12.1%]. CD4 counts were available for 319 participants (74%); the median CD4 count was 75cells/L [interquartile range (IQR) 34-129cells/L]. Participants with a negative cryptococcal antigenuria screening test had a median CD4 count of 79cells/L (IQR 36-129cells/L), while participants with a positive cryptococcal test had a median CD4 count of 41cells/L (IQR 10-112cells/L). The estimated prevalence of cryptococcal antigenuria among participants with CD4 counts <50cells/L was 12.5% (95% CI 7.0-20.1%), which was significantly higher than that among participants with CD4 counts of 50-200cells/L (4.8%; 95% CI 2.3-8.7%). ConclusionsNearly 1 in 10 newly diagnosed HIV-infected adults with CD4 counts <200cells/L in KwaZulu-Natal had evidence of cryptococcal antigenuria. Point-of-care CD4 count testing and cryptococcal antigen screening may rapidly identify cryptococcosis at the time of HIV diagnosis. C1 [Drain, P. K.; Losina, E.; Freedberg, K. A.; Bassett, I. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kleene, J. M.] Stony Brook Sch Med, Stony Brook, NY USA. [Coleman, S. M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Losina, E.; Freedberg, K. A.] Harvard Univ, Sch Med, Boston, MA USA. [Katz, J. N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Giddy, J.] McCord Hosp, Durban, South Africa. [Ross, D.] St Marys Hosp, Durban, South Africa. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM pdrain@partners.org FU Harvard Global Health Institute; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; Program in AIDS Clinical Research Training [T32 AI007433]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; National Institute of Allergy and Infectious Disease [K23 AI108293, R01 AI058736]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24 AR057827]; National Center for Research Resources (the Harvard Catalyst) [UL1 RR 025758] FX Financial support: Research reported in this publication was supported by the Harvard Global Health Institute, the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988), The Program in AIDS Clinical Research Training [grant T32 AI007433 (PKD)], the National Institute of Mental Health [R01 MH090326 (IVB) and R01 MH073445 (RPW)], the National Institute of Allergy and Infectious Disease [K23 AI108293 (PKD) and R01 AI058736 (KAF)], the Harvard University Center for AIDS Research (P30 AI060354), the National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24 AR057827 (EL)], and the National Center for Research Resources (the Harvard Catalyst UL1 RR 025758). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other funding agencies. NR 15 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD NOV PY 2015 VL 16 IS 10 BP 640 EP 644 DI 10.1111/hiv.12263 PG 5 WC Infectious Diseases SC Infectious Diseases GA CU1IU UT WOS:000363275300008 PM 25958770 ER PT J AU Paras, ML Shenoy, ES Hsu, HE Walensky, RP Hooper, DC AF Paras, Molly L. Shenoy, Erica S. Hsu, Heather E. Walensky, Rochelle P. Hooper, David C. TI Housestaff Knowledge Related to Urinary Catheter Use and Catheter-Associated Urinary Tract Infections SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID PREVENTION; STRATEGIES; PHYSICIANS AB Despite published catheter-associated urinary tract infection prevention guidelines, inappropriate catheter use is common. We surveyed housestaff about their knowledge of catheter-associated urinary tract infections at a teaching hospital and found most are aware of prevention guidelines; however, their application to clinical scenarios and catheter practices fall short of national goals. C1 [Paras, Molly L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.] Harvard Univ, Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Infect Dis, Boston, MA 02114 USA. [Hsu, Heather E.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. RP Paras, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Infect Dis, Cox 5,55 Fruit St, Boston, MA 02114 USA. EM mparas@partners.org FU Doris Duke Charitable Foundation; Massachusetts General Hospital Departmental Funds; National Institutes of Health [T32 A107061]; Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard University; Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award) [UL1 TR001102] FX Doris Duke Charitable Foundation (grant to Harvard Medical School to fund Clinical Research Fellows, to H.E.H.); Massachusetts General Hospital Departmental Funds (to D.C.H. and E.S.S.); National Institutes of Health (training grant T32 A107061 to E.S.S.); the Harvard Center for AIDS Research (to R.P.W.); 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 UL1 TR001102); and financial contributions from Harvard University and its affiliated academic health care centers. NR 10 TC 1 Z9 2 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2015 VL 36 IS 11 BP 1355 EP 1357 DI 10.1017/ice.2015.189 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA CU1HG UT WOS:000363270800018 PM 26278269 ER PT J AU Bae, K Yoo, HS Lamoury, G Boyle, F Rosenthal, DS Oh, B AF Bae, Kyeore Yoo, Hwa-Seung Lamoury, Gillian Boyle, Frances Rosenthal, David S. Oh, Byeongsang TI Acupuncture for Aromatase Inhibitor-Induced Arthralgia: A Systematic Review SO INTEGRATIVE CANCER THERAPIES LA English DT Review DE acupuncture; breast cancer; aromatase inhibitors; arthralgia; joint pain; pain management ID STAGE BREAST-CANCER; ADJUVANT ENDOCRINE THERAPY; JOINT SYMPTOMS; RISK-FACTORS; MUSCULOSKELETAL SYMPTOMS; RHEUMATOID-ARTHRITIS; POSTMENOPAUSAL WOMEN; AMERICAN SOCIETY; CLINICAL-TRIALS; PAIN AB Background. Aromatase inhibitors (AIs) are commonly used as adjunctive hormone treatment for early breast cancer patients. The major side effect of AIs is arthralgia, which affects adherence. Previous reviews suggested that acupuncture is effective in the management of cancer-related pain. The aim of this review is to evaluate the effects of acupuncture on arthralgia caused by AIs. Methods. This article examined randomized controlled trials (RCTs) measuring the effects of acupuncture on joint symptoms caused by AIs within 8 medical databases till May 2014. The quality of the articles was evaluated according to the Cochrane risk of bias (ROB) tool. Results. Four RCTs were identified in medical journals. Two studies were conducted with manual acupuncture and 2 studies were electroacupuncture. The range of sample size was between 32 and 67. One RCT showed significant improvement in the acupuncture group compared with the sham control group and another RCT showed a statistical difference between the electroacupuncture and waitlist group. The other 2 studies showed no statistical differences between control and acupuncture groups. Two studies conducted blood analysis to elucidate the mechanism of efficacy of acupuncture for arthralgia. The 2 positive studies had a lower ROB and 2 studies had a high ROB. Conclusions. The systematic review suggests that acupuncture has potential benefits to improve arthralgia caused by AIs. However, further trials of adequate sample size, appropriate control group, and longer follow-up are necessary to investigate the efficacy of acupuncture in AI-induced arthralgia. C1 [Bae, Kyeore; Lamoury, Gillian; Oh, Byeongsang] Royal N Shore Hosp, Sydney Med Sch, Sydney, NSW, Australia. [Bae, Kyeore; Yoo, Hwa-Seung] Daejeon Univ, Dunsan Korean Med Hosp, East West Canc Ctr, Taejon, South Korea. [Lamoury, Gillian; Boyle, Frances] Mater Hosp, Sydney Med Sch, Sydney, NSW, Australia. [Rosenthal, David S.; Oh, Byeongsang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bae, K (reprint author), Daejeon Univ, Dunsan Korean Med Hosp, East West Canc Ctr, Taejon, South Korea. EM kyeorebae@gmail.com NR 51 TC 2 Z9 2 U1 4 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 EI 1552-695X J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD NOV PY 2015 VL 14 IS 6 BP 496 EP 502 DI 10.1177/1534735415596573 PG 7 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA CT8JW UT WOS:000363063200001 PM 26220605 ER PT J AU Matthews, PE Le, T Delmar, J Okulicz, JF AF Matthews, P. E. Le, T. Delmar, J. Okulicz, J. F. TI Virologic suppression among HIV-infected US Air Force members in a highly-structured programme with free access to care SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; treatment; antiretroviral therapy; HAART; AIDS; Air Force; military; continuum of care; treatment cascade ID ELVITEGRAVIR/COBICISTAT/EMTRICITABINE/TENOFOVIR DISOPROXIL FUMARATE; ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; CLINICAL-OUTCOMES; INITIAL TREATMENT; EARLY RETENTION; DOUBLE-BLIND; ENGAGEMENT; PREVENTION; HEALTH AB The United States Air Force HIV programme has several features that may enhance antiretroviral therapy outcomes, including free access to healthcare and mandatory clinical visits every six months at a single centre. We evaluated viral load suppression (<50copies/ml) after 12 months of initial antiretroviral therapy, with extension to 18 and 24 months. Active duty Air Force members were categorised by year of antiretroviral therapy initiation: 2000-2005 (n=95, 36.1%) and 2006-2011 (n=168, 63.9%). The median months from HIV diagnosis to initial antiretroviral therapy were shorter in the 2000-2005 group (2.4, IQR 1.2-5.9) compared with the 2006-2011 group (12.6, IQR 2.6-29.0; p<0.001). Viral load suppression was greater in the 2006-2011 group compared with the 2000-2005 group at 12 months (93.2% versus 78.6%, p=0.002) and 18 months (91.8% versus 80.3%, p=0.03), and trended higher at 24 months (90.8% versus 82.5%; p=0.15). Factors associated with viral load suppression at 12 months in multivariate models included antiretroviral therapy initiation during 2006-2011 (OR 5.22, 95% CI 1.50-18.18) and CD4 count at antiretroviral therapy initiation (OR 2.29, 95% CI 1.19-14.43 per 100cells/mu l increase). Structured programmes that minimise traditional barriers to care combined with the use of contemporary antiretroviral therapy regimens can achieve clinic-wide viral load suppression in >90% of patients. C1 [Matthews, P. E.; Delmar, J.; Okulicz, J. F.] San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Le, T.] South Texas Vet Hlth Care Syst, Vet Affairs Res Ctr, AIDS & HIV I Infect & Ctr Personalized Med, San Antonio, TX USA. [Le, T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Okulicz, JF (reprint author), San Antonio Mil Med Ctr, 3551 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM jason.f.okulicz.mil@mail.mil NR 26 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 EI 1758-1052 J9 INT J STD AIDS JI Int. J. STD AIDS PD NOV PY 2015 VL 26 IS 13 BP 951 EP 959 DI 10.1177/0956462414563631 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU2CY UT WOS:000363331400006 PM 25505041 ER PT J AU Menendez, ME Lu, N Unizony, S Choi, HK Ring, D AF Menendez, Mariano E. Lu, Na Unizony, Sebastian Choi, Hyon K. Ring, David TI Surgical site infection in hand surgery SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Surgical site infection; Hand surgery; Complication; Patient safety; Quality improvement ID CARPAL-TUNNEL RELEASE; TOXIC SHOCK SYNDROME; RISK-FACTORS; ANTIBIOTIC-PROPHYLAXIS; ORTHOPEDIC-SURGERY; SPINE SURGERY; IMPACT; EVENTS AB As ambulatory surgery becomes increasingly common, there is growing interest in assessing, monitoring, and tracking complications that occur secondary to outpatient procedures. We sought to determine the rates of 14- and 30-day acute care visits for surgical site infection after outpatient hand surgery, and to identify associated factors. Using the California State Ambulatory Surgery database for 2010 and 2011, we identified 44,305 patients undergoing common outpatient hand surgery procedures. Cases were linked to the State Emergency Department and the State Inpatient databases for postoperative acute care visits (e.g. hospitalizations, emergency department or ambulatory surgical visits) related to surgical site infection. Postoperative acute care visits for surgical site infection occurred in 1.7 per 1,000 hand surgery procedures (0.17 %) at 14 days, and 3.3 per 1,000 (0.33 %) at 30 days. Thirty-day infection rates were lowest after ganglion cyst (0.15 %) and deQuervain surgery (0.25 %), and highest following cubital tunnel release (0.56 %) and trapeziometacarpal arthroplasty (0.49 %). Fifty-three percent of postoperative visits were treated in the emergency department setting, 37 % in the inpatient setting, and 10 % required an additional outpatient surgical procedure. Patients with government-funded insurance-Medicaid in particular-and those residing in rural areas had higher odds of postoperative acute care visits for surgical site infection. Diabetes, obesity, and tobacco use were not associated with increased risk for infection leading to an acute care visit. The rates of postoperative acute care visits for surgical site infection after ambulatory hand procedures are low but not negligible-particularly given how common hand surgery is, and the fact that many of these events entail hospitalizations or additional ambulatory procedures. Reasons for the increased risk of acute care visits for infection among publicly insured and rural patients merit additional research. C1 [Menendez, Mariano E.; Ring, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr,Dept Orthopaed Surg, Boston, MA 02114 USA. [Lu, Na; Choi, Hyon K.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [Lu, Na; Unizony, Sebastian; Choi, Hyon K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Yawkey Ctr,Dept Orthopaed Surg, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org NR 36 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD NOV PY 2015 VL 39 IS 11 BP 2191 EP 2198 DI 10.1007/s00264-015-2849-9 PG 8 WC Orthopedics SC Orthopedics GA CU0ZP UT WOS:000363248700014 PM 26156713 ER PT J AU Howe, YJ O'Rourke, JA Yatchmink, Y Viscidi, EW Jones, RN Morrow, EM AF Howe, Yamini J. O'Rourke, Julia A. Yatchmink, Yvette Viscidi, Emma W. Jones, Richard N. Morrow, Eric M. TI Female Autism Phenotypes Investigated at Different Levels of Language and Developmental Abilities SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Sex differences; Diagnosis of autism spectrum disorder ID DIAGNOSTIC OBSERVATION SCHEDULE; SIMONS SIMPLEX COLLECTION; HIGH-FUNCTIONING AUTISM; DSM-IV-TR; SPECTRUM DISORDERS; SEX-DIFFERENCES; GENERAL-POPULATION; TREATMENT NETWORK; HEALTH-CARE; CHILDREN AB This study investigated the differences in clinical symptoms between females and males with autism spectrum disorder (ASD) across three verbal ability groups (nonverbal, phrase and fluent speech), based on which Autism Diagnostic Observation Schedule module was administered to 5723 individuals in four research datasets. In the Simons Simplex Collection and Autism Treatment Network, females with ASD and phrase or fluent speech had lower cognitive, adaptive, and social abilities than males. In the Autism Genetics Resource Exchange and the Autism Consortium, females with phrase or fluent speech had similar or better adaptive and social abilities than males. Females who were nonverbal had similar cognitive, adaptive, and social abilities as males. Population-based longitudinal studies of verbally fluent females with ASD are needed. C1 [Howe, Yamini J.; Yatchmink, Yvette] Brown Univ, Hasbro Childrens Rhode Isl Hosp, Dept Pediat, Div Dev Behav Pediat, Providence, RI 02912 USA. [O'Rourke, Julia A.] Massachusetts Gen Hosp Children, Lurie Ctr Autism, Lexington, MA USA. [O'Rourke, Julia A.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Viscidi, Emma W.] Brown Univ, Dept Community Hlth Epidemiol, Div Biol & Med, Providence, RI 02912 USA. [Jones, Richard N.; Morrow, Eric M.] Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Morrow, Eric M.] Emma Pendleton Bradley Hosp, Dev Disorders Genet Res Program, Providence, RI USA. RP Morrow, EM (reprint author), Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. EM Eric_Morrow@Brown.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU NIH [P20GM103645-01A1, R01MH105442-01, R01MH102418]; Burroughs Wellcome Fund; Maternal Child Health Bureau (MCHB) [T77MC09797]; National Institute of Mental Health [1U24MH081810]; Autism Speaks FX EMM has received support from NIH P20GM103645-01A1, R01MH105442-01, R01MH102418, and a Career Award in Medical Science from the Burroughs Wellcome Fund. YJH received support from the Maternal Child Health Bureau (MCHB) under training Grant T77MC09797. We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The AGRE is a program of Autism Speaks and is supported, in part, by Grant 1U24MH081810 from the National Institute of Mental Health to Clara M. Lajonchere (PI). We would also like to acknowledge datasets used for the analyses obtained from the Autism Treatment Network (ATN) Database. Funding support for ATN was provided by Autism Speaks. We would like to thank the ATN participants and the ATN Research Group for their valuable contribution to this research. The Autism Consortium is a Boston-based clinical and research collaboration, with 17 institutional members and 125 individual scientist and clinician members, who are collectively dedicated to catalyzing progress in understanding autism and related neurodevelopmental disorders in order to improve diagnosis, clinical care and treatment. With data and samples collected from 525+ families who participated in clinical research, the Consortium's repository is made available for use by the autism research community. The authors are grateful to the Consortium, its members and the families who have made this vital resource possible. We are also grateful to all of the families at the participating SSC Simplex Collection (SSC) sites, as well as the principal investigators (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, E. Wijsman). NR 51 TC 4 Z9 4 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD NOV PY 2015 VL 45 IS 11 SI SI BP 3537 EP 3549 DI 10.1007/s10803-015-2501-y PG 13 WC Psychology, Developmental SC Psychology GA CT8LC UT WOS:000363066900013 PM 26100851 ER PT J AU Tilford, JM Payakachat, N Kuhlthau, KA Pyne, JM Kovacs, E Bellando, J Williams, DK Brouwer, WBF Frye, RE AF Tilford, J. Mick Payakachat, Nalin Kuhlthau, Karen A. Pyne, Jeffrey M. Kovacs, Erica Bellando, Jayne Williams, D. Keith Brouwer, Werner B. F. Frye, Richard E. TI Treatment for Sleep Problems in Children with Autism and Caregiver Spillover Effects SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Child health; Caregiver health; Child sleep habits; Quality adjusted life year; Cost-effectiveness analysis ID QUALITY-OF-LIFE; SPECTRUM DISORDERS; COST-EFFECTIVENESS; HEALTH UTILITIES; INSOMNIA; INSTRUMENT; MELATONIN; SYSTEM; SCORES; FAMILY AB Sleep problems in children with autism spectrum disorders (ASD) are under-recognized and under-treated. Identifying treatment value accounting for health effects on family members (spillovers) could improve the perceived cost-effectiveness of interventions to improve child sleep habits. A prospective cohort study (N = 224) was conducted with registry and postal survey data completed by the primary caregiver. We calculated quality of life outcomes for the child and the primary caregiver associated with treatments to improve sleep in the child based on prior clinical trials. Predicted treatment effects for melatonin and behavioral interventions were similar in magnitude for the child and for the caregiver. Accounting for caregiver spillover effects associated with treatments for the child with ASD increases treatment benefits and improves cost-effectiveness profiles. C1 [Tilford, J. Mick] Univ Arkansas Med Sci, Dept Hlth Policy & Management, Little Rock, AR 72205 USA. [Tilford, J. Mick; Payakachat, Nalin] Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, Little Rock, AR 72205 USA. [Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kuhlthau, Karen A.] Massachusetts Gen Hosp, Ctr Adolescent Hlth Policy, Boston, MA 02114 USA. [Pyne, Jeffrey M.] Univ Arkansas Med Sci, Ctr Mental Healthcare & Outcomes Res, Cent Arkansas Vet Healthcare Syst & Psychiat Res, Little Rock, AR 72205 USA. [Kovacs, Erica] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. [Bellando, Jayne; Frye, Richard E.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Williams, D. Keith] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Brouwer, Werner B. F.] Erasmus Univ, Dept Hlth Policy & Management, Rotterdam, Netherlands. RP Tilford, JM (reprint author), Univ Arkansas Med Sci, Dept Hlth Policy & Management, Little Rock, AR 72205 USA. EM tilfordmickj@uams.edu FU National Institute of Mental Health [R01MH089466, R03MH102495]; US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3MC11054] FX The project was supported by a Grant (R01MH089466) with JMT and KAK serving as principal investigators and a Grant (R03MH102495) with NP as the principal investigator both from the National Institute of Mental Health. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors acknowledge the members of the Autism Treatment Network for use of the data. The data for the study were collected as part of the Autism Treatment Network, a program of Autism Speaks. Further support came from a cooperative agreement (UA3MC11054) 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 work described in this article represents the independent efforts of the authors with no restrictions from the funding source or the Autism Treatment Network. None of the authors of this study reported a conflict of interest associated with the preparation of the manuscript. Maria Melguizo, Nupur Chowdhury, Rebecca Rieger and Latunja Sockwell provided excellent research assistance. NR 57 TC 3 Z9 3 U1 4 U2 25 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD NOV PY 2015 VL 45 IS 11 SI SI BP 3613 EP 3623 DI 10.1007/s10803-015-2507-5 PG 11 WC Psychology, Developmental SC Psychology GA CT8LC UT WOS:000363066900019 PM 26126749 ER PT J AU Qin, WP Li, XD Peng, YZ Harlow, LM Ren, YS Wu, YJ Li, JL Qin, YW Sun, J Zheng, SJ Brown, T Feng, JQ Ke, HZ Bauman, WA Cardozo, CC AF Qin, Weiping Li, Xiaodong Peng, Yuanzhen Harlow, Lauren M. Ren, Yinshi Wu, Yingjie Li, Jiliang Qin, Yiwen Sun, Jie Zheng, Shijia Brown, Tom Feng, Jian Q. Ke, Hua Zhu Bauman, William A. Cardozo, Christopher C. TI Sclerostin antibody preserves the morphology and structure of osteocytes and blocks the severe skeletal deterioration after motor-complete spinal cord injury in rats SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE PRECLINICAL STUDIES; ANABOLICS; OSTEOCYTES; STROMAL; STEM CELLS; WNT; -CATENIN; LRPS ID BONE-FORMATION; MECHANICAL STIMULATION; OSTEOPOROSIS; MODEL; IMMOBILIZATION; EXPRESSION; DENSITY; MUSCLE; MASS; IDENTIFICATION AB Unloading, neural lesions, and hormonal disorders after acute motor-complete spinal cord injury (SCI) cause one of the most severe forms of bone loss, a condition that has been refractory to available interventions tested to date. Thus, these features related to acute SCI provide a unique opportunity to study complex bone problems, potential efficacious interventions, and mechanisms of action that are associated with these dramatic pathological changes. This study was designed to explore the therapeutic potential of sclerostin antibody (Scl-Ab) in a rat model of bone loss after motor-complete SCI, and to investigate mechanisms underlying bone loss and Scl-Ab action. SCI rats were administered Scl-Ab (25 mg/kg/week) or vehicle beginning 7 days after injury then weekly for 7 weeks. SCI resulted in significant decreases in bone mineral density (-25%) and trabecular bone volume (-67%) at the distal femur; Scl-Ab completely prevented these deteriorations of bone in SCI rats, concurrent with markedly increased bone formation. Scanning electron microscopy revealed that SCI reduced numbers of osteocytes and dendrites concomitant with a morphology change from a spindle to round shape; Scl-Ab corrected these abnormalities in osteocytes. In ex vivo cultures of bone marrow cells, Scl-Ab inhibited osteoclastogenesis, and promoted osteoblastogenesis accompanied by increases in mRNA levels of LRP5, osteoprotegerin (OPG), and the OPG/RANKL ratio, and a decrease in DKK1 mRNA. Our findings provide the first evidence that robust bone loss after acute motor-complete SCI can be blocked by Scl-Ab, at least in part, through the preservation of osteocyte morphology and structure and related bone remodeling. Our findings support the inhibition of sclerostin as a promising approach to mitigate the striking bone loss that ensues after acute motor-complete SCI, and perhaps other conditions associated with disuse osteoporosis as a consequence of neurological disorders. (c) 2015 American Society for Bone and Mineral Research C1 [Qin, Weiping; Peng, Yuanzhen; Harlow, Lauren M.; Qin, Yiwen; Zheng, Shijia; Bauman, William A.; Cardozo, Christopher C.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY USA. [Qin, Weiping; Wu, Yingjie; Bauman, William A.; Cardozo, Christopher C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Li, Xiaodong; Brown, Tom; Ke, Hua Zhu] Amgen Inc, Thousand Oaks, CA 91320 USA. [Ren, Yinshi; Feng, Jian Q.] Texas A&M Univ, Baylor Coll Dent, Dallas, TX USA. [Wu, Yingjie; Sun, Jie] Dalian Med Univ, Inst Gene Engn Anim Models Human Dis, Dalian, Peoples R China. [Li, Jiliang] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46205 USA. [Bauman, William A.; Cardozo, Christopher C.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Cardozo, Christopher C.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. RP Qin, WP (reprint author), James J Peters Veteran Affairs Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM weiping.qin@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B1313-R, B0687-R, B9212-C] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (grants B1313-R and B0687-R to WQ; B9212-C to WAB). Amgen Inc. and UCB Pharma provided Scl-Ab. NR 55 TC 7 Z9 7 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2015 VL 30 IS 11 BP 1994 EP 2004 DI 10.1002/jbmr.2549 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU1MV UT WOS:000363286900006 PM 25974843 ER PT J AU Carbone, LD Hovey, KM Andrews, CA Thomas, F Sorensen, MD Crandall, CJ Watts, NB Bethel, M Johnson, KC AF Carbone, Laura D. Hovey, Kathleen M. Andrews, Christopher A. Thomas, Fridtjof Sorensen, Mathew D. Crandall, Carolyn J. Watts, Nelson B. Bethel, Monique Johnson, Karen C. TI Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE DXA; AGING; DXA; OSTEOPOROSIS; GENERAL POPULATION STUDIES; MENOPAUSE ID BONE-MINERAL DENSITY; POPULATION-BASED COHORT; KIDNEY-STONES; POSTMENOPAUSAL WOMEN; UNITED-STATES; D SUPPLEMENTATION; DIETARY CALCIUM; LUMBAR SPINE; RISK; FRACTURES AB Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow-up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow-up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis. (c) 2015 American Society for Bone and Mineral Research. C1 [Carbone, Laura D.; Bethel, Monique] Dept Vet Affairs Med Ctr, Subspecialty Serv, Augusta, GA USA. [Carbone, Laura D.; Bethel, Monique] Georgia Regents Univ, Dept Med, Rheumatol Sect, Augusta, GA 30912 USA. [Hovey, Kathleen M.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA. [Andrews, Christopher A.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Thomas, Fridtjof; Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Sorensen, Mathew D.] Dept Vet Affairs Med Ctr, VA Puget Sound Hlth Care Syst, Div Urol, Seattle, WA USA. [Sorensen, Mathew D.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. [Crandall, Carolyn J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Watts, Nelson B.] Mercy Hlth Osteoporosis & Bone Hlth Serv, Cincinnati, OH USA. RP Carbone, LD (reprint author), Georgia Regents Univ, Dept Med, Rheumatol Sect, 1120 15th St,BI 5086, Augusta, GA 30912 USA. EM lcarbone@gru.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services. The WHI publications committee approved the final version of this manuscript. This material is the result of work supported with resources and the use of facilities at the Charlie Norwood Veterans Affairs Medical Center. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. NR 48 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2015 VL 30 IS 11 BP 2096 EP 2102 DI 10.1002/jbmr.2553 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU1MV UT WOS:000363286900016 PM 25990099 ER PT J AU Ring, D AF Ring, D. TI Commentary on Minimal important changes and differences in elective hand surgery. J. N. Rodrigues, N. T. Mabvuure, D. Nikkhah, Z. Shariff and T. R. C. Davis. J Hand Surg Eur. 2015, 40: 900-12 SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Hand Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand Surg, Boston, MA 02114 USA. EM dring@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 EI 2043-6289 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD NOV PY 2015 VL 40 IS 9 BP 913 EP 913 DI 10.1177/1753193415578592 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA CU3ZE UT WOS:000363464500003 PM 26494907 ER PT J AU Goncalves, I den Ruijter, H Nahrendorf, M Pasterkamp, G AF Goncalves, I. den Ruijter, H. Nahrendorf, M. Pasterkamp, G. TI Detecting the vulnerable plaque in patients SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE atherosclerosis; noninvasive imaging; vulnerable plaque ID ACUTE CORONARY SYNDROME; CAROTID INTIMA-MEDIA; IN-VIVO MRI; ISCHEMIC CEREBROVASCULAR EVENTS; INCIDENT CARDIOVASCULAR EVENTS; POSITRON-EMISSION-TOMOGRAPHY; OPTICAL COHERENCE TOMOGRAPHY; LOW-RISK INDIVIDUALS; NAPKIN-RING SIGN; ATHEROSCLEROTIC PLAQUE AB Atherosclerosis is a systemic condition that eventually evolves into vulnerable plaques and cardiovascular events. Pathology studies reveal that rupture-prone atherosclerotic plaques have a distinct morphology, namely a thin, inflamed fibrous cap covering a large lipidic and necrotic core. With the fast development of imaging techniques in the last decades, detecting vulnerable plaques thereby identifying individuals at high risk for cardiovascular events has become of major interest. Yet, in current clinical practice, there is no routine use of any vascular imaging modality to assess plaque characteristics as each unique technique has its pros and cons. This review describes the techniques that may evolve into screening tool for the detection of the vulnerable plaque. Finally, it seems that plaque morphology has been changing in the last decades leading to a higher prevalence of stable' atherosclerotic plaques, possibly due to the implementation of primary prevention strategies or other approaches. Therefore, the nomenclature of vulnerable plaque lesions should be very carefully defined in all studies. C1 [Goncalves, I.] Lund Univ, Dept Cardiol & Clin Sci Malmo, Skane Univ Hosp, Malmo, Sweden. [den Ruijter, H.; Pasterkamp, G.] UMCU, Lab Expt Cardiol, Utrecht, Netherlands. [den Ruijter, H.; Pasterkamp, G.] UMCU, Res Lab Clin Chem LKCH, Utrecht, Netherlands. [Nahrendorf, M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Goncalves, I (reprint author), Skane Univ Hosp, Clin Res Ctr, House 91,Plan12,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden. EM Isabel.Goncalves@med.lu.se NR 95 TC 3 Z9 3 U1 4 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 EI 1365-2796 J9 J INTERN MED JI J. Intern. Med. PD NOV PY 2015 VL 278 IS 5 BP 520 EP 530 DI 10.1111/joim.12414 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CU1JX UT WOS:000363278500008 PM 26306911 ER PT J AU Kilbane, C Ramirez-Zamora, A Ryapolova-Webb, E Qasim, S Glass, GA Starr, PA Ostrem, JL AF Kilbane, Camilla Ramirez-Zamora, Adolfo Ryapolova-Webb, Elena Qasim, Salman Glass, Graham A. Starr, Philip A. Ostrem, Jill L. TI Is one large target better than two? Response SO JOURNAL OF NEUROSURGERY LA English DT Letter ID DEEP BRAIN-STIMULATION; THALAMIC-STIMULATION; TREMOR C1 [Kilbane, Camilla] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Ryapolova-Webb, Elena; Qasim, Salman; Glass, Graham A.; Starr, Philip A.; Ostrem, Jill L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Glass, Graham A.; Starr, Philip A.; Ostrem, Jill L.] San Francisco VA Med Ctr, Parkinsons Dis Res, Educ & Clin Ctr, San Francisco, CA USA. [Ramirez-Zamora, Adolfo] Albany Med Coll, Albany, NY 12208 USA. RP Kilbane, C (reprint author), Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2015 VL 123 IS 5 BP 1349 EP 1350 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CU3QL UT WOS:000363439800039 PM 26870866 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI A Comparison of the Charlson and Elixhauser Comorbidity Measures to Predict Inpatient Mortality After Proximal Humerus Fracture SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE proximal humerus fracture; mortality; Charlson; Elixhauser; comorbidity; comparison; risk adjustment ID IN-HOSPITAL MORTALITY; ADMINISTRATIVE DATA; RISK-ADJUSTMENT; ORTHOPEDIC-SURGERY; HIP-FRACTURES; UNITED-STATES; INDEX; VALIDATION; DATABASES; COMPLICATIONS AB Objectives:Proximal humerus fractures are very common in infirm elderly patients and are associated with appreciable inpatient mortality. We sought to compare the discriminative ability of the Charlson and Elixhauser comorbidity measures for predicting inpatient mortality after proximal humerus fractures.Methods:Data from the Nationwide Inpatient Sample (2002-2011) were obtained. We constructed 2 main multivariable logistic regression models, with inpatient mortality as the dependent variable and 1 of the 2 comorbidity scores, as well as age and sex, as independent variables. A base model that contained only age and sex was also evaluated. The predictive performance of the Charlson and Elixhauser comorbidity measures was assessed and compared using the area under the receiver operating characteristic curve (AUC) derived from these regression models.Results:Elixhauser comorbidity adjustment provided better discrimination of inpatient mortality [AUC = 0.840, 95% confidence interval (CI), 0.828-0.853] than the Charlson model (AUC = 0.786, 95% CI, 0.771-0.801) and the base model without comorbidity adjustment (AUC = 0.722, 95% CI, 0.705-0.740). In terms of relative improvement in predictive ability, the Elixhauser score performed 46% better than the Charlson score.Conclusions:Given that inadequate comorbidity risk adjustment can unfairly penalize hospitals and surgeons that care for a disproportionate share of infirm and sick patients, wider adoption of the Elixhauser measure for mortality prediction after proximal humerus fractureand perhaps other musculoskeletal injuriesmerits to be considered.Level of Evidence:Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. C1 [Menendez, Mariano E.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM dring@partners.org NR 53 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD NOV PY 2015 VL 29 IS 11 BP 488 EP 493 DI 10.1097/BOT.0000000000000380 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CU2SZ UT WOS:000363375100002 PM 26165266 ER PT J AU Teunis, T Mulder, F Nota, SP Milne, LW Dyer, GSM Ring, D AF Teunis, Teun Mulder, Frans Nota, Sjoerd P. Milne, Leslie W. Dyer, George S. M. Ring, David TI No Difference in Adverse Events Between Surgically Treated Reduced and Unreduced Distal Radius Fractures SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE adverse events; distal radius; fracture; reduction; unstable ID PLATE FIXATION; COMPLICATIONS AB Objectives:To determine if closed reduction is worthwhile for the subset of patients who choose operative treatment before attempted reduction of their distal radius fracture. We hypothesize that there are no differences in (1) adverse events and (2) subsequent surgeries between patients treated with manipulative reduction compared with those that were splinted without reduction.Design:Retrospective cohort study.Setting:Three affiliated urban hospitals in a single city in the United States.Patients/Participants:One thousand five hundred eleven consecutive adult patients who underwent open reduction and internal fixation of their distal radius fracture between January 1, 2007, and December 31, 2012, of whom 102 (7%) were not reduced before surgery.Intervention:Manipulative reduction compared with splinting without reduction.Main Outcome Measurements:Adverse events were defined as any infections, hematomas treated operatively, disproportionate finger stiffness, (transient) neuropathology after surgery, delayed carpal tunnel release, malunion, reoperation for loss of alignment, hardware removal, and tendon ruptures within 1 year after surgery. Outcome measures were grouped to determine the overall adverse event rate and subsequent surgery rate.Results:We found no difference in specific adverse events between unreduced and reduced fractures. After adjusting for possible confounding variables by logistic regression, we found no difference in overall rates of adverse events (adjusted odds ratio unreduced fractures 1.2, 95% confidence interval 0.67-2.0) and subsequent surgeries (adjusted odds ratio unreduced fractures 0.65, 95% confidence interval 0.23-1.8).Conclusions:Leaving the fracture unreduced before surgery was not associated with increased adverse events or subsequent surgeries. For patients who make an informed decision to undergo operative treatment for their closed neurovascular intact displaced distal radius fracture, manipulative reduction may not be helpful.Level of Evidence:Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. C1 [Teunis, Teun; Mulder, Frans; Nota, Sjoerd P.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Milne, Leslie W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. [Dyer, George S. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu FU Wright Medical (Memphis, TN); Skeletal Dynamics (Miami, FL); Biomet (Warsaw, IN); AO North America (Paoli, PA); AO International (Dubendorf, Switzerland) FX One of the authors (D.R.) certifies that he, or a member of his immediate family, has or may receive payments or benefits during the study period from Wright Medical (USD less than 10,000) (Memphis, TN); Skeletal Dynamics (USD less than 10,000) (Miami, FL); Biomet (USD less than 10,000) (Warsaw, IN); AO North America (USD less than 10,000) (Paoli, PA); and AO International (USD less than 10,000) (Dubendorf, Switzerland). The remaining authors report no conflict of interest. NR 8 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD NOV PY 2015 VL 29 IS 11 BP 521 EP 525 DI 10.1097/BOT.0000000000000379 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA CU2SZ UT WOS:000363375100008 PM 26489056 ER PT J AU Claessen, FMAP Peters, RM Verbeek, DO Helfet, DL Ring, D AF Claessen, Femke M. A. P. Peters, Rinne M. Verbeek, Diederik O. Helfet, David L. Ring, David TI Factors associated with radial nerve palsy after operative treatment of diaphyseal humeral shaft fractures SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Diaphyseal humerus fracture; radial nerve palsy; humerus trauma ID MANAGEMENT; ENTRAPMENT AB Background: The radial nerve is at risk after diaphyseal humeral fracture or surgery to repair the fracture. We hypothesized that there are no factors associated with iatrogenic radial nerve palsy and, secondarily, that there are no factors associated with traumatic radial nerve palsy or radial nerve palsy of any type. Methods: We analyzed 325 adult patients who underwent operative treatment of a diaphyseal humerus fracture at 6 hospitals between January 2002 and November 2014 to determine factors associated with a radial nerve palsy. We excluded patients with pathologic fractures, fractures with massive bone loss, prior surgery in another hospital, periprosthetic fractures, and if no operative note was available. Results: In patients without a traumatic radial nerve palsy, an iatrogenic radial nerve palsy occurred in 18 of 259 diaphyseal humeral fractures (7%). The surgical approach was associated with iatrogenic radial nerve palsy (P = .034). No factors were associated with traumatic radial nerve palsy (66 of 325 patients [20%]) of the humeral diaphysis. Open fractures, location of fracture, and high-energy trauma were significantly associated with radial nerve palsy of any type (84 of 325 patients [26%]). Conclusions: Patients and surgeons should keep in mind that iatrogenic transient dysfunction of the radial nerve will occur in approximately 1 in 5 patients treated with lateral exposure of the humerus, in 1 in 9 patients treated with posterior exposure, and in 1 in 25 patients with an anterolateral exposure. (C) 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Claessen, Femke M. A. P.; Peters, Rinne M.] Massachusetts Gen Hosp, Hand Surg, Boston, MA 02114 USA. [Verbeek, Diederik O.; Helfet, David L.] Hosp Special Surg, Combined Orthopaed Trauma, New York, NY 10021 USA. [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Surg,Yawkey Ctr, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@mgh.harvard.edu OI Ring, David/0000-0002-6506-4879 NR 32 TC 5 Z9 5 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD NOV PY 2015 VL 24 IS 11 BP E307 EP E311 DI 10.1016/j.jse.2015.07.012 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA CU1FE UT WOS:000363264600002 PM 26341025 ER PT J AU Suenaga, M Yamada, S Fuchs, BC Fujii, T Kanda, M Tanaka, C Kobayashi, D Fujiwara, M Tanabe, KK Kodera, Y AF Suenaga, Masaya Yamada, Suguru Fuchs, Bryan C. Fujii, Tsutomu Kanda, Mitsuro Tanaka, Chie Kobayashi, Daisuke Fujiwara, Michitaka Tanabe, Kenneth K. Kodera, Yasuhiro TI CD44 single nucleotide polymorphism and isoform switching may predict gastric cancer recurrence SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE CD44; single nucleotide polymorphism; gastric cancer; isoform switching; disease recurrence ID COLORECTAL-CANCER; PERIPHERAL-BLOOD; CELLS; EXPRESSION; CARCINOMA; MARKER; ADENOCARCINOMA; METAANALYSIS; ASSOCIATION; CONCORDANCE AB Background and ObjectivesThe clinical implications of single nucleotide polymorphisms (SNPs) in CD44 remain unclear. This study examined the relationships of CD44 SNPs with clinicopathological parameters and prognosis in Japanese gastric cancer patients. MethodsThe CD44 SNPs were analyzed in 11 gastric cancer cell lines and 517 clinical specimens. The expression of CD44 standard (CD44s) and CD44 variant 9 isoform (CD44v9) transcripts were measured by quantitative real-time polymerase chain reaction. ResultsThe CD44 rs187116 A/A, A/G, and G/G genotypes were present in 10.3%, 45.1%, and 44.7% of patients, respectively. The presence of CD44 rs187116 A/G or G/G genotypes was significantly associated with positive peritoneal washing cytology (P=0.012). Disease-free survival of patients with these genotypes was significantly worse than in those with the A/A genotype (P=0.039). Multivariate analysis showed that the CD44 rs187116 was independently prognostic of disease-free survival (P=0.047). The CD44s/CD44v9 ratio was significantly lower in patients with the CD44 rs187116 A/A genotype than in those with the A/G (P=0.046) and G/G (P=0.047) genotypes. ConclusionsThe CD44 rs187116 genotype could predict disease recurrence in Japanese gastric cancer patients, and the SNP was associated with CD44 isoform switching. J. Surg. Oncol. 2015;112:622-628. (c) 2015 Wiley Periodicals, Inc. C1 [Suenaga, Masaya; Yamada, Suguru; Fujii, Tsutomu; Kanda, Mitsuro; Tanaka, Chie; Kobayashi, Daisuke; Fujiwara, Michitaka; Kodera, Yasuhiro] Nagoya Univ, Grad Sch Med, Dept Gastroenterol Surg Surg 2, Nagoya, Aichi 4668550, Japan. [Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol,Canc Ctr, Boston, MA USA. RP Yamada, S (reprint author), Nagoya Univ, Grad Sch Med, Dept Gastroenterol Surg Surg 2, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM suguru@med.nagoya-u.ac.jp RI Kodera, Yasuhiro/M-4912-2014; Kobayashi, Daisuke/M-4910-2014; tanaka, chie/M-5052-2014; Fujii, Tsutomu/M-4838-2014; Kanda, Mitsuro/M-4891-2014 NR 42 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV 1 PY 2015 VL 112 IS 6 BP 622 EP 628 DI 10.1002/jso.24056 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA CU5RD UT WOS:000363588800010 PM 26416034 ER PT J AU Stebbins, WG Gusev, J Higgins, HW Nelson, A Govindarajulu, U Neel, V AF Stebbins, William G. Gusev, Julia Higgins, H. William Nelson, Andrew Govindarajulu, Usha Neel, Victor TI Evaluation of patient satisfaction with second intention healing versus primary surgical closure SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID PREDICTORS; SURGERY C1 [Stebbins, William G.] Vanderbilt Univ, Med Ctr, Dept Dermatol, Nashville, TN USA. [Gusev, Julia; Nelson, Andrew; Neel, Victor] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Higgins, H. William] Brown Univ, Dept Dermatol, Providence, RI 02903 USA. [Govindarajulu, Usha] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Higgins, HW (reprint author), Brown Univ, Dept Dermatol, 593 Eddy St,APC 10th Floor, Providence, RI 02903 USA. EM williamhiggins@brown.edu NR 5 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2015 VL 73 IS 5 BP 865 EP 867 DI 10.1016/j.jaad.2015.07.019 PG 4 WC Dermatology SC Dermatology GA CU1HL UT WOS:000363271400031 PM 26475539 ER PT J AU Danesh, MJ Kimball, AB AF Danesh, Melissa J. Kimball, Alexa Boer TI Pyrithione zinc as a general management strategy for hidradenitis suppurativa SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 [Danesh, Melissa J.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Kimball, Alexa Boer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 2 TC 1 Z9 1 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2015 VL 73 IS 5 BP E175 EP E175 DI 10.1016/j.jaad.2015.07.026 PG 1 WC Dermatology SC Dermatology GA CU1HL UT WOS:000363271400006 PM 26475559 ER PT J AU Jemec, GBE Kimball, AB AF Jemec, Gregor B. E. Kimball, Alexa B. TI Hidradenitis suppurativa: Epidemiology and scope of the problem SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE comorbidities; epidemiology; hidradenitis suppurativa ID PATIENT CLAIMS DATA; UNITED-STATES; PREVALENCE; PATTERNS AB Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving painful, deep abscesses and chronic, draining sinus tracts. Because of the variable signs and symptoms displayed by patients, it remains widely unrecognized and difficult to treat, resulting in significant diagnostic delay and inconsistent treatment process. No medical specialty has successfully designated a criterion standard of treatment, resulting in variable care and unmet patient needs. Widespread causes and effects of HS are difficult to determine because the prevalence is dependent on a variety of things, including how and where data are collected, resulting in significant bias. Therefore, the task must be to assess existing studies to produce a best estimate of prevalence. In addition, the 3 types of studies available for HS (ie, self-report, registry-based, and group examination studies) must be evaluated because each offers important insights into who is impacted by this disease. The exact prevalence of HS remains unknown because of the difficulty in collecting and extrapolating data and the usefulness of studies; however, high comorbidity and disease severity is observed, resulting in increased hospital visits for patients with HS-nearly double that of other diseases. Finally, comparisons between HS and psoriasis are worth mentioning because the similarities are clear, but the severity of HS appears to be more debilitating in many aspects of life. This article will address the epidemiology of HS through current available research. C1 [Jemec, Gregor B. E.] Univ Copenhagen, Roskilde Hosp, Dept Dermatol, Roskilde, Denmark. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St, Boston, MA 02114 USA. EM akimball@partners.org OI Jemec, Gregor/0000-0002-0712-2540 FU AbbVie Corporation FX This publication was supported through funding provided by AbbVie Corporation. NR 22 TC 11 Z9 11 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2015 VL 73 IS 5 SU 1 BP S4 EP S7 DI 10.1016/j.jaad.2015.07.052 PG 4 WC Dermatology SC Dermatology GA CU4IE UT WOS:000363490300003 PM 26470614 ER PT J AU Kohorst, JJ Kimball, AB Davis, MDP AF Kohorst, John J. Kimball, Alexa B. Davis, Mark D. P. TI Systemic associations of hidradenitis suppurativa SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE acne inversa; arthritis; depression; disease associations; hidradenitis suppurativa; inflammatory bowel disease; metabolic syndrome; smoking; spondyloarthropathy ID FOLLICULAR OCCLUSION TRIAD; PYODERMA-GANGRENOSUM; ACNE CONGLOBATA; AUTOINFLAMMATORY SYNDROME; METABOLIC SYNDROME; DISEASE SEVERITY; ARTHRITIS; SPONDYLOARTHRITIS; COMORBIDITIES; PREVALENCE AB Hidradenitis suppurativa (HS) is a progressive, inflammatory disease that affects mostly young women and appears to be caused by inflammation of hair follicles in areas of friction in the body (eg, the axillae, groin, perineum, and medial aspects of the thighs). Given this pathophysiology, one might expect comorbidities that contribute to inflammation and friction. Observed comorbidities fall into several categories: obesity and the metabolic syndrome, hormone-related disorders, deleterious health habits and mood, autoimmune disease, inflammatory disease and finally, the risk of skin cancer and sequelae of nonhealing wounds. The available literature on comorbid diseases of HS is limited but rapidly increasing. In this review, we summarize recent and major studies of HS disease association. C1 [Kohorst, John J.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA USA. [Davis, Mark D. P.] Mayo Clin, Dept Dermatol, Rochester, MN 55905 USA. RP Davis, MDP (reprint author), Mayo Clin, Dept Dermatol, 200 First St SW, Rochester, MN 55905 USA. EM davis.mark2@mayo.edu FU AbbVie Corporation FX This publication was supported through funding provided by AbbVie Corporation. NR 53 TC 6 Z9 6 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2015 VL 73 IS 5 SU 1 BP S27 EP S35 DI 10.1016/j.jaad.2015.07.055 PG 9 WC Dermatology SC Dermatology GA CU4IE UT WOS:000363490300008 PM 26470611 ER PT J AU Al-Halabi, H Sayegh, K Digamurthy, SR Niemierko, A Piotrowska, Z Willers, H Sequist, LV AF Al-Halabi, Hani Sayegh, Karl Digamurthy, Subba R. Niemierko, Andrzej Piotrowska, Zofia Willers, Henning Sequist, Lecia V. TI Pattern of Failure Analysis in Metastatic EGFR-Mutant Lung Cancer Treated with Tyrosine Kinase Inhibitors to Identify Candidates for Consolidation Stereotactic Body Radiation Therapy SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Metastatic lung cancer; EGFR mutation; SBRT ID PHASE I/II TRIAL; ACQUIRED-RESISTANCE; OLIGOPROGRESSIVE DISEASE; SOFT-TISSUE; RADIOTHERAPY; GEFITINIB; OLIGOMETASTASES; MUTATIONS; CHEMOTHERAPY; METAANALYSIS AB Introduction: The role of stereotactic body radiation therapy (SBRT) in patients with metastatic lung cancer harboring epidermal growth factor receptor (EGFR) mutations is not defined. We evaluated the pattern of failure in patients receiving tyrosine kinase inhibitor (TKI) therapy to identify candidates for consolidation SBRT. Methods: Computed tomography scans were reviewed in a cohort of EGFR-mutant patients enrolled on prospective TKI trials. Initial progression in sites of original disease (primary/metastatic) or new sites was classified as original site failure (OF) or distant site failure (DF), respectively. Simultaneous OF/DF was labeled ODF. Disease characteristics were analyzed for associations with patterns of failure using actuarial competing risks methodology. Results: Complete serial imaging was available in 49 patients with measurable disease. Median time to any progression was 8.3 months. The majority failed initially in original disease sites with OF, ODF, and DF frequencies being 47.0%, 32.6%, and 20.4%, respectively. Primary tumor size was the most significant predictor of OF in univariate and multivariate analysis (p = 0.004). Median time to progression was 3 months shorter in patients with OF compared with DF. Ten patients (20%) were retroactively classified as consolidation SBRT candidates based on the extent of disease at time of best response to TKI therapy, and in seven of these, initial progression occurred in original tumor sites. Conclusion: Initial progression of TKI-treated cancers occurred predominantly in original disease sites. Consolidation SBRT was judged feasible in a subset of patients following maximum TKI response and may have prevented oligoprogression in most of these. In addition, we hypothesize that consolidation SBRT for residual disease could delay subsequent metastatic reseeding. C1 [Al-Halabi, Hani; Niemierko, Andrzej; Willers, Henning] Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, Boston, MA 02114 USA. [Sayegh, Karl; Digamurthy, Subba R.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Piotrowska, Zofia; Sequist, Lecia V.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA. RP Sequist, LV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA. EM hwillers@mgh.harvard.edu; lvsequist@partners.org FU Canadian Association of Radiation Oncology-Elekta Fellowship Award FX Hani Al-Halabi received salary support from the Canadian Association of Radiation Oncology-Elekta Fellowship Award. NR 40 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2015 VL 10 IS 11 BP 1601 EP 1607 DI 10.1097/JTO.0000000000000648 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CU1WL UT WOS:000363312700012 PM 26313684 ER PT J AU Gao, X Sholl, LM Nishino, M Heng, JC Janne, PA Oxnard, GR AF Gao, Xin Sholl, Lynette M. Nishino, Mizuki Heng, Jennifer C. Jaenne, Pasi A. Oxnard, Geoffrey R. TI Clinical Implications of Variant ALK FISH Rearrangement Patterns SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Anaplastic lymphoma kinase rearrangement; Crizotinib; Non-small-cell lung cancer; Fluorescence in situ hybridization ID ANAPLASTIC LYMPHOMA KINASE; CELL LUNG-CANCER; GENE REARRANGEMENT; EML4-ALK FUSION; EGFR; ADENOCARCINOMAS; CRIZOTINIB; GUIDELINE; FEATURES; THERAPY AB Introduction: Break-apart fluorescence in situ hybridization (FISH) is the FDA-approved assay for detecting anaplastic lymphoma kinase (ALK) rearrangements in non-small-cell lung cancer (NSCLC), identifying patients who can gain dramatic benefit from ALK kinase inhibitors. Assay interpretation can be technically challenging, and either splitting of the 5 and 3 probes or loss of the 5 probe constitute rearrangement. We hypothesized that there may be clinical differences depending on rearrangement pattern on FISH. Methods: An IRB-approved database of NSCLC patients at Dana-Farber Cancer Institute was queried for ALK rearrangement. Clinical characteristics and response to crizotinib were reviewed. Immunohistochemistry (IHC) and targeted next-generation sequencing (NGS) were obtained when available. Results: Of 1614 NSCLC patients with ALK testing, 82 patients (5.1%) had ALK rearrangement by FISH: 30 patients with split signals, 25 patients with 5 deletion, and 27 patients with details unavailable. Patients with 5 deletion were older (p = 0.01) and tended to have more extensive smoking histories (p = 0.08). IHC was positive for ALK rearrangement in all 27 patients with FISH split signals, whereas three of 21 patients with FISH 5 deletion had negative IHC (p = 0.05). Targeted NGS on two of three cases with discordant FISH and IHC results did not identify ALK rearrangement, instead finding driver mutations in EGFR and KRAS. Patients with 5 deletion treated with crizotinib had a smaller magnitude of tumor response (p = 0.03). Conclusions: Patients with 5 deletion on ALK FISH harbor features less typical of ALK-rearranged tumors, potentially indicating that some cases with this variant are false positives. Corroborative testing with IHC or NGS may be beneficial. C1 [Gao, Xin; Sholl, Lynette M.; Nishino, Mizuki; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nishino, Mizuki; Heng, Jennifer C.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Oxnard, GR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Oxnard@dfci.harvard.edu FU Wong Family Fellowship in Translational Oncology; Harold and Gail Kirstein Lung Cancer Research Fund; NCI [1K23CA157631]; Bristol-Myers Squibb; Pfizer; Chugai Pharmaceuticals; AstraZeneca; Sanofi; Clovis; Novartis; Genentech; Boehringer-Ingelheim; [R01CA136851] FX Sources of supported are Wong Family Fellowship in Translational Oncology, Harold and Gail Kirstein Lung Cancer Research Fund, 1K23CA157631 (NCI), and R01CA136851. LMS retains board membership with Genentech. MN receives consulting fees from Bristol-Myers Squibb. PAJ has received consulting fees from Pfizer and Chugai Pharmaceuticals. GRO has received consulting fees from AstraZeneca, Sanofi, Clovis, Novartis, Genentech, Boehringer-Ingelheim and honoraria from Chugai. NR 19 TC 11 Z9 11 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2015 VL 10 IS 11 BP 1648 EP 1652 DI 10.1097/JTO.0000000000000665 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA CU1WL UT WOS:000363312700018 PM 26536196 ER PT J AU Ndhlovu, ZM Stampouloglou, E Cesa, K Mavrothalassitis, O Alvino, DM Li, JZ Wilton, S Karel, D Piechocka-Trocha, A Chen, H Pereyra, F Walker, BD AF Ndhlovu, Zaza M. Stampouloglou, Eleni Cesa, Kevin Mavrothalassitis, Orestes Alvino, Donna Marie Li, Jonathan Z. Wilton, Shannon Karel, Daniel Piechocka-Trocha, Alicja Chen, Huabiao Pereyra, Florencia Walker, Bruce D. TI The Breadth of Expandable Memory CD8(+) T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LONG-TERM SURVIVORS; I DOWN-REGULATION; DISEASE PROGRESSION; REPLICATION CAPACITY; ESCAPE MUTATIONS; LYMPHOCYTE EPITOPES; IMMUNE-RESPONSES; HOMOSEXUAL-MEN; CTL RESPONSE AB Previous studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated the in vivo relevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8(+)T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (P = 0.01) as well as treated progressors (P = 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (P = 0.9 for Nef as determined by a Kruskal-Wallis test; P = 0.6 for Env as determined by a Kruskal-Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (r = -0.6; P = 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8(+)T cell feature that would be desirable in a vaccine-induced T cell response. IMPORTANCE Many studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8(+)T lymphocytes, is at least partially involved in the durable control of HIV replication. HIV controllers maintain a large proportion of Gag-specific expandable memory CD8(+)T cells involved in ongoing viral suppression. These data suggest that induction of this cell subset by future HIV vaccines may be important for narrowing possible routes of rapid escape from vaccine-induced CD8(+)T cell responses. C1 [Ndhlovu, Zaza M.; Stampouloglou, Eleni; Cesa, Kevin; Mavrothalassitis, Orestes; Alvino, Donna Marie; Wilton, Shannon; Karel, Daniel; Piechocka-Trocha, Alicja; Walker, Bruce D.] MIT, Ragon Inst, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Ndhlovu, Zaza M.; Stampouloglou, Eleni; Cesa, Kevin; Mavrothalassitis, Orestes; Alvino, Donna Marie; Wilton, Shannon; Karel, Daniel; Piechocka-Trocha, Alicja; Walker, Bruce D.] Harvard Univ, Cambridge, MA 02138 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Li, Jonathan Z.; Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Ndhlovu, Zaza M.; Walker, Bruce D.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, Durban, South Africa. [Chen, Huabiao] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Charlestown, MA USA. [Chen, Huabiao] Harvard Univ, Sch Med, Charlestown, MA USA. RP Walker, BD (reprint author), MIT, Ragon Inst, Massachusetts Gen Hosp, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM bwalker@mgh.harvard.edu FU International HIV Controllers Study (IHCS); Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation; AIDS Healthcare Foundation; Harvard University Center for AIDS Research (CFAR); NIH-funded program [P30 AI060354]; NIH; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; FIC; OAR; Howard Hughes Medical Institute; Mark and Lisa Schwartz Foundation; Dan and Marjorie Sullivan Foundation FX The International HIV Controllers Study (IHCS) (www.hivcontrollers.org), Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation, and the AIDS Healthcare Foundation funded the cohort. Other funders include the Harvard University Center for AIDS Research (CFAR), an NIH-funded program (P30 AI060354) which is supported by NIH cofunding and participating institutes and centers, including the NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, FIC, and OAR (F.P. and B.D.W); the Howard Hughes Medical Institute (B.D.W.); the Mark and Lisa Schwartz Foundation (B.D.W.); and the Dan and Marjorie Sullivan Foundation (Z.M.N.). NR 76 TC 8 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2015 VL 89 IS 21 BP 10735 EP 10747 DI 10.1128/JVI.01527-15 PG 13 WC Virology SC Virology GA CU3ZP UT WOS:000363465900002 PM 26269189 ER PT J AU Sun, H Kim, D Li, XD Kiselinova, M Ouyang, ZY Vandekerckhove, L Shang, H Rosenberg, ES Yu, XG Lichterfeld, M AF Sun, Hong Kim, Dhohyung Li, Xiaodong Kiselinova, Maja Ouyang, Zhengyu Vandekerckhove, Linos Shang, Hong Rosenberg, Eric S. Yu, Xu G. Lichterfeld, Mathias TI Th1/17 Polarization of CD4 T Cells Supports HIV-1 Persistence during Antiretroviral Therapy SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR GATA-3; TH17 CELLS; ANTIBODY-RESPONSES; GENE-EXPRESSION; INFECTION; RESERVOIR; LATENT; DIFFERENTIATION; IDENTIFICATION AB The ability to persist long term in latently infected CD4 T cells represents a characteristic feature of HIV-1 infection and the predominant barrier to efforts aiming at viral eradication and cure. Yet, increasing evidence suggests that only small subsets of CD4 T cells with specific developmental and maturational profiles are able to effectively support HIV-1 long-term persistence. Here, we analyzed how the functional polarization of CD4 T cells shapes and structures the reservoirs of HIV-1-infected cells. We found that CD4 T cells enriched for a Th1/17 polarization had elevated susceptibilities to HIV-1 infection in ex vivo assays, harbored high levels of HIV-1 DNA in persons treated with antiretroviral therapy, and made a disproportionately increased contribution to the viral reservoir relative to their contribution to the CD4 T memory cell pool. Moreover, HIV-1 DNA levels in Th1/17 cells remained stable over many years of antiretroviral therapy, resulting in a progressively increasing contribution of these cells to the viral reservoir, and phylogenetic studies suggested preferential long-term persistence of identical viral sequences during prolonged antiretroviral treatment in this cell compartment. Together, these data suggest that Th1/17 CD4 T cells represent a preferred site for HIV-1 DNA long-term persistence in patients receiving antiretroviral therapy. IMPORTANCE Current antiretroviral therapy is very effective in suppressing active HIV-1 replication but does not fully eliminate virally infected cells. The ability of HIV-1 to persist long term despite suppressive antiretroviral combination therapy represents a perplexing aspect of HIV-1 disease pathogenesis, since most HIV-1 target cells are activated, short-lived CD4 T cells. This study suggests that CD4 T helper cells with Th1/17 polarization have a preferential role as a long-term reservoir for HIV-1 infection during antiretroviral therapy, possibly because these cells may imitate some of the functional properties traditionally attributed to stem cells, such as the ability to persist for extremely long periods of time and to repopulate their own pool size through homeostatic self-renewal. These observations support the hypothesis that HIV-1 persistence is driven by small subsets of long-lasting stem cell-like CD4 T cells that may represent particularly promising targets for clinical strategies aiming at HIV-1 eradication and cure. C1 [Sun, Hong; Kim, Dhohyung; Li, Xiaodong; Kiselinova, Maja; Ouyang, Zhengyu; Yu, Xu G.; Lichterfeld, Mathias] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Sun, Hong; Shang, Hong] China Med Univ, Affiliated Hosp 1, Key Lab AIDS Immunol, Natl Hlth & Family Planning Commiss, Shenyang, Peoples R China. [Kiselinova, Maja] Univ Ghent, HIV Translat Res Unit, B-9000 Ghent, Belgium. [Kiselinova, Maja] Univ Hosp, Ghent, Belgium. [Rosenberg, Eric S.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Lichterfeld, Mathias] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Lichterfeld, M (reprint author), Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. EM mlichterfeld@partners.org FU U.S. National Institutes of Health [AI116228, AI089339, AI098487, AI106468]; Research Foundation Flanders (FWO) [1.8.020.09.N.00]; Special Research-BOF grant from Ghent University [01 N02712]; FWO Travel Grant for Long Stay Abroad [V427314N]; Ragon Institute of MGH, MIT, and Harvard; NIH [AI074415] FX This work was supported by the U.S. National Institutes of Health (grants AI116228 and AI089339 to X.G.Y. and AI098487 and AI106468 to M.L.). L.V. is supported by the Research Foundation Flanders (FWO; grant 1.8.020.09.N.00). M.K. is supported by a Special Research-BOF grant from Ghent University (grant 01 N02712) and an FWO Travel Grant for Long Stay Abroad (grant V427314N). PBMC sample collection was supported by the Ragon Institute of MGH, MIT, and Harvard and by NIH grant AI074415. NR 46 TC 10 Z9 10 U1 4 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2015 VL 89 IS 22 BP 11284 EP 11293 DI 10.1128/JVI.01595-15 PG 10 WC Virology SC Virology GA CU4AC UT WOS:000363467200011 PM 26339043 ER PT J AU Drain, PK Garrett, NJ AF Drain, Paul K. Garrett, Nigel J. TI The arrival of a true point-of-care molecular assay-ready for global implementation? SO LANCET GLOBAL HEALTH LA English DT Editorial Material C1 [Drain, Paul K.] Univ Washington, Sch Med, Dept Global Hlth, Seattle, WA 98104 USA. [Drain, Paul K.] Univ Washington, Sch Publ Hlth, Dept Global Hlth, Seattle, WA 98104 USA. [Drain, Paul K.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98104 USA. [Drain, Paul K.] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98104 USA. [Drain, Paul K.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Garrett, Nigel J.] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Durban, South Africa. RP Drain, PK (reprint author), Univ Washington, Sch Med, Dept Global Hlth, Seattle, WA 98104 USA. EM pkdrain@uw.edu NR 11 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 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD NOV PY 2015 VL 3 IS 11 BP E663 EP E664 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU1FI UT WOS:000363265000006 PM 26475005 ER PT J AU Bergmark, RW Ishman, SL Scangas, GA Cunningham, MJ Sedaghat, AR AF Bergmark, Regan W. Ishman, Stacey L. Scangas, George A. Cunningham, Michael J. Sedaghat, Ahmad R. TI Socioeconomic determinants of overnight and weekend emergency department use for acute rhinosinusitis SO LARYNGOSCOPE LA English DT Article DE Sinusitis; emergency service; hospital; healthcare disparities; healthcare delivery; insurance; socioeconomic factors ID PRIMARY-CARE; HEALTH-CARE; MEDICAID; ACCESS; DISPARITIES; SINUSITIS; SERVICES; BARRIERS; CHILDREN; QUALITY AB Objectives/Hypothesis Prior work has shown Medicaid and self-pay insurance status is associated with emergency department (ED), rather than outpatient clinic, presentation for uncomplicated acute rhinosinusitis (ARS). We investigate whether the disparate use of ED resources for this nonemergent condition by patients with Medicaid and self-pay insurance can be attributed to presentation overnight or on weekends. Study Design Cross-sectional survey of 990,849 patients from the 2009 and 2010 National Hospital Ambulatory Medical Care Survey presenting to EDs with uncomplicated ARS. Patients with orbital and intracranial complications of ARS were excluded. Methods Univariate and multivariate associations identified demographic and socioeconomic characteristics, including insurance status, which were independently associated with overnight (between 5 pm and 7 am) or daytime weekend ED presentation for uncomplicated ARS. Results Medicaid or self-pay insurance status was associated with evening/overnight ED presentation (odds ratio=1.88, P =.018) in comparison to private or Medicare insurance. However, weekend daytime ED presentation was not associated with Medicaid or self-pay insurance statuses (P=.144). Income and education levels of patients' zip codes, taken as markers of socioeconomic status, were not associated with either evening/overnight or daytime weekend ED presentation for uncomplicated ARS (P>.05). Conclusions ARS patients with Medicaid or self-pay status, previously shown to preferentially use EDs for uncomplicated ARS, were more likely to present for overnight ED care compared to patients with private insurance or Medicare. These findings suggest a potential lack of access to extended-hours primary care during evenings and nights for Medicaid patients. C1 [Bergmark, Regan W.; Scangas, George A.; Sedaghat, Ahmad R.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Bergmark, Regan W.; Scangas, George A.; Cunningham, Michael J.; Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Ishman, Stacey L.] Cincinnati Childrens Hosp Med Ctr, Div Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA. [Ishman, Stacey L.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Med, Cincinnati, OH 45229 USA. [Ishman, Stacey L.] Univ Cincinnati, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Cunningham, Michael J.] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM ahmad_sedaghat@meei.harvard.edu NR 24 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2015 VL 125 IS 11 BP 2441 EP 2446 DI 10.1002/lary.25390 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XO UT WOS:000363387200010 PM 26014375 ER PT J AU Kass, JI Lee, SC Abberbock, S Seethala, RR Duvvuri, U AF Kass, Jason I. Lee, Steve C. Abberbock, Shira Seethala, Raja R. Duvvuri, Umamaheswar TI Adenosquamous carcinoma of the head and neck: Molecular analysis using CRTC-MAML FISH and survival comparison with paired conventional squamous cell carcinoma SO LARYNGOSCOPE LA English DT Article DE Adenosquamous; carcinoma; CRCT-MAML; FISH ID MUCOEPIDERMOID CARCINOMA; TRANSLOCATION; FUSION AB Objectives/HypothesisAdenosquamous carcinoma (ASC) is a rare variant of head-and-neck squamous cell carcinoma (HNSCC) generally thought to be uniformly aggressive with poor prognosis. However, it remains unknown how overall survival compare with conventional HNSCC. Here we report for the first time that ASC does not necessarily indicate a worse prognosis than conventional HNSCC. Study Design Case-control retrospective study. Methods Forty-two primary tumors of the head and neck, treated with curative intent, were identified. Next, 2:1 matching of HNSCC was performed using the following matching criteria: gender, site, pathologic tumor stage, and pathologic node stage. Successful matching was performed for 32 of 42 tumors. Additionally, 20 samples were sent for break-apart FISH testing to evaluate for the presence of the CRTC1-MAML2 translocation. Results There was a 1.8:1 male to female ratio, with a mean age of 62 years (range 38-84). The layrnx was the most common site (26%), followed by oropharynx (24%), oral cavity (19%), and sinonasal (17%). Kaplan-Meier analysis of adenosquamous and matched HNSCC showed similar survival curves. Median survival times for ASC and HNSCC were 4 and 6 years, respectively. A random-effects Cox model with Gamma frailty revealed no statistical difference between the two groups (P=0.25). All cases of ASC were negative for the CRTC1-MAML2 translocation. Conclusion This study directly compares primary ASC with HNSCC. No difference in overall survival was detected in contradistinction to the previously thought uniformly poor prognosis. We also highlight the importance of the CRTC1-MAML2 translocation in distinguishing ASC from mucoepidermoid carcinoma. C1 [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, VA Pittsburgh Hlth Syst, Pittsburgh, PA 15261 USA. [Kass, Jason I.] Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15261 USA. [Seethala, Raja R.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15261 USA. [Abberbock, Shira] Univ Pittsburgh, Inst Canc, Dept Biostat, Pittsburgh, PA 15261 USA. [Lee, Steve C.] Loma Linda Med Ctr, Dept Otolaryngol, Loma Linda, CA USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol, VA Pittsburgh Hlth Syst, Eye & Ear Bldg,Suite 500,200 Lothrop St, Pittsburgh, PA 15261 USA. EM duvvuriu@upmc.edu NR 10 TC 3 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2015 VL 125 IS 11 BP E371 EP E376 DI 10.1002/lary.25519 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA CU2XO UT WOS:000363387200003 PM 26255977 ER PT J AU Patel, D AF Patel, Dhiren TI Pharmacotherapy for the management of obesity SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review DE Obesity; Weight loss; Pharmacotherapy; Obesity management ID CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE; TYPE-2 DIABETES-MELLITUS; NEURONS REGULATE ENERGY; WEIGHT-LOSS; CONTROLLED-TRIAL; OVERWEIGHT ADULTS; ECONOMIC BURDEN; PHASE-3 TRIAL; UNITED-STATES; BODY-WEIGHT AB In the last 30 years, obesity has rapidly increased and obesity-related comorbidities have surged. Once considered to be a problem only in developed nations, obesity has become a global epidemic. Consequently, the costs associated with managing overweight-and obesity worldwide are astronomical. The objective of this mini-review is to provide an overview of current options available for obesity management, with a focus on anti-obesity pharmacotherapies. The impact of weight loss on improving obesity-related comorbidities and risk factors has been well documented. Although established clinical guidelines suggest comprehensive lifestyle modification to induce weight loss, many patients do not respond to lifestyle interventions and may not qualify for bariatric surgery. For these patients, pharmacotherapy may serve as a therapeutic option. Several anti-obesity pharmacotherapies, such as phentermine, are indicated for short-term use and are not required to demonstrate clinically meaningful weight loss (i.e., >5%). For long-term weight management, the FDA has approved 5 agents so far-orlistat, lorcaserin, phentermine/topiramate, naltrexone/bupropion, and liraglutide. These drugs have shown efficacy in enabling patients to achieve clinically meaningful weight loss and improving cardiometabolic parameters. Healthcare practitioners can help alleviate the obesity epidemic by tailoring these pharmacotherapies based on individual needs, comorbidities, and associated drug safety concerns. (C) 2015 Elsevier Inc. All rights reserved. C1 [Patel, Dhiren] MCPHS Univ, Pharm Practice, Boston, MA 02115 USA. [Patel, Dhiren] VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Patel, D (reprint author), MCPHS Univ, Pharm Practice, 179 Longwood Ave, Boston, MA 02115 USA. EM Dhiren.patel1@mcphs.edu FU Imprint Publication Science, New York, NY, USA; Eisai FX Editorial support was provided by Imprint Publication Science, New York, NY, USA, with funding from Eisai. Eisai had no involvement in the development of this manuscript. NR 57 TC 16 Z9 17 U1 4 U2 27 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2015 VL 64 IS 11 BP 1376 EP 1385 DI 10.1016/j.metabol.2015.08.001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CU3PJ UT WOS:000363437000002 PM 26342499 ER PT J AU Vaid, M Singh, T Prasad, R Katiyar, SK AF Vaid, Mudit Singh, Tripti Prasad, Ram Katiyar, Santosh K. TI Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis SO MOLECULAR CARCINOGENESIS LA English DT Article DE apoptosis; silymarin; melanoma; cell proliferation; angiogenesis; tumor xenograft ID MATRIX METALLOPROTEINASES; CUTANEOUS MELANOMA; KINASE INHIBITORS; ANTICANCER DRUGS; BCL-2 FAMILY; SKIN-CANCER; DEATH; PHOTOCARCINOGENESIS; MECHANISMS; EPIDEMIOLOGY AB Cutaneous malignant melanoma is the leading cause of death from skin diseases and is often associated with activating mutations of the proto-oncogene BRAF. To develop more effective strategies for the prevention or treatment of melanoma, we have examined the inhibitory effects of silymarin, a flavanoid from Silybum marianum, on melanoma cells. Using A375 (BRAF-mutated) and Hs294t (non BRAF-mutated but highly metastatic) human melanoma cell lines, we found that in vitro treatment with silymarin resulted in a dose-dependent: (i) reduction in cell viability; (ii) enhancement of either Go/G1 (A375) or G2-M (Hs294t) phase cell cycle arrest with corresponding alterations in cyclins and cyclin-dependent kinases; and (iii) induction of apoptosis. The silymarin-induced apoptosis of human melanoma cells was associated with a reduction in the levels of anti-apoptotic proteins (Bcl-2 and Bcl-xl), an increase in the levels of pro-apoptotic protein (Bax), and activation of caspases. Further, oral administration of silymarin (500mg/kg body weight/2x a week) significantly inhibited (60%, P<0.01) the growth of BRAF-mutated A375 melanoma tumor xenografts, and this was associated with: (i) inhibition of cell proliferation; (ii) induction of apoptosis of tumor cells; (iii) alterations in cell cycle regulatory proteins; and (iv) reduced expression of tumor angiogenic biomarkers in tumor xenograft tissues. These results indicate that silymarin may have a chemotherapeutic effect on human melanoma cell growth and warrant its further evaluation. (c) 2014 Wiley Periodicals, Inc. C1 [Vaid, Mudit; Singh, Tripti; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. FU Veterans Administration Merit Review Award [1I01BX001410] FX Grant sponsor: Veterans Administration Merit Review Award; Grant number: 1I01BX001410 NR 42 TC 2 Z9 3 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 2015 VL 54 IS 11 BP 1328 EP 1339 DI 10.1002/mc.22208 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA CU0PX UT WOS:000363220700009 PM 25174976 ER PT J AU Schmidt, HD McFarland, KN Darnell, SB Huizenga, MN Sangrey, GR Cha, JHJ Pierce, RC Sadri-Vakili, G AF Schmidt, H. D. McFarland, K. N. Darnell, S. B. Huizenga, M. N. Sangrey, G. R. Cha, J-H J. Pierce, R. C. Sadri-Vakili, G. TI ADAR2-dependent GluA2 editing regulates cocaine seeking SO MOLECULAR PSYCHIATRY LA English DT Article ID GLUTAMATE-RECEPTOR SUBUNITS; AMPA RECEPTORS; RELATIVE ABUNDANCE; CA2+ PERMEABILITY; MESSENGER-RNA; BRAIN; GLUR2; ADENOSINE; CHANNELS; NEURONS AB Activation of AMPA receptors (AMPARs) in the nucleus accumbens is necessary for the reinstatement of cocaine-seeking behavior, an animal model of drug craving and relapse. AMPARs are tetrameric protein complexes that consist of GluA1-4 subunits, of which GluA2 imparts calcium permeability. Adenosine deaminase acting on RNA 2 (ADAR2) is a nuclear enzyme that is essential for editing GluA2 pre-mRNA at Q/R site 607. Unedited GluA2(Q) subunits form calcium-permeable AMPARs (CP-AMPARs), whereas edited GluA2(R) subunits form calcium-impermeable channels (CI-AMPARs). Emerging evidence suggests that the reinstatement of cocaine seeking is associated with increased synaptic expression of CP-AMPARs in the nucleus accumbens. However, the role of GluA2 Q/R site editing and ADAR2 in cocaine seeking is unclear. In the present study, we investigated the effects of forced cocaine abstinence on GluA2 Q/R site editing and ADAR2 expression in the nucleus accumbens. Our results demonstrate that 7 days of cocaine abstinence is associated with decreased GluA2 Q/R site editing and reduced ADAR2 expression in the accumbens shell, but not core, of cocaine-experienced rats compared with yoked saline controls. To examine the functional significance of ADAR2 and GluA2 Q/R site editing in cocaine seeking, we used viral-mediated gene delivery to overexpress ADAR2b in the accumbens shell. Increased ADAR2b expression in the shell attenuated cocaine priming-induced reinstatement of drug seeking and was associated with increased GluA2 Q/R site editing and surface expression of GluA2-containing AMPARs. Taken together, these findings support the novel hypothesis that an increased contribution of accumbens shell CP-AMPARs containing unedited GluA2(Q) promotes cocaine seeking. Therefore, CP-AMPARs containing unedited GluA2(Q) represent a novel target for cocaine addiction pharmacotherapies. C1 [Schmidt, H. D.; Pierce, R. C.] Univ Penn, Dept Psychiat, Perelman Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. [McFarland, K. N.] Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA. [Darnell, S. B.; Huizenga, M. N.; Sangrey, G. R.; Sadri-Vakili, G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Cha, J-H J.] Merck, N Wales, PA USA. RP Sadri-Vakili, G (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, MIND Bldg 114,16th St,R2200, Charlestown, MA 02129 USA. EM gsadrivakili@partners.org FU [DA022339]; [DA033641]; [K02 DA18678]; [K01 DA030445] FX We thank Dr Mary O'Connell for her advice and expertise on ADAR2b antibodies. This work was supported by DA022339 (HDS, RCP and GS-V), DA033641 (HDS, RCP and GS-V), K02 DA18678 (RCP) and K01 DA030445 (HDS). NR 30 TC 5 Z9 5 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2015 VL 20 IS 11 BP 1460 EP 1466 DI 10.1038/mp.2014.134 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA CU3ZK UT WOS:000363465300020 PM 25349168 ER PT J AU Geng, J Sun, XF Wang, P Zhang, SH Wang, XZ Wu, HT Hong, LX Xie, CC Li, X Zhao, H Liu, QX Jiang, MT Chen, QH Zhang, JJ Li, Y Song, SY Wang, HR Zhou, RB Johnson, RL Chien, KY Lin, SC Han, JH Avruch, J Chen, LF Zhou, DW AF Geng, Jing Sun, Xiufeng Wang, Ping Zhang, Shihao Wang, Xiaozhen Wu, Hongtan Hong, Lixin Xie, Changchuan Li, Xun Zhao, Hao Liu, Qingxu Jiang, Mingting Chen, Qinghua Zhang, Jinjia Li, Yang Song, Siyang Wang, Hong-Rui Zhou, Rongbin Johnson, Randy L. Chien, Kun-Yi Lin, Sheng-Cai Han, Jiahuai Avruch, Joseph Chen, Lanfen Zhou, Dawang TI Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity SO NATURE IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; HIPPO PATHWAY; SIGNALING PATHWAY; PROTEIN-KINASE; RAC GTPASE; T-CELLS; IMMUNODEFICIENCY; PHOSPHORYLATION; RECOGNITION; ACTIVATION AB Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity. C1 [Geng, Jing; Sun, Xiufeng; Wang, Ping; Zhang, Shihao; Wang, Xiaozhen; Wu, Hongtan; Hong, Lixin; Xie, Changchuan; Zhao, Hao; Liu, Qingxu; Jiang, Mingting; Chen, Qinghua; Zhang, Jinjia; Li, Yang; Song, Siyang; Wang, Hong-Rui; Lin, Sheng-Cai; Han, Jiahuai; Chen, Lanfen; Zhou, Dawang] Xiamen Univ, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Signaling Network, Sch Life Sci, Xiamen, Peoples R China. [Li, Xun] Xiamen Univ, Coll Med, Affiliated Hosp 1, Dept Lab Med, Xiamen, Peoples R China. [Zhou, Rongbin] Univ Sci & Technol China, Inst Immunol, Hefei 230026, Peoples R China. [Zhou, Rongbin] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Innovat Ctr Cell Signaling Network, Sch Life Sci, Hefei 230026, Peoples R China. [Zhou, Rongbin] Univ Sci & Technol China, Med Ctr, Hefei 230026, Peoples R China. [Johnson, Randy L.] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Chien, Kun-Yi] Chang Gung Univ, Coll Med, Kwei Shan, Taiwan. [Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Zhou, DW (reprint author), Xiamen Univ, State Key Lab Cellular Stress Biol, Innovat Ctr Cell Signaling Network, Sch Life Sci, Xiamen, Peoples R China. EM chenlanfen@xmu.edu.cn; dwzhou@xmu.edu.cn RI Chen, Lanfen/B-7975-2016; Han, J/G-4671-2010; OI Chen, Lanfen/0000-0002-9413-1284; Zhou, Dawang/0000-0002-9053-5249 FU National Basic Research Program (973) of China [2015CB910502]; China's 1000 Young Talents Program; 111 Projects [B12001, B06016]; Fundamental Research Funds for the Central Universities of China-Xiamen University [CXB2014004, 20720140551, 2013121034, 20720140537]; National Natural Science Foundation of China [31270918, 81222030, J1310027, 81372617, 81422018, U1405225, 81472229, 81302529]; Natural Science Foundation of Fujian [2013106011, 2014D007]; US National Institutes of Health [RO1 CA136567]; Massachusetts General Hospital FX Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), China's 1000 Young Talents Program (D.Z. and L.C.), the 111 Projects (B12001 and B06016), the Fundamental Research Funds for the Central Universities of China-Xiamen University (CXB2014004 to J.Z.; 20720140551 to L.C.; and 2013121034 and 20720140537 to D.Z.), the National Natural Science Foundation of China (31270918, 81222030 and J1310027 to D.Z.; 81372617, 81422018 and U1405225 to L.C.; 81472229 to L.H.; and 81302529 to XL.), the Natural Science Foundation of Fujian (2013106011 to D.Z. and 2014D007 to X.L.), the US National Institutes of Health (RO1 CA136567 for J.A.) and institutional funds from Massachusetts General Hospital (for J.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 15 Z9 19 U1 6 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2015 VL 16 IS 11 BP 1142 EP 1152 DI 10.1038/ni.3268 PG 11 WC Immunology SC Immunology GA CT8VW UT WOS:000363096000008 PM 26414765 ER PT J AU Pollack, A Kontorovich, AR Fuster, V Dec, GW AF Pollack, Ari Kontorovich, Amy R. Fuster, Valentin Dec, G. William TI Viral myocarditis-diagnosis, treatment options, and current controversies SO NATURE REVIEWS CARDIOLOGY LA English DT Review ID CARDIOVASCULAR MAGNETIC-RESONANCE; VENTRICULAR ENDOMYOCARDIAL BIOPSY; POSITRON-EMISSION-TOMOGRAPHY; PARVOVIRUS B19-ASSOCIATED MYOCARDITIS; AMERICAN-HEART-ASSOCIATION; GIANT-CELL MYOCARDITIS; SUDDEN CARDIAC DEATH; DILATED CARDIOMYOPATHY; IN-VIVO; INFLAMMATORY CARDIOMYOPATHY AB Myocarditis-a frequent cause of dilated cardiomyopathy and sudden cardiac death-typically results from cardiotropic viral infection followed by active inflammatory destruction of the myocardium. Characterization of this disease has been hampered by its heterogeneous clinical presentations and diverse aetiologies. Advances in cardiac MRI and molecular detection of viruses by endomyocardial biopsy have improved our ability to diagnose and understand the pathophysiological mechanisms of this elusive disease. However, therapeutic options are currently limited for both the acute and chronic phases of myocarditis. Several randomized, controlled trials have demonstrated potential benefit with immunosuppressive and immunomodulatory therapies, but further investigations are warranted. In this Review, we explore the pathophysiology, natural history, and modes of diagnosis of myocarditis, as well as evidence-based treatment strategies. As novel imaging techniques and human in vitro models of the disease emerge, the landscape of therapies for myocarditis is poised to improve. C1 [Pollack, Ari; Kontorovich, Amy R.; Fuster, Valentin] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. [Dec, G. William] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pollack, A (reprint author), Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM ari.pollack@mountsinai.org RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 97 TC 20 Z9 21 U1 3 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 EI 1759-5010 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD NOV PY 2015 VL 12 IS 11 BP 670 EP 680 DI 10.1038/nrcardio.2015.108 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU4CN UT WOS:000363474000010 PM 26194549 ER PT J AU Zhao, LZ Arbel-Ornath, M Wang, XY Betensky, RA Greenberg, SM Frosch, MP Bacskai, BJ AF Zhao, Lingzhi Arbel-Ornath, Michal Wang, Xueying Betensky, Rebecca A. Greenberg, Steven M. Frosch, Matthew P. Bacskai, Brian J. TI Matrix metalloproteinase 9-mediated intracerebral hemorrhage induced by cerebral amyloid angiopathy SO NEUROBIOLOGY OF AGING LA English DT Article DE Cerebral amyloid angiopathy (CAA); Matrix metalloproteinase (MMP); Intracerebral hemorrhage; Multiphoton microscopy; Amyloid-beta ID BLOOD-BRAIN-BARRIER; TRANSGENIC MOUSE MODEL; ALZHEIMER-DISEASE; MULTIPHOTON MICROSCOPY; ISCHEMIC-STROKE; IN-VIVO; MATRIX-METALLOPROTEINASE-9; MICE; INHIBITION; LEAKAGE AB Cerebral amyloid angiopathy (CAA), the deposition of amyloid-beta in cerebrovascular walls, is the most common cause of lobar hemorrhagic stroke. Previous studies show that cerebrovascular amyloid-b induces expression and activation of matrix metalloproteinase 9 (MMP-9) in cerebral vessels of amyloid precursor protein transgenic mice. Here, we extended these findings and evaluated MMP-9 expression in postmortem brain tissues of human CAA cases. MMP-9 colocalized with CAA, correlated with the severity of the vascular pathology, and was detected in proximity to microbleeds. We characterized a novel assay using longitudinal multiphoton microscopy and a novel tracer to visualize and quantify the magnitude and kinetics of hemorrhages in three dimensions in living mouse brains. We demonstrated that topical application of recombinant MMP-9 resulted in a time-and dose-dependent cerebral hemorrhage. Amyloid precursor protein mice with significant CAA developed more extensive hemorrhages which also appeared sooner after exposure to MMP-9. Our data suggest an important role for MMP-9 in development of hemorrhages in the setting of CAA. Inhibition of MMP-9 may present a preventive strategy for CAA-associated hemorrhage. (C) 2015 Elsevier Inc. All rights reserved. C1 [Zhao, Lingzhi; Arbel-Ornath, Michal; Wang, Xueying; Greenberg, Steven M.; Frosch, Matthew P.; Bacskai, Brian J.] Massachusetts Gen Hosp, Alzheimer Res Unit, Dept Neurol, Charlestown, MA 02129 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org OI Wang, Xueying/0000-0002-2399-8083 FU NIH [EB00768, S10 RR025645] FX The authors thank Dr Peter Davies (The Feinstein Institute for Medical Research, Manhasset, NY) for providing the PHF1 antibody. Drs Julia Gregory, Ksenia Kastanenka, and Alberto Serrano-Pozo (Massachusetts General Hospital, Boston, MA) for their valuable discussion and suggestions on the project. The authors also acknowledge support from grants NIH EB00768 and S10 RR025645. NR 45 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2015 VL 36 IS 11 BP 2963 EP 2971 DI 10.1016/j.neurobiolaging.2015.07.016 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CU1LA UT WOS:000363281700007 PM 26248866 ER PT J AU Barral, S Vardarajan, BN Reyes-Dumeyer, D Faber, KM Bird, TD Tsuang, D Bennett, DA Rosenberg, R Boeve, BF Graff-Radford, NR Goate, AM Farlow, M Lantigua, R Medrano, MZ Wang, XB Kamboh, MI Barmada, MM Schaid, DJ Foroud, T Weamer, EA Ottman, R Sweet, RA Mayeux, R AF Barral, Sandra Vardarajan, Badri N. Reyes-Dumeyer, Dolly Faber, Kelley M. Bird, Thomas D. Tsuang, Debby Bennett, David A. Rosenberg, Roger Boeve, Bradley F. Graff-Radford, Neill R. Goate, Alison M. Farlow, Martin Lantigua, Rafael Medrano, Martin Z. Wang, Xinbing Kamboh, M. Ilyas Barmada, Mahmud Muhiedine Schaid, Daniel J. Foroud, TatianaM. Weamer, Elise A. Ottman, Ruth Sweet, Robert A. Mayeux, Richard CA NIA-LOAD NCRAD Family Study Grp TI Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families SO NEUROBIOLOGY OF AGING LA English DT Article DE Late-onset Alzheimer's disease; Psychosis; Genome-wide linkage analysis; Association analysis; Non-Hispanic Caucasian and Caribbean; Hispanic ancestry populations ID NEUROPSYCHIATRIC INVENTORY; NATIONAL INSTITUTE; LINKAGE ANALYSIS; HALLUCINATIONS; DEMENTIA; DELUSIONS; SYMPTOMS; BEHAVIOR; HEALTH; RISK AB Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt] logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 x 10(-7)). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (p(meta) = 5.1 x 10(-5)). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (p(meta) = 1.0 x 10(-5)) in a meta-analysis of the CH cohort and an additional non-Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. C1 [Barral, Sandra; Vardarajan, Badri N.; Reyes-Dumeyer, Dolly; Lantigua, Rafael; Mayeux, Richard] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Barral, Sandra; Vardarajan, Badri N.; Reyes-Dumeyer, Dolly; Lantigua, Rafael; Ottman, Ruth; Mayeux, Richard] New York Presbyterian Hosp, New York, NY 10032 USA. [Barral, Sandra; Vardarajan, Badri N.; Reyes-Dumeyer, Dolly; Ottman, Ruth; Mayeux, Richard] Columbia Univ, Med Ctr, GH Sergievsky Ctr, New York, NY 10032 USA. [Barral, Sandra; Vardarajan, Badri N.; Reyes-Dumeyer, Dolly; Ottman, Ruth; Mayeux, Richard] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Faber, Kelley M.; Foroud, TatianaM.] Indiana Univ, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. [Bird, Thomas D.; Tsuang, Debby] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas D.; Tsuang, Debby] Univ Washington, Dept Med, Seattle, WA USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Rosenberg, Roger] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Boeve, Bradley F.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Graff-Radford, Neill R.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Goate, Alison M.] Icanhn Sch Med Mt Sinai, New York, NY USA. [Farlow, Martin] Indiana Univ, Dept Neurol, Ctr Alzheimers Dis & Related Disorders, Indianapolis, IN 46204 USA. [Lantigua, Rafael] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. [Medrano, Martin Z.] Pontificia Univ Catolica Madre & Maestra, Dept Geriatr, Santiago, Dominican Rep. [Wang, Xinbing; Kamboh, M. Ilyas; Barmada, Mahmud Muhiedine] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Wang, Xinbing] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Weamer, Elise A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ottman, Ruth] Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY 10032 USA. [Ottman, Ruth] New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC, Pittsburgh, PA USA. RP Mayeux, R (reprint author), Columbia Univ, Med Ctr, GH Sergievsky Ctr, New York, NY 10032 USA. EM rpm2@cumc.columbia.edu RI Tsuang, Debby/L-7234-2016; Ottman, Ruth/O-2371-2013; OI Tsuang, Debby/0000-0002-4716-1894; Kamboh, M. Ilyas/0000-0002-3453-1438; Barmada, M Michael/0000-0002-3604-6460 FU National Institute on Aging [R01AG041797, U24AG026395, R37AG015473, AG030653, AG0 41718, AG005133, U24AG21886, AG027224] FX Study participants were enrolled under federal grants R01AG041797, U24AG026395, R37AG015473, AG030653, AG0 41718, AG005133, U24AG21886, and AG027224 from the National Institute on Aging. 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 US Government. We would like to acknowledge Dr Andrew P. Morris for his useful contribution, assisting with the analysis, and interpretation of the MANTRA results and Dr. Jurg Ott for his contribution to evaluate linkage heterogeneity. NR 39 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2015 VL 36 IS 11 AR 3116.e9 DI 10.1016/j.neurobiolaging.2015.08.006 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA CU1LA UT WOS:000363281700024 PM 26359528 ER PT J AU Bethoux, F Rogers, HL Nolan, KJ Abrams, GM Annaswamy, T Brandstater, M Browne, B Burnfield, JM Feng, WW Freed, MJ Geis, C Greenberg, J Gudesblatt, M Ikramuddin, F Jayaraman, A Kautz, SA Lutsep, HL Madhavan, S Meilahn, J Pease, WS Rao, N Seetharama, S Sethi, P Turk, MA Wallis, RA Kufta, C AF Bethoux, Francois Rogers, Helen L. Nolan, Karen J. Abrams, Gary M. Annaswamy, Thiru Brandstater, Murray Browne, Barbara Burnfield, Judith M. Feng, Wuwei Freed, Mitchell J. Geis, Carolyn Greenberg, Jason Gudesblatt, Mark Ikramuddin, Farha Jayaraman, Arun Kautz, Steven A. Lutsep, Helmi L. Madhavan, Sangeetha Meilahn, Jill Pease, William S. Rao, Noel Seetharama, Subramani Sethi, Pramod Turk, Margaret A. Wallis, Roi Ann Kufta, Conrad TI Long-Term Follow-up to a Randomized Controlled Trial Comparing Peroneal Nerve Functional Electrical Stimulation to an Ankle Foot Orthosis for Patients With Chronic Stroke SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE functional electrical stimulation; ankle foot orthosis; stroke rehabilitation; gait speed; foot drop; quality of life ID DROPPED FOOT; WALKING PERFORMANCE; HEMIPLEGIC PATIENTS; CHRONIC HEMIPARESIS; GAIT VELOCITY; SPEED; NEUROPROSTHESIS; INDIVIDUALS; BALANCE; RELIABILITY AB Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle foot orthoses (AFO) for treatment of foot drop poststroke, but few long-term, randomized controlled comparisons exist. Objective. Compare changes in gait quality and function between FES and AFOs in individuals with foot drop poststroke over a 12-month period. Methods. Follow-up analysis of an unblinded randomized controlled trial (ClinicalTrials.gov #NCT01087957) conducted at 30 rehabilitation centers comparing FES to AFOs over 6 months. Subjects continued to wear their randomized device for another 6 months to final 12-month assessments. Subjects used study devices for all home and community ambulation. Multiply imputed intention-to-treat analyses were utilized; primary endpoints were tested for noninferiority and secondary endpoints for superiority. Primary endpoints: 10 Meter Walk Test (10MWT) and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test (6MWT), GaitRite Functional Ambulation Profile, and Modified Emory Functional Ambulation Profile (mEFAP). Results. A total of 495 subjects were randomized, and 384 completed the 12-month follow-up. FES proved noninferior to AFOs for all primary endpoints. Both FES and AFO groups showed statistically and clinically significant improvement for 10MWT compared with initial measurement. No statistically significant between-group differences were found for primary or secondary endpoints. The FES group demonstrated statistically significant improvements for 6MWT and mEFAP Stair-time subscore. Conclusions. At 12 months, both FES and AFOs continue to demonstrate equivalent gains in gait speed. Results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings. C1 [Bethoux, Francois] Cleveland Clin, Cleveland, OH 44106 USA. [Rogers, Helen L.; Kufta, Conrad] Innovat Neurotron, Austin, TX USA. [Nolan, Karen J.] Kessler Fdn, W Orange, NJ USA. [Nolan, Karen J.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Abrams, Gary M.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Annaswamy, Thiru] VA North Texas Hlth Care Syst, Dallas, TX USA. [Annaswamy, Thiru] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Brandstater, Murray] Loma Linda Univ, Med Ctr, Loma Linda, CA 92350 USA. [Browne, Barbara] Magee Mem Rehabilitat Ctr, Philadelphia, PA USA. [Burnfield, Judith M.] Madonna Rehabil Hosp, Inst Rehabil Sci & Engn, Lincoln, NE USA. [Feng, Wuwei; Kautz, Steven A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Freed, Mitchell J.] Florida Hosp Neurosci & Orthoped Res Inst, Orlando, FL USA. [Geis, Carolyn] Halifax Hlth Ctr Neurosci, Daytona Beach, FL USA. [Greenberg, Jason] Helen Hayes Hosp, W Haverstraw, NY USA. [Gudesblatt, Mark] South Shore Neurol Associates, Patchogue, NY USA. [Ikramuddin, Farha] Univ Minnesota Fairview, Minneapolis, MN USA. [Jayaraman, Arun] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Madhavan, Sangeetha] Univ Illinois, Chicago, IL USA. [Meilahn, Jill] Marshfield Clin Res Fdn, Marshfield, WI USA. [Pease, William S.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Rao, Noel] Marianjoy Rehabil Hosp, Wheaton, IL USA. [Seetharama, Subramani] Hartford Hosp, Hartford, CT 06115 USA. [Sethi, Pramod] Guilford Neurol Associates, Greensboro, NC USA. [Turk, Margaret A.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Wallis, Roi Ann] West Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Wallis, Roi Ann] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Bethoux, F (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM bethouf@ccf.org OI Nolan, PhD, Karen J/0000-0002-4667-0873 FU Innovative Neurotronics, Inc. FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Innovative Neurotronics, Inc. NR 42 TC 5 Z9 5 U1 6 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD NOV-DEC PY 2015 VL 29 IS 10 BP 911 EP 922 DI 10.1177/1545968315570325 PG 12 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CU2BP UT WOS:000363326800001 PM 25653225 ER PT J AU Rolston, JD Ramos, AD Heath, S Englot, DJ Lim, DA AF Rolston, John D. Ramos, Alexander D. Heath, Susan Englot, Dario J. Lim, Daniel A. TI Thalamotomy-Like Effects From Partial Removal of a Ventral Intermediate Nucleus Deep Brain Stimulator Lead in a Patient With Essential Tremor: Case Report SO NEUROSURGERY LA English DT Article DE Deep brain stimulation; Essential tremor; Thalamotomy; Ventral intermediate nucleus; Zona incerta ID HIGH-FREQUENCY STIMULATION; THALAMIC-STIMULATION; SUBTHALAMIC NUCLEUS; ELECTRICAL-STIMULATION; PARKINSONS-DISEASE; ZONA INCERTA; FOLLOW-UP; COMPLICATIONS; SUPPRESSION; ULTRASOUND AB BACKGROUND AND IMPORTANCE:The ventral intermediate nucleus of the thalamus is a primary target of deep brain stimulation (DBS) in patients with essential tremor. Despite reliable control of contralateral tremor, there is sometimes a need for lead revision in cases of infection, hardware malfunction, or failure to relieve symptoms. Here, we present the case of a patient undergoing revision after ventral intermediate nucleus (Vim) DBS failed to control his tremor. During the electrode removal, the distal portion of the lead was found to be tightly adherent to tissue within the deep brain. Partial removal of the electrode in turn caused weakness, paresthesias, and tremor control similar to the effects produced by thalamotomy or thalamic injury.CLINICAL PRESENTATION:A 48-year-old man with essential tremor had bilateral Vim DBS leads implanted 10 years earlier but had poor control of his tremor and ultimately opted for surgical revision with lead placement in the zona incerta. During attempted removal of his right lead, the patient became somnolent with contralateral weakness and paresthesias. The procedure was aborted, and postoperative neuroimaging was immediately obtained, showing no signs of stroke or hemorrhage. The patient had almost complete control of his left arm tremor postoperatively, and his weakness soon resolved.CONCLUSION:To the best of our knowledge, this is the first reported case of cerebral injury after DBS revision and offers insights into the mechanism of high-frequency electric stimulation compared with lesions. That is, although high-frequency stimulation failed to control this patient's tremor, thalamotomy-like injury was completely effective.ABBREVIATIONS:DBS, deep brain stimulationVim, ventral intermediate nucleusZI, zona incerta C1 [Rolston, John D.; Ramos, Alexander D.; Englot, Dario J.; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Heath, Susan] San Francisco VA Parkinsons Dis Res Educ & Clin C, San Francisco, CA USA. [Lim, Daniel A.] San Francisco VA Med Ctr, Surg Serv, San Francisco, CA USA. RP Lim, DA (reprint author), 35 Med Ctr Way,RMB 1037, San Francisco, CA 94143 USA. EM daniel.lim@ucsf.edu RI Englot, Dario/C-3656-2013 OI Englot, Dario/0000-0001-8373-690X FU California Institute for Regenerative Medicine [CIRM RT2-01975]; Veterans Affairs [1I01 BX000252-04]; Shurl and Kay Curci Foundation; Sontag Foundation FX Research activities of Dr Lim are supported by grants from the California Institute for Regenerative Medicine (CIRM RT2-01975), the Veterans Affairs (1I01 BX000252-04), the Shurl and Kay Curci Foundation, and the Sontag Foundation. Dr Lim is a consultant to Accurexa, Inc. S. Heath is a consultant and educator for Medtronic and has a relative who is employed by Medtronic. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. NR 44 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2015 VL 77 IS 5 BP E831 EP E837 DI 10.1227/NEU.0000000000000906 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA CU1NX UT WOS:000363289700001 PM 26200771 ER PT J AU Muller, RT Abedi, F Cruzat, A Witkin, D Baniasadi, N Cavalcanti, BM Jamali, A Chodosh, J Dana, R Pavan-Langston, D Hamrah, P AF Mueller, Rodrigo T. Abedi, Farshad Cruzat, Andrea Witkin, Deborah Baniasadi, Neda Cavalcanti, Bernardo M. Jamali, Arsia Chodosh, James Dana, Reza Pavan-Langston, Deborah Hamrah, Pedram TI Degeneration and Regeneration of Subbasal Corneal Nerves after Infectious Keratitis A Longitudinal In Vivo Confocal Microscopy Study SO OPHTHALMOLOGY LA English DT Article ID CONTACT-LENS WEAR; OCULAR SURFACE; PENETRATING KERATOPLASTY; NEUROTROPHIC KERATITIS; LONG-TERM; ACANTHAMOEBA; SENSITIVITY; LASIK; INFLAMMATION; TOXICITY AB Purpose: To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during the acute phase, cessation of treatment, and the recovery phase by in vivo confocal microscopy (IVCM). Design: Prospective, longitudinal, case-control, single-center study. Participants: Fifty-six eyes of 56 patients with the diagnosis of bacterial (n = 28), fungal (n = 15), or Acanthamoeba (n = 13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group. Methods: Corneal sensation and serial IVCM of the central cornea were performed prospectively using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany). The IVCM images were assessed at 3 time points: at the acute phase (first visit to the cornea service), at cessation of antimicrobial treatment, and up to 6 months after the resolution of infection. Main Outcome Measures: Total nerve number and length, main nerve trunks, branching, and corneal sensation were assessed during the follow-up period. Results: Corneal nerves were reduced significantly during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47 +/- 0.69 mm/mm(2) versus 20.59 +/- 1.06 mm/mm(2) (P < 0.0001). At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49 +/- 0.94 mm/mm(2); P = 0.02) and nerve branch length (4.80 +/- 0.37 mm/mm(2); P = 0.005). During the recovery phase, after resolution of infection, corneal nerves regenerated further, including total nerve length (12.13 +/- 1.97 mm/mm(2); P = 0.005), main nerve trunk length (5.80 +/- 1.00 mm/mm(2); P = 0.01), and nerve branch length (6.33 +/- 0.76 mm/mm(2); P = 0.003) as compared with the acute phase, but were still significantly lower when compared with controls (P < 0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r = 0.47; P = 0.0009). Conclusions: Patients with IK who sustain profound loss of corneal nerves during the acute phase of infection demonstrate increased corneal nerve density during the first 6 months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not recover fully and remains low compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning. (C) 2015 by the American Academy of Ophthalmology. C1 [Mueller, Rodrigo T.; Abedi, Farshad; Cruzat, Andrea; Witkin, Deborah; Baniasadi, Neda; Cavalcanti, Bernardo M.; Chodosh, James; Dana, Reza; Pavan-Langston, Deborah; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA USA. [Mueller, Rodrigo T.] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. [Hamrah, Pedram] Tufts Univ, Sch Med, New England Eye Ctr, Tufts Med Ctr,Boston Image Reading Ctr, Boston, MA 02111 USA. [Hamrah, Pedram] Tufts Univ, Sch Med, New England Eye Ctr, Tufts Med Ctr,Cornea Serv, Boston, MA 02111 USA. RP Hamrah, P (reprint author), Tufts Univ, Sch Med, Boston Image Reading Ctr, Cornea Serv,New England Eye Ctr,Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. EM phamrah@tuftsmedicalcenter.org FU National Institutes of Health, Bethesda, Maryland [K08-EY020575]; Career Development Award from Research to Prevent Blindness, Inc., New York, New York; Senior Scientific Investigator Award from Research to Prevent Blindness (New York, NY); Falk Medical Research Trust (Chicago, IL); MEEI Foundation (Boston, MA) FX Supported by the National Institutes of Health, Bethesda, Maryland (grant no.: K08-EY020575 [P.H.]); a Career Development Award from Research to Prevent Blindness, Inc., New York, New York (P.H.); a Senior Scientific Investigator Award from Research to Prevent Blindness (New York, NY) (J.C.); the Falk Medical Research Trust (Chicago, IL) (P.H., J.C.); and the MEEI Foundation (Boston, MA) (P.H.). The funding organizations had no role in the design or conduct of this research. NR 52 TC 6 Z9 7 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2015 VL 122 IS 11 BP 2200 EP 2209 DI 10.1016/j.ophtha.2015.06.047 PG 10 WC Ophthalmology SC Ophthalmology GA CU4IQ UT WOS:000363491800021 PM 26256833 ER PT J AU Yuan, AN Kurtz, SL Barysauskas, CM Pilotte, AP Wagner, AJ Treister, NS AF Yuan, Anna Kurtz, Sharyn L. Barysauskas, Constance M. Pilotte, Amy P. Wagner, Andrew J. Treister, Nathaniel S. TI Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors SO ORAL ONCOLOGY LA English DT Article DE Oral adverse events; Oral toxicities; Oral dysesthesia; Tyrosine kinase inhibitors; Targeted cancer therapy; Stomatitis; Mucositis; Oral complications; Sunitinib; Sutent ID RENAL-CELL CARCINOMA; GASTROINTESTINAL STROMAL TUMORS; SUNITINIB; TRIAL; SORAFENIB; SAFETY; MANAGEMENT; TOXICITIES; EFFICACY AB Objectives: This study characterized the incidence and clinical features of oral adverse events among cancer patients who received VEGFR-directed multitargeted tyrosine kinase inhibitor (VR-TKI) therapies. Methods: Electronic medical records of adult cancer patients treated with sunitinib, sorafenib, regorafenib, pazopanib, cabozantinib, imatinib, and bevacizumab therapy at Dana-Farber Cancer Institute from 2009 to 2012 were reviewed. Data collected included patient characteristics, oral and non-oral adverse events, and time to onset. Time oral adverse event-free was the primary outcome. Results: A total of 747 patients with 806 individual courses of therapy were treated for a median of 3.9 months with sunitinib (n = 161), sorafenib (n = 172), regorafenib (n = 15), pazopanib (n = 132), cabozantinib (n = 23), imatinib (n = 144), or bevacizumab (n = 159) for lung cancer (21%), gastrointestinal stromal tumor (15%), and metastatic renal cell carcinoma (13%). An oral adverse event was reported in 23.7% of patients at a median of 1.9 months after starting therapy. The most commonly reported oral adverse event was oral mucosal sensitivity (dysesthesia), occurring in 12% of patients, typically without clinical findings. Multivariate models showed patients who received VR-TKI therapy were at greater risk of any oral adverse event compared with patients treated with imatinib or bevacizumab. Patients receiving VR-TKI therapy who developed an oral adverse event were also at increased risk for hand-foot skin reaction (15.9%). Conclusions: VR-TKI associated oral adverse events are characterized primarily by dysesthesia with lack of clinical signs. Oral dysesthesia is more commonly associated with VR-TKIs than with bevacizumab or imatinib. Management is largely empirical and requires further investigation. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Yuan, Anna; Treister, Nathaniel S.] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Yuan, Anna; Treister, Nathaniel S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Kurtz, Sharyn L.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. [Barysauskas, Constance M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Pilotte, Amy P.] Rhode Isl Hosp, Ctr Comprehens Canc, Dept Med Oncol, Greenwich, RI 02818 USA. [Wagner, Andrew J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Wagner, Andrew J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Yuan, AN (reprint author), Brigham & Womens Hosp, Div Oral Med, 75 Francis St, Boston, MA 02115 USA. EM annayuan@post.harvard.edu NR 26 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD NOV PY 2015 VL 51 IS 11 BP 1026 EP 1033 DI 10.1016/j.oraloncology.2015.09.003 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA CU4GG UT WOS:000363484800015 PM 26403941 ER PT J AU Al Tamimi, AS Zaheer, S Ng, DC Osmany, S AF Al Tamimi, Ammad Shanoon Zaheer, Sumbul Ng, David Chee Osmany, Saabry TI The incidence and sites of Nasopharyngeal carcinoma (NPC) metastases on FDG PET/CT scans SO ORAL ONCOLOGY LA English DT Article DE Nasopharyngeal carcinoma; FDG PET/CT; Distant metastases; Diaphragm ID POSITRON-EMISSION-TOMOGRAPHY; F-18-FDG PET AB Introduction: The only investigation to determine if a whole body FDG PET/CT scan is helpful in the evaluation of NPC is a study from Stanford. In this study, 26 patients with whole body PET/CT, were evaluated for lesions below adrenals and showed that 7.7% of distant metastases were below adrenals. Our study comparing distant metastases below diaphragm with Stanford study to evaluate the need for whole body PET/CT. Material and methods: Reports of NPC patients in Singapore General Hospital were reviewed. The lesions were analyzed for total number and number below diaphragm. The lesions below the diaphragm were further analyzed if they were solitary or involved multiple areas and if any additional lesions were above diaphragm. Results: 717 reports were included in final analysis. The number of FDG avid lesions in these reports was 709. Distant metastases represented 352 of the 709 lesions. The number of lesions below diaphragm was 152, of the lesions below diaphragm only 16 of lesions have no co-existing distant metastases above diaphragm. From these lesions, there were only 12 solitary lesions. The other 4 has concurrent metastases but all localized below diaphragm. Conclusion: Compared to Stanford study, number of reports is more representative in this study and the yield is much lower (7.7% versus 2.26%). From the results of our study we can consider limiting the scan area from vertex to below diaphragm. However, the symptoms and clinical presentation of the patient will further direct the requesting physician in the area to be imaged. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Al Tamimi, Ammad Shanoon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Nucl Med & Mol Imaging Div, Boston, MA 02114 USA. [Zaheer, Sumbul; Ng, David Chee] Singapore Gen Hosp, Dept Nucl Med & PET, Singapore, Singapore. [Osmany, Saabry] RadLink Diagnost Imaging, Singapore, Singapore. RP Al Tamimi, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Nucl Med & Mol Imaging Div, 55 Fruit St,White 427, Boston, MA 02114 USA. EM he77@hotmail.com OI Al Tamimi, Ammad/0000-0001-9030-7345 NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD NOV PY 2015 VL 51 IS 11 BP 1047 EP 1050 DI 10.1016/j.oraloncology.2015.08.001 PG 4 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA CU4GG UT WOS:000363484800018 PM 26315255 ER PT J AU Malla, SR Qin, Y Mareninova, OA Elperin, JM Lotshaw, EM Ohmuraya, M French, SW Gukovskaya, AS Gukovsky, I AF Malla, S. R. Qin, Y. Mareninova, O. A. Elperin, J. M. Lotshaw, E. M. Ohmuraya, M. French, S. W. Gukovskaya, A. S. Gukovsky, I. TI Atg5 Deficiency Worsens Cerulein Pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 [Malla, S. R.; Qin, Y.; Mareninova, O. A.; Elperin, J. M.; Lotshaw, E. M.; Gukovskaya, A. S.; Gukovsky, I.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Malla, S. R.; Qin, Y.; Mareninova, O. A.; Elperin, J. M.; Lotshaw, E. M.; Gukovskaya, A. S.; Gukovsky, I.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ohmuraya, M.] Kumamoto Univ, Kumamoto 860, Japan. [French, S. W.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2015 VL 44 IS 8 BP 1395 EP 1395 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU2AQ UT WOS:000363324000181 ER PT J AU Morales-Oyarvide, V Mino-Kenudson, M Ferrone, CR Warshaw, AL Lillemoe, KD Fernandez-del Castillo, C AF Morales-Oyarvide, V. Mino-Kenudson, M. Ferrone, C. R. Warshaw, A. L. Lillemoe, K. D. Fernandez-del Castillo, C. TI Recent-Onset Diabetes in IPMN: An Independent Predictor of Invasive Carcinoma and Intestinal-Type Histology SO PANCREAS LA English DT Meeting Abstract C1 [Morales-Oyarvide, V.; Ferrone, C. R.; Warshaw, A. L.; Lillemoe, K. D.; Fernandez-del Castillo, C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mino-Kenudson, M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2015 VL 44 IS 8 BP 1399 EP 1400 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU2AQ UT WOS:000363324000199 ER PT J AU Vegh, ET Lotshaw, EM Shalbueva, N Mareninova, OA Elperin, JM French, SW Hegyi, P Rakonczay, Z Gukovsky, I Gukovskaya, AS AF Vegh, E. T. Lotshaw, E. M. Shalbueva, N. Mareninova, O. A. Elperin, J. M. French, S. W. Hegyi, P. Rakonczay, Z. Gukovsky, I. Gukovskaya, A. S. TI Defective Lysosomal Hydrolase Trafficking Causes Spontaneous Pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 [Vegh, E. T.; Lotshaw, E. M.; Shalbueva, N.; Mareninova, O. A.; Elperin, J. M.; Gukovsky, I.; Gukovskaya, A. S.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Vegh, E. T.; Lotshaw, E. M.; Shalbueva, N.; Mareninova, O. A.; Elperin, J. M.; Gukovsky, I.; Gukovskaya, A. S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Vegh, E. T.; Hegyi, P.; Rakonczay, Z.] Univ Szeged, Dept Med 1, Szeged, Hungary. [French, S. W.] Harbor UCLA Med Ctr, Torrance, CA 90509 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 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2015 VL 44 IS 8 BP 1422 EP 1422 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU2AQ UT WOS:000363324000291 ER PT J AU Wang, RX Chu, CY Nissen, NN Lewis, MS Palanisamy, N Edderkaoui, M Annamalai, A Lewis, S Zhau, HE Pandol, SJ Chung, LWK AF Wang, R. X. Chu, C. Y. Nissen, N. N. Lewis, M. S. Palanisamy, N. Edderkaoui, M. Annamalai, A. Lewis, S. Zhau, H. E. Pandol, S. J. Chung, L. W. K. TI Novel Patient-Derived CTC-Xenograft Models for the Study of Pancreatic Cancer Biology, Metastasis and Therapy SO PANCREAS LA English DT Meeting Abstract C1 [Wang, R. X.; Chu, C. Y.; Nissen, N. N.; Edderkaoui, M.; Annamalai, A.; Lewis, S.; Zhau, H. E.; Pandol, S. J.; Chung, L. W. K.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Lewis, M. S.; Pandol, S. J.] VA Greater Los Angeles Hlth Syst, Los Angeles, CA USA. [Palanisamy, N.] Henry Ford Hlth Syst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2015 VL 44 IS 8 BP 1423 EP 1423 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU2AQ UT WOS:000363324000296 ER PT J AU Zanconato, A Zheng, H Ferrone, CR Dias-Santos, D Lillemoe, KD Fernandez-del Castillo, C AF Zanconato, A. Zheng, H. Ferrone, C. R. Dias-Santos, D. Lillemoe, K. D. Fernandez-del Castillo, C. TI Factors Associated With Early Disease-Related Mortality Following Contemporary Resection for Pancreatic Adenocarnicoma SO PANCREAS LA English DT Meeting Abstract C1 [Zanconato, A.; Zheng, H.; Ferrone, C. R.; Dias-Santos, D.; Lillemoe, K. D.; Fernandez-del Castillo, C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD NOV PY 2015 VL 44 IS 8 BP 1428 EP 1429 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CU2AQ UT WOS:000363324000317 ER PT J AU Roh, MR Eliades, P Gupta, S Tsao, H AF Roh, Mi Ryung Eliades, Philip Gupta, Sameer Tsao, Hensin TI Genetics of melanocytic nevi SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE congenital melanocytic nevi; acquired melanocytic nevi; Spitz nevi; blue nevi; genetics ID STEM-CELL FACTOR; ORAL TRANEXAMIC ACID; ESTROGEN-RECEPTOR; POSTINFLAMMATORY HYPERPIGMENTATION; STIMULATING HORMONE; GROWTH-FACTOR; MELANOCORTIN-1 RECEPTOR; INCREASED EXPRESSION; MELASMA LESIONS; DOWN-REGULATION AB Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial 'driver' mutations are thought to trigger the establishment of benign nevi. After this initial phase of the cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene-induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy. C1 [Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer; Tsao, Hensin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02115 USA. [Roh, Mi Ryung] Yonsei Univ, Coll Med, Cutaneous Biol Res Inst, Dept Dermatol, Seoul 120749, South Korea. [Eliades, Philip] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Tsao, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02115 USA. EM htsao@partners.org FU NIH [K24 CA149202]; National Research Foundation of Korea - Ministry of Education, Science, and Technology [2011-0022376]; Melanoma Research Foundation FX This scholarly work was made possible by a grant from the NIH (K24 CA149202 to HT), a grant from the Basic Science Research Program through the National Research Foundation of Korea, which is funded by the Ministry of Education, Science, and Technology (2011-0022376 to MRR), a Melanoma Research Foundation Student Grant (to SG), and the generous donors to the MGH on behalf of melanoma research. We also would like to apologize to the numerous other authors whose contributions we could not cite in this short review because of space considerations. NR 123 TC 13 Z9 13 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 EI 1755-148X J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD NOV PY 2015 VL 28 IS 6 BP 661 EP 672 DI 10.1111/pcmr.12412 PG 12 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA CU3DL UT WOS:000363404000007 PM 26300491 ER PT J AU Clark, KB AF Clark, Kevin B. TI Insight and analysis problem solving in microbes to machines SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Cognition; Decision making; Emergent computation; Heuristics; Information processing; Intelligence; Natural computing ID ANIMAL COGNITION; AMEBOID ORGANISM; QUANTUM-THEORY; INTELLIGENCE; COMPLEX; CONSCIOUSNESS; PERFORMANCE; COMPUTATION; HEURISTICS; NETWORKS AB A key feature for obtaining solutions to difficult problems, insight is oftentimes vaguely regarded as a special discontinuous intellectual process and/or a cognitive restructuring of problem representation or goal approach. However, this nearly century-old state of art devised by the Gestalt tradition to explain the non-analytical or non-trial-and-error, goal-seeking aptitude of primate mentality tends to neglect problem-solving capabilities of lower animal phyla, Kingdoms other than Animalia, and advancing smart computational technologies built from biological, artificial, and composite media. Attempting to provide an inclusive, precise definition of insight, two major criteria of insight, discontinuous processing and problem restructuring, are here reframed using terminology and statistical mechanical properties of computational complexity classes. Discontinuous processing becomes abrupt state transitions in algorithmic/heuristic outcomes or in types of algorithms/heuristics executed by agents using classical and/or quantum computational models. And problem restructuring becomes combinatorial reorganization of resources, problem-type substitution, and/or exchange of computational models. With insight bounded by computational complexity, humans, ciliated protozoa, and complex technological networks, for example, show insight when restructuring time requirements, combinatorial complexity, and problem type to solve polynomial and nondeterministic polynomial decision problems. Similar effects are expected from other problem types, supporting the idea that insight might be an epiphenomenon of analytical problem solving and consequently a larger information processing framework. Thus, this computational complexity definition of insight improves the power, external and internal validity, and reliability of operational parameters with which to classify, investigate, and produce the phenomenon for computational agents ranging from microbes to man-made devices. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Clark, Kevin B.] Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. [Clark, Kevin B.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA. [Clark, Kevin B.] Univ Illinois, Natl Ctr Supercomp Applicat, Extreme Sci & Engn Discovery Environm XSEDE, Urbana, IL 61801 USA. [Clark, Kevin B.] Univ Illinois, Beckman Inst Adv Sci & Technol, NIH Ctr Macromol Modeling & Bioinformat, Theoret & Computat Biophys Grp,BioCoRE, Urbana, IL 61801 USA. RP Clark, KB (reprint author), 4229 SE Harney St, Portland, OR 97206 USA. EM kbclarkphd@yahoo.com NR 88 TC 0 Z9 0 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD NOV PY 2015 VL 119 IS 2 BP 183 EP 193 DI 10.1016/j.pbiomolbio.2015.08.018 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA CU2KR UT WOS:000363352900007 PM 26278642 ER PT J AU Markt, SC Shui, IM Unger, RH Urun, Y Berg, CD Black, A Brennan, P Bueno-De-Mesquita, HB Gapstur, SM Giovannucci, E Haiman, C Henderson, B Hoover, RN Hunter, DJ Key, TJ Khaw, KT Canzian, F Larranga, N Le Marchand, L Ma, J Naccarati, A Siddiq, A Stampfer, MJ Stattin, P Stevens, VL Stram, DO Tjonneland, A Travis, RC Trichopoulos, D Ziegler, RG Lindstrom, S Kraft, P Mucci, LA Choueiri, TK Wilson, KM AF Markt, Sarah C. Shui, Irene M. Unger, Robert H. Urun, Yuksel Berg, Christine D. Black, Amanda Brennan, Paul Bueno-de-Mesquita, H. Bas Gapstur, Susan M. Giovannucci, Edward Haiman, Christopher Henderson, Brian Hoover, Robert N. Hunter, David J. Key, Timothy J. Khaw, Kay-Tee Canzian, Federico Larranga, Nerea Le Marchand, Loic Ma, Jing Naccarati, Alessio Siddiq, Afshan Stampfer, Meir J. Stattin, Par Stevens, Victoria L. Stram, Daniel O. Tjonneland, Anne Travis, Ruth C. Trichopoulos, Dimitrios Ziegler, Regina G. Lindstrom, Sara Kraft, Peter Mucci, Lorelei A. Choueiri, Toni K. Wilson, Kathryn M. TI ABO Blood Group Alleles and Prostate Cancer Risk: Results from the Breast and Prostate Cancer Cohort Consortium (BPC3) SO PROSTATE LA English DT Article DE ABO; blood type; prostate cancer; genetic epidemiology ID ASSOCIATION AB BACKGROUND. ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. METHODS. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score >= 8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). RESULTS. We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95% CI = 0.87-1.08; Type B: OR = 0.92, 95% CI = n0.77-1.09; Type AB: OR = 1.25, 95% CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. CONCLUSIONS. ABO blood type was not associated with risk of aggressive prostate cancer. Prostate 75: 1677-1681, 2015. (C) 2015 Wiley Periodicals, Inc. C1 [Markt, Sarah C.; Shui, Irene M.; Unger, Robert H.; Giovannucci, Edward; Hunter, David J.; Ma, Jing; Stampfer, Meir J.; Trichopoulos, Dimitrios; Lindstrom, Sara; Kraft, Peter; Mucci, Lorelei A.; Wilson, Kathryn M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Shui, Irene M.; Hunter, David J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Urun, Yuksel] Ankara Univ, Fac Med, Dept Med Oncol, TR-06100 Ankara, Turkey. [Berg, Christine D.] Johns Hopkins Med, Dept Radiat Oncol, Baltimore, MD USA. [Black, Amanda] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Brennan, Paul; Hoover, Robert N.; Ziegler, Regina G.] Int Agcy Res Canc, F-69372 Lyon, France. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol, Utrecht, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Hepatol, Utrecht, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol, London, England. [Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Dept Biostat, London, England. [Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Prevent Med, Kuala Lumpur, Malaysia. [Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Giovannucci, Edward; Stevens, Victoria L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Haiman, Christopher; Henderson, Brian; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hunter, David J.; Lindstrom, Sara; Kraft, Peter] Harvard Univ, TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA. [Key, Timothy J.; Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England. [Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Sch Clin Med, Cambridge, England. [Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Larranga, Nerea] BIODonostia Res Inst, Basque Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain. [Larranga, Nerea] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA. [Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA USA. [Naccarati, Alessio] HuGeF Fdn, Mol & Genet Epidemiol Unit, Turin, Italy. [Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England. [Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90187 Umea, Sweden. [Tjonneland, Anne] Danish Canc Soc Res Ctr, Copenhagen, Denmark. [Trichopoulos, Dimitrios] Acad Athens, Bureau Epidemiol Res, Athens, Greece. [Trichopoulos, Dimitrios] Hellenic Hlth Fdn, Athens, Greece. [Choueiri, Toni K.] Dana Farber Canc Inst, Dept Genitourinary Oncol, Boston, MA 02115 USA. RP Markt, SC (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave Room 920A, Boston, MA 02115 USA. EM sec110@mail.harvard.edu FU US National Institutes of Health, National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758, R01 CA63464, P01 CA33619, R37 CA54281, UM1 CA164973]; Intramural Research Program of the Division of Cancer Epidemiology and Cancer Prevention (PLCO); Intramural Research Program of the Division of Cancer Epidemiology and Cancer Prevention (ATBC); Division of Cancer Epidemiology and Genetics; Danish Cancer (Danish study Diet, Cancer and Health); Cancer Research EPIC study of vitamin D and prostate cancer and the EPIC-UK cohorts; Medical Research Council (EPIC study of vitamin D and prostate cancer and the EPIC-UK cohorts); (EPIC-Greece) Foundation; Health Research Fund (EPIC-Spain); Regional Government of Andalucia [6236]; Regional Government of Asturias [6236]; Regional Government of Basque Country [6236]; Regional Government of Murcia [6236]; Navarra (EPIC-Spain); ISCIII (EPIC-Spain) [RD06/0020]; Sicilian government, Aire-Onlus Ragusa (Italy)(EPIC-Italy); European Commission (MORGEN-EPIC); International Agency for Research on (MORGEN-EPIC); Dutch Ministry of Public (MORGEN-EPIC); Welfare and Sports (MORGEN-EPIC); Statistics (MORGEN-EPIC); National Cancer Institute at the National Institutes of Health Training Grant; U.S. Army Department of Defense Prostate Cancer Post-doctoral Fellowship; Prostate Cancer Foundation Young Investigators FX Grant sponsor: US National Institutes of Health, National Cancer Institute; Grant numbers: U01-CA98233 (PHS, HPFS); U01-CA98710 (CPS2); U01-CA98216 (EPIC); U01-CA98758; R01 CA63464; P01 CA33619; R37 CA54281; UM1 CA164973 (MEC); Grant sponsor: Intramural Research Program of the Division of Cancer Epidemiology and Cancer Prevention (PLCO and ATBC); Grant sponsor: Division of Cancer Epidemiology and Genetics; Grant sponsor: Danish Cancer (Danish study Diet, Cancer and Health); Grant sponsor: Cancer Research EPIC study of vitamin D and prostate cancer and the EPIC-UK cohorts; Grant sponsor: Medical Research Council (EPIC study of vitamin D and prostate cancer and the EPIC-UK cohorts); Grant sponsor: (EPIC-Greece) Foundation; Grant sponsor: Health Research Fund (EPIC-Spain); Grant sponsor: Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra (EPIC-Spain); Grant sponsor: ISCIII (EPIC-Spain); Grant number: RD06/0020; Grant sponsor: Sicilian government, Aire-Onlus Ragusa (Italy)(EPIC-Italy); Grant sponsor: European Commission (MORGEN-EPIC); Grant sponsor: International Agency for Research on (MORGEN-EPIC); Grant sponsor: Dutch Ministry of Public (MORGEN-EPIC); Grant sponsor: Welfare and Sports (MORGEN-EPIC); Grant sponsor: Statistics (MORGEN-EPIC); Grant sponsor: National Cancer Institute at the National Institutes of Health Training Grant; Grant number: (to SCM); Grant sponsor: U.S. Army Department of Defense Prostate Cancer Post-doctoral Fellowship; Grant number: (to IMS); Grant sponsor: Prostate Cancer Foundation Young Investigators; Grant number: (to LAM and KMW). NR 8 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD NOV 1 PY 2015 VL 75 IS 15 BP 1677 EP 1681 DI 10.1002/pros.23035 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA CU0PJ UT WOS:000363219200001 PM 26268879 ER PT J AU Winters, B Plymate, S Zeliadt, SB Holt, S Zhang, XT Hu, E Lin, DW Morrissey, C Wooldridge, B Gore, JL Porter, MP Wright, JL AF Winters, Brian Plymate, Stephen Zeliadt, Steven B. Holt, Sarah Zhang, Xiaotun Hu, Elaine Lin, Daniel W. Morrissey, Colm Wooldridge, Bryan Gore, John L. Porter, Michael P. Wright, Jonathan L. TI Metformin Effects on Biochemical Recurrence and Metabolic Signaling in the Prostate SO PROSTATE LA English DT Article DE prostate cancer; metformin; AMPK; insulin signaling; veterans affairs ID ACTIVATED PROTEIN-KINASE; CANCER-SPECIFIC MORTALITY; BREAST-CANCER; RADICAL PROSTATECTOMY; DIABETIC-PATIENTS; LUNG-CANCER; RISK; INSULIN; MEN; SURVIVAL AB BACKGROUND. Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). METHODS. Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. RESULTS. One thousand seven hundred and thirty four men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa. CONCLUSION. Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. Prostate 75: 1694-1703, 2015. (C) 2015 Wiley Periodicals, Inc. C1 [Winters, Brian; Holt, Sarah; Zhang, Xiaotun; Lin, Daniel W.; Morrissey, Colm; Wooldridge, Bryan; Gore, John L.; Porter, Michael P.; Wright, Jonathan L.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. [Plymate, Stephen] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Plymate, Stephen; Zeliadt, Steven B.; Hu, Elaine] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Plymate, Stephen; Zeliadt, Steven B.; Hu, Elaine] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Zeliadt, Steven B.; Lin, Daniel W.; Wright, Jonathan L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Winters, B (reprint author), Univ Washington, Sch Med, Dept Urol, 1959 NE Pacific,Box 356510, Seattle, WA 98195 USA. EM wintersb@uw.edu FU National Cancer Institute [P50CA097186]; Fred Hutchinson Cancer Research Center FX Grant sponsor: National Cancer Institute; Grant number: P50CA097186; Grant sponsor: Fred Hutchinson Cancer Research Center. NR 45 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD NOV 1 PY 2015 VL 75 IS 15 BP 1694 EP 1703 DI 10.1002/pros.23049 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA CU0PJ UT WOS:000363219200003 PM 26201966 ER PT J AU Gold, M El Khoury, J AF Gold, Maike El Khoury, Joseph TI beta-amyloid, microglia, and the inflammasome in Alzheimer's disease SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Microglia; Macrophage; NLRP3 inflammasome; beta-amyloid; Alzheimer's disease ID CENTRAL-NERVOUS-SYSTEM; APPSW TRANSGENIC MICE; NLRP3 INFLAMMASOME; PROINFLAMMATORY CYTOKINE; STERILE INFLAMMATION; CASPASE-1 ACTIVATION; NALP3 INFLAMMASOME; P2X(7) RECEPTOR; SENILE DEMENTIA; HOST-DEFENSE AB There is extensive evidence that accumulation of mononuclear phagocytes including microglial cells, monocytes, and macrophages at sites of beta-amyloid (A beta) deposition in the brain is an important pathological feature of Alzheimer's disease (AD) and related animal models, and the concentration of these cells clustered around A beta deposits is several folds higher than in neighboring areas of the brain [1-5]. Microglial cells phagocytose and clear debris, pathogens, and toxins, but they can also be activated to produce inflammatory cytokines, chemokines, and neurotoxins [6]. Over the past decade, the roles of microglial cells in AD have begun to be clarified, and we proposed that these cells play a dichotomous role in the pathogenesis of AD [4, 6-11]. Microglial cells are able to clear soluble and fibrillar A beta, but continued interactions of these cells with A beta can lead to an inflammatory response resulting in neurotoxicity. Inflammasomes are inducible high molecular weight protein complexes that are involved in many inflammatory pathological processes. Recently, A beta was found to activate the NLRP3 inflammasome in microglial cells in vitro and in vivo thereby defining a novel pathway that could lead to progression of AD [12-14]. In this manuscript, we review possible steps leading to A beta-induced inflammasome activation and discuss how this could contribute to the pathogenesis of AD. C1 [Gold, Maike; El Khoury, Joseph] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP El Khoury, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. EM jelkhoury@mgh.harvard.edu FU Max Kade Foundation; NIH [NS059005, AG032349, AI082660] FX Maike Gold is a postdoctoral Research Fellow of the Max Kade Foundation. Part of the work described here was supported by NIH grants NIH grants NS059005, AG032349, and AI082660 to Joseph El Khoury. NR 61 TC 12 Z9 13 U1 6 U2 42 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 EI 1863-2300 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD NOV PY 2015 VL 37 IS 6 BP 607 EP 611 DI 10.1007/s00281-015-0518-0 PG 5 WC Immunology; Pathology SC Immunology; Pathology GA CU1HO UT WOS:000363271700004 PM 26251237 ER PT J AU Winkelman, JW Blackwell, T Stone, K Ancoli-Israel, S Tranah, GJ Redline, S AF Winkelman, John W. Blackwell, Terri Stone, Katie Ancoli-Israel, Sonia Tranah, Gregory J. Redline, Susan CA Osteoporotic Fractures Men MrOS TI Genetic associations of periodic limb movements of sleep in the elderly for the MrOS sleep study SO SLEEP MEDICINE LA English DT Article DE Periodic limb movements of sleep; Single-nucleotide polymorphism; Restless legs syndrome; BTBD9; MEIS1 ID RESTLESS LEGS SYNDROME; OSTEOPOROTIC FRACTURES; MOTOR RESTLESSNESS; RISK-FACTOR; OLDER MEN; VARIANTS; BTBD9; MEIS1; MAP2K5/SKOR1; VARIABILITY AB Objective: The objective of this study was to assess the relationship between single-nucleotide polymorphisms associated with restless legs syndrome and periodic limb movements of sleep in a population cohort of elderly individuals. Methods: Single-nucleotide polymorphisms previously associated with periodic limb movements of sleep or restless legs syndrome were analyzed in 2356 white male participants in the Osteoporotic Fractures in Men Sleep Study cohort. The associations between single-nucleotide polymorphisms and polysomnographically measured periodic limb movement index >= 15 were examined with logistic regression adjusted for age, ancestry markers, and periodic limb movements of sleep risk factors. Results: Of the men in this cohort, 61% had a periodic limb movement index >= 15. Significant associations were observed between a periodic limb movement index >= 15 and the number of risk alleles for the two BTBD9 single-nucleotide polymorphisms (rs9357271[T], odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.20-1.58; and rs3923809[A], OR = 1.43, 95% CI 1.26-1.63), one of the MEIS1 single-nucleotide polymorphisms (rs2300478[G], OR = 1.31, 95% CI 1.14-1.51) and the mitogen-activated protein kinase kinase 5 (MAP2K5)/Ski family transcriptional corepressor 1 (SKOR1) single-nucleotide polymorphism (rs1026732[G], OR = 1.16, 95% CI 1.02-1.31). In a multivariable model controlling for each of the two MEIS1 single-nucleotide polymorphisms, the rs6710341[A] single-nucleotide polymorphism became a significant risk allele (OR = 1.59, 95% CI 1.26-2.00). Conclusions: Our findings confirm an association between the BTBD9, MEIS1, and MAP2K5/SKOR1 singlenucleotide polymorphisms and periodic limb movements of sleep in an elderly cohort not selected for the presence of restless legs syndrome. (C) 2015 Elsevier B.V. All rights reserved. C1 [Winkelman, John W.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Winkelman, John W.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Blackwell, Terri; Stone, Katie; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 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. [Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Redline, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA. EM JWWINKELMAN@partners.org FU National Institutes of Health; National Institute on Aging (NIA); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Advancing Translational Sciences (NCATS); NIH Roadmap for Medical Research [U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128]; National Heart, Lung, and Blood Institute (NHLBI) [R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, R01 HL070839]; NIA [1R01AG030474] FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the grant numbers U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. The National Heart, Lung, and Blood Institute (NHLBI) provides funding for the MrOS Sleep ancillary study "Outcomes of Sleep Disorders in Older Men" under the following grant numbers: R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. Genetics data were funded by grant 1R01AG030474 from the NIA. NR 31 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD NOV PY 2015 VL 16 IS 11 BP 1360 EP 1365 DI 10.1016/j.sleep.2015.07.017 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CU4CL UT WOS:000363473700009 PM 26498236 ER PT J AU Fuchs, HF Broderick, RC Harnsberger, CR Chang, DC Mclemore, EC Ramamoorthy, S Horgan, S AF Fuchs, Hans F. Broderick, Ryan C. Harnsberger, Cristina R. Chang, David C. Mclemore, Elisabeth C. Ramamoorthy, Sonia Horgan, Santiago TI Variation of outcome and charges in operative management for diverticulitis SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Diverticulitis; Colorectal surgery; Laparoscopic; Outcomes research; Quality control; Bowel ID UNITED-STATES; SURGICAL-PROCEDURES; COLORECTAL-CANCER; DISEASE; SURGERY; OVERUSE; PATTERNS; UNDERUSE; QUALITY AB Outcomes after surgery for diverticulitis are of continued interest to improve quality of care. The aim of this study was to assess variations in mortality, length of stay, and patient charges between geographic regions of the United States. A retrospective analysis of the Nationwide Inpatient Sample database was performed. Adults with diverticulitis who underwent laparoscopic or open segmental colectomy were identified using ICD-9 codes. Subset analyses were performed by state and then compared. Outcomes included mortality, length of stay (LOS), and total charges. Results were adjusted for age, race, gender, findings of peritonitis, stoma placement, Charlson comorbidity index, and insurance status on multivariate analysis. 148,874 patients underwent segmental colectomy for diverticulitis from 1998 to 2010. Using California as the comparison state and after adjusting for covariates, in-hospital mortality was significantly higher in the State of New York (OR 1.32; 95 % CI 1.13-1.55; P < 0.05) and Mississippi (OR 2.84; 95 % CI 1.24-6.51, P < 0.02). Wisconsin had a significant lower mortality rate (OR 0.74; 95 % CI 0.59-0.94, P < 0.01). LOS was 1.4 days longer in New York and 0.54 days shorter in Wisconsin than in California (P < 0.01). Patients with age > 40 years, findings of peritonitis, and without private insurance had higher in-hospital mortality and longer length of stay. Average hospital charges differed dramatically between the states in the observation period. The highest hospital charges occurred in California, Nebraska, and Nevada while lowest occurred in Maryland, Wisconsin and Utah. Patients who undergo surgical treatment for diverticulitis in the United States have high geographic variation in mortality, LOS, and hospital charges despite adjusting for demographic and socioeconomic factors. Further analysis should be performed to identify the causes of outlier regions, with the goal of improving and standardizing best practices. C1 [Fuchs, Hans F.; Broderick, Ryan C.; Harnsberger, Cristina R.; Chang, David C.; Mclemore, Elisabeth C.; Ramamoorthy, Sonia; Horgan, Santiago] Univ Calif San Diego, Dept Surg, Ctr Future Surg, Div Minimally Invas Surg, La Jolla, CA 92093 USA. [Fuchs, Hans F.] Univ Cologne, Dept Gen Surg, D-50931 Cologne, Germany. [Chang, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Fuchs, HF (reprint author), Univ Calif San Diego, Dept Surg, Ctr Future Surg, Div Minimally Invas Surg, 9500 Gilman Dr,MC 0740, La Jolla, CA 92093 USA. EM hfuchs@ucsd.edu NR 31 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD NOV PY 2015 VL 29 IS 11 BP 3090 EP 3096 DI 10.1007/s00464-014-4046-0 PG 7 WC Surgery SC Surgery GA CT8JC UT WOS:000363060700007 PM 25539698 ER PT J AU Hashimoto, DA Sirimanna, P Gomez, ED Beyer-Berjot, L Ericsson, KA Williams, NN Darzi, A Aggarwal, R AF Hashimoto, Daniel A. Sirimanna, Pramudith Gomez, Ernest D. Beyer-Berjot, Laura Ericsson, K. A. Williams, Noel N. Darzi, Ara Aggarwal, Rajesh TI Deliberate practice enhances quality of laparoscopic surgical performance in a randomized controlled trial: from arrested development to expert performance SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Education; Imaging & VR; Cholecystectomy ID REALITY TRAINING CURRICULUM; TECHNICAL SKILLS; ADVERSE EVENTS; SURGERY; ACQUISITION; SIMULATION; EDUCATION; COLORADO; UTAH AB This study investigated whether deliberate practice leads to an increase in surgical quality in virtual reality (VR) laparoscopic cholecystectomies (LC). Previous research has suggested that sustained DP is effective in surgical training. Fourteen residents were randomized into deliberate practice (n = 7) or control training (n = 7). Both groups performed ten sessions of two VR LCs. Each session, the DP group was assigned 30 min of DP activities in between LCs while the control group viewed educational videos or read journal articles. Performance was assessed on speed and dexterity; quality was rated with global (GRS) and procedure-specific (PSRS) rating scales. All participants then performed five porcine LCs. Both groups improved over 20 VR LCs in time, dexterity, and global rating scales (all p < 0.05). After 20 LCs, there were no differences in speed or dexterity between groups. The DP group achieved higher quality of VR surgical performance than control for GRS (26 vs. 20, p = 0.001) and PSRS (18 vs. 15, p = 0.001). For VR cases, DP subjects plateaued at GRS = 25 after ten cases and control group at GRS = 20 after five cases. At completion of VR training, 100 % of the DP group reached target quality of performance (GRS a parts per thousand yen 21) compared with 30 % in the control group. There were no significant differences for improvements in time or dexterity over five porcine LCs. This study suggests that DP leads to higher quality performance in VR LC than standard training alone. Standard training may leave individuals in a state of "arrested development" compared with DP. C1 [Hashimoto, Daniel A.; Sirimanna, Pramudith; Beyer-Berjot, Laura; Darzi, Ara] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Biosurg & Surg Technol, London, England. [Hashimoto, Daniel A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Gomez, Ernest D.; Williams, Noel N.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ericsson, K. A.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. [Aggarwal, Rajesh] McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada. [Aggarwal, Rajesh] McGill Univ, Fac Med, Arnold & Blema Steinberg Med Simulat Ctr, Montreal, PQ H2X 3P9, Canada. RP Aggarwal, R (reprint author), McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada. EM dahashimoto@partners.org; rajesh.aggarwal@mcgill.ca FU National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health [TL1TR000138] FX The authors would like to thank Steve Marchington and Kenneth Miller for their administrative and logistical support in arranging materials for use in this study. We thank Dr. Steve Siegel for his assistance with the manuscript and Dr. Andrew Cucchiara for his biostatistical support. The authors are grateful to Drs. Emma Meagher and Karen Kerr for administrative support and assistance in facilitating institutional collaboration. Daniel Hashimoto and Ernest Gomez were partly supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant TL1TR000138. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 27 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD NOV PY 2015 VL 29 IS 11 BP 3154 EP 3162 DI 10.1007/s00464-014-4042-4 PG 9 WC Surgery SC Surgery GA CT8JC UT WOS:000363060700016 PM 25539697 ER PT J AU Shin, JU Lee, WJ Tran, TN Jung, I Lee, JH AF Shin, Jung U. Lee, Won Jai Thanh-Nga Tran Jung, Inhee Lee, Ju Hee TI Hsp70 Knockdown by siRNA Decreased Collagen Production in Keloid Fibroblasts SO YONSEI MEDICAL JOURNAL LA English DT Article DE Heat shock proteins; keloids; Hsp70 ID MATRIX METALLOPROTEINASE-2 MMP-2; PROCOLLAGEN MESSENGER-RNAS; INDUCED GASTRIC-LESIONS; HEAT-SHOCK RESPONSE; HYPERTROPHIC SCAR; GENE-EXPRESSION; PROTECTIVE ROLE; ACTIVATION; DISEASE; CELLS AB Purpose: There are currently no consistently effective treatments for the excessive collagen produced by keloid fibroblasts. Previously, we reported that heat shock protein 70 (Hsp70) is up-regulated in keloid fibroblasts and keloid tissue. We, therefore, investigated whether Hsp70 is related to excessive collagen production in keloid fibroblasts. Materials and Methods: We inhibited Hsp70 in keloid fibroblasts by RNA interference and examined the resulting collagen expression. Thus, we selected small interfering RNAs (siRNAs) specific for human Hsp70, transfected them into keloid fibroblasts, and evaluated the resulting phenotypes and protein production using real-time polymerase chain reaction (PCR), Western blot, and a collagen assay. Results: The siRNAs dramatically suppressed Hsp70 mRNA expression, resulting in a decrease in collagen production in the keloid fibroblasts compared with controls. The siRNAs did not influence the viability of the keloid fibroblasts. Conclusion: Hsp70 overexpression likely plays an important role in the excessive collagen production by keloid fibroblasts. RNA interference has therapeutic potential for the treatment of keloids. C1 [Shin, Jung U.; Jung, Inhee; Lee, Ju Hee] Yonsei Univ, Coll Med, Dept Dermatol, Severance Hosp,Cutaneous Biol Res Inst, Seoul 03722, South Korea. [Lee, Won Jai] Yonsei Univ, Coll Med, Dept Plast & Reconstruct Surg, Severance Hosp,Inst Human Tissue Restorat, Seoul 03722, South Korea. [Thanh-Nga Tran] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Thanh-Nga Tran] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. RP Lee, JH (reprint author), Yonsei Univ, Coll Med, Dept Dermatol, Severance Hosp,Cutaneous Biol Res Inst, 50-1 Yonsei Ro, Seoul 03722, South Korea. EM juhee@yuhs.ac FU National Research Foundation of Korea (NRF) - Ministry of Science, ICT and future Planning [NRF-2010-0010475]; Yonsei University College of Medicine [6-2010-0057] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (NRF-2010-0010475). This study was also supported by a faculty research grant of Yonsei University College of Medicine (6-2010-0057). NR 44 TC 2 Z9 2 U1 0 U2 2 PU YONSEI UNIV COLL MEDICINE PI SEOUL PA 50-1 YONSEI-RO, SEODAEMUN-GU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 EI 1976-2437 J9 YONSEI MED J JI Yonsei Med. J. PD NOV 1 PY 2015 VL 56 IS 6 BP 1619 EP 1626 DI 10.3349/ymj.2015.56.6.1619 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CU4JN UT WOS:000363494600021 PM 26446645 ER PT J AU Bejjani, C Snow, AL Judge, KS Bass, DM Morgan, RO Wilson, N Walder, A Looman, WJ McCarthy, C Kunik, ME AF Bejjani, Carla Snow, A. Lynn Judge, Katherine S. Bass, David M. Morgan, Robert O. Wilson, Nancy Walder, Annette Looman, Wendy J. McCarthy, Catherine Kunik, Mark E. TI Characteristics of Depressed Caregivers of Veterans With Dementia SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE caregiver; depression; veterans; dementia; elders ID ALZHEIMER-DISEASE PATIENTS; FAMILY CAREGIVERS; INFORMAL CAREGIVERS; SELF-EFFICACY; MENTAL-HEALTH; SYMPTOMS; CARE; PREVALENCE; STRESS; COMMUNITY AB This study examined the characteristics of caregivers and persons with dementia (PWD) to determine their association with caregiver depression. Participants included 508 PWD (veterans) and 486 caregivers from Boston, Houston, Providence, Beaumont (Texas), and Oklahoma City, identified from diagnoses from medical records and recruited from February 2007 to July 2009, for a larger study evaluating Partners in Dementia Care, a care-coordination intervention. Characteristics evaluated for PWD included activities of daily living, instrumental activities of daily living, cognitive impairment, and disruptive behavior. Caregiver characteristics evaluated included caregiver unmet needs, support-service use, and number of informal helpers. Caregiver depression was measured using the Iowa form 11-item Center for Epidemiologic Studies Depression Scale. Depressed caregivers reported significantly more unmet needs than the nondepressed caregivers. Depressed caregivers also reported a high frequency of disruptive behavior in their PWD. Caregiver perceptions of unmet needs may be an important target for intervention. C1 [Bejjani, Carla; Wilson, Nancy; Walder, Annette; Kunik, Mark E.] Michael E DeBakey VA Med Ctr 152, VA HSR&D Houston Ctr Excellence, Houston, TX 77030 USA. [Bejjani, Carla] Baylor Coll Med, Houston, TX 77030 USA. [Snow, A. Lynn] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. [Snow, A. Lynn] Tuscaloosa VA Med Ctr, Res & Dev Serv, Tuscaloosa, AL USA. [Judge, Katherine S.] Cleveland State Univ, Dept Psychol, Cleveland, OH 44115 USA. [Judge, Katherine S.; Bass, David M.; McCarthy, Catherine; Kunik, Mark E.] Benjamin Rose Inst Aging, Margaret Blenkner Res Inst, Cleveland, OH USA. [Morgan, Robert O.] Univ Texas Houston, Sch Publ Hlth, Dept Management Policy & Community Hlth, Houston, TX USA. [Wilson, Nancy] Baylor Coll Med, Dept Internal Med, Sect Geriatr, Houston, TX 77030 USA. [Walder, Annette] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Kunik, Mark E.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Kunik, Mark E.] Educ & Clin Ctr, VA South Cent Mental Illness Res, Houston, TX USA. RP Kunik, ME (reprint author), Michael E DeBakey VA Med Ctr 152, VA HSR&D Houston Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mkunik@bcm.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Washington, D.C. [IIR 04-238-3]; Alzheimer's Association [IIRG-08-89058]; Robert Wood Johnson Foundation [57816]; VA HSR&D Houston Center of Excellence [HFP90-020]; Michael E. DeBakey VA Medical Center, Houston, TX FX The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Grant No. IIR 04-238-3 from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Washington, D.C.; Grant No. IIRG-08-89058 from the Alzheimer's Association; and Grant #57816 from the Robert Wood Johnson Foundation. It was also supported in part by the resources and facilities of the VA HSR&D Houston Center of Excellence (HFP90-020), Michael E. DeBakey VA Medical Center, Houston, TX. NR 52 TC 0 Z9 0 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 EI 1938-2731 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD NOV PY 2015 VL 30 IS 7 BP 672 EP 678 DI 10.1177/1533317512461555 PG 7 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA CT7KZ UT WOS:000362994900003 PM 23070578 ER PT J AU Cohen, BE Edmondson, D Kronish, IM AF Cohen, Beth E. Edmondson, Donald Kronish, Ian M. TI State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Review DE anxiety disorders; blood pressure; cardiovascular disease; coronary heart disease; depression; hypertension; PTSD; stress ID CORONARY-HEART-DISEASE; RANDOMIZED-CONTROLLED-TRIAL; INDUCED MYOCARDIAL-ISCHEMIA; COMORBIDITY SURVEY REPLICATION; LONG-TERM OUTCOMES; FOLLOW-UP; SECONDARY PREVENTION; COLLABORATIVE CARE; BLOOD-PRESSURE; RISK-FACTOR AB The notion that psychological states can influence physical health is hardly new, and perhaps nowhere has the mind-body connection been better studied than in cardiovascular disease (CVD). Recently, large prospective epidemiologic studies and smaller basic science studies have firmly established a connection between CVD and several psychological conditions, including depression, chronic psychological stress, posttraumatic stress disorder (PTSD), and anxiety. In addition, numerous clinical trials have been conducted to attempt to prevent or lessen the impact of these conditions on cardiovascular health. In this article, we review studies connecting depression, stress/PTSD, and anxiety to CVD, focusing on findings from the last 5 years. For each mental health condition, we first examine the epidemiologic evidence establishing a link with CVD. We then describe studies of potential underlying mechanisms and finally discuss treatment trials and directions for future research. C1 [Cohen, Beth E.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Cohen, Beth E.] San Francisco VA Med Ctr, Gen Internal Med, San Francisco, CA USA. [Edmondson, Donald; Kronish, Ian M.] Columbia Univ, Dept Med, Med Ctr, Ctr Behav Cardiovasc Hlth, New York, NY USA. RP Cohen, BE (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM beth.cohen@ucsf.edu RI Edmondson, Donald/G-7486-2016 FU National Heart, Lung, and Blood Institute (NHLBI) [K23 HL 094765]; American Heart Association; NHLBI [K23 HL098359, R01 HL117832]; National Center for Advancing Translational Sciences [UL1 TR000040] FX Dr B.E.C. received support from the National Heart, Lung, and Blood Institute (NHLBI) (K23 HL 094765) and the American Heart Association. Dr I.M.K. received support from the NHLBI (K23 HL098359) and from the National Center for Advancing Translational Sciences (UL1 TR000040), and Dr D.E. received support from the NHLBI (R01 HL117832). The funding sources did not have any role in the preparation of the manuscript. NR 89 TC 18 Z9 19 U1 12 U2 58 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 2015 VL 28 IS 11 BP 1295 EP 1302 DI 10.1093/ajh/hpv047 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CT5HV UT WOS:000362840500001 PM 25911639 ER PT J AU Baggett, TP Chang, YC Porneala, BC Bharel, M Singer, DE Rigotti, NA AF Baggett, Travis P. Chang, Yuchiao Porneala, Bianca C. Bharel, Monica Singer, Daniel E. Rigotti, Nancy A. TI Disparities in Cancer Incidence, Stage, and Mortality at Boston Health Care for the Homeless Program SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID FORCE RECOMMENDATION STATEMENT; C VIRUS-INFECTION; SUBSTANCE USE DISORDERS; SHELTER-BASED CLINICS; HEPATITIS-C; LOS-ANGELES; DEATH CERTIFICATES; SINGLE HOMELESS; URBAN HOMELESS; MENTAL-HEALTH AB Introduction: Homeless people have a high burden of cancer risk factors and suboptimal rates of cancer screening, but the epidemiology of cancer has not been well described in this population. We assessed cancer incidence, stage, and mortality in homeless adults relative to general population standards. Methods: We cross-linked a cohort of 28,033 adults seen at Boston Health Care for the Homeless Program in 2003-2008 to Massachusetts cancer registry and vital registry records. We calculated age-standardized cancer incidence and mortality ratios (SIRs and SMRs). We examined tobacco use among incident cases and estimated smoking-attributable fractions. Trend tests were used to compare cancer stage distributions with those in Massachusetts adults. Analyses were conducted in 2012-2015. Results: During 90,450 person-years of observation, there were 361 incident cancers (SIR=1.13, 95% CI=1.02, 1.25) and 168 cancer deaths (SMR=1.88, 95% CI=1.61, 2.19) among men, and 98 incident cancers (SIR=0.93, 95% CI=0.76, 1.14) and 38 cancer deaths (SMR=1.61, 95% CI=1.14, 2.20) among women. For both sexes, bronchus and lung cancer was the leading type of incident cancer and cancer death, exceeding Massachusetts estimates more than twofold. Oropharyngeal and liver cancer cases and deaths occurred in excess among men, whereas cervical cancer cases and deaths occurred in excess among women. About one third of incident cancers were smoking-attributable. Colorectal, female breast, and oropharyngeal cancers were diagnosed at more-advanced stages than in Massachusetts adults. Conclusions: Efforts to reduce cancer disparities in homeless people should include addressing tobacco use and enhancing participation in evidence-based screening. (C) 2015 American Journal of Preventive Medicine C1 [Baggett, Travis P.; Chang, Yuchiao; Porneala, Bianca C.; Singer, Daniel E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Baggett, Travis P.; Chang, Yuchiao; Bharel, Monica; Singer, Daniel E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA. [Bharel, Monica] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Bharel, Monica] Massachusetts Dept Publ Hlth, Boston, MA USA. RP Baggett, TP (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM tbaggett@mgh.harvard.edu FU National Institute on Drug Abuse at the NIH [K23DA034008]; American Cancer Society [122269-IRG-12-070-01-IRG] FX This study was supported by award K23DA034008 to Dr. Baggett from the National Institute on Drug Abuse at the NIH and by award 122269-IRG-12-070-01-IRG to Dr. Baggett from the American Cancer Society. The sponsors had no role in any aspect of this study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or American Cancer Society. At the time of the study, Dr. Bharel was also affiliated with the Boston Health Care for the Homeless Program and Division of General Internal Medicine, Massachusetts General Hospital. NR 60 TC 1 Z9 1 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2015 VL 49 IS 5 BP 694 EP 702 DI 10.1016/j.amepre.2015.03.038 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA CT7MK UT WOS:000362998600005 PM 26143955 ER PT J AU Ramos-Kuri, M Rapti, K Mehel, H Zhang, SH Dhandapany, PS Liang, LF Garcia-Carranca, A Bobe, R Fischmeister, R Adnot, S Lebeche, D Hajjar, RJ Lipskaia, L Chemaly, ER AF Ramos-Kuri, Manuel Rapti, Kleopatra Mehel, Hind Zhang, Shihong Dhandapany, Perundurai S. Liang, Lifan Garcia-Carranca, Alejandro Bobe, Regis Fischmeister, Rodolphe Adnot, Serge Lebeche, Djamel Hajjar, Roger J. Lipskaia, Larissa Chemaly, Elie R. TI Dominant negative Ras attenuates pathological ventricular remodeling in pressure overload cardiac hypertrophy SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Heart failure; Cardiac hypertrophy; Ras oncogene; Pathological hypertrophy; Physiological hypertrophy; Ras inhibition ID PROTEIN-KINASE-C; MYOCARDIAL HYPERTROPHY; GENE-TRANSFER; DEPENDENT PATHWAYS; BINDING PROTEINS; ANGIOTENSIN-II; RAF-1 KINASE; IN-VIVO; MYOCYTES; ACTIVATION AB The importance of the oncogene Ras in cardiac hypertrophy is well appreciated. The hypertrophic effects of the constitutively active mutant Ras-Val12 are revealed by clinical syndromes due to the Ras mutations and experimental studies. We examined the possible anti-hypertrophic effect of Ras inhibition in vitro using rat neonatal cardiomyocytes (NRCM) and in vivo in the setting of pressure-overload left ventricular (LV) hypertrophy (POH) in rats. Ras functions were modulated via adenovirus directed gene transfer of active mutant Ras-Val12 or dominant negative mutant N17-DN-Ras (DN-Ras). Ras-Val12 expression in vitro activates NFAT resulting in pro-hypertrophic and cardio-toxic effects on NRCM beating and Z-line organization. In contrast, the DN-Ras was antihypertrophic on NRCM, inhibited NFAT and exerted cardio-protective effects attested by preserved NRCM beating and Z line structure. Additional experiments with silencing H-Ras gene strategy corroborated the antihypertrophic effects of siRNA-H-Ras on NRCM. In vivo, with the POH model, both Ras mutants were associated with similar hypertrophy two weeks after simultaneous induction of POH and Ras-mutant gene transfer. However, LV diameters were higher and LV fractional shortening lower in the Ras-Val12 group compared to control and DN-Ras. Moreover, DN-Ras reduced the cross-sectional area of cardiomyocytes in vivo, and decreased the expression of markers of pathologic cardiac hypertrophy. In isolated adult cardiomyocytes after 2 weeks of POH and Ras-mutant gene transfer, DN-Ras improved sarcomere shortening and calcium transients compared to Ras-Val12. Overall, DN-Ras promotes a more physiological form of hypertrophy, suggesting an interesting therapeutic target for pathological cardiac hypertrophy. (C) 2015 Elsevier B.V. All rights reserved. C1 [Ramos-Kuri, Manuel; Rapti, Kleopatra; Zhang, Shihong; Liang, Lifan; Lebeche, Djamel; Hajjar, Roger J.; Lipskaia, Larissa; Chemaly, Elie R.] Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, New York, NY 10029 USA. [Dhandapany, Perundurai S.] Icahn Sch Med Mt Sinai, Dept Pediat, Mount Sinai, NY 10029 USA. [Ramos-Kuri, Manuel] Ctr Invest Social Avanzada, Queretaro 76190, Mexico. [Ramos-Kuri, Manuel; Liang, Lifan; Lebeche, Djamel; Hajjar, Roger J.; Chemaly, Elie R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Ramos-Kuri, Manuel] Univ Panamericana, Mol Biol Lab, Mexico City, DF, Mexico. [Ramos-Kuri, Manuel; Garcia-Carranca, Alejandro] Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico. [Adnot, Serge; Lipskaia, Larissa] UPEC, INSERM, U955, F-94010 Creteil, France. [Adnot, Serge; Lipskaia, Larissa] UPEC, Hop Henri Mondor, Dept Physiol, AP HP, F-94010 Creteil, France. [Bobe, Regis] Univ Paris 11, INSERM, U770, Le Kremlin Bicetre, France. [Mehel, Hind; Fischmeister, Rodolphe] INSERM, UMR S 1180, LabEx LERMIT DHU TORINO, Chatenay Malabry, France. [Mehel, Hind; Fischmeister, Rodolphe] Univ Paris 11, Fac Pharm, F-92290 Chatenay Malabry, France. RP Ramos-Kuri, M (reprint author), Ctr Invest Social Avanzada, Ave Fray Luis Leon 1000, Queretaro 76190, Mexico. EM manuel.ramos@cisav.org RI BOBE, Regis/F-4951-2016 OI BOBE, Regis/0000-0002-8225-9117 FU NIH [RO1 HL083156, HL080498, HL093183, P20HL100396]; Association Francaise contre les Myopathies [AFM 16442]; NIHNHLBI [T32HL007824]; AHA-SDG [15SDG23250005] FX This study was supported in part by NIH RO1 HL083156, HL080498, HL093183, and P20HL100396 (RJH); Association Francaise contre les Myopathies (AFM 16442; LL, RJH); NIHNHLBI T32HL007824 (ERC); as well as the AHA-SDG (15SDG23250005) for (PSD). NR 45 TC 2 Z9 2 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV PY 2015 VL 1853 IS 11 BP 2870 EP 2884 DI 10.1016/j.bbamcr.2015.08.006 PN A PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CT8LV UT WOS:000363069000003 PM 26260012 ER PT J AU Dib, B Lin, HJ Maidana, DE Tian, B Miller, JB Bouzika, P Miller, JW Vavvas, DG AF Dib, Bernard Lin, Haijiang Maidana, Daniel E. Tian, Bo Miller, John B. Bouzika, Peggy Miller, Joan W. Vavvas, Demetrios G. TI Mitochondrial DNA has a pro-inflammatory role in AMD SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Age-related macular degeneration; Retinal pigment epithelium; Mitochondrial DNA; Inflammation; NLRP3 inflammasome ID NF-KAPPA-B; RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; NLRP3 INFLAMMASOME; CHOROIDAL NEOVASCULARIZATION; OXIDATIVE STRESS; ARPE-19 CELLS; MALATTIA LEVENTINESE; AQUEOUS-HUMOR AB Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly of industrialized nations, and there is increasing evidence to support a role for chronic inflammation in its pathogenesis. Mitochondrial DNA (mtDNA) has been recently reported to be pro-inflammatory in various diseases such as Alzheimer's and heart failure. Here, we report that intracellular mtDNA induces ARPE-19 cells to secrete inflammatory cytokines IL-6 and IL-8, which have been consistently associated with AMD onset and progression. The induction was dependent on the size of mtDNA, but not on specific sequence. Oxidative stress plays a major role in the development of AMD, and our findings indicate that mtDNA induces IL-6 and IL-8 more potently when oxidized. Cytokine induction was mediated by STING (Stimulator of Interferon Genes) and NF-kappa B as evidenced by abrogation of the cytokine response with the use of specific inhibitors (siRNA and BAY 11-7082, respectively). Finally, mtDNA primed the NLRP3 inflammasome. This study contributes to our understanding of the potential pro-inflammatory role of mtDNA in the pathogenesis of AMD. (C) 2015 Elsevier B.V. All rights reserved. C1 [Dib, Bernard; Lin, Haijiang; Maidana, Daniel E.; Tian, Bo; Miller, John B.; Bouzika, Peggy; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu FU NEI [R21EY023079-01A1, EY014104]; Yeatts Family Foundation; Loefflers Family Fund; research to prevent blindness foundation; Bayer Healthcare Global Ophthalmology Award; Macula Society Research Grant FX The authors would like to thank Mien Hoang and Keiko Kataoka for their technical support. This work was supported by: NEI R21EY023079-01A1 (DGV); the Yeatts Family Foundation (DGV, JWM); the Loefflers Family Fund (DGV, JWM); the 2013 Macula Society Research Grant award (DGV); a Physician Scientist Award (DGV), an unrestricted grant (JWM) from the research to prevent blindness foundation; NEI grant EY014104 (Meei Core Grant); and Bayer Healthcare 2013 Global Ophthalmology Award (DEM). NR 84 TC 4 Z9 4 U1 3 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV PY 2015 VL 1853 IS 11 BP 2897 EP 2906 DI 10.1016/j.bbamcr.2015.08.012 PN A PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CT8LV UT WOS:000363069000005 PM 26305120 ER PT J AU Bhatia, K Takayesu, JK Arbelaez, C Peak, D Nadel, ES AF Bhatia, Kriti Takayesu, James Kimo Arbelaez, Christian Peak, David Nadel, Eric S. TI An Innovative Educational and Mentorship Program for Emergency Medicine Women Residents to Enhance Academic Development and Retention SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID CAREER; PHYSICIANS AB Given the discrepancy between men and women's equal rates of medical school matriculation and their rates of academic promotion and leadership role acquisition, the need to provide mentorship and education to women in academic medicine is becoming increasingly recognized. Numerous large-scale programs have been developed to provide support and resources for women's enrichment and retention in academic medicine. Analyses of contributory factors to the aforementioned discrepancy commonly cite insufficient mentoring and role modeling as well as challenges with organizational navigation. Since residency training has been shown to be a critical juncture for making the decision to pursue an academic career, there is a need for innovative and tailored educational and mentorship programs targeting residents. Acknowledging residents' competing demands, we designed a program to provide easily accessible mentorship and contact with role models for our trainees at the departmental and institutional levels. We believe that this is an important step towards encouraging women's pursuit of academic careers. Our model may be useful to other emergency medicine residencies looking to provide such opportunities for their women residents. C1 [Bhatia, Kriti; Arbelaez, Christian; Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Takayesu, James Kimo; Peak, David; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Bhatia, K (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House,Room 236-C, Boston, MA 02115 USA. EM kbhatia1@partners.org NR 12 TC 0 Z9 0 U1 2 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1481-8035 EI 1481-8043 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD NOV PY 2015 VL 17 IS 6 BP 685 EP 688 DI 10.1017/cem.2015.17 PG 4 WC Emergency Medicine SC Emergency Medicine GA CT8SC UT WOS:000363085800012 PM 25915003 ER PT J AU Davies, NM Gaunt, TR Lewis, SJ Holly, J Donovan, JL Hamdy, FC Kemp, JP Eeles, R Easton, D Kote-Jarai, Z Al Olama, AA Benlloch, S Muir, K Giles, GG Wiklund, F Gronberg, H Haiman, CA Schleutker, J Nordestgaard, BG Travis, RC Neal, D Pashayan, N Khaw, KT Stanford, JL Blot, WJ Thibodeau, S Maier, C Kibel, AS Cybulski, C Cannon-Albright, L Brenner, H Park, J Kaneva, R Batra, J Teixeira, MR Pandha, H Lathrop, M Smith, GD Martin, RM AF Davies, Neil M. Gaunt, Tom R. Lewis, Sarah J. Holly, Jeff Donovan, Jenny L. Hamdy, Freddie C. Kemp, John P. Eeles, Rosalind Easton, Doug Kote-Jarai, Zsofia Al Olama, Ali Amin Benlloch, Sara Muir, Kenneth Giles, Graham G. Wiklund, Fredrik Gronberg, Henrik Haiman, Christopher A. Schleutker, Johanna Nordestgaard, Borge G. Travis, Ruth C. Neal, David Pashayan, Nora Khaw, Kay-Tee Stanford, Janet L. Blot, William J. Thibodeau, Stephen Maier, Christiane Kibel, Adam S. Cybulski, Cezary Cannon-Albright, Lisa Brenner, Hermann Park, Jong Kaneva, Radka Batra, Jyotsna Teixeira, Manuel R. Pandha, Hardev Lathrop, Mark Smith, George Davey Martin, Richard M. CA PRACTICAL Consortium TI The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium SO CANCER CAUSES & CONTROL LA English DT Article DE Height; Body mass index; Prostate cancer; Mendelian randomization; Single nucleotide polymorphisms; Instrumental variables analysis ID BODY-MASS INDEX; CONTROL-STUDY PROTECT; GROWTH-FACTORS; INSTRUMENTAL VARIABLES; GENETIC-VARIANTS; RISK-FACTORS; LEG LENGTH; OBESITY; METAANALYSIS; DISEASE AB Background Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods We conducted a case-control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man's number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade < 0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication. C1 [Davies, Neil M.; Gaunt, Tom R.; Lewis, Sarah J.; Donovan, Jenny L.; Smith, George Davey; Martin, Richard M.] Univ Bristol, Sch Social & Community Med, Bristol BS10 5NB, Avon, England. [Davies, Neil M.; Gaunt, Tom R.; Lewis, Sarah J.; Kemp, John P.; Smith, George Davey; Martin, Richard M.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS10 5NB, Avon, England. [Holly, Jeff] Univ Bristol, Sch Clin Sci, Bristol BS10 5NB, Avon, England. [Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg, Oxford, England. [Kemp, John P.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia. [Eeles, Rosalind; Kote-Jarai, Zsofia] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London SW3 6JJ, England. [Easton, Doug; Al Olama, Ali Amin; Benlloch, Sara] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge, England. [Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England. [Giles, Graham G.] Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland. [Schleutker, Johanna] Univ Tampere, Inst Biomed Technol BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna] FimLab Labs, Tampere, Finland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. [Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Neal, David] Univ Cambridge, Addenbrookes Hosp, Surg Oncol Urooncol S4, Cambridge CB2 2QQ, England. [Neal, David] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England. [Pashayan, Nora] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Lab, Cambridge CB2 2QQ, England. [Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Cambridge CB2 0SR, England. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA. [Thibodeau, Stephen] Mayo Clin, Rochester, MN USA. [Maier, Christiane] Univ Hosp, Dept Urol, Ulm, Germany. [Maier, Christiane] Univ Hosp, Inst Human Genet, Ulm, Germany. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kibel, Adam S.] Washington Univ, St Louis, MO USA. [Cybulski, Cezary] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland. [Cannon-Albright, Lisa] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Park, Jong] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA. [Kaneva, Radka] Med Univ Sofia, Mol Med Ctr, Sofia 1431, Bulgaria. [Kaneva, Radka] Med Univ Sofia, Dept Med Chem & Biochem, Sofia 1431, Bulgaria. [Batra, Jyotsna] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Prostate Canc Res Ctr Qld, Brisbane, Qld 4001, Australia. [Batra, Jyotsna] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal. [Pandha, Hardev] Univ Surrey, Guildford GU2 7XH, Surrey, England. [Pashayan, Nora] UCL, Dept Appl Hlth Res, London WC1E 7HB, England. [Lathrop, Mark] Ctr Natl Genotypage, Commiss Energie Atom, Evry, France. [Lathrop, Mark] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Martin, Richard M.] Natl Inst Hlth Res, Bristol Nutr Biomed Res Unit, Bristol, Avon, England. RP Martin, RM (reprint author), Univ Bristol, Sch Social & Community Med, Bristol BS10 5NB, Avon, England. EM neil.davies@bristol.ac.uk; richard.martin@bristol.ac.uk RI Teixeira, Manuel/E-4885-2011; Paulo, Paula/F-1441-2016; Gaunt, Tom/O-3918-2014; Batra, Jyotsna/B-4130-2011; Davey Smith, George/A-7407-2013; Brenner, Hermann/B-4627-2017; OI Teixeira, Manuel/0000-0002-4896-5982; Paulo, Paula/0000-0001-8387-2127; Gaunt, Tom/0000-0003-0924-3247; Davey Smith, George/0000-0002-1407-8314; Brenner, Hermann/0000-0002-6129-1572; Kierzek, Andrzej/0000-0002-2605-9057; Eeles, Rosalind/0000-0002-3698-6241; Lewis, Sarah/0000-0003-4311-6890; albright, lisa/0000-0003-2602-3668; Kemp, John/0000-0002-9105-2249; Giles, Graham/0000-0003-4946-9099 FU World Cancer Research Fund [2011/419]; Cancer Research UK [C18281/A19169, C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135]; Canadian Institutes of Health Research; European Commission's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative [1 U19 CA 148537-01]; UK Health Technology Assessment (HTA) Programme of the NIH Research [HTA 96/20/99, ISRCTN20141297]; National Cancer Research Institute (NCRI); Medical Research Council and Cancer Research UK [G0500966/75466]; MRC; University of Bristol [G0600705, MC_UU_12013/1,9] FX Support for the analysis was provided by the World Cancer Research Fund (2011/419) and Cancer Research UK (C18281/A19169). The CRUK study and the PRACTICAL consortium were supported by the Canadian Institutes of Health Research; the European Commission's Seventh Framework Programme Grant agreement number 223175 (HEALTH-F2-2009-223175); Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135; and the National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative Grant No. 1 U19 CA 148537-01 (the GAME-ON initiative). The ProtecT study is funded by the UK Health Technology Assessment (HTA) Programme of the NIH Research (HTA 96/20/99; ISRCTN20141297). The authors thank the provision of the additional epidemiological data by the NHS R&D Directorate supported Prodigal study and the ProMPT (Prostate Mechanisms of Progression and Treatment) collaboration which is supported by the National Cancer Research Institute (NCRI) formed by the Department of Health, the Medical Research Council and Cancer Research UK (G0500966/75466). RAE and ZKJ are supported by Cancer Research UK Grant C5047/A7357 and the NIHR Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. RMM was supported by the National Institute for Health Research Bristol Nutrition Biomedical Research Unit based at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. FCH, DEN and JLD are NIHR Senior Investigators. The Integrative Epidemiology Unit is supported by the MRC and the University of Bristol (G0600705, MC_UU_12013/1,9). No funding body has influenced data collection, analysis, or its interpretations. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. This publication is the work of the authors, who serve as the guarantors for the contents of this paper. NR 50 TC 10 Z9 10 U1 5 U2 23 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2015 VL 26 IS 11 BP 1603 EP 1616 DI 10.1007/s10552-015-0654-9 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CT3CV UT WOS:000362685200007 PM 26387087 ER PT J AU Tucker-Seeley, RD Selk, S Adams, I Allen, JD Sorensen, G AF Tucker-Seeley, R. D. Selk, S. Adams, I. Allen, J. D. Sorensen, G. TI Tobacco use among low-income housing residents: does hardship motivate quit attempts? SO CANCER CAUSES & CONTROL LA English DT Article DE Hardship; Tobacco use; Low income; Public housing ID RANDOMIZED CONTROLLED-TRIAL; 4 COUNTRY SURVEY; SMOKING-CESSATION; FINANCIAL STRESS; NICOTINE DEPENDENCE; SMOKERS; INCENTIVES; BELIEFS; SAMPLE; ADULTS AB The purpose of this study was to examine material hardship among smokers to determine whether such hardship was positively associated with current attempts to quit tobacco use. We analyzed cross-sectional data from the Health in Common (HIC) study, an observational study to investigate social and physical determinants of cancer risk-related behaviors among residents of low-income housing in three cities in the Boston metropolitan area. In this study, three indicators of hardship were used: food hardship, financial hardship, and material hardship (food and financial hardship combined). Logistic regression models were used to obtain the odds of currently trying to quit among current smokers in the HIC (n = 170) across hardship types experienced, adjusting for sociodemographic and psychosocial factors. Fully adjusted models revealed no statistically significant association between trying to quit tobacco use and indicators of material hardship: food hardship and financial hardship present (OR 1.33 (0.42-4.2); food hardship and no financial hardship OR 3.83 (0.97-15.13); and financial hardship but no food hardship OR 0.5 (0.1-2.39). These findings suggest that even in the presence of material hardship, low-income housing resident tobacco users are not more likely to quit tobacco use; therefore, cessation efforts focused on the financial benefits of quitting may be insufficient to motivate quit attempts among low-income smokers. C1 [Tucker-Seeley, R. D.; Selk, S.; Sorensen, G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Tucker-Seeley, R. D.; Adams, I.; Sorensen, G.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Allen, J. D.] Tufts Univ, Dept Publ Hlth & Community Med, Boston, MA 02111 USA. RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 747, Boston, MA 02215 USA. EM retucker@hsph.harvard.edu FU National Cancer Institute [5RO1CA111310-04, 5K05CA108663-05]; K01 career development award [CA169041-01] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by funding from National Cancer Institute Grants 5RO1CA111310-04 and 5K05CA108663-05. (Principal Investigator: G. Sorensen). Dr. Tucker-Seeley is supported by K01 career development award (Grant# CA169041-01). NR 32 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2015 VL 26 IS 11 BP 1699 EP 1707 DI 10.1007/s10552-015-0662-9 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA CT3CV UT WOS:000362685200016 PM 26376892 ER PT J AU Lantos, PM Branda, JA Boggan, JC Chudgar, SM Wilson, EA Ruffin, F Fowler, V Auwaerter, PG Nigrovic, LE AF Lantos, Paul M. Branda, John A. Boggan, Joel C. Chudgar, Saumil M. Wilson, Elizabeth A. Ruffin, Felicia Fowler, Vance Auwaerter, Paul G. Nigrovic, Lise E. TI Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Borrelia burgdorferi; Lyme; serology; positive predictive value; diagnostic testing ID EASTERN UNITED-STATES; BORRELIA-BURGDORFERI; LABORATORY EVALUATION; KNEE MONOARTHRITIS; ASEPTIC-MENINGITIS; CLINICAL-PRACTICE; ENDEMIC REGION; FACIAL PALSY; CHILDREN; PREVALENCE AB Background. Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. Methods. We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). Results. During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. Conclusions. In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting. C1 [Lantos, Paul M.] Duke Univ, Med Ctr, Div Pediat Infect Dis, Durham, NC 27710 USA. [Lantos, Paul M.; Boggan, Joel C.; Chudgar, Saumil M.] Duke Univ, Med Ctr, Div Internal Med, Durham, NC 27710 USA. [Ruffin, Felicia; Fowler, Vance] Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. [Wilson, Elizabeth A.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nigrovic, Lise E.] Boston Childrens Hosp, Div Emergency Med, Boston, MA USA. [Auwaerter, Paul G.] Johns Hopkins Med Inst, Div Infect Dis, Baltimore, MD 21205 USA. RP Lantos, PM (reprint author), Duke Univ, Med Ctr, Dept Internal Med, DUMC 100800, Durham, NC 27710 USA. EM paul.lantos@duke.edu OI Chudgar, Saumil/0000-0003-3107-7919; Boggan, Joel/0000-0003-3564-2807 FU National Center for Advancing Translational Sciences of NIH [KL2 TR001115]; Ken and Sherrilyn Fisher Center for Environmental Infectious Diseases; National Institute for Allergy and Infectious Diseases, NIH [K24 AI093969]; Boston Children's Hospital FX This work was supported by the National Center for Advancing Translational Sciences of the NIH (grant KL2 TR001115 to P. M. L.), the Ken and Sherrilyn Fisher Center for Environmental Infectious Diseases (P. G. A.), the National Institute for Allergy and Infectious Diseases, NIH (grant K24 AI093969 to F. R. and V. F.), and Boston Children's Hospital (pilot research grant to L. E. N.). NR 33 TC 7 Z9 7 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 2015 VL 61 IS 9 BP 1374 EP 1380 DI 10.1093/cid/civ584 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6XI UT WOS:000362956000004 PM 26195017 ER PT J AU Jones, BE Jones, MM Huttner, B Stoddard, G Brown, KA Stevens, VW Greene, T Sauer, B Madaras-Kelly, K Rubin, M Goetz, MB Samore, M AF Jones, Barbara E. Jones, Makoto M. Huttner, Benedikt Stoddard, Gregory Brown, Kevin Antoine Stevens, Vanessa W. Greene, Tom Sauer, Brian Madaras-Kelly, Karl Rubin, Michael Goetz, Matthew Bidwell Samore, Matthew TI Trends in Antibiotic Use and Nosocomial Pathogens in Hospitalized Veterans With Pneumonia at 128 Medical Centers, 2006-2010 SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE pneumonia; antibiotic use; HCAP; nosocomial pathogens; drug-resistant pneumonia ID CARE-ASSOCIATED PNEUMONIA; COMMUNITY-ACQUIRED PNEUMONIA; RESISTANT PATHOGENS; RISK-FACTORS; HEALTH; THERAPY; INFECTIONS; OUTCOMES; ASSOCIATION; MORTALITY AB Background. In 2005, pneumonia practice guidelines recommended broad-spectrum antibiotics for patients with risk factors for nosocomial pathogens. The impact of these recommendations on the ability of providers to match treatment with nosocomial pathogens is unknown. Methods. Among hospitalizations with a principal diagnosis of pneumonia at 128 Department of Veterans Affairs medical centers from 2006 through 2010, we measured annual trends in antibiotic selection; initial blood or respiratory cultures positive for methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter species; and alignment between antibiotic coverage and culture results for MRSA and P. aeruginosa, calculating sensitivity, specificity, and diagnostic odds ratio using a 2 x 2 contingency table. Results. In 95 511 hospitalizations for pneumonia, initial use of vancomycin increased from 16% in 2006 to 31% in 2010, and piperacillin-tazobactam increased from 16% to 27%, and there was a decrease in both ceftriaxone (from 39% to 33%) and azithromycin (change from 39% to 36%) (P < .001 for all). The proportion of hospitalizations with cultures positive for MRSA decreased (from 2.5% to 2.0%; P < .001); no change was seen for P. aeruginosa (1.9% to 2.0%; P = .14) or Acinetobacter spp. (0.2% to 0.2%; P = .17). For both MRSA and P. aeruginosa, sensitivity increased (from 46% to 65% and 54% to 63%, respectively; P < .001) and specificity decreased (from 85% to 69% and 76% to 68%; P < .001), with no significant changes in diagnostic odds ratio (decreases from 4.6 to 4.1 [P = .57] and 3.7 to 3.2 [P = .95], respectively). Conclusions. Between 2006 and 2010, we found a substantial increase in the use of broad-spectrum antibiotics for pneumonia despite no increase in nosocomial pathogens. The ability of providers to accurately match antibiotic coverage to nosocomial pathogens remains low. C1 [Jones, Barbara E.] SLC VA Hlth Syst & Univ Utah, Div Pulm & Crit Care Med, Coll Pharm, Salt Lake City, UT 84132 USA. [Jones, Makoto M.; Sauer, Brian; Rubin, Michael; Samore, Matthew] SLC VA Hlth Syst & Univ Utah, Div Epidemiol, Coll Pharm, Salt Lake City, UT 84132 USA. [Jones, Makoto M.] SLC VA Hlth Syst & Univ Utah, Div Infect Dis, Coll Pharm, Salt Lake City, UT 84132 USA. [Stevens, Vanessa W.] SLC VA Hlth Syst & Univ Utah, Pharmacotherapy Outcomes Res Ctr, Coll Pharm, Salt Lake City, UT 84132 USA. [Brown, Kevin Antoine] Univ Utah, Salt Lake City VA Hlth Syst, Salt Lake City, UT USA. [Stoddard, Gregory; Greene, Tom] Univ Utah, Div Epidemiol, Salt Lake City, UT USA. [Madaras-Kelly, Karl] Boise VA Med Ctr, Pocatello, ID USA. [Madaras-Kelly, Karl] Idaho State Univ, Coll Pharm, Pocatello, ID 83209 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, Div Infect Dis, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [Huttner, Benedikt] Univ Hosp Geneva, Infect Control Program, Geneva, Switzerland. [Huttner, Benedikt] Univ Hosp Geneva, Div Infect Dis, Geneva, Switzerland. RP Jones, BE (reprint author), SLC VA Hlth Syst & Univ Utah, Div Pulm & Crit Care Med, 30N 1900 E 701 Wintrobe, Salt Lake City, UT 84132 USA. EM barbara.jones@hsc.utah.edu RI Huttner, Benedikt/M-5616-2014; OI Huttner, Benedikt/0000-0002-1749-9464; Goetz, Matthew/0000-0003-4542-992X; Stevens, Vanessa/0000-0001-8933-5453; Brown, Kevin Antoine/0000-0002-1483-2188 FU National Institutes of Health FX This work was supported by the National Institutes of Health (training grant to B. E. J.). NR 35 TC 7 Z9 7 U1 1 U2 9 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 2015 VL 61 IS 9 BP 1403 EP 1410 DI 10.1093/cid/civ629 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6XI UT WOS:000362956000008 PM 26223995 ER PT J AU Labreche, MJ Graber, CJ Nguyen, HM AF Labreche, Matthew J. Graber, Christopher J. Nguyen, Hien M. TI Recent Updates on the Role of Pharmacokinetics-pharmacodynamics in Antimicrobial Susceptibility Testing as Applied to Clinical Practice SO CLINICAL INFECTIOUS DISEASES LA English DT Review DE pharmacokinetics; pharmacodynamics; breakpoints; susceptibility testing ID LACTAMASE-PRODUCING ENTEROBACTERIACEAE; INFECTIOUS-DISEASES SOCIETY; MONTE-CARLO-SIMULATION; STREPTOCOCCUS-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; EXTENDED-SPECTRUM; INTERPRETIVE CRITERIA; ORAL CEPHALOSPORINS; TRACT-INFECTIONS; CRITICALLY-ILL AB Given current challenges in antimicrobial resistance and drug development, infectious diseases clinicians must rely on their own ingenuity to effectively treat infections while preserving the current antimicrobial armamentarium. An understanding of pharmacokinetics (PK), pharmacodynamics (PD), antimicrobial susceptibility testing (AST), and how these concepts relate, is essential to this task. In this review, we discuss how and why PK-PD impacts AST and the way infectious diseases are being treated, with a particular focus on vancomycin for methicillin-resistant Staphylococcus aureus, penicillin for Streptococcus pneumoniae, and an update on cephalosporins for Enterobacteriaceae. Finally, we address how new ideas to exploit PK-PD can promote innovative study design and bring about more rapid regulatory review of new antimicrobials. C1 [Labreche, Matthew J.; Nguyen, Hien M.] Kaiser Permanente Northwest, Portland, OR USA. [Graber, Christopher J.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Nguyen, HM (reprint author), 9900 SE Sunnyside Rd, Clackamas, OR 97015 USA. EM hien.m.nguyen@kp.org NR 49 TC 4 Z9 4 U1 2 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 2015 VL 61 IS 9 BP 1446 EP 1452 DI 10.1093/cid/civ498 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6XI UT WOS:000362956000016 PM 26105168 ER PT J AU Garrison, LE Lucas, CE Demirjian, A Sonel, AF Hicks, LA AF Garrison, Laurel E. Lucas, Claressa E. Demirjian, Alicia Sonel, Ali F. Hicks, Lauri A. TI The Case for Routine Environmental Testing for Legionella Bacteria in Healthcare Facility Water Distribution Systems-Reconciling CDC Position and Guidance Regarding Risk Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Garrison, Laurel E.; Lucas, Claressa E.; Demirjian, Alicia; Hicks, Lauri A.] Natl Ctr Immunizat & Resp Dis, Div Bacterial Dis, Atlanta, GA USA. [Demirjian, Alicia] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30329 USA. [Sonel, Ali F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sonel, Ali F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Garrison, LE (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS C-25, Atlanta, GA 30329 USA. EM lee5@cdc.gov NR 2 TC 1 Z9 1 U1 2 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 2015 VL 61 IS 9 BP 1488 EP 1488 DI 10.1093/cid/civ591 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CT6XI UT WOS:000362956000022 PM 26195018 ER PT J AU Zou, L Chen, HH Li, D Xu, GQ Feng, Y Chen, C Wang, L Sosnovik, DE Chao, W AF Zou, Lin Chen, Howard H. Li, Dan Xu, Ganqiong Feng, Yan Chen, Chan Wang, Larry Sosnovik, David E. Chao, Wei TI Imaging Lymphoid Cell Death In Vivo During Polymicrobial Sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE apoptosis; imaging; immunosuppression; lymphocyte cell death; necrosis; sepsis ID ACUTE MYOCARDIAL-INFARCTION; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTOR-3; ACUTE KIDNEY INJURY; ANNEXIN-V; GENOMIC RESPONSES; INDUCED APOPTOSIS; CECAL LIGATION; MORTALITY; SURVIVAL AB Objectives: Cell death in lymphatic organs, such as the spleen, is in part responsible for immunosuppression and contributes to mortality during sepsis. An early and noninvasive detection of lymphoid cell death could thus have significant clinical implications. Here, we tested in vivo imaging of lymphoid cell death using a near-infrared annexin V (AV-750). Design: Animal study. Setting: Laboratory investigation. Subjects: C57BL/6J wild-type and toll-like receptor 3 knockout mice. Interventions: Mild and severe polymicrobial sepsis was induced with cecum ligation and puncture. Serum cytokines and acute kidney injury markers were tested by immunoassay and quantitative reverse transcription-polymerase chain reaction, respectively. Sepsis-induced lymphoid cell death was detected by fluorescent AV-750 accumulation in the thorax and abdomen (in vivo), in isolated organs (ex vivo), and in isolated cells (flow cytometry). Caspase-3 cleavage/activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining were tested for apoptosis. Measurements and Main Results: Severe sepsis induced marked apoptosis in the thymus, spleen, and liver as demonstrated by cleaved caspase-3 and an increase in caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. A significant increase in fluorescent AV-750 signal was seen in the thoracic and upper abdominal fields and associated with the severity of sepsis. The in vivo thoracic and abdominal AV-750 fluorescent signal was attributed to the thymus, liver, and spleen as determined by ex vivo imaging and highly correlated with the levels of cell death in thymocytes and splenocytes, respectively, as measured by flow cytometry. Compared with wild-type septic mice, toll-like receptor 3 septic mice had attenuated abdominal AV-750 fluorescent signal, reduced ex vivo fluorescence in the spleen, and decreased splenocyte cell death. Conclusions: In vivo AV-750 fluorescent imaging provides spatially resolved and organ-specific detection of lymphoid cell death during polymicrobial sepsis. The AV-750 fluorescent intensity in the thoracic and abdominal fields is associated with sepsis severity and well correlated with sepsis-induced cell death in the thymus and spleen, respectively. C1 [Zou, Lin; Chen, Howard H.; Li, Dan; Xu, Ganqiong; Feng, Yan; Chen, Chan; Wang, Larry; Sosnovik, David E.; Chao, Wei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02163 USA. RP Chao, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02163 USA. EM wchao@mgh.harvard.edu FU International Anesthesia Research Society; National Institutes of Health (NIH) [K99 HL121152]; NIH [HL093038, HL112831]; Harvard Center for the Studies of Inflammatory Bowel Disease [GM097259, DK043351] FX Dr. Zou received a mentored research award from the International Anesthesia Research Society. Dr. Chen received grant support from the National Institutes of Health (NIH) (K99 HL121152). Dr. Sosnovik received grant support for this research from the NIH (HL093038 and HL112831). Dr. Chao received support for this research from the NIH and Harvard Center for the Studies of Inflammatory Bowel Disease (GM097259 and DK043351). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 49 TC 3 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2015 VL 43 IS 11 BP 2303 EP 2312 DI 10.1097/CCM.0000000000001254 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA CT5CX UT WOS:000362826200005 PM 26335111 ER PT J AU Murphy, DJ Rubinson, L Blum, J Isakov, A Bhagwanjee, S Cairns, CB Cobb, JP Sevransky, JE AF Murphy, David J. Rubinson, Lewis Blum, James Isakov, Alexander Bhagwanjee, Statish Cairns, Charles B. Cobb, J. Perren Sevransky, Jonathan E. CA US Critical Illness Injury Trials TI Development of a Core Clinical Dataset to Characterize Serious Illness, Injuries, and Resource Requirements for Acute Medical Responses to Public Health Emergencies SO CRITICAL CARE MEDICINE LA English DT Article DE consensus; data collection; disasters; emergencies; intensive care units ID UNITED-STATES; SYNDROMIC SURVEILLANCE; DELPHI TECHNIQUE; CARE; MORTALITY; ALGORITHMS; SEVERITY; PROTOCOL; DISEASES; OUTCOMES AB Objectives: In developed countries, public health systems have become adept at rapidly identifying the etiology and impact of public health emergencies. However, within the time course of clinical responses, shortfalls in readily analyzable patient-level data limit capabilities to understand clinical course, predict outcomes, ensure resource availability, and evaluate the effectiveness of diagnostic and therapeutic strategies for seriously ill and injured patients. To be useful in the timeline of a public health emergency, multi-institutional clinical investigation systems must be in place to rapidly collect, analyze, and disseminate detailed clinical information regarding patients across prehospital, emergency department, and acute care hospital settings, including ICUs. As an initial step to near real-time clinical learning during public health emergencies, we sought to develop an all-hazards core dataset to characterize serious illness and injuries and the resource requirements for acute medical response across the care continuum. Subjects: A multidisciplinary panel of clinicians, public health professionals, and researchers with expertise in public health emergencies. Design: Group consensus process. Interventions: The consensus process included regularly scheduled conference calls, electronic communications, and an in-person meeting to generate candidate variables. Candidate variables were then reviewed by the group to meet the competing criteria of utility and feasibility resulting in the core dataset. Measurements and Main Results: The 40-member panel generated 215 candidate variables for potential dataset inclusion. The final dataset includes 140 patient-level variables in the domains of demographics and anthropometrics (7), prehospital (11), emergency department (13), diagnosis (8), severity of illness (54), medications and interventions (38), and outcomes (9). Conclusions: The resulting all-hazard core dataset for seriously ill and injured persons provides a foundation to facilitate rapid collection, analyses, and dissemination of information necessary for clinicians, public health officials, and policymakers to optimize public health emergency response. Further work is needed to validate the effectiveness of the dataset in a variety of emergency settings. C1 [Murphy, David J.; Sevransky, Jonathan E.] Emory Univ, Dept Med, Div Pulm Allergy Sleep & Crit Care Med, Atlanta, GA 30322 USA. [Rubinson, Lewis] Univ Maryland, Sch Med, Div Trauma Crit Care, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA. [Blum, James] Emory Univ, Dept Anesthesiol, Atlanta, GA 30303 USA. [Isakov, Alexander] Emory Univ, Dept Emergency Med, Atlanta, GA 30303 USA. [Bhagwanjee, Statish] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Cairns, Charles B.] Univ Arizona, Coll Med, Dept Emergency Med, Tucson, AZ USA. [Cobb, J. Perren] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. [Cobb, J. Perren] Harvard Univ, Sch Med, Boston, MA USA. [Cobb, J. Perren] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Murphy, DJ (reprint author), Emory Univ, Sch Med, Div Pulm Allergy Sleep & Crit Care Med, 49 Jesse Hill Jr Dr FOB, Atlanta, GA 30303 USA. EM david.j.murphy@emory.edu FU Biomedical Advanced Research and Development Authority [HHSO 100201100062P]; National Institutes of Health (NIH)/Food and Drug Administration/Biomedical Advanced Research and Development Authority (BARDA); NIH; Department of Health and Human Services: ASPR; UW; HHS/ASPR; Office of the U.S. Assistant Secretary for Preparedness and Response; U.S. ASPR; ASPR; ASPR/BARDA; Abbott Laboratory FX Supported, in part, by Assistant Secretary for Preparedness and Response-Biomedical Advanced Research and Development Authority (contract no. HHSO 100201100062P).; Dr. Murphy's institution received support for travel from Health and Human Services (HHS)/Assistant Secretary for Preparedness and Response (ASPR). Dr. Rubinson disclosed government work. His institution received grant support from the National Institutes of Health (NIH)/Food and Drug Administration/Biomedical Advanced Research and Development Authority (BARDA; he is a subcontractor on one awarded and a second site principal investigator for an award relevant to disasters under review). Dr. Blum consulted for Retia Medical. His institution received grant support from the NIH, has patents with the University of Michigan, and received support for travel from the ASPR. Dr. Bhagwanjee received support for article research from the Department of Health and Human Services: ASPR and disclosed government work. His institution received grant support and support for travel from UW. Dr. Cairns consulted for bioMerieux and Teva. His institution received grant support and support for travel from the HHS/ASPR. Dr. Cobb received support for article research from Office of the U.S. Assistant Secretary for Preparedness and Response. His institution received grant support from the U.S. ASPR (this work was performed in part with support from a contract from ASPR to U.S. Critical Illness and Injury Trials Group) and received grant support from ASPR/BARDA (the work reported herein was used for preliminary data to support ongoing work, new contract pending). Dr. Sevransky's institution received grant support from Abbott Laboratory (biomarker discovery project). Dr. Isakov has disclosed that he does not have any potential conflicts of interest. NR 36 TC 0 Z9 0 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2015 VL 43 IS 11 BP 2403 EP 2408 DI 10.1097/CCM.0000000000001274 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA CT5CX UT WOS:000362826200017 PM 26308434 ER PT J AU Sigakis, MJG Bittner, EA AF Sigakis, Matthew J. G. Bittner, Edward A. TI Ten Myths and Misconceptions Regarding Pain Management in the ICU SO CRITICAL CARE MEDICINE LA English DT Review DE analgesia; analgesics; critical care; pain assessment; pain management; quality improvement ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL PATIENTS; QUALITY-OF-LIFE; RESPIRATORY-DISTRESS-SYNDROME; OPIOID-INDUCED HYPERALGESIA; ANALGESIA-BASED SEDATION; CHEST TUBE REMOVAL; MECHANICAL VENTILATION; PROCEDURAL PAIN; POSTTRAUMATIC-STRESS AB Objectives: The aim of this article is to expose common myths and misconceptions regarding pain assessment and management in critically ill patients that interfere with effective care. We comprehensively review the literature refuting these myths and misconceptions and describe evidence-based strategies for improving pain management in the ICU. Data Sources: Current peer-reviewed academic journals, as well as standards and guidelines from professional societies. Study Selection: The most current evidence was selected for review based on the highest degree of supportive evidence. Data Extraction: Data were obtained via medical search databases, including OvidSP, and the National Library of Medicine's MEDLINE database via PubMed. Data Synthesis: After a comprehensive literature review, conclusions were drawn based on the strength of evidence and the most current understanding of pain management practices in ICU. Conclusions: Myths and misconceptions regarding management of pain in the ICU are prevalent. Review of current evidence refutes these myths and misconceptions and provides insights and recommendations to ensure best practices. C1 [Sigakis, Matthew J. G.] Univ Michigan, Sch Med, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. RP Sigakis, MJG (reprint author), Univ Michigan, Sch Med, Dept Anesthesiol, Ann Arbor, MI 48109 USA. EM msigakis@med.umich.edu NR 123 TC 2 Z9 2 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2015 VL 43 IS 11 BP 2468 EP 2478 DI 10.1097/CCM.0000000000001256 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA CT5CX UT WOS:000362826200025 PM 26308433 ER PT J AU Cheng, KH Chu, CS Kuo, PL Lai, WT AF Cheng, Kai-Hung Chu, Chih-Sheng Kuo, Po-Lin Lai, Wen-Ter TI More Evidences Are Needed Before We Downgrade Antilipidemic Therapy Among Patients With High Risk of, or Suffering From, Myocardial Infarction Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID PERCUTANEOUS CORONARY INTERVENTION; PARADOX C1 [Cheng, Kai-Hung; Chu, Chih-Sheng] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Cardiol, Kaohsiung, Taiwan. [Cheng, Kai-Hung; Chu, Chih-Sheng] Kaohsiung Med Univ, Fac Med, Coll Med, Kaohsiung, Taiwan. [Cheng, Kai-Hung; Chu, Chih-Sheng] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung, Taiwan. [Cheng, Kai-Hung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Kuo, Po-Lin] Kaohsiung Med Univ, Coll Med, Inst Clin Med, Kaohsiung, Taiwan. [Lai, Wen-Ter] Kaohsiung Med Univ Hosp, Dept Internal Med, Div Cardiol, Kaohsiung, Taiwan. [Lai, Wen-Ter] Kaohsiung Med Univ, Coll Med, Fac Med, Kaohsiung, Taiwan. RP Cheng, KH (reprint author), Kaohsiung Med Univ Hosp, Dept Internal Med, Div Cardiol, Kaohsiung, Taiwan. NR 4 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 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2015 VL 43 IS 11 BP E532 EP E533 DI 10.1097/CCM.0000000000001228 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA CT5CW UT WOS:000362826100015 PM 26468724 ER PT J AU Osborn, EA Jaffer, FA AF Osborn, Eric A. Jaffer, Farouc A. TI Imaging inflammation and neovascularization in atherosclerosis: clinical and translational molecular and structural imaging targets SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE atherosclerosis; inflammation; molecular imaging; neovascularization ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; ARTERIAL INFLAMMATION; CAROTID ATHEROSCLEROSIS; PLAQUE INFLAMMATION; F-18-FDG PET/CT; INHIBITOR; HYPOXIA; ACTIVATION; ATHEROMAS AB Purpose of reviewThe purpose of this study is to showcase advances in molecular imaging of atheroma biology in living individuals.Recent findings(18)F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) continues to be the predominant molecular imaging approach for clinical applications, particularly in the large arterial beds. Recently, there has been significant progress in imaging of neovascularization and inflammation to delineate high-risk atheroma and to evaluate drug efficacy. In addition, new hardware detection technology and imaging agents are enabling in-vivo imaging of new targets on diverse imaging platforms.SummaryIn this review, we present recent exciting developments in molecular and structural imaging of atherosclerotic plaque inflammation and neovascularization. Building upon prior studies, these advances develop key technology that will play an important role in propelling new diagnostic and therapeutic strategies identifying high-risk plaque phenotypes and assessing new plaque stabilization therapies in clinical trials. C1 [Osborn, Eric A.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Cardiol Div, Boston, MA USA. [Osborn, Eric A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Jaffer, FA (reprint author), Cardiovasc Res Ctr, Simches Res Bldg,3206 185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu FU National Institutes of Health [R01 HL108229, R01 HL122388-01A1]; American Heart Association [13GRNT1760040]; Harvard Catalyst Medical Research Investigator Training Award/National Institutes of Health [KL2 TR001100] FX This work was supported by National Institutes of Health R01 HL108229 and R01 HL122388-01A1, American Heart Association Grant-in-Aid #13GRNT1760040 (F.A.J.); Harvard Catalyst Medical Research Investigator Training Award/National Institutes of Health KL2 TR001100 (E.A.O.). NR 45 TC 1 Z9 1 U1 4 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0268-4705 EI 1531-7080 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2015 VL 30 IS 6 BP 671 EP 680 DI 10.1097/HCO.0000000000000226 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CT1NH UT WOS:000362564700016 PM 26398413 ER PT J AU Neagu, MR Reardon, DA AF Neagu, Martha R. Reardon, David A. TI An Update on the Role of Immunotherapy and Vaccine Strategies for Primary Brain Tumors SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Review DE GBM; Immunotherapy; Checkpoint blockade; Vaccines; Autologous T cells; CAR T cells; Rindopepimut; EGFRvIII ID NEWLY-DIAGNOSED GLIOBLASTOMA; REGULATORY T-CELLS; HIGH-GRADE GLIOMA; PEPTIDE VACCINATION; RECURRENT GLIOBLASTOMA; METASTATIC MELANOMA; MALIGNANT GLIOMAS; CTLA-4 BLOCKADE; CLINICAL-TRIAL; ADJUVANT TEMOZOLOMIDE AB Existing therapies for glioblastoma (GBM), the most common malignant primary brain tumor in adults, have fallen short of improving the dismal patient outcomes, with an average 14-16-month median overall survival. The biological complexity and adaptability of GBM, redundancy of dysregulated signaling pathways, and poor penetration of therapies through the blood-brain barrier contribute to poor therapeutic progress. The current standard of care for newly diagnosed GBM consists of maximal safe resection, followed by fractionated radiotherapy combined with concurrent temozolomide (TMZ) and 6-12 cycles of adjuvant TMZ. At progression, bevacizumab with or without additional chemotherapy is an option for salvage therapy. The recent FDA approval of sipuleucel-T for prostate cancer and ipilumimab, nivolumab, and pembrolizumab for select solid tumors and the ongoing trials showing clinical efficacy and response durability herald a new era of cancer treatment with the potential to change standard-of-care treatment across multiple cancers. The evaluation of various immunotherapeutics is advancing for GBM, putting into question the dogma of the CNS as an immuno-privileged site. While the field is yet young, both active immunotherapy involving vaccine strategies and cellular therapy as well as reversal of GBM-induced global immune-suppression through immune checkpoint blockade are showing promising results and revealing essential immunological insights regarding kinetics of the immune response, immune evasion, and correlative biomarkers. The future holds exciting promise in establishing new treatment options for GBM that harness the patients' own immune system by activating it with immune checkpoint inhibitors, providing specificity using vaccine therapy, and allowing for modulation and enhancement by combinatorial approaches. C1 [Neagu, Martha R.; Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neagu, Martha R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, G4200,44 Binney St, Boston, MA 02115 USA. EM david_reardon@dfci.harvard.edu FU National Institutes of Health [K12CA090354] FX Martha R. Neagu has received financial support through a grant from the National Institutes of Health (K12CA090354). NR 104 TC 8 Z9 8 U1 2 U2 31 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 EI 1534-6277 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD NOV PY 2015 VL 16 IS 11 AR UNSP 54 DI 10.1007/s11864-015-0371-3 PG 18 WC Oncology SC Oncology GA CT7WY UT WOS:000363026900003 PM 26454859 ER PT J AU Bordeianou, L Hicks, CW Olariu, A Savitt, L Pulliam, SJ Weinstein, M Rockwood, T Sylla, P Kuo, J Wakamatsu, M AF Bordeianou, Liliana Hicks, Caitlin W. Olariu, Adriana Savitt, Lieba Pulliam, Samantha J. Weinstein, Milena Rockwood, Todd Sylla, Patricia Kuo, James Wakamatsu, May TI Effect of Coexisting Pelvic Floor Disorders on Fecal Incontinence Quality of Life Scores: A Prospective, Survey-Based Study SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Fecal incontinence; Fecal Incontinence Quality of Life; Fecal Incontinence Severity Index; Pelvic floor disorders; Quality of life; Urinary incontinence ID UROGENITAL DISTRESS INVENTORY; URINARY-INCONTINENCE; PSYCHOMETRIC EVALUATION; IMPACT QUESTIONNAIRE; ANAL INCONTINENCE; ORGAN PROLAPSE; SEVERITY INDEX; SHORT FORMS; WOMEN; INSTRUMENT AB BACKGROUND: The association between an objective measure of fecal incontinence severity and patient-reported quality of life is poorly understood. OBJECTIVE: The purpose of this study was to evaluate patients with various degrees of fecal incontinence to determine whether their quality of life as measured by the Fecal Incontinence Quality of Life Scale is affected by coexisting pelvic floor disorders. DESIGN: This was a prospective, survey-based study. SETTINGS: The study was conducted at a tertiary pelvic floor disorders center. PATIENTS: Included patients were all of those presenting between January 2007 and March 2014. MAIN OUTCOME MEASURES: Survey data were analyzed to determine the association between Fecal Incontinence Severity Index and Fecal Incontinence Quality of Life Scale, as well as scores from the Constipation Severity Instrument, Pelvic Floor Impact Questionnaire, Pelvic Organ Distress Inventory, and Urinary Distress Inventory. RESULTS: A total of 585 patients reported fecal incontinence ranging from none (n = 191) to mild/moderate (n = 159) to severe (n = 235). As expected, patients with severe fecal incontinence have worse scores on all fecal incontinence quality-of-life subscales (lifestyle, coping/behavior, depression/self-perception, and embarrassment) and worse colorectal/anal symptoms than those with mild/moderate or no fecal incontinence (p < 0.0001). Patients with severe fecal incontinence also have worse bladder/urinary symptoms (p 0.0001). Pelvic organ prolapse and constipation symptoms were similar between groups (p 0.61). After correcting for baseline differences in patient comorbidities and bladder/urinary symptoms, a significant association persisted between Fecal Incontinence Severity Index and all of the subscales of the fecal incontinence quality-of-life instrument (p < 0.0001). However, urinary distress scores also remained significantly associated with all of the fecal incontinence quality-of-life subscales except for embarrassment after risk adjustment (p < 0.01). LIMITATIONS: Nongeneral population and a lack of patient data on previous medical management of fecal incontinence were limitations of this study. CONCLUSIONS: The Fecal Incontinence Quality of Life Scale correlates strongly with instruments measuring both fecal and urinary incontinence. This underscores the importance of quantifying the presence or absence of coexistent urinary leakage in studies where a drop in fecal incontinence quality of life is considered a primary end point. C1 [Bordeianou, Liliana; Hicks, Caitlin W.; Olariu, Adriana; Savitt, Lieba; Pulliam, Samantha J.; Weinstein, Milena; Sylla, Patricia; Wakamatsu, May] Massachusetts Gen Hosp, Pelv Floor Disorders Ctr, Boston, MA 02114 USA. [Hicks, Caitlin W.] Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. [Rockwood, Todd] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Kuo, James] Brandeis Univ, Waltham, MA USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@mgh.harvard.edu NR 33 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD NOV PY 2015 VL 58 IS 11 BP 1091 EP 1097 DI 10.1097/DCR.0000000000000459 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA CT6RK UT WOS:000362939900010 PM 26445183 ER PT J AU Weisskopf, MG Cudkowicz, ME Johnson, N AF Weisskopf, Marc G. Cudkowicz, Merit E. Johnson, Norman TI Military Service and Amyotrophic Lateral Sclerosis in a Population-based Cohort SO EPIDEMIOLOGY LA English DT Article ID GULF-WAR VETERANS; ALZHEIMERS-DISEASE; SURROGATE RESPONDENTS; UNITED-STATES; ALS; MORTALITY; SMOKING; RISK; EPIDEMIOLOGY; EXPOSURE AB Background: Military service has been suggested to be associated with an increased risk of amyotrophic lateral sclerosis (ALS), but only one prospective studyof a volunteer cohorthas examined this question. Methods: We prospectively assessed the relation between service in the military and ALS mortality among participants in the National Longitudinal Mortality Study, a population-representative cohort of U.S. men and women surveyed from 1973 through 2002. Participant follow-up was conducted from 1979 through 2002 for ALS mortality. There were 696,743 men and 392,571 women who were 25 years old or more with military service data. In this group, there were 375 male ALS deaths and 96 female ALS deaths. Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards. Results: Men who served in the military had an increased adjusted ALS death rate [HR: 1.23; 95% confidence interval (CI): 0.98, 1.53] compared with those who did not serve. An increase in ALS mortality was found among those who served during World War II (HR: 1.47; 95% CI: 1.13, 1.91) but not during other time periods. This pattern of results was similar for women, but with larger confidence intervals (HR for military service: 1.26; 95% CI: 0.29, 5.59; HR for service during World War II: 2.03; 95% CI: 0.45, 9.05). Conclusions: Military personnel have an increased risk of ALS, which may be specific to certain service periods although there was no data on actual deployment. Because of the longer follow-up time for World War II veterans, we cannot rule out that increased risk for those who served during other periods would be seen with further follow-up. C1 [Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Cudkowicz, Merit E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Norman] US Bur Census, Ctr Adm Records & Applicat, Washington, DC USA. RP Weisskopf, MG (reprint author), Harvard Univ, TH Chan Harvard Sch Publ Hlth, EOME, Dept Environm Hlth,Landmark Ctr, 3rd Floor East,POB 15697, Boston, MA 02215 USA. EM mweissko@hsph.harvard.edu FU Muscular Dystrophy Association [MDA239243]; NIH grant [NS 082105]; Agency for Toxic Substances and Disease Registry's National ALS Registry program FX This work was supported by grant #MDA239243 from the Muscular Dystrophy Association, NIH grant #NS 082105, and funding from the Agency for Toxic Substances and Disease Registry's National ALS Registry program. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; nor in the decision to submit the manuscript for publication. NR 42 TC 9 Z9 9 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2015 VL 26 IS 6 BP 831 EP 838 DI 10.1097/EDE.0000000000000376 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CT1JF UT WOS:000362553900009 PM 26414854 ER PT J AU Deng, LQ Bensing, B Yang, WM Li, RH Ware, J Varki, A Sullam, P Zhang, H AF Deng, Lingquan Bensing, Barbara Yang, Weiming Li, Renhao Ware, Jerry Varki, Ajit Sullam, Paul Zhang, Hui TI Evaluating interactions between bacterial SRR adhesins and human platelet glycoprotein GPIba by glycoproteomics approaches SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology on Glycobiology - Accelerating Impact across the Biomedical Sciences CY DEC 01-04, 2015 CL San Francisco, CA SP Soc Glycobiol C1 [Deng, Lingquan; Yang, Weiming; Zhang, Hui] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Bensing, Barbara; Sullam, Paul] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Bensing, Barbara; Sullam, Paul] Univ Calif San Francisco, San Francisco, CA 94121 USA. [Li, Renhao] Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorders Ctr, Atlanta, GA 30322 USA. [Ware, Jerry] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. [Varki, Ajit] Univ Calif San Diego, Dept Cellular & Mol Med, Glycobiol Res & Training Ctr, San Diego, CA 92093 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 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2015 VL 25 IS 11 MA 61 BP 1247 EP 1247 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT7JR UT WOS:000362991500055 ER PT J AU Yu, WH Draghi, M Arevalo, C Zhao, P Lauffenburger, D Wells, L Alter, G AF Yu, Wen-Han Draghi, Monia Arevalo, Claudia Zhao, Peng Lauffenburger, Douglas Wells, Lance Alter, Galit TI Identification of broadly neutralizing antibody-HIV envelop glycans interaction fingerprints for HIV vaccine immunogen design SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology on Glycobiology - Accelerating Impact across the Biomedical Sciences CY DEC 01-04, 2015 CL San Francisco, CA SP Soc Glycobiol C1 [Yu, Wen-Han; Lauffenburger, Douglas] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Yu, Wen-Han; Draghi, Monia; Arevalo, Claudia; Alter, Galit] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Yu, Wen-Han; Draghi, Monia; Arevalo, Claudia; Alter, Galit] Harvard Univ, Cambridge, MA 02138 USA. [Zhao, Peng; Wells, Lance] Univ Georgia, Dept Biochem & Mol Biol, Complex Carbohydrate Res Ctr, Athens, GA 30602 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 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2015 VL 25 IS 11 MA 71 BP 1251 EP 1251 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT7JR UT WOS:000362991500065 ER PT J AU Dykstra, B Lee, J Donnelly, C Mortensen, L Lin, C Rossi, D Sackstein, R AF Dykstra, Bradford Lee, Jungmin Donnelly, Conor Mortensen, Luke Lin, Charles Rossi, Derrick Sackstein, Robert TI Comparative analysis of enforced a(1,3)-fucosylation using intracellular and extracellular methods SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology on Glycobiology - Accelerating Impact across the Biomedical Sciences CY DEC 01-04, 2015 CL San Francisco, CA SP Soc Glycobiol C1 [Dykstra, Bradford; Donnelly, Conor; Sackstein, Robert] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dykstra, Bradford; Lee, Jungmin; Donnelly, Conor; Lin, Charles; Rossi, Derrick; Sackstein, Robert] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lin, Charles] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Jungmin; Rossi, Derrick] Boston Childrens Hosp, Boston, MA USA. [Mortensen, Luke] Univ Georgia, Athens, GA 30602 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 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2015 VL 25 IS 11 MA 150 BP 1280 EP 1281 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CT7JR UT WOS:000362991500144 ER EF