FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Radomski, TR Good, CB Thorpe, CT Zhao, XH Marcum, ZA Glassman, PA Lowe, J Mor, MK Fine, MJ Gellad, WF AF Radomski, Thomas R. Good, Chester B. Thorpe, Carolyn T. Zhao, Xinhua Marcum, Zachary A. Glassman, Peter A. Lowe, John Mor, Maria K. Fine, Michael J. Gellad, Walid F. TI Variation in Formulary Management Practices Within the Department of Veterans Affairs Health Care System SO JOURNAL OF MANAGED CARE & SPECIALTY PHARMACY LA English DT Article ID MEDICAL-CENTER; NATIONAL FORMULARY; THERAPY; PHARMACY; COST; LOVASTATIN; BREAKING; PROGRAM; IMPACT; SWITCH AB BACKGROUND: All Department of Veterans Affairs Medical Centers (VAMCs) operate under a single national drug formulary, yet substantial variation in prescribing and spending exists across facilities. Local management of the national formulary may differ across VAMCs and may be one cause of this variation. OBJECTIVE: To characterize variation in the management of nonformulary medication requests and pharmacy and therapeutics (P&T) committee member perceptions of the formulary environment at VAMCs nationwide. METHODS: We performed an online survey of the chief of pharmacy and an additional staff pharmacist and physician on the P&T committee at all VAMCs. Respondents were asked questions regarding criteria for use for nonformulary medications, specific procedures for ordering nonformulary medications in general and specific lipid-lowering and diabetes agents, the appeals. process, and the formulary environment at their VAMCs. We compared responses across facilities and between chiefs of pharmacy, pharmacists, and physicians. RESULTS: A total of 212 chief pharmacists (n=80), staff pharmacists (n=78), and physicians (n=54) responded, for an overall response rate of 49%. In total, 107/143 (75%) different VAMCs were represented. The majority of VAMCs reported adhering to national criteria for use, with 38 (36%) being very adherent and 69 (65%) being mostly adherent. There was substantial variation between VAMCs regarding how nonformulary drugs were ordered, evaluated, and appealed. The nonformulary lipid-lowering drugs ezetimibe, rosuvastatin, and atorvastatin were viewable to providers in the order entry screen at 67 (63%), 67 (63%), and 64 (60%) VAMCs, respectively. The nonformulary diabetes medication pioglitazone was only viewable at 58 (55%) VAMCs. In the remaining VAMCs, providers could not order these nonformulary drugs through the normal order-entry process. For questions about the formulary environment, physician respondent perceptions differed from those of staff pharmacists and chief pharmacists. Compared with pharmacy chiefs and staff pharmacists, physicians were less likely to agree that providers at their VAMC prescribed too many nonformulary medications (47% and 44% vs. 12%, P<0.001), more likely to agree that providers must jump through too many hoops to prescribe nonformulary medication (5% and 3% vs. 25%, P<0.001), and more likely to agree that providers make an effort to convert new patients from non-formulary to formulary lipid-lowering (65% and 73% vs. 94%, P<0.02) and diabetic medications (49% and 50% vs. 88%, P<0.001). CONCLUSIONS: Although the Department of Veterans Affairs (VA) operates under a single national formulary, we found significant differences among VAMCs regarding their management of nonformulary medication requests. We also found differences among formulary leaders regarding their perception of the environment in which their VAMC's formulary is managed. These findings have important implications not just for VA, but for any organization that develops, implements, and manages drug formularies across multiple facilities. Copyright (C) 2016, Academy of Managed Care Pharmacy. All rights reserved. C1 [Gellad, Walid F.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Univ Dr 151c, Pittsburgh, PA 15240 USA. [Radomski, Thomas R.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med,Clin Instructor, Pittsburgh, PA USA. [Radomski, Thomas R.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity REs & Promotion, Clin Res Fellow, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Hines, IL USA. [Good, Chester B.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Core Investigator, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA USA. [Good, Chester B.] US Dept Vet Affairs, Pharm Benefits Management Serv, VA Ctr Medication Safety, Med Advisory Panel, Hines, IL USA. [Thorpe, Carolyn T.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Core Investigator, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, 718 Salk Hall, Pittsburgh, PA USA. [Zhao, Xinhua] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Statistic, Pittsburgh, PA USA. [Marcum, Zachary A.] Univ Pittsburgh, Sch Med, Dept Med, Dept Geriatr Med, Pittsburgh, PA USA. [Glassman, Peter A.] Calif State Univ Los Angeles, David Geffen Sch Med, Dept Med,Staff Phys, Clin Med,VA Greater Los Angles Hlthcare Syst, Los Angeles, CA USA. [Glassman, Peter A.] US Dept Vet Affairs, VA Ctr Med Safety Pharm Benefits Management Serv, Hines, IL USA. [Lowe, John] US Dept Vet Affairs, Pharm Benefits Management Serv, Pharm Compliance & Efficiency, Hines, IL USA. [Mor, Maria K.] VA Pittsburgh Hlthcare Syst, Biostat & Informat Core, Ctr Hlth Equtiy Res & Promotion, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Fine, Michael J.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Pittsburgh, PA USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Gellad, Walid F.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Pittsburgh, PA USA. RP Gellad, WF (reprint author), VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promotion, Pittsburgh, PA USA. EM walid.gellad@va.gov FU Health Resources and Services Administration T32 Training Grant; VA HSR&D Career Development Award FX Radomski is funded by a Health Resources and Services Administration T32 Training Grant. Gellad is funded by a VA HSR&D Career Development Award. The authors have no other conflicts of interest to disclose. NR 26 TC 2 Z9 2 U1 0 U2 0 PU ACAD MANAGED CARE PHARMACY PI ALEXANDRIA PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA SN 2376-0540 EI 2376-1032 J9 J MANAG CARE SPEC PH JI J. Manag. Care Spec. Pharm. PD FEB PY 2016 VL 22 IS 2 BP 114 EP U113 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA DN1BU UT WOS:000376802100003 PM 27015250 ER PT J AU Liu, XR Liu, J Zhao, SF Zhang, HY Cai, W Cai, MF Ji, XM Leak, RK Gao, YQ Chen, J Hu, XM AF Liu, Xiangrong Liu, Jia Zhao, Shangfeng Zhang, Haiyue Cai, Wei Cai, Mengfei Ji, Xunming Leak, Rehana K. Gao, Yanqin Chen, Jun Hu, Xiaoming TI Interleukin-4 Is Essential for Microglia/Macrophage M2 Polarization and Long-Term Recovery After Cerebral Ischemia SO STROKE LA English DT Article DE flow cytometry; interleukin-4; macrophages; neurological function; stroke ID BRAIN-INJURY; CNS REMYELINATION; SEX-DIFFERENCES; WHITE-MATTER; MICROGLIA; IL-4; STROKE; MICE; MACROPHAGES; DYNAMICS AB Background and Purpose-Interleukin-4 (IL-4) is a unique cytokine that may contribute to brain repair by regulating microglia/macrophage functions. Thus, we examined the effect of IL-4 on long-term recovery and microglia/macrophage polarization in 2 well-established stroke models. Methods-Transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion was induced in wild-type and IL-4 knockout C57/BL6 mice. In a separate cohort of wild-type animals, IL-4 (60 ng/d for 7 days) or vehicle was infused into the cerebroventricle after transient middle cerebral artery occlusion. Behavioral outcomes were assessed by the Rotarod, corner, foot fault, and Morris water maze tests. Neuronal tissue loss was verified by 2 independent neuron markers. Markers of classically activated (M1) and alternatively activated (M2) microglia were assessed by real-time polymerase chain reaction, immunofluorescence, and flow cytometry. Results-Loss of IL-4 exacerbated sensorimotor deficits and impaired cognitive functions <= 21 days post injury. In contrast to the delayed deterioration of neurological functions, IL-4 deficiency increased neuronal tissue loss only in the acute phase (5 days) after stroke and had no impact on neuronal tissue loss 14 or 21 days post injury. Loss of IL-4 promoted expression of M1 microglia/macrophage markers and impaired expression of M2 markers at 5 and 14 days post injury. Administration of IL-4 into the ischemic brain also enhanced long-term functional recovery. Conclusions-The cytokine IL-4 improves long-term neurological outcomes after stroke, perhaps through M2 phenotype induction in microglia/macrophages. These results are the first to suggest that immunomodulation with IL-4 is a promising approach to promote long-term functional recovery after stroke. C1 [Liu, Xiangrong; Zhao, Shangfeng; Zhang, Haiyue; Cai, Wei; Chen, Jun; Hu, Xiaoming] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Liu, Xiangrong; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Beijing, Peoples R China. [Liu, Jia; Cai, Mengfei; Gao, Yanqin; Chen, Jun; Hu, Xiaoming] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Chen, Jun; Hu, Xiaoming] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Hu, XM (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM hux2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU National Institutes of Health [NS092618, NS095671, NS089534]; American Heart Association [13SDG14570025]; Chinese Natural Science Foundation [81471209, 81171149, 81371306, 81228008]; Veteran's Affairs research career scientist award FX This work was supported by the National Institutes of Health grants NS092618 (to Dr Hu), NS095671 and NS089534 (to Dr Chen), grant 13SDG14570025 from the American Heart Association (to Dr Hu), the Chinese Natural Science Foundation grants 81471209 (to Dr Liu), 81171149, 81371306 (to Dr Gao), and 81228008 (to Dr Chen). Dr Chen is also supported by a Veteran's Affairs research career scientist award. NR 30 TC 8 Z9 9 U1 11 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2016 VL 47 IS 2 BP 498 EP + DI 10.1161/STROKEAHA.115.012079 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DN4MD UT WOS:000377040200042 PM 26732561 ER PT J AU Viswanathan, A Greenberg, SM Scheltens, P AF Viswanathan, Anand Greenberg, Steven M. Scheltens, Philip TI Role of Vascular Disease in Alzheimer-Like Progressive Cognitive Impairment SO STROKE LA English DT Editorial Material DE cognitive impairment; coronary artery disease; dementia; hypertension; lacunar infarct; stroke ID SMALL-VESSEL DISEASE; CEREBRAL AMYLOID ANGIOPATHY; RISK-FACTORS; DEMENTIA; DECLINE; OLDER; MICROINFARCTS; INFARCTION; STATEMENT; DIAGNOSIS C1 [Viswanathan, Anand; Greenberg, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Hemorrhag Stroke Res Program,Stroke Res Ctr, Boston, MA 02114 USA. [Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. RP Greenberg, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org FU NIA NIH HHS [K23AG02872605, P50 AG005134, P50AG005134, R01AG047975, R01 AG047975] NR 28 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2016 VL 47 IS 2 BP 577 EP 580 DI 10.1161/STROKEAHA.115.009010 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DN4MD UT WOS:000377040200057 PM 26604252 ER PT J AU Bartlett, ST Markmann, JF Johnson, P Korsgren, O Hering, BJ Scharp, D Kay, TWH Bromberg, J Odorico, JS Weir, GC Bridges, N Kandaswamy, R Stock, P Friend, P Gotoh, M Cooper, DKC Park, CG O'Connell, P Stabler, C Matsumoto, S Ludwig, B Choudhary, P Kovatchev, B Rickels, MR Sykes, M Wood, K Kraemer, K Hwa, A Stanley, E Ricordi, C Zimmerman, M Greenstein, J Montanya, E Otonkoski, T AF Bartlett, Stephen T. Markmann, James F. Johnson, Paul Korsgren, Olle Hering, Bernhard J. Scharp, David Kay, Thomas W. H. Bromberg, Jonathan Odorico, Jon S. Weir, Gordon C. Bridges, Nancy Kandaswamy, Raja Stock, Peter Friend, Peter Gotoh, Mitsukazu Cooper, David K. C. Park, Chung-Gyu O'Connell, Phillip Stabler, Cherie Matsumoto, Shinichi Ludwig, Barbara Choudhary, Pratik Kovatchev, Boris Rickels, Michael R. Sykes, Megan Wood, Kathryn Kraemer, Kristy Hwa, Albert Stanley, Edward Ricordi, Camillo Zimmerman, Mark Greenstein, Julia Montanya, Eduard Otonkoski, Timo TI Report from IPITA-TTS Opinion Leaders Meeting on the Future of beta-Cell Replacement SO TRANSPLANTATION LA English DT Article ID PLURIPOTENT STEM-CELLS; PANCREAS-KIDNEY TRANSPLANTATION; ISLET ALLOGRAFT SURVIVAL; SUBCUTANEOUS INSULIN INFUSION; CLOSED-LOOP CONTROL; ASSOCIATION CONSENSUS STATEMENT; PORCINE ENDOGENOUS RETROVIRUS; UNDERTAKING CLINICAL-TRIALS; TYPE-2 DIABETES-MELLITUS; ANTITHYMOCYTE GLOBULIN INDUCTION C1 [Bartlett, Stephen T.] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. [Markmann, James F.; Bromberg, Jonathan] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. [Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. [Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Korsgren, Olle] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Hering, Bernhard J.; Kandaswamy, Raja] Univ Minnesota, Dept Surg, Schulze Diabet Inst, Box 242 UMHC, Minneapolis, MN 55455 USA. [Scharp, David] Prodo Labs LLC, Irvine, CA USA. [Scharp, David] Scharp Lacy Res Inst, Irvine, CA USA. [Kay, Thomas W. H.] St Vincents Hosp, St Vincents Inst Med Res, Dept Med, Fitzroy, Vic 3065, Australia. [Kay, Thomas W. H.] Univ Melbourne, Melbourne, Vic 3010, Australia. [Odorico, Jon S.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Div Transplantat, Madison, WI USA. [Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weir, Gordon C.] Harvard Univ, Sch Med, Boston, MA USA. [Bridges, Nancy; Kraemer, Kristy] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Stock, Peter] Univ San Francisco, Med Ctr, Div Transplantat, San Francisco, CA 94117 USA. [Gotoh, Mitsukazu] Fukushima Med Univ, Dept Surg, Fukushima, Japan. [Cooper, David K. C.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Park, Chung-Gyu] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Xenotransplantat Res Ctr,Dept Microbiol & Immunol, Seoul, South Korea. [O'Connell, Phillip] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia. [Stabler, Cherie; Ricordi, Camillo] Univ Miami, Sch Med, Diabet Res Inst, Coral Gables, FL 33124 USA. [Matsumoto, Shinichi] Natl Ctr Global Hlth & Med, Tokyo, Japan. [Matsumoto, Shinichi] Otsuka Pharmaceut Factory Inc, Naruto, Japan. [Ludwig, Barbara] Tech Univ Dresden, Dept Med 3, D-01062 Dresden, Germany. [Ludwig, Barbara] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Ctr, Paul Langerhans Inst Dresden, Dresden, Germany. [Ludwig, Barbara] DZD German Ctr Diabet Res, Dresden, Germany. [Choudhary, Pratik] Kings Coll London, Weston Educ Ctr, Diabet Res Grp, London WC2R 2LS, England. [Kovatchev, Boris] Univ Virginia, Ctr Diabet Technol, Charlottesville, VA USA. [Rickels, Michael R.] Univ Penn, Dept Med, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Sykes, Megan] Coulmbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA. [Hwa, Albert] Juvenile Diabet Res Fdn, New York, NY USA. [Stanley, Edward] Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Stanley, Edward] Monash Univ, Melbourne, Vic 3004, Australia. [Zimmerman, Mark] BetaLogics, Raritan, NJ USA. [Greenstein, Julia] Juvenile Diabet Res Fdn, Discovery Res, New York, NY USA. [Montanya, Eduard] Univ Barcelona, Hosp Univ Bellvitge, CIBERDEM, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain. [Otonkoski, Timo] Univ Helsinki, Childrens Hosp, Helsinki, Finland. [Otonkoski, Timo] Univ Helsinki, Biomedicum Stem Cell Ctr, Helsinki, Finland. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT 517, Boston, MA 02114 USA. EM jmarkmann@partners.org RI Stabler, Cherie/E-8227-2011; OI Ricordi, Camillo/0000-0001-8092-7153 FU Diabetes Research and Wellness Foundation; Dompe Pharmaceuticals; beta-O2 Technologies LTD; Novartis Pharmaceuticals; Sanofi; JDRF FX This work was supported by generous educational grants by the Diabetes Research and Wellness Foundation and Dompe Pharmaceuticals. Additional funding was provided by beta-O2 Technologies LTD, Novartis Pharmaceuticals, Sanofi and the JDRF. NR 381 TC 10 Z9 10 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD FEB PY 2016 VL 100 SU 2 BP S1 EP S44 DI 10.1097/TP.0000000000001055 PG 44 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DN5QN UT WOS:000377125300001 PM 26840096 ER PT J AU Sousa, C AF Sousa, Cristina TI The Scientific Methods of Biology, Starting with Charles Darwin SO AMERICAN BIOLOGY TEACHER LA English DT Article DE Darwin; theory of evolution; inductionist method; hypothetico-deductive method; inquiry; questions ID UNIVERSAL COMMON ANCESTRY; ESCHERICHIA-COLI; KEY INNOVATION; EVOLUTION; POPULATION; SCIENCE; LIFE AB The choice of the scientific method to be used depends on the question to be investigated, the type of study being performed, and the maturity of the particular subdiscipline. I review the scientific methods frequently used in biology since Darwin, the aspects of the nature of science relevant for teaching and learning about evolution, and some recent studies that tested the theory of evolution and some of its features. I also present some guidelines for teachers, within an inquiry-based instructional framework, to facilitate students' understanding that hypothesis-driven and observation-driven studies are equally important and responsible for the advancement of scientific knowledge in the field of biology, both in the past and in the present. C1 [Sousa, Cristina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sousa, Cristina] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sousa, Cristina] Univ Porto, Fac Ciencias, Rua Campo Alegre 823, P-4100 Oporto, Portugal. RP Sousa, C (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Sousa, C (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.; Sousa, C (reprint author), Univ Porto, Fac Ciencias, Rua Campo Alegre 823, P-4100 Oporto, Portugal. EM up199502480@fc.up.pt FU Faculdade de Ciencias, Universidade do Porto, Portugal FX Special thanks to the ones who inspired me. The views expressed in this paper are my own. I thank the anonymous reviewers for useful comments and suggestions and Faculdade de Ciencias, Universidade do Porto, Portugal, for financial support. NR 58 TC 0 Z9 0 U1 16 U2 24 PU NATL ASSOC BIOLOGY TEACHERS INC PI RESTON PA 12030 SUNRISE VALLEY DR, #110, RESTON, VA 20191 USA SN 0002-7685 EI 1938-4211 J9 AM BIOL TEACH JI Am. Biol. Teach. PD FEB PY 2016 VL 78 IS 2 BP 109 EP 117 DI 10.1525/abt.2016.78.2.109 PG 9 WC Biology; Education, Scientific Disciplines SC Life Sciences & Biomedicine - Other Topics; Education & Educational Research GA DN0PL UT WOS:000376765700004 ER PT J AU Gibson, TE Bashan, A Cao, HT Weiss, ST Liu, YY AF Gibson, Travis E. Bashan, Amir Cao, Hong-Tai Weiss, Scott T. Liu, Yang-Yu TI On the Origins and Control of Community Types in the Human Microbiome SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID HUMAN GUT MICROBIOME; INTESTINAL MICROBIOTA; INTERACTION STRENGTH; FOOD-WEB; STABILITY; ENTEROTYPES; NETWORKS; MODELS; ASSOCIATIONS; ECOLOGY AB Microbiome-based stratification of healthy individuals into compositional categories, referred to as "enterotypes" or "community types", holds promise for drastically improving personalized medicine. Despite this potential, the existence of community types and the degree of their distinctness have been highly debated. Here we adopted a dynamic systems approach and found that heterogeneity in the interspecific interactions or the presence of strongly interacting species is sufficient to explain community types, independent of the topology of the underlying ecological network. By controlling the presence or absence of these strongly interacting species we can steer the microbial ecosystem to any desired community type. This open-loop control strategy still holds even when the community types are not distinct but appear as dense regions within a continuous gradient. This finding can be used to develop viable therapeutic strategies for shifting the microbial composition to a healthy configuration. C1 [Gibson, Travis E.; Bashan, Amir; Cao, Hong-Tai; Weiss, Scott T.; Liu, Yang-Yu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Cao, Hong-Tai] Univ So Calif, Dept Elect Engn, Los Angeles, CA 90089 USA. [Cao, Hong-Tai] Zhejiang Univ, Coll Elect Engn, Chu Kochen Honors Coll, Hangzhou 310003, Zhejiang, Peoples R China. [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Liu, YY (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.; Liu, YY (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM yyl@channing.harvard.edu FU National Institutes of Health [R01 HL091528]; John Templeton Foundation [51977] FX STW was supported by the National Institutes of Health (http://www.nih.gov) under grant number R01 HL091528 and TEG, YYL and AB were supported by the John Templeton Foundation (https://www.templeton.org) under grant number (51977). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 3 Z9 4 U1 10 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD FEB PY 2016 VL 12 IS 2 AR e1004688 DI 10.1371/journal.pcbi.1004688 PG 21 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA DM8AL UT WOS:000376582900031 PM 26866806 ER PT J AU Wang, T Ren, Z Ding, Y Fang, Z Sun, Z MacDonald, ML Sweet, RA Wang, JR Chen, W AF Wang, Ting Ren, Zhao Ding, Ying Fang, Zhou Sun, Zhe MacDonald, Matthew L. Sweet, Robert A. Wang, Jieru Chen, Wei TI FastGGM: An Efficient Algorithm for the Inference of Gaussian Graphical Model in Biological Networks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID EXPRESSION DATA; ASTHMA; LASSO; DISCOVERY; SELECTION AB Biological networks provide additional information for the analysis of human diseases, beyond the traditional analysis that focuses on single variables. Gaussian graphical model (GGM), a probability model that characterizes the conditional dependence structure of a set of random variables by a graph, has wide applications in the analysis of biological networks, such as inferring interaction or comparing differential networks. However, existing approaches are either not statistically rigorous or are inefficient for high-dimensional data that include tens of thousands of variables for making inference. In this study, we propose an efficient algorithm to implement the estimation of GGM and obtain p-value and confidence interval for each edge in the graph, based on a recent proposal by Ren et al., 2015. Through simulation studies, we demonstrate that the algorithm is faster by several orders of magnitude than the current implemented algorithm for Ren et al. without losing any accuracy. Then, we apply our algorithm to two real data sets: transcriptomic data from a study of childhood asthma and proteomic data from a study of Alzheimer's disease. We estimate the global gene or protein interaction networks for the disease and healthy samples. The resulting networks reveal interesting interactions and the differential networks between cases and controls show functional relevance to the diseases. In conclusion, we provide a computationally fast algorithm to implement a statistically sound procedure for constructing Gaussian graphical model and making inference with high-dimensional biological data. The algorithm has been implemented in an R package named "FastGGM". C1 [Wang, Ting; Wang, Jieru; Chen, Wei] Univ Pittsburgh, Dept Pediat, Childrens Hosp Pittsburgh UPMC, Div Pulm Med Allergy & Immunol, Pittsburgh, PA 15260 USA. [Ren, Zhao] Univ Pittsburgh, Dept Stat, Pittsburgh, PA USA. [Ding, Ying; Fang, Zhou; Sun, Zhe; Chen, Wei] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [MacDonald, Matthew L.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [Chen, Wei] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. RP Chen, W (reprint author), Univ Pittsburgh, Dept Pediat, Childrens Hosp Pittsburgh UPMC, Div Pulm Med Allergy & Immunol, Pittsburgh, PA 15260 USA.; Chen, W (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.; Chen, W (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. EM wei.chen@chp.edu OI Ding, Ying/0000-0003-1352-1000 FU VAPHS [BX000542]; UPMC Competitive Medical Research Fund; [MH16804]; [AG05133]; [AG027224]; [HG007358]; [P30CA047904] FX This work is supported by grants MH16804 (MLM), AG05133 (RAS), AG027224 (RAS), VAPHS grant BX000542 (RAS), UPMC Competitive Medical Research Fund (YD) and HG007358 (WC). The Biomedical Mass Spectrometry Center and UPCI Cancer Proteomics Facility are supported in part by award P30CA047904. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 2 Z9 2 U1 3 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD FEB PY 2016 VL 12 IS 2 AR e1004755 DI 10.1371/journal.pcbi.1004755 PG 16 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA DM8AL UT WOS:000376582900026 PM 26872036 ER PT J AU Spector, M AF Spector, Myron TI An auspicious decade for biomedical materials SO BIOMEDICAL MATERIALS LA English DT Editorial Material C1 [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. EM mspector@research.bwh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD FEB PY 2016 VL 11 IS 1 AR 010201 DI 10.1088/1748-6041/11/1/010201 PG 2 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DL2TX UT WOS:000375489200001 ER PT J AU Memic, A Alhadrami, HA Hussain, MA Aldhahri, M Al Nowaiser, F Al-Hazmi, F Oklu, R Khademhosseini, A AF Memic, Adnan Alhadrami, Hani A. Hussain, M. Asif Aldhahri, Musab Al Nowaiser, Fozia Al-Hazmi, Faten Oklu, Rahmi Khademhosseini, Ali TI Hydrogels 2.0: improved properties with nanomaterial composites for biomedical applications SO BIOMEDICAL MATERIALS LA English DT Article DE nanocomposite; hydrogel; biomedical applications; tissue engineering; drug delivery; network structure; stimuli-responsive ID CONTROLLED DRUG-RELEASE; NANOCOMPOSITE HYDROGELS; MECHANICAL-PROPERTIES; REGENERATIVE MEDICINE; BONE REGENERATION; HYBRID HYDROGELS; CLICK CHEMISTRY; GRAPHENE OXIDE; CARDIAC TISSUE; SCAFFOLDS AB The incorporation of nanomaterials in hydrogels (hydrated networks of crosslinked polymers) has emerged as a useful method for generating biomaterials with tailored functionality. With the available engineering approaches it is becoming much easier to fabricate nanocomposite hydrogels that display improved performance across an array of electrical, mechanical, and biological properties. In this review, we discuss the fundamental aspects of these materials as well as recent developments that have enabled their application. Specifically, we highlight synthesis and fabrication, and the choice of nanomaterials for multifunctionality as ways to overcome current material property limitations. In addition, we review the use of nanocomposite hydrogels within the framework of biomedical and pharmaceutical disciplines. C1 [Memic, Adnan; Aldhahri, Musab] King Abdulaziz Univ, Ctr Nanotechnol, Jeddah 21413, Saudi Arabia. [Memic, Adnan; Khademhosseini, Ali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Ctr Biomed Engn, Cambridge, MA 02138 USA. [Alhadrami, Hani A.] King Abdulaziz Univ, Fac Appl Med Sci, Dept Med Lab Technol, Jeddah 21413, Saudi Arabia. [Alhadrami, Hani A.] King Abdulaziz Univ, Ctr Innovat Personalized Med, Jeddah 21413, Saudi Arabia. [Alhadrami, Hani A.] King Abdulaziz Univ, King Fahd Med Res Ctr, Ctr Excellence Genom Med Res, Jeddah 21413, Saudi Arabia. [Hussain, M. Asif] King Abdulaziz Univ, Fac Engn, Dept Elect & Comp Engn, Jeddah 21413, Saudi Arabia. [Aldhahri, Musab] King Abdulaziz Univ, Fac Sci, Dept Biol, Jeddah, Saudi Arabia. [Al Nowaiser, Fozia] King Abdulaziz Univ, Dept Chem, Jeddah 21413, Saudi Arabia. [Al-Hazmi, Faten; Khademhosseini, Ali] King Abdulaziz Univ, Dept Phys, Jeddah 21413, Saudi Arabia. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging & Intervent Radiol, Boston, MA 02115 USA. [Khademhosseini, Ali] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Khademhosseini, Ali] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Memic, A (reprint author), King Abdulaziz Univ, Ctr Nanotechnol, Jeddah 21413, Saudi Arabia.; Memic, A; Khademhosseini, A (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Ctr Biomed Engn, Cambridge, MA 02138 USA.; Khademhosseini, A (reprint author), King Abdulaziz Univ, Dept Phys, Jeddah 21413, Saudi Arabia.; Khademhosseini, A (reprint author), Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.; Khademhosseini, A (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM amemic@kau.edu.sa; alik@rics.bwh.harvard.edu RI Hussain, Mohammad/K-3524-2012; Memic, Adnan/I-6138-2013; Faculty of, Sciences, KAU/E-7305-2017; OI Memic, Adnan/0000-0003-4639-8168; Khademhosseini, Ali/0000-0001-6322-8852 FU Deanship of Scientific Research (DSR), King Abdulaziz University [18-130-1434-HiCi]; National Science Foundation [EFRI-1240443]; IMMODGEL [602694]; National Institutes of Health [EB012597, AR057837, DE021468, HL099073, AI105024, AR063745] FX This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, under grant number 18-130-1434-HiCi. The authors, therefore, acknowledge technical and financial support. The authors would like to acknowledge funding from the National Science Foundation (EFRI-1240443), IMMODGEL (602694), and the National Institutes of Health (EB012597, AR057837, DE021468, HL099073, AI105024, AR063745). NR 88 TC 3 Z9 3 U1 29 U2 50 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD FEB PY 2016 VL 11 IS 1 AR 014104 DI 10.1088/1748-6041/11/1/014104 PG 15 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DL2TX UT WOS:000375489200005 PM 26694229 ER PT J AU Spector, M Lim, TC AF Spector, Myron Lim, Teck Chuan TI Injectable biomaterials: a perspective on the next wave of injectable therapeutics SO BIOMEDICAL MATERIALS LA English DT Article DE injectable matrices; stroma; gelatin; hyaluronic acid; covalent cross-linking ID MESENCHYMAL STEM-CELLS; SUBSTRATE STIFFNESS; MACULAR DEGENERATION; STROKE CAVITY; IN-VITRO; TISSUE; DIFFERENTIATION; SCAFFOLDS; HYDROGELS; DELIVERY AB We are experiencing a new wave of injectable therapeutics (namely/injectable biomaterials) to complement injectable drugs and injectable biologics, and to serve as the basis for injectable combinatorial therapeutics. Injectable biomaterials contribute to the treatment of the fluid-filled defects which often result from disease and injury, by providing the missing physical framework (i.e. the stroma). However, while injectable matrices may be necessary for the successful treatment of certain lesions, they will not likely be sufficient. Chemoattractants for select endogenous cells, or cells themselves, may need to be incorporated into the matrix prior to its injection to ensure the necessary cellular repopulation of the cavitary defect. These agents and others (drugs and biologics) delivered by the matrix represent the new category of injectable combinatorial therapeutics. C1 [Spector, Myron; Lim, Teck Chuan] VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA. [Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Dept Orthoped, Sch Med, Boston, MA 02115 USA. [Lim, Teck Chuan] Harvard Massachusetts Inst Technol, Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lim, Teck Chuan] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore. RP Spector, M (reprint author), VA Boston Healthcare Syst, Tissue Engn, Boston, MA 02130 USA.; Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Orthoped, Sch Med, Boston, MA 02115 USA. EM mspector@research.bwh.harvard.edu NR 67 TC 2 Z9 2 U1 3 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD FEB PY 2016 VL 11 IS 1 AR 014110 DI 10.1088/1748-6041/11/1/014110 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DL2TX UT WOS:000375489200011 PM 26836246 ER PT J AU Spiro, A Settersten, RA Aldwin, CM AF Spiro, Avron, III Settersten, Richard A. Aldwin, Carolyn M. TI Long-term Outcomes of Military Service in Aging and the Life Course: A Positive Re-envisioning SO GERONTOLOGIST LA English DT Article DE Health; Mental health; Well-being; Veterans; Resilience ID WORLD-WAR-II; STRESS-DISORDER SYMPTOMS; COMBAT; RESILIENCE; VETERANS; HEALTH; VIETNAM; TRAUMA; SPAN; PERSPECTIVE AB Most research on military service focuses on its short-term negative consequences, especially the mental and physical injuries of those deployed in warzones. However, studies of long-term outcomes reveal surprisingly positive effects of military service-both those early in adulthood that grow over time and others that can emerge later in life. These multidomain effects have been found in veterans of World War II and the Korean War and are now being seen in veterans of the Vietnam War. Although some are directly attributable to public policies such as the GI Bill, which facilitate educational and economic gains, there are personal developmental gains as well, including autonomy, emotional maturity and resilience, mastery, and leadership skills, that lead to better health and well-being in later life. These long-term effects vary across persons, change over time within persons, and often reflect processes of cumulative advantage and disadvantage. We propose a life-span model of the effects of military service that provides a perspective for probing both long-term positive and negative outcomes for aging veterans. We further explicate the model by focusing on both sociocultural dynamics and individual processes. We identify public-use data that can be examined to evaluate this model, and offer a set of questions that can be used to assess military service. Finally, we outline an agenda for dedicated inquiry into such effects and consider policy implications for the health and well-being of aging veterans in later life. C1 [Spiro, Avron, III] Boston Univ, VA Boston Healthcare Syst, Sch Publ Hlth, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Settersten, Richard A.] Oregon State Univ, Coll Publ Hlth & Human Sci, Hallie E Ford Ctr Hlth Children & Families, Corvallis, OR 97331 USA. [Aldwin, Carolyn M.] Oregon State Univ, Coll Publ Hlth & Human Sci, Ctr Hlth Aging Res, Corvallis, OR 97331 USA. RP Spiro, A (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,151MAV, Boston, MA 02130 USA. EM aspiro3@bu.edu FU National Institute on Aging [R24-AG039343]; Clinical Science Research and Development Service, U.S. Department of Veterans Affairs FX Preparation of this article was supported by the National Institute on Aging (R24-AG039343 to A. Spiro and C. M. Aldwin) and a Senior Research Career Scientist Award from the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs (to A. Spiro). NR 54 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 IS 1 SI SI BP 5 EP 13 DI 10.1093/geront/gnv093 PG 9 WC Gerontology SC Geriatrics & Gerontology GA DJ5AW UT WOS:000374220200002 PM 26655859 ER PT J AU Davison, EH Kaiser, AP Spiro, A Moye, J King, LA King, DW AF Davison, Eve H. Kaiser, Anica Pless Spiro, Avron, III Moye, Jennifer King, Lynda A. King, Daniel W. TI From Late-Onset Stress Symptomatology to Later-Adulthood Trauma Reengagement in Aging Combat Veterans: Taking a Broader View SO GERONTOLOGIST LA English DT Article DE Life review; Veterans; Life course/life span; Meaning-making; Posttraumatic growth ID POSTTRAUMATIC-STRESS; OLDER-ADULTS; MENTAL-HEALTH; ERA VETERANS; LATER LIFE; DISORDER; REMINISCENCE; EXPERIENCES; PREVALENCE; RISK AB About a decade ago we proposed the notion of late-onset stress symptomatology, to characterize the later-life emergence of symptoms related to early-life warzone trauma among aging combat Veterans. We hypothesized that aging-related challenges (role transition and loss, death of family members and friends, physical and cognitive decline) might lead to increased reminiscence, and possibly distress, among Veterans who had previously dealt successfully with earlier traumatic events. Recently, we have reexamined our earlier ideas, to better reflect our developing understanding of this phenomenon, and to incorporate more contemporary perspectives on posttraumatic growth and resilience. As a result, we have broadened our conceptualization to later-adulthood trauma reengagement (LATR). We suggest that in later life many combat Veterans confront and rework their wartime memories in an effort to find meaning and build coherence. Through reminiscence, life review, and wrestling with issues such as integrity versus despair, they intentionally reengage with experiences they avoided or managed successfully earlier in life, perhaps without resolution or integration. This article links LATR to classic gerontologic notions, and elaborates how the LATR process can lead positively to personal growth or negatively to increased symptomatology. We also address the role of preventive intervention in enhancing positive outcomes for Veterans who reengage with their wartime memories in later life. C1 [Davison, Eve H.; Kaiser, Anica Pless; King, Lynda A.; King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Davison, Eve H.; Kaiser, Anica Pless] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Moye, Jennifer] VA Boston Healthcare Syst, Brockton, MA USA. [Moye, Jennifer] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02215 USA. [King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Davison, EH (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM eve.davison@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Behavioral Science Division of the VA National Center for Posttraumatic Stress Disorder, VA Boston Healthcare System; U.S. Department of Veteran Affairs, Clinical Science RD Service FX This research was supported by funding from the Behavioral Science Division of the VA National Center for Posttraumatic Stress Disorder, VA Boston Healthcare System. Avron Spiro was supported by a Senior Research Career Scientist award from the U.S. Department of Veteran Affairs, Clinical Science R&D Service. NR 44 TC 3 Z9 3 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 IS 1 SI SI BP 14 EP 21 DI 10.1093/geront/gnv097 PG 8 WC Gerontology SC Geriatrics & Gerontology GA DJ5AW UT WOS:000374220200003 PM 26553735 ER PT J AU Padula, CB Weitlauf, JC Rosen, AC Reiber, G Cochrane, BB Naughton, MJ Li, WJ Rissling, M Yaffe, K Hunt, JR Stefanick, ML Goldstein, MK Espeland, MA AF Padula, Claudia B. Weitlauf, Julie C. Rosen, Allyson C. Reiber, Gayle Cochrane, Barbara B. Naughton, Michelle J. Li, Wenjun Rissling, Michelle Yaffe, Kristine Hunt, Julie R. Stefanick, Marcia L. Goldstein, Mary K. Espeland, Mark A. TI Longitudinal Cognitive Trajectories of Women Veterans from the Women's Health Initiative Memory Study SO GERONTOLOGIST LA English DT Article DE Women; Veterans; Cognition; Cognitive decline; Risk factors ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; RISK-FACTORS; CARDIOVASCULAR-DISEASE; HORMONE-THERAPY; IMPAIRMENT; DEMENTIA; DECLINE; DYSLIPIDEMIA AB Purpose of the Study: A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI). Design and Methods: We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods. Results: Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke). Implications: Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve. C1 [Padula, Claudia B.; Weitlauf, Julie C.; Rosen, Allyson C.] VA Palo Alto Hlth Care Syst, Sierra Pacific MIRECC, 3801 Miranda Ave, Palo Alto, CA 94304 USA. [Padula, Claudia B.; Weitlauf, Julie C.; Rosen, Allyson C.] Stanford Univ, Dept Psychiat & Behav Sci, 3801 Miranda Ave, Palo Alto, CA 94304 USA. [Weitlauf, Julie C.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Palo Alto, CA USA. [Reiber, Gayle] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Naughton, Michelle J.] Ohio State Univ, Coll Med, Div Populat Sci, Columbus, OH 43210 USA. [Li, Wenjun] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Li, Wenjun] Univ Massachusetts, Sch Med, Dept Prevent & Behav Med, Worcester, MA USA. [Rissling, Michelle] Mid Atlantic MIRECC, Durham VA Med Ctr, Durham, NC USA. [Yaffe, Kristine] Sierra Pacif MIRECC, San Francisco VA Med Ctr, UCSF Dept Psychiat Neurol & Epidemiol & Biostat, San Francisco, CA USA. [Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Stanford Ctr Prevent Res, Dept Med, Stanford, CA 94305 USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Goldstein, Mary K.] Stanford Univ, Sch Med, VA Palo Alto Hlth Care Syst, GRECC,Dept Med,Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA. [Espeland, Mark A.] Wake Forest Sch Med, Dept Biostat Sci, One Med Ctr Blvd, Winston Salem, NC USA. RP Padula, CB (reprint author), VA Palo Alto Hlth Care Syst, Sierra Pacific MIRECC, 3801 Miranda Ave, Palo Alto, CA 94304 USA.; Padula, CB (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM padula@stanford.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health; U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health; and the U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 46 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 IS 1 SI SI BP 115 EP 125 DI 10.1093/geront/gnv663 PG 11 WC Gerontology SC Geriatrics & Gerontology GA DJ5AW UT WOS:000374220200013 PM 26615021 ER PT J AU Karel, MJ Teri, L McConnell, E Visnic, S Karlin, BE AF Karel, Michele J. Teri, Linda McConnell, Eleanor Visnic, Stephanie Karlin, Bradley E. TI Effectiveness of Expanded Implementation of STAR-VA for Managing Dementia-Related Behaviors Among Veterans SO GERONTOLOGIST LA English DT Article DE Interdisciplinary training; Dementia; Challenging behaviors; Veterans; Nursing homes ID LONG-TERM-CARE; NEUROPSYCHIATRIC SYMPTOMS; HEALTH; MANAGEMENT; TOOLKIT; ANXIETY; HOMES AB Purpose of the Study: Nonpharmacological, psychosocial approaches are first-line treatments for managing behavioral symptoms in dementia, but they can be challenging to implement in long-term care settings. The Veterans Health Administration implemented STAR-VA, an interdisciplinary behavioral approach for managing challenging dementia-related behaviors in its Community Living Center (CLCs, nursing home care) settings. This study describes how the program was implemented and provides an evaluation of Veteran clinical outcomes and staff feedback on the intervention. Design and Methods: One mental health professional and registered nurse team from 17 CLCs completed STAR-VA training, which entailed an experiential workshop followed by 6 months of expert consultation as they worked with their teams to implement STAR-VA with Veterans identified to have challenging dementia-related behaviors. The frequency and severity of target behaviors and symptoms of depression, anxiety, and agitation were evaluated at baseline and at intervention completion. Staff provided feedback regarding STAR-VA feasibility and impact. Results: Seventy-one Veterans completed the intervention. Behaviors clustered into 6 types: care refusal or resistance, agitation, aggression, vocalization, wandering, and other. Frequency and severity of target behaviors and symptoms of depression, anxiety, and agitation all significantly decreased, with overall effect sizes of 1 or greater. Staff rated both benefits for Veterans and program feasibility favorably. Implications: This evaluation supports the feasibility and effectiveness of STAR-VA, an interdisciplinary, behavioral intervention for managing challenging behaviors among residents with dementia in CLCs. C1 [Karel, Michele J.] US Dept Vet Affairs, Mental Hlth Serv, Cent Off, Washington, DC USA. [Teri, Linda] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [McConnell, Eleanor] Durham VA Geriatr Res Educ & Clin Ctr, Durham, NC USA. [McConnell, Eleanor] Duke Univ, Sch Med, Durham, NC USA. [Visnic, Stephanie] Vet Affairs Ann Arbor Healthcare Syst, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. [Karlin, Bradley E.] Educ Dev Ctr Inc, New York, NY USA. [Karlin, Bradley E.] Northeastern Univ, Bouve Coll Hlth Sci, Sch Nursing, Boston, MA 02115 USA. RP Karel, MJ (reprint author), VA Cent Off, Mental Hlth Serv 10P4M, 1575 1 St NW, Washington, DC 20420 USA. EM Michele.Karel@va.gov FU Mental Health Services, U. S. Department of Veterans Affairs (VA) Central Office FX This project was supported by Mental Health Services, U. S. Department of Veterans Affairs (VA) Central Office. NR 36 TC 4 Z9 4 U1 3 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 IS 1 SI SI BP 126 EP 134 DI 10.1093/geront/gnv068 PG 9 WC Gerontology SC Geriatrics & Gerontology GA DJ5AW UT WOS:000374220200014 PM 26185155 ER PT J AU Sandoughdaran, S Sadeghipour, H Sadeghipour, HR AF Sandoughdaran, Saleh Sadeghipour, Hamed Sadeghipour, Hamid Reza TI Effect of acute lithium administration on penile erection: involvement of nitric oxide system SO INTERNATIONAL JOURNAL OF REPRODUCTIVE BIOMEDICINE LA English DT Article DE Lithium; Erectile dysfunction; Nitric oxide ID NONCHOLINERGIC-MEDIATED RELAXATION; ENDOTHELIUM-DEPENDENT RELAXATION; RAT CORPUS CAVERNOSUM; FORCED SWIMMING TEST; SEXUAL FUNCTION; BIPOLAR DISORDER; CYCLOOXYGENASE PATHWAYS; MOOD DISORDERS; MANIC PATIENTS; L-ARGININE AB Background: Lithium has been the treatment of choice for bipolar disorder (BD) for many years. Although erectile dysfunction is a known adverse effect of this drug, the mechanism of action by which lithium affects erectile function is still unknown. Objective: The aim was to investigate the possible involvement of nitric oxide (NO) in modulatory effect of lithium on penile erection (PE). We further evaluated the possible role of Sildenafil in treatment of lithium-induced erectile dysfunction. Materials and Methods: Erectile function was determined using rat model of apomorphine-induced erections. For evaluating the effect of lithium on penile erection, rats received intraperitoneal injection of graded doses of lithium chloride 30 mins before subcutaneous injection of apomorphine. To determine the possible role of NO pathway, sub-effective dose of N (G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, was administered 15 min before administration of sub-effective dose of lithium chloride. In other separate experimental groups, sub-effective dose of the nitric oxide precursor, L-arginine, or Sildenafil was injected into the animals 15 min before administration of a potent dose of lithium. 30 min after administration of lithium chloride, animals were assessed in apomorphine test. Serum lithium levels were measured 30 min after administration of effective dose of lithium. Results: Lithium at 50 and 100 mg/kg significantly decreased number of PE (p<0.001), whereas at lower doses (5, 10 and 30 mg/kg) had no effect on apomorphine induced PE. The serum Li+ level of rats receiving 50 mg/kg lithium was 1 +/- 0.15 mmol/L which is in therapeutic range of lithium. The inhibitory effect of Lithium was blocked by administration of sub-effective dose of nitric oxide precursor L-arginine (100 mg/kg) (p<0.001) and sildenafil (3.5 mg/kg) (p<0.001) whereas pretreatment with a low and sub-effective dose of L-NAME (10 mg/kg) potentiated sub-effective dose of lithium, (p<0.001). Conclusion: These results suggest acute treatments with lithium cause erectile dysfunction in an in-vivo rat model. Furthermore it seems that the NO pathway might play role in erectile dysfunction associated with lithium treatment. Findings also suggest that Sildenafil may be effective in treatment of lithium-associated erectile dysfunction. C1 [Sandoughdaran, Saleh] Shahid Beheshti Univ Med Sci, Shohada E Tajrish Hosp, Dept Radiat Oncol, Fac Med, Tehran, Iran. [Sadeghipour, Hamed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Sadeghipour, Hamid Reza] Univ Tehran Med Sci, Sch Med, Dept Physiol, Tehran, Iran. RP Sadeghipour, HR (reprint author), Univ Tehran Med Sci, Dept Physiol, Poursina Ave, Tehran, Iran. EM sadeghipour@tums.ac.ir NR 49 TC 0 Z9 0 U1 0 U2 0 PU SHAHID SADOUGHI UNIV MEDICAL SCIENCES YAZD PI YAZD PA RESEARCH & CLINICAL CENTER FOR INFERTILITY, PO BOX 89195-999, YAZD, 89195-741, IRAN SN 2476-4108 EI 2476-3772 J9 Int J Reprod Biomed JI Int. J. Reprod. Biomed. PD FEB PY 2016 VL 14 IS 2 BP 109 EP 116 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DL4BW UT WOS:000375579000006 PM 27200425 ER PT J AU Dinh, KT Golden, KE Ponce, DPM Raja, AS Miller, ES AF Dinh, Kathryn T. Golden, Katie E. Ponce, Daphne P. Morrison Raja, Ali S. Miller, Emily S. TI AN UNUSUAL TREATMENT FOR CARDIAC ISCHEMIA SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID COMPRESSION C1 [Dinh, Kathryn T.] Harvard Univ, Sch Med, Boston, MA 02118 USA. [Golden, Katie E.; Ponce, Daphne P. Morrison; Raja, Ali S.; Miller, Emily S.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA 02118 USA. [Golden, Katie E.; Ponce, Daphne P. Morrison; Raja, Ali S.; Miller, Emily S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Golden, Katie E.; Ponce, Daphne P. Morrison] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. RP Miller, ES (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02118 USA. NR 9 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 FEB PY 2016 VL 50 IS 2 BP 325 EP 329 PG 5 WC Emergency Medicine SC Emergency Medicine GA DI2BB UT WOS:000373299600034 PM 26514309 ER PT J AU Patel, SG Ahnen, DJ Kinney, AY Horick, N Finkelstein, DM Hill, DA Lindor, NM MaCrae, F Lowery, JT AF Patel, Swati G. Ahnen, Dennis J. Kinney, Anita Y. Horick, Nora Finkelstein, Dianne M. Hill, Deirdre A. Lindor, Noralane M. MaCrae, Finlay Lowery, Jan T. TI Knowledge and Uptake of Genetic Counseling and Colonoscopic Screening Among Individuals at Increased Risk for Lynch Syndrome and their Endoscopists from the Family Health Promotion Project SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; SOCIETY-TASK-FORCE; RANDOMIZED-TRIAL; HEREDITARY; SURVEILLANCE; MANAGEMENT; BEHAVIOR; HNPCC; GUIDELINES; CRITERIA AB OBJECTIVES: Individuals whose families meet the Amsterdam II clinical criteria for hereditary non-polyposis colorectal cancer are recommended to be referred for genetic counseling and to have colonoscopic screening every 1-2 years. To assess the uptake and knowledge of guideline-based genetic counseling and colonoscopic screening in unaffected members of families who meet Amsterdam II criteria and their treating endoscopists. METHODS: Participants in the Family Health Promotion Project who met the Amsterdam II criteria were surveyed regarding their knowledge of risk-appropriate guidelines for genetic counseling and colonoscopy screening. Endoscopy/pathology reports were obtained from patients screened during the study to determine the follow-up recommendations made by their endoscopists. Survey responses were compared using Fisher's Exact and the. 2 test. Concordance in participant/provider-reported surveillance interval was assessed using the kappa statistic. RESULTS: Of the 165 participants, the majority (98%) agreed that genetics and family history are important predictors of CRC, and 63% had heard of genetic testing for CRC, although only 31% reported being advised to undergo genetic counseling by their doctor, and only 7% had undergone genetic testing. Only 26% of participants reported that they thought they should have colonoscopy every 1-2 years and 30% of endoscopists for these participants recommended 1-2-year follow-up colonoscopy. There was a 65% concordance (weighted kappa 0.42, 95% CI 0.24-0.61) between endoscopist recommendations and participant reports regarding screening intervals. CONCLUSIONS: A minority of individuals meeting Amsterdam II criteria in this series have had genetic testing and reported accurate knowledge of risk-appropriate screening, and only a small percentage of their endoscopists provided them with the appropriate screening recommendations. There was moderate concordance between endoscopist recommendations and participant knowledge suggesting that future educational interventions need to target both health-care providers and their patients. C1 [Patel, Swati G.; Ahnen, Dennis J.] Univ Colorado, Div Gastroenterol & Hepatol, Dept Med, Aurora, CO USA. [Patel, Swati G.] Vet Adm Med Ctr, Denver, CO USA. [Ahnen, Dennis J.] Gastroenterol Rockies, Boulder, CO USA. [Kinney, Anita Y.] Univ New Mexico, Dept Internal Med, Albequerque, NM USA. [Horick, Nora; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Finkelstein, Dianne M.] Harvard Univ, Boston, MA 02115 USA. [Hill, Deirdre A.] Univ New Mexico, Dept Internal Med, Div Epidemiol, Albuquerque, NM 87131 USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [MaCrae, Finlay] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Dept Colorectal Med & Genet, Melbourne, Vic 3010, Australia. [Lowery, Jan T.] Univ Colorado, Sch Publ Hlth, Aurora, CO USA. RP Patel, SG (reprint author), 12631 East 17th Ave,Campus Box 158, Aurora, CO 80045 USA. EM Swati.Patel@ucdenver.edu FU National Cancer Institute [UM1 CA167551]; USC Consortium Colorectal Cancer Family Registry [U01/U24CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01/U24CA074800]; Seattle Colorectal Cancer Family Registry [U01/U24CA074794]; Cancer Surveillance System of the Fred Hutchinson Cancer Research Center [N01-CN-67009, N01-PC-35142]; Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute [HHSN2612013000121]; Fred Hutchinson Cancer Research Center; National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000035C] FX This work was supported by grant UM1 CA167551 from the National Cancer Institute and through cooperative agreements with the following CCFR centers: USC Consortium Colorectal Cancer Family Registry U01/U24CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01/U24CA074800), and Seattle Colorectal Cancer Family Registry (U01/U24CA074794). Seattle CCFR research was also supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which was funded by Control Nos. N01-CN-67009 (1996-2003) and N01-PC-35142 (2003-2010) and Contract No. HHSN2612013000121 (2010-2017) from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center. Similarly, the collection of cancer incidence data used in this study for LA country was also supported by the California Department of Public Health, as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885, and the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000035C awarded to the University of Southern California. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute, any of the collaborating centers in the Colon Cancer Family Registry (CCFR), the State of California Department of Public Health, or the Centers for Disease Control and Prevention or their Contractors and Subcontractors, nor does mention of trade names, commercial products, or organizations imply endorsement. NR 24 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2016 VL 111 IS 2 BP 285 EP 293 DI 10.1038/ajg.2015.397 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DL1NS UT WOS:000375399500026 PM 26856748 ER PT J AU Reardon, DA Gokhale, PC Klein, SR Ligon, KL Rodig, SJ Ramkissoon, SH Jones, KL Conway, AS Liao, XY Zhou, J Wen, PY Van Den Abbeele, AD Hodi, FS Qin, L Kohl, NE Sharpe, AH Dranoff, G Freeman, GJ AF Reardon, David A. Gokhale, Prafulla C. Klein, Sarah R. Ligon, Keith L. Rodig, Scott J. Ramkissoon, Shakti H. Jones, Kristen L. Conway, Amy Saur Liao, Xiaoyun Zhou, Jun Wen, Patrick Y. Van Den Abbeele, Annick D. Hodi, F. Stephen Qin, Lei Kohl, Nancy E. Sharpe, Arlene H. Dranoff, Glenn Freeman, Gordon J. TI Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID NEWLY-DIAGNOSED GLIOBLASTOMA; EXPRESSION; TUMORS; CELLS; IMMUNOTHERAPY; BEVACIZUMAB; SURVIVAL; TIM-3; TRIAL AB Inhibition of immune checkpoints, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and its ligand PD-L1, has demonstrated exciting and durable remissions across a spectrum of malignancies. Combinatorial regimens blocking complementary immune checkpoints further enhance the therapeutic benefit. The activity of these agents for patients with glioblastoma, a generally lethal primary brain tumor associated with significant systemic and microenvironmental immunosuppression, is not known. We therefore systematically evaluated the antitumor efficacy of murine antibodies targeting a broad panel of immune checkpoint molecules, including CTLA-4, PD-1, PD-L1, and PD-L2 when administered as single-agent therapy and in combinatorial regimens against an orthotopic, immunocompetent murine glioblastoma model. In these experiments, we observed long-term tumor-free survival following single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy in 50%, 20%, and 15% of treated animals, respectively. Combination therapy of anti-CTLA-4 plus anti-PD-1 cured 75% of the animals, even against advanced, later-stage tumors. In long-term survivors, tumor growth was not seen upon intracranial tumor rechallenge, suggesting that tumor-specific immune memory responses were generated. Inhibitory immune checkpoint blockade quantitatively increased activated CD8(+) and natural killer cells and decreased suppressive immune cells in the tumor microenvironment and draining cervical lymph nodes. Our results support prioritizing the clinical evaluation of PD-1, PD-L1, and CTLA-4 single-agent targeted therapy as well as combination therapy of CTLA-4 plus PD-1 blockade for patients with glioblastoma. (C) 2015 AACR. C1 [Reardon, David A.; Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Neurooncol, 75 Francis St, Boston, MA 02115 USA. [Reardon, David A.; Klein, Sarah R.; Ligon, Keith L.; Liao, Xiaoyun; Hodi, F. Stephen; Dranoff, Glenn; Freeman, Gordon J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA. [Gokhale, Prafulla C.] Brigham & Womens Hosp, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, 75 Francis St, Boston, MA 02115 USA. [Gokhale, Prafulla C.; Jones, Kristen L.; Conway, Amy Saur; Van Den Abbeele, Annick D.; Qin, Lei; Kohl, Nancy E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Lurie Family Imaging Ctr, 75 Francis St, Boston, MA 02115 USA. [Ligon, Keith L.; Ramkissoon, Shakti H.; Zhou, Jun] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, 75 Francis St, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Van Den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Van Den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Kohl, Nancy E.] Blueprint Med, 38 Sidney St, Cambridge, MA 02139 USA. [Dranoff, Glenn] Novartis Inst BioMed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 2134, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu FU NIH from NCI [U54CA163125, P50 CA101942] FX NIH funding support was from NCI U54CA163125 and NCI P50 CA101942 (to A.S. Conway and G.J. Freeman). NR 21 TC 13 Z9 13 U1 6 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD FEB PY 2016 VL 4 IS 2 BP 124 EP 135 DI 10.1158/2326-6066.CIR-15-0151 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA DL1QV UT WOS:000375407800006 PM 26546453 ER PT J AU Kopacz, MS Rasmussen, KA Searle, RF Wozniak, BM Titus, CE AF Kopacz, Marek S. Rasmussen, Kathy A. Searle, Robert F. Wozniak, Barbara M. Titus, Caitlin E. TI Veterans, guilt, and suicide risk: An opportunity to collaborate with chaplains? SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Editorial Material ID PASTORAL CARE SERVICES; MOOD DISORDERS; DEPRESSION; FORGIVENESS; PERSONNEL; IDEATION; THERAPY; COMBAT; SHAME C1 [Kopacz, Marek S.; Rasmussen, Kathy A.; Titus, Caitlin E.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. [Rasmussen, Kathy A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Searle, Robert F.] US Dept Vet Affairs, Canandaigua VA Med Ctr, Canandaigua, NY USA. [Wozniak, Barbara M.] Jagiellonian Univ, Coll Med, Dept Med Sociol, Epidemiol & Prevent Med, Krakow, Poland. RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov NR 40 TC 1 Z9 1 U1 1 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 EI 1939-2869 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD FEB PY 2016 VL 83 IS 2 BP 101 EP 105 DI 10.3949/ccjm.83a.15070 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA DK3TR UT WOS:000374840800006 PM 26871385 ER PT J AU Hernandez, N Pais, VM AF Hernandez, Natalia Pais, Vernon M., Jr. TI Diagnostic and management considerations for nephrolithiasis in the gravid patient SO CLINICAL NEPHROLOGY LA English DT Article DE urolithiasis; kidney stones; pregnancy; imaging; metabolic evaluation; treatment ID PREGNANT-WOMEN; KIDNEY-STONES; UROLITHIASIS; CALCULI; URETEROSCOPY; TOMOGRAPHY; UROGRAPHY; EXPOSURE AB Renal colic is recognized as one of the most common causes of non-obstetric hospitalization during pregnancy. Furthermore, both symptomatic urolithiasis and its management have been associated with preterm labor, markedly amplifying the "typical" concerns of either pregnancy or stone passage alone. As those specializing in the care of stone disease are likely to be involved in the management of suspected renal colic in the pregnant woman, it is imperative to be informed of strategies and pitfalls in the evaluation and treatment of urinary tract stones in this population. C1 [Hernandez, Natalia] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Pais, Vernon M., Jr.] Geisel Sch Med Dartmouth, Dept Surg, Urol Sect, Lebanon, NH 03766 USA. RP Pais, VM (reprint author), Geisel Sch Med Dartmouth, Dept Surg, Urol Sect, Lebanon, NH 03766 USA. EM Vernon.m.pais.jr@hitchcock.org NR 38 TC 0 Z9 0 U1 1 U2 2 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD FEB PY 2016 VL 85 IS 2 BP 70 EP 76 DI 10.5414/CN108770 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DL2MY UT WOS:000375470600002 PM 26709525 ER PT J AU Hsu, WC Lau, KHK Huang, RY Ghiloni, S Le, H Gilroy, S Abrahamson, M Moore, J AF Hsu, William C. Lau, Ka Hei Karen Huang, Ruyi Ghiloni, Suzanne Le, Hung Gilroy, Scott Abrahamson, Martin Moore, John TI Utilization of a Cloud-Based Diabetes Management Program for Insulin Initiation and Titration Enables Collaborative Decision Making Between Healthcare Providers and Patients SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID TO-TARGET TRIAL; GLUCOSE-LOWERING DRUGS; CENTERED APPROACH; NAIVE PEOPLE; NPH INSULIN; ADD-ON; DETEMIR; GLARGINE; HYPERGLYCEMIA; MAINTENANCE AB Background: Overseeing proper insulin initiation and titration remains a challenging task in diabetes care. Recent advances in mobile technology have enabled new models of collaborative care between patients and healthcare providers (HCPs). We hypothesized that the adoption of such technology could help individuals starting basal insulin achieve better glycemic control compared with standard clinical practice. Materials and Methods: This was a 12 +/- 2-week randomized controlled study with 40 individuals with type 2 diabetes who were starting basal insulin due to poor glycemic control. The control group (n = 20) received standard face-to-face care and phone follow-up as needed in a tertiary center, whereas the intervention group (n = 20) received care through the cloud-based diabetes management program where regular communications about glycemic control and insulin doses were conducted via patient self-tracking tools, shared decision-making interfaces, secure text messages, and virtual visits (audio, video, and shared screen control) instead of office visits. Results: By intention-to-treat analysis, the intervention group achieved a greater hemoglobin A1c decline compared with the control group (3.2 +/- 1.5% vs. 2.0% +/- 2.0%; P = 0.048). The Diabetes Treatment Satisfaction Questionnaire showed a significant improvement in the intervention group compared with the control group (an increase of 10.1 +/- 11.7 vs. 2.1 +/- 6.5 points; P = 0.01). HCPs spent less time with patients in the intervention group compared with those in the control group (65.9 min per subject vs. 81.6 min per subject). However, the intervention group required additional training time to use the mobile device. Conclusions: Mobile health technology could be an effective tool in sharing data, enhancing communication, and improving glycemic control while enabling collaborative decision making in diabetes care. C1 [Hsu, William C.; Lau, Ka Hei Karen; Ghiloni, Suzanne; Abrahamson, Martin] Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02115 USA. [Huang, Ruyi] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Huang, Ruyi] E Da Hosp, Kaohsiung, Taiwan. [Huang, Ruyi] I Shou Univ, Sch Med, Kaohsiung, Taiwan. [Le, Hung] Univ Massachusetts, Sch Med, Worcester, MA USA. [Gilroy, Scott; Moore, John] MIT, Media Lab, Cambridge, MA 02139 USA. RP Hsu, WC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02115 USA. EM william.hsu@joslin.harvard.edu NR 28 TC 5 Z9 5 U1 2 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB PY 2016 VL 18 IS 2 BP 59 EP 67 DI 10.1089/dia.2015.0160 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DK8EW UT WOS:000375161000004 PM 26645932 ER PT J AU Greenblatt, EE Winkler, T Harris, RS Kelly, VJ Kone, M Katz, I Martin, AR Caillibotte, G Venegas, J AF Greenblatt, Elliot Eliyahu Winkler, Tilo Harris, Robert Scott Kelly, Vanessa Jane Kone, Mamary Katz, Ira Martin, Andrew R. Caillibotte, George Venegas, Jose TI What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY LA English DT Article DE aerosol deposition; asthma; bronchoconstriction; escape fractions; sedimentation; ventilation ID REGIONAL VENTILATION; INHALED PARTICLES; DELIVERY; AIR; METHACHOLINE; MODELS AB Background: A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability. Methods: A theoretical framework was formulated to integrate four factors affecting aerosol deposition: differences in ventilation, in how air vs. aerosol distribute at each bifurcation, in the fraction of aerosol escaping feeding airways, and in the fraction of aerosol reaching the periphery that is exhaled. These factors were quantified in 12 of the subjects using PET-CT measurements of relative specific deposition sD*, relative specific ventilation sV* (measured with dynamic PET or estimated as change in expansion between two static HRCTs), average lobar expansion F-VOL, and breathing frequency measured during aerosol inhalation f(N). Results: The fraction of the variance of sD* explained by sV* (0.38), by bifurcation effects (0.38), and by differences in deposition along feeding airways (0.31) were similar in magnitude. We could not directly estimate the contribution of aerosol that was exhaled. Differences in expansion did not explain any fraction of the variability in sD* among lobes. The dependence of sD* on sV* was high in subjects breathing with low f(N), but weakened among those breathing faster. Finally, sD*/sV* showed positive dependence on F-VOL among low f(N) subjects, while the dependence was negative among high f(N) subjects. Conclusion: The theoretical framework allowed us to analyze experimentally measured aerosol deposition imaging data. When considering bronchoconstricted asthmatic subjects, a dynamic measurement of ventilation is required to evaluate its effect on aerosol transport. The mechanisms behind the identified effects of f(N) and F-VOL on aerosol deposition need further study and may have important implications for aerosol therapy in subjects with heterogeneous ventilation. C1 [Greenblatt, Elliot Eliyahu] MIT, Dept Mech Engn, Boston, MA USA. [Greenblatt, Elliot Eliyahu; Winkler, Tilo; Harris, Robert Scott; Kelly, Vanessa Jane; Kone, Mamary; Venegas, Jose] Massachusetts Gen Hosp, Edwards 410A 55 Fruit St, Boston, MA 02114 USA. [Greenblatt, Elliot Eliyahu; Winkler, Tilo; Harris, Robert Scott; Kelly, Vanessa Jane; Kone, Mamary; Venegas, Jose] Harvard Univ, Sch Med, Boston, MA USA. [Katz, Ira; Caillibotte, George] Air Liquide Sante Int, R&D Med, Les Loges En Josas, France. [Katz, Ira] Lafayette Coll, Dept Mech Engn, Easton, PA 18042 USA. [Martin, Andrew R.] Univ Alberta, Dept Mech Engn, Edmonton, AB, Canada. RP Venegas, J (reprint author), Massachusetts Gen Hosp, Edwards 410A 55 Fruit St, Boston, MA 02114 USA. EM jvenegas@alum.mit.edu FU National Institutes of Health [R01HL68011]; American Air Liquide Inc. FX Research reported in this publication was supported by the National Institutes of Health under award number R01HL68011. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by American Air Liquide Inc., and Aerogen is thanked for providing the vibrating mesh nebulizers NR 25 TC 2 Z9 2 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1941-2711 EI 1941-2703 J9 J AEROSOL MED PULM D JI J. Aerosol Med. Pulm. Drug Deliv. PD FEB PY 2016 VL 29 IS 1 BP 57 EP 75 DI 10.1089/jamp.2014.1197 PG 19 WC Respiratory System SC Respiratory System GA DL1SE UT WOS:000375411500007 ER PT J AU Ash, SY Cardet, JC Kusa, T Camargo, C Israel, E AF Ash, Samuel Y. Cardet, Juan Carlos Kusa, Tope Camargo, Carlos, Jr. Israel, Elliot TI Insulin Resistance Modifies the Association Between Obesity and Current Asthma in Adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Ash, Samuel Y.; Israel, Elliot] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Cardet, Juan Carlos] Brigham & Womens Hosp, Med, 75 Francis St, Boston, MA 02115 USA. [Kusa, Tope] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 30 BP AB10 EP AB10 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005400031 ER PT J AU Balekian, DS Linnemann, RW Castro, VM Perlis, R Thadhani, R Camargo, C AF Balekian, Diana S. Linnemann, Rachel W. Castro, Victor M. Perlis, Roy Thadhani, Ravi Camargo, Carlos, Jr. TI Pre-Birth Cohort Study of Atopic Dermatitis and Severe Bronchiolitis during Infancy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Balekian, Diana S.; Camargo, Carlos, Jr.] Harvard Univ, Sch Med, Dept Med, Div Rheumatol Allergy & Immunol,Massachusetts Gen, Boston, MA USA. [Linnemann, Rachel W.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp,Div Pediat Pulmonol, Boston, MA 02115 USA. [Castro, Victor M.] Partners HealthCare Syst, Res Informat Syst & Comp, Boston, MA USA. [Castro, Victor M.] Massachusetts Gen Hosp, Dept Neurol, Comp Sci Lab, Boston, MA 02114 USA. [Perlis, Roy] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Ctr Expt Drugs & Diagnost, Boston, MA 02115 USA. [Perlis, Roy] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Psychiat & Neurodev Genet, Boston, MA 02115 USA. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Dept Med, Boston, MA USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 137 IS 2 SU S MA 475 BP AB145 EP AB145 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402166 ER PT J AU Banerji, A Blumenthal, KG Lai, KH Zhou, L AF Banerji, Aleena Blumenthal, Kimberly G. Lai, Kenneth H. Zhou, Li TI Epidemiology and Incidence of ACE Inhibitor Angioedema Utilizing a Large Electronic Health Record SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Banerji, Aleena] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Cambridge, MA 02138 USA. [Blumenthal, Kimberly G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Allergy & Immunol,Div Rheumatol Allergy & Immunol, Boston, MA USA. [Lai, Kenneth H.] Partners HealthCare Syst, Boston, MA USA. [Zhou, Li] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 144 BP AB45 EP AB45 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005401083 ER PT J AU Bernstein, JA Wedner, HJ Busse, PJ Banerji, A Cicardi, M Sufritti, C Brooks, EG Cheifitz, A Schwartz, LB Akin, C Sexton, D Stevens, C Stolz, LE Viswanathan, M Faucette, R Biedenkapp, JC Chyung, YH Adelman, B AF Bernstein, Jonathan A. Wedner, H. James Busse, Paula J. Banerji, Aleena Cicardi, Marco Sufritti, C. Brooks, Edward G. Cheifitz, Adam Schwartz, Lawrence B. Akin, Cem Sexton, Daniel Stevens, Chris Stolz, Leslie E. Viswanathan, Malini Faucette, Ryan Biedenkapp, Joseph C. Chyung, Yung H. Adelman, Burt TI Refined Method for Collection of Plasma Samples to Evaluate the Role of Plasma Kallikrein in Various Disease States SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Bernstein, Jonathan A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Wedner, H. James] Washington Univ, Sch Med, St Louis, MO USA. [Busse, Paula J.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Boston, MA USA. [Cicardi, Marco] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy. [Sufritti, C.] Univ Milan, Milan, Italy. [Brooks, Edward G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Cheifitz, Adam] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schwartz, Lawrence B.] Virginia Commonwealth Univ, Richmond, VA USA. [Akin, Cem] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Sexton, Daniel; Stevens, Chris; Stolz, Leslie E.; Viswanathan, Malini; Faucette, Ryan; Biedenkapp, Joseph C.; Chyung, Yung H.; Adelman, Burt] Dyax Corp, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 809 BP AB248 EP AB248 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005404005 ER PT J AU Beukema, KR Leung, J Virkud, Y Shen, AH Patil, SU Ramakrishna, J Shreffler, W AF Beukema, Koen R. Leung, John Virkud, Yamini Shen, Alice H. Patil, Sarita U. Ramakrishna, Jyoti Shreffler, Wayne TI Patients from Low-Income Families Referred for Oral Food Challenge Were More Likely to Pass SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Beukema, Koen R.; Leung, John; Shen, Alice H.; Ramakrishna, Jyoti] Tufts Med Ctr, Div Allergy & Immunol, Boston, MA USA. [Virkud, Yamini; Patil, Sarita U.] Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Massachusetts Gen Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 137 IS 2 SU S MA 416 BP AB126 EP AB126 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402106 ER PT J AU Blumenthal, KG Lai, KH Wickner, PG Goss, FR Seger, DL Slight, SP Topaz, M Chang, FY Zhou, L AF Blumenthal, Kimberly G. Lai, Kenneth H. Wickner, Paige G. Goss, Foster R. Seger, Diane L. Slight, Sarah P. Topaz, Maxim Chang, Frank Y. Zhou, Li TI Reported Incidence of Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs in the Electronic Health Record SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Blumenthal, Kimberly G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Blumenthal, Kimberly G.; Topaz, Maxim; Zhou, Li] Harvard Univ, Sch Med, Boston, MA USA. [Lai, Kenneth H.; Seger, Diane L.; Chang, Frank Y.] Partners HealthCare Syst, Boston, MA USA. [Wickner, Paige G.] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Dept Med,Brigham & Womens Hosp, Chestnut Hill, MA USA. [Goss, Foster R.] Univ Colorado, Aurora, CO USA. [Seger, Diane L.; Slight, Sarah P.; Topaz, Maxim; Chang, Frank Y.; Zhou, Li] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Slight, Sarah P.] Univ Durham, Durham, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 639 BP AB196 EP AB196 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005403085 ER PT J AU Davis-Lorton, MA Busse, PJ Banerji, A Shennak, M Lumry, WR Wedner, HJ Jacobs, JS Baker, JW Bernstein, JA Lockey, RF Li, HH Craig, TJ Marco-Cicardi Riedl, MA Al-Ghazawi, A Soo, C Iarrobino, R Sexton, D TenHoor, C Faucette, R Biedenkapp, JC Chyung, YH Adelman, B AF Davis-Lorton, Mark A. Busse, Paula J. Banerji, Aleena Shennak, Mustafa Lumry, William R. Wedner, H. James Jacobs, Joshua S. Baker, James W. Bernstein, Jonathan A. Lockey, Richard F. Li, H. Henry Craig, Timothy J. Marco-Cicardi Riedl, Marc A. Al-Ghazawi, Ahmad Soo, Carolyn Iarrobino, Ryan Sexton, Daniel TenHoor, Christopher Faucette, Ryan Biedenkapp, Joseph C. Chyung, Yung H. Adelman, Burt TI Pharmacodynamic Effect of DX-2930 on Plasma Kallikrein in Hereditary Angioedema Patients SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Davis-Lorton, Mark A.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Busse, Paula J.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Shennak, Mustafa; Al-Ghazawi, Ahmad] Triumpharma, Amman, Jordan. [Lumry, William R.] AARA Res Ctr, Dallas, TX USA. [Wedner, H. James] Washington Univ, Sch Med, St Louis, MO USA. [Jacobs, Joshua S.] Allergy & Asthma Clin Res, Walnut Creek, CA USA. [Baker, James W.] James W Baker MD LLC, Lake Oswego, OR USA. [Bernstein, Jonathan A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Lockey, Richard F.] Univ S Florida, Morsani Coll Med, Tampa, FL USA. [Li, H. Henry] Inst Asthma & Allergy, Chevy Chase, MD USA. [Craig, Timothy J.] Penn State Univ, Coll Med, Hershey, PA USA. [Marco-Cicardi] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy. [Riedl, Marc A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Soo, Carolyn; Iarrobino, Ryan; Sexton, Daniel; TenHoor, Christopher; Faucette, Ryan; Biedenkapp, Joseph C.; Chyung, Yung H.; Adelman, Burt] Dyax Corp, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 821 BP AB252 EP AB252 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005404017 ER PT J AU Grant, T Dantzer, J Keet, C Peng, R Krevans, M Hagberg, K Curtin-Brosnan, J Shreffler, W Matsui, E AF Grant, Torie Dantzer, Jennifer Keet, Corinne Peng, Roger Krevans, Mary Hagberg, Karol Curtin-Brosnan, Jean Shreffler, Wayne Matsui, Elizabeth TI Eczema Is an Independent Risk Factor for Incident Mouse Skin Test Sensitivity Among Employees at a Mouse Production and Research Facility SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Grant, Torie; Dantzer, Jennifer; Keet, Corinne; Curtin-Brosnan, Jean; Matsui, Elizabeth] Johns Hopkins Sch Med, Div Pediat Allergy Immunol, Baltimore, MD USA. [Peng, Roger] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Krevans, Mary; Hagberg, Karol] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. [Shreffler, Wayne] Massachusetts Gen Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 473 BP AB144 EP AB144 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402164 ER PT J AU Hesterberg, PE Virkud, Y Southwick, C Alejos, AR Stieb, ES Shreffler, W AF Hesterberg, Paul E. Virkud, Yamini Southwick, Caroline Alejos, Alexandra R. Stieb, Elisabeth S. Shreffler, Wayne TI Analysis of Oral Food Challenges for Almond Hypersensitivity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Hesterberg, Paul E.; Alejos, Alexandra R.; Stieb, Elisabeth S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Virkud, Yamini] Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. [Southwick, Caroline] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Shreffler, Wayne] Massachusetts Gen Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 137 IS 2 SU S MA 410 BP AB124 EP AB124 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402100 ER PT J AU Hickey, AJ Virkud, Y Washburn, C Smith, N Patil, SU Shreffler, W AF Hickey, Alanna J. Virkud, Yamini Washburn, Cecilia Smith, Neal Patil, Sarita U. Shreffler, Wayne TI Peanut and Arah2 Specific Immunoglobulin E Is Predictive of Sustained Unresponsiveness Following Peanut Oral Immunotherapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Hickey, Alanna J.] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Virkud, Yamini; Patil, Sarita U.] Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. [Washburn, Cecilia; Smith, Neal] Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Massachusetts Gen Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 632 BP AB194 EP AB194 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005403078 ER PT J AU Jacobs, JS Busse, PJ Banerji, A Shennak, M Lumry, WR Davis-Lorton, MA Wedner, HJ Baker, JW Bernstein, JA Lockey, RF Li, HH Craig, TJ Marco-Cicardi Riedl, MA Al-Ghazawi, A Soo, C Iarrobino, R Sexton, D TenHoor, C Faucette, R Biedenkapp, JC Chyung, YH Adelman, B AF Jacobs, Joshua S. Busse, Paula J. Banerji, Aleena Shennak, Mustafa Lumry, William R. Davis-Lorton, Mark A. Wedner, H. James Baker, James W. Bernstein, Jonathan A. Lockey, Richard F. Li, H. Henry Craig, Timothy J. Marco-Cicardi Riedl, Marc A. Al-Ghazawi, Ahmad Soo, Carolyn Iarrobino, Ryan Sexton, Daniel TenHoor, Christopher Faucette, Ryan Biedenkapp, Joseph C. Chyung, Yung H. Adelman, Burt TI Relationship Between Drug Exposure and Clinical Response Observed in the Phase 1b Study of DX-2930 in Subjects with Hereditary Angioedema SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Jacobs, Joshua S.] Allergy & Asthma Clin Res, Walnut Creek, CA USA. [Busse, Paula J.] Mt Sinai Sch Med, New York, NY USA. [Banerji, Aleena] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shennak, Mustafa; Al-Ghazawi, Ahmad] Triumpharma, Amman, Jordan. [Lumry, William R.] AARA Res Ctr, Dallas, TX USA. [Davis-Lorton, Mark A.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Wedner, H. James] Washington Univ, Sch Med, St Louis, MO USA. [Baker, James W.] James W Baker MD LLC, Lake Oswego, OR USA. [Bernstein, Jonathan A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Lockey, Richard F.] Univ S Florida, Dept Internal Med, Morsani Coll Med, Div Allergy & Immunol, Tampa, FL 33612 USA. [Li, H. Henry] Inst Asthma & Allergy, Chevy Chase, MD USA. [Craig, Timothy J.] Penn State Univ, Coll Med, Hershey, PA USA. [Marco-Cicardi] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy. [Riedl, Marc A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Soo, Carolyn; Iarrobino, Ryan; Sexton, Daniel; TenHoor, Christopher; Faucette, Ryan; Biedenkapp, Joseph C.; Chyung, Yung H.; Adelman, Burt] Dyax Corp, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 819 BP AB251 EP AB251 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005404015 ER PT J AU Ling, MF Islam, SA Hamilos, DL Cho, JL Griffith, JW Harris, RS Kwok, WW Moon, JJ Medoff, BD Luster, AD AF Ling, Morris F. Islam, Sabina A. Hamilos, Daniel L. Cho, Josalyn L. Griffith, Jason W. Harris, R. Scott Kwok, William W. Moon, James J. Medoff, Benjamin D. Luster, Andrew D. TI Allergen-Specific CD4+T Cells in Human Asthma Have an Increased Capacity to Respond to Innate Type 2 Signals SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Ling, Morris F.; Islam, Sabina A.; Hamilos, Daniel L.; Cho, Josalyn L.; Griffith, Jason W.; Harris, R. Scott; Moon, James J.; Medoff, Benjamin D.; Luster, Andrew D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ling, Morris F.; Islam, Sabina A.; Hamilos, Daniel L.; Cho, Josalyn L.; Griffith, Jason W.; Harris, R. Scott; Moon, James J.; Medoff, Benjamin D.; Luster, Andrew D.] Harvard Univ, Sch Med, Boston, MA USA. [Kwok, William W.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 5 BP AB2 EP AB2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005400006 ER PT J AU McMilin, CR Grant, C Morton, SMB Camargo, C AF McMilin, Colleen R. Grant, Cameron Morton, Susan M. B. Camargo, Carlos, Jr. TI Risk Factors for Childhood Peanut Allergy in a Large Birth Cohort Study: Growing up in New Zealand SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [McMilin, Colleen R.; Grant, Cameron; Morton, Susan M. B.] Univ Auckland, Ctr Longitudinal Res He Ara Ki Mua, Auckland 1, New Zealand. [McMilin, Colleen R.] Montana State Univ, Bozeman, MT 59717 USA. [Grant, Cameron] Univ Auckland, Paediat Child & Youth Hlth, Auckland, New Zealand. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Med, Boston, MA USA. [Camargo, Carlos, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA L21 BP AB395 EP AB395 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005404146 ER PT J AU Minhas, JS Wickner, PG Long, AA Banerji, A Blumenthal, KG AF Minhas, Jasmit S. Wickner, Paige G. Long, Aidan A. Banerji, Aleena Blumenthal, Kimberly G. TI Immune-Mediated Reactions to Vancomycin: A Systematic Review SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Minhas, Jasmit S.] Tufts Univ, Sch Med, Lahey Hosp & Med Ctr, Burlington, MA USA. [Wickner, Paige G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Chestnut Hill, MA USA. [Long, Aidan A.; Banerji, Aleena; Blumenthal, Kimberly G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 137 IS 2 SU S MA 140 BP AB44 EP AB44 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005401079 ER PT J AU Otani, I Lumry, WR Li, HH Chase, C Craig, TJ Riedl, MA Zuraw, BL Banerji, A AF Otani, Iris Lumry, William R. Li, Huamin Henry Chase, Chevy Craig, Timothy J. Riedl, Marc A. Zuraw, Bruce L. Banerji, Aleena TI Subcutaneous Icatibant for the Treatment of Acute Attacks of Hereditary Angioedema: Comparison of Self-Administration to Administration at a Medical Facility SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Otani, Iris] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lumry, William R.] AARA Res Ctr, Allergy & Asthma Specialists, Dallas, TX USA. [Li, Huamin Henry] Inst Asthma & Allergy, Hershey, PA USA. [Chase, Chevy; Craig, Timothy J.] Penn State Univ, Dept Med & Pediat, Hershey, PA USA. [Riedl, Marc A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Zuraw, Bruce L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Immunol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 817 BP AB250 EP AB250 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005404013 ER PT J AU Patel, AM Lee, JXW Pham, AQ Yusin, JS AF Patel, Anil M. Lee, Joyce X. W. Pham, Andrew Q. Yusin, Joseph S. TI Self-Injectable Epinephrine Adherence Survey Amongst Veterans SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Patel, Anil M.; Lee, Joyce X. W.; Pham, Andrew Q.; Yusin, Joseph S.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 602 BP AB184 EP AB184 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005403048 ER PT J AU Patil, SU Steinbrecher, J Ma, A Smith, N Washburn, C Hickey, A Southwick, C Tracy, L Ruiter, B Virkud, Y Schneider, M Shreffler, W AF Patil, Sarita U. Steinbrecher, Johanna Ma, Alex Smith, Neal Washburn, Cecilia Hickey, Alanna Southwick, Caroline Tracy, Lauren Ruiter, Bert Virkud, Yamini Schneider, Michael Shreffler, Wayne TI Early Peanut OIT-Induced Suppression of Basophil Reactivity Is a Marker of Sustained Unresponsiveness SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Patil, Sarita U.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Boston, MA USA. [Patil, Sarita U.; Virkud, Yamini] Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. [Steinbrecher, Johanna; Smith, Neal; Washburn, Cecilia] Massachusetts Gen Hosp, Dept Rheumatol Allergy & Immunol, Charlestown, MA USA. [Ma, Alex] NYU, Coll Dent, New York, NY USA. [Ma, Alex] Massachusetts Gen Hosp, Charlestown, MA USA. [Hickey, Alanna; Southwick, Caroline; Tracy, Lauren] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Ruiter, Bert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schneider, Michael] BUHLMANN Labs AG, Basel, Switzerland. [Shreffler, Wayne] Massachusetts Gen Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 419 BP AB127 EP AB127 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402109 ER PT J AU Pham, AQ Lee, JXW Lin, C Liang, E Yusin, JS AF Pham, Andrew Q. Lee, Joyce Xiang Wu Lin, Connie Liang, Emily Yusin, Joseph S. TI Characterization of Patients with Low Ige Levels SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Pham, Andrew Q.; Lee, Joyce Xiang Wu; Yusin, Joseph S.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Lin, Connie; Liang, Emily] Cedars Sinai Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 573 BP AB174 EP AB174 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005403019 ER PT J AU Philipp, AT Jones, AH Zeitz, H Yusin, JS AF Philipp, Ami Thakor Jones, Alesia Hawkins Zeitz, Howard Yusin, Joseph S. TI Adolescent Asthmatics' Use of the Internet and Other Management Strategies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Philipp, Ami Thakor; Yusin, Joseph S.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Jones, Alesia Hawkins] Univ Illinois, Coll Med, Rockford, IL 61107 USA. [Zeitz, Howard] Univ Illinois, Coll Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 4 U2 4 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 FEB PY 2016 VL 137 IS 2 SU S MA 322 BP AB99 EP AB99 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402013 ER PT J AU Sokol, CL Camire, R Jones, M Luster, AD AF Sokol, Caroline L. Camire, Ryan Jones, Michael Luster, Andrew D. TI CCR8 Mediated Cell Migration Controls Th2 Differentiation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Sokol, Caroline L.; Camire, Ryan; Luster, Andrew D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, Michael] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 137 IS 2 SU S MA 240 BP AB73 EP AB73 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005401178 ER PT J AU Tuttle, KSL Stieb, ES Hesterberg, PE Shreffler, W Virkud, Y AF Tuttle, Katherine S. L. Stieb, Elisabeth S. Hesterberg, Paul E. Shreffler, Wayne Virkud, Yamini TI Mild Ocular and Nasal Symptoms Are Not Indicative of Reactions during Open Oral Food Challenges SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Tuttle, Katherine S. L.] Massachusetts Gen Hosp Children, Boston, MA USA. [Stieb, Elisabeth S.; Hesterberg, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shreffler, Wayne] Massachusetts Gen Hosp, Dept Pediat, Div Allergy & Immunol, Boston, MA 02114 USA. [Shreffler, Wayne] Harvard Univ, Sch Med, Boston, MA USA. [Virkud, Yamini] Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 411 BP AB125 EP AB125 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402101 ER PT J AU Virkud, Y Croteau-Chonka, DC Weiss, ST Lasky-Su, J AF Virkud, Yamini Croteau-Chonka, Damien C. Weiss, Scott T. Lasky-Su, Jessica TI Gene Expression Networks of Allergic Asthma As Characterized By IgE Levels Among Costa Rican Children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Virkud, Yamini] Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. [Croteau-Chonka, Damien C.] Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Sch Med,Dept Med, Boston, MA 02115 USA. [Weiss, Scott T.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. [Lasky-Su, Jessica] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 341 BP AB105 EP AB105 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402031 ER PT J AU Wedner, HJ Busse, PJ Banerji, A Shennak, M Lumry, WR Davis-Lorton, MA Jacobs, JS Baker, JW Bernstein, JA Lockey, RF Li, HH Craig, TJ Cicardi, M Riedl, MA Al-Ghazawi, A Soo, C Iarrobino, R Sexton, D TenHoor, C Faucette, R Biedenkapp, JC Chyung, YH Adelman, B AF Wedner, H. James Busse, Paula J. Banerji, Aleena Shennak, Mustafa Lumry, William R. Davis-Lorton, Mark A. Jacobs, Joshua S. Baker, James W. Bernstein, Jonathan A. Lockey, Richard F. Li, H. Henry Craig, Timothy J. Cicardi, Marco Riedl, Marc A. Al-Ghazawi, Ahmad Soo, Carolyn Iarrobino, Ryan Sexton, Daniel TenHoor, Christopher Faucette, Ryan Biedenkapp, Joseph C. Chyung, Yung H. Adelman, Burt TI Modeling and Analyses to Identify Potential Dosing Regimens of DX-2930 for the Long-Term Prophylaxis of Hereditary Angioedema SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Wedner, H. James] Washington Univ, Sch Med, St Louis, MO USA. [Busse, Paula J.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Shennak, Mustafa; Al-Ghazawi, Ahmad] Triumpharma, Amman, Jordan. [Lumry, William R.] AARA Res Ctr, Dallas, TX USA. [Davis-Lorton, Mark A.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Jacobs, Joshua S.] Allergy & Asthma Clin Res, Walnut Creek, CA USA. [Baker, James W.] James W Baker MD LLC, Lake Oswego, OR USA. [Bernstein, Jonathan A.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Lockey, Richard F.] Univ S Florida, Morsani Coll Med, Tampa, FL USA. [Li, H. Henry] Inst Asthma & Allergy, Chevy Chase, MD USA. [Craig, Timothy J.] Penn State Univ, Coll Med, Hershey, PA USA. [Cicardi, Marco] Univ Milan, Luigi Sacco Hosp, Dept Biomed & Clin Sci Luigi Sacco, Milan, Italy. [Riedl, Marc A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Soo, Carolyn; Iarrobino, Ryan; Sexton, Daniel; TenHoor, Christopher; Faucette, Ryan; Biedenkapp, Joseph C.; Chyung, Yung H.; Adelman, Burt] Dyax Corp, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 822 BP AB252 EP AB252 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005404018 ER PT J AU Wolfson, AR Sokol, CL Luster, AD AF Wolfson, Anna R. Sokol, Caroline L. Luster, Andrew D. TI The Role of Human Dendritic Cells in Cutaneous Allergen Recognition and Immune Activation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Wolfson, Anna R.; Sokol, Caroline L.; Luster, Andrew D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2016 VL 137 IS 2 SU S MA 77 BP AB25 EP AB25 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005401016 ER PT J AU Wong, AG Wong, JT AF Wong, Alanna G. Wong, Johnson T. TI Dermatographism, Atopic Dermatitis and Other Atopic/Related Non-Atopic Disorders SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 04-07, 2016 CL Los Angeles, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Wong, Alanna G.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. [Wong, Johnson T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 137 IS 2 SU S MA 503 BP AB154 EP AB154 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA DK6BI UT WOS:000375005402194 ER PT J AU MacPherson, H Hammerschlag, R Coeytaux, RR Davis, RT Harris, RE Kong, JT Langevin, HM Lao, LX Milley, RJ Napadow, V Schnyer, RN Stener-Victorin, E Witt, CM Wayne, PM AF MacPherson, Hugh Hammerschlag, Richard Coeytaux, Remy R. Davis, Robert T. Harris, Richard E. Kong, Jiang-Ti Langevin, Helene M. Lao, Lixing Milley, Ryan J. Napadow, Vitaly Schnyer, Rosa N. Stener-Victorin, Elisabet Witt, Claudia M. Wayne, Peter M. TI Unanticipated Insights into Biomedicine from the Study of Acupuncture SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID TRADITIONAL CHINESE ACUPUNCTURE; INTRINSIC BRAIN CONNECTIVITY; IRRITABLE-BOWEL-SYNDROME; LOW-BACK-PAIN; PLACEBO ANALGESIA; SHAM ACUPUNCTURE; RANDOMIZED-TRIAL; CHRONIC HEADACHE; CLINICAL-TRIALS; TISSUE STRETCH AB Research into acupuncture has had ripple effects beyond the field of acupuncture. This paper identifies five exemplars to illustrate that there is tangible evidence of the way insights gleaned from acupuncture research have informed biomedical research, practice, or policy. The first exemplar documents how early research into acupuncture analgesia has expanded into neuroimaging research, broadening physiologic understanding and treatment of chronic pain. The second describes how the acupuncture needle has become a tool to enhance biomedical knowledge of connective tissue. The third exemplar, which illustrates use of a modified acupuncture needle as a sham device, focuses on emergent understanding of placebo effects and, in turn, on insights into therapeutic encounters in treatments unrelated to acupuncture. The fourth exemplar documents that two medical devices now in widespread use were inspired by acupuncture: transcutaneous electrical nerve stimulators for pain control and antinausea wrist bands. The final exemplar describes how pragmatic clinical trial designs applied in acupuncture research have informed current general interest in comparative effectiveness research. In conclusion, these exemplars of unanticipated outcomes of acupuncture research comprise an additional rationale for continued support of basic and clinical research evaluating acupuncture and other under-researched therapies. C1 [MacPherson, Hugh] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Hammerschlag, Richard; Milley, Ryan J.] Oregon Coll Oriental Med, Res Dept, Portland, OR USA. [Hammerschlag, Richard] Inst Integrat Hlth, Baltimore, MD USA. [Coeytaux, Remy R.] Duke Clin Res Inst, Durham, NC USA. [Coeytaux, Remy R.] Duke Univ, Dept Community & Family Med, Durham, NC USA. [Davis, Robert T.] Stromatec Inc, Burlington, VT USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Kong, Jiang-Ti] Stanford Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Stanford, CA USA. [Langevin, Helene M.; Wayne, Peter M.] Brigham & Womens Hosp, Osher Ctr Integrat Med, 75 Francis St, Boston, MA 02115 USA. [Langevin, Helene M.; Wayne, Peter M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lao, Lixing] Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China. [Lao, Lixing] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. [Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, Vitaly] Logan Univ, Dept Radiol, Chesterfield, MO USA. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Schnyer, Rosa N.] Univ Texas Austin, Sch Nursing, Austin, TX 78712 USA. [Stener-Victorin, Elisabet] Univ Gothenburg, Sahlgrenska Acad, Dept Physiol, Inst Neurosci & Physiol, Gothenburg, Sweden. [Witt, Claudia M.] Univ Zurich, Univ Zurich Hosp, Inst Complementary & Integrat Med, Zurich, Switzerland. RP MacPherson, H (reprint author), Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. EM hugh.macpherson@york.ac.uk OI Stener-Victorin, Elisabet/0000-0002-3424-1502; Lao, Lixing/0000-0003-0198-9714 FU NCCIH NIH HHS [K23 AT008477]; NIDA NIH HHS [T32 DA035165] NR 84 TC 3 Z9 3 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD FEB PY 2016 VL 22 IS 2 BP 101 EP 107 DI 10.1089/acm.2015.0184 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DK7QO UT WOS:000375121000001 PM 26745452 ER PT J AU Taibbi, G Kim, JD Bakir, BH Shenoy, SR Pearce, WA Taroyan, G Birdsong, OC Loucks, EK Vizzeri, G AF Taibbi, Giovanni Kim, James D. Bakir, Belal H. Shenoy, Sudhir R. Pearce, William A. Taroyan, Gregory Birdsong, Orry C. Loucks, Emma K. Vizzeri, Gianmarco TI Correlation and Agreement Between Cirrus HD-OCT "RNFL Thickness Map" and Scan Circle Retinal Nerve Fiber Layer Thickness Measurements SO JOURNAL OF GLAUCOMA LA English DT Article DE retinal nerve fiber layer; RNFL thickness map; scan circle; spectral-domain OCT ID OPTICAL COHERENCE TOMOGRAPHY; GLAUCOMA DIAGNOSIS; REPRODUCIBILITY; EYES AB Purpose: To evaluate the correlation and agreement between optical coherence tomography (Cirrus HD-OCT) retinal nerve fiber layer (RNFL) thickness map and scan circle RNFL thickness measurements. Methods: ImageJ and custom Perl scripts were used to derive RNFL thickness measurements from RNFL thickness maps of optic disc scans of healthy and glaucomatous eyes. Average, quadrant, and clock-hour RNFL thickness of the map, and RNFL thickness of the areas inside/outside the scan circle were obtained. Correlation and agreement between RNFL thickness map and scan circle RNFL thickness measurements were evaluated using R-2 and Bland-Altman plots, respectively. Results: A total of 104 scans from 26 healthy eyes and 120 scans from 30 glaucomatous eyes were analyzed. RNFL thickness map and scan circle measurements were highly reproducible (eg, in healthy eyes, average RNFL thickness coefficients of variation were 2.14% and 2.52% for RNFL thickness map and scan circle, respectively) and highly correlated (0.55 <= R-2 <= 0.98). In general, the scan circle provided greater RNFL thickness than the RNFL thickness map in corresponding sectors and the differences tended to increase as RNFL thickness increased. The width of the 95% limits of agreement ranged between 5.28 and 36.80 mu m in healthy eyes, and between 11.69 and 42.89 mu m in glaucomatous eyes. Conclusions: Despite good correlation between RNFL thickness map and scan circle measurements, agreement was generally poor, suggesting that RNFL thickness assessment over the entire scan area may provide additional clinically relevant information to the conventional scan circle analysis. In the absence of available measurements from the entire peripapillary region, the RNFL thickness maps can be used to investigate localized RNFL thinning in areas not intercepted by the scan circle. C1 [Taibbi, Giovanni; Kim, James D.; Bakir, Belal H.; Shenoy, Sudhir R.; Pearce, William A.; Taroyan, Gregory; Birdsong, Orry C.; Loucks, Emma K.; Vizzeri, Gianmarco] Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, 301 Univ Blvd, Galveston, TX 77555 USA. [Bakir, Belal H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Vizzeri, G (reprint author), Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, 301 Univ Blvd, Galveston, TX 77555 USA. EM givizzer@utmb.edu FU Research to Prevent Blindness (RPB) FX Supported in part by an unrestricted grant from Research to Prevent Blindness (RPB) to the University of Texas Medical Branch, Galveston, TX. RPB had no role in: 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 24 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 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD FEB PY 2016 VL 25 IS 2 BP 208 EP 216 DI 10.1097/IJG.0000000000000149 PG 9 WC Ophthalmology SC Ophthalmology GA DK3MD UT WOS:000374819800025 PM 25264997 ER PT J AU Murphy, RM Bakir, B O'Brien, C Wiggs, JL Pasquale, LR AF Murphy, Rory M. Bakir, Belal O'Brien, Colm Wiggs, Janey L. Pasquale, Louis R. TI Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis SO JOURNAL OF GLAUCOMA LA English DT Article DE drug-induced secondary angle-closure glaucoma; causative drugs; Naranjo scale ID TOPIRAMATE-ASSOCIATED ACUTE; INDUCED ACUTE MYOPIA; TRANSIENT MYOPIA; UVEAL EFFUSION; CHOROIDAL EFFUSION; CATARACT-SURGERY; ULTRASOUND BIOMICROSCOPY; SULFONAMIDE DERIVATIVES; PAROXETINE; ACETAZOLAMIDE AB Purpose: We performed a literature synthesis to identify the full spectrum of compounds implicated in drug-induced, bilateral secondary angle-closure glaucoma (2 degrees ACG). Methods: Systematic PubMed literature review identified relevant bilateral 2 degrees ACG case reports. We evaluated these reports with both the Naranjo adverse drug reaction probability scale to assess the causality of reported drug reactions and a 2 degrees ACG scale scoring system we developed to determine the likelihood that the event represented bilateral 2 degrees ACG. Two independent graders performed these analyses and their scores were averaged for interpretation. The Naranjo scale ranges from -4 to +13 and the drug reaction was considered definite if the score was >= 9, probable if 5 to 8, possible if 1 to 4, and doubtful if <= 0. The 2 degrees ACG score ranges from 0 to 7. We considered a 2 degrees ACG score of >= 4 as evidence of significant likelihood that the drug reaction represented bilateral 2 degrees ACG. Results: No drug had a definite Naranjo score, but the following drug entities had probable Naranjo scores and 2 degrees ACG scores >= 4: acetazolamide, "anorexiant mix," bupropion, cabergoline, " ecstasy," escitalopram, flavoxate, flucloxacillin, hydrochlorothiazide, hydrochlorothiazide/triamterene, mefenamic acid, methazolamide, oseltamivir, topiramate, topiramate/bactrim, and venlafaxine. Root chemical analysis revealed that sulfur-containing and non-sulfur-containing compounds contributed to bilateral 2 degrees ACG. Conclusions: Several compound preparations were implicated in drug-induced bilateral 2 degrees ACG. Treating physicians should be aware that some forms of recreational drug use, which the patient may not admit to, could contribute to this vision-threatening side effect. C1 [Murphy, Rory M.; O'Brien, Colm] Univ Coll Dublin, Sch Med, Dublin 2, Ireland. [Bakir, Belal; Wiggs, Janey L.; Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. [Pasquale, Louis R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. RP Pasquale, LR (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM louis_pasquale@meei.harvard.edu FU Harvard Glaucoma Center of Excellence; Harvard Medical School Distinguished Ophthalmology Scholar Award FX Supported by Harvard Glaucoma Center of Excellence (L.R.P. and J.L.W.) and a Harvard Medical School Distinguished Ophthalmology Scholar Award (L.R.P.). NR 72 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 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD FEB PY 2016 VL 25 IS 2 BP E99 EP E105 DI 10.1097/IJG.0000000000000270 PG 7 WC Ophthalmology SC Ophthalmology GA DK3MD UT WOS:000374819800008 PM 25943730 ER PT J AU Kirkwood, CM MacDonald, ML Schempf, TA Vatsavayi, AV Ikonomovic, MD Koppel, JL Ding, Y Sun, M Kofler, JK Lopez, OL Yates, NA Sweet, RA AF Kirkwood, Caitlin M. MacDonald, Matthew L. Schempf, Tadhg A. Vatsavayi, Anil V. Ikonomovic, Milos D. Koppel, Jeremy L. Ding, Ying Sun, Mai Kofler, Julia K. Lopez, Oscar L. Yates, Nathan A. Sweet, Robert A. TI Altered Levels of Visinin-Like Protein 1 Correspond to Regional Neuronal Loss in Alzheimer Disease and Frontotemporal Lobar Degeneration SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; Frontotemporal lobar degeneration; Human postmortem brain tissue; Visinin-like 1 protein (Vilip-1) ID CEREBROSPINAL-FLUID; COGNITIVE DECLINE; TANGLE FORMATION; BRAIN-INJURY; LEWY BODIES; BIOMARKER; DEMENTIA; CONSORTIUM; PATHOLOGY; VILIP-1 AB Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure Vilip-1 peptide levels in the entorhinal cortex (ERC) and the superior frontal gyrus (SF) from cases with early to moderate stage AD, frontotemporal lobar degeneration (FTLD), and cognitively and neuropathologically normal elderly controls. We found that Vilip-1 levels were significantly lower in the ERC, but not in SF, of AD subjects compared to normal controls. In FTLD cases, Vilip-1 levels in the SF were significantly lower than in normal controls. These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of ERC neuron loss in AD. C1 [Kirkwood, Caitlin M.; MacDonald, Matthew L.; Schempf, Tadhg A.; Sweet, Robert A.] Univ Pittsburgh, Sch Hlth Sci, Translat Neurosci Program, Pittsburgh, PA USA. [Kirkwood, Caitlin M.; MacDonald, Matthew L.; Schempf, Tadhg A.; Ikonomovic, Milos D.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Sch Hlth Sci, Pittsburgh, PA USA. [Ikonomovic, Milos D.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Sch Hlth Sci, Pittsburgh, PA 15260 USA. [Kofler, Julia K.] Univ Pittsburgh, Dept Pathol, Sch Hlth Sci, Pittsburgh, PA USA. [MacDonald, Matthew L.; Ding, Ying; Sun, Mai; Yates, Nathan A.] Univ Pittsburgh, Biomed Mass Spectrometry Ctr, Sch Hlth Sci, Pittsburgh, PA USA. [Kirkwood, Caitlin M.; Yates, Nathan A.] Univ Pittsburgh, Dept Cell Biol, Sch Hlth Sci, Pittsburgh, PA USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Vatsavayi, Anil V.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Koppel, Jeremy L.] Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY USA. [Koppel, Jeremy L.] Feinstein Inst Med Res, Manhasset, NY USA. [Koppel, Jeremy L.] North Shore LIJ Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY USA. RP Sweet, RA (reprint author), 3811 OHara St,BST W1645, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu OI Ding, Ying/0000-0003-1352-1000 FU VAPHS [BX000542]; [MH16804]; [AG05133]; [AG014449]; [AG027224]; [P30CA047904] FX This work was supported by grants MH16804 (MLM), AG05133 (OLL), AG014449 (MDI), AG027224 (RAS), and VAPHS grant BX000542 (RAS). The Biomedical Mass Spectrometry Center and UPCI Cancer Proteomics Facility are supported in part by award P30CA047904. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 41 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 2016 VL 75 IS 2 BP 175 EP 182 DI 10.1093/jnen/nlv018 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA DK9DN UT WOS:000375230800008 PM 26769253 ER PT J AU Shapiro, CL Jacobsen, PB Henderson, T Hurria, A Nekhlyudov, L Ng, A Surbone, A Mayer, DK Rowland, JH AF Shapiro, Charles L. Jacobsen, Paul B. Henderson, Tara Hurria, Arti Nekhlyudov, Larissa Ng, Andrea Surbone, Antonella Mayer, Deborah K. Rowland, Julia H. TI ASCO Core Curriculum for Cancer Survivorship Education SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID CLINICAL-PRACTICE GUIDELINE; QUALITY-OF-LIFE; AMERICAN SOCIETY; CHILDHOOD-CANCER; BREAST-CANCER; FERTILITY PRESERVATION; DEPRESSIVE SYMPTOMS; ADULT SURVIVORS; FOLLOW-UP; CARE AB The number of individuals who will be diagnosed with cancer and experience personal cures (ie, dying from some other cause and not cancer) or live for extended periods after cancer treatment is increasing exponentially. By 2025, there will be nearly 20 million survivors, approximately two thirds over the age of 60. The ASCO Survivorship Committee, in partnership with ASCO Professional Committee, has developed this core curriculum and competencies for health care providers, training programs, and policymaking organizations. Adapted from Institute of Medicine recommendations for survivorship care, the curriculum and competencies include surveillance for recurrence and second malignancies; long-term and late effects; health promotion and prevention; psychosocial well-being; and special populations including adolescent and young adult survivors, older adult cancer survivors, and the caregivers of cancer survivors. Finally, an area the importance of which cannot be emphasized enough is communication and care coordination. It is our belief that doctors and other allied health professionals require special expertise tomanagethe exponentially expanding evidence-based and best practice recommendations to provide care for cancer survivors. C1 [Shapiro, Charles L.] Icahn Sch Med Mt Sinai, One Gustave Levy Pl,Box 1079, New York, NY 10029 USA. NYU, Sch Med, New York, NY USA. Univ Tampa, Tampa, FL 33606 USA. Univ Chicago, Chicago, IL 60637 USA. City Hope Natl Med Ctr, Duarte, CA USA. Harvard Vanguard Med Associates, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. NCI, Bethesda, MD 20892 USA. RP Shapiro, CL (reprint author), Icahn Sch Med Mt Sinai, One Gustave Levy Pl,Box 1079, New York, NY 10029 USA. EM charles.shapiro@mssm.edu NR 71 TC 3 Z9 3 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD FEB PY 2016 VL 12 IS 2 BP 145 EP + DI 10.1200/JOP.2015.009449 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LS UT WOS:000374325300017 PM 26813926 ER PT J AU Kamal, AH Quinn, D Gilligan, TD Davis, BC Dalby, CK Bretsch, J McNiff, KK Jacobson, JO AF Kamal, Arif H. Quinn, Doris Gilligan, Timothy D. Davis, Barbara Corning Dalby, Carole K. Bretsch, Jennifer McNiff, Kristen K. Jacobson, Joseph O. TI Feasibility and Effectiveness of a Pilot Program to Facilitate Quality Improvement Learning in Oncology: Experience of the American Society of Clinical Oncology Quality Training Program SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; IMPROVING DOCUMENTATION; COMMUNICATION; CHEMOTHERAPY; OUTCOMES AB Purpose Studies have demonstrated that structured training programs can improve health professionals' skills in performing clinical care or research. We sought to develop and test a novel quality training program (QTP) tailored to oncology clinicians. Methods The American Society of Clinical Oncology QTP consisted of three in-person learning sessions and four phases: prework, planning, implementation, and sustain and spread. We measured two primary outcomes: program feasibility and effectiveness. Feasibility was evaluated by recording participation. Effectiveness was measured using the Kirkpatrick model, which evaluates four outcomes: reaction, learning, behavior, and results. We collected qualitative feedback through a focus group of participants and mixed quantitative-qualitative results from a 6-month follow-up evaluation survey. Results are presented using descriptive statistics. Results We received feedback from of 80% of participants who took part in 92% of in-person program days. QTP deliverables were completed by 100% of teams; none withdrew from the program. Regarding reaction, 100% of respondents expressed interest in actively contributing to future QTP courses. For learning, most teams continued to use the core methodology tools (eg, project charter, aims statements) after the program. Regarding behavior, when asked about intention to serve as a local quality improvement leader, a majority said they "definitely will" serve as: team leader on a specific project (75%), project champion or sponsor (75%), or teacher or trainer for others (64%). In evaluating outcomes, 50% reported applying learned methodology to new projects at their local institution. Conclusion We demonstrate one of the first feasible and effective training programs to facilitate quality improvement learning for oncology clinicians. C1 Duke Canc Inst, Durham, NC USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Cleveland Clin, Cleveland, OH 44106 USA. Partners North Shore Med Ctr, Miami, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Soc Clin Oncol, Alexandria, VA USA. RP Kamal, AH (reprint author), Duke Clin Res Inst, DUMC Box 3841,10 Bryan Searle Dr, Durham, NC 27710 USA. EM arif.kamal@duke.edu NR 18 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD FEB PY 2016 VL 12 IS 2 BP 177 EP + DI 10.1200/JOP.2015.004762 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LS UT WOS:000374325300029 PM 26286099 ER PT J AU Meyer, LA Bohlke, K Wright, AA AF Meyer, Larissa A. Bohlke, Kari Wright, Alexi A. TI Postoperative Radiation Therapy for Endometrial Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material ID STATISTICS C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Amer Soc Clin Oncol, Alexandria, VA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD FEB PY 2016 VL 12 IS 2 BP 182 EP + DI 10.1200/JOP.2015.007005 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DJ6LS UT WOS:000374325300032 PM 26265171 ER PT J AU Burgio, KL Williams, BR Dionne-Odom, JN Redden, DT Noh, H Goode, PS Kvale, E Bakitas, M Bailey, FA AF Burgio, Kathryn L. Williams, Beverly R. Dionne-Odom, J. Nicholas Redden, David T. Noh, Hyunjin Goode, Patricia S. Kvale, Elizabeth Bakitas, Marie Bailey, F. Amos TI Racial Differences in Processes of Care at End of Life in VA Medical Centers: Planned Secondary Analysis of Data from the BEACON Trial SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID SMALL-SAMPLE ADJUSTMENTS; NURSING-HOME RESIDENTS; IN-HOSPITAL DEATH; ADVANCE DIRECTIVES; ETHNIC DISPARITIES; HEALTH EQUITY; OLDER-ADULTS; VETERANS; SYSTEM; CANCER AB Background: Racial differences exist for a number of health conditions, services, and outcomes, including end-of-life (EOL) care. Objective: The aim of the study was to examine differences in processes of care in the last 7 days of life between African American and white inpatients. Methods: Secondary analysis was conducted of data collected in the Best Practices for End-of-Life Care for Our Nation's Veterans (BEACON) trial (conducted 2005-2011). Subjects were 4891 inpatient decedents in six Veterans Administration Medical Centers. Data were abstracted from decedents' medical records. Multi-variable analyses were conducted to examine the relationship between race and each of 18 EOL processes of care controlling for patient characteristics, study site, year of death, and whether the observation was pre- or post-intervention. Results: The sample consisted of 1690 African American patients (34.6%) and 3201 white patients (65.4%). African Americans were less likely to have: do not resuscitate (DNR) orders (odds ratio [ OR]: 0.67; p = 0.004), advance directives (OR: 0.71; p = 0.023), active opioid orders (OR: 0.64, p = 0.0008), opioid medications administered (OR: 0.61, p = 0.004), benzodiazepine orders (OR: 0.68, p < 0.0001), benzodiazepines administered (OR: 0.61, p < 0.0001), antipsychotics administered (OR: 0.73, p = 0.004), and steroids administered (OR: 0.76, p = 0.020). Racial differences were not found for other processes of care, including palliative care consultation, pastoral care, antipsychotic and steroid orders, and location of death. Conclusions: Racial differences exist in some but not all aspects of EOL care. Further study is needed to understand the extent to which racial differences reflect different patient needs and preferences and whether interventions are needed to reduce disparities in patient/family education or access to quality EOL care. C1 [Burgio, Kathryn L.; Williams, Beverly R.; Redden, David T.; Goode, Patricia S.; Kvale, Elizabeth; Bakitas, Marie; Bailey, F. Amos] Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Dept Vet Affairs, Birmingham, AL USA. [Burgio, Kathryn L.; Williams, Beverly R.; Redden, David T.; Goode, Patricia S.; Kvale, Elizabeth; Bakitas, Marie; Bailey, F. Amos] Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Dept Vet Affairs, Atlanta, GA USA. [Burgio, Kathryn L.; Williams, Beverly R.; Goode, Patricia S.; Kvale, Elizabeth; Bailey, F. Amos] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Dionne-Odom, J. Nicholas; Bakitas, Marie] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Redden, David T.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Noh, Hyunjin] Univ Alabama, Tuscaloosa, AL USA. [Bailey, F. Amos] Univ Colorado, Dept Med, Denver, CO USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, 11G 700 South 19th St, Birmingham, AL 35233 USA. EM kburgio@uabmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service ("Intervention to Improve Care at Life's End in VA Medical Centers'') [IIR 03-126]; University of Alabama at Birmingham Cancer Prevention and Control Training Program [5R25CA047888]; National Palliative Care Research Center Career Development Award FX This research was supported by a Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (IIR 03-126, "Intervention to Improve Care at Life's End in VA Medical Centers''; PI: K.L. Burgio, Co-PI: F.A. Bailey). The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Kathryn Burgio, PhD, is director of the Deep South Resource Center for Minority Aging Research (RCMAR; P30AG031054). J. Nicholas Dionne-Odom, PhD, is a post-doctoral fellow supported by the University of Alabama at Birmingham Cancer Prevention and Control Training Program (5R25CA047888) and by a National Palliative Care Research Center Career Development Award. Hyunjin Noh, PhD, is a scholar with the Deep South Resource Center for Minority Aging Research (RCMAR; P30AG031054). NR 56 TC 1 Z9 1 U1 0 U2 3 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 FEB PY 2016 VL 19 IS 2 SI SI BP 157 EP 163 DI 10.1089/jpm.2015.0311 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DK9SA UT WOS:000375270400009 PM 26840851 ER PT J AU Huang, CHS Crowther, M Allen, RS DeCoster, J Kim, G Azuero, C Ang, XY Kvale, E AF Huang, Chao-Hui Sylvia Crowther, Martha Allen, Rebecca S. DeCoster, Jamie Kim, Giyeon Azuero, Casey Ang, Xinying Kvale, Elizabeth TI A Pilot Feasibility Intervention to Increase Advance Care Planning among African Americans in the Deep South SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; HEALTH LITERACY; DECISION-MAKING; PALLIATIVE CARE; END; DISPARITIES; COMMUNITY; BARRIERS; PREFERENCES AB Background: Despite growing efforts to facilitate advance care planning (ACP) to decrease health disparities in palliative care, low completion rates of advance directives (AD) have been consistently found among African Americans. Objective: The objective was to examine the feasibility of a multicomponent ACP intervention program that integrates motivational interviewing, evidence-based ACP facilitation program (Respecting Choices (R)), and health-literacy adjusted AD. This pilot study aims to address the unique barriers to ACP engagement among African Americans in the Deep South. Methods: The design was a mixed-method randomized controlled trial design. Analysis of covariance (ANCOVA) and thematic content analysis (TCA) were conducted to identify barriers and facilitators for ACP engagement and to assess feasibility, knowledge, and intention to complete an AD. Thirty community-dwelling African Americans (mean age M=55.43, SD = 6.71, range = 47-73) were recruited from the Deep South and randomly assigned to receive intervention (n = 15) or educational material (n = 15) at a local university medical center. Results: All participants (n = 30) reported high satisfaction (M= 4.81, SD = 0.44, max score = 5) and increased intent to complete an AD at postintervention. A significant increase in knowledge on AD from baseline to postintervention was observed in the intervention group-t(14)=-3.06, p = 0.01, d = 1.67); no significant change was found for control. Lack of information, mistrust of doctors, and avoidance of discussing death were primary barriers to ACP discussions. Facilitators include ACP education, decreased mistrust, and proactive initiation of ongoing ACP discussions. Conclusions: Feasibility data revealed successful implementation of a brief intervention to increase ACP engagement and willingness to complete an AD among southern African Americans. C1 [Huang, Chao-Hui Sylvia; Azuero, Casey; Kvale, Elizabeth] Univ Alabama Birmingham, Dept Med, Ctr Palliat & Support Care, CH-19 Suite 219 933 19th St South, Birmingham, AL 35205 USA. [Huang, Chao-Hui Sylvia; Crowther, Martha; Allen, Rebecca S.; Kim, Giyeon; Azuero, Casey] Univ Alabama, Alabama Inst Aging, Tuscaloosa, AL USA. [Crowther, Martha; Allen, Rebecca S.; Kim, Giyeon; Azuero, Casey; Ang, Xinying] Univ Alabama, Dept Psychol, Box 870348, Tuscaloosa, AL 35487 USA. [DeCoster, Jamie] Univ Virginia, Ctr Adv Study Teaching & Learning, Charlottesville, VA USA. [Ang, Xinying] East Virginia Med Sch, Dept Psychiat & Behav Sci, Nortolk, VA USA. [Azuero, Casey; Kvale, Elizabeth] Birmingham VA Med Ctr, Birmingham, AL USA. RP Huang, CHS (reprint author), Univ Alabama Birmingham, Dept Med, Ctr Palliat & Support Care, CH-19 Suite 219 933 19th St South, Birmingham, AL 35205 USA. EM chhuang@uabmc.edu OI Allen, Rebecca Sue/0000-0002-2563-4996 NR 40 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD FEB PY 2016 VL 19 IS 2 SI SI BP 164 EP 173 DI 10.1089/jpm.2015.0334 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DK9SA UT WOS:000375270400010 PM 26840852 ER PT J AU Sanders, JJ Robinson, MT Block, SD AF Sanders, Justin J. Robinson, Maisha T. Block, Susan D. TI Factors Impacting Advance Care Planning among African Americans: Results of a Systematic Integrated Review SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; INCOME OLDER-ADULTS; DECISION-MAKING; HEALTH-CARE; TREATMENT PREFERENCES; ETHNIC-DIFFERENCES; ADVANCED CANCER; MEDICAL-CARE; NEAR-DEATH AB Background: African Americans (AA) are more likely to receive worse end-of-life (EOL) care and are less likely to participate in advance care planning (ACP) than white Americans. Objective: Our goal was to understand factors impacting ACP among AA and explore their interactions, in order to guide further research and intervention development. Methods: We systematically identified, using Medline, Embase, and World of Science databases, the quantitative and qualitative ACP literature in which AA were included. We assessed the quality of these studies and evaluated the literature in an iterative and integrative fashion, using themes developed from the qualitative literature to understand and categorize findings from the quantitative literature. Results: Thirty-eight mostly moderate and low quality quantitative studies focused largely on advance directive (AD) completion. Whereas most conclude that AA, when compared with white Americans, prefer more aggressive care, participate less in ACP, and are more likely to informally discuss EOL care than to formally document wishes, study findings were contradictory in a number of domains. Fourteen qualitative studies revealed a number of themes that informed the development of an empirically derived model to explain the relationship of factors impacting ACP for AA along historical and structural axes. Conclusions: The multiple factors that impact ACP for AA are inter-related and may result in part from historical realities that shape contemporary experience. We know little from the data about how best to improve ACP in AA. That AA appear to prefer informal discussions about ACP to formal documentation of preferences suggests that future research should focus on improving ACP conversations among clinicians, patients, and their families in order to improve the receipt of goal-concordant care at EOL. C1 [Sanders, Justin J.; Block, Susan D.] Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Sanders, Justin J.; Block, Susan D.] Ariadne Labs, Boston, MA USA. [Robinson, Maisha T.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Sanders, JJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Justin_Sanders@dfci.harvard.edu NR 99 TC 1 Z9 1 U1 5 U2 6 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 FEB PY 2016 VL 19 IS 2 SI SI BP 202 EP 227 DI 10.1089/jpm.2015.0325 PG 26 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DK9SA UT WOS:000375270400015 PM 26840857 ER PT J AU Sood, RF Gibran, NS Arnoldo, BD Gamelli, RL Herndon, DN Tompkins, RG AF Sood, Ravi F. Gibran, Nicole S. Arnoldo, Brett D. Gamelli, Richard L. Herndon, David N. Tompkins, Ronald G. CA Inflammation Host Response Injury TI Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article; Proceedings Paper CT 100th Annual Clinical Congress of the American-College-of-Surgeons (ACS) CY OCT 26-30, 2014 CL San Francisco, CA SP Amer Coll Surg DE Burn mortality; inflammatory response to injury; genomic storm; transcriptome profiling ID THROMBOEMBOLIC COMPLICATIONS; THERMAL-INJURY; HOST RESPONSE; RISK-FACTORS; MORTALITY; MODELS; DEATH; EPIDEMIOLOGY; INFLAMMATION; PROBABILITY AB BACKGROUND: In the patient with burn injury, older age, larger percentage of total body surface area (TBS) burned, and inhalation injury are established risk factors for death, which typically results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated with these three risk factors. METHODS: We performed a retrospective analysis of the Glue Grant database. From 2003 to 2010, 324 adults with 20% or greater TBS burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within 1 week after burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold change threshold of 1.5 and false discovery rate of 0.05. RESULTS: After adjusting for potential confounders, age greater than 60 years (relative risk [RR], 4.53; 95% confidence interval [CI], 2.93-6.99), burn size greater than 40% TBS (RR, 4.24; 95% CI, 2.61-6.91), and inhalation injury (RR, 2.08; 95% CI, 1.35-3.21) were independently associated with mortality. No genes were differentially expressed in association with age greater than 60 years or inhalation injury. Fifty-one probe sets representing 39 unique genes were differentially expressed in leukocytes from patients with burn size greater than 40% TBS; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of proinflammatory cytokines. CONCLUSION: Among adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the "genomic storm" induced by a 20% or greater than TBS burned. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns greater than 40% TBS. (Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Sood, Ravi F.; Gibran, Nicole S.] Univ Washington, Harborview Med Ctr, Dept Surg, UW Med Reg Burn Ctr, Seattle, WA 98104 USA. [Arnoldo, Brett D.] Univ Texas Southwestern, Sch Med, Dept Surg, Dallas, TX USA. [Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. Shriners Hosp Children, Galveston, TX 77550 USA. [Gamelli, Richard L.] Loyola Univ, Stritch Sch Med, Dept Surg, Chicago, IL 60611 USA. [Tompkins, Ronald G.] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sood, RF (reprint author), Univ Washington, Harborview Med Ctr, Box 359796,325 Ninth Ave, Seattle, WA 98104 USA. EM rfsood@uw.edu FU NIGMS NIH HHS [R24 GM102656, T32 GM007037, U54 GM62119, U54 GM062119] NR 42 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD FEB PY 2016 VL 80 IS 2 BP 250 EP 257 DI 10.1097/TA.0000000000000905 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA DK9EY UT WOS:000375234800017 PM 26517785 ER PT J AU Simis, M Di Lazzaro, V Kirton, A Pennisi, G Bella, R Kim, YH Takeuchi, N Khedr, EM Rogers, LM Harvey, R Koganemaru, S Turman, B Tarlaci, S Gagliardi, RJ Fregni, F AF Simis, Marcel Di Lazzaro, Vincenzo Kirton, Adam Pennisi, Giovanni Bella, Rita Kim, Yun-Hee Takeuchi, Naoyuki Khedr, Eman M. Rogers, Lynn M. Harvey, Richard Koganemaru, Satoko Turman, Bulent Tarlaci, Sultan Gagliardi, Rubens J. Fregni, Felipe TI Neurophysiological measurements of affected and unaffected motor cortex from a cross-sectional, multi-center individual stroke patient data analysis study SO NEUROPHYSIOLOGIE CLINIQUE-CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Cerebrovascular disease; Cortical excitability; Transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; UPPER-LIMB RECOVERY; EVOKED-POTENTIALS; CORTICAL EXCITABILITY; ISCHEMIC-STROKE; HAND FUNCTION; PARETIC HAND; INHIBITION; PLASTICITY; REHABILITATION AB Objectives. - Transcranial magnetic stimulation (TMS) has been used to measure cortical excitability as a functional measurement of corticomotor pathways. Given its potential application as an assessment tool in stroke, we aimed to analyze the correlation of TMS parameters with clinical features in stroke using data from 10 different centers. Methods. - Data of 341 patients with a clinical diagnosis of stroke were collected from studies assessing cortical excitability using TMS. We used a multivariate regression model in which the baseline cortical excitability parameter "resting Motor Threshold (rMT)" was the. main outcome and the demographic, anatomic and clinical characteristics were included as independent variables. Results. - The variable "severity of motor deficit" consistently remained significant in predicting rMT in the affected hemisphere, with a positive beta coefficient, in the multivariate models after sensitive analyses and adjusting for important confounders such as site center. Additionally, we found that the correlations between "age" or "time since stroke" and the rMT in the affected hemisphere were significant, as well as the interaction between "time since stroke" and "severity of motor deficit". Conclusions. - We have shown that severity of motor deficit is an important predictor for rMT in the affected hemisphere. Additionally, time since stroke seems to be an effect modifier for the correlation between motor deficit and rMT. In the unaffected motor cortex, these correlations were not significant. We discuss these findings in the context of stroke rehabilitation. (C) 2016 Published by Elsevier Masson SAS. C1 [Simis, Marcel; Fregni, Felipe] Harvard Univ, Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Simis, Marcel; Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Lab Neuromodulat, Boston, MA 02115 USA. [Simis, Marcel; Gagliardi, Rubens J.] Santa Casa Med Sch, Div Neurol, Sao Paulo, Brazil. [Simis, Marcel] Univ Sao Paulo, Sch Med, Gen Hosp, Phys & Rehabil Med Inst, Sao Paulo, Brazil. [Di Lazzaro, Vincenzo] Univ Campus Biomed, Inst Neurol, Rome, Italy. [Kirton, Adam] Univ Calgary, Alberta Childrens Hosp Res Inst, Calgary Pediat Stroke Program, Calgary, AB, Canada. [Pennisi, Giovanni; Bella, Rita] Univ Catania, Sect Neurosci, Dept GF Ingrassia, Catania, Italy. [Kim, Yun-Hee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Heart Vasc Stroke Inst,Dept Phys & Rehabil Med, Seoul, South Korea. [Takeuchi, Naoyuki] Tohoku Univ, Grad Sch Med, Dept Phys Med & Rehabil, Sendai, Miyagi 980, Japan. [Khedr, Eman M.] Assiut Univ Hosp, Fac Med, Dept Neurol, Assiut, Egypt. [Rogers, Lynn M.; Harvey, Richard] Rehabil Inst Chicago, Sensory Motor Performance Program, Chicago, IL 60611 USA. [Rogers, Lynn M.; Harvey, Richard] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Koganemaru, Satoko] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. [Turman, Bulent] Bond Univ, Sch Med, Robina, Australia. [Tarlaci, Sultan] Sifa Univ, Izmir, Turkey. RP Fregni, F (reprint author), Spaulding Rehabil Hosp, Neuromodulat Ctr, 79-96,13th St, Charlestown, MA 02129 USA. EM Fregni.Felipe@mgh.harvard.edu RI Kirton, Adam/L-8875-2016; Kim, Yun Hee/F-4600-2014 FU Nexstim Corporation; CAPES [9722/11-4]; FAPESP [2009/02059-7]; KOSEF grant - Korean government [M10644000022-06N4400-02210]; Samsung Medical Center Clinical Research Development Program [CRDP CRS-110-05-1] FX Some data collection in this study was funded by Nexstim Corporation. Dr. Simis was funded by CAPES (9722/11-4) and Santa Casa de Sao Paulo Medical School received a grant from FAPESP (2009/02059-7). Yun-Hee Kim was supported by a KOSEF grant (M10644000022-06N4400-02210) funded by the Korean government and by the Samsung Medical Center Clinical Research Development Program (#CRDP CRS-110-05-1). NR 43 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0987-7053 EI 1769-7131 J9 NEUROPHYSIOL CLIN JI Neurophysiol. Clin.-Clin. Neurophysiol. PD FEB PY 2016 VL 46 IS 1 BP 53 EP 61 DI 10.1016/j.neucli.2016.01.003 PG 9 WC Clinical Neurology; Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DK9GM UT WOS:000375238900007 PM 26970808 ER PT J AU O'Donnell, AJ Bogner, HR Cronholm, PF Kellom, K Miller-Day, M McClintock, HFD Kaye, EM Gabbay, R AF O'Donnell, Alison J. Bogner, Hillary R. Cronholm, Peter F. Kellom, Katherine Miller-Day, Michelle McClintock, Heather F. de Vries Kaye, Elise M. Gabbay, Robert TI Stakeholder Perspectives on Changes in Hypertension Care Under the Patient-Centered Medical Home SO PREVENTING CHRONIC DISEASE LA English DT Article ID GENERAL-PRACTICE; BLOOD-PRESSURE; MANAGEMENT; BARRIERS; OUTCOMES AB Introduction Hypertension is a major modifiable risk factor for cardiovascular and kidney disease, yet the proportion of adults whose hypertension is controlled is low. The patient-centered medical home (PCMH) is a model for care delivery that emphasizes patient-centered and team-based care and focuses on quality and safety. Our goal was to investigate changes in hypertension care under PCMH implementation in a large multipayer PCMH demonstration project that may have led to improvements in hypertension control. Methods The PCMH transformation initiative conducted 118 semistructured interviews at 17 primary care practices in southeastern Pennsylvania between January 2011 and January 2012. Clinicians (n = 47), medical assistants (n = 26), office administrators (n = 12), care managers (n = 11), front office staff (n = 7), patient educators (n = 4), nurses (n = 4), social workers (n = 4), and other administrators (n = 3) participated in interviews. Study personnel used thematic analysis to identify themes related to hypertension care. Results Clinicians described difficulties in expanding services under PCMH to meet the needs of the growing number of patients with hypertension as well as how perceptions of hypertension control differed from actual performance. Staff and office administrators discussed achieving patient-centered hypertension care through patient education and self-management support with personalized care plans. They indicated that patient report cards were helpful tools. Participants across all groups discussed a team-and systems-based approach to hypertension care. Conclusion Practices undergoing PCMH transformation may consider stakeholder perspectives about patient-centered, team-based, and systems- based approaches as they work to optimize hypertension care. C1 [Bogner, Hillary R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, 9 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [O'Donnell, Alison J.; Bogner, Hillary R.; Kellom, Katherine; McClintock, Heather F. de Vries; Kaye, Elise M.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. [Miller-Day, Michelle] Chapman Univ, Dept Hlth & Strateg Commun, Orange, CA USA. [Gabbay, Robert] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bogner, HR (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, 9 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM hillary.bogner@uphs.upenn.edu FU Agency for Healthcare Research and Quality [5R18HS019150]; Aetna Foundation; American Heart Association award [13GRNT17000021]; National Institute of Mental Health R21 [MH094940]; National Institute of Mental Health R34 [MH085880] FX This project was supported by a grant from the Agency for Healthcare Research and Quality (no. 5R18HS019150) and funds from Aetna Foundation. Dr Bogner was supported by an American Heart Association award (no. 13GRNT17000021), a National Institute of Mental Health R21 (no. MH094940), and a National Institute of Mental Health R34 (no. MH085880). NR 25 TC 0 Z9 0 U1 1 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD FEB PY 2016 VL 13 AR E28 DI 10.5888/pcd13.150383 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DK8TV UT WOS:000375202100013 PM 26916899 ER PT J AU Feldman, DR Lorch, A Kramar, A Albany, C Einhorn, LH Giannatempo, P Necchi, A Flechon, A Boyle, H Chung, P Huddart, RA Bokemeyer, C Tryakin, A Sava, T Winquist, EW De Giorgi, U Aparicio, J Sweeney, CJ Cedermark, GC Beyer, J Powles, T AF Feldman, Darren R. Lorch, Anja Kramar, Andrew Albany, Costantine Einhorn, Lawrence H. Giannatempo, Patrizia Necchi, Andrea Flechon, Aude Boyle, Helen Chung, Peter Huddart, Robert A. Bokemeyer, Carsten Tryakin, Alexey Sava, Teodoro Winquist, Eric William De Giorgi, Ugo Aparicio, Jorge Sweeney, Christopher J. Cedermark, Gabriella Cohn Beyer, Jorg Powles, Thomas TI Brain Metastases in Patients With Germ Cell Tumors: Prognostic Factors and Treatment Options-An Analysis From the Global Germ Cell Cancer Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHEMOTHERAPY; EXPERIENCE; MANAGEMENT AB Purpose To define characteristics, treatment response, and outcomes of men with brain metastases (BM) from germ cell tumors (GCT). Patients and Methods Data from 523 men with BM from GCT were collected retrospectively from 46 centers in 13 countries by using standardized questionnaires. Clinical features were correlated with overall survival (OS) as the primary end point. Results BM were present at initial diagnosis in 228 men (group A) and at relapse in 295 men (group B). OS at 3 years (3-year OS) was superior in group A versus group B (48% v 27%; P<.001). Multiple BM and the presence of liver or bone metastasis were independent adverse prognostic factors in both groups; primary mediastinal nonseminoma (group A) and elevations of a-fetoprotein of 100 ng/mL or greater or of human chorionic gonadotropin of 5,000 U/L or greater (group B) were additional independent adverse prognostic factors. Depending on these factors, the 3-year OS ranged from 0% to70% in group A and from 6% to 52% in group B. In group A, 99% of patients received chemotherapy; multimodality treatment or high-dose chemotherapy was not associated with statistically improved survival in multivariable analysis. In group B, only 54% of patients received chemotherapy; multimodality treatment was associated with improved survival compared with single-modality therapy (hazard ratio, 0.51; 95% CI, 0.36 to 0.73; P<.001), as was high-dose compared with conventional-dose chemotherapy (hazard ratio, 0.41; 95% CI, 0.24 to 0.70; P = .001). Conclusion Men with BM from GCT have poor OS, particularly if additional risk factors are present. High-dose chemotherapy and multimodality treatment seemed to improve survival probabilities in men with BM at relapse. C1 [Feldman, Darren R.] Cornell Univ, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Feldman, Darren R.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Lorch, Anja] Univ Hosp Dusseldorf, Dusseldorf, Germany. [Albany, Costantine] Univ Hosp Eppendorf, Hamburg, Germany. [Kramar, Andrew] Ctr Oscar Lambret, F-59020 Lille, France. [Flechon, Aude; Boyle, Helen] Ctr Leon Berard, F-69373 Lyon, France. [Albany, Costantine; Einhorn, Lawrence H.] Indiana Univ, Bloomington, IN USA. [Giannatempo, Patrizia; Necchi, Andrea] Fdn Ist Ricovero & Cura Carattere Sci, Ist Nazl Tumori, Milan, Italy. [Sava, Teodoro] Azienda Osped Univ Integrata Verona, Verona, Italy. [De Giorgi, Ugo] Ist Ricovero & Cura Carattere Sci, Ist Sci Romagnolo Studio & Cura Tumori, Meldola, Italy. [Chung, Peter] Univ Toronto, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Winquist, Eric William] London Hlth Sci Ctr, London, ON, Canada. [Huddart, Robert A.] Royal Marsden Hosp, London SW3 6JJ, England. [Powles, Thomas] St Bartholomews Hosp, London, England. [Tryakin, Alexey] Blokhins Russian Canc Res Ctr, Moscow, Russia. [Aparicio, Jorge] Univ Hosp Le Fe, Valencia, Spain. [Sweeney, Christopher J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sweeney, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Cedermark, Gabriella Cohn] Karolinska Inst, Stockholm, Sweden. [Cedermark, Gabriella Cohn] Karolinska Univ Hosp, Stockholm, Sweden. [Beyer, Jorg] Univ Spital Zurich, Zurich, Switzerland. RP Beyer, J (reprint author), Univ Zurich Hosp, Dept Oncol, Raemistr 100, CH-8091 Zurich, Switzerland. EM joerg.beyer@usz.ch OI Feldman, Darren/0000-0003-2424-4635; Necchi, Andrea/0000-0002-3007-2756 FU NCI NIH HHS [P30 CA008748] NR 13 TC 4 Z9 4 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2016 VL 34 IS 4 BP 345 EP + DI 10.1200/JCO.2015.62.7000 PG 13 WC Oncology SC Oncology GA DJ6NZ UT WOS:000374331500013 PM 26460295 ER PT J AU Wang, XD Harshman, LC Xie, WL Nakabayashi, M Qu, FF Pomerantz, MM Lee, GSM Kantoff, PW AF Wang, Xiaodong Harshman, Lauren C. Xie, Wanling Nakabayashi, Mari Qu, Fangfang Pomerantz, Mark M. Lee, Gwo-Shu Mary Kantoff, Philip W. TI Association of SLCO2B1 Genotypes With Time to Progression and Overall Survival in Patients Receiving Androgen-Deprivation Therapy for Prostate Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CASTRATION RESISTANCE; TESTOSTERONE; EXPRESSION; DEHYDROEPIANDROSTERONE; IDENTIFICATION; TRANSPORTER; ABIRATERONE; METABOLISM; MECHANISMS; ESTROGENS AB Purpose To validate the association of three previously demonstrated SLCO2B1 germline variants with time to progression (TTP) in patients receiving androgen-deprivation therapy (ADT), and to evaluate if the SLCO2B1 genetic variants impacted overall survival (OS) for prostate cancer (PC). Patients and Methods Three single nucleotide polymorphisms (SNPs), exonic SNP rs12422149 and intronic SNPs rs1789693 and rs1077858, were genotyped in an independent validation cohort of 616 patients with PC who were treated with ADT at the Dana-Farber Cancer Institute from 1996 to 2013. Multivariable Cox proportional hazards regression adjusting for known prognostic factors estimated the association of these genetic variants with TTP and OS in patients receiving ADT. The expression of SLCO2B1 was examined in prostatectomy samples, and the impact of SLCO2B1 expression level on DHEAS (dehydroepiandrosterone sulfate) uptake was evaluated in cell lines. Results The association between exonic SNP rs12422149 and TTP in patients treated with ADT was confirmed in univariable (P = .019) and multivariable analyses (adjusted hazard ratio, 1.31; 95% CI, 1.00 to 1.72 for GG v AA/AG; P = .049). Because OS had not been previously evaluated, we examined the association in the combined initial and validation cohorts (N = 1,094). The intronic SNP rs1077858 was associated with OS in both univariable (P = .009; Bonferroni's method adjusted P = .027) and multivariable analyses (adjusted hazard ratio, 1.35; 95% CI, 1.07 to 1.71 for GG v AA/AG; P = .012). SLCO2B1 expression in normal prostate tissue and in 22RV1 cells carrying the major allele of SNP rs1077858 was significantly lower than in cells carrying the risk allele. We show in vitro that SLCO2B1 expression levels correlated with DHEAS uptake by PC cells. Conclusion The association of SNP rs1077858 with OS may be a result of differential SLCO2B1 expression and the consequent increased uptake of DHEAS and subsequent resistance to ADT, which, in turn, may contribute to decreased OS. C1 [Wang, Xiaodong; Harshman, Lauren C.; Xie, Wanling; Nakabayashi, Mari; Qu, Fangfang; Pomerantz, Mark M.; Lee, Gwo-Shu Mary; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM philip_kantoff@dfci.harvard.edu FU Dana-Farber Prostate Cancer SPORE Grant [P50CA090381]; Department of Defense [W81XWH-14-1-0515]; Prostate Cancer Foundation FX Supported by Dana-Farber Prostate Cancer SPORE Grant No. P50CA090381 and Grant No. W81XWH-14-1-0515 from the Department of Defense (P.W.K.) and by a Prostate Cancer Foundation Young Investigator Award (L.C.H.). NR 36 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2016 VL 34 IS 4 BP 352 EP + DI 10.1200/JCO.2015.62.5988 PG 16 WC Oncology SC Oncology GA DJ6NZ UT WOS:000374331500014 PM 26668348 ER PT J AU Abramson, JS Ferry, JA Muse, VV Lanuti, M AF Abramson, Jeremy S. Ferry, Judith A. Muse, Victorine V. Lanuti, Michael TI Extranodal Marginal Zone Lymphoma Presenting As Miliary Lung Disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID B-CELL LYMPHOMA; CLINICAL ACTIVITY; TISSUE LYMPHOMA; DIFFERENT SITES; MALT LYMPHOMAS; SURVIVAL; FEATURES C1 [Abramson, Jeremy S.; Ferry, Judith A.; Muse, Victorine V.; Lanuti, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2016 VL 34 IS 4 BP E27 EP E30 DI 10.1200/JCO.2013.50.6501 PG 4 WC Oncology SC Oncology GA DJ6NZ UT WOS:000374331500003 PM 24912892 ER PT J AU Spence, RT Panieri, E Rayne, SL Harrison, EM Bhangu, AA Fitzgerald, JE AF Spence, Richard Trafford Panieri, Eugenio Rayne, Sarah Louise Harrison, Ewen Munro Bhangu, Aneel Amir Fitzgerald, James Edward TI Collaboration is key to strengthening surgical research capacity in sub-Saharan Africa SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Editorial Material ID IMPACT C1 [Spence, Richard Trafford] Massachusetts Gen Hosp, Dept Gen Surg, Codman Ctr, Boston, MA 02114 USA. [Spence, Richard Trafford; Panieri, Eugenio] Univ Cape Town, Fac Hlth Sci, Dept Surg, ZA-7700 Rondebosch, South Africa. [Rayne, Sarah Louise] Univ Witwatersrand, Fac Hlth Sci, Dept Surg, Johannesburg, South Africa. [Harrison, Ewen Munro] Univ Edinburgh, Surg Clin, Edinburgh EH8 9YL, Midlothian, Scotland. [Harrison, Ewen Munro] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Bhangu, Aneel Amir] Univ Birmingham, Acad Dept Surg, Birmingham, W Midlands, England. [Bhangu, Aneel Amir] Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England. [Fitzgerald, James Edward] Royal Free Hosp NHS, Dept Gen Surg, Barnet Hosp Campus, London, England. RP Spence, RT (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Codman Ctr, Boston, MA 02114 USA.; Spence, RT (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Surg, ZA-7700 Rondebosch, South Africa. EM rtspence@mgh.harvard.edu NR 11 TC 0 Z9 1 U1 0 U2 1 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 EI 2078-5135 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD FEB PY 2016 VL 106 IS 2 BP 125 EP 126 DI 10.7196/SAMJ.2016.v106i2.10183 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DK3IJ UT WOS:000374810000001 PM 26821888 ER PT J AU Spence, RT Panieri, E Rayne, SL AF Spence, R. T. Panieri, E. Rayne, S. L. CA GlobalSurg South Africa Collaborat TI A multicentre evaluation of emergency abdominal surgery in South Africa: Results from the GlobalSurg-1 South Africa study SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID QUALITY AB Background. GlobalSurg-1 was a multicentre, international, prospective cohort study conducted to address the global lack of surgical outcomes data. Six South African (SA) hospitals participated in the landmark surgical outcomes study. In this subsequent study, we collated the data from these six local participants and hypothesised that the location of surgery was an independent risk factor for an adverse outcome following emergency intraperitoneal surgery. Methods. Participating hospitals contributed 30-day outcomes data of consecutive emergency intraperitoneal surgical operations performed during a 2-week period between July and November 2014. The six heterogeneous hospital cohorts were compared by categorical confounders. The primary outcome measure was in-hospital mortality; secondary outcome measures were in-hospital morbidity and length of stay of >14 days. The unadjusted association between hospital and adverse outcome and the univariate association between categorical confounders and adverse outcome were tested. Significant associations were further tested by a multivariate stepwise forward logistic regression model built for each outcome of interest. Results. Six hospitals (designated 1-6) contributed outcomes data for 169 operations. The mean age of the patients was 34.9 years.(range 9-82), 116 (68.6%) were male, and the majority (37.2%) presented as a result of trauma. Hospital 5 was associated with 76-fold increased odds of in-hospital death and 58-fold increased odds of a major in-hospital complication, and hospital 3 was: associated with 3-fold increased odds of any in-hospital complication. The final model predicting in-hospital death had a receiver operating characteristic curve statistic of 0.8892. Conclusion. The hospital is an independent risk factor for risk-adjusted adverse outcomes following emergency intraperitoneal surgery in SA. C1 [Spence, R. T.] Massachusetts Gen Hosp, Dept Gen Surg, Codman Ctr, Boston, MA 02114 USA. [Spence, R. T.; Panieri, E.] Univ Cape Town, Fac Hlth Sci, Dept Surg, ZA-7700 Rondebosch, South Africa. [Rayne, S. L.] Univ Witwatersrand, Dept Surg, Fac Hlth Sci, ZA-2001 Johannesburg, South Africa. RP Spence, RT (reprint author), Massachusetts Gen Hosp, Dept Gen Surg, Codman Ctr, Boston, MA 02114 USA.; Spence, RT (reprint author), Univ Cape Town, Fac Hlth Sci, Dept Surg, ZA-7700 Rondebosch, South Africa. EM rtspence@mgh.harvard.edu NR 10 TC 0 Z9 1 U1 0 U2 1 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 EI 2078-5135 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD FEB PY 2016 VL 106 IS 2 BP 163 EP 168 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DK3IJ UT WOS:000374810000018 PM 26821895 ER PT J AU Bastian, LA Gray, KE DeRycke, E Mirza, S Gierisch, JM Haskell, SG Magruder, KM Wakelee, HA Wang, AG Ho, GYF LaCroix, AZ AF Bastian, Lori A. Gray, Kristen E. DeRycke, Eric Mirza, Shireen Gierisch, Jennifer M. Haskell, Sally G. Magruder, Kathryn M. Wakelee, Heather A. Wang, Ange Ho, Gloria Y. F. LaCroix, Andrea Z. TI Differences in Active and Passive Smoking Exposures and Lung Cancer Incidence Between Veterans and Non-Veterans in the Women's Health Initiative SO GERONTOLOGIST LA English DT Article DE Lung cancer; Smoking; Tobacco; Women Veterans ID NEVER-SMOKERS; CIGARETTE-SMOKING; RISK-FACTORS; US MILITARY; TOBACCO USE; MORTALITY; PREVALENCE; PROMOTION; BEHAVIORS; TRENDS AB Introduction: Women Veterans may have higher rates of both active and passive tobacco exposure than their civilian counterparts, thereby increasing their risk for lung cancer. Purpose of the Study: To compare differences in active and passive smoking exposure and lung cancer incidence among women Veterans and non-Veterans using prospective data from the Women's Health Initiative (WHI). Design and Methods: We used data from the WHI, which collected longitudinal demographic, clinical, and laboratory data on 161,808 postmenopausal women. We employed linear and multinomial regression and generalized linear models to compare active and passive smoking exposure between Veterans and non-Veterans and Cox proportional hazards models to estimate differences in lung cancer incidence rates. Results: After adjustment, Veterans had 2.54 additional pack years of smoking compared with non-Veterans (95% confidence interval [CI] 1.68, 3.40). Veterans also had a 1% increase in risk of any passive smoking exposure (95% CI 1.00, 1.02) and a 9% increase in risk of any workplace exposure (95% CI 1.07, 1.11) compared with non-Veterans. After adjustment for age and smoking exposures, Veterans did not have a higher risk of lung cancer compared with non-Veterans (relative risk = 1.06 95% CI 0.86, 1.30). Implications: Women Veterans had higher rates of tobacco use and exposure to passive smoking, which were associated with a higher risk for lung cancer compared with non-Veterans. Clinicians who care for Veterans need to be aware that older women Veterans have more exposures to risk factors for lung cancer. C1 [Bastian, Lori A.; DeRycke, Eric; Mirza, Shireen] VA Connecticut, 555 Willard Ave, Newington, CT 06111 USA. [Bastian, Lori A.] Univ Connecticut, Div Gen Internal Med, Farmington, CT USA. [Gray, Kristen E.] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [Gray, Kristen E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Mirza, Shireen] Univ Connecticut, Dept Med, Newington, CT USA. [Gierisch, Jennifer M.] Durham VA Med Ctr, Durham, NC USA. [Gierisch, Jennifer M.] Duke Univ, Dept Med, Durham, NC USA. [Haskell, Sally G.] Womens Hlth Serv, VA Off Patient Care, Washington, DC USA. [Haskell, Sally G.] VA Connecticut Hlth Care Syst, West Haven, CT USA. [Haskell, Sally G.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. [Magruder, Kathryn M.] VA Med Ctr, Charleston, SC USA. [Wakelee, Heather A.] Stanford Univ, Dept Med, Oncol, Stanford, CA 94305 USA. [Wang, Ange] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Ho, Gloria Y. F.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA. RP Bastian, LA (reprint author), VA Connecticut, 555 Willard Ave, Newington, CT 06111 USA. EM lori.bastian@va.gov FU National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C]; U.S. Department of Veterans Affairs; Health Service Research Development [CRE 12-008]; VA Health Services Research and Development (HSRD) [TPP 61-029]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOP14-439]; VA Office of Women's Health FX The Women's Health Initiative programs are funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services through contracts, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C. Dr. Bastian was supported by the U.S. Department of Veterans Affairs; Health Service Research & Development CRE 12-008. Dr. Gray was supported by VA Health Services Research and Development (HSR&D) Postdoctoral Fellowship (TPP 61-029). This research was also supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOP14-439 and the VA Office of Women's Health. NR 36 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S102 EP S111 DI 10.1093/geront/gnv664 PG 10 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500011 PM 26768384 ER PT J AU Bastian, LA Hayes, PM Haskell, SG Atkins, D Reiber, GE LaCroix, AZ Yano, EM AF Bastian, Lori A. Hayes, Patricia M. Haskell, Sally G. Atkins, David Reiber, Gayle E. LaCroix, Andrea Z. Yano, Elizabeth M. TI Improving Our Understanding of Health Issues in Older Women Veterans SO GERONTOLOGIST LA English DT Editorial Material ID CARE C1 [Bastian, Lori A.; Haskell, Sally G.] Vet Affairs VA Connecticut Healthcare Syst, PRIME Ctr, West Haven, CT USA. [Bastian, Lori A.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Hayes, Patricia M.; Haskell, Sally G.] Vet Hlth Adm, Womens Hlth Serv, Washington, DC USA. [Haskell, Sally G.] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Atkins, David] Hlth Serv Res & Dev Serv, Dept Vet Affairs, Washington, DC USA. [Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA. [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR&D, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Bastian, LA (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave Mail Code 151, West Haven, CT 06516 USA. EM lori.bastian@va.gov FU National Heart, Lung and Blood Institute, National Institute of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Department of Veterans Affairs Health Services Research and Development VA HSRD FOP [FOP 14-439, SDR 10-012]; VA Women's Health Services; VA HSR&D VA Senior Research Career Scientist Awards [RCS 98-353, RCS 05-195] FX The WHI program is funded by the National Heart, Lung and Blood Institute, National Institute of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.; This work was also supported by the Department of Veterans Affairs Health Services Research and Development VA HSR&D FOP 14-439 and SDR 10-012, and the VA Women's Health Services. Dr. Reiber's and Yano's efforts were supported by VA HSR&D VA Senior Research Career Scientist Awards (Reiber Project RCS 98-353 and Yano Project RCS 05-195). NR 19 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S10 EP S13 DI 10.1093/geront/gnv672 PG 4 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500003 PM 26768383 ER PT J AU Callegari, LS Gray, KE Zephyrin, LC Harrington, LB Gerber, MR Cochrane, BB Weitlauf, JC Bean-Mayberry, B Bastian, LA Mattocks, KM Haskell, SG Katon, JG AF Callegari, Lisa S. Gray, Kristen E. Zephyrin, Laurie C. Harrington, Laura B. Gerber, Megan R. Cochrane, Barbara B. Weitlauf, Julie C. Bean-Mayberry, Bevanne Bastian, Lori A. Mattocks, Kristin M. Haskell, Sally G. Katon, Jodie G. TI Hysterectomy and Bilateral Salpingo-Oophorectomy: Variations by History of Military Service and Birth Cohort SO GERONTOLOGIST LA English DT Article DE Women Veterans; Hysterectomy; Bilateral salpingo-oophorectomy ID NATIONALLY REPRESENTATIVE SAMPLE; CHRONIC PELVIC PAIN; WOMENS HEALTH; UNITED-STATES; CARDIOVASCULAR-DISEASE; URINARY-INCONTINENCE; POSTMENOPAUSAL WOMEN; OVARIAN CONSERVATION; BEHAVIORAL-MODEL; LONG-TERM AB Introduction: Little is known about hysterectomy and bilateral salpingo-oophorectomy (BSO), which are associated with both health risks and benefits, among women Veterans. Purpose of the Study: To compare the prevalence of hysterectomy with or without BSO, and early hysterectomy, between postmenopausal Veterans and non-Veterans. Design and Methods: We used baseline data from the Women's Health Initiative Clinical Trial and Observational Study. Multinomial logistic regression models examined differences in the prevalence of hysterectomy (neither hysterectomy nor BSO, hysterectomy without BSO, and hysterectomy with BSO) between Veterans and non-Veterans. Generalized linear models were used to determine whether early hysterectomy (before age 40) differed between Veterans and non-Veterans. Analyses were stratified by birth cohort (<65, >= 65 years at enrollment). Results: The unadjusted prevalence of hysterectomy without BSO was similar among Veterans and non-Veterans in both birth cohorts (<65: 22% vs 21%; >= 65: 22% vs 21%). The unadjusted prevalence of hysterectomy with BSO was equivalent among Veterans and non-Veterans in the >65 cohort (21%), but higher among Veterans in the <65 cohort (22% vs 19%). In adjusted analyses, although no differences were observed in the >65 cohort, Veterans in the <65 cohort had higher odds of hysterectomy without BSO (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03, 1.36) and with BSO (OR 1.26, 95% CI 1.10, 1.45), as well as elevated risk of early hysterectomy (relative risk 1.32, 95% CI 1.19, 1.47), compared with non-Veterans. Implications: Aging women Veterans may have higher prevalence of hysterectomy and BSO than non-Veterans. This information contributes to understanding the health needs and risks of women Veterans and can inform clinical practice and policy for this population. C1 [Callegari, Lisa S.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Callegari, Lisa S.; Gray, Kristen E.; Katon, Jodie G.] VA Puget Sound Hlth Care Syst, HSR&D, 1660 South Columbian Way S-152, Seattle, WA 98108 USA. [Gray, Kristen E.; Katon, Jodie G.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Zephyrin, Laurie C.; Haskell, Sally G.; Katon, Jodie G.] VA Off Patient Care, Womens Hlth Serv, Washington, DC USA. [Zephyrin, Laurie C.] VA New York Harbor, New York, NY USA. [Zephyrin, Laurie C.] NYU, Langone Sch Med, Dept Obstet & Gynecol, New York, NY 10003 USA. [Zephyrin, Laurie C.] Vet Hlth Adm, Dept Vet Affairs, Washington, DC USA. [Harrington, Laura B.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Gerber, Megan R.] VA Boston Healthcare Syst, Boston, MA USA. [Gerber, Megan R.] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Cochrane, Barbara B.] Univ Washington, Sch Nursing, de Tornyay Ctr Hlth Aging, Seattle, WA 98195 USA. [Cochrane, Barbara B.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Weitlauf, Julie C.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Weitlauf, Julie C.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Bean-Mayberry, Bevanne] VA Greater Angeles Hlth Care Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Bean-Mayberry, Bevanne] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. [Bastian, Lori A.] VA Connecticut, West Haven, CT USA. [Bastian, Lori A.] Univ Connecticut, Div Gen Internal Med, Farmington, CT USA. [Mattocks, Kristin M.] VA Cent Western Massachusetts, Leeds, W Yorkshire, England. [Mattocks, Kristin M.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Haskell, Sally G.] VA Connecticut Hlth Care Syst, New Haven, CT USA. RP Callegari, LS (reprint author), VA Puget Sound Hlth Care Syst, HSR&D, 1660 South Columbian Way S-152, Seattle, WA 98108 USA. EM lisa.callegari@va.gov FU National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C]; VA Health Services Research and Development (HSR D) [TPM 61-041, TPP 61-029]; U.S. Department of Veterans Affairs; Office of Patient Care Services; Women's Health Services; VA Puget Sound Center of Innovation for Veteran-Centered and Value-Driven Care; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOP14-439]; VA Office of Women's Health FX The Women's Health Initiative programs are funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services through contracts, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C. WHI Investigators: Program Office: (National Heart, Lung, and Blood Institute, Bethesda, MD) Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg. Investigators and Academic Centers: (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar Health Research Institute/ Howard University, Washington, DC) Barbara V. Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L. Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker. Women's Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker. Drs. Callegari and Gray were supported by VA Health Services Research and Development (HSR& D) Postdoctoral Fellowships (TPM 61-041 and TPP 61-029, respectively). Dr. Katon was supported by the U.S. Department of Veterans Affairs; Office of Patient Care Services; Women's Health Services and the VA Puget Sound Center of Innovation for Veteran-Centered and Value-Driven Care. The research reported here was also supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOP14-439 and the VA Office of Women's Health. NR 53 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S67 EP S77 DI 10.1093/geront/gnv666 PG 11 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500008 PM 26768393 ER PT J AU Gray, KE Katon, JG Rillamas-Sun, E Bastian, LA Nelson, KM LaCroix, AZ Reiber, GE AF Gray, Kristen E. Katon, Jodie G. Rillamas-Sun, Eileen Bastian, Lori A. Nelson, Karin M. LaCroix, Andrea Z. Reiber, Gayle E. TI Association Between Chronic Conditions and Physical Function Among Veteran and Non-Veteran Women With Diabetes SO GERONTOLOGIST LA English DT Article DE Physical function; Diabetes; Veterans; Women's issues; Chronic illness ID POSTTRAUMATIC-STRESS-DISORDER; LOWER-EXTREMITY DISABILITY; CENTERED MEDICAL HOME; QUALITY-OF-LIFE; OLDER WOMEN; MILITARY SERVICE; UNITED-STATES; HEALTH SURVEY; SELF-REPORTS; MELLITUS AB Purpose of the Study: To compare the number of chronic conditions among a list of 12 and their association with physical function among postmenopausal non-Veteran and Veteran women with diabetes. Design and Methods: Among women with diabetes from the Women's Health Initiative, we compared the average number of chronic conditions between non-Veterans and Veterans and the association between total number of chronic conditions on subsequent RAND-36 physical function. To examine associations between each condition and subsequent physical function, we compared women with diabetes plus one chronic condition to women with diabetes alone using linear regression in separate models for each condition and for non-Veterans and Veterans. Results: Both non-Veterans (N = 23,542) and Veterans (N = 618) with diabetes had a median of 3 chronic conditions. Decreases in physical function for each additional condition were larger among Veterans than non-Veterans (-6.3 vs. -4.1 points). Decreases in physical function among women with diabetes plus one chronic condition were greater than that reported for diabetes alone for all combinations and were more pronounced among Veterans (non-Veterans: -11.1 to -24.2, Veterans: -16.6 to -40.4 points). Hip fracture, peripheral artery disease, cerebrovascular disease, and coronary disease in combination with diabetes were associated with the greatest decreases in physical function. Implications: Chronic conditions were common among postmenopausal women with diabetes and were associated with large declines in physical function, particularly among Veterans. Interventions to prevent and reduce the impact of these conditions and facilitate coordination of care among women with diabetes may help them maintain physical function. C1 [Gray, Kristen E.; Katon, Jodie G.; Rillamas-Sun, Eileen; Nelson, Karin M.; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. [Gray, Kristen E.; Katon, Jodie G.; Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Katon, Jodie G.] Womens Hlth Serv, VA Off Patient Care, Washington, DC USA. [Rillamas-Sun, Eileen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Bastian, Lori A.] VA Connecticut Healthcare Syst, PRIME Ctr, West Haven, CT USA. [Bastian, Lori A.] Univ Connecticut, Ctr Hlth, Div Gen Internal Med, Farmington, CT USA. [Nelson, Karin M.] VA Puget Sound Hlth Care Syst, Gen Internal Med Serv, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Epidemiol, San Diego, CA 92103 USA. [Reiber, Gayle E.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Gray, KE (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way S-152, Seattle, WA 98108 USA. EM kristen.gray2@va.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201 100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; U.S. Department of Veterans Affairs Health Services Research & Development Program [TPP 61-029]; U.S. Department of Veterans Affairs Office of Patient Care, Women's Health Services; VA Puget Sound Center of Innovation for Veteran-Centered and Value-Driven Care; Department of Veterans Affairs Health Services Research and Development VA HSRD [FOP 14-439]; VA Office of Women's Health; VA HSR&D Senior Research Career Scientist Award [RCS 98-353] 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 (grant numbers HHSN268201100046C, HHSN268201100001C, HHSN268201 100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C).; WHI Investigators-Program Office: Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller (National Heart, Lung, and Blood Institute, Bethesda, MD). Clinical Coordinating Center: Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles Kooperberg (Fred Hutchinson Cancer Research Center, Seattle, WA). Investigators and Academic Centers: JoAnn E. Manson (Brigham and Women's Hospital, Harvard Medical School, Boston, MA); Barbara V. Howard (MedStar Health Research Institute/Howard University, Washington, DC); Marcia L. Stefanick (Stanford Prevention Research Center, Stanford, CA); Rebecca Jackson (The Ohio State University, Columbus, OH); Cynthia A. Thomson (University of Arizona, Tucson/Phoenix, AZ); Jean Wactawski-Wende (University at Buffalo, Buffalo, NY); Marian Limacher (University of Florida, Gainesville/Jacksonville, FL); Robert Wallace (University of Iowa, Iowa City/Davenport, IA); Lewis Kuller (University of Pittsburgh, Pittsburgh, PA); and Sally Shumaker (Wake Forest University School of Medicine, Winston-Salem, NC). Women's Health Initiative Memory Study: Sally Shumaker (Wake Forest University School of Medicine, Winston-Salem, NC). For a list of all the investigators who have contributed to WHI science, please visit: https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20I nvestigator%20Long%20List.pdf This work was also supported by the U.S. Department of Veterans Affairs Health Services Research & Development Program (Postdoctoral Fellowship TPP 61-029 to K. E. Gray); U.S. Department of Veterans Affairs Office of Patient Care, Women's Health Services; and the VA Puget Sound Center of Innovation for Veteran-Centered and Value-Driven Care (to J. G. Katon). This work was also supported by the Department of Veterans Affairs Health Services Research and Development VA HSR&D FOP 14-439; the VA Office of Women's Health; and a VA HSR&D Senior Research Career Scientist Award (Project RCS 98-353 to G. E. Reiber). NR 75 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S112 EP S125 DI 10.1093/geront/gnv675 PG 14 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500012 PM 26768385 ER PT J AU Katon, JG Gray, KE Gerber, MR Harrington, LB Woods, NF Weitlauf, JC Bean-Mayberry, B Goldstein, KM Hunt, JR Katon, WJ Haskell, SG McCutcheon, SJ Gass, ML Gibson, CJ Zephyrin, LC AF Katon, Jodie G. Gray, Kristen E. Gerber, Megan R. Harrington, Laura B. Woods, Nancy F. Weitlauf, Julie C. Bean-Mayberry, Bevanne Goldstein, Karen M. Hunt, Julie R. Katon, Wayne J. Haskell, Sally G. McCutcheon, Susan J. Gass, Margery L. Gibson, Carolyn J. Zephyrin, Laurie C. TI Vasomotor Symptoms and Quality of Life Among Veteran and Non-Veteran Postmenopausal Women SO GERONTOLOGIST LA English DT Article DE Veterans; Vasomotor symptoms; Quality of life; Depression; Obesity ID MENOPAUSAL HOT FLUSHES; MIDLIFE WOMEN; FUNCTIONAL DISABILITY; HORMONE-THERAPY; MENTAL-HEALTH; NIGHT SWEATS; PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; RANDOMIZED-TRIAL; CHILDHOOD ABUSE AB Introduction: Vasomotor symptoms (VMS), including hot flashes and night sweats, are common among postmenopausal women and are associated with reduced health related quality of life (HRQOL). Purpose of the Study: To determine whether Veterans are more likely to report VMS than non-Veterans, and whether the association of VMS with HRQOL varies by Veteran status. Design and Methods: We used data from the Women's Health Initiative Observational Study, including self-reported baseline VMS presence and severity, and HRQOL at follow-up Year 3 (RAND Short Form 36-Item Health Survey). Employing generalized linear models we estimated whether Veteran status was associated with any VMS. We estimated the association between any VMS and HRQOL using linear regression, stratified by Veteran status. Interaction terms were added separately to determine whether the association varied by baseline depression, obesity, or smoking status. Results: The final analyses included 77,153 postmenopausal women (2,004 Veterans). After adjustment, Veterans were no more likely than non-Veterans to report any VMS at baseline (relative risk [RR] 0.97, 95% confidence interval [CI] 0.90-1.04) or moderate to severe VMS (RR 1.03, 95% CI 0.89-1.18). Any VMS was associated with decreased HRQOL at Year 3, particularly among Veterans (mean difference range: Veterans -2.7 to -4.6, p-values <.001; non-Veterans -2.2 to -2.6, 95% CI -0.13 to -0.09, p values <.001). Baseline depression and obesity, but not smoking, amplified the negative association between VMS and HRQOL. Implications: Multicondition care models for postmenopausal Veteran and non-Veteran women are needed that incorporate management strategies for VMS, weight, and depression. C1 [Katon, Jodie G.; Gray, Kristen E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, 1660 South Columbian Way,S-152, Seattle, WA 98108 USA. [Katon, Jodie G.; Haskell, Sally G.; McCutcheon, Susan J.; Zephyrin, Laurie C.] VA Off Patient Care, Womens Hlth Serv, Washington, DC USA. [Gray, Kristen E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Gerber, Megan R.] VA Boston Healthcare Syst, Boston, MA USA. [Harrington, Laura B.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Woods, Nancy F.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Weitlauf, Julie C.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Weitlauf, Julie C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Bean-Mayberry, Bevanne] VA Greater Los Angeles Hlth Care Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Bean-Mayberry, Bevanne] VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med, Los Angeles, CA USA. [Goldstein, Karen M.] Durham VA Med Ctr, Durham, NC USA. [Goldstein, Karen M.] Duke Univ, Sch Med, Dept Gen Internal Med, Durham, NC USA. [Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Katon, Wayne J.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Haskell, Sally G.] VA Connecticut Hlth Care Syst, New Haven, CT USA. [Gass, Margery L.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Mayfield Hts, OH USA. [Gibson, Carolyn J.] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Zephyrin, Laurie C.] NYU, Langone Sch Medicine, Dept Obstet & Gynecol, New York, NY 10003 USA. RP Katon, JG (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, 1660 South Columbian Way,S-152, Seattle, WA 98108 USA. EM jodie.katon@va.gov OI Gerber, Megan/0000-0002-8444-5554 FU National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C]; U.S. Department of Veterans Affairs; Office of Patient Care; Women's Health Services; VA Puget Sound Center of Innovation for Veteran-Centered; Value-Driven Care; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOP14-439]; VA Office of Women's Health FX The Women's Health Initiative programs are funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; U.S. Department of Health and Human Services through contracts, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C. Dr. J Katon was supported by the U.S. Department of Veterans Affairs; Office of Patient Care; Women's Health Services and the VA Puget Sound Center of Innovation for Veteran-Centered; and Value-Driven Care. The research reported here was also supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOP14-439 and the VA Office of Women's Health. NR 80 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S40 EP S53 DI 10.1093/geront/gnv104 PG 14 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500006 PM 26220418 ER PT J AU LaCroix, AZ Rillamas-Sun, E Woods, NF Weitlauf, J Zaslavsky, O Shih, R LaMonte, MJ Bird, C Yano, EM LeBoff, M Washington, D Reiber, G AF LaCroix, Andrea Z. Rillamas-Sun, Eileen Woods, Nancy F. Weitlauf, Julie Zaslavsky, Oleg Shih, Regina LaMonte, Michael J. Bird, Chloe Yano, Elizabeth M. LeBoff, Meryl Washington, Donna Reiber, Gayle TI Aging Well Among Women Veterans Compared With Non-Veterans in the Women's Health Initiative SO GERONTOLOGIST LA English DT Article DE Healthy aging; disability; Quality of life; Women Veterans ID QUALITY-OF-LIFE; CARE UTILIZATION; SOCIAL SUPPORT; OLDER WOMEN; RESILIENCE; OUTCOMES; THERAPY; STRESS; SCALE; USERS AB Purpose of the Study: To examine whether Veteran status influences (a) women's survival to age 80 years without disease and disability and (b) indicators of successful, effective, and optimal aging at ages 80 years and older. Design and Methods: The Women's Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50-79 years from 1993 to 1998. We compared successful aging indicators collected in 2011-2012 via mailed questionnaire among 33,565 women (921 Veterans) who reached the age of 80 years and older, according to Veteran status. A second analysis focused on women with intact mobility at baseline who could have reached age 80 years by December 2013. Multinominal logistic models examined Veteran status in relation to survival to age 80 years without major disease or mobility disability versus having prevalent or incident disease, having mobility disability, or dying prior to age 80 years. Results: Women Veterans aged 80 years and older reported significantly lower perceived health, physical function, life satisfaction, social support, quality of life, and purpose in life scale scores compared with non-Veterans. The largest difference was in physical function scores (53.0 for Veterans vs 59.5 for non-Veterans; p < .001). Women Veterans were significantly more likely to die prior to age 80 years than non-Veteran WHI participants (multivariate adjusted odds ratio = 1.20; 95% confidence interval, 1.04-1.38). In both Veteran and non-Veteran women, healthy survival was associated with not smoking, higher physical activity, healthy body weight, and fewer depressive symptoms. C1 [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Epidemiol, San Diego, CA 92103 USA. [Rillamas-Sun, Eileen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Woods, Nancy F.] Univ Washington, Seattle WHI Clin Ctr, Biobehav Nursing, Seattle, WA 98195 USA. [Weitlauf, Julie] VA Palo Alto Hlth Care Syst, Sierra Pacific MIRECC, Palo Alto, CA USA. [Weitlauf, Julie] Ctr Innovat Implementat, La Jolla, CA USA. [Weitlauf, Julie] Stanford Univ, Dept Psychiat & Behav Sci, Stanford Canc Inst, Palo Alto, CA 94304 USA. [Zaslavsky, Oleg] Univ Haifa, Fac Hlth Sci & Social Welf, IL-31999 Haifa, Israel. [Shih, Regina] RAND Corp, Arlington, VA USA. [LaMonte, Michael J.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY USA. [Bird, Chloe] RAND Corp, Santa Monica, CA USA. [Yano, Elizabeth M.; Washington, Donna] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [LeBoff, Meryl] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens,Dept Med, Boston, MA USA. [Reiber, Gayle] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP LaCroix, AZ (reprint author), Univ Calif San Diego, Div Epidemiol, Dept Family Med & Publ Hlth, 9500 Gilman Dr 0725, La Jolla, CA 92093 USA. EM alacroix@ucsd.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSRD) Service [FOP14-439]; VA Office of Women's Health; VA HSR&D Senior Research Career Scientist awards [98-353, 05-195] 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 through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.; This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSR&D) Service FOP14-439 and the VA Office of Women's Health. Drs. Reiber and Yano were funded through VA HSR&D Senior Research Career Scientist awards (RCS # 98-353 and RCS # 05-195, respectively). NR 44 TC 1 Z9 1 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S14 EP S26 DI 10.1093/geront/gnv124 PG 13 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500004 PM 26768388 ER PT J AU Lehavot, K Rillamas-Sun, E Weitlauf, J Kimerling, R Wallace, RB Sadler, AG Woods, NF Shipherd, JC Mattocks, K Cirillo, DJ Stefanick, ML Simpson, TL AF Lehavot, Keren Rillamas-Sun, Eileen Weitlauf, Julie Kimerling, Rachel Wallace, Robert B. Sadler, Anne G. Woods, Nancy Fugate Shipherd, Jillian C. Mattocks, Kristin Cirillo, Dominic J. Stefanick, Marcia L. Simpson, Tracy L. TI Mortality in Postmenopausal Women by Sexual Orientation and Veteran Status SO GERONTOLOGIST LA English DT Article DE All-cause mortality; Women Veterans; Sexual minority ID MENTAL-HEALTH; GAY; DISPARITIES; ADULTS; RISK; POPULATIONS; DISORDERS; LESBIANS; DESIGN; STIGMA AB Purpose of the Study: To examine differences in all-cause and cause-specific mortality by sexual orientation and Veteran status among older women. Design and Methods: Data were from the Women's Health Initiative, with demographic characteristics, psychosocial factors, and health behaviors assessed at baseline (1993-1998) and mortality status from all available data sources through 2014. Women with baseline information on lifetime sexual behavior and Veteran status were included in the analyses (N = 137,639; 1.4% sexual minority, 2.5% Veteran). The four comparison groups included sexual minority Veterans, sexual minority non-Veterans, heterosexual Veterans, and heterosexual non-Veterans. Cox proportional hazard models were used to estimate mortality risk adjusted for demographic, psychosocial, and health variables. Results: Sexual minority women had greater all-cause mortality risk than heterosexual women regardless of Veteran status (hazard ratio [HR] = 1.20, 95% confidence interval [CI]: 1.07-1.36) and women Veterans had greater all-cause mortality risk than non-Veterans regardless of sexual orientation (HR = 1.14, 95% CI: 1.06-1.22), but the interaction between sexual orientation and Veteran status was not significant. Sexual minority women were also at greater risk than heterosexual women for cancer-specific mortality, with effects stronger among Veterans compared to non-Veterans (sexual minority x Veteran HR = 1.70, 95% CI: 1.01-2.85). Implications: Postmenopausal sexual minority women in the United States, regardless of Veteran status, may be at higher risk for earlier death compared to heterosexuals. Sexual minority women Veterans may have higher risk of cancer-specific mortality compared to their heterosexual counterparts. Examining social determinants of longevity may be an important step to understanding and reducing these disparities. C1 [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1600 South Columbian Way, Seattle, WA 98108 USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rillamas-Sun, Eileen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Rillamas-Sun, Eileen] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1600 South Columbian Way, Seattle, WA 98108 USA. [Weitlauf, Julie] VA Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA. [Weitlauf, Julie] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Palo Alto, CA USA. [Weitlauf, Julie] Stanford Canc Inst, Stanford, CA USA. [Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [Sadler, Anne G.] Iowa City VA Med Ctr, Iowa City, IA USA. [Woods, Nancy Fugate] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Natl Ctr PTSD Womens Hlth Sci, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Shipherd, Jillian C.] LGBT Program Patient Care Serv, Washington, DC USA. [Mattocks, Kristin] VA Cent Western Massachusetts, Leeds, W Yorkshire, England. [Mattocks, Kristin] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Cirillo, Dominic J.] Univ Iowa, Univ Rochester, Sch Med & Dent, Dept Epidemiol,Dept Publ Hlth Sci, Iowa City, NY USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, 1600 South Columbian Way, Seattle, WA 98108 USA. [Lehavot, Keren] VA Puget Sound Hlth Care Syst, 1600 South Columbian Way, Seattle, WA 98108 USA. RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, 1600 South Columbian Way, Seattle, WA 98108 USA. EM keren.lehavot@va.gov OI Cirillo, Dominic/0000-0001-7017-221X FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOB14-439]; VA Office of Women's Health; Clinical Science Research and Development (CSR&D) Career Development Award [IK2 CX000867] FX The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.; The research reported here was supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOB14-439 and by the VA Office of Women's Health. Dr. Lehavot was supported by a Clinical Science Research and Development (CSR&D) Career Development Award (IK2 CX000867). NR 45 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 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S150 EP S162 DI 10.1093/geront/gnv125 PG 13 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500015 PM 26768389 ER PT J AU Simpson, TL Rillamas-Sun, E Lehavot, K Timko, C Rubin, A Cucciare, MA Williams, EC Padula, CB Hunt, JR Hoggatt, KJ AF Simpson, Tracy L. Rillamas-Sun, Eileen Lehavot, Keren Timko, Christine Rubin, Amy Cucciare, Michael A. Williams, Emily C. Padula, Claudia B. Hunt, Julie R. Hoggatt, Katherine J. TI Alcohol Consumption Levels and All-Cause Mortality Among Women Veterans and Non-Veterans Enrolled in the Women's Health Initiative SO GERONTOLOGIST LA English DT Article DE Mortality risk; Drinking; Veteran status; Postmenopausal women; Health behavior practices ID RISK; SAMPLE; MEN; PARTICIPANTS; METAANALYSIS; INDICATORS; DISORDERS; FREQUENCY; DRINKING; DESIGN AB Purpose: To address research gaps regarding women Veterans' alcohol consumption and mortality risk as compared to non-Veterans, the current study evaluated whether alcohol consumption amounts differed between women Veterans and non-Veterans, whether Veterans and non-Veterans within alcohol consumption groups differed on all-cause mortality, and whether Veteran status modified the association between alcohol consumption and all-cause mortality. Design and Methods: Six alcohol consumption groups were created using baseline data from the Women's Health Initiative Program (N = 145,521): lifelong abstainers, former drinkers, less than 1 drink/week (infrequent drinkers), 1-7 drinks/week (moderate drinkers), 8-14 drinks/week (moderately heavy drinkers), and 15 or more drinks/week (heavy drinkers). The proportions of Veteran and non-Veteran women within each alcohol consumption category were compared. Mortality rates within each alcohol consumption category were compared by Veteran status. Cox proportional hazard models, including a multiplicative interaction term for Veteran status, were fit to estimate adjusted mortality hazard (rate) ratios for each alcohol consumption category relative to a reference group of either lifelong abstainers or moderate drinkers. Results: Women Veterans were less likely to be lifelong abstainers than non-Veterans. Women Veterans who were former or moderate drinkers had higher age-adjusted mortality rates than did non-Veterans within these alcohol consumption categories. In the fully adjusted multivariate models, Veteran status did not modify the association between alcohol consumption category and mortality with either lifelong abstainers or moderate drinkers as referents. Implications: The results suggest that healthcare providers may counsel Veteran and non-Veteran women in similar ways regarding safe and less safe levels of alcohol consumption. C1 [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy L.; Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, 1600 South Columbian Way, Seattle, WA 98108 USA. [Rillamas-Sun, Eileen; Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Rillamas-Sun, Eileen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Lehavot, Keren; Williams, Emily C.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Timko, Christine] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Hlth Serv Res & Dev, Palo Alto, CA USA. [Timko, Christine] Stanford Univ, Menlo Pk, CA USA. [Rubin, Amy] VA Boston Hlth Care Syst, Gen Internal Med Sect, Boston, MA USA. [Rubin, Amy] VA Boston Hlth Care Syst, Natl Ctr PTSD, Boston, MA USA. [Rubin, Amy] Boston Univ, Boston, MA 02215 USA. [Cucciare, Michael A.] Cent Arkansas Vet Hlth Care Syst, Ctr Mental Hlth Care & Outcomes Res CeMHOR, Little Rock, AR USA. [Cucciare, Michael A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Williams, Emily C.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, 1600 South Columbian Way, Seattle, WA 98108 USA. [Padula, Claudia B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Hoggatt, Katherine J.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Hoggatt, Katherine J.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Simpson, TL (reprint author), Univ Washington, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, 1600 South Columbian Way, Seattle, WA 98108 USA. EM tracy.simpson@va.gov FU National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOP14-439]; VA Office of Women's Health; Clinical Science Research and Development (CSR&D) Career Development Award [IK2 CX000867]; Career Development Award from VA Health Services Research Development [CDA 12-276] FX The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.; This research was also supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOP14-439 and the VA Office of Women's Health.; Dr. Lehavot was supported by a Clinical Science Research and Development (CSR&D) Career Development Award (IK2 CX000867). Dr. Williams was supported by a Career Development Award from VA Health Services Research & Development (CDA 12-276). NR 39 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S138 EP S149 DI 10.1093/geront/gnv667 PG 12 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500014 PM 26768387 ER PT J AU Washington, DL Gray, K Hoerster, KD Katon, JG Cochrane, BB LaMonte, MJ Weitlauf, JC Groessl, E Bastian, L Vitolins, MZ Tinker, L AF Washington, Donna L. Gray, Kristen Hoerster, Katherine D. Katon, Jodie G. Cochrane, Barbara B. LaMonte, Michael J. Weitlauf, Julie C. Groessl, Erik Bastian, Lori Vitolins, Mara Z. Tinker, Lesley TI Trajectories in Physical Activity and Sedentary Time Among Women Veterans in the Women's Health Initiative SO GERONTOLOGIST LA English DT Article DE Women Veterans; Health behavior; Physical activity; Sedentary lifestyle; Sedentary behavior; Health trajectory; Longitudinal Study; Postmenopausal ID LONGITUDINAL DATA-ANALYSIS; OLDER-ADULTS; CARDIOVASCULAR-DISEASE; POPULATION HEALTH; UNITED-STATES; PREVALENCE; BEHAVIOR; PREVENTION; QUESTIONNAIRE; MORTALITY AB Purpose of the Study: Trajectories of physical activity (PA) and sedentary time (ST) after military separation are likely important determinants of women's health outcomes later in life, because low PA and high ST are known contributors to premature mortality risk. Our objective was to compare longitudinal trajectories of recreational PA and ST between Veteran and non-Veteran postmenopausal women from the Women's Health Initiative (WHI). Design and Methods: Women Veteran (n = 3,719) and non-Veteran (n = 141,800) WHI participants were included. Self-reported participation in recreational PA, converted to metabolic equivalent (MET)-hours/week, was prospectively assessed over 8 years. Self-reported ST, defined as hours/day sitting or lying down, was collected at baseline and at Years 3 and 6. Generalized estimating equations were used to compare trajectories of PA and ST between Veterans and non-Veterans, adjusted for demographics and lifestyle behaviors. Results: Veterans had higher baseline PA than non-Veterans (13.2 vs 12.5 MET-hours/week, p = .03). PA declined for both groups, with a steeper decline among Veterans (change/visit year -0.19 vs -0.02 MET-hours/week; interaction p < .001). At baseline, Veterans and non-Veterans had similar levels of ST (107.2 vs 105.9 hours/week, p = 0.42). Over time, ST remained stable among Veterans but declined slightly among non-Veterans (change/visit year -0.19 vs -0.49 hours/week; interaction p = .01). C1 [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev HSR&D, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. [Gray, Kristen; Hoerster, Katherine D.; Katon, Jodie G.] VA Puget Sound Hlth Care Syst Hlth Serv Res & Dev, Seattle, WA USA. [Gray, Kristen; Katon, Jodie G.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA USA. [Hoerster, Katherine D.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA. [Katon, Jodie G.] VA Off Patient Care, Womens Hlth Serv, Seattle, WA USA. [Cochrane, Barbara B.; Tinker, Lesley] Univ Washington, Sch Nursing, Seattle, WA USA. [Cochrane, Barbara B.; Tinker, Lesley] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [LaMonte, Michael J.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY USA. [Weitlauf, Julie C.] VA Palo Alto Hlth Care Syst, Sierra Pacific MIRECC, Palo Alto, CA USA. [Weitlauf, Julie C.] Ctr Innovat Implementat, Seattle, WA USA. [Weitlauf, Julie C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Groessl, Erik] VA San Diego Hlth Serv Res & Dev Unit, San Diego, CA USA. [Groessl, Erik] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Bastian, Lori] VA Connecticut Healthcare Syst, New Haven, CT USA. [Vitolins, Mara Z.] Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOP14-439]; VA Office of Women's Health 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 through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.r This research was also supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOP14-439 and the VA Office of Women's Health. NR 49 TC 0 Z9 0 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S27 EP S39 DI 10.1093/geront/gnv676 PG 13 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500005 PM 26768390 ER PT J AU Washington, DL Bird, CE LaMonte, MJ Goldstein, KM Rillamas-Sun, E Stefanick, ML Woods, NF Bastian, LA Gass, M Weitlauf, JC AF Washington, Donna L. Bird, Chloe E. LaMonte, Michael J. Goldstein, Karen M. Rillamas-Sun, Eileen Stefanick, Marcia L. Woods, Nancy F. Bastian, Lori A. Gass, Margery Weitlauf, Julie C. TI Military Generation and Its Relationship to Mortality in Women Veterans in the Women's Health Initiative SO GERONTOLOGIST LA English DT Article DE Women Veterans; Mortality; Cohort effect; Longitudinal study ID UNITED-STATES; WAR; SERVICE; CANCER; RISK; LIFE AB Purpose of the Study: Women's military roles, exposures, and associated health outcomes have changed over time. However, mortality risk-within military generations or compared with non-Veteran women-has not been assessed. Using data from the Women's Health Initiative (WHI), we examined all-cause and cause-specific mortality by Veteran status and military generation among older women. Design and Methods: WHI participants (3,719 Veterans; 141,802 non-Veterans), followed for a mean of 15.2 years, were categorized into pre-Vietnam or Vietnam/after generations based on their birth cohort. We used cox proportional hazards models to examine the association between Veteran status and mortality by generation. Results: After adjusting for sociodemographic characteristics and WHI study arm, all-cause mortality hazard rate ratios (HRs) for Veterans relative to non-Veterans were 1.16 (95% CI: 1.09-1.23) for pre-Vietnam and 1.16 (95% CI: 0.99-1.36) for Vietnam/after generations. With additional adjustment for health behaviors and risk factors, this excess mortality rate persisted for pre-Vietnam but attenuated for Vietnam/after generations. After further adjustment for medical morbidities, across both generations, Veterans and non-Veterans had similar all-cause mortality rates. Relative to non-Veterans, adjusting for sociodemographics and WHI study arm, pre-Vietnam generation Veterans had higher cancer, cardiovascular, and trauma-related morality rates; Vietnam/after generation Veterans had the highest trauma-related mortality rates (HR = 2.93, 1.64-5.23). Implications: Veterans' higher all-cause mortality rates were limited to the pre-Vietnam generation, consistent with diminution of the healthy soldier effect over the life course. Mechanisms underlying Vietnam/after generation Veteran trauma-related mortality should be elucidated. Efforts to modify salient health risk behaviors specific to each military generation are needed. C1 [Washington, Donna L.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, VA Hlth Serv Res & Dev HSR&D, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Bird, Chloe E.] RAND Corp, Pardee Rand Grad Sch, Santa Monica, CA USA. [LaMonte, Michael J.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Epidemiol & Environm Hlth, Buffalo, NY USA. [Goldstein, Karen M.] Durham VA Hlth Care Syst, Durham, NC USA. [Rillamas-Sun, Eileen] Fred Hutchinson Canc Res Ctr, Seatle, WA USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Stanford Ctr Hlth Res Women & Sex Differences Med, Stanford, CA 94305 USA. [Woods, Nancy F.] Univ Washington, Sch Nursing, Div Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Bastian, Lori A.] VA Connecticut, West Haven, CT USA. [Bastian, Lori A.] Univ Connecticut, Ctr Hlth, West Haven, CT USA. [Gass, Margery] North Amer Menopause Soc, Mayfield Hts, OH USA. [Weitlauf, Julie C.] Sierra Pacific MIRECC, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Weitlauf, Julie C.] Ctr Innovat Implementat, San Diego, CA USA. [Weitlauf, Julie C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [FOP14-439]; VA Office of Women's Health 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 through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The research reported here was supported by Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service FOP14-439 and the VA Office of Women's Health. NR 40 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S126 EP S137 DI 10.1093/geront/gnv669 PG 12 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500013 PM 26768386 ER PT J AU Weitlauf, JC Washington, DL Stefanick, ML AF Weitlauf, Julie C. Washington, Donna L. Stefanick, Marcia L. TI Who Are the Women Veterans in the Women's Health Initiative? SO GERONTOLOGIST LA English DT Editorial Material ID MILITARY SERVICE; MORTALITY; CANCER C1 [Weitlauf, Julie C.] Stanford Univ, Sch Med, Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific MIRECC, Palo Alto, CA 94304 USA. [Weitlauf, Julie C.] Stanford Univ, Sch Med, Ctr Implementat Innovat Ci2i, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford Prevent Res Ctr Stanford, Stanford, CA 94305 USA. RP Weitlauf, JC (reprint author), Stanford Univ, Sch Med, Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific MIRECC, Palo Alto, CA 94304 USA.; Weitlauf, JC (reprint author), Stanford Univ, Sch Med, Ctr Implementat Innovat Ci2i, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. EM wjulie1@stanford.edu FU Women's Mental Health and Aging Core of the Sierra Pacific Mental Illness, Research, Education and Clinical Center (MIRECC); VA Office of Women's Health and VA Health Services Research and Development [VA HSRD FOP 14-439] FX This editorial was supported, in part, by the Women's Mental Health and Aging Core of the Sierra Pacific Mental Illness, Research, Education and Clinical Center (MIRECC) and the VA Office of Women's Health and VA Health Services Research and Development (VA HSR&D FOP 14-439). NR 22 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2016 VL 56 SU 1 BP S6 EP S9 DI 10.1093/geront/gnv674 PG 4 WC Gerontology SC Geriatrics & Gerontology GA DJ5BJ UT WOS:000374221500002 PM 26768392 ER PT J AU Hoguet, A Grajewski, A Hodapp, E Chang, TCP AF Hoguet, Ambika Grajewski, Alana Hodapp, Elizabeth Chang, Ta Chen Peter TI A retrospective survey of childhood glaucoma prevalence according to Childhood Glaucoma Research Network classification SO INDIAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Childhood glaucoma; glaucoma; glaucoma categorization ID PRIMARY CONGENITAL GLAUCOMA; PEDIATRIC GLAUCOMA; OPTIC DISK; EPIDEMIOLOGY; EXPERIENCE AB Purpose: To evaluate the Childhood Glaucoma Research Network (CGRN) classification system and describe the prevalence of each subtype according to this classification. Materials and Methods: Retrospectively, the medical records of 205 consecutive childhood glaucoma and glaucoma suspect patients at an urban tertiary care center were reviewed. The initial diagnosis and new diagnosis according to CGRN classification were recorded. Results: All patients fit one of the seven categories of the new classification. Seventy-one percent of diagnoses were changed upon reclassification. Twenty-three percent of patients had primary glaucoma (juvenile open-angle glaucoma and primary congenital glaucoma [PCG]); 36% had secondary glaucoma (glaucoma associated with nonacquired ocular anomalies; glaucoma associated with nonacquired systemic disease or syndrome; glaucoma associated with acquired condition; and glaucoma following cataract surgery); and 39% were glaucoma suspect. Of the patients diagnosed with glaucoma, PCG was the most common diagnosis, seen in 32% of patients. Conclusion: The CGRN classification provides a useful method of classifying childhood glaucoma. C1 [Hoguet, Ambika; Grajewski, Alana; Hodapp, Elizabeth; Chang, Ta Chen Peter] Univ Miami, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL USA. [Hoguet, Ambika] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Hoguet, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM ambika_hoguet@meei.harvard.edu RI Chang, Ta/D-7752-2017 NR 21 TC 0 Z9 0 U1 0 U2 0 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 0301-4738 EI 1998-3689 J9 INDIAN J OPHTHALMOL JI Indian J. Ophthalmol. PD FEB PY 2016 VL 64 IS 2 BP 118 EP 123 DI 10.4103/0301-4738.179716 PG 6 WC Ophthalmology SC Ophthalmology GA DJ4GQ UT WOS:000374163800004 PM 27050345 ER PT J AU Ramage, AE Litz, BT Resick, PA Woolsey, MD Dondanville, KA Young-McCaughan, S Borah, AM Borah, EV Peterson, AL Fox, PT AF Ramage, Amy E. Litz, Brett T. Resick, Patricia A. Woolsey, Mary D. Dondanville, Katherine A. Young-McCaughan, Stacey Borah, Adam M. Borah, Elisa V. Peterson, Alan L. Fox, Peter T. CA STRONG STAR Consortium TI Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE post-traumatic stress disorder; FDG PET; glucose metabolism; fear ID FUNCTIONAL CONNECTIVITY; BRAIN NETWORKS; PSYCHOMETRIC PROPERTIES; CINGULATE CORTEX; AMYGDALA VOLUME; WAR VETERANS; METAANALYSIS; PTSD; RELIABILITY; ANXIETY AB Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with 18fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger-(n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolismin precuneus and dorsal anterior cingulate and lower metabolismin left amygdala (R-2 = 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolismand lower right amygdala metabolism( R-2 = 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context. C1 [Ramage, Amy E.; Dondanville, Katherine A.; Young-McCaughan, Stacey; Borah, Elisa V.; Peterson, Alan L.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Ramage, Amy E.; Woolsey, Mary D.; Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 7703 Floyd Curl Dr,MSC 6240, San Antonio, TX 78229 USA. [Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Washington, DC USA. [Litz, Brett T.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [Resick, Patricia A.] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC USA. [Borah, Adam M.] Carl R Darnall Army Med Ctr, Ft Hood, TX USA. [Peterson, Alan L.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Pok Fu Lam, Hong Kong, Peoples R China. RP Ramage, AE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 7703 Floyd Curl Dr,MSC 6240, San Antonio, TX 78229 USA. EM ramagea@uthscsa.edu FU Psychological Health and Traumatic Brain Injury Research Program [W81XWH-08-02-109, W81XWH-08-02-0112, W81XWH-08-02-0114, W81XWH-08-02-0116]; U.S. Department of Defense, Defense Health Program; U.S. Department of Veterans Affairs, Office of Research & Development through the Psychological Health and Traumatic Brain Injury Research Program (PH/TBI RP), Consortium to Alleviate PTSD (CAP) [W81XWH-13-2-0065] FX The data collection for this study was conducted with support to the STRONG STAR Multidisciplinary PTSD Research Consortium from the U.S. Department of Defense through the U.S. Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Psychological Health and Traumatic Brain Injury Research Program awards W81XWH-08-02-109 (Alan Peterson), W81XWH-08-02-0112 (Peter Fox), W81XWH-08-02-0114 (Brett Litz), and W81XWH-08-02-0116 (Patricia Resick). The analysis and interpretation of data for this study was supported by the U.S. Department of Defense, Defense Health Program and the U.S. Department of Veterans Affairs, Office of Research & Development through the Psychological Health and Traumatic Brain Injury Research Program (PH/TBI RP), Consortium to Alleviate PTSD (CAP) award W81XWH-13-2-0065. NR 58 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 EI 1749-5024 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD FEB PY 2016 VL 11 IS 2 BP 234 EP 242 DI 10.1093/scan/nsv102 PG 9 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA DJ5DL UT WOS:000374226900005 PM 26373348 ER PT J AU Tirumani, SH Souza, D Krajewski, KM Jagannathan, JP Ramaiya, NH Shinagare, AB AF Tirumani, Sree Harsha Souza, Daniel Krajewski, Katherine M. Jagannathan, Jyothi P. Ramaiya, Nikhil H. Shinagare, Atul B. TI Impact of histologic subtype and sarcomatoid transformation on metastasis in renal cell carcinoma: a single institute experience in 149 patients SO ABDOMINAL RADIOLOGY LA English DT Article DE Clear cell renal cell carcinoma; Papillary renal cell carcinoma; Sarcomatoid renal cell carcinoma; Metastasis; Survival ID PROGNOSTIC VALUE; NEPHRECTOMY; SURVIVAL; SYSTEM; SURVEILLANCE; PAPILLARY; DISEASE; SITES AB Purpose: To compare the metastatic pattern and outcome of clear cell RCC (ccRCC) and papillary RCC (pRCC), and to assess the impact of sarcomatoid transformation on the disease spread and prognosis. Materials and methods: This IRB-approved, HIPAA-compliant retrospective study included 149 consecutive patients (108 men; mean age 58 years; range 25-86) with metastatic RCC (ccRCC = 116, pRCC = 33), identified from imaging database. All available imaging studies and electronic records of these patients were reviewed to document pathological features, distribution and timing of metastasis, and survival. The metastatic pattern and survival was first compared between the ccRCC and pRCC groups, and then between those with and without sarcomatoid transformation; all 27 cases of sarcomatoid transformation occurred in the ccRCC group. Results: Metastases were noted at presentation in 62 (42%) and after median 13 months in the remaining 87 (58%) patients. Lymph nodes (134/149), lung (125/149), and bone (60/149) were the most common metastatic sites, which did not differ between the RCC subtypes. Pancreatic (p = 0.0014) and renal (p = 0.046) metastases were more common in ccRCC, lymphangitic spread (p = 0.0003) and peritoneal metastasis (p = 0.039) more common in pRCC. In ccRCC, sarcomatoid transformation was associated with high-grade tumors (p < 0.0001), more frequently demonstrated lymphangitic (p = 0.016), pleural (p = 0.0018), and peritoneal metastases (p = 0.0002), and had shorter metastasis-free survival and overall survival (log-rank test, p < 0.0001). In the absence of sarcomatoid transformation, ccRCC had longer metastasis-free interval (median 22 months compared to 6 months) (p = 0.0238) and overall survival (median survival 48 months vs. 25 months) (p = 0.0193) compared to pRCC. Conclusion: Histologic subtype, as well as the presence of sarcomatoid transformation, affects the metastatic pattern and metastasis-free survival of RCC. In the absence of sarcomatoid transformation, ccRCC has a better outcome than pRCC. C1 [Tirumani, Sree Harsha; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. [Tirumani, Sree Harsha; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Souza, Daniel] Harvard Univ, Brigham & Womens Faulkner Hosp, Sch Med, Dept Radiol, 1153 Ctr St, Boston, MA 02130 USA. RP Tirumani, SH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Sreeharsha_Tiru-mani@DFCI.HARVARD.EDU FU Radiologic Society of North America (RSNA) FX The investigator A.B.S is a recipient of Radiologic Society of North America (RSNA) research grant starting from July 2014. No disclosures for the remaining authors. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD FEB PY 2016 VL 41 IS 2 BP 295 EP 302 DI 10.1007/s00261-015-0569-7 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ3MP UT WOS:000374109900011 PM 26867911 ER PT J AU Phillips, CH Keraliya, AR Shinagare, AB Ramaiya, NH Tirumani, H AF Phillips, Catherine H. Keraliya, Abhishek R. Shinagare, Atul B. Ramaiya, Nikhil H. Tirumani, Harsha TI Update on the imaging of malignant perivascular epithelioid cell tumors (PEComas) SO ABDOMINAL RADIOLOGY LA English DT Article DE Malignant PEComa; CT; MRI; PET/CT ID OF-THE-LITERATURE; RENAL ANGIOMYOLIPOMA; MTOR INHIBITION; CARCINOMA; FEATURES; KIDNEY; PNEUMONITIS; NEOPLASMS; SIROLIMUS; UTERUS AB Malignant perivascular epithelioid cell tumors (PEComas) are a histologic group of mesenchymal neoplasms that share a distinctive histological phenotype, the perivascular epithelioid cell. These tumors are known for their perivascular distribution. Malignant PEComas have a female predominance and are associated with aggressive disease and poor prognosis, making timely diagnosis critical to management. Imaging features of malignant PEComas are nonspecific and mimic other benign and malignant neoplasms. Surgery is the mainstay in the management of malignant PEComas. Promising novel molecular targeted therapies like mTOR inhibitors have been shown to be effective in the metastatic setting. The aim of this review is to familiarize radiologists with the imaging appearances of and potential therapies for primary and metastatic malignant PEComa. C1 [Phillips, Catherine H.; Keraliya, Abhishek R.; Shinagare, Atul B.; Ramaiya, Nikhil H.; Tirumani, Harsha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Keraliya, Abhishek R.; Shinagare, Atul B.; Ramaiya, Nikhil H.; Tirumani, Harsha] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. RP Tirumani, H (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.; Tirumani, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Sreeharsha_Tirumani@DFCI.HARVARD.EDU NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD FEB PY 2016 VL 41 IS 2 BP 368 EP 376 DI 10.1007/s00261-015-0568-8 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DJ3MP UT WOS:000374109900024 PM 26867923 ER PT J AU Janne, P AF Janne, Pasi TI Mechanisms of resistance to EGFR inhibitors in lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 4th AACR International Conference on Frontiers in Basic Cancer Research CY OCT 23-26, 2015 CL Philadelphia, PA SP Amer Assoc Canc Res C1 [Janne, Pasi] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2016 VL 76 SU 3 MA IA31 PG 1 WC Oncology SC Oncology GA DJ4FB UT WOS:000374159700092 ER PT J AU Day, MA Ehde, DM Ward, LC Hartoonian, N Alschuler, KN Turner, AP Kraft, GH Jensen, MP AF Day, Melissa A. Ehde, Dawn M. Ward, L. Charles Hartoonian, Narineh Alschuler, Kevin N. Turner, Aaron P. Kraft, George H. Jensen, Mark P. TI An Empirical Investigation of a Biopsychosocial Model of Pain in Multiple Sclerosis SO CLINICAL JOURNAL OF PAIN LA English DT Article DE multiple sclerosis; biopsychosocial model; structural equation model; pain ID QUALITY-OF-LIFE; LARGE COMMUNITY SAMPLE; MAJOR DEPRESSION; MEDIATING ROLE; PRIMARY-CARE; FATIGUE; PREVALENCE; SEVERITY; OUTCOMES; IMPACT AB Objectives: Pain is a significant problem for many individuals with multiple sclerosis (MS). Pain is often associated with other MS symptoms (eg, physical, sensorimotor, cognitive declines), and both pain and MS symptoms are hypothesized to contribute to psychosocial problems (eg, depression), other symptoms (eg, fatigue, sleep disturbance), and functional impairments (eg, pain interference). On the basis of a biopsychosocial model, we sought to: (1) examine the associations between pain, MS symptoms, depression, psychosocial, and functional variables and (2) identify possible risk and protective factors associated with pain in MS. Materials and Methods: A cross-sectional survey was completed by 424 individuals with MS. Pain, MS symptoms, demographics, MS diagnostic factors, and psychosocial and functional variables were assessed. Data were analyzed by structural equation models. Results: Participants were predominantly white (92%), middle-aged (mean=50.7 y), and female (80%). Results indicated that pain severity and depression accounted for > 50% of the variance in pain interference. Although pain contributed minimally to fatigue and sleep quality, depression and MS symptoms predicted 49% of the variance in fatigue, and depression was largely responsible for the 40% of predicted variance in sleep quality. Identified risk factors for pain were low educational attainment and lack of a committed/marital relationship, even while controlling for diagnostic and other key demographic variables. Discussion: Results highlight the importance of targeting interventions toward improving coping skills and social support within the context of pain and MS. Research is needed to determine whether effectively targeting depression in MS results in improvements of other critical psychosocial and physical functioning domains. C1 [Day, Melissa A.] Univ Queensland, Sch Psychol, 1100 Nudgee Rd, Brisbane, Qld 4014, Australia. [Ehde, Dawn M.; Hartoonian, Narineh; Alschuler, Kevin N.; Turner, Aaron P.; Kraft, George H.; Jensen, Mark P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hartoonian, Narineh; Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Ward, L. Charles] VA Med Ctr, Psychol Serv, Tuscaloosa, AL USA. [Hartoonian, Narineh; Turner, Aaron P.] VA MS Ctr Excellence, Seattle, WA USA. RP Day, MA (reprint author), Univ Queensland, Sch Psychol, 1100 Nudgee Rd, Brisbane, Qld 4014, Australia. EM Melissa.Day@acu.edu.au FU Department of Education, NIDRR, Washington, DC [H133B080025]; National Institutes of Health, Bethesda, Maryland [5U01AR052171-03]; National Multiple Sclerosis Society, New York City, NY [MB 0026, MB 0008] FX Supported by grants from the Department of Education, NIDRR grant number H133B080025, Washington, DC; National Institutes of Health, Grant 5U01AR052171-03, Bethesda, Maryland; and the National Multiple Sclerosis Society, Grants MB 0026 and MB 0008, New York City, NY. The authors declare no conflict of interest. NR 42 TC 1 Z9 2 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD FEB PY 2016 VL 32 IS 2 BP 155 EP 163 DI 10.1097/AJP.0000000000000240 PG 9 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DI9MW UT WOS:000373828000009 PM 26741742 ER PT J AU Robbins, J Humpal, NS Banaszynski, K Hind, J Rogus-Pulia, N AF Robbins, JoAnne Humpal, Naomi S. Banaszynski, Kelsey Hind, Jacqueline Rogus-Pulia, Nicole TI Age-Related Differences in Pressures Generated During Isometric Presses and Swallows by Healthy Adults SO DYSPHAGIA LA English DT Article DE Swallowing; Dysphagia; Tongue strength; Aging; Deglutition; Deglutition disorders ID TONGUE STRENGTH; OLDER-ADULTS; RISK-FACTOR; DYSPHAGIA; PREVALENCE; SARCOPENIA; MUSCLES; IMPACT AB The aim of this prospective observational study was to determine the associations among age, maximum lingual isometric pressures, and maximum swallow pressures in specific regions of the tongue. Individuals 21 years and older who reported normal swallowing were enrolled. Seventy-one healthy adults were stratified by age into young (21-40 years), middle (41-60), and old (61-82) groups. Maximum pressures were measured for each individual during isometric tongue press tasks as well as saliva, 5, and 10 mL thin liquid bolus swallows at 5 sensors located on the hard palate: front, middle, left, right, and back. Lower maximum lingual pressures for all tasks were associated with increased age (p < 0.04). Saliva pressures exhibited a different pressure pattern than bolus swallows with pressures higher than bolus swallows on middle (p < 0.03) and back (p < 0.05) tongue sensors but not in the front. Diminished swallow pressure reserve (maximum isometric pressure-maximum swallow pressure) also was found with increased age (p < 0.03). Isometric pressures were greater than swallow pressures in young and middle age groups at both the front (p < 0.04) and back (p < 0.03) sensors, but only significantly greater at the front sensor for the oldest group (p < 0.04). Older healthy adults have lower lingual isometric pressures and lower swallow pressures than younger healthy adults. Elders have a decreased swallow pressure reserve to draw upon during occasions of physiological stress. While the exact mechanisms for age-related decline in lingual pressures remain unclear, they are likely due, at least in part, to sarcopenia. Saliva, 5, and 10 mL thin boluses also exhibit different age-related declines in pressure at specific sensors, indicating they may elicit different muscle activation patterns. C1 [Robbins, JoAnne; Rogus-Pulia, Nicole] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison GRECC, 2500 Overlook Terrace,Room D4220, Madison, WI 53705 USA. [Robbins, JoAnne; Rogus-Pulia, Nicole] Univ Wisconsin, Dept Med, SMPH, Madison, WI 53706 USA. [Humpal, Naomi S.] Univ Wisconsin, Coll Engn, Dept Biomed Engn, Madison, WI 53706 USA. [Banaszynski, Kelsey] WhiteWave Foods, 1900 Cherry St, Louisville, CO USA. [Hind, Jacqueline] Swallow Solut LLC, 401 Charmany Dr, Madison, WI 53719 USA. RP Rogus-Pulia, N (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison GRECC, 2500 Overlook Terrace,Room D4220, Madison, WI 53705 USA.; Rogus-Pulia, N (reprint author), Univ Wisconsin, Dept Med, SMPH, Madison, WI 53706 USA. EM npulia@wisc.edu NR 26 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0179-051X EI 1432-0460 J9 DYSPHAGIA JI Dysphagia PD FEB PY 2016 VL 31 IS 1 BP 90 EP 96 DI 10.1007/s00455-015-9662-x PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA DI8IP UT WOS:000373745000010 PM 26525059 ER PT J AU Fried, HI Nathan, BR Rowe, AS Zabramski, JM Andaluz, N Bhimraj, A Guanci, MM Seder, DB Singh, JM AF Fried, Herbert I. Nathan, Barnett R. Rowe, A. Shaun Zabramski, Joseph M. Andaluz, Norberto Bhimraj, Adarsh Guanci, Mary McKenna Seder, David B. Singh, Jeffrey M. TI The Insertion and Management of External Ventricular Drains: An Evidence-Based Consensus Statement SO NEUROCRITICAL CARE LA English DT Review DE EVD; External ventricular drain; Ventriculostomy; Ventriculostomy-related infection; Ventriculostomy associated infection; VAI; VRI; Hydrocephalus; ICP; Monitoring; CSF drainage; Hemorrhage; Antibiotics; Antibiotic coated catheter; Antimicrobial coated catheter; Antibiotic prophylaxis; DVT; Deep venous thrombosis; DVT prophylaxis; Thromboembolism; Intraventricular antibiotics ID CRITICALLY-ILL PATIENTS; INTERMITTENT PNEUMATIC COMPRESSION; TRAUMATIC BRAIN-INJURY; INTENSIVE-CARE-UNIT; VENA-CAVA FILTERS; VENOUS THROMBOEMBOLISM PROPHYLAXIS; ANEURYSMAL SUBARACHNOID HEMORRHAGE; ACUTE INTRACEREBRAL HEMORRHAGE; PROSPECTIVE RANDOMIZED-TRIAL; DEEP-VEIN THROMBOSIS AB External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of highquality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors' view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations. C1 [Fried, Herbert I.] Univ Colorado, Denver, CO 80202 USA. [Fried, Herbert I.] Denver Hlth Med Ctr, Denver, CO USA. [Nathan, Barnett R.] Univ Virginia, Charlottesville, VA USA. [Rowe, A. Shaun] Univ Tennessee, Hlth Sci Ctr, Coll Pharm, Knoxville, TN USA. [Zabramski, Joseph M.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Zabramski, Joseph M.] Scottsdale Osborn Med Ctr, Scottsdale, AZ USA. [Andaluz, Norberto] Univ Cincinnati, Univ Cincinnati Coll Med, Inst Neurosci, Cincinnati, OH USA. [Andaluz, Norberto] Mayfield Clin, Cincinnati, OH USA. [Bhimraj, Adarsh] Cleveland Clin, Cleveland, OH 44106 USA. [Guanci, Mary McKenna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seder, David B.] Maine Med Ctr, Dept Crit Care Serv, Portland, ME 04102 USA. [Seder, David B.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Singh, Jeffrey M.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Singh, Jeffrey M.] Toronto Western Hosp, Krembil Neurosci Ctr, Toronto, ON M5T 2S8, Canada. RP Nathan, BR (reprint author), Univ Virginia, Charlottesville, VA USA. EM brn3a@virginia.edu NR 164 TC 7 Z9 7 U1 6 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2016 VL 24 IS 1 BP 61 EP 81 DI 10.1007/s12028-015-0224-8 PG 21 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DJ3JO UT WOS:000374101300005 PM 26738503 ER PT J AU Hirsch, KG Mlynash, M Eyngorn, I Pirsaheli, R Okada, A Komshian, S Chen, C Mayer, SA Meschia, JF Bernstein, RA Wu, O Greer, DM Wijman, CA Albers, GW AF Hirsch, K. G. Mlynash, M. Eyngorn, I. Pirsaheli, R. Okada, A. Komshian, S. Chen, C. Mayer, S. A. Meschia, J. F. Bernstein, R. A. Wu, O. Greer, D. M. Wijman, C. A. Albers, G. W. TI Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest SO NEUROCRITICAL CARE LA English DT Article DE Cardiac arrest; MRI; DWI; Coma; Prognosis ID AMERICAN-HEART-ASSOCIATION; SELF-FULFILLING PROPHECY; NONTRAUMATIC COMA; PROGNOSTIC VALUE; CARE COMMITTEE; BRAIN-INJURY; MRI; HYPOTHERMIA; RESUSCITATION; CARDIOPULMONARY AB Background The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion- weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort. Methods DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome. Results 125 patients were included in the analysis. 33 patients (26 %) had a good outcome. An ADC value of less than 650 9 10(-6) mm(2) /s in >= 10 % of brain volume was highly specific [91 % (95 % CI 75-98)] and had a good sensitivity [72 % (95 % CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 9 10(-6) mm 2 /s in > 22 % of brain volume was needed to achieve 100 % specificity for poor outcome. Conclusions In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 9 10(-6) mm 2 /s in >= 10 % of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100 % specific for poor outcome. C1 [Hirsch, K. G.; Mlynash, M.; Eyngorn, I.; Pirsaheli, R.; Komshian, S.; Wijman, C. A.; Albers, G. W.] Stanford Univ, Med Ctr, Sch Med, Dept Neurol & Neurol Sci,Stanford Stroke & Neuroc, Stanford, CA 94305 USA. [Okada, A.] Stanford Univ, Dept Med, Sch Med, Div Oncol, Stanford, CA 94305 USA. [Chen, C.] Sutter Pacific Med Fdn, Dept Neurol, San Francisco, CA USA. [Mayer, S. A.] Icahn Sch Med Mt Sinai, Dept Neurol, Mt Sinai Healthcare Syst, New York, NY 10029 USA. [Mayer, S. A.] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA. [Meschia, J. F.] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA. [Bernstein, R. A.] Northwestern Univ, Feinberg Sch Med, Davee Dept Neurol, Chicago, IL 60611 USA. [Wu, O.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr, Boston, MA USA. [Greer, D. M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Hirsch, KG (reprint author), Stanford Univ, Med Ctr, Sch Med, Dept Neurol & Neurol Sci,Stanford Stroke & Neuroc, Stanford, CA 94305 USA. EM kghirsch@yahoo.com NR 31 TC 1 Z9 1 U1 3 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2016 VL 24 IS 1 BP 82 EP 89 DI 10.1007/s12028-015-0179-9 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DJ3JO UT WOS:000374101300006 PM 26156112 ER PT J AU Sheth, KN Elm, JJ Beslow, LA Sze, GK Kimberly, WT AF Sheth, Kevin N. Elm, Jordan J. Beslow, Lauren A. Sze, Gordon K. Kimberly, W. Taylor TI Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design SO NEUROCRITICAL CARE LA English DT Article DE Ischemic stroke; Cerebral edema; Malignant infarction; Large stroke; Clinical trials; MRI ID MIDDLE CEREBRAL-ARTERY; NONSELECTIVE CATION CHANNEL; HEALTH-CARE PROFESSIONALS; ADULT-RAT BRAIN; ISCHEMIC-STROKE; DECOMPRESSIVE CRANIECTOMY; TERRITORY INFARCTION; REACTIVE ASTROCYTES; ASSOCIATION; PREVENTION AB Background Patients with large territory infarction are at high risk of cerebral edema and neurological deterioration, including death. Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction. Methods GAMES-RP is a prospective, randomized, double-blind, multicenter trial designed to evaluate RP-1127 in patients at high risk for the development of malignant cerebral edema. The study population consisted of subjects with a clinical diagnosis of acute severe anterior circulation ischemic stroke with a baseline diffusionweighted image lesion between 82 and 300 cm(3) who are 18-80 years of age. The target time from symptom onset to start of study infusion was <= 10 h. Subjects were randomized to RP-1127 (glyburide for injection) or placebo and treated with a continuous infusion for 72 h. Results The primary efficacy outcome was a composite of the modified Rankin Scale and the incidence of decompressive craniectomy, assessed at 90 days. Safety outcomes were the frequency and severity of adverse events, with a focus on cardiac-and glucose-related serious adverse events. Conclusions GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies. C1 [Sheth, Kevin N.; Beslow, Lauren A.] Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 15 York St,LCI 1003, New Haven, CT 06510 USA. [Elm, Jordan J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA. [Beslow, Lauren A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Sze, Gordon K.] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 55 Fruit St, Boston, MA 02114 USA. RP Sheth, KN (reprint author), Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 15 York St,LCI 1003, New Haven, CT 06510 USA.; Kimberly, WT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, 55 Fruit St, Boston, MA 02114 USA. EM kevin.sheth@yale.edu; wtkimberly@mgh.harvard.edu FU Remedy Pharmaceuticals FX The sponsor of this phase II study, GAMES-RP, is Remedy Pharmaceuticals. NR 30 TC 5 Z9 6 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2016 VL 24 IS 1 BP 132 EP 139 DI 10.1007/s12028-015-0189-7 PG 8 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA DJ3JO UT WOS:000374101300014 PM 26268138 ER PT J AU Rauh-Hain, JA Vargas, RJ Clemmer, J Clark, RM Bradford, LS Growdon, WB Goodman, A Boruta, DM Schorge, JO del Carmen, MG AF Rauh-Hain, Jose Alejandro Vargas, Roberto J. Clemmer, Joel Clark, Rachel M. Bradford, Leslie S. Growdon, Whitfield B. Goodman, Annekathryn Boruta, David M., II Schorge, John O. del Carmen, Marcela G. TI Mucinous Adenocarcinoma of the Endometrium Compared With Endometrioid Endometrial Cancer A SEER Analysis SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE mucinous endometrial cancer; endometrioid endometrial cancers; survival ID CARCINOMA AB Objective:Mucinous endometrial cancer (MEC) is a rare histologic subtype of endometrial cancers. The purpose of this study is to compare the outcomes of patients with MEC with patients with endometrioid endometrial cancers (EEC), and to determine whether there are significant clinicopathologic differences between these tumors.Methods:Surveillance, Epidemiology, and End Results (SEER) Program data for 1988 to 2009 was reviewed. Demographic and clinical data were compared. The impact of histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model.Results:The study group consisted of 104,659 women, 103,097 (98.5%) had EEC and 1562 (1.5%) MEC. The mean age at diagnosis for EEC and MEC was 62 and 63.4, respectively (P<0.001). MEC tumors were more frequently classified as grade 1 (51.3% vs. 44%; P<0.001). In patients with MEC, a higher rate of pelvic lymph node metastasis (16.3% vs. 10.4%; P<0.001) was noted, but not para-aortic lymph node metastasis (5.1% vs. 4%; P=0.1). After adjusting for race, period of diagnosis, SEER registry, marital status, stage, age, surgery, radiotherapy, grade, histology, and lymph node dissection, there was no difference in survival between MEC and EEC (hazard ratio 0.90; 95% confidence interval, 0.78-1.05).Conclusions:Mucinous histology does not significantly affect survival when compared with endometrioid histology in endometrial cancer. Patients with MEC were more likely to have positive pelvic lymph nodes at the time of surgery. C1 [Rauh-Hain, Jose Alejandro; Vargas, Roberto J.; Clemmer, Joel; Clark, Rachel M.; Bradford, Leslie S.; Growdon, Whitfield B.; Goodman, Annekathryn; Boruta, David M., II; Schorge, John O.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Deborah Kelly Center, Massachusetts General Hospital, Boston, MA FX Supported by the Deborah Kelly Center, Massachusetts General Hospital, Boston, MA. NR 18 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 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2016 VL 39 IS 1 BP 43 EP 48 DI 10.1097/COC.0000000000000015 PG 6 WC Oncology SC Oncology GA DI5CH UT WOS:000373515200008 PM 24390270 ER PT J AU Buchbinder, EI Desai, A AF Buchbinder, Elizabeth I. Desai, Anupam TI CTLA-4 and PD-1 Pathways Similarities, Differences, and Implications of Their Inhibition SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Review DE cytotoxic T-lymphocyte-associated antigen 4; CTLA-4; programmed death 1; PD-1; immune checkpoint ID CELL LUNG-CANCER; LONG-TERM SAFETY; REGULATORY T-CELLS; DEATH-LIGAND 1; ADVANCED MELANOMA; UNTREATED MELANOMA; PROGRAMMED DEATH-1; IN-VIVO; METASTATIC MELANOMA; RECEIVING NIVOLUMAB AB The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function. Inhibition of these targets, resulting in increased activation of the immune system, has led to new immunotherapies for melanoma, non-small cell lung cancer, and other cancers. Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues. The clinical profiles of immuno-oncology agents inhibiting these 2 checkpoints may vary based on their mechanistic differences. This article provides an overview of the CTLA-4 and PD-1 pathways and implications of their inhibition in cancer therapy. C1 [Buchbinder, Elizabeth I.] Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA. [Buchbinder, Elizabeth I.; Desai, Anupam] Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. [Desai, Anupam] Beth Israel Deaconess Med Ctr, Biol Therapy Program, Boston, MA 02215 USA. RP Buchbinder, EI (reprint author), Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA.; Buchbinder, EI (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM elizabeth_buchbinder@dfci.harvard.edu FU Bristol-Myers Squibb; Genentech; Merck FX E.I.B. received research funding from Bristol-Myers Squibb, Genentech, and Merck; spouse previously employed by Merck. A.D. declares no conflicts of interest. NR 90 TC 17 Z9 18 U1 5 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2016 VL 39 IS 1 BP 98 EP 106 DI 10.1097/COC.0000000000000239 PG 9 WC Oncology SC Oncology GA DI5CH UT WOS:000373515200017 PM 26558876 ER PT J AU Frakt, AB Pizer, SD AF Frakt, Austin B. Pizer, Steven D. TI The Promise and Perils of Big Data in Healthcare SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material C1 [Frakt, Austin B.] Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Frakt, Austin B.] Harvard Univ, Boston, MA 02115 USA. [Pizer, Steven D.] Northeastern Univ, Boston, MA 02115 USA. RP Frakt, AB (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,152H, Boston, MA 20130 USA. EM frakt@bu.edu FU Health Services Research and Development Service of the US Department of Veterans Affairs [IIR 10-136] FX This work supported by Health Services Research and Development Service of the US Department of Veterans Affairs (grant no. IIR 10-136), which did not in any way participate in the writing of or exert any influence over the content of this manuscript. NR 5 TC 1 Z9 1 U1 7 U2 13 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2016 VL 22 IS 2 BP 98 EP 99 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DI5WR UT WOS:000373571700006 PM 26885669 ER PT J AU Stoeckle, JD Sittler, R Davidson, GE AF Stoeckle, John D. Sittler, Ruth Davidson, Gerald E. TI Social Work in a Medical Clinic: The Nature and Course of Referrals to the Social Worker SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Stoeckle, John D.] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care, Boston, MA 02114 USA. RP Stoeckle, JD (reprint author), Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2016 VL 106 IS 2 BP 232 EP 234 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DI3VY UT WOS:000373429000021 ER PT J AU Maier, MM Ross, DB Chartier, M Belperio, PS Backus, LI AF Maier, Marissa M. Ross, David B. Chartier, Maggie Belperio, Pamela S. Backus, Lisa I. TI Cascade of Care for Hepatitis C Virus Infection Within the US Veterans Health Administration SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GENOTYPE 1 INFECTION; UNITED-STATES; PLUS RIBAVIRIN; AFFAIRS CARE; PREVALENCE; SOFOSBUVIR; LEDIPASVIR AB Objectives. We measured the quality of HCV care using a cascade of HCV care model. Methods. We estimated the number of patients diagnosed with chronic HCV, linked to HCV care, treated with HCV antivirals, and having achieved a sustained virologic response (SVR) in the electronic medical record data from the Veterans Health Administration's Corporate Data Warehouse and the HCV Clinical Case Registry in 2013. Results. Of the estimated 233 898 patients with chronic HCV, 77% (181 168) were diagnosed, 69% (160 794) were linked to HCV care, 17% (39 388) were treated with HCV antivirals, and 7% (15 983) had achieved SVR. Conclusions. This Cascade of HCV Care provides a clinically relevant model to measure the quality of HCV care within a health care system and to compare HCV care across health systems. C1 [Maier, Marissa M.] Vet Hlth Adm, VA Portland Hlth Care Syst, Portland, OR USA. [Maier, Marissa M.; Ross, David B.; Chartier, Maggie] VHA, Off Publ Hlth, HIV Hepatitis & Publ Hlth Pathogens Programs, Washington, DC USA. [Ross, David B.] VA Washington DC Hlth Care Syst, Washington, DC USA. [Chartier, Maggie] VHA, VA San Francisco Hlth Care Syst, San Francisco, CA USA. [Belperio, Pamela S.] VHA, VA Greater Angeles Hlth Care Syst, Los Angeles, CA USA. [Belperio, Pamela S.; Backus, Lisa I.] VHA, Off Publ Hlth Populat Hlth, Washington, DC USA. [Backus, Lisa I.] VHA, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Maier, MM (reprint author), VA Portland Hlth Care Syst, 3710 SW US Vet Hosp Rd,Mail Code P3ID, Portland, OR 97239 USA. EM Marissa.Maier@va.gov NR 18 TC 2 Z9 2 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2016 VL 106 IS 2 BP 353 EP 358 DI 10.2105/AJPH.2015.302927 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DI3VY UT WOS:000373429000043 PM 26562129 ER PT J AU Souter, I Lee, A Murtadi, G AF Souter, Irene Lee, Amy Murtadi, Gheed TI IS THERE AN ASSOCIATION BETWEEN ABO BLOOD TYPE AND OVARIAN RESERVE IN WOMEN UNDERGOING INTRAUTERINE INSEMINATION (IUI)+/- OVULATION INDUCTION (OI)? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 64th Annual Meeting of the Pacific-Coast-Reproductive-Society CY MAR 09-13, 2016 CL Rancho Mirage, CA SP Pacific Coast Reprod Soc C1 [Souter, Irene; Lee, Amy; Murtadi, Gheed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 2 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 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2016 VL 105 IS 2 SU S MA P-61 BP E38 EP E39 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DI3NK UT WOS:000373405200072 ER PT J AU Woolverton, A Spalding, AL Warikoo, NK Dunn, EC Richmond, TK AF Woolverton, Alice Spalding, Allegra L. Warikoo, Natasha K. Dunn, Erin C. Richmond, Tracy K. TI BODY SHAPE AND SIZE CONCERNS AND DIET CULTURE IN URBAN ADOLESCENTS ATTENDING SUBURBAN HIGH SCHOOLS SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 [Woolverton, Alice; Spalding, Allegra L.] Boston Childrens Hosp, Boston, MA USA. [Warikoo, Natasha K.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Dunn, Erin C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Richmond, Tracy K.] Harvard Univ, Sch Med, Boston Childrens Hosp, Cambridge, MA 02138 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 1054-139X EI 1879-1972 J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2016 VL 58 IS 2 SU S MA 118 BP S63 EP S63 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA DI3VW UT WOS:000373428800119 ER PT J AU Dy, SM Herr, K Bernacki, RE Kamal, AH Walling, AM Ersek, M Norton, SA AF Dy, Sydney Morss Herr, Keela Bernacki, Rachelle E. Kamal, Arif H. Walling, Anne M. Ersek, Mary Norton, Sally A. TI Methodological Research Priorities in Palliative Care and Hospice Quality Measurement SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Palliative care; pain measurement; hospice care; quality of health care; quality indicators; advance care planning; patient satisfaction ID OF-LIFE CARE; CANCER CARE; INDICATORS; RECOMMENDATIONS; MEDICINE; MODEL; PAIN AB Quality measurement is a critical tool for improving palliative care and hospice, but significant research is needed to improve the application of quality indicators. We defined methodological priorities for advancing the science of quality measurement in this field based on discussions of the Technical Advisory Panel of the Measuring What Matters consensus project of the American Academy of Hospice and Palliative Medicine and Hospice and Palliative Nurses Association and a subsequent strategy meeting to better clarify research challenges, priorities, and quality measurement implementation strategies. In this article, we describe three key priorities: 1) defining the denominator(s) (or the population of interest) for palliative care quality indicators, 2) developing methods to measure quality from different data sources, and 3) conducting research to advance the development of patient/family-reported indicators. We then apply these concepts to the key quality domain of advance care planning and address relevance to implementation of indicators in improving care. Developing the science of quality measurement in these key areas of palliative care and hospice will facilitate improved quality measurement across all populations with serious illness and care for patients and families. (C) 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. C1 [Dy, Sydney Morss] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Herr, Keela] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Bernacki, Rachelle E.] Dana Farber Canc Inst, Div Adult Palliat Care, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Bernacki, Rachelle E.] Ariadne Labs, Boston, MA USA. [Bernacki, Rachelle E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bernacki, Rachelle E.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Kamal, Arif H.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA. [Ersek, Mary] Univ Penn, Corporal Michael J Crescenz VA Med Ctr Philadelph, Philadelphia, PA 19104 USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Walling, Anne M.] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Walling, Anne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Norton, Sally A.] Univ Rochester, Sch Nursing, Rochester, NY USA. RP Dy, SM (reprint author), Room 609,624 North Broadway, Baltimore, MD 21205 USA. EM sdy@jhsph.edu FU AHRQ HHS [K08 HS023681] NR 30 TC 4 Z9 4 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 BP 155 EP 162 DI 10.1016/j.jpainsymman.2015.10.019 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900005 PM 26596877 ER PT J AU Ullrich, C AF Ullrich, Christina TI Mental Health Services for Parents Who Lost a Child to Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Editorial Material ID GRIEF; IMPACT C1 [Ullrich, Christina] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ullrich, C (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 BP 301 EP 302 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900023 ER PT J AU Earnshaw, L Buckholz, G Thomas, JD Gustin, J Hamstra, S Jacobsen, J Levine, S Misra, S Morrison, L Radwany, SM Reid, T Barnett, MD Landzaat, L McCormick, W AF Earnshaw, Lori Buckholz, Gary Thomas, Jane deLima Gustin, Jillian Hamstra, Stanley Jacobsen, Juliet Levine, Stacie Misra, Sumathi Morrison, Laura Radwany, Steven M. Reid, Thomas Barnett, Michael David Landzaat, Lindy McCormick, Wayne TI Fellowship Directors' Program: Higher Ground-Helping Our HPM Fellowships Continue to Grow and Thrive in an Era of Rapid Change SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Earnshaw, Lori] Univ Louisville, Louisville, KY 40292 USA. [Buckholz, Gary] Univ Calif San Diego, San Diego, CA 92103 USA. [Thomas, Jane deLima] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gustin, Jillian] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Hamstra, Stanley] Milestones Res & Evaluat, Chicago, IL USA. [Jacobsen, Juliet] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levine, Stacie] Univ Chicago, Chicago, IL 60637 USA. [Misra, Sumathi] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Morrison, Laura] Yale Univ, Sch Med, New Haven, CT USA. [Radwany, Steven M.] Summa Hlth Syst, Akron, OH USA. [Reid, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnett, Michael David] Univ Alabama Birmingham, Birmingham, AL USA. [Landzaat, Lindy] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [McCormick, Wayne] Univ Washington, Harborview Med Ctr, 325 9Th Ave, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA P04 BP 308 EP 308 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900035 ER PT J AU Dahlin, C Lynch, M Lappen, K Long, B AF Dahlin, Constance Lynch, Maureen Lappen, Kerstin Long, Bronwyn TI ACHPN Certification Review: Advanced Practice Registered Nurse SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Dahlin, Constance] Hosp & Palliat Nurses Assoc, Pittsburgh, PA USA. [Lynch, Maureen] Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA USA. [Lappen, Kerstin] Minneapolis Clin, Minnesota Oncol, Minneapolis, MN USA. [Long, Bronwyn] Natl Jewish Hlth, Denver, CO 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA P06 BP 309 EP 309 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900037 ER PT J AU Sanchez-Reilly, S Periyakoil, V Kapo, J Thomas, JD O'Neill, L AF Sanchez-Reilly, Sandra Periyakoil, Vyjeyanthi Kapo, Jennifer Thomas, Jane deLima O'Neill, Lynn TI From Surviving to Thriving: A Self-Care Path to Resilience SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Sanchez-Reilly, Sandra] UT Hlth Sci Ctr, San Antonio, TX USA. [Periyakoil, Vyjeyanthi] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Kapo, Jennifer] Yale Univ, Bethany, CT USA. [Thomas, Jane deLima] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Neill, Lynn] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA P14 BP 312 EP 312 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900045 ER PT J AU Rosenberg, L Chittenden, E Greenwald, J Jacobsen, J AF Rosenberg, Leah Chittenden, Eva Greenwald, Jeffrey Jacobsen, Juliet TI Setting the Agenda: What do Academic Hospitalists Want to Learn from Their Palliative Care Colleagues? SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Rosenberg, Leah; Chittenden, Eva; Greenwald, Jeffrey; Jacobsen, Juliet] Massachusetts Gen Hosp, Boston, MA 02114 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH310B BP 321 EP 321 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900063 ER PT J AU Brock, K Cohen, H Sourkes, B Good, J Halamek, L AF Brock, Katharine Cohen, Harvey Sourkes, Barbara Good, Julie Halamek, Louis TI Improving Training in Palliative Care for Pediatric Fellows - A Simulation-Based Multi-Institution Trial SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Brock, Katharine] Boston Childrens, Dana Farber Canc Inst, Boston, MA USA. [Cohen, Harvey; Halamek, Louis] Stanford Univ, Stanford, CA 94305 USA. [Sourkes, Barbara] Lucile Packard Childrens Hosp Stanford, Palo Alto, CA USA. [Good, Julie] Packard Childrens Hosp Stanford, Palo Alto, CA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH311B BP 323 EP 324 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900067 ER PT J AU Rosenberg, A Orellana, L Dussel, V Wolfe, J AF Rosenberg, Abby Orellana, Liliana Dussel, Veronica Wolfe, Joanne TI Quality of Life in Children with Advanced Cancer: A Report from the Pediquest Study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Rosenberg, Abby] Seattle Childrens Hosp, Seattle, WA USA. [Orellana, Liliana] Deakin Univ, Burwood, Vic, Australia. [Dussel, Veronica] Boston Childrens Hosp, Boston, MA USA. [Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Orellana, Liliana/S-3302-2016 OI Orellana, Liliana/0000-0003-3736-4337 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH311C BP 324 EP 324 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900068 ER PT J AU Ullrich, C London, W Guo, DJ Lehmann, L Wolfe, J Sridharan, M Koch, R AF Ullrich, Christina London, Wendy Guo, Dongjing Lehmann, Leslie Wolfe, Joanne Sridharan, Madhumithra Koch, Richard TI The Role of Pediatric Palliative Care (PPC) in Children Who Undergo Stem Cell Transplantation (SCT) and Do Not Survive SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Ullrich, Christina; Lehmann, Leslie; Wolfe, Joanne; Koch, Richard] Dana Farber Canc Inst, Boston, MA 02115 USA. [London, Wendy] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Guo, Dongjing; Sridharan, Madhumithra] Boston Childrens Hosp, Boston, MA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH311D BP 324 EP 325 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900069 ER PT J AU Hagiwara, Y Healy, J Ghannam, S Lee, S Sanchez-Reilly, S AF Hagiwara, Yuya Healy, Jennifer Ghannam, Sammar Lee, Shuko Sanchez-Reilly, Sandra TI Development and Validation of a Family Meeting OSCE Assessment Tool (FMOSCEAT) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Hagiwara, Yuya] Avera Med Grp Palliat Med, San Antonio, TX USA. [Healy, Jennifer; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ghannam, Sammar] Univ Texas San Antonio, San Antonio, TX USA. [Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH331A BP 332 EP 333 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900084 ER PT J AU Berger, J Nabati, L AF Berger, Jeffrey Nabati, Lida TI Physician Assisted Dying Position Statement: The AAHPM Ethics Committee Reports on Its Work SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Berger, Jeffrey] Winthrop Hosp, Mineola, NY USA. [Nabati, Lida] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH352 BP 336 EP 336 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900091 ER PT J AU Levine, D Johnson, LM Ullrich, C Baker, J AF Levine, Deena Johnson, Liza-Marie Ullrich, Christina Baker, Justin TI When to Say When: Helping the Team and Family Recognize when Death is Inevitable After Pediatric Bone Marrow Transplant SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Levine, Deena; Johnson, Liza-Marie; Baker, Justin] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Ullrich, Christina] 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH356 BP 338 EP 338 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900095 ER PT J AU Vick, J Pertsch, N Hutchings, M Neville, B Bernacki, R AF Vick, Judith Pertsch, Nathan Hutchings, Mathilde Neville, Bridget Bernacki, Rachelle TI The Utility of the Surprise Question in Identifying Patients Most at Risk of Death SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Vick, Judith] Johns Hopkins Univ, Baltimore, MD USA. [Pertsch, Nathan; Bernacki, Rachelle] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hutchings, Mathilde; Neville, Bridget] Ariadne Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH360D BP 342 EP 342 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900102 ER PT J AU LeBlanc, T El-Jawahri, A Tulsky, J Abernethy, A AF LeBlanc, Thomas El-Jawahri, Areej Tulsky, James Abernethy, Amy TI Using the Distress Thermometer to Highlight Palliative Care Needs of Patients with Acute Myeloid Leukemia (AML) SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [LeBlanc, Thomas] Duke Univ, Sch Med, Durham, NC USA. [El-Jawahri, Areej] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tulsky, James] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abernethy, Amy] Flatiron Hlth, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA TH361B BP 343 EP 344 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900104 ER PT J AU Abrahm, J Balboni, T Cheville, A Ferrone, M AF Abrahm, Janet Balboni, Tracy Cheville, Andrea Ferrone, Marco TI Update on Spinal Cord Compression: The Key Role of the Hospice or Palliative Care Clinician SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Abrahm, Janet; Balboni, Tracy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abrahm, Janet] Brigham Womens, Boston, MA USA. [Cheville, Andrea] Mayo Clin, Kasson, MN USA. [Ferrone, Marco] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR412 BP 349 EP 349 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900116 ER PT J AU Back, A Jackson, V Steinhauser, K Kamal, A AF Back, Anthony Jackson, Vicki Steinhauser, Karen Kamal, Arif TI A New Framework for Resilience Skills to Prevent Burnout and Ensure Sustainability SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Back, Anthony] Univ Washington, Seattle, WA 98195 USA. [Jackson, Vicki] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jackson, Vicki] Harvard Univ, Sch Med, Boston, MA USA. [Steinhauser, Karen] Duke Med Ctr, Durham, NC USA. [Kamal, Arif] Duke Canc Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR413 BP 349 EP 350 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900117 ER PT J AU Jacobsen, J Earnshaw, L Thomas, JD AF Jacobsen, Juliet Earnshaw, Lori Thomas, Jane deLima TI Finding the Right Fit: How to Use the Evidence to Make a Great Hire SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Jacobsen, Juliet] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jacobsen, Juliet] Harvard Univ, Boston, MA 02115 USA. [Earnshaw, Lori] Univ Louisville, Louisville, KY 40292 USA. [Thomas, Jane deLima] 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR417 BP 351 EP 351 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900121 ER PT J AU Mireles, C Healy, J Lee, S Sanchez-Reilly, S Kapp, B AF Mireles, Christina Healy, Jennifer Lee, Shuko Sanchez-Reilly, Sandra Kapp, Bethany TI Nurses Have the Magic Touch: Determining the Effect of Embedding a Palliative Care Nurse Within the MICU SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Mireles, Christina; Healy, Jennifer; Sanchez-Reilly, Sandra; Kapp, Bethany] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR420A BP 354 EP 355 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900127 ER PT J AU Zehm, A Kamdar, M AF Zehm, April Kamdar, Mihir TI Not Just Another Pretty Face: Botulinum Toxin Gives Symptom Control in Palliative Care a Facelift SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Zehm, April; Kamdar, Mihir] Massachusetts Gen Hosp, Boston, MA 02114 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR436 BP 359 EP 359 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900136 ER PT J AU Amdur, S Seetharama, A Lee, S Ross, J Sanchez-Reilly, S AF Amdur, Shira Seetharama, Aparna Lee, Shuko Ross, Jeanette Sanchez-Reilly, Sandra TI Good Mourning, YouTube! Grieving and Bereaving on the World's Most Popular Video Sharing Website SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Amdur, Shira; Seetharama, Aparna; Ross, Jeanette; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Seetharama, Aparna; Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR461D BP 373 EP 374 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900162 ER PT J AU Jacobsen, J Jackson, V Rinehart, T AF Jacobsen, Juliet Jackson, Vicki Rinehart, Todd TI Building a Feedback Culture: How to Teach Your Team to Give and Receive Feedback for Maximal Performance and Growth SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Jacobsen, Juliet; Jackson, Vicki; Rinehart, Todd] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jacobsen, Juliet] Harvard Univ, Boston, MA 02115 USA. [Jackson, Vicki] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR475 BP 376 EP 376 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900168 ER PT J AU Doyle, K Skoniecki, D Gheihman, G AF Doyle, Kathleen Skoniecki, Debra Gheihman, Galina TI Long Term Collaboration for Building Sustainable Palliative Care in Belarus SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Doyle, Kathleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Skoniecki, Debra] Brigham & Womens Hosp, Rowley, MA USA. [Gheihman, Galina] Harvard Univ, Sch Med, Boston, MA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR477 BP 377 EP 378 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900170 ER PT J AU Paladino, J Lamas, D Lakin, J Epstein, S Bernacki, R AF Paladino, Joanna Lamas, Daniela Lakin, Joshua Epstein, Samantha Bernacki, Rachelle TI Delivering More, Better and Earlier Goals of Care Conversations to Seriously Ill Oncology Patients in the Clinical Setting SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Paladino, Joanna; Lakin, Joshua; Epstein, Samantha; Bernacki, Rachelle] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lamas, Daniela] Brigham & Womens Hosp, 75 Francis St, 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA FR481C BP 380 EP 380 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900175 ER PT J AU Battista, V Hwang, JM Mosher, P Muriel, A AF Battista, Vanessa Hwang, Jennifer Minarcik Mosher, Pamela Muriel, Anna TI "The Doctor Is In'': The Role of Child Psychiatrists in Pediatric Palliative Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Battista, Vanessa; Hwang, Jennifer Minarcik] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Mosher, Pamela] IWK Hlth Ctr, Toronto, ON, Canada. [Muriel, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Muriel, Anna] Brigham Womens Hosp, Boston, MA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA SA502 BP 387 EP 387 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900185 ER PT J AU Braun, I Nabati, L AF Braun, Ilana Nabati, Lida TI Developing Institutional Medical Marijuana Guidelines: Understanding Law and Science SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Braun, Ilana; Nabati, Lida] 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA SA524 BP 396 EP 397 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900205 ER PT J AU Zhang, HP Barysauskas, C Lindvall, C Rickerson, E Selvaggi, K AF Zhang, Haipeng Barysauskas, Constance Lindvall, Charlotta Rickerson, Elizabeth Selvaggi, Kathy TI The Intensive Palliative Care Unit (IPCU): Changing Outcomes for Hospitalized Cancer Patients in an Academic Medical Center SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Zhang, Haipeng; Barysauskas, Constance; Selvaggi, Kathy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lindvall, Charlotta] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rickerson, Elizabeth] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S741 BP 429 EP 429 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900264 ER PT J AU Collins, M Horton, D Worster, B AF Collins, Molly Horton, Daniel Worster, Brooke TI Feasibility of Outpatient Advance Care Planning Discussions: Adventures of a Primary Care Physician SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Collins, Molly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Horton, Daniel] Rutgers Biomed & Hlth Sci, New Brunswick, NJ USA. [Worster, Brooke] Jefferson Univ Hosp, Philadelphia, PA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S761 BP 441 EP 441 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900284 ER PT J AU Petrillo, L McMahan, R Sudore, R AF Petrillo, Laura McMahan, Ryan Sudore, Rebecca TI What Is a Serious Medical Decision? Patients' And Surrogates' Perceptions of Serious Decisions and What Is Important in Making Them SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Petrillo, Laura] San Francisco Dept Vet Affairs, San Francisco, CA USA. [Petrillo, Laura; McMahan, Ryan; Sudore, Rebecca] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sudore, Rebecca] San Francisco Vet Adm Med Ctr, San Francisco, CA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S766 BP 443 EP 444 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900289 ER PT J AU Veeder, H Stowers, K Linden, J Lee, S Sanchez-Reilly, S AF Veeder, Heather Stowers, Katie Linden, James Lee, Shuko Sanchez-Reilly, Sandra TI Protecting Our Vulnerable Population: Screening for Mistreatment in Palliative Care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Veeder, Heather; Stowers, Katie; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Linden, James] Univ Hawaii Manoa, Honolulu, HI 96822 USA. [Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S776 BP 449 EP 450 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900299 ER PT J AU Williams, S Lee, S Healy, J Sanchez-Reilly, S AF Williams, Sherry Lee, Shuko Healy, Jennifer Sanchez-Reilly, Sandra TI How Come They Don't Come? Identifying Reasons of No-Shows Among a Palliative Care Outpatient Clinic SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Williams, Sherry; Healy, Jennifer; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Williams, Sherry; Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S775 BP 449 EP 449 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900298 ER PT J AU Liaw, SN Sullivan, A Joselow, M Duncan, J Wolfe, J AF Liaw, Shih-Ning Sullivan, Amy Joselow, Marsha Duncan, Janet Wolfe, Joanne TI Impact of an Interprofessional Training Program in Pediatric Palliative Care on Interprofessional Competencies and Career Development of Former Fellows SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Liaw, Shih-Ning; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sullivan, Amy] Harvard Univ, Sch Med, Boston, MA USA. [Joselow, Marsha; Duncan, Janet] Dana Farber Canc Inst, Boston Childrens Hosp, 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S780 BP 451 EP 452 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900303 ER PT J AU Kapp, B Mireles, C Sanchez-Reilly, S Healy, J Lee, S AF Kapp, Bethany Mireles, Christina Sanchez-Reilly, Sandra Healy, Jennifer Lee, Shuko TI Benefits of Palliative Care in the MICU SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Kapp, Bethany; Mireles, Christina; Sanchez-Reilly, Sandra; Healy, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S781 BP 452 EP 453 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900304 ER PT J AU May, L Sanchez-Reilly, S Frausto, E Lee, S Garcia, J AF May, Linda Sanchez-Reilly, Sandra Frausto, Edggar Lee, Shuko Garcia, Jessica TI Yes, I Can Live with Less Pain: A Pain Educational Intervention Improving Patient-Centered Care and Attitudes Among Older Adults SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [May, Linda; Sanchez-Reilly, Sandra; Frausto, Edggar] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lee, Shuko] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Garcia, Jessica] Symptom Management Consultants, Houston, TX 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S784 BP 454 EP 454 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900307 ER PT J AU Sanders, J Sterba, K Ford, D Block, S AF Sanders, Justin Sterba, Katherine Ford, Dee Block, Susan TI The Acceptability to African Americans of a Structured Conversation Guide to Improve Advance Care Planning (ACP) in the Setting of Cancer: A Tiered Focus Group Study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Sanders, Justin; Block, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sterba, Katherine; Ford, Dee] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S786 BP 455 EP 456 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900309 ER PT J AU Klein, D Dinardo, D Hwa, S Superson, J Chang, V Olson, E AF Klein, David Dinardo, Daniel Hwa, Stephanie Superson, Jennifer Chang, Victor Olson, Ellen TI Comparison of Symptoms in Patients with Lung Cancer and Hepatocellular Cancer Referred for Palliative Care at a VA Medical Center SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Klein, David] Hosp New York, Queens, NY USA. [Dinardo, Daniel] St Johns Episcopal Hosp, Merrick, NY USA. [Hwa, Stephanie] James J Peters VA Med Ctr, New York, NY USA. [Superson, Jennifer] James J Peters VA Med Ctr, Brooklyn, NY USA. [Chang, Victor] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Olson, Ellen] James J Peters Vet Adm Med Ctr, Bronx, NY 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S791 BP 458 EP 458 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900314 ER PT J AU Monskaya, M Pruskowski, J Garcia, Y Chang, V Olson, E AF Monskaya, Milena Pruskowski, Jennifer Garcia, Yleana Chang, Victor Olson, Ellen TI Dosing of Analgesics for Patients with Liver Cancer or Lung Cancer SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Monskaya, Milena] JJPMC, Brooklyn, NY USA. [Pruskowski, Jennifer] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Garcia, Yleana] Kaweah Delta Hlth Care Dist, Visalia, CA USA. [Chang, Victor] Vet Adm New Jersey Hlth Care Syst, E Orange, NJ USA. [Olson, Ellen] James J Peters Vet Adm Med Ctr, Bronx, NY 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S792 BP 458 EP 459 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900315 ER PT J AU Rabinowitz, E Sawicki, G Ullrich, C AF Rabinowitz, Elliot Sawicki, Gregory Ullrich, Christina TI The End-of-Life Experience of Patients with Cystic Fibrosis and the Role of Pediatric Palliative Care Consultation SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Meeting Abstract CT Annual Assembly of the American-Academy-of-Hospice-and-Palliative-Medicine and the Hospice-and-Palliative-Nurses-Association CY MAR 09-12, 2016 CL Chicago, IL SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc C1 [Rabinowitz, Elliot; Ullrich, Christina] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sawicki, Gregory] Boston Childrens Hosp, Boston, MA 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 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2016 VL 51 IS 2 MA S800 BP 463 EP 463 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA DI4MB UT WOS:000373472900323 ER PT J AU Aas, M Blokland, GAM Chawner, SJRA Choi, SW Estrada, J Forsingdal, A Friedrich, M Ganesham, S Hall, L Haslinger, D Huckins, L Loken, E Malan-Muller, S Martin, J Misiewicz, Z Pagliaroli, L Pardinas, AF Pisanu, C Quadri, G Santoro, ML Shaw, AD Ranlund, S Song, J Tesli, M Tropeano, M van der Voet, M Wolfe, K Cormack, FK DeLisi, L AF Aas, Monica Blokland, Gabriella A. M. Chawner, Samuel J. R. A. Choi, Shing-Wan Estrada, Jose Forsingdal, Annika Friedrich, Maximilian Ganesham, Suhas Hall, Lynsey Haslinger, Denise Huckins, Laura Loken, Erik Malan-Muller, Stefanie Martin, Joanna Misiewicz, Zuzanna Pagliaroli, Luca Pardinas, Antonio F. Pisanu, Claudia Quadri, Giorgia Santoro, Marcos L. Shaw, Alex D. Ranlund, Siri Song, Jie Tesli, Martin Tropeano, Maria van der Voet, Monique Wolfe, Kate Cormack, Freida K. DeLisi, Lynn TI Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014 SO PSYCHIATRIC GENETICS LA English DT Review DE attention-deficit hyperactivity disorder; bipolar disorder; genetics; genomics; International Society of Psychiatric Genetics; mood disorder; schizophrenia; World Congress of Psychiatric Genetics ID GENOME-WIDE ASSOCIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; RECEPTOR BETA(2) SUBUNIT; DE-NOVO MUTATIONS; DEFICIT HYPERACTIVITY DISORDER; LEUKOCYTE TELOMERE LENGTH; COSTA-RICAN POPULATION; HUMAN GUT MICROBIOME; STAR-ASTERISK-D; BIPOLAR DISORDER AB The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported. (c) 2016 Wolters Kluwer Health, Inc. All rights reserved. C1 [Aas, Monica; Tesli, Martin] Univ Oslo, Oslo Univ Hosp, NORMENT, Oslo, Norway. [Blokland, Gabriella A. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Psychiat,Psychiat & Neur, Boston, MA USA. [Blokland, Gabriella A. M.] BroInst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [DeLisi, Lynn] Harvard Univ, Sch Med, Brockton VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Estrada, Jose] Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Neurosci, El Paso, TX USA. [Loken, Erik] Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Cormack, Freida K.] Inst Psychiat Res, Neurosci Res Bldg,320 W 15th St, Indianapolis, IN 46202 USA. [Chawner, Samuel J. R. A.; Martin, Joanna; Pardinas, Antonio F.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales. [Hall, Lynsey] Univ Edinburgh, Royal Edinburgh Hosp, Sch Clin Sci, Div Psychiat, Edinburgh, Midlothian, Scotland. [Huckins, Laura] Wellcome Trust Sanger Inst, Hinxton, England. [Ranlund, Siri] UCL, Div Psychiat, London WC1E 6BT, England. [Quadri, Giorgia; Wolfe, Kate] UCL, Div Psychiat, Mol Psychiat Lab, London WC1E 6BT, England. [Tropeano, Maria] UCL, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC1E 6BT, England. [Choi, Shing-Wan] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Forsingdal, Annika] H Lundbeck & Co AS, Dept Synapt Transmiss, Valby, Denmark. [Friedrich, Maximilian] Univ Wurzburg, Dept Psychiat, Div Mol Psychiat, Wurzburg, Germany. [Haslinger, Denise] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60054 Frankfurt, Germany. [Ganesham, Suhas] Natl Inst Mental Hlth & NeuroSci, Bangalore, Karnataka, India. [Malan-Muller, Stefanie] Univ Stellenbosch, Fac Med & Hlth Sci, SA MRC Ctr TB Res,div Mol Biol & Human Genet, DST NRF Ctr Excellence Biomed TB Res,Dept Psychia, Cape Town, South Africa. [Misiewicz, Zuzanna] Univ Helsinki, Fac Biol & Environm Sci, Dept Biosci, Helsinki, Finland. [Pagliaroli, Luca] Semmelweis Univ, Inst Med Chem Mol Biol & Pathobiochem, H-1085 Budapest, Hungary. [Pisanu, Claudia] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Monserrato, Italy. [Santoro, Marcos L.] Univ Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo, Brazil. [Shaw, Alex D.] Neurosci Res Australia, Barker St Randwick, Sydney, NSW, Australia. [Song, Jie] Karolinska Inst, Dept Med Epidemiol & Biostat, Solna, Sweden. [van der Voet, Monique] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. RP Cormack, FK (reprint author), Inst Psychiat Res, Neurosci Res Bldg,320 W 15th St, Indianapolis, IN 46202 USA. EM fcormack@iupui.edu RI Tropeano, Maria/E-7611-2011; van der Voet, Monique/F-5772-2012; OI Tropeano, Maria/0000-0002-5156-7539; pagliaroli, luca/0000-0001-5539-4789; Chawner, Samuel/0000-0002-2590-2874; van der Voet, Monique/0000-0002-8829-1767; Pisanu, Claudia/0000-0002-9151-4319; Pardinas, Antonio/0000-0001-6845-7590; Blokland, Gabriella/0000-0003-0566-444X; Malan-Muller, Stefanie/0000-0003-0639-0129; Ranlund, Siri/0000-0003-2899-6746 FU NIH [R13AA017055] FX This report was made possible by a grant from NIH R13AA017055. Each summary is the subjective understanding of the rapporteur for each session. The data reported are as heard during the presentation and where possible, all statements have been checked with the speaker for accuracy. However, the speakers are not responsible for any of the information contained in this report. NR 218 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0955-8829 EI 1473-5873 J9 PSYCHIAT GENET JI Psychiatr. Genet. PD FEB PY 2016 VL 26 IS 1 BP 1 EP 47 DI 10.1097/YPG.0000000000000112 PG 47 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA DI4YZ UT WOS:000373506600001 PM 26565519 ER PT J AU Dale, T Hutcheson, K Mohamed, ASR Lewin, JS Gunn, GB Rao, AUK Kalpathy-Cramer, J Frank, SJ Garden, AS Messer, JA Warren, B Lai, SY Beadle, BM Morrison, WH Phan, J Skinner, H Gross, N Ferrarotto, R Weber, RS Rosenthal, DI Fuller, CD AF Dale, Timothy Hutcheson, Katherine Mohamed, Abdallah S. R. Lewin, Jan S. Gunn, G. Brandon Rao, Arvind U. K. Kalpathy-Cramer, Jayashree Frank, Steven J. Garden, Adam S. Messer, Jay A. Warren, Benjamin Lai, Stephen Y. Beadle, Beth M. Morrison, William H. Phan, Jack Skinner, Heath Gross, Neil Ferrarotto, Renata Weber, Randal S. Rosenthal, David I. Fuller, Clifton D. CA MD Anderson Head & Neck Canc Sympt TI Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: Dose-volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Dysphagia; Intensity-modulated radiation therapy; Oropharyngeal cancer; Mylohyoid; Geniohyoid; Dose-volume ID SQUAMOUS-CELL CARCINOMA; PATIENT-RATED XEROSTOMIA; FACTORS AFFECTING PLACEMENT; GASTROSTOMY TUBE PLACEMENT; LOWER CRANIAL NEUROPATHY; NORMAL TISSUE TOXICITY; LOCALLY-ADVANCED HEAD; NECK-CANCER TREATMENT; QUALITY-OF-LIFE; INDUCTION CHEMOTHERAPY AB Purpose/objective(s): We sought to identify swallowing muscle dose-response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. Materials/methods: T1-4 N0-3 MO oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following >= 12 months post-IMRT: videofluoroscopyiendoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), masseter (MM), buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose-volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose-volume effects associated with chronic-RAD, for use in a multivariate (MV) model. Results: Of 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving >= 69 Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal ambng tested MV models (AUC 0.835). Conclusion: In addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Dale, Timothy; Mohamed, Abdallah S. R.; Gunn, G. Brandon; Frank, Steven J.; Garden, Adam S.; Messer, Jay A.; Warren, Benjamin; Beadle, Beth M.; Morrison, William H.; Phan, Jack; Skinner, Heath; Rosenthal, David I.; Fuller, Clifton D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Hutcheson, Katherine; Lewin, Jan S.; Lai, Stephen Y.; Gross, Neil; Weber, Randal S.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Rao, Arvind U. K.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Ferrarotto, Renata] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Head & Neck Oncol, Houston, TX 77030 USA. [Dale, Timothy] Baylor Coll Med, Houston, TX 77030 USA. [Mohamed, Abdallah S. R.] Univ Alexandria, Dept Clin Oncol, Alexandria, Egypt. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Fuller, Clifton D.] Univ Texas Houston, Grad Sch Biomed Sci, Med Phys Program, Houston, TX USA. [Messer, Jay A.; Warren, Benjamin] Univ Texas Hlth Sci Ctr Houston, Sch Med, Houston, TX 77030 USA. RP Fuller, CD (reprint author), Dept Radiat Oncol, Head & Neck Sect, 1515 Holcombe Blvd,Unit 0097, Houston, TX 77030 USA. EM cdfuller@mdanderson.org OI Fuller, Clifton/0000-0002-5264-3994; Mohamed, Abdallah/0000-0003-2064-7613 FU National Science Foundation, Division of Mathematical Sciences Quantitative Approaches to Biomedical Big Data (QuBBD) Program [NSF 1557559]; National Institutes of Health/National Cancer Institute's Paul Calabresi Clinical Oncology Award Program [K12 CA088084-06]; National Institutes of Health/National Cancer Institute's Clinician Scientist Loan Repayment Program [L30 CA136381-02]; SWOG/Hope Foundation; General Electric Healthcare/MD Anderson Center for Advanced Biomedical Imaging; Elekta AB/MD Anderson Department of Radiation Oncology Seed Grant; Center for Radiation Oncology Research at MD Anderson Cancer Center; MD Anderson Institutional Research Grant Program; National Institutes of Health/National Institute for Dental and Craniofacial Research [1R56DE025248-01]; National Cancer Institute [R03 CA188162]; National Institutes of Health Cancer Center Support (Core) Grant [CA016672] FX Dr. Fuller received/receives grant and/or salary support from: National Science Foundation, Division of Mathematical Sciences Quantitative Approaches to Biomedical Big Data (QuBBD) Program (NSF 1557559); the National Institutes of Health/National Cancer Institute's Paul Calabresi Clinical Oncology Award Program (K12 CA088084-06) and Clinician Scientist Loan Repayment Program (L30 CA136381-02); the SWOG/Hope Foundation Dr. Charles A. Coltman, Jr., Fellowship in Clinical Trials; a General Electric Healthcare/MD Anderson Center for Advanced Biomedical Imaging In Kind Award; an Elekta AB/MD Anderson Department of Radiation Oncology Seed Grant; the Center for Radiation Oncology Research at MD Anderson Cancer Center; and the MD Anderson Institutional Research Grant Program. Drs. Lai, Mohamed, and Fuller are supported by a grant award-from the National Institutes of Health/National Institute for Dental and Craniofacial Research (1R56DE025248-01). Dr. Hutcheson receives grant support from the MD Anderson Institutional Research Grant Program and the National Cancer Institute (R03 CA188162). This work was supported in part infrastructure support by National Institutes of Health Cancer Center Support (Core) Grant CA016672 to The University of Texas MD Anderson Cancer Center. These listed funders/supporters played no role in the study design, collection, analysis, interpretation of data, manuscript writing, or decision to submit the report for publication. NR 83 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD FEB PY 2016 VL 118 IS 2 BP 304 EP 314 DI 10.1016/j.radonc.2016.01.019 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI3SY UT WOS:000373420000015 ER PT J AU Maleki, N Bernstein, C Napadow, V Field, A AF Maleki, Nasim Bernstein, Carolyn Napadow, Vitaly Field, Alison TI Migraine and Puberty: Potential Susceptible Brain Sites SO SEMINARS IN PEDIATRIC NEUROLOGY LA English DT Review ID STEROID-HORMONES; STEM ACTIVATION; SEX-DIFFERENCES; FUNCTIONAL CONNECTIVITY; AFFECTIVE-DISORDERS; FEMALE MIGRAINEURS; STRESS RESPONSES; ADOLESCENT BRAIN; ALLOSTATIC LOAD; ANTERIOR INSULA AB Puberty is a sensitive and critical period for brain development. The relationship between developmental processes in the brain during puberty and the onset of migraine disease in relation to the potential sites of susceptibility in the brain remains largely unknown. There are few data on how such processes interact with each other in influencing the migraine onset during puberty or even later in adulthood. Focusing on the migraine brain during pubertal development may provide us with a "window of opportunity" both to better understand the mechanisms of the disease and, also more importantly, to effectively intervene. (C) 2016 Elsevier Inc. All rights reserved. C1 [Maleki, Nasim] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maleki, Nasim] Boston Childrens Hosp, Dept Anesthesia, Boston, MA USA. [Bernstein, Carolyn] Harvard Univ, Sch Med, Dept Anesthesia, Beth Israel Deaconess Hosp, Boston, MA 02115 USA. [Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Napadow, Vitaly] Brigham & Womens Hosp, Dept Anesthesiol, 75 Francis St, Boston, MA 02115 USA. [Field, Alison] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Field, Alison] Harvard Univ, Sch Med, Dept Pediat, Boston Childrens Hosp, Boston, MA 02115 USA. [Field, Alison] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Field, Alison] Brown Univ, Sch Publ Heath, Dept Epidemiol, Providence, MA USA. RP Maleki, N (reprint author), Massachusetts Gen Hosp, Div Psychiat Neuroimaging, Bldg 120,2nd Ave,Suite 101E, Charlestown, MA USA. EM nasim.maleki@childrens.harvard.edu NR 102 TC 0 Z9 0 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1071-9091 EI 1558-0776 J9 SEMIN PEDIATR NEUROL JI Semin. Pediatr. Neurol. PD FEB PY 2016 VL 23 IS 1 BP 53 EP 59 DI 10.1016/j.spen.2016.01.011 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA DI7DD UT WOS:000373658400013 PM 27017023 ER PT J AU Apelo, SIA Neuman, JC Baar, EL Syed, FA Cummings, NE Brar, HK Pumper, CP Kimple, ME Lamming, DW AF Apelo, Sebastian I. Arriola Neuman, Joshua C. Baar, Emma L. Syed, Faizan A. Cummings, Nicole E. Brar, Harpreet K. Pumper, Cassidy P. Kimple, Michelle E. Lamming, Dudley W. TI Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system SO AGING CELL LA English DT Article DE aging; mechanistic target of rapamycin; mice; rapamycin ID MAMMALIAN LIFE-SPAN; INSULIN-RESISTANCE; T-CELLS; MICE; MTORC2; EXPRESSION; RICTOR; RESPONSES; QUALITY; TISSUE AB Inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA-approved drug rapamycin has been shown to promote lifespan and delay age-related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long-term prophylactic use of rapamycin as a therapy for age-related diseases. While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. We hypothesized that different rapamycin dosing schedules or the use of FDA-approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Here, we identified an intermittent rapamycin dosing schedule with minimal effects on glucose tolerance, and we find that this schedule has a reduced impact on pyruvate tolerance, fasting glucose and insulin levels, beta cell function, and the immune system compared to daily rapamycin treatment. Further, we find that the FDA-approved rapamycin analogs everolimus and temsirolimus efficiently inhibit mTORC1 while having a reduced impact on glucose and pyruvate tolerance. Our results suggest that many of the negative side effects of rapamycin treatment can be mitigated through intermittent dosing or the use of rapamycin analogs. C1 [Apelo, Sebastian I. Arriola; Baar, Emma L.; Syed, Faizan A.; Cummings, Nicole E.; Brar, Harpreet K.; Pumper, Cassidy P.; Kimple, Michelle E.; Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI USA. [Apelo, Sebastian I. Arriola; Neuman, Joshua C.; Baar, Emma L.; Syed, Faizan A.; Cummings, Nicole E.; Brar, Harpreet K.; Pumper, Cassidy P.; Kimple, Michelle E.; Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA. [Neuman, Joshua C.; Kimple, Michelle E.; Lamming, Dudley W.] Univ Wisconsin, Interdisciplinary Grad Program Nutr Sci, Madison, WI USA. [Cummings, Nicole E.; Kimple, Michelle E.; Lamming, Dudley W.] Univ Wisconsin, Endocrinol & Reprod Physiol Grad Training Program, Madison, WI USA. [Lamming, Dudley W.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. RP Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA. EM dlamming@medicine.wisc.edu OI Lamming, Dudley/0000-0002-0079-4467 FU National Institute of Health/National Institute on Aging [AG041765]; UW-Madison School of Medicine and Public Health; UW-Madison Department of Medicine; American Diabetes Association [1-14-BS-115]; NIH/NIDDK [R01 DK102598]; University of Wisconsin Carbone Cancer Center Support Grant [P30 CA014520]; UW Institute on Aging [NIA T32 AG000213] FX The Lamming lab is supported by a K99/R00 Pathway to Independence Award to D.W.L. from the National Institute of Health/National Institute on Aging (AG041765), as well as startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. This work was also supported by grants from the American Diabetes Association (1-14-BS-115) and the NIH/NIDDK (R01 DK102598) to M.E.K. D.W.L. is a member of the UW-Carbone Cancer Center (UWCCC), and use of the UWCCC Flow Cytometry Laboratory, a Shared Service of the UWCCC, was supported in part by the University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520. J.C.N. is supported in part by a training grant from the UW Institute on Aging (NIA T32 AG000213). This work was supported using facilities and resources at the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government. NR 42 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD FEB PY 2016 VL 15 IS 1 BP 28 EP 38 DI 10.1111/acel.12405 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DH6CQ UT WOS:000372879000004 ER PT J AU Martin, SA DeMuth, TM Miller, KN Pugh, TD Polewski, MA Colman, RJ Eliceiri, KW Beasley, TM Johnson, SC Anderson, RM AF Martin, Stephen A. DeMuth, Tyler M. Miller, Karl N. Pugh, Thomas D. Polewski, Michael A. Colman, Ricki J. Eliceiri, Kevin W. Beasley, Timothy Mark Johnson, Sterling C. Anderson, Rozalyn M. TI Regional metabolic heterogeneity of the hippocampus is nonuniformly impacted by age and caloric restriction SO AGING CELL LA English DT Article DE aging; metabolism; caloric restriction; hippocampus; mitochondria; neuroprotection ID GLYCOGEN-SYNTHASE KINASE-3; RHESUS-MONKEYS; ALZHEIMERS-DISEASE; OXIDATIVE-METABOLISM; ENERGY-METABOLISM; CELLS; FLUORESCENCE; NADH; PGC-1-ALPHA; BRAIN AB The hippocampus is critical for cognition and memory formation and is vulnerable to age-related atrophy and loss of function. These phenotypes are attenuated by caloric restriction (CR), a dietary intervention that delays aging. Here, we show significant regional effects in hippocampal energy metabolism that are responsive to age and CR, implicating metabolic pathways in neuronal protection. In situ mitochondrial cytochrome c oxidase activity was region specific and lower in aged mice, and the impact of age was region specific. Multiphoton laser scanning microscopy revealed region- and age-specific differences in nicotinamide adenine dinucleotide (NAD)-derived metabolic cofactors. Age-related changes in metabolic parameters were temporally separated, with early and late events in the metabolic response to age. There was a significant regional impact of age to lower levels of PGC-1 alpha, a master mitochondrial regulator. Rather than reversing the impact of age, CR induced a distinct metabolic state with decreased cytochrome c oxidase activity and increased levels of NAD(P) H. Levels of hippocampal PGC-1 alpha were lower with CR, as were levels of GSK3 beta, a key regulator of PGC-1 alpha turnover and activity. Regional distribution and colocalization of PGC-1 alpha and GSK3 beta in mouse hippocampus was similar in monkeys. Furthermore, the impact of CR to lower levels of both PGC-1 alpha and GSK3 beta was also conserved. The studies presented here establish the hippocampus as a highly varied metabolic environment, reveal cell-type and regional specificity in the metabolic response to age and delayed aging by CR, and suggest that PGC-1 alpha and GSK3 beta play a role in implementing the neuroprotective program induced by CR. C1 [Martin, Stephen A.; DeMuth, Tyler M.; Miller, Karl N.; Pugh, Thomas D.; Polewski, Michael A.; Johnson, Sterling C.; Anderson, Rozalyn M.] SMPH, Dept Med, Div Geriatr, Madison, WI 53705 USA. [Colman, Ricki J.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Eliceiri, Kevin W.] Univ Wisconsin, Lab Opt & Computat Instrumentat, Madison, WI 53706 USA. [Beasley, Timothy Mark] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Beasley, Timothy Mark] Birmingham Atlanta Vet Adm Hosp, GRECC, Birmingham, AL 35294 USA. [Johnson, Sterling C.; Anderson, Rozalyn M.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. RP Anderson, RM (reprint author), William S Middleton VA Hosp, GRECC D5214,2500 Overlook Terrace, Madison, WI 53705 USA. EM rmanderson@medicine.wisc.edu FU NIH/NIA R01 [AG037000, AG043125]; ADRC [AG033514]; UW Institute on Aging [AG000213]; UW Department of Nutritional Sciences [DK007665] FX This work was supported by NIH/NIA R01 grants AG037000, AG043125, and ADRC grant AG033514. SAM and KNM are supported by T32 fellowships from the UW Institute on Aging AG000213 and the UW Department of Nutritional Sciences DK007665, respectively. The study was conducted with the use of resources and facilities at the William S. Middleton Memorial Veterans Hospital, Madison, WI. NR 47 TC 3 Z9 3 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD FEB PY 2016 VL 15 IS 1 BP 100 EP 110 DI 10.1111/acel.12418 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DH6CQ UT WOS:000372879000011 PM 26521867 ER PT J AU Baar, EL Carbajal, KA Ong, IM Lamming, DW AF Baar, Emma L. Carbajal, Kathryn A. Ong, Irene M. Lamming, Dudley W. TI Sex- and tissue-specific changes in mTOR signaling with age in C57BL/6J mice SO AGING CELL LA English DT Article DE aging; mice; mTOR; mTORC1; mTORC2; rapamycin; sexual dimorphism ID LIFE-SPAN; CALORIC RESTRICTION; DIETARY RESTRICTION; S6 KINASE; RAPAMYCIN; LONGEVITY; EXPRESSION; RESVERATROL; SENSITIVITY; INHIBITION AB Inhibition of the mTOR (mechanistic Target Of Rapamycin) signaling pathway robustly extends the lifespan of model organisms including mice. The precise molecular mechanisms and physiological effects that underlie the beneficial effects of rapamycin are an exciting area of research. Surprisingly, while some data suggest that mTOR signaling normally increases with age in mice, the effect of age on mTOR signaling has never been comprehensively assessed. Here, we determine the age-associated changes in mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2) signaling in the liver, muscle, adipose, and heart of C57BL/6J. Nia mice, the lifespan of which can be extended by rapamycin treatment. We find that the effect of age on several different readouts of mTORC1 and mTORC2 activity varies by tissue and sex in C57BL/6J. Nia mice. Intriguingly, we observed increased mTORC1 activity in the liver and heart tissue of young female mice compared to male mice of the same age. Tissue and substrate-specific results were observed in the livers of HET3 and DBA/2 mouse strains, and in liver, muscle and adipose tissue of F344 rats. Our results demonstrate that aging does not result in increased mTOR signaling in most tissues and suggest that rapamycin does not promote lifespan by reversing or blunting such an effect. C1 [Baar, Emma L.; Carbajal, Kathryn A.; Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Baar, Emma L.; Carbajal, Kathryn A.; Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA. [Ong, Irene M.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Ong, Irene M.; Lamming, Dudley W.] Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA. RP Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA. EM dlamming@medicine.wisc.edu FU National Institute of Health/NIA [AG041765]; UW-Madison School of Medicine and Public Health; UW-Madison Department of Medicine; Research Supplement to Promote Diversity in Health-Related Research [AG041765-04S1]; University of Wisconsin Carbone Cancer Center Support Grant [P30 CA014520]; Clinical and Translational Science Award (CTSA) program through the NIH National Center for Advancing Translational Sciences (NCATS) [UL1TR000427] FX The Lamming lab is supported by a K99/R00 Pathway to Independence Award to DWL from the National Institute of Health/NIA (AG041765), as well as startup funds from the UW-Madison School of Medicine and Public Health and the UW-Madison Department of Medicine. KAC was supported in part by a Research Supplement to Promote Diversity in Health-Related Research (AG041765-04S1). IO is supported by the University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520 and the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. This work was supported using facilities and resources from the William S. Middleton Memorial Veterans Hospital. This work does not represent the views of the Department of Veterans Affairs or the United States Government. NR 45 TC 9 Z9 9 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD FEB PY 2016 VL 15 IS 1 BP 155 EP 166 DI 10.1111/acel.12425 PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA DH6CQ UT WOS:000372879000017 PM 26695882 ER PT J AU Scahill, L Sukhodolsky, DG Anderberg, E Dimitropoulos, A Dziura, J Aman, MG McCracken, J Tierney, E Hallett, V Katz, K Vitiello, B McDougle, C AF Scahill, Lawrence Sukhodolsky, Denis G. Anderberg, Emily Dimitropoulos, Anastasia Dziura, James Aman, Michael G. McCracken, James Tierney, Elaine Hallett, Victoria Katz, Karol Vitiello, Benedetto McDougle, Christopher TI Sensitivity of the modified Children's Yale-Brown Obsessive Compulsive Scale to detect change: Results from two multi-site trials SO AUTISM LA English DT Article DE autism spectrum disorder; clinical trials; outcome measurement; repetitive behavior; risperidone ID AUTISM-SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; ABERRANT BEHAVIOR CHECKLIST; REPETITIVE BEHAVIORS; PEDIATRIC PSYCHOPHARMACOLOGY; CLINICAL-TRIAL; RESEARCH UNITS; DOUBLE-BLIND; PLACEBO; ADOLESCENTS AB Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all three active treatment groups showed significant improvement (effect sizes: 0.74-0.88). There were no differences between active treatment groups. These results indicate that the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder has acceptable test-retest as evidenced by the medium to high correlations in the placebo group and demonstrated sensitivity to change with treatment. C1 [Scahill, Lawrence] Emory Univ, Atlanta, GA 30322 USA. [Sukhodolsky, Denis G.; Dziura, James; Katz, Karol] Yale Univ, New Haven, CT 06520 USA. [Anderberg, Emily] Univ Washington, Brigham Young Univ, Seattle, WA 98195 USA. [Dimitropoulos, Anastasia] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Aman, Michael G.] Ohio State Univ, Columbus, OH 43210 USA. [McCracken, James] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Tierney, Elaine] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Hallett, Victoria] Kings Coll London, London WC2R 2LS, England. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD USA. [McDougle, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scahill, L (reprint author), Emory Univ, Marcus Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA. EM lawrence.scahill@emory.edu OI Sukhodolsky, Denis/0000-0002-5401-792X FU US National Institute of Mental Health [N01MH70009, U10MH66764, R01MH099021] FX This research received grant funding from the US National Institute of Mental Health contract N01MH70009, grants U10MH66764, R01MH099021 (L. Scahill, Principal Investigator) NR 40 TC 0 Z9 0 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD FEB PY 2016 VL 20 IS 2 BP 145 EP 152 DI 10.1177/1362361315574889 PG 8 WC Psychology, Developmental SC Psychology GA DH6DB UT WOS:000372880100003 PM 25882391 ER PT J AU Hulten, E Aslam, S Osborne, M Abbasi, S Bittencourt, MS Blankstein, R AF Hulten, Edward Aslam, Saira Osborne, Michael Abbasi, Siddique Bittencourt, Marcio Sommer Blankstein, Ron TI Cardiac sarcoidosis-state of the art review SO CARDIOVASCULAR DIAGNOSIS AND THERAPY LA English DT Review DE Cardiac sarcoidosis; cardiac MRI; cardiac positron emission tomography (cardiac PET); review ID POSITRON-EMISSION-TOMOGRAPHY; CARDIOVASCULAR MAGNETIC-RESONANCE; PROGNOSTIC VALUE; F-18-FDG PET; RHYTHM ABNORMALITIES; DIAGNOSIS; MANAGEMENT; INFLAMMATION; SCINTIGRAPHY; INVOLVEMENT AB Sarcoidosis is a multi-system inflammatory disorder of unknown etiology resulting in formation of non-caseating granulomas. Cardiac involvement-which is associated with worse prognosis-has been detected in approximately 25% of individuals based on autopsy or cardiac imaging studies. Nevertheless, the diagnosis of cardiac sarcoidosis is challenging due to the low yield of endomyocardial biopsy, and the limited accuracy of various clinical criteria. Thus, no gold standard diagnostic criterion exists. This review will summarize the pathophysiology, diagnosis, and treatment of cardiac sarcoidosis with a focus on advanced cardiovascular imaging, We review the evidence to support a role for cardiac magnetic resonance (CMR) imaging in the initial evaluation of selected patients with suspected cardiac sarcoidosis, with cardiac positron emission tomography (PET) as an alternative or complementary initial diagnostic test in a subgroup of patients in whom CMR may be contra-indicated or when CMR is negative with continued clinical concern for myocardial inflammation. In addition to the diagnostic value of these tests, CMR and PET are also useful in identifying patients who have higher risk of adverse events such as ventricular tachycardia or death, in whom preventive therapies such as defibrillators should be more strongly considered. Although no randomized controlled trials for treatment of cardiac sarcoidosis exist, immunosuppressive therapy is often used. We review emerging evidence regarding the use of cardiac PET to identify and quantity the amount of myocardial inflammation as well as to guide the use of immunotherapy. Future studies are needed to determine the benefit of imaging guided therapies aimed at improving patient outcomes. C1 [Hulten, Edward; Aslam, Saira] Walter Reed Natl Mil Med Ctr, Div Med, Serv Cardiol, Bethesda, MD USA. [Hulten, Edward; Aslam, Saira] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Hulten, Edward; Abbasi, Siddique; Blankstein, Ron] Brigham & Womens Hosp, Dept Med, Noninvas Cardiovasc Imaging Program, 75 Francis St, Boston, MA 02115 USA. [Hulten, Edward; Abbasi, Siddique; Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Noninvas Cardiovasc Imaging Program, 75 Francis St, Boston, MA 02115 USA. [Hulten, Edward; Osborne, Michael; Abbasi, Siddique; Blankstein, Ron] Harvard Univ, Sch Med, Boston, MA USA. [Osborne, Michael] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bittencourt, Marcio Sommer] Univ Hosp, Ctr Clin & Epidemiol Res, Sao Paulo, Brazil. [Bittencourt, Marcio Sommer] Univ Sao Paulo, Sao Paulo State Canc Inst, Sao Paulo, Brazil. [Bittencourt, Marcio Sommer] Hosp Israelita Albert Einstein, Prevent Med Ctr, Sao Paulo, Brazil. RP Blankstein, R (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.; Blankstein, R (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM rblankstein@partners.org RI Bittencourt, Marcio/C-1444-2011 OI Bittencourt, Marcio/0000-0002-3711-1754 NR 60 TC 6 Z9 6 U1 1 U2 1 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2223-3652 EI 2223-3660 J9 CARDIOVASC DIAGN THE JI Cardiovisc. Diagn. Ther. PD FEB PY 2016 VL 6 IS 1 BP 50 EP 63 DI 10.3978/j.issn.2223-3652.2015.12.13 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DH5XP UT WOS:000372865900008 PM 26885492 ER PT J AU Feng, Y Tsai, TY Li, JS Rubash, HE Li, GA Freiberg, A AF Feng, Yong Tsai, Tsung-Yuan Li, Jing-Sheng Rubash, Harry E. Li, Guoan Freiberg, Andrew TI In-vivo analysis of flexion axes of the knee: Femoral condylar motion during dynamic knee flexion SO CLINICAL BIOMECHANICS LA English DT Article DE Knee kinematics; Fluoroscopy; Condylar motion; Surgical transepicondylar axis; Clinical transepicondylar axis; Geometrical center axis ID IMAGE-MATCHING TECHNIQUE; TRANSEPICONDYLAR AXIS; DISTAL FEMUR; EPICONDYLAR AXIS; VIRTUAL-REALITY; KINEMATICS; ARTHROPLASTY; ALIGNMENT; JOINT; MORPHOLOGY AB Background: Transepicondylar axis and geometrical center axis are widely used for investigation of the knee kinematics and component alignment in total knee arthroplasty. However, the kinematic characteristics of these knee axes are not well defined in literature. This study investigated the femoral condylar motion during a dynamic flexion of the knee using different flexion axes. Methods: Twenty healthy knees (10 males and 10 females) were CT scanned to create 3D anatomic models. The subjects performed a single leg flexion from full extension to maximum flexion while the knees were imaged using fluoroscopes. The femoral condyle translations in anterior-posterior and proximal-distal directions were described using clinical transepicondylar axis, surgical transepicondylar axis and geometrical center axis. Findings: The subjects achieved 9.4 (SD 3.0) hyperextension at full extension and 116.4 (SD 9.0) at maximum flexion of the knee. The anterior-posterior translations of the three flexion axes were different for the medial condyle, but similar for the lateral condyle. Substantial variations of the condylar motion in proximal-distal direction were measured along the flexion path using these axes. While the surgical transepicondylar axis maintained condyle heights from full extension to 60 of flexion, geometrical center axis showed little changes in condyle heights from 30 to maximum knee flexion. The condyles moved distally beyond 90 flexion using both transepicondylar axes. Interpretation: The femoral condylar motion measurement is sensitive to the selection of flexion axis. The different kinematic features of these axes provide an insightful reference when selecting a flexion axis in total knee arthroplasty component alignment. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Feng, Yong] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Orthopaed Surg, 600 Yishan Rd, Shanghai 200233, Peoples R China. [Feng, Yong; Tsai, Tsung-Yuan; Li, Jing-Sheng; Rubash, Harry E.; Li, Guoan; Freiberg, Andrew] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM Fengyongxsh@gmail.com; Tsai.Tsung-Yuan@mgh.harvard.edu; LiJing-Sheng@mgh.harvard.edu; Hrubash@partners.org; Li.Guoan@mgh.harvard.edu; Afreiberg@mgh.harvard.edu FU National Key Clinical Specialist Construction Project of China; National Institutes of Health [R01 AR055612] FX This study was supported by the National Key Clinical Specialist Construction Project of China and National Institutes of Health Grant (R01 AR055612). No other competing interests declared. NR 36 TC 0 Z9 0 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD FEB PY 2016 VL 32 BP 102 EP 107 DI 10.1016/j.clinbiomech.2015.12.006 PG 6 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA DH3LV UT WOS:000372689400015 PM 26777272 ER PT J AU Fazeli, PK Teoh, JG Lam, EL Gerweck, AV Wexler, TL Teo, EP Russell, BM Durst, R McCarty, D Weiner, RB Picard, MH Klibanski, A Miller, KK AF Fazeli, Pouneh K. Teoh, Jonathan G. Lam, Eleanor L. Gerweck, Anu V. Wexler, Tamara L. Teo, Eliza P. Russell, Brian M. Durst, Ronen McCarty, David Weiner, Rory B. Picard, Michael H. Klibanski, Anne Miller, Karen K. TI Effect of growth hormone treatment on diastolic function in patients who have developed growth hormone deficiency after definitive treatment of acromegaly SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE Acromegaly; Growth hormone deficiency; Diastolic dysfunction; Cardiovascular risk ID QUALITY-OF-LIFE; CARDIOVASCULAR RISK-FACTORS; GH REPLACEMENT THERAPY; DUTCH NATIONAL REGISTRY; BODY-COMPOSITION; ADULT PATIENTS; CARDIAC-PERFORMANCE; INSULIN-RESISTANCE; IMPROVES; HYPOPITUITARISM AB Objective: Although growth hormone (GH) replacement is prescribed for patients with hypopituitarism due to many etiologies, it is not routinely prescribed for patients with GH deficiency (GHD) after cure of acromegaly (acroGHD). This study was designed to investigate the effect of GH replacement on cardiac parameters in acroGHD. Design: We prospectively evaluated for 12 months 23 patients with acroGHD: 15 subjects on GH replacement and eight subjects not on GH replacement. Main outcome measures included LV mass corrected for body surface area (LVM/BSA) and measures of diastolic dysfunction (E/A ratio and deceleration time), as assessed by echocardiography. Results: After 12 months of follow-up, there were no differences between the GH-treated group and the untreated group in LVM/BSA (GH: 74.4 +/- 22.5 g/m(2) vs untreated: 72.9 +/- 21.3 g/m(2), p = 0.89), E/A ratio (GH: 1.21 +/- 0.39 vs untreated: 1.08 +/- 0.39, p = 0.50) or deceleration time (GH: 224.5 +/- 60.1 ms vs untreated: 260 +/- 79.8 ms, p = 032). The overall degree of diastolic function was similar between the groups with 42.9% of untreated subjects and 50% of GH-treated subjects (p = 0.76) classified as having normal diastolic function at follow-up. Conclusions: There were no significant differences in LVM/BSA or parameters of diastolic function in patients with a history of acromegaly treated for GHD as compared to those who were untreated. These data are reassuring with respect to cardiovascular safety with GH use after treatment for acromegaly, although further longer term study is necessary to evaluate the safety and efficacy of GH treatment in this population. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Fazeli, Pouneh K.; Lam, Eleanor L.; Gerweck, Anu V.; Wexler, Tamara L.; Russell, Brian M.; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. [Teoh, Jonathan G.; Teo, Eliza P.; Durst, Ronen; McCarty, David; Weiner, Rory B.; Picard, Michael H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fazeli, Pouneh K.; Teoh, Jonathan G.; Lam, Eleanor L.; Wexler, Tamara L.; Teo, Eliza P.; Durst, Ronen; McCarty, David; Weiner, Rory B.; Picard, Michael H.; Klibanski, Anne; Miller, Karen K.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM pkfazeli@partners.org RI Fazeli, Pouneh/R-4827-2016; OI Fazeli, Pouneh/0000-0003-1731-2927; Picard, Michael/0000-0002-9264-3243 FU Pfizer; Harvard Clinical and Translational Science Center [UL1 RR025758]; National Center for Research Resources; NIH [M01-RR-01066, K23 DK094820] FX The project described was supported by two investigator-initiated grants from Pfizer and grant number UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, and NIH grants M01-RR-01066 and K23 DK094820 (Fazeli). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 53 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 1096-6374 EI 1532-2238 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD FEB PY 2016 VL 26 BP 17 EP 23 DI 10.1016/j.ghir.2015.12.003 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DI1GM UT WOS:000373244600004 PM 26774401 ER PT J AU Srinivasa, S Suresh, C Mottla, J Hamarneh, SR Irazoqui, JE Frontera, W Torriani, M Stanley, T Makimura, H AF Srinivasa, Suman Suresh, Caroline Mottla, Jay Hamarneh, Sulaiman R. Irazoqui, Javier E. Frontera, Walter Torriani, Martin Stanley, Takara Makimura, Hideo TI FNDC5 relates to skeletal muscle IGF-I and mitochondrial function and gene expression in obese men with reduced growth hormone SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE lrisin; FNDC5; Growth hormone; IGF-I; Skeletal muscle; Mitochondrial; Obesity ID MESSENGER-RNA EXPRESSION; PHOSPHOCREATINE RECOVERY; IRISIN LEVELS; EXERCISE; SERUM; MYOKINE; HUMANS; BIOPSY; PLASMA; YOUNG AB Objective: To investigate the relationship of skeletal muscle FNDC5 mRNA expression and circulating irisin to the GH/IGF-I axis and to skeletal muscle mitochondrial function and mitochondria-related gene expression in obese men. Design: Fifteen abdominally obese men with reduced growth hormone received 12 weeks of recombinant human GH (rhGH). Before and after treatment, they underwent P-31-magnetic resonance spectroscopy to evaluate phosphocreatine (PCr) recovery as a measure of mitochondrial function and skeletal muscle biopsy to assess expression of mitochondrial-related genes. Serum irisin and IGF-I and skeletal muscle FNDC5 and IGF-I mRNA were measured. Results: At baseline, skeletal muscle FNDC5 mRNA was significantly and positively associated with IGF-I mRNA (rho = 0.81, P = 0.005) and rate of PCr recovery (rho = 0.79, P = 0.006). Similar relationships of circulating irisin to IGF-I mRNA (rho = 0.63, P = 0.05) and rate of PCr recovery (rho = 0.48, P = 0.08) were demonstrated, but were not as robust as those with muscle FNDC5 expression. Both serum irisin and skeletal muscle FNDC5 mRNA were significantly associated with PPAR gamma (rho = 0.73, P = 0.02 and rho = 0.85, P = 0.002), respectively. In addition, FNDC5 mRNA was correlated with skeletal muscle PGC-1 alpha (rho = 0.68, P = 0.03), NRF1 (rho = 0.66, P = 0.04) and TFAM (rho = 0.79, P = 0.007) mRNA. Neither serum irisin nor muscle mRNA expression of FNDC5 changed with rhGH treatment. Conclusion: These novel data in skeletal muscle demonstrate that local expression of FNDC5 is associated with mRNA expression of IGF-I and mitochondrial function and mitochondria-related gene expression in obese subjects with reduced growth hormone and suggest a potential role for FNDC5 acting locally in muscle in a low GH state. Further studies are needed to clarify the relationship between the GH/IGF-I axis and irisin. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Srinivasa, Suman; Suresh, Caroline; Stanley, Takara; Makimura, Hideo] Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. [Srinivasa, Suman; Suresh, Caroline; Hamarneh, Sulaiman R.; Irazoqui, Javier E.; Torriani, Martin; Stanley, Takara; Makimura, Hideo] Harvard Univ, Sch Med, Boston, MA USA. [Mottla, Jay] Georgetown Univ, Sch Med, Washington, DC USA. [Hamarneh, Sulaiman R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Irazoqui, Javier E.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Lab Comparat Immunol, Boston, MA 02114 USA. [Frontera, Walter] Vanderbilt Univ, Med Ctr, Dept Phys Med & Rehabil, Nashville, TN USA. [Frontera, Walter] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Frontera, Walter] Univ Puerto Rico, Sch Med, Dept Physiol, San Juan, PR USA. [Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Stanley, Takara] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Srinivasa, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM ssrinivasa@mgh.harvard.edu OI Irazoqui, Javier/0000-0001-6553-1329 FU NIH [K23DK087857, 1UL1RR025758-04, 8UL1TR000170-05, M01RR01066, UL1 TR001102]; National Center for Research Resources; National Center for Advancing Translational Sciences FX Funding was provided by NIH K23DK087857 (HM). The project described was supported by NIH 1UL1RR025758-04, 8UL1TR000170-05, M01RR01066, and UL1 TR001102 to the Harvard Clinical and Translational Science Center, from the National Center for Research Resources and National Center for Advancing Translational Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health. NR 23 TC 3 Z9 3 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 1096-6374 EI 1532-2238 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD FEB PY 2016 VL 26 BP 36 EP 41 DI 10.1016/j.ghir.2015.12.008 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA DI1GM UT WOS:000373244600007 PM 26774404 ER PT J AU Chidi, AP Rogal, S Bryce, CL Fine, MJ Good, CB Myaskovsky, L Rustgi, VK Tsung, A Smith, KJ AF Chidi, Alexis P. Rogal, Shari Bryce, Cindy L. Fine, Michael J. Good, Chester B. Myaskovsky, Larissa Rustgi, Vinod K. Tsung, Allan Smith, Kenneth J. TI Cost-Effectiveness of New Antiviral Regimens for Treatment-Naive US Veterans with Hepatitis C SO HEPATOLOGY LA English DT Article ID GENOTYPE 1 INFECTION; UNITED-STATES VETERANS; ALL-CAUSE MORTALITY; VIRUS-INFECTION; CHRONIC HCV; COMPENSATED CIRRHOSIS; LIVER-TRANSPLANTATION; PEGYLATED INTERFERON; VIROLOGICAL RESPONSE; SOFOSBUVIR AB Recently approved, interferon-free medication regimens for treating hepatitis C are highly effective, but extremely costly. We aimed to identify cost-effective strategies for managing treatment-naive U.S. veterans with new hepatitis C medication regimens. We developed a Markov model with 1-year cycle length for a cohort of 60-year-old veterans with untreated genotype 1 hepatitis C seeking treatment in a typical year. We compared using sofosbuvir/ledipasvir or ombitasvir/ritonavir/paritaprevir/dasabuvir to treat: (1) any patient seeking treatment; (2) only patients with advanced fibrosis or cirrhosis; or (3) patients with advanced disease first and healthier patients 1 year later. The previous standard of care, sofosbuvir/simeprevir or sofosbuvir/pegylated interferon/ribavirin, was included for comparison. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die. Complications were less likely after sustained virological response. We calculated the incremental cost per quality-adjusted life year (QALY) and varied model inputs in one-way and probabilistic sensitivity analyses. We used the Veterans Health Administration perspective with a lifetime time horizon and 3% annual discounting. Treating any patient with ombitasvir-based therapy was the preferred strategy ($ 35,560; 14.0 QALYs). All other strategies were dominated (greater costs/QALY gained than more effective strategies). Varying treatment efficacy, price, and/or duration changed the preferred strategy. In probabilistic sensitivity analysis, treating any patient with ombitasvir-based therapy was cost-effective in 70% of iterations at a $ 50,000/QALY threshold and 65% of iterations at a $ 100,000/QALY threshold. Conclusion: Managing any treatment-naive genotype 1 hepatitis C patient with ombitasvir-based therapy is the most economically efficient strategy, although price and efficacy can impact cost-effectiveness. It is economically unfavorable to restrict treatment to patients with advanced disease or use a staged treatment strategy. C1 [Chidi, Alexis P.; Rogal, Shari; Bryce, Cindy L.; Fine, Michael J.; Good, Chester B.; Myaskovsky, Larissa; Smith, Kenneth J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, 3471 Fifth Ave,Suite 300, Pittsburgh, PA 15213 USA. [Chidi, Alexis P.; Rogal, Shari; Fine, Michael J.; Good, Chester B.; Myaskovsky, Larissa; Smith, Kenneth J.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Chidi, Alexis P.; Tsung, Allan] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. [Bryce, Cindy L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. [Good, Chester B.] US Dept Vet Affairs, VA Ctr Medicat Safety, Hines, IL USA. [Rustgi, Vinod K.] Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. RP Chidi, AP (reprint author), Univ Pittsburgh, Sch Med, Div Gen Internal Med, 3471 Fifth Ave,Suite 300, Pittsburgh, PA 15213 USA. EM apc10@pitt.edu OI Bryce, Cindy/0000-0001-6356-6675 FU National Center for Advancing Translational Sciences of the National Institutes of Health [TL1TR000145] FX AC was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number TL1TR000145. 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 VA Healthcare Systems. NR 56 TC 7 Z9 7 U1 2 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 FEB PY 2016 VL 63 IS 2 BP 428 EP 436 DI 10.1002/hep.28327/suppinfo PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DI1ZZ UT WOS:000373296800001 PM 26524695 ER PT J AU Bachhuber, MA Maughan, BC Mitra, N Feingold, J Starrels, JL AF Bachhuber, Marcus A. Maughan, Brandon C. Mitra, Nandita Feingold, Jordyn Starrels, Joanna L. TI Prescription monitoring programs and emergency department visits involving benzodiazepine misuse: Early evidence from 11 United States metropolitan areas SO INTERNATIONAL JOURNAL OF DRUG POLICY LA English DT Article DE Benzodiazepines; Prescription drug misuse; Health policy; Public policy; Public health ID PHARMACOLOGICAL-TREATMENT; OPIOID ANALGESICS; ABUSE; DISORDERS; ANXIETY; ASSOCIATION; GUIDELINES; IMPACT AB Background: Emergency department (ED) visits involving benzodiazepines have increased in the United States. Most states have created prescription monitoring programs (PMPs) to improve drug prescribing safety. To determine the association between PMP implementation and ED visits involving benzodiazepine misuse, we conducted a retrospective analysis of data from 11 metropolitan areas in the United States from 2004 to 2011. Methods: We estimated rates of ED visits per 100,000 residents involving benzodiazepine misuse from the Drug Abuse Warning Network dataset. Dates of PMP implementation were obtained from program administrators. We used linear regression models to assess whether PMP implementation was associated with a change in ED visits involving benzodiazepines. Models were adjusted for calendar quarter, metropolitan area, and metropolitan area-specific linear time trends. Results: Rates of ED visits involving benzodiazepine misuse increased in all metropolitan areas during the study period. PMP implementation was not associated with a change in ED visits (mean difference: 0.9 [95% CI:-0.09 to 1.9] visits per 100,000 population per quarter; p = 0.08). When analyzed by number of years after implementation, PMPs were associated with a higher visit rate in year one (0.8 [95% CI: 0.2-1.5]; p = 0.011), but not in year two (0.3 [95% CI: 2.1-2.81; p = 0.78) or year three or later (2.1 [95% CI: 0.4-4.7]; p = 0.10). Conclusion: We did not find evidence that PMP implementation was associated with reductions in ED visits involving benzodiazepine misuse. Future work should identify PMP features and capabilities that improve benzodiazepine safety. Published by Elsevier B.V. C1 [Bachhuber, Marcus A.; Maughan, Brandon C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Bachhuber, Marcus A.; Maughan, Brandon C.; Mitra, Nandita] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Bachhuber, Marcus A.; Maughan, Brandon C.] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Feingold, Jordyn] Univ Penn, Philadelphia, PA 19104 USA. [Starrels, Joanna L.] Montefiore Med Ctr, Albert Einstein Coll Med, Div Gen Internal Med, Bronx, NY 10467 USA. RP Bachhuber, MA (reprint author), 1303-A Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM marcus.bachhuber@gmail.com; bmaughan@gmail.com; nanditam@mail.med.upenn.edu; jordyn.feingold@gmail.com; jostarre@montefiore.org OI Bachhuber, Marcus/0000-0002-5610-8382 FU National Institute on Drug Abuse [K23DA027719]; Division of General Internal Medicine, Perelman School of Medicine, University of Pennsylvania FX This study was supported by funding from the National Institute on Drug Abuse (K23DA027719) and a Matt Slap Pilot Research Award from the Division of General Internal Medicine, Perelman School of Medicine, University of Pennsylvania. The funding bodies had no role in 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 32 TC 3 Z9 3 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0955-3959 EI 1873-4758 J9 INT J DRUG POLICY JI Int. J. Drug Policy PD FEB PY 2016 VL 28 BP 120 EP 123 DI 10.1016/j.drugpo.2015.08.005 PG 4 WC Substance Abuse SC Substance Abuse GA DH3LJ UT WOS:000372688200015 PM 26345658 ER PT J AU Wells, JA Glassman, AR Jampol, LM Aiello, LP Antoszyk, AN Baker, CW Bressler, NM Browning, DJ Connor, CG Elman, MJ Ferris, FL Friedman, SM Melia, M Pieramici, DJ Sun, JK Beck, RW AF Wells, John A. Glassman, Adam R. Jampol, Lee M. Aiello, Lloyd Paul Antoszyk, Andrew N. Baker, Carl W. Bressler, Neil M. Browning, David J. Connor, Crystal G. Elman, Michael J. Ferris, Frederick L. Friedman, Scott M. Melia, Michele Pieramici, Dante J. Sun, Jennifer K. Beck, Roy W. CA Diabetic Retinopathy Clinical Res TI Association of Baseline Visual Acuity and Retinal Thickness With 1-Year Efficacy of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema SO JAMA OPHTHALMOLOGY LA English DT Article AB IMPORTANCE Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment. OBJECTIVE To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography. DESIGN, SETTING, AND PARTICIPANTS Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015. INTERVENTIONS Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol. MAIN OUTCOMES AND MEASURES One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (>400 mu m) or thinner (250 to 399 mu m) CST. RESULTS In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39%(17% to 60%) for aflibercept vs bevacizumab, 25%(5% to 46%) for ranibizumab vs bevacizumab, and 13%(-8% to 35%) for aflibercept vs ranibizumab. CONCLUSIONS AND RELEVANCE These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients. C1 [Wells, John A.] Palmetto Retina Ctr, W Columbia, SC 33647 USA. [Glassman, Adam R.; Connor, Crystal G.; Melia, Michele; Beck, Roy W.] Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. [Jampol, Lee M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Aiello, Lloyd Paul; Sun, Jennifer K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Antoszyk, Andrew N.; Browning, David J.] Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA. [Baker, Carl W.] Paducah Retinal Ctr, Paducah, KY USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA. [Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA. [Friedman, Scott M.] Florida Retina Consultants, Winter Haven, FL USA. [Pieramici, Dante J.] Calif Retina Consultants, Santa Barbara, CA USA. RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA. EM drcrstat2@jaeb.org OI VanderBeek, Brian L./0000-0003-4953-118X FU National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services [EY14231, EY23207]; Genentech; National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services (National Institutes of Health) [EY18817 from the] FX This study was supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services (grants EY14231, EY23207, and EY18817 from the National Institutes of Health). Regeneron Pharmaceutical provided the aflibercept and Genentech provided the ranibizumab for the study. Genentech also provided funding for blood pressure cuffs and the collection of serum and urine that are not part of the main study results reported herein. NR 3 TC 8 Z9 8 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD FEB PY 2016 VL 134 IS 2 BP 127 EP 134 DI 10.1001/jamaophthalmol.2015.4599 PG 8 WC Ophthalmology SC Ophthalmology GA DH1JK UT WOS:000372540000007 PM 26605836 ER PT J AU Gubitosi-Klug, RA Sun, WJ Cleary, PA Braffett, BH Aiello, LP Das, A Tamborlane, W Klein, R AF Gubitosi-Klug, Rose A. Sun, Wanjie Cleary, Patricia A. Braffett, Barbara H. Aiello, Lloyd Paul Das, Arup Tamborlane, William Klein, Ronald CA Writing Team DCCT EDIC Res Grp TI Effects of Prior Intensive Insulin Therapy and Risk Factors on Patient-Reported Visual Function Outcomes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort SO JAMA OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; ANGELES-LATINO-EYE; FUNCTION-QUESTIONNAIRE; MACULAR EDEMA; PROYECTO VER; NEI-VFQ; TYPE-1; RETINOPATHY; MELLITUS; EPIDEMIOLOGY AB IMPORTANCE Preservation of vision in patients with diabetes mellitus is critical. Interventions to improve glycemic control through early intensive treatment of diabetes reduce rates of severe retinopathy and preserve visual acuity. OBJECTIVE To assess the effects of prior intensive insulin treatment and risk factors on patient-reported visual function in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. DESIGN, SETTING, AND PARTICIPANTS Cohort study of 1184 participants with type 1 diabetes from the DCCT/EDIC study (randomized clinical trial followed by an observational follow-up study) who completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) during EDIC years 17 through 20 (September 1, 2009, through April 30, 2014) in 28 institutions across the United States and Canada. MAIN OUTCOMES AND MEASURES The primary outcome was the composite NEI-VFQ-25 score. Secondary outcomes were visual acuity (measured by the Early Treatment Diabetic Retinopathy Study protocol), retinopathy level (determined by masked grading of stereoscopic color fundus photographs), and NEI-VFQ-25 subscale scores. The composite NEI-VFQ-25 scale and its subscales were scored 0 to 100, corresponding to poor to excellent function, respectively. RESULTS The overall average NEI-VFQ-25 score for 1184 DCCT/EDIC participants (mean [SD] age, 52.3 [6.9] years; 48% female) with a 30-year duration of diabetes was high (all participants: median, 91.7; interquartile range [IQR], 89.7-96.9; intensive treatment [n = 605]: median, 94.7; IQR, 91.0-97.2; conventional treatment [n = 579]: median, 94.0; IQR, 88.4-96.1; P = .006 for intensive vs conventional). After adjustment for sex, age, hemoglobin A(1c) level, and retinopathy level at DCCT baseline, the former intensive treatment group had a significant, albeit modest, improvement in overall NEI-VFQ-25 score compared with the former conventional diabetes treatment group (median difference, -1.0; 95% CI, -1.7 to -0.3; P = .006). This beneficial treatment effect was fully attributed to the prior glycemic control in DCCT (explained treatment effect: 100%). Those with visual acuity worse than 20/100 reported the largest decline in visual function (median difference, -21.0; 95% CI, -40.5 to -1.6; P = .03). CONCLUSIONS AND RELEVANCE In the DCCT/EDIC cohort, patient-reported visual function remains high in both treatment groups, comparable to previous reports of overall health-related quality of life. Intensive diabetes therapy modestly improved NEI-VFQ-25 score 30 years after the start of the DCCT, the benefit underestimated owing to more nonparticipants from the conventional treatment group. Visual acuity had the greatest effect on patient-reported visual function from among all risk factors. C1 [Gubitosi-Klug, Rose A.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Sun, Wanjie; Cleary, Patricia A.; Braffett, Barbara H.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Das, Arup] Univ New Mexico, Albuquerque, NM 87131 USA. [Tamborlane, William] Yale Univ, Sch Med, New Haven, CT USA. [Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. RP Gubitosi-Klug, RA (reprint author), Rainbow Babies & Childrens Hosp, Univ Hosp Case Med Ctr, Room 737,11100 Euclid Ave, Cleveland, OH 44106 USA. EM rose.gubitosi-klug@case.edu FU Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK094176, U01 DK094157]; National Eye Institute, National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical Translational Science Center Program FX The DCCT/EDIC study has been supported by cooperative agreement grants (1982-1993, 2012-2017) and contracts (1982-2012) with the Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases (current grants U01 DK094176 and U01 DK094157) and by the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and the Clinical Translational Science Center Program (2006-present). The following industry contributors have provided free or discounted supplies or equipment to support participants' adherence to the study: Abbott Diabetes Care, Animas, Bayer Diabetes Care, Becton Dickinson, Eli Lilly and Co, Extend Nutrition, Insulet Corp, Lifescan, Medtronic Diabetes, Nipro Home Diagnostics, Nova Diabetes Care, Omron, Perrigo Diabetes Care, Roche Diabetes Care, and sanofi-aventis. NR 37 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD FEB PY 2016 VL 134 IS 2 BP 137 EP 145 DI 10.1001/jamaophthalmol.2015.4606 PG 9 WC Ophthalmology SC Ophthalmology GA DH1JK UT WOS:000372540000009 ER PT J AU Sun, JK Cavallerano, JD Silva, PS AF Sun, Jennifer K. Cavallerano, Jerry D. Silva, Paolo S. TI Future Promise of and Potential Pitfalls for Automated Detection of Diabetic Retinopathy SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID TELEMEDICINE C1 [Sun, Jennifer K.; Cavallerano, Jerry D.; Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. [Sun, Jennifer K.; Cavallerano, Jerry D.; Silva, Paolo S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Sun, JK (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM jennifer.sun@joslin.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD FEB PY 2016 VL 134 IS 2 BP 210 EP 211 DI 10.1001/jamaophthalmol.2015.5099 PG 2 WC Ophthalmology SC Ophthalmology GA DH1JK UT WOS:000372540000021 PM 26720257 ER PT J AU Lane, AM Kim, IK Gragoudas, ES AF Lane, Anne Marie Kim, Ivana K. Gragoudas, Evangelos S. TI Long-term Risk of Melanoma-Related Mortality After Uveal Melanoma Reply SO JAMA OPHTHALMOLOGY LA English DT Letter ID PROTON-BEAM THERAPY; YOUNG-PATIENTS; PROGNOSIS C1 [Lane, Anne Marie; Kim, Ivana K.; Gragoudas, Evangelos S.] Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM evangelos_gragoudas@meei.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD FEB PY 2016 VL 134 IS 2 BP 239 EP 240 DI 10.1001/jamaophthalmol.2015.5235 PG 2 WC Ophthalmology SC Ophthalmology GA DH1JK UT WOS:000372540000031 PM 26720744 ER PT J AU Shaffer, KM Kim, Y Llabre, MM Carver, CS AF Shaffer, Kelly M. Kim, Youngmee Llabre, Maria M. Carver, Charles S. TI Dyadic associations between cancer-related stress and fruit and vegetable consumption among colorectal cancer patients and their family caregivers SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Perceived cancer-related stress; Fruit and vegetable consumption; Cancer patients; Family caregivers; Dyadic data analysis ID QUALITY-OF-LIFE; BREAST-CANCER; PROSTATE-CANCER; RHEUMATOID-ARTHRITIS; SPOUSAL CAREGIVERS; TEACHABLE MOMENT; HEALTH PRACTICES; STYLE BEHAVIORS; CHRONIC ILLNESS; SURVIVORS AB This study examined how stress from cancer affects fruit and vegetable consumption (FVC) in cancer patients and their family caregivers during the year following diagnosis. Colorectal cancer patients and their caregivers (92 dyads) completed questionnaires at two (T1), six (T2), and 12 months post-diagnosis (T3). Individuals reported perceived cancer-related stress (CRS) at T1 and days of adequate FVC at T1 through T3. Both patients and caregivers reported inadequate FVC during the first year post-diagnosis. Latent growth modeling with actor-partner interdependence modeling revealed that, at T1, one's own greater CRS was associated with one's partner having fewer concurrent days of adequate FVC (ps = .01). Patients' greater CRS predicted their own more pronounced rebound pattern in FVC (p = .01); both patients' and caregivers' CRS marginally predicted their partners' change in FVC (p = .09). Findings suggest that perceived stress from cancer hinders FVC around the diagnosis, but motivates positive dietary changes by the end of the first year. C1 [Shaffer, Kelly M.; Kim, Youngmee; Llabre, Maria M.; Carver, Charles S.] Univ Miami, Dept Psychol, 5665 Ponce Leon Blvd, Coral Gables, FL 33146 USA. [Shaffer, Kelly M.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med, Boston, MA 02114 USA. [Kim, Youngmee; Carver, Charles S.] Stanford Univ, Ctr Adv Study Behav Sci, Stanford, CA 94305 USA. RP Shaffer, KM (reprint author), Univ Miami, Dept Psychol, 5665 Ponce Leon Blvd, Coral Gables, FL 33146 USA.; Shaffer, KM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Behav Med, Boston, MA 02114 USA. EM k.shaffer3@umail.miami.edu OI Kim, Youngmee/0000-0002-3109-6362; carver, charles/0000-0002-3688-8545; Shaffer, Kelly/0000-0002-9749-8006 FU American Cancer Society National Home Office; National Cancer Institute (NCI) [F31 CA189431-01A1] FX This study was funded by the American Cancer Society National Home Office, intramural research to Dr. Kim, and National Cancer Institute (NCI) grant F31 CA189431-01A1 funded Ms. Shaffer's time. NR 56 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD FEB PY 2016 VL 39 IS 1 BP 75 EP 84 DI 10.1007/s10865-015-9665-y PG 10 WC Psychology, Clinical SC Psychology GA DH8AC UT WOS:000373014500007 PM 26245160 ER PT J AU McMillan, MT Vollmer, CM Asbun, HJ Ball, CG Bassi, C Beane, JD Berger, AC Bloomston, M Callery, MP Christein, JD Dixon, E Drebin, JA Fernandez-Del Castillo, C Fisher, WE Fong, ZV Haverick, E House, MG Hughes, SJ Kent, TS Kunstman, JW Malleo, G McElhany, AL Salem, RR Soares, K Sprys, MH Valero, V Watkins, AA Wolfgang, CL Behrman, SW AF McMillan, Matthew T. Vollmer, Charles M., Jr. Asbun, Horacio J. Ball, Chad G. Bassi, Claudio Beane, Joal D. Berger, Adam C. Bloomston, Mark Callery, Mark P. Christein, John D. Dixon, Elijah Drebin, Jeffrey A. Fernandez-Del Castillo, Carlos Fisher, William E. Fong, Zhi Ven Haverick, Ericka House, Michael G. Hughes, Steven J. Kent, Tara S. Kunstman, John W. Malleo, Giuseppe McElhany, Amy L. Salem, Ronald R. Soares, Kevin Sprys, Michael H. Valero, Vicente, III Watkins, Ammara A. Wolfgang, Christopher L. Behrman, Stephen W. TI The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Pancreatic fistula; ISGPF grade C; Risk assessment ID POSTOPERATIVE PANCREATIC FISTULA; RISK-FACTORS; MANAGEMENT; COMPLICATIONS AB Introduction International Study Group of Pancreatic Fistula (ISGPF) grade C postoperative pancreatic fistulas (POPF) are the greatest contributor to major morbidity and mortality following pancreatoduodenectomy (PD); however, their infrequent occurrence has hindered deeper analysis. This study sought to develop a predictive algorithm, which could facilitate effective management of this challenging complication. Methods Data were accrued from 4301 PDs worldwide. Demographics, postoperative management, and microbiological characteristics of grade C POPFs were evaluated. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) preoperative and intraoperative variables were compared between grade C POPFs and a 639-case sample of non-grade C POPFs. Risk factors for grade C POPF formation were identified using regression analysis. Results Grade C POPFs developed in 79 patients (1.8 %). Deaths (90 days) occurred in 2.0 % (N = 88) of the overall series, with 35 % (N = 25) occurring in the presence of a grade C POPF. Reoperations occurred 72.2 % of the time. The rates of single-and multi-system organ failure were 28.2 and 39.7 %, respectively. Mortality rates escalated with pulmonary, renal, and neurologic organ failure, but they were unaffected by reoperation(s). The median number of complications incurred was four (IQR: 2-5), and the median duration of hospital stay was 32 (IQR: 21-54) days. Warning signs for impending grade C POPFs most often presented on postoperative day (POD) 6. Adjuvant chemotherapy might have benefited 55.7 % of grade C POPF patients, yet it was delayed in 25.6 % and never delivered in 67.4 % of these patients. Predictive models for grade C POPF occurrence based on preoperative factors alone and preoperative and intraoperative factors yielded areas under the receiver operating characteristic curve of 0.73 and 0.84 (both P < 0.000001), respectively. Conclusion This global study represents the largest analysis of grade C POPFs following PD. It describes the severe burden that grade C POPFs incur on patients, with high rates of reoperation and infection, while also potentially worsening overall survival by causing death and delay/omission of adjuvant therapy. Additionally, aggressive clinical management for these POPFs did not improve or worsen 90-day mortality. Predictive tools developed through these data may provide value in managing this difficult complication. C1 [McMillan, Matthew T.; Vollmer, Charles M., Jr.; Drebin, Jeffrey A.; Sprys, Michael H.] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Asbun, Horacio J.] Mayo Clin, Dept Surg, Jacksonville, FL 32224 USA. [Ball, Chad G.; Dixon, Elijah] Univ Calgary, Dept Surg, Calgary, AB, Canada. [Bassi, Claudio; Malleo, Giuseppe] Univ Verona, Dept Surg, I-37100 Verona, Italy. [Beane, Joal D.; House, Michael G.] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46204 USA. [Berger, Adam C.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. [Bloomston, Mark; Haverick, Ericka] Ohio State Univ, Wexner Med Ctr, Dept Surg, Columbus, OH 43210 USA. [Callery, Mark P.; Kent, Tara S.; Watkins, Ammara A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02115 USA. [Christein, John D.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Fernandez-Del Castillo, Carlos; Fong, Zhi Ven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Fisher, William E.; McElhany, Amy L.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Hughes, Steven J.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA. [Kunstman, John W.; Salem, Ronald R.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Soares, Kevin; Valero, Vicente, III; Wolfgang, Christopher L.] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. [Behrman, Stephen W.] Univ Tennessee, Ctr Hlth Sci, Dept Surg, Memphis, TN 38163 USA. RP Vollmer, CM (reprint author), Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA. EM charles.vollmer@uphs.upenn.edu NR 31 TC 7 Z9 7 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2016 VL 20 IS 2 BP 262 EP 276 DI 10.1007/s11605-015-2884-2 PG 15 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DI0BD UT WOS:000373158900009 PM 26162925 ER PT J AU Zhang, IY Zhao, J Fernandez-del Castillo, C Braun, Y Razmdjou, S Warshaw, AL Lillemoe, KD Ferrone, CR AF Zhang, Irene Y. Zhao, Jing Fernandez-del Castillo, Carlos Braun, Yvonne Razmdjou, Shadi Warshaw, Andrew L. Lillemoe, Keith D. Ferrone, Cristina R. TI Operative Versus Nonoperative Management of Nonfunctioning Pancreatic Neuroendocrine Tumors SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Nonfunctioning; Pancreatic neuroendocrine tumor; Surgery; Resection; Size ID ENDOCRINE TUMORS; NEOPLASMS; OUTCOMES; DENSITY; SIZE AB Introduction Surgical resection is the only curative treatment for pancreatic neuroendocrine tumors (PNETs), but pancreatic operations carry a significant morbidity. We investigated whether the resection of small, asymptomatic nonfunctioning PNETs is beneficial. Clinicopathologic factors were retrospectively reviewed for all PNET cases from 1998 to 2014. Methods Kaplan-Meier survival and multivariable regression analyses were performed. A total of 249 patients had nonfunctioning PNETs with adequate follow-up, of whom 193 were resected and 56 were observed. Median age was 56 years, and 48 % of the patients were female. Results Overall, the resected patients had a significantly longer survival (OS) (p = 0.001). However, for the patients with PNETs <= 2.5 cm in size and without metastasis at presentation, tumor size significantly modified the effect of resection on overall survival (p < 0.05). The protective effect of resection increased as tumor size increased. An operation became a significant predictor of overall survival for tumors > 1.5 cm (p = 0.050 or less for larger tumors) but was not significant for tumors < 1.5 cm (p = 0.317 or more for smaller tumors), controlling for age-adjusted Charlson comorbidity index. Conclusion Resection of nonfunctioning PNETs over 1.5 cm is independently and significantly associated with a longer survival. However, the benefit of resection for tumors under 1.5 cm is unclear. C1 [Zhang, Irene Y.; Zhao, Jing; Fernandez-del Castillo, Carlos; Braun, Yvonne; Razmdjou, Shadi; Warshaw, Andrew L.; Lillemoe, Keith D.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Wang 460,15 Parkman St, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Massachusetts Gen Hosp, Wang 460,15 Parkman St, Boston, MA 02114 USA. EM cferrone@partners.org FU Loeffler Family; Warshaw Foundation FX Generous support from the Loeffler Family and the Warshaw Foundation is acknowledged. NR 18 TC 4 Z9 5 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2016 VL 20 IS 2 BP 277 EP 283 DI 10.1007/s11605-015-3043-5 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DI0BD UT WOS:000373158900010 PM 26691146 ER PT J AU Rudnicki, M Armstrong, JH Clark, C Marcus, SG Sacks, L Moser, AJ Reid-Lombardo, K AF Rudnicki, Marek Armstrong, John H. Clark, Clancy Marcus, Stuart G. Sacks, Lee Moser, A. James Reid-Lombardo, KMarie CA Public Policy Advocacy Comm SSAT TI Expected and Unexpected Consequences of the Affordable Care Act: The Impact on Patients and Surgeons-Pro and Con Arguments SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Affordable care act; ACA; Patient protection and affordable care act; PPACA; Health care reform; Health care quality; Health care delivery; Accountable care organizations; SSAT; Public policy; Public policy committee; Health policy; Obamacare ID UNITED-STATES; HEALTH-CARE; ERA AB The Patient Protection and Affordable Care Act (PPACA), called the Affordable Care Act (ACA) or "bamaCare" for short, was enacted in 2010. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract (SSAT) hosted a debate with an expert panel to discuss the ACA and its impact on surgical care after the first year of patient enrollment. The purpose of this debate was to focus on the impact of ACA on the public and surgeons. At the core of the ACA are insurance industry reforms and expanded coverage, with a goal of improved clinical outcomes and reduced costs of care. We have observed supportive and opposing views on ACA. Nonetheless, we will witness major shifts in health care delivery as well as restructuring of our relationship with payers, institutions, and patients. With the rapidly changing health care landscape, surgeons will become key members of health systems and will likely need to lead transition from solo-practice to integrated care systems. The full effects of the ACA remain unrealized, but its implementation has begun to change the map of the American health care system and will surely impact the practice of surgery. Herein, we provide a synopsis of the "pro" and "con" arguments for the expected and unexpected consequences of the ACA on society and surgeons. C1 [Rudnicki, Marek] Advocate Illinois Mason Med Ctr, Dept Surg, Chicago, IL USA. [Armstrong, John H.] Univ S Florida, Dept Surg, Morsani Coll Med, Tampa, FL 33620 USA. [Clark, Clancy] Wake Forest Baptist Hlth, Dept Surg, Winston Salem, NC USA. [Marcus, Stuart G.] St Vincents Med Ctr, Dept Surg, Bridgeport, CT USA. [Sacks, Lee] Advocate Hlth Care, Downers Grove, IL USA. [Moser, A. James] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Inst Hepatobiliary & Pancreat Surg, Boston, MA 02215 USA. [Moser, A. James] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. [Public Policy Advocacy Comm SSAT] Soc Surg Alimentary Tract, Beverly, MA USA. [Reid-Lombardo, KMarie] Mayo Clin, Dept Surg, Rochester, MN 55902 USA. [Reid-Lombardo, KMarie] Mayo Clin, Div Subspecialty Gen Surg, 200 First St SW, Rochester, MN 55902 USA. RP Reid-Lombardo, K (reprint author), Mayo Clin, Dept Surg, Rochester, MN 55902 USA.; Reid-Lombardo, K (reprint author), Mayo Clin, Div Subspecialty Gen Surg, 200 First St SW, Rochester, MN 55902 USA. EM kmariemd@gmail.com NR 38 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2016 VL 20 IS 2 BP 351 EP 360 DI 10.1007/s11605-015-3032-8 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA DI0BD UT WOS:000373158900036 PM 26589524 ER PT J AU Kasckow, J Youk, A Anderson, SJ Dew, MA Butters, MA Marron, MM Begley, AE Szanto, K Dombrovski, AY Mulsant, BH Lenze, EJ Reynolds, CF AF Kasckow, John Youk, Ada Anderson, Stewart J. Dew, Mary Amanda Butters, Meryl A. Marron, Megan M. Begley, Amy E. Szanto, Katalin Dombrovski, Alexander Y. Mulsant, Benoit H. Lenze, Eric J. Reynolds, Charles F., III TI Trajectories of suicidal ideation in depressed older adults undergoing antidepressant treatment SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Suicide; Trajectory; Antidepressant; Depression; Late life ID NEUROPSYCHOLOGICAL STATUS; PSYCHIATRIC OUTPATIENTS; REPEATABLE BATTERY; SAS PROCEDURE; RISK-FACTORS; ATTEMPTERS; SCALE; BEHAVIOR AB Suicide is a public health concern in older adults. Recent cross sectional studies suggest that impairments in executive functioning, memory and attention are associated with suicidal ideation in older adults. It is unknown whether these neuropsychological features predict persistent suicidal ideation. We analyzed data from 468 individuals >= age 60 with major depression who received venlafaxine XR monotherapy for up to 16 weeks. We used latent class growth modeling to classify groups of individuals based on trajectories of suicidal ideation. We also examined whether cognitive dysfunction predicted suicidal ideation while controlling for time-dependent variables including depression severity, and age and education. The optimal model using a zero inflated Poisson link classified individuals into four groups, each with a distinct temporal trajectory of suicidal ideation: those with 'minimal suicidal ideation' across time points; those with 'low suicidal ideation'; those with 'rapidly decreasing suicidal ideation'; and those with 'high and persistent suicidal ideation'. Participants in the 'high and persistent suicidal ideation' group had worse scores relative to those in the "rapidly decreasing suicidal ideation" group on the Color-Word 'inhibition/switching' subtest from the Delis-Kaplan Executive Function Scale, worse attention index scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and worse total RBANS index scores. These findings suggest that individuals with poorer ability to switch between inhibitory and non-inhibitory responses as well as worse attention and worse overall cognitive status are more likely to have persistently higher levels of suicidal ideation. Clinicaltrial.gov number: NCF00892047. Published by Elsevier Ltd. C1 [Kasckow, John] Univ DR C, VA Pittsburgh Hlth Care Syst, Behav Hlth, Pittsburgh, PA 15240 USA. [Kasckow, John] Univ DR C, VA Pittsburgh Hlth Care Syst, MIRECC, Pittsburgh, PA 15240 USA. [Kasckow, John] Univ DR C, VA Pittsburgh Hlth Care Syst, CHERP, Pittsburgh, PA 15240 USA. [Kasckow, John; Dew, Mary Amanda; Butters, Meryl A.; Begley, Amy E.; Szanto, Katalin; Dombrovski, Alexander Y.; Mulsant, Benoit H.; Reynolds, Charles F., III] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Kasckow, John; Youk, Ada; Anderson, Stewart J.; Dew, Mary Amanda] Univ Pittsburgh, Grad Sch Publ Hlth, Biostat, Pittsburgh, PA 15213 USA. [Dew, Mary Amanda; Marron, Megan M.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol, Pittsburgh, PA 15213 USA. [Mulsant, Benoit H.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Mulsant, Benoit H.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Lenze, Eric J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Kasckow, J (reprint author), Univ DR C, VA Pittsburgh Hlth Care Syst, Behav Hlth, Pittsburgh, PA 15240 USA. EM kasckowjw@upmc.edu OI Youk, Ada/0000-0001-6912-9759 FU NIH [R01-MH083660, P30 MH090333]; UPMC Endowment in Geriatric Psychiatry; Taylor Family Institute for Innovative Psychiatric Research; National Center for Advancing Translational Sciences; Campbell Family Mental Health Research Institute FX Supported by NIH grant R01-MH083660, P30 MH090333, the UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences and the Campbell Family Mental Health Research Institute. NR 40 TC 1 Z9 1 U1 1 U2 1 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 FEB PY 2016 VL 73 BP 96 EP 101 DI 10.1016/j.jpsychires.2015.11.004 PG 6 WC Psychiatry SC Psychiatry GA DI1JD UT WOS:000373251500012 PM 26708830 ER PT J AU Gainor, JF Chi, AS Logan, J Hu, RL Oh, KS Brastianos, PK Shih, HA Shaw, AT AF Gainor, Justin F. Chi, Andrew S. Logan, Jennifer Hu, Ranliang Oh, Kevin S. Brastianos, Priscilla K. Shih, Helen A. Shaw, Alice T. TI Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Relapsing on Standard Dose Alectinib SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Alectinib; ALK; Anaplastic lymphoma kinase; Leptomeningeal metastases ID ALK INHIBITOR ALECTINIB; LEPTOMENINGEAL CARCINOMATOSIS; BRAIN METASTASES; WEEKLY ERLOTINIB; CRIZOTINIB; RESISTANCE; CERITINIB; TUMORS; DNA AB The central nervous system (CNS) is an important and increasingly recognized site of treatment failure in anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC) patients receiving ALK inhibitors. In this report, we describe two ALK-positive patients who experienced initial improvements in CNS metastases on standard dose alectinib (600 mg twice daily), but who subsequently experienced recurrences with symptomatic leptomeningeal metastases. Both patients were dose-escalated to alectinib 900 mg twice daily, resulting in repeat clinical and radiographic responses. Our results suggest that dose intensification of alectinib may be necessary to overcome incomplete ALK inhibition in the CNS and prolong the durability of responses in patients with CNS metastases, particularly those with leptomeningeal carcinomatosis. (C) 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. C1 [Gainor, Justin F.; Logan, Jennifer; Brastianos, Priscilla K.; Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hu, Ranliang] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Oh, Kevin S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gainor, JF (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM jgainor@partners.org FU NCI NIH HHS [5R01CA164273, C06 CA059267, C06CA059267, R01 CA164273] NR 19 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD FEB PY 2016 VL 11 IS 2 BP 256 EP 260 DI 10.1016/j.jtho.2015.10.010 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA DH9CP UT WOS:000373094300013 PM 26845119 ER PT J AU Rosen, AK Chen, Q Shwartz, M Pilver, C Mull, HJ Itani, KFM Borzecki, A AF Rosen, Amy K. Chen, Qi Shwartz, Michael Pilver, Corey Mull, Hillary J. Itani, Kamal F. M. Borzecki, Ann TI Does Use of a Hospital-wide Readmission Measure Versus Condition-specific Readmission Measures Make a Difference for Hospital Profiling and Payment Penalties? SO MEDICAL CARE LA English DT Article DE quality of care; hospital performance; readmissions; pay-for-performance; hospital profiling ID ADMINISTRATIVE CLAIMS MEASURE; UNPLANNED READMISSION; 30-DAY READMISSIONS; HEART-FAILURE; PERFORMANCE; RATES AB Background: The Centers for Medicare and Medicaid Services (CMS) use public reporting and payment penalties as incentives for hospitals to reduce readmission rates. In contrast to the current condition-specific readmission measures, CMS recently developed an all-condition, 30-day all-cause hospital-wide readmission measure (HWR) to provide a more comprehensive view of hospital performance. Objectives: We examined whether assessment of hospital performance and payment penalties depends on the readmission measure used. Research Design: We used inpatient data to examine readmissions for patients discharged from VA acute-care hospitals from Fiscal Years 2007-2010. We calculated risk-standardized 30-day readmission rates for 3 condition-specific measures (heart failure, acute myocardial infarction, and pneumonia) and the HWR measure, and examined agreement between the HWR measure and each of the condition-specific measures on hospital performance. We also assessed the effect of using different readmission measures on hospitals' payment penalties. Results: We found poor agreement between the condition-specific measures and the HWR measure on those hospitals identified as low or high performers (eg, among those hospitals classified as poor performers by the heart failure readmission measure, only 28.6% were similarly classified by the HWR measure). We also found differences in whether a hospital would experience payment penalties. The HWR measure penalized only 60% of those hospitals that would have received penalties based on at least 1 of the condition-specific measures. Conclusions: The condition-specific measures and the HWR measure provide a different picture of hospital performance. Future research is needed to determine which measure aligns best with CMS's overall goals to reduce hospital readmissions and improve quality. C1 [Rosen, Amy K.; Chen, Qi; Pilver, Corey; Mull, Hillary J.; Borzecki, Ann] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA. [Rosen, Amy K.; Mull, Hillary J.; Itani, Kamal F. M.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02215 USA. [Shwartz, Michael] Boston Univ, Questrom Sch Business, Operat & Technol Management Dept, Boston, MA 02215 USA. [Itani, Kamal F. M.] VA Boston Healthcare Syst, Boston, MA USA. [Borzecki, Ann] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Boston, MA 02215 USA. [Borzecki, Ann] Boston Univ, Sch Med, Dept Gen Med, Boston, MA 02118 USA. RP Rosen, AK (reprint author), Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave, Boston, MA 02130 USA. EM akrosen@bu.edu FU VA Health Services Research and Development Service (HSRD) [IIR-09-369] FX Supported by the VA Health Services Research and Development Service (HSR&D), Grant # IIR-09-369, Amy Rosen, Principal Investigator. NR 30 TC 2 Z9 2 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD FEB PY 2016 VL 54 IS 2 BP 155 EP 161 DI 10.1097/MLR.0000000000000455 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DH6XI UT WOS:000372935000008 PM 26595224 ER PT J AU Sacks, GD Lawson, EH Dawes, AJ Weiss, RE Russell, MM Brook, RH Zingmond, DS Ko, CY AF Sacks, Greg D. Lawson, Elise H. Dawes, Aaron J. Weiss, Robert E. Russell, Marcia M. Brook, Robert H. Zingmond, David S. Ko, Clifford Y. TI Variation in Hospital Use of Postacute Care After Surgery and the Association With Care Quality SO MEDICAL CARE LA English DT Article DE hospital quality; variation in care; care coordination; surgery; post-acute care ID POST-ACUTE CARE; GEOGRAPHIC-VARIATION; SURGICAL QUALITY; HEALTH-CARE; IMPROVEMENT PROGRAM; AMERICAN-COLLEGE; MEDICARE; DISCHARGE; REHABILITATION; PREFERENCES AB Background: Little is known about hospital use of postacute care after surgery and whether it is related to measures of surgical quality. Research Design: We used data merged between a national surgery registry, Medicare inpatient claims, the Area Resource File, and the American Hospital Association Annual Survey (2005-2008). Using bivariate and multivariate analyses, we calculated hospital-level, risk-adjusted rates of postacute care use for both inpatient facilities (IF) and home health care (HHC), and examined the association of these rates with hospital quality measures, including mortality, complications, readmissions, and length of stay. Results: Of 112,620 patients treated at 217 hospitals, 18.6% were discharged to an IF, and 19.9% were discharged with HHC. Even after adjusting for differences in patient and hospital characteristics, hospitals varied widely in their use of both IF (mean, 20.3%; range, 2.7%-39.7%) and HHC (mean, 22.3%; range, 3.1%-57.8%). A hospital's risk-adjusted postoperative mortality rate or complication rate was not significantly associated with its use of postacute care, but higher 30-day readmission rates were associated with higher use of IF (24.1% vs. 21.2%, P=0.03). Hospitals with longer average length of stay used IF less frequently (19.4% vs. 24.4%, P < 0.01). Conclusions: Hospitals vary widely in their use of postacute care. Although hospital use of postacute care was not associated with risk-adjusted complication or mortality rates, hospitals with high readmission rates and shorter lengths of stay used inpatient postacute care more frequently. To reduce variations in care, better criteria are needed to identify which patients benefit most from these services. C1 [Sacks, Greg D.; Lawson, Elise H.; Dawes, Aaron J.; Russell, Marcia M.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave 72-215 CHS, Los Angeles, CA 90095 USA. [Sacks, Greg D.; Dawes, Aaron J.; Russell, Marcia M.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Weiss, Robert E.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Brook, Robert H.] RAND Corp, Santa Monica, CA USA. [Brook, Robert H.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Brook, Robert H.; Zingmond, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Sacks, GD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave 72-215 CHS, Los Angeles, CA 90095 USA. EM gsacks@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 NR 34 TC 0 Z9 0 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD FEB PY 2016 VL 54 IS 2 BP 172 EP 179 DI 10.1097/MLR.0000000000000463 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DH6XI UT WOS:000372935000010 PM 26595222 ER PT J AU Kinnier, CV Ju, MLH Kmiecik, T Barnard, C Halverson, T Yang, AD Caprini, J Kreutzer, L Bilimoria, KY AF Kinnier, Christine V. Ju, Mila H. Kmiecik, Thomas Barnard, Cindy Halverson, Terri Yang, Anthony D. Caprini, Joseph Kreutzer, Lindsey Bilimoria, Karl Y. TI Development of a Novel Composite Process Measure for Venous Thromboembolism Prophylaxis SO MEDICAL CARE LA English DT Article DE hospital compare; process measure; postoperative complications; venous thromboembolism ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; HIP-ARTHROPLASTY; HOSPITAL FACTORS; RISK-ASSESSMENT; FOOT PUMP; SURGERY; QUALITY; PATIENT; CARE AB Background: Postoperative venous thromboembolism (VTE) is important clinically, and VTE quality metrics are used in public reporting and pay-for-performance programs. However, current VTE outcome measures are not valid due to surveillance bias, and the Surgical Care Improvement Project (SCIP-VTE-2) process measure only requires prophylaxis within 24 hours of surgery. Objectives: We sought to (1) develop a novel measure of VTE prophylaxis that requires early ambulation, mechanical prophylaxis, and chemoprophylaxis throughout the hospitalization, and (2) compare hospital performance on the SCIP-VTE-2 process measure to this novel measure. Research Design: A new composite measure of ambulation, sequential compression device (SCD), and chemoprophylaxis component measures was developed. The ambulation component required daily ambulation, the SCD component required documentation of continuous use, and the chemoprophylaxis component required patient-appropriate and medication-appropriate dosing and administration. Requirements could also be met with component-specific exceptions. Surgical patients at an academic center from 2012 to 2013 were assessed for SCIP-VTE-2 and composite measure adherence. Results: Of 786 patients, 589 (74.9%) passed the ambulation measure, 494 (62.8%) passed the SCD measure, and 678 (86.3%) passed the chemoprophylaxis measure. A total of 268 (91.8%) SCD failures and 46 (42.6%) chemoprophylaxis failures were ordered but not administered. When comparing the 2 measures, 784 (99.7%) passed SCIP-VTE-2, whereas only 364 (46.3%) passed the composite measure (P < 0.001). Conclusions: This new measure incorporates the critical aspects of VTE prevention to ensure defect-free care. After additional evaluation, this composite VTE prophylaxis measure with appropriate exclusion criteria may be a better alternative to existing VTE process and outcome measures. C1 [Kinnier, Christine V.; Ju, Mila H.; Kmiecik, Thomas; Yang, Anthony D.; Kreutzer, Lindsey; Bilimoria, Karl Y.] Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Dept Surg, 633 St Clair St,Suite 20, Chicago, IL 60611 USA. [Kinnier, Christine V.; Ju, Mila H.; Kmiecik, Thomas; Yang, Anthony D.; Kreutzer, Lindsey; Bilimoria, Karl Y.] Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Ctr Healthca, 633 St Clair St,Suite 20, Chicago, IL 60611 USA. [Kinnier, Christine V.; Ju, Mila H.; Barnard, Cindy; Halverson, Terri; Yang, Anthony D.; Bilimoria, Karl Y.] NW Mem Hosp, Chicago, IL 60611 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Caprini, Joseph] NorthShore Univ Hlth Syst, Evanston, IL USA. RP Bilimoria, KY (reprint author), Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Dept Surg, 633 St Clair St,Suite 20, Chicago, IL 60611 USA.; Bilimoria, KY (reprint author), Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr,Ctr Healthca, 633 St Clair St,Suite 20, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu FU Surgical Outcomes and Quality Improvement Center at Northwestern University; Marshall K Bartlett scholarship at Massachusetts General Hospital FX Supported by the Surgical Outcomes and Quality Improvement Center at Northwestern University and by the Marshall K Bartlett scholarship at Massachusetts General Hospital. NR 37 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD FEB PY 2016 VL 54 IS 2 BP 210 EP 217 DI 10.1097/MLR.0000000000000474 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DH6XI UT WOS:000372935000015 PM 26683781 ER PT J AU Sada, Y Hou, J Richardson, P El-Serag, H Davila, J AF Sada, Yvonne Hou, Jason Richardson, Peter El-Serag, Hashem Davila, Jessica TI Validation of Case Finding Algorithms for Hepatocellular Cancer From Administrative Data and Electronic Health Records Using Natural Language Processing SO MEDICAL CARE LA English DT Article DE hepatocellular cancer; natural language processing; pathology; radiology ID UNITED-STATES; CARCINOMA; VETERANS; SYSTEM AB Background:Accurate identification of hepatocellular cancer (HCC) cases from automated data is needed for efficient and valid quality improvement initiatives and research. We validated HCC International Classification of Diseases, 9th Revision (ICD-9) codes, and evaluated whether natural language processing by the Automated Retrieval Console (ARC) for document classification improves HCC identification.Methods:We identified a cohort of patients with ICD-9 codes for HCC during 2005-2010 from Veterans Affairs administrative data. Pathology and radiology reports were reviewed to confirm HCC. The positive predictive value (PPV), sensitivity, and specificity of ICD-9 codes were calculated. A split validation study of pathology and radiology reports was performed to develop and validate ARC algorithms. Reports were manually classified as diagnostic of HCC or not. ARC generated document classification algorithms using the Clinical Text Analysis and Knowledge Extraction System. ARC performance was compared with manual classification. PPV, sensitivity, and specificity of ARC were calculated.Results:A total of 1138 patients with HCC were identified by ICD-9 codes. On the basis of manual review, 773 had HCC. The HCC ICD-9 code algorithm had a PPV of 0.67, sensitivity of 0.95, and specificity of 0.93. For a random subset of 619 patients, we identified 471 pathology reports for 323 patients and 943 radiology reports for 557 patients. The pathology ARC algorithm had PPV of 0.96, sensitivity of 0.96, and specificity of 0.97. The radiology ARC algorithm had PPV of 0.75, sensitivity of 0.94, and specificity of 0.68.Conclusions:A combined approach of ICD-9 codes and natural language processing of pathology and radiology reports improves HCC case identification in automated data. C1 [Sada, Yvonne; Hou, Jason; Richardson, Peter; El-Serag, Hashem; Davila, Jessica] Michael E DeBakey Vet Adm Med Ctr, Houston, TX 77030 USA. [Sada, Yvonne; Hou, Jason; Richardson, Peter; El-Serag, Hashem; Davila, Jessica] Baylor Coll Med, Houston, TX 77030 USA. [Sada, Yvonne; Hou, Jason; Richardson, Peter; El-Serag, Hashem; Davila, Jessica] Baylor Coll Med, Hlth Serv Res & Dev Sect, Houston, TX 77030 USA. [Sada, Yvonne] Baylor Coll Med, Dept Oncol, Houston, TX 77030 USA. [Hou, Jason; El-Serag, Hashem] Baylor Coll Med, Dept Gastroenterol, Houston, TX 77030 USA. RP Sada, Y (reprint author), Michael E DeBakey Vet Adm Med Ctr, HSR&D Ctr Excellence 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM yhlam@bcm.edu FU National Cancer Institute [R01 CA160738]; Michael E. DeBakey Veterans Affairs Medical Center; Dan Duncan Cancer Center, Houston, TX FX Supported in part by the National Cancer Institute (R01 CA160738, PI: J.D.), the facilities and resources of the Houston Veterans Affairs Health Services Research and Development Center of Excellence (HFP90-020), Michael E. DeBakey Veterans Affairs Medical Center, and the Dan Duncan Cancer Center, Houston, TX. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veteran Affairs. NR 14 TC 5 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD FEB PY 2016 VL 54 IS 2 BP E9 EP E14 DI 10.1097/MLR.0b013e3182a30373 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DH6XJ UT WOS:000372935100001 PM 23929403 ER PT J AU Grimaldi, G Argyropoulos, GP Bastian, A Cortes, M Davis, NJ Edwards, DJ Ferrucci, R Fregni, F Galea, JM Hamada, M Manto, M Miall, RC Morales-Quezada, L Pope, PA Priori, A Rothwell, J Tomlinson, SP Celnik, P AF Grimaldi, Giuliana Argyropoulos, Georgios P. Bastian, Amy Cortes, Mar Davis, Nicholas J. Edwards, Dylan J. Ferrucci, Roberta Fregni, Felipe Galea, Joseph M. Hamada, Masahi Manto, Mario Miall, R. Chris Morales-Quezada, Leon Pope, Paul A. Priori, Alberto Rothwell, John Tomlinson, S. Paul Celnik, Pablo TI Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease SO NEUROSCIENTIST LA English DT Review DE transcranial; direct current stimulation; ctDCS; cerebellum; modeling; motor; plasticity; cognitive; working memory; emotion; language; safety; learning ID HUMAN MOTOR CORTEX; PAIRED ASSOCIATIVE STIMULATION; MAGNETIC STIMULATION; WORKING-MEMORY; VISUOMOTOR ROTATION; PREFRONTAL CORTEX; STROKE PATIENTS; DC STIMULATION; EXCITABILITY; PLASTICITY AB The cerebellum is critical for both motor and cognitive control. Dysfunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human cerebellar function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of cerebellar-motor cortex connectivity, likely via cerebellar-thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions. C1 [Grimaldi, Giuliana; Manto, Mario] ULB Erasme, Unite Etud Mouvement, Brussels, Belgium. [Argyropoulos, Georgios P.] Univ London, Dept Psychol, Brain Act & Cognit Lab, Egham, Surrey, England. [Bastian, Amy; Celnik, Pablo] Johns Hopkins Univ, Sch Med, Dept Neurosci, 707 N Broadway Room G04, Baltimore, MD 21205 USA. [Cortes, Mar; Edwards, Dylan J.] Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurol, White Plains, NY USA. [Cortes, Mar; Edwards, Dylan J.] Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurosci, White Plains, NY USA. [Davis, Nicholas J.] Univ Coll Swansea, Dept Psychol, Swansea SA2 8PP, W Glam, Wales. [Davis, Nicholas J.] Univ Milan, Dept Med Surg Pathophysiol & Transplants, Milan, Italy. [Ferrucci, Roberta; Priori, Alberto] Osped Maggiore Milano, Fdn IRCCS Ca Granda, Clin Ctr Neurotechnol Neurostimulat & Movement Di, Milan, Italy. [Fregni, Felipe; Morales-Quezada, Leon] Harvard Univ, Spaulding Rehabil Hosp, Ctr Neuromodulat, Boston, MA 02115 USA. [Fregni, Felipe; Morales-Quezada, Leon] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Galea, Joseph M.; Miall, R. Chris; Pope, Paul A.] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. [Hamada, Masahi] Univ Tokyo, Dept Neurol, Tokyo, Japan. [Rothwell, John] UCL, Inst Neurol, London, England. [Tomlinson, S. Paul] Bangor Univ, Sch Psychol, Bangor, Gwynedd, Wales. [Celnik, Pablo] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, 707 N Broadway Room G04, Baltimore, MD 21205 USA. RP Celnik, P (reprint author), Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Dept Phys Med & Rehabil, 707 N Broadway Room G04, Baltimore, MD 21205 USA. EM pcelnik@jhmi.edu RI Ferrucci, Roberta/K-6081-2016; Argyropoulos, Georgios/R-1339-2016; OI Ferrucci, Roberta/0000-0001-5109-9483; Argyropoulos, Georgios/0000-0001-8267-6861; Galea, Joseph M/0000-0002-0009-4049 FU FNRS-Belgium; Wellcome Trust [WT087554]; National Institutes of Health (NIH) [R01HD069776, 1R01HD053793, R01HD073147] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: MM is supported by the FNRS-Belgium. RCM and PAP are supported by the Wellcome Trust (Grant ref. WT087554). DJE and MC are supported by the National Institutes of Health (NIH) Grant R01HD069776. PC is supported by NIH grant 1R01HD053793 and R01HD073147. NR 89 TC 15 Z9 15 U1 6 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD FEB PY 2016 VL 22 IS 1 BP 83 EP 97 DI 10.1177/1073858414559409 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DH8LZ UT WOS:000373046000011 PM 25406224 ER PT J AU Faje, A AF Faje, Alexander TI Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights SO PITUITARY LA English DT Review DE Ipilimumab; Hypophysitis; Hypopituitarism; CTLA-4 ID IPILIMUMAB-INDUCED HYPOPHYSITIS; IMMUNE CHECKPOINT INHIBITORS; IGG SUBCLASS PATTERN; METASTATIC MELANOMA; LUNG-CANCER; AUTOIMMUNE HYPOPHYSITIS; ANTI-CTLA-4 ANTIBODY; ADVERSE EVENTS; COMPLEMENT CONCENTRATION; SINGLE-INSTITUTION AB Introduction Advances in immunotherapy have transformed the management of metastatic melanoma and generated encouraging results in the treatment of other malignancies. Autoimmune side effects from these agents, termed immune-related adverse events (IRAEs), are diverse and can include multiple endocrinopathies. Ipilimumab-induced hypophysitis (IH) is a recently recognized endocrine IRAE. Methods This review summarizes published data and experience from our center on the incidence, presentation and management, and proposed mechanisms for immunotherapyrelated hypophysitis, with a focus on patients treated with ipilimumab (Ipi). Conclusion Hypophysitis occurs in a significant minority of patients treated with Ipi, in contrast to the relative rarity of idiopathic autoimmune hypophysitis or hypophysitis after treatment with other immunotherapies. Recently published cohorts have described the clinical presentation and management of IH and longitudinal outcomes in these patients. Additional studies with Ipi and other emerging agents have helped identify potential risk factors for the development of immunotherapy-related hypophysitis and possible underlying mechanisms for IH. Clarification of the mechanism(s) for IH may enhance our understanding of idiopathic autoimmune hypophysitis and could have potential therapeutic applications. C1 [Faje, Alexander] Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, 55 Fruit St, Boston, MA 02114 USA. [Faje, Alexander] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. RP Faje, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, 55 Fruit St, Boston, MA 02114 USA.; Faje, A (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM afaje@partners.org NR 87 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-341X EI 1573-7403 J9 PITUITARY JI Pituitary PD FEB PY 2016 VL 19 IS 1 BP 82 EP 92 DI 10.1007/s11102-015-0671-4 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DH6WG UT WOS:000372932200010 PM 26186958 ER PT J AU O'Neill, BT Segkos, K Kasper, EM Pallotta, JA AF O'Neill, Brian T. Segkos, Konstantinos Kasper, Ekkehard M. Pallotta, Johanna A. TI Non-metastatic squamous cell carcinoma within a Rathke's cleft cyst SO PITUITARY LA English DT Review DE Pituitary; Cancer; Squamous cell carcinoma; Rathke's cleft cyst; Epithelial cyst ID MALIGNANT-TRANSFORMATION; EPIDERMOID CARCINOMA; POSTERIOR-FOSSA; PITUITARY; CRANIOPHARYNGIOMA; MANAGEMENT; RECURRENCE; RESECTION; FEATURES; OUTCOMES AB Introduction Primary intracranial and sellar squamous cell carcinoma is an extremely rare entity, usually caused by malignant transformation of epidermoid cysts, or very rarely other non-malignant epithelial cysts. Malignant transformation of a Rathke's cleft cyst has never been described. Case Description We present a 49-year-old male patient who presented with a 3-month history of progressive frontotemporal headaches. Imaging revealed a 1.2 cm cystic pituitary mass consistent with a hemorrhagic Rathke's cleft cyst. The patient underwent trans-sphenoidal resection of the pituitary cyst, and pathologic analysis revealed a squamous cell carcinoma lining a Rathke's cleft cyst. Extensive imaging and otorhinolaryngologic evaluation revealed no primary source for metastasis. Conclusions We feel this represents the first case of a patient with a pituitary lesion in which presentation and MRI imaging were consistent with Rathke's cleft cyst, yet histology revealed squamous cell carcinoma in situ. C1 [O'Neill, Brian T.; Pallotta, Johanna A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Dept Med,Med Sch, Boston, MA 02215 USA. [O'Neill, Brian T.] Harvard Univ, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Sch Med, 1 Joslin Pl,Rm 605, Boston, MA 02215 USA. [Segkos, Konstantinos] Univ Massachusetts, Sch Med, Worcester, MA USA. [Kasper, Ekkehard M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurosurg, Sch Med, Boston, MA 02215 USA. RP O'Neill, BT (reprint author), Harvard Univ, Sect Integrat Physiol & Metab, Joslin Diabet Ctr, Sch Med, 1 Joslin Pl,Rm 605, Boston, MA 02215 USA. EM brian.o'neill@joslin.harvard.edu FU NIH T32 training Grant [T32DK007260]; K08 training Award [K08DK100543] FX B.T.O. was supported by an NIH T32 training Grant (T32DK007260) and by a K08 training Award (K08DK100543). We would like to thank Dr. Matthew Anderson from the Department of Pathology at Beth Israel Deaconess Medical Center and Dr. William C. Faquin from the Department of Pathology at Massachusetts General Hospital for assistance with the diagnosis. We would also like to thank Dr. Anand Mahadevan from the Department of Radiation Oncology at Beth Israel Deaconess Medical Center for assistance with treatment of the patient. NR 28 TC 0 Z9 0 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1386-341X EI 1573-7403 J9 PITUITARY JI Pituitary PD FEB PY 2016 VL 19 IS 1 BP 105 EP 109 DI 10.1007/s11102-015-0638-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DH6WG UT WOS:000372932200012 PM 25715776 ER PT J AU Fouts, DE Matthias, MA Adhikarla, H Adler, B Amorim-Santos, L Berg, DE Bulach, D Buschiazzo, A Chang, YF Galloway, RL Haake, DA Haft, DH Hartskeerl, R Ko, AI Levett, PN Matsunaga, J Mechaly, AE Monk, JM Nascimento, ALT Nelson, KE Palsson, B Peacock, SJ Picardeau, M Ricaldi, JN Thaipandungpanit, J Wunder, EA Yang, XF Zhang, JJ Vinetz, JM AF Fouts, Derrick E. Matthias, Michael A. Adhikarla, Haritha Adler, Ben Amorim-Santos, Luciane Berg, Douglas E. Bulach, Dieter Buschiazzo, Alejandro Chang, Yung-Fu Galloway, Renee L. Haake, David A. Haft, Daniel H. Hartskeerl, Rudy Ko, Albert I. Levett, Paul N. Matsunaga, James Mechaly, Ariel E. Monk, Jonathan M. Nascimento, Ana L. T. Nelson, Karen E. Palsson, Bernhard Peacock, Sharon J. Picardeau, Mathieu Ricaldi, Jessica N. Thaipandungpanit, Janjira Wunder, Elsio A., Jr. Yang, X. Frank Zhang, Jun-Jie Vinetz, Joseph M. TI What Makes a Bacterial Species Pathogenic?: Comparative Genomic Analysis of the Genus Leptospira SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID COMPLEMENT REGULATOR C4BP; FAINEI SEROVAR HURSTBRIDGE; VIRULENCE-ASSOCIATED GENES; OUTER-MEMBRANE PROTEINS; LPS BIOSYNTHETIC LOCI; DNA-DNA HYBRIDIZATION; SIGNAL PEPTIDASE-II; L-GLUTAMATE OXIDASE; ESCHERICHIA-COLI; BORRELIA-BURGDORFERI AB Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts. C1 [Fouts, Derrick E.; Haft, Daniel H.; Nelson, Karen E.] J Craig Venter Inst, Rockville, MD USA. [Matthias, Michael A.; Berg, Douglas E.; Vinetz, Joseph M.] Univ Calif San Diego, Sch Med, Div Infect Dis, Dept Med, La Jolla, CA 92093 USA. [Adhikarla, Haritha; Amorim-Santos, Luciane; Ko, Albert I.; Wunder, Elsio A., Jr.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA. [Adler, Ben] Monash Univ, Dept Microbiol, Australian Res Council, Ctr Excellence Struct & Funct Microbial Gen, Clayton, Vic 3168, Australia. [Amorim-Santos, Luciane; Ko, Albert I.; Wunder, Elsio A., Jr.] Fundacao Oswaldo Cruz MS, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil. [Bulach, Dieter] Monash Univ, Victorian Bioinformat Consortium, Clayton, Vic, Australia. [Buschiazzo, Alejandro; Mechaly, Ariel E.] Inst Pasteur, Lab Mol & Struct Microbiol, Montevideo, Uruguay. [Buschiazzo, Alejandro] Inst Pasteur, Dept Struct Biol & Chem, Paris, France. [Chang, Yung-Fu] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA. [Galloway, Renee L.] Ctr Dis Control & Prevent, BSPB, DHCPP, NCEZID,OID,CDC,DHHS, Atlanta, GA USA. [Haake, David A.; Matsunaga, James] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Haake, David A.; Matsunaga, James] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hartskeerl, Rudy] Royal Trop Inst KIT, WHO FAO OIE, Amsterdam, Netherlands. [Hartskeerl, Rudy] Royal Trop Inst KIT, Natl Collaborating Ctr Reference & Res Leptospiro, KIT Biomed Res, Amsterdam, Netherlands. [Levett, Paul N.] Govt Saskatchewan, Dis Control Lab Regina, Saskatoon, SK, Canada. [Monk, Jonathan M.; Palsson, Bernhard] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Nascimento, Ana L. T.] Inst Butantan, Ctr Biotecnol, Sao Paulo, SP, Brazil. [Nascimento, Ana L. T.] Univ Sao Paulo, Programa Interunidades Biotecnol, Inst Ciencias Biomed, Sao Paulo, SP, Brazil. [Peacock, Sharon J.] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. [Picardeau, Mathieu] Inst Pasteur, Biol Spirochetes Unit, Natl Reference Ctr, Paris, France. [Picardeau, Mathieu] WHO Collaborating Ctr Leptospirosis, Paris, France. [Ricaldi, Jessica N.; Vinetz, Joseph M.] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Fac Med Alberto Hurtado, Lima, Peru. [Thaipandungpanit, Janjira] Mahidol Univ, Fac Trop Med, Bangkok, Thailand. [Yang, X. Frank; Zhang, Jun-Jie] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Vinetz, Joseph M.] Univ Peruana Cayetano Heredia, Inst Med Alexander von Humboldt, Lima, Peru. RP Fouts, DE (reprint author), J Craig Venter Inst, Rockville, MD USA.; Fouts, DE; Vinetz, JM (reprint author), Univ Calif San Diego, Sch Med, Div Infect Dis, Dept Med, La Jolla, CA 92093 USA.; Vinetz, JM (reprint author), Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Fac Med Alberto Hurtado, Lima, Peru.; Vinetz, JM (reprint author), Univ Peruana Cayetano Heredia, Inst Med Alexander von Humboldt, Lima, Peru. EM dfouts@jcvi.org; jvinetz@ucsd.edu RI Ko, Albert/P-2343-2015; Wunder, Elsio/C-2733-2013; zhang, junjie/P-2376-2015; OI zhang, junjie/0000-0002-5108-2072; Nascimento, Ana Lucia /0000-0003-4851-0870; Mechaly, Ariel/0000-0002-5305-7495 FU federal funds from National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200900007C]; U.S. Public Health Service [U19AI115658, R01AI108276, D43TW007120, K24AI068903, R21AI115273, R01AI052473, R25TW009338, U01AI088752, R01TW009504, R01AI121207]; ANII (Uruguay) [FSA_1_2013_1_12557, ALI_1_2014_1_4982] FX This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under Contract Number HHSN272200900007C. This work was also supported in part by the following U.S. Public Health Service grants: U19AI115658 (JMV), R01AI108276 (JMV), D43TW007120 (JMV), K24AI068903 (JMV), R21AI115273 (MAM), R01AI052473 (AIK), U01AI088752 (AIK), R25TW009338 (AIK), R01TW009504 (AIK), and R01AI121207 (AIK). In addition, support to the A. Buschiazzo team was provided in part by grants FSA_1_2013_1_12557 and ALI_1_2014_1_4982 from ANII (Uruguay). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 214 TC 13 Z9 13 U1 9 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD FEB PY 2016 VL 10 IS 2 AR e0004403 DI 10.1371/journal.pntd.0004403 PG 57 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DH1TH UT WOS:000372567300024 PM 26890609 ER PT J AU Fazio, N Buzzoni, R Baudin, E Antonuzzo, L Hubner, RA Lahner, H De Herder, WW Raderer, M Teule, A Capdevila, J Libutti, SK Kulke, MH Shah, M Dey, D Turri, S Aimone, P Massacesi, C Verslype, C AF Fazio, Nicola Buzzoni, Roberto Baudin, Eric Antonuzzo, Lorenzo Hubner, Richard A. Lahner, Harald De Herder, Wouter W. Raderer, Markus Teule, Alexandre Capdevila, Jaume Libutti, Steven K. Kulke, Matthew H. Shah, Manisha Dey, Debarshi Turri, Sabine Aimone, Paola Massacesi, Cristian Verslype, Chris TI A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours SO ANTICANCER RESEARCH LA English DT Article DE BEZ235; everolimus; mTOR; PI3K; pNETs ID ADVANCED SOLID TUMORS; ENDOCRINE TUMORS; PI3K INHIBITOR; PATHWAY; MANAGEMENT; STRATEGIES; TARGET; SAFETY; PNETS AB Background: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimusresistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436). Patients and Methods: In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progressionfree survival (PFS) rate of >= 60% in stage 1. Results: As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%). Conclusion: BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2. C1 [Fazio, Nicola] European Inst Oncol, Milan, Italy. [Buzzoni, Roberto] IRCCS Natl Tumor Inst, Milan, Italy. [Baudin, Eric] Inst Gustave Roussy, Villejuif, France. [Antonuzzo, Lorenzo] Careggi Univ Hosp, Florence, Italy. [Hubner, Richard A.] Christie NHS Fdn Trust, Manchester, Lancs, England. [Lahner, Harald] Univ Duisburg Essen, Essen, Germany. [Raderer, Markus] Erasmus MC, Rotterdam, Netherlands. [Raderer, Markus] Univ Hosp Vienna, Vienna, Austria. Catalan Inst Oncol, Barcelona, Spain. [Capdevila, Jaume] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. [Libutti, Steven K.] Montefiore Med Ctr, New York, NY USA. [Libutti, Steven K.] Albert Einstein Coll Med, New York, NY USA. [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shah, Manisha] Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. [Shah, Manisha] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Dey, Debarshi] Novartis Healthcare Private Ltd, Hyderabad, Andhra Pradesh, India. [Turri, Sabine; Aimone, Paola] Novartis Pharma AG, Basel, Switzerland. [Massacesi, Cristian] Novartis Oncol, Paris, France. [Verslype, Chris] Univ Hosp Leuven, Leuven, Belgium. RP Fazio, N (reprint author), European Inst Oncol IEO, Unit Gastrointestinal Med Oncol & Neuroendocrine, Via Ripamonti 435, I-20141 Milan, Italy. EM nicola.fazio@ieo.it FU Novartis Pharmaceuticals Corporation FX The Authors are grateful to Sara Pusceddu MD, Cristina Bregant MD, and Laura Concas MSc for scientific discussions and additional data. They acknowledge Francesca Spada MD (European Institute of Oncology, Milan, Italy) for her scientific and clinical expertise. They also thank the patients who participated in this study. Medical editorial assistance was provided by Kate Gaffey Ph.D. and Nirmal Jethwa Ph.D. and was funded by Novartis Pharmaceuticals Corporation. NR 28 TC 7 Z9 7 U1 4 U2 6 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD FEB PY 2016 VL 36 IS 2 BP 713 EP 719 PG 7 WC Oncology SC Oncology GA DG7GS UT WOS:000372253400029 PM 26851029 ER PT J AU Pinheiro, AP Rezaii, N Nestor, PG Rauber, A Spencer, KM Niznikiewicz, M AF Pinheiro, Ana P. Rezaii, Neguine Nestor, Paul G. Rauber, Andreia Spencer, Kevin M. Niznikiewicz, Margaret TI Did you or I say pretty, rude or brief? An ERP study of the effects of speaker's identity on emotional word processing SO BRAIN AND LANGUAGE LA English DT Article ID EVENT-RELATED POTENTIALS; SELF-VOICE RECOGNITION; HUMAN AUDITORY-CORTEX; BRAIN POTENTIALS; COROLLARY DISCHARGE; INITIATED SOUNDS; SPOKEN LANGUAGE; SCHIZOPHRENIA; ATTENTION; INTEGRATION AB During speech comprehension, multiple cues need to be integrated at a millisecond speed, including semantic information, as well as voice identity and affect cues. A processing advantage has been demonstrated for self-related stimuli when compared with non-self stimuli, and for emotional relative to neutral stimuli. However, very few studies investigated self-other speech discrimination and, in particular, how emotional valence and voice identity interactively modulate speech processing. In the present study we probed how the processing of words' semantic valence is modulated by speaker's identity (self vs. non-self voice). Sixteen healthy subjects listened to 420 prerecorded adjectives differing in voice identity (self vs. non self) and semantic valence (neutral, positive and negative), while electroencephalographic data were recorded. Participants were instructed to decide whether the speech they heard was their own (self speech condition), someone else's (non-self speech), or if they were unsure. The ERP results demonstrated interactive effects of speaker's identity and emotional valence on both early (N1, P2) and late (Late Positive Potential - LPP) processing stages: compared with non-self speech, self-speech with neutral valence elicited more negative N1 amplitude, self-speech with positive valence elicited more positive P2 amplitude, and self-speech with both positive and negative valence elicited more positive LPP. ERP differences between self and non-self speech occurred in spite of similar accuracy in the recognition of both types of stimuli. Together, these findings suggest that emotion and speaker's identity interact during speech processing, in line with observations of partially dependent processing of speech and speaker information. (c) 2016 Published by Elsevier Inc. C1 [Pinheiro, Ana P.] Univ Minho, Neuropsychophysiol Lab, Psychol Res Ctr CIPsi, Sch Psychol, P-4710957 Braga, Portugal. [Pinheiro, Ana P.; Rezaii, Neguine; Nestor, Paul G.; Niznikiewicz, Margaret] Harvard Univ, Lab Neurosci, VA Boston Healthcare Syst Brockton Div, Dept Psychiat,Med Sch,Clin Neurosci Div, Brockton, MA 02401 USA. [Pinheiro, Ana P.] Univ Lisbon, Fac Psychol, P-1699 Lisbon, Portugal. [Nestor, Paul G.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Rauber, Andreia] Univ Tubingen, Int Studies Computat Linguist, Tubingen, Germany. [Spencer, Kevin M.] Harvard Univ, Sch Med, Neural Dynam Lab, Res Serv,VA Boston Healthcare Syst, Boston, MA USA. [Spencer, Kevin M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pinheiro, AP (reprint author), Univ Minho, Neuropsychophysiol Lab, CIPsi, Sch Psychol, Campus Gualtar, P-4710957 Braga, Portugal. EM ana.pinheiro@psi.uminho.pt FU Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [IF/00334/2012, PTDC/PSI-PCL/116626/2010, PTDC/MHN-PCN/3606/2012]; FEDER (European Regional Development Fund, Portugal) (Fundo Europeu de Desenvolvimento Regional) through the European program QREN (Quadro de Referencia Estrategico Nacional); FEDER (European Regional Development Fund, Portugal) (Fundo Europeu de Desenvolvimento Regional) through the European program COMPETE (Operational Programme 'Thematic Factors of Competitiveness', Portugal) (Programa Operacional Factores de Competitividade) FX This work was supported by Grants IF/00334/2012, PTDC/PSI-PCL/116626/2010 and PTDC/MHN-PCN/3606/2012 funded by Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and FEDER (European Regional Development Fund, Portugal) (Fundo Europeu de Desenvolvimento Regional) through the European programs QREN (Quadro de Referencia Estrategico Nacional), and COMPETE (Operational Programme 'Thematic Factors of Competitiveness', Portugal) (Programa Operacional Factores de Competitividade), awarded to A.P.P. NR 85 TC 1 Z9 1 U1 8 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD FEB PY 2016 VL 153 BP 38 EP 49 DI 10.1016/j.bandl.2015.12.003 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA DH1QW UT WOS:000372561000005 PM 26894680 ER PT J AU Mihos, CG Santana, O AF Mihos, Christos G. Santana, Orlando TI Is an adjunctive subvalvular repair during mitral annuloplasty for secondary mitral regurgitation effective in preventing recurrent regurgitation? SO INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY LA English DT Article DE Functional mitral regurgitation; Ischaemic mitral regurgitation; Mitral valve repair; Secondary mitral regurgitation; Subvalvular repair ID PAPILLARY-MUSCLE APPROXIMATION; ISCHEMIC CARDIOMYOPATHY AB A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is an adjunctive subvalvular repair during mitral annuloplasty for secondary mitral regurgitation effective in preventing recurrent regurgitation? Altogether, 353 studies were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. The best evidence regarding adjunctive subvalvular repair during mitral annuloplasty for secondary mitral regurgitation was from retrospective analyses. The studies reported outcomes of mitral valve repair (MVr) with annuloplasty alone (ring MVr) versus adjunctive papillary muscle approximation (PMA; n = 3), papillary muscle relocation (PMR; n = 3), secondary chordal cutting (n = 2) and PMA + PMR (n = 1). All but one study included concomitant coronary artery bypass grafting, whereas additional ventriculoplasty was performed in three studies. Follow-up ranged from 1 month to 5 years. The performance of PMA was associated with a lower mitral regurgitation (MR) grade when combined with ventriculoplasty in one study, whereas a greater improvement in left ventricular end-diastolic diameter and left ventricular ejection fraction at follow-up was observed with PMA alone in a separate study. Three studies of ring + PMR reported a reduction in >= 2+ recurrent MR, whereas two studies also observed a greater reduction in left ventricular end-diastolic diameter. The two studies on secondary chordal cutting reported a lower MR grade, lower recurrence of >= 2+ MR and a greater left ventricular ejection fraction at follow-up. Combining PMA + PMR + ventriculoplasty significantly reduced left ventricular end-systolic volume index at short-term follow-up in one study. Finally, none of the studies reported a significant difference in operative mortality between ring MVr (0-13%) versus ring MVr + subvalvular repair (0-15%). We conclude that an adjunctive subvalvular repair performed at the time of mitral annuloplasty for secondary MR can be safely performed, improves the durability of valve repair and enhances left ventricular reverse remodelling. C1 [Mihos, Christos G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02140 USA. [Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA. RP Mihos, CG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02140 USA. EM cmihos@mgh.harvard.edu NR 10 TC 4 Z9 4 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1569-9293 EI 1569-9285 J9 INTERACT CARDIOV TH JI Interact Cardiovasc. Thorac. Surg. PD FEB PY 2016 VL 22 IS 2 BP 216 EP 221 DI 10.1093/icvts/ivv328 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG9QY UT WOS:000372420100019 PM 26612406 ER PT J AU Siedner, MJ Kim, JH Nakku, RS Bibangambah, P Hemphill, L Triant, VA Haberer, JE Martin, JN Mocello, AR Boumii, Y Kwon, DS Tracy, RP Burdo, T Huang, Y Cao, HY Okello, S Bangsberg, DR Hunt, PW AF Siedner, Mark J. Kim, June-Ho Nakku, Ruth Sentongo Bibangambah, Prossy Hemphill, Linda Triant, Virginia A. Haberer, Jessica E. Martin, Jeffrey N. Mocello, A. Rain Boumii, Yap Kwon, Douglas S. Tracy, Russell P. Burdo, Tricia Huang, Yong Cao, Huyen Okello, Samson Bangsberg, David R. Hunt, Peter W. TI Persistent Immune Activation and Carotid Atherosclerosis in HIV-Infected Ugandans Receiving Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV; AIDS; Uganda; aging; inflammation; atherosclerosis; carotid intima media thickness; antiretroviral therapy ID INTIMA-MEDIA THICKNESS; ACUTE MYOCARDIAL-INFARCTION; T-CELL-ACTIVATION; SUBCLINICAL VASCULAR-DISEASE; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; SOLUBLE CD14; MICROBIAL TRANSLOCATION; MONOCYTE ACTIVATION; ARTERY INTIMA AB Background. Human immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa. Methods.Beginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged > 40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT). Results.A total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01). Conclusions.Persistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region. C1 [Siedner, Mark J.; Triant, Virginia A.; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hemphill, Linda] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Siedner, Mark J.; Kim, June-Ho; Haberer, Jessica E.; Kwon, Douglas S.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA. [Siedner, Mark J.; Hemphill, Linda; Triant, Virginia A.; Haberer, Jessica E.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, June-Ho] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Kwon, Douglas S.] MIT, Ragon Inst MGH, Boston, MA USA. [Kwon, Douglas S.] Harvard Univ, Boston, MA 02115 USA. [Burdo, Tricia] Boston Coll, Chestnut Hill, MA 02167 USA. [Martin, Jeffrey N.; Mocello, A. Rain; Huang, Yong; Cao, Huyen; Hunt, Peter W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tracy, Russell P.] Univ Vermont, Burlington, VT 05405 USA. [Nakku, Ruth Sentongo; Bibangambah, Prossy; Okello, Samson; Bangsberg, David R.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Boumii, Yap] Epictr Res Base, Mbarara, Uganda. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA. EM msiedner@mgh.harvard.edu OI Okello, Samson/0000-0001-7377-6094 FU National Institutes of Health [R21HL124712, K23MH099916, R56AI100765, R21AI078774, R01MH054907, P01AI027763, P01AI076174]; Harvard Center for AIDS Research; Doris Duke Charitable Foundation; Sullivan Family Foundation FX This work was supported by the National Institutes of Health (grants R21HL124712, K23MH099916, R56AI100765, R21AI078774, R01MH054907, P01AI027763 and P01AI076174), the Harvard Center for AIDS Research, the Doris Duke Charitable Foundation, and the Sullivan Family Foundation. NR 51 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2016 VL 213 IS 3 BP 370 EP 378 DI 10.1093/infdis/jiv450 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DG9XB UT WOS:000372436000007 PM 26347573 ER PT J AU Jones, CN Dimisko, L Forrest, K Judice, K Poznansky, MC Markmann, JF Vyas, JM Irimia, D AF Jones, Caroline N. Dimisko, Laurie Forrest, Kevin Judice, Kevin Poznansky, Mark C. Markmann, James F. Vyas, Jatin M. Irimia, Daniel TI Human Neutrophils Are Primed by Chemoattractant Gradients for Blocking the Growth of Aspergillus fumigatus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE neutrophil; microfluidics; A. fumigatus; host-pathogen interaction; chemoattractants ID CHRONIC GRANULOMATOUS-DISEASE; ANTIFUNGAL IMMUNITY; CANDIDA-ALBICANS; CHEMOTAXIS; INVITRO; CONIDIA; HYPHAE; INFECTIONS; PHAGOCYTES; MIGRATION AB The contribution of human neutrophils to the protection against fungal infections by Aspergillus fumigatus is essential but not fully understood. Whereas healthy people can inhale spores of A. fumigatus without developing disease, neutropenic patients and those receiving immunosuppressive drugs have a higher incidence of invasive fungal infections. To study the role of neutrophils in protection against A. fumigatus infections, we developed an in vitro assay in which the interactions between human neutrophils and A. fumigatus were observed in real time, at single-cell resolution, in precisely controlled conditions. We measured the outcomes of neutrophil-fungus interactions and found that human neutrophils have a limited ability to migrate toward A. fumigatus and block the growth of A. fumigatus conidia (proportion with growth blocked, 69%). The blocking ability of human neutrophils increased to 85.1% when they were stimulated by uniform concentrations of fMLP and was enhanced further, to 99.4%, in the presence of chemoattractant gradients. Neutrophils from patients receiving immunosuppressive treatment after transplantation were less effective against the fungus than those from healthy donors, and broader heterogeneity exists between patients, compared with healthy individuals. Further studies using this microfluidic platform will help understand the relevance of innate immune deficiencies responsible for the higher risk of fungal infections in patients with immunosuppressive disease. C1 [Jones, Caroline N.; Dimisko, Laurie; Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. [Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. [Jones, Caroline N.; Dimisko, Laurie; Markmann, James F.; Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Poznansky, Mark C.] Massachusetts Gen Hosp, Vaccine & Immunotherapy Ctr, Boston, MA 02114 USA. [Poznansky, Mark C.; Vyas, Jatin M.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Poznansky, Mark C.; Vyas, Jatin M.] Harvard Univ, Sch Med, Boston, MA USA. [Forrest, Kevin; Judice, Kevin] Cidara Therapeut, San Diego, CA USA. RP Irimia, D (reprint author), MGH CNY, 114 16th St,1404, Boston, MA 02129 USA. EM dirimia@hms.harvard.edu FU Cidara Therapeutics; National Institutes of Health [GM092804, EB002503] FX This work was supported by Cidara Therapeutics under a research agreement managed by the Massachusetts General Hospital (to D. I. and J. M. V.) and by the National Institutes of Health (grant GM092804 to D. I. and grant EB002503 to the BioMEMS Resource Center [for all microfabrication work]). NR 35 TC 2 Z9 2 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2016 VL 213 IS 3 BP 465 EP 475 DI 10.1093/infdis/jiv419 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DG9XB UT WOS:000372436000019 PM 26272935 ER PT J AU Conant, EF Beaber, EF Sprague, BL Herschorn, SD Weaver, DL Onega, T Tosteson, ANA McCarthy, AM Poplack, SP Haas, JS Armstrong, K Schnall, MD Barlow, WE AF Conant, Emily F. Beaber, Elisabeth F. Sprague, Brian L. Herschorn, Sally D. Weaver, Donald L. Onega, Tracy Tosteson, Anna N. A. McCarthy, Anne Marie Poplack, Steven P. Haas, Jennifer S. Armstrong, Katrina Schnall, Mitchell D. Barlow, William E. CA PROSPR Consortium TI Breast cancer screening using tomosynthesis in combination with digital mammography compared to digital mammography alone: a cohort study within the PROSPR consortium SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer screening; Mammography; Digital breast tomosynthesis AB Digital breast tomosynthesis (DBT) is emerging as the new standard of care for breast cancer screening based on improved cancer detection coupled with reductions in recall compared to screening with digital mammography (DM) alone. However, many prior studies lack follow-up data to assess false negatives examinations. The purpose of this study is to assess if DBT is associated with improved screening outcomes based on follow-up data from tumor registries or pathology. Retrospective analysis of prospective cohort data from three research centers performing DBT screening in the PROSPR consortium from 2011 to 2014 was performed. Recall and biopsy rates were assessed from 198,881 women age 40-74 years undergoing screening (142,883 DM and 55,998 DBT examinations). Cancer, cancer detection, and false negative rates and positive predictive values were assessed on examinations with one year of follow-up. Logistic regression was used to compare DBT to DM adjusting for research center, age, prior breast imaging, and breast density. There was a reduction in recall with DBT compared to DM (8.7 vs. 10.4 %, p < 0.0001), with adjusted OR = 0.68 (95 % CI = 0.65-0.71). DBT demonstrated a statistically significant increase in cancer detection over DM (5.9 vs. 4.4/1000 screened, adjusted OR = 1.45, 95 % CI = 1.12-1.88), an improvement in PPV1 (6.4 % for DBT vs. 4.1 % for DM, adjusted OR = 2.02, 95 % CI = 1.54-2.65), and no significant difference in false negative rates for DBT compared to DM (0.46 vs. 0.60/1000 screened, p = 0.347). Our data support implementation of DBT screening based on increased cancer detection, reduced recall, and no difference in false negative screening examinations. C1 [Conant, Emily F.; Schnall, Mitchell D.] Univ Penn, Perelman Sch Med, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. [Beaber, Elisabeth F.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Sprague, Brian L.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA. [Sprague, Brian L.; Herschorn, Sally D.; Weaver, Donald L.] Univ Vermont, Ctr Canc, Burlington, VT USA. [Herschorn, Sally D.] Univ Vermont, Dept Radiol, Burlington, VT USA. [Weaver, Donald L.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Onega, Tracy; Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dept Community & Family Med, Lebanon, NH USA. [Onega, Tracy; Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Onega, Tracy; Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Lebanon, NH USA. [McCarthy, Anne Marie; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Poplack, Steven P.] Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. [Barlow, William E.] Canc Res & Biostat, Seattle, WA USA. RP Conant, EF (reprint author), Univ Penn, Perelman Sch Med, Dept Radiol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM emily.conant@uphs.upenn.edu OI Conant, Emily/0000-0001-9331-644X FU National Cancer Institute (NCI) [U01CA163304, U54CA163303, P01 CA154292, U54CA163307, U54CA163313] FX This work was supported by the National Cancer Institute (NCI)-funded Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium (Grant numbers U01CA163304 to M.T., W.B.; U54CA163303 and P01 CA154292 to D.L.W., B.S., S.H.; U54CA163307 to A.N.A.T., T.O., J.H.; U54CA163313 to E.F.C., K.A., M.S.) NR 16 TC 6 Z9 6 U1 5 U2 7 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 FEB PY 2016 VL 156 IS 1 BP 109 EP 116 DI 10.1007/s10549-016-3695-1 PG 8 WC Oncology SC Oncology GA DG7IU UT WOS:000372258800012 PM 26931450 ER PT J AU Russo, M Siravegna, G Blaszkowsky, LS Corti, G Crisafulli, G Ahronian, LG Mussolin, B Kwak, EL Buscarino, M Lazzari, L Valtorta, E Truini, M Jessop, NA Robinson, HE Hong, TS Mino-Kenudson, M Di Nicolantonio, F Thabet, A Sartore-Bianchi, A Siena, S Iafrate, AJ Bardelli, A Corcoran, RB AF Russo, Mariangela Siravegna, Giulia Blaszkowsky, Lawrence S. Corti, Giorgio Crisafulli, Giovanni Ahronian, Leanne G. Mussolin, Benedetta Kwak, Eunice L. Buscarino, Michela Lazzari, Luca Valtorta, Emanuele Truini, Mauro Jessop, Nicholas A. Robinson, Hayley E. Hong, Theodore S. Mino-Kenudson, Mari Di Nicolantonio, Federica Thabet, Ashraf Sartore-Bianchi, Andrea Siena, Salvatore Iafrate, A. John Bardelli, Alberto Corcoran, Ryan B. TI Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer SO CANCER DISCOVERY LA English DT Article ID ACQUIRED-RESISTANCE; EGFR BLOCKADE; INTRATUMOR HETEROGENEITY; LUNG ADENOCARCINOMA; COLON-CANCER; EVOLUTION; MUTATIONS; EMERGENCE; INHIBITOR; CETUXIMAB AB How genomic heterogeneity associated with acquired resistance to targeted agents affects response to subsequent therapy is unknown. We studied EGFR blockade in colorectal cancer to assess whether tissue and liquid biopsies can be integrated with radiologic imaging to monitor the impact of individual oncogenic alterations on lesion-specific responses. Biopsy of a patient's progressing liver metastasis following prolonged response to cetuximab revealed a MEK1(K57T) mutation as a novel mechanism of acquired resistance. This lesion regressed upon treatment with panitumumab and the MEK inhibitor trametinib. In circulating tumor DNA (ctDNA), mutant MEK1 levels declined with treatment, but a previously unrecognized KRAS(Q61H) mutation was also identified that increased despite therapy. This same KRAS mutation was later found in a separate nonresponding metastasis. In summary, parallel analyses of tumor biopsies and serial ctDNA monitoring show that lesion-specific radiographic responses to subsequent targeted therapies can be driven by distinct resistance mechanisms arising within separate tumor lesions in the same patient. SIGNIFICANCE: Molecular heterogeneity ensuing from acquired resistance drives lesion-specific responses to subsequent targeted therapies. Analysis of a single-lesion biopsy is inadequate to guide selection of subsequent targeted therapies. ctDNA profiles allow the detection of concomitant resistance mechanisms residing in separate metastases and assessment of the effect of therapies designed to overcome resistance. (C) 2015 AACR. C1 [Russo, Mariangela; Siravegna, Giulia; Corti, Giorgio; Crisafulli, Giovanni; Mussolin, Benedetta; Buscarino, Michela; Lazzari, Luca; Di Nicolantonio, Federica; Bardelli, Alberto] IRCCS, Candiolo Canc Inst FPO, Turin, Italy. [Russo, Mariangela; Siravegna, Giulia; Di Nicolantonio, Federica; Bardelli, Alberto] Univ Turin, Dept Oncol, Turin, Italy. [Russo, Mariangela] IFOM, Milan, Italy. [Blaszkowsky, Lawrence S.; Ahronian, Leanne G.; Kwak, Eunice L.; Hong, Theodore S.; Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th Floor, Boston, MA 02129 USA. [Blaszkowsky, Lawrence S.; Ahronian, Leanne G.; Kwak, Eunice L.; Corcoran, Ryan B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Valtorta, Emanuele; Truini, Mauro; Sartore-Bianchi, Andrea; Siena, Salvatore] Osped Maggiore Niguarda, Niguarda Canc Ctr, Milan, Italy. [Jessop, Nicholas A.; Robinson, Hayley E.; Mino-Kenudson, Mari; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02129 USA. [Thabet, Ashraf] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Corcoran, RB (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th Floor, Boston, MA 02129 USA.; Bardelli, A (reprint author), Univ Turin, Dept Oncol, FPO, IRCCS, SP 142,Km 3-95, I-10060 Candiolo, TO, Italy. EM alberto.bardelli@unito.it; rbcorcoran@partners.org RI Di Nicolantonio, Federica/A-2503-2011 OI Di Nicolantonio, Federica/0000-0001-9618-2010 FU NIH/NCI Gastrointestinal Cancer SPORE [P50 CA127003]; Damon Runyon Clinical Investigator Award; NIH/NCI [1K08CA166510]; European Community [602901]; IMI [115749]; AIRC [9970]; AIRC IG [12812]; Fondazione Piemontese per la Ricerca sul Cancro-ONLUS; Ministero dell'Istruzione, dell'Universita e della Ricerca, progetto PRIN FX This study was supported by grants from the NIH/NCI Gastrointestinal Cancer SPORE P50 CA127003, a Damon Runyon Clinical Investigator Award, and NIH/NCI 1K08CA166510 (all to R.B. Corcoran); by the European Community's Seventh Framework Programme under grant agreement no. 602901 MErCuRIC (A. Bardelli); IMI contract no. 115749 CANCER-ID (A. Bardelli); AIRC 2010 Special Program Molecular Clinical Oncology 5 per mille, Project no. 9970 (A. Bardelli, S. Siena); AIRC IG no. 12812 (A. Bardelli); Fondazione Piemontese per la Ricerca sul Cancro-ONLUS 5 per mille 2010 e 2011 Ministero della Salute (A. Bardelli); and Ministero dell'Istruzione, dell'Universita e della Ricerca, progetto PRIN 2010-2011 (A. Bardelli). NR 22 TC 29 Z9 30 U1 10 U2 18 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 FEB PY 2016 VL 6 IS 2 BP 147 EP 153 DI 10.1158/2159-8290.CD-15-1283 PG 7 WC Oncology SC Oncology GA DG8HF UT WOS:000372323000023 PM 26644315 ER PT J AU Roberts, NJ Norris, AL Petersen, GM Bondy, ML Brand, R Gallinger, S Kurtz, RC Olson, SH Rustgi, AK Schwartz, AG Stoffel, E Syngal, S Zogopoulos, G Ali, SZ Axilbund, J Chaffee, KG Chen, YC Cote, ML Childs, EJ Douville, C Goes, FS Herman, JM Iacobuzio-Donahue, C Kramer, M Makohon-Moore, A McCombie, RW McMahon, KW Niknafs, N Parla, J Pirooznia, M Potash, JB Rhim, AD Smith, AL Wang, YX Wolfgang, CL Wood, LD Zandi, PP Goggins, M Karchin, R Eshleman, JR Papadopoulos, N Kinzler, KW Vogelstein, B Hruban, RH Klein, AP AF Roberts, Nicholas J. Norris, Alexis L. Petersen, Gloria M. Bondy, Melissa L. Brand, Randall Gallinger, Steven Kurtz, Robert C. Olson, Sara H. Rustgi, Anil K. Schwartz, Ann G. Stoffel, Elena Syngal, Sapna Zogopoulos, George Ali, Syed Z. Axilbund, Jennifer Chaffee, Kari G. Chen, Yun-Ching Cote, Michele L. Childs, Erica J. Douville, Christopher Goes, Fernando S. Herman, Joseph M. Iacobuzio-Donahue, Christine Kramer, Melissa Makohon-Moore, Alvin McCombie, Richard W. McMahon, K. Wyatt Niknafs, Noushin Parla, Jennifer Pirooznia, Mehdi Potash, James B. Rhim, Andrew D. Smith, Alyssa L. Wang, Yuxuan Wolfgang, Christopher L. Wood, Laura D. Zandi, Peter P. Goggins, Michael Karchin, Rachel Eshleman, James R. Papadopoulos, Nickolas Kinzler, Kenneth W. Vogelstein, Bert Hruban, Ralph H. Klein, Alison P. TI Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer SO CANCER DISCOVERY LA English DT Article ID LI-FRAUMENI SYNDROME; CLONAL HEMATOPOIESIS; INCREASED RISK; MUTATIONS; PREDISPOSITION; SUSCEPTIBILITY; ALIGNMENT; VARIANTS; TOOLKIT AB Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genomes of 638 patients with familial pancreatic cancer and the tumor exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A, and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identifi cation of susceptibility genes in other common cancer types. SIGNIFICANCE: The genetic basis of disease susceptibility in the majority of patients with familial pancreatic cancer is unknown. We whole genome sequenced 638 patients with familial pancreatic cancer and demonstrate that the genetic underpinning of inherited pancreatic cancer is highly heterogeneous. This has significant implications for the management of patients with familial pancreatic cancer. (C) 2015 AACR. C1 [Roberts, Nicholas J.; Norris, Alexis L.; Ali, Syed Z.; Axilbund, Jennifer; Makohon-Moore, Alvin; Wood, Laura D.; Goggins, Michael; Eshleman, James R.; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Roberts, Nicholas J.; McMahon, K. Wyatt; Wang, Yuxuan; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert] Johns Hopkins Med Inst, Ludwig Ctr, 1650 Orleans St, Baltimore, MD 21231 USA. [Roberts, Nicholas J.; McMahon, K. Wyatt; Wang, Yuxuan; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert] Johns Hopkins Med Inst, Howard Hughes Med Inst, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Petersen, Gloria M.; Chaffee, Kari G.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Bondy, Melissa L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Brand, Randall] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Rustgi, Anil K.; Rhim, Andrew D.] Univ Penn, Perelman Sch Med, Pancreat Canc Translat Ctr Excellence, Abramson Canc Ctr,Div Gastroenterol,Dept Med, Philadelphia, PA 19104 USA. [Rustgi, Anil K.; Rhim, Andrew D.] Univ Penn, Perelman Sch Med, Pancreat Canc Translat Ctr Excellence, Abramson Canc Ctr,Div Gastroenterol,Dept Genet, Philadelphia, PA 19104 USA. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Stoffel, Elena] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Syngal, Sapna] Dana Farber Canc Inst, Populat Sci Div, Boston, MA 02115 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Zogopoulos, George; Smith, Alyssa L.] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada. [Zogopoulos, George; Smith, Alyssa L.] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada. [Chen, Yun-Ching; Douville, Christopher; Niknafs, Noushin] Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD USA. [Childs, Erica J.; Klein, Alison P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Goes, Fernando S.; Pirooznia, Mehdi; Zandi, Peter P.] Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Herman, Joseph M.; Wood, Laura D.; Goggins, Michael; Eshleman, James R.; Hruban, Ralph H.; Klein, Alison P.] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. [Iacobuzio-Donahue, Christine] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Kramer, Melissa; McCombie, Richard W.; Parla, Jennifer] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA. [Parla, Jennifer] InGenious Targeting Lab, Ronkonkoma, NY USA. [Potash, James B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Rhim, Andrew D.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Wolfgang, Christopher L.] Johns Hopkins Med Inst, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Med Inst, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA. RP Roberts, NJ; Hruban, RH; Klein, AP (reprint author), Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA.; Kinzler, KW; Vogelstein, B (reprint author), Johns Hopkins Med Inst, Ludwig Ctr, 1650 Orleans St, Baltimore, MD 21231 USA.; Roberts, NJ (reprint author), Johns Hopkins Med Inst, Dept Pathol, 1550 Orleans St, Baltimore, MD 21231 USA.; Hruban, RH (reprint author), Johns Hopkins Med Inst, Dept Pathol, 600 N Wolfe St, Baltimore, MD 21287 USA.; Klein, AP (reprint author), Johns Hopkins Med Inst, Dept Oncol, 1550 Orleans St, Baltimore, MD 21231 USA. EM nrobert8@jhmi.edu; kinzlke@jhmi.edu; vogelbe@jhmi.edu; rhruban@jhmi.edu; aklein1@jhmi.edu RI Gallinger, Steven/E-4575-2013 FU Lustgarten Foundation for Pancreatic Cancer Research; Sol Goldman Pancreatic Cancer Research Center; Howard Hughes Medical Institute; Virginia and D.K. Ludwig Fund for Cancer Research; Stringer Foundation; Rolfe Foundation for Cancer Research; Joseph C. Monastra Foundation; Gerald O. Mann Charitable Foundation; Ladies Auxiliary to the Veterans of Foreign Wars; Weston Garfield Foundation; NIH [P50-CA062924, P50-CA102701, K99-CA190889, K01-MH093809, P30-CA006973, R01-CA57345, R01-CA97075, R01-CA154823, R01-DK060694, R01-MH087979] FX This work was generously supported by Dennis Troper and Susan Wojcicki, the Lustgarten Foundation for Pancreatic Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Howard Hughes Medical Institute, the Virginia and D.K. Ludwig Fund for Cancer Research, the Stringer Foundation, the Rolfe Foundation for Cancer Research, the Joseph C. Monastra Foundation, the Gerald O. Mann Charitable Foundation (Harriet and Allan Wulfstat, Trustees), the Ladies Auxiliary to the Veterans of Foreign Wars, the friends and family of Roger L. Kerns Sr., the Weston Garfield Foundation, the NIH Specialized Programs of Research Excellence P50-CA062924 and P50-CA102701, and NIH grants K99-CA190889, K01-MH093809, P30-CA006973, R01-CA57345, R01-CA97075, R01-CA154823, R01-DK060694, and R01-MH087979. NR 49 TC 15 Z9 15 U1 3 U2 10 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 FEB PY 2016 VL 6 IS 2 BP 166 EP 175 DI 10.1158/2159-8290.CD-15-0402 PG 10 WC Oncology SC Oncology GA DG8HF UT WOS:000372323000025 PM 26658419 ER PT J AU Le Pen, J Laurent, M Sarosiek, K Vuillier, C Gautier, F Montessuit, S Martinou, JC Letai, A Braun, F Juin, PP AF Le Pen, J. Laurent, M. Sarosiek, K. Vuillier, C. Gautier, F. Montessuit, S. Martinou, J. C. Letai, A. Braun, F. Juin, P. P. TI Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL SO CELL DEATH & DISEASE LA English DT Article ID DNA-BINDING DOMAIN; BAX ACTIVATION; FAMILY-MEMBERS; PROTEIN; OLIGOMERIZATION; BIM; PERMEABILIZATION; TRANSCRIPTION; CHEMOTHERAPY; DISRUPTION AB Proapoptotic molecules directly targeting the BCL-2 family network are promising anticancer therapeutics, but an understanding of the cellular stress signals that render them effective is still elusive. We show here that the tumor suppressor p53, at least in part by transcription independent mechanisms, contributes to cell death induction and full activation of BAX by BH3 mimetic inhibitors of BCL-xL. In addition to mildly facilitating the ability of compounds to derepress BAX from BCL-xL, p53 also provides a death signal downstream of anti-apoptotic proteins inhibition. This death signal cooperates with BH3-induced activation of BAX and it is independent from PUMA, as enhanced p53 can substitute for PUMA to promote BAX activation in response to BH3 mimetics. The acute sensitivity of mitochondrial priming to p53 revealed here is likely to be critical for the clinical use of BH3 mimetics. C1 [Le Pen, J.; Laurent, M.; Vuillier, C.; Gautier, F.; Braun, F.; Juin, P. P.] Univ Nantes, Team Cell Survival & Tumor Escape Breast Canc 8, Inst Rech Sante, UMR 892,INSERM,CNRS 6299, Nantes, France. [Sarosiek, K.; Letai, A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Gautier, F.; Juin, P. P.] Ctr Lutte Canc Rene Gauducheau, Inst Cancerol Ouest, St Herblain, France. [Montessuit, S.; Martinou, J. C.] Univ Geneva, Dept Cell Biol, Geneva, Switzerland. [Braun, F.] Univ Paris Diderot, Inst Biol Physiochim, CNRS FRE3630, Sorbonne Paris Cite, 13 Rue Pierre & Marie Curie, F-75005 Paris, France. RP Braun, F; Juin, PP (reprint author), INSERM, U892, 9 Quai Moncousu, F-44035 Nantes, France. EM braun@ibpc.fr; philippe.juin@univ-nantes.fr RI JUIN, Philippe/H-3636-2014; OI JUIN, Philippe/0000-0002-4997-3888; BRAUN, Frederique/0000-0001-5871-6042 FU INSERM Region; Ministere de la Recherche et de l'Enseignement Superieur; Region Pays de la Loire (CIMATH2); Ligue contre le Cancer [R13137]; ARC [R15083NN] FX We thank members of the 'Cell Survival and Tumor Escape in Breast Cancer' laboratory for their technical advice, fruitful comments and enthusiasm. We thank Thanos Halazonetis for his kind sharing of the p53 (79-393) construct. We thank Cecile Couriaud for her technical help in the preparation of lentivirus particles. We thank Philippe Hulin for his technical support at the Cellular and Tissular Imaging Core Facility of Nantes University (MicroPICell). JLP and CV are supported by grants from INSERM Region and the Ministere de la Recherche et de l'Enseignement Superieur respectively. This work was supported by Region Pays de la Loire (CIMATH2), Ligue contre le Cancer (R13137) and ARC (R15083NN). NR 47 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD FEB PY 2016 VL 7 AR e2083 DI 10.1038/cddis.2015.400 PG 10 WC Cell Biology SC Cell Biology GA DG5FU UT WOS:000372102400003 PM 26844698 ER PT J AU Grossi, LM Lee, AF Schuler, A Ryan, JL Prentky, RA AF Grossi, Laura M. Lee, Austin F. Schuler, Ann Ryan, Julie L. Prentky, Robert A. TI Sexualized behaviors in cohorts of children in the child welfare system SO CHILD ABUSE & NEGLECT LA English DT Article DE Childhood; Sexualized behavior; Base rate; Sexual development; Child welfare ID MALTREATMENT; DECADE; ADOLESCENCE; IMPACT; ABUSE; AGE AB The current retrospective archival study investigated the patterns of normative sexualized behavior (NSB), problematic sexualized behavior (PSB), and sexual perpetration for three age cohorts of boys and girls in a high-risk child welfare sample. All children in the present sample had exhibited some form of PSB in the past. We hypothesized that the incidence rates (IR) of NSBs would increase linearly from the early childhood cohort (Ages 2/3-7) to the middle childhood cohort (Ages 8-11) to the preadolescence/adolescence cohort (Ages 12-17), for girls and boys. Although the base rate of sexual behaviors generally increases as children age, children tend to hide sexual behaviors starting at an early age. We therefore hypothesized that a concave quadratic trend would be evident for most PSBs. We further predicted that older children would have a greater incidence of PSB, as well as more victims, compared with younger children. We found the predicted upward linear trend for NSB for both girls and boys, with minimal IR differences between the early childhood and middle childhood cohorts. IRs were remarkably high and comparable across age groups for both boys and girls, with respect to the same three PSBs. For the two perpetration history variables, there was a concave effect, with girls and boys in the middle childhood cohort exhibiting the lowest IR. Results are explained in the context of previously established patterns of sexualized behavior, as well as the reporting of such behaviors. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Grossi, Laura M.; Prentky, Robert A.] Fairleigh Dickinson Univ, Sch Psychol T WH1 01, Metropolitan Campus,1000 River Rd, Teaneck, NJ 07666 USA. [Lee, Austin F.] Bentley Univ, Dept Math Sci, 175 Forest St, Waltham, MA 02452 USA. [Lee, Austin F.] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. [Schuler, Ann] Justice Resource Inst, 160 Gould St,Suite 300, Needham, MA 02494 USA. [Ryan, Julie L.] William James Coll, 1 Wells Ave, Newton, MA 02459 USA. RP Prentky, RA (reprint author), Fairleigh Dickinson Univ, Sch Psychol T WH1 01, Metropolitan Campus,1000 River Rd, Teaneck, NJ 07666 USA. FU National Institute of Justice [2002-IJ-CX-0029] FX This project was supported by grants from the National Institute of Justicefrom July, 2002 through April, 2006 [2002-IJ-CX-0029]. NR 38 TC 0 Z9 0 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 EI 1873-7757 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD FEB PY 2016 VL 52 BP 49 EP 61 DI 10.1016/j.chiabu.2015.12.014 PG 13 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA DG3ER UT WOS:000371952800008 PM 26774533 ER PT J AU Barshop, K Staller, K AF Barshop, Kenneth Staller, Kyle TI New Pathways, New Targets: Visceral Hypersensitivity Pathogenesis in Irritable Bowel Syndrome SO CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY LA English DT Editorial Material C1 [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Staller, Kyle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol,Ctr Neurointestinal Hlth, 55 Fruit St, Boston, MA 02114 USA. RP Staller, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol,Ctr Neurointestinal Hlth, 55 Fruit St, Boston, MA 02114 USA. EM kstaller@mgh.harvard.edu OI Staller, Kyle/0000-0003-4925-4290 NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2155-384X J9 CLIN TRANSL GASTROEN JI Clin. Transl. Gastroenterol. PD FEB PY 2016 VL 7 AR e146 DI 10.1038/ctg.2016.12 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DG5GX UT WOS:000372106200005 PM 26913769 ER PT J AU Conley, SB AF Conley, Susanne B. TI Central Line-Associated Bloodstream Infection Prevention: Standardizing Practice Focused on Evidence-Based Guidelines SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article DE chemotherapy; febrile neutropenia; supportive care; oncology nurses ID CARE-ASSOCIATED INFECTIONS; VENOUS CATHETER CARE; CANCER AB Central venous access devices (CVADs) are integral to the treatment and provision of supportive care for many patients with cancer. Central venous catheters are the most frequent cause of healthcare-associated bloodstream infections. Healthcare-associated bloodstream infections can be prevented when evidence-based practices are followed consistently over time. Establishing nursing best practice with CVADs in the ambulatory setting presents additional challenges because of multiple providers, caregivers, and policies. This article identifies evidence-based practice strategies implemented at a comprehensive ambulatory cancer center to standardize best nursing practice for central lines. At a Glance Central line care must reflect knowledge of risk factors associated with central line-associated bloodstream infection. Central line care must be guided by credible evidence-based standards that focus on central line-associated bloodstream infection prevention. Standardizing port access and dressing practice by implementing evidence-based policies are associated with measurable improvement in patient outcomes. C1 [Conley, Susanne B.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Conley, SB (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM susanne_conley@dfci.harvard.edu NR 16 TC 0 Z9 0 U1 9 U2 13 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 EI 1538-067X J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD FEB PY 2016 VL 20 IS 1 BP 23 EP 26 DI 10.1188/16.CJON.23-26 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA DG1HU UT WOS:000371817800008 PM 26800401 ER PT J AU Sundt, TM AF Sundt, Thoralf M. TI Early risk; late reward? SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Editorial Material DE Aortic valve replacement; Ross procedure; Shared decision-making ID AORTIC-VALVE-REPLACEMENT; ROSS PROCEDURE; MECHANICAL VALVE; REOPERATIONS; MANAGEMENT; SELECTION C1 [Sundt, Thoralf M.] Harvard Univ, Div Cardiac Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sundt, TM (reprint author), Harvard Univ, Div Cardiac Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM tsundt@partners.org NR 10 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 FEB PY 2016 VL 49 IS 2 BP 520 EP 521 DI 10.1093/ejcts/ezv103 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DG1IF UT WOS:000371819300030 PM 25777056 ER PT J AU Mathisen, DJ AF Mathisen, Douglas J. TI Re: Video-assisted thoracoscopic surgery versus open lobectomy for primary non-small-cell lung cancer: a propensity-matched analysis of outcome from the European Society of Thoracic Surgeon database SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Editorial Material DE Database; Video-assisted thoracoscopic surgery; Lobectomy C1 [Mathisen, Douglas J.] Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 3 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 FEB PY 2016 VL 49 IS 2 BP 609 EP 610 DI 10.1093/ejcts/ezv167 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DG1IF UT WOS:000371819300046 PM 25920462 ER PT J AU Valero, MD Hancock, KE Liberman, MC AF Valero, Michelle D. Hancock, Kenneth E. Liberman, M. Charles TI The middle ear muscle reflex in the diagnosis of cochlear neuropathy SO HEARING RESEARCH LA English DT Article DE Cochlear neuropathy; Hidden hearing loss; Acoustic overexposure; Middle-ear muscle reflex; Medial olivocochlear reflex; Wideband reflectance ID ACOUSTIC STAPEDIUS REFLEX; AUDITORY-NERVE FIBERS; HAIR CELL LOSS; PRODUCT OTOACOUSTIC EMISSIONS; SENSORINEURAL HEARING-LOSS; PHARMACOLOGICAL-PROPERTIES; ACETYLCHOLINE-RECEPTOR; OLIVOCOCHLEAR REFLEX; IMPEDANCE AUDIOMETRY; CENTRAL PROJECTIONS AB Cochlear neuropathy, i.e. the loss of auditory nerve fibers (ANFs) without loss of hair cells, may cause hearing deficits without affecting threshold sensitivity, particularly if the subset of ANFs with high thresholds and low spontaneous rates (SRS) is preferentially lost, as appears to be the case in both aging and noise-damaged cochleas. Because low-SR fibers may also be important drivers of the medial olivocochlear reflex (MOCR) and middle-ear muscle reflex (MEMR), these reflexes might be sensitive metrics of cochlear neuropathy. To test this hypothesis, we measured reflex strength and reflex threshold in mice with noise-induced neuropathy, as documented by confocal analysis of immunostained cochlear whole-mounts. To assay the MOCR, we measured contra-noise modulation of ipsilateral distortion product otoacoustic emissions (DPOAEs) before and after the administration of curare to block the MEMR or curare + strychnine to also block the MOCR. The modulation of DPOAEs was 1) dominated by the MEMR in anesthetized mice, with a smaller contribution from the MOCR, and 2) significantly attenuated in neuropathic mice, but only when the MEMR was intact. We then measured MEMR growth functions by monitoring contra-noise induced changes in the wideband reflectance of chirps presented to the ipsilateral ear. We found 1) that the changes in wideband reflectance were mediated by the MEMR alone, and 2) that MEMR threshold was elevated and its maximum amplitude was attenuated in neuropathic mice. These data suggest that the MEMR may be valuable in the early detection of cochlear neuropathy. Published by Elsevier B.V. C1 [Valero, Michelle D.; Hancock, Kenneth E.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. [Valero, Michelle D.; Hancock, Kenneth E.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Valero, MD (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA.; Valero, MD (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM Michelle_Valero@meei.harvard.edu FU National Institute on Deafness and other Communicative Disorders [R01 DC 00188, P30 DC 05209, F32 DC 014405] FX We thank Christopher Shera and John Guinan for aid in experimental design, and John Guinan for reviewing an earlier version of this manuscript. We also thank Leslie Liberman for expert assistance in cochlear dissection and immunostaining for a subset of the cochleas. Research supported by grants from the National Institute on Deafness and other Communicative Disorders: R01 DC 00188 (MCL), P30 DC 05209 (MCL), and F32 DC 014405 (MDV). NR 92 TC 3 Z9 3 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD FEB PY 2016 VL 332 BP 29 EP 38 DI 10.1016/j.heares.2015.11.005 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA DG3BJ UT WOS:000371944200004 PM 26657094 ER PT J AU Aghagolzadeh, M Truccolo, W AF Aghagolzadeh, Mehdi Truccolo, Wilson TI Inference and Decoding of Motor Cortex Low-Dimensional Dynamics via Latent State-Space Models SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Brain-machine interfaces (BMI); collective dynamics; neural encoding; point processes ID NEURAL POPULATION-DYNAMICS; GRASP; REACH; VARIABILITY AB Motor cortex neuronal ensemble spiking activity exhibits strong low-dimensional collective dynamics (i.e., coordinated modes of activity) during behavior. Here, we demonstrate that these low-dimensional dynamics, revealed by unsupervised latent state-space models, can provide as accurate or better reconstruction of movement kinematics as direct decoding from the entire recorded ensemble. Ensembles of single neurons were recorded with triple microelectrode arrays (MEAs) implanted in ventral and dorsal premotor (PMv, PMd) and primary motor (M1) cortices while nonhuman primates performed 3-D reach-to-grasp actions. Low-dimensional dynamics were estimated via various types of latent state-space models including, for example, Poisson linear dynamic system (PLDS) models. Decoding from low-dimensional dynamics was implemented via point process and Kalman filters coupled in series. We also examined decoding based on a predictive subsampling of the recorded population. In this case, a supervised greedy procedure selected neuronal subsets that optimized decoding performance. When comparing decoding based on predictive subsampling and latent state-space models, the size of the neuronal subset was set to the same number of latent state dimensions. Overall, our findings suggest that information about naturalistic reach kinematics present in the recorded population is preserved in the inferred low-dimensional motor cortex dynamics. Furthermore, decoding based on unsupervised PLDS models may also outperform previous approaches based on direct decoding from the recorded population or on predictive subsampling. C1 [Aghagolzadeh, Mehdi; Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Truccolo, Wilson] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Truccolo, Wilson] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Providence, RI 02912 USA. RP Aghagolzadeh, M; Truccolo, W (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA.; Truccolo, W (reprint author), Brown Univ, Inst Brain Sci, Providence, RI 02912 USA.; Truccolo, W (reprint author), US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Providence, RI 02912 USA. EM Mehdi_Aghagolzadeh@Brown.edu; Wilson_Truccolo@Brown.edu FU National Institute of Neurological Disorders and Stroke (NINDS) [NS057389, R01 NS25074]; Defense Advanced Research Projects Agency [DARPA REPAIR N66001-10-C-2010]; Pablo J. Salame'88 Goldman Sachs endowed Assistant Professorship in Computational Neuroscience FX This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), K01 Career Award NS057389 and R01 NS25074, by the Defense Advanced Research Projects Agency (DARPA REPAIR N66001-10-C-2010), and by the Pablo J. Salame'88 Goldman Sachs endowed Assistant Professorship in Computational Neuroscience. NR 28 TC 3 Z9 3 U1 0 U2 0 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 FEB PY 2016 VL 24 IS 2 BP 272 EP 282 DI 10.1109/TNSRE.2015.2470527 PG 11 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA DG4FP UT WOS:000372027300008 PM 26336135 ER PT J AU Ohshima, M Yamaguchi, Y Ambe, K Horie, M Saito, A Nagase, T Nakashima, K Ohki, H Kawai, T Abiko, Y Micke, P Kappert, K AF Ohshima, Mitsuhiro Yamaguchi, Yoko Ambe, Kimiharu Horie, Masafumi Saito, Akira Nagase, Takahide Nakashima, Keisuke Ohki, Hidero Kawai, Toshihisa Abiko, Yoshimitsu Micke, Patrick Kappert, Kai TI Fibroblast VEGF-receptor 1 expression as molecular target in periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE fibroblasts; Flt-1; gene expression; gingiva; periodontal disease; vascular endothelial growth factor ID ENDOTHELIAL GROWTH-FACTOR; GINGIVAL CREVICULAR FLUID; IN-VITRO; FLT-1; DISEASES; INFLAMMATION; ANGIOGENESIS; PROGRESSION; INHIBITOR; FLK-1/KDR AB AimDegradation of extracellular matrices is an integral part in periodontitis. For antagonizing this pathophysiological mechanism, we aimed at identifying gene expression profiles in disease progression contributing periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention. Materials and MethodsApplying an exploratory analysis using a small number of microarrays in combination with a three dimensional (3D) invitro culture model that incorporates some aspects of periodontitis, PAFs were initially characterized by gene-expression analyses, followed by targeted gene down-regulation and pharmacological intervention in vitro. Further, immunohistochemistry was applied for phosphorylation analyses in tissue specimens. ResultsPAFs were characterized by 42 genes being commonly up-regulated >1.5-fold, and by five genes that were concordantly down-regulated (<0.7-fold). Expression of vascular endothelial growth factor (VEGF)-receptor 1 (Flt-1) was highly enhanced, and was thus further explored in invitro culture models of periodontal fibroblasts without accounting for the microbiome. Phosphorylation of the VEGF-receptor 1 was enhanced in PAFs. Receptor inhibition by a specific VEGF-receptor inhibitor or intrinsic down-regulation by RNAi of the VEGF-receptor kinase in 3D gel cultures resulted in significant reduction in collagen degradation associated with increased tissue inhibitor of metalloproteinase expression, suggesting that Flt-1 may contribute to periodontitis. ConclusionBased on the finding that VEGF-receptor kinase inhibition impaired collagen degradation pathways, Flt-1 may represent a candidate for therapeutic approaches in periodontitis. C1 [Ohshima, Mitsuhiro] Ohu Univ, Sch Pharmaceut Sci, Dept Biochem, Misumido 31-1, Koriyama, Fukushima 9638611, Japan. [Yamaguchi, Yoko] Nihon Univ, Sch Dent, Dept Biochem, Tokyo 101, Japan. [Ambe, Kimiharu] Ohu Univ, Sch Dent, Dept Morphol Biol, Misumido 31-1, Koriyama, Fukushima 9638611, Japan. [Horie, Masafumi; Saito, Akira; Nagase, Takahide] Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan. [Horie, Masafumi; Saito, Akira; Nagase, Takahide] Univ Tokyo, Fac Med, Tokyo 113, Japan. [Nakashima, Keisuke] Kyushu Dent Univ, Dept Oral Funct, Div Periodontol, Fukuoka, Japan. [Ohki, Hidero] Nihon Univ, Sch Dent, Dept Oral Surg 1, Tokyo, Japan. [Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Cambridge, MA USA. [Abiko, Yoshimitsu] Nihon Univ, Sch Dent, Dept Mol Biol & Biochem, Matsudo, Chiba 271, Japan. [Micke, Patrick] Univ Uppsala Hosp, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Kappert, Kai] Charite, CCR, Inst Lab Med Clin Chem & Pathobiochem, D-13353 Berlin, Germany. RP Ohshima, M (reprint author), Ohu Univ, Sch Pharmaceut Sci, Dept Biochem, Misumido 31-1, Koriyama, Fukushima 9638611, Japan. EM m-ohshima@pha.ohu-u.ac.jp FU Japan Society for the Promotion of Science, Sato Fund, Nihon University School of Dentistry (KAKENHI) [25460137, 24593129, 15K15768]; Dental Research Center, Nihon University School of Dentistry; Utsukushima (Beautiful Fukushima) Next-Generation Medical Industry Agglomeration Project; Marga und Walter Boll-Stiftung FX This study was supported by Grants-in-Aid for Scientific Research (KAKENHI, #25460137, #24593129, #15K15768) from the Japan Society for the Promotion of Science, Sato Fund, Nihon University School of Dentistry for 2013-14, a Grant from the Dental Research Center, Nihon University School of Dentistry for 2014-15, and by Utsukushima (Beautiful Fukushima) Next-Generation Medical Industry Agglomeration Project. K.K. was supported Marga und Walter Boll-Stiftung (210-04-10). NR 44 TC 2 Z9 2 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD FEB PY 2016 VL 43 IS 2 BP 128 EP 137 DI 10.1111/jcpe.12495 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DG1LA UT WOS:000371828300004 PM 26932322 ER PT J AU Bruckel, JT Jaffer, FA O'Brien, C Stone, L Pomerantsev, E Yeh, RW AF Bruckel, Jeffrey T. Jaffer, Farouc A. O'Brien, Cashel Stone, Luke Pomerantsev, Eugene Yeh, Robert W. TI Angina Severity, Depression, and Response to Percutaneous Revascularization in Patients With Chronic Total Occlusion of Coronary Arteries SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE coronary disease; stents; percutaneous coronary intervention; depression ID HEART-DISEASE; MAJOR DEPRESSION; UNITED-STATES; REGISTRY; RISK; INTERVENTION; VALIDATION; SYMPTOMS; OUTCOMES; IMPACT AB Objectives. This study sought to quantify depression rates in patients referred for percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), assess its relationship to baseline angina symptoms, and compare angina improvement after CTO-PCI between depressed and non-depressed patients. Background. Depression is common among patients with chronic angina, and portends poor prognosis. CTOs are a common cause of angina. The relationships between angina, depression, and CTO intervention are unknown. Methods. We collected baseline and 30-day post-PCI data on angina (Seattle Angina Questionnaire [SAQ7]), dyspnea (Rose Dyspnea Scale [RDS]), and depression status (Patient Health Questionnaire [PHQ-2]) on 45 consecutive patients referred for CTO-PCI between October 2013 and October 2014. Results. Depression (PHQ-2 score >= 3) was present in 18/45 patients (40%) at baseline. Baseline SAQ7 Summary and SAQ7 Angina Frequency scores for depressed patients were 35.4 (range, 28.4-42.4) and 54.4 (range, 43.0-65.8), compared with 67.3 (range, 57.5-77.1) and 77.8 (range, 68.5-87.1) for non-depressed patients (P<.001 and P=.01, respectively). Following CTO-PCI, the mean improvement in SAQ7 Summary and SAQ7 Angina Frequency scores was 48.5 (range, 35.4-61.5) and 32.8 (range, 21.0-44.5) for patients with depression, compared with 16.5 (range, 5.87-27.2) and 12.6 (range, 3.0-22.2) for patients without depression (P<.001 and P=.01, respectively). Following PCI, the presence of depression was reduced (72% relative reduction vs baseline; P=.01). Conclusions. Depression identifies patients more limited by angina and more likely to respond to CTO-PCI compared with non-depressed patients. Depression screening may be indicated for patients with CTO, as 67% of CTO patients were not receiving treatment for depression. C1 [Bruckel, Jeffrey T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bruckel, Jeffrey T.] Edward P Lawrence Ctr Qual & Safety, Boston, MA USA. [Jaffer, Farouc A.; O'Brien, Cashel; Stone, Luke; Pomerantsev, Eugene; Yeh, Robert W.] Corrigan Minehan Heart Ctr, Div Cardiol, Boston, MA USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB800,55 Fruit St, Boston, MA 02114 USA. EM ryeh@mgh.harvard.edu FU Partners Healthcare; Hassenfeld Scholars Program FX The collection of patient-reported outcomes was funded by Partners Healthcare. The study was also supported by the Hassenfeld Scholars Program. NR 37 TC 1 Z9 1 U1 0 U2 1 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 EI 1557-2501 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD FEB PY 2016 VL 28 IS 2 BP 44 EP + PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DG5TC UT WOS:000372140500006 PM 26477043 ER PT J AU Morris, NA Kaplan, TB Linnoila, J Cho, T AF Morris, Nicholas A. Kaplan, Tamara B. Linnoila, Jenny Cho, Tracey TI HSV encephalitis-induced anti-NMDAR encephalitis in a 67-year-old woman: report of a case and review of the literature SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE Encephalitis; Autoimmune diseases; Post-infectious; Viral infections; All neuropsychology/behavior ID HERPES-SIMPLEX ENCEPHALITIS; D-ASPARTATE RECEPTOR; VIRUS ENCEPHALITIS; ACYCLOVIR THERAPY; CASE SERIES; FOLLOW-UP; RELAPSE; ANTIBODIES; CHILDREN; EXPERIENCE AB Herpes simplex virus (HSV) encephalitis can induce an autoimmune encephalitis mediated by autoantibodies against the N-methyl-D-aspartate receptor (NMDAR). Post-HSV NMDAR encephalitis and de novo NMDAR encephalitis have been more commonly described in children and young adults. We describe the case of a 67-year-old woman with post-HSV NMDAR encephalitis and review the relevant literature. Clinical, serological, neurophysiological, and imaging evaluations were undertaken in the evaluation of this patient. A literature review was performed. Nearly 2 months after a typical course of HSV encephalitis confirmed by HSV polymerase chain reaction studies from the spinal fluid and treated with intravenous acyclovir, a 67-year-old woman suffered neurological deterioration. There was no evidence of active HSV infection, but NMDAR antibodies were found in her serum and spinal fluid. The patient improved after initiation of immunosuppressive therapy. All patients who experience new or recurrent neurological symptoms following recovery from HSV encephalitis should be evaluated for postinfectious autoimmune encephalitis, including NMDAR encephalitis. C1 [Morris, Nicholas A.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA. [Kaplan, Tamara B.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02114 USA. [Kaplan, Tamara B.; Linnoila, Jenny; Cho, Tracey] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kaplan, TB (reprint author), Brigham & Womens Hosp, Dept Neurol, Boston, MA 02114 USA.; Kaplan, TB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM nam2185@cumc.columbia.edu; tbkaplan@partners.org; jlinnoila@partners.org; tcho@partners.org NR 43 TC 3 Z9 3 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2016 VL 22 IS 1 BP 33 EP 37 DI 10.1007/s13365-015-0364-9 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DG2WH UT WOS:000371930500006 PM 26139017 ER PT J AU Thakur, KT Lyons, JL Smith, BR Shinohara, RT Mateen, FJ AF Thakur, Kiran T. Lyons, Jennifer L. Smith, Bryan R. Shinohara, Russell T. Mateen, Farrah J. TI Stroke in HIV-infected African Americans: a retrospective cohort study SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Stroke; African American; Human immunodeficiency virus; Disparity; United States AB The risk of having a first stroke is nearly twice as high among African Americans compared to Caucasians. HIV/AIDS is an independent risk factor for stroke. Our study aimed to report the risk factors and short-term clinical outcomes of African Americans with HIV infection and newonset stroke admitted at the Johns Hopkins Hospitals (2000-2012). Multivariate linear regression was used to examine the association between potential predictors and odds of an unfavorable outcome, defined as a higher modified Rankin Scale (mRS) score on hospital discharge. African Americans comprised 105/125 (84 %) of HIV-infected new-onset stroke inpatients (median age 50 years; 69 % men; median CD4 140/mL; ischemic 77 %; 39 % taking highly active antiretroviral therapy). Vascular risk factors were common: hypertension (67 %), cigarette smoking (66 %), dyslipidemia (42 %), hepatitis C (48 %), intravenous drug abuse (32 %), and prior myocardial infarction (29 %). Prior aspirin and statin use were uncommon (18 %, 9 %). Unfavorable outcome (mRS score 46, n=22 of 90 available records) was noted in 24% of patients, including seven in-hospital deaths. On multivariate analyses, higher CD4 count on hospital admission was associated with a lower mRS (-0.2 mRS points per 1 unit increase in CD4, 95 % CI (-0.3, 0), p=0.03). Intracerebral hemorrhage was also associated with a lower mRS (1.0 points lower, 95 % CI (0.2, 1.8) compared to ischemic stroke, p=0.01) after adjustment for other potential predictors. This underscores the importance of HIV infection on functional stroke outcomes beyond its recognized influence on stroke risk. C1 [Thakur, Kiran T.] Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY USA. [Lyons, Jennifer L.; Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. [Lyons, Jennifer L.] Brigham & Womens Hosp, Div Neuroinfect Dis, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Smith, Bryan R.] NINDS, Sect Infect Nervous Syst, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Shinohara, Russell T.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St,627, Boston, MA 02114 USA. RP Mateen, FJ (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St,627, Boston, MA 02114 USA. EM ktt2115@cumc.columbia.edu; fmateen@partners.org FU Canadian Institutes of Health Research NR 13 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2016 VL 22 IS 1 BP 50 EP 55 DI 10.1007/s13365-015-0363-x PG 6 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DG2WH UT WOS:000371930500008 PM 26155903 ER PT J AU Bank, AM Batra, A Colorado, RA Lyons, JL AF Bank, Anna M. Batra, Ayush Colorado, Rene A. Lyons, Jennifer L. TI Myeloradiculopathy associated with chikungunya virus infection SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Chikungunya; Viralmyelopathy; Infectious myelopathy; Myelopathy ID TRANSVERSE MYELITIS; FEVER; EPIDEMIC; REGION; DENGUE; INDIA AB Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset. C1 [Bank, Anna M.; Batra, Ayush; Colorado, Rene A.; Lyons, Jennifer L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Bank, Anna M.; Batra, Ayush; Colorado, Rene A.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Bank, Anna M.; Batra, Ayush; Colorado, Rene A.; Lyons, Jennifer L.] Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. RP Bank, AM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.; Bank, AM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.; Bank, AM (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM abank@partners.org NR 18 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2016 VL 22 IS 1 BP 125 EP 128 DI 10.1007/s13365-015-0372-9 PG 4 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DG2WH UT WOS:000371930500016 PM 26306687 ER PT J AU Atefi, SR Seoane, F Kamalian, S Rosenthal, ES Lev, MH Bonmassar, G AF Atefi, Seyed Reza Seoane, Fernando Kamalian, Shervin Rosenthal, Eric S. Lev, Michael H. Bonmassar, Giorgio TI Intracranial hemorrhage alters scalp potential distribution in bioimpedance cerebral monitoring: Preliminary results from FEM simulation on a realistic head model and human subjects SO MEDICAL PHYSICS LA English DT Article DE scalp equipotential lines; bioimpedance; intracranial hemorrhage; prehospital triage; FEM simulations ID ELECTRICAL-IMPEDANCE TOMOGRAPHY; NEAR-INFRARED SPECTROSCOPY; INTRACEREBRAL HEMORRHAGE; ISCHEMIC-STROKE; DIELECTRIC-PROPERTIES; BIOLOGICAL TISSUES; BRAIN HEMORRHAGE; UTILITY; MANAGEMENT; SPECTRUM AB Purpose: Current diagnostic neuroimaging for detection of intracranial hemorrhage (ICH) is limited to fixed scanners requiring patient transport and extensive infrastructure support. ICH diagnosis would therefore benefit from a portable diagnostic technology, such as electrical bioimpedance (EBI). Through simulations and patient observation, the authors assessed the influence of unilateral ICH hematomas on quasisymmetric scalp potential distributions in order to establish the feasibility of EBI technology as a potential tool for early diagnosis. Methods: Finite element method (FEM) simulations and experimental left right hemispheric scalp potential differences of healthy and damaged brains were compared with respect to the asymmetry caused by ICH lesions on quasisymmetric scalp potential distributions. In numerical simulations, this asymmetry was measured at 25 kHz and visualized on the scalp as the normalized potential difference between the healthy and ICH damaged models. Proof-of-concept simulations were extended in a pilot study of experimental scalp potential measurements recorded between 0 and 50 kHz with the authors' custom-made bioimpedance spectrometer. Mean left right scalp potential differences recorded from the frontal, central, and parietal brain regions of ten healthy control and six patients suffering from acute/subacute ICH were compared. The observed differences were measured at the 5% level of significance using the two-sample Welch t test. Results: The 3D-anatomically accurate FEM simulations showed that the normalized scalp potential difference between the damaged and healthy brain models is zero everywhere on the head surface, except in the vicinity of the lesion, where it can vary up to 5%. The authors' preliminary experimental results also confirmed that the left right scalp potential difference in patients with ICH (e.g., 64 mV) is significantly larger than in healthy subjects (e.g., 20.8 mV; P < 0.05). Conclusions: Realistic, proof-of-concept simulations confirmed that ICH affects quasisymmetric scalp potential distributions. Pilot clinical observations with the authors' custom-made bioimpedance spectrometer also showed higher left right potential differences in the presence of ICH, similar to those of their simulations, that may help to distinguish healthy subjects from ICH patients. Although these pilot clinical observations are in agreement with the computer simulations, the small sample size of this study lacks statistical power to exclude the influence of other possible confounders such as age, sex, and electrode positioning. The agreement with previously published simulation-based and clinical results, however, suggests that EBI technology may be potentially useful for ICH detection. (C) 2016 American Association of Physicists in Medicine. C1 [Atefi, Seyed Reza; Kamalian, Shervin; Lev, Michael H.; Bonmassar, Giorgio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Atefi, Seyed Reza; Bonmassar, Giorgio] Harvard Univ, Sch Med, MGH, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Atefi, Seyed Reza; Seoane, Fernando] Royal Inst Technol, Sch Technol & Hlth, S-14152 Huddinge, Sweden. [Seoane, Fernando] Univ Boras, Acad Care Wellbeing & Working Life, S-50190 Boras, Sweden. [Rosenthal, Eric S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bonmassar, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Bonmassar, G (reprint author), Harvard Univ, Sch Med, MGH, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM giorgio.bonmassar@nmr.mgh.harvard.edu OI Rosenthal, Eric/0000-0003-3900-356X; Seoane Martinez, Fernando/0000-0002-6995-967X FU Swedish Royal Academy of Engineering Sciences Hans Werthen Fund FX The authors would like to thank the Swedish Royal Academy of Engineering Sciences Hans Werthen Fund. The authors would also like to thank Peter Serano for his support with the simulations. CIMIT U.S. Army Medical Research Acquisition Activity Cooperative Agreement (No. W81XWH-14-2-0008), NIH/NIBIB Point-of-Care Center for Emerging Neurotechnologies (POC-CENT) (No. 5U54EB007954-04). Study design: M.H.L., G.B., and E.S.R. Clinical data analysis: S.R.A., G.B., F.S., M.H.L., and E.S.R. Simulations: S.R.A. and G.B. Data collections: S.K. and S.R.A. The paper was written by S.R.A., S.K., F.S., G.B., and E.S.R. The authors report no conflicts of interest in conducting the research. NR 54 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 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD FEB PY 2016 VL 43 IS 2 BP 675 EP 686 DI 10.1118/1.4939256 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG4GO UT WOS:000372030000009 PM 26843231 ER PT J AU Wang, MD Guo, N Hu, GS El Fakhri, G Zhang, H Li, QZ AF Wang, Mengdie Guo, Ning Hu, Guangshu El Fakhri, Georges Zhang, Hui Li, Quanzheng TI A novel approach to assess the treatment response using Gaussian random field in PET SO MEDICAL PHYSICS LA English DT Article DE therapeutic assessment; Gaussian random field; PET imaging ID POSITRON-EMISSION-TOMOGRAPHY; FAMILYWISE ERROR RATE; SOLID TUMORS; IMAGE-RECONSTRUCTION; EVALUATION CRITERIA; NOISE PROPERTIES; REGISTRATION; RESOLUTION; ALGORITHM; SCANNER AB Purpose: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. Methods: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (1282 pixels) with lesions of various diameters (2-6 mm), multiple tumor-to-background contrasts (3-10), and different changes in intensity (6.25%-30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. Results: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with 1 correlation coefficient. Conclusions: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion. (C) 2016 American Association of Physicists in Medicine. C1 [Wang, Mengdie; Hu, Guangshu; Zhang, Hui] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. [Wang, Mengdie; Guo, Ning; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [El Fakhri, Georges; Li, Quanzheng] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Zhang, H (reprint author), Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China.; Li, QZ (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.; Li, QZ (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM hzhang@mail.tsinghua.edu.cn; li.quanzheng@mgh.harvard.edu FU China Scholarship Council (CSC) [201306210270]; NIBIB [R01EB013293] FX This work was supported in part by the scholarship from China Scholarship Council (CSC, No. 201306210270) and NIBIB No. R01EB013293. NR 43 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 43 IS 2 BP 833 EP 842 DI 10.1118/1.4939879 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG4GO UT WOS:000372030000026 ER PT J AU Xu, H Xu, KX He, HSH Zang, CZ Chen, CH Chen, YW Qin, Q Wang, S Wang, CF Hu, SG Li, FG Long, H Brown, M Liu, XS AF Xu, Han Xu, Kexin He, Housheng H. Zang, Chongzhi Chen, Chen-Hao Chen, Yiwen Qin, Qian Wang, Su Wang, Chenfei Hu, Shengen Li, Fugen Long, Henry Brown, Myles Liu, X. Shirley TI Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression SO MOLECULAR CANCER RESEARCH LA English DT Article ID RESISTANT PROSTATE-CANCER; ANDROGEN RECEPTOR; RNA-SEQ; CELLS; METHYLATION; LYMPHOMA; BREAST; PHOSPHORYLATION; PROLIFERATION; PROGRESSION AB Overexpression of EZH2 is frequently linked to the advanced and metastatic stage of cancers. The mechanisms of its oncogenic function can be context specific, and may vary depending on the protein complexes that EZH2 interacts with. To identify novel transcriptional collaborators of EZH2 in cancers, a computational approach was developed that integrates protein-DNA binding data, cell perturbation gene expression data, and compendiums of tumor expression profiles. This holistic approach identified E2F1, a known mediator of the Rb tumor suppressor, as a transcriptional collaborator of EZH2 in castration-resistant prostate cancer. Subsequent analysis and experimental validation found EZH2 and E2F1 cobind to a subset of chromatin sites lacking H3K27 trimethylation, and activate genes that are critical for prostate cancer progression. The collaboration of EZH2 and E2F1 in transcriptional regulation is also observed in diffuse large B-cell lymphoma cell lines, where activation of the transcriptional network is concordant with the cellular response to the EZH2 inhibitor. (C) 2015 AACR. C1 [Xu, Han; Xu, Kexin; He, Housheng H.; Zang, Chongzhi; Chen, Chen-Hao; Chen, Yiwen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Xu, Han; Xu, Kexin; He, Housheng H.; Zang, Chongzhi; Chen, Chen-Hao; Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Xu, Han; Xu, Kexin; He, Housheng H.; Zang, Chongzhi; Chen, Chen-Hao; Chen, Yiwen; Qin, Qian; Wang, Su; Wang, Chenfei; Hu, Shengen; Li, Fugen; Long, Henry; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Xu, Kexin; He, Housheng H.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Xu, Kexin; He, Housheng H.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA USA. [Liu, X. Shirley] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. RP Brown, M (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.; Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Brown, M (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Liu, XS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu; xsliu@jimmy.harvard.edu RI Zang, Chongzhi/D-1445-2011; OI Brown, Myles/0000-0002-8213-1658 FU NIH [GM056211, HG4069, 1K99CA178199-01A1, K99CA172948, K99CA175290]; Prostate Cancer Foundation Young Investigator award; Dana-Farber Cancer Institute supports; National Science Foundation of China [NSFC 31329003] FX This work was funded by NIH grants (GM056211 and HG4069 to X. Shirley Liu, 1K99CA178199-01A1 to Kexin Xu, K99CA172948 to Househeng H. He, and K99CA175290 to Yiwen Chen), Prostate Cancer Foundation Young Investigator award (to Kexin Xu), Dana-Farber Cancer Institute supports (to the Center of Functional Cancer Epigenetics), and National Science Foundation of China (NSFC 31329003 to X. Shirley Lu). NR 48 TC 1 Z9 1 U1 6 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2016 VL 14 IS 2 BP 163 EP 172 DI 10.1158/1541-7786.MCR-15-0313 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DG3XI UT WOS:000372003900003 PM 26659825 ER PT J AU Gannon, HS Kaplan, N Tsherniak, A Vazquez, F Weir, BA Hahn, WC Meyerson, M AF Gannon, Hugh S. Kaplan, Nathan Tsherniak, Aviad Vazquez, Francisca Weir, Barbara A. Hahn, William C. Meyerson, Matthew TI Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy SO MOLECULAR CANCER RESEARCH LA English DT Article ID LUNG ADENOCARCINOMA; CANCER-THERAPY; MUTATIONS; MAP2K1; EFFICACY; PATIENT; TRIAL; SENSITIVITY; EVEROLIMUS; KINASE AB The identification of somatic genetic alterations that confer sensitivity to pharmacologic inhibitors has led to new cancer therapies. To identify mutations that confer an exceptional dependency, shRNA-based loss-of-function data were analyzed from a dataset of numerous cell lines to reveal genes that are essential in a small subset of cancer cell lines. Once these cell lines were determined, detailed genomic characterization from these cell lines was utilized to ascertain the genomic aberrations that led to this extreme dependency. This method, in a large subset of lung cancer cell lines, yielded a single lung adenocarcinoma cell line, NCI-H1437, which is sensitive to RNA interference of MAP2K1 expression. Notably, NCI-H1437 is the only lung cancer cell line included in the dataset with a known activating mutation in MAP2K1 (Q56P). Subsequent validation using shRNA and CRISPR-Cas9 confirmed MAP2K1 dependency. In vitro and in vivo inhibitor studies established that NCI-H1437 cells are sensitive to MEK1 inhibitors, including the FDA-approved drug trametinib. Like NCI-H1437 cells, the MAP2K1-mutant cell lines SNU-C1 (colon) and OCUM-1 (gastric) showed decreased viability after MAP2K1 depletion via Cas9-mediated gene editing. Similarly, these cell lines were particularly sensitive to trametinib treatment compared with control cell lines. On the basis of these data, cancers that harbor driver mutations in MAP2K1 could benefit from treatment with MEK1 inhibitors. Furthermore, this functional data mining approach provides a general method to experimentally test genomic features that confer dependence in tumors. C1 [Gannon, Hugh S.; Kaplan, Nathan; Tsherniak, Aviad; Vazquez, Francisca; Weir, Barbara A.; Hahn, William C.; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. [Gannon, Hugh S.; Kaplan, Nathan; Vazquez, Francisca; Weir, Barbara A.; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Hahn, William C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM matthew_meyerson@dfci.harvard.edu FU NIH [F32 CA196141, U01 CA176058]; American Cancer Society Research Professorship; NIH (NCI) [1R35 CA197568]; NIH (DOD) [W81XWH-12-1-0269] FX This work was supported by the NIH (F32 CA196141, U01 CA176058, NCI 1R35 CA197568, and DOD W81XWH-12-1-0269) and the American Cancer Society Research Professorship. NR 32 TC 2 Z9 2 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD FEB PY 2016 VL 14 IS 2 BP 207 EP 215 DI 10.1158/1541-7786.MCR-15-0321 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA DG3XI UT WOS:000372003900007 PM 26582713 ER PT J AU Yoo, B Kavishwar, A Ross, A Pantazopoulos, P Moore, A Medarova, Z AF Yoo, Byunghee Kavishwar, Amol Ross, Alana Pantazopoulos, Pamela Moore, Anna Medarova, Zdravka TI In Vivo Detection of miRNA Expression in Tumors Using an Activatable Nanosensor SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Nanosensors; miRNA; Oligonucleotides; Activatable probes; Fluorescence; Magnetic nanoparticles; Cancer; Metastasis ID BREAST-CANCER; IMAGING-SYSTEM; MICRORNAS; CELLS; METASTASIS; MIR-B-10; SITU; NANOPARTICLES; HYBRIDIZATION; MICROARRAY AB Purpose: The development of tools for the analysis of microRNA (miRNA) function in tumors can advance our diagnostic and prognostic capabilities. Here, we describe the development of technology for the profiling of miRNA expression in the tumors of live animals. Procedures: The approach is based on miRNA nanosensors consisting of sensor oligonucleotides conjugated to magnetic nanoparticles for systemic delivery. Feasibility was demonstrated for the detection of miR-10b, implicated in epithelial to mesenchymal transition and the development of metastasis. The miR-10b nanosensor was tested in vivo in two mouse models of cancer. In the first model, mice were implanted subcutaneously with MDA-MB-231-luc-D3H2LN tumors, in which miR-10b was inhibited. In the second model, mice were implanted bilaterally with metastatic MDA-MB-231 and nonmetastatic MCF-7 cells. The nanosensors were injected intravenously, and fluorescence intensity in the tumors was monitored over time. Results: We showed that the described nanosensors are capable of discriminating between tumors based on their expression of miR-10b. Radiant efficiency was higher in the miR-10b-active tumors than in the miR-10b-inhibited tumors and in the MDA-MB-231 tumors relative to the MCF-7 tumors. Conclusions: The described technology provides an important tool that could be used to answer questions about microRNA function in cancer. C1 [Yoo, Byunghee; Kavishwar, Amol; Ross, Alana; Pantazopoulos, Pamela; Moore, Anna; Medarova, Zdravka] Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Mol Imaging Lab, Boston, MA 02129 USA. [Yoo, Byunghee; Kavishwar, Amol; Ross, Alana; Pantazopoulos, Pamela; Moore, Anna; Medarova, Zdravka] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Moore, Anna; Medarova, Zdravka] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Moore, A; Medarova, Z (reprint author), Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Mol Imaging Lab, Boston, MA 02129 USA.; Moore, A; Medarova, Z (reprint author), Harvard Univ, Sch Med, Boston, MA 02129 USA.; Moore, A; Medarova, Z (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. EM amoore@helix.mgh.harvard.edu; zmedarova@mgh.harvard.edu OI Kavishwar, Amol/0000-0001-8214-6625 FU National Cancer Institute [R01CA16346101A1]; Young Investigator Award by the Breast Cancer Alliance [5T32CA009502] FX The study was supported under grants R01CA16346101A1 from the National Cancer Institute to ZM, the Young Investigator Award by the Breast Cancer Alliance to ZM, and 5T32CA009502 to AM. NR 40 TC 0 Z9 0 U1 7 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2016 VL 18 IS 1 BP 70 EP 78 DI 10.1007/s11307-015-0863-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG7JX UT WOS:000372261700008 PM 25987466 ER PT J AU Herraiz, JL Herranz, E Cal-Gonzalez, J Vaquero, JJ Desco, M Cusso, L Udias, JM AF Herraiz, Joaquin L. Herranz, Elena Cal-Gonzalez, Jacobo Vaquero, Juan J. Desco, Manuel Cusso, Lorena Udias, Jose M. TI Automatic Cardiac Self-Gating of Small-Animal PET Data SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE List-mode; PET; Small animal; Cardiac gating; Self-gating ID GATED PET; RECONSTRUCTION; TOMOGRAPHY; SOFTWARE; SCANNER; 1ST AB Purpose: The cardiac gating signal (CGS) in positron emission tomography (PET) studies is usually obtained from an electrocardiography (ECG) monitor. In this work, we propose a method to obtain the CGS in small-animal PET using the acquired list-mode data without using any hardware or end-user input. Procedures: The CGS was obtained from the number of coincidences over time acquired in the lines-of-response connected with the cardiac region. This region is identified in the image as its value changes with frequencies in the range of 3 to 12 Hz. The procedure was tested in a study with 29 Wistar rats and 6 mice injected with 2-deoxy-2-[F-18]fluoro-D-glucose, which underwent a 45-min single-bed list-mode PET scan of the heart syncronized with an ECG. The estimated signals and the reconstructed images using eight-gated frames were compared with the ones obtained using the ECG signal from the monitor. Results: The differences of the PET-based CGS with respect to the ECG relative to the duration of the heartbeats were 5.6 % in rats and 11.0 % in mice. The reconstructed gated images obtained from the proposed method do not differ qualitatively with respect to the ones obtained with the ECG. The quantitative analysis of both set of images were performed measuring the volume of the left ventricle (LV) of the rats in the end-of-systole and end-of-diastole phase. The differences found in these parameters between both methods were below 12.1 % in the ESV and 9.3 % in the EDV with a 95 % confidence interval, which are comparable to the accuracy (7 %) of the method used for segmenting the LV. Conclusion: The proposed method is able to provide a valid and accurate CGS in small-animal PET list-mode data. C1 [Herraiz, Joaquin L.] MIT, Madrid MIT M Vis Consortium, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Herraiz, Joaquin L.; Udias, Jose M.] Univ Complutense Madrid, CEI Moncloa, Grp Fis Nucl, Madrid, Spain. [Herranz, Elena] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Herranz, Elena] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cal-Gonzalez, Jacobo] Med Univ Vienna, Ctr Med Phys & Biomed Engn, Vienna, Austria. [Vaquero, Juan J.; Desco, Manuel; Cusso, Lorena] Univ Carlos III Madrid, Dept Ingn Biomed & Ingn Aerosp, Leganes, Spain. [Vaquero, Juan J.; Desco, Manuel; Cusso, Lorena] Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain. [Desco, Manuel; Cusso, Lorena] Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain. RP Herraiz, JL (reprint author), MIT, Madrid MIT M Vis Consortium, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Herraiz, JL (reprint author), Univ Complutense Madrid, CEI Moncloa, Grp Fis Nucl, Madrid, Spain. EM herraiz@mit.edu RI Udias, Jose/A-7523-2010; Vaquero, Juan Jose/D-3033-2009; LOPEZ HERRAIZ, JOAQUIN/E-9234-2010; Desco, Manuel/D-2822-2009 OI Udias, Jose/0000-0003-3714-764X; Vaquero, Juan Jose/0000-0001-9200-361X; LOPEZ HERRAIZ, JOAQUIN/0000-0001-7208-8863; Desco, Manuel/0000-0003-0989-3231 FU Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid (Spain) through the Madrid-MIT M+Vision Consortium, Comunidad de Madrid [S2013/MIT-3024 TOPUS-CM]; UCM [910059]; CPAN (Consolider-Ingenio [CSPD-2007-00042]; RIC-RETIC network, Spanish MINECO [RD12/0042/0057]; Ministerio de Ciencia e Innovacion, Spanish Government (ENTEPRASE) [PSE-300000-2009-5, TEC2007-64731/TCM]; European Regional funds 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, Comunidad de Madrid (S2013/MIT-3024 TOPUS-CM), UCM (Grupos UCM, 910059), CPAN (Consolider-Ingenio 2010, CSPD-2007-00042), RIC-RETIC network, Spanish MINECO (RD12/0042/0057), Ministerio de Ciencia e Innovacion, Spanish Government (ENTEPRASE grant, PSE-300000-2009-5 and TEC2007-64731/TCM), and European Regional funds. NR 20 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD FEB PY 2016 VL 18 IS 1 BP 109 EP 116 DI 10.1007/s11307-015-0868-y PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DG7JX UT WOS:000372261700012 PM 26054381 ER PT J AU Kalkhoran, S Padilla, JL Neilands, TB Ling, PM AF Kalkhoran, Sara Padilla, James L. Neilands, Torsten B. Ling, Pamela M. TI Multiple tobacco product use among young adult bar patrons in New Mexico SO PREVENTIVE MEDICINE LA English DT Article DE Electronic cigarettes; Tobacco use; Tobacco products; Young adult ID ELECTRONIC CIGARETTE USE; HIGH-SCHOOL-STUDENTS; HARD-TO-REACH; COLLEGE-STUDENTS; UNITED-STATES; INDUSTRY DOCUMENTS; SMOKELESS TOBACCO; NICOTINE PRODUCTS; HOOKAH SMOKING; DUAL-USE AB Introduction. Use of non-cigarette tobacco products is common, and e-cigarette use is increasing among young adults. We aimed to identify use of other tobacco products among young adult bar patrons in the context of a bar-based intervention to decrease cigarette smoking. Methods. 2291 cross-sectional surveys were collected from young adults in bars in Albuquerque, New Mexico using time-location sampling between 2011 and 2013 (N = 1142 in 2011, N = 1149 in 2012-2013), 2 and 3 years into an intervention to reduce cigarette use, and analyzed in 2014-2015. Participants reported current (i.e. past 30-day) use of cigarettes, snus, dip, cigarillos, hookah, and e-cigarettes, demographics, and tobacco-related attitudes. Multiple imputation was used to account for planned missing data. Logistic regression determined correlates of multiple tobacco product use. Results. Cigarette smoking in the population decreased during the intervention from 43% to 37%. Over 60% of current cigarette smokers reported poly-use, most frequently with e-cigarettes (46%) and hookah (44%), followed by cigarillos (24%), dip (15%), and snus (14%) in 2012-2013. Among cigarette smokers, current e-cigarette use increased, while use of other products decreased during the intervention. Odds of poly-use (versus smoking cigarettes only) were greater among males and those reporting past 30-day binge drinking, and lower in those who strongly believed secondhand smoke exposure is harmful. Conclusions. Among young adult bar patrons in Albuquerque, New Mexico, most cigarette smokers reported currently using at least one other tobacco product. Public health interventions should address use of all tobacco products, use of which may rise despite decreased cigarette use. (C) 2015 Published by Elsevier Inc. C1 [Kalkhoran, Sara; Ling, Pamela M.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [Padilla, James L.] New Mexico Dept Hlth, Tobacco Use Prevent & Control Program, Albuquerque, NM USA. [Neilands, Torsten B.] Univ Calif San Francisco, Dept Med, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. [Ling, Pamela M.] Univ Calif San Francisco, Cardiovasc Res Inst, Ctr Tobacco Control Res & Educ, San Francisco, CA 94143 USA. [Kalkhoran, Sara] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Kalkhoran, Sara] Harvard Univ, Sch Med, Boston, MA USA. RP Ling, PM (reprint author), Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Ctr Tobacco Control Res & Educ, 530 Parnassus Ave,Suite 366, San Francisco, CA 94143 USA. EM pamela.ling@ucsf.edu FU NIH NRSA [T32HP19025]; National Cancer Institute [U01-154240]; New Mexico Department of Health Tobacco Use Prevention and Control Program FX This work was supported by NIH NRSA T32HP19025 (Kalkhoran), and the National Cancer Institute (U01-154240). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The study sponsors had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. The authors thank the New Mexico Department of Health Tobacco Use Prevention and Control Program for funding young adult tobacco intervention efforts related to this study. NR 60 TC 3 Z9 3 U1 3 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD FEB PY 2016 VL 83 BP 16 EP 21 DI 10.1016/j.ypmed.2015.11.024 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DG2XD UT WOS:000371933200004 PM 26666395 ER PT J AU Bendapudi, PK Makar, RS AF Bendapudi, Pavan K. Makar, Robert S. TI An Algorithmic Approach to the Diagnosis and Management of the Thrombotic Microangiopathies SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID HEMOLYTIC-UREMIC SYNDROME; SEVERE ADAMTS13 DEFICIENCY; THROMBOCYTOPENIC PURPURA; CLINICAL PRESENTATION; PROSPECTIVE COHORT; PLASMA-EXCHANGE; OUTCOMES; UTILITY; IMPACT C1 [Bendapudi, Pavan K.; Makar, Robert S.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, GRJ-148,55 Fruit St, Boston, MA 02114 USA. [Bendapudi, Pavan K.] Massachusetts Gen Hosp, Div Hematol, GRJ-148,55 Fruit St, Boston, MA 02114 USA. [Bendapudi, Pavan K.] Harvard Univ, Sch Med, Boston, MA USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, GRJ-148,55 Fruit St, Boston, MA 02114 USA. EM rmakar@mgh.harvard.edu NR 23 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2016 VL 145 IS 2 BP 152 EP 154 DI 10.1093/ajcp/aqw003 PG 3 WC Pathology SC Pathology GA DF6DW UT WOS:000371447100002 PM 26864515 ER PT J AU Kluk, MJ Ho, C Yu, HB Chen, BJ Neuberg, DS Dal Cin, P Woda, BA Pinkus, GS Rodig, SJ AF Kluk, Michael J. Ho, Caleb Yu, Hongbo Chen, Benjamin J. Neuberg, Donna S. Dal Cin, Paola Woda, Bruce A. Pinkus, Geraldine S. Rodig, Scott J. TI MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE B-cell lymphoma; Diffuse large B-cell lymphoma; Burkitt lymphoma; MYC; Immunohistochemistry; Fluorescence in situ hybridization ID RITUXIMAB PLUS CYCLOPHOSPHAMIDE; BURKITT-LYMPHOMA; PROGNOSTIC-SIGNIFICANCE; BIOMARKER CONSORTIUM; PROTEIN EXPRESSION; MESSENGER-RNA; COPY NUMBER; GENE; BCL2; TRANSLOCATION AB Objectives: Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice. Methods: We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review. Results: Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20%-100%). There was no statistically significant association between IHC score and MYC copy number. Conclusions: Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MY C fluorescence in situ hybridization are both recommended to identify MYC-driven B-cell lymphomas. C1 [Kluk, Michael J.; Ho, Caleb; Dal Cin, Paola; Pinkus, Geraldine S.; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Amory 3rd Floor,75 Francis St, Boston, MA 02115 USA. [Yu, Hongbo; Chen, Benjamin J.; Woda, Bruce A.] Univ Massachusetts, Mem Med Ctr, Dept Pathol, Worcester, MA 01605 USA. [Yu, Hongbo; Chen, Benjamin J.; Woda, Bruce A.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Rodig, SJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Amory 3rd Floor,75 Francis St, Boston, MA 02115 USA. EM srodig@partners.org NR 37 TC 2 Z9 2 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2016 VL 145 IS 2 BP 166 EP 179 DI 10.1093/ajcp/aqv028 PG 14 WC Pathology SC Pathology GA DF6DW UT WOS:000371447100005 PM 26834124 ER PT J AU Rudolf, JW Lewandrowski, EL Lewandrowski, KB Januzzi, JL Bajwa, EK Baron, JM AF Rudolf, Joseph W. Lewandrowski, Elizabeth L. Lewandrowski, Kent B. Januzzi, James L. Bajwa, Ednan K. Baron, Jason M. TI ST2 Predicts Mortality and Length of Stay in a Critically III Noncardiac Intensive Care Unit Population SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Suppression of tumorigenicity 2; ST2; High-sensitivity troponin T; hsTnT; Cardiac biomarker; Clinical decision support ID EMERGENCY-DEPARTMENT PATIENTS; DECOMPENSATED HEART-FAILURE; LONG-TERM MORTALITY; FAMILY-MEMBER ST2; SOLUBLE ST2; INTERLEUKIN-1 RECEPTOR; MYOCARDIAL-INFARCTION; TROPONIN-T; PROTEIN; CELLS AB Objectives: The biomarker suppression of tumorigenicity 2 (ST2) is a well-established clinical biomarker of cardiac strain and is frequently elevated in a variety of cardiac conditions. Here, we sought to evaluate the prognostic value of ST2 in critically ill medical intensive care unit (MICU) patients without primary) cardiac illness. Methods: We measured ST2 and high-sensitivity troponin T (hsTnT) on plasma specimens collected on 441 patients following admission to a noncardiac MICU and evaluated the prognostic power of ST2 both alone and in multivariate models. Results: Of these critically ill patients, 96% exhibited ST2 concentrations above the reference interval. ST2 concentrations were highly predictive of intensive care unit and hospital length of stay, as well as in-hospital mortality, with high concentrations predicting a poor prognosis. Rates of in-hospital mortality were more than four times higher in patients with ST2 concentrations in the highest compared with the lowest quartile. In multivariate analysis, ST2 remained an important predictor of death after adjustment for age, hsTnT, and common diagnoses. Conclusions: ST2 is increased and predictive of prognosis in critically ill patients without primary cardiac disease, suggesting that critically ill patients may often have unrecognized cardiac injury. Clinical decision support algorithms incorporating ST2 and hsTnT results may be useful in patient risk stratification. C1 [Rudolf, Joseph W.; Lewandrowski, Elizabeth L.; Lewandrowski, Kent B.; Baron, Jason M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bajwa, Ednan K.] Massachusetts Gen Hosp, Div Pulm Crit Care, Boston, MA 02114 USA. [Rudolf, Joseph W.; Lewandrowski, Elizabeth L.; Lewandrowski, Kent B.; Januzzi, James L.; Bajwa, Ednan K.; Baron, Jason M.] Harvard Univ, Sch Med, Boston, MA USA. RP Baron, JM (reprint author), Massachusetts Gen Hosp, Med Director Core Lab, 55 Fruit St,GRJ-239C, Boston, MA 02114 USA. EM jmbaron@partners.org FU Critical Diagnostics, San Diego, CA; Roche Diagnostics, Indianapolis, IN; Roche Diagnostics FX This study was supported in part by Critical Diagnostics, San Diego, CA and Roche Diagnostics, Indianapolis, IN. Critical Diagnostics performed the ST2 testing. Roche Diagnostics provided reagents for hsTnT testing and grant funding for the previous study investigating hsTnT (in the absence to ST2). Grant funding was used to cover PI (ELL) time required to oversee the hsTnT study as well as laboratory resources required to perform the testing. NR 38 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 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2016 VL 145 IS 2 BP 203 EP 210 DI 10.1093/ajcp/aqv082 PG 8 WC Pathology SC Pathology GA DF6DW UT WOS:000371447100008 PM 26857195 ER PT J AU Sclocco, R Kim, J Garcia, RG Sheehan, JD Beissner, F Bianchi, AM Cerutti, S Kuo, B Barbieri, R Napadow, V AF Sclocco, Roberta Kim, Jieun Garcia, Ronald G. Sheehan, James D. Beissner, Florian Bianchi, Anna M. Cerutti, Sergio Kuo, Braden Barbieri, Riccardo Napadow, Vitaly TI Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea SO CEREBRAL CORTEX LA English DT Article DE brain-gut interactions; motion sickness; neuroimaging; parasympathetic; sympathetic ID HEART-RATE-VARIABILITY; MOTION-SICKNESS; EMOTIONAL EXPERIENCE; PERCEPTION; INTEROCEPTION; METAANALYSIS; RECORDINGS; COMPONENTS; AROUSAL; HUMANS AB While autonomic outflow is an important co-factor of nausea physiology, central control of this outflow is poorly understood. We evaluated sympathetic (skin conductance level) and cardiovagal (high-frequency heart rate variability) modulation, collected synchronously with functional MRI (fMRI) data during nauseogenic visual stimulation aimed to induce vection in susceptible individuals. Autonomic data guided analysis of neuroimaging data, using a stimulus-based (analysis windows set by visual stimulation protocol) and percept-based (windows set by subjects' ratings) approach. Increased sympathetic and decreased parasympathetic modulation was associated with robust and anti-correlated brain activity in response to nausea. Specifically, greater autonomic response was associated with reduced fMRI signal in brain regions such as the insula, suggesting an inhibitory relationship with premotor brainstem nuclei. Interestingly, some sympathetic/parasympathetic specificity was noted. Activity in default mode network and visual motion areas was anti-correlated with parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical activity was anti-correlated with sympathetic outflow during recovery, soon after cessation of nauseogenic stimulation. These results suggest divergent central autonomic control for sympathetic and parasympathetic response to nausea. Autonomic outflow and the central autonomic network underlying ANS response to nausea may be an important determinant of overall nausea intensity and, ultimately, a potential therapeutic target. C1 [Sclocco, Roberta; Kim, Jieun; Garcia, Ronald G.; Beissner, Florian; Napadow, Vitaly] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Sclocco, Roberta; Bianchi, Anna M.; Cerutti, Sergio] Politecn Milan, Dept Elect Informat & Bioengn, Via Golgi 39, I-20133 Milan, Italy. [Sclocco, Roberta; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Sheehan, James D.; Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Garcia, Ronald G.] Univ Santander UDES, Sch Med, Bucaramanga, Colombia. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP Sclocco, R (reprint author), Politecn Milan, Dept Elect Informat & Bioengn, Via Golgi 39, I-20133 Milan, Italy. EM roberta.sclocco@polimi.it OI Sclocco, Roberta/0000-0001-8837-5218; Garcia, Ronald Gerardo/0000-0002-8325-9944 FU National Institutes of Health [P01-AT006663, R01-AT007550, R01-AR064367, K23-DK069614, R21-AR057920]; National Center for Research Resources (Harvard Clinical and Translational Science Center) [P41RR14075, CRC 1 UL1 RR025758]; MGH Department of Anesthesia, Critical Care and Pain Medicine; International Foundation of Functional Gastrointestinal Disorders FX This work was supported by the National Institutes of Health (grant numbers P01-AT006663, R01-AT007550, and R01-AR064367 to VN, K23-DK069614 to BK, and R21-AR057920 to VN, BK and RB); the National Center for Research Resources (P41RR14075; CRC 1 UL1 RR025758, Harvard Clinical and Translational Science Center); the MGH Department of Anesthesia, Critical Care and Pain Medicine and the International Foundation of Functional Gastrointestinal Disorders. NR 45 TC 8 Z9 8 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2016 VL 26 IS 2 BP 485 EP 497 DI 10.1093/cercor/bhu172 PG 13 WC Neurosciences SC Neurosciences & Neurology GA DF7FE UT WOS:000371522500003 PM 25115821 ER PT J AU Jacobsen, MM Walensky, RP AF Jacobsen, Margo M. Walensky, Rochelle P. TI Modeling and Cost-Effectiveness in HIV Prevention SO CURRENT HIV/AIDS REPORTS LA English DT Article DE HIV; Prevention; Cost-effectiveness; Modeling; Science of prevention; Review ID TO-CHILD TRANSMISSION; PREEXPOSURE PROPHYLAXIS; SERODISCORDANT COUPLES; AFRICAN WOMEN; SOUTH-AFRICA; ANTIRETROVIRAL PROPHYLAXIS; UNITED-STATES; INFECTION; IMPACT; MEN AB With HIV funding plateauing and the number of people living with HIV increasing due to the rollout of life-saving antiretroviral therapy, policy makers are faced with increasingly tighter budgets to manage the ongoing HIV epidemic. Cost-effectiveness and modeling analyses can help determine which HIV interventions may be of best value. Incidence remains remarkably high in certain populations and countries, making prevention key to controlling the spread of HIV. This paper briefly reviews concepts in modeling and cost-effectiveness methodology and then examines results of recently published cost-effectiveness analyses on the following HIV prevention strategies: condoms and circumcision, behavioral- or community-based interventions, prevention of mother-to-child transmission, HIV testing, pre-exposure prophylaxis, and treatment as prevention. We find that the majority of published studies demonstrate cost-effectiveness; however, not all interventions are affordable. We urge continued research on combination strategies and methodologies that take into account willingness to pay and budgetary impact. C1 [Jacobsen, Margo M.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr RPW, MMJ, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Jacobsen, Margo M.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Internal Med RPW, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp RPW, Div Infect Dis, Boston, MA USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res RPW, Boston, MA USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr RPW, MMJ, 50 Staniford St,9th Floor, Boston, MA 02114 USA.; Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med RPW, 50 Staniford St,9th Floor, Boston, MA 02114 USA.; Walensky, RP (reprint author), Brigham & Womens Hosp RPW, Div Infect Dis, Boston, MA USA.; Walensky, RP (reprint author), Harvard Univ, Sch Med, Ctr AIDS Res RPW, Boston, MA USA. EM rwalensky@partners.org FU National Institutes of Health; LeClair Ryan FX Rochelle P. Walensky reports grants from the National Institutes of Health and personal fees from LeClair Ryan. NR 60 TC 0 Z9 0 U1 4 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1548-3568 EI 1548-3576 J9 CURR HIV-AIDS REP JI Curr. Hiv/Aids Rep. PD FEB PY 2016 VL 13 IS 1 BP 64 EP 75 DI 10.1007/s11904-016-0303-2 PG 12 WC Infectious Diseases SC Infectious Diseases GA DG1CM UT WOS:000371802900008 PM 26830283 ER PT J AU Ingelfinger, JR Kalantar-Zadeh, K Schaefer, F AF Ingelfinger, J. R. Kalantar-Zadeh, K. Schaefer, F. CA World Kidney Day Steering Comm TI Averting the legacy of kidney disease: focus on childhood SO INTERNAL MEDICINE JOURNAL LA English DT Editorial Material ID RENAL REPLACEMENT THERAPY; PROSPECTIVE COHORT; CHILDREN; EPIDEMIOLOGY; INJURY; FAILURE C1 [Ingelfinger, J. R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Ingelfinger, J. R.] Massachusetts Gen Hosp, Mass Gen Hosp Children, Dept Pediat Nephrol, Boston, MA 02114 USA. [Kalantar-Zadeh, K.] Univ Calif Irvine, Sch Med, Dept Med Pediat & Publ Hlth, Div Nephrol & Hypertens, Irvine, CA 92717 USA. [Kalantar-Zadeh, K.] Vet Affairs VA Long Beach Hlth Care Syst, Long Beach, CA USA. [Kalantar-Zadeh, K.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Schaefer, F.] Heidelberg Univ, Dept Pediat, Div Pediat Nephrol, Ctr Pediat & Adolescent Med, Heidelberg, Germany. RP Ingelfinger, JR (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.; Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, Mass Gen Hosp Children, Dept Pediat Nephrol, Boston, MA 02114 USA. OI Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 16 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1444-0903 EI 1445-5994 J9 INTERN MED J JI Intern. Med. J. PD FEB PY 2016 VL 46 IS 2 BP 133 EP 138 DI 10.1111/imj.12972 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DF1AS UT WOS:000371071400001 PM 26899885 ER PT J AU Schoenfeld, AJ Grady, D AF Schoenfeld, Adam Jacob Grady, Deborah TI Adverse Effects Associated With Proton Pump Inhibitors SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID METAANALYSIS; IMPACT; RISK C1 [Schoenfeld, Adam Jacob; Grady, Deborah] Univ Calif San Francisco, 3333 Calif St,Ste 265,POB 0936, San Francisco, CA 94118 USA. [Grady, Deborah] San Francisco VA Med Ctr, Med, San Francisco, CA USA. RP Schoenfeld, AJ (reprint author), Univ Calif San Francisco, 3333 Calif St,Ste 265,POB 0936, San Francisco, CA 94118 USA. EM Adam.Schoenfeld@ucsf.edu NR 12 TC 12 Z9 13 U1 0 U2 5 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 FEB PY 2016 VL 176 IS 2 BP 172 EP 174 DI 10.1001/jamainternmed.2015.7927 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DD0RR UT WOS:000369627600007 PM 26751904 ER PT J AU Wong, SPY Vig, EK Taylor, JS Burrows, NR Liu, CF Williams, DE Hebert, PL O'Hare, AM AF Wong, Susan P. Y. Vig, Elizabeth K. Taylor, Janelle S. Burrows, Nilka R. Liu, Chuan-Fen Williams, Desmond E. Hebert, Paul L. O'Hare, Ann M. TI Timing of Initiation of Maintenance Dialysis A Qualitative Analysis of the Electronic Medical Records of a National Cohort of Patients From the Department of Veterans Affairs SO JAMA INTERNAL MEDICINE LA English DT Article ID DECISION-MAKING; HEALTH-CARE; KIDNEY-DISEASE; SURVIVAL; COMORBIDITY; MORTALITY; HARMFUL; TRENDS; START; AGE AB IMPORTANCE There is often considerable uncertainty about the optimal time to initiate maintenance dialysis in individual patients and little medical evidence to guide this decision. OBJECTIVE To gain a better understanding of the factors influencing the timing of initiation of dialysis in clinical practice. DESIGN, SETTING, AND PARTICIPANTS A qualitative analysis was conducted using the electronic medical records from the Department of Veterans Affairs (VA) of a national random sample of 1691 patients for whom the decision to initiate maintenance dialysis occurred in the VA between January 1, 2000, and December 31, 2009. Data analysis took place from June 1 to November 30, 2014. MAIN OUTCOMES AND MEASURES Central themes related to the timing of initiation of dialysis as documented in patients' electronic medical records. RESULTS Of the 1691 patients, 1264 (74.7%) initiated dialysis as inpatients and 1228 (72.6%) initiated dialysis with a hemodialysis catheter. Cohort members met with a nephrologist during an outpatient clinic visit a median of 3 times (interquartile range, 0-6) in the year prior to initiation of dialysis. The mean (SD) estimated glomerular filtration rate at the time of initiation for cohort members was 10.4 (5.7) mL/min/1.73m(2). The timing of initiation of dialysis reflected the complex interplay of at least 3 interrelated and dynamic processes. The first was physician practices, which ranged from practices intended to prepare patients for dialysis to those intended to forestall the need for dialysis by managing the signs and symptoms of uremia with medical interventions. The second process was sources of momentum. Initiation of dialysis was often precipitated by clinical events involving acute illness or medical procedures. In these settings, the imperative to treat often seemed to override patient choice. The third process was patient-physician dynamics. Interactions between patients and physicians were sometimes adversarial, and physician recommendations to initiate dialysis sometimes seemed to conflict with patient priorities. CONCLUSIONS AND RELEVANCE The initiation of maintenance dialysis reflects the care practices of individual physicians, sources of momentum for initiation of dialysis, interactions between patients and physicians, and the complex interplay of these dynamic processes over time. Our findings suggest opportunities to improve communication between patients and physicians and to better align these processes with patients' values, goals, and preferences. C1 [Wong, Susan P. Y.; Vig, Elizabeth K.; O'Hare, Ann M.] Univ Washington, Dept Med, 1959 NE Pacific St,POB 356521, Seattle, WA 98195 USA. [Vig, Elizabeth K.; O'Hare, Ann M.] VA Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA. [Taylor, Janelle S.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Burrows, Nilka R.] Ctr Dis Control & Prevent, Chron Kidney Dis Initiat, Div Diabet Translat, Atlanta, GA USA. [Liu, Chuan-Fen; Hebert, Paul L.] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev Ctr Innovat, Washington, DC USA. [Liu, Chuan-Fen; Hebert, Paul L.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Williams, Desmond E.] Ctr Dis Control & Prevent, Liberia Country Off, Div Global Hlth Protect, Atlanta, GA USA. RP Wong, SPY (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,POB 356521, Seattle, WA 98195 USA. EM spywong@uw.edu FU United States Department of Veterans Affairs [VA IIR 09-094]; VA Puget Sound Healthcare System [IAA 15FED1505101-0001]; Centers for Disease Control and Prevention [IAA 15FED1505101-0001]; Clinical Scientist in Nephrology Fellowship from the American Kidney Fund; Department of Veterans Affairs Health Services Research and Development Service; National Institutes of Health FX This study was supported by grant VA IIR 09-094 from the United States Department of Veterans Affairs and by Interagency Agreement IAA 15FED1505101-0001 between the VA Puget Sound Healthcare System and the Centers for Disease Control and Prevention. Dr Wong is supported by the Clinical Scientist in Nephrology Fellowship from the American Kidney Fund. Drs O'Hare, Hebert, and Liu reported having received research funding from the Department of Veterans Affairs Health Services Research and Development Service. Dr O'Hare also reported having received research funding from the National Institutes of Health and an honorarium from the American Society of Nephrology. NR 36 TC 7 Z9 7 U1 0 U2 2 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 FEB PY 2016 VL 176 IS 2 BP 228 EP 235 DI 10.1001/jamainternmed.2015.7412 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DD0RR UT WOS:000369627600017 PM 26809745 ER PT J AU Odejide, OO Cronin, AM Condron, N Earle, CC Wolfe, J Abel, GA AF Odejide, Oreofe O. Cronin, Angel M. Condron, Nolan Earle, Craig C. Wolfe, Joanne Abel, Gregory A. TI Timeliness of End-of-Life Discussions for Blood Cancers: A National Survey of Hematologic Oncologists SO JAMA INTERNAL MEDICINE LA English DT Letter ID CARE; PHYSICIANS C1 [Odejide, Oreofe O.; Cronin, Angel M.; Condron, Nolan; Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. [Odejide, Oreofe O.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Lymphoma, Boston, MA 02215 USA. [Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada. [Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Leukemia, Boston, MA 02215 USA. RP Odejide, OO (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. EM oreofe_odejide@dfci.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB PY 2016 VL 176 IS 2 BP 263 EP 265 DI 10.1001/jamainternmed.2015.6599 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DD0RR UT WOS:000369627600031 PM 26720644 ER PT J AU Mercuri, M Pascual, TNB Mahmarian, JJ Shaw, LJ Rehani, MM Paez, D Einstein, AJ AF Mercuri, Mathew Pascual, Thomas N. B. Mahmarian, John J. Shaw, Leslee J. Rehani, Madan M. Paez, Diana Einstein, Andrew J. CA INCAPS Investigators Grp TI Comparison of Radiation Doses and Best-Practice Use forMyocardial Perfusion Imaging in US and Non-US Laboratories: Findings From the IAEA (International Atomic Energy Agency) Nuclear Cardiology Protocols Study SO JAMA INTERNAL MEDICINE LA English DT Letter ID EXPOSURE C1 [Mercuri, Mathew; Einstein, Andrew J.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Med,Div Cardiol, 622 W 168th St,PH 10-203, New York, NY 10032 USA. [Pascual, Thomas N. B.; Paez, Diana] IAEA, Div Human Hlth, Sect Nucl Med & Diagnost Imaging, A-1400 Vienna, Austria. [Mahmarian, John J.] Houston Methodist DeBakey Heart & Vasc Ctr, Dept Cardiol, Houston, TX USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. [Rehani, Madan M.] IAEA, Radiat Protect Patients Unit, A-1400 Vienna, Austria. [Rehani, Madan M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Rehani, Madan M.] Harvard Univ, Sch Med, Boston, MA USA. [Einstein, Andrew J.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Radiol, New York, NY 10032 USA. RP Einstein, AJ (reprint author), Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Med,Div Cardiol, 622 W 168th St,PH 10-203, New York, NY 10032 USA. EM andrew.einstein@columbia.edu RI Lahoutte, Tony/O-6381-2016; Maffioli, Lorenzo Stefano/Q-4985-2016; OI Maffioli, Lorenzo Stefano/0000-0002-8867-2447; Al-Mallah, Mouaz/0000-0003-2348-0484 NR 6 TC 1 Z9 1 U1 0 U2 2 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 FEB PY 2016 VL 176 IS 2 BP 266 EP 269 DI 10.1001/jamainternmed.2015.7102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DD0RR UT WOS:000369627600033 PM 26720424 ER PT J AU Good, CB McConnell, M Downs, JR AF Good, Chester B. McConnell, Mark Downs, John R. TI Finding the Balance of Less Is More SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Good, Chester B.] Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Med, Pittsburgh, PA USA. [McConnell, Mark] Oscar G Johnson Vet Affairs Med Clin, Primary Care, Iron Mt, MI USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Med, San Antonio, TX 78229 USA. RP Good, CB (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Med, Univ Dr C, Pittsburgh, PA 15240 USA. EM chester.good@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 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD FEB PY 2016 VL 176 IS 2 BP 282 EP 283 DI 10.1001/jamainternmed.2015.8089 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA DD0RR UT WOS:000369627600045 PM 26830244 ER PT J AU Joffe, H Bromberger, JT AF Joffe, Hadine Bromberger, Joyce T. TI Shifting Paradigms About Hormonal Risk Factors for Postmenopausal Depression Age at Menopause as an Indicator of Cumulative Lifetime Exposure to Female Reproductive Hormones SO JAMA PSYCHIATRY LA English DT Editorial Material C1 [Joffe, Hadine] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Joffe, Hadine] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Bromberger, Joyce T.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Bromberger, Joyce T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Joffe, H (reprint author), Brigham & Womens Hosp, 75 Francis St,BB232C, Boston, MA 02115 USA. EM hjoffe@partners.org FU National Institutes of Health [R01MH082922, U01AG012531]; [U01AG012546] FX Dr Joffe's time was supported by National Institutes of Health grants R01MH082922 and U01AG012531 and Dr Bromberger's by grant U01AG012546. NR 7 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 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD FEB PY 2016 VL 73 IS 2 BP 111 EP 112 DI 10.1001/jamapsychiatry.2015.2701 PG 2 WC Psychiatry SC Psychiatry GA DF8MS UT WOS:000371612500007 PM 26746695 ER PT J AU Harris, JP Struzyna, LA Murphy, PL Adewole, DO Kuo, E Cullen, DK AF Harris, J. P. Struzyna, L. A. Murphy, P. L. Adewole, D. O. Kuo, E. Cullen, D. K. TI Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain SO JOURNAL OF NEURAL ENGINEERING LA English DT Article DE neurotransplantation; transplantation; bioengineering; cell replacement; axonal tracts; tissue engineering; biomaterials ID LONG-TERM SURVIVAL; STEM-CELL TRANSPLANTATION; SPINAL-CORD-INJURY; NERVOUS-SYSTEM; IN-VITRO; CARBOXYMETHYL CELLULOSE; FUNCTIONAL RECOVERY; PARKINSONS-DISEASE; CHONDROITINASE ABC; NEURITE OUTGROWTH AB Objective. Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach. We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results. The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter-white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 +/- 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 mu N of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance. Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain. The micro-TENN approach may offer the ability to treat several disorders that disrupt the connectome, including Parkinson's disease, traumatic brain injury, stroke, and brain tumor excision. C1 [Harris, J. P.; Struzyna, L. A.; Murphy, P. L.; Adewole, D. O.; Kuo, E.; Cullen, D. K.] Univ Penn, Perelman Sch Med, Dept Neurosurg, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. [Harris, J. P.; Struzyna, L. A.; Adewole, D. O.; Kuo, E.; Cullen, D. K.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Struzyna, L. A.; Adewole, D. O.] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. RP Cullen, DK (reprint author), Univ Penn, Perelman Sch Med, Dept Neurosurg, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA.; Cullen, DK (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. EM dkacy@mail.med.upenn.edu FU Penn Medicine Neuroscience Center; National Science Foundation [DGE-1321851]; National Institutes of Health [T32-NS043126, T32-GM007517]; Department of Veterans Affairs (RRD Merit Review) [B1097-I]; US Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program [W81XWH-13-207 004] FX Financial support was provided by the Penn Medicine Neuroscience Center, National Science Foundation (Graduate Research Fellowship DGE-1321851), National Institutes of Health (T32-NS043126 & T32-GM007517), Department of Veterans Affairs (RR&D Merit Review #B1097-I), and the US Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program (#W81XWH-13-207 004). The authors would like to thank Rob Mauck and Mike Hast in the Penn Center for Musculoskeletal Disorders Core for help in mechanical testing. Additional thanks go to Vincent Wu, Norma Alexis Brown, Alan He, Camila Robles-Oteiza, and Parker Schabel for technical contributions. NR 83 TC 2 Z9 3 U1 7 U2 23 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD FEB PY 2016 VL 13 IS 1 AR 016019 DI 10.1088/1741-2560/13/1/016019 PG 19 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA DF7XD UT WOS:000371570200020 PM 26760138 ER PT J AU Barch, DM Verfaellie, M Rao, SM AF Barch, Deanna M. Verfaellie, Mieke Rao, Stephen M. TI Introduction to JINS Special Issue on Human Brain Connectivity in the Modern Era: Relevance to Understanding Health and Disease SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Editorial Material ID INTRINSIC FUNCTIONAL CONNECTIVITY; RESTING-STATE; DISCONNEXION SYNDROMES; ORGANIZATION; NETWORKS; CORTEX; SCHIZOPHRENIA; ANIMALS; TRAINS; MRI C1 [Barch, Deanna M.] Washington Univ, St Louis, MO USA. [Verfaellie, Mieke] VA Boston Healthcare Syst, Boston, MA USA. [Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rao, Stephen M.] Cleveland Clin, Cleveland, OH 44106 USA. RP Barch, DM (reprint author), Washington Univ, St Louis, MO USA. NR 28 TC 1 Z9 1 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 101 EP 104 DI 10.1017/S1355617716000047 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200001 PM 27314141 ER PT J AU Hayes, JP Bigler, ED Verfaellie, M AF Hayes, Jasmeet P. Bigler, Erin D. Verfaellie, Mieke TI Traumatic Brain Injury as a Disorder of Brain Connectivity SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE Diffusion tensor imaging; white matter; fMRI; neural networks; corpus callosum; diffuse axonal injury ID DIFFUSE AXONAL INJURY; WHITE-MATTER INTEGRITY; TENSOR IMAGING FINDINGS; DEFAULT-MODE NETWORK; POSTTRAUMATIC-STRESS-DISORDER; SPORTS-RELATED CONCUSSION; AFGHANISTAN WAR VETERANS; RESTING-STATE FMRI; MINOR HEAD-INJURY; FUNCTIONAL CONNECTIVITY AB Objectives: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI)-related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. Methods: We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. Results: The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. Conclusions: TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. C1 [Hayes, Jasmeet P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Hayes, Jasmeet P.; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hayes, Jasmeet P.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Bigler, Erin D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Bigler, Erin D.] Brigham Young Univ, Ctr Neurosci, Provo, UT 84602 USA. [Bigler, Erin D.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA. [Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. RP Hayes, JP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM jphayes@bu.edu FU Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Award [I21 RX001594]; National Center for PTSD; VA Clinical Science Research and Development Service FX There are no financial disclosures or conflicts of interest to report for any of the authors. This work was supported in part by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service Award number I21 RX001594, the National Center for PTSD and the VA Clinical Science Research and Development Service. NR 160 TC 7 Z9 7 U1 5 U2 16 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 120 EP 137 DI 10.1017/S1355617715000740 PG 18 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200003 PM 26888612 ER PT J AU Teipel, S Grothe, MJ Zhou, J Sepulcre, J Dyrba, M Sorg, C Babiloni, C AF Teipel, Stefan Grothe, Michel J. Zhou, Juan Sepulcre, Jorge Dyrba, Martin Sorg, Christian Babiloni, Claudio TI Measuring Cortical Connectivity in Alzheimer's Disease as a Brain Neural Network Pathology: Toward Clinical Applications SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE Dementia diagnosis; Prognosis; PET; MRI; EEG; Treatment trials ID MILD COGNITIVE IMPAIRMENT; RESTING-STATE FMRI; DEFAULT-MODE NETWORK; WHITE-MATTER INTEGRITY; INTRINSIC FUNCTIONAL CONNECTIVITY; VARIANT FRONTOTEMPORAL DEMENTIA; INDEPENDENT COMPONENT ANALYSIS; DIFFUSION-TENSOR; AMYLOID-BETA; STRUCTURAL CONNECTIVITY AB Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer's disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior-posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. C1 [Teipel, Stefan] Univ Rostock, Dept Psychosomat Med, D-18055 Rostock, Germany. [Teipel, Stefan; Grothe, Michel J.; Dyrba, Martin] German Ctr Neurodegenerat Dis, DZNE, Gehlsheimer Str 20, D-18147 Rostock, Germany. [Zhou, Juan] Duke NUS Grad Med Sch, Neurosci & Behav Disorders Program, Ctr Cognit Neurosci, Singapore, Singapore. [Sepulcre, Jorge] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA USA. [Sorg, Christian] Tech Univ Munich, TUM NIC Neuroimaging Ctr, Dept Psychiat & Neuroradiol, D-80290 Munich, Germany. [Babiloni, Claudio] Univ Roma La Sapienza, Dept Physiol & Pharmacol V Erspamer, Piazzale Aldo Moro 5, I-00185 Rome, Italy. [Babiloni, Claudio] IRCCS San Raffaele Pisana Rome, Rome, Italy. RP Teipel, S (reprint author), German Ctr Neurodegenerat Dis, DZNE, Gehlsheimer Str 20, D-18147 Rostock, Germany. EM stefan.teipel@med.uni-rostock.de OI Grothe, Michel/0000-0003-2600-9022 FU "SinDem" (German Ministry of Research, BMBF) [16SV7091]; "AgeGain" (German Ministry of Research, BMBF); "GRIDCORE" (Italian Ministry of Health) [RF-2010-2319113]; "CONNAGE" (Italian Ministry of University and Technological Research, PRIN) [2010SH7H3F] FX The present review was developed and granted in the framework of the following projects: "SinDem" (German Ministry of Research, BMBF, 16SV7091), "AgeGain" (German Ministry of Research, BMBF), "GRIDCORE" (Italian Ministry of Health, RF-2010-2319113) and "CONNAGE" (Italian Ministry of University and Technological Research, PRIN2010-2011, prot. 2010SH7H3F). There are no conflicts of interest related to this manuscript. NR 236 TC 8 Z9 8 U1 15 U2 21 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 138 EP 163 DI 10.1017/S1355617715000995 PG 26 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200004 PM 26888613 ER PT J AU Unger, A Alm, KH Collins, JA O'Leary, JM Olson, IR AF Unger, Ashley Alm, Kylie H. Collins, Jessica A. O'Leary, Jacquelyn M. Olson, Ingrid R. TI Variation in White Matter Connectivity Predicts the Ability to Remember Faces and Discriminate Their Emotions SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Diffusion imaging; Faces; Emotion; Prosopagnosia; Face memory; Hypoemotionality ID INFERIOR LONGITUDINAL FASCICULUS; TRAUMATIC BRAIN-INJURY; TEMPORAL-LOBE; VISUAL HYPOEMOTIONALITY; STRUCTURAL CONNECTIVITY; DIFFUSION MRI; RECOGNITION; MEMORY; TRACTOGRAPHY; STIMULATION AB Objectives: The extended face network contains clusters of neurons that perform distinct functions on facial stimuli. Regions in the posterior ventral visual stream appear to perform basic perceptual functions on faces, while more anterior regions, such as the ventral anterior temporal lobe and amygdala, function to link mnemonic and affective information to faces. Anterior and posterior regions are interconnected by a long-range white matter tracts; however, it is not known if variation in connectivity of these pathways explains cognitive performance. Methods: Here, we used diffusion imaging and deterministic tractography in a cohort of 28 neurologically normal adults ages 18-28 to examine microstructural properties of visual fiber pathways and their relationship to certain mnemonic and affective functions involved in face processing. We investigated how inter-individual variability in two tracts, the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), related to performance on tests of facial emotion recognition and face memory. Results: Results revealed that microstructure of both tracts predicted variability in behavioral performance indexed by both tasks, suggesting that the ILF and IFOF play a role in facilitating our ability to discriminate emotional expressions in faces, as well as to remember unique faces. Variation in a control tract, the uncinate fasciculus, did not predict performance on these tasks. Conclusions: These results corroborate and extend the findings of previous neuropsychology studies investigating the effects of damage to the ILF and IFOF, and demonstrate that differences in face processing abilities are related to white matter microstructure, even in healthy individuals. C1 [Unger, Ashley; Alm, Kylie H.; O'Leary, Jacquelyn M.; Olson, Ingrid R.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Collins, Jessica A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Olson, IR (reprint author), Temple Univ, Weiss Hall,1701 N 13th St, Philadelphia, PA 19122 USA. EM iolson@temple.edu FU National Institutes of Health grant [RO1 MH091113] FX We thank Hyden Zhang, Vanessa Troiani, Lauren Harris, and Tehila Nugiel for assistance with participant testing and tract tracing. This work was supported by a National Institutes of Health grant to I. Olson (RO1 MH091113). The content 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 declare no competing or conflicting financial interests. NR 56 TC 2 Z9 2 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 180 EP 190 DI 10.1017/S1355617715001009 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200006 PM 26888615 ER PT J AU Ly, M Adluru, N Destiche, DJ Lu, SY Oh, JM Hoscheidt, SM Alexander, AL Okonkwo, OC Rowley, HA Sager, MA Johnson, SC Bendlin, BB AF Ly, Martina Adluru, Nagesh Destiche, Daniel J. Lu, Sharon Y. Oh, Jennifer M. Hoscheidt, Siobhan M. Alexander, Andrew L. Okonkwo, Ozioma C. Rowley, Howard A. Sager, Mark A. Johnson, Sterling C. Bendlin, Barbara B. TI Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Aging; Task-related functional connectivity; fMRI; gPPI; Fractional anisotropy; Episodic recognition ID WHITE-MATTER MICROSTRUCTURE; AGE-RELATED DIFFERENCES; ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; ENTORHINAL CORTEX; WORKING-MEMORY; OLDER-ADULTS; PREFRONTAL CORTEX; COGNITIVE DECLINE; BRAIN ACTIVITY AB Objectives: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. Methods: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. Results: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. Conclusions: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain-at least in part-connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. C1 [Ly, Martina; Oh, Jennifer M.; Hoscheidt, Siobhan M.; Okonkwo, Ozioma C.; Sager, Mark A.; Johnson, Sterling C.; Bendlin, Barbara B.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Ly, Martina; Oh, Jennifer M.; Hoscheidt, Siobhan M.; Okonkwo, Ozioma C.; Rowley, Howard A.; Sager, Mark A.; Johnson, Sterling C.; Bendlin, Barbara B.] Univ Wisconsin, Sch Med & Publ Hlth, Alzheimers Dis Res Ctr, Madison, WI 53792 USA. [Ly, Martina; Hoscheidt, Siobhan M.; Okonkwo, Ozioma C.; Sager, Mark A.; Johnson, Sterling C.; Bendlin, Barbara B.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53792 USA. [Ly, Martina] Univ Wisconsin, Neurosci Training Program, Madison, WI 53792 USA. [Ly, Martina; Adluru, Nagesh; Destiche, Daniel J.; Lu, Sharon Y.; Alexander, Andrew L.] Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI 53792 USA. [Alexander, Andrew L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Psychiat, Madison, WI 53792 USA. [Alexander, Andrew L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med Phys, Madison, WI 53792 USA. RP Bendlin, BB (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Alzheimers Dis Res Ctr, Madison, WI 53792 USA.; Bendlin, BB (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. EM bbb@medicine.wisc.edu FU National Institutes of Health [R01 AG037639, R01 AG027161, ADRC P50 AG033514, R01 AG021155, T32 GM007507, T32 AG000213]; Veterans Administration Merit Review Grant [I01CX000165]; Waisman Center Core Grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30 HD003352-45] FX This work was supported by the National Institutes of Health (B.B.B., R01 AG037639), (S.C.J., R01 AG027161), (ADRC P50 AG033514), (S.C.J., R01 AG021155), (T32 GM007507), (T32 AG000213); Veterans Administration Merit Review Grant (S.C.J., I01CX000165); and the Waisman Center Core Grant (P30 HD003352-45) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The project was also facilitated by the facilities and resources at the Geriatric Research, Education, and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison, WI. The authors gratefully acknowledge Nancy Davenport, Amy Hawley, Sandra Harding, Caitlin Cleary, Jay Fruehling, Chuck Illingworth, and the support of researchers and staff at the Waisman Center, University of Wisconsin, Madison, where imaging data were collected. Above all, we thank our dedicated volunteers for their participation in this research. Ly, Adluru, Destiche, Lu, Oh, Hoscheidt, Okonkwo, Sager, Johnson, and Bendlin report no conflicts of interest. Rowley has provided consultation to and/or received honoraria from GE Healthcare, Bracco, Lundbeck, HL Gore, and Eli Lilly. Alexander is part owner and Chief Operating Officer of inSERT, Inc. NR 89 TC 0 Z9 0 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 191 EP 204 DI 10.1017/S1355617715001216 PG 14 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200007 PM 26888616 ER PT J AU Putcha, D Ross, RS Cronin-Golomb, A Janes, AC Stern, CE AF Putcha, Deepti Ross, Robert S. Cronin-Golomb, Alice Janes, Amy C. Stern, Chantal E. TI Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson's Disease SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Cognitive impairment; Functional magnetic resonance imaging; Intrinsic connectivity networks; Neurodegeneration; Default mode network; Salience network ID INTRINSIC CONNECTIVITY NETWORKS; TEST-RETEST RELIABILITY; SCALE BRAIN NETWORKS; FUNCTIONAL CONNECTIVITY; DOPAMINE DYSFUNCTION; CINGULATE CORTEX; WORKING-MEMORY; BASAL GANGLIA; RESTING BRAIN; IMPAIRMENT AB Objectives: Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. Methods: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. Results: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Conclusions: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease. C1 [Putcha, Deepti; Ross, Robert S.; Cronin-Golomb, Alice; Stern, Chantal E.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Putcha, Deepti; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ross, Robert S.] Univ New Hampshire, Dept Psychol, Durham, NH 03824 USA. [Janes, Amy C.] Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr,Dept Psychiat, Belmont, MA USA. RP Putcha, D (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington Mall, Boston, MA 02215 USA. EM dputcha@bu.edu FU National Institute of Health [R01 NS067128]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; NIH Shared Instrumentation Grant Program; High-End Instrumentation Grant Program [S10RR022976, S10RR019933]; [K01DA029645] FX The authors declare no competing financial interests. This work was supported by the National Institute of Health R01 NS067128. Scanning was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, which receives funding from P41EB015896, a Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR022976 and S10RR019933. We also acknowledge salary funding for ACJ from grant number K01DA029645. Drs. Janes and Stern share co-last authorship. NR 78 TC 0 Z9 0 U1 3 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 205 EP 215 DI 10.1017/S1355617715000892 PG 11 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200008 PM 26888617 ER PT J AU Yeo, RA Ryman, SG van den Heuvel, MP de Reus, MA Jung, RE Pommy, J Mayer, AR Ehrlich, S Schulz, SC Morrow, EM Manoach, D Ho, BC Sponheim, SR Calhoun, VD AF Yeo, Ronald A. Ryman, Sephira G. van den Heuvel, Martijn P. de Reus, Marcel A. Jung, Rex E. Pommy, Jessica Mayer, Andrew R. Ehrlich, Stefan Schulz, S. Charles Morrow, Eric M. Manoach, Dara Ho, Beng-Choon Sponheim, Scott R. Calhoun, Vince D. TI Graph Metrics of Structural Brain Networks in Individuals with Schizophrenia and Healthy Controls: Group Differences, Relationships with Intelligence, and Genetics SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Cognitive; White matter; Graph theory; Brain; Copy number variation; Connectivity ID RICH-CLUB ORGANIZATION; GENERAL COGNITIVE-ABILITY; COPY NUMBER DELETIONS; SMALL-WORLD NETWORKS; CONNECTIVITY; DYNAMICS; MATTER; GROWTH; MRI AB Objectives: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. Methods: Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. Results: The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivityconnections among high degree rich club nodes, feeder connections to these rich club nodes, and local connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. Conclusions: Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA. C1 [Yeo, Ronald A.; Ryman, Sephira G.; Jung, Rex E.; Pommy, Jessica; Mayer, Andrew R.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Ryman, Sephira G.; Mayer, Andrew R.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [van den Heuvel, Martijn P.; de Reus, Marcel A.] Univ Med Ctr Utrecht, Brain Ctr Rudolph Magnus, Dept Psychiat, Utrecht, Netherlands. [Jung, Rex E.] Univ New Mexico, Dept Neurosurg, Albuquerque, NM 87131 USA. [Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Morrow, Eric M.] Brown Univ, Dept Biochem Mol Biol & Cell Biol, Mol Med Lab, Providence, RI 02912 USA. [Manoach, Dara] Massachusetts Gen Hosp, Psychiat Neuroimaging & Athinoula A Martinos Ctr, Charlestown, MA USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Sponheim, Scott R.] Minneapolis Vet Adm Hlth Care Syst, Minneapolis, NM USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. RP Yeo, RA (reprint author), Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. EM ryeo@unm.edu FU Department of Energy [DE-FG02-08ER64581]; National Institute Health [5P20RR021938, 1RC1MH089257, R01EB005846] FX The authors report no conflicts of interest. The first author gratefully acknowledges the training and mentoring provided by Drs. Edith Kaplan and Norman Geschwind. This work was supported by grants from the Department of Energy under Award Number DE-FG02-08ER64581, and the National Institute Health (grants 5P20RR021938, 1RC1MH089257, and R01EB005846). NR 59 TC 2 Z9 2 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 EI 1469-7661 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD FEB PY 2016 VL 22 IS 2 SI SI BP 240 EP 249 DI 10.1017/S1355617715000867 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA DF8TE UT WOS:000371631200011 PM 26888620 ER PT J AU Erlendsson, AM Doukas, AG Farinelli, WA Bhayana, B Anderson, RR Haedersdal, M AF Erlendsson, Andres M. Doukas, Apostolos G. Farinelli, William A. Bhayana, Brijesh Anderson, R. Rox Haedersdal, Merete TI Fractional laser-assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE active filling; drug delivery; laser; laser-assisted drug delivery ID ORGAN TRANSPLANT RECIPIENTS; HISTOLOGICAL CHARACTERIZATION; PERCUTANEOUS-ABSORPTION; PARTITION-COEFFICIENTS; TRANSDERMAL DELIVERY; PHOTODYNAMIC THERAPY; MACROMOLECULES; MICROPORATION; PERMEABILITY; DICLOFENAC AB Background and ObjectiveAblative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug-induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser-generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous deposition and delivery kinetics; (iii) biodistribution and diffusion pattern, estimated by mathematical simulation. MethodsFranz diffusion chambers (FCs) were used to evaluate the PVP-technique, comparing passive (AFXL) and active (AFXL+PVP) channel filling. A fractional CO2-laser generated superficial (225 mu m;17.5mJ/channel) and deep (1200 mu m; 130.5mJ/channel) channels, and PVP was delivered as a 3-minutes cycle of 1 minute pressure (+1.0atm), 1 minute vacuum (-1.0atm), and 1 minute pressure (+1.0atm). Filling of laser channels was visualized with a colored biomarker liquid (n=12 FCs, n=588 channels). Nuclear magnetic resonance quantified intracutaneous deposition of topically applied polyethylene glycol (PEG400) over time (10 minutes, 1 hour, and 4 hours), investigated with (n=36 FCs) and without (n=30 FCs) PVP-filling. Two-dimensional mathematical simulation was used to simulate intradermal biodistribution and diffusion at a depth of 1,000 mu m. ResultsActive filling with application of PVP increased the number of filled laser channels. At a depth of 1,000 mu m, filling increased from 44% (AFXL) to 94% with one PVP cycle (AFXL+PVP; P<0.01). Active filling greatly enhanced intracutaneous deposition of PEG400, resulting in a rapid delivery six-folding uptake at 10 minutes (AFXL 54 mu g/ml vs. AFXL+PVP 303 mu g/ml, P<0.01). AFXL alone generated an inhomogeneous uptake of PEG400, which greatly improved with active filling, resulting in a uniform uptake within the entire tissue. ConclusionActive filling with PVP secures filling of laser channels and induces a deeper, greater, more rapid delivery than conventional AFXL. This delivery technique has promise to improve treatment efficacy for medical treatments of dermally invasive lesions, such as BCCs. (c) 2015 Wiley Periodicals, Inc. C1 [Erlendsson, Andres M.; Doukas, Apostolos G.; Farinelli, William A.; Bhayana, Brijesh; Anderson, R. Rox; Haedersdal, Merete] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St,Their 2, Boston, MA 02114 USA. [Erlendsson, Andres M.; Haedersdal, Merete] Bispebjerg Hosp, Dept Dermatol, Bispebjerg Bakke 24, DK-2400 Copenhagen NV, Denmark. RP Erlendsson, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St,Their 2, Boston, MA 02114 USA. EM andres.erlendsson@gmail.com NR 31 TC 5 Z9 5 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2016 VL 48 IS 2 SI SI BP 116 EP 124 DI 10.1002/lsm.22374 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA DF6YO UT WOS:000371504500004 PM 26280816 ER PT J AU Kositratna, G Evers, M Sajjadi, A Manstein, D AF Kositratna, Garuna Evers, Michael Sajjadi, Amir Manstein, Dieter TI Rapid fibrin plug formation within cutaneous ablative fractional CO2 laser lesions SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE laser-assisted; ablative fractional lasers; gateways; transcutaneous; transdermal; transport; drug delivery; cell delivery; substance delivery; time course; time dependence; fibrin plug formation ID ASSISTED DRUG-DELIVERY; MEDIATED PHOTODYNAMIC THERAPY; ORGAN TRANSPLANT RECIPIENTS; RANDOMIZED CONTROLLED-TRIAL; RESURFACING DEVICE; ACTINIC KERATOSES; LASER TREATMENT; PHOTOTHERMOLYSIS; SCARS; COAGULATION AB BackgroundAblative fractional laser procedures have been shown to facilitate topical drug delivery into the skin. Past studies have mainly used ex vivo models to demonstrate enhanced drug delivery and in vivo studies have investigated laser created channels over a time course of days and weeks rather than within the first few minutes and hours after exposures. We have noticed rapid in vivo fibrin plug formation within ablative fractional laser lesions impairing passage through the laser created channels. Material and MethodsIn vivo laser exposures were performed in a porcine model. A fractional CO2 laser (AcuPulse system, AcuScan 120 handpiece, Lumenis, Inc., Yokneam, Israel) was programmed in quasi-continuous wave (QCW) mode, at 40W, 50mJ per pulse, 5% coverage, nominal 120 mu m spot size, 8x8mm square pattern, 169 MTZs per scan. Six millimeters punch biopsies were procured at 0, 2, 5, 10, 15, 30, 60, 90 minutes after completion of each scan, then fixed in 10% formalin. 12 repeats were performed of each time point. Skin samples were processed for serial vertically cut paraffin sections (5m collected every 25m) then H&E and special immunohistochemistry staining for fibrin and platelet. Dimensions of Microscopic Treatment Zones (MTZs) and extent of fibrin plug were assessed and quantified histologically. Ex vivo laser exposures of the identical laser parameter were performed on porcine and human skin at different storage conditions. ResultsHistology procured at various predetermined time intervals after in vivo fractional CO2 laser exposures revealed a rapidly forming fibrin plug initiating at the bottom of the MTZ lesions. At longer time intervals, the fibrin plug was extending towards the superficial sections. Within the first 5 minutes, more than 25% length of the entire laser-ablated channel was filled with a fibrin plug. With increased time intervals, the cavity was progressively filled with a fibrin plug. At 90 minutes, more than 90% length of the entire laser-ablated channel was occluded. Ex vivo exposures failed to produce any significant fibrin plug formation. ConclusionsThe current study has demonstrated rapid fibrin plug formation after ablative fractional laser procedures. It was shown that the passage through laser created pathways is critically time dependent for in vivo exposures. In contrast, ex vivo exposures do not exhibit such time dependent passage capacity. In particular, drug, substance, and cell delivery studies for ablative fractional laser treatments should take early fibrin plug formation into consideration and further investigate the impact on transdermal delivery. (c) 2015 Wiley Periodicals, Inc. C1 [Kositratna, Garuna; Evers, Michael; Sajjadi, Amir; Manstein, Dieter] Massachusetts Gen Hosp, Res Inst, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA 02129 USA. [Kositratna, Garuna; Evers, Michael; Sajjadi, Amir; Manstein, Dieter] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kositratna, G (reprint author), Cutaneous Biol Res Ctr, 149,13th St,Fl 3, Boston, MA 02114 USA. EM gkositratna@mgh.harvard.edu NR 42 TC 1 Z9 1 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2016 VL 48 IS 2 SI SI BP 125 EP 132 DI 10.1002/lsm.22412 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA DF6YO UT WOS:000371504500005 PM 26388136 ER PT J AU Feng, X Doherty, S Yaroslavsky, I Altshuler, G Yaroslavsky, AN AF Feng, Xin Doherty, Sean Yaroslavsky, Ilya Altshuler, Gregory Yaroslavsky, Anna N. TI Polarization enhanced wide-field imaging for evaluating dermal changes caused by non-ablative fractional laser treatment SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE collagen; in vivo imaging; polarization imaging; skin rejuvenation ID OPTICAL COHERENCE TOMOGRAPHY; SKIN AB Background and ObjectiveLaser non-ablative fractional treatment (NAFT) is an important part of armamentarium of modern dermatology. Recently, such treatments have become available in at-home setting due to advent of self-application NAFT devices. Safety and clinical efficacy of NAFT are well established in multiple studies. Less information is available on morphological and functional changes in tissue occurring as a result of NAFT. Polarization-enhanced multispectral wide-field imaging device allows for in vivo real time visualization of dermal structures. The objective of this study is to use this imaging modality to monitor early effects of the home-use NAFT on collagen networks. Materials and MethodsEight subjects (skin types I-III) used a commercially available NAFT device (wavelength 1410nm, energy per pulse up to 15mJ) to treat peri-orbital wrinkles in standard recommended mode, that is daily, for a period of two weeks. In each session, subjects applied a pre-treatment gel to the peri-orbital areas and then used the device, delivering 8-10 applications to each side of the face without overlap. Subjects were asked to use the highest device setting. Cross-polarized 440nm wide-field images were acquired from peri-orbital areas before and two weeks after the onset of the treatment regimen. Wide-field images were normalized and thresholded to a level of 40% brightness to emphasize collagen structure. Collagen content was quantitatively determined from thresholded collagen images. Improvement in collagen content at two weeks of daily treatments was assessed. ResultsEight subjects (age 24-53 years) completed the study. Cross-polarized 440nm wide-field images clearly delineated collagen networks. Quantitative assessment of collagen images revealed statistically significant (P<0.05) improvement of collagen content at a time point of two weeks. Seven out of eight subjects showed varying degree of improvement. The increase of collagen content in responders ranged from 1-26%, with the mean improvement of 11%. Subjects in their early 40s showed the best improvement in comparison to younger and older age groups. ConclusionsPolarization-enhanced multispectral wide-field reflectance imaging method is a suitable technique for noninvasive in vivo assessment of dermal structures. Post-treatment images, taken three days after the last treatment session, demonstrate that non-ablative fractional treatment resulted in increased dermal collagen content as measured by the polarization-enhanced technique as early as two weeks post onset of the treatments. However, further studies with a larger number of subjects and longer treatment period are required to determine the optimal regimen and how long the results will last. (c) 2015 Wiley Periodicals, Inc. C1 [Feng, Xin; Yaroslavsky, Anna N.] Univ Massachusetts Lowell, Adv Biophoton Lab, Lowell, MA 01854 USA. [Doherty, Sean] Boston Plast Surg Associates, Concord, MA 01742 USA. [Yaroslavsky, Ilya; Altshuler, Gregory] Palomar Med Technol Inc, Burlington, MA 01803 USA. [Yaroslavsky, Anna N.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yaroslavsky, AN (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Anna_Yaroslavsky@uml.edu FU Palomar Medical Technologies FX Contract grant sponsor: Palomar Medical Technologies. NR 12 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2016 VL 48 IS 2 SI SI BP 150 EP 156 DI 10.1002/lsm.22390 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA DF6YO UT WOS:000371504500008 PM 26304187 ER PT J AU Shek, SYN Yeung, CK Chan, JCY Chan, HHL AF Shek, Samantha Y. N. Yeung, Chi K. Chan, Johnny C. Y. Chan, Henry H. L. TI The efficacy of a combination non-thermal focused ultrasound and radiofrequency device for noninvasive body contouring in Asians SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE body contouring; focused ultrasound; radiofrequency; UltraShape (R); adipose tissue; fat ID SAFETY AB Background and ObjectiveSeveral studies have been published on the first generation non-thermal focused ultrasound with an average improvement of 0-3.95cm reported [1,2]. We aim to investigate the efficacy of the second-generation non-thermal focused ultrasound device with a combined radiofrequency hand piece. With the addition of radiofrequency energy, the temperature of the adipose tissue is raised before focused ultrasound is applied. This facilitates the mechanical disruption of fat cells by focused ultrasound. Study Design and MethodsTwenty subjects were recruited and underwent three treatments biweekly. Caliper reading, abdominal circumference, and standardized photographs were taken with the Vectra((R)) system at all visits. We aim to have the subjects stand and hold the same position and the photograph taken after exhalation. Caliper and circumference measurements carry uncertainty. It is impossible to eliminate all uncertainties but can be improved by having the same trained physician assistant perform the measurement at the same site and taking an average of three readings. Pain score and satisfaction were recorded by means of the visual analogue scale. The efficacy is defined by a statistically significant improvement in circumferential improvement based on intention-to-treat analysis. ResultsSeventeen subjects completed the treatment schedule. Abdominal circumference showed statistically significant improvement at 2 weeks post-second treatment (P=0.023) and almost all subsequent follow-ups. Caliper readings were statistically significant at 2 weeks post-second treatment (P=0.013) and almost all follow-ups. The mean pain score reported was 2.3 on the visual analog scale and 6% were unsatisfied with the overall treatments. Six incidents of wheal formation appeared immediately after treatment all of which subsided spontaneously within several hours. ConclusionThe combination non-thermal focused ultrasound and radiofrequency device is effective for improving body contour in Asians. Lasers Surg. Med. 48:203-207, 2016. (c) 2015 Wiley Periodicals, Inc. C1 [Shek, Samantha Y. N.; Yeung, Chi K.; Chan, Johnny C. Y.; Chan, Henry H. L.] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Shek, SYN (reprint author), Hong Kong Dermatol & Laser Ctr, 11-F Silver Fortune Plaza,1 Wellington St, Hong Kong, Hong Kong, Peoples R China. EM samantha@hhlchan.com FU Asia Pacific Medical Advisory Board of Syneron(R) Medical Ltd. FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and have disclosed the following: Dr. Henry HL Chan is currently the chairman of Asia Pacific Medical Advisory Board of Syneron (R) Medical Ltd. He holds stock options, free use of equipment, fees to conduct trial, and honorarium from the company. NR 10 TC 1 Z9 1 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2016 VL 48 IS 2 SI SI BP 203 EP 207 DI 10.1002/lsm.22406 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA DF6YO UT WOS:000371504500017 PM 26352171 ER PT J AU Deng, L Xu-Monette, ZY Loghavi, S Manyam, GC Xia, Y Visco, C Huh, J Zhang, L Zhai, Q Wang, Y Qiu, L Dybkaer, K Chiu, A Perry, AM Zhang, S Tzankov, A Rao, H Abramson, J Sohani, AR Xu, M Hsi, ED Zhu, J Ponzoni, M Wang, S Li, L Zhang, M Ferreri, AJM Parsons, BM Li, Y Piris, MA Medeiros, LJ Young, KH AF Deng, L. Xu-Monette, Z. Y. Loghavi, S. Manyam, G. C. Xia, Y. Visco, C. Huh, J. Zhang, L. Zhai, Q. Wang, Y. Qiu, L. Dybkaer, K. Chiu, A. Perry, A. M. Zhang, S. Tzankov, A. Rao, H. Abramson, J. Sohani, A. R. Xu, M. Hsi, E. D. Zhu, J. Ponzoni, M. Wang, S. Li, Ling Zhang, M. Ferreri, A. J. M. Parsons, B. M. Li, Y. Piris, M. A. Medeiros, L. J. Young, K. H. TI Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium SO LEUKEMIA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; DOXORUBICIN-BASED THERAPY; NF-KAPPA-B; PROGNOSTIC-FACTORS; ELDERLY-PATIENTS; GENE-EXPRESSION; INFERIOR SURVIVAL AB Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a unique subtype of DLBCL. The impact of rituximab on survival and patterns of treatment failure in PT-DLBCL patient remain controversial. We analyzed the clinical and biological feature of 280 PTDLBCL cases, 64% of which were treated with rituximab-containing regimens. Although most (95%) patients achieved complete remission, a continuous risk of relapse was observed. Rituximab significantly reduced the cumulative risk of relapse (P= 0.022) and improved both progression-free survival (PFS, P= 0.012) and overall survival (OS, P= 0.027) of PT-DLBCL patients (5-year PFS, 56% vs 36%; 5-year OS, 68% vs 48%). Central nervous system and contralateral testis were the most common sites of relapse, but other extranodal and nodal sites of relapse were also observed. Most cases of PT-DLBCL had a non-germinal center B-cell like (84%) immunophenotype and an activated B-cell like (86%) gene expression profile (GEP) subtype. The distinctive GEP signature of primary testicular lymphoma was relevant to tumor cell proliferation, dysregulated expression of adhesion molecules and immune response, likely accounting for the poor outcome. Accordingly, forkhead box P1 transcription factor (FOXP1) and T-cell leukemia/lymphoma 1 (TCL1) oncogenic activation were confirmed and predicted a significant trend of poor survival. This study provides valuable observations for better understanding of both clinical and biological features in PT-DLBCL patients. C1 [Deng, L.; Xu-Monette, Z. Y.; Loghavi, S.; Xia, Y.; Medeiros, L. J.; Young, K. H.] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Manyam, G. C.; Zhang, L.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Visco, C.] San Bortolo Hosp, Vicenza, Italy. [Huh, J.] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Zhai, Q.; Wang, Y.; Qiu, L.] CAMS, Tianjin Med Univ Canc Inst & Hosp, Inst Hematol, 5, Tianjin, Peoples R China. [Zhai, Q.; Wang, Y.; Qiu, L.] PUMC, 5, Tianjin, Peoples R China. [Dybkaer, K.] Aalborg Univ Hosp, Aalborg, Denmark. [Chiu, A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Perry, A. M.] Univ Manitoba, Winnipeg, MB, Canada. [Zhang, S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Tzankov, A.] Univ Hosp, Basel, Switzerland. [Rao, H.] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China. [Sohani, A. R.] Massachusetts Gen Hosp, 12, Boston, MA 02114 USA. [Sohani, A. R.] Harvard Univ, Sch Med, 12, Boston, MA USA. [Xu, M.] Yale Univ, Sch Med, New Haven, CT USA. [Hsi, E. D.; Li, Y.] Cleveland Clin, Cleveland, OH 44106 USA. [Zhu, J.] Peking Univ, Canc Hosp & Inst, Beijing 100871, Peoples R China. [Ponzoni, M.; Ferreri, A. J. M.] Ist Sci San Raffaele, Milan, Italy. [Wang, S.] Natl Univ Singapore Hosp, Singapore, Singapore. [Li, Ling; Zhang, M.] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China. [Parsons, B. M.] Gunderson Med Fdn, La Crosse, WI USA. [Piris, M. A.] Hosp Univ Marques Valdecilla, Santander, Spain. [Young, K. H.] Univ Texas Houston, Sch Med, Grad Sch Biomed Sci, Houston, TX USA. RP Young, KH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM khyoung@mdanderson.org RI Manyam, Ganiraju/E-9150-2012; Piris, Miguel/B-7067-2008; OI Manyam, Ganiraju/0000-0001-6006-8961; Piris, Miguel/0000-0001-5839-3634; Tzankov, Alexandar/0000-0002-1100-3819 FU National Cancer Institute/National Institutes of Health [R01CA138688, 1RC1CA146299, P5OCA136411, P50CA142509]; University of Texas MD Anderson Cancer Center Lymphoma Moonshot Program; Institutional Research and Development Fund; Institutional Research Grant Award; MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award; MD Anderson Cancer Center Myeloma SPORE Research Development Program Award; Gundersen Lutheran Medical Foundation Award; Michael and Susan Dell Foundation; Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center; Roche Molecular System; Gilead Sciences Pharmaceutical; Seattle Genetics; Dai Sanyo Pharmaceutical; Adaptive Biotechnology; HTG Molecular Diagnostics FX This study was supported by the National Cancer Institute/National Institutes of Health (R01CA138688 and 1RC1CA146299 to YL and KHY). KHY is supported by The University of Texas MD Anderson Cancer Center Lymphoma Moonshot Program, Institutional Research and Development Fund, an Institutional Research Grant Award, an MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award, an MD Anderson Cancer Center Myeloma SPORE Research Development Program Award and the Gundersen Lutheran Medical Foundation Award, and is partially supported by the National Cancer Institute/National Institutes of Health (P5OCA136411 and P50CA142509). GCM is supported by a grant from the Michael and Susan Dell Foundation. Dr Xu-Monette is the recipient of the Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center. KHY also receives research support from Roche Molecular System, Gilead Sciences Pharmaceutical, Seattle Genetics, Dai Sanyo Pharmaceutical, Adaptive Biotechnology, and HTG Molecular Diagnostics. NR 68 TC 5 Z9 5 U1 3 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD FEB PY 2016 VL 30 IS 2 BP 361 EP 372 DI 10.1038/leu.2015.237 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA DF7TB UT WOS:000371559400014 PM 26308769 ER PT J AU Prabhala, RH Fulciniti, M Pelluru, D Rashid, N Nigroiu, A Nanjappa, P Pai, C Lee, S Prabhala, NS Bandi, RL Smith, R Lazo-Kallanian, SB Valet, S Raje, N Gold, JS Richardson, PG Daley, JF Anderson, KC Ettenberg, SA Di Padova, F Munshi, NC AF Prabhala, R. H. Fulciniti, M. Pelluru, D. Rashid, N. Nigroiu, A. Nanjappa, P. Pai, C. Lee, S. Prabhala, N. S. Bandi, R. L. Smith, R. Lazo-Kallanian, S. B. Valet, S. Raje, N. Gold, J. S. Richardson, P. G. Daley, J. F. Anderson, K. C. Ettenberg, S. A. Di Padova, F. Munshi, N. C. TI Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma SO LEUKEMIA LA English DT Article ID ANTI-INTERLEUKIN-17 MONOCLONAL-ANTIBODY; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; BONE-MARROW; T-CELLS; DENDRITIC CELLS; INTERLEUKIN 17; SERUM-LEVELS; LUNG-CANCER; GROWTH AB We have previously demonstrated that interleukin-17A (IL-17) producing T helper 17 cells are significantly elevated in blood and bone marrow (BM) in multiple myeloma (MM) and IL-17A promotes MM cell growth via the expression of IL-17 receptor. In this study, we evaluated anti-human IL-17A human monoclonal antibody (mAb), AIN457 in MM. We observe significant inhibition of MM cell growth by AIN457 both in the presence and the absence of BM stromal cells (BMSCs). Although IL-17A induces IL-6 production, AIN457 significantly downregulated IL-6 production and MM cell adhesion in MM-BMSC co-culture. AIN457 also significantly inhibited osteoclast cell differentiation. More importantly, in the SCIDhu model of human myeloma administration of AIN457 weekly for 4 weeks after the first detection of tumor in mice led to a significant inhibition of tumor growth and reduced bone damage compared with isotype control mice. To understand the mechanism of action of anti-IL-17A mAb, we report, here, that MM cells express IL-17A. We also observed that IL-17A knockdown inhibited MM cell growth and their ability to induce IL-6 production in co-cultures with BMSC. These pre-clinical observations suggest efficacy of AIN457 in myeloma and provide the rationale for its clinical evaluation for anti-myeloma effects and for improvement of bone disease. C1 [Prabhala, R. H.; Fulciniti, M.; Nigroiu, A.; Pai, C.; Lee, S.; Prabhala, N. S.; Gold, J. S.; Munshi, N. C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Med, 1400 VFW Pk Way, Boston, MA 02132 USA. [Prabhala, R. H.; Rashid, N.; Bandi, R. L.; Gold, J. S.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Prabhala, R. H.; Fulciniti, M.; Pelluru, D.; Nanjappa, P.; Smith, R.; Lazo-Kallanian, S. B.; Richardson, P. G.; Daley, J. F.; Anderson, K. C.; Munshi, N. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. [Valet, S.; Raje, N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ettenberg, S. A.] Novartis Inst Biomed Res, Cambridge, MA USA. [Di Padova, F.] Novartis Inst Biomed Res, Basel, Switzerland. RP Prabhala, RH; Munshi, NC (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Med, 1400 VFW Pk Way, Boston, MA 02132 USA.; Prabhala, RH; Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM rao_prabhala@dfci.harvard.ed; nikhil_munshi@dfci.harvard.edu FU Department of Veterans Affairs Merit Review Award1 [101 BX001584-01]; NIH grants [RO1-124929, PO1-155258, P50-100707, PO1-78378]; Department of Veterans Affairs Office of Research and Development through a Career Development Award-2; MMRF senior award FX This work is supported by: Department of Veterans Affairs Merit Review Award1 101 BX001584-01, NIH grants RO1-124929 and PO1-155258 (NCM) and P50-100707, and PO1-78378, (NCM and KCA). JSG is supported by the Department of Veterans Affairs Office of Research and Development through a Career Development Award-2. This work is also supported by MMRF senior award to RHP. NR 56 TC 4 Z9 4 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD FEB PY 2016 VL 30 IS 2 BP 379 EP 389 DI 10.1038/leu.2015.228 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA DF7TB UT WOS:000371559400016 PM 26293646 ER PT J AU Jiang, H Acharya, C An, G Zhong, M Feng, X Wang, L Dasilva, N Song, Z Yang, G Adrian, F Qiu, L Richardson, P Munshi, NC Tai, YT Anderson, KC AF Jiang, H. Acharya, C. An, G. Zhong, M. Feng, X. Wang, L. Dasilva, N. Song, Z. Yang, G. Adrian, F. Qiu, L. Richardson, P. Munshi, N. C. Tai, Y-T Anderson, K. C. TI SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide SO LEUKEMIA LA English DT Article ID ANTIBODY-DRUG-CONJUGATE; MEMBRANE PERMEABILIZATION; LEUKEMIA-CELLS; HUMAN LYMPHOMA; PLASMA-CELLS; DEXAMETHASONE; MALIGNANCIES; CYTOGENETICS; ELOTUZUMAB; MATURATION AB The anti-CD38 monoclonal antibody SAR650984 (SAR) is showing promising clinical activity in treatment of relapsed and refractory multiple myeloma (MM). Besides effector-mediated antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity, we here define molecular mechanisms of SAR-directed MM cell death and enhanced anti-MM activity triggered by SAR with Pomalidomide (Pom). Without Fc-cross-linking agents or effector cells, SAR specifically induces homotypic aggregation (HA) associated cell death in MM cells dependent on the level of cell surface CD38 expression, actin cytoskeleton and membrane lipid raft. SAR and its F(ab)'2 fragments trigger caspase 3/7-dependent apoptosis in MM cells highly expressing CD38, even with p53 mutation. Importantly, SAR specifically induces lysosome-dependent cell death (LCD) by enlarging lysosomes and increasing lysosomal membrane permeabilization associated with leakage of cathepsin B and LAMP-1, regardless of the presence of interleukin-6 or bone marrow stromal cells. Conversely, the lysosomal vacuolar H+-ATPase inhibitor blocks SAR-induced LCD. SAR further upregulates reactive oxygen species. Pom enhances SAR-induced direct and indirect killing even in MM cells resistant to Pom/Len. Taken together, SAR is the first therapeutic monoclonal antibody mediating direct cytotoxicity against MM cells via multiple mechanisms of action. Our data show that Pom augments both direct and effector cell-mediated MM cytotoxicity of SAR, providing the framework for combination clinical trials. C1 [Jiang, H.; Acharya, C.; An, G.; Zhong, M.; Feng, X.; Wang, L.; Dasilva, N.; Richardson, P.; Munshi, N. C.; Tai, Y-T; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, 44 Binney St, Boston, MA 02115 USA. [Jiang, H.; Acharya, C.; An, G.; Zhong, M.; Feng, X.; Wang, L.; Dasilva, N.; Richardson, P.; Munshi, N. C.; Tai, Y-T; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, 44 Binney St, Boston, MA 02115 USA. [Jiang, H.] Second Mil Med Univ, Chang Zheng Hosp, Dept Hematol, Myeloma & Lymphoma Ctr, Shanghai, Peoples R China. [Song, Z.; Yang, G.; Adrian, F.] Sanofi Oncol, Cambridge, MA USA. [Qiu, L.] CAMS, Inst Hematol, Tianjin, Peoples R China. [Qiu, L.] PUMC, Tianjin, Peoples R China. RP Tai, YT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02215 USA. EM yu-tzu_tai@dfci.harvard.edu FU National Institutes of Health Grants [801050947, PO1-CA078378]; DF/HCC SPORE in Multiple Myeloma [P50CA100707]; KCA is an American Cancer Society Clinical Research Professor FX We thank Dr Ti Cai (former employee at Sanofi, currently at EMD Serono, Inc.) for helpful input and all clinical and laboratory members of the Jerome Lipper Multiple Myeloma Center of the Dana-Farber Cancer Institute for support and help for this study. Funding: National Institutes of Health Grants 801050947, PO1-CA078378 and DF/HCC SPORE in Multiple Myeloma P50CA100707; KCA is an American Cancer Society Clinical Research Professor. NR 45 TC 16 Z9 16 U1 4 U2 7 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 FEB PY 2016 VL 30 IS 2 BP 399 EP 408 DI 10.1038/leu.2015.240 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA DF7TB UT WOS:000371559400018 PM 26338273 ER PT J AU Sood, R Hansen, NF Donovan, FX Carrington, B Bucci, D Maskeri, B Young, A Trivedi, NS Kohlschmidt, J Stone, RM Caligiuri, MA Chandrasekharappa, SC Marcucci, G Mullikin, JC Bloomfield, CD Liu, P AF Sood, R. Hansen, N. F. Donovan, F. X. Carrington, B. Bucci, D. Maskeri, B. Young, A. Trivedi, N. S. Kohlschmidt, J. Stone, R. M. Caligiuri, M. A. Chandrasekharappa, S. C. Marcucci, G. Mullikin, J. C. Bloomfield, C. D. Liu, P. TI Somatic mutational landscape of AML with inv(16) or t(8;21) identifies patterns of clonal evolution in relapse leukemia SO LEUKEMIA LA English DT Letter ID ACUTE MYELOID-LEUKEMIA; GROUP-B; ADULT; CANCER; MDS C1 [Sood, R.; Liu, P.] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA. [Sood, R.; Carrington, B.] NHGRI, Zebrafish Core, NIH, Bethesda, MD 20892 USA. [Hansen, N. F.; Mullikin, J. C.] NHGRI, Comparat Genom Anal Unit, NIH, Bethesda, MD 20892 USA. [Donovan, F. X.; Chandrasekharappa, S. C.] NHGRI, Genom Core, NIH, Bethesda, MD 20892 USA. [Bucci, D.; Kohlschmidt, J.; Caligiuri, M. A.; Marcucci, G.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Maskeri, B.; Young, A.; Mullikin, J. C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Trivedi, N. S.] NHGRI, Bioinformat & Sci Programming Core, NIH, Bethesda, MD 20892 USA. [Kohlschmidt, J.] Mayo Clin, Alliance Clin Trials Oncol Stat & Data Ctr, Rochester, MN USA. [Stone, R. M.] Harvard Univ, Med Oncol Hematol Malignancies, Dana Farber Canc Inst, Boston, MA 02115 USA. [Chandrasekharappa, S. C.] NHGRI, Canc Genom Unit, NIH, Bethesda, MD 20892 USA. [Marcucci, G.] Hematol Malignancies & Stem Cell Transplantat Ins, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA. RP Liu, P (reprint author), NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA. EM pliu@mail.nih.gov FU Intramural NIH HHS [Z01 HG000030-14, Z01 HG000030-13]; NCI NIH HHS [U10 CA180861, U10 CA180850, P30 CA016058, P50 CA140158, U10 CA101140] NR 17 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD FEB PY 2016 VL 30 IS 2 BP 501 EP 504 DI 10.1038/leu.2015.141 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA DF7TB UT WOS:000371559400030 PM 26139325 ER PT J AU Devaraj, SGT Fiskus, W Shah, B Qi, J Sun, B Iyer, SP Sharma, S Bradner, JE Bhalla, KN AF Devaraj, S. G. T. Fiskus, W. Shah, B. Qi, J. Sun, B. Iyer, S. P. Sharma, S. Bradner, J. E. Bhalla, K. N. TI HEXIM1 induction is mechanistically involved in mediating anti-AML activity of BET protein bromodomain antagonist SO LEUKEMIA LA English DT Letter ID ACUTE MYELOID-LEUKEMIA; INHIBITION; ASSOCIATION; CANCER; CELLS; 7SK C1 [Devaraj, S. G. T.; Shah, B.; Sun, B.; Iyer, S. P.] Houston Methodist Res Inst, Houston, TX USA. [Fiskus, W.] Baylor Coll Med, Houston, TX 77030 USA. [Qi, J.; Bradner, J. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sharma, S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Bhalla, K. N.] Univ Texas Houston, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. RP Bhalla, KN (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM kbhalla@mdanderson.org FU NCI NIH HHS [CA 100632, P30 CA016672, P50 CA100632, R01 CA171338, R01 CA173877] NR 15 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD FEB PY 2016 VL 30 IS 2 BP 504 EP 508 DI 10.1038/leu.2015.142 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA DF7TB UT WOS:000371559400031 PM 26148704 ER PT J AU Hugos, CL Chen, YY Chen, ZQ Turner, A Haselkorn, JK Chiara, T McCoy, SC Bever, C Bourdette, D AF Hugos, Cinda L. Chen, Yiyi Chen, Zunqiu Turner, Aaron Haselkorn, Jodie K. Chiara, Toni McCoy, Sean C. Bever, Christopher Bourdette, Dennis TI A multicenter randomized controlled trial in people with multiple sclerosis comparing the effects of two group programs on fatigue and self-efficacy SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT ACTRIMS Forum CY FEB 18-20, 2016 CL New Orleans, LA SP ACTRIMS C1 [Hugos, Cinda L.; Bourdette, Dennis] VA Portland Hlth Care Syst, Portland, OR USA. [Chen, Yiyi; Chen, Zunqiu] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chen, Zunqiu; Turner, Aaron; Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Chiara, Toni; McCoy, Sean C.] North Florida South Georgia Vet Hlth Syst, Gainesville, FL USA. [Bever, Christopher] VA Maryland Hlth Care Syst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2016 VL 22 SU 1 MA P065 BP 33 EP 34 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DF9CE UT WOS:000371657100077 ER PT J AU Wang, CN Schroeder, FA Wey, HY Hooker, JM AF Wang, Changning Schroeder, Frederick A. Wey, Hsiao-Ying Hooker, Jacob M. TI Imaging-assisted development of novel histone deacetylase inhibitors for multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Meeting Abstract CT ACTRIMS Forum CY FEB 18-20, 2016 CL New Orleans, LA SP ACTRIMS C1 [Wang, Changning] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. [Schroeder, Frederick A.; Wey, Hsiao-Ying; Hooker, Jacob M.] Massachusetts Gen Hosp, Charlestown, MA USA. 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD FEB PY 2016 VL 22 SU 1 MA P072 BP 36 EP 37 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DF9CE UT WOS:000371657100083 ER PT J AU Durazzo, TC Mattsson, N Weiner, MW AF Durazzo, Timothy C. Mattsson, Niklas Weiner, Michael W. CA Alzheimer's Dis Neuroimaging TI Interaction of Cigarette Smoking History With APOE Genotype and Age on Amyloid Level, Glucose Metabolism, and Neurocognition in Cognitively Normal Elders SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; PROCESSING-SPEED; RISK-FACTORS; IMPAIRMENT; DEMENTIA; BIOMARKERS; BETA AB Introduction: Chronic cigarette smoking is associated with increased risk for Alzheimer's disease (AD). The goal of this study was to determine if smoking history moderated the associations of age and APOE genotype (the most robust risk factors for AD) on brain amyloid deposition, glucose metabolism, and neurocognition in cognitively-normal elders. Methods: Participants (n = 264) were grouped according to their APOE epsilon 4 carrier status (epsilon 4 carrier: APOE4+; non-epsilon 4 carrier: APOE4-) and smoking status (smokers: at least 1 year of smoking during lifetime; never-smokers: no history of smoking). Approximately 89% of the smoking sample was former-smokers. We specifically tested for interactions of smoking status with APOE epsilon 4 carrier status and age on measures of cortical amyloid deposition, glucose metabolism, and neurocognition. Results: (1) smoking status interacted with APOE epsilon 4 carrier status, where smoker APOE4+ showed lower glucose metabolism and poorer auditory-verbal learning and memory than never-smoking APOE4-, never-smoking APOE4+, and smoking APOE4-; (2) smoking status interacted with age on measures of semantic fluency, processing speed/set-shifting and global neurocognition; smokers, irrespective of APOE epsilon 4 carrier status, demonstrated poorer performance with increasing age than never-smokers; and (3) smoking APOE4+ and never-smoking APOE4+ showed greater cortical amyloid deposition than never-smoking APOE4-and smoking APOE4-. Conclusions: The findings indicate consideration of smoking history is essential to both better understand the factors associated with neurobiological and neurocognitive abnormalities in elders, and the risk for development of AD-related neuropathology. C1 [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu OI Preda, Adrian /0000-0003-3373-2438 FU National Institutes of Health [NIH DA24136]; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435]; Dana Foundation FX The study sponsors had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication. This work was supported by the National Institutes of Health (NIH DA24136 to TCD) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. All data collection and sharing for this project was supported by ADNI. ADNI is funded by the National Institute on Aging (U01 AG024904 to MWW), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co, Medpace, Inc, Merck and Co, Inc, Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc, and Wyeth, as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University Southern California. This research was also supported by NIH grants P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435, and The Dana Foundation. The above funding agencies 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. Original data used in preparation of this article were obtained from the ADNI database (www.loni.usc.edu/ADNI). As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data, but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Authorship _List.pdf. NR 51 TC 3 Z9 3 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2016 VL 18 IS 2 BP 204 EP 211 DI 10.1093/ntr/ntv075 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA DE0FV UT WOS:000370301200013 PM 25847292 ER PT J AU Walsh, KS Noll, RB Annett, RD Patel, SK Patenaude, AF Embry, L AF Walsh, Karin S. Noll, Robert B. Annett, Robert D. Patel, Sunita K. Patenaude, Andrea F. Embry, Leanne TI Standard of Care for Neuropsychological Monitoring in Pediatric Neuro-Oncology: Lessons From the Children's Oncology Group (COG) SO PEDIATRIC BLOOD & CANCER LA English DT Review DE late effects; pediatric oncology; psychology ID CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; NEUROCOGNITIVE STATUS; COST-EFFECTIVENESS; ADULT SURVIVORS; BRAIN-TUMORS; OUTCOMES; HEALTH; MEDULLOBLASTOMA AB As the mortality of pediatric cancers has decreased, focus on neuropsychological morbidities of treatment sequelae have increased. Neuropsychological evaluations are essential diagnostic tools that assess cognitive functioning and neurobiological integrity. These tests provide vital information to support ongoing medical care, documenting cognitive morbidity and response to interventions. We frame standards for neuropsychological monitoring of pediatric patients with CNS malignancy or who received cancer-directed therapies involving the CNS and discuss billing for these services in the United States in the context of clinical research. We describe a cost-effective, efficient model of neuropsychological monitoring that may increases access to neuropsychological care. (c) 2015 Wiley Periodicals, Inc. C1 [Walsh, Karin S.] Childrens Natl Hlth Syst, Dept Pediat Neuropsychol, Washington, DC USA. [Walsh, Karin S.] George Washington Univ, Sch Med, Washington, DC USA. [Noll, Robert B.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. [Annett, Robert D.] Univ Colorado Denver, Childrens Hosp Colorado, Aurora, CO USA. [Patel, Sunita K.] City Hope Natl Med Ctr, Behav Res Sect, Dept Pediat, Med Ctr, Duarte, CA USA. [Patenaude, Andrea F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Embry, Leanne] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat Hematol Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RP Embry, L (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat Hematol Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM EmbryL@uthscsa.edu FU NCI NIH HHS [U10 CA180886] NR 32 TC 3 Z9 3 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2016 VL 63 IS 2 BP 191 EP 195 DI 10.1002/pbc.25759 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DD9MD UT WOS:000370248900002 PM 26451963 ER PT J AU Vrooman, LM Kirov, II Dreyer, ZE Kelly, M Hijiya, N Brown, P Drachtman, RA Messinger, YH Ritchey, AK Hale, GA Maloney, K Lu, Y Plourde, PV Silverman, LB AF Vrooman, Lynda M. Kirov, Ivan I. Dreyer, ZoAnn E. Kelly, Michael Hijiya, Nobuko Brown, Patrick Drachtman, Richard A. Messinger, Yoav H. Ritchey, A. Kim Hale, Gregory A. Maloney, Kelly Lu, Yuan Plourde, Paul V. Silverman, Lewis B. TI Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia SO PEDIATRIC BLOOD & CANCER LA English DT Article DE acute lymphoblastic leukemia; childhood ALL; clinical trials; Erwinia asparaginase; pharmacokinetics ID HYPERSENSITIVITY REACTIONS; ANTIBODIES; PHARMACOKINETICS AB Background. Erwinia asparaginase is antigenically distinct from E. coli-derived asparaginase and may be used after E. coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E. coli-derived asparaginase. Patients and Methods. Between 2012 and 2013, 30 patients (age 1-17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA >= 0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA >= 0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities. Results. Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA >= 0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63-95%) 48 hr post-dose 5 (mean +/- SD; 0.32 IU/ml +/- 0.23), and in 43% (95% CI, 22-66%) 72 hr post-dose 6 (mean +/- SD; 0.089 IU/ml +/- 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%. Conclusions. IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (>= 0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated. (c) 2015 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc. C1 [Vrooman, Lynda M.; Silverman, Lewis B.] Boston Childrens Hosp, Div Hematol Oncol, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Kirov, Ivan I.] Childrens Hosp Orange Cty, Div Oncol, Orange, CA 92668 USA. [Dreyer, ZoAnn E.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Kelly, Michael] Childrens Hosp Wisconsin, Div Pediat Hematol Oncol & Bone Marrow Transplant, Milwaukee, WI 53201 USA. [Hijiya, Nobuko] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Hijiya, Nobuko] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Brown, Patrick] Johns Hopkins Univ, Sch Med, Pediat Oncol, Baltimore, MD USA. [Drachtman, Richard A.] Rutgers Canc Inst New Jersey, Dept Pediat Oncol, New Brunswick, NJ USA. [Messinger, Yoav H.] Childrens Hosp & Clin Minnesota, Pediat Hematol Oncol, Minneapolis, MN USA. [Ritchey, A. Kim] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA. [Hale, Gregory A.] All Childrens Hosp, Dept Hematol Oncol, St Petersburg, FL USA. [Maloney, Kelly] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO USA. [Lu, Yuan; Plourde, Paul V.] Jazz Pharmaceut, Palo Alto, CA USA. RP Vrooman, LM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM lynda_vrooman@dfci.harvard.edu FU Jazz Pharmaceuticals plc FX Grant sponsor: Jazz Pharmaceuticals plc NR 19 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2016 VL 63 IS 2 BP 228 EP 233 DI 10.1002/pbc.25757 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DD9MD UT WOS:000370248900008 PM 26376459 ER PT J AU Buchbinder, D Oeffinger, K Franco-Villalobos, C Yasui, Y Alderfer, MA Armstrong, GT Casillas, J Ford, J Krull, KR Leisenring, W Recklitis, C Robison, LL Zeltzer, LK Lown, EA AF Buchbinder, David Oeffinger, Kevin Franco-Villalobos, Conrado Yasui, Yutaka Alderfer, Melissa A. Armstrong, Gregory T. Casillas, Jacqueline Ford, Jennifer Krull, Kevin R. Leisenring, Wendy Recklitis, Christopher Robison, Leslie L. Zeltzer, Lonnie K. Lown, E. Anne TI Tobacco Use Among Siblings of Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE childhood cancer survivors; health behavior; siblings; smoking; tobacco ID ADOLESCENT SUBSTANCE USE; ADULT SURVIVORS; EPIDEMIOLOGIC SURVEY; ALCOHOL-CONSUMPTION; SMOKING; ADJUSTMENT; DEPENDENCE; STRESS; LIFE; PREVALENCE AB Background. Having a brother or sister with childhood cancer may influence health behaviors during adulthood. The aim of this study was to compare tobacco use in siblings of survivors with peers and to identify factors associated with sibling tobacco use. Procedures. A retrospective cohort study was conducted using adult siblings (N = 1,974) of 5+ year cancer survivors in the Childhood Cancer Survivor Study (CCSS) and participants (N = 24,105, weighted to match CCSS) in the 2007 National Health Interview Survey. Self-reported tobacco use, sociodemographic, and cancer-related risk factors were analyzed. Results. Siblings were equally likely to have ever smoked compared to their peers (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.93-1.12). Siblings were less likely to be current smokers (OR 0.83, 95% CI 0.73-0.94), but more likely to be former smokers (OR 1.21, 95% CI 1.08-1.35). Siblings with low education were more likely to ever smoke (OR 1.51, 95% CI 1.15-2.00) and be current smokers (OR 1.67, 95% CI 1.24-2.26) compared to their peers. Among siblings, risk factors for current tobacco use included the following: low income <$20,000 (OR 1.66, 95% CI 1.09-2.54), low education (OR 6.68, 95% CI 4.07-10.97), psychological distress (OR 5.36, 95% CI 2.21-13.02), and heavy alcohol use (OR 3.68, 95% CI 2.50-5.41). Conclusions. Siblings of survivors take up smoking at similar rates to their peers, but are more likely to quit. Efforts are needed to address disparities by providing greater psychosocial support and education for the lowest socioeconomic status families facing childhood cancer. (c) 2015 Wiley Periodicals, Inc. C1 [Buchbinder, David] Childrens Hosp Orange Cty, Dept Pediat, Div Hematol, Orange, CA 92668 USA. [Oeffinger, Kevin; Ford, Jennifer] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Franco-Villalobos, Conrado; Yasui, Yutaka] Univ Alberta, Sch Publ & Hlth, Dept Biostat, Edmonton, AB T6G 2M7, Canada. [Alderfer, Melissa A.] Nemours Childrens Hlth Syst, Ctr Healthcare Delivery Sci, Wilmington, DE USA. [Alderfer, Melissa A.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. [Armstrong, Gregory T.; Krull, Kevin R.; Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St, Memphis, TN 38105 USA. [Casillas, Jacqueline; Zeltzer, Lonnie K.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Casillas, Jacqueline; Zeltzer, Lonnie K.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA. [Recklitis, Christopher] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Lown, E. Anne] Univ Calif San Francisco, Dept Social & Behav Sci, San Francisco, CA USA. RP Buchbinder, D (reprint author), Childrens Hosp Orange Cty, Dept Pediat, Div Hematol, Orange, CA 92668 USA.; Buchbinder, D (reprint author), CHOC Childrens Hosp, 1201 W La Veta Ave, Orange, CA 92868 USA. EM dbuchbinder@choc.org OI Zeltzer, Lonnie/0000-0001-9306-9450 FU National Cancer Institute [U24 CA55727]; American Lebanese Syrian Associated Charities (ALSAC) FX Grant sponsor: National Cancer Institute; Grant number: U24 CA55727; Grant sponsor: American Lebanese Syrian Associated Charities (ALSAC) NR 44 TC 0 Z9 0 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2016 VL 63 IS 2 BP 326 EP 333 DI 10.1002/pbc.25719 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DD9MD UT WOS:000370248900022 PM 26305712 ER PT J AU Wallace, ZS Lu, N Unizony, S Stone, JH Choi, HK AF Wallace, Zachary S. Lu, Na Unizony, Sebastian Stone, John H. Choi, Hyon K. TI Improved survival in granulomatosis with polyangiitis: A general population-based study SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE Autoantibody; Granulomatosis with polyangiitis; Epidemiology; Cyclophosphamide ID ANTIBODY-ASSOCIATED VASCULITIS; ANCA-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; MICROSCOPIC POLYANGIITIS; SYSTEMIC VASCULITIS; FOLLOW-UP; CYCLOPHOSPHAMIDE; MAINTENANCE; COHORT; CLASSIFICATION AB Background: Granulomatosis with polyangiitis (GPA) is associated with an increased risk of mortality; however, recent mortality trends in GPA are unknown. We evaluated this issue in a general population context. Methods: Using data collected between 1992 and 2013 by The Health Improvement Network in the United Kingdom, we identified individuals diagnosed as incident cases of GPA and up to 10 non-GPA controls matched on sex, age, year of birth, and year of GPA diagnosis. The cohort was divided into two based on the year of diagnosis (i.e., 1992-2002 and 2003-2013) to evaluate changes in mortality. We calculated hazard ratios for death using a Cox-proportional hazards model and the rate differences using an additive hazard model, while adjusting for potential confounders. Results: We identified 465 cases of GPA (mean age: 60 years, 52% male). The early cohort (1992-2002) GPA patients had considerably higher mortality rates than the late cohort (2003-2013) (i.e., 72.0 vs. 35.7 cases per 1000 person-years), as compared with a moderate improvement in the comparison cohorts between the two periods (19.8 vs. 17.0 cases per 1000 person-years). The corresponding absolute mortality rate difference was 52.2 (95% CI: 25.1-792) cases and 18.7 (95% CI: 8.3-29.1) cases per 1000 person-years (p for interaction = 0.025). The resulting HRs for mortality were 4.34 (95% CI: 2.72-6.92) and 2.41 (95% CI: 1.74-3.34), respectively (p for interaction = 0.043). Conclusion: This population-based study suggests that survival of GPA patients has improved considerably over the past 2 decades, affirming the benefits of recent trends in the management of GPA and its complications. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wallace, Zachary S.; Lu, Na; Unizony, Sebastian; Stone, John H.; Choi, Hyon K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Lu, Na; Choi, Hyon K.] Boston Univ, Sch Med, Clin Epidemiol & Training Unit, Boston, MA 02118 USA. RP Wallace, ZS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA. EM zswallace@partners.org FU NIAMS NIH HHS [T32 AR007258] NR 29 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 0049-0172 EI 1532-866X J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD FEB PY 2016 VL 45 IS 4 BP 483 EP 489 DI 10.1016/j.semarthrit.2015.07.009 PG 7 WC Rheumatology SC Rheumatology GA DF8ZS UT WOS:000371650600014 PM 26323883 ER PT J AU Tsai, AC Tomlinson, M Comulada, WS Rotheram-Borus, MJ AF Tsai, Alexander C. Tomlinson, Mark Comulada, W. Scott Rotheram-Borus, Mary Jane TI Food insufficiency, depression, and the modifying role of social support: Evidence from a population-based, prospective cohort of pregnant women in peri-urban South Africa SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Food insufficiency; Depression; Social support; South Africa ID RANDOMIZED CONTROLLED-TRIAL; COMMON MENTAL-DISORDERS; MIDDLE-INCOME COUNTRIES; ALCOHOL-USE; POSTPARTUM DEPRESSION; PSYCHOSOCIAL PROBLEMS; POSTNATAL DEPRESSION; MATERNAL DEPRESSION; NUTRITIONAL-STATUS; CAPE-TOWN AB Rationale: Food insecurity has emerged as an important, and potentially modifiable, risk factor for depression. Few studies have brought longitudinal data to bear on investigating this association in sub-Saharan Africa. Objective: To estimate the association between food insufficiency and depression symptom severity, and to determine the extent to which any observed associations were modified by social support. Methods and results: We conducted a secondary analysis of population-based, longitudinal data collected from 1238 pregnant women during a three-year cluster-randomized trial of a home visiting intervention in Cape Town, South Africa. Surveys were conducted at baseline, 6 months, 18 months, and 36 months (85% retention). A validated, single-item food insufficiency measure inquired about the number of days of hunger in the past week. Depression symptom severity was measured using the Xhosa version of the 10 item Edinburgh Postnatal Depression Scale. In multivariable regression models with cluster-correlated robust estimates of variance, lagged food insufficiency had a strong and statistically significant association with depression symptom severity (beta = 0.70; 95% CI, 0.46-0.94), suggesting a 6.5% relative difference in depression symptom severity per day of hunger. In stratified analyses, food insufficiency had a statistically significant association with depression only among women with low levels of instrumental support. Using quantile regression, we found that the adverse impacts of food insufficiency were experienced to a greater degree by women in the upper end of the conditional distribution of depression symptom severity. Estimates from fixed-effects regression models and fixed-effects quantile regression models, accounting for unobserved confounding by time-invariant characteristics, were similar. Conclusions: Food insufficiency was associated with depression symptom severity, particularly for women in the upper end of the conditional depression distribution. Instrumental social support buffered women against the adverse impacts of food insufficiency. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, MGH Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Tomlinson, Mark] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. [Comulada, W. Scott; Rotheram-Borus, Mary Jane] Univ Calif Los Angeles, Ctr HIV Identificat Prevent & Treatment Serv, Los Angeles, CA USA. [Comulada, W. Scott; Rotheram-Borus, Mary Jane] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, MGH Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health (NIH) [R01AA017104]; Center for HIV Identification, Prevention, and Treatment Services [R24AA022919, P30MH058107]; UCLA Center for AIDS Research [P30AI028697]; National Center for Advancing Translational Science through the UCLA Clinical and Translational Science Institute [UL1TR000124]; National Research Foundation of South Africa; [K23MH096620] FX This study was funded by U.S. National Institutes of Health (NIH) R01AA017104 and supported by R24AA022919, P30MH058107 (Center for HIV Identification, Prevention, and Treatment Services), P30AI028697 (UCLA Center for AIDS Research), and UL1TR000124 (National Center for Advancing Translational Science through the UCLA Clinical and Translational Science Institute). The authors also acknowledge salary support through K23MH096620 (ACT) and the National Research Foundation of South Africa (MT). MT is a lead investigator with the Centre of Excellence in Human Development, University of Witwatersrand, South Africa. NR 92 TC 7 Z9 7 U1 6 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 2016 VL 151 BP 69 EP 77 DI 10.1016/j.socscimed.2015.12.042 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DG1QG UT WOS:000371842000008 PM 26773296 ER PT J AU Keung, EZ Fairweather, M Raut, CP AF Keung, Emily Z. Fairweather, Mark Raut, Chandrajit P. TI The Role of Surgery in Metastatic Gastrointestinal Stromal Tumors SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Review DE Gastrointestinal stromal tumor; GIST; Metastatic; Metastasectomy; Surgery; Cytoreduction; Debulking; Imatinib; Sunitinib; Regorafenib; Tyrosine kinase inhibitor ID NEOADJUVANT/ADJUVANT IMATINIB MESYLATE; TYROSINE-KINASE INHIBITOR; PHASE-II TRIAL; TERM-FOLLOW-UP; SURGICAL-MANAGEMENT; ADJUVANT IMATINIB; C-KIT; ADVANCED/METASTATIC GIST; RESIDUAL DISEASE; RANDOMIZED-TRIAL AB Gastrointestinal stromal tumors (GISTs) are the most common sarcomas and mesenchymal neoplasms of the gastrointestinal tract. Macroscopically complete (R0/R1) resection is the standard treatment for localized resectable GIST with adjuvant imatinib therapy recommended for patients with intermediate or high-risk disease. In patients with advanced unresectable or metastatic GIST, imatinib has significantly improved outcomes. However, while most patients achieve partial response (PR) or stable disease (SD) on imatinib (with maximal response typically seen by 6 months on treatment), approximately half will develop secondary resistance by 2 years. Available data suggest that cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved. The benefit of surgery in patients with focal tumor progression on imatinib is unclear, but may be considered. Patients with multifocal progression undergoing surgery generally have poor outcomes. Thus, surgery should be considered in patients with metastatic GIST whose disease responds to imatinib with a goal of performing R0/R1 resection. Optimal timing of surgery is unclear but should be considered between 6 months and 2 years after starting imatinib. Although surgery in patients with metastatic GIST treated with sunitinib is feasible, incomplete resections are common, complication rates are high, and survival benefit is unclear. Therefore, a careful multidisciplinary consultation is required to determine optimal treatment options on a case-by-case basis. Finally, patients with metastatic GIST should resume tyrosine kinase inhibitor treatment postoperatively. C1 [Keung, Emily Z.; Fairweather, Mark; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Keung, Emily Z.; Fairweather, Mark; Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02115 USA. RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.; Raut, CP (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM craut@bwh.harvard.edu NR 47 TC 1 Z9 1 U1 2 U2 5 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 FEB PY 2016 VL 17 IS 2 AR 8 DI 10.1007/s11864-015-0384-y PG 12 WC Oncology SC Oncology GA DF5KZ UT WOS:000371391900003 PM 26820287 ER PT J AU Jeong, S Park, J Pathania, D Castro, CM Weissleder, R Lee, H AF Jeong, Sangmoo Park, Jongmin Pathania, Divya Castro, Cesar M. Weissleder, Ralph Lee, Hakho TI Integrated Magneto-Electrochemical Sensor for Exosome Analysis SO ACS NANO LA English DT Article DE extracellular vesicles; electrochemical sensing cancer; diagnostics; point-of-care ID EPITHELIAL OVARIAN-CANCER; PANCREATIC-CANCER; FLOW-CYTOMETRY; MICROVESICLES; CELLS; GLIOBLASTOMA; MICRORNA; RNA; OVEREXPRESSION; MICROPARTICLES AB Extracellular vesicles, including exosomes, are nanoscale membrane particles that carry molecular information on parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magneto electrochemical assay: exosomes are immunomagnetically captured from patient samples and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables (i) highly sensitive, cell-specific exosome detection and (ii) sensor miniaturization and scale-up for high-throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the simultaneous profiling of multiple protein markers within an hour, outperforming conventional methods in assay sensitivity and speed. C1 [Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. [Castro, Cesar M.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Canc, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. [Jeong, Sangmoo] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. RP Lee, H (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu OI Park, Jongmin/0000-0001-8338-9346 FU U.S. NIH [R01-HL113156, R01-EB00462605, P01CA069246, T32CA79443, K12CA087723-11A1]; Ovarian Cancer Research Fund Liz Tilberis Early Career Award; DOD Ovarian Cancer Research Program Award [W81XWH-14-1-0279]; Basic Science Research Program - Ministry of Education, South Korea [NRF-2014R1A6A3A03060030] FX The authors thank Dr. Breakefield (Massachusetts General Hospital) for many helpful discussions and granting the use of laboratory resources, and Dr. Birrer (Massachusetts General Hospital) for the gift of the OVCA420 cells. This work was supported in part by U.S. NIH Grants R01-HL113156 (to H.L.), R01-EB00462605 (to R.W.), P01CA069246 (to R.W.), T32CA79443 (to RW.), K12CA087723-11A1 (to C.M.C.), Ovarian Cancer Research Fund Liz Tilberis Early Career Award (to C.M.C.), DOD Ovarian Cancer Research Program Award W81XWH-14-1-0279 (to H.L. and C.M.C.), and Basic Science Research Program (NRF-2014R1A6A3A03060030 to J.P.) funded by the Ministry of Education, South Korea. NR 52 TC 13 Z9 13 U1 40 U2 108 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD FEB PY 2016 VL 10 IS 2 BP 1802 EP 1809 DI 10.1021/acsnano.5b07584 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA DE9VL UT WOS:000370987400014 PM 26808216 ER PT J AU Tsai, AC Venkataramani, AS AF Tsai, Alexander C. Venkataramani, Atheendar S. TI Syndemics and Health Disparities: A Methodological Note SO AIDS AND BEHAVIOR LA English DT Article DE AIDS/HIV; Social determinants ID UNSTABLY HOUSED WOMEN; ADVERSE CHILDHOOD EXPERIENCES; FRACTIONAL FACTORIAL-DESIGNS; DISEASE INTERACTION CONCEPT; HIV RISK; PSYCHOSOCIAL PROBLEMS; SUBSTANCE-ABUSE; MULTICOMPONENT INTERVENTIONS; BEHAVIORAL INTERVENTIONS; EMPIRICAL TESTS AB In the theory of syndemics, diseases are hypothesized to co-occur in particular temporal or geographical contexts due to harmful social conditions (disease concentration) and to interact at the level of populations and individuals, with mutually enhancing deleterious consequences for HIV risk (disease interaction). Since its original elaboration more than 20 years ago, the epidemiological literature on syndemic problems has followed a questionable trajectory, stemming from the use of a specific type of regression model specification that conveys very little information about the theory of syndemics. In this essay we critically review the dominant approaches to modeling in the literature on syndemics; highlight the stringent assumptions implicit in these models; and describe some meaningful public health implications of the resulting analytical ambiguities. We conclude with specific recommendations for empirical work in this area moving forward. C1 [Tsai, Alexander C.; Venkataramani, Atheendar S.] Massachusetts Gen Hosp, MGH Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA. [Tsai, Alexander C.; Venkataramani, Atheendar S.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Venkataramani, Atheendar S.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, MGH Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA.; Tsai, AC (reprint author), Harvard Ctr Populat & Dev Studies, Cambridge, MA USA.; Tsai, AC (reprint author), Mbarara Univ Sci & Technol, Mbarara, Uganda. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health [K23MH096620] FX The authors acknowledge salary support through U.S. National Institutes of Health K23MH096620 (A.C.T.). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 5 Z9 5 U1 4 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD FEB PY 2016 VL 20 IS 2 BP 423 EP 430 DI 10.1007/s10461-015-1260-2 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DE0UX UT WOS:000370341600020 PM 26662266 ER PT J AU Shao, HL Chung, J Issadore, D AF Shao, Huilin Chung, Jaehoon Issadore, David TI Diagnostic technologies for circulating tumour cells and exosomes SO BIOSCIENCE REPORTS LA English DT Review DE cancer; circulating tumour cells; exosomes; molecular diagnostics; technologies ID LUNG-CANCER PATIENTS; EXTRACELLULAR VESICLES; PROSTATE-CANCER; BREAST-CANCER; LABEL-FREE; MICROFLUIDIC DEVICE; PROTEOMICS ANALYSIS; LIQUID BIOPSY; MICROVESICLES; BLOOD AB Circulating tumour cells (CTCs) and exosomes are promising circulating biomarkers. They exist in easily accessible blood and carry large diversity of molecular information. As such, they can be easily and repeatedly obtained for minimally invasive cancer diagnosis and monitoring. Because of their intrinsic differences in counts, size and molecular contents, CTCs and exosomes pose unique sets of technical challenges for clinical translation - CTCs are rare whereas exosomes are small. Novel technologies are underway to overcome these specific challenges to fully harness the clinical potential of these circulating biomarkers. Herein, we will overview the characteristics of CTCs and exosomes as valuable circulating biomarkers and their associated technical challenges for clinical adaptation. Specifically, we will describe emerging technologies that have been developed to address these technical obstacles and the unique clinical opportunities enabled by technological innovations. C1 [Shao, Huilin] Agcy Sci Technol & Res, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore. [Shao, Huilin] Natl Neurosci Inst, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. [Shao, Huilin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Chung, Jaehoon] Agcy Sci Technol & Res, Inst Microelect, 11 Sci Pk Rd, Singapore 117685, Singapore. [Issadore, David] Univ Penn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. RP Shao, HL (reprint author), Agcy Sci Technol & Res, Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore.; Shao, HL (reprint author), Natl Neurosci Inst, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.; Shao, HL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM hshao@imcb.a-star.edu.sg FU Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore [1521480027] FX This work was supported by the Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore [ grant number 1521480027 ( to H.S.)]. NR 75 TC 1 Z9 1 U1 12 U2 29 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0144-8463 EI 1573-4935 J9 BIOSCIENCE REP JI Biosci. Rep. PD FEB 1 PY 2016 VL 36 AR e00292 DI 10.1042/BSR20150180 PN 1 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DF4DG UT WOS:000371296900012 ER PT J AU Sinisalo, J Vlachopoulou, E Marchesani, M Nokelainen, J Mayranpaa, MI Lappalainen, J Paakkanen, R Wennerstrom, A Salli, K Niemi, HJ Mannisto, S Salo, P Junttila, J Eskola, M Nikus, K Arstila, TP Perola, M Huikuri, H Karhunen, PJ Kovanen, PT Palotie, A Havulinna, AS Lluis-Ganella, C Marrugat, J Elosua, R Salomaa, V Nieminen, MS Lokki, ML AF Sinisalo, Juha Vlachopoulou, Efthymia Marchesani, Marja Nokelainen, Johanna Mayranpaa, Mikko I. Lappalainen, Jani Paakkanen, Riitta Wennerstrom, Annika Salli, Krista Niemi, Heikki J. Mannisto, Satu Salo, Perttu Junttila, Juhani Eskola, Markku Nikus, Kjell Arstila, T. Petteri Perola, Markus Huikuri, Heikki Karhunen, Pekka J. Kovanen, Petri T. Palotie, Aarno Havulinna, Aki S. Lluis-Ganella, Carla Marrugat, Jaume Elosua, Roberto Salomaa, Veikko Nieminen, Markku S. Lokki, Marja-Liisa TI Novel 6p21.3 Risk Haplotype Predisposes to Acute Coronary Syndrome SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE expression experiments; human leukocyte antigen; BTNL2; single nucleotide polymorphism; MHC; genetics; association studies; haplotype; regulatory T cell; acute coronary syndrome ID GENOME-WIDE ASSOCIATION; MAJOR HISTOCOMPATIBILITY COMPLEX; ACUTE MYOCARDIAL-INFARCTION; SPLICE-SITE MUTATION; ARTERY-DISEASE; SUSCEPTIBILITY LOCI; FINNISH POPULATION; HLA-ANTIGEN; HUMAN MHC; GENOTYPE AB Background- The HLA-DRB1*01 allele of the human leukocyte antigen has been associated with acute coronary syndrome. Genome-wide association studies have revealed associations with human leukocyte antigen and non-human leukocyte antigen genes of 3 major histocompatibility complex gene classes but not at allelic level. Methods and Results- We conducted a large-scale genetic analysis on a case-control cohort comprising 5376 acute coronary syndrome cases and 4852 unrelated controls from 4 populations of 2 European countries. We analyzed the risk candidate allele of HLA-DRB1*01 by genomic real-time polymerase chain reaction together with high-density single nucleotide polymorphisms of the major histocompatibility complex to precisely identify risk loci for acute coronary syndrome with effective clinical implications. We found a risk haplotype for the disease containing single nucleotide polymorphisms from BTNL2 and HLA-DRA genes and the HLA-DRB1*01 allele. The association of the haplotype appeared in 3 of the 4 populations, and the direction of the effect was consistent in the fourth. Coronary samples from subjects homozygous for the disease-associated haplotype showed higher BTNL2 mRNA levels (r=0.760; P < 0.00001).We localized, with immunofluorescence staining, BTNL2 in CD68-positive macrophages of the coronary artery plaques. In homozygous cases, BTNL2 blocking, in T-cell stimulation assays, enhanced CD4(+)FOXP3(+) regulatory T cell proliferation significantly (blocking versus nonblocking; P < 0.05). Conclusions- In cases with the risk haplotype for acute coronary syndrome, these results suggest involvement of enhanced immune reactions. BTNL2 may have an inhibitory effect on FOXP3(+) T cell proliferation, especially in patients homozygous for the risk alleles. Clinical Trial Registration- [GRAPHICS] ; Unique Identifier: NCT00417534. C1 [Vlachopoulou, Efthymia; Marchesani, Marja; Nokelainen, Johanna; Paakkanen, Riitta; Wennerstrom, Annika; Salli, Krista; Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, Haartmaninkatu 3,POB 21, FI-00014 Helsinki, Finland. [Sinisalo, Juha; Nieminen, Markku S.] Helsinki Univ Hosp, HUH Heart & Lung Ctr, FI-00029 Helsinki, Finland. [Mayranpaa, Mikko I.] Univ Helsinki, Haartman Inst, Dept Pathol, FI-00014 Helsinki, Finland. [Niemi, Heikki J.; Arstila, T. Petteri] Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FI-00014 Helsinki, Finland. [Lappalainen, Jani; Kovanen, Petri T.] Wihuri Res Inst, SF-00140 Helsinki, Finland. [Mannisto, Satu; Salo, Perttu; Perola, Markus; Havulinna, Aki S.; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Salo, Perttu; Perola, Markus; Palotie, Aarno] Inst Mol Med Finland FIMM, Helsinki, Finland. [Junttila, Juhani; Huikuri, Heikki] Univ Hosp Oulu, Med Res Ctr, Oulu, Finland. [Junttila, Juhani; Huikuri, Heikki] Univ Oulu, Oulu, Finland. [Eskola, Markku] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Nikus, Kjell; Karhunen, Pekka J.] Tampere Univ Hosp, Ctr Heart, Tampere, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lluis-Ganella, Carla; Marrugat, Jaume; Elosua, Roberto] Hosp del Mar, Med Res Inst IMIM, Cardiovasc Epidemiol & Genet Res Grp, Barcelona, Spain. RP Lokki, ML (reprint author), Univ Helsinki, Haartman Inst, Transplantat Lab, Haartmaninkatu 3,POB 21, FI-00014 Helsinki, Finland.; Sinisalo, J (reprint author), Helsinki Univ Hosp, HUH Heart & Lung Ctr, Div Cardiol, Haartmaninkatu 4,POB 340, FI-00029 Helsinki, Finland. EM juha.sinisalo@hus.fi; maisa.lokki@helsinki.fi OI Mannisto, Satu/0000-0002-8668-3046; Sinisalo, Juha/0000-0002-0169-5137 FU Academy of Finland [129388, 136635]; Aarne Koskelo Foundation; Helsinki University Central Hospital; Tampere University Hospital special government funds [TYH7215, TKK2012005, TYH2012209]; Finnish Foundation for Cardiovascular research; Otto A. Malm Foundation; Biomedicum Helsinki Foundation; European Science Foundation (ESF) European Cooperation in the field of Scientific and Technical Research (COST) of Action [BM0803]; Finnish Medical Foundation; Academy of Finland, Helsinki, Finland; Finnish Funding Agency for Technology and Innovation, Helsinki, Finland; Finnish Cultural Foundation; State Scholarships Foundation (IKY) of Greece; Operational Programme Education and Lifelong Learning from the European Social Fund (ESF); National Strategic Reference Framework (NSRF); Spanish Ministry of Economy and Innovation through the Carlos III Health Institute (Programa HERACLES de la Red de Investigacion Cardiovascular) [RD12/0042, PS09/00456]; European Funds for Development (ERDF-FEDER); Catalan Research and Technology Innovation Interdepartmental Commission [SGR 1195] FX The study was supported by grants from the Academy of Finland (No. 129388 to Dr Nieminen, No 136635 to Dr Salomaa), the Aarne Koskelo Foundation, Helsinki University Central Hospital, and Tampere University Hospital special government funds (EVO No TYH7215, No TKK2012005, No TYH2012209), the Finnish Foundation for Cardiovascular research, the Otto A. Malm Foundation, the Biomedicum Helsinki Foundation, and the European Science Foundation (ESF) European Cooperation in the field of Scientific and Technical Research (COST) of Action BM0803, and the Finnish Medical Foundation. The Wihuri Research Institute is maintained by the Jenny and Antti Wihuri Foundation. The Fincell study was supported by the Academy of Finland, Helsinki, Finland, and the ARTEMIS study by the Finnish Funding Agency for Technology and Innovation, Helsinki, Finland. The Pirkanmaa Regional Fund belongs to the Finnish Cultural Foundation. The study was in part supported by the graduate program funded by the State Scholarships Foundation (IKY) of Greece, 2011-2012, by the resources of the Operational Programme Education and Lifelong Learning from the European Social Fund (ESF) and the National Strategic Reference Framework (NSRF) 2007-2013. The REGICOR study was supported by the Spanish Ministry of Economy and Innovation through the Carlos III Health Institute (Programa HERACLES de la Red de Investigacion Cardiovascular RD12/0042, PS09/00456), European Funds for Development (ERDF-FEDER), and by the Catalan Research and Technology Innovation Interdepartmental Commission (SGR 1195). NR 41 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 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD FEB PY 2016 VL 9 IS 1 BP 55 EP 63 DI 10.1161/CIRCGENETICS.115.001226 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA DF0FI UT WOS:000371014100008 PM 26679868 ER PT J AU Yu, B Pulit, SL Hwang, SJ Brody, JA Amin, N Auer, PL Bis, JC Boerwinkle, E Burke, GL Chakravarti, A Correa, A Dreisbach, AW Franco, OH Ehret, GB Franceschini, N Hofman, A Lin, DY Metcalf, GA Musani, SK Muzny, D Palmas, W Raffel, L Reiner, A Rice, K Rotter, JI Veeraraghavan, N Fox, E Guo, XQ North, KE Gibbs, RA van Duijn, CM Psaty, BM Levy, D Newton-Cheh, C Morrison, AC AF Yu, Bing Pulit, Sara L. Hwang, Shih-Jen Brody, Jennifer A. Amin, Najaf Auer, Paul L. Bis, Joshua C. Boerwinkle, Eric Burke, Gregory L. Chakravarti, Aravinda Correa, Adolfo Dreisbach, Albert W. Franco, Oscar H. Ehret, Georg B. Franceschini, Nora Hofman, Albert Lin, Dan-Yu Metcalf, Ginger A. Musani, Solomon K. Muzny, Donna Palmas, Walter Raffel, Leslie Reiner, Alex Rice, Ken Rotter, Jerome I. Veeraraghavan, Narayanan Fox, Ervin Guo, Xiuqing North, Kari E. Gibbs, Richard A. van Duijn, Cornelia M. Psaty, Bruce M. Levy, Daniel Newton-Cheh, Christopher Morrison, Alanna C. CA CHARGE Consortium Natl Heart Lung Blood Inst GO ESP TI Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and Hypertension Risk SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetic variation; hypertension; genome-wide association study; exome; blood pressure ID GENOME-WIDE ASSOCIATION; PULSE PRESSURE; MEAN ARTERIAL; DESIGN; MUTATIONS; TRAITS; GENES; OBJECTIVES; LOCI; ATHEROSCLEROSIS AB Background- Rare genetic variants influence blood pressure (BP). Methods and Results- Whole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of approximate to 170 000 common variants (minor allele frequency, >= 1%; statistical significance, P <= 2.9x10(-7)) and gene-based tests of rare variants (minor allele frequency, < 1%; approximate to 17 000 genes; statistical significance, P <= 1.5x10(-6)) were evaluated for each trait and ancestry, followed by multiethnic meta-analyses. In the first-stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsynonymous variants, or indels) in CLCN6 were associated with lower diastolic BP (cumulative minor allele frequency, 1.3%; beta=-3.20; P=4.1x10(-6)) and were independent of a nearby common variant (rs17367504) previously associated with BP. CLCN6 rare variants were also associated with lower systolic BP (beta=-4.11; P=2.8x10(-4)), mean arterial pressure (beta=-3.50; P=8.9x10(-6)), and reduced hypertension risk (odds ratio, 0.72; P=0.017). Meta-analysis of the 2-stage discovery samples showed that CLCN6 was associated with lower diastolic BP at exome-wide significance (cumulative minor allele frequency, 1.1%; beta=-3.30; P=5.0x10(-7)). Conclusions- These findings implicate the effect of rare coding variants in CLCN6 in BP variation and offer new insights into BP regulation. C1 [Yu, Bing; Boerwinkle, Eric; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Pressler St,Suite 453E, Houston, TX 77030 USA. [Pulit, Sara L.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Pulit, Sara L.; Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Cambridge, MA USA. [Hwang, Shih-Jen; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Hwang, Shih-Jen; Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Brody, Jennifer A.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. [Amin, Najaf; Franco, Oscar H.; Hofman, Albert; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Auer, Paul L.] Univ Wisconsin Milwaukee, Sch Publ Hlth, Biostat, Milwaukee, WI USA. [Boerwinkle, Eric; Metcalf, Ginger A.; Muzny, Donna; Veeraraghavan, Narayanan; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Burke, Gregory L.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [Ehret, Georg B.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA. [Dreisbach, Albert W.; Musani, Solomon K.; Fox, Ervin] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS USA. [Ehret, Georg B.] Univ Hosp Geneva, Dept Specialties Internal Med, Div Cardiol, Geneva, Switzerland. [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Palmas, Walter] Columbia Univ, Med Ctr, Dept Med, New York, NY USA. [Raffel, Leslie] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Raffel, Leslie] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Clin & Translat Sci Inst, Los Angeles, CA 90048 USA. [Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Rotter, Jerome I.; Guo, Xiuqing] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Levy, Daniel] Boston Univ, Sch Med, Boston, MA 02215 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Morrison, AC (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Pressler St,Suite 453E, Houston, TX 77030 USA. EM alanna.c.morrison@uth.tmc.edu FU National Heart, Lung, and Blood Institute (NHLBI) [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924]; NHLBI [RC2 HL-102925, RC2 HL-102926, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268-201100009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C, R01HL087641, R01HL59367, R01HL086694, N01-HC-25195, HHSN268201200036C, HHSN268200800007C, N01HC55222N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393]; National Institutes of Health through the American Recovery and Reinvestment Act [5RC2HL102419]; Affymetrix, Inc [N02-HL-6-4278]; National Institute on Aging [R01AG023629R01AG023629]; National Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268-201300050C]; National Institute on Minority Health and Health Disparities; MESA [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Center for Research Resources [UL1-TR-000040, UL1-RR-025005]; National Center for Advancing Translational Sciences, CTSI grant [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center [DK063491]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268-201100004C, HHSN271201100004C]; European Commission FP6 STRP grant [018947 (LSHG-CT-2006-01947)]; European Community's Seventh Framework Programme by the European Commission [HEALTH-F4-2007-201413, QLG2-CT-2002-01254]; Netherlands Organization for Scientific Research; Russian Foundation for Basic Research [NWO-RFBR 047.017.043]; ZonMw [91111025]; Hersenstichting Nederland [F2013[1]-28]; Netherlands Organisation of Scientific Research Netherlands Organisation for Scientific Research (NWO) Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/NWO [050-060-810]; Netherlands Consortium for Healthy Ageing (NCHA); NGI/NWO [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; complementation project of the Biobanking and Biomolecular Research Infrastructure Netherlands [CP2010-41]; Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly; Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam FX Funding for GO Exome Sequencing Project was provided by National Heart, Lung, and Blood Institute (NHLBI) grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO), and RC2 HL-102924 (WHISP). The exome sequencing was performed through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). Funding support for Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium was provided by the National Institutes of Health through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Sequencing was carried out at the Baylor Genome Center (U54 HG003273). The Atherosclerosis Risk in Communities (ARIC) study is carried out as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268-201100009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C), R01HL087641, R01HL59367, and R01HL086694. The Framingham Heart Study (FHS) was conducted and supported by the NHLBI in collaboration with Boston University (contract no. N01-HC-25195), and its contract with Affymetrix, Inc, for genome-wide genotyping services (contract no. N02-HL-6-4278), for quality control by FHS investigators using genotypes in the SNP Health Association Resource project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis computing resources at Boston University Medical Campus. The Cardiovascular Health Study (CHS) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through R01AG023629R01AG023629 from the National Institute on Aging. The Jackson Heart Study (JHS) was supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268-201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. The Multi-Ethnic Study of Atherosclerosis (MESA) was supported by the MESA contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and by grants UL1-TR-000040 and UL1-RR-025005 from National Center for Research Resources. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Women's Health Initiative (WHI) program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268-201100004C, and HHSN271201100004C." The Erasmus Rucphen Family (ERF) study as a part of European Special Populations Research Network was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme Quality of Life and Management of the Living Resources of 5th Framework Programme (no.; QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing analysis in ERF was supported by the ZonMw grant (project 91111025). N. Amin was supported by the Hersenstichting Nederland (project no. F2013[1]-28). The generation and management of GWAS genotype data for the Rotterdam Study (RS) were supported by the Netherlands Organisation of Scientific Research Netherlands Organisation for Scientific Research (NWO) Investments (no. 175.010.2005.011 and 911-03-012). This study was funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/NWO (project nr. 050-060-810) and Netherlands Consortium for Healthy Ageing (NCHA). The generation and management of the exome sequencing data for the RS were executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. The exome sequencing data set was funded by the NGI/NWO-sponsored NCHA (project no. 050-060-810), by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a complementation project of the Biobanking and Biomolecular Research Infrastructure Netherlands (http://www.bbmri.nl; project no. CP2010-41). The RS was funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. NR 43 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD FEB PY 2016 VL 9 IS 1 BP 64 EP 70 DI 10.1161/CIRCGENETICS.115.001215 PG 7 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA DF0FI UT WOS:000371014100009 PM 26658788 ER PT J AU Belalcazar, LM Papandonatos, GD Erar, B Peter, I Alkofide, H Balasubramanyam, A Brautbar, A Kahn, SE Knowler, WC Ballantyne, CM McCaffery, JM Huggins, GS AF Belalcazar, L. Maria Papandonatos, George D. Erar, Bahar Peter, Inga Alkofide, Hadeel Balasubramanyam, Ashok Brautbar, Ariel Kahn, Steven E. Knowler, William C. Ballantyne, Christie M. McCaffery, Jeanne M. Huggins, Gordon S. CA Look AHEAD Study TI Lifestyle Intervention for Weight Loss and Cardiometabolic Changes in the Setting of Glucokinase Regulatory Protein Inhibition Glucokinase Regulatory Protein-Leu446Pro Variant in Look AHEAD SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE lifestyle; GCKR; behavioral intervention; triglycerides; C-reactive protein; obesity; diabetes mellitus ID C-REACTIVE PROTEIN; FASTING PLASMA-GLUCOSE; TYPE-2 DIABETES RISK; CARDIOVASCULAR-DISEASE; TRIGLYCERIDE LEVELS; REDUCING LIPIDS; INDIVIDUALS; HOMEOSTASIS; ASSOCIATION; PREVALENCE AB Background- Glucokinase regulatory protein (GCKR) inhibitors offer a novel treatment approach for glucose control in diabetes mellitus; however, their cardiometabolic effects, particularly in relation to increased triglycerides and C-reactive protein (CRP) levels, are of concern. GCKR Leu446Pro is a common variant associated with reduced GCKR function, increased triglycerides, and CRP. Methods and Results- We investigated whether a 1-year intensive lifestyle intervention (ILI) for weight loss would avert the unfavorable cardiometabolic effects associated with GCKR Leu446Pro when compared with a diabetes mellitus support and education arm in overweight/obese individuals with type 2 diabetes mellitus with triglyceride (n=3214) and CRP (n=1411) data participating in a randomized lifestyle intervention study for weight loss, Action for Health in Diabetes Mellitus (Look AHEAD). Once demographics, medication use and baseline adiposity, and fitness were accounted for, ILI did not modify the baseline association of GCKR-Leu446Pro with elevated triglycerides (beta +/- SE=0.067 +/- 0.013, P=1.5x10(-7) and beta +/- SE=0.052 +/- 0.015, P=5x10(-4)) or with elevated CRP (beta +/- SE=0.136 +/- 0.034, P=5.1x10(-5)and beta +/- SE=0.903 +/- 0.038, P=0.015) in the overall sample and Non-Hispanic Whites, respectively. The lack of a protective effect from ILI at 1 year when compared with diabetes mellitus support and education (ILI versus diabetes mellitus support and education interaction for triglyceride and CRP change, respectively: P=0.64 and 0.37 in the overall sample; P=0.27 and 0.05 in Non-Hispanic Whites) persisted after additional adjustment for changes in adiposity and fitness. Conclusions- Moderate improvements in adiposity and fitness with ILI did not mitigate the adverse cardiometabolic effects of GCKR inhibition in overweight/obese individuals with diabetes mellitus. C1 [Belalcazar, L. Maria; Ballantyne, Christie M.] Univ Texas Med Branch, Dept Internal Med, Div Endocrinol & Metab, Galveston, TX 77555 USA. [Papandonatos, George D.; Erar, Bahar] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Alkofide, Hadeel] Tufts Univ, Sackler Sch Biomed Res, Clin Translat Sci Program, Boston, MA 02111 USA. [Balasubramanyam, Ashok] Baylor Coll Med, Div Endocrinol Diabet & Metab, Diabet Res Ctr, Translat Metab Unit, Houston, TX 77030 USA. [Brautbar, Ariel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA. [Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [McCaffery, Jeanne M.] Miriam Hosp, Dept Psychiat & Human Behav, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. [McCaffery, Jeanne M.] Brown Med Sch, Providence, RI USA. [Huggins, Gordon S.] Tufts Med Ctr, Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Huggins, Gordon S.] Tufts Univ, Boston, MA 02111 USA. RP Huggins, GS (reprint author), Tufts Med Ctr, MCRI Ctr Translat Genom, Boston, MA 02111 USA.; Huggins, GS (reprint author), Tufts Univ, Sch Med, Boston, MA 02111 USA. EM ghuggins@tuftsmedicalcenter.org OI Papandonatos, George/0000-0001-6770-932X; Kahn, Steven/0000-0001-7307-9002 FU Department of Health and Human Services from the National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; National Institutes of Health (NIH) Office of Research on Women's Health; Centers for Disease Control and Prevention; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center [M01RR000056 44]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346]; [DK090043-02]; [X01 HG006659]; [HL09051401] FX This study was funded by DK090043-02 and X01 HG006659 (Drs Papandonatos, McCaffery, Huggins) and HL09051401 (Drs Belalcazar and Ballantyne). Look AHEAD was supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; National Institutes of Health (NIH) Office of Research on Women's Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (IHS) provided personnel, medical oversight, and use of facilities. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the IHS or other funding sources. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056 44) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson, LifeScan Inc; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever. NR 32 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 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD FEB PY 2016 VL 9 IS 1 BP 71 EP 78 DI 10.1161/CIRCGENETICS.115.001192 PG 8 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA DF0FI UT WOS:000371014100010 PM 26578543 ER PT J AU Leasure, A Kimberly, WT Sansing, LH Kahle, KT Kronenberg, G Kunte, H Simard, JM Sheth, KN AF Leasure, Audrey Kimberly, W. Taylor Sansing, Lauren H. Kahle, Kristopher T. Kronenberg, Golo Kunte, Hagen Simard, J. Marc Sheth, Kevin N. TI Treatment of Edema Associated With Intracerebral Hemorrhage SO CURRENT TREATMENT OPTIONS IN NEUROLOGY LA English DT Review DE Intracerebral hemorrhage; Perihematomal edema; Secondary brain injury; Hyperosmolar therapy; ICP ID INITIAL CONSERVATIVE TREATMENT; REDUCES PERIHEMORRHAGIC EDEMA; DECREASED PERIHEMATOMAL EDEMA; MINIMALLY INVASIVE SURGERY; BLOOD-PRESSURE REDUCTION; DECOMPRESSIVE HEMICRANIECTOMY; BRAIN EDEMA; NEUROLOGICAL DETERIORATION; PLASMINOGEN-ACTIVATOR; PERIHAEMATOMAL EDEMA AB Opinion statement Cerebral edema (i.e., "brain swelling") is a common complication following intracerebral hemorrhage (ICH) and is associated with worse clinical outcomes. Perihematomal edema (PHE) accumulates during the first 72 h after hemorrhage, and during this period, patients are at risk of clinical deterioration due to the resulting tissue shifts and brain herniation. First-line medical therapies for patients symptomatic of PHE include osmotic agents, such as mannitol in low-or high-dose bolus form, or boluses of hypertonic saline (HTS) at varied concentrations with or without subsequent continuous infusion. Decompressive craniectomy may be required for symptomatic edema refractory to osmotherapy. Other strategies that reduce PHE such as hypothermia and minimally invasive surgery have shown promise in pilot studies and are currently being evaluated in larger clinical trials. Ongoing basic, translational, and clinical research seek to better elucidate the pathophysiology of PHE to identify novel strategies to prevent edema formation as a next major advance in the treatment of ICH. C1 [Leasure, Audrey; Sansing, Lauren H.; Sheth, Kevin N.] Yale Univ, Sch Med, Dept Neurol, 333 Cedar St, New Haven, CT 06510 USA. [Kimberly, W. Taylor] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. [Kahle, Kristopher T.] Yale Program Neurogenet, Dept Neurosurg & Pediat, 333 Cedar St, New Haven, CT 06510 USA. [Kronenberg, Golo; Kunte, Hagen] Charite, Dept Neurol, Charitepl 1, D-10117 Berlin, Germany. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Neurosurg, 22 S Greene St, Baltimore, MD 21201 USA. RP Leasure, A (reprint author), Yale Univ, Sch Med, Dept Neurol, 333 Cedar St, New Haven, CT 06510 USA. EM audrey.leasure@yale.edu FU National Institutes of Health-NINDS; American Heart Association; Remedy Pharmaceuticals, Inc.; National Institutes of Health FX W. Taylor Kimberly reports grants from the National Institutes of Health-NINDS, American Heart Association, and Remedy Pharmaceuticals, Inc.; Lauren H. Sansing reports grants from the National Institutes of Health. NR 76 TC 2 Z9 2 U1 3 U2 9 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1092-8480 EI 1534-3138 J9 CURR TREAT OPTION NE JI Curr. Treat. Options Neurol. PD FEB PY 2016 VL 18 IS 2 AR 9 DI 10.1007/s11940-015-0392-z PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA DF5KT UT WOS:000371391300004 PM 26874842 ER PT J AU Barnard, K Bergenstal, R Laffel, L Weissberg-Benchell, J Hood, K Heinemann, L Sullivan, S Miller, KM AF Barnard, K. Bergenstal, R. Laffel, L. Weissberg-Benchell, J. Hood, K. Heinemann, L. Sullivan, S. Miller, K. M. TI ARTIFICIAL PANCREAS PSYCHOSOCIAL MEASURES PROJECT SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 [Laffel, L.] Harvard Univ, Sch Med, Genet & Epidemiol Sect, Joslin Diabet Ctr, Cambridge, MA 02138 USA. [Weissberg-Benchell, J.] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Chicago, IL 60611 USA. [Hood, K.] Stanford Univ, Sch Med, Psychiat & Behav Sci, Stanford, CA 94305 USA. [Miller, K. M.] Jaeb Ctr Hlth Res, 15310 Amberly Dr, Tampa, FL 33647 USA. [Barnard, K.] Bournemouth Univ, Poole BH12 5BB, Dorset, England. [Sullivan, S.] Leona M & Harry B Helmsley Charitable Trust, 230 Pk Ave,Suite 659, New York, NY 10169 USA. [Bergenstal, R.] Int Diabet Ctr, 3800 Pk Nicollet Blvd, Minneapolis, MN 55416 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB 1 PY 2016 VL 18 SU 1 MA 009 BP A4 EP A4 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD1HU UT WOS:000369672700010 ER PT J AU Gnasso, A Spadea, MF Scaramuzzino, S Pileggi, G Zaffino, P Carallo, C AF Gnasso, A. Spadea, M. F. Scaramuzzino, S. Pileggi, G. Zaffino, P. Carallo, C. TI A DEVICE ACQUIRING, DIGITIZING, AND SENDING THE RESULTS OF EVERY GLUCOMETER IN DIGITAL FORMAT FOR TELEMEDICINE PURPOSES SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 [Gnasso, A.; Scaramuzzino, S.; Pileggi, G.; Zaffino, P.] Magna Graecia Univ Catanzaro, Dept Clin & Expt Med, Catanzaro, Italy. [Spadea, M. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spadea, M. F.] Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. [Carallo, C.] Univ London Imperial Coll Sci Technol & Med, Dept Chem Engn, London SW7 2AZ, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB 1 PY 2016 VL 18 SU 1 MA 224 BP A90 EP A90 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD1HU UT WOS:000369672700226 ER PT J AU Laffel, L AF Laffel, L. TI PSYCHOSOCIAL OUTCOMES OF CGM USE IN CHILDREN AND TEENS WITH TYPE 1 DIABETES SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 [Laffel, L.] Joslin Diabet Ctr, Pediat, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD FEB 1 PY 2016 VL 18 SU 1 MA 040 BP A14 EP A15 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD1HU UT WOS:000369672700041 ER PT J AU Prieto, A Escapa, IF Martinez, V Dinjaski, N Herencias, C de la Pena, F Tarazona, N Revelles, O AF Prieto, Auxiliadora Escapa, Isabel F. Martinez, Virginia Dinjaski, Nina Herencias, Cristina de la Pena, Fernando Tarazona, Natalia Revelles, Olga TI A holistic view of polyhydroxyalkanoate metabolism in Pseudomonas putida SO ENVIRONMENTAL MICROBIOLOGY LA English DT Review ID MEDIUM-CHAIN-LENGTH; RALSTONIA-EUTROPHA H16; IN-VIVO IMMOBILIZATION; BDELLOVIBRIO-BACTERIOVORUS; ACID GRANULES; HYDROXYALKANOIC ACIDS; GENE-EXPRESSION; BACTERIAL POLYHYDROXYALKANOATES; ENGINEERED PSEUDOMONAS; ALCALIGENES-EUTROPHUS AB Polyhydroxyalkanoate (PHA) metabolism has been traditionally considered as a futile cycle involved in carbon and energy storage. The use of cutting-edge technologies linked to systems biology has improved our understanding of the interaction between bacterial physiology, PHA metabolism and other cell functions in model bacteria such as Pseudomonas putidaKT2440. PHA granules or carbonosomes are supramolecular complexes of biopolyester and proteins that are essential for granule segregation during cell division, and for the functioning of the PHA metabolic route as a continuous cycle. The simultaneous activities of PHA synthase and depolymerase ensure the carbon flow to the transient demand for metabolic intermediates to balance the storage and use of carbon and energy. PHA cycle also determines the number and size of bacterial cells. The importance of PHAs as nutrients for members of the microbial community different to those that produce them is illustrated here via examples of bacterial predators such as Bdellovibrio bacteriovorus that prey on PHA producers and produces specific extra-cellular depolymerases. PHA hydrolysis confers Bdellovibrio ecological advantages in terms of motility and predation efficiency, demonstrating the importance of PHA producers predation in population dynamics. Metabolic modulation strategies for broadening the portfolio of PHAs are summarized and their properties are compiled. C1 [Prieto, Auxiliadora; Escapa, Isabel F.; Martinez, Virginia; Dinjaski, Nina; Herencias, Cristina; de la Pena, Fernando; Tarazona, Natalia; Revelles, Olga] CSIC, Ctr Invest Biol, Dept Environm Biol, Plaza Murillo 2, E-28040 Madrid, Spain. [Escapa, Isabel F.] Forsyth Inst, Cambridge, MA USA. [Martinez, Virginia] Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Horsholm, Denmark. [Dinjaski, Nina] Tufts Univ, Ctr Sci & Technol, Medford, MA 02155 USA. RP Prieto, A (reprint author), CSIC, Ctr Invest Biol, Dept Environm Biol, Plaza Murillo 2, E-28040 Madrid, Spain. EM auxi@cib.csic.es OI Martinez, Virginia/0000-0002-4977-4176 FU Ministerio of Economia y Competitividad, Espana [BIO2010-21049, BIO2013-44878-R, 201120E092, 201120E050]; Department of Science Technology and Innovation-Colciencias, Colombia FX This work was supported by the Ministerio of Economia y Competitividad, Espana (BIO2010-21049, BIO2013-44878-R, 201120E092, 201120E050). Natalia Tarazona is a PhD student granted by the Department of Science Technology and Innovation-Colciencias, Colombia. NR 114 TC 6 Z9 6 U1 14 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-2912 EI 1462-2920 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD FEB PY 2016 VL 18 IS 2 BP 341 EP 357 DI 10.1111/1462-2920.12760 PG 17 WC Microbiology SC Microbiology GA DF3GR UT WOS:000371232600007 PM 25556983 ER PT J AU Wilkoff, BL Fauchier, L Stiles, MK Morillo, CA Al-Khatib, SM Almendral, J Aguinaga, L Berger, RD Cuesta, A Daubert, JP Dubner, S Ellenbogen, KA Estes, NAM Fenelon, G Garcia, FC Gasparini, M Haines, DE Healey, JS Hurtwitz, JL Keegan, R Kolb, C Kuck, KH Marinskis, G Martinelli, M Mcguire, M Molina, LG Okumura, K Proclemer, A Russo, AM Singh, JP Swerdlow, CD Teo, WS Uribe, W Viskin, S Wang, CC Zhang, S AF Wilkoff, Bruce L. Fauchier, Laurent Stiles, Martin K. Morillo, Carlos A. Al-Khatib, Sana M. Almendral, Jesus Aguinaga, Luis Berger, Ronald D. Cuesta, Alejandro Daubert, James P. Dubner, Sergio Ellenbogen, Kenneth A. Estes, N. A. Mark, III Fenelon, Guilherme Garcia, Fermin C. Gasparini, Maurizio Haines, David E. Healey, Jeff S. Hurtwitz, Jodie L. Keegan, Roberto Kolb, Christof Kuck, Karl-Heinz Marinskis, Germanas Martinelli, Martino Mcguire, Mark Molina, Luis G. Okumura, Ken Proclemer, Alessandro Russo, Andrea M. Singh, Jagmeet P. Swerdlow, Charles D. Teo, Wee Siong Uribe, William Viskin, Sami Wang, Chun-Chieh Zhang, Shu TI 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing SO EUROPACE LA English DT Article DE Implantable cardioverter-defibrillator; Bradycardia mode and rate; Tachycardia detection; Tachycardia therapy; Defibrillation testing; Programming ID CARDIAC-RESYNCHRONIZATION THERAPY; QUALITY-OF-LIFE; FAST VENTRICULAR-TACHYCARDIA; SICK-SINUS SYNDROME; DUAL-CHAMBER DEFIBRILLATORS; REDUCE INAPPROPRIATE SHOCKS; PRIMARY PREVENTION PATIENTS; RATE-RESPONSIVE PACEMAKERS; RANDOMIZED CLINICAL-TRIAL; LONG-DETECTION INTERVAL C1 [Wilkoff, Bruce L.] Cleveland Clin, Cleveland, OH 44106 USA. [Fauchier, Laurent] CHU Trousseau, Tours, France. [Stiles, Martin K.] Waikato Hosp, Hamilton, New Zealand. [Morillo, Carlos A.; Healey, Jeff S.] McMaster Univ, Populat Hlth Res Inst, Div Cardiol, Dept Med, Hamilton, ON, Canada. [Al-Khatib, Sana M.; Daubert, James P.] Duke Univ, Med Ctr, Durham, NC USA. [Almendral, Jesus] Univ CEU San Pablo, Grp HM Hosp, Madrid, Spain. [Aguinaga, Luis] Ctr Privado Cardiol, San Miguel De Tucuman, Argentina. [Berger, Ronald D.] Johns Hopkins Univ, Baltimore, MD USA. [Cuesta, Alejandro] Inst Cardiol Infantil, Serv Arritmias, Montevideo, Uruguay. [Dubner, Sergio] Clin & Maternidad Suizo Argentina & Arcos Sanator, Buenos Aires, DF, Argentina. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Estes, N. A. Mark, III] Tufts Univ New England Med Ctr, 750 Washington St, Boston, MA 02111 USA. [Fenelon, Guilherme] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Garcia, Fermin C.] Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA. [Gasparini, Maurizio] Humanitas Res Hosp, Milan, Italy. [Haines, David E.] William Beaumont Hosp, Div Cardiol, Royal Oak, MI 48072 USA. [Hurtwitz, Jodie L.] North Texas Heart Ctr, Dallas, TX USA. [Keegan, Roberto] Hosp Privado Sur, Bahia Blanca, Buenos Aires, Argentina. [Kolb, Christof] Deutsch Herzzentrum Munich, Munich, Germany. [Kuck, Karl-Heinz] Allgemeines Krankenhaus St Georg, Hamburg, Germany. [Marinskis, Germanas] Vilnius Univ, Clin Cardiac & Vasc Dis, Vilnius, Lithuania. [Martinelli, Martino] Univ Sao Paulo, Inst Coracao, Sao Paulo, Brazil. [Mcguire, Mark] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Molina, Luis G.] Mexicos Natl Univ, Mexicos Gen Hosp, Mexico City, DF, Mexico. [Okumura, Ken] Hirosaki Univ, Grad Sch Med, Hirosaki, Aomori, Japan. [Proclemer, Alessandro] Azienda Osped Univ S Maria Misericordia Udine, Udine, Italy. [Russo, Andrea M.] Cooper Univ Hosp, Camden, NJ USA. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Swerdlow, Charles D.] Cedars Sinai Med Ctr, Beverly Hills, CA USA. [Teo, Wee Siong] Natl Heart Ctr Singapore, Singapore, Singapore. [Uribe, William] San Vicente Fdn, CES Cardiol & Ctr Especializados, Medellin Y Rionegro, Colombia. [Viskin, Sami] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. [Viskin, Sami] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Wang, Chun-Chieh] Chang Gung Mem Hosp, 199 Tung Hwa N Rd, Taipei 10591, Taiwan. [Zhang, Shu] Peking Union Med Coll, Natl Ctr Cardiovasc Dis, Beijing 100021, Peoples R China. [Zhang, Shu] Peking Union Med Coll, Beijing Fu Wai Hosp, Beijing 100021, Peoples R China. [Zhang, Shu] China Acad Med Sci, Beijing, Peoples R China. [Fauchier, Laurent; Almendral, Jesus; Gasparini, Maurizio; Kolb, Christof; Kuck, Karl-Heinz; Marinskis, Germanas; Proclemer, Alessandro; Viskin, Sami] EHRA, Cleveland, OH USA. [Stiles, Martin K.; Mcguire, Mark; Okumura, Ken; Teo, Wee Siong; Wang, Chun-Chieh; Zhang, Shu] APHRS, New York, NY USA. [Morillo, Carlos A.; Aguinaga, Luis; Cuesta, Alejandro; Dubner, Sergio; Garcia, Fermin C.; Keegan, Roberto; Molina, Luis G.; Uribe, William] Sociedad Latinoamericana Estimulac Cardiaca & Ele, Madrid, Spain. [Estes, N. A. Mark, III] AHA, Madrid, Spain. [Hurtwitz, Jodie L.] ACC, New York, NY USA. RP Wilkoff, BL (reprint author), Cleveland Clin, Cleveland, OH 44106 USA. RI Martinelli, Martino/D-9785-2012; Boriani, Giuseppe/A-4852-2015; OI Martinelli, Martino/0000-0003-4440-8078; Boriani, Giuseppe/0000-0002-9820-4815; Di Biase, Luigi/0000-0001-6508-4047 NR 222 TC 6 Z9 6 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 EI 1532-2092 J9 EUROPACE JI Europace PD FEB 1 PY 2016 VL 18 IS 2 BP 159 EP 183 DI 10.1093/europace/euv411 PG 25 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DF3LB UT WOS:000371244400001 PM 26585598 ER PT J AU Grants, JM Ying, LTL Yoda, A You, CC Okano, H Sawa, H Taubert, S AF Grants, Jennifer M. Ying, Lisa T. L. Yoda, Akinori You, Charlotte C. Okano, Hideyuki Sawa, Hitoshi Taubert, Stefan TI The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans SO GENETICS LA English DT Article DE Mediator complex; CDK8; MED23; MED15; EGFR; Notch ID RNA-POLYMERASE-II; C-ELEGANS; MAP KINASE; ETS-DOMAIN; TRANSCRIPTION CONTROL; TYROSINE KINASE; SYNMUV GENES; INDUCTION; COMPLEX; CDK8 AB Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals. C1 [Grants, Jennifer M.; Taubert, Stefan] Univ British Columbia, Dept Med Genet, 950 W 28th Ave,Room 3018, Vancouver, BC V5Z 4H4, Canada. [Grants, Jennifer M.; Ying, Lisa T. L.; You, Charlotte C.; Taubert, Stefan] Univ British Columbia, Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. [Yoda, Akinori; Okano, Hideyuki; Sawa, Hitoshi] Osaka Univ, Grad Sch Med, Div Neuroanat, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. [Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1088345, Japan. [Sawa, Hitoshi] Natl Inst Genet, Multicellular Org Lab, Mishima, Shizuoka 4110801, Japan. [Yoda, Akinori] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Taubert, S (reprint author), Univ British Columbia, Dept Med Genet, 950 W 28th Ave,Room 3018, Vancouver, BC V5Z 4H4, Canada. EM taubert@cmmt.ubc.ca RI Hidokano, Hideyuki/J-5973-2013 FU National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]; Canadian Institute of Health Research [MOP-93713]; Natural Sciences and Engineering Research Council of Canada [RGPIN 386398-13]; Canada Foundation for Innovation; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Vanier Canada Graduate Scholarship; University of British Columbia; Canada Research Chair; Child and Family Research Institute FX We thank all Taubert lab members for critical discussions; Shirley Chen for help with experiments; R. Barbeau, C. Eisley, A. Barczak, and D. Erle from the Sandler Asthma Basic Research Center Functional Genomics Core Facility (University of California San Francisco) for help with microarray gene expression profiling; J. Ewbank for EASE analysis of gene expression arrays; J. Escobar for advice on scoring VPC induction; I. Greenwald for GS5096 arEx1098 [lag-2p(min)::YFP]; S. Mitani for cdk-8(tm1238) and cic-1 (tm3740) mutants; and D. Moerman and J. Ward for comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440). This work was supported by grants from Canadian Institute of Health Research (MOP-93713), Natural Sciences and Engineering Research Council of Canada (RGPIN 386398-13), Canada Foundation for Innovation (all to S.T.), and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to H.S.). J.M.G. was supported by Vanier Canada Graduate Scholarship, Natural Sciences and Engineering Research Council of Canada Canada Graduate Scholarship-Masters, Child and Family Research Institute, and University of British Columbia scholarships, and S. T. by a Canada Research Chair. The authors declare no competing financial interests. NR 84 TC 2 Z9 2 U1 8 U2 10 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD FEB PY 2016 VL 202 IS 2 BP 583 EP + DI 10.1534/genetics.115.180265 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA DF4FY UT WOS:000371304600020 PM 26715664 ER PT J AU Cardozo, ER Karmon, AE Gold, J Petrozza, JC Styer, AK AF Cardozo, E. R. Karmon, A. E. Gold, J. Petrozza, J. C. Styer, A. K. TI Reproductive outcomes in oocyte donation cycles are associated with donor BMI SO HUMAN REPRODUCTION LA English DT Article DE body mass index; obesity; oocyte; oocyte donor; in vitro fertilization; oocyte recipient; reproductive outcomes; oocyte quality ID BODY-MASS INDEX; IN-VITRO FERTILIZATION; MULTIVARIATE-ANALYSIS; UTERINE RECEPTIVITY; PREGNANCY OUTCOMES; OBESITY; TECHNOLOGY; WOMEN; DETERMINANTS; MITOCHONDRIA AB When adjusting for recipient BMI, is donor body mass index (BMI) associated with IVF outcomes in donor oocyte IVF cycles? Increasing oocyte donor BMI is associated with a reduction in clinical pregnancy and live birth rates. Increased BMI has been associated with suboptimal reproductive outcomes, particularly in assisted reproductive technology (ART) cycles. However, it remains unclear if this association implies an effect of BMI on oocyte quality and/or endometrial receptivity. A retrospective cohort study of two hundred and thirty five consecutive fresh donor oocyte IVF cycles from 1 January 2007 through 31 December 2013 at the Massachusetts General Hospital (MGH) Fertility Center. Analyses included a total of 202 oocyte donors and 235 total cycles. Following adjustments for recipient BMI, the relationship between donor BMI (categorized into quartiles) and IVF outcomes was assessed. In the entire (anonymous and known) donor population, a reduced odds of clinical pregnancy (P-trend = 0.046) and live birth (P-trend = 0.06) was observed with increasing BMI quartile. Compared with quartile 1 (BMI 17.8-21.1), odds ratio (OR) (95% CI) of clinical pregnancy was 0.9 (0.4-2.0), 0.5 (0.2-1.1) and 0.5 (0.2-1.1), and OR of live birth was 1.1 (0.5-2.6), 0.6 (0.3-1.2) and 0.6 (0.3-1.2) for quartiles 2 through 4 respectively. In anonymous donors only, the odds of clinical pregnancy (P-trend = 0.02) and live birth (P-trend = 0.03) also declined as BMI quartile increased. Compared with quartile 1 (BMI 17.8-21.1), odds ratio (OR) (95% CI) of clinical pregnancy was 0.7 (0.3-1.7), 0.5 (0.2-1.1) and 0.4 (0.1-0.9), and OR of live birth was 0.9 (0.4-2.2), 0.5 (0.3-1.2) and 0.4 (0.2-1.1) for quartiles 2 through 4 respectively. Limitations include the retrospective design, sample size and data from a single institution. Clinical application may not be limited to oocyte donors, though caution should be used prior to applying these principles to the general population. Data should not be interpreted to mean that all oocyte donors should be restricted to a BMI of less than 21.2 kg/m(2). Following adjustments for the respective BMI of the oocyte donor and recipient, this study demonstrates an association of preconception BMI with subsequent IVF outcomes. The observations of this study are consistent with prior animal studies, suggest a possible effect of BMI at the oocyte level prior to fertilization and implantation, and warrant further investigation. None. C1 [Cardozo, E. R.; Karmon, A. E.; Gold, J.; Petrozza, J. C.; Styer, A. K.] Massachusetts Gen Hosp, Vincent Reprod Med & IVF, Vincent Dept Obstet & Gynecol, Yawkey 10A,55 Fruit St, Boston, MA 02114 USA. [Cardozo, E. R.; Karmon, A. E.; Petrozza, J. C.; Styer, A. K.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Cardozo, ER (reprint author), Massachusetts Gen Hosp, Vincent Reprod Med & IVF, Vincent Dept Obstet & Gynecol, Yawkey 10A,55 Fruit St, Boston, MA 02114 USA. EM ecardozo@mgh.harvard.edu FU Deborah Kelly Center for Outcomes Research of the Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital FX We would like to express our gratitude to the Deborah Kelly Center for Outcomes Research of the Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital for generous support of this study. NR 39 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 2016 VL 31 IS 2 BP 385 EP 392 DI 10.1093/humrep/dev298 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DF2DC UT WOS:000371149400018 PM 26677960 ER PT J AU Orlandi, RR Kingdom, TT Hwang, PH Smith, TL Alt, JA Baroody, FM Batra, PS Bernal-Sprekelsen, M Bhattacharyya, N Chandra, RK Chiu, A Citardi, MJ Cohen, NA DelGaudio, J Desrosiers, M Dhong, HJ Douglas, R Ferguson, B Fokkens, WJ Georgalas, C Goldberg, A Gosepath, J Hamilos, DL Han, JK Harvey, R Hellings, P Hopkins, C Jankowski, R Javer, AR Kern, R Kountakis, S Kowalski, ML Lane, A Lanza, DC Lebowitz, R Lee, HM Lin, SY Lund, V Luong, A Mann, W Marple, BF McMains, KC Metson, R Naclerio, R Nayak, JV Otori, N Palmer, JN Parikh, SR Passali, D Peters, A Piccirillo, J Poetker, DM Psaltis, AJ Ramadan, HH Ramakrishnan, VR Riechelmann, H Roh, HJ Rudmik, L Sacks, R Schlosser, RJ Senior, BA Sindwani, R Stankiewicz, JA Stewart, M Tan, BK Toskala, E Voegels, R Wang, DY Weitzel, EK Wise, S Woodworth, BA Wormald, PJ Wright, ED Zhou, B Kennedy, DW AF Orlandi, Richard R. Kingdom, Todd T. Hwang, Peter H. Smith, Timothy L. Alt, Jeremiah A. Baroody, Fuad M. Batra, Pete S. Bernal-Sprekelsen, Manuel Bhattacharyya, Neil Chandra, Rakesh K. Chiu, Alexander Citardi, Martin J. Cohen, Noam A. DelGaudio, John Desrosiers, Martin Dhong, Hun-Jong Douglas, Richard Ferguson, Berrylin Fokkens, Wytske J. Georgalas, Christos Goldberg, Andrew Gosepath, Jan Hamilos, Daniel L. Han, Joseph K. Harvey, Richard Hellings, Peter Hopkins, Claire Jankowski, Roger Javer, Amin R. Kern, Robert Kountakis, Stilianos Kowalski, Marek L. Lane, Andrew Lanza, Donald C. Lebowitz, Richard Lee, Heung-Man Lin, Sandra Y. Lund, Valerie Luong, Amber Mann, Wolf Marple, Bradley F. McMains, Kevin C. Metson, Ralph Naclerio, Robert Nayak, Jayakar V. Otori, Nobuyoshi Palmer, James N. Parikh, Sanjay R. Passali, Desiderio Peters, Anju Piccirillo, Jay Poetker, David M. Psaltis, Alkis J. Ramadan, Hassan H. Ramakrishnan, Vijay R. Riechelmann, Herbert Roh, Hwan-Jung Rudmik, Luke Sacks, Raymond Schlosser, Rodney J. Senior, Brent A. Sindwani, Raj Stankiewicz, James A. Stewart, Michael Tan, Bruce K. Toskala, Elina Voegels, Richard Wang, De Yun Weitzel, Erik K. Wise, Sarah Woodworth, Bradford A. Wormald, Peter-John Wright, Erin D. Zhou, Bing Kennedy, David W. TI International Consensus Statement on Allergy and Rhinology: Rhinosinusitis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Review DE rhinosinusitis; chronic rhinosinusitis; acute rhinosinusitis; recurrent acute rhinosinusitis; evidence-based medicine; systematic review; endoscopic sinus surgery ID ENDOSCOPIC SINUS SURGERY; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; EXACERBATED RESPIRATORY-DISEASE; PRIMARY CILIARY DYSKINESIA; ACUTE MAXILLARY SINUSITIS; FUROATE NASAL SPRAY; REFRACTORY CHRONIC RHINOSINUSITIS; PLACEBO-CONTROLLED TRIAL; MIDDLE TURBINATE RESECTION AB BackgroundThe body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). MethodsEvidence-based reviews with recommendations (EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR) was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. ResultsThe resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS) with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. ConclusionAs a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower-level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. C1 [Orlandi, Richard R.; Alt, Jeremiah A.] Univ Utah, Salt Lake City, UT 84112 USA. [Kingdom, Todd T.; Ramakrishnan, Vijay R.] Univ Colorado, Boulder, CO 80309 USA. [Hwang, Peter H.; Nayak, Jayakar V.] Stanford Univ, Stanford, CA 94305 USA. [Smith, Timothy L.] Oregon Hlth & Sci Univ, Eugene, OR USA. [Baroody, Fuad M.; Naclerio, Robert] Univ Chicago, Chicago, IL 60637 USA. [Batra, Pete S.] Rush Univ, Chicago, IL 60612 USA. [Bernal-Sprekelsen, Manuel] Univ Barcelona, E-08007 Barcelona, Spain. [Bhattacharyya, Neil; Metson, Ralph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Chandra, Rakesh K.] Vanderbilt Univ, Nashville, TN USA. [Chiu, Alexander] Univ Arizona, Tucson, AZ 85721 USA. [Citardi, Martin J.; Luong, Amber] Univ Texas Houston, Sch Med, Houston, TX USA. [Cohen, Noam A.; Palmer, James N.; Kennedy, David W.] Univ Penn, Philadelphia, PA 19104 USA. [DelGaudio, John; Wise, Sarah] Emory Univ, Atlanta, GA 30322 USA. [Desrosiers, Martin] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Dhong, Hun-Jong] Samsung Med Ctr, Seoul, South Korea. [Douglas, Richard] Univ Auckland, Auckland 1, New Zealand. [Ferguson, Berrylin] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Fokkens, Wytske J.] Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands. [Georgalas, Christos] Leiden Univ Hosp, Leiden, Netherlands. [Georgalas, Christos] Hygeia Hosp, Athens, Greece. [Goldberg, Andrew] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gosepath, Jan] Dr Horst Schmidt Klin, Wiesbaden, Germany. [Hamilos, Daniel L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Han, Joseph K.] Eastern Virginia Med Sch, Norfolk, VA USA. [Harvey, Richard; Sacks, Raymond] Univ New S Wales, Sydney, NSW 2052, Australia. [Harvey, Richard] Macquarie Univ, N Ryde, NSW 2109, Australia. [Hellings, Peter] Univ Hosp Leuven, Louvain, Belgium. [Hopkins, Claire] Guys Hosp, London, England. [Jankowski, Roger] Univ Lorraine, Nancy, France. [Javer, Amin R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kern, Robert; Peters, Anju; Tan, Bruce K.] Northwestern Univ, Evanston, IL 60208 USA. [Kountakis, Stilianos] Georgia Regents Univ, Augusta, GA USA. [Kowalski, Marek L.] Med Univ Lodz, Lodz, Poland. [Lane, Andrew; Lin, Sandra Y.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Lanza, Donald C.] Sinus & Nasal Inst Florida, St Petersburg, FL USA. [Lebowitz, Richard] Fnd New York Univ, New York, NY USA. [Lee, Heung-Man] Korea Univ, Seoul, South Korea. [Lund, Valerie] Royal Natl Throat Nose & Ear Hosp, Grays Inn Rd, London WC1X 8DA, England. [Marple, Bradley F.] Univ Texas Southwestern, Dallas, TX USA. [McMains, Kevin C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Otori, Nobuyoshi] Jikei Univ, Tokyo, Japan. [Parikh, Sanjay R.] Univ Washington, Seattle, WA 98195 USA. [Passali, Desiderio] Univ Siena, I-53100 Siena, Italy. [Piccirillo, Jay] Washington Univ, St Louis, MO 63130 USA. [Poetker, David M.] Med Coll Wisconsin, Madison, WI USA. [Psaltis, Alkis J.; Wormald, Peter-John] Univ Adelaide, Adelaide, SA 5005, Australia. [Ramadan, Hassan H.] W Virginia Univ, Morgantown, WV 26506 USA. [Riechelmann, Herbert] Med Univ Innsbruck, A-6020 Innsbruck, Austria. [Roh, Hwan-Jung] Pusan Natl Univ, Pusan, South Korea. [Rudmik, Luke] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Schlosser, Rodney J.] Med Univ S Carolina, Charleston, SC USA. [Senior, Brent A.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Sindwani, Raj] Cleveland Clin Fdn, Cleveland, OH USA. [Stankiewicz, James A.] Loyola Univ, New Orleans, LA 70118 USA. [Stewart, Michael] Weill Cornell Med Coll, New York, NY USA. [Toskala, Elina] Temple Univ, Philadelphia, PA 19122 USA. [Voegels, Richard] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. [Wang, De Yun] Natl Univ Singapore, Singapore 117548, Singapore. [Weitzel, Erik K.] San Antonio Mil Med Ctr, San Antonio, TX USA. [Woodworth, Bradford A.] Univ Alabama Birmingham, Birmingham, AL USA. [Wright, Erin D.] Univ Alberta, Edmonton, AB T6G 2M7, Canada. [Zhou, Bing] Capital Med Univ, Beijing, Peoples R China. RP Orlandi, RR (reprint author), 50 North Med Dr, Salt Lake City, UT 84132 USA. EM richard.orlandi@hsc.utah.edu OI Cohen, Noam/0000-0002-9462-3932 NR 1461 TC 29 Z9 29 U1 5 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD FEB PY 2016 VL 6 SU 1 SI SI BP S22 EP S209 DI 10.1002/alr.21695 PG 188 WC Otorhinolaryngology SC Otorhinolaryngology GA DF2DZ UT WOS:000371151900002 PM 26889651 ER PT J AU Bansal, N Simmons, KD Epstein, AJ Morris, JB Kelz, RR AF Bansal, Neha Simmons, Kristina D. Epstein, Andrew J. Morris, Jon B. Kelz, Rachel R. TI Using Patient Outcomes to Evaluate General Surgery Residency Program Performance SO JAMA SURGERY LA English DT Article ID QUALITY-OF-CARE; TRAINING-PROGRAMS; COST-EFFECTIVENESS; MORTALITY-RATES; FAILURE; RESCUE; STAY AB IMPORTANCE To evaluate and financially reward general surgery residency programs based on performance, performance must first be defined and measureable. OBJECTIVE To assess general surgery residency program performance using the objective clinical outcomes of patients operated on by program graduates. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted of discharge records from 349 New York and Florida hospitals between January 1, 2008, and December 31, 2011. The records comprised 230 769 patients undergoing 1 of 24 general surgical procedures performed by 454 surgeons from 73 general surgery residency programs. Analysis was conducted from June 4, 2014, to June 16, 2015. MAIN OUTCOMES AND MEASURES In-hospital death; development of 1 or more postoperative complications before discharge; prolonged length of stay, defined as length of stay greater than the 75th percentile when compared with patients undergoing the same procedure type at the same hospital; and failure to rescue, defined as in-hospital death after the development of 1 or more postoperative complications. RESULTS Patients operated on by surgeons trained in residency programs that were ranked in the top tertile were significantly less likely to experience an adverse event than were patients operated on by surgeons trained in residency programs that were ranked in the bottom tertile. Adjusted adverse event rates for patients operated on by surgeons trained in programs that were ranked in the top tertile and those who were operated on by surgeons trained in programs that were ranked in the bottom tertile were, respectively, 0.483% vs 0.476% for death, 9.68% vs 10.79% for complications, 16.76% vs 17.60% for prolonged length of stay, and 2.68% vs 2.98% for failure to rescue (all P < .001). The differences remained significant in procedure-specific subset analyses. The rankings were significantly correlated among some but not all outcome measures. The magnitude of the effect of the residency program on the outcomes achieved by the graduates decreased with increasing years of practice. Within the analyses of surgeons within 20, 10, and 5 years of practice, the relative difference in adjusted adverse event rates across the individual models between the top and bottom tertiles ranged from 1.5% to 12.3%(20 years), 9.1% to 33.8% (10 years), and 8.0% to 44.4%(5 years). CONCLUSIONS AND RELEVANCE Objective data were successfully used to rank the clinical outcomes achieved by graduates of general surgery residency programs. Program rankings differed by the outcome measured. The magnitude of differences across programs was small. Careful consideration must be used when identifying potential targets for payment-for-performance initiatives in graduate medical education. C1 [Bansal, Neha; Epstein, Andrew J.; Morris, Jon B.; Kelz, Rachel R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bansal, Neha; Simmons, Kristina D.; Morris, Jon B.; Kelz, Rachel R.] Univ Penn Hlth Syst, Dept Surg, Ctr Surg & Hlth Econ, 3400 Spruce St,4 Silverstein Bldg, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Kelz, Rachel R.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kelz, RR (reprint author), Univ Penn Hlth Syst, Dept Surg, Ctr Surg & Hlth Econ, 3400 Spruce St,4 Silverstein Bldg, Philadelphia, PA 19104 USA. EM rachel.kelz@uphs.upenn.edu NR 33 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD FEB PY 2016 VL 151 IS 2 BP 111 EP 119 DI 10.1001/jamasurg.2015.3637 PG 9 WC Surgery SC Surgery GA DF4LH UT WOS:000371319200003 PM 26510131 ER PT J AU Hatoum, IJ Blackstone, R Hunter, TD Francis, DM Steinbuch, M Harris, JL Kaplan, LM AF Hatoum, Ida J. Blackstone, Robin Hunter, Tina D. Francis, Diane M. Steinbuch, Michael Harris, Jason L. Kaplan, Lee M. TI Clinical Factors Associated With Remission of Obesity-Related Comorbidities After Bariatric Surgery SO JAMA SURGERY LA English DT Article ID IMPAIRS HYPERTENSION RESOLUTION; WEIGHT-LOSS SURGERY; Y GASTRIC BYPASS; MEDICAL THERAPY; METAANALYSIS; OVERWEIGHT; STATEMENT; RISK AB IMPORTANCE Little is known about comorbidity remission after bariatric surgery during typical clinical care across diverse and geographically distributed populations. OBJECTIVE To estimate the improvement in obesity-related comorbidities after bariatric surgery and to identify clinical factors associated with these responses using a large representative population of patients. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included all patients (N = 33 718) with a recorded Current Procedural Terminology code for Roux-en-Y gastric bypass (RYGB) or adjustable gastric banding (AGB) in the MarketScan Commercial Claims and Encounters Medicare Supplemental Databases from January 1, 2005, to June 30, 2010, and who had continuous enrollment from 6 months or more before to 12 months after surgery. MAIN OUTCOMES AND MEASURES Comorbidities before and after surgery were identified using both diagnoses (from International Classification of Diseases, Ninth Revision [ICD-9] codes) and prescription drug fills. Remission was based on a record of the comorbidity within 6 months before surgery, without record of the condition 18 months after surgery, using both ICD-9 codes and medication fills, as applicable. Multivariable logistic regression models were developed to identify factors associated with remission of diabetes and hypertension. RESULTS Among the 33 718 patients, 13 comorbidities with at least 1% prevalence before surgery were identified. Both RYGB and AGB led to statistically and clinically significant reductions in these comorbidities; remission rates for all comorbidities were higher after RYGB than AGB. For comorbidities that could be defined using both ICD-9 and prescription drug fill codes, prevalence was higher before and lower after surgery when measured by fill codes. Diagnoses using ICD-9 codes, but not prescription fill codes, increased in the 3 months before surgery. In multivariable logistic regression models for remission of diabetes mellitus after RYGB and AGB, age (RYGB: odds ratio [OR], 0.976; 95% CI, 0.965-0.988 and AGB: OR, 0.982; 95% CI, 0.971-0.933), procedure year (RYGB: OR, 1.11; 95% CI, 1.012-1.218 and AGB: OR, 1.185; 95% CI, 1.039-1.351), preoperative insulin use (RYGB: OR, 0.14; 95% CI, 0.114-0.171; AGB: OR, 0.174; 95% CI, 0.131-0.230), preoperative sulfonylurea use (RYGB: OR, 0.616; 95% CI, 0.505-0.752 and AGB: OR, 0.449; 95% CI, 0.357-0.566), and other antidiabetic medication use (RYGB: OR, 0.747; 95% CI, 0.568-0.981 and AGB: OR, 0.506; 95% CI, 0.359-0.715) were significantly associated with response after both procedures. For remission of hypertension, age (RYGB: OR, 0.964; 95% CI, 0.957-0.972 and AGB: OR, 0.968; 95% CI, 0.959-0.977), number of preoperative antihypertensive medications (RYGB: OR, 0.104; 95% CI, 0.067-0.161 and AGB: OR, 0.239; 95% CI, 0.140-0.408), and preoperative diuretic use (RYGB: OR, 1.729; 95% CI, 1.462-2.045 and AGB: OR, 1.648; 95% CI, 1.380-1.967) were significantly associated with response after both procedures. CONCLUSIONS AND RELEVANCE Analysis of a large, representative administrative database confirmed established predictors and revealed novel variables associated with comorbidity remission after bariatric surgery. Incorporating these factors into clinical tools to assess an individual patient's risk-to-benefit profile for these procedures could enhance patient selection and the overall use of surgery for the treatment of obesity and metabolic disease. C1 [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Hatoum, Ida J.; Kaplan, Lee M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Blackstone, Robin] Scottsdale Healthcare Bariatr Ctr, Scottsdale, AZ USA. [Hunter, Tina D.] S2 Stat Solut, Cincinnati, OH USA. [Francis, Diane M.; Steinbuch, Michael; Harris, Jason L.] Ethicon Inc, Cincinnati, OH USA. [Francis, Diane M.; Steinbuch, Michael; Harris, Jason L.] Johnson & Johnson, New Brunswick, NJ USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8219, Boston, MA 02129 USA. EM lmkaplan@partners.org FU National Institutes of Health [DK093257, DK100613, DKO88661, DK090956]; Ethicon Endo-Surgery FX This work was supported by National Institutes of Health grants DK093257 (Dr Hatoum), DK100613 (Dr Hatoum), DKO88661 (Dr Kaplan), and DK090956 (Dr Kaplan), as well as research grants from Ethicon Endo-Surgery (Dr Kaplan). NR 40 TC 2 Z9 2 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD FEB PY 2016 VL 151 IS 2 BP 130 EP 137 DI 10.1001/jamasurg.2015.3231 PG 8 WC Surgery SC Surgery GA DF4LH UT WOS:000371319200007 PM 26465084 ER PT J AU Hollis, RH Singletary, BA McMurtrie, JT Graham, LA Richman, JS Holcomb, CN Itani, KM Maddox, TM Hawn, MT AF Hollis, Robert H. Singletary, Brandon A. McMurtrie, James T. Graham, Laura A. Richman, Joshua S. Holcomb, Carla N. Itani, Kamal M. Maddox, Thomas M. Hawn, Mary T. TI Blood Transfusion and 30-Day Mortality in Patients With Coronary Artery Disease and Anemia Following Noncardiac Surgery SO JAMA SURGERY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-PRACTICE GUIDELINE; CELL TRANSFUSION; RESTRICTIVE TRANSFUSION; POSTOPERATIVE OUTCOMES; CARDIAC-SURGERY; OLDER PATIENTS; ASSOCIATION; TRIAL; REQUIREMENTS AB IMPORTANCE Although liberal blood transfusion thresholds have not been beneficial following noncardiac surgery, it is unclear whether higher thresholds are appropriate for patients who develop postoperative myocardial infarction (MI). OBJECTIVE To evaluate the association between postoperative blood transfusion and mortality in patients with coronary artery disease and postoperative MI following noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study involving Veterans Affairs facilities from January 1, 2000, to December 31, 2012. A total of 7361 patients with coronary artery disease who underwent inpatient noncardiac surgery and had a nadir postoperative hematocrit between 20% and 30%. Patients with significant bleeding, including any preoperative blood transfusion or transfusion of greater than 4 units during the intraoperative or postoperative setting, were excluded. Mortality rates were compared using both logistic regression and propensity score matching. Patients were stratified by postoperative nadir hematocrit and the presence of postoperative MI. EXPOSURE Initial postoperative blood transfusion. MAIN OUTCOMES AND MEASURES The 30-day postoperative mortality rate. RESULTS Of the 7361 patients, 2027 patients (27.5%) received at least 1 postoperative blood transfusion. Postoperative mortality occurred in 267 (3.6%), and MI occurred in 271 (3.7%). Among the 5334 patients without postoperative blood transfusion, lower nadir hematocrit was associated with an increased risk for mortality (hematocrit of 20% to <24%: 7.3%; 24% to <27%: 3.7%; and 27% to 30%: 1.6%; P < .01). In patients with postoperative MI, blood transfusion was associated with lower mortality, for those with hematocrit of 20% to 24% (odds ratio, 0.28; 95% CI, 0.13-0.64). In patients without postoperative MI, transfusion was associated with significantly higher mortality for those with hematocrit of 27% to 30% (odds ratio, 3.21; 95% CI, 1.85-5.60). CONCLUSIONS AND RELEVANCE These findings support a restrictive postoperative transfusion strategy in patients with stable coronary artery disease following noncardiac surgery. However, interventional studies are needed to evaluate the use of a more liberal transfusion strategy in patients who develop postoperative MI. C1 [Hollis, Robert H.; Singletary, Brandon A.; McMurtrie, James T.; Graham, Laura A.; Richman, Joshua S.; Holcomb, Carla N.; Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, 1922 7th Ave S,KB 428, Birmingham, AL 35294 USA. [Hollis, Robert H.; Singletary, Brandon A.; McMurtrie, James T.; Graham, Laura A.; Richman, Joshua S.; Holcomb, Carla N.; Hawn, Mary T.] Birmingham Vet Adm Hosp, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Itani, Kamal M.] Boston Univ, Dept Surg, VA Boston Hlth Care Syst, Boston, MA 02215 USA. [Itani, Kamal M.] Harvard Univ, Sch Med, Boston, MA USA. [Maddox, Thomas M.] Univ Colorado, Sch Med, VA Eastern Colorado Hlth Care Syst, Denver, CO USA. RP Hawn, MT (reprint author), Univ Alabama Birmingham, Dept Surg, Sect Gastrointestinal Surg, 1922 7th Ave S,KB 428, Birmingham, AL 35294 USA. EM mhawn@uabmc.edu FU VA Health Services Research & Development grant [IIR 09-347]; National Institutes of Health [T32 CA091078-13]; VA Career Development Awards FX This study was supported by a VA Health Services Research & Development grant (IIR 09-347). Dr Hollis is supported by grant T32 CA091078-13 from the National Institutes of Health. Drs Richman and Maddox are supported by VA Career Development Awards. NR 37 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD FEB PY 2016 VL 151 IS 2 BP 139 EP 145 DI 10.1001/jamasurg.2015.3420 PG 7 WC Surgery SC Surgery GA DF4LH UT WOS:000371319200009 PM 26444569 ER PT J AU Sobel, M Tang, GL AF Sobel, Michael Tang, Gale L. TI Inflammation, Endoleaks, and Aortic Remodeling-The Chicken or the Egg SO JAMA SURGERY LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Dept Surg, Div Vasc Surg, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Sobel, M (reprint author), Univ Washington, Div Vasc Surg, Dept Surg, VA Puget Sound Hlth Care Syst, 1660 Columbian Way S, Seattle, WA 98108 USA. EM sobelm@uw.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD FEB PY 2016 VL 151 IS 2 BP 154 EP 154 DI 10.1001/jamasurg.2015.3246 PG 1 WC Surgery SC Surgery GA DF4LH UT WOS:000371319200012 PM 26502236 ER PT J AU MacIntosh, PW Grob, SR Stagner, AM Kazlas, MA Jakobiec, FA Yoon, MK Lee, NG AF MacIntosh, Peter W. Grob, Seanna R. Stagner, Anna M. Kazlas, Melanie A. Jakobiec, Frederick A. Yoon, Michael K. Lee, Nahyoung Grace TI Multicentric myofibromatosis presenting as a large congenital eyelid myofibroma SO JOURNAL OF AAPOS LA English DT Article ID INFANTILE MYOFIBROMATOSIS; OCCLUSION AB Infantile myofibromatosis is a rare mesenchymal neoplasm that commonly involves the head and neck but rarely the eyelid. We report the case of a newborn boy referred for evaluation of a left eyelid lesion that occluded the visual axis. Urgent biopsy was performed to evaluate for malignancy. Histopathologic analysis demonstrated myofibroma. Although these lesions have been reported to regress spontaneously, debulking surgery was performed to prevent sensory or anisometropic amblyopia. Follow-up systemic evaluation revealed numerous subcutaneous and deep soft tissue lesions. There was no visceral involvement. C1 [MacIntosh, Peter W.; Stagner, Anna M.; Yoon, Michael K.; Lee, Nahyoung Grace] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. [MacIntosh, Peter W.; Grob, Seanna R.; Kazlas, Melanie A.; Jakobiec, Frederick A.; Yoon, Michael K.; Lee, Nahyoung Grace] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Stagner, Anna M.; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Kazlas, Melanie A.] Massachusetts Eye & Ear Infirm, Pediat Ophthalmol & Strabismus, Boston, MA 02114 USA. RP Yoon, MK (reprint author), 243 Charles St,10th Floor, Boston, MA 02114 USA. EM Michael_Yoon@meei.harvard.edu NR 10 TC 0 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD FEB PY 2016 VL 20 IS 1 BP 70 EP 73 DI 10.1016/j.jaapos.2015.08.013 PG 4 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA DF2PV UT WOS:000371187200016 PM 26917077 ER PT J AU Zaman, T Boyd, JW AF Zaman, Tauheed Boyd, J. Wesley TI The Authors Reply to Cannabis Use Disorders and ADHD SO JOURNAL OF ADDICTION MEDICINE LA English DT Letter C1 [Zaman, Tauheed] UCSF, San Francisco VA Med Ctr, Addict & Recovery Treatment Serv, San Francisco, CA USA. [Boyd, J. Wesley] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Boyd, J. Wesley] Harvard Univ, Sch Med, Ctr Bioeth, Cambridge, MA 02138 USA. RP Boyd, JW (reprint author), Cambridge Hlth Alliance, 26 Cent St, Somerville, MA 02143 USA. EM jwboyd@cha.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD FEB PY 2016 VL 10 IS 1 BP 70 EP 71 DI 10.1097/ADM.0000000000000185 PG 2 WC Substance Abuse SC Substance Abuse GA DE0CS UT WOS:000370293000013 ER PT J AU Funke, BH AF Funke, Birgit H. TI Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Editorial Material C1 [Funke, Birgit H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Funke, Birgit H.] Harvard Univ, Sch Med, Boston, MA USA. [Funke, Birgit H.] Partners HealthCare Personalized Med, Mol Med Lab, 65 Landsdowne St, Cambridge, MA 02139 USA. RP Funke, BH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Funke, BH (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Funke, BH (reprint author), Partners HealthCare Personalized Med, Mol Med Lab, 65 Landsdowne St, Cambridge, MA 02139 USA. EM bfunke@partners.org NR 3 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 EI 1937-5395 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD FEB PY 2016 VL 9 IS 1 BP 1 EP 2 DI 10.1007/s12265-015-9667-8 PG 2 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA DF3OV UT WOS:000371255100001 PM 26739320 ER PT J AU Shen, Q Huang, SL Duong, TQ AF Shen, Qiang Huang, Shiliang Duong, Timothy Q. TI T-2*-weighted fMRI time-to-peak of oxygen challenge in ischemic stroke SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Functional MRI; focal ischemia; perfusion-weighted MRI; diffusion-weighted MRI; BOLD contrast ID PERFUSION MRI; POSTISCHEMIC HYPERPERFUSION; QUANTITATIVE PERFUSION; FUNCTIONAL MRI; TISSUE FATE; DIFFUSION; PENUMBRA; REPERFUSION; RAT; STIMULATION AB T-2*-weighted MRI of transient oxygen challenge (OC) showed exaggerated OC percent changes in the ischemic tissue at risk compared to normal tissue. One ambiguity is that regions with high vascular density also showed exaggerated OC percent changes. This study explored time-to-peak (TTP) of the OC percent changes to improve the utility of T-2*-weighted OC MRI. Experiments were performed longitudinally at 30 min, 150 min and 24 h after transient (60-min) stroke in rats. Ischemic core, normal, and mismatch tissue were classified pixel-by-pixel based on apparent diffusion coefficient and cerebral blood flow. Major findings were: (i) Delayed OC TTP was localized to and corresponded well with the perfusion-diffusion mismatch. (ii) By contrast, the exaggerated OC percent changes were less localized, with changes not only in the at-risk tissue but also in some areas of the contralesional hemisphere with venous vessel origins. (iii) The OC time-course of the mismatch tissue was biphasic, with a faster initial increase followed by a slower increase. (iv) At-risk tissue with delayed TTP and exaggerated OC was normal after reperfusion and the at-risk tissue was mostly (83 +/- 18%) rescued by reperfusion as indicated by normal 24-h T-2. OC TTP offers unique information toward better characterization of at-risk tissue in ischemic stroke. C1 [Shen, Qiang; Huang, Shiliang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Shen, Qiang; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Shen, Q; Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM shenq3@uthscsa.edu; duongt@uthscsa.edu FU NIH [R01-NS45879]; American Heart Association [EIA 0940104N, SDG 0830293N, 12BGIA9300047] FX This work was supported by the NIH (grant no. R01-NS45879) and the American Heart Association (grant nos. EIA 0940104N, SDG 0830293N and 12BGIA9300047). NR 24 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 2016 VL 36 IS 2 BP 283 EP 291 DI 10.1177/0271678X15606461 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA DF4EG UT WOS:000371299800004 PM 26661164 ER PT J AU Lee, J Wu, WC Boas, DA AF Lee, Jonghwan Wu, Weicheng Boas, David A. TI Early capillary flux homogenization in response to neural activation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Neurovascular coupling; capillaries; cerebral blood flow measurement; microscopy; optical imaging ID OPTICAL COHERENCE TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; CORTEX AB This Brief Communication reports early homogenization of capillary network flow during somatosensory activation in the rat cerebral cortex. We used optical coherence tomography and statistical intensity variation analysis for tracing changes in the red blood cell flux over hundreds of capillaries nearly at the same time with 1-s resolution. We observed that while the mean capillary flux exhibited a typical increase during activation, the standard deviation of the capillary flux exhibited an early decrease that happened before the mean flux increase. This network-level data is consistent with the theoretical hypothesis that capillary flow homogenizes during activation to improve oxygen delivery. C1 [Lee, Jonghwan; Wu, Weicheng; Boas, David A.] Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, 149 13th St,Rm 2276, Charlestown, MA 02129 USA. RP Lee, J (reprint author), Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, 149 13th St,Rm 2276, Charlestown, MA 02129 USA. EM jonghwan@nmr.mgh.harvard.edu FU NIH [K99-EB014879, R01-EB000790, P01-NS055104]; AFOSR (MFEL) [FA9550-07-1-0101] FX This study was supported by the NIH (K99-EB014879, R01-EB000790, P01-NS055104) and the AFOSR (MFEL FA9550-07-1-0101). NR 13 TC 4 Z9 4 U1 0 U2 2 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 FEB PY 2016 VL 36 IS 2 BP 375 EP 380 DI 10.1177/0271678X15605851 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA DF4EG UT WOS:000371299800011 PM 26661145 ER PT J AU Rigotti, NA AF Rigotti, Nancy A. TI Training Future Physicians to Deliver Tobacco Cessation Treatment SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID SMOKING-CESSATION C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Div Gen Internal Med, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Dept Med, Tobacco Res & Treatment Ctr, Div Gen Internal Med, Boston, MA 02114 USA.; Rigotti, NA (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM nrigotti@partners.org NR 8 TC 0 Z9 0 U1 0 U2 4 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 FEB PY 2016 VL 31 IS 2 BP 144 EP 146 DI 10.1007/s11606-015-3560-7 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DF2GQ UT WOS:000371161000004 PM 26747628 ER PT J AU Gellad, WF AF Gellad, Walid F. TI The Veterans Choice Act and Dual Health System Use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID CARE C1 [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr,151C, Pittsburgh, PA 15240 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr,151C, Pittsburgh, PA 15240 USA. EM walid.gellad@va.gov FU HSRD VA [I01 HX001765] NR 3 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2016 VL 31 IS 2 BP 153 EP 154 DI 10.1007/s11606-015-3492-2 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DF2GQ UT WOS:000371161000008 PM 26289922 ER PT J AU Satake, E Matsushita, R Kitsuda, K Ohtaka, K Nagata, E Yamaguchi, R Sano, S Fujisawa, Y Nakanishi, T Nakagawa, Y Ohzeki, T AF Satake, Eiichiro Matsushita, Rie Kitsuda, Kazuteru Ohtaka, Kohnosuke Nagata, Eiko Yamaguchi, Rie Sano, Shinichiro Fujisawa, Yasuko Nakanishi, Toshiki Nakagawa, Yuichi Ohzeki, Takehiko TI Urinary myo-inositol levels in Japanese schoolchildren with normal glucose tolerance SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE diabetes screening; glucose intolerance; myo-inositol (MI); urinary myo-inositol (UMI) ID DIABETES-MELLITUS; CHIRO-INOSITOL; OBESE CHILDREN; MYO-INOSITOL; INTOLERANCE; COMPLICATIONS; ADOLESCENTS; PREVALENCE; METABOLISM; EXCRETION AB Background: Urinary myo-inositol (UMI) level is elevated in adult diabetic patients, and also increases after glucose loading. However, the relationship between UMI and plasma glucose levels in children is unknown. We aimed to assess whether UMI is a practical marker for glucose intolerance in children or not. Methods: In Study 1 (328 schoolchildren), fasting and postprandial UMI were measured, with Delta UMI defined as the difference between fasting and postprandial UMI levels. In Study 2, oral glucose tolerance tests and UMI measurements were conducted in 18 children with suspected having diabetes. Results: For Study 1,Delta UMI was observed [-0.65 (-3.9, 1.35) mg/g creatinine]. For Study 2, children with diabetes or impaired glucose tolerance had a significantly higher Delta UMI than children with normal glucose tolerance. Conclusions: These studies demonstrated the normal range of UMI in children and possibility of a novel biomarker for early detection of glucose intolerance in children. C1 [Satake, Eiichiro] Joslin Diabet Ctr, Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. [Satake, Eiichiro; Matsushita, Rie; Ohtaka, Kohnosuke; Nagata, Eiko; Yamaguchi, Rie; Fujisawa, Yasuko; Nakanishi, Toshiki] Hamamatsu Univ Sch Med, Dept Pediat, Hamamatsu, Shizuoka 4313192, Japan. [Satake, Eiichiro] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Satake, Eiichiro] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kitsuda, Kazuteru] Sagamihara Kyodo Hosp, Dept Pediat, Sagamihara, Kanagawa, Japan. [Sano, Shinichiro] Chutoen Gen Med Ctr, Dept Pediat, Kakegawa, Shizuoka, Japan. [Nakagawa, Yuichi] Shiraume Toyooka Hosp, Iwata, Shizuoka, Japan. [Ohzeki, Takehiko] Kyoritsu Womens Univ, Chiyoda Ku, Tokyo, Japan. RP Satake, E (reprint author), Joslin Diabet Ctr, Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA.; Satake, E (reprint author), Hamamatsu Univ Sch Med, Dept Pediat, Hamamatsu, Shizuoka 4313192, Japan.; Satake, E (reprint author), Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.; Satake, E (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM eiichiro.satake@joslin.harvard.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-018X EI 2191-0251 J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD FEB PY 2016 VL 29 IS 2 BP 179 EP 184 DI 10.1515/jpem-2015-0107 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA DF3CN UT WOS:000371221400010 PM 26360496 ER PT J AU Beben, T Ix, JH Shlipak, MG Sarnak, MJ Fried, LF Hoofnagle, AN Chonchol, M Kestenbaum, BR de Boer, IH Rifkin, DE AF Beben, Tomasz Ix, Joachim H. Shlipak, Michael G. Sarnak, Mark J. Fried, Linda F. Hoofnagle, Andrew N. Chonchol, Michel Kestenbaum, Bryan R. de Boer, Ian H. Rifkin, Dena E. TI Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE fibroblast growth factor 23; frailty; mortality ID LOW VITAMIN-D; OLDER-ADULTS; PARATHYROID-HORMONE; 25-HYDROXYVITAMIN D; MUSCLE STRENGTH; CYSTATIN-C; DISEASE; MEN; INFLAMMATION; ASSOCIATION AB ObjectivesTo evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality. DesignCross-sectional analysis for frailty and longitudinal cohort analysis for mortality. SettingCardiovascular Health Study. ParticipantsCommunity-dwelling individuals (N= 2,977; mean age 77.94.7, 40% male, 83% white). MeasurementsThe predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality. ResultsMean estimated glomerular filtration rate (eGFR) was 64 +/- 17mL/min per 1.73m(2). Median FGF-23 was 70.3RU/mL (interquartile range 53.4-99.2); 52% were prefrail, and 13% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38% (95% confidence interval (CI)=17-62%) higher odds of frailty than of nonfrailty and 16% (95% CI=3-30%) higher odds of prefrailty. FGF-23 (hazard ratio (HR)=1.16, 95% CI=1.10-1.23) and frailty (HR=1.82, 95% CI=1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other. ConclusionIn a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes. C1 [Beben, Tomasz; Ix, Joachim H.; Rifkin, Dena E.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Beben, Tomasz; Ix, Joachim H.; Rifkin, Dena E.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.] Veteran Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Nephrol Sect, Pittsburgh, PA USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Chonchol, Michel] Univ Colorado, Div Renal Dis & Hypertens, Denver, CO 80202 USA. [Kestenbaum, Bryan R.; de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Kestenbaum, Bryan R.; de Boer, Ian H.] Univ Washington, Kidney Res Inst, Dept Med, Seattle, WA 98195 USA. RP Beben, T (reprint author), 9500 Gilman Dr 9111H, La Jolla, CA 92093 USA. EM tbeben@ucsd.edu FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC 55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295]; National Institute on Aging [R01AG 023629]; American Heart Association [14EIA18560026]; National Institutes of Health [T32 HL007261, RO1 HL096851, R01 HL096851, K23 DK091521, R01 HL073208, R01 AG027002, R01 DK087726] FX The CHS was supported by Contracts HHSN268201200036C, HHSN268200800007C, N01HC 55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and Grant U01HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG 023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, NHLBI, or CHS. Dr. Beben was supported by Grant T32 HL007261, Dr. Ix by Grant RO1 HL096851, Dr. Ix by Grant R01 HL096851 and an American Heart Association Established Investigator Award 14EIA18560026, Dr. Rifkin by Grant K23 DK091521, Dr. Shlipak by Grant R01 HL073208, Dr. Sarnak by Grant R01 AG027002, and Dr. De Boer by Grant R01 DK087726 all from the National Institutes of Health, except where otherwise noted. NR 33 TC 0 Z9 0 U1 2 U2 6 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 FEB PY 2016 VL 64 IS 2 BP 270 EP 276 DI 10.1111/jgs.13951 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FX UT WOS:000371159000003 PM 26889836 ER PT J AU Wang, SY Aldridge, MD Gross, CP Canavan, M Cherlin, E Johnson-Hurzeler, R Bradley, E AF Wang, Shi-Yi Aldridge, Melissa D. Gross, Cary P. Canavan, Maureen Cherlin, Emily Johnson-Hurzeler, Rosemary Bradley, Elizabeth TI Transitions Between Healthcare Settings of Hospice Enrollees at the End of Life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospice; transitions in care; end-of-life care ID MARKET-STRUCTURE; HEART-FAILURE; NURSING-HOME; CANCER; POPULATION; INDICATORS; FACILITIES; INPATIENT; VARIABLES; PATTERNS AB ObjectivesTo characterize the number and types of care transitions in the last 6months of life of individuals who used hospice and to examine factors associated with having multiple transitions in care. DesignRetrospective cohort study. SettingOne hundred percent fee-for-service Medicare decedent claims data. ParticipantsMedicare beneficiaries aged 66 and older who died between July 1, 2011, and December 31, 2011, and were enrolled in hospice at some time during the last 6months of life. MeasurementsHierarchical generalized linear modeling was used to identify individual, hospice, and regional factors associated with transitions. The sequence of transitions across healthcare settings was described. Healthcare transitions after hospice enrollment included from and to the hospital, skilled nursing facility, home health agency program, hospice, or home without receiving any service in these four healthcare settings. ResultsOf 311,090 hospice decedents, 31,675 (10.2%) had at least one transition after hospice enrollment, and this varied substantially across the United States; 6.6% of all decedents had more than one transition in care after hospice enrollment (range 2-19 transitions). Of hospice users with transitions, 53.4% were admitted to hospitals, 17.7% were admitted to skilled nursing facilities, 9.6% used home health agencies, and 25.8% had transitions to home without receiving the services from the healthcare settings examined. In adjusted analyses, decedents who were younger, nonwhite, enrolled in a for-profit or small hospice program, or had less access to hospital-based palliative care had significantly higher odds of having at least one transition. ConclusionA notable proportion of hospice users experience at least one transition in care in the last 6months of life, suggesting that further research on the effect of transitions on users and families is warranted. C1 [Wang, Shi-Yi] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, 60 Coll St New, New Haven, CT 06520 USA. [Wang, Shi-Yi; Gross, Cary P.] Yale Univ, Yale Canc Ctr, Canc Outcomes Publ Policy & Effectiveness Res Ctr, New Haven, CT 06520 USA. [Aldridge, Melissa D.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Aldridge, Melissa D.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, Gen Internal Med Sect, New Haven, CT 06520 USA. [Canavan, Maureen; Cherlin, Emily; Bradley, Elizabeth] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT 06520 USA. [Johnson-Hurzeler, Rosemary] John D Thompson Hosp Inst Educ Training & Res In, Branford, CT USA. RP Wang, SY (reprint author), Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, 60 Coll St New, New Haven, CT 06520 USA. EM shiyi.wang@yale.edu FU Medtronic, Inc.; Johnson Johnson, Inc.; 21st Century Oncology; National Cancer Institute [1R01CA116398-01A2]; National Institute of Nursing Research [1R01NR013499-01A1] FX Dr. Gross receives support from Medtronic, Inc., Johnson & Johnson, Inc., and 21st Century Oncology. These sources of support were not used for any portion of the current manuscript. None of the other coauthors have conflicts to report.; This study was supported by Grant 1R01CA116398-01A2 from the National Cancer Institute (Drs. Aldridge and Bradley), the John D. Thompson Foundation (Dr. Bradley), and Grant 1R01NR013499-01A1 from the National Institute of Nursing Research (Dr. Aldridge). NR 41 TC 3 Z9 3 U1 1 U2 2 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 FEB PY 2016 VL 64 IS 2 BP 314 EP 322 DI 10.1111/jgs.13939 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FX UT WOS:000371159000009 PM 26889841 ER PT J AU Naples, JG Hanlon, JT Schmader, KE Semla, TP AF Naples, Jennifer G. Hanlon, Joseph T. Schmader, Kenneth E. Semla, Todd P. TI Recent Literature on Medication Errors and Adverse Drug Events in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE medication errors; adverse drug events; literature ID RANDOMIZED CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; ADVANCED DEMENTIA; CLINICAL-TRIAL; CARE; PEOPLE; INTERVENTION; FALLS; POLYPHARMACY; PHARMACIST AB Medication errors and adverse drug events are common in older adults, but locating literature addressing these issues is often challenging. The objective of this article is to summarize recent studies addressing medication errors and adverse drug events in a single location to improve accessibility for individuals working with older adults. A comprehensive literature search for studies published in 2014 was conducted, and 51 potential articles were identified. After critical review, 17 studies were selected for inclusion based on innovation; rigorous observational or experimental study designs; and use of reliable, valid measures. Four articles characterizing potentially inappropriate prescribing and interventions to optimize medication regimens were annotated and critiqued in detail. The authors hope that health policy-makers and clinicians find this information helpful in improving the quality of care for older adults. C1 [Naples, Jennifer G.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Naples, Jennifer G.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Sch Med, Div Geriatr,Dept Med, Durham, NC 27710 USA. [Schmader, Kenneth E.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Semla, Todd P.] Pharm Benefits Management Serv, Dept Vet Affairs, Hines, IL USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. RP Semla, TP (reprint author), Pharm Benefits Management 10P4P, Hines, IL 60141 USA. EM t-semla@northwestern.edu FU National Institute of Aging (NIA) [T32-AG021885]; NIA [P30AG024827, K07AG033174, R01AG037451, P30AG028716]; Donoghue Foundation; Agency for Healthcare Research and Quality [R18 HS023779]; Veterans Affairs Health Services Research and Development Service Merit Awards [IIR 12-379, IIR 14-297] FX Dr. Naples's fellowship is supported by National Institute of Aging (NIA) Grant T32-AG021885. Dr. Hanlon is supported by NIA Grants P30AG024827, K07AG033174, and R01AG037451; a grant from the Donoghue Foundation; grant R18 HS023779 from the Agency for Healthcare Research and Quality, and Veterans Affairs Health Services Research and Development Service Merit Awards IIR 12-379 and IIR 14-297. Dr. Schmader is supported by NIA Grant P30AG028716. NR 35 TC 1 Z9 1 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 2016 VL 64 IS 2 BP 401 EP 408 DI 10.1111/jgs.13922 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FX UT WOS:000371159000022 PM 26804210 ER PT J AU Rogus-Pulia, N Rusche, N Hind, JA Zielinski, J Gangnon, R Safdar, N Robbins, J AF Rogus-Pulia, Nicole Rusche, Nicole Hind, Jacqueline A. Zielinski, Jill Gangnon, Ronald Safdar, Nasia Robbins, JoAnne TI Effects of Device-Facilitated Isometric Progressive Resistance Oropharyngeal Therapy on Swallowing and Health-Related Outcomes in Older Adults with Dysphagia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dysphagia; oropharyngeal; lingual; strengthening; pneumonia ID PENETRATION-ASPIRATION SCALE; LINGUAL EXERCISE; STROKE PATIENTS; PNEUMONIA; PERFORMANCE; STRENGTH; PEOPLE; COST AB Swallowing disorders (dysphagia) are associated with malnutrition, aspiration pneumonia, and mortality in older adults. Strengthening interventions have shown promising results, but the effectiveness of treating dysphagia in older adults remains to be established. The Swallow STRengthening OropharyNGeal (Swallow STRONG) Program is a multidisciplinary program that employs a specific approach to oropharyngeal strengtheningdevice-facilitated (D-F) isometric progressive resistance oropharyngeal (I-PRO) therapywith the goal of reducing health-related sequelae in veterans with dysphagia. Participants completed 8 weeks of D-F I-PRO therapy while receiving nutritional counseling and respiratory status monitoring. Assessments were completed at baseline, 4, and 8 weeks. At each visit, videofluoroscopic swallowing studies were performed. Dietary and swallowing-related quality of life questionnaires were administered. Long-term monitoring for 6-17 months after enrollment allowed for comparison of pneumonia incidence and hospitalizations to the 6-17 months before the program. Veterans with dysphagia confirmed with videofluoroscopy (N = 56; 55 male, 1 female; mean age 70) were enrolled. Lingual pressures increased at anterior (effect estimate = 92.5, P < .001) and posterior locations (effect estimate = 85.4, P < .001) over 8 weeks. Statistically significant improvements occurred on eight of 11 subscales of the Quality of Life in Swallowing Disorders (SWAL-QOL) Questionnaire (effect estimates = 6.5-19.5, P < .04) and in self-reported sense of effort (effect estimate = -18.1, P = .001). Higher Functional Oral Intake Scale scores (effect estimate = 0.4, P = .02) indicated that participants were able to eat less-restrictive diets. There was a 67% reduction in pneumonia diagnoses, although the difference was not statistically significant. The number of hospital admissions decreased significantly (effect estimate = 0.96; P = .009) from before to after enrollment. Findings suggest that the Swallow STRONG multidisciplinary oropharyngeal strengthening program may be an effective treatment for older adults with dysphagia. C1 [Rogus-Pulia, Nicole] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Rogus-Pulia, Nicole; Robbins, JoAnne] Univ Wisconsin, Div Gastroenterol, Madison, WI USA. [Rogus-Pulia, Nicole; Robbins, JoAnne] Univ Wisconsin, Div Hepatol, Madison, WI USA. [Rogus-Pulia, Nicole; Robbins, JoAnne] Univ Wisconsin, Speech Swallowing & Dining Enhancement Program, Madison, WI USA. [Rusche, Nicole] Swallow STRengthening OropharyNGeal Program, Madison, WI USA. [Hind, Jacqueline A.] Swallow Solut LLC, Clin Affairs, Madison, WI USA. [Zielinski, Jill] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Div Infect Dis, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Dept Med, Madison, WI USA. [Gangnon, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Safdar, Nasia; Robbins, JoAnne] Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Rogus-Pulia, N (reprint author), 2500 Overlook Terrace,Madison GRECC 11G, Madison, WI 53705 USA. EM npulia@wisc.edu FU Geriatrics and Extended Care division of the VA through a T21 Non-Institutional Long Term Care grant FX Funding was provided by the Geriatrics and Extended Care division of the VA through a T21 Non-Institutional Long Term Care grant. The authors would like to acknowledge Sue McCartney, MS, RD, for providing nutritional support and counseling and Kevin Bjork, MS, NP, for monitoring participants' respiratory health. NR 20 TC 1 Z9 1 U1 2 U2 3 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 FEB PY 2016 VL 64 IS 2 BP 417 EP 424 DI 10.1111/jgs.13933 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DF2FX UT WOS:000371159000024 PM 26804715 ER PT J AU Forman, DE AF Forman, Daniel E. TI Cardiac Rehabilitation: The Mandate Grows SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID AMERICAN-HEART-ASSOCIATION; PREVENTION; EXERCISE; DELIVERY C1 [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, 3471 Fifth Ave,Ste 500, Pittsburgh, PA 15213 USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, Med, Pittsburgh, PA USA. RP Forman, DE (reprint author), Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, 3471 Fifth Ave,Ste 500, Pittsburgh, PA 15213 USA. EM formand@pitt.edu NR 20 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 2016 VL 91 IS 2 BP 125 EP 128 DI 10.1016/j.mayocp.2015.12.009 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DF3MN UT WOS:000371248500004 PM 26847999 ER PT J AU Gordon, M Rysinska, A Garland, A Rolfson, O Aspberg, S Eisler, T Garellick, G Stark, A Hailer, NP Skoldenberg, O AF Gordon, Max Rysinska, Agata Garland, Anne Rolfson, Ola Aspberg, Sara Eisler, Thomas Garellick, Goran Stark, Andre Hailer, Nils P. Skoldenberg, Olof TI Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty A Nationwide Cohort Study SO MEDICINE LA English DT Article ID REPLACEMENT; MORTALITY; OSTEOARTHRITIS; OSTEOLYSIS; REGISTER; CALCIFICATION; INFLAMMATION; DISEASE; SWEDISH; EVENTS AB Total hip arthroplasty is a common and important treatment for osteoarthritis patients. Long-term cardiovascular effects elicited by osteoarthritis or the implant itself remain unknown. The purpose of the present study was to determine if there is an increased risk of late cardiovascular mortality and morbidity after total hip arthroplasty surgery. A nationwide matched cohort study with data on 91,527 osteoarthritis patients operated on, obtained from the Swedish Hip Arthroplasty Register. A control cohort (n = 270,688) from the general Swedish population was matched 1:3 to each case by sex, age, and residence. Mean follow-up time was 10 years (range, 7-21). The exposure was presence of a hip replacement for more than 5 years. The primary outcome was cardiovascular mortality after 5 years. Secondary outcomes were total mortality and re-admissions due to cardiovascular events. During the first 5 to 9 years, the arthroplasty cohort had a lower cardiovascular mortality risk compared with the control cohort. However, the risk in the arthroplasty cohort increased over time and was higher than in controls after 8.8 years (95% confidence interval [CI] 7.0-10.5). Between 9 and 13 years postoperatively, the hazard ratio was 1.11 (95% CI 1.05-1.17). Arthroplasty patients were also more frequently admitted to hospital for cardiovascular reasons compared with controls, with a rate ratio of 1.08 (95% CI 1.06-1.11). Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation when compared with controls. C1 [Gordon, Max; Rysinska, Agata; Aspberg, Sara; Eisler, Thomas; Stark, Andre; Skoldenberg, Olof] Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden. [Garland, Anne; Hailer, Nils P.] Univ Uppsala Hosp, Inst Surg Sci, Dept Orthoped, Uppsala, Sweden. [Rolfson, Ola; Garellick, Goran] Registerctr VGR, Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Rolfson, Ola; Garellick, Goran] Univ Gothenburg, Sahlgrenska Acad, Dept Orthoped, Inst Clin Sci, Gothenburg, Sweden. [Rolfson, Ola] Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA. [Rolfson, Ola] Harvard Univ, Sch Med, Boston, MA USA. RP Aspberg, S (reprint author), Danderyd Hosp, Dept Cardiol, S-18288 Stockholm, Sweden. EM sara.aspberg@ki.se OI Gordon, Max/0000-0002-8080-5815; Rolfson, Ola/0000-0001-6534-1242 FU Ugglas Stiftelse; Ake Wiberg stiftelse; Loo and Hans Ostermans Stiftelse; Sven Noren foundation; Stockholm County Council; Karolinska Institutet FX This study was supported by grants from the Ugglas Stiftelse, Ake Wiberg stiftelse, Loo and Hans Ostermans Stiftelse, Sven Noren foundation, and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institutet. NR 37 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD FEB PY 2016 VL 95 IS 6 BP 1 EP 7 AR e2662 DI 10.1097/MD.0000000000002662 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DE5ET UT WOS:000370654700001 PM 26871792 ER PT J AU Alexander, BM AF Alexander, Brian Michael TI Radiation de-intensification for patients with glioblastoma and poor prognostic features-how much do we really know? SO NEURO-ONCOLOGY LA English DT Editorial Material ID RADIOTHERAPY; THERAPY; OLDER; TEMOZOLOMIDE; MULTIFORME; TRIAL C1 [Alexander, Brian Michael] Dana Farber Brigham & Womens Canc Ctr, Radiat Oncol, Boston, MA USA. RP Alexander, BM (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. EM bmalexander@lroc.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD FEB PY 2016 VL 18 IS 2 BP 147 EP 148 DI 10.1093/neuonc/nov311 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DF8HB UT WOS:000371597200001 PM 26803808 ER PT J AU Aizer, AA Abedalthagafi, M Bi, WL Horvath, MC Arvold, ND Al-Mefty, O Lee, EQ Nayak, L Rinne, ML Norden, AD Reardon, DA Wen, PY Ligon, KL Ligon, AH Beroukhim, R Dunn, IF Santagata, S Alexander, BM AF Aizer, Ayal A. Abedalthagafi, Malak Bi, Wenya Linda Horvath, Margaret C. Arvold, Nils D. Al-Mefty, Ossama Lee, Eudocia Q. Nayak, Lakshmi Rinne, Mikael L. Norden, Andrew D. Reardon, David A. Wen, Patrick Y. Ligon, Keith L. Ligon, Azra H. Beroukhim, Rameen Dunn, Ian F. Santagata, Sandro Alexander, Brian M. TI A prognostic cytogenetic scoring system to guide the adjuvant management of patients with atypical meningioma SO NEURO-ONCOLOGY LA English DT Article DE atypical; copy number; meningioma; recurrence; resected ID CHILDHOOD-CANCER SURVIVOR; CENTRAL-NERVOUS-SYSTEM; ANAPLASTIC MENINGIOMAS; BRAIN-TUMORS; IRRADIATION; RECURRENCE; RADIATION; STROKE; MALIGNANCIES; RADIOTHERAPY AB The appropriate use of adjuvant therapy in patients with gross totally resected atypical meningioma requires an accurate assessment of recurrence risk. We sought to determine whether cytogenetic/genetic characterization may facilitate better estimation of the probability of recurrence. We first analyzed our clinical database, including high-resolution DNA copy number data, to identify 11 common copy number aberrations in a pilot cohort of meningiomas of all grades. We summed these aberrations to devise a cytogenetic abnormality score (CAS) and determined the CAS from archived tissue of a separate cohort of 32 patients with gross totally resected atypical meningioma managed with surgery alone. Propensity score adjusted Cox regression was used to determine whether the CAS was predictive of recurrence. An association between higher CAS and higher grade was noted in our pilot cohort with heterogeneity among atypical tumors. Among the 32 patients who underwent gross total resection of an atypical meningioma, the CAS was not significantly associated with age, gender, performance status, or tumor size/location but was associated with the risk of recurrence on univariable analysis (hazard ratio per aberration = 1.52; 95% CI = 1.08-2.14; P = .02). After adjustment, the impact of the dichotomized number of copy aberrations remained significantly associated with recurrence risk (hazard ratio = 4.47; 95% CI = 1.01-19.87; P = .05). The number of copy number aberrations is strongly associated with recurrence risk in patients with atypical meningioma following gross total resection and may inform the appropriate use of adjuvant radiation therapy in these patients or be useful for stratification in clinical trials. C1 [Aizer, Ayal A.; Horvath, Margaret C.; Arvold, Nils D.; Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Abedalthagafi, Malak; Ligon, Keith L.; Ligon, Azra H.; Santagata, Sandro] Dana Farber Brigham & Womens Canc Ctr, Dept Pathol, Boston, MA USA. [Bi, Wenya Linda; Al-Mefty, Ossama; Dunn, Ian F.] Dana Farber Brigham & Womens Canc Ctr, Dept Neurosurg, Boston, MA USA. [Lee, Eudocia Q.; Nayak, Lakshmi; Rinne, Mikael L.; Norden, Andrew D.; Reardon, David A.; Wen, Patrick Y.; Beroukhim, Rameen] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Beroukhim, R; Alexander, BM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.; Santagata, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.; Dunn, IF (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. EM rameen_beroukhim@dfci.harvard.edu; idunn@partners.org; ssantagata@partners.org; brian_alexander@dfci.harvard.edu FU Joint Center for Radiation Therapy (Boston, MA) FX This work was supported by an internal grant provided by the Joint Center for Radiation Therapy (Boston, MA). NR 27 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD FEB PY 2016 VL 18 IS 2 BP 269 EP 274 DI 10.1093/neuonc/nov177 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DF8HB UT WOS:000371597200015 PM 26323607 ER PT J AU Thakore, NP Samantaray, S Park, S Nozaki, K Smith, JA Cox, A Krause, J Banik, NL AF Thakore, Nakul P. Samantaray, Supriti Park, Sookyoung Nozaki, Kenkichi Smith, Joshua A. Cox, April Krause, James Banik, Naren L. TI Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury SO NEUROCHEMICAL RESEARCH LA English DT Article DE Spinal cord injury; Muscle atrophy; Protein degradation; Protein synthesis; Inflammation; E3-ubiquitin ligases ID CROSS-SECTIONAL AREA; SKELETAL-MUSCLE; PROTEIN-METABOLISM; MESSENGER-RNA; RAT SOLEUS; EXPRESSION; CALPAIN; ATROPHY; STIMULATION; HUMANS AB To clarify the molecular changes of sublesional muscle in the acute phase of spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post injury, and gastrocnemius muscles were excised. Morphological examination revealed no significant changes in the muscle fiber diameter between the sham and injury rats. Western blot analyses performed on the visibly red, central portion of the gastrocnemius muscle showed significantly higher expression of muscle specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and significantly lower expression of phosphorylated Akt-1/2/3 in the injury group compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF-alpha), and caspase-1, also had a significantly higher expression in the injury group; although, the mRNA levels of TNF-alpha and IL-6 did not show any significant difference between the sham and injury groups. These results suggest activation of protein degradation, deactivation of protein synthesis, and development of inflammatory reaction occurring in the sublesional muscles in the acute phase of SCI before overt muscle atrophy is seen. C1 [Thakore, Nakul P.; Samantaray, Supriti; Park, Sookyoung; Nozaki, Kenkichi; Smith, Joshua A.; Cox, April; Banik, Naren L.] Med Univ S Carolina, Dept Neurosurg & Neurol, 96 Jonathan Lucas St,309 CSB,MSC 606, Charleston, SC 29425 USA. [Park, Sookyoung] Kyungnam Univ, Dept Phys Therapy, Chang Won, South Korea. [Krause, James] Med Univ S Carolina, Dept Hlth Sci & Res, Coll Hlth Profess, Charleston, SC 29425 USA. [Nozaki, Kenkichi] Univ Alabama Birmingham, Dept Neurol, Div Neuromuscular Dis, UAB Stn, Birmingham, AL 35294 USA. [Banik, Naren L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Banik, NL (reprint author), Med Univ S Carolina, Dept Neurosurg & Neurol, 96 Jonathan Lucas St,309 CSB,MSC 606, Charleston, SC 29425 USA.; Banik, NL (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM baniknl@musc.edu FU National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NINDS-NIH) [NS031622]; Ralph H. Johnson Veterans Administration Medical Center [1IOBX001262, 1IOBX002349-01]; State of South Carolina Spinal Cord Injury Research Foundation [SCIRF 2012-001]; National Institutes of Health from the Extramural Research Facilities Program of the National Center for Research Resources [C06 RR015455] FX We would like to acknowledge Ms. Margaret Romonov for her assistance in the muscle biopsy slicing and H&E staining and Dr. Varduhi H. Knaryan for valuable discourse. The funding for this project was provided in part by R01 Grants from National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NINDS-NIH; NS031622), Ralph H. Johnson Veterans Administration Medical Center (1IOBX001262 and 1IOBX002349-01) and the State of South Carolina Spinal Cord Injury Research Foundation (SCIRF 2012-001). This work was conducted in a facility constructed with support from the National Institutes of Health, Grant Number C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. NR 44 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 2016 VL 41 IS 1-2 SI SI BP 44 EP 52 DI 10.1007/s11064-015-1696-9 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA DF5SO UT WOS:000371412800006 PM 26290268 ER PT J AU Shah, RV Allison, MA Lima, JAC Abbasi, SA Eisman, A Lai, C Jerosch-Herold, M Budoff, M Murthy, VL AF Shah, Ravi V. Allison, M. A. Lima, J. A. C. Abbasi, S. A. Eisman, A. Lai, C. Jerosch-Herold, M. Budoff, M. Murthy, V. L. TI Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article DE Obesity; Adiposity; Metabolic syndrome; C-reactive protein; Insulin; Adiponectin ID ADIPOSE-TISSUE FIBROSIS; INSULIN-RESISTANCE; HUMAN OBESITY; INFLAMMATION; EXPRESSION AB Background and aims: Fat radiodensity, as measured by fat attenuation on computed tomography (CT), has emerged as a potential biomarker of "fat quality." We sought to characterize the relationship between fat radiodensity and quantity in subcutaneous, visceral, and intermuscular fat depots, and its role in inflammation, insulin resistance, and metabolic syndrome (MetS). Methods and results: We studied 1511 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT for measurement of regional fat distribution and radiodensity, along with biomarker assessments and adjudication of incident metabolic syndrome (MetS). Linear, logistic and Cox regression analyses were used to measure association between fat radiodensity and (1) fat quantity, (2) biomarkers of cardiometabolic dysfunction, and (3) both prevalent and incident MetS. In each fat depot, radiodensity was strongly and inversely associated with quantity (e. g., visceral fat radiodensity vs. quantity: rho = -0.82, P < 0.01). After adjustment for age, sex and race, lower visceral fat radiodensity was associated with greater C-reactive protein, leptin and insulin, but lower adiponectin (P < 0.01 for all). After full adjustment for cardiovascular disease risk factors, visceral (but not subcutaneous or intermuscular) fat radiodensity was associated with prevalent MetS (OR = 0.96, 95% CI = 0.93-0.99, P = 0.01). Moreover, lower visceral fat radiodensity was associated with incident MetS after the same adjustment (HR = 0.95, 95% CI 0.93-0.98, P < 0.01). However, this association became non-significant after further adjustment for visceral fat quantity. Conclusion: Fat radiodensity is strongly correlated with fat quantity and relevant inflammatory biomarkers. Fat radiodensity (especially for visceral fat) may be a complementary, easily assessed marker of cardiometabolic risk. (C) 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. C1 [Shah, Ravi V.; Lai, C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Allison, M. A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Lima, J. A. C.] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA. [Abbasi, S. A.] Brown Univ, Dept Cardiol, Providence, RI 02912 USA. [Eisman, A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jerosch-Herold, M.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Noninvas Cardiovasc Imaging Sect, 75 Francis St, Boston, MA 02115 USA. [Jerosch-Herold, M.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Budoff, M.] Univ Calif Los Angeles, Dept Cardiol & Med, Los Angeles, CA USA. [Murthy, V. L.] Univ Michigan, Dept Med, Cardiovasc Med Div, Ann Arbor, MI 48109 USA. [Murthy, V. L.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. RP Murthy, VL (reprint author), Univ Michigan, Med Radiol, 1500 E Med Ctr Dr,SPC 5873, Ann Arbor, MI 48109 USA.; Shah, RV (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, 330 Brookline Ave, Boston, MA 02215 USA. EM rshah1@bidmc.harvard.edu; vlmurthy@med.umich.edu OI Murthy, Venkatesh/0000-0002-7901-1321; Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute [R01 HL071739, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01 HC 95169] FX This research was supported by grant number R01 HL071739 and contracts N01-HC-95159 through N01-HC-95165 and N01 HC 95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. NR 28 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 EI 1590-3729 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD FEB PY 2016 VL 26 IS 2 BP 114 EP 122 DI 10.1016/j.numecd.2015.12.002 PG 9 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA DF3SF UT WOS:000371266900004 PM 26817938 ER PT J AU Broder-Fingert, S Shui, A Ferrone, C Iannuzzi, D Cheng, ER Giauque, A Connors, S McDougle, CJ Donelan, K Neumeyer, A Kuhlthau, K AF Broder-Fingert, Sarabeth Shui, Amy Ferrone, Christine Iannuzzi, Dorothea Cheng, Erika R. Giauque, Ann Connors, Susan McDougle, Christopher J. Donelan, Karen Neumeyer, Ann Kuhlthau, Karen TI A Pilot Study of Autism-Specific Care Plans During Hospital Admission SO PEDIATRICS LA English DT Article ID SPECTRUM DISORDERS; PHYSICAL-DISABILITIES; CHILDREN; PEOPLE; ADOLESCENTS; MANAGEMENT; SERVICES; BEHAVIOR AB BACKGROUND AND OBJECTIVE: Hospital admissions can be difficult for patients with autism spectrum disorder (ASD). We created an autism-specific care plan (ACP) to help improve the hospital experience for patients with ASD, and we tested feasibility and acceptability and compared the experience of care for children with and without an ACP. METHODS: We performed a nonrandomized, retrospective chart review of all patients with ASD and a hospital admission from January 2013 to December 2013 (n = 142) to determine feasibility of the intervention. We then mailed surveys to all 142 families to measure experience with the ACP and to compare experience of care in those who did and did not have an ACP. Using multivariable linear regression we assessed the association of experience of care with ACP use while adjusting for covariates. RESULTS: The ACP was well tolerated by parents and used frequently by staff. Compared with parents who did not use the ACP, parents who used the ACP reported a better experience relating to their general hospital experience (B = 1.48, P < .001) and staff attention to their child's ASD-specific needs (B = 3.07, P < .001). CONCLUSIONS: According to this pilot study, care plans are feasible and hold promise to improve the experience of care for children with ASD and their families in the hospital setting. C1 [Broder-Fingert, Sarabeth] Boston Univ, Sch Med, Boston Med Ctr, Div Gen Pediat, Boston, MA 02215 USA. [Broder-Fingert, Sarabeth; Cheng, Erika R.; Kuhlthau, Karen] Harvard Univ, Sch Med, MassGen Hosp Children, Div Gen Acad Pediat,Dept Pediat, Boston, MA USA. [Broder-Fingert, Sarabeth; Ferrone, Christine; Iannuzzi, Dorothea; Giauque, Ann; Connors, Susan; McDougle, Christopher J.; Neumeyer, Ann] Harvard Univ, Sch Med, MassGen Hosp, Lurie Ctr Autism, Lexington, MA USA. [Shui, Amy] MassGen Hosp, Ctr Biostat, Boston, MA USA. [Donelan, Karen] MassGen Hosp, Mongan Inst Hlth Policy, Boston, MA USA. RP Broder-Fingert, S (reprint author), Boston Univ, Sch Med, Div Gen Pediat, 850 Harrison Ave,Room 322, Boston, MA 02118 USA. EM sarabeth.broder-fingert@bmc.org FU MassGeneral Hospital for Children; Nancy Lurie Marks Family Foundation; US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054] FX Supported by MassGeneral Hospital for Children; Nancy Lurie Marks Family Foundation to the Massachusetts General Hospital; and Cooperative Agreement (UA3 MC 11054) from the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. NR 25 TC 0 Z9 0 U1 4 U2 5 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 FEB PY 2016 VL 137 SU 2 BP S196 EP S204 DI 10.1542/peds.2015-2851R PG 9 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700017 PM 26908475 ER PT J AU Ezell, J Shui, A Sanders, K Veenstra-VanderWeele, J AF Ezell, Jordan Shui, Amy Sanders, Kevin Veenstra-VanderWeele, Jeremy TI Pattern of Diagnosis and Co-occurring Symptoms in Adopted Children With Autism Spectrum Disorder SO PEDIATRICS LA English DT Article ID COGNITIVE-DEVELOPMENT; EARLY ADVERSITY; CATCH-UP; SLEEP; PRIVATION; METAANALYSIS; PREVALENCE; ATTACHMENT AB OBJECTIVES: To determine whether adopted children with autism spectrum disorder (ASD) differ from the general ASD population in terms of diagnosis, internalizing and externalizing behaviors, sleep problems, and medications. METHODS: We studied 163 adoptees in the Autism Speaks Autism Treatment Network (ATN) in comparison with 5624 nonadopted ATN participants (aged 1.5-17.6 years; mean [SD] = 6.2 [3.4] years). Gender, age, race, ethnicity, IQ, and categorical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ASD diagnosis were tested for differences by group (adopted versus nonadopted) by using independent-samples t tests for continuous variables and Fisher's exact tests for categorical variables. Logistic or linear regression models were used to examine the association between adoption status and several outcome variables, after controlling for covariates. RESULTS: After controlling for demographics and diagnosis, there were significant differences in group characteristics, including greater propensity for externalizing behavior (P < .001), internalizing behavior (P = .001), and sleep problems (P < .001) in the adopted population. Adoptees were also prescribed psychotropic medications (P < .001) more often than the nonadoptees. Adoptees received a diagnosis of pervasive developmental disorder-not otherwise specified significantly more frequently than controls (odds ratio = 1.8; CI = 1.3-2.5; P < .001), despite no significant difference in symptoms on standardized measures. CONCLUSIONS: These results suggest that the population of adopted children with ASD differs from the general ASD population both with regard to diagnostic subtype and co-occurring behavioral problems. Future research should evaluate the contributions of specific factors associated with adoption such as biological family history, pregnancy history, early childhood experience, and age at adoption. C1 [Ezell, Jordan; Sanders, Kevin] Vanderbilt Univ, Dept Pediat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Shui, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Veenstra-VanderWeele, Jeremy] Columbia Univ, Dept Psychiat, New York, NY USA. [Veenstra-VanderWeele, Jeremy] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Veenstra-VanderWeele, J (reprint author), 1051 Riverside Dr,Mail Unit 78, New York, NY 10025 USA. EM jv2511@columbia.edu FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC11054] FX This activity was supported by Autism Speaks and cooperative agreement UA3 MC11054 through the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program to the Massachusetts General Hospital. This work was conducted through the Autism Speaks Autism Treatment Network. NR 40 TC 0 Z9 0 U1 4 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 FEB PY 2016 VL 137 SU 2 BP S90 EP S97 DI 10.1542/peds.2015-2851G PG 8 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700006 PM 26908482 ER PT J AU Fung, LK Mahajan, R Nozzolillo, A Bernal, P Krasner, A Jo, B Coury, D Whitaker, A Veenstra-Vanderweele, J Harden, AY AF Fung, Lawrence K. Mahajan, Rajneesh Nozzolillo, Alixandra Bernal, Pilar Krasner, Aaron Jo, Booil Coury, Daniel Whitaker, Agnes Veenstra-Vanderweele, Jeremy Harden, Antonio Y. TI Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis SO PEDIATRICS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED CROSSOVER; CONTROLLED PILOT TRIAL; DOUBLE-BLIND; SPECTRUM DISORDERS; PEDIATRIC-PATIENTS; CHILDREN; RISPERIDONE; ARIPIPRAZOLE; ADOLESCENTS AB BACKGROUND: Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families. Although many medications have been tested for IA in ASDs in randomized controlled trials (RCTs), critical quantitative analyses of these trials are lacking in the literature. OBJECTIVES: To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD. DATA SOURCES: Studies were identified from Medline, PsycINFO, Embase, and review articles. METHODS: Original articles on placebo-controlled RCTs of pharmacologic treatments of IA in youth age 2 to 17 years with ASD were included. Data items included study design, study goals, details of study participants, details of intervention, study results, statistical methods, side effects, and risks of bias. The primary study outcome measure was the effect size of reduction in the Aberrant Behavioral Checklist-Irritability (ABC-I) scores in the medication group, as compared with placebo, in RCTs using parallel groups design. RESULTS: Forty-six RCTs were identified. Compared with placebo, 3 compounds resulted in significant improvement in ABC-I at the end of treatment. Risperidone and aripiprazole were found to be the most effective, with the largest effect sizes. Sedation, extrapyramidal sides effects, and weight gain were assessed quantitatively. CONCLUSIONS: Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies. C1 [Fung, Lawrence K.; Jo, Booil; Harden, Antonio Y.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Mahajan, Rajneesh] Kennedy Krieger Inst, Baltimore, MD USA. [Mahajan, Rajneesh] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Nozzolillo, Alixandra] MassGen Hosp Children, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA USA. [Bernal, Pilar] Kaiser Permanente No Calif, San Jose, CA USA. [Krasner, Aaron; Whitaker, Agnes; Veenstra-Vanderweele, Jeremy] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Coury, Daniel] Ohio State Univ, Dept Dev & Behav Pediat, Columbus, OH 43210 USA. RP Harden, AY (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, 401 Quarry Rd, Stanford, CA 94305 USA. EM hardanay@stanford.edu OI Fung, Lawrence/0000-0002-5738-0396 FU US Department of Health and Human Services, Health Resources and Services Administration (HRSA), Maternal and Child Health Research Program [UA3 MC11054] FX Supported by cooperative agreement UA3 MC11054 through the US Department of Health and Human Services, Health Resources and Services Administration (HRSA), Maternal and Child Health Research Program to the Massachusetts General Hospital. This work was conducted through the Autism Speaks Autism Treatment Network serving as the Autism Intervention Research Network on Physical Health. The views expressed in this article do not necessarily reflect the views of Autism Speaks, Inc or HRSA. NR 64 TC 3 Z9 3 U1 1 U2 11 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 FEB PY 2016 VL 137 SU 2 BP S124 EP S135 AR e20152851K DI 10.1542/peds.2015-2851K PG 12 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700010 PM 26908468 ER PT J AU Greenlee, JL Mosley, AS Shui, AM Veenstra-VanderWeele, J Gotham, KO AF Greenlee, Jessica L. Mosley, Angela S. Shui, Amy M. Veenstra-VanderWeele, Jeremy Gotham, Katherine O. TI Medical and Behavioral Correlates of Depression History in Children and Adolescents With Autism Spectrum Disorder SO PEDIATRICS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; GASTROINTESTINAL DISORDERS; INTERNALIZING SYMPTOMS; MAJOR DEPRESSION; SOMATIC SYMPTOMS; ANXIETY; COMORBIDITY; PREVALENCE AB BACKGROUND AND OBJECTIVES: Depression is commonly associated with autism spectrum disorder (ASD) across the life span. We sought to identify medical and behavioral problems associated with a history of a parent-reported diagnosis of depression in a large sample of school-aged children and adolescents with ASD. METHODS: A sample of 1272 participants (aged 6-17 years; mean [SD]: 9.56 [2.79] years) from the Autism Speaks Autism Treatment Network consortium were divided into "ever-depressed" (n = 89) and "nondepressed" (n = 1183) groups on the basis of caregiver endorsement of children's current or previous diagnoses of depression. RESULTS: In total, 7.0% of children with ASD (4.8% of those aged 6-12 years and 20.2% of those aged 13-17 years) were reported to have a history of a depression diagnosis. Positive depression history was associated with greater chronological age, higher IQ, and Asperger disorder diagnosis. After controlling for age, IQ, and within-spectrum categorical diagnosis, the ever-depressed group exhibited significantly greater rates of seizure disorders (odds ratio = 2.64) and gastrointestinal problems (odds ratio = 2.59) and trend-level differences in aggression, somatic complaints, and social impairments. The groups did not differ in autism severity, repetitive behaviors, sleep problems, eating problems, self-injurious behavior, or current intervention use. CONCLOSIONS: Co-occurring depression is a particularly common problem in higher-functioning older children within the Autism Treatment Network. Our findings indicate that children with ASD and a history of a depression diagnosis are more likely to also have co-occurring medical problems, although the presence and direction of causality is unclear. C1 [Greenlee, Jessica L.] Virginia Commonwealth Univ, Dept Psychol, Box 2018, Richmond, VA 23284 USA. [Mosley, Angela S.; Gotham, Katherine O.] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN USA. [Shui, Amy M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Veenstra-VanderWeele, Jeremy] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. RP Gotham, KO (reprint author), Vanderbilt Bill Wilkerson Ctr, 1215 21st Ave South,Room 8310, Nashville, TN 37232 USA. EM katherine.gotham@vanderbilt.edu FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC11054]; National Institute of Mental Health grants [K01-MH103500, T32-MH18921]; Autism Speaks FX This activity was supported by Autism Speaks and cooperative agreement UA3 MC11054 through the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program to the Massachusetts General Hospital, and by National Institute of Mental Health grants K01-MH103500 and T32-MH18921. This work was conducted through the Autism Speaks Autism Treatment Network. NR 51 TC 0 Z9 0 U1 7 U2 13 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 FEB PY 2016 VL 137 SU 2 BP S105 EP S114 AR e201528511 DI 10.1542/peds.2015-2851I PG 10 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700008 PM 26908466 ER PT J AU Kuhlthau, KA Delahaye, J Erickson-Warfield, M Shui, A Crossman, M van der Weerd, E AF Kuhlthau, Karen A. Delahaye, Jennifer Erickson-Warfield, Marji Shui, Amy Crossman, Morgan van der Weerd, Emma TI Health Care Transition Services for Youth With Autism Spectrum Disorders: Perspectives of Caregivers SO PEDIATRICS LA English DT Article ID NATIONAL-SURVEY; DEVELOPMENTAL-DISABILITIES; SYMPTOM SEVERITY; YOUNG-ADULTS; CHILDREN; NEEDS; QUESTIONNAIRE; DISPARITIES; CORTISOL; ALLERGY AB BACKGROUND AND OBJECTIVE: This paper seeks to describe the experience of youth with autism spectrum disorder (ASD) in making the health care transition (HCT) to adult care. METHODS: We surveyed 183 parents and guardians of youth with ASD, assessing the extent to which youth and families experienced and desired HCT services, their satisfaction with services, and obstacles to transition. Descriptive statistics were used to examine HCT measures and Fisher's exact and t tests assessed whether demographic or health measures were associated with service receipt. Any measures with a P value <.05 were included in a logistic regression model, with service receipt as the dependent variable. RESULTS: The receipt of transition services was low overall, with rates for individual services ranging from 3% to 33% and only 60% of the sample receiving any transition service. Despite these low rates, a majority of respondents reported wanting services (73.3%-91.6%), and satisfaction for received services was high (89%-100%). Regression analyses showed depression to be the only variable significantly associated with service receipt. Youth who were identified by their caregivers as having depression experienced a higher rate of transition service receipt than those not identified as having depression. CONCLUSIONS: Findings suggest that there is a great need to address the provision of HCT services for youth with ASD. Although families who received HCT services were generally satisfied, overall rates of service receipt were quite low, and those who were not provided with services generally desired them. C1 [Kuhlthau, Karen A.; Delahaye, Jennifer; van der Weerd, Emma] Massachusetts Gen Hosp, Dept Pediat, 125 Nashua St,Suite 860, Boston, MA 02114 USA. [Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, 125 Nashua St,Suite 860, Boston, MA 02114 USA. [Erickson-Warfield, Marji; Crossman, Morgan] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA. [Shui, Amy] Massachusetts Gen Hosp, Dept Biostat, 125 Nashua St,Suite 860, Boston, MA 02114 USA. RP Kuhlthau, KA (reprint author), Harvard Univ, Sch Med, 125 Nashua St,Suite 860, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [R40 MC 19925] FX Funded by grant R40 MC 19925 through the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program (PI Karen Kuhlthau). NR 40 TC 0 Z9 0 U1 2 U2 5 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 FEB PY 2016 VL 137 SU 2 BP S158 EP S166 AR e20152851N DI 10.1542/peds.2015-2851N PG 9 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700013 PM 26908471 ER PT J AU Malow, BA Katz, T Reynolds, AM Shui, A Carno, M Connolly, HV Coury, D Bennett, AE AF Malow, Beth A. Katz, Terry Reynolds, Ann M. Shui, Amy Carno, Margaret Connolly, Heidi V. Coury, Daniel Bennett, Amanda E. TI Sleep Difficulties and Medications in Children With Autism Spectrum Disorders: A Registry Study SO PEDIATRICS LA English DT Article ID ABERRANT BEHAVIOR CHECKLIST; QUALITY-OF-LIFE; TYPICAL DEVELOPMENT; CLINICAL-SAMPLE; ADOLESCENTS; PREVALENCE; INSOMNIA; VALIDITY AB OBJECTIVES: Sleep difficulties are common in children with autism spectrum disorders, with wide-ranging effects on the child's daytime behavior. We reviewed data within our Autism Speaks Autism Treatment Network Registry to determine the prevalence of sleep difficulties and patterns of medication use. METHODS: Data from 1518 children ages 4 to 10 years were analyzed to determine the number of children documented to have sleep difficulties by parent-completed questionnaires and clinician-completed forms and how these findings related to the use of sleep medications. RESULTS: The Children's Sleep Habits Questionnaire total score was >= 41 (associated with clinically significant sleep problems in past research) in 71% of children. The prevalence of sleep diagnoses was less frequent (30% of children aged 4-10 years; P < .0001). Medications for sleep were prescribed in 46% of 4- to 10-year-olds given a sleep diagnosis. The most common medication used for sleep was melatonin followed by alpha-agonists, with a variety of other medications taken for sleep (anticonvulsants, antidepressants, atypical antipsychotics, and benzodiazepines). Children taking medications for sleep had worse daytime behavior and pediatric quality of life than children not taking sleep medications. CONCLUSIONS: Parent concerns about sleep may not be reflected in the information gathered during a clinic visit, supporting the need to develop screening practice pathways for sleep in autism spectrum disorders. Furthermore, many medications taken for sleep have adverse effects, supporting the need for evidence-based interventions in this population. C1 [Malow, Beth A.] Vanderbilt Univ, Sch Med, Dept Neurol, Sleep Disorders Div, 221 Kirkland Hall, Nashville, TN 37235 USA. [Katz, Terry; Reynolds, Ann M.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Shui, Amy] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Carno, Margaret; Connolly, Heidi V.] Univ Rochester, Dept Pediat, Rochester, NY USA. [Coury, Daniel] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA. [Bennett, Amanda E.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Malow, BA (reprint author), Vanderbilt Univ, Med Ctr, 1161 21st Ave South,Room A-0116, Nashville, TN 37232 USA. EM beth.malow@vanderbilt.edu OI Reynolds, Ann/0000-0002-0836-746X FU US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC11054] FX This Network activity was supported by Autism Speaks and cooperative agreement UA3 MC11054 through the US Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program to the Massachusetts General Hospital. This work was conducted through the Autism Speaks Autism Treatment Network. NR 26 TC 2 Z9 2 U1 5 U2 16 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 FEB PY 2016 VL 137 SU 2 BP S98 EP S104 DI 10.1542/peds.2015-2851H PG 7 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700007 PM 26908483 ER PT J AU McGuire, K Fung, LK Hagopian, L Vasa, RA Mahajan, R Bernal, P Silberman, AE Wolfe, A Coury, DL Hardan, AY Veenstra-VanderWeele, J Whitaker, AH AF McGuire, Kelly Fung, Lawrence K. Hagopian, Louis Vasa, Roma A. Mahajan, Rajneesh Bernal, Pilar Silberman, Anna E. Wolfe, Audrey Coury, Daniel L. Hardan, Antonio Y. Veenstra-VanderWeele, Jeremy Whitaker, Agnes H. TI Irritability and Problem Behavior in Autism Spectrum Disorder: A Practice Pathway for Pediatric Primary Care SO PEDIATRICS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTELLECTUAL DISABILITY; MENTAL-HEALTH; YOUNG-CHILDREN; GASTROINTESTINAL SYMPTOMS; DEVELOPMENTAL DISORDERS; CHALLENGING BEHAVIORS; PSYCHIATRIC-DISORDERS; ADOLESCENTS; COMMUNICATION AB OBJECTIVE: Pediatric primary care providers (PCPs) caring for patients with autism spectrum disorder (ASD) often encounter irritability (vocal or motoric outbursts expressive of anger, frustration, or distress) and problem behavior (directed acts of aggression toward other people, self, or property). The Autism Intervention Research Network on Physical Health and Autism Speaks Autism Treatment Network charged a multidisciplinary workgroup with developing a practice pathway to assist PCPs in the evaluation and treatment of irritability and problem behavior (I/PB). METHODS: The workgroup reviewed the literature on the evaluation and treatment of contributory factors for I/PB in ASD. The workgroup then achieved consensus on the content and sequence of each step in the pathway. RESULTS: The practice pathway is designed to help the PCP generate individualized treatment plans based on contributing factors identified in each patient. These factors may include medical conditions, which the PCP is in a key position to address; functional communication challenges that can be addressed at school or at home; psychosocial stressors that may be ameliorated; inadvertent reinforcement of I/PB; and co-occurring psychiatric conditions that can be treated. The pathway provides guidance on psychotropic medication use, when indicated, within an individualized treatment plan. In addition to guidance on assessment, referral, and initial treatment, the pathway includes monitoring of treatment response and periodic reassessment. CONCLUSIONS: The pediatric PCP caring for the patient with ASD is in a unique position to help generate an individualized treatment plan that targets factors contributing to I/PB and to implement this plan in collaboration with parents, schools, and other providers. C1 [McGuire, Kelly; Silberman, Anna E.; Veenstra-VanderWeele, Jeremy; Whitaker, Agnes H.] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. [McGuire, Kelly; Silberman, Anna E.; Veenstra-VanderWeele, Jeremy; Whitaker, Agnes H.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [McGuire, Kelly] Maine Behav Healthcare, Ctr Autism & Dev Disorders, South Portland, ME USA. [Fung, Lawrence K.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Fung, Lawrence K.; Hardan, Antonio Y.] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Dept Behav Psychol, Baltimore, MD USA. [Vasa, Roma A.; Mahajan, Rajneesh] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Vasa, Roma A.; Mahajan, Rajneesh] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Bernal, Pilar] Childrens Hlth Council, Psychiat, Palo Alto, CA USA. [Wolfe, Audrey] MassGen Hosp Children, Boston, MA USA. [Coury, Daniel L.] Nationwide Childrens Hosp, Columbus, OH USA. [Veenstra-VanderWeele, Jeremy] New York Presbyterian Hosp, Ctr Autism & Developing Brain, White Plains, NY USA. RP Whitaker, AH (reprint author), 1051 Riverside Dr,Unit 74, New York, NY 10032 USA. EM whitakea@nyspi.columbia.edu OI Fung, Lawrence/0000-0002-5738-0396 FU Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services (HHS) [UA3 MC11054]; Autism Intervention Research Network on Physical Health; Marilyn and James Simons Family Giving FX Supported by the Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services (HHS) under cooperative agreement UA3 MC11054, Autism Intervention Research Network on Physical Health. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred from, the HRSA, HHS, or the US government. Conducted through the Autism Speaks Autism Treatment Network, serving as the Autism Intervention Research Network on Physical Health. Funding was also provided by Marilyn and James Simons Family Giving (Drs McGuire, Siberman, and Whitaker). NR 71 TC 2 Z9 2 U1 9 U2 19 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 FEB PY 2016 VL 137 SU 2 BP S136 EP S148 DI 10.1542/peds.2015-2851L PG 13 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700011 PM 26908469 ER PT J AU Murray, DS Fedele, A Shui, A Coury, DL AF Murray, Donna S. Fedele, Angie Shui, Amy Coury, Daniel L. TI The Autism Speaks Autism Treatment Network Registry Data: Opportunities for Investigators SO PEDIATRICS LA English DT Article ID QUALITY-OF-LIFE; SPECTRUM DISORDERS; CHILDREN; ADOLESCENTS; MANAGEMENT; SYMPTOMS; PREVALENCE; HEALTH AB OBJECTIVE: Patient registries can effectively collect data over a long period of time to provide a better understanding of the typical presentation of specific conditions. The autism spectrum disorders (ASDs) have experienced a marked increase in reported prevalence over the past 20 years for reasons that are not completely clear. The Autism Treatment Network (ATN) Registry was established to facilitate investigations into a variety of questions critical to expanding our understanding of ASDs. Here we describe the establishment of the registry, its components, some of its findings to date, and opportunities for further use of this data. METHODS: Participants are eligible for enrollment into the ATN registry if they are between the ages of 2.0 and 17.6 years at the time of enrollment and meet criteria for ASD as determined by clinical consensus on the basis of specific diagnostic measures (Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule, Second Edition; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition/Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). Baseline measures include demographics, autism assessment, cognitive assessment data, behavioral data, sleep habits, quality of life, sensory data, and treatments. Several of the measures are collected at annual follow-up visits. RESULTS: More than 6800 children with ASD have been enrolled in the Autism Speaks ATN registry. Data from the registry have been reported at numerous scientific meetings and in several publications and have led to new recommendations for best practices in the management of ASD. CONCLUSIONS: A patient registry for children and adolescents with ASD has had and will continue to have a significant impact on care for this population. Investigators are encouraged to query this database to further its impact by testing novel hypotheses and conducting preliminary proof-of-concept analyses. C1 [Murray, Donna S.; Fedele, Angie; Shui, Amy; Coury, Daniel L.] Autism Speaks Autism Treatment Network, Boston, MA USA. [Murray, Donna S.] Cincinnati Childrens Hosp Med Ctr, Kelly OLeary Ctr Autism Spectrum Disorders, Div Dev & Behav Pediat, Cincinnati, OH 45229 USA. [Murray, Donna S.; Fedele, Angie; Shui, Amy; Coury, Daniel L.] 20th Resources & Serv Adm, Autism Intervent Res Network Phys Hlth, Rockville, MD USA. [Shui, Amy] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Coury, Daniel L.] Nationwide Childrens Hosp, Dev & Behav Pediat, Columbus, OH USA. [Coury, Daniel L.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. RP Murray, DS (reprint author), Autism Speaks, 85 Devonshire St,9th Floor, Boston, MA 02109 USA. EM donna.murray@autismspeaks.org FU Autism Speaks FX The Autism Speaks Autism Treatment Network registry is funded by Autism Speaks. NR 21 TC 0 Z9 0 U1 6 U2 7 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 FEB PY 2016 VL 137 SU 2 BP S72 EP S78 AR e20152851E DI 10.1542/peds.2015-2851E PG 7 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700004 PM 26908480 ER PT J AU Perrin, JM Coury, DL Klatka, K Winklosky, B Wolfe, A Murray, D Kuhlthau, KA AF Perrin, James M. Coury, Daniel L. Klatka, Kirsten Winklosky, Brian Wolfe, Audrey Murray, Donna Kuhlthau, Karen A. TI The Autism Intervention Research Network on Physical Health and the Autism Speaks Autism Treatment Network SO PEDIATRICS LA English DT Article ID QUALITY-OF-LIFE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SPECTRUM DISORDERS; BEHAVIORAL-CHARACTERISTICS; CHILDREN; ADOLESCENTS; MANAGEMENT; MEDICATION; SYMPTOMS; CARE AB Over 10 years, the Autism Intervention Research Network on Physical Health (AIR-P) and the Autism Speaks Autism Treatment Network (ATN) have collaborated to produce much of the material presented in this supplement and have been pioneers in bringing attention to the medical needs of children and adolescents with autism spectrum disorders (ASDs) and related conditions. Whereas, until recently, medical complaints (eg, abdominal pain, poor sleep, or disruptive behaviors) were typically considered part of the disorder and therefore not requiring specific attention, today clinicians throughout the country directly assess and treat these associated conditions. The combined AIR-P/ATN network has developed systematic ways to assess and treat coexisting conditions, focusing on those for which management was previously highly variable or sporadic and has shared those methods broadly with the larger parent and professional communities. The active involvement of families and young people with ASD has helped the network identify key issues for individuals and families and focus its attention accordingly. Although clinicians may have limited new, evidence-based options for treating autism directly, they now have systematic ways to evaluate and manage coexisting conditions. In turn, families have learned about new ways to help their children and improve their functioning and outcomes. C1 [Perrin, James M.; Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Perrin, James M.; Coury, Daniel L.; Klatka, Kirsten; Winklosky, Brian; Wolfe, Audrey; Kuhlthau, Karen A.] MassGen Hosp Children, Autism Intervent Res Network Phys Hlth, Boston, MA USA. [Coury, Daniel L.] Ohio State Univ, Nationwide Childrens Hosp, Sch Med, Dept Pediat, Columbus, OH 43210 USA. [Murray, Donna] Autism Speaks Autism Treatment Network, Boston, MA USA. RP Perrin, JM (reprint author), Harvard Univ, MassGen Hosp Children, Sch Med, Dept Pediat, 125 Nashua St,Suite 860, Boston, MA 02114 USA. FU Health Resources and Services Administration of the US Department of Health and Human Services under Autism Intervention Research Network on Physical Health [UA3 MC11054] FX This project was supported by the Health Resources and Services Administration of the US Department of Health and Human Services under cooperative agreement UA3 MC11054, Autism Intervention Research Network on Physical Health. This work was conducted through the Autism Speaks Autism Treatment Network serving as the Autism Intervention Research Network on Physical Health. NR 18 TC 1 Z9 1 U1 7 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 FEB PY 2016 VL 137 SU 2 BP S67 EP S71 AR e20152851D DI 10.1542/peds.2015-2851D PG 5 WC Pediatrics SC Pediatrics GA DF5LR UT WOS:000371393700003 PM 26908479 ER PT J AU Tackett, MJ Nash, L Stucky, KJ Nierenberg, B AF Tackett, M. Jan Nash, Laurie Stucky, Kirk Jeffrey Nierenberg, Barry TI Supervision in Rehabilitation Psychology: Application of Beatrice Wright's Value-Laden Beliefs and Principles SO REHABILITATION PSYCHOLOGY LA English DT Article DE supervision; rehabilitation; mentoring; clinical training; residency training ID COMPETENCE AB Clinical supervision is of critical importance for training subsequent generations of psychologists. Specialty training in rehabilitation psychology requires exposure to specific knowledge, skills, and attitudes related to disability and specialized supervision and mentorship. In the literature to date, minimal guidance exists regarding supervision training and methods specifically for rehabilitation psychologists. This article aims to provoke discussion regarding supervision practice and dissemination of the values fundamental to our specialty. The foundational wisdom of Dr. Beatrice Wright (1983) is applied for the purposes of this endeavor. Examples of clinical supervision scenarios are presented as teaching vignettes to demonstrate ways in which supervisors and mentors can incorporate this content, promote discussion, and apply it to real-world practice. Impact and Implications This article describes the importance of specialty clinical supervision in rehabilitation psychology. In addition, a model is advanced for providing supervision and values clarification based on foundational rehabilitation psychology literature. This article suggests ongoing dissemination of core rehabilitation psychology values through supervision and mentoring relationships, as well as processes for improving supervision practice in the specialty. C1 [Tackett, M. Jan] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. [Tackett, M. Jan] Univ Washington, Seattle, WA 98195 USA. [Nash, Laurie] Shepherd Ctr, Atlanta, GA USA. [Stucky, Kirk Jeffrey] Hurley Med Ctr, Flint, MI USA. [Nierenberg, Barry] Nova SE Univ, Ctr Psychol Studies, Ft Lauderdale, FL 33314 USA. RP Tackett, MJ (reprint author), Univ Washington, Seattle Div, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM meredith.tackett@va.gov NR 16 TC 1 Z9 1 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FEB PY 2016 VL 61 IS 1 BP 74 EP 81 DI 10.1037/rep0000070 PG 8 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA DF4EZ UT WOS:000371302000008 PM 26881309 ER PT J AU Liu, Y Mallampalli, RK AF Liu, Yuan Mallampalli, Rama K. TI Small molecule therapeutics targeting F-box proteins in cancer SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE Ubiquitin; E3 ligase; F-box protein; Small molecule inhibitor; Cancer ID SCF UBIQUITIN-LIGASE; NF-KAPPA-B; CELL-CYCLE ARREST; PHOSPHORYLATION-DEPENDENT UBIQUITINATION; ANAPHASE PROMOTING COMPLEX/CYCLOSOME; TUMOR-SUPPRESSOR; BETA-TRCP; C-MYC; MEDIATED DEGRADATION; SKP2 PROTEIN AB The ubiquitin proteasome system (UPS) plays vital roles in maintaining protein equilibrium mainly through proteolytic degradation of targeted substrates. The archetypical SCF ubiquitin E3 ligase complex contains a substrate recognition subunit F-box protein that recruits substrates to the catalytic ligase core for its polyubiquitylation and subsequent proteasomal degradation. Several well-characterized F-box proteins have been demonstrated that are tightly linked to neoplasia. There is mounting information characterizing F-box protein-substrate interactions with the rationale to develop unique therapeutics for cancer treatment. Here we review that how F-box proteins function in cancer and summarize potential small molecule inhibitors for cancer therapy. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Liu, Yuan; Mallampalli, Rama K.] Univ Pittsburgh, Ctr Excellence, Acute Lung Injury, Dept Med, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, UPMC Montefiore, Pulm Allergy & Crit Care Med, Dept Med, NW628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU US National Institutes of Health [HL096376, P01 HL114453]; United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; United States Department of Veterans Affairs FX The authors apologize for the omission of many colleagues' work owing to space constraints. Work in the Mallampalli laboratory is partly supported by the US National Institutes of Health R01 Grant HL096376 and P01 HL114453 (to R.K.M.), and is partly supported by the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development and by a Merit Review award from the United States Department of Veterans Affairs (to R.K.M.). NR 177 TC 3 Z9 3 U1 1 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD FEB PY 2016 VL 36 BP 105 EP 119 DI 10.1016/j.semcancer.2015.09.014 PG 15 WC Oncology SC Oncology GA DF7QY UT WOS:000371553900011 PM 26427329 ER PT J AU Lilly, E Sellitto, C Milstone, LM White, TW AF Lilly, Evelyn Sellitto, Caterina Milstone, Leonard M. White, Thomas W. TI Connexin channels in congenital skin disorders SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Connexin; Epidermis; Mutation; Genetic disease; Hemichannel; Gap junction ID ICHTHYOSIS-DEAFNESS SYNDROME; INCREASED HEMICHANNEL ACTIVITY; CAUSE ERYTHROKERATODERMIA VARIABILIS; HIDROTIC ECTODERMAL DYSPLASIA; GAP-JUNCTION FORMATION; DERMAL DUCT NEVUS; 26 GENE GJB2; KID SYNDROME; OCULODENTODIGITAL DYSPLASIA; MISSENSE MUTATION AB Gap junctions and hemichannels comprised of connexins influence epidermal proliferation and differentiation. Significant advances in our understanding of the functional role of connexins in the skin have been made by studying the diseases caused by connexin mutations. Eleven clinically defined cutaneous disorders with an overlapping spectrum of phenotypes are caused by mutations in five different connexin genes, highlighting that disease presentation must be deciphered with an understanding of how connexin functions are affected. Increasing evidence suggests that the skin diseases produced by connexin mutations result from dominant gains of function. In palmoplantar keratoderma with deafness, the connexin 26 mutations transdominantly alter the function of wild-type connexin 43 and create leaky heteromeric hemichannels. In keratitis-ichthyosis-deafness syndrome, different connexin 26 mutations can either form dominant hemichannels with altered calcium regulation or increased calcium permeability, leading to clinical subtypes of this syndrome. It is only with detailed understanding of these subtle functional differences that we can hope to create successful pathophysiology driven therapies for the connexin skin disorders. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Lilly, Evelyn; Milstone, Leonard M.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Sellitto, Caterina; White, Thomas W.] SUNY Stony Brook, Dept Physiol & Biophys, T5-147,Basic Sci Tower, Stony Brook, NY 11794 USA. [Lilly, Evelyn] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Lilly, Evelyn] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP White, TW (reprint author), SUNY Stony Brook, Dept Physiol & Biophys, T5-147,Basic Sci Tower, Stony Brook, NY 11794 USA. EM thomas.white@stonybrook.edu OI White, Thomas/0000-0002-3285-7434 FU NIH from the NIAMS [R01 AR59505] FX Our work was supported by the NIH grant R01 AR59505 (TWW) from the NIAMS. NR 103 TC 3 Z9 3 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD FEB PY 2016 VL 50 BP 4 EP 12 DI 10.1016/j.semcdb.2015.11.018 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DF3PQ UT WOS:000371257500002 PM 26775130 ER PT J AU Bawden, CS Mclaughlan, CJ Rudiger, SR Reid, SJ Patassini, S Handley, RR Waldvogel, HJ Morton, AJ Macdonald, ME Gusella, JF Faull, RLM Snell, RG AF Bawden, C. S. Mclaughlan, C. J. Rudiger, S. R. Reid, S. J. Patassini, S. Handley, R. R. Waldvogel, H. J. Morton, A. J. Macdonald, M. E. Gusella, J. F. Faull, R. L. M. Snell, R. G. TI A Model of Huntington's disease in Sheep SO TRANSGENIC RESEARCH LA English DT Meeting Abstract C1 [Bawden, C. S.; Mclaughlan, C. J.; Rudiger, S. R.] South Australian Res & Dev Inst, Adelaide, SA, Australia. [Reid, S. J.; Patassini, S.; Handley, R. R.; Waldvogel, H. J.; Faull, R. L. M.; Snell, R. G.] Univ Auckland, Ctr Brain Res, Auckland 1, New Zealand. [Morton, A. J.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. [Macdonald, M. E.; Gusella, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 EI 1573-9368 J9 TRANSGENIC RES JI Transgenic Res. PD FEB PY 2016 VL 25 IS 1 BP 105 EP 106 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA DF2FA UT WOS:000371155500020 ER PT J AU Zaman, T Boyd, JW AF Zaman, Tauheed Boyd, J. Wesley TI The Authors Reply to Cannabis Use Disorders and ADHD SO JOURNAL OF ADDICTION MEDICINE LA English DT Letter C1 [Zaman, Tauheed] UCSF, San Francisco VA Med Ctr, Addict & Recovery Treatment Serv, San Francisco, CA USA. [Boyd, J. Wesley] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Boyd, J. Wesley] Harvard Univ, Sch Med, Ctr Bioeth, Cambridge, MA 02138 USA. RP Boyd, JW (reprint author), Cambridge Hlth Alliance, 26 Cent St, Somerville, MA 02143 USA. EM jwboyd@cha.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD FEB PY 2016 VL 10 IS 1 BP 70 EP 71 DI 10.1097/ADM.0000000000000185 PG 2 WC Substance Abuse SC Substance Abuse GA DE0CV UT WOS:000370293300002 ER PT J AU Wagner, FF Lundh, M Kaya, T McCarren, P Zhang, YL Chattopadhyay, S Gale, JP Galbo, T Fisher, SL Meier, BC Vetere, A Richardson, S Morgan, NG Christensen, DP Gilbert, TJ Hooker, JM Leroy, M Walpita, D Mandrup-Poulsen, T Wagner, BK Holson, EB AF Wagner, Florence F. Lundh, Morten Kaya, Taner McCarren, Patrick Zhang, Yan-Ling Chattopadhyay, Shrikanta Gale, Jennifer P. Galbo, Thomas Fisher, Stewart L. Meier, Bennett C. Vetere, Amedeo Richardson, Sarah Morgan, Noel G. Christensen, Dan Ploug Gilbert, Tamara J. Hooker, Jacob M. Leroy, Melanie Walpita, Deepika Mandrup-Poulsen, Thomas Wagner, Bridget K. Holson, Edward B. TI An Isochemogenic Set of Inhibitors To Define the Therapeutic Potential of Histone Deacetylases in beta-Cell Protection SO ACS CHEMICAL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; HDAC INHIBITORS; OXIDATIVE-STRESS; IN-VIVO; CANCER BIOLOGY; APOPTOSIS; RATS; MECHANISM; DISEASES; KINETICS AB Modulation of histone deacetylase (HDAC) activity has been implicated as a potential therapeutic strategy for multiple diseases. However, it has been difficult to dissect the role of individual HDACs due to a lack of selective small-molecule inhibitors. Here, we report the synthesis of a series of highly potent and isoform-selective class I HDAC inhibitors, rationally designed by exploiting minimal structural changes to the clinically experienced HDAC inhibitor CI-994. We used this toolkit of isochemogenic or chemically matched inhibitors to probe the role of class I HDACs in beta-cell pathobiology and demonstrate for the first time that selective inhibition of an individual HDAC isoform retains beneficial biological activity and mitigates mechanism-based toxicities. The highly selective HDAC3 inhibitor BRD3308 suppressed pancreatic beta-cell apoptosis induced by inflammatory cytokines, as expected, or now glucolipotoxic stress, and increased functional insulin release. In addition, BRD3308 had no effect on human megakaryocyte differentiation, while inhibitors of HDAC1 and 2 were toxic. Our findings demonstrate that the selective inhibition of HDAC3 represents a potential path forward as a therapy to protect pancreatic beta-cells from inflammatory cytokines and nutrient overload in diabetes. C1 [Wagner, Florence F.; Kaya, Taner; Zhang, Yan-Ling; Gale, Jennifer P.; Hooker, Jacob M.; Leroy, Melanie; Holson, Edward B.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Lundh, Morten; McCarren, Patrick; Chattopadhyay, Shrikanta; Meier, Bennett C.; Vetere, Amedeo; Gilbert, Tamara J.; Walpita, Deepika; Wagner, Bridget K.] Broad Inst Harvard & MIT, Ctr Sci Therapeut, 415 Main St, Cambridge, MA 02142 USA. [Lundh, Morten; Christensen, Dan Ploug; Mandrup-Poulsen, Thomas] Univ Copenhagen, Dept Biomed Sci, DK-1165 Copenhagen, Denmark. [Galbo, Thomas] Yale Univ, Dept Internal Med, New Haven, CT 06520 USA. [Fisher, Stewart L.] SL Fisher Consulting LLC, POB 3052, Framingham, MA 01701 USA. [Richardson, Sarah; Morgan, Noel G.] Univ Exeter, Royal Devon & Exeter Hosp, Sch Med, Exeter EX2 5DW, Devon, England. [Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Mandrup-Poulsen, Thomas] Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden. RP Wagner, BK (reprint author), Broad Inst Harvard & MIT, Ctr Sci Therapeut, 415 Main St, Cambridge, MA 02142 USA.; Holson, EB (reprint author), 400 Technol Sq,10th Floor, Cambridge, MA 02139 USA. EM bwagner@broadinstitute.org; eholson@atlasventure.com FU Stanley Medical Research Institute; Type 1 Diabetes Pathfinder award (NIDDK) FX We thank M. Weiwer, D. Fass, S. Haggarty, A. Schroeder, and M. Lewis for assistance and helpful discussions. This work was supported by the Stanley Medical Research Institute and a Type 1 Diabetes Pathfinder award (NIDDK, to B.K.W.). NR 49 TC 7 Z9 7 U1 3 U2 4 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 FEB PY 2016 VL 11 IS 2 BP 363 EP 374 DI 10.1021/acschembio.5b00640 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DE6TZ UT WOS:000370767800009 PM 26640968 ER PT J AU McCutchan, PK Liu, X LeardMann, CA Smith, TC Boyko, EJ Gore, KL Freed, MC Engel, CC AF McCutchan, Phoebe K. Liu, Xian LeardMann, Cynthia A. Smith, Tyler C. Boyko, Edward J. Gore, Kristie L. Freed, Michael C. Engel, Charles C. TI Deployment, combat, and risk of multiple physical symptoms in the US military: a prospective cohort study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Signs and symptoms; Military medicine; Military personnel; Veterans health; Cohort studies ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CLINICAL-TRIAL; PERSIAN-GULF-WAR; SOMATIC SYMPTOMS; MILLENNIUM COHORT; PRIMARY-CARE; CHRONIC PAIN; IRAQ WAR; SERVICE MEMBERS; HEALTH OUTCOMES AB Purpose: Multiple physical symptoms (MPS) have historically been observed after deployment to a combat zone and are often disabling in nature. This study examined longitudinal trends in MPS status and its relationship to deployment in U.S. military service members. Methods: Using longitudinal data from panel 1 participants in the Millennium Cohort Study (n = 76,924), MPS status was assessed at three time points (2001-2008) using the 15 -item Patient Health Questionnaire. Probability of reporting MPS was analyzed using mixed-effects multinomial logit regression, with time and deployment experience as main explanatory variables. Results: After adjustment for demographic, military, and health characteristics, service members who deployed with combat were significantly more likely to report MPS at each time point compared with those not deployed (odds ratio [OR] and 95% confidence interval [CI] for wave 1 =1.49 [1.47-1.52], wave 2 = 1.73 [1.69-1.78], wave 3 = 2.08 [2.03-2.12]), and those who deployed without combat (OR and CI for wave 1 = 2.66 [2.59-2.74], wave 2 = 1.81 [1.75-1.87]; wave 3 = 1.68 [1.63-1.74]). Conclusions: Longitudinal trends indicate that the probability of reporting MPS has increased consistently over time only for those deployed, regardless of combat experience. (C) 2016 Elsevier Inc. All rights reserved. C1 [McCutchan, Phoebe K.; Liu, Xian; Freed, Michael C.] Def Ctr Excellence Psychol Hlth, Deployment Hlth Clin Ctr, Silver Spring, MD USA. [McCutchan, Phoebe K.; Liu, Xian; Freed, Michael C.] Def Ctr Traumat Brain Injury, Deployment Hlth Clin Ctr, Silver Spring, MD USA. [McCutchan, Phoebe K.; Liu, Xian; LeardMann, Cynthia A.] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA. [Liu, Xian; Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [LeardMann, Cynthia A.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA USA. [Smith, Tyler C.] Natl Univ, Sch Hlth & Human Serv, Dept Community Hlth, San Diego, CA USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Gore, Kristie L.; Engel, Charles C.] RAND Corp, Behav & Policy Sci, Arlington, VA USA. [McCutchan, Phoebe K.] Amer Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. [Freed, Michael C.] NIMH, Div Serv & Intervent Res, Serv Res & Clin Epidemiol Branch, 6001 Execut Blvd, Bethesda, MD 20892 USA. [Engel, Charles C.] RAND Corp, Behav & Policy Sci, 20 Pk Plaza,Suite 920, Boston, MA 02116 USA. RP McCutchan, PK (reprint author), Amer Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM phoebe.mccutchan@gmail.com FU Management Information Division, U.S. Defense Manpower Data Center (Seaside, CA); Military Operational Medicine Research Program; U.S. Army Medical Research and Materiel Command (Fort Detrick, MD); Military Operational Medicine Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland - Department of Defense [60002]; Deployment Health Clinical Center; VA Puget Sound Health Care System FX In addition to the authors, the Millennium Cohort Study team includes Richard Armenta, PhD, Lauren Bauer, MPH, Madeline Cross, James Davies, CPT Carrie Donoho, PhD, CDR Dennis Faix, MD, Lt Col Susan Farrish, MD, Toni Geronimo, Kathleen Gunn, William Lee, Hector Lemus, PhD, Gordon Lynch, Denise Lovec-Jenkins, David Luxton PhD, Danielle Mitchell, Kristin Motylinski, Anna Nagel, MPH, Chiping Nieh, PhD, Chris O'Malley, MPH, Serguey Parkhomovsky, Anet Petrosyan, Christopher Phillips, MD, MPH, Teresa Powell, MPH, Ben Porter, PhD, Rudy Rull, PhD, Kari Sausedo, MA, Beverly Sheppard, Steven Speigle, Evelyn Sun, MPH, Valerie Stander, PhD, Laura Tobin, MPH, Daniel Trone, PhD, Jennifer Walstrom, from the Deployment Health Research Department, Naval Health Research Center, San Diego, CA. We thank Hector Lemus, PhD (Naval Health Research Center, San Diego, CA) for his contribution in providing statistical support and consultation for this study. In addition, we thank Michelle LeWark from the Naval Health Research Center (San Diego, CA) for her technical review and editing of this article. We appreciate the support from the Management Information Division, U.S. Defense Manpower Data Center (Seaside, CA); Military Operational Medicine Research Program and U.S. Army Medical Research and Materiel Command (Fort Detrick, MD).; The Millennium Cohort Study is funded through the Military Operational Medicine Research Program of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland (supported by the Department of Defense, under work unit no. 60002). The Deployment Health Clinical Center provided funding for P.K.M., X.L., K.L.G, and M.C.F.'s efforts in this project. VA Puget Sound Health Care System provided support for E.J.B's participation in this research. The funding organizations had no role in the design and conduct of the study; collection, analysis, or preparation of data; or preparation, review, or approval of the article. NR 58 TC 1 Z9 1 U1 5 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2016 VL 26 IS 2 BP 122 EP 128 DI 10.1016/j.annepidem.2015.12.001 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DE8MG UT WOS:000370889500006 PM 26781443 ER PT J AU Villatte, JL Vilardaga, R Villatte, M Vilardaga, JCP Atkins, DC Hayes, SC AF Villatte, Jennifer L. Vilardaga, Roger Villatte, Matthieu Vilardaga, Jennifer C. Plumb Atkins, David C. Hayes, Steven C. TI Acceptance and Commitment Therapy modules: Differential impact on treatment processes and outcomes SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Acceptance and commitment therapy; Component analysis; Modular design; Single case experimental design; Acceptance; Values; Mindfulness; Therapy process ID RANDOMIZED EFFECTIVENESS TRIAL; PSYCHOTHERAPY PROCESS; ANXIETY DISORDERS; TREATMENT DESIGNS; MENTAL-ILLNESS; METAANALYSIS; COMPONENT; INTERVENTIONS; MINDFULNESS; ATTITUDES AB A modular, transdiagnostic approach to treatment design and implementation may increase the public health impact of evidence-based psychosocial interventions. Such an approach relies on algorithms for selecting and implementing treatment components intended to have a specific therapeutic effect, yet there is little evidence for how components function independent of their treatment packages when employed in clinical service settings. This study aimed to demonstrate the specificity of treatment effects for two components of Acceptance and Commitment Therapy (ACT), a promising candidate for modularization. A randomized, nonconcurrent, multiple-baseline across participants design was used to examine component effects on treatment processes and outcomes in 15 adults seeking mental health treatment. The ACT OPEN module targeted acceptance and cognitive defusion; the ACT ENGAGED module targeted values-based activation and persistence. According to Tau-U analyses, both modules produced significant improvements in psychiatric symptoms, quality of life, and targeted therapeutic processes. ACT ENGAGED demonstrated greater improvements in quality of life and values-based activation. ACT OPEN showed greater improvements in symptom severity, acceptance, and defusion. Both modules improved awareness and non-reactivity, which were mutually targeted, though using distinct intervention procedures. Both interventions demonstrated high treatment acceptability, completion, and patient satisfaction. Treatment effects were maintained at 3-month follow up. ACT components should be considered for inclusion in a modular approach to implementing evidence-based psychosocial interventions for adults. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Villatte, Jennifer L.; Vilardaga, Roger; Atkins, David C.] Univ Washington, Dept Psychiat & Behav Sci, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. [Villatte, Matthieu] Evidence Based Practice Inst, Seattle, WA USA. [Vilardaga, Jennifer C. Plumb] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Hayes, Steven C.] Univ Nevada, Dept Psychol, Reno, NV 89557 USA. RP Villatte, JL (reprint author), Univ Washington, Dept Psychiat & Behav Sci, 1959 NE Pacific St,Box 356560, Seattle, WA 98195 USA. EM villatte@uw.edu; vilardag@uw.edu; matt@ebpi.org; jennifer.plumbvilardaga@va.gov; datkins@uw.edu; hayes@unr.edu OI Atkins, David/0000-0002-5781-9880; Hayes, Steven/0000-0003-4399-6859 FU National Institute of Mental Health [F31MH096341]; [T32MH096341] FX First author J.L.V. was assisted in the preparation of this manuscript by grant number F31MH096341 from the National Institute of Mental Health. First author J.L.V. and second author R.V. were assisted in preparation of this manuscript by grant number T32MH096341. The content 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, who had no involvement in the design or execution of the study. NR 59 TC 1 Z9 1 U1 7 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD FEB PY 2016 VL 77 BP 52 EP 61 DI 10.1016/j.brat.2015.12.001 PG 10 WC Psychology, Clinical SC Psychology GA DE8PR UT WOS:000370899200007 PM 26716932 ER PT J AU Larsen, SE Stirman, SW Smith, BN Resick, PA AF Larsen, Sadie E. Stirman, Shannon Wiltsey Smith, Brian N. Resick, Patricia A. TI Symptom exacerbations in trauma-focused treatments: Associations with treatment outcome and non-completion SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Posttraumatic stress disorder; Cognitive processing therapy; Prolonged exposure; Symptom exacerbations; Cognitive behavioral therapy ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-PROCESSING THERAPY; EYE-MOVEMENT DESENSITIZATION; RANDOMIZED CLINICAL-TRIAL; ADMINISTERED PTSD SCALE; EXPOSURE THERAPY; BEHAVIORAL THERAPY; PROLONGED EXPOSURE; SUDDEN GAINS; PSYCHOLOGICAL TREATMENTS AB Trauma-focused treatments are underutilized, partially due to clinician concerns that they will cause symptom exacerbation or dropout. We examined a sample of women undergoing Prolonged Exposure (PE), Cognitive Processing Therapy (CPT), and a version of CPT (CPT-C) without a written trauma narrative to investigate the possibility of symptom exacerbation. Participants (n = 192) were drawn from two RCT's. Participants were administered self-report measures of PTSD symptoms (i.e., the PTSD Symptom Scale or Posttraumatic Diagnostic Scale [PSS/PDS]) and the Clinician-Administered PTSD Scale. Exacerbations were defined as increases greater than 6.15 points on the PSS/PDS. A minority of participants experienced PTSD exacerbations during treatment, and there were no significant differences across treatment type (28.6% in CPT, 20.0% in PE, and 14.7% in CPT-C). Neither diagnostic nor trauma-related factors at pre-treatment predicted symptom exacerbations. Those who experienced exacerbations had higher post-treatment PSS/PDS scores and were more likely to retain a PTSD diagnosis (both small but statistically significant effects). However, even those who experienced an exacerbation experienced clinically significant improvement by end of treatment. Further, symptom exacerbations were not related to treatment non-completion. These results indicate that trauma-focused treatments are safe and effective, even for the minority of individuals who experience temporary symptom increases. Published by Elsevier Ltd. C1 [Larsen, Sadie E.] Clement J Zablocki VA Med Ctr, Psychol Serv, Milwaukee, WI USA. [Larsen, Sadie E.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Madison, WI USA. [Stirman, Shannon Wiltsey] VA Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Stirman, Shannon Wiltsey] Stanford Univ, Stanford, CA 94305 USA. [Smith, Brian N.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Smith, Brian N.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Resick, Patricia A.] Duke Univ, Durham, NC 27706 USA. RP Larsen, SE (reprint author), Behav Hlth Ctr, 1155 North Mayfair Rd, Milwaukee, WI 53226 USA. EM selarsen@mcw.edu OI Resick, Patricia/0000-0002-2203-2404; Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU NIMH [1-R01-MH51509, 2-R01-MH51509] FX This manuscript was funded by NIMH grants #1-R01-MH51509 and 2-R01-MH51509 awarded to Patricia Resick. It is partially the result of work supported with resources and the use of facilities at the Clement J. Zablocki VAMC, Milwaukee, WI. NR 57 TC 6 Z9 6 U1 6 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD FEB PY 2016 VL 77 BP 68 EP 77 DI 10.1016/j.brat.2015.12.009 PG 10 WC Psychology, Clinical SC Psychology GA DE8PR UT WOS:000370899200009 PM 26731171 ER PT J AU Onorati, F Mainardi, LT Sirca, F Russo, V Barbieri, R AF Onorati, Francesco Mainardi, Luca Tommaso Sirca, Fabiola Russo, Vincenzo Barbieri, Riccardo TI Nonlinear analysis of pupillary dynamics SO BIOMEDICAL ENGINEERING-BIOMEDIZINISCHE TECHNIK LA English DT Article DE autonomic nervous system (ANS); detrended fluctuation analysis (DFA); nonlinearity measures; piecewise linear regression (PLR); pupillary dynamics ID HEART-RATE-VARIABILITY; TIME-SERIES; LIGHT REFLEX; NEUROVISCERAL INTEGRATION; RESPIRATORY FLUCTUATIONS; LYAPUNOV EXPONENTS; STRANGE ATTRACTORS; DELAYED-FEEDBACK; SAMPLE ENTROPY; NERVOUS-SYSTEM AB Pupil size reflects autonomic response to different environmental and behavioral stimuli, and its dynamics have been linked to other autonomic correlates such as cardiac and respiratory rhythms. The aim of this study is to assess the nonlinear characteristics of pupil size of 25 normal subjects who participated in a psychophysiological experimental protocol with four experimental conditions, namely "baseline", "anger", "joy", and "sadness". Nonlinear measures, such as sample entropy, correlation dimension, and largest Lyapunov exponent, were computed on reconstructed signals of spontaneous fluctuations of pupil dilation. Nonparametric statistical tests were performed on surrogate data to verify that the nonlinear measures are an intrinsic characteristic of the signals. We then developed and applied a piecewise linear regression model to detrended fluctuation analysis (DFA). Two join-points and three scaling intervals were identified: slope alpha(0), at slow time scales, represents a persistent nonstationary long-range correlation, whereas alpha(1) and alpha(2), at middle and fast time scales, respectively, represent long-range power-law correlations, similarly to DFA applied to heart rate variability signals. Of the computed complexity measures, alpha(0) showed statistically significant differences among experimental conditions (p < 0.001). Our results suggest that (a) pupil size at constant light condition is characterized by nonlinear dynamics, (b) three well-defined and distinct long-memory processes exist at different time scales, and (c) autonomic stimulation is partially reflected in nonlinear dynamics. C1 [Onorati, Francesco; Mainardi, Luca Tommaso] Politecn Milan, DEIB, I-20133 Milan, Italy. [Onorati, Francesco; Sirca, Fabiola; Russo, Vincenzo] IULM Univ, Behav & Brain Lab, Milan, Italy. [Barbieri, Riccardo] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Barbieri, Riccardo] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Onorati, F (reprint author), Politecn Milan, DEIB, I-20133 Milan, Italy.; Onorati, F (reprint author), IULM Univ, Behav & Brain Lab, Milan, Italy. EM francesco.onorati@polimi.it NR 75 TC 1 Z9 1 U1 6 U2 9 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0013-5585 EI 1862-278X J9 BIOMED ENG-BIOMED TE JI Biomed. Eng.-Biomed. Tech. PD FEB PY 2016 VL 61 IS 1 SI SI BP 95 EP 106 DI 10.1515/bmt-2015-0027 PG 12 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA DE9LF UT WOS:000370958300010 PM 26351899 ER PT J AU Miller, CL Coopey, SB Rafferty, E Gadd, M Smith, BL Specht, MC AF Miller, Cynthia L. Coopey, Suzanne B. Rafferty, Elizabeth Gadd, Michele Smith, Barbara L. Specht, Michelle C. TI Comparison of intra-operative specimen mammography to standard specimen mammography for excision of non-palpable breast lesions: a randomized trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Mammography; Wire localization; Lumpectomy; Intra-operative imaging ID LOCALIZATION; BIOPSY; RADIOGRAPHY; CARCINOMA; SURGERY; MARGINS; RE AB Standard specimen mammography (SSM) is performed in the radiology department after wire-localized excision of non-palpable breast lesions to confirm the presence of the target and evaluate margins. Alternatively, intra-operative specimen mammography (ISM) allows surgeons to view images in the operating room (OR). We conducted a randomized study comparing ISM and SSM. Women undergoing wire-localized excision for breast malignancy or imaging abnormality were randomized to SSM or ISM. For SSM, the specimen was transported to the radiology department for imaging and interpretation. For ISM, the specimen was imaged in the OR for interpretation by the surgeon and sent for SSM. Interpretation time was from specimen leaving OR until radiologist interpretation for SSM and from placement in ISM device until surgeon interpretation for ISM. Procedure and interpretation times were compared. Concordance between ISM and SSM for target and margins was evaluated. 72 patients were randomized, 36 ISM and 36 SSM. Median procedure times were similar, 48.5 (17-138) min for ISM, and 54 (17-40) min for SSM (p = 0.72), likely since specimens in both groups traveled to radiology for SSM. Median interpretation time was significantly shorter with ISM, 1 (0.5-2.0) and 9 (4-16) min for ISM and SSM, respectively (p < 0.0001). Among specimens with ISM and SSM, concordance was 100 % (35/35) for target and 93 % (14/15) for margins. In this randomized trial, use of ISM compared with SSM significantly reduced interpretation times, while accurately identifying the target. This could result in decreased operative costs from shorter OR times with use of ISM. C1 [Miller, Cynthia L.] Harvard Univ, Sch Med, Boston, MA USA. [Coopey, Suzanne B.; Gadd, Michele; Smith, Barbara L.; Specht, Michelle C.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [Rafferty, Elizabeth] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Specht, MC (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. EM mspecht@partners.org NR 14 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 FEB PY 2016 VL 155 IS 3 BP 513 EP 519 DI 10.1007/s10549-016-3700-8 PG 7 WC Oncology SC Oncology GA DF0UR UT WOS:000371055100012 PM 26872902 ER PT J AU Hassett, MJ Jiang, W Habel, LA Nekhlyudov, L Achacoso, N Acton, L Schnitt, SJ Schrag, D Punglia, RS AF Hassett, Michael J. Jiang, Wei Habel, Laurel A. Nekhlyudov, Larissa Achacoso, Ninah Acton, Luana Schnitt, Stuart J. Schrag, Deb Punglia, Rinaa S. TI Characteristics of second breast events among women treated with breast-conserving surgery for DCIS in the community SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; DCIS; Recurrence; Second breast cancer; Hormone receptor; Grade ID CARCINOMA-IN-SITU; SURGICAL ADJUVANT BREAST; LOCAL RECURRENCE; SCREENING MAMMOGRAPHY; TERM OUTCOMES; CANCER; RADIOTHERAPY; RISK; THERAPY; TRIAL AB We examined the clinical/pathologic features of ipsilateral second breast cancers (IP-SBCs) following breast-conserving surgery (BCS) for DCIS among community-treated patients and ascertained the degree of correlation between the features of index DCIS and IP-SBC events. From a Cancer Research Network cohort of DCIS patients diagnosed 1990-2001 and treated with BCS, we identified women who subsequently developed an ipsilateral DCIS or invasive breast cancer. All index DCIS tumors underwent expert pathology review. Pathologic characteristics of IP-SBCs were abstracted from available medical records. Logistic regression was used to examine associations between pathologic characteristics and identify factors associated with invasive versus non-invasive IP-SBC. Of 1969 DCIS patients, 182 developed an IP-SBC within a median of 38 months (range 6-160). IP-SBCs were slightly more commonly non-invasive (53 %) versus invasive (47 %). Of invasive IP-SBCs, 31 % were high grade, 67 % were < 20 mm, 74 % were estrogen receptor positive, 7 % were HER2 positive, and 16 % were node positive. Of non-invasive IP-SBCs, 33 % were high grade. Comparing index DCIS and IP-SBC specimens, there was moderate-high correlation for HR status and grade. Among patients with IP-SBCs, those who were younger and whose index DCIS tumors were HR negative had shorter intervals (within 3 years) between index and IP-SBC diagnoses. No index DCIS feature was statistically significantly associated with an IP-SBC that was invasive versus non-invasive. Understanding the characteristics of SBCs and identifying correlations between these and index DCIS events could influence treatment choices for DCIS, and may help patients and providers develop treatment paradigms for SBCs. C1 [Hassett, Michael J.; Schrag, Deb] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA. [Jiang, Wei] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Habel, Laurel A.; Achacoso, Ninah; Acton, Luana] Kaiser Permanente, Div Res, Oakland, CA USA. [Nekhlyudov, Larissa] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Dept Med, Boston, MA USA. [Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Hassett, Michael J.; Schrag, Deb; Punglia, Rinaa S.] Harvard Univ, Sch Med, Boston, MA USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, 450 Brookline Ave, Boston, MA 02215 USA.; Hassett, MJ (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM michael_hassett@dfci.harvard.edu; wjiang3@partners.org; laurel.habel@kp.org; larissa_nekhlyudov@harvardpilgrim.org; ninah.s.achacoso@nsmtp.kp.org; luana.acton@kp.org; sschnitt@caregroup.harvard.edu; deb_schrag@dfci.harvard.edu; rpunglia@lroc.harvard.edu FU Agency for Healthcare Research and Quality [HHSA290200500161]; National Institutes of Health [R01 CA81302, U19 CA079689]; Susan G. Komen for the Cure Career Catalyst Award FX This work was supported by contract # HHSA290200500161 from the Agency for Healthcare Research and Quality and by the National Institutes of Health (R01 CA81302 to L.A.H.; U19 CA079689 to Ed Wagner). Dr. Hassett received salary support from a Susan G. Komen for the Cure Career Catalyst Award. The views expressed in this article are those of the authors, and no official endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services is intended or should be inferred. NR 35 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2016 VL 155 IS 3 BP 541 EP 549 DI 10.1007/s10549-016-3692-4 PG 9 WC Oncology SC Oncology GA DF0UR UT WOS:000371055100015 PM 26843057 ER PT J AU Nelson, SH Marinac, CR Patterson, RE Nechuta, SJ Flatt, SW Caan, BJ Kwan, ML Poole, EM Chen, WY Shu, XO Pierce, JP AF Nelson, Sandahl H. Marinac, Catherine R. Patterson, Ruth E. Nechuta, Sarah J. Flatt, Shirley W. Caan, Bette J. Kwan, Marilyn L. Poole, Elizabeth M. Chen, Wendy Y. Shu, Xiao-ou Pierce, John P. TI Impact of very low physical activity, BMI, and comorbidities on mortality among breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Sedentary behavior; Lifestyle factors; Diabetes; Obesity; Body mass index ID BODY-MASS INDEX; ACTIVITY QUESTIONNAIRE; WEIGHT CHANGE; WOMEN; OBESITY; DIAGNOSIS; METAANALYSIS; RISK; ASSOCIATION; VALIDATION AB The purpose of this study was to examine post-diagnosis BMI, very low physical activity, and comorbidities, as predictors of breast cancer-specific and all-cause mortality. Data from three female US breast cancer survivor cohorts were harmonized in the After Breast Cancer Pooling Project (n = 9513). Delayed entry Cox proportional hazards models were used to examine the impact of three post-diagnosis lifestyle factors: body mass index (BMI), select comorbidities (diabetes only, hypertension only, or both), and very low physical activity (defined as physical activity < 1.5 MET h/week) in individual models and together in multivariate models for breast cancer and all-cause mortality. For breast cancer mortality, the individual lifestyle models demonstrated a significant association with very low physical activity but not with the selected comorbidities or BMI. In the model that included all three lifestyle variables, very low physical activity was associated with a 22 % increased risk of breast cancer mortality (HR 1.22, 95 % CI 1.05, 1.42). For all-cause mortality, the three individual models demonstrated significant associations for all three lifestyle predictors. In the combined model, the strength and significance of the association of comorbidities (both hypertension and diabetes versus neither: HR 2.16, 95 % CI 1.79, 2.60) and very low physical activity (HR 1.35, 95 % CI 1.22, 1.51) remained unchanged, but the association with obesity was completely attenuated. These data indicate that after active treatment, very low physical activity, consistent with a sedentary lifestyle (and comorbidities for all-cause mortality), may account for the increased risk of mortality, with higher BMI, that is seen in other studies. C1 [Nelson, Sandahl H.; Marinac, Catherine R.; Patterson, Ruth E.; Flatt, Shirley W.; Pierce, John P.] Univ Calif San Diego, Moores UCSD Canc Ctr, Div Populat Sci, Canc Prevent & Control Program, La Jolla, CA 92093 USA. [Nelson, Sandahl H.; Marinac, Catherine R.; Patterson, Ruth E.; Pierce, John P.] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA. [Nechuta, Sarah J.; Shu, Xiao-ou] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA. [Caan, Bette J.; Kwan, Marilyn L.] Kaiser Permanente, Div Res, Oakland, CA USA. [Poole, Elizabeth M.; Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Poole, Elizabeth M.; Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pierce, JP (reprint author), Univ Calif San Diego, Moores UCSD Canc Ctr, Div Populat Sci, Canc Prevent & Control Program, La Jolla, CA 92093 USA.; Pierce, JP (reprint author), Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA. EM jppierce@ucsd.edu FU National Cancer Institute at National Institutes of Health [3R01 CA118229-03S1]; National Cancer Institute [1R03CA171013, F31CA183125]; women's healthy eating & living study (Susan G. Komen Foundation) [KG100988]; Life After Cancer Epidemiology Study (National Cancer Institute) [R01 CA129059]; Nurses' Health Study [P01 CA87969, UM1 CA186107] FX This Pooling Project was supported by the National Cancer Institute at the National Institutes of Health (3R01 CA118229-03S1). Additional support was provided by the National Cancer Institute (1R03CA171013 and F31CA183125). Support for the individual cohorts included in the present report came from women's healthy eating & living study (Susan G. Komen Foundation, KG100988); Life After Cancer Epidemiology Study (National Cancer Institute, R01 CA129059); and the Nurses' Health Study (P01 CA87969 and UM1 CA186107). NR 30 TC 6 Z9 6 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 FEB PY 2016 VL 155 IS 3 BP 551 EP 557 DI 10.1007/s10549-016-3694-2 PG 7 WC Oncology SC Oncology GA DF0UR UT WOS:000371055100016 PM 26861056 ER PT J AU Vaz-Luis, I Hughes, ME Cronin, A Rugo, HS Edge, SB Moy, B Theriault, RL Hassett, MJ Winer, EP Lin, NU AF Vaz-Luis, Ines Hughes, Melissa E. Cronin, Angel Rugo, Hope S. Edge, Stephen B. Moy, Beverly Theriault, Richard L. Hassett, Michael J. Winer, Eric P. Lin, Nancy U. TI Trends in the use of mastectomy in women with small node-negative breast cancer treated at US academic centers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Mastectomy; Bilateral mastectomy; Breast-conserving surgery; Stage I; Patterns of care ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; STAGE-I; CONSERVING THERAPY; SURGICAL-TREATMENT; RANDOMIZED-TRIAL; UNITED-STATES; GEOGRAPHIC-VARIATION; COMORBIDITY INDEX; SURGERY; CARCINOMA AB Breast-conserving surgery (BCS) provides equivalent survival outcomes to unilateral mastectomy. There is no survival advantage to bilateral mastectomy in average risk breast cancer. Among a cohort of breast cancer patients expected to be candidates for BCS, we examined choice of surgery and factors associated with it. A prospective cohort study of unilateral clinical Stage I breast cancer patients treated at National Comprehensive Cancer Network centers from 2000 to 2009 was performed. The proportion of patients who initially underwent mastectomy versus BCS and time to definitive surgery and chemotherapy were examined. Of 10,249 patients, 23 % underwent mastectomy as an initial surgery. No decline in the use of mastectomy as initial surgery was found. There was significant institutional variation, with rates of initial mastectomy ranging from 14 to 30 % (adjusted odds ratio: 0.42-1.38). Tumor characteristics were associated with surgical option, but with small absolute differences. Of those who received initial mastectomy, 22 % had bilateral mastectomy, with an increase over time (2000:13 % vs. 2009:30 %) and substantial institutional variation (11-34 %). Women treated with initial mastectomy had longer median times from diagnosis to complete definitive surgery (6 vs. 4 weeks) and to start of adjuvant chemotherapy (12 vs. 11 weeks). Among Stage I breast cancer, the overall use of mastectomy did not change significantly over 10 years; however, an increasing proportion of women with unilateral cancer had bilateral mastectomy, and there was wide variation in type of surgery by institution. Further studies to assess reasons for the observed wide variation are warranted. C1 [Vaz-Luis, Ines; Hughes, Melissa E.; Cronin, Angel; Hassett, Michael J.; Winer, Eric P.; Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rugo, Hope S.] Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, San Francisco, CA 94143 USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Moy, Beverly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Vaz-Luis, I (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM InesV_Luis@dfci.harvard.edu FU Fundacao para a Ciencia e Tecnologia-HMSP [ICS/0004/201]; National Cancer Institute Specialized Program of Research Excellence in Breast Cancer [NIH P50 CA089393] FX This work was supported by Fundacao para a Ciencia e Tecnologia-HMSP-ICS/0004/201, National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (NIH P50 CA089393). NR 34 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2016 VL 155 IS 3 BP 569 EP 578 DI 10.1007/s10549-016-3707-1 PG 10 WC Oncology SC Oncology GA DF0UR UT WOS:000371055100018 PM 26868124 ER PT J AU Pineda-Juarez, JA Sanchez-Ortiz, NA Castillo-Martinez, L Orea-Tejeda, A Cervantes-Gaytan, R Keirns-Davis, C Perez-Ocampo, C Quiroz-Bautista, K Tenorio-Dupont, M Ronquillo-Martinez, A AF Antonio Pineda-Juarez, Juan Alonso Sanchez-Ortiz, Nestor Castillo-Martinez, Lilia Orea-Tejeda, Arturo Cervantes-Gaytan, Rocio Keirns-Davis, Candace Perez-Ocampo, Carlos Quiroz-Bautista, Karla Tenorio-Dupont, Monica Ronquillo-Martinez, Alberto TI Changes in body composition in heart failure patients after a resistance exercise program and branched chain amino acid supplementation SO CLINICAL NUTRITION LA English DT Article DE Resistance exercise; Branched chain amino acids; Heart failure ID QUALITY-OF-LIFE; MUSCLE STRENGTH; DISEASE; ASSOCIATION; CACHEXIA AB Background & aims: Heart Failure (HF) is a complex syndrome, which can include the physiological, neural hormonal and metabolic complications known as "Cardiac Cachexia" (CC). In the development of CC there is a release of catabolic cytokines (Tumor Necrosis Factor-alpha, interleukins 1 and 6) that cause a decrease of fat free mass and fat mass. These changes in body composition might be reversed with a therapeutic combination of resistance exercise and branched chain amino acid supplementation (BCAA). Aim: Evaluate changes in body composition after a resistance exercise program and BCAA supplementation in patients with HR. Methods: In a randomized clinical trial with 3 month of follow-up anthropometric body composition analysis and stress tests were evaluated at the beginning and in the end of the study. Patients were divided into two groups; the experimental group performed the resistance exercise program and received 10 g/day BCAA supplementation, and the control group only performed the resistance exercise program. Both groups were provided with individualized diets and conventional medical treatment. Results: Changes were found in hip circumference between the groups (p = 0.02), and muscle strength was increased in the experimental group (8%) and the control group (11.4%) with no difference between them. METS and VO(2)Max also increased in experimental and control groups (16.6% and 50.1% respectively). Regarding changes in symptoms, improvements in fatigue (45.4%), decubitus intolerance (21.8%) and dyspnea (25.4%) were observed in the overall sample. Conclusion: Improvements in physical and functional capacities are attributed to resistance exercise program but not to the BCAA supplementation. (C) 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Antonio Pineda-Juarez, Juan; Alonso Sanchez-Ortiz, Nestor; Castillo-Martinez, Lilia; Orea-Tejeda, Arturo] Inst Nacl Ciencias Med & Nutr SZ, Heart Failure Clin, Providencia 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. [Cervantes-Gaytan, Rocio; Perez-Ocampo, Carlos; Quiroz-Bautista, Karla; Tenorio-Dupont, Monica; Ronquillo-Martinez, Alberto] Inst Nacl Ciencias Med & Nutr SZ, Rehabil Serv, Mexico City 03100, DF, Mexico. [Keirns-Davis, Candace] Massachusetts Gen Hosp, Interpreter Serv, Boston, MA 02114 USA. RP Orea-Tejeda, A (reprint author), Inst Nacl Ciencias Med & Nutr SZ, Heart Failure Clin, Providencia 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. EM oreatart@gmail.com; mieshe@comcast.net RI Castillo-Martinez, Lilia/H-3750-2013 NR 30 TC 2 Z9 2 U1 4 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 EI 1532-1983 J9 CLIN NUTR JI Clin. Nutr. PD FEB PY 2016 VL 35 IS 1 BP 41 EP 47 DI 10.1016/j.clnu.2015.02.004 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DE8RY UT WOS:000370905600007 PM 25726428 ER PT J AU Singh, J Ramachandaran, R AF Singh, Jasvinder A. Ramachandaran, Rekha TI Does rural residence impact total ankle arthroplasty utilization and outcomes? SO CLINICAL RHEUMATOLOGY LA English DT Article DE Outcomes; Residence; Rural; Total ankle arthroplasty; Urban; Utilization ID INPATIENT SAMPLE NIS; OPEN APPENDECTOMY; REPLACEMENT; POPULATION; DATABASE AB The objective of this study was to compare total ankle arthroplasty (TAA) utilization and outcomes by patient residence. We used the Nationwide Inpatient Sample (NIS) from 2003 to 2011 to compare utilization and outcomes (post-arthroplasty discharge disposition, length of hospitalization, and mortality) by rural vs. urban residence. Ten thousand eight hundred thirty-three patients in urban and 3,324 patients in rural area underwent TAA. Compared to rural residents, urban residents had: lower mean age, 62.4 vs. 61.8 years (p < 0.0001); higher percent of women, 49 vs. 56 % (p = 0.0008); and lower proportion of Whites, 93 vs. 86 % (p = 0.0005). There were rural-urban disparities in TAA utilization in 2003 (0.32 vs. 0.39/100,000; p = 0.021), but not in 2011 (1.19 vs. 1.17/100,00; p = 0.80). TAA outcomes did not differ by rural vs. urban residence: (1) 11.3 % rural vs. 14.2 % urban residents were discharged to an inpatient facility (p = 0.098); (2) length of hospital stay above the median stay, was 44.8 vs. 42.2 % (p = 0.30); and (3) mortality was 0.2 vs. 0.1 %, respectively (p = 0.81). Multivariable-adjusted logistic regression models did not show any significant differences in discharge to home, length of stay, or mortality, by residence. Our study demonstrated an absence of any evidence of rural-urban differences in TAA outcomes. The rural-urban differences in TAA utilization noted in 2003 were no longer significant in 2011. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit SMART C, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Ramachandaran, Rekha] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, J (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.; Singh, J (reprint author), Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit SMART C, Birmingham, AL USA. EM Jasvinder.md@gmail.com FU Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) [U19 HS021110]; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) [P50 AR060772, U34 AR062891]; National Institute of Aging (NIA) [U01 AG018947]; National Cancer Institute (NCI) [U10 CA149950]; Patient Centered Outcomes Research Institute (PCORI) [CE-1304-6631] FX JAS is supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (AHRQ CERTs) U19 HS021110; National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) P50 AR060772 and U34 AR062891; National Institute of Aging (NIA) U01 AG018947; National Cancer Institute (NCI) U10 CA149950; and research contract CE-1304-6631 from the Patient Centered Outcomes Research Institute (PCORI). JAS is also supported by the resources and the use of facilities at the VA Medical Center at Birmingham, Alabama, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 EI 1434-9949 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD FEB PY 2016 VL 35 IS 2 BP 381 EP 386 DI 10.1007/s10067-015-2908-z PG 6 WC Rheumatology SC Rheumatology GA DE7MN UT WOS:000370821300014 PM 25771850 ER PT J AU Annapureddy, N Elsallabi, O Baker, J Sreih, AG AF Annapureddy, Narender Elsallabi, Osama Baker, Joshua Sreih, Antoine G. TI Patient-reported outcomes in ANCA-associated vasculitis. A comparison between Birmingham Vasculitis Activity Score and routine assessment of patient index data 3 SO CLINICAL RHEUMATOLOGY LA English DT Article DE ANCA-associated Vasculitis; Disease activity measures; Patient-Reported Outcomes; RAPID3; Validation of measures ID QUALITY-OF-LIFE; HEALTH-ASSESSMENT QUESTIONNAIRE; PRIMARY SYSTEMIC VASCULITIS; GRANULOMATOSIS; WEGENERS; DISEASE; MDHAQ AB The objective of this study was to determine health-related quality of life (HRQoL) in patients with ANCA-associated vasculitis (AAV) as measured by the "routine assessment of patient index data 3" (RAPID3) and whether RAPID3 is correlated with disease activity as determined by the Birmingham Vasculitis Activity Score (BVAS). Data from patients at an academic institution vasculitis clinic seen between Jan 2010 and Jan 2012 were collected using chart review. BVAS and RAPID3 scores were calculated at each patient visit. RAPID3 was compared between patients in remission (BVAS = 0) and patients with active disease (BVAS > =1) at all visits for four consecutive visits, when data available, at least 3 months apart during the period mentioned. Robust generalized estimating equations (GEE) in linear regression models evaluated associations between the RAPID3 and BVAS over all available observations, adjusting for intra-subject correlations. Thirty-four patients were included in the study, 26 had granulomatosis with polyangiitis (GPA), five microscopic polyangiitis (MPA), and three eosinophilic granulomatosis with polyangiitis (EGPA). Patients at first visit had impaired HRQoL as measured by RAPID3 [6.8 (3.1-12.6)]. The median RAPID3 scores were higher in patients with active disease as compared to patients in remission (7.0 vs. 3.0, p = 0.115; 8.8 vs. 1.0, p = 0.011; 6.1 vs. 2.0, p = 0.032; and 11.7 vs. 2.0, p = 0.128 for visits 1, 2, 3, and 4, respectively). In longitudinal GEE models incorporating all observations there was a strong association between the RAPID3 (per 1 unit) and BVAS (per 1 unit) [beta 0.21 (0.10, 0.32) p < 0.001]. RAPID3 can be used to measure HRQoL in patients with AAV. RAPID3 correlated significantly with BVAS. RAPID3 can discriminate between disease states in AAV. This instrument may help document patient experience and add to clinical decisions. C1 [Annapureddy, Narender] Vanderbilt Univ, Div Rheumatol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Elsallabi, Osama] Creighton Univ, Dept Med, Omaha, NE 68178 USA. [Baker, Joshua] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Baker, Joshua; Sreih, Antoine G.] Univ Penn, Div Rheumatol, 3400 Spruce St,1407 Penn Tower, Philadelphia, PA 19104 USA. [Baker, Joshua] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Annapureddy, Narender; Sreih, Antoine G.] Rush Univ, Div Rheumatol, Chicago, IL 60612 USA. RP Sreih, AG (reprint author), Univ Penn, Div Rheumatol, 3400 Spruce St,1407 Penn Tower, Philadelphia, PA 19104 USA.; Sreih, AG (reprint author), Rush Univ, Div Rheumatol, Chicago, IL 60612 USA. EM antoine.sreih@uphs.upenn.edu OI Annapureddy, Narender/0000-0002-4012-3406 NR 18 TC 2 Z9 2 U1 3 U2 3 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 EI 1434-9949 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD FEB PY 2016 VL 35 IS 2 BP 395 EP 400 DI 10.1007/s10067-015-2921-2 PG 6 WC Rheumatology SC Rheumatology GA DE7MN UT WOS:000370821300016 PM 25822996 ER PT J AU Conde, T Goncalves, OF Pinheiro, AP AF Conde, Tatiana Goncalves, Oscar F. Pinheiro, Ana P. TI The effects of stimulus complexity on the preattentive processing of self-generated and nonself voices: An ERP study SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Self-generated voice; Nonself voice; Stimulus complexity; Event-related potentials; Mismatch negativity; P3a ID HUMAN AUDITORY-CORTEX; MISMATCH NEGATIVITY MMN; COROLLARY DISCHARGE DYSFUNCTION; EVENT-RELATED P3A; SPEECH-PERCEPTION; ELECTROPHYSIOLOGICAL EVIDENCE; ERROR-DETECTION; LANGUAGE-FAMILIARITY; BRAIN RESPONSES; PITCH FEEDBACK AB The ability to differentiate one's own voice from the voice of somebody else plays a critical role in successful verbal self-monitoring processes and in communication. However, most of the existing studies have only focused on the sensory correlates of self-generated voice processing, whereas the effects of attentional demands and stimulus complexity on self-generated voice processing remain largely unknown. In this study, we investigated the effects of stimulus complexity on the preattentive processing of self and nonself voice stimuli. Event-related potentials (ERPs) were recorded from 17 healthy males who watched a silent movie while ignoring prerecorded self-generated (SGV) and nonself (NSV) voice stimuli, consisting of a vocalization (vocalization category condition: VCC) or of a disyllabic word (word category condition: WCC). All voice stimuli were presented as standard and deviant events in four distinct oddball sequences. The mismatch negativity (MMN) ERP component peaked earlier for NSV than for SGV stimuli. Moreover, when compared with SGV stimuli, the P3a amplitude was increased for NSV stimuli in the VCC only, whereas in the WCC no significant differences were found between the two voice types. These findings suggest differences in the time course of automatic detection of a change in voice identity. In addition, they suggest that stimulus complexity modulates the magnitude of the orienting response to SGV and NSV stimuli, extending previous findings on self-voice processing. C1 [Conde, Tatiana; Goncalves, Oscar F.; Pinheiro, Ana P.] Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CIPsi, P-4710057 Braga, Portugal. [Goncalves, Oscar F.] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Spaulding Ctr Neuromodulat,Med Sch, Boston, MA USA. [Goncalves, Oscar F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Goncalves, Oscar F.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Pinheiro, Ana P.] Harvard Univ, Sch Med, Dept Psychiat, Cognit Neurosci Lab, Boston, MA 02115 USA. RP Pinheiro, AP (reprint author), Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CIPsi, P-4710057 Braga, Portugal.; Pinheiro, AP (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Cognit Neurosci Lab, Boston, MA 02115 USA. EM ana.pinheiro@psi.uminho.pt RI Goncalves, Oscar/G-5278-2010; OI Goncalves, Oscar/0000-0003-2735-9155; Pinheiro, Ana/0000-0002-7981-3682 FU Fundacao para a Ciencia e a Tecnologia (FCT, Portugal); Fundo Europeu de Desenvolvimento Regional; FCT [SFRH/BD/77681/2011]; [IF/00334/2012]; [PTDC/PSI-PCL/116626/2010]; [PTDC/MHN-PCN/3606/2012] FX This work was supported by Grant Numbers IF/00334/2012, PTDC/PSI-PCL/116626/2010, and PTDC/MHN-PCN/3606/2012, funded by the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and the Fundo Europeu de Desenvolvimento Regional through the European programs Quadro de Referencia Estrategico Nacional and Programa Operacional Factores de Competitividade, awarded to A.P.P., and by FCT Doctoral Grant Number SFRH/BD/77681/2011, awarded to T.C. NR 132 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD FEB PY 2016 VL 16 IS 1 BP 106 EP 123 DI 10.3758/s13415-015-0376-1 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DE7UL UT WOS:000370842100009 PM 26415897 ER PT J AU Buttner, MM Bormann, JE Weingart, K Andrews, T Ferguson, M Afari, N AF Buttner, Melissa M. Bormann, Jill E. Weingart, Kimberly Andrews, Taylor Ferguson, Marjorie Afari, Niloofar TI Multi-site evaluation of a complementary, spiritually-based intervention for Veterans: The Mantram Repetition Program SO COMPLEMENTARY THERAPIES IN CLINICAL PRACTICE LA English DT Article DE Complementary therapies; Dissemination; Mindfulness; Program evaluation; Relaxation techniques; Veterans ID WELL-BEING SCALE; POSTTRAUMATIC-STRESS-DISORDER; ALTERNATIVE MEDICINE USE; FUNCTIONAL ASSESSMENT; TRIAL; PTSD; CARE AB Background: Mental and physical symptoms affect Veterans' quality of life. Despite available conventional treatments, an increasing number of Veterans are seeking complementary approaches to symptom management. Research on the Mantram Repetition Program (MRP), a spiritually-based intervention, has shown significant improvements in psychological distress and spiritual well-being in randomized trials. However, these findings have not been replicated in real-world settings. Methods: In this naturalistic study, we analyzed outcomes from 273 Veterans who participated in MRP at six sites and explored outcomes based on facilitator training methods. Measures included satisfaction and symptoms of anxiety, depression, and somatization using the Brief Symptom Inventory-18; Functional Assessment of Chronic Illness Therapy-Spiritual Well-being questionnaire; and the Mindfulness Attention Awareness Scale. Results: There were significant improvements in all outcomes ( p's <.001) regardless of how facilitators were trained. Patient satisfaction was high. Conclusion: The MRP was disseminated successfully yielding improvements in psychological distress, spiritual well-being, and mindfulness. Published by Elsevier Ltd. C1 [Buttner, Melissa M.; Bormann, Jill E.; Afari, Niloofar] VA San Diego Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Buttner, Melissa M.; Bormann, Jill E.; Weingart, Kimberly; Andrews, Taylor; Afari, Niloofar] VA San Diego Healthcare Syst, San Diego, CA USA. [Buttner, Melissa M.; Afari, Niloofar] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Buttner, Melissa M.; Ferguson, Marjorie] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Bormann, Jill E.] Univ San Diego, Hahn Sch Nursing & Hlth Sci, San Diego, CA 92110 USA. RP Bormann, JE (reprint author), San Diego Healthcare Syst, 3350 La Jolla Village Dr 111n-1, San Diego, CA 92161 USA. EM Jill.Bormann@va.gov FU Department of Veterans Affairs; VA San Diego Healthcare System; Center of Excellence for Stress and Mental Health (CESAMH) FX This material is based upon work supported by the Department of Veterans Affairs, VA San Diego Healthcare System, and the Center of Excellence for Stress and Mental Health (CESAMH). We thank Ms. Jan Wong and Ms. Suzanne Milligan from VA Employee Education Services (EES) for their assistance in implementing the 2-Day Facilitator Trainings. We especially thank all of the clinicians who brought the Mantram Repetition Program to their facilities and especially all the Veterans who participated in this project. None of the authors have any conflicts of interest to declare. The views expressed in this paper are those of the authors only and do not reflect the official policy or position of the institutions with which the authors are affiliated, nor the Department of Veteran's Affairs, or the United States Government. NR 28 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1744-3881 EI 1873-6947 J9 COMPLEMENT THER CLIN JI Complement. Ther. Clin. Pract. PD FEB PY 2016 VL 22 BP 74 EP 79 DI 10.1016/j.ctcp.2015.12.008 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DE7YW UT WOS:000370854000015 PM 26850810 ER PT J AU Kopacz, MS Connery, AL Bishop, TM Bryan, CJ Drescher, KD Currier, JM Pigeon, WR AF Kopacz, Marek S. Connery, April L. Bishop, Todd M. Bryan, Craig J. Drescher, Kent D. Currier, Joseph M. Pigeon, Wilfred R. TI Moral injury: A new challenge for complementary and alternative medicine SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article DE Moral injury; Pastoral care; Mindfulness; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-PROCESSING THERAPY; MENTAL-HEALTH; SUICIDAL IDEATION; PSYCHOMETRIC EVALUATION; INTEGRATIVE MEDICINE; MINDFULNESS PROGRAM; MILITARY PERSONNEL; SERVICE MEMBERS; PASTORAL CARE AB Moral injury represents an emerging clinical construct recognized as a source of morbidity in current and former military personnel. Finding effective ways to support those affected by moral injury remains a challenge for both biomedical and complementary and alternative medicine. This paper introduces the concept of moral injury and suggests two complementary and alternative medicine, pastoral care and mindfulness, which may prove useful in supporting military personnel thought to be dealing with moral injury. Research strategies for developing an evidence-base for applying these, and other, complementary and alternative medicine modalities to moral injury are discussed. Published by Elsevier Ltd C1 [Kopacz, Marek S.; Bishop, Todd M.; Pigeon, Wilfred R.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY USA. [Connery, April L.] US Dept Vet Affairs, Canandaigua VA Med Ctr, Canandaigua, NY USA. [Bishop, Todd M.; Pigeon, Wilfred R.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Bryan, Craig J.] Univ Utah, Natl Ctr Vet Studies, Salt Lake City, UT USA. [Drescher, Kent D.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Disseminat & Training Div, Menlo Pk, CA USA. [Currier, Joseph M.] Univ S Alabama, Dept Psychol, CCP, Mobile, AL 36688 USA. RP Kopacz, MS (reprint author), Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA. EM marek.kopacz@va.gov OI Bishop, Todd/0000-0001-8551-2117; Bryan, Craig/0000-0002-9714-0733 FU Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs, VISN 2 Center of Excellence for Suicide Prevention; VA's VISN 2 Center of Excellence for Suicide Prevention in Canandaigua, NY FX Dr. Bishop is supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs, VISN 2 Center of Excellence for Suicide Prevention. This work was funded, in part, by the VA's VISN 2 Center of Excellence for Suicide Prevention in Canandaigua, NY. The views expressed are those of the authors and do not reflect the official policy or position of the Department of Veterans Affairs or the U.S. Government. The authors gratefully acknowledge the contribution of Jeffrey Millegan, MD, MPH, FAPA, and Constance M. Cass, MPA, to the development of this paper. NR 79 TC 2 Z9 2 U1 2 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0965-2299 EI 1873-6963 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD FEB PY 2016 VL 24 BP 29 EP 33 DI 10.1016/j.ctim.2015.11.003 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DE8NY UT WOS:000370894100006 PM 26860798 ER PT J AU Chiang, SR Levin, HS Wilde, E Haneef, Z AF Chiang, Sharon Levin, Harvey S. Wilde, Elisabeth Haneef, Zulfi TI White matter structural connectivity changes correlate with epilepsy duration in temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Temporal lobe epilepsy; Diffusion tensor imaging; Progression; Mean diffusivity; Fractional anisotropy ID DIFFUSION-TENSOR MRI; HIPPOCAMPAL SCLEROSIS; QUANTITATIVE MRI; AUTOMATED SEGMENTATION; ABNORMALITIES; NETWORKS; BRAIN; FEATURES; VOLUMES; CORTEX AB Purpose: Temporal lobe epilepsy (TLE) is thought to be a network disease and structural changes using diffusion tensor imaging (DTI) have been shown. However, lateralized differences in the structural integrity of TLE, as well as changes in structural integrity with longer disease duration, have not been well defined. Methods: We examined the fractional anisotropy (FA) and mean diffusivity (MD) in the hippocampus, as well as its primary (cingulum and fornix) and remote (uncinate and external capsule) connections in both right and left TLE. Changes in diffusion measures over the disease course were examined by correlating FA and MD in the various structures with epilepsy duration. The potential for each measure of anisotropy and diffusivity as a marker of TLE laterality was investigated using random forest (RF) analysis. Results: MD was increased in the bilateral hippocampus, cingulum, fornix and the right external capsule in both left and right TLE compared to controls. In addition, left TLE exhibited an increased MD in the ipsilateral uncinate fasciculus and bilateral external capsules. A decrease in FA was seen in the left cingulum in left TLE. RF analysis demonstrated that MD of the right hippocampus and FA of the left external capsule were important predictors of TLE laterality. An association of increased MD with epilepsy duration was seen in the left hippocampus in left TLE. Conclusion: Evidence of disrupted white matter architecture in the hippocampus and its primary and remote connections were demonstrated in TLE. While changes in the hippocampus and cingulum were more prominent in right TLE, remote changes were more prominent in left TLE. MD of the right hippocampus and FA of the left external capsule were found to be the strongest structural predictors of TLE laterality. Changes associated with duration of epilepsy indicated that changes in structural integrity may be progressive over the disease course. This study illustrates the potential of structural diffusion tensor imaging in elucidating pathophysiology, enhancing diagnosis and assisting prognostication. (C) 2015 Elsevier B.V. All rights reserved. C1 [Chiang, Sharon] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Levin, Harvey S.; Wilde, Elisabeth] Baylor Coll Med, Dept Phys Med, Houston, TX 77030 USA. [Haneef, Zulfi] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Haneef, Zulfi] Michael E DeBakey VA Med Ctr, Neurol Care Line, Houston, TX USA. [Levin, Harvey S.] Michael E De Bakey Vet Affairs Med Ctr, Houston, TX USA. RP Chiang, SR (reprint author), Rice Univ, Dept Stat, Houston, TX 77251 USA. EM sc4712@rice.edu; hlevin@bcm.edu; ewilde@bcm.edu; zulfi.haneef@bcm.edu FU National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences [2T15LM007093-21]; National Institutes of Health [5T32CA096520-07]; Moody Foundation; Epilepsy Foundation of America; Baylor College of Medicine Computational and Integrative Biomedical Research Center Seed Grant Awards FX Sharon Chiang's contributions to this article include study concept or design, statistical analysis, drafting/revising the manuscript for content, and analysis/interpretation of data. Harvey S. Levin's contributions to this article include revising the manuscript for content. Elisabeth Wilde's contributions to this article include revising the manuscript for content. Zulfi Haneef's contributions to this article include study concept or design, drafting/revising the manuscript for content, analysis/interpretation of data, study supervision, and obtaining funding. The authors acknowledge Raja Muthupillai, Claudio Arenas, Cynthia Calija, Sikawat Thanaviratananich, and Christina Thomas for help with methodology, recruitment, and data collection. Funding for the design and conduct of this study; for the collection, management, analysis, and interpretation of the data; and for the preparation, review, and approval of the manuscript was provided by the Epilepsy Foundation of America. Support for this publication was provided by the National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences (Grant #2T15LM007093-21) (SC); the National Institutes of Health (Grant #5T32CA096520-07) (SC); the Moody Foundation (HSL); Epilepsy Foundation of America (Research Grants Program) (ZH); and the Baylor College of Medicine Computational and Integrative Biomedical Research Center Seed Grant Awards (ZH). NR 58 TC 4 Z9 5 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 2016 VL 120 BP 37 EP 46 DI 10.1016/j.eplepsyres.2015.12.002 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DE9ZQ UT WOS:000370998800007 PM 26709881 ER PT J AU Torolira, D Suchomelova, L Wasterlain, CG Niquet, J AF Torolira, Daniel Suchomelova, Lucie Wasterlain, Claude G. Niquet, Jerome TI Widespread neuronal injury in a model of cholinergic status epilepticus in postnatal day 7 rat pups SO EPILEPSY RESEARCH LA English DT Article DE Immature brain; Seizures; Fluoro-Jade B; Active caspase-3; Neonate; Hippocampus ID EARLY-LIFE SEIZURES; RECURRENT NEONATAL SEIZURES; LONG-TERM CONSEQUENCES; NERVE AGENT EXPOSURE; MEDIODORSAL NUCLEUS; EXCITATORY ACTIONS; BRAIN-DEVELOPMENT; 12-DAY-OLD RATS; IMMATURE RATS; HIPPOCAMPUS AB Objective: Status Epilepticus (SE) is common in neonates and infants, and is associated with neuronal injury and adverse developmental outcomes. However, the role of SE in this injury is uncertain. Until now, we have lacked an animal model in which seizures result in neuronal injury in rodent models at ages below postnatal day 12 (P12) unless seizures are combined with inflammatory stressors. Methods: We induced SE with high-dose lithium and pilocarpine in P7 rats, which are developmentally close to human neonates. Several EEG measures and O-2 saturation were recorded during the 6 h following initiation of SE. We assessed neuronal injury at 6 and 24 h post-SE onset using Fluoro-Jade B staining (FJB) and caspase-3a immunoreactivity (IR). Results: EEGs showed continuous polyspikes activity for 54.3 +/- 6.7 min, while O-2 saturation showed no significant hypoxemia. By 24 h after SE onset, significant neuronal injury was observed in CA1/subiculum, CA3, dentate gyrus, thalamus, neocortex, amygdala, piriform cortex, lateral entorhinal cortex, hypothalamus, caudate putamen, globus pallidus, ventral pallidum, and nucleus accumbens. At 24 h post-SE, caspase-3a IR was significantly increased in CA1/subiculum, thalamus, and neocortex compared to sham, and caspase-3a IR neurons had fragmented nuclei, suggesting that SE triggered an irreversible form of cell injury. Significance: In conclusion, we have developed a model of cholinergic SE in P7 rat pups, which combines high survival (69.9% survival at 24 h) and widespread brain injury. These studies suggest that the immature brain is vulnerable to severe forms of SE. Published by Elsevier B.V. C1 [Torolira, Daniel; Suchomelova, Lucie; Wasterlain, Claude G.; Niquet, Jerome] Vet Affairs Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, Los Angeles, CA 90073 USA. [Wasterlain, Claude G.; Niquet, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Wasterlain, Claude G.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Niquet, J (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, 11301 Wilshire Blvd,Bldg 114,Room 139, Los Angeles, CA 90073 USA. EM jniquet@ucla.edu FU Merit Review Award from the United States (U.S.) Department of Veterans Affairs (Biomedical Laboratory Research and Development Service) [I01 BX000273-07]; NINDS [UO1 NS074926] FX This work was supported in part by Merit Review Award # I01 BX000273-07 from the United States (U.S.) Department of Veterans Affairs (Biomedical Laboratory Research and Development Service) and NINDS (grant UO1 NS074926; CW). NR 42 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 2016 VL 120 BP 47 EP 54 DI 10.1016/j.eplepsyres.2015.11.005 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DE9ZQ UT WOS:000370998800008 PM 26709882 ER PT J AU Imamura, H Matsumoto, R Takaya, S Nakagawa, T Shimotake, A Kikuchi, T Sawamoto, N Kunieda, T Mikuni, N Miyamoto, S Fukuyama, H Takahashi, R Ikeda, A AF Imamura, Hisaji Matsumoto, Riki Takaya, Shigetoshi Nakagawa, Tomokazu Shimotake, Akihiro Kikuchi, Takayuki Sawamoto, Nobukatsu Kunieda, Takeharu Mikuni, Nobuhiro Miyamoto, Susumu Fukuyama, Hidenao Takahashi, Ryosuke Ikeda, Akio TI Network specific change in white matter integrity in mesial temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE FDG-PET; Diffusion tractography; Mesial temporal lobe epilepsy; Epileptic activity; Seizure propagation ID INTERICTAL GLUCOSE HYPOMETABOLISM; POSITRON-EMISSION-TOMOGRAPHY; TRACTOGRAPHY; DIFFUSION; BRAIN; AMYGDALOHIPPOCAMPECTOMY; CONNECTIONS; METABOLISM; SCLEROSIS; PATTERNS AB Objectives: To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). Methods: We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. Results: Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. Conclusion: The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation. (C) 2015 Elsevier B.V. All rights reserved. C1 [Imamura, Hisaji; Nakagawa, Tomokazu; Shimotake, Akihiro; Sawamoto, Nobukatsu; Takahashi, Ryosuke] Kyoto Univ, Dept Neurol, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. [Matsumoto, Riki; Ikeda, Akio] Kyoto Univ, Dept Epilepsy Movement Disorders & Physiol, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. [Takaya, Shigetoshi; Fukuyama, Hidenao] Kyoto Univ, Human Brain Res Ctr, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. [Kikuchi, Takayuki; Kunieda, Takeharu; Mikuni, Nobuhiro; Miyamoto, Susumu] Kyoto Univ, Dept Neurosurg, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. [Mikuni, Nobuhiro] Sapporo Med Univ, Dept Neurosurg, Chuo Ku, S1 W17, Sapporo, Hokkaido 0608556, Japan. [Takaya, Shigetoshi] Kyoto Univ, Radioisotope Res Ctr, Kyoto 6068315, Japan. [Takaya, Shigetoshi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Imamura, Hisaji] Fukui Red Cross Hosp, Dept Neurol, 4 Tsukimi, Fukui 9188501, Japan. RP Matsumoto, R; Ikeda, A (reprint author), Kyoto Univ, Dept Epilepsy Movement Disorders & Physiol, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 6068507, Japan. EM imamurah@kuhp.kyoto-u.ac.jp; matsumot@kuhp.kyoto-u.ac.jp; shig.t@kuhp.kyoto-u.ac.jp; tnakaga@kuhp.kyoto-u.ac.jp; smtk@kuhp.kyoto-u.ac.jp; tkik@kuhp.kyoto-u.ac.jp; sawa@kuhp.kyoto-u.ac.jp; kuny@kuhp.kyoto-u.ac.jp; mikunin@sapmed.ac.jp; miy@kuhp.kyoto-u.ac.jp; fukuyama@kuhp.kyoto-u.ac.jp; ryosuket@kuhp.kyoto-u.ac.jp; akio@kuhp.kyoto-u.ac.jp RI Matsumoto, Riki/I-8397-2016 OI Matsumoto, Riki/0000-0003-3985-9210 FU Ministry of Education, Culture, Sports, Science and Technology of Japan/JSPS [26282218, 26560465, 15H05874]; Ministry of Health, Labor and Welfare of Japan [H21-023]; Takeda Science Foundation; Kato Memorial Trust for Nambyo Research; GlaxoSmithKline K.K.; NIHON KOHDEN CORPORATION; Otsuka Pharmaceutical Co.; UCB Japan Co, Ltd. FX This study is supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan/JSPS (26282218, 26560465 to Riki Matsumoto and 15H05874 to Akio Ikeda), the Ministry of Health, Labor and Welfare of Japan (H21-023 to Shigetoshi Takaya), the Takeda Science Foundation (to Shigetoshi Takaya), and the Kato Memorial Trust for Nambyo Research (to Riki Matsumoto).; Department of Epilepsy Movement Disorders and Physiology is an endowment department, supported with a grant from GlaxoSmithKline K.K., NIHON KOHDEN CORPORATION, Otsuka Pharmaceutical Co., and UCB Japan Co, Ltd. NR 27 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 2016 VL 120 BP 65 EP 72 DI 10.1016/j.eplepsyres.2015.12.003 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DE9ZQ UT WOS:000370998800010 PM 26735187 ER PT J AU Stanton, RC AF Stanton, R. C. TI Diabetic Kidney Disease and Hypertension SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Review DE diabetic nephropathy; hypertension; RAAS inhibition ID BLOOD-PRESSURE CONTROL; CORONARY-ARTERY-DISEASE; CHRONIC RENAL-DISEASE; CARDIOVASCULAR OUTCOMES; PRIMARY ALDOSTERONISM; NEPHROPATHY; MELLITUS; TRIAL; PROGRESSION; SODIUM AB Achieving blood pressure (BP) goals is an essential goal for both primary and secondary prevention of diabetic kidney disease (DKD). Even though there is universal agreement about the importance of controlling BP, there are many issues about many aspects of hypertension management for DKD patients. These issues include: what is the optimal BP for the prevention or slowing of progression of DKD patients; what is the best method for diagnosing hypertension and monitoring BP, and what are the best medicines to use to treat hypertension in DKD patients. In this review, these issues as well as others will be discussed. C1 [Stanton, R. C.] Joslin Diabet Ctr, One Joslin Pl, Boston, MA USA. RP Stanton, RC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Chief Kidney & Hypertens Sect,Med, One Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu NR 48 TC 1 Z9 1 U1 1 U2 2 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 EI 1439-3646 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD FEB PY 2016 VL 124 IS 2 BP 93 EP 98 DI 10.1055/s-0035-1559760 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DF1CU UT WOS:000371076800006 PM 26575123 ER PT J AU Constantinou, C Apidianakis, Y Psychogios, N Righi, V Mindrinos, MN Khan, N Swartz, HM Szeto, HH Tompkins, RG Rahme, LG Tzika, AA AF Constantinou, Caterina Apidianakis, Yiorgos Psychogios, Nikolaos Righi, Valeria Mindrinos, Michael N. Khan, Nadeem Swartz, Harold M. Szeto, Hazel H. Tompkins, Ronald G. Rahme, Laurence G. Tzika, A. Aria TI In vivo high-resolution magic angle spinning magnetic and electron paramagnetic resonance spectroscopic analysis of mitochondria-targeted peptide in Drosophila melanogaster with trauma-induced thoracic injury SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE nuclear magnetic resonance; electron paramagnetic resonance; high-resolution magic angle spinning; mitochondria; Drosophila melanogaster; biomarkers; insulin signaling; aging ID INTRAMYOCELLULAR LIPID-CONTENT; HUMAN SKELETAL-MUSCLE; HR-MAS SPECTROSCOPY; INSULIN-RESISTANCE; BURN-TRAUMA; OXIDATIVE STRESS; ANTIOXIDANTS PROTECT; INDUCED APOPTOSIS; RELAXATION-TIMES; GENE-EXPRESSION AB Trauma is the most common cause of mortality among individuals aged between 1 and 44 years and the third leading cause of mortality overall in the US. In this study, we examined the effects of trauma on the expression of genes in Drosophila melanogaster, a useful model for investigating genetics and physiology. After trauma was induced by a non-lethal needle puncture of the thorax, we observed the differential expression of genes encoding for mitochondrial uncoupling proteins, as well as those encoding for apoptosis-related and insulin signaling-related proteins, thus indicating muscle functional dysregulation. These results prompted us to examine the link between insulin signaling and mitochondrial dysfunction using in vivo nuclear magnetic resonance (NMR) with complementary electron paramagnetic resonance (EPR) spectroscopy. Trauma significantly increased insulin resistance biomarkers, and the NMR spectral profile of the aged flies with trauma-induced thoracic injury resembled that of insulin-resistant chico mutant flies. In addition, the mitochondrial redox status, as measured by EPR, was significantly altered following trauma, indicating mitochondrial uncoupling. A mitochondria-targeted compound, Szeto-Schiller (SS)-31 that promotes adenosine triphosphate (ATP) synthesis normalized the NMR spectral profile, as well as the mitochondrial redox status of the flies with trauma-induced thoracic injury, as assessed by EPR. Based on these findings, we propose a molecular mechanism responsible for trauma-related mortality and also propose that trauma sequelae in aging are linked to insulin signaling and mitochondrial dysfunction. Our findings further suggest that SS-31 attenuates trauma-associated pathological changes. C1 [Constantinou, Caterina; Psychogios, Nikolaos; Righi, Valeria; Tzika, A. Aria] Harvard Univ, Sch Med, NMR Surg Lab, Boston, MA 02115 USA. [Constantinou, Caterina; Apidianakis, Yiorgos; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg,Massachusetts Gen Hosp, Mol Surg Lab,Ctr Surg Innovat & Bioengn, Boston, MA 02115 USA. [Constantinou, Caterina; Apidianakis, Yiorgos; Rahme, Laurence G.] Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02115 USA. [Psychogios, Nikolaos; Righi, Valeria; Tzika, A. Aria] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mindrinos, Michael N.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. [Khan, Nadeem; Swartz, Harold M.] Geisel Sch Med, Dept Diagnost Radiol, EPR Ctr Viable Syst, Lebanon, NH USA. [Szeto, Hazel H.] Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. [Tompkins, Ronald G.] Harvard Univ, Sch Med, Dept Surg,Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Boston, MA 02115 USA. [Constantinou, Caterina] Univ Patras, Dept Med, Pharmacol Unit, Rio Achaias 26500, Greece. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen & Shriners Burns Inst, NMR Surg Lab,Dept Surg, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu OI Apidianakis, Yiorgos/0000-0002-7465-3560; Constantinou, Caterina/0000-0003-3589-0739 FU Defense Medical Research and Development Program (DMRDP) [DM103014]; Shriner's Hospital for Children research grants [8893, 8892] FX The present study was supported in part by a grant from DM103014 of the Defense Medical Research and Development Program (DMRDP) to Laurence G. Rahme (Aria A. Tzika, co-investigator), and Shriner's Hospital for Children research grants to Aria A. Tzika (no. 8893) and Laurence G. Rahme (no. 8892). The authors also thank Dr Ann Power Smith (Write Science Right, Las Vegas, NV, USA) for providing editorial assistance. The SS peptide technology has been licensed for commercial development to Stealth Peptides Inc. by the Cornell Research Foundation (CRF), and both CRF and Hazel H. Szeto have financial interests. We would also like to thank Dr Robert Perrimon for providing the chico flies. NR 75 TC 0 Z9 0 U1 2 U2 8 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 EI 1791-244X J9 INT J MOL MED JI Int. J. Mol. Med. PD FEB PY 2016 VL 37 IS 2 BP 299 EP 308 DI 10.3892/ijmm.2015.2426 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DE7ZL UT WOS:000370855500004 PM 26648055 ER PT J AU Ahearn, TU Pettersson, A Ebot, EM Gerke, T Graff, RE Morais, CL Hicks, JL Wilson, KM Rider, JR Sesso, HD Fiorentino, M Flavin, R Finn, S Giovannucci, EL Loda, M Stampfer, MJ De Marzo, AM Mucci, LA Lotan, TL AF Ahearn, Thomas U. Pettersson, Andreas Ebot, Ericka M. Gerke, Travis Graff, Rebecca E. Morais, Carlos L. Hicks, Jessica L. Wilson, Kathryn M. Rider, Jennifer R. Sesso, Howard D. Fiorentino, Michelangelo Flavin, Richard Finn, Stephen Giovannucci, Edward L. Loda, Massimo Stampfer, Meir J. De Marzo, Angelo M. Mucci, Lorelei A. Lotan, Tamara L. TI A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GENOMIC DELETION; BIOCHEMICAL RECURRENCE; RADICAL PROSTATECTOMY; AFRICAN-AMERICAN; GENE FUSIONS; PROTEIN LOSS; HIGH-RISK; PROGRESSION; MEN; HETEROGENEITY AB Background: PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort. Methods: In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2: ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided. Results: On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinicalpathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors. Conclusions: PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer. C1 [Ahearn, Thomas U.; Pettersson, Andreas; Ebot, Ericka M.; Gerke, Travis; Graff, Rebecca E.; Wilson, Kathryn M.; Rider, Jennifer R.; Sesso, Howard D.; Giovannucci, Edward L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Stampfer, Meir J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Pettersson, Andreas] Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden. [Graff, Rebecca E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Morais, Carlos L.; Hicks, Jessica L.; De Marzo, Angelo M.; Lotan, Tamara L.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Wilson, Kathryn M.; Rider, Jennifer R.; Giovannucci, Edward L.; Stampfer, Meir J.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Wilson, Kathryn M.; Rider, Jennifer R.; Giovannucci, Edward L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Fiorentino, Michelangelo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. [Flavin, Richard; Finn, Stephen] Trinity Coll Dublin, Dept Histopathol Res, Dublin, Ireland. [Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [De Marzo, Angelo M.; Lotan, Tamara L.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Ahearn, Thomas U.; De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. RP Ahearn, TU (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM tahearn@hsph.harvard.edu OI Rider, Jennifer/0000-0002-2637-6036; Finn, Stephen/0000-0002-8628-5814 FU National Institute of Health [R01CA136578, R01CA141298, UM1 CA167552, P50 CA090381, R25 CA112355, T32 CA09001]; Prostate Cancer Foundation; Patrick C. Walsh Prostate Cancer Research Fund; Swedish Research Council [2009-7309]; Royal Physiographic Society in Lund; American Cancer Society - Ellison Foundation [PF-14-140-01-CCE]; Office of the Assistant Secretary of Defense for Health Affairs [W81XWH-14-1-0250]; National Cancer Institute [CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute (Bethesda, MD) [HL-26490, HL-34595] FX This work was supported by National Institute of Health (grant numbers R01CA136578, R01CA141298, UM1 CA167552, P50 CA090381, R25 CA112355 to REG, and T32 CA09001 to TUA and EME); the Prostate Cancer Foundation Young Investigators Awards to LAM, TLL, JRR, and KMW; the Patrick C. Walsh Prostate Cancer Research Fund; the Swedish Research Council (Reg. No. 2009-7309) to AP and the Royal Physiographic Society in Lund to AP; the American Cancer Society - Ellison Foundation Postdoctoral Fellowship (PF-14-140-01-CCE) to TUA; Office of the Assistant Secretary of Defense for Health Affairs under Award No. W81XWH-14-1-0250 to EME; and the Physicians' Health Study is supported by grants CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute (Bethesda, MD). NR 48 TC 6 Z9 6 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD FEB PY 2016 VL 108 IS 2 AR djv346 DI 10.1093/jnci/djv346 PG 9 WC Oncology SC Oncology GA DF2EP UT WOS:000371153900016 ER PT J AU Askoxylakis, V Ferraro, GB Kodack, DP Badeaux, M Shankaraiah, RC Seano, G Kloepper, J Vardam, T Martin, JD Naxerova, K Bezwada, D Qi, XL Selig, MK Brachtel, E Duda, DG Huang, PG Fukumura, D Engelman, JA Jain, RK AF Askoxylakis, Vasileios Ferraro, Gino B. Kodack, David P. Badeaux, Mark Shankaraiah, Ram C. Seano, Giorgio Kloepper, Jonas Vardam, Trupti Martin, John D. Naxerova, Kamila Bezwada, Divya Qi, Xiaolong Selig, Martin K. Brachtel, Elena Duda, Dan G. Huang, Peigen Fukumura, Dai Engelman, Jeffrey A. Jain, Rakesh K. TI Preclinical Efficacy of Ado-trastuzumab Emtansine in the Brain Microenvironment SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID METASTATIC BREAST-CANCER; LAPATINIB PLUS CAPECITABINE; NERVOUS-SYSTEM METASTASES; EXPLORATORY ANALYSIS; MITOTIC CATASTROPHE; SURGICAL RESECTION; CLINICAL-PRACTICE; PHASE-II; THERAPY; T-DM1 AB Background: Central nervous system (CNS) metastases represent a major problem in the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer because of the disappointing efficacy of HER2-targeted therapies against brain lesions. The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has shown efficacy in trastuzumab-resistant systemic breast cancer. Here, we tested the hypothesis that T-DM1 could overcome trastuzumab resistance in murine models of brain metastases. Methods: We treated female nude mice bearing BT474 or MDA-MB-361 brain metastases (n = 9-11 per group) or cancer cells grown in organotypic brain slice cultures with trastuzumab or T-DM1 at equivalent or equipotent doses. Using intravital imaging, molecular techniques and histological analysis we determined tumor growth, mouse survival, cancer cell apoptosis and proliferation, tumor drug distribution, and HER2 signaling. Data were analyzed with one-way analysis of variance (ANOVA), Kaplan-Meier analysis, and Coefficient of Determination. All statistical tests were two-sided. Results: T-DM1 delayed the growth of HER2-positive breast cancer brain metastases compared with trastuzumab. These findings were consistent between HER2-driven and PI3K-driven tumors. The activity of T-DM1 resulted in a survival benefit (median survival for BT474 tumors: 28 days for trastuzumab vs 112 days for T-DM1, hazard ratio = 6.2, 95% confidence interval = 6.1 to 85.84, P < .001). No difference in drug distribution or HER2-signaling was revealed between the two groups. However, T-DM1 led to a statistically significant increase in tumor cell apoptosis (one-way ANOVA for ApopTag, P < .001), which was associated with mitotic catastrophe. Conclusions: T-DM1 can overcome resistance to trastuzumab therapy in HER2-driven or PI3K-driven breast cancer brain lesions due to the cytotoxicity of the DM1 component. Clinical investigation of T-DM1 for patients with CNS metastases from HER2-positive breast cancer is warranted. C1 [Askoxylakis, Vasileios; Ferraro, Gino B.; Kodack, David P.; Badeaux, Mark; Shankaraiah, Ram C.; Seano, Giorgio; Kloepper, Jonas; Vardam, Trupti; Martin, John D.; Naxerova, Kamila; Bezwada, Divya; Qi, Xiaolong; Duda, Dan G.; Huang, Peigen; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Edwin L Steele Labs, Dept Radiat Oncol, Boston, MA 02114 USA. [Selig, Martin K.; Brachtel, Elena] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Edwin L Steele Labs Tumor Biol, Cox 7,100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Martin, John/L-6892-2016; Seano, Giorgio/R-6611-2016 OI Martin, John/0000-0002-9828-8203; Seano, Giorgio/0000-0002-7294-302X FU Department of Defense (DoD) Breast Cancer Research Innovator Award [W81XWH-10-1-0016]; National Cancer Institute at the National Institutes of Health (NCI/Federal Share Proton Beam Program Income) [R01-CA126642, P01-CA080124, R01-CA096915, S10-RR027070]; German Research Foundation (Deutsche Forschungsgemeinschaft DFG) [AS 422-2/1]; Fondation SolidarImmun FX This work was supported by the Department of Defense (DoD) Breast Cancer Research Innovator Award (W81XWH-10-1-0016 to RKJ), the National Cancer Institute at the National Institutes of Health (R01-CA126642 to RKJ, P01-CA080124 to RKJ and DF, R01-CA096915 to DF, and S10-RR027070 to DF, NCI/Federal Share Proton Beam Program Income to RKJ), the German Research Foundation (Deutsche Forschungsgemeinschaft DFG, AS 422-2/1 to VA), and the Fondation SolidarImmun (to JK). NR 34 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD FEB PY 2016 VL 108 IS 2 AR djv313 DI 10.1093/jnci/djv313 PG 10 WC Oncology SC Oncology GA DF2EP UT WOS:000371153900005 ER PT J AU Brastianos, PK Shankar, GM Gill, CM Taylor-Weiner, A Nayyar, N Panka, DJ Sullivan, RJ Frederick, DT Abedalthagafi, M Jones, PS Dunn, IF Nahed, BV Romero, JM Louis, DN Getz, G Cahill, DP Santagata, S Curry, WT Barker, FG AF Brastianos, Priscilla K. Shankar, Ganesh M. Gill, Corey M. Taylor-Weiner, Amaro Nayyar, Naema Panka, David J. Sullivan, Ryan J. Frederick, Dennie T. Abedalthagafi, Malak Jones, Pamela S. Dunn, Ian F. Nahed, Brian V. Romero, Javier M. Louis, David N. Getz, Gad Cahill, Daniel P. Santagata, Sandro Curry, William T., Jr. Barker, Fred G., II TI Dramatic Response of BRAF V600E Mutant Papillary Craniopharyngioma to Targeted Therapy SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MELANOMA; INHIBITION; MUTATIONS; CANCER; BLOOD AB We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our treatment of a man age 39 years with multiply recurrent BRAF V600E craniopharyngioma using dabrafenib (150 mg, orally twice daily) and trametinib (2 mg, orally twice daily). After 35 days of treatment, tumor volume was reduced by 85%. Mutations that commonly mediate resistance to MAPK pathway inhibition were not detected in a post-treatment sample by whole exome sequencing. A blood-based BRAF V600E assay detected circulating BRAF V600E in the patient's blood. Re-evaluation of the existing management paradigms for craniopharyngioma is warranted, as patient morbidity might be reduced by noninvasive mutation testing and neoadjuvant-targeted treatment. C1 [Brastianos, Priscilla K.; Sullivan, Ryan J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brastianos, Priscilla K.; Gill, Corey M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shankar, Ganesh M.; Jones, Pamela S.; Nahed, Brian V.; Cahill, Daniel P.; Curry, William T., Jr.; Barker, Fred G., II] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Frederick, Dennie T.] Harvard Univ, Sch Med, Dept Surg Oncol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Louis, David N.; Getz, Gad] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brastianos, Priscilla K.; Gill, Corey M.; Nayyar, Naema; Louis, David N.] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Romero, Javier M.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Taylor-Weiner, Amaro; Getz, Gad] Brigham & Womens Hosp, Broad Inst, 75 Francis St, Boston, MA 02115 USA. [Abedalthagafi, Malak; Santagata, Sandro] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. [Panka, David J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. RP Brastianos, PK; Barker, FG (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM pbrastianos@mgh.harvard.edu; barker@helix.mgh.harvard.edu OI Brastianos, Priscilla/0000-0003-4470-8425; Cahill, Daniel/0000-0003-2552-6546 FU K12 grant [2K12CA090354-11]; Brain Science Foundation; Susan G. Komen for the Cure; American Brain Tumor Association; Terri Brodeur Breast Cancer Foundation; Conquer Cancer Foundation FX PKB is funded by a K12 grant (2K12CA090354-11), the Brain Science Foundation, Susan G. Komen for the Cure, Terri Brodeur Breast Cancer Foundation, Conquer Cancer Foundation, the American Brain Tumor Association. NR 16 TC 6 Z9 6 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD FEB PY 2016 VL 108 IS 2 AR djv310 DI 10.1093/jnci/djv310 PG 5 WC Oncology SC Oncology GA DF2EP UT WOS:000371153900004 ER PT J AU Kastrinos, F Ojha, RP Leenen, C Alvero, C Mercado, RC Balmana, J Valenzuela, I Balaguer, F Green, R Lindor, NM Thibodeau, SN Newcomb, P Win, AK Jenkins, M Buchanan, DD Bertario, L Sala, P Hampel, H Syngal, S Steyerberg, EW AF Kastrinos, Fay Ojha, Rohit P. Leenen, Celine Alvero, Carmelita Mercado, Rowena C. Balmana, Judith Valenzuela, Irene Balaguer, Francesc Green, Roger Lindor, Noralane M. Thibodeau, Stephen N. Newcomb, Polly Win, Aung Ko Jenkins, Mark Buchanan, Daniel D. Bertario, Lucio Sala, Paola Hampel, Heather Syngal, Sapna Steyerberg, Ewout W. CA Lynch Syndrome Prediction Model Va TI Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POPULATION-BASED COHORT; MISMATCH-REPAIR GENES; GERMLINE MUTATIONS; COLON-CANCER; BETHESDA GUIDELINES; HEREDITARY; IDENTIFICATION; MLH1; MSH2; VALIDATION AB Background: Recent guidelines recommend the Lynch Syndrome prediction models MMRPredict, MMRPro, and PREMM1,2,6 for the identification of MMR gene mutation carriers. We compared the predictive performance and clinical usefulness of these prediction models to identify mutation carriers. Methods: Pedigree data from CRC patients in 11 North American, European, and Australian cohorts (6 clinic- and 5 population-based sites) were used to calculate predicted probabilities of pathogenic MLH1, MSH2, or MSH6 gene mutations by each model and gene-specific predictions by MMRPro and PREMM1,2,6. We examined discrimination with area under the receiver operating characteristic curve (AUC), calibration with observed to expected (O/E) ratio, and clinical usefulness using decision curve analysis to select patients for further evaluation. All statistical tests were two-sided. Results: Mutations were detected in 539 of 2304 (23%) individuals from the clinic- based cohorts (237 MLH1, 251 MSH2, 51 MSH6) and 150 of 3451 (4.4%) individuals from the population-based cohorts (47 MLH1, 71 MSH2, 32 MSH6). Discrimination was similar for clinic- and population-based cohorts: AUCs of 0.76 vs 0.77 for MMRPredict, 0.82 vs 0.85 for MMRPro, and 0.85 vs 0.88 for PREMM1,2,6. For clinic- and population-based cohorts, O/E deviated from 1 for MMRPredict (0.38 and 0.31, respectively) and MMRPro (0.62 and 0.36) but were more satisfactory for PREMM1,2,6 (1.0 and 0.70). MMRPro or PREMM1,2,6 predictions were clinically useful at thresholds of 5% or greater and in particular at greater than 15%. Conclusions: MMRPro and PREMM1,2,6 can well be used to select CRC patients from genetics clinics or population-based settings for tumor and/or germline testing at a 5% or higher risk. If no MMR deficiency is detected and risk exceeds 15%, we suggest considering additional genetic etiologies for the cause of cancer in the family. C1 [Kastrinos, Fay] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Kastrinos, Fay] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY USA. [Ojha, Rohit P.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, 332 N Lauderdale St, Memphis, TN 38105 USA. [Leenen, Celine] Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands. [Alvero, Carmelita] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Mercado, Rowena C.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Balmana, Judith] Univ Hosp Vall Hebron, Dept Oncol, Barcelona, Spain. [Valenzuela, Irene] Univ Hosp Vall Hebron, Dept Genet, Barcelona, Spain. [Balaguer, Francesc] CIBERehd, IDIBAPS, Hosp Clin Barcelona, Dept Gastroenterol, Barcelona, Spain. [Green, Roger] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Div Mol Genet, Rochester, MN USA. [Newcomb, Polly] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Win, Aung Ko; Jenkins, Mark; Buchanan, Daniel D.] Univ Melbourne, Ctr Biostat & Epidemiol, Melbourne Sch Populat & Global Hlth, Parkville, Vic 3052, Australia. [Bertario, Lucio; Sala, Paola] Fdn IRCCS Ist Nazl Tumori, Unit Hereditary Digest Tract Tumors, Dept Prevent & Predict Med, Milan, Italy. [Hampel, Heather] Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Steyerberg, Ewout W.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Buchanan, Daniel D.] Univ Melbourne, Genet Epidemiol Lab, Oncogen Grp, Parkville, Vic 3052, Australia. RP Kastrinos, F (reprint author), Columbia Univ, Med Ctr, Div Digest & Liver Dis, Herbert Irving Comprehens Canc Ctr, 161 Ft Washington Ave,Suite 862, New York, NY 10032 USA. EM fk18@columbia.edu RI BALAGUER, FRANCESC/G-2389-2016; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Carracedo, Angel/0000-0003-1085-8986; Ojha, Rohit/0000-0003-0595-8990; Brunet, Joan/0000-0003-1945-3512; Bessa Caserras, Xavier/0000-0003-4680-1228; Valenzuela, Irene/0000-0003-2350-6058; Win, Aung Ko/0000-0002-2794-5261 FU National Cancer Institute [K07 CA151769-02, R01 CA132829, K24 CA113433]; Australasian Colorectal Cancer Family Registry [U01 CA097735]; University of Southern California (USC) Colorectal Cancer Family Registry [U01 CA074799]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; University of Hawaii Colorectal Cancer Family Registry [U01 CA074806] FX This work was supported by the National Cancer Institute (K07 CA151769-02 to FK; R01 CA132829 and K24 CA113433 to SS) and through cooperative agreements with members of the Colon Cancer Family Registry and PIs including Australasian Colorectal Cancer Family Registry (U01 CA097735), the University of Southern California (USC) Colorectal Cancer Family Registry (U01 CA074799), the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), the Seattle Colorectal Cancer Family Registry (U01 CA074794), and the University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR. NR 39 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 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD FEB PY 2016 VL 108 IS 2 AR djv308 DI 10.1093/jnci/djv308 PG 9 WC Oncology SC Oncology GA DF2EP UT WOS:000371153900002 ER PT J AU Kim, JJ Tosteson, ANA Zauber, AG Sprague, BL Stout, NK Alagoz, O Trentham-Dietz, A Armstrong, K Pruitt, SL Rutter, CM AF Kim, Jane J. Tosteson, Anna N. A. Zauber, Ann G. Sprague, Brian L. Stout, Natasha K. Alagoz, Oguzhan Trentham-Dietz, Amy Armstrong, Katrina Pruitt, Sandi L. Rutter, Carolyn M. CA Population-Based Res Optimizing TI Cancer Models and Real-World Data: Better Together SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SERVICES TASK-FORCE; COST-EFFECTIVENESS ANALYSIS; COLORECTAL-CANCER; CERVICAL-CANCER; NATURAL-HISTORY; PERSONALIZED REGIMENS; HUMAN-PAPILLOMAVIRUS; CLINICAL-PRACTICE; CONCEPTUAL-MODEL; RISK AB Decision-analytic models are increasingly used to inform health policy decisions. These models synthesize available data on disease burden and intervention effectiveness to project estimates of the long-term consequences of care, which are often absent when clinical or policy decisions must be made. While models have been influential in informing US cancer screening guidelines under ideal conditions, incorporating detailed data on real-world screening practice has been limited given the complexity of screening processes and behaviors throughout diverse health delivery systems in the United States. We describe the synergies that exist between decision-analytic models and health care utilization data that are increasingly accessible through research networks that assemble data from the growing number of electronic medical record systems. In particular, we present opportunities to enrich cancer screening models by grounding analyses in real-world data with the goals of projecting the harms and benefits of current screening practices, evaluating the value of existing and new technologies, and identifying the weakest links in the cancer screening process where efforts for improvement may be most productively focused. We highlight the example of the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR), a collaboration to harmonize and analyze screening process and outcomes data on breast, colorectal, and cervical cancers across seven research centers. The pairing of models with such data can create more robust models to not only better inform policy but also inform health care systems about best approaches to improve the provision of cancer screening in the United States. C1 [Kim, Jane J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dept Med, Lebanon, NH USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA. [Sprague, Brian L.] Univ Vermont, Dept Surg, Burlington, VT 05405 USA. [Sprague, Brian L.] Univ Vermont, Ctr Canc, Burlington, VT USA. [Stout, Natasha K.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02115 USA. [Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Alagoz, Oguzhan] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI USA. [Trentham-Dietz, Amy] Univ Wisconsin, Populat Hlth Sci & Carbone Canc Ctr, Madison, WI USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Pruitt, Sandi L.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75230 USA. [Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA. RP Kim, JJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. EM jkim@hsph.harvard.edu NR 24 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD FEB PY 2016 VL 108 IS 2 AR djv316 DI 10.1093/jnci/djv316 PG 5 WC Oncology SC Oncology GA DF2EP UT WOS:000371153900008 ER PT J AU Meeks, HD Song, HL Michailidou, K Bolla, MK Dennis, J Wang, Q Barrowdale, D Frost, D McGuffog, L Ellis, S Feng, BJ Buys, SS Hopper, JL Southey, MC Tesoriero, A James, PA Bruinsma, F Campbell, IG Broeks, A Schmidt, MK Hogervorst, FBL Beckman, MW Fasching, PA Fletcher, O Johnson, N Sawyer, EJ Riboli, E Banerjee, S Menon, U Tomlinson, I Burwinkel, B Hamann, U Marme, F Rudolph, A Janavicius, R Tihomirova, L Tung, N Garber, J Cramer, D Terry, KL Poole, EM Tworoger, SS Dorfling, CM van Rensburg, EJ Godwin, AK Guenel, P Truong, T Stoppa-Lyonnet, D Damiola, F Mazoyer, S Sinilnikova, OM Isaacs, C Maugard, C Bojesen, SE Flyger, H Gerdes, AM Hansen, TVO Jensen, A Kjaer, SK Hogdall, C Hogdall, E Pedersen, IS Thomassen, M Benitez, J Gonzalez-Neira, A Osorio, A de la Hoya, M Segura, PP Diez, O Lazaro, C Brunet, J Anton-Culver, H Eunjung, L John, EM Neuhausen, SL Ding, YC Castillo, D Weitzel, JN Ganz, PA Nussbaum, RL Chan, SB Karlan, BY Lester, J Wu, A Gayther, S Ramus, SJ Sieh, W Whittermore, AS Monteiro, ANA Phelan, CM Terry, MB Piedmonte, M Offit, K Robson, M Levine, D Moysich, KB Cannioto, R Olson, SH Daly, MB Nathanson, KL Domchek, SM Lu, KH Liang, D Hildebrant, MAT Ness, R Modugno, F Pearce, L Goodman, MT Thompson, PJ Brenner, H Butterbach, K Meindl, A Hahnen, E Wappenschmidt, B Brauch, H Bruning, T Blomqvist, C Khan, S Nevanlinna, H Pelttari, LM Aittomaki, K Butzow, R Bogdanova, NV Dork, T Lindblom, A Margolin, S Rantala, J Kosma, VM Mannermaa, A Lambrechts, D Neven, P Claes, KBM Van Maerken, T Chang-Claude, J Flesch-Janys, D Heitz, F Varon-Mateeva, R Peterlongo, P Radice, P Viel, A Barile, M Peissel, B Manoukian, S Montagna, M Oliani, C Peixoto, A Teixeira, MR Collavoli, A Hallberg, E Olson, JE Goode, EL Hart, SN Shimelis, H Cunningham, JM Giles, GG Milne, RL Healey, S Tucker, K Haiman, CA Henderson, BE Goldberg, MS Tischkowitz, M Simard, J Soucy, P Eccles, DM Le, N Borresen-Dale, AL Kristensen, V Salvesen, HB Bjorge, L Bandera, EV Risch, H Zheng, W Beeghly-Fadiel, A Cai, H Pylkas, K Tollenaar, RAEM van der Ouweland, AMW Andrulis, IL Knight, JA Narod, S Devilee, P Winqvist, R Figueroa, J Greene, MH Mai, PL Loud, JT Garcia-Closas, M Schoemaker, MJ Czene, K Darabi, H McNeish, I Siddiquil, N Glasspool, R Kwong, A Park, SK Teo, SH Yoon, SY Matsuo, K Hosono, S Woo, YL Gao, YT Foretova, L Singer, CF Rappaport-Feurhauser, C Friedman, E Laitman, Y Rennert, G Imyanitov, EN Hulick, PJ Olopade, OI Senter, L Olah, E Doherty, JA Schildkraut, J Koppert, LB Kiemeney, LA Massuger, LFAG Cook, LS Pejovic, T Li, JM Borg, A Ouml;fverholm, A Rossing, MA Wentzensen, N Henriksson, K Cox, A Cross, SS Pasini, BJ Shah, M Kabisch, M Torres, D Jakubowska, A Lubinski, J Gronwald, J Agnarsson, BA Kupryjanczyk, J Moes-Sosnowska, J Fostira, F Konstantopoulou, I Slager, S Jones, M Antoniou, AC Berchuck, A Swerdlow, A Chenevix-Trench, G Dunning, AM Pharoah, PDP Hall, P Easton, DF Couch, FJ Spurdle, AB Goldgar, DE AF Meeks, Huong D. Song, Honglin Michailidou, Kyriaki Bolla, Manjeet K. Dennis, Joe Wang, Qin Barrowdale, Daniel Frost, Debra McGuffog, Lesley Ellis, Steve Feng, Bingjian Buys, Saundra S. Hopper, John L. Southey, Melissa C. Tesoriero, Andrea James, Paul A. Bruinsma, Fiona Campbell, Ian G. Broeks, Annegien Schmidt, Marjanka K. Hogervorst, Frans B. L. Beckman, Matthias W. Fasching, Peter A. Fletcher, Olivia Johnson, Nichola Sawyer, Elinor J. Riboli, Elio Banerjee, Susana Menon, Usha Tomlinson, Ian Burwinkel, Barbara Hamann, Ute Marme, Frederik Rudolph, Anja Janavicius, Ramunas Tihomirova, Laima Tung, Nadine Garber, Judy Cramer, Daniel Terry, Kathryn L. Poole, Elizabeth M. Tworoger, Shelley S. Dorfling, Cecilia M. van Rensburg, Elizabeth J. Godwin, Andrew K. Guenel, Pascal Truong, Therese Stoppa-Lyonnet, Dominique Damiola, Francesca Mazoyer, Sylvie Sinilnikova, Olga M. Isaacs, Claudine Maugard, Christine Bojesen, Stig E. Flyger, Henrik Gerdes, Anne-Marie Hansen, Thomas V. O. Jensen, Allen Kjaer, Susanne K. Hogdall, Claus Hogdall, Estrid Pedersen, Inge Sokilde Thomassen, Mads Benitez, Javier Gonzalez-Neira, Anna Osorio, Ana de la Hoya, Miguel Perez Segura, Pedro Diez, Orland Lazaro, Conxi Brunet, Joan Anton-Culver, Hoda Eunjung, Lee John, Esther M. Neuhausen, Susan L. Ding, Yuan Chun Castillo, Danielle Weitzel, Jeffrey N. Ganz, Patricia A. Nussbaum, Robert L. Chan, Salina B. Karlan, Beth Y. Lester, Jenny Wu, Anna Gayther, Simon Ramus, Susan J. Sieh, Weiva Whittermore, Alice S. Monteiro, Alvaro N. A. Phelan, Catherine M. Terry, Mary Beth Piedmonte, Marion Offit, Kenneth Robson, Mark Levine, Douglas Moysich, Kirsten B. Cannioto, Rikki Olson, Sara H. Daly, Mary B. Nathanson, Katherine L. Domchek, Susan M. Lu, Karen H. Liang, Dong Hildebrant, Michelle A. T. Ness, Roberta Modugno, Francesmary Pearce, Leigh Goodman, Marc T. Thompson, Pamela J. Brenner, Hermann Butterbach, Katja Meindl, Alfons Hahnen, Eric Wappenschmidt, Barbara Brauch, Hiltrud Bruening, Thomas Blomqvist, Carl Khan, Sofia Nevanlinna, Heli Pelttari, Liisa M. Aittomaeki, Kristiina Butzow, Ralf Bogdanova, Natalia V. Doerk, Thilo Lindblom, Annika Margolin, Sara Rantala, Johanna Kosma, Veli-Matti Mannermaa, Arto Lambrechts, Diether Neven, Patrick Claes, Kathleen B. M. Van Maerken, Tom Chang-Claude, Jenny Flesch-Janys, Dieter Heitz, Florian Varon-Mateeva, Raymonda Peterlongo, Paolo Radice, Paolo Viel, Alessandra Barile, Monica Peissel, Bernard Manoukian, Siranoush Montagna, Marco Oliani, Cristina Peixoto, Ana Teixeira, Manuel R. Collavoli, Anita Hallberg, Emily Olson, Janet E. Goode, Ellen L. Hart, Steven N. Shimelis, Hermela Cunningham, Julie M. Giles, Graham G. Milne, Roger L. Healey, Sue Tucker, Kathy Haiman, Christopher A. Henderson, Brian E. Goldberg, Mark S. Tischkowitz, Marc Simard, Jacques Soucy, Penny Eccles, Diana M. Le, Nhu Borresen-Dale, Anne-Lise Kristensen, Vessela Salvesen, Helga B. Bjorge, Line Bandera, Elisa V. Risch, Harvey Zheng, Wei Beeghly-Fadiel, Alicia Cai, Hui Pylkas, Katri Tollenaar, Robert A. E. M. van der Ouweland, Ans M. W. Andrulis, Irene L. Knight, Julia A. Narod, Steven Devilee, Peter Winqvist, Robert Figueroa, Jonine Greene, Mark H. Mai, Phuong L. Loud, Jennifer T. Garcia-Closas, Montserrat Schoemaker, Minouk J. Czene, Kamila Darabi, Hatef McNeish, Iain Siddiquil, Nadeem Glasspool, Rosalind Kwong, Ava Park, Sue K. Teo, Soo Hwang Yoon, Sook-Yee Matsuo, Keitaro Hosono, Satoyo Woo, Yin Ling Gao, Yu-Tang Foretova, Lenka Singer, Christian F. Rappaport-Feurhauser, Christine Friedman, Eitan Laitman, Yael Rennert, Gad Imyanitov, Evgeny N. Hulick, Peter J. Olopade, Olufunmilayo I. Senter, Leigha Olah, Edith Doherty, Jennifer A. Schildkraut, Joellen Koppert, Linetta B. Kiemeney, Lambertus A. Massuger, Leon F. A. G. Cook, Linda S. Pejovic, Tanja Li, Jingmei Borg, Ake Ofverholm, Anna Rossing, Mary Anne Wentzensen, Nicolas Henriksson, Karin Cox, Angela Cross, Simon S. Pasini, Barbara J. Shah, Mitul Kabisch, Maria Torres, Diana Jakubowska, Anna Lubinski, Jan Gronwald, Jacek Agnarsson, Bjarni A. Kupryjanczyk, Jolanta Moes-Sosnowska, Joanna Fostira, Florentia Konstantopoulou, Irene Slager, Susan Jones, Michael Antoniou, Antonis C. Berchuck, Andrew Swerdlow, Anthony Chenevix-Trench, Georgia Dunning, Alison M. Pharoah, Paul D. P. Hall, Per Easton, Douglas F. Couch, Fergus J. Spurdle, Amanda B. Goldgar, David E. CA EMBRACE kConFab Investigators Australia Ovarian Canc Study Grp HEBON GEMO Study Collaborators OCGN PRostate Canc Assoc Grp TI BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GERM-LINE MUTATION; PANCREATIC-CANCER; SUSCEPTIBILITY GENE; DNA RECOMBINATION; ESTROGEN-RECEPTOR; FAMILY-HISTORY; FANCONI-ANEMIA; LOCI; CONSORTIUM AB Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations. C1 [Meeks, Huong D.; Goldgar, David E.] Univ Utah, Huntsman Canc Inst, Canc Control & Populat Sci, Salt Lake City, UT USA. [Song, Honglin; Pasini, Barbara J.; Shah, Mitul; Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England. [Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Barrowdale, Daniel; Frost, Debra; McGuffog, Lesley; Ellis, Steve; Antoniou, Antonis C.; Pharoah, Paul D. P.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Feng, Bingjian; Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA. [Buys, Saundra S.] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.; Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Tesoriero, Andrea] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. [kConFab Investigators] KConFab Kathleen Cuningham Consortium Res Familia, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [James, Paul A.] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia. [James, Paul A.] Univ Melbourne, Dept Oncol, Melbourne, Vic, Australia. [Bruinsma, Fiona; Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Campbell, Ian G.] Univ Melbourne, Peter MacCallum Canc Ctr, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia. [Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia. [Australia Ovarian Canc Study Grp] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia. [Broeks, Annegien; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [HEBON] Netherlands Canc Inst, Hereditary Breast & Ovarian Canc Res Grp Netherla, Coordinating Ctr, Amsterdam, Netherlands. [Beckman, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynaecol & Ostetr, D-91054 Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Fletcher, Olivia; Johnson, Nichola; Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Fletcher, Olivia; Johnson, Nichola; Swerdlow, Anthony] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Sawyer, Elinor J.] Guys Hosp, Kings Coll London, Div Canc Studies, Res Oncol, London SE1 9RT, England. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Banerjee, Susana] Royal Marsden NHS Fdn Trust, London, England. [Menon, Usha] Univ Coll London Elizabeth Garrett Anderson EGA, Inst Womens Hlth, Womens Canc, London, England. [Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England. [Burwinkel, Barbara] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany. [Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany. [Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany. [Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany. [Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Vilnius, Lithuania. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA. [Cramer, Daniel; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.; Spurdle, Amanda B.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.; Spurdle, Amanda B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Guenel, Pascal; Truong, Therese] Natl Inst Hlth & Med Res, Ctr Res Epidemiol & Populat Hlth CESP, Environm Epidemiol Canc, INSERM,U1018, Villejuif, France. [Guenel, Pascal; Truong, Therese] Univ Paris Sud, Villejuif, France. [GEMO Study Collaborators] UNICANCER Genet Grp, GEMO Study Natl Canc Genet Network, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, Paris, France. [Stoppa-Lyonnet, Dominique] INSERM, U830, Inst Curie, Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.] Univ Lyon, Ctr Rech Cancerol Lyon, INSERM,U1052, CNRS UMR 5286, Lyon, France. [Sinilnikova, Olga M.] Hosp Civils Pyon, Ctr Leon Berard, Unite Mixte Genet Constitutionelle Canc Frequents, Lyon, France. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Maugard, Christine] Hop Univ Strasbourg, CHRU Nouvel, Lab Diagnost Genet, Hop Civil, Strasbourg, France. [Maugard, Christine] Hop Univ Strasbourg, CHRU Nouvel, Serv Oncohematol, Hop Civil, Strasbourg, France. [Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark. 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[Fostira, Florentia; Konstantopoulou, Irene] Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, Inst Nucl & Radiol Sci & Technol, Energy & Safety, Athens, Greece. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Goldgar, DE (reprint author), Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA. EM david.goldgar@hsc.utah.edu RI Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; Knight, Julia/A-6843-2012; Teixeira, Manuel/E-4885-2011; Teo, Soo-hwang/H-2353-2014; Zheng, Wei/O-3351-2013; Li, Jingmei/I-2904-2012; Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; Bruning, Thomas/G-8120-2015; Andrulis, Irene/E-7267-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Osorio, Ana/I-4324-2014; Woo, Yin Ling/B-5198-2010; Dork, Thilo/J-8620-2012 OI Dunning, Alison Margaret/0000-0001-6651-7166; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; Glasspool, Rosalind/0000-0002-5000-1680; Schoemaker, Minouk/0000-0001-8403-2234; Cox, Angela/0000-0002-5138-1099; Ramus, Susan/0000-0003-0005-7798; Barrowdale, Daniel/0000-0003-1661-3939; Khan, Sofia/0000-0003-4185-8882; Brunet, Joan/0000-0003-1945-3512; Teixeira, Manuel/0000-0002-4896-5982; Zheng, Wei/0000-0003-1226-070X; Li, Jingmei/0000-0001-8587-7511; Gronwald, Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; Bruning, Thomas/0000-0001-9560-5464; Osorio, Ana/0000-0001-8124-3984; Woo, Yin Ling/0000-0003-1742-1066; FU Government of Canada through Genome Canada; Canadian Institutes of Health Research; Ministere de l'Economie, de l'Innovation et des Exportations du Quebec through Genome Quebec; National Health and Medical Research Council (NHMRC) Senior Research Fellowship; Australian NHMRC Project [1010719]; National Institutes of Health (NIH) [CA128978, CA116167]; NIH specialized program of research excellence in breast cancer [P50 CA116201]; Breast Cancer Research Foundation; Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) data management and analysis through Cancer Research-UK grant [C12292/A11174]; Cancer Research UK [C1287/A10118, C1287/A12014, C1287/A 10710, C12292/ A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/ A10692, C8197/A16565]; European Community's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]; European Union COST programme [BM0606]; Ovarian Cancer Research Fund [PPD/RPCI.07]; US National Cancer Institute Genetic Associations and Mechanisms in Oncology (GAME-ON) Post-Genome Wide Association Study (GWAS) Initiative [U19-CA148112]; Wellcome Trust [076113]; European Community's Seventh Framework Programme (COGS) [223175 (HEALTH-F2-2009-223175)]; National Institutes of Health [CA128978]; Post-Cancer GWAS initiative (GAME-ON initiative) [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure; Breast Cancer Research Foundation,; Ovarian Cancer Research Fund FX This work was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research and the Ministere de l'Economie, de l'Innovation et des Exportations du Quebec through Genome Quebec.; Amanda Spurdle is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship, and aspects of this research were funded by Australian NHMRC Project grant ID #1010719. This work was also supported in part by National Institutes of Health (NIH) grants CA128978 and CA116167, an NIH specialized program of research excellence in breast cancer to the Mayo Clinic (P50 CA116201), and the Breast Cancer Research Foundation. The The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) data management and analysis is funded through Cancer Research-UK grant C12292/A11174. Breast Cancer Association Consortium (BCAC) data management was funded by Cancer Research UK (C1287/A10118 and C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175). BCAC meetings have been funded by the European Union COST programme (BM0606). Ovarian Cancer Association Consortium (OCAC) is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute Genetic Associations and Mechanisms in Oncology (GAME-ON) Post-Genome Wide Association Study (GWAS) Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. A full list of the investigators who contributed to the generation of the data is available at http://www.wtccc.org.uk/. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by the Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute.; Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/ A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/ A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. NR 54 TC 1 Z9 1 U1 5 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD FEB PY 2016 VL 108 IS 2 AR djv315 DI 10.1093/jnci/djv315 PG 10 WC Oncology SC Oncology GA DF2EP UT WOS:000371153900007 ER PT J AU Koenig, KM Ong, KL Lau, EC Vail, TP Berry, DJ Rubash, HE Kurtz, S Bozic, KJ AF Koenig, Karl M. Ong, Kevin L. Lau, Edmund C. Vail, Thomas P. Berry, Daniel J. Rubash, Harry E. Kurtz, Steven Bozic, Kevin J. TI The Use of Hyaluronic Acid and Corticosteroid Injections Among Medicare Patients With Knee Osteoarthritis SO JOURNAL OF ARTHROPLASTY LA English DT Article DE hyaluronic acid; corticosteroid injections; osteoarthritis; knee osteoarthritis; intra-articular injections ID METAANALYSIS; VISCOSUPPLEMENTATION AB Introduction: Hyaluronic acid (HA) and corticosteroid (CS) injections are frequently used in the management of osteoarthritis (OA) of the knee, despite a lack of strong evidence supporting their efficacy in the literature. The purpose of this study is to evaluate trends in HA and CS usage in Medicare patients over the past 15 years. Methods: The Medicare 5% national sample database was used to identify 581,022 patients (representing an estimated 11.6 million) with a diagnosis of knee OA between 1999 and 2013. Results: The percentage of newly diagnosed knee OA patients who received any injection trended from 39% in 1999 to 47% in 2006 and then declined to 37.5% in 2013. However, the mean number of injections per newly diagnosed OA patient nearly doubled from 0.27 to 0.45 for CS and from 0.18 to 0.36 for HA. Among those having both HA and CS injections, 69% had CS as first-line treatment, whereas 31% had HA first. Conclusion: The percentage of newly diagnosed knee OA patients receiving injections peaked in 2007 and then decreased steadily through 2013, as did the proportion of patients receiving HA injections as first-line therapy. However, the number of injections per patient has increased significantly over the past 15 years in both groups. C1 [Koenig, Karl M.] Dartmouth Hitchcock Med Ctr, Dept Orthopaed Surg, Lebanon, NH 03766 USA. [Ong, Kevin L.; Kurtz, Steven] Exponent Inc, Philadelphia, PA USA. [Lau, Edmund C.] Exponent Inc, Menlo Pk, CA USA. [Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. [Berry, Daniel J.; Kurtz, Steven] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. [Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bozic, Kevin J.] Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, 1400 Barbara Jordan Blvd,Suite 1-114, Austin, TX 78723 USA. RP Bozic, KJ (reprint author), Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, 1400 Barbara Jordan Blvd,Suite 1-114, Austin, TX 78723 USA. NR 10 TC 3 Z9 3 U1 0 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD FEB PY 2016 VL 31 IS 2 BP 351 EP 355 DI 10.1016/j.arth.2015.08.024 PG 5 WC Orthopedics SC Orthopedics GA DE5HS UT WOS:000370662700002 PM 26421601 ER PT J AU Gaziano, JM Concato, J Brophy, M Fiore, L Pyarajan, S Breeling, J Whitbourne, S Deen, J Shannon, C Humphries, D Guarino, P Aslan, M Anderson, D LaFleur, R Hammond, T Schaa, K Moser, J Huang, G Muralidhar, S Przygodzki, R O'Leary, TJ AF Gaziano, John Michael Concato, John Brophy, Mary Fiore, Louis Pyarajan, Saiju Breeling, James Whitbourne, Stacey Deen, Jennifer Shannon, Colleen Humphries, Donald Guarino, Peter Aslan, Mihaela Anderson, Daniel LaFleur, Rene Hammond, Timothy Schaa, Kendra Moser, Jennifer Huang, Grant Muralidhar, Sumitra Przygodzki, Ronald O'Leary, Timothy J. TI Million Veteran Program: A mega-biobank to study genetic influences on health and disease SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Genomics; Cohort studies; Genotyping; Exome sequencing; Whole-genome sequencing; Veterans ID HAPLOTYPE MAP; HUMAN GENOME; EPIDEMIOLOGY; CONSORTIUM AB Objective: To describe the design and ongoing conduct of the Million Veteran Program (MW), as an observational cohort study and mega-biobank in the Department of Veterans Affairs (VA) health care system. Study Design and Setting: Data are being collected from participants using questionnaires, the VA electronic health record, and a blood sample for genomic and other testing. Several ongoing projects are linked to MVP, both as peer-reviewed research studies and as activities to help develop an infrastructure for future, broad-based research uses. Results: Formal planning for MVP commenced in 2009; the protocol was approved in 2010, and enrollment began in 2011. As of August 3, 2015, and with a steady state of approximate to 50 recruiting sites nationwide, N = 397,104 veterans have been enrolled. Among N = 199,348 with currently available genotyping data, most participants (as expected) are male (92.0%) between the ages of 50 and 69 years (55.0%). On the basis of self-reported race, white (77.2%) and African American (13.5%) populations are well represented. Conclusions: By helping to promote the future integration of genetic testing in health care delivery, including clinical decision making, the MVP is designed to contribute to the development of precision medicine. Published by Elsevier Inc. C1 [Gaziano, John Michael; Brophy, Mary; Fiore, Louis; Pyarajan, Saiju; Breeling, James; Whitbourne, Stacey; Deen, Jennifer; Shannon, Colleen; Humphries, Donald] VA Boston Healthcare Syst, MAVERIC, VA Cooperat Studies Program, 150 S Huntington Ave, Boston, MA 02130 USA. [Gaziano, John Michael] Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. [Concato, John; Guarino, Peter; Aslan, Mihaela; Anderson, Daniel; LaFleur, Rene] VA Connecticut Healthcare Syst, CERC, VA Cooperat Studies Program, 950 Campbell Ave,151B, West Haven, CT 06516 USA. [Concato, John; Guarino, Peter; Aslan, Mihaela] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Brophy, Mary; Fiore, Louis] Boston Univ, Sch Med, Dept Internal Med, Boston, MA 02118 USA. [Hammond, Timothy; Schaa, Kendra; Moser, Jennifer; Huang, Grant; Muralidhar, Sumitra; Przygodzki, Ronald; O'Leary, Timothy J.] Vet Hlth Adm, Off Res & Dev, 810 Vermont Ave NW,10P9, Washington, DC 20420 USA. [Schaa, Kendra] Medstar Washington Hosp Ctr, 110 Irving St NW, Washington, DC 20010 USA. RP Concato, J (reprint author), VA Connecticut Healthcare Syst, CERC, VA Cooperat Studies Program, 950 Campbell Ave,151B, West Haven, CT 06516 USA.; Concato, J (reprint author), Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. EM john.concato@va.gov OI Concato, John/0000-0003-2846-0503; Przygodzki, Ronald/0000-0002-1238-262X FU Office of Research and Development, Department of Veterans Affairs FX The research was funded by the Office of Research and Development, Department of Veterans Affairs. NR 17 TC 13 Z9 14 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 2016 VL 70 BP 214 EP 223 DI 10.1016/j.jclinepi.2015.09.016 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DE5NE UT WOS:000370676900025 PM 26441289 ER PT J AU Chen, S Whitson, H Quinones, A Thielke, S AF Chen, Sunny Whitson, Heather Quinones, Ana Thielke, Stephen TI Comparative health and self-rated health are equivalently associated with health indicators among older adults SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Letter ID MORTALITY; ASSESSMENTS C1 [Chen, Sunny; Thielke, Stephen] Puget Sound VA Med Ctr, Geriatr Res Educ & Clin Ctr, GRECC S-182,1660 South Columbian Way, Seattle, WA 98108 USA. [Whitson, Heather] Duke Univ, Med Ctr, Dept Med Geriatr & Ophthalmol, DUMC Box 3003, Durham, NC 27710 USA. [Whitson, Heather] Duke Univ, Med Ctr, Aging Ctr, DUMC Box 3003, Durham, NC 27710 USA. [Whitson, Heather] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, 508 Fulton St,3rd Floor GRECC, Durham, NC 27705 USA. [Quinones, Ana] Oregon Hlth & Sci Univ, Sch Publ Hlth, 3181 SW Sam Jackson Pk Rd,Mail Code CB669, Portland, OR 97239 USA. [Quinones, Ana] Oregon Hlth & Sci Univ, Portland VA Med Ctr, 3181 SW Sam Jackson Pk Rd,Mail Code CB669, Portland, OR 97239 USA. [Thielke, Stephen] Univ Washington, Dept Psychiat & Behav Sci, 1959 Pacific St,Box 356560, Seattle, WA 98195 USA. RP Thielke, S (reprint author), Puget Sound VA Med Ctr, Geriatr Res Educ & Clin Ctr, GRECC S-182,1660 South Columbian Way, Seattle, WA 98108 USA.; Thielke, S (reprint author), Univ Washington, Dept Psychiat & Behav Sci, 1959 Pacific St,Box 356560, Seattle, WA 98195 USA. EM sthielke@u.washington.edu OI Quinones, Ana/0000-0001-6554-7734 FU NHLBI NIH HHS [R25 HL105430, R25HL105430]; NIA NIH HHS [R01 AG043438, K23-AG-032867, K23 AG032867, P30-AG-028716, P30 AG028716]; NIMH NIH HHS [K23 MH093591] NR 8 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 2016 VL 70 BP 279 EP 280 DI 10.1016/j.jclinepi.2015.08.022 PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DE5NE UT WOS:000370676900041 PM 26386324 ER PT J AU Lessard, SJ Rivas, DA So, K Koh, HJ Queiroz, AL Hirshman, MF Fielding, RA Goodyear, LJ AF Lessard, Sarah J. Rivas, Donato A. So, Kawai Koh, Ho-Jin Queiroz, Andre Lima Hirshman, Michael F. Fielding, Roger A. Goodyear, Laurie J. TI The AMPK-related kinase SNARK regulates muscle mass and myocyte survival SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DIFFERENT FIBER TYPES; SKELETAL-MUSCLE; SARCOPENIC OBESITY; MYOSIN PHOSPHATASE; LEAN MASS; NUAK2; IDENTIFICATION; MORTALITY; APOPTOSIS; GROWTH AB The maintenance of skeletal muscle mass is critical for sustaining health; however, the mechanisms responsible for muscle loss with aging and chronic diseases, such as diabetes and obesity, are poorly understood. We found that expression of a member of the AMPK-related kinase family, the SNF1-AMPK-related kinase (SNARK, also known as NUAK2), increased with muscle cell differentiation. SNARK expression increased in skeletal muscles from young mice exposed to metabolic stress and in muscles from healthy older human subjects. The regulation of SNARK expression in muscle with differentiation and physiological stress suggests that SNARK may function in the maintenance of muscle mass. Consistent with this hypothesis, decreased endogenous SNARK expression (using siRNA) in cultured muscle cells resulted in increased apoptosis and decreased cell survival under conditions of metabolic stress. Likewise, muscle-specific transgenic animals expressing a SNARK dominant-negative inactive mutant (SDN) had increased myonuclear apoptosis and activation of apoptotic mediators in muscle. Moreover, animals expressing SDN had severe, age-accelerated muscle atrophy and increased adiposity, consistent with sarcopenic obesity. Reduced SNARK activity, in vivo and in vitro, caused downregulation of the Rho kinase signaling pathway, a key mediator of cell survival. These findings reveal a critical role for SNARK in myocyte survival and the maintenance of muscle mass with age. C1 [Lessard, Sarah J.; So, Kawai; Koh, Ho-Jin; Queiroz, Andre Lima; Hirshman, Michael F.; Goodyear, Laurie J.] Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, 75 Francis St, Boston, MA 02115 USA. [Lessard, Sarah J.; Koh, Ho-Jin; Goodyear, Laurie J.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Lessard, Sarah J.; Koh, Ho-Jin; Goodyear, Laurie J.] Harvard Univ, Sch Med, One Joslin Pl, Boston, MA 02215 USA. [Rivas, Donato A.; Fielding, Roger A.] Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, 75 Francis St, Boston, MA 02115 USA.; Goodyear, LJ (reprint author), Harvard Univ, Sch Med, One Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu OI Rivas, Donato/0000-0002-4500-6233 FU NIH [AR42238, DK068626, P30 DK036836, P30DK040561]; Joslin Diabetes Center Diabetes Research Center [P30 DK36836]; American Physiological Society (Physiological Genomics); Canadian Diabetes Association; US Department of Agriculture (USDA) [58-1950-0014] FX This work was supported by NIH grants to L.J. Goodyear (AR42238 and DK068626) and the Joslin Diabetes Center Diabetes Research Center (P30 DK36836). H.J. Koh was supported by NIH grants (P30 DK036836 and P30DK040561). S.J. Lessard was supported by postdoctoral fellowships from the American Physiological Society (Physiological Genomics) and the Canadian Diabetes Association. This material is based upon the work supported by the US Department of Agriculture (USDA), under agreement 58-1950-0014. NR 44 TC 3 Z9 3 U1 2 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2016 VL 126 IS 2 BP 560 EP 570 DI 10.1172/JCI79197 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DE5NI UT WOS:000370677300018 PM 26690705 ER PT J AU Creech, SK Swift, R Zlotnick, C Taft, C Street, AE AF Creech, Suzannah K. Swift, Robert Zlotnick, Caron Taft, Casey Street, Amy E. TI Combat Exposure, Mental Health, and Relationship Functioning Among Women Veterans of the Afghanistan and Iraq Wars SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE combat; women veterans; family functioning; relationships; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-GUARD SOLDIERS; FAMILY ADJUSTMENT; ALCOHOL MISUSE; PTSD SYMPTOMS; RELATIONSHIP SATISFACTION; IDENTIFICATION TEST; COUPLE ADJUSTMENT; OEF/OIF VETERANS; COMPETENCE SCALE AB This study examined associations between warzone exposures to combat with postdeployment relationship and family functioning in 134 women who deployed to the conflicts in Afghanistan and Iraq. Survey invitations were sent by mail to 600 randomly selected women who experienced recent military deployments and were residing in New England. The web-based survey included measures of combat exposure, posttraumatic stress disorder (PTSD) symptoms, alcohol misuse, postdeployment stress exposure, family functioning, intimate relationship satisfaction, and parenting. Multivariate linear regression with bootstrapping estimates of indirect effects was used to examine whether PTSD symptoms and alcohol misuse accounted for associations between women's combat exposure and their postdeployment relationship and family functioning. Results indicated that women's PTSD symptoms had a direct and negative effect on postdeployment family functioning and on intimate relationship satisfaction. There was no direct association between combat exposure or alcohol misuse with any of the family or relationship functioning variables, however, the indirect association from combat to postdeployment family functioning (b = -.13, SE = 0.07, 95% confidence interval [CI]: -33, -.03) and intimate relationship satisfaction (b = -.25, SE = 0.18, 95% CI: -.79, -.001) was significant and negative through its association with PTSD symptoms. Parenting satisfaction was significantly and negatively associated with postdeployment stress only. This study is among the first to characterize the impact of deployment experiences on women veterans' relationship and family functioning. Findings suggest that women veterans who have been exposed to combat and who have higher levels of PTSD symptoms may benefit from relationship and family focused services after deployment. C1 [Creech, Suzannah K.] Providence VA Med Ctr, Providence, RI USA. [Creech, Suzannah K.] VHA VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX USA. [Creech, Suzannah K.; Swift, Robert; Zlotnick, Caron] Brown Univ, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Swift, Robert] Brown Univ, Providence VA Med Ctr, Providence, RI 02912 USA. [Zlotnick, Caron] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Taft, Casey] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Taft, Casey] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Street, Amy E.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Womens Hlth Sci Div,Natl Ctr PTSD, Boston, MA 02215 USA. [Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Creech, SK (reprint author), VHA VISN 17 Ctr Excellence, 4800 Mem Dr 151 C, Waco, TX 76711 USA. EM suzannah.creech@va.gov OI Creech, Suzannah/0000-0002-6582-1673 FU VHA VISN 1 Career Development Award [V1CDA2011-11]; Department of Veterans Affairs FX Suzannah Creech's effort on this project was supported by VHA VISN 1 Career Development Award Number V1CDA2011-11, with additional support from the Department of Veterans Affairs. The contents of 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 56 TC 2 Z9 2 U1 4 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 EI 1939-1293 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD FEB PY 2016 VL 30 IS 1 BP 43 EP 51 DI 10.1037/fam0000145 PG 9 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA DF1EO UT WOS:000371082000006 PM 26348108 ER PT J AU Morrill, MI Hawrilenko, M Cordova, JV AF Morrill, Melinda Ippolito Hawrilenko, Matt Cordova, James V. TI A Longitudinal Examination of Positive Parenting Following an Acceptance-Based Couple Intervention SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE positive parenting; couples; acceptance; multilevel modeling; fathering ID MARRIAGE CHECKUP; PSYCHOMETRIC PROPERTIES; RELATIONSHIP QUALITY; CHILD RELATIONSHIPS; TRAINING-PROGRAM; MARITAL CONFLICT; FAMILIES; ADJUSTMENT; BEHAVIOR; THERAPY AB Positive parenting practices have been shown to be essential for healthy child development, and yet have also been found to be particularly challenging for parents to enact and maintain. This article explores an innovative approach for increasing positive parenting by targeting specific positive emotional processes within marital relationships. Couple emotional acceptance is a powerful mechanism that has repeatedly been found to improve romantic relationships, but whether these effects extend to the larger family environment is less well understood. The current longitudinal study examined the impact of improved relational acceptance after a couple intervention on mother's and father's positive parenting. Participants included 244 parents (122 couples) in the Marriage Checkup (MC) study, a randomized, controlled, acceptance-based, intervention study. Data indicated that both women and men experienced significantly greater felt acceptance 2 weeks after the MC intervention, treatment women demonstrated greater positive parenting 2 weeks after the intervention, and all treatment participants' positive parenting was better maintained than control couple's 6 months later. Importantly, although mothers' positive parenting was not influenced by different levels of felt acceptance, changes in father's positive parenting were positively associated with changes in felt acceptance. As men felt more accepted by their wives, their levels of positive parenting changed in kind, and this effect on positive parenting was found to be mediated by felt acceptance 2 weeks after the MC. Overall, findings supported the potential benefits of targeting couple acceptance to generate positive cascades throughout the larger family system. C1 [Morrill, Melinda Ippolito] Harvard Univ, Sch Med, Lab Adult Dev, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Hawrilenko, Matt; Cordova, James V.] Clark Univ, Frances L Hiatt Sch Psychol, Worcester, MA 01610 USA. RP Morrill, MI (reprint author), Massachusetts Gen Hosp, 151 Merrimac St,2nd Floor, Boston, MA 02114 USA. EM mimorrill@mgh.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD45281]; National Institute of Aging [R01AG045230] FX Support for this project was provided by a grant (R01HD45281) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to James V. Cordova, and by a grant (R01AG045230) from the National Institute of Aging to Robert J. Waldinger. NR 64 TC 0 Z9 0 U1 5 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 EI 1939-1293 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD FEB PY 2016 VL 30 IS 1 BP 104 EP 113 DI 10.1037/fam0000162 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA DF1EO UT WOS:000371082000012 PM 26551659 ER PT J AU Taylor, KS Kucyi, A Millar, PJ Murai, H Kimmerly, DS Morris, BL Bradley, TD Floras, JS AF Taylor, Keri S. Kucyi, Aaron Millar, Philip J. Murai, Hisayoshi Kimmerly, Derek S. Morris, Beverley L. Bradley, T. Douglas Floras, John S. TI Association between resting-state brain functional connectivity and muscle sympathetic burst incidence SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE microneurography; obstructive sleep apnea; resting-state magnetic resonance imaging; salience network; sympathetic nervous system ID ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; OBSTRUCTIVE SLEEP-APNEA; INDEPENDENT COMPONENT ANALYSIS; AUTONOMIC NERVOUS-SYSTEM; BLOOD-PRESSURE; MACAQUE MONKEYS; INSULAR CORTEX; HEART-FAILURE; CARDIOVASCULAR FUNCTION AB The insula (IC) and cingulate are key components of the central autonomic network and central nodes of the salience network (SN), a set of spatially distinct but temporally correlated brain regions identified with resting-state (task free) functional MRI (rsMRI). To examine the SN's involvement in sympathetic outflow, we tested the hypothesis that individual differences in intrinsic connectivity of the SN correlate positively with resting postganglionic muscle sympathetic nerve activity (MSNA) burst incidence (BI) in subjects without and with obstructive sleep apnea (OSA). Overnight polysomnography, 5-min rsMRI, and fibular MSNA recording were performed in 36 subjects (mean age 57 yr; 10 women, 26 men). Independent component analysis (ICA) of the entire cohort identified the SN as including bilateral IC, pregenual anterior cingulate cortex (pgACC), midcingulate cortex (MCC), and the temporoparietal junction (TPJ). There was a positive correlation between BI and the apnea-hypopnea index (AHI) (P < 0.001), but dual-regression analysis identified no differences in SN functional connectivity between subjects with no or mild OSA (n = 17) and moderate or severe (n = 19) OSA. Correlation analysis relating BI to the strength of connectivity within the SN revealed large (i.e., spatial extent) and strong correlations for the left IC (P < 0.001), right pgACC/MCC (P < 0.006), left TPJ (P < 0.004), thalamus (P < 0.035), and cerebellum (P < 0.013). Indexes of sleep apnea were unrelated to BI and the strength of SN connectivity. There were no relationships between BI and default or sensorimotor network connectivity. This study links connectivity within the SN to MSNA, demonstrating several of its nodes to be key sympathoexcitatory regions. C1 [Taylor, Keri S.; Millar, Philip J.; Murai, Hisayoshi; Kimmerly, Derek S.; Morris, Beverley L.; Bradley, T. Douglas; Floras, John S.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Taylor, Keri S.; Millar, Philip J.; Murai, Hisayoshi; Kimmerly, Derek S.; Morris, Beverley L.; Bradley, T. Douglas; Floras, John S.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. [Kucyi, Aaron] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Kucyi, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kimmerly, Derek S.] Dalhousie Univ, Fac Hlth Profess, Sch Hlth & Human Performance, Halifax, NS, Canada. RP Floras, JS (reprint author), Toronto Gen Hosp, Clin Cardiovasc Physiol Lab, ES6-414,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM john.floras@utoronto.ca FU Heart and Stroke Foundation of Ontario (HSFO) [NA 6407]; Canadian Institutes of Health Research; Bluma Appel International Fellowship of the Mount Sinai Hospital Department of Medicine Research Fund FX This work was supported by a Grant-in-Aid from the Heart and Stroke Foundation of Ontario (HSFO, Grant NA 6407). K. S. Taylor and P. J. Millar are recipients of a Canadian Institutes of Health Research Postdoctoral Fellowship. P. J. Millar also held a Heart and Stroke Foundation of Canada Post-Doctoral Fellowship. H. Murai was supported by a Bluma Appel International Fellowship of the Mount Sinai Hospital Department of Medicine Research Fund. D. S. Kimmerly was supported by a Canadian Institutes of Health Research Postdoctoral Fellowship. T. D. Bradley holds the Clifford Nordal Chair in Sleep Apnea and Rehabilitation Research. J. S. Floras holds the Canada Research Chair in Integrative Cardiovascular Biology. NR 126 TC 1 Z9 1 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB 1 PY 2016 VL 115 IS 2 BP 662 EP 673 DI 10.1152/jn.00675.2015 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DF2EW UT WOS:000371154800005 PM 26538607 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI Ambulatory blood pressure monitoring to diagnose hypertension-an idea whose time has come SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Med, Reno, NV 89557 USA. [Bloch, Michael J.] Renown Inst Heart & Vasc Hlth, Vasc Care, Reno, NV USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. RP Bloch, MJ (reprint author), Univ Nevada, Sch Med, Dept Internal Med, Vasc Care,Renown Heart & Vasc Inst, Reno, NV 89557 USA. EM Michael@bluesprucemed.com NR 7 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD FEB PY 2016 VL 10 IS 2 BP 89 EP 91 DI 10.1016/j.jash.2015.10.010 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DE8MB UT WOS:000370889000001 PM 26654344 ER PT J AU Marshall, AL Levine, M Howell, ML Chang, Y Riklin, E Parry, BA Callahan, RT Okechukwu, I Ayres, AM Nahed, BV Goldstein, JN AF Marshall, A. L. Levine, M. Howell, M. L. Chang, Y. Riklin, E. Parry, B. A. Callahan, R. T. Okechukwu, I. Ayres, A. M. Nahed, B. V. Goldstein, J. N. TI Dose-associated pulmonary complication rates after fresh frozen plasma administration for warfarin reversal SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE blood component transfusion; fresh frozen plasma; pulmonary edema; warfarin ID ACUTE LUNG INJURY; PROTHROMBIN COMPLEX CONCENTRATE; CIRCULATORY OVERLOAD; HEMORRHAGIC COMPLICATIONS; INTRACEREBRAL HEMORRHAGE; TRANSFUSION; ANTICOAGULATION; THERAPY; SUPPORT; TRALI AB Essentials Fresh frozen plasma (FFP) may be associated with a dose-based risk of pulmonary complications. Patients received FFP for warfarin reversal at a large academic hospital over a 3-year period. Almost 20% developed pulmonary complications, and the risk was highest after >3units of FFP. The risk of pulmonary complications remained significant in multivariable analysis. Summary Background Fresh frozen plasma (FFP) is often administered to reverse warfarin anticoagulation. Administration has been associated with pulmonary complications, but it is unclear whether this risk is dose-related. Aims We sought to characterize the incidence and dose relationship of pulmonary complications, including transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI), after FFP administration for warfarin reversal. Methods We performed a structured retrospective review of patients who received FFP for warfarin reversal in the emergency department (ED) of an academic tertiary-care hospital over a 3-year period. Logistic regression was used to explore the relationship between FFP dose and risk of pulmonary events. Results Two hundred and fifty-one patients met the inclusion criteria. Overall, 49 patients (20%) developed pulmonary complications, including 30 (12%) with TACO, two (1%) with TRALI, and 17 (7%) with pulmonary edema not meeting the criteria for TACO. Pulmonary complications were significantly more frequent in those who received >3units of FFP (34.0% versus 15.6%, 95% confidence interval for risk difference 7.9%-8.9%). After stratification by subtype of complication, only the risk of TACO was statistically significant (28.3% versus 7.6%, 95% confidence interval for risk difference 8.2%-16.6%). In multivariable analysis controlling for age, sex, initial systolic blood pressure, and intravenous fluids given in the ED, >3 units of FFP remained a significant risk factor for pulmonary complications (odds ratio2.49, 95% confidence interval1.21-5.13). Conclusions Almost 20% of patients who received FFP for warfarin reversal developed pulmonary complications, primarily TACO, and this risk increased with >3units of FFP. Clinicians should be aware of and prepared to manage these complications. C1 [Marshall, A. L.] Mayo Clin, Rochester, MN USA. [Levine, M.] Univ So Calif, Los Angeles, CA USA. [Howell, M. L.; Chang, Y.; Riklin, E.; Parry, B. A.; Callahan, R. T.; Okechukwu, I.; Ayres, A. M.; Nahed, B. V.; Goldstein, J. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgoldstein@mgh.harvard.edu RI Goldstein, Joshua/H-8953-2016 FU CSL Behring FX The study was entirely planned and performed by our research team. Although funding for the study was obtained in part from a grant from CSL Behring, CSL Behring had no influence on the manuscript at any stage. NR 34 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 14 IS 2 BP 324 EP 330 DI 10.1111/jth.13212 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DE5GM UT WOS:000370659400012 PM 26644327 ER PT J AU Hingorani, A LaMuraglia, GM Henke, P Meissner, MH Loretz, L Zinszer, KM Driver, VR Frykberg, R Carman, TL Marston, W Mills, JL Murad, MH AF Hingorani, Anil LaMuraglia, Glenn M. Henke, Peter Meissner, Mark H. Loretz, Lorraine Zinszer, Kathya M. Driver, Vickie R. Frykberg, Robert Carman, Teresa L. Marston, William Mills, Joseph L., Sr. Murad, Mohammad Hassan TI The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PERIPHERAL ARTERIAL-DISEASE; PRESSURE WOUND THERAPY; LOWER-EXTREMITY AMPUTATION; VACUUM-ASSISTED CLOSURE; CRITICAL LIMB ISCHEMIA; TRANSCUTANEOUS OXYGEN-TENSION; GLOBAL CONSENSUS GUIDELINES; CUSTOM-MADE FOOTWEAR; GROWTH FACTOR-BB AB Background: Diabetes mellitus continues to grow in global prevalence and to consume an increasing amount of health care resources. One of the key areas of morbidity associated with diabetes is the diabetic foot. To improve the care of patients with diabetic foot and to provide an evidence-based multidisciplinary management approach, the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine developed this clinical practice guideline. Methods: The committee made specific practice recommendations using the Grades of Recommendation Assessment, Development, and Evaluation system. This was based on five systematic reviews of the literature. Specific areas of focus included (1) prevention of diabetic foot ulceration, (2) off-loading, (3) diagnosis of osteomyelitis, (4) wound care, and (5) peripheral arterial disease. Results: Although we identified only limited high-quality evidence for many of the critical questions, we used the best available evidence and considered the patients' values and preferences and the clinical context to develop these guidelines. We include preventive recommendations such as those for adequate glycemic control, periodic foot inspection, and patient and family education. We recommend using custom therapeutic footwear in high-risk diabetic patients, including those with significant neuropathy, foot deformities, or previous amputation. In patients with plantar diabetic foot ulcer (DFU), we recommend off-loading with a total contact cast or irremovable fixed ankle walking boot. In patients with a new DFU, we recommend probe to bone test and plain films to be followed by magnetic resonance imaging if a soft tissue abscess or osteomyelitis is suspected. We provide recommendations on comprehensive wound care and various debridement methods. For DFUs that fail to improve (>50% wound area reduction) after a minimum of 4 weeks of standard wound therapy, we recommend adjunctive wound therapy options. In patients with DFU who have peripheral arterial disease, we recommend revascularization by either surgical bypass or endovascular therapy. Conclusions: Whereas these guidelines have addressed five key areas in the care of DFUs, they do not cover all the aspects of this complex condition. Going forward as future evidence accumulates, we plan to update our recommendations accordingly. C1 [Hingorani, Anil] NYU Lutheran Med Ctr, 150 55th St, Brooklyn, NY 11220 USA. [LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [LaMuraglia, Glenn M.] Harvard Univ, Sch Med, Boston, MA USA. [Henke, Peter] Univ Michigan, Ann Arbor, MI 48109 USA. [Meissner, Mark H.] Univ Washington, Seattle, WA 98195 USA. [Loretz, Lorraine] UMass Mem, Worcester, MA USA. [Zinszer, Kathya M.] Geisinger Hlth Syst, Danville, PA USA. [Driver, Vickie R.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Frykberg, Robert] Carl T Hayden Vet Affairs Med Ctr, Phoenix, AZ USA. [Carman, Teresa L.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Marston, William] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Mills, Joseph L., Sr.] Baylor Coll Med, Houston, TX 77030 USA. [Murad, Mohammad Hassan] Mayo Clin, Rochester, MN USA. RP Hingorani, A (reprint author), NYU Lutheran Med Ctr, 150 55th St, Brooklyn, NY 11220 USA. EM ahingorani67@gmail.com OI Mills, Joseph/0000-0002-4955-4384 NR 180 TC 14 Z9 16 U1 5 U2 15 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 FEB PY 2016 VL 63 IS 2 SU S BP 3S EP 21S DI 10.1016/j.jvs.2015.10.003 PG 19 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DE6XK UT WOS:000370777900002 PM 26804367 ER PT J AU Kishnani, PS Dickson, PI Muldowney, L Lee, JJ Rosenberg, A Abichandani, R Bluestone, JA Burton, BK Dewey, M Freitas, A Gavin, D Griebel, D Hogan, M Holland, S Tanpaiboon, P Turka, LA Utz, JJ Wang, YM Whitley, CB Kazi, ZB Pariser, AR AF Kishnani, Priya S. Dickson, Patricia I. Muldowney, Laurie Lee, Jessica J. Rosenberg, Amy Abichandani, Rekha Bluestone, Jeffrey A. Burton, Barbara K. Dewey, Maureen Freitas, Alexandra Gavin, Derek Griebel, Donna Hogan, Melissa Holland, Stephen Tanpaiboon, Pranoot Turka, Laurence A. Utz, Jeanine J. Wang, Yow-Ming Whitley, Chester B. Kazi, Zoheb B. Pariser, Anne R. TI Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Immune tolerance; Lysosomal storage diseases; Enzyme replacement therapy; Inborn errors of metabolism; Neutralizing antibodies; Orphan drugs; Rare diseases ID INFANTILE POMPE DISEASE; FABRY-DISEASE; MUCOPOLYSACCHARIDOSIS-I; INTRAVENOUS IMMUNOGLOBULIN; NEUTRALIZING ANTIBODIES; CLINICAL-OUTCOMES; AGALSIDASE-ALPHA; DISORDERS; EFFICACY; SAFETY AB The US Food and Drug Administration (FDA) and National Organization for Rare Disease (NORD) convened a public workshop titled "Immune Responses to Enzyme Replacement Therapies: Role of Immune Tolerance Induction" to discuss the impact of anti-drug antibodies (ADAs) on efficacy and safety of enzyme replacement therapies (ERTs) intended to treat patients with lysosomal storage diseases (LSDs). Participants in the workshop included FDA staff, clinicians, scientists, patients, industry, and advocacy group representatives. The risks and benefits of implementing prophylactic immune tolerance induction (ITI) to reduce the potential clinical impact of antibody development were considered. Complications due to immune responses to ERT are being recognized with increasing experience and lengths of exposure to ERTs to treat several LSDs. Strategies to mitigate immune responses and to optimize therapies are needed. Discussions during the workshop resulted in the identification of knowledge gaps and future areas of research, as well as the following proposals from the participants: (1) systematic collection of longitudinal data on immunogenicity to better understand the impact of ADAs on long-term clinical outcomes; (2) development of disease-specific biomarkers and outcome measures to assess the effect of ADAs and ITI on efficacy and safety; (3) development of consistent approaches to ADA assays to allow comparisons of immunogenicity data across different products and disease groups, and to expedite reporting of results; (4) establishment of a system to widely share data on antibody titers following treatment with ERTs; (5) identification of components of the protein that are immunogenic so that triggers and components of the immune responses can be targeted in ITI; and (6) consideration of early ITI in patients who are at risk of developing clinically relevant ADA that have been demonstrated to worsen treatment outcomes. Published by Elsevier Inc. C1 [Kishnani, Priya S.; Kazi, Zoheb B.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [Dickson, Patricia I.] Harbor UCLA Med Ctr, Div Med Genet, Los Angeles Biomed Res Inst, Torrance, CA 90505 USA. [Muldowney, Laurie; Lee, Jessica J.; Dewey, Maureen; Griebel, Donna] US FDA, Div Gastroenterol & Inborn Errors Metab Prod, Off New Drugs, CDER, Silver Spring, MD 20993 USA. [Rosenberg, Amy] US FDA, Div Therapeut Proteins, Off Biotechnol Prod, CDER, Silver Spring, MD 20993 USA. [Abichandani, Rekha] Shire, Lexington, MA 02421 USA. [Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Burton, Barbara K.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp, Chicago, IL 60611 USA. [Freitas, Alexandra; Gavin, Derek] Natl Org Rare Disorders, Washington, DC 20036 USA. [Hogan, Melissa] Saving Case & Friends Inc, Thompsons Stn, TN 37179 USA. [Holland, Stephen] Natl MPS Soc, Durham, NC 27709 USA. [Tanpaiboon, Pranoot] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA 02129 USA. [Utz, Jeanine J.; Whitley, Chester B.] Univ Minnesota, Masonic Childrens Hosp, Minneapolis, MN 55455 USA. [Wang, Yow-Ming] US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, OTS,CDER, Silver Spring, MD 20993 USA. [Pariser, Anne R.] US FDA, OTS, CDER, 10903 New Hampshire Ave,W021-4607, Silver Spring, MD 20993 USA. RP Pariser, AR (reprint author), US FDA, OTS, CDER, 10903 New Hampshire Ave,W021-4607, Silver Spring, MD 20993 USA. EM priya.kishnani@duke.edu; pdickson@labiomed.org; laurie.muldowney@fda.hhs.gov; jessica.j.lee@fda.hhs.gov; amy.rosenberg@fda.hhs.gov; rabichan@shire.com; jeff.bluestone@ucsf.edu; bburton@luriechildrens.org; maureen.dewey@fda.hhs.gov; afreitas@rarediseases.org; dgavin@rarediseases.org; donna.griebel@fda.hhs.gov; melissa@savingcase.com; steve.holland@thomsonreuters.com; ptanpaib@childrensnational.org; lturka@partners.org; utz002@umn.edu; yowming.wang@fda.hhs.gov; whitley@umn.edu; zoheb.kazi@dm.duke.edu; anne.pariser@fda.hhs.gov OI Kazi, Zoheb/0000-0002-0447-2764 FU NIAID NIH HHS [R01 AI046643] NR 56 TC 2 Z9 2 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 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 BP 66 EP 83 DI 10.1016/j.ymgme.2015.11.001 PG 18 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100341 PM 26597321 ER PT J AU Balwani, M Burrow, TA Charrow, J Goker-Alpan, O Kaplan, P Kishnani, PS Mistry, P Ruskin, J Weinreb, N AF Balwani, Manisha Burrow, Thomas Andrew Charrow, Joel Goker-Alpan, Ozlem Kaplan, Paige Kishnani, Priya S. Mistry, Pramod Ruskin, Jeremy Weinreb, Neal TI Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Gaucher disease type 1; Eliglustat; Substrate reduction therapy; Enzyme replacement therapy ID ENZYME REPLACEMENT THERAPY; QUALITY-OF-LIFE; ORAL ELIGLUSTAT; NON-INFERIORITY; OPEN-LABEL; IMIGLUCERASE; DIAGNOSIS; REGISTRY; TRIAL; GLUCOCEREBROSIDASE AB In Gaucher disease, deficient activity of acid beta-glucosidase results in accumulation of its substrates, glucosylceramide and glucosylsphingosine, within the lysosomes of cells primarily in the spleen, liver, bone marrow, and occasionally the lung. The multisystem disease is predominantly characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Enzyme replacement therapy with recombinant human acid beta-glucosidase has been the first-line therapy for Gaucher disease type 1 for more than two decades. Eliglustat, a novel oral substrate reduction therapy, was recently approved in the United States and the European Union as a first -line treatment for adults with Gaucher disease type 1. Eliglustat inhibits glucosylceramide synthase, thereby decreasing production of the substrate glucosylceramide and reducing its accumulation. Although existing recommendations for the care of patients with Gaucher disease remain in effect, unique characteristics of eliglustat require additional investigation and monitoring. A panel of physicians with expertise in Gaucher disease and experience with eliglustat in the clinical trials provide guidance regarding the use of eliglustat, including considerations before starting therapy and monitoring of patients on eliglustat therapy. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Balwani, Manisha] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, One Gustave L Levy Pl,Box 1497, New York, NY 10029 USA. [Burrow, Thomas Andrew] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave,MLC 4006, Cincinnati, OH 45229 USA. [Charrow, Joel] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Div Genet Birth Defects & Metab, Dept Pediat,Feinberg Sch Med, 225 East Chicago Ave, Chicago, IL 60611 USA. [Goker-Alpan, Ozlem] O&O Alpan LLC, Lysosomal Disorders Unit, 11212 Waples Mill Rd, Fairfax, VA 22030 USA. [Kaplan, Paige] Childrens Hosp Philadelphia, Lysosomal Ctr, Div Genet, Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Kishnani, Priya S.] Duke Univ, Sch Med, Dept Pediat, DUMC 103856,595 Lasalle St,GSRB 1,4th Floor, Durham, NC 27710 USA. [Mistry, Pramod] Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. [Ruskin, Jeremy] Massachusetts Gen Hosp, Electrophysiol Lab, Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. [Weinreb, Neal] Univ Res Fdn Lysosomal Storage Dis Inc, 7367 Wexford Terrace, Boca Raton, FL 33433 USA. RP Weinreb, N (reprint author), Univ Res Fdn Lysosomal Storage Dis Inc, 7367 Wexford Terrace, Boca Raton, FL 33433 USA. EM manisha.balwani@mssm.edu; thomas.burrow@cchmc.org; jcharrow@northwestern.edu; ogokeralpan@oandoalpan.com; kaplan@email.chop.edu; kishn001@mc.duke.edu; pramod.mistry@yale.edu; jruskin@mgh.harvard.edu; boneal@winning.com NR 51 TC 5 Z9 5 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 BP 95 EP 103 DI 10.1016/j.ymgme.2015.09.002 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100343 PM 26387627 ER PT J AU Cox, G Eichler, F Sathe, S Kissell, J Hamed, A Kahn, S AF Cox, Gerald Eichler, Florian Sathe, Swati Kissell, Julie Hamed, Alaa Kahn, Susan TI Functional performance in patients with late-onset Tay-Sachs and Sandhoff diseases SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Cox, Gerald; Kissell, Julie; Hamed, Alaa] Genzyme, Cambridge, MA USA. [Eichler, Florian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sathe, Swati] Rutgers New Jersey Med Sch, Newark, NJ USA. [Kahn, Susan] Natl Tay Sachs & Allied Dis Assoc, Brighton, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 70 BP S37 EP S37 DI 10.1016/j.ymgme.2015.12.228 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100071 ER PT J AU Eichler, FS Kyu, JB AF Eichler, Florian S. Kyu, Jun Byung TI The role of complement system in GM2 gangliosidoses: Implications for Tay-Sachs and Sandhoff disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Eichler, Florian S.; Kyu, Jun Byung] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 7 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 87 BP S42 EP S42 DI 10.1016/j.ymgme.2015.12.245 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100088 ER PT J AU Giugliani, R Fietz, M Al-Sayed, M Burke, D Cohen-Pfeffer, J Cooper, JD de Halac, IN Dvorakova, L Izzo, E Jahnova, H Lukacs, Z Mole, S Pearce, D Schulz, A Specchio, N Xin, W Miller, N AF Giugliani, Roberto Fietz, Michael Al-Sayed, Moeenaldeen Burke, Derek Cohen-Pfeffer, Jessica Cooper, Jonathan D. Noher de Halac, Ines Dvorakova, Lenka Izzo, Emanuela Jahnova, Helena Lukacs, Zoltan Mole, Sara Pearce, David Schulz, Angela Specchio, Nicola Xin, Winnie Miller, Nicole TI Expert recommendations for the laboratory diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Diagnostic algorithm and best practice guidelines for a timely diagnosis SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Giugliani, Roberto] HCPA, Serv Genet Med, Porto Alegre, RS, Brazil. [Fietz, Michael] Dept Diagnost Genom, Nedlands, WA, Australia. [Al-Sayed, Moeenaldeen] Alfaisal Univ, Riyadh, Saudi Arabia. [Al-Sayed, Moeenaldeen] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Burke, Derek] Great Ormond St Hosp Sick Children, London, England. [Cohen-Pfeffer, Jessica; Izzo, Emanuela; Miller, Nicole] BioMarin Pharmaceut, Novato, CA USA. [Cooper, Jonathan D.] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Noher de Halac, Ines] Univ Nacl Cordoba, Fac Ciencias Med, RA-5000 Cordoba, Argentina. [Dvorakova, Lenka; Jahnova, Helena] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic. [Dvorakova, Lenka; Jahnova, Helena] Gen Univ Hosp Prague, Prague, Czech Republic. [Lukacs, Zoltan] Univ Hamburg, Med Ctr, Newborn Screening & Metab Diagnost Unit, Hamburg, Germany. [Mole, Sara] UCL, Mol Cell Biol Lab, MRC, Mol Cell Biol, London, England. [Pearce, David] Sanford Childrens Hlth Res Ctr, Sioux Falls, SD USA. [Schulz, Angela] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, Hamburg, Germany. [Specchio, Nicola] Bambino Gesu Pediat Hosp, Dept Neurosci, Rome, Italy. [Xin, Winnie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurogenet DNA Diagnost Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 143 BP S61 EP S61 DI 10.1016/j.ymgme.2015.12.301 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100144 ER PT J AU Hughes, D Boyd, S Giraldo, P Gonzalez, D Holida, M Goker-Alpan, O Megawa, G Atta, M Nicholls, K Schiffmann, R Tuffaha, A Visootsak, J Barisoni, L Colvin, R Jannette, JC Alon, S Krupko, J Szlaifer, M Brill-Almon, E Chertkoff, R AF Hughes, Derralynn Boyd, Simeon Giraldo, Pilar Gonzalez, Derlis Holida, Myrl Goker-Alpan, Ozlem Megawa, Gustavo Atta, Mohamed Nicholls, Kathy Schiffmann, Raphael Tuffaha, Ahmad Visootsak, Jeannie Barisoni, Laura Colvin, Robert Jannette, J. Charles Alon, Sari Krupko, Jenny Szlaifer, Mali Brill-Almon, Einat Chertkoff, Raul TI Novel treatment for Fabry disease: IV administration of plant derived alpha-gal-A enzyme safety and efficacy interim report SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Hughes, Derralynn] Univ Colege London, London, England. [Boyd, Simeon] UC Davis Med Ctr, Scramento, CA USA. [Giraldo, Pilar] Hosp Dia Quiron, Zaragoza, Spain. [Gonzalez, Derlis] Inst Privado Hematol Invest Clin, Asuncion, Paraguay. [Holida, Myrl] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Goker-Alpan, Ozlem] O&O Alpan LLC, Fairfax, VA USA. [Megawa, Gustavo; Atta, Mohamed] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Nicholls, Kathy] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Schiffmann, Raphael] Baylor Res Inst, Dallas, TX USA. [Tuffaha, Ahmad] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Visootsak, Jeannie] Emory Univ Hosp, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. [Barisoni, Laura] Univ Miami, Miami, FL USA. [Colvin, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jannette, J. Charles] Univ N Carolina, Chapel Hill, NC USA. [Alon, Sari; Krupko, Jenny; Szlaifer, Mali; Brill-Almon, Einat; Chertkoff, Raul] Protalix Biotherapeut, Carmiel, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 138 BP S59 EP S59 DI 10.1016/j.ymgme.2015.12.296 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100139 ER PT J AU Karaa, AA Haxton, E Yerramilli-Rao, P Giannikopoulos, O Pollak, L Morgan, A Sharma, N Kubilus, K Khan, S Sathe, S Tifft, C Pan, J Eichler, F AF Karaa, A. Amel Haxton, Elizabeth Yerramilli-Rao, Padmaja Giannikopoulos, Ourania Pollak, Lauren Morgan, Amy Sharma, Nutan Kubilus, Kim Khan, Susan Sathe, Swati Tifft, Cynthia Pan, Jessica Eichler, Florian TI Retrospective survey of late onset Tay-Sachs disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Karaa, A. Amel; Haxton, Elizabeth; Giannikopoulos, Ourania; Pollak, Lauren; Morgan, Amy; Sharma, Nutan; Kubilus, Kim; Pan, Jessica; Eichler, Florian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yerramilli-Rao, Padmaja] Novartis Inst BioMed Res, Boston, MA USA. [Khan, Susan] NTSAD, Brighton, MA USA. [Sathe, Swati] Rutgers New Jersey Med Sch, Newark, NJ USA. [Tifft, Cynthia] Childrens Natl, Washington, DC USA. NR 0 TC 0 Z9 0 U1 5 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 154 BP S64 EP S65 DI 10.1016/j.ymgme.2015.12.312 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100155 ER PT J AU Laney, DA Clark, V Holida, M AF Laney, Dawn A. Clark, Virginia Holida, Myrl TI The impact of Fabry disease on reproductive fitness SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Laney, Dawn A.] Emory, Decatur, GA USA. [Clark, Virginia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Holida, Myrl] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 170 BP S70 EP S70 DI 10.1016/j.ymgme.2015.12.328 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100171 ER PT J AU Schulz, A Adams, HR Blohm, M Cohen-Pfeffer, JL de los Reyes, E Denecke, J Drago, K Fairhurst, C Frazier, M Guelbert, N Kiss, S Kofler, A Lawson, J Lehwald, L Leung, MA Mikhailova, S Mink, JW Nickel, M Shediac, R Sims, K Specchio, N Topcu, M von Lobbecke, I West, A Williams, RE AF Schulz, Angela Adams, Heather R. Blohm, Martin Cohen-Pfeffer, Jessica L. de los Reyes, Emily Denecke, Jonas Drago, Kristen Fairhurst, Charlie Frazier, Margie Guelbert, Norberto Kiss, Szilard Kofler, Annamaria Lawson, John Lehwald, Lenora Leung, Mary-Anne Mikhailova, Svetlana Mink, Jonathan W. Nickel, Miriam Shediac, Renee Sims, Katherine Specchio, Nicola Topcu, Meral von Loebbecke, Ina West, Andrea Williams, Ruth E. TI Expert opinion on the management of CLN2 disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 12th Annual WORLD Symposium CY FEB 29-MAR 04, 2016 CL San Diego, CA C1 [Schulz, Angela; Blohm, Martin; Denecke, Jonas; Nickel, Miriam] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Adams, Heather R.; Mink, Jonathan W.] Univ Rochester, Sch Med, Rochester, NY USA. [Cohen-Pfeffer, Jessica L.; Shediac, Renee] BioMarin Pharmaceut Inc, Novato, CA USA. [de los Reyes, Emily; Lehwald, Lenora] Nationwide Childrens Hosp, Columbus, OH USA. [Drago, Kristen] Joumeycare Children, Chicago, IL USA. [Fairhurst, Charlie; Leung, Mary-Anne; Williams, Ruth E.] Evelina London Childrens Hosp, London, England. [Frazier, Margie] BDSRA, Columbus, OH USA. [Guelbert, Norberto] Childrens Hosp Cordoba, Cordoba, Argentina. [Kiss, Szilard] Weill Cornell Med Coll, New York, NY USA. [Kofler, Annamaria; Specchio, Nicola] Bambino Gesu Pediat Hosp, IRCCS, Rome, Italy. [Lawson, John] Sydney Childrens Hosp, Sydney, NSW, Australia. [Mikhailova, Svetlana] Russian Reg Pediat Hosp, Moscow, Russia. [Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Topcu, Meral] Hacettepe Univ, Ankara, Turkey. [West, Andrea] BDFA, Farnborough, Hants, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 2016 VL 117 IS 2 MA 274 BP S103 EP S104 DI 10.1016/j.ymgme.2015.12.432 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DE8LS UT WOS:000370888100275 ER PT J AU Ibrahim-Verbaas, CA Bressler, J Debette, S Schuur, M Smith, AV Bis, JC Davies, G Trompet, S Smith, JA Wolf, C Chibnik, LB Liu, Y Vitart, V Kirin, M Petrovic, K Polasek, O Zgaga, L Fawns-Ritchie, C Hoffmann, P Karjalainen, J Lahti, J Llewellyn, DJ Schmidt, CO Mather, KA Chouraki, V Sun, Q Resnick, SM Rose, LM Oldmeadow, C Stewart, M Smith, BH Gudnason, V Yang, Q Mirza, SS Jukema, JW Dejager, PL Harris, TB Liewald, DC Amin, N Coker, LH Stegle, O Lopez, OL Schmidt, R Teumer, A Ford, I Karbalai, N Becker, JT Jonsdottir, MK Au, R Fehrmann, RSN Herms, S Nalls, M Zhao, W Turner, ST Yaffe, K Lohman, K van Swieten, JC Kardia, SLR Knopman, DS Meeks, WM Heiss, G Holliday, EG Schofield, PW Tanaka, T Stott, DJ Wang, J Ridker, P Gow, AJ Pattie, A Starr, JM Hocking, LJ Armstrong, NJ McLachlan, S Shulman, JM Pilling, LC Eiriksdottir, G Scott, RJ Kochan, NA Palotie, A Hsieh, YC Eriksson, JG Penman, A Gottesman, RF Oostra, BA Yu, L DeStefano, AL Beiser, A Garcia, M Rotter, JI Nothen, MM Hofman, A Slagboom, PE Westendorp, RGJ Buckley, BM Wolf, PA Uitterlinden, AG Psaty, BM Grabe, HJ Bandinelli, S Chasman, DI Grodstein, F Roikkonen, K Lambert, JC Porteous, DJ Price, JF Sachdev, PS Ferrucci, L Attia, JR Rudan, I Hayward, C Wright, AF Wilson, JF Cichon, S Franke, L Schmidt, H Ding, J de Craen, AJM Fornage, M Bennett, DA Deary, IJ Ikram, MA Launer, LJ Fitzpatrick, AL Seshadri, S van Duijn, CM Mosley, TH AF Ibrahim-Verbaas, C. A. Bressler, J. Debette, S. Schuur, M. Smith, A. V. Bis, J. C. Davies, G. Trompet, S. Smith, J. A. Wolf, C. Chibnik, L. B. Liu, Y. Vitart, V. Kirin, M. Petrovic, K. Polasek, O. Zgaga, L. Fawns-Ritchie, C. Hoffmann, P. Karjalainen, J. Lahti, J. Llewellyn, D. J. Schmidt, C. O. Mather, K. A. Chouraki, V. Sun, Q. Resnick, S. M. Rose, L. M. Oldmeadow, C. Stewart, M. Smith, B. H. Gudnason, V. Yang, Q. Mirza, S. S. Jukema, J. W. Dejager, P. L. Harris, T. B. Liewald, D. C. Amin, N. Coker, L. H. Stegle, O. Lopez, O. L. Schmidt, R. Teumer, A. Ford, I. Karbalai, N. Becker, J. T. Jonsdottir, M. K. Au, R. Fehrmann, R. S. N. Herms, S. Nalls, M. Zhao, W. Turner, S. T. Yaffe, K. Lohman, K. van Swieten, J. C. Kardia, S. L. R. Knopman, D. S. Meeks, W. M. Heiss, G. Holliday, E. G. Schofield, P. W. Tanaka, T. Stott, D. J. Wang, J. Ridker, P. Gow, A. J. Pattie, A. Starr, J. M. Hocking, L. J. Armstrong, N. J. McLachlan, S. Shulman, J. M. Pilling, L. C. Eiriksdottir, G. Scott, R. J. Kochan, N. A. Palotie, A. Hsieh, Y-C Eriksson, J. G. Penman, A. Gottesman, R. F. Oostra, B. A. Yu, L. DeStefano, A. L. Beiser, A. Garcia, M. Rotter, J. I. Noethen, M. M. Hofman, A. Slagboom, P. E. Westendorp, R. G. J. Buckley, B. M. Wolf, P. A. Uitterlinden, A. G. Psaty, B. M. Grabe, H. J. Bandinelli, S. Chasman, D. I. Grodstein, F. Roikkonen, K. Lambert, J-C Porteous, D. J. Price, J. F. Sachdev, P. S. Ferrucci, L. Attia, J. R. Rudan, I. Hayward, C. Wright, A. F. Wilson, J. F. Cichon, S. Franke, L. Schmidt, H. Ding, J. de Craen, A. J. M. Fornage, M. Bennett, D. A. Deary, I. J. Ikram, M. A. Launer, L. J. Fitzpatrick, A. L. Seshadri, S. van Duijn, C. M. Mosley, T. H. CA Generation Scotland TI GWAS for executive function and processing speed suggests involvement of the CADM2 gene SO MOLECULAR PSYCHIATRY LA English DT Article ID ONSET ALZHEIMERS-DISEASE; GENOME-WIDE ASSOCIATION; COGNITIVE FUNCTION; LINKAGE ANALYSIS; COMMON VARIANTS; LOCI; INTELLIGENCE; EXPRESSION; DISORDER; SCHIZOPHRENIA AB To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value = 3.12 x 10(-8)) and in the joint discovery and replication meta-analysis (P-value = 3.28 x 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value= 4x10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value = 7.22 x 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value = 1.36 x 10(-11)) and neuron cell-cell adhesion (P-value = 1.48 x 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed. C1 [Ibrahim-Verbaas, C. A.; Schuur, M.; Amin, N.; Oostra, B. A.; van Duijn, C. M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Ibrahim-Verbaas, C. A.; Schuur, M.; van Swieten, J. C.; Ikram, M. A.] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Bressler, J.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA. [Debette, S.; Au, R.; DeStefano, A. L.; Beiser, A.; Wolf, P. A.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Debette, S.] Univ Bordeaux, Epidemiol & Biostat, U897, INSERM, Bordeaux, France. [Debette, S.] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France. [Smith, A. V.; Gudnason, V.; Eiriksdottir, G.] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, A. V.; Gudnason, V.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Bis, J. C.; Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Davies, G.; Fawns-Ritchie, C.; Liewald, D. C.; Gow, A. J.; Pattie, A.; Starr, J. M.; Deary, I. J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Trompet, S.; Jukema, J. W.] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Trompet, S.; de Craen, A. J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands. [Smith, J. A.; Zhao, W.; Kardia, S. L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Wolf, C.; Karbalai, N.] Max Planck Inst Psychiat, RG Stat Genet, Munich, Germany. [Chibnik, L. B.; Dejager, P. L.] Brigham & Womens Hosp, Div Neurol, Program Translat Neuropsychiat Gen, Boston, MA 02115 USA. [Liu, Y.; Lohman, K.] Wake Forest Sch Med, Dept Epidemiol, Winston Salem, NC USA. [Petrovic, K.; Schmidt, R.; Schmidt, H.] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Kirin, M.; Stewart, M.; McLachlan, S.; Price, J. F.; Rudan, I.; Wilson, J. F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Petrovic, K.; Schmidt, R.; Schmidt, H.] Med Univ & Gen Hosp Graz, Dept Neurol, Graz, Austria. [Polasek, O.] Univ Split, Dept Publ Hlth, Split, Croatia. [Zgaga, L.] Trintiy Coll Dublin, Dept Publ Hlth & Primary Care, Dublin, Ireland. [Hoffmann, P.; Cichon, S.] Res Ctr Juelich, Inst Neurosci & Med INM1, Julich, Germany. [Hoffmann, P.; Herms, S.; Cichon, S.] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland. [Hoffmann, P.; Herms, S.; Noethen, M. 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M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Rose, L. M.; Ridker, P.; Chasman, D. I.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Oldmeadow, C.; Holliday, E. G.; Scott, R. J.; Attia, J. R.] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia. [Oldmeadow, C.; Holliday, E. G.; Scott, R. J.; Attia, J. R.] Univ Newcastle, Fac Hlth, Newcastle, NSW 2300, Australia. [Smith, B. H.] Univ Dundee, Med Res Inst, Dundee, Scotland. [Yang, Q.; Au, R.; DeStefano, A. L.; Beiser, A.; Wolf, P. A.; Seshadri, S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Yang, Q.; Wang, J.; DeStefano, A. L.; Beiser, A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mirza, S. S.; Hofman, A.; Uitterlinden, A. G.; Ikram, M. A.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Mirza, S. S.; Hofman, A.; Uitterlinden, A. G.; Ikram, M. A.; van Duijn, C. M.] Netherlands Consortium Hlth Ageing, Leiden, Netherlands. [Harris, T. B.; Garcia, M.; Launer, L. J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Liewald, D. C.; Gow, A. J.; Deary, I. J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Coker, L. H.] Wake Forest Sch Med, Div Publ Hlth Sci & Neurol, Winston Salem, NC USA. [Stegle, O.] Max Planck Inst Intelligent Syst, Max Planck Inst Dev Biol, Tubingen, Germany. [Lopez, O. L.; Becker, J. T.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Teumer, A.] Univ Med Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany. [Ford, I.] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland. [Becker, J. T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Becker, J. T.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Jonsdottir, M. K.] Landspitali Hosp, Reykjavik, Iceland. [Nalls, M.] NIA, Lab Neurogenet, Bethesda, MD 20892 USA. [Turner, S. T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA. [Yaffe, K.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, K.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Knopman, D. S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Meeks, W. M.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA. [Heiss, G.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Schofield, P. W.] Univ Newcastle, Fac Hlth, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Tanaka, T.; Ferrucci, L.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Stott, D. J.] Univ Glasgow, Dept Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Starr, J. M.] Alzheimer Scotland Res Ctr, Edinburgh, Midlothian, Scotland. [Hocking, L. J.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Armstrong, N. J.] Garvan Inst Med Res, Canc Res Program, Sydney, NSW, Australia. [Armstrong, N. J.] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia. [Armstrong, N. J.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia. [Shulman, J. M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Shulman, J. M.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Dept Mol & Human Genet, Houston, TX 77030 USA. [Pilling, L. C.] Univ Exeter, Sch Med, Epidemiol & Publ Hlth Grp, Exeter, Devon, England. [Kochan, N. A.; Sachdev, P. S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia. [Palotie, A.] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England. [Palotie, A.] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Palotie, A.] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Palotie, A.] Univ Cent Hosp, Helsinki, Finland. [Hsieh, Y-C] Taipei Med Univ, Sch Publ Hlth, Taipei, Taiwan. [Eriksson, J. G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, J. G.] Natl Inst Hlth & Welf, Helsinki, Finland. [Eriksson, J. G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, J. G.] Vasa Cent Hosp, Vaasa, Finland. [Penman, A.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA. [Gottesman, R. F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Yu, L.; Bennett, D. A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Rotter, J. I.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA. [Rotter, J. I.] Harbor UCLA Med Ctr, Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Rotter, J. I.] Harbor UCLA Med Ctr, Dept Pediat, Div Genet Outcomes, Torrance, CA 90509 USA. [Noethen, M. M.] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany. [Slagboom, P. E.] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands. [Westendorp, R. G. J.] Leiden Acad Vital & Ageing, Leiden, Netherlands. [Buckley, B. M.] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland. [Uitterlinden, A. G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Psaty, B. M.; Fitzpatrick, A. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, B. M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Grabe, H. J.] HELIOS Hosp Stralsund, Univ Med Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Ibrahim-Verbaas, C. A.; Bressler, J.; Debette, S.; Schuur, M.; Smith, A. V.; Bis, J. C.; Davies, G.; Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy. [Porteous, D. J.] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. [Ding, J.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Fornage, M.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Ikram, M. A.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Mosley, T. H.] Univ Mississippi, Med Ctr, Dept Med & Neurol, Jackson, MS 39216 USA. RP Mosley, TH (reprint author), Univ Mississippi, Med Ctr, Dept Med Geriatr, 2500 North State St, Jackson, MS 39216 USA. EM tmosley@umc.edu RI Smith, Albert Vernon/K-5150-2015; Lambert, jean-charles/A-9553-2014; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Slagboom, P. Eline/R-4790-2016; Fehrmann, Rudolf/E-2551-2011; Polasek, Ozren/B-6002-2011; Gudnason, Vilmundur/K-6885-2015 OI van Swieten, John /0000-0001-6278-6844; Lahti, Jari/0000-0002-4310-5297; Nothen, Markus/0000-0002-8770-2464; Sachdev, Perminder/0000-0002-9595-3220; Smith, Blair/0000-0002-5362-9430; Beiser, Alexa/0000-0001-8551-7778; Smith, Jennifer/0000-0002-3575-5468; Gow, Alan/0000-0002-3320-4531; Raikkonen, Katri/0000-0003-3124-3470; Smith, Albert Vernon/0000-0003-1942-5845; Lambert, jean-charles/0000-0003-0829-7817; Franke, Lude/0000-0002-5159-8802; Slagboom, P. Eline/0000-0002-2875-4723; Fehrmann, Rudolf/0000-0002-7516-315X; Polasek, Ozren/0000-0002-5765-1862; Stegle, Oliver/0000-0002-8818-7193; Zgaga, Lina/0000-0003-4089-9703; Hocking, Lynne J/0000-0002-2414-2826; Gudnason, Vilmundur/0000-0001-5696-0084 FU National Foundation for Alzheimer's disease and related disorders; Institut Pasteur de Lille; Centre National de Genotypage; Inserm; FRC (fondation pour la recherche sur le cerveau); Rotary; LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease); MEDIALZ Project - ERDF (European Regional Development Fund) [11001003]; Conseil Regional Nord Pas de Calais; Fondation pour la Recherche Medicale; Caisse Nationale Maladie des Travailleurs Salaries; Direction Generale de la Sante; MGEN; Institut de la Longevite; Agence Francaise de Securite Sanitaire des Produits de Sante; Aquitaine and Bourgogne Regional Councils; Fondation de France; joint French Ministry of Research/INSERM 'Cohortes et collections de donnees biologiques' program; Eisai; Wellcome Trust; British Heart Foundation; Chief Scientist Office of the Scottish Executive; NIA [N01-AG-12100]; National Heart, Lung and Blood Institute Contracts [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL70825, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; NIH Roadmap for Medical Research; Austrian Science Fond (FWF) [P20545-P05, P13180]; Intramural Research Program of the NIH, National Institute on Aging; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC850863, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [R01AG023629, R01AG15928, R01AG20098, R01AG027058]; National Center for Advancing Translational Sciences; CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]; Medical Research Council (UK); European Commission Framework 6 project EUROSPAN [LSHG-CT-2006-018947]; Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]; Netherlands Organization for Scientific Research (NWO); Internationale Stichting Alzheimer Onderzoek (ISAO); Hersenstichting Nederland (HSN); Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI); Russian Foundation for Basic Research (RFBR); National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278, U01 HL096917, R01 HL093029]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Neurological Disorders and Stroke [NS17950]; National Institute of Aging [U01 AG049505, AG033193, AG008122, AG16495]; Agence National de la Recherche; Leducq Foundation; National Heart, Lung and Blood Institute [HL054464, HL054457, HL054481, HL071917, HL87660, HL043851, HL080467]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [NS041558]; Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6]; Scottish Funding Council [HR03006]; Academy of Finland; Finnish Diabetes Research Society; Folkhalsan Research Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet; Signe and Ane Gyllenberg Foundation; University of Helsinki; Ministry of Education; Ahokas Foundation; Emil Aaltonen Foundation; Juho Vainio Foundation; Wellcome Trust [WT089062]; University of Newcastle's Strategic Initiative Fund; Vincent Fairfax Family Foundation; Hunter Medical Research Institute; Italian Ministry of Health [ICS 110.1RS97.71]; US National Institute on Aging [N01[AG]916413, N01[AG]821336, 263 MD 9164 13, 263 MD 821336]; Intramural Research Program, National Institute on Aging, National Institutes of Health; BBSRC; Royal Society; Chief Scientist Office of the Scottish Government; Research Into Ageing; UK Biotechnology and Biological Sciences Research Council (BBSRC); Engineering and Physical Sciences Research Council (EPSRC); Economic and Social Research Council (ESRC); MRC; NHMRC [401184]; Australian National Health & Medical Research Council [350833, 568969]; Capacity Building Grant [568940]; NHMRC Project [525453]; National Institutes of Health [CA87969, CA49449, HL34594, U01HG004399, DK058845, CA65725, CA67262, CA50385, 5UO1CA098233, EY09611, EY015473, HG004728, HL35464, CA55075, CA134958, DK070756]; MRC Human Genetics Unit; Arthritis Research UK; European Union [LSHG-CT-2006-018947]; Bristol-Myers Squibb; Netherlands Heart Foundation [2001 D 032]; European commission [223004]; Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]; Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project [050-060-810]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission 49 (DG XII); Municipality of Rotterdam; ZonMW Veni Grant [916.13.054]; NIA Grants [P30AG10161, R01AG15819, R01AG17917, R01AG30146, K08AG34290, K25AG41906]; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; National Cancer Institute [CA047988]; Donald W Reynolds Foundation; Fondation Leducq; Amgen FX CS: The work was made possible by the generous participation of the control subjects and their families. This work was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille, the Centre National de Genotypage, Inserm, FRC (fondation pour la recherche sur le cerveau) and Rotary. This work has been developed and supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease). JCL was funded by the MEDIALZ Project (Grant 11001003) financed by ERDF (European Regional Development Fund) and Conseil Regional Nord Pas de Calais. The Three-City Study was performed as part of a collaboration between the Institut National de la Sante et de la Recherche Medicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthelabo. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Agence Francaise de Securite Sanitaire des Produits de Sante, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM 'Cohortes et collections de donnees biologiques' program. Lille Genopole received an unconditional grant from Eisai.; AAA: We thank the cohort participants and team members who contributed to this study. Phenotype collection and DNA extraction were supported by the Wellcome Trust, the British Heart Foundation and the Chief Scientist Office of the Scottish Executive. The AAA Trial was performed and the database is maintained by members of the University of Edinburgh Molecular Epidemiology Research Group in the Centre for Population Health Sciences. We also thank staff at the Wellcome Trust Clinical Research Facility in Edinburgh where some of the research clinics and genotyping were undertaken.; AGES: Aging Gene-Environment Susceptibility-Reykjavik Study: The research has been funded by NIA Contract N01-AG-12100 with contributions from NEI, NIDCD and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament).; ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute Contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C), R01HL70825, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute Contract U01HG004402; and National Institutes of Health Contract HHSN268200625226C. We thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; ASPS: We thank Ing. Johann Semmler and Irmgard Polzl for creating the DNA bank and for supervising the quality management of the biobanking and DNA analyses. The ASPS is funded by the Austrian Science Fond (FWF) Grant Number P20545-P05 and P13180.; BLSA: Baltimore Longitudinal Study of Aging (BLSA): The Baltimore Longitudinal Study of Aging is supported by the Intramural Research Program of the NIH, National Institute on Aging.; Cardiovascular Health Study: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, and R01HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629, R01AG15928, R01AG20098, and R01AG027058 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHSNHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.; CROATIA-Korcula: The CROATIA-Korcula study was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (Contract No. LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants to IR (108-1080315-0302). We would like to acknowledge the invaluable contributions of the recruitment team in Korcula, the administrative teams in Croatia and Edinburgh and the people of Korcula. The SNP genotyping for the CROATIA-Korcula cohort was performed in Helmholtz Zentrum Munchen, Neuherberg, Germany.; CROATIA-Vis: The CROATIA-Vis study was funded by grants from the Medical Research Council (UK) and Republic of Croatia Ministry of Science, Education and Sports research grants to IR (108-1080315-0302). We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Vis cohort was performed in the core genotyping laboratory of the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, Scotland.; ERF: This study was financially supported by the Netherlands Organization for Scientific Research (NWO), the Internationale Stichting Alzheimer Onderzoek (ISAO), the Hersenstichting Nederland (HSN) and the Centre for Medical Systems Biology (CMSB) in the framework of the Netherlands Genomics Initiative (NGI) and by the Russian Foundation for Basic Research (RFBR). We thank the participants from the Genetic Research in Isolated Populations, Erasmus Rucphen Family, who made this work possible. Also, we thank Petra Veraart for collecting all genealogical data.; FHS: This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278) and Grants (U01 HL096917 and R01 HL093029). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This study was also supported by grants from the National Institute of Neurological Disorders and Stroke (NS17950) and the National Institute of Aging (U01 AG049505, AG033193, AG008122, AG16495). The content is solely the responsibility of the authors and does not necessarily represent the official views of NINDS, NHLBI, NIA, NIH or AHA. Dr. Debette is a recipient of a Chaire d'Excellence grant from the Agence National de la Recherche and a grant from the Leducq Foundation.; GENOA: Support for the Genetic Epidemiology Network of Arteriopathy (GENOA) was provided by the National Heart, Lung and Blood Institute (HL054464, HL054457, HL054481, HL071917 and HL87660) and the National Institute of Neurological Disorders and Stroke (NS041558) of the National Institutes of Health. Genotyping was performed at the Mayo Clinic (S.T.T., Mariza de Andrade, Julie Cunningham) and was made possible by the University of Texas Health Sciences Center (Eric Boerwinkle, Megan L Grove-Gaona). We would also like to thank the families that participated in the GENOA study.; GS: We are grateful to the GS Executive Committee Professors Blair H. Smith, David J. Porteous, Sandosh Padmanabhan and Dr. Lynne J. Hocking, and all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006].; HBCS: We thank all study participants as well as everybody involved in the Helsinki Birth Cohort Study. Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation, Juho Vainio Foundation and Wellcome Trust (Grant Number WT089062).; Health ABC: 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). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.; Hunter: The authors would like to thank the men and women participating in the HCS as well as all the staff, investigators and collaborators who have supported or been involved in the project to date. The cohort was made possible with support from the University of Newcastle's Strategic Initiative Fund, the Vincent Fairfax Family Foundation and the Hunter Medical Research Institute.; InCHIANTI: The Invechhiare in Chianti (InCHIANTI) Study was supported as a targeted project (ICS 110.1RS97.71) by the Italian Ministry of Health, by the US National Institute on Aging (Contracts N01[AG]916413, N01[AG]821336, 263 MD 9164 13, and 263 MD 821336), and, in part, by the Intramural Research Program, National Institute on Aging, National Institutes of Health.; LBC1921/LBC1936: We thank the cohort participants and team members who contributed to these studies. Phenotype collection in the Lothian Birth Cohort 1921 was supported by the BBSRC, The Royal Society and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Research Into Ageing (continues as part of Age UK The Disconnected Mind project). Genotyping of the cohorts was funded by the UK Biotechnology and Biological Sciences Research Council (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 (G0700704/84698). Funding from the BBSRC, Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC) and MRC is gratefully acknowledged.; MAS: We would like to acknowledge and thank the Sydney MAS participants and the Research Team for their contributions and assistance. We would like to specifically acknowledge the support and contributions of Professor Henry Brodaty (Chief Investigator), Dr Simone Reppermund (Study Co-ordinator), Professor Peter Schofield, Dr Arezoo Assareh and Dr John Kwok to this work. DNA was extracted by Genetic Repositories Australia, an Enabling Facility supported by NHMRC Grant 401184. DNA sample preparation was undertaken in the laboratory of Professor Peter Schofield and Dr John Kwok, Neuroscience Research Australia, with the assistance of Dr Arezoo Assareh. Genotyping was performed by the Ramaciotti Centre, University of New South Wales. Sydney MAS is supported by the Australian National Health & Medical Research Council Program Grants 350833 and 568969. Karen Mather is supported by the Capacity Building Grant 568940. Nicola Armstrong is supported by the NHMRC Project Grant 525453.; Hippocampal eQTL: The hippocampal gene expression study was supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Genome Research Network (IG) MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia, under the auspices of the National Genome Research Network plus (NGFNplus)).; NHS: This study was supported by research Grants CA87969, CA49449, HL34594, U01HG004399, DK058845, CA65725, CA67262, CA50385, 5UO1CA098233, EY09611, EY015473, HG004728, HL35464, CA55075, CA134958 and DK070756 from the National Institutes of Health. The genotyping was partly supported by an unrestricted grant from Merck Research Laboratories. Dr Sun is supported by career development award K99HL098459 from the National Heart, Lung and Blood Institute. Supported in part by NIH.; ORCADES: ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the MRC Human Genetics Unit, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (Contract No. LSHG-CT-2006-018947). DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the invaluable contributions of Lorraine Anderson and the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney.; PROSPER: The PROSPER study was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Prof. Dr JW Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (Grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (Grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging Grant 050-060-810).; RS: The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database, and Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the 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 49 (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. Dr Ikram was supported by a ZonMW Veni Grant: 916.13.054.; RUSH: Supported in part by NIA Grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, K08AG34290 and K25AG41906.; SHIP: SHIP is part of the Community Medicine Research net of the University Medicine of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. The SHIP authors are grateful to Holger Prokisch and Thomas Meitinger (Helmholtz Zentrum Munchen) for the genotyping of the SHIP-TREND cohort.; WGHS: The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung and Blood Institute and CA047988 from the National Cancer Institute, the Donald W Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. NR 59 TC 4 Z9 4 U1 7 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2016 VL 21 IS 2 BP 189 EP 197 DI 10.1038/mp.2015.37 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA DE7LI UT WOS:000370817800005 PM 25869804 ER PT J AU Qin, H Samuels, JF Wang, Y Zhu, Y Grados, MA Riddle, MA Greenberg, BD Knowles, JA Fyer, AJ McCracken, JT Murphy, DL Rasmussen, SA Cullen, BA Piacentini, J Geller, D Stewart, SE Pauls, D Bienvenu, OJ Goes, FS Maher, B Pulver, AE Valle, D Lange, C Mattheisen, M McLaughlin, NC Liang, KY Nurmi, EL Askland, KD Nestadt, G Shugart, YY AF Qin, H. Samuels, J. F. Wang, Y. Zhu, Y. Grados, M. A. Riddle, M. A. Greenberg, B. D. Knowles, J. A. Fyer, A. J. McCracken, J. T. Murphy, D. L. Rasmussen, S. A. Cullen, B. A. Piacentini, J. Geller, D. Stewart, S. E. Pauls, D. Bienvenu, O. J. Goes, F. S. Maher, B. Pulver, A. E. Valle, D. Lange, C. Mattheisen, M. McLaughlin, N. C. Liang, K-Y Nurmi, E. L. Askland, K. D. Nestadt, G. Shugart, Y. Y. TI Whole-genome association analysis of treatment response in obsessive-compulsive disorder SO MOLECULAR PSYCHIATRY LA English DT Article ID WIDE ASSOCIATION; GENETICS; LINKAGE; GRIN2B; GENES; POLYMORPHISMS; TRANSPORTER; SLC1A1; DISP1; SCAN AB Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n = 514) or 'non-response' (n = 290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P = 1.76 x 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P < 10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 x 10(-6) and 8.41 x 10(-6), respectively. The other 35 variations with signals of potential significance (P < 10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR) = 0.0097) and the serotonergic system (FDR = 0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed. C1 [Qin, H.; Shugart, Y. Y.] NIMH, Unit Stat Genom, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. [Samuels, J. F.; Wang, Y.; Grados, M. A.; Riddle, M. A.; Cullen, B. A.; Bienvenu, O. J.; Goes, F. S.; Maher, B.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Zhu, Y.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Greenberg, B. D.; Rasmussen, S. A.; Pauls, D.] Brown Univ, Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Knowles, J. A.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Fyer, A. J.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Geller, D.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Geller, D.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, S. E.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Pulver, A. E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Valle, D.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Valle, D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Valle, D.] Johns Hopkins Univ, Sch Med, Inst Human Genet, Dept Mol Biol & Genet, Baltimore, MD USA. [Lange, C.; Mattheisen, M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lange, C.; Mattheisen, M.] Univ Bonn, Dept Genom Math, Bonn, Germany. [Mattheisen, M.] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Mattheisen, M.] Aarhus Univ, Ctr Integrated Sequencing ISEQ, Aarhus, Denmark. [McLaughlin, N. C.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Liang, K-Y] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Nurmi, E. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Askland, K. D.] Brown Univ, Warren Alpert Sch Med, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Shugart, YY (reprint author), NIMH, Unit Stat Genom, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. EM yin.yao@nih.gov OI Mattheisen, Manuel/0000-0002-8442-493X; Samuels, Jack/0000-0002-6715-7905 FU NIMH [MH071507, MH079489, MH079487, MH079488, MH079494]; IRP [MH002930-04] FX This project is a multiple sites collaborative project of OCD Collaborative Genetics Association Study (OCGAS), which is a collaboration among investigators at seven sites in the United States (namely Brown University, Columbia University, University of Southern California, Johns Hopkins University, Massachusetts General Hospital, University of California at Los Angeles, and the National Institute of Mental Health) funded by NIMH Grant Numbers: MH071507, MH079489, MH079487, MH079488 and MH079494. Qin and Shugart are both supported by IRP (Project number MH002930-04). The views expressed in this presentation do not necessarily represent the views of the NIMH, NIH, HHS or the United States Government. NR 39 TC 6 Z9 7 U1 2 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 FEB PY 2016 VL 21 IS 2 BP 270 EP 276 DI 10.1038/mp.2015.32 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA DE7LI UT WOS:000370817800014 PM 25824302 ER PT J AU Guney, E Menche, J Vidal, M Barabasi, AL AF Guney, Emre Menche, Joerg Vidal, Marc Barabasi, Albert-Laszlo TI Network-based in silico drug efficacy screening SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; HUMAN-DISEASE; COMPREHENSIVE RESOURCE; ALZHEIMER-DISEASE; PROTEIN; IDENTIFICATION; INTERACTOME; INTEGRATION; PATHOLOGY; PROFILES AB The increasing cost of drug development together with a significant drop in the number of new drug approvals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases to introduce a drug-disease proximity measure that quantifies the interplay between drugs targets and diseases. By correcting for the known biases of the interactome, proximity helps us uncover the therapeutic effect of drugs, as well as to distinguish palliative from effective treatments. Our analysis of 238 drugs used in 78 diseases indicates that the therapeutic effect of drugs is localized in a small network neighborhood of the disease genes and highlights efficacy issues for drugs used in Parkinson and several inflammatory disorders. Finally, network-based proximity allows us to predict novel drug-disease associations that offer unprecedented opportunities for drug repurposing and the detection of adverse effects. C1 [Guney, Emre; Menche, Joerg; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res CCNR, 177 Huntington Ave,11th Floor, Boston, MA 02115 USA. [Guney, Emre; Menche, Joerg; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, 177 Huntington Ave,11th Floor, Boston, MA 02115 USA. [Guney, Emre; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, 450 Brookline Ave, Boston, MA 02215 USA. [Guney, Emre; Vidal, Marc; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA. [Menche, Joerg; Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, Nador Utca 9, H-1051 Budapest, Hungary. [Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Networks Res CCNR, 177 Huntington Ave,11th Floor, Boston, MA 02115 USA.; Barabasi, AL (reprint author), Northeastern Univ, Dept Phys, 177 Huntington Ave,11th Floor, Boston, MA 02115 USA.; Barabasi, AL (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, 450 Brookline Ave, Boston, MA 02215 USA.; Barabasi, AL (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA.; Barabasi, AL (reprint author), Cent European Univ, Ctr Network Sci, Nador Utca 9, H-1051 Budapest, Hungary.; Barabasi, AL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM alb@neu.edu RI Menche, Jorg/G-3994-2015; Guney, Emre/B-2568-2017 OI Menche, Jorg/0000-0002-1583-6404; Guney, Emre/0000-0002-3466-6535 FU National Institutes of Health (NIH) [P50-HG004233-CEGS, 1U01HL108630-01-MapGen] FX We would like to thank Atanas Kamburov, Susan Ghiassian, Maksim Kitsak, Amitabh Sharma, Istvan Kovacs, Yves Jacob, Michael Calderwood, David E. Hill, and the members of CCNR and CCSB for fruitful discussions, and Joseph Loscalzo for his insights into the nosology and MeSH ontology. This work was supported by National Institutes of Health (NIH) grants P50-HG004233-CEGS and 1U01HL108630-01-MapGen. NR 49 TC 9 Z9 9 U1 10 U2 19 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 FEB PY 2016 VL 7 AR 10331 DI 10.1038/ncomms10331 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF1WQ UT WOS:000371130500001 PM 26831545 ER PT J AU Kilpelainen, TO Carli, JFM Skowronski, AA Sun, Q Kriebel, J Feitosa, MF Hedman, AK Drong, AW Hayes, JE Zhao, JH Pers, TH Schick, U Grarup, N Kutalik, Z Trompet, S Mangino, M Kristiansson, K Beekman, M Lyytikainen, LP Eriksson, J Henneman, P Lahti, J Tanaka, T Luan, JA Del Greco, F Pasko, D Renstrom, F Willems, SM Mahajan, A Rose, LM Guo, XQ Liu, YM Kleber, ME Perusse, L Gaunt, T Ahluwalia, TS Sung, YJ Ramos, YF Amin, N Amuzu, A Barroso, I Bellis, C Blangero, J Buckley, BM Bohringer, S Chen, YDI de Craen, AJN Crosslin, DR Dale, CE Dastani, Z Day, FR Deelen, J Delgado, GE Demirkan, A Finucane, FM Ford, I Garcia, ME Gieger, C Gustafsson, S Hallmans, G Hankinson, SE Havulinna, AS Herder, C Hernandez, D Hicks, AA Hunter, DJ Illig, T Ingelsson, E Ioan-Facsinay, A Jansson, JO Jenny, NS Jorgensen, ME Jorgensen, T Karlsson, M Koenig, W Kraft, P Kwekkeboom, J Laatikainen, T Ladwig, KH LeDuc, CA Lowe, G Lu, YC Marques-Vidal, P Meisinger, C Menni, C Morris, AP Myers, RH Mannisto, S Nalls, MA Paternoster, L Peters, A Pradhan, AD Rankinen, T Rasmussen-Torvik, LJ Rathmann, W Rice, TK Richards, JB Ridker, PM Sattar, N Savage, DB Soderberg, S Timpson, NJ Vandenput, L van Heemst, D Uh, HW Vohl, MC Walker, M Wichmann, HE Widen, E Wood, AR Yao, J Zeller, T Zhang, YY Meulenbelt, I Kloppenburg, M Astrup, A Sorensen, TIA Sarzynski, MA Rao, DC Jousilahti, P Vartiainen, E Hofman, A Rivadeneira, F Uitterlinden, AG Kajantie, E Osmond, C Palotie, A Eriksson, JG Heliovaara, M Knekt, PB Koskinen, S Jula, A Perola, M Huupponen, RK Viikari, JS Kahonen, M Lehtimaki, T Raitakari, OT Mellstrom, D Lorentzon, M Casas, JP Bandinelli, S Marz, W Isaacs, A van Dijk, KW van Duijn, CM Harris, TB Bouchard, C Allison, MA Chasman, DI Ohlsson, C Lind, L Scott, RA Langenberg, C Wareham, NJ Ferrucci, L Frayling, TM Pramstaller, PP Borecki, IB Waterworth, DM Bergmann, S Waeber, G Vollenweider, P Vestergaard, H Hansen, T Pedersen, O Hu, FB Slagboom, PE Grallert, H Spector, TD Jukema, JW Klein, RJ Schadt, EE Franks, PW Lindgren, CM Leibel, RL Loos, RJF AF Kilpelainen, Tuomas O. Carli, Jayne F. Martin Skowronski, Alicja A. Sun, Qi Kriebel, Jennifer Feitosa, Mary F. Hedman, Asa K. Drong, Alexander W. Hayes, James E. Zhao, Jinghua Pers, Tune H. Schick, Ursula Grarup, Niels Kutalik, Zoltan Trompet, Stella Mangino, Massimo Kristiansson, Kati Beekman, Marian Lyytikainen, Leo-Pekka Eriksson, Joel Henneman, Peter Lahti, Jari Tanaka, Toshiko Luan, Jian'an Del Greco M, Fabiola Pasko, Dorota Renstrom, Frida Willems, Sara M. Mahajan, Anubha Rose, Lynda M. Guo, Xiuqing Liu, Yongmei Kleber, Marcus E. Perusse, Louis Gaunt, Tom Ahluwalia, Tarunveer S. Sung, Yun Ju Ramos, Yolande F. Amin, Najaf Amuzu, Antoinette Barroso, Ines Bellis, Claire Blangero, John Buckley, Brendan M. Bohringer, Stefan Chen, Yii-Der I. de Craen, Anton J. N. Crosslin, David R. Dale, Caroline E. Dastani, Zari Day, Felix R. Deelen, Joris Delgado, Graciela E. Demirkan, Ayse Finucane, Francis M. Ford, Ian Garcia, Melissa E. Gieger, Christian Gustafsson, Stefan Hallmans, Goran Hankinson, Susan E. Havulinna, Aki S. Herder, Christian Hernandez, Dena Hicks, Andrew A. Hunter, David J. Illig, Thomas Ingelsson, Erik Ioan-Facsinay, Andreea Jansson, John-Olov Jenny, Nancy S. Jorgensen, Marit E. Jorgensen, Torben Karlsson, Magnus Koenig, Wolfgang Kraft, Peter Kwekkeboom, Joanneke Laatikainen, Tiina Ladwig, Karl-Heinz LeDuc, Charles A. Lowe, Gordon Lu, Yingchang Marques-Vidal, Pedro Meisinger, Christa Menni, Cristina Morris, Andrew P. Myers, Richard H. Mannisto, Satu Nalls, Mike A. Paternoster, Lavinia Peters, Annette Pradhan, Aruna D. Rankinen, Tuomo Rasmussen-Torvik, Laura J. Rathmann, Wolfgang Rice, Treva K. Richards, J. Brent Ridker, Paul M. Sattar, Naveed Savage, David B. Soderberg, Stefan Timpson, Nicholas J. Vandenput, Liesbeth van Heemst, Diana Uh, Hae-Won Vohl, Marie-Claude Walker, Mark Wichmann, Heinz-Erich Widen, Elisabeth Wood, Andrew R. Yao, Jie Zeller, Tanja Zhang, Yiying Meulenbelt, Ingrid Kloppenburg, Margreet Astrup, Arne Sorensen, Thorkild I. A. Sarzynski, Mark A. Rao, D. C. Jousilahti, Pekka Vartiainen, Erkki Hofman, Albert Rivadeneira, Fernando Uitterlinden, Andre G. Kajantie, Eero Osmond, Clive Palotie, Aarno Eriksson, Johan G. Heliovaara, Markku Knekt, Paul B. Koskinen, Seppo Jula, Antti Perola, Markus Huupponen, Risto K. Viikari, Jorma S. Kahonen, Mika Lehtimaki, Terho Raitakari, Olli T. Mellstrom, Dan Lorentzon, Mattias Casas, Juan P. Bandinelli, Stefanie Maerz, Winfried Isaacs, Aaron van Dijk, Ko W. van Duijn, Cornelia M. Harris, Tamara B. Bouchard, Claude Allison, Matthew A. Chasman, Daniel I. Ohlsson, Claes Lind, Lars Scott, Robert A. Langenberg, Claudia Wareham, Nicholas J. Ferrucci, Luigi Frayling, Timothy M. Pramstaller, Peter P. Borecki, Ingrid B. Waterworth, Dawn M. Bergmann, Sven Waeber, Gerard Vollenweider, Peter Vestergaard, Henrik Hansen, Torben Pedersen, Oluf Hu, Frank B. Slagboom, P. Eline Grallert, Harald Spector, Tim D. Jukema, J. W. Klein, Robert J. Schadt, Erik E. Franks, Paul W. Lindgren, Cecilia M. Leibel, Rudolph L. Loos, Ruth J. F. TI Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels SO NATURE COMMUNICATIONS LA English DT Article ID EARLY-ONSET OBESITY; GENE-EXPRESSION; PLASMA LEPTIN; ADIPOSE-TISSUE; SERUM LEPTIN; RECOMBINANT LEPTIN; INSULIN-RESISTANCE; PROVIDES INSIGHTS; WEIGHT-LOSS; FAT MASS AB Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P < 10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P < 5 x 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. C1 [Kilpelainen, Tuomas O.; Pers, Tune H.; Grarup, Niels; Ahluwalia, Tarunveer S.; Sorensen, Thorkild I. A.; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, Univ Pk 1,DIKU Bldg, DK-2100 Copenhagen, Denmark. [Kilpelainen, Tuomas O.; Zhao, Jinghua; Luan, Jian'an; Day, Felix R.; Finucane, Francis M.; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Loos, Ruth J. F.] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England. [Kilpelainen, Tuomas O.; Schick, Ursula; Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Carli, Jayne F. Martin] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. [Skowronski, Alicja A.] Columbia Univ, Inst Human Nutr, New York, NY 10032 USA. [Sun, Qi; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Sun, Qi; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Sun, Qi; Franks, Paul W.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kriebel, Jennifer; Gieger, Christian; Illig, Thomas; Grallert, Harald] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany. [Kriebel, Jennifer; Gieger, Christian; Ladwig, Karl-Heinz; Meisinger, Christa; Peters, Annette; Grallert, Harald] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany. [Kriebel, Jennifer; Herder, Christian; Meisinger, Christa; Peters, Annette; Grallert, Harald] German Ctr Diabet Res DZD, D-85764 Munich, Germany. [Feitosa, Mary F.; Rao, D. C.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Hedman, Asa K.; Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, S-75085 Uppsala, Sweden. [Hedman, Asa K.; Gustafsson, Stefan; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol, S-75185 Uppsala, Sweden. [Hedman, Asa K.; Drong, Alexander W.; Mahajan, Anubha; Morris, Andrew P.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Hayes, James E.] Cornell Univ, Weill Cornell Grad Sch Med Sci, Cell & Dev Biol Grad Program, New York, NY 10021 USA. [Hayes, James E.; Klein, Robert J.; Schadt, Erik E.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Pers, Tune H.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Pers, Tune H.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Pers, Tune H.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Pers, Tune H.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Pers, Tune H.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Pers, Tune H.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Kutalik, Zoltan] Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland. [Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Trompet, Stella; Jukema, J. W.] Leiden Univ, Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands. [Trompet, Stella; de Craen, Anton J. N.; van Heemst, Diana] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 Leiden, Netherlands. [Mangino, Massimo; Menni, Cristina; Richards, J. Brent; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Mangino, Massimo] Guys & St Thomas Fdn Trust, Biomed Res Ctr, Natl Inst Hlth Res, London SE1 9RT, England. [Kristiansson, Kati; Havulinna, Aki S.; Laatikainen, Tiina; Mannisto, Satu; Jousilahti, Pekka; Vartiainen, Erkki; Kajantie, Eero; Eriksson, Johan G.; Heliovaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus] Natl Inst Hlth & Welf, Dept Hlth, FI-00271 Helsinki, Finland. [Kristiansson, Kati; Widen, Elisabeth; Palotie, Aarno; Perola, Markus] Univ Helsinki, Inst Mol Med Finland, FI-00290 Helsinki, Finland. [Beekman, Marian; Ramos, Yolande F.; Bohringer, Stefan; Deelen, Joris; Uh, Hae-Won; Meulenbelt, Ingrid; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, FI-33101 Tampere, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FI-33014 Tampere, Finland. [Eriksson, Joel; Vandenput, Liesbeth; Mellstrom, Dan; Lorentzon, Mattias; Ohlsson, Claes] Univ Gothenburg, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden. [Henneman, Peter; Demirkan, Ayse; van Dijk, Ko W.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 Leiden, Netherlands. [Henneman, Peter] Amsterdam Med Ctr, Dept Clin Genet, NL-1081 HV Amsterdam, Netherlands. [Lahti, Jari] Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, FI-00290 Helsinki, Finland. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA. [Del Greco M, Fabiola; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy. [Pasko, Dorota; Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England. [Renstrom, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, S-20502 Malmo, Sweden. [Renstrom, Frida; Hallmans, Goran] Umea Univ, Dept Biobank Res, S-90187 Umea, Sweden. [Willems, Sara M.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Rose, Lynda M.; Pradhan, Aruna D.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. [Guo, Xiuqing; Chen, Yii-Der I.; Yao, Jie] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, LABioMed, Dept Pediat, Torrance, CA 90502 USA. [Liu, Yongmei] Wake Forest Sch Med, Ctr Human Genet, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Kleber, Marcus E.; Delgado, Graciela E.; Maerz, Winfried] Heidelberg Univ, Dept Med 5, Med Fac Mannheim, D-68167 Mannheim, Germany. [Perusse, Louis] Univ Laval, Dept Kinesiol, Quebec City, PQ G1V 0A6, Canada. [Perusse, Louis; Vohl, Marie-Claude] Inst Nutr & Funct Foods, Quebec City, PQ G1V 0A6, Canada. [Gaunt, Tom; Paternoster, Lavinia; Timpson, Nicholas J.; Sorensen, Thorkild I. A.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England. [Gaunt, Tom; Paternoster, Lavinia; Timpson, Nicholas J.; Sorensen, Thorkild I. A.] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England. [Ahluwalia, Tarunveer S.] Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Ledreborg Alle, DK-2820 Copenhagen, Denmark. [Ahluwalia, Tarunveer S.; Jorgensen, Marit E.; Vestergaard, Henrik] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Sung, Yun Ju; Rice, Treva K.; Rao, D. C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63108 USA. [Sung, Yun Ju; Rice, Treva K.; Rao, D. C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Amin, Najaf; Demirkan, Ayse; Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands. [Amuzu, Antoinette; Dale, Caroline E.] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Keppel St, London WC1E 7HT, England. [Barroso, Ines; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. [Barroso, Ines] Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Inst Metab Sci, Cambridge CB2 0QQ, England. [Barroso, Ines; Savage, David B.] Univ Cambridge, Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Cambridge CB2 0QQ, England. [Bellis, Claire] Agcy Sci Technol & Res Singapore, Genome Inst Singapore, Human Genet, Singapore 138672, Singapore. [Bellis, Claire] Queensland Univ Technol, Genom Res Ctr, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Bellis, Claire; Blangero, John] Texas Biomed Res Inst, San Antonio, TX 78245 USA. [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork T12 YT57, Ireland. [Crosslin, David R.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Crosslin, David R.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Dastani, Zari] McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G4, Canada. [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland. [Garcia, Melissa E.] NHLBI, NIH, Bldg 10, Bethesda, MD USA. [Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Hankinson, Susan E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Herder, Christian] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany. [Hernandez, Dena; Nalls, Mike A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Hunter, David J.; Hu, Frank B.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany. [Illig, Thomas] Hannover Med Sch, Inst Human Genet, D-30625 Hannover, Germany. [Ingelsson, Erik] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Ioan-Facsinay, Andreea; Kwekkeboom, Joanneke; Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2333 Leiden, Netherlands. [Jansson, John-Olov] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, S-41345 Gothenburg, Sweden. [Jenny, Nancy S.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Lab Clin Biochem Res, Burlington, VT 05405 USA. [Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark. [Jorgensen, Torben] Aalborg Univ, Fac Med, DK-9100 Aalborg, Denmark. [Jorgensen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark. [Karlsson, Magnus] Lund Univ, Skane Univ Hosp, Dept Clin Sci & Orthopaed Surg, Clin & Mol Osteoporosis Res Unit, S-21428 Malmo, Sweden. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med Cardiol 2, D-89081 Ulm, Germany. [Koenig, Wolfgang] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80636 Munich, Germany. [Koenig, Wolfgang; Peters, Annette] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80539 Munich, Germany. [Kraft, Peter] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. [Laatikainen, Tiina] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, FI-70211 Kuopio, Finland. [Laatikainen, Tiina] Hosp Dist North Karelia, FI-80210 Joensuu, Finland. [Ladwig, Karl-Heinz] Tech Univ Munich, Klinikum Rechts Isar, Dept Psychosomat Med & Psychotherapy, D-81675 Munich, Germany. [LeDuc, Charles A.; Zhang, Yiying; Leibel, Rudolph L.] Columbia Univ, Dept Pediat, Div Mol Genet, New York, NY 10029 USA. [Lowe, Gordon] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland. [Marques-Vidal, Pedro; Waeber, Gerard; Vollenweider, Peter] Univ Lausanne Hosp, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3GA, Merseyside, England. [Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Pradhan, Aruna D.; Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Rankinen, Tuomo; Sarzynski, Mark A.; Bouchard, Claude] Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. [Rasmussen-Torvik, Laura J.] Northwestern Feinberg Sch Med, Prevent Med, Chicago, IL 60611 USA. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany. [Richards, J. Brent] McGill Univ, Dept Med Human Genet & Epidemiol, Montreal, PQ H3A 0G4, Canada. [Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow G12 8QQ, Lanark, Scotland. [Soderberg, Stefan] Umea Univ, Cardiol & Heart Ctr, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden. [Vohl, Marie-Claude] Univ Laval, Sch Nutr, Quebec City, PQ G1V 0A6, Canada. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Wichmann, Heinz-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, D-80336 Munich, Germany. [Wichmann, Heinz-Erich] Klinikum Grosshadern, D-80336 Munich, Germany. [Wichmann, Heinz-Erich] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany. [Wichmann, Heinz-Erich] Tech Univ Munich, Inst Med Stat & Epidemiol, D-81675 Munich, Germany. [Zeller, Tanja] German Ctr Cardiovasc Res DZHK eV, D-20246 Hamburg, Germany. [Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, D-20246 Hamburg, Germany. [Kloppenburg, Margreet] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands. [Astrup, Arne] Univ Copenhagen, Fac Sci, Dept Nutr Exercise & Sports, DK-1165 Copenhagen, Denmark. [Sorensen, Thorkild I. A.] Bispebjerg Hosp, Inst Prevent Med, DK-2000 Copenhagen, Denmark. [Sorensen, Thorkild I. A.] Frederiksberg Univ Hosp, Inst Prevent Med, DK-2000 Copenhagen, Denmark. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Kajantie, Eero] Univ Helsinki, Cent Hosp, Childrens Hosp, FI-00014 Helsinki, Finland. [Kajantie, Eero] Univ Helsinki, FI-00014 Helsinki, Finland. [Kajantie, Eero] Oulu Univ, Cent Hosp, MRC Oulu, Dept Obstet & Gynaecol, SF-90220 Oulu, Finland. [Kajantie, Eero] Univ Oulu, SF-90220 Oulu, Finland. [Osmond, Clive] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England. [Palotie, Aarno] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FI-00014 Helsinki, Finland. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Huupponen, Risto K.] Univ Turku, Dept Pharmacol Drug Dev & Therapeut, FI-20520 Turku, Finland. [Huupponen, Risto K.] Turku Univ Hosp, Clin Pharmacol Unit, FI-20520 Turku, Finland. [Viikari, Jorma S.] Turku Univ Hosp, Div Med, FI-20520 Turku, Finland. [Viikari, Jorma S.] Univ Turku, Dept Med, FI-20520 Turku, Finland. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, FI-33521 Tampere, Finland. [Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FI-33014 Tampere, Finland. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FI-2051 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FI-20520 Turku, Finland. [Casas, Juan P.] UCL, Farr Inst Hlth Informat, London NW1 2DA, England. [Bandinelli, Stefanie] Azienda Sanit Firenze, Geriatr Unit, I-50122 Florence, Italy. [Maerz, Winfried] Synlab Serv LLC, Synlab Acad, D-68161 Mannheim, Germany. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8010 Graz, Austria. [van Duijn, Cornelia M.] Ctr Med Syst Biol, NL-2300 RC Leiden, Netherlands. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Allison, Matthew A.] Univ Calif San Diego, Family & Prevent Med, La Jolla, CA 92161 USA. [Lind, Lars] Uppsala Univ, Dept Med Sci, Cardiovasc Epidemiol, S-75185 Uppsala, Sweden. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23562 Lubeck, Germany. [Waterworth, Dawn M.] GlaxoSmithKline, King Of Prussia, PA 19406 USA. [Bergmann, Sven] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, DK-5230 Odense, Denmark. [Jukema, J. W.] Interuniv Cardiol Inst Netherlands, NL-3511 EP Utrecht, Netherlands. [Jukema, J. W.] Durrer Ctr Cardiogenet Res, NL-1105 AZ Amsterdam, Netherlands. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden. [Lindgren, Cecilia M.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Lindgren, Cecilia M.] Univ Oxford, Big Data Inst, S Parks Rd, Oxford OX1 2JD, England. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Kilpelainen, TO (reprint author), Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, Univ Pk 1,DIKU Bldg, DK-2100 Copenhagen, Denmark.; Kilpelainen, TO; Loos, RJF (reprint author), Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.; Kilpelainen, TO; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. EM tuomas.kilpelainen@sund.ku.dk; ruth.loos@mssm.edu RI Grallert, Harald/B-3424-2013; Sarzynski, Mark/A-9798-2014; Bouchard, Claude/A-7637-2009; Ladwig, Karl-Heinz/B-5351-2014; Fox, Laura /C-6249-2016; Peters, Annette/A-6117-2011; Slagboom, P. Eline/R-4790-2016; Colaus, PsyColaus/K-6607-2013; Feitosa, Mary/K-8044-2012; Grarup, Niels/K-2807-2015; mangino, massimo/F-5134-2011; Gaunt, Tom/O-3918-2014; Hicks, Andrew/E-9518-2017; OI Ladwig, Karl-Heinz/0000-0003-0710-1720; Slagboom, P. Eline/0000-0002-2875-4723; Feitosa, Mary/0000-0002-0933-2410; Grarup, Niels/0000-0001-5526-1070; mangino, massimo/0000-0002-2167-7470; Gaunt, Tom/0000-0003-0924-3247; Hicks, Andrew/0000-0001-6320-0411; Menni, Cristina/0000-0001-9790-0571; Kristiansson, Kati/0000-0003-4688-107X; Gieger, Christian/0000-0001-6986-9554; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Mannisto, Satu/0000-0002-8668-3046; Mellstrom, Dan/0000-0003-2761-3723; Meisinger, Christa/0000-0002-9026-6544; Hedman, Asa/0000-0001-5413-204X; Vandenput, Liesbeth/0000-0002-1712-6131; Jorgensen, Torben/0000-0001-9453-2830; Allison, Matthew/0000-0003-0777-8272; Vestergaard, Henrik/0000-0003-3090-269X; Peters, Annette/0000-0001-6645-0985; Timpson, Nicholas/0000-0002-7141-9189; Lahti, Jari/0000-0002-4310-5297; Kleber, Marcus/0000-0003-0663-7275 FU Academy of Finland [41071, 117787, 118065, 121584, 124282, 126925, 129494, 129322, 129378, 130326, 134309, 134791, 136895, 139635, 250207, 263836, 286284, 263924]; Ahokas Foundation; ALF/LUA research grant in Gothenburg; Amgen; Augustinus Foundation; Becket Foundation; Bristol-Myers Squibb; British Heart Foundation programme [PG/13/66/30442, PG/07/131/24254]; Canadian Institutes of Health Research [FRCN-CCT-83028]; Centre for Medical Systems Biology; Danish Centre for Health Technology Assessment; Danish Council for Independent Research [DFF-1333-00124, DFF-1331-00730B]; Danish Diabetes Association; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; Department of Health Policy Research Programme [0090049]; Diabetes UK; Donald W. Reynolds Foundation; Dutch Arthritis Association [DAA 2010_017]; Dutch government [NWO 184.021.007]; Emil Aaltonen Foundation; Erasmus MC; Erasmus University; European Commission [FP6-LSHG-CT-2006-018947, FP6-LSHG-CT-2006-01947, HEALTH-F2-2008-201865-GEFOS, FP7-201668, FP7-223004, FP7-259679, FP7-305739, FP7-IDEAS-ERC-323195]; European Regional Development Fund; EUROSPAN; Faculty of Biology and Medicine of Lausanne; Finnish Centre for Pensions; Finnish Cultural Foundation; Finnish Diabetes Research Society; Finnish Foundation of Cardiovascular Research; Finnish Foundation for Pediatric Research; Finnish National Institute for Health and Welfare; Finnish Special Governmental Subsidy for Health Sciences; Finska Lakaresallskapet; Folkhalsan Research Foundation; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; German Center for Diabetes Research (DZD); German Federal Ministry of Education and Research; GlaxoSmithKline; Goran Gustafsson Foundation; Heart Foundation of Northern Sweden; Helmholtz Zentrum Munchen; Ib Henriksen Foundation; Innovation-Oriented Research Program on Genomics (SenterNovem) [IGE05007]; Italian Ministry of Health [ICS110.1/RF97.71]; John W. Barton Sr. Chair in Genetics and Nutrition; Juho Vainio Foundation; King's College London; Knut and Alice Wallenberg Foundation; Turku University Hospital Medical Fund [X51001, 9M048, 9N035]; Leiden University Medical Centre; Li Ka Shing Foundation; Liv och Halsa; Local Government Pensions Institution; Ludwig-Maximilians-Universitat; Lundbeck Foundation; Lundberg Foundation; Medical Research Council [MC_U106179471, MC_UU_12013/3, MC_UU_12013/8]; Medical Research Council-GlaxoSmithKline pilot programme grant [G0701863]; Ministry of Education, Culture and Science of the Netherlands; Ministry of health, Welfare and Sports of the Netherlands; Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano; Danish Ministry of Internal Affairs and Health; Munich Center of Health Sciences; Municipality of Rotterdam; National Cancer Institute [CA047988]; National Eye Institute; National Institute on Aging (Intramural research programme) [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, 263MD9164, 263 MD 821336]; National Institute for Health Research; National Institutes of Health [DK52431, HG004399, HG004446, CA087969, CA055075, DK058845, CA65725, CA49449, CA67262, CA50385, UO1CA098233]; Netherlands Brain Foundation (HersenStichting Nederland); Netherlands Consortium for Healthy Aging [050-060-810]; Netherlands Genomics Initiative; Netherlands Heart Foundation [2001 D 032]; Netherlands Organization for Scientific Research [175-010-2005-011, 904-61-095, 911-03-012, 911-03-016, 917-66-344]; Netherlands Organization for the Health Research and Development; National Heart, Lung, and Blood Institute [5R01HL068891, 5R01HL087700, R01HL117078, HHSN26800625226C, HHSN268200782096C, HL-043851, HL-045670, HL080467, N01-HC95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N02-HL-64278, N01-HC-65226, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, R01-HL-088451, R00-HL-098459, U01-HG007033, UL1-RR-24156, UL1-RR-25005, UL1-TR-000040, UL1-TR-001079]; National Health Service Foundation Trust; National Institutes of Diabetes and Digestive and Kidney Diseases [1R01DK080015, R01DK089256, 5R01DK068336, 5R01DK075681, 5R01DK07568102]; Novo Nordisk; Novo Nordisk Foundation; New York Obesity Nutrition Research Center Pilot and Feasilibity Grant [DK-26687]; Orion-Farmos Research Foundation; Pfizer Inc.; Paavo Nurmi Foundation; Pahlssons Foundation; Research Foundation of Copenhagen County; Roche Pharmaceuticals; Research Institute for Diseases in the Elderly (RIDE2) [014-93-015]; Samfundet Folkhalsan; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; South Tyrolean Sparkasse Foundation; Swedish Diabetes Association; Swedish Diabetes Foundation; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation [20140422]; Swedish Research Council [2012-1397]; Swiss Institute of Bioinformatics; Swiss National Science Foundation [3100AO-116323/1, 33CSCO-122661, 33CS30-139468, 33CS30-148401]; Tampere Tuberculosis Foundation; Torsten and Ragnar Soderberg's Foundation; Umea University Career Development Award; Unilever Colworth; Wellcome Trust [WT064890, WT089062, WT090532, WT098017, WT098051, WT091551, 081917/Z/07/Z, 086596/Z/08/Z]; Wellcome Trust Centre for Human Genetics core funding [090532]; Wissenschaftsoffensive TMO; Yrjo Jahnsson Foundation; Kuopio University Hospital Medical Fund; Tampere University Hospital Medical Fund FX The full list of acknowledgements appears in the Supplementary Information. Funding for this study was provided by the Academy of Finland (41071, 117787, 118065, 121584, 124282, 126925, 129494, 129322, 129378, 130326, 134309, 134791, 136895, 139635, 250207, 263836, 286284 and 263924); Ahokas Foundation; ALF/LUA research grant in Gothenburg; Amgen; Augustinus Foundation; Becket Foundation; Bristol-Myers Squibb; British Heart Foundation programme (PG/13/66/30442 and PG/07/131/24254); Canadian Institutes of Health Research (FRCN-CCT-83028); Centre for Medical Systems Biology; Danish Centre for Health Technology Assessment; Danish Council for Independent Research (DFF-1333-00124 and DFF-1331-00730B); Danish Diabetes Association; Danish Heart Foundation; Danish Pharmaceutical Association; Danish Research Council; Department of Health Policy Research Programme (0090049); Diabetes UK; Donald W. Reynolds Foundation; Dutch Arthritis Association (DAA 2010_017); Dutch government (NWO 184.021.007); Emil Aaltonen Foundation; Erasmus MC; Erasmus University; European Commission (FP6-LSHG-CT-2006-018947, FP6-LSHG-CT-2006-01947, HEALTH-F2-2008-201865-GEFOS, FP7-201668, FP7-223004, FP7-259679, FP7-305739 and FP7-IDEAS-ERC-323195); European Regional Development Fund; EUROSPAN; Faculty of Biology and Medicine of Lausanne; Finnish Centre for Pensions; Finnish Cultural Foundation; Finnish Diabetes Research Society; Finnish Foundation of Cardiovascular Research; Finnish Foundation for Pediatric Research; Finnish National Institute for Health and Welfare; Finnish Special Governmental Subsidy for Health Sciences; Finska Lakaresallskapet; Folkhalsan Research Foundation; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; German Center for Diabetes Research (DZD); German Federal Ministry of Education and Research; GlaxoSmithKline; Goran Gustafsson Foundation; Heart Foundation of Northern Sweden; Helmholtz Zentrum Munchen; Ib Henriksen Foundation; Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007); Italian Ministry of Health (ICS110.1/RF97.71); John W. Barton Sr.; r Chair in Genetics and Nutrition; Juho Vainio Foundation; King's College London; Knut and Alice Wallenberg Foundation; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001, 9M048, 9N035); Leiden University Medical Centre; Li Ka Shing Foundation; Liv och Halsa; Local Government Pensions Institution; Ludwig-Maximilians-Universitat; Lundbeck Foundation; Lundberg Foundation; Medical Research Council (MC_U106179471, MC_UU_12013/3, and MC_UU_12013/8); Medical Research Council-GlaxoSmithKline pilot programme grant (G0701863); Ministry of Education, Culture and Science of the Netherlands; Ministry of health, Welfare and Sports of the Netherlands; Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano; Danish Ministry of Internal Affairs and Health; Munich Center of Health Sciences; Municipality of Rotterdam; National Cancer Institute (CA047988); National Eye Institute; National Institute on Aging (Intramural research programme, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, 263MD9164 and 263 MD 821336); National Institute for Health Research; National Institutes of Health (DK52431, HG004399, HG004446, CA087969, CA055075, DK058845, CA65725, CA49449, CA67262, CA50385 and UO1CA098233); Netherlands Brain Foundation (HersenStichting Nederland); Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Genomics Initiative; Netherlands Heart Foundation (2001 D 032); Netherlands Organization for Scientific Research (175-010-2005-011, 904-61-095, 911-03-012, 911-03-016, 917-66-344 and 911-03-012); Netherlands Organization for the Health Research and Development; National Heart, Lung, and Blood Institute (5R01HL068891, 5R01HL087700, R01HL117078, HHSN26800625226C, HHSN268200782096C, HL-043851, HL-045670, HL080467, N01-HC95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, N02-HL-64278, N01-HC-65226, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258, R01-HL-071259, R01-HL-088451, R00-HL-098459, U01-HG007033, UL1-RR-24156, UL1-RR-25005, UL1-TR-000040 and UL1-TR-001079); National Health Service Foundation Trust; National Institutes of Diabetes and Digestive and Kidney Diseases (1R01DK080015, R01DK089256, 5R01DK068336, 5R01DK075681 and 5R01DK07568102); Novo Nordisk; Novo Nordisk Foundation; New York Obesity Nutrition Research Center Pilot and Feasilibity Grant (DK-26687); Orion-Farmos Research Foundation; Pfizer Inc.; Paavo Nurmi Foundation; Pahlssons Foundation; Research Foundation of Copenhagen County; Roche Pharmaceuticals; Research Institute for Diseases in the Elderly (014-93-015; RIDE2); Samfundet Folkhalsan; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; South Tyrolean Sparkasse Foundation; Swedish Diabetes Association; Swedish Diabetes Foundation; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20140422); Swedish Research Council (2012-1397); Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 33CSCO-122661, 33CS30-139468 and 33CS30-148401); Tampere Tuberculosis Foundation; Torsten and Ragnar Soderberg's Foundation; Umea University Career Development Award; Unilever Colworth; Wellcome Trust (WT064890, WT089062, WT090532, WT098017, WT098051, WT091551, 081917/Z/07/Z and 086596/Z/08/Z); Wellcome Trust Centre for Human Genetics core funding (090532); Wissenschaftsoffensive TMO; Yrjo Jahnsson Foundation. NR 70 TC 3 Z9 3 U1 6 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 FEB PY 2016 VL 7 AR 10494 DI 10.1038/ncomms10494 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF0EQ UT WOS:000371012200001 PM 26833098 ER PT J AU Koyama, S Akbay, EA Li, YY Herter-Sprie, GS Buczkowski, KA Richards, WG Gandhi, L Redig, AJ Rodig, SJ Asahina, H Jones, RE Kulkarni, MM Kuraguchi, M Palakurthi, S Fecci, PE Johnson, BE Janne, PA Engelman, JA Gangadharan, SP Costa, DB Freeman, GJ Bueno, R Hodi, FS Dranoff, G Wong, KK Hammerman, PS AF Koyama, Shohei Akbay, Esra A. Li, Yvonne Y. Herter-Sprie, Grit S. Buczkowski, Kevin A. Richards, William G. Gandhi, Leena Redig, Amanda J. Rodig, Scott J. Asahina, Hajime Jones, Robert E. Kulkarni, Meghana M. Kuraguchi, Mari Palakurthi, Sangeetha Fecci, Peter E. Johnson, Bruce E. Janne, Pasi A. Engelman, Jeffrey A. Gangadharan, Sidharta P. Costa, Daniel B. Freeman, Gordon J. Bueno, Raphael Hodi, F. Stephen Dranoff, Glenn Wong, Kwok-Kin Hammerman, Peter S. TI Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints SO NATURE COMMUNICATIONS LA English DT Article ID CELL LUNG-CANCER; ANTI-PD-L1 ANTIBODY; ANTITUMOR IMMUNITY; TIM-3; TUMORS; IMMUNOTHERAPY; SAFETY; ACTIVATION; EXHAUSTION; INHIBITOR AB Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade. C1 [Koyama, Shohei; Freeman, Gordon J.; Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Koyama, Shohei; Freeman, Gordon J.; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA. [Koyama, Shohei; Akbay, Esra A.; Li, Yvonne Y.; Herter-Sprie, Grit S.; Asahina, Hajime; Johnson, Bruce E.; Janne, Pasi A.; Freeman, Gordon J.; Hodi, F. Stephen; Dranoff, Glenn; Wong, Kwok-Kin; Hammerman, Peter S.] Brigham & Womens Hosp, Depatment Med, Boston, MA 02115 USA. [Koyama, Shohei; Akbay, Esra A.; Li, Yvonne Y.; Herter-Sprie, Grit S.; Asahina, Hajime; Johnson, Bruce E.; Janne, Pasi A.; Freeman, Gordon J.; Hodi, F. Stephen; Dranoff, Glenn; Wong, Kwok-Kin; Hammerman, Peter S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Akbay, Esra A.; Li, Yvonne Y.; Herter-Sprie, Grit S.; Buczkowski, Kevin A.; Gandhi, Leena; Redig, Amanda J.; Asahina, Hajime; Johnson, Bruce E.; Janne, Pasi A.; Hodi, F. Stephen; Dranoff, Glenn; Wong, Kwok-Kin; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Dept Thorac Surg, Boston, MA 02115 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Jones, Robert E.; Kulkarni, Meghana M.; Kuraguchi, Mari; Palakurthi, Sangeetha; Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Fecci, Peter E.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Gangadharan, Sidharta P.; Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hammerman, Peter S.] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Dranoff, G (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA.; Dranoff, G; Wong, KK; Hammerman, PS (reprint author), Brigham & Womens Hosp, Depatment Med, Boston, MA 02115 USA.; Dranoff, G; Wong, KK; Hammerman, PS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Wong, KK (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA.; Hammerman, PS (reprint author), Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA. EM glenn_dranoff@dfci.harvard.edu; kwong1@partners.org; peter_hammerman@dfci.harvard.edu OI Costa, Daniel/0000-0002-0689-395X; Gandhi, Leena/0000-0002-2398-9179; Koyama, Shohei/0000-0002-6897-9417 FU Clinical Investigator Award from Damon Runyon Cancer Research Foundation; Developmental Project Grant from NCI [P50 CA090578]; Starr Consortium for Cancer Research; NIH/NCI [P01 CA120964, 5R01CA163896-04, 1R01CA195740-01, 5R01CA140594-07, 5R01CA122794-10, 5R01CA166480-04]; Gross-Loh Family Fund for Lung Cancer Research; Susan Spooner Family Lung Cancer Research Fund at Dana-Farber Cancer Institute; Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award; Kanae Foundation for the Promotion of Medical Science Fellowship Award; Deutsche Forschungsgemeinschaft [HE 6897/1-1]; Claudia Adams Barr Program for Innovative Cancer Research; NIH [R01AI08995]; American Cancer Society [RSG 11-186]; NCI [CA090578]; Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant [SU2C-AACR-DT17-15] FX We thank Dana-Farber flow core facility (Suzan Lazo-Kallanian, John Daley, Kristen Cowens, Steven Paul) for help with flow cytometry anlaysis, Harvard Medical School Rodent Pathology Core for tissue processing and Brigham and Women's Pathology Core and Mei Zhang for help with tissue stainings, Xiaoen Wang for help with mouse MRI, and the Dana-Farber Center for Cancer Genome Discovery for RNA sequencing.P.S.H. is supported by a Clinical Investigator Award from the Damon Runyon Cancer Research Foundation, a Developmental Project Grant from NCI P50 CA090578 and the Starr Consortium for Cancer Research. K.-K.W. is supported by NIH/NCI P01 CA120964, 5R01CA163896-04, 1R01CA195740-01, 5R01CA140594-07, 5R01CA122794-10 and 5R01CA166480-04 grants and support from Gross-Loh Family Fund for Lung Cancer Research and Susan Spooner Family Lung Cancer Research Fund at Dana-Farber Cancer Institute. S.K. is supported by Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award and The Kanae Foundation for the Promotion of Medical Science Fellowship Award. G.S.H.-S. is supported by the Deutsche Forschungsgemeinschaft (HE 6897/1-1) and the Claudia Adams Barr Program for Innovative Cancer Research. G.J.F. is supported by NIH R01AI08995. D.B.C. is supported by American Cancer Society grant RSG 11-186 and NCI grant CA090578. P.S.H., K.-K.W. J.A.E. and P.A.J. are supported by a Stand Up To Cancer-American Cancer Society Lung Cancer Dream Team Translational Research Grant (Grant Number: SU2C-AACR-DT17-15). Stand Up To Cancer is a programme of the Entertainment Industry Foundation. NR 37 TC 37 Z9 40 U1 17 U2 34 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 FEB PY 2016 VL 7 AR 10501 DI 10.1038/ncomms10501 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF1YK UT WOS:000371135600001 PM 26883990 ER PT J AU Lu, AT Hannon, E Levine, ME Hao, K Crimmins, EM Lunnon, K Kozlenkov, A Mill, J Dracheva, S Horvath, S AF Lu, Ake T. Hannon, Eilis Levine, Morgan E. Hao, Ke Crimmins, Eileen M. Lunnon, Katie Kozlenkov, Alexey Mill, Jonathan Dracheva, Stella Horvath, Steve TI Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; DNA METHYLATION AGE; HUMAN LONGEVITY; HUMAN BRAIN; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; LIFE-SPAN; HUMAN TISSUES; CELL-TYPES; CLOCK AB DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 x 10(-8)) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P = 6.9 x 10(-18)) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis-effect on DHX57 (P = 4.4 x 10(-5)). Gene sets found by our GWAS analysis of cerebellar age acceleration exhibit significant overlap with those of Alzheimer's disease (P = 4.4 x 10(-15)), age-related macular degeneration (P = 6.4 x 10(-6)), and Parkinson's disease (P = 2.6 x 10(-4)). Overall, our results demonstrate the utility of a new paradigm for understanding aging and age-related diseases: it will be fruitful to use epigenetic tissue age as endophenotype in GWAS. C1 [Lu, Ake T.; Levine, Morgan E.; Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Hannon, Eilis; Lunnon, Katie; Mill, Jonathan] Univ Exeter, Sch Med, Exeter EX2 5DW, Devon, England. [Hao, Ke] Icahn Sch Med Mt Sinai, Friedman Brain Inst, Dept Genet & Genom Sci, New York, NY 10029 USA. [Crimmins, Eileen M.] Univ So Calif, Davis Sch Gerontol, Ethel Percy Andrus Gerontol Ctr, 3715 McClintock Ave, Los Angeles, CA 90089 USA. [Kozlenkov, Alexey; Dracheva, Stella] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Kozlenkov, Alexey; Dracheva, Stella] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Kozlenkov, Alexey; Dracheva, Stella] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Mill, Jonathan] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA. RP Horvath, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.; Horvath, S (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA. EM shorvath@mednet.ucla.edu RI Mill, Jonathan/B-3276-2010; OI Mill, Jonathan/0000-0003-1115-3224; Lunnon, Katie/0000-0001-7570-6065; Hannon, Eilis/0000-0001-6840-072X FU National Institutes of Health [NIA/NIH 5R01AG042511-02] FX The study was supported by the National Institutes of Health (NIA/NIH 5R01AG042511-02). NR 56 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD FEB PY 2016 VL 7 AR 10561 DI 10.1038/ncomms10561 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF0FM UT WOS:000371014500003 PM 26830004 ER PT J AU Lu, YC Day, FR Gustafsson, S Buchkovich, ML Na, JB Bataille, V Cousminer, DL Dastani, Z Drong, AW Esko, T Evans, DM Falchi, M Feitosa, MF Ferreira, T Hedman, AK Haring, R Hysi, PG Iles, MM Justice, AE Kanoni, S Lagou, V Li, R Li, X Locke, A Lu, C Magi, R Perry, JRB Pers, TH Qi, QB Sanna, M Schmidt, EM Scott, WR Shungin, D Teumer, A Vinkhuyzen, AAE Walker, RW Westra, HJ Zhang, MF Zhang, WH Zhao, JH Zhu, ZH Afzal, U Ahluwalia, TS Bakker, SJL Bellis, C Bonnefond, A Borodulin, K Buchman, AS Cederholm, T Choh, AC Choi, HJ Curran, JE de Groot, LCPGM De Jager, PL Dhonukshe-Rutten, RAM Enneman, AW Eury, E Evans, DS Forsen, T Friedrich, N Fumeron, F Garcia, ME Gartner, S Han, BG Havulinna, AS Hayward, C Hernandez, D Hillege, H Ittermann, T Kent, JW Kolcic, I Laatikainen, T Lahti, J Leach, IM Lee, CG Lee, JY Liu, T Liu, YF Lobbens, S Loh, M Lyytikainen, LP Medina-Gomez, C Michaelsson, K Nalls, MA Nielson, CM Oozageer, L Pascoe, L Paternoster, L Polasek, O Ripatti, S Sarzynski, MA Shin, CS Narancic, NS Spira, D Srikanth, P Steinhagen-Thiessen, E Sung, YJ Swart, KMA Taittonen, L Tanaka, T Tikkanen, E van der Velde, N van Schoor, NM Verweij, N Wright, AF Yu, L Zmuda, JM Eklund, N Forrester, T Grarup, N Jackson, AU Kristiansson, K Kuulasmaa, T Kuusisto, J Lichtner, P Luan, JA Mahajan, A Mannisto, S Palmer, CD Ried, JS Scott, RA Stancakova, A Wagner, PJ Demirkan, A Doring, A Gudnason, V Kiel, DP Kuhnel, B Mangino, M Mcknight, B Menni, C O'Connell, JR Oostra, BA Shuldiner, AR Song, KJ Vandenput, L van Duijn, CM Vollenweider, P White, CC Boehnke, M Boettcher, Y Cooper, RS Forouhi, NG Gieger, C Grallert, H Hingorani, A Jorgensen, T Jousilahti, P Kivimaki, M Kumari, M Laakso, M Langenberg, C Linneberg, A Luke, A Mckenzie, CA Palotie, A Pedersen, O Peters, A Strauch, K Tayo, BO Wareham, NJ Bennett, DA Bertram, L Blangero, J Bluher, M Bouchard, C Campbell, H Cho, NH Cummings, SR Czerwinski, SA Demuth, I Eckardt, R Eriksson, JG Ferrucci, L Franco, OH Froguel, P Gansevoort, RT Hansen, T Harris, TB Hastie, N Heliovaara, M Hofman, A Jordan, JM Jula, A Kahonen, M Kajantie, E Knekt, PB Koskinen, S Kovacs, P Lehtimaki, T Lind, L Liu, YM Orwoll, ES Osmond, C Perola, M Perusse, L Raitakari, OT Rankinen, T Rao, DC Rice, TK Rivadeneira, F Rudan, I Salomaa, V Sorensen, TIA Stumvoll, M Tonjes, A Towne, B Tranah, GJ Tremblay, A Uitterlinden, AG van der Harst, P Vartiainen, E Viikari, JS Vitart, V Vohl, MC Volzke, H Walker, M Wallaschofski, H Wild, S Wilson, JF Yengo, L Bishop, DT Borecki, IB Chambers, JC Cupples, LA Dehghan, A Deloukas, P Fatemifar, G Fox, C Furey, TS Franke, L Han, JL Hunter, DJ Karjalainen, J Karpe, F Kaplan, RC Kooner, JS McCarthy, MI Murabito, JM Morris, AP Bishop, JAN North, KE Ohlsson, C Ong, KK Prokopenko, I Richards, JB Schadt, EE Spector, TD Widen, E Willer, CJ Yang, J Ingelsson, E Mohlke, KL Hirschhorn, JN Pospisilik, JA Zillikens, MC Lindgren, C Kilpelainen, TO Loos, RJF AF Lu, Yingchang Day, Felix R. Gustafsson, Stefan Buchkovich, Martin L. Na, Jianbo Bataille, Veronique Cousminer, Diana L. Dastani, Zari Drong, Alexander W. Esko, Tonu Evans, David M. Falchi, Mario Feitosa, Mary F. Ferreira, Teresa Hedman, Asa K. Haring, Robin Hysi, Pirro G. Iles, Mark M. Justice, Anne E. Kanoni, Stavroula Lagou, Vasiliki Li, Rui Li, Xin Locke, Adam Lu, Chen Magi, Reedik Perry, John R. B. Pers, Tune H. Qi, Qibin Sanna, Marianna Schmidt, Ellen M. Scott, William R. Shungin, Dmitry Teumer, Alexander Vinkhuyzen, Anna A. E. Walker, Ryan W. Westra, Harm-Jan Zhang, Mingfeng Zhang, Weihua Zhao, Jing Hua Zhu, Zhihong Afzal, Uzma Ahluwalia, Tarunveer Singh Bakker, Stephan J. L. Bellis, Claire Bonnefond, Amelie Borodulin, Katja Buchman, Aron S. Cederholm, Tommy Choh, Audrey C. Choi, Hyung Jin Curran, Joanne E. de Groot, Lisette C. P. G. M. De Jager, Philip L. Dhonukshe-Rutten, Rosalie A. M. Enneman, Anke W. Eury, Elodie Evans, Daniel S. Forsen, Tom Friedrich, Nele Fumeron, Frederic Garcia, Melissa E. Gartner, Simone Han, Bok-Ghee Havulinna, Aki S. Hayward, Caroline Hernandez, Dena Hillege, Hans Ittermann, Till Kent, Jack W. Kolcic, Ivana Laatikainen, Tiina Lahti, Jari Leach, Irene Mateo Lee, Christine G. Lee, Jong-Young Liu, Tian Liu, Youfang Lobbens, Stephane Loh, Marie Lyytikainen, Leo-Pekka Medina-Gomez, Carolina Michaelsson, Karl Nalls, Mike A. Nielson, Carrie M. Oozageer, Laticia Pascoe, Laura Paternoster, Lavinia Polasek, Ozren Ripatti, Samuli Sarzynski, Mark A. Shin, Chan Soo Narancic, Nina Smolej Spira, Dominik Srikanth, Priya Steinhagen-Thiessen, Elisabeth Sung, Yun Ju Swart, Karin M. A. Taittonen, Leena Tanaka, Toshiko Tikkanen, Emmi van der Velde, Nathalie van Schoor, Natasja M. Verweij, Niek Wright, Alan F. Yu, Lei Zmuda, Joseph M. Eklund, Niina Forrester, Terrence Grarup, Niels Jackson, Anne U. Kristiansson, Kati Kuulasmaa, Teemu Kuusisto, Johanna Lichtner, Peter Luan, Jian'an Mahajan, Anubha Mannisto, Satu Palmer, Cameron D. Ried, Janina S. Scott, Robert A. Stancakova, Alena Wagner, Peter J. Demirkan, Ayse Doring, Angela Gudnason, Vilmundur Kiel, Douglas P. Kuhnel, Brigitte Mangino, Massimo Mcknight, Barbara Menni, Cristina O'Connell, Jeffrey R. Oostra, Ben A. Shuldiner, Alan R. Song, Kijoung Vandenput, Liesbeth van Duijn, Cornelia M. Vollenweider, Peter White, Charles C. Boehnke, Michael Boettcher, Yvonne Cooper, Richard S. Forouhi, Nita G. Gieger, Christian Grallert, Harald Hingorani, Aroon Jorgensen, Torben Jousilahti, Pekka Kivimaki, Mika Kumari, Meena Laakso, Markku Langenberg, Claudia Linneberg, Allan Luke, Amy Mckenzie, Colin A. Palotie, Aarno Pedersen, Oluf Peters, Annette Strauch, Konstantin Tayo, Bamidele O. Wareham, Nicholas J. Bennett, David A. Bertram, Lars Blangero, John Bluher, Matthias Bouchard, Claude Campbell, Harry Cho, Nam H. Cummings, Steven R. Czerwinski, Stefan A. Demuth, Ilja Eckardt, Rahel Eriksson, Johan G. Ferrucci, Luigi Franco, Oscar H. Froguel, Philippe Gansevoort, Ron T. Hansen, Torben Harris, Tamara B. Hastie, Nicholas Heliovaara, Markku Hofman, Albert Jordan, Joanne M. Jula, Antti Kahonen, Mika Kajantie, Eero Knekt, Paul B. Koskinen, Seppo Kovacs, Peter Lehtimaki, Terho Lind, Lars Liu, Yongmei Orwoll, Eric S. Osmond, Clive Perola, Markus Perusse, Louis Raitakari, Olli T. Rankinen, Tuomo Rao, D. C. Rice, Treva K. Rivadeneira, Fernando Rudan, Igor Salomaa, Veikko Sorensen, Thorkild I. A. Stumvoll, Michael Tonjes, Anke Towne, Bradford Tranah, Gregory J. Tremblay, Angelo Uitterlinden, Andre G. van der Harst, Pim Vartiainen, Erkki Viikari, Jorma S. Vitart, Veronique Vohl, Marie-Claude Volzke, Henry Walker, Mark Wallaschofski, Henri Wild, Sarah Wilson, James F. Yengo, Loic Bishop, D. Timothy Borecki, Ingrid B. Chambers, John C. Cupples, L. Adrienne Dehghan, Abbas Deloukas, Panos Fatemifar, Ghazaleh Fox, Caroline Furey, Terrence S. Franke, Lude Han, Jiali Hunter, David J. Karjalainen, Juha Karpe, Fredrik Kaplan, Robert C. Kooner, Jaspal S. McCarthy, Mark I. Murabito, Joanne M. Morris, Andrew P. Bishop, Julia A. N. North, Kari E. Ohlsson, Claes Ong, Ken K. Prokopenko, Inga Richards, J. Brent Schadt, Eric E. Spector, Tim D. Widen, Elisabeth Willer, Cristen J. Yang, Jian Ingelsson, Erik Mohlke, Karen L. Hirschhorn, Joel N. Pospisilik, John Andrew Zillikens, M. Carola Lindgren, Cecilia Kilpelainen, Tuomas Oskari Loos, Ruth J. F. TI y New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; MASS INDEX; INSULIN-RESISTANCE; COMMON VARIANTS; GENETIC ARCHITECTURE; SUSCEPTIBILITY LOCI; IDENTIFIES COMMON; PROVIDES INSIGHTS; ENERGY-BALANCE; CUTANEOUS NEVI AB To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P < 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk. C1 [Lu, Yingchang; Walker, Ryan W.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Lu, Yingchang; Walker, Ryan W.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Day, Felix R.; Perry, John R. B.; Zhao, Jing Hua; Luan, Jian'an; Scott, Robert A.; Forouhi, Nita G.; Langenberg, Claudia; Wareham, Nicholas J.; Ong, Ken K.; Kilpelainen, Tuomas Oskari; Loos, Ruth J. F.] Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge CB2 0QQ, England. [Gustafsson, Stefan; Hedman, Asa K.; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, S-75085 Uppsala, Sweden. [Gustafsson, Stefan; Hedman, Asa K.; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol, S-75185 Uppsala, Sweden. [Buchkovich, Martin L.; Furey, Terrence S.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Na, Jianbo] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA. [Bataille, Veronique] West Herts NHS Trust, Hemel Hempstead HP2 4AD, Herts, England. [Bataille, Veronique; Falchi, Mario; Hysi, Pirro G.; Sanna, Marianna; Mangino, Massimo; Menni, Cristina; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England. [Cousminer, Diana L.; Ripatti, Samuli; Tikkanen, Emmi; Kristiansson, Kati; Wagner, Peter J.; Palotie, Aarno; Perola, Markus; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland, FI-00290 Helsinki, Finland. [Dastani, Zari; Li, Rui; Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Human Genet, Montreal, PQ H3T 1E2, Canada. [Drong, Alexander W.; Ferreira, Teresa; Hedman, Asa K.; Lagou, Vasiliki; Magi, Reedik; Mahajan, Anubha; McCarthy, Mark I.; Morris, Andrew P.; Prokopenko, Inga; Lindgren, Cecilia] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Esko, Tonu; Magi, Reedik; Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia. [Esko, Tonu; Palmer, Cameron D.; Hunter, David J.; Hirschhorn, Joel N.; Lindgren, Cecilia] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA. [Esko, Tonu; Pers, Tune H.; Palmer, Cameron D.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.; Palmer, Cameron D.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.; Palmer, Cameron D.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Evans, David M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia. [Evans, David M.; Paternoster, Lavinia; Sorensen, Thorkild I. A.; Fatemifar, Ghazaleh] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England. [Falchi, Mario; Sanna, Marianna; Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London W12 0NN, England. [Feitosa, Mary F.; Rao, D. C.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA. [Haring, Robin; Friedrich, Nele; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany. [Haring, Robin] European Univ Appl Sci, Fac Appl Publ Hlth, D-18055 Rostock, Germany. [Iles, Mark M.; Bishop, D. Timothy; Bishop, Julia A. N.] Univ Leeds, Canc Res UK Leeds Ctr, Leeds Inst Canc & Pathol, Leeds LS9 7TF, W Yorkshire, England. [Justice, Anne E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Kanoni, Stavroula; Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England. [Kanoni, Stavroula; Ripatti, Samuli; Palotie, Aarno; Deloukas, Panos] Wellcome Trust Sanger Inst, Human Genet, Cambridge CB10 1SA, England. [Lagou, Vasiliki; Karpe, Fredrik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Li, Xin; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Locke, Adam; Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Lu, Chen; White, Charles C.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Pers, Tune H.; Ahluwalia, Tarunveer Singh; Grarup, Niels; Pedersen, Oluf; Hansen, Torben; Sorensen, Thorkild I. A.; Kilpelainen, Tuomas Oskari] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark. [Pers, Tune H.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA. [Pers, Tune H.] Statens Serum Inst, Dept Epidemiol Res, DK-2100 Copenhagen, Denmark. [Qi, Qibin; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Popualt Hlth, Bronx, NY 10461 USA. [Schmidt, Ellen M.; Willer, Cristen J.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA. [Scott, William R.; Zhang, Weihua; Afzal, Uzma; Loh, Marie; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England. [Scott, William R.; Zhang, Weihua; Afzal, Uzma; Oozageer, Laticia; Chambers, John C.; Kooner, Jaspal S.] Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England. [Shungin, Dmitry] Lund Univ, Ctr Diabet, Dept Clin Sci, Genet & Mol Epidemiol Unit,Skane Univ Hosptial, S-20502 Malmo, Sweden. [Shungin, Dmitry] Umea Univ, Dept Publ Hlth & Clin Med, Med Unit, S-90187 Umea, Sweden. [Shungin, Dmitry] Umea Univ, Dept Odontol, S-90185 Umea, Sweden. [Teumer, Alexander; Ittermann, Till; Volzke, Henry] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany. [Teumer, Alexander] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany. [Vinkhuyzen, Anna A. E.; Zhu, Zhihong; Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Westra, Harm-Jan; De Jager, Philip L.; Walker, Mark] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Westra, Harm-Jan] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02446 USA. [Westra, Harm-Jan] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02446 USA. [Westra, Harm-Jan] Harvard Univ, Sch Med, Boston, MA 02446 USA. [Westra, Harm-Jan] Partners Ctr Personalized Genet Med, Boston, MA 02446 USA. [Zhang, Mingfeng] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Ahluwalia, Tarunveer Singh] Univ Copenhagen, Fac Hlth & Med Sceinces, Copenhagen Prospect Studies Asthma Childhood, DK-2200 Copenhagen, Denmark. [Ahluwalia, Tarunveer Singh] Gentofte Univ Hosp, Danish Pediat Asthma Ctr, DK-2200 Copenhagen, Denmark. [Ahluwalia, Tarunveer Singh] Steno Diabet Ctr AS, DK-2820 Gentofte, Denmark. [Bakker, Stephan J. L.; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-9700 RB Groningen, Netherlands. [Bellis, Claire; Kent, Jack W.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX 78245 USA. [Bonnefond, Amelie; Eury, Elodie; Lobbens, Stephane; Froguel, Philippe; Yengo, Loic] CNRS UMR 8199, F-59019 Lille, France. [Bonnefond, Amelie; Eury, Elodie; Lobbens, Stephane; Froguel, Philippe; Yengo, Loic] European Genom Inst Diabet, F-59000 Lille, France. [Bonnefond, Amelie; Eury, Elodie; Lobbens, Stephane; Froguel, Philippe; Yengo, Loic] Univ Lille 2, F-59000 Lille, France. [Borodulin, Katja; Havulinna, Aki S.; Laatikainen, Tiina; Eklund, Niina; Kristiansson, Kati; Mannisto, Satu; Wagner, Peter J.; Jousilahti, Pekka; Eriksson, Johan G.; Heliovaara, Markku; Jula, Antti; Kajantie, Eero; Knekt, Paul B.; Koskinen, Seppo; Perola, Markus; Salomaa, Veikko; Vartiainen, Erkki] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland. [Buchman, Aron S.; Yu, Lei; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Cederholm, Tommy] Uppsala Univ, Dept Publ Hlth & Caring Sci, Clin Nutr & Metab, S-75185 Uppsala, Sweden. [Choh, Audrey C.; Czerwinski, Stefan A.; Towne, Bradford] Wright State Univ, Boonshoft Sch Med, Lifespan Hlth Res Ctr, Dayton, OH 45420 USA. [Choi, Hyung Jin] Seoul Natl Univ, Coll Med, Dept Anat, Seoul 03080, South Korea. [Curran, Joanne E.; Blangero, John] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Brownsville, TX 78520 USA. [de Groot, Lisette C. P. G. M.; Dhonukshe-Rutten, Rosalie A. M.] Wageningen Univ, Dept Human Nutr, NL-6700 EV Wageningen, Netherlands. [De Jager, Philip L.; Fox, Caroline] Harvard Univ, Sch Med, Boston, MA 02115 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA. [Enneman, Anke W.; Medina-Gomez, Carolina; van der Velde, Nathalie; Rivadeneira, Fernando; Uitterlinden, Andre G.; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Evans, Daniel S.; Cummings, Steven R.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA. [Forsen, Tom; Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, FI-00014 Helsinki, Finland. [Fumeron, Frederic] Ctr Rech Cordeliers, INSERM, UMR S 1138, F-75006 Paris, France. [Fumeron, Frederic] Univ Paris 06, Sorbonne Univ, Ctr Rech Cordeliers, UMR S 1138, F-75006 Paris, France. [Fumeron, Frederic] Univ Paris 05, Sorbonne Paris Cite, Ctr Rech Cordeliers, UMR S 1138, F-75006 Paris, France. [Fumeron, Frederic] Univ Paris Diderot, Sorbonne Paris Cite, Ctr Rech Cordeliers, UMR S 1138, F-75006 Paris, France. [Garcia, Melissa E.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Gartner, Simone] Univ Med Greifswald, Dept Med A, D-17475 Greifswald, Germany. [Han, Bok-Ghee; Lee, Jong-Young] Natl Inst Hlth, Ctr Genome Sci, Osong Hlth Technol Adm Complex, Chungcheongbuk Do 370914, South Korea. [Hayward, Caroline; Wright, Alan F.; Hastie, Nicholas; Vitart, Veronique; Wilson, James F.] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Hernandez, Dena; Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Hillege, Hans; Leach, Irene Mateo; Verweij, Niek; van der Harst, Pim; Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. [Kolcic, Ivana; Polasek, Ozren] Univ Split, Dept Publ Hlth, Fac Med, Split 21000, Croatia. [Laatikainen, Tiina] Hosp Dist North Karelia, FI-80210 Joensuu, Finland. [Laatikainen, Tiina] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, FI-70211 Kuopio, Finland. [Lahti, Jari; Eriksson, Johan G.] Folkhalsan Res Ctr, FI-00290 Helsinki, Finland. [Lahti, Jari] Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland. [Lee, Christine G.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Lee, Christine G.] Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 USA. [Liu, Tian] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Liu, Tian] Max Planck Inst Human Dev, D-14194 Berlin, Germany. [Liu, Youfang; Jordan, Joanne M.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27599 USA. [Loh, Marie] ASTAR, TLGM, 8A Biomed Grove,Immunos,Level 5, Singapore 138648, Singapore. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FI-33014 Tampere, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FI-33520 Tampere, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, FI-33520 Tampere, Finland. [Medina-Gomez, Carolina; van Duijn, Cornelia M.; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Zillikens, M. Carola] NCHA, NGI, Rotterdam, Netherlands. [Medina-Gomez, Carolina; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Michaelsson, Karl] Uppsala Univ, Dept Surg Sci, Orthoped, S-75185 Uppsala, Sweden. [Nielson, Carrie M.; Srikanth, Priya] Oregon Hlth & Sci Univ, Sch Publ Hlth, Portland, OR 97239 USA. [Nielson, Carrie M.; Srikanth, Priya; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97239 USA. [Pascoe, Laura] Newcastle Univ, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Polasek, Ozren; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland. [Ripatti, Samuli; Tikkanen, Emmi] Univ Helsinki, Hjelt Inst, FI-00014 Helsinki, Finland. [Sarzynski, Mark A.; Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA. [Shin, Chan Soo] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea. [Narancic, Nina Smolej] Inst Anthropol Res, Zagreb 10000, Croatia. [Spira, Dominik; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja; Eckardt, Rahel] Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13347 Berlin, Germany. [Spira, Dominik; Steinhagen-Thiessen, Elisabeth] Charite, Lipid Clin, Interdisciplinary Metab Ctr, D-13353 Berlin, Germany. [Sung, Yun Ju; Rao, D. C.; Rice, Treva K.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Swart, Karin M. A.; van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands. [Swart, Karin M. A.; van Schoor, Natasja M.] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1081 BT Amsterdam, Netherlands. [Taittonen, Leena] Univ Oulu, Dept Pediat, FI-90014 Oulu, Finland. [Taittonen, Leena] Vaasa Cent Hosp, Dept Pediat, FI-65100 Vaasa, Finland. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Forrester, Terrence; Mckenzie, Colin A.] Univ W Indies, Res Inst Trop Med, Trop Metab Res Unit, Mona JMAAW15, Jamaica. [Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio 70210, Finland. [Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70210, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, Kuopio 70029, Finland. [Lichtner, Peter] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany. [Ried, Janina S.; Kuhnel, Brigitte; Gieger, Christian; Strauch, Konstantin] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany. [Stancakova, Alena] Univ Eastern Finland, Dept Med, Kuopio 70210, Finland. [Stancakova, Alena] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Demirkan, Ayse; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands. [Doring, Angela] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany. [Doring, Angela; Kuhnel, Brigitte; Gieger, Christian; Grallert, Harald; Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany. [Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. [Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kiel, Douglas P.] Inst Aging Res Hebrew Senior Life, Boston, MA 02131 USA. [Kuhnel, Brigitte; Gieger, Christian; Grallert, Harald; Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany. [Mcknight, Barbara] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Mcknight, Barbara] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98109 USA. [Mcknight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [O'Connell, Jeffrey R.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Program Personalized & Genom Med,Div Endocrinol D, Baltimore, MD 21201 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21042 USA. [Song, Kijoung] GlaxoSmithKline, Genet Projects Clin Platforms & Sci, Philadelphia, PA 19112 USA. [Vandenput, Liesbeth; Ohlsson, Claes] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med & Clin N, S-41345 Gothenburg, Sweden. [van Duijn, Cornelia M.] Ctr Med Syst Biol, NL-2300 Leiden, Netherlands. [Vollenweider, Peter] Univ Hosp Lausanne CHUV, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Vollenweider, Peter] Univ Lausanne, CH-1011 Lausanne, Switzerland. [Boettcher, Yvonne; Bluher, Matthias; Kovacs, Peter; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany. [Boettcher, Yvonne; Bluher, Matthias; Stumvoll, Michael; Tonjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany. [Cooper, Richard S.; Luke, Amy; Tayo, Bamidele O.] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 61053 USA. [Grallert, Harald] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany. [Hingorani, Aroon] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England. [Jorgensen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark. [Jorgensen, Torben] Aalborg Univ, Fac Med, DK-9220 Aalborg, Denmark. [Jorgensen, Torben] Res Ctr Prevent & Hlth, DK-2600 Capital Region Denmark, Denmark. [Kivimaki, Mika; Kumari, Meena; Langenberg, Claudia] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England. [Linneberg, Allan] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark. [Palotie, Aarno] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany. [Bertram, Lars] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, London W6 8RP, England. [Bertram, Lars] Med Univ Lubeck, Inst Neurogenet, Lubeck Interdisciplinary Platform Genome Analyt, D-23562 Lubeck, Germany. [Bertram, Lars] Med Univ Lubeck, Inst Integrat & Expt Genom, Lubeck Interdisciplinary Platform Genome Analyt, D-23562 Lubeck, Germany. [Cho, Nam H.] Ajou Univ, Sch Med, Dept Prevent Med, Suwon 443721, Kyoung Gi, South Korea. [Demuth, Ilja] Charite, Inst Med & Human Genet, D-13353 Berlin, Germany. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, DK-5000 Odense, Denmark. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, FI-33521 Tampere, Finland. [Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FI-33014 Tampere, Finland. [Kajantie, Eero] Helsinki Univ Hosp, Childrens Hosp, FI-00029 Helsinki, Finland. [Kajantie, Eero] Univ Helsinki, FI-00029 Helsinki, Finland. [Kajantie, Eero] Oulu Univ Hosp, MRC Oulu, Dept Obstet & Gynecol, FI-90029 Oulu, Finland. [Kajantie, Eero] Univ Oulu, FI-90029 Oulu, Finland. [Lind, Lars] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden. [Liu, Yongmei] Wake Forest Sch Med, Ctr Human Genet, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Osmond, Clive] Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England. [Perusse, Louis; Tremblay, Angelo] Univ Laval, Dept Kinesiol, Quebec City, PQ G1V 0A6, Canada. [Perusse, Louis; Vohl, Marie-Claude] Univ Laval, Inst Nutr & Funct Foods, Quebec City, PQ G1V 0A6, Canada. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FI-20521 Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FI-20520 Turku, Finland. [Rao, D. C.; Rice, Treva K.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Sorensen, Thorkild I. A.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, DK-2000 Frederiksberg, Denmark. [van der Harst, Pim] Netherlands Heart Inst, Interuniv Cardiol Inst Netherlands, Durrer Ctr Cardiogenet Res, NL-3501 DG Utrecht, Netherlands. [Vohl, Marie-Claude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Viikari, Jorma S.] Univ Turku, Dept Med, FI-20521 Turku, Finland. [Vohl, Marie-Claude] Univ Laval, Sch Nutr, Quebec City, PQ G1V 0A6, Canada. [Volzke, Henry; Wallaschofski, Henri] DZHK German Ctr Cardiovasc Res, D-17475 Greifswald, Germany. [Volzke, Henry] DZD German Ctr Diabet Res, D-17475 Greifswald, Germany. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Wild, Sarah] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland. [Borecki, Ingrid B.] Regeneron Pharmaceut Inc, Regeneron Genet Ctr, Analyt Genet Grp, Tarrytown, NY 10591 USA. [Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London W12 0HS, England. [Cupples, L. Adrienne; Fox, Caroline] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Dehghan, Abbas] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia. [Furey, Terrence S.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Han, Jiali] Melvin & Bren Simon Canc Ctr, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA. [Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Karpe, Fredrik; McCarthy, Mark I.] Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W12 0NN, England. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Murabito, Joanne M.] NHLBIs & Boston Univ Framingham Heart Study, Framingham, MA 01702 USA. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3GA, Merseyside, England. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Ong, Ken K.] UCL, MRC Unit Lifelong Hlth & Ageing, London WC1B 5JU, England. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England. [Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Med, Montreal, PQ H3T 1E2, Canada. [Richards, J. Brent] Kings Coll London, Dept Twin Res, London SE1 1E7, England. [Richards, J. Brent] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Div Endocrinol, Montreal, PQ H3T 1E2, Canada. [Schadt, Eric E.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA. [Schadt, Eric E.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Willer, Cristen J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Ingelsson, Erik] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Pospisilik, John Andrew] Max Planck Inst Immunobiol & Epigenet, Dept Epigenet, D-76108 Freiburg, Germany. [Lindgren, Cecilia] Univ Oxford, Big Data Inst, Oxford OX3 7LJ, England. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.; Loos, RJF (reprint author), Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge CB2 0QQ, England.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.; Loos, RJF (reprint author), Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. EM ruth.loos@mssm.edu RI Polasek, Ozren/B-6002-2011; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Grallert, Harald/B-3424-2013; Colaus, PsyColaus/K-6607-2013; Verweij, Niek/A-4499-2017; Sarzynski, Mark/A-9798-2014; Bertram, Lars/K-3889-2015; Yang, Jian/A-5852-2010; Yengo, Loic/D-2692-2017; Grarup, Niels/K-2807-2015; mangino, massimo/F-5134-2011; Franke, Lude/P-7036-2016; Karjalainen, Juha/P-8624-2016; Peters, Annette/A-6117-2011; Deloukas, Panos/B-2922-2013; Bouchard, Claude/A-7637-2009 OI Polasek, Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Bertram, Lars/0000-0002-0108-124X; Yang, Jian/0000-0003-2001-2474; Yengo, Loic/0000-0002-4272-9305; Grarup, Niels/0000-0001-5526-1070; mangino, massimo/0000-0002-2167-7470; Franke, Lude/0000-0002-5159-8802; Deloukas, Panos/0000-0001-9251-070X; FU Aase and Ejner Danielsens Foundation; Academy of Finland; Agency for Health Care Policy Research; Ahokas Foundation; ALFEDIAM; ALK-Abello A/S (Horsholm, Denmark); Althingi (the Icelandic Parliament); ANR ('Agence Nationale de la 359 Recherche'); American Heart Association; Ardix Medical; Arthritis Research UK; Association Diabete Risque Vasculaire, the Federation Francaise de Cardiologie; AstraZeneca; Australian Research Council; Bayer Diagnostics; BBSRC; Becton Dickinson; BMBF (DEEP); Boehringer Ingelheim Foundation; Boston University School of Medicine; British Heart Foundation; British Skin Foundation; Canadian Institutes of Health Research; Cancer Research UK; Cardionics; Centers for Disease Control and Prevention/Association of Schools of Public Health; Chief Scientist Office of the Scottish Government; Cohortes Sante TGIR; CMSB; CPER ('Contrat de Projets Etat-Region'); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research; Danish Medical Research Council; Department of Health, UK; Deutsche Forschungsgemeinschaft; Deutshe Forschungsgemeinschaft [SFB992]; DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland); Diabetes UK; Dutch Dairy Association (NZO); Dutch Kidney Foundation; Dutch Inter University Cardiology Institute Netherlands (ICIN); Emil Aaltonen Foundation; ENGAGE consortium; Food Standards Agency, UK; Erasmus Medical Center; Erasmus University; Estonian Government; European Commission; European Community's Seventh Framework Programme; European Research Council; European Research Council [ERC-StG-281641]; European Union framework program 6 EUROSPAN project; European Union; European Union (EU_FP7_NoE 'Epigenesys'); Faculty of Biology and Medicine of Lausanne; Federal State of Mecklenburg-West Pomerania; Federal Ministry of Education and Research (German Obesity Biomaterial Bank); Finnish Cardiovascular Research Foundation; Finnish Centre for Pensions; Finnish Cultural Foundation; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research; Finnish Special Governmental Subsidy for Health Sciences; Finska Lakaresallskapet; Folkhalsan Research Foundation; German Bundesministerium fuer Forschung und Technology; German Diabetes Association; German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF); German Research Council; GlaxoSmithKline; Goran Gustafsson Foundation; Health and Safety Executive, UK; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Illinois Department of Public Health; INSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante); Integrated Research and Treatment Centre (IFB); Juho Vainio Foundation; John D and Catherine T MacArthur Foundation Research Networks; John W. Barton Sr Chair in Genetics and Nutrition; Kompetenznetz Adipositas; King's College London; Knut och Alice Wallenberg Foundation; Kuopio University Hospital Medical Fund; Tampere University Hospital Medical Fund; Turku University Hospital Medical Fund; Kuopio University Hospital; La Fondation de France; Li Ka Shing Foundation; Liv och Halsa; Local Government Pensions Institution (KEVA); Ludwig-Maximilians-Universitat; Lundbeck Foundation; Lundberg Foundation; Max-Planck Institute; Medical Research Council, UK; MEKOS Laboratories Denmark; Merck Sante; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs and Social Ministry of the Federal State of Mecklenburg-West Pomerania; Ministry of Economic Affairs, Agriculture and Innovation, The Netherlands; Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport of the Republic of Croatia; MRC Centre for Causal Analyses in Translational Epidemiology (MRC CAiTE); MRC-GlaxoSmithKline; MRC Human Genetics Unit; Munich Center of Health Sciences (MC Health); Municipality of Rotterdam; National Center for Advancing Translational Sciences, CTSI; National Center for Research Resources (NCRR); National Genome Research Institute, Korean Center for Disease Control and Prevention; National Heart Lung and Blood Institute (NHLBI); National Heart, Lung and Blood Institute's Framingham Heart Study; National Institute for Health and Welfare (THL); National Institute for Health Research (NIHR); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Health; National Center for Advancing Translational Sciences; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC); National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA); Netherlands Consortium Healthy Ageing (NCHA); Netherlands Genomics Initiative (NGI); Netherlands Heart Foundation; Netherlands Organisation for Scientific Research (NWO); Netherlands Organization for the Health Research and Development (ZonMw); Novo Nordisk; Novo Nordisk Foundation; ONIVINS; Orion-Farmos Research Foundation; Paavo Nurmi Foundation; Pierre Fabre; Research Centre for Prevention and Health, the Capital Region of Denmark; Research Institute for Diseases in the Elderly (RIDE); Research into Ageing, UK; Roche; Royal Swedish Academy of Science; Russian Foundation for Basic Research; Sanger Institute; Samfundet Folkhalsan; SFD ('Societe Francophone du 358 Diabete'); Siemens Healthcare; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland (KELA); State of Bavaria; Stroke Association, UK; Swedish Diabetes Foundation; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Research Council; Swedish Research Council for Infrastructures; Swiss National Science Foundation; Sylvia AMP; Charles Viertel Charitable Foundation; Tampere Tuberculosis Foundation; Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Soderberg's Foundation; Translational Genomics Research Institute; Unilever UK; University Cancer Research Fund at UNC Chapel Hill; University of Eastern Finland; University of Maryland General Clinical Research Center; Uppsala University; Uppsala University Hospital; USDA National Institute of Food and Agriculture; VA Clinical Science Research and Development; Velux Foundation; VU University Medical Center; Wageningen University; Wellcome Trust FX A full list of acknowledgements can be found in the Supplementary Notes. This work was supported by the following: Aase and Ejner Danielsens Foundation; Academy of Finland; Agency for Health Care Policy Research; Ahokas Foundation; ALFEDIAM; ALK-Abello A/S (Horsholm, Denmark); Althingi (the Icelandic Parliament); ANR ('Agence Nationale de la 359 Recherche'); American Heart Association; Ardix Medical; Arthritis Research UK; Association Diabete Risque Vasculaire, the Federation Francaise de Cardiologie; AstraZeneca; Australian Research Council; Bayer Diagnostics; BBSRC; Becton Dickinson; BMBF (DEEP); Boehringer Ingelheim Foundation; Boston University School of Medicine; British Heart Foundation; British Skin Foundation; Canadian Institutes of Health Research; Cancer Research UK; Cardionics; Centers for Disease Control and Prevention/Association of Schools of Public Health; Chief Scientist Office of the Scottish Government; Cohortes Sante TGIR; CMSB; CPER ('Contrat de Projets Etat-Region'); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research; Danish Medical Research Council; Department of Health, UK; Deutsche Forschungsgemeinschaft; Deutshe Forschungsgemeinschaft (SFB992); DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland); Diabetes UK; Dutch Dairy Association (NZO); Dutch Kidney Foundation; Dutch Inter University Cardiology Institute Netherlands (ICIN); Emil Aaltonen Foundation; ENGAGE consortium; Food Standards Agency, UK; Erasmus Medical Center; Erasmus University; Estonian Government; European Commission; European Community's Seventh Framework Programme; European Research Council; European Research Council (ERC-StG-281641); European Union framework program 6 EUROSPAN project; European Union; European Union (EU_FP7_NoE 'Epigenesys'); Faculty of Biology and Medicine of Lausanne; Federal State of Mecklenburg-West Pomerania; Federal Ministry of Education and Research (German Obesity Biomaterial Bank); Finnish Cardiovascular Research Foundation; Finnish Centre for Pensions; Finnish Cultural Foundation; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research; Finnish Special Governmental Subsidy for Health Sciences; Finska Lakaresallskapet; Folkhalsan Research Foundation; German Bundesministerium fuer Forschung und Technology; German Diabetes Association; German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung, BMBF); German Research Council; GlaxoSmithKline; Goran Gustafsson Foundation; Health and Safety Executive, UK; Helmholtz Zentrum Munchen-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Illinois Department of Public Health; INSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante); Integrated Research and Treatment Centre (IFB); Juho Vainio Foundation; John D and Catherine T MacArthur Foundation Research Networks; John W.; r Barton Sr Chair in Genetics and Nutrition; Kompetenznetz Adipositas; King's College London; Knut och Alice Wallenberg Foundation; Kuopio, Tampere and Turku University Hospital Medical Funds; Kuopio University Hospital; La Fondation de France; Li Ka Shing Foundation; Liv och Halsa; Local Government Pensions Institution (KEVA); Ludwig-Maximilians-Universitat; Lundbeck Foundation; Lundberg Foundation; Max-Planck Institute; Medical Research Council, UK; MEKOS Laboratories Denmark; Merck Sante; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs and Social Ministry of the Federal State of Mecklenburg-West Pomerania; Ministry of Economic Affairs, Agriculture and Innovation, The Netherlands; Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport of the Republic of Croatia; MRC Centre for Causal Analyses in Translational Epidemiology (MRC CAiTE); MRC-GlaxoSmithKline; MRC Human Genetics Unit; Munich Center of Health Sciences (MC Health); Municipality of Rotterdam; National Center for Advancing Translational Sciences, CTSI; National Center for Research Resources (NCRR); National Genome Research Institute, Korean Center for Disease Control and Prevention; National Heart Lung and Blood Institute (NHLBI); National Heart, Lung and Blood Institute's Framingham Heart Study; National Institute for Health and Welfare (THL); National Institute for Health Research (NIHR); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Health; National Center for Advancing Translational Sciences; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC); National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA); Netherlands Consortium Healthy Ageing (NCHA); Netherlands Genomics Initiative (NGI); Netherlands Heart Foundation; Netherlands Organisation for Scientific Research (NWO); Netherlands Organization for the Health Research and Development (ZonMw); Novo Nordisk; Novo Nordisk Foundation; ONIVINS; Orion-Farmos Research Foundation; Paavo Nurmi Foundation; Pierre Fabre; Research Centre for Prevention and Health, the Capital Region of Denmark; Research Institute for Diseases in the Elderly (RIDE); Research into Ageing, UK; Roche; Royal Swedish Academy of Science; Russian Foundation for Basic Research; Sanger Institute; Samfundet Folkhalsan; SFD ('Societe Francophone du 358 Diabete'); Siemens Healthcare; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland (KELA); State of Bavaria; Stroke Association, UK; Swedish Diabetes Foundation; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Research Council; Swedish Research Council for Infrastructures; Swiss National Science Foundation; Sylvia & Charles Viertel Charitable Foundation; Tampere Tuberculosis Foundation; Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Soderberg's Foundation; Translational Genomics Research Institute; Unilever UK; University Cancer Research Fund at UNC Chapel Hill; University of Eastern Finland; University of Maryland General Clinical Research Center; Uppsala University; Uppsala University Hospital; USDA National Institute of Food and Agriculture; VA Clinical Science Research and Development; Velux Foundation; VU University Medical Center; Wageningen University; Wellcome Trust. NR 70 TC 12 Z9 12 U1 6 U2 11 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 FEB PY 2016 VL 7 AR 10495 DI 10.1038/ncomms10495 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF0EQ UT WOS:000371012200002 PM 26833246 ER PT J AU Roy, J Kim, B Hill, E Visconti, P Krapf, D Vinegoni, C Weissleder, R Brown, D Breton, S AF Roy, Jeremy Kim, Bongki Hill, Eric Visconti, Pablo Krapf, Dario Vinegoni, Claudio Weissleder, Ralph Brown, Dennis Breton, Sylvie TI Tyrosine kinase-mediated axial motility of basal cells revealed by intravital imaging SO NATURE COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR RECEPTOR; EPITHELIAL-CELLS; IN-VIVO; MOUSE EPIDIDYMIS; PROTEIN-KINASE; H+-ATPASE; SRC; MICE; PHOSPHORYLATION; DIFFERENTIATION AB Epithelial cells are generally considered to be static relative to their neighbours. Basal cells in pseudostratified epithelia display a single long cytoplasmic process that can cross the tight junction barrier to reach the lumen. Using in vivo microscopy to visualize the epididymis, a model system for the study of pseudostratified epithelia, we report here the surprising discovery that these basal cell projections-which we call axiopodia-periodically extend and retract over time. We found that axiopodia extensions and retractions follow an oscillatory pattern. This movement, which we refer to as periodic axial motility (PAM), is controlled by c-Src and MEK1/2-ERK1/2. Therapeutic inhibition of tyrosine kinase activity induces a retraction of these projections. Such unexpected cell motility may reflect a novel mechanism by which specialized epithelial cells sample the luminal environment. C1 [Roy, Jeremy; Kim, Bongki; Hill, Eric; Vinegoni, Claudio; Weissleder, Ralph; Brown, Dennis; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Nephrol Div, Boston, MA 02114 USA. [Roy, Jeremy; Kim, Bongki; Hill, Eric; Vinegoni, Claudio; Weissleder, Ralph; Brown, Dennis; Breton, Sylvie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Visconti, Pablo; Krapf, Dario; Brown, Dennis] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Roy, Jeremy] AGADA Biosci Inc, Halifax, NS B3H 0A8, Canada. [Krapf, Dario] UNR, CONICET, Inst Biol Mol & Celular Rosario, RA-2000 Rosario, Santa Fe, Argentina. RP Breton, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Nephrol Div, Boston, MA 02114 USA.; Breton, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. EM breton.sylvie@mgh.harvard.edu FU NCI NIH HHS [P50 CA086355, P50CA086355]; NCRR NIH HHS [S10 RR031563, S10 RR031563-01, S10RR0266360]; NICHD NIH HHS [HD040793, R01 HD040793]; NIDDK NIH HHS [DK43351, DK097124, P30 DK043351, P30 DK057521, DK57521, R01 DK097124] NR 38 TC 1 Z9 1 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD FEB PY 2016 VL 7 AR 10666 DI 10.1038/ncomms10666 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DF0HY UT WOS:000371021000018 PM 26868824 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Reflections on 2015 SO ONCOLOGIST LA English DT Editorial Material C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM bchabner@partners.org 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 FEB PY 2016 VL 21 IS 2 BP 129 EP 130 DI 10.1634/theoncologist.2016-0005 PG 2 WC Oncology SC Oncology GA DF1BQ UT WOS:000371073800003 PM 26786261 ER PT J AU Stenehjem, DD Bellows, BK Yager, KM Jones, J Kaldate, R Siebert, U Brixner, DI AF Stenehjem, David D. Bellows, Brandon K. Yager, Kraig M. Jones, Joshua Kaldate, Rajesh Siebert, Uwe Brixner, Diana I. TI Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Cost-utility analysis; Cost-effectiveness analysis; Non-small cell lung cancer; Prognostic test; Economic analysis ID VINORELBINE PLUS CISPLATIN; BREAST-CANCER; COMPLETE RESECTION; TUMOR RECURRENCE; GENE SIGNATURE; RISK; PROLIFERATION; QUALITY; ADENOCARCINOMA; PROGRESSION AB Background. A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Materials and Methods. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov micro-simulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. Results. Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. Conclusion. The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. C1 [Stenehjem, David D.; Bellows, Brandon K.; Brixner, Diana I.] Univ Utah, Coll Pharm, Pharmacotherapy Outcomes Res Ctr, Dept Pharmacotherapy, Salt Lake City, UT 84112 USA. [Brixner, Diana I.] Univ Utah, Program Personalized Hlth, Salt Lake City, UT USA. [Stenehjem, David D.] Univ Utah Hosp & Clin, Huntsman Canc Inst, Salt Lake City, UT USA. [Bellows, Brandon K.] SelectHealth, Salt Lake City, UT USA. [Yager, Kraig M.; Jones, Joshua; Kaldate, Rajesh] Myriad Genet Inc, Salt Lake City, UT USA. [Siebert, Uwe; Brixner, Diana I.] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Hlth Serv Res & Hlth Technol Asses, Tyrol, Austria. [Siebert, Uwe; Brixner, Diana I.] Oncotyrol Ctr Personalized Canc Med, Area Hlth Technol Assessment & Bioinformat 4, Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Program,Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Stenehjem, DD (reprint author), Univ Utah, Coll Pharm, Dept Pharmacotherapy, 30 South 2000 East,Room 4834, Salt Lake City, UT 84112 USA. EM David.stenehjem@hsc.utah.edu FU Myriad Genetics Laboratories, Inc. (Salt Lake City, UT) FX This research was funded by a grant from Myriad Genetics Laboratories, Inc. (Salt Lake City, UT), of which Kraig M. Yager, Joshua Jones, and Rajesh Kaldate are employees. NR 42 TC 1 Z9 1 U1 1 U2 2 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 FEB PY 2016 VL 21 IS 2 BP 196 EP 204 DI 10.1634/theoncologist.2015-0162 PG 9 WC Oncology SC Oncology GA DF1BQ UT WOS:000371073800013 PM 26614710 ER PT J AU Fathi, AT Nahed, BV Wander, SA Iafrate, AJ Borger, DR Hu, RL Thabet, A Cahill, DP Perry, AM Joseph, CP Muzikansky, A Chi, AS AF Fathi, Amir T. Nahed, Brian V. Wander, Seth A. Iafrate, A. John Borger, Darrell R. Hu, Ranliang Thabet, Ashraf Cahill, Daniel P. Perry, Ashley M. Joseph, Christelle P. Muzikansky, Alona Chi, Andrew S. TI Elevation of Urinary 2-Hydroxyglutarate in IDH-Mutant Glioma SO ONCOLOGIST LA English DT Article DE Isocitrate dehydrogenase; 2-Hydroxyglutarate; Glioma; Novel biomarkers; Targeted therapies ID ISOCITRATE DEHYDROGENASE 1; ONCOMETABOLITE 2-HYDROXYGLUTARATE; MUTATIONAL ANALYSIS; MALIGNANT GLIOMAS; DIFFERENTIATION; TUMORS; ASTROCYTOMAS; CANCER; CLASSIFICATION; GLIOBLASTOMA AB Background. Recurrent mutations in the isocitrate dehydrogenase1 (IDH1) and IDH2 genes, which are frequent in gliomas, result in marked accumulation of the metabolic by-product 2-hydroxyglutarate (2-HG) within tumors. In other malignancies, such as acute myeloid leukemia, presence of IDH mutation is associated with elevated 2-HG levels in serum or urine compartments. Circulating 2-HG in patients with glial malignancies has not been thoroughly investigated. Methods. In this study, we analyzed 2-HG levels in the serum and urine of a large set of patients with IDH-mutant and IDH-wild-type glioma, and the cerebrospinal fluid (CSF) from a subset of this cohort. Results. We found that 2-HG was elevated in the urine of patients with IDH-mutant versus IDH-wild-type glioma, although no significant differences in 2-HG levels were observed in the serum or the small set of CSF samples obtained. Among patients with IDH-mutant glioma, 2-HG levels did not differ based on the histopathologic grade, genetic subtype (TP53 mutant or 1p/19q codeleted), presence of a canonical (IDH1 R132H) or non-canonical (any other IDH variant) mutation, or treatment type. Conclusion. Our finding suggests that urinary 2-HG is increased among patients with IDH-mutant gliomas, and may representa future surrogate, noninvasive biomarker to aid in diagnosis, prognosis, and management. C1 [Fathi, Amir T.; Wander, Seth A.; Perry, Ashley M.; Joseph, Christelle P.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Nahed, Brian V.; Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Iafrate, A. John; Borger, Darrell R.] Massachusetts Gen Hosp, Ctr Canc, Translat Res Lab, Dept Pathol, Boston, MA 02114 USA. [Hu, Ranliang; Thabet, Ashraf] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Div Hematol Oncol, Boston, MA 02114 USA. [Chi, Andrew S.] Harvard Univ, Sch Med, Boston, MA USA. RP Fathi, AT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. EM afathi@partners.org OI Cahill, Daniel/0000-0003-2552-6546 FU NCI NIH HHS [P50 CA165962] NR 39 TC 3 Z9 3 U1 3 U2 6 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 FEB PY 2016 VL 21 IS 2 BP 214 EP 219 DI 10.1634/theoncologist.2015-0342 PG 6 WC Oncology SC Oncology GA DF1BQ UT WOS:000371073800015 PM 26834160 ER PT J AU Turnell, A Rasmussen, V Butow, P Juraskova, I Kirsten, L Wiener, L Patenaude, A Hoekstra-Weebers, J Grassi, L AF Turnell, Adrienne Rasmussen, Victoria Butow, Phyllis Juraskova, Ilona Kirsten, Laura Wiener, Lori Patenaude, Andrea Hoekstra-Weebers, Josette Grassi, Luigi CA IPOS Res Comm TI An exploration of the prevalence and predictors of work-related well-being among psychosocial oncology professionals: An application of the job demands-resources model SO PALLIATIVE & SUPPORTIVE CARE LA English DT Article DE Cancer; Oncology; Psychosocial oncology; Burnout; Work engagement; Job demands-resources ID FAMILY CONFLICT; BURNOUT; HEALTH; ENGAGEMENT; SUPERVISION; INDICATORS; VALIDATION AB Objective: Burnout is reportedly high among oncology healthcare workers. Psychosocial oncologists may be particularly vulnerable to burnout. However, their work engagement may also be high, counteracting stress in the workplace. This study aimed to document the prevalence of both burnout and work engagement, and the predictors of both, utilizing the job demands-resources (JD-R) model, within a sample of psychosocial oncologists. Method: Psychosocial-oncologist (N = 417) clinicians, recruited through 10 international and national psychosocial-oncology societies, completed an online questionnaire. Measures included demographic and work characteristics, burnout (the MBI-HSS Emotional Exhaustion (EE) and Depersonalization (DP) subscales), the Utrecht Work Engagement Scale, and measures of job demands and resources. Results: High EE and DP was reported by 20.2 and 6.6% of participants, respectively, while 95.3% reported average to high work engagement. Lower levels of job resources and higher levels of job demands predicted greater burnout, as predicted by the JD-R model, but the predicted interaction between these characteristics and burnout was not significant. Higher levels of job resources predicted higher levels of work engagement. Significance of results: Burnout was surprisingly low and work engagement high in this sample. Nonetheless, one in five psychosocial oncologists have high EE. Our results suggest that both the positive (resources) and negative (demands) aspects of this work environment have an on impact burnout and engagement, offering opportunities for intervention. Theories such as the JD-R model can be useful in guiding research in this area. C1 [Turnell, Adrienne; Rasmussen, Victoria; Butow, Phyllis; Juraskova, Ilona] Univ Sydney, Sch Psychol, Level 6 North,Lifehouse C39Z, Sydney, NSW 2006, Australia. [Butow, Phyllis; Juraskova, Ilona; Kirsten, Laura] Univ Sydney, Sch Psychol, Ctr Med Psychol & Evidence Based Decis Making, Sydney, NSW 2006, Australia. [Butow, Phyllis; Juraskova, Ilona] Univ Sydney, Psychooncol Cooperat Res Grp, Sydney, NSW 2006, Australia. [Kirsten, Laura] Sydney West Canc Network, Nepean Canc Care Ctr, Sydney, NSW, Australia. [Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Patenaude, Andrea] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Hoekstra-Weebers, Josette] Univ Groningen, Univ Med Ctr Groningen, Wenckebach Inst, Groningen, Netherlands. [Grassi, Luigi] Int Psychooncol Soc, Charlottesville, VA USA. RP Butow, P (reprint author), Univ Sydney, Sch Psychol, Level 6 North,Lifehouse C39Z, Sydney, NSW 2006, Australia. EM phyllis.butow@sydney.edu.au FU International Psycho-Oncology Society; International Society of Paediatric Oncology; American Psychosocial Oncology Society; British Psychosocial Oncology Society; Canadian Association of Psychosocial Oncology; Dutch Society for Psychosocial Oncology; Oncology Social Work Australia; Australian Psychosocial Oncology Society; Australian Psycho-OncologyCo-Operative Research Group; British Faculty for Oncology and Palliative Care FX We would like to thank the International Psycho-Oncology Society, International Society of Paediatric Oncology, American Psychosocial Oncology Society, British Psychosocial Oncology Society, Canadian Association of Psychosocial Oncology, Dutch Society for Psychosocial Oncology, Oncology Social Work Australia, Australian Psychosocial Oncology Society, Australian Psycho-OncologyCo-Operative Research Group, and the British Faculty for Oncology and Palliative Care for their support of this study. NR 44 TC 0 Z9 0 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1478-9515 EI 1478-9523 J9 PALLIAT SUPPORT CARE JI Palliat. Support Care PD FEB PY 2016 VL 14 IS 1 BP 33 EP 41 DI 10.1017/S1478951515000693 PG 9 WC Health Policy & Services SC Health Care Sciences & Services GA DE8BI UT WOS:000370860400006 PM 26653250 ER PT J AU Taylor, KM Saint-Hilaire, MH Sudarsky, L Simon, DK Hersh, B Sparrow, D Hu, H Weisskopf, MG AF Taylor, Kathryn M. Saint-Hilaire, Marie-Helene Sudarsky, Lewis Simon, David K. Hersh, Bonnie Sparrow, David Hu, Howard Weisskopf, Marc G. TI Head injury at early ages is associated with risk of Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Head injury; Parkinson's disease; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; MICROGLIAL ACTIVATION; INFLAMMATION; EXPOSURE AB Introduction: The literature on the effect of head injuries on the risk of PD is inconclusive. Some researchers have hypothesized that studies that have seen an effect are simply capturing injury related to pre-clinical PD. However in animal models brain inflammation, which can be initiated by head trauma, has been shown to produce PD-like effects. Furthermore, animal studies have found that early life inflammation in particular is of relevance for PD pathology. Methods: We conducted an unmatched case control study of 379 neurologist confirmed PD patients and 230 controls from the greater Boston, Massachusetts area with questionnaire data on history of head injury and other covariates. We used multivariable logistic regression to estimate adjusted odds ratios (OR) and their corresponding 95% confidence intervals (CI) for PD. Results: When we excluded injuries that occurred less than 10 years prior to the diagnosis of PD (in order to avoid reverse causation), we found an increased risk of PD associated with a head injury that resulted in a loss of consciousness, but it did not reach statistical significance (OR = 1.57; 95% CI = 0.89-2.80). We found a significant (p = 0.04) effect of age at first head injury. For every 5 year earlier age at first head injury with loss of consciousness the OR for PD was 1.37 (95% CI: 1.01-1.86). Conclusion: Our results suggest that head injury in early life increases the risk of PD. (C) 2015 Published by Elsevier Ltd. C1 [Taylor, Kathryn M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr,Landmark Bldg,3rd Floor, Boston, MA 02215 USA. [Saint-Hilaire, Marie-Helene] Boston Univ, Dept Neurol, Med Ctr, 72 East Concord St,C3, Boston, MA 02118 USA. [Sudarsky, Lewis] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. [Simon, David K.] Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. [Simon, David K.] Harvard Univ, Sch Med, Dept Neurol, 330 Brookline Ave, Boston, MA 02215 USA. [Hersh, Bonnie] Harvard Vanguard Med Associates, 133 Brookline Ave, Boston, MA 02215 USA. [Sparrow, David] VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. [Sparrow, David] Boston Univ, Sch Publ Hlth, 715 Albany St, Boston, MA 02118 USA. [Sparrow, David] Boston Univ, Sch Med, 715 Albany St, Boston, MA 02118 USA. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Epidemiol, 6th Floor,155 Coll St, Toronto, ON, Canada. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Global Hlth, 6th Floor,155 Coll St, Toronto, ON, Canada. [Hu, Howard] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Environm Hlth, 6th Floor,155 Coll St, Toronto, ON, Canada. [Weisskopf, Marc G.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol & Environm Hlth, 677 Huntington Ave, Boston, MA 02115 USA. RP Taylor, KM (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr,Landmark Bldg,3rd Floor, Boston, MA 02215 USA. EM kmt691@mail.harvard.edu; neuromsh@bu.edu; lsudarsky@partners.com; dsimon1@bidmc.harvard.edu; bonnie_hersh@vmed.org; david.sparrow@va.gov; howard.hu@utoronto.ca; mweissko@hsph.harvard.edu OI Hu, Howard/0000-0002-3676-2707 FU National Institute of Health, National Institute of Environmental Health Sciences [R01-ES010798, P01-ES000002]; National Institute of Health: IMSD Academic Training grant [R25 GM055353]; National Institute for Occupational Safety and Health: ERC training grant [T42 OH008416]; VA Research Career Scientist award FX This work was supported by the National Institute of Health, National Institute of Environmental Health Sciences (R01-ES010798 and P01-ES000002 (M W.)), National Institute of Health: IMSD Academic Training grant (R25 GM055353 (K.T.)), the National Institute for Occupational Safety and Health: ERC training grant (T42 OH008416 (K T.)) and VA Research Career Scientist award (D.S.) NR 26 TC 3 Z9 3 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD FEB PY 2016 VL 23 BP 57 EP 61 DI 10.1016/j.parkreldis.2015.12.005 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DE8KW UT WOS:000370885900009 PM 26725141 ER PT J AU Taylor, RL Medarova, Z Briles, WE AF Taylor, R. L., Jr. Medarova, Z. Briles, W. E. TI Immune effects of chicken non-MHC alloantigens SO POULTRY SCIENCE LA English DT Article DE alloantigen; blood group; erythrocyte ID ROUS SARCOMAS; BLOOD-GROUPS; VIRAL ONCOGENESIS; GENETIC-VARIATION; SURFACE-ANTIGENS; EIMERIA-TENELLA; MAREKS-DISEASE; T-CELL; SYSTEMS; COMPLEX AB Alloantigen systems are a broad group of molecules found on various cell types, including erythrocytes and lymphocytes. These alloantigens, identified via specific polyclonal or monoclonal antibodies or molecular methods, have demonstrated effects on immune responses. Erythrocyte alloantigens include the A, B, C, D, E, H, I, J, K, L, N, P, and R systems. Highly polymorphic alloantigen B has been identified as the chicken major histocompatibility complex (MHC). The other twelve systems have a variable degree of polymorphism as well as impact on immune measurements or responses against pathogens. Selection for immune characters altered allele frequencies for particular alloantigen systems. Three lymphocyte alloantigens, Bu-1, Ly-4 and Th-1 have more limited polymorphism but still influence responses against viral pathogens, Rous sarcoma virus and Marek's disease. Together, these erythrocyte and lymphocyte systems contribute to the overall immunity. Identification of the specific alloantigen proteins remains crucial to understanding their immune contribution. C1 [Taylor, R. L., Jr.] W Virginia Univ, Div Anim & Nutr Sci, Morgantown, WV 26506 USA. [Medarova, Z.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Briles, W. E.] No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. RP Taylor, RL (reprint author), W Virginia Univ, Div Anim & Nutr Sci, Morgantown, WV 26506 USA. EM bob.taylor@mail.wvu.edu FU National Science Foundation [DCB-8718672, DCB-9020138, MCB-9631979] FX The technical assistance of Linda Yates and Renee Kopulos, Department of Biological Sciences, Northern Illinois University, DeKalb, IL 60115 and Lynda Caron, Department of Animal and Nutritional Sciences, University of New Hampshire, Durham, NH 03824 is gratefully acknowledged. Unpublished data provided by Drs. Hans Abplanalp, Chris Ashwell and Muquarrab Qureshi enhanced this paper. Alloantigen typing antisera preparation was funded through National Science Foundation grants DCB-8718672, DCB-9020138 and MCB-9631979. NR 50 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0032-5791 EI 1525-3171 J9 POULTRY SCI JI Poult. Sci. PD FEB PY 2016 VL 95 IS 2 BP 447 EP 457 DI 10.3382/ps/pev331 PG 11 WC Agriculture, Dairy & Animal Science SC Agriculture GA DF0WN UT WOS:000371060000023 PM 26527702 ER PT J AU Wivagg, CN Wellington, S Gomez, JE Hung, DT AF Wivagg, Carl N. Wellington, Samantha Gomez, James E. Hung, Deborah T. TI Loss of a Class A Penicillin-Binding Protein Alters beta-Lactam Susceptibilities in Mycobacterium tuberculosis SO ACS INFECTIOUS DISEASES LA English DT Article DE actinobacteria; carbapenem; cephalosporin; loss of function; PonA2; target site modification ID RESUSCITATION-PROMOTING FACTORS; DRUG-RESISTANT TUBERCULOSIS; MEROPENEM-CLAVULANATE; ESCHERICHIA-COLI; CELL-WALL; ENTEROCOCCUS-FAECIUM; MECHANISM; L,D-TRANSPEPTIDASE; PEPTIDOGLYCAN; ANTIBIOTICS AB Recent studies have renewed interest in beta-lactam antibiotics as a potential treatment for Mycobacterium tuberculosis infection. To explore the opportunities and limitations of this approach, we sought to better understand potential resistance mechanisms to beta-lactam antibiotics in M. tuberculosis. We identified mutations in the penicillin-binding protein (PBP) ponA2 that were able to confer some degree of resistance to the cephalosporin subclass of beta-lactams. Surprisingly, deletion of ponA2 also confers resistance, demonstrating that beta-lactam resistance can spontaneously arise from PBP loss of function. We show that ponA2 mutants resistant to the cephalosporin subclass of beta-lactams in fact show increased susceptibility to meropenem, a carbapenem that is known to target L,D-transpeptidases, thereby suggesting that in the absence of PonA2, an alternative mode of peptidoglycan synthesis likely becomes essential. Consistent with this hypothesis, a negative genetic selection identified the L,D-transpeptidase ldtMt2 as essential in the absence of ponA2. The mechanism of beta-lactam resistance we outline is consistent with emerging models of beta-lactam killing, while the investigation of ponA2 downstream and synthetic lethal genes sheds light on the mechanism of cell wall biosynthesis and the interaction between conventional PBPs and L,D-transpeptidases. C1 [Wivagg, Carl N.; Wellington, Samantha; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. [Gomez, James E.; Hung, Deborah T.] Broad Inst, 415 Main St, Cambridge, MA 02142 USA. [Wellington, Samantha; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Richard B Simches Res Ctr, 185 Cambridge St,Seventh Floor, Boston, MA 02114 USA. [Wellington, Samantha; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, 185 Cambridge St,Seventh Floor, Boston, MA 02114 USA. RP Hung, DT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA.; Hung, DT (reprint author), Massachusetts Gen Hosp, Ctr Computat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hung@molbio.mgh.harvard.edu OI Wivagg, Carl/0000-0001-9617-7625 NR 38 TC 1 Z9 1 U1 7 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-8227 J9 ACS INFECT DIS JI ACS Infect. Dis. PD FEB PY 2016 VL 2 IS 2 BP 104 EP 110 DI 10.1021/acsinfecdis.5b00119 PG 7 WC Chemistry, Medicinal; Infectious Diseases SC Pharmacology & Pharmacy; Infectious Diseases GA DE1OP UT WOS:000370396600001 PM 27624961 ER PT J AU AbouEzzeddine, OF Lala, A Khazanie, PP Shah, R Ho, JE Chen, HH Pang, PS McNulty, SE Anstrom, KJ Hernandez, AF Redfield, MM AF AbouEzzeddine, Omar F. Lala, Anuradha Khazanie, Prateeti P. Shah, Ravi Ho, Jennifer E. Chen, Horng H. Pang, Peter S. McNulty, Steven E. Anstrom, Kevin J. Hernandez, Adrian F. Redfield, Margaret M. CA NHLBI Heart Failure Clinical Res TI Evaluation of a provocative dyspnea severity score in acute heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID CLINICAL-OUTCOMES; ASSOCIATION; TRIALS; RELIEF; REHOSPITALIZATION; STRATEGIES; MANAGEMENT; MORTALITY; THERAPY; SYMPTOM AB Background The acute heart failure (AHF) Syndromes International Working Group proposed that dyspnea be assessed under standardized, incrementally provocative maneuvers and called for studies to assess the feasibility of this approach. We sought to assess the feasibility and statistical characteristics of a novel provocative dyspnea severity score (pDS) versus the traditional dyspnea visual analog scale (DVAS) in an AHF trial. Methods At enrollment, 24, 48 and 72 hours, 230 ROSE-AHF patients completed a DVAS. Dyspnea was then assessed with 5-point Likert dyspnea scales administered during 4 stages (A: upright-with O-2, B: upright-without O-2, C: supine-without O-2 and D: exercise-without O-2). Patients with moderate or less dyspnea were eligible for the next stage. Results At enrollment, oxygen withdrawal and supine provocation were highly feasible (>= 97%), provoking more severe dyspnea (>= 1 Likert point) in 24% and 42% of eligible patients, respectively. Exercise provocation had low feasibility with 38% of eligible patients unable to exercise due to factors other than dyspnea. A pDS was constructed from Likert scales during the 3 feasible assessment conditions (A-C). Relative to DVAS, the distribution of the pDS was more skewed with a high "ceiling effect" at enrollment (23%) limiting sensitivity to change. Change in pDS was not related to decongestion or 60-day outcomes. Conclusions Although oxygen withdrawal and supine provocation are feasible and elicit more severe dyspnea, exercise provocation had unacceptable feasibility in this AHF cohort. The statistical characteristics of a pDS based on feasible provocation measures do not support its potential as a robust dyspnea assessment tool in AHF. C1 [AbouEzzeddine, Omar F.; Chen, Horng H.; Redfield, Margaret M.] Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. [Lala, Anuradha] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Lala, Anuradha] Mt Sinai Hosp, Icahn Sch Med, New York, NY 10029 USA. [Khazanie, Prateeti P.] Duke Univ, Med Ctr, Durham, NC USA. [Khazanie, Prateeti P.] Duke Heart Ctr, Durham, NC USA. [Shah, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ho, Jennifer E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Pang, Peter S.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [McNulty, Steven E.; Anstrom, Kevin J.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. RP AbouEzzeddine, OF (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA. EM Abouezzeddine.Omar@mayo.edu OI ABOUEZZEDDINE, OMAR/0000-0003-3256-3660 FU NHLBI/NCATS, Alere; Amgen; Bristol Myers Squibb; GlaxoSmithKline; Novartis FX HHC has no specific COI related to this work; however, he reports that he and Mayo Clinic have patented and licensed designer natriuretic peptides to Anexon Inc and Capricor Therapeutics. Dr Chen is the co-founder of Zumbro Discovery. PSP has no specific COI related to this work; however, he has or has had the following relationships with the following entities over the last 3 years where a conflict of interest might be perceived given dyspnea is a common end point in clinical trials. Consultant for:, Bayer, BG Medicine, the Medicines Co, Otsuka, Intersection Medical, Janssen, Medtronic, Novartis, Trevena, scPharmaceuticals, Cardioxyl, Roche Diagnostics. Honoraria: Relypsa, Palatin Technologies, Abbott Research Grants: NHLBI/NCATS, Alere. AFH has no specific COI related to this work. However, he reports grants from Amgen, Bristol Myers Squibb, GlaxoSmithKline and Novartis, outside the submitted work. All others report no disclosures relevant to this manuscript. NR 20 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD FEB PY 2016 VL 172 BP 34 EP 41 DI 10.1016/j.ahj.2015.10.009 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD1CS UT WOS:000369659400005 PM 26856213 ER PT J AU Eisen, A Giugliano, RP Ruff, CT Nordio, F Gogia, HS Awasty, VR Henderson, DA Mercuri, MF Rutman, H Antman, EM Braunwald, E AF Eisen, Alon Giugliano, Robert P. Ruff, Christian T. Nordio, Francesco Gogia, Harinder S. Awasty, Vivek R. Henderson, David A. Mercuri, Michele F. Rutman, Howard Antman, Elliott M. Braunwald, Eugene TI Edoxaban vs warfarin in patients with nonvalvular atrial fibrillation in the US Food and Drug Administration approval population: An analysis from the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial SO AMERICAN HEART JOURNAL LA English DT Article ID INHIBITOR EDOXABAN; PREDICTING STROKE AB Background Edoxaban is a specific anti-Xa inhibitor that, in comparison to warfarin, has been found to be noninferior for the prevention of stroke or systemic embolism (SSE) and to reduce bleeding significantly in patients with nonvalvular atrial fibrillation (AF). The US Food and Drug Administration (FDA) approved the higher-dose edoxaban regimen (60/30 mg) in patients with AF and a creatinine clearance of <= 95 mL/min. We report for the first time the clinical characteristics, efficacy, and safety of the FDA-approved population in the ENGAGE AF-TIMI 48 trial. Methods The patients included had been treated with either warfarin or edoxaban 60/30 mg and had a creatinine clearance of <= 95 mL/min. The primary efficacy was SSE, and the principal safety end point was major bleeding (International Society on Thrombosis and Haemostasis classification). Median follow-up was 2.8 years. Results Patients in the FDA-approved cohort were older, were more likely female, and had higher CHADS(2) and HAS-BLED scores, as compared with patients not included in the FDA label. The primary end point occurred in 1.63%/y with edoxaban vs 2.02%/y with warfarin (hazard ratio [HR] 0.81, 95% CI 0.67-0.97, P = .023). Edoxaban significantly reduced the rate of hemorrhagic stroke (HR 0.47, 95% CI 0.31-0.72, P < .001) and cardiovascular death (HR 0.84, 95% CI 0.73-0.97, P = .015). Ischemic stroke rates were similar between the treatment groups (1.31%/y vs 1.39%/y, P = .97). Major bleeding was significantly lower with edoxaban (3.16%/y vs 3.77%/y; HR 0.84, 95% CI 0.72-0.98, P = .023). Conclusion In the FDA-approved cohort of the ENGAGE AF-TIMI 48 trial, treatment with edoxaban 60/30 mg was superior to warfarin in the prevention of SSE and significantly reduced cardiovascular death and bleeding, especially fatal bleeding and hemorrhagic stroke. C1 [Eisen, Alon; Giugliano, Robert P.; Ruff, Christian T.; Nordio, Francesco; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Eisen, Alon; Giugliano, Robert P.; Ruff, Christian T.; Nordio, Francesco; Antman, Elliott M.; Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gogia, Harinder S.] Anaheim Reg Med Ctr, Anaheim, CA USA. [Awasty, Vivek R.] Marion Gen Hosp, Marion, OH USA. [Henderson, David A.] Florida Hosp Mem Med Ctr, Daytona Beach, FL USA. [Mercuri, Michele F.] Daiichi Sankyo Pharma Dev, Edison, NJ USA. [Rutman, Howard] Daiichi Sankyo Inc, Parsippany, NJ USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM ebraunwald@partners.org FU Daiichi-Sankyo; Merck; Johnson Johnson; Sanofi; AstraZeneca; Eisai; Intarcia; Merck Co; Glaxo Smith Kline; Genyzme; Medicines Co; Theravance; Sanofi-Aventis; Menarini; Medscape FX Drs Eisen, Nordio, Gogia, Awasty, and Henderson have no disclosures. Drs Mercuri and Rutman are employees of Daiichi Sankyo, which funded this trial. Dr Giugliano has served as a consultant and had received honoraria from Bristol-Myers Squibb, Janssen, Daiichi-Sankyo, Merck, and Sanofi, and grant support through his institution from Daiichi-Sankyo, Merck, Johnson & Johnson, Sanofi, and AstraZeneca. Dr Ruff reports grant support through his institution from Daiichi-Sankyo; has served as a consultant and received honoraria from Daiichi-Sankyo, Boehringer Ingelheim, and Bristol-Myers Squibb; and reports receiving grant support through his institution outside the submitted work from AstraZeneca, Eisai, and Intarcia. Dr Antman reports receiving grant support through his institution from Daiichi-Sankyo. Dr Braunwald reports grants (through the Brigham and Women's Hospital) and personal fees for lectures from Daiichi-Sankyo. He has received grants (through the Brigham and Women's Hospital) from AstraZeneca, Merck & Co, and Glaxo Smith Kline; personal fees for consultancies from Genyzme, Medicines Co, Theravance, and Sanofi-Aventis; and honoraria for lectures from Menarini and Medscape. NR 17 TC 2 Z9 2 U1 1 U2 8 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 FEB PY 2016 VL 172 BP 144 EP 151 DI 10.1016/j.ahj.2015.11.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD1CS UT WOS:000369659400018 PM 26856226 ER PT J AU Griffis, HM Band, RA Ruther, M Harhay, M Asch, DA Hershey, JC Hill, S Nadkarni, L Kilaru, A Branas, CC Shofer, F Nichol, G Becker, LB Merchant, RM AF Griffis, Heather M. Band, Roger A. Ruther, Matthew Harhay, Michael Asch, David A. Hershey, John C. Hill, Shawndra Nadkarni, Lindsay Kilaru, Austin Branas, Charles C. Shofer, Frances Nichol, Graham Becker, Lance B. Merchant, Raina M. TI Employment and residential characteristics in relation to automated external defibrillator locations SO AMERICAN HEART JOURNAL LA English DT Article ID HOSPITAL CARDIAC-ARREST; PUBLIC-ACCESS DEFIBRILLATION; AMERICAN-HEART-ASSOCIATION; UNITED-STATES; SURVIVAL; NEIGHBORHOOD; RESOURCES; PLACEMENT; CPR AB Background Survival from out-of-hospital cardiac arrest (OHCA) is generally poor and varies by geography. Variability in automated external defibrillator (AED) locations may be a contributing factor. To inform optimal placement of AEDs, we investigated AED access in a major US city relative to demographic and employment characteristics. Methods and Results This was a retrospective analysis of a Philadelphia AED registry (2,559 total AEDs). The 2010 US Census and the Local Employment Dynamics database by ZIP code was used. Automated external defibrillator access was calculated as the weighted areal percentage of each ZIP code covered by a 400-m radius around each AED. Of 47 ZIP codes, only 9% (4) were high-AED-service areas. In 26% (12) of ZIP codes, less than 35% of the area was covered by AED service areas. Higher-AED-access ZIP codes were more likely to have a moderately populated residential area (P = .032), higher median household income (P = .006), and higher paying jobs (P =. 008). Conclusions The locations of AEDs vary across specific ZIP codes; select residential and employment characteristics explain some variation. Further work on evaluating OHCA locations, AED use and availability, and OHCA outcomes could inform AED placement policies. Optimizing the placement of AEDs through this work may help to increase survival. C1 [Griffis, Heather M.; Band, Roger A.; Nadkarni, Lindsay; Kilaru, Austin; Branas, Charles C.; Shofer, Frances; Becker, Lance B.; Merchant, Raina M.] Univ Penn, Perelman Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. [Ruther, Matthew] Univ Colorado, Dept Geog, Boulder, CO 80309 USA. [Harhay, Michael; Branas, Charles C.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Asch, David A.; Merchant, Raina M.] Univ Penn, Penn Med Ctr Innovat, Philadelphia, PA 19104 USA. [Asch, David A.; Hershey, John C.; Hill, Shawndra] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Nichol, Graham] Univ Washington, Harborview Ctr Prehospital Emergency Care, Dept Med, Seattle, WA 98195 USA. RP Merchant, RM (reprint author), Univ Penn, Perelman Sch Med, 423 Guardian St,1022 Blockley, Philadelphia, PA 19104 USA. EM raina.merchant@uphs.upenn.edu OI Harhay, Michael/0000-0002-0553-674X FU National Institutes of Health (NTH), K23 Grant [10714038]; Physio-Control Seattle, Washington; Zoll Medical, Boston MA; Cardiac Science, Bothell, Washington; Philips Medical Seattle, Washington; Medtronic Foundation Heart Rescue Project; Penn University Research Fund; McCabe Fund, American Heart Association Beginning; NIH; Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, WA; Medtronic Foundation, Minnesota; Resuscitation Outcomes Consortium (NIH) [U01 HL077863-05]; Evaluation of Video Self-Instruction in Compressions-Only CPR; Randomized Trial of Hemofiltration After Resuscitation from Cardiac Arrest (NHLBI) [R21 HL093641-01A1]; Randomized Field Trial of Cold Saline IV After Resuscitation from Cardiac Arrest (NHLBI) [R01 HL089554-03]; Resychronization/Defibrillation for Advanced Heart Failure Trial (RAF) [200211UCT-110607]; Novel Methods of Measuring Health Disparities [1RC2HL101759-01]; Cascade Cardiac Resuscitation System (Medtronic Foundation); Gambro Renal Inc, Lakewood, CO; Sotera Wireless, San Diego, CA; Lifebridge Medizintechnik AG; Ampfing, Germany; American Heart Association (AHA) Executive Database Steering Committee; Lifeline EMS Task. Force; AHA Resuscitation Science Symposium Planning Committee; AHA Advanced Cardiac Life Support Subcommittee; AHA Epidemiology and Statistics Committee; Pacific Mountain Affiliate Board of Directors, AHA FX R.M.M. has received grant/research support from the National Institutes of Health (NTH), K23 Grant 10714038, and pilot funding from Physio-Control Seattle, Washington; Zoll Medical, Boston MA; Cardiac Science, Bothell, Washington; Philips Medical Seattle, Washington; The Medtronic Foundation Heart Rescue Project; The Penn University Research Fund; and the McCabe Fund, American Heart Association Beginning Grant in Aid. R.A.B., J.C., O.S., H.G., A.L., J.M.A., K.L., L.N., E.S., L.S., and F.S. have no disclosures. C.C.B. has received grant/research support from NIH. D.A.A. has received grant/research support from NIH and is a consultant to VAL Health. G.N. discloses the following: Resuscitation Outcomes Consortium (NIH U01 HL077863-05) 2004-2015; co-principal investigator (co-PI), Evaluation of Video Self-Instruction in Compressions-Only CPR (Asmund S. Laerdal Foundation for Acute Medicine) 2007-2010; PI, Randomized Trial of Hemofiltration After Resuscitation from Cardiac Arrest (NHLBI R21 HL093641-01A1) 2009-2011; PI, Randomized Field Trial of Cold Saline IV After Resuscitation from Cardiac Arrest (NHLBI R01 HL089554-03) 2007-2012: co-investigator (Co-I), Resychronization/Defibrillation for Advanced Heart Failure Trial (RAF 200211UCT-110607) 2003-2010; Co-I, Novel Methods of Measuring Health Disparities (1RC2HL101759-01) 2009-2011; Co-I, Cascade Cardiac Resuscitation System (Medtronic Foundation) 2010-2015; PI, Research Collaborator: Gambro Renal Inc, Lakewood, CO; Sotera Wireless, San Diego, CA; Lifebridge Medizintechnik AG; Ampfing, Germany; Other Chair, American Heart Association (AHA) Executive Database Steering Committee; Chair, Mission: Lifeline EMS Task. Force; Co-Chair, AHA Resuscitation Science Symposium Planning Committee; Member, AHA Advanced Cardiac Life Support Subcommittee; Member, AHA Epidemiology and Statistics Committee; Member, Pacific Mountain Affiliate Board of Directors, AHA. He also received travel reimbursement from AHA. L.B.B. has received grant/research support from Philips Healthcare, Seattle, WA; Laerdal Medical, Stavanger, Norway; NIH, Bethesda, MD; Cardiac Science, Bothell, WA; and Medtronic Foundation, Minnesota. He also received speaker honoraria/consultant fees from Philips Healthcare, Seattle, WA. NR 30 TC 2 Z9 2 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 FEB PY 2016 VL 172 BP 185 EP 191 DI 10.1016/j.ahj.2015.09.022 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD1CS UT WOS:000369659400024 PM 26856232 ER PT J AU Kolb, SJ Coffey, CS Yankey, JW Krosschell, K Arnold, WD Rutkove, SB Swoboda, KJ Reyna, SP Sakonju, A Darras, BT Shell, R Kuntz, N Castro, D Iannaccone, ST Parsons, J Connolly, AM Chiriboga, CA McDonald, C Burnette, WB Werner, K Thangarajh, M Shieh, PB Finanger, E Cudkowicz, ME McGovern, MM McNeil, DE Finkel, R Kaye, E Kingsley, A Renusch, SR McGovern, VL Wang, XQ Zaworski, PG Prior, TW Burghes, AHM Bartlett, A Kissel, JT AF Kolb, Stephen J. Coffey, Christopher S. Yankey, Jon W. Krosschell, Kristin Arnold, W. David Rutkove, Seward B. Swoboda, Kathryn J. Reyna, Sandra P. Sakonju, Ai Darras, Basil T. Shell, Richard Kuntz, Nancy Castro, Diana Iannaccone, Susan T. Parsons, Julie Connolly, Anne M. Chiriboga, Claudia A. McDonald, Craig Burnette, W. Bryan Werner, Klaus Thangarajh, Mathula Shieh, Perry B. Finanger, Erika Cudkowicz, Merit E. McGovern, Michelle M. McNeil, D. Elizabeth Finkel, Richard Kaye, Edward Kingsley, Allison Renusch, Samantha R. McGovern, Vicki L. Wang, Xueqian Zaworski, Phillip G. Prior, Thomas W. Burghes, Arthur H. M. Bartlett, Amy Kissel, John T. CA NeuroNEXT Clinical Trial Network NN101 SMA Biomarker Investigators TI Baseline results of the NeuroNEXT spinal muscular atrophy infant biomarker study SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID ELECTRICAL-IMPEDANCE MYOGRAPHY; SMN2 COPY NUMBER; NATURAL-HISTORY; SINGLE NUCLEOTIDE; CLINICAL-TRIALS; GENE SMN2; PROTEIN; SURVIVAL; SEVERITY; SMA AB ObjectiveThis study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA). MethodsThis prospective, multi-center natural history study targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits. ResultsEnrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 2.2 mV) was significantly reduced compared to controls (5.5 +/- 2.0 mV). Electrical impedance myography (EIM) high-frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts. InterpretationBy the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit. C1 [Kolb, Stephen J.; Arnold, W. David; Kingsley, Allison; Bartlett, Amy; Kissel, John T.] Ohio State Univ, Dept Neurol, Wexner Med Ctr, Hamilton Hall,Room 337B,1645 Neil Ave, Columbus, OH 43210 USA. [Kolb, Stephen J.; Renusch, Samantha R.; McGovern, Vicki L.; Wang, Xueqian; Burghes, Arthur H. M.] Ohio State Univ, Dept Biol Chem & Pharmacol, Wexner Med Ctr, Hamilton Hall,Room 337B,1645 Neil Ave, Columbus, OH 43210 USA. [Coffey, Christopher S.; Yankey, Jon W.] Univ Iowa, Dept Biostat, NeuroNEXT Data Coordinating Ctr, Iowa City, IA USA. [Krosschell, Kristin] Northwestern Univ, Feinberg Sch Med, Dept Phys Therapy, Chicago, IL 60611 USA. [Krosschell, Kristin] Northwestern Univ, Dept Human Movement Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [Krosschell, Kristin] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA. [Arnold, W. David] Ohio State Univ, Wexner Med Ctr, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. [Rutkove, Seward B.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Swoboda, Kathryn J.; Reyna, Sandra P.; Sakonju, Ai] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Swoboda, Kathryn J.; Reyna, Sandra P.; Sakonju, Ai] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Swoboda, Kathryn J.; Reyna, Sandra P.; Cudkowicz, Merit E.; McGovern, Michelle M.] Massachusetts Gen Hosp, Dept Neurol, NeuroNEXT Clin Coordinating Ctr, Boston, MA 02114 USA. [Darras, Basil T.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Shell, Richard] Nationwide Childrens Hosp, Columbus, OH USA. [Kuntz, Nancy] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Castro, Diana; Iannaccone, Susan T.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Parsons, Julie] Univ Colorado, Sch Med, Childrens Hosp Colorado, Aurora, CO USA. [Connolly, Anne M.] Washington Univ, Sch Med, St Louis, MO USA. [Chiriboga, Claudia A.] Columbia Coll Phys & Surg, Dept Neurol, New York, NY USA. [McDonald, Craig] Univ Calif Davis, Davis, CA 95616 USA. [Burnette, W. Bryan] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. [Werner, Klaus] SUNY Upstate Med Ctr, Syracuse, NY USA. [Thangarajh, Mathula] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Shieh, Perry B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Finanger, Erika] Dorenbecher Childrens Hosp, Portland, OR USA. [McNeil, D. Elizabeth] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Finkel, Richard] Nemours Childrens Hosp, Orlando, FL USA. [Kaye, Edward] Sarepta Therapeut, Cambridge, MA USA. [Zaworski, Phillip G.] PharmOptima, Portage, MI USA. [Prior, Thomas W.] Ohio State Wexner Med Ctr, Dept Mol Pathol, Columbus, OH USA. RP Kolb, SJ (reprint author), Ohio State Univ, Dept Neurol, Wexner Med Ctr, Hamilton Hall,Room 337B,1645 Neil Ave, Columbus, OH 43210 USA.; Kolb, SJ (reprint author), Ohio State Univ, Dept Biol Chem & Pharmacol, Wexner Med Ctr, Hamilton Hall,Room 337B,1645 Neil Ave, Columbus, OH 43210 USA. EM stephen.kolb@osumc.edu OI Arnold, W. David/0000-0001-9889-7036 FU NCATS NIH HHS [UL1 TR000445]; NICHD NIH HHS [K12 HD001097, U54 HD087011]; NINDS NIH HHS [K08 NS067282, U01 NS077179, U01 NS077352, U01 NS079163, U10 NS077267] NR 37 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD FEB PY 2016 VL 3 IS 2 BP 132 EP 145 DI 10.1002/acn3.283 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD9SA UT WOS:000370264700007 PM 26900585 ER PT J AU Dimopoulos, MA Kastritis, E Ghobrial, IM AF Dimopoulos, M. A. Kastritis, E. Ghobrial, I. M. TI Waldenstrom's macroglobulinemia: a clinical perspective in the era of novel therapeutics SO ANNALS OF ONCOLOGY LA English DT Review DE efficacy; novel agents; safety; treatment guidelines; Waldenstrom's macroglobulinemia ID PHASE-II TRIAL; WEEKLY BORTEZOMIB; HEMATOLOGIC MALIGNANCIES; MONOCLONAL-ANTIBODY; REGULATES SURVIVAL; UNTREATED PATIENTS; PRIMARY THERAPY; RITUXIMAB; DEXAMETHASONE; COMBINATION AB Waldenstrom's macroglobulinemia (WM) is a rare, low-grade malignancy with no established standard of care. Rituximab regimens are most commonly used, supported by their efficacy in hematologic malignancies, including WM. A growing number of investigational regimens for WM have been evaluated in phase II clinical trials, including single-agent and combination strategies that include newer-generation monoclonal antibodies (ofatumumab and alemtuzumab), proteasome inhibitors (bortezomib and carfilzomib), immunomodulatory agents (thalidomide and lenalidomide), phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin pathway inhibitors (everolimus and perifosene), a Bruton's tyrosine kinase inhibitor (ibrutinib), and a histone deacetylase inhibitor (panobinostat). Other novel agents are in early-stage development for WM. International treatment guidelines for WM suggest suitable regimens in the newly diagnosed and relapsed/refractory settings, in accordance with patient age, disease presentation, and efficacy and safety profiles of particular drugs. These factors must be considered when choosing appropriate therapy for individual patients with WM, to maximize response and prolong survival, while minimizing the risk of adverse events. This review article provides a clinical perspective of the modern management of patients with WM, in the context of available trial data for novel regimens and recently updated treatment guidelines. C1 [Dimopoulos, M. A.; Kastritis, E.] Univ Athens, Sch Med, Dept Clin Therapeut, 80 Vas Sofias, Athens 11528, Greece. [Ghobrial, I. M.] Dana Farber Canc Ctr, Med Oncol, Boston, MA USA. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, 80 Vas Sofias, Athens 11528, Greece.; Dimopoulos, MA (reprint author), Univ Athens, Alexandra Hosp, Dept Clin Therapeut, 80 Vas Sofias, Athens 11528, Greece. EM mdimop@med.uoa.gr FU Onyx Pharmaceuticals, Inc., an Amgen subsidiary FX This work was supported by Onyx Pharmaceuticals, Inc., an Amgen subsidiary (no grant number). NR 48 TC 3 Z9 3 U1 3 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 FEB PY 2016 VL 27 IS 2 BP 233 EP 240 DI 10.1093/annonc/mdv572 PG 8 WC Oncology SC Oncology GA DD8TF UT WOS:000370199100005 PM 26598544 ER PT J AU Graff, JN Baciarello, G Armstrong, AJ Higano, CS Iversen, P Flaig, TW Forer, D Parli, T Phung, D Tombal, B Beer, TM Sternberg, CN AF Graff, J. N. Baciarello, G. Armstrong, A. J. Higano, C. S. Iversen, P. Flaig, T. W. Forer, D. Parli, T. Phung, D. Tombal, B. Beer, T. M. Sternberg, C. N. TI Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL SO ANNALS OF ONCOLOGY LA English DT Article DE metastatic castration-resistant prostate cancer; enzalutamide; PREVAIL trial; elderly patients ID QUALITY-OF-LIFE; DOCETAXEL-BASED CHEMOTHERAPY; ABIRATERONE ACETATE; ELDERLY-PATIENTS; TRIAL; PAIN; MEN; SURVIVAL; IMPACT; FALLS AB Background: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged >= 75 years who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. Patients and methods: PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged = 75 years (elderly) and men aged <75 years was pre-specified for the coprimary end points and adverse events (AEs). Results: Among 609 elderly patients (35%) who participated in PREVAIL, median treatment duration was 16.6 and 5.0 months in the enzalutamide and placebo arms, respectively. In the elderly subgroup, OS was greater with enzalutamide than with placebo [32.4 months (95% confidence interval (CI) 27.7-not yet reached] versus 25.1 months (95% CI 22.6-28.0); hazard ratio (HR) = 0.61 (95% CI 0.47-0.79); P = 0.0001], as was rPFS [not yet reached (95% CI 12.3-not yet reached) versus 3.7 months (95% CI 3.6-5.3); HR = 0.17 (95% CI 0.12-0.24); P < 0.0001]. Irrespective of treatment assignment, incidence of AEs was similar between the two age groups, except for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. Conclusions: Elderly men benefited from treatment with enzalutamide in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged <75 years. Age and enzalutamide treatment were associated with a higher incidence of falls. C1 [Graff, J. N.; Beer, T. M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Graff, J. N.] Portland VA Med Ctr, Div Oncol, Portland, OR USA. [Baciarello, G.; Sternberg, C. N.] San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy. [Armstrong, A. J.] Duke Univ, Med Ctr, Div Med Oncol, Durham, NC 27706 USA. [Armstrong, A. J.] Duke Univ, Med Ctr, Div Urol, Durham, NC 27706 USA. [Armstrong, A. J.] Duke Canc Inst, Durham, England. [Higano, C. S.] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. [Higano, C. S.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Iversen, P.] Univ Copenhagen, Rigshosp, Copenhagen Prostate Canc Ctr, Copenhagen, Denmark. [Flaig, T. W.] Univ Colorado, Ctr Canc, Dept Med Oncol, Aurora, CO USA. [Forer, D.; Parli, T.] Medivat Inc, San Francisco, CA USA. [Phung, D.] Astellas Pharma Global Dev Inc, Leiden, Netherlands. [Tombal, B.] Clin Univ St Luc, Dept Urol, Brussels, Belgium. RP Graff, JN (reprint author), Oregon Hlth & Sci Univ, Knight Canc Ctr, Portland VA Med Ctr, Div Oncol, MC CH14R,3303 SW Bond Ave, Portland, OR 97239 USA. EM graffj@ohsu.edu FU Medivation, Inc.; Astellas Pharma Global Development, Inc. FX Medivation, Inc., and Astellas Pharma Global Development, Inc., funded the PREVAIL trial, provided the study drug and collaborated with the investigators on protocol design, data analysis and interpretation, and preparation of this report, including the support of medical writing and editorial services (no grant number). NR 24 TC 6 Z9 6 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 FEB PY 2016 VL 27 IS 2 BP 286 EP 294 DI 10.1093/annonc/mdv542 PG 10 WC Oncology SC Oncology GA DD8TF UT WOS:000370199100013 PM 26578735 ER PT J AU Colwell, AS Smith, BL AF Colwell, Amy S. Smith, Barbara L. TI Complications After Mastectomy and Immediate Breast Reconstruction for Breast Cancer: How Does the Community Compare? SO ANNALS OF SURGERY LA English DT Article ID NIPPLE-SPARING MASTECTOMY; OUTCOMES; TRENDS C1 [Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Div Plast Surg, Sch Med, Boston, MA 02114 USA. [Colwell, Amy S.; Smith, Barbara L.] Harvard Univ, Massachusetts Gen Hosp, Div Surg Oncol, Sch Med, Boston, MA 02114 USA. RP Colwell, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Surg Oncol, Sch Med, Boston, MA 02114 USA. EM acolwell@mgh.harvard.edu NR 5 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2016 VL 263 IS 2 BP 228 EP 229 DI 10.1097/SLA.0000000000001584 PG 2 WC Surgery SC Surgery GA DD8TP UT WOS:000370200100004 PM 26655925 ER PT J AU Cohen, ME Liu, YM Ko, CY Hall, BL AF Cohen, Mark E. Liu, Yaoming Ko, Clifford Y. Hall, Bruce L. TI Improved Surgical Outcomes for ACS NSQIP Hospitals Over Time Evaluation of Hospital Cohorts With up to 8 Years of Participation SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; profiling; risk adjustment; surgical quality improvement; time trends ID SURVEILLANCE BIAS; AMERICAN-COLLEGE; SITE INFECTIONS; QUALITY; PROGRAM AB Background:The American College of Surgeons, National Surgical Quality Improvement Program (ACS NSQIP) surgical quality feedback models are recalibrated every 6 months, and each hospital is given risk-adjusted, hierarchical model, odds ratios that permit comparison to an estimated average NSQIP hospital at a particular point in time. This approach is appropriate for relative benchmarking, and for targeting quality improvement efforts, but does not permit evaluation of hospital or program-wide changes in quality over time. We report on long-term improvement in surgical outcomes associated with participation in ACS NSQIP.Study Design:ACS NSQIP data (2006-2013) were used to create prediction models for mortality, morbidity (any of several distinct adverse outcomes), and surgical site infection (SSI). For each model, for each hospital, and for year of first participation (hospital cohort), hierarchical model observed/expected (O/E) ratios were computed. The primary performance metric was the within-hospital trend in logged O/E ratios over time (slope) for mortality, morbidity, and SSI.Results:Hospital-averaged log O/E ratio slopes were generally negative, indicating improving performance over time. For all hospitals, 62%, 70%, and 65% of hospitals had negative slopes for mortality, morbidity, and any SSI, respectively. For hospitals currently in the program for at least 3 years, 69%, 79%, and 71% showed improvement in mortality, morbidity, and SSI, respectively. For these hospitals, we estimate 0.8%, 3.1%, and 2.6% annual reductions (with respect to prior year's rates) for mortality, morbidity, and SSI, respectively.Conclusions:Participation in ACS NSQIP is associated with reductions in adverse events after surgery. The magnitude of quality improvement increases with time in the program. C1 [Cohen, Mark E.; Liu, Yaoming; Ko, Clifford Y.; Hall, Bruce L.] Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 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. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] John Cochran Vet Affairs Med Ctr, St Louis, MO USA. [Hall, Bruce L.] BJC Healthcare, St Louis, MO USA. RP Cohen, ME (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL USA. EM markcohen@facs.org NR 14 TC 24 Z9 24 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2016 VL 263 IS 2 BP 267 EP 273 DI 10.1097/SLA.0000000000001192 PG 7 WC Surgery SC Surgery GA DD8TP UT WOS:000370200100012 PM 25723845 ER PT J AU Chidi, AP Bryce, CL Myaskovsky, L Fine, MJ Geller, DA Landsittel, DP Tsung, A AF Chidi, Alexis P. Bryce, Cindy L. Myaskovsky, Larissa Fine, Michael J. Geller, David A. Landsittel, Douglas P. Tsung, Allan TI Differences in Physician Referral Drive Disparities in Surgical Intervention for Hepatocellular Carcinoma A Retrospective Cohort Study SO ANNALS OF SURGERY LA English DT Article DE access to care; HCC; health care disparities; liver cancer; socioeconomic status ID STAGE BREAST-CANCER; UNITED-STATES; GEOGRAPHIC DISPARITIES; TREATMENT CHOICES; TRAVEL-TIME; CARE; ACCESS; SURVIVAL; THERAPY; OUTCOMES AB Objective:To determine whether sociodemographic and geographic factors are associated with referral for surgery and receipt of recommended surgical intervention.Background:Surgical interventions confer survival advantages compared with palliative therapies for hepatocellular carcinoma (HCC), but disparities exist in use of surgical intervention. Few have investigated referral for surgery as a potential barrier to surgical intervention, and little is known about the effects of patient geographic factors, including proximity to surgical centers.Methods:Data were abstracted from the Pennsylvania Cancer Registry for patients with a diagnosis of HCC from 2006 to 2011. Using hospital procedure volume data from the Pennsylvania Health Care Cost Containment Council, we calculated proximity to a surgical center. We used multivariable logistic regression to determine whether geographic, racial, socioeconomic, and clinical factors were associated with referral for surgery and receipt of a recommended surgical intervention.Results:Of 3576 patients with HCC, 41.0% were referred for surgery. Patients who lived closer to a surgical center were less likely to be referred for surgery (adjusted odds ratio=0.79; 95% confidence interval, 0.68-0.92). Surgical referral was less likely among older, male patients with Medicaid insurance and advanced tumor stage at diagnosis. Of those referred, 1276 (87.0%) underwent surgical intervention. Proximity to a surgical center was not associated with receipt of surgical intervention (P=0.27). Patients with distant tumor stage at diagnosis were less likely to receive recommended surgical intervention (adjusted odds ratio=0.27; 95% confidence interval, 0.15-0.50).Conclusions:Geographic and sociodemographic disparities in referral for surgery may be major barriers to surgical intervention for patients with HCC. C1 [Chidi, Alexis P.; Geller, David A.; Tsung, Allan] Univ Pittsburgh, Dept Surg, Div Hepatobiliary & Pancreat Surg, Pittsburgh, PA USA. [Chidi, Alexis P.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bryce, Cindy L.; Myaskovsky, Larissa; Fine, Michael J.; Landsittel, Douglas P.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Bryce, Cindy L.; Myaskovsky, Larissa; Fine, Michael J.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. RP Tsung, A (reprint author), UPMC Liver Canc Ctr, Montefiore Hosp, Div Hepatobiliary & Pancreat Surg, 3459 Fifth Ave,7 South, Pittsburgh, PA 15213 USA. EM tsunga@upmc.edu OI Bryce, Cindy/0000-0001-6356-6675 FU National Institutes of Health [T35DK065521, TL1TR000145, UL1TR000005] FX Supported by the National Institutes of Health (T35DK065521, TL1TR000145, UL1TR000005). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest. NR 31 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2016 VL 263 IS 2 BP 362 EP 368 DI 10.1097/SLA.0000000000001111 PG 7 WC Surgery SC Surgery GA DD8TP UT WOS:000370200100025 PM 25563883 ER PT J AU Kinnier, CV Paruch, JL Dahlke, AR Wayne, JD Benson, A Winchester, DP Bilimoria, KY AF Kinnier, Christine V. Paruch, Jennifer L. Dahlke, Allison R. Wayne, Jeffrey D. Benson, Al B., III Winchester, David P. Bilimoria, Karl Y. TI Assessing Awareness and Implementation of a Recommendation for Surgical Innovation Committees: A Survey of Academic Institutions (vol 262, pg 941, 2015) SO ANNALS OF SURGERY LA English DT Article ID LYMPH-NODE BIOPSY; CANCER DATA-BASE; EARLY-STAGE MELANOMA; UNITED-STATES; COLON-CANCER; CUTANEOUS MELANOMA; MITOTIC RATE; SENTINEL; DISSECTION; PATTERNS C1 [Kinnier, Christine V.; Dahlke, Allison R.; Wayne, Jeffrey D.; Bilimoria, Karl Y.] Robert H Lurie Comprehens Canc Ctr, Northwestern Inst Comparat Effectiveness Res NICE, Chicago, IL USA. [Kinnier, Christine V.; Dahlke, Allison R.; Wayne, Jeffrey D.; Bilimoria, Karl Y.] Northwestern Univ, Surg Oncol & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Paruch, Jennifer L.] 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. [Benson, Al B., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Dept Med,Feinberg Sch Med, Chicago, IL 60611 USA. [Winchester, David P.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Winchester, David P.] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, 633 N St Clair St,Suite 20, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu NR 35 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2016 VL 263 IS 2 BP 392 EP 398 DI 10.1097/SLA.0000000000001623 PG 7 WC Surgery SC Surgery GA DD8UZ UT WOS:000370203700001 ER PT J AU Kinnier, CV Paruch, JL Dahlke, AR Wayne, JD Benson, AB Winchester, DP Bilimoria, KY AF Kinnier, Christine V. Paruch, Jennifer L. Dahlke, Allison R. Wayne, Jeffrey D. Benson, Al B., III Winchester, David P. Bilimoria, Karl Y. TI Adjusted Hospital Sentinel Lymph Node Positivity Rates in Melanoma A Novel Potential Measure of Quality SO ANNALS OF SURGERY LA English DT Article DE low-volume hospitals; National Cancer Data Base; quality improvement; sentinel lymph node biopsy; survival ID CANCER DATA-BASE; OPTIMAL SURGEON EXPERIENCE; EARLY-STAGE MELANOMA; UNITED-STATES; COLON-CANCER; CUTANEOUS MELANOMA; MITOTIC RATE; BIOPSY; DISSECTION; PATTERNS AB Objective:Our objectives were to examine whether hospital characteristics are associated with lower- and higher-than-expected sentinel lymph node biopsy (SLNB) positivity rates and whether hospitals with lower- or higher-than-expected SLNB positivity rates have worse patient outcomes.Background:Surgeon and pathologist SLNB technical errors may lead to incorrect melanoma staging. A hospital's SLNB positivity rate may reflect its SLNB proficiency for melanoma, but this has never been investigated.Methods:Stage IA-III melanoma patients undergoing SLNB were identified from the National Cancer Data Base (2004-2010). Hospital-level SLNB positivity rates were adjusted for patient- and tumor factors. Hospitals were divided into terciles of adjusted SLNB positivity rates. Hospital characteristics (using multinomial logistic regression) and survival (using Cox modeling) were examined across terciles.Results:Of 33,639 SLNB patients (from 646 hospitals), 2916 (8.7%) had at least 1 positive lymph node. Hospitals with lower- (low tercile) and higher-than-expected (high tercile) SLNB positivity rates were more likely to be low-volume hospitals (low tercile: relative risk ratio (RRR)=2.57, P=0.002; high tercile: RRR=2.3, P=0.004) compared to hospitals with expected rates (middle tercile). Stage I patients treated at lower-than-expected SLNB positivity rate hospitals had worse 5-year survival than those treated at expected SLNB positivity rate hospitals (90.0% vs 91.9%, P=0.014; hazard ratio=1.28, 95% CI: 1.05-1.57); survival differences were not observed by SLNB positivity rates for stage II/III.Conclusions:Adjusted hospital SLNB positivity rates varied widely. Surgery at hospitals with lower-than-expected SLNB positivity rates was associated with decreased survival. Hospital SLNB positivity rates may be a novel measure to confidentially report to hospitals for internal quality assessment. C1 [Kinnier, Christine V.; Dahlke, Allison R.; Wayne, Jeffrey D.; Bilimoria, Karl Y.] Robert H Lurie Comprehens Canc Ctr, Northwestern Inst Comparat Effectiveness Res NICE, Chicago, IL USA. [Kinnier, Christine V.; Dahlke, Allison R.; Wayne, Jeffrey D.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Oncol & Qual Improvement Ctr, Chicago, IL 60611 USA. [Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Paruch, Jennifer L.] 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. [Benson, Al B., III] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Dept Med,Div Hematol Oncol, Chicago, IL 60611 USA. [Winchester, David P.] Amer Coll Surg, Canc Programs, Chicago, IL USA. [Winchester, David P.] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA. RP Bilimoria, KY (reprint author), Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, 633 N St Clair St,Suite 20, Chicago, IL 60611 USA. EM k-bilimoria@northwestern.edu FU National Comprehensive Cancer Network; American Cancer Society; Northwestern Institute for Comparative Effectiveness Research in Oncology; Massachusetts General Hospital FX This work is funded by the National Comprehensive Cancer Network, the American Cancer Society, and the Northwestern Institute for Comparative Effectiveness Research in Oncology. CVK is funded by the Marshall K. Bartlett research fellowship at Massachusetts General Hospital. The authors declare no conflicts of interest. NR 34 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 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2016 VL 263 IS 2 BP 392 EP 398 DI 10.1097/SLA.0000000000001052 PG 7 WC Surgery SC Surgery GA DD8TP UT WOS:000370200100029 ER PT J AU Miller, CL Colwell, AS Horick, N Skolny, MN Jammallo, LS O'Toole, JA Shenouda, MN Sadek, BT Swaroop, MN Ferguson, CM Smith, BL Specht, MC Taghian, AG AF Miller, Cynthia L. Colwell, Amy S. Horick, Nora Skolny, Melissa N. Jammallo, Lauren S. O'Toole, Jean A. Shenouda, Mina N. Sadek, Betro T. Swaroop, Meyha N. Ferguson, Chantal M. Smith, Barbara L. Specht, Michelle C. Taghian, Alphonse G. TI Immediate Implant Reconstruction Is Associated With a Reduced Risk of Lymphedema Compared to Mastectomy Alone A Prospective Cohort Study SO ANNALS OF SURGERY LA English DT Article DE autologous; breast reconstruction; immediate reconstruction; implant; lymphedema; mastectomy ID CANCER-RELATED LYMPHEDEMA; DELAYED BREAST RECONSTRUCTION; SENTINEL NODE BIOPSY; QUALITY-OF-LIFE; ARM LYMPHEDEMA; POSTMASTECTOMY RECONSTRUCTION; PSYCHOLOGICAL IMPACT; GROUP TRIAL; FOLLOW-UP; DISSECTION AB Objective:We sought to determine the risk of lymphedema associated with immediate breast reconstruction compared to mastectomy alone.Background:Immediate breast reconstruction is increasingly performed at the time of mastectomy. Few studies have examined whether breast reconstruction impacts development of lymphedema.Methods:A total of 616 patients with breast cancer who underwent 891 mastectomies between 2005 and 2013 were prospectively screened for lymphedema at our institution, with 22.2 months' median follow-up. Mastectomies were categorized as immediate implant, immediate autologous, or no reconstruction. Arm measurements were performed preoperatively and during postoperative follow-up using a Perometer. Lymphedema was defined as 10% or more arm volume increase compared to preoperative. Kaplan-Meier and Cox regression analyses were performed to determine lymphedema rates and risk factors.Results:Of 891 mastectomies, 65% (580/891) had immediate implant, 11% (101/891) immediate autologous, and 24% (210/891) no reconstruction. The two-year cumulative incidence of lymphedema was as follows: 4.08% [95% confidence interval (CI): 2.59-6.41%] implant, 9.89% (95% CI: 4.98-19.1%) autologous, and 26.7% (95% CI: 20.4-34.4%) no reconstruction. By multivariate analysis, immediate implant [hazards ratio (HR): 0.352, P<0.0001] but not autologous (HR: 0.706, P=0.2151) reconstruction was associated with a significantly reduced risk of lymphedema compared to no reconstruction. Axillary lymph node dissection (P<0.0001), higher body mass index (P<0.0001), and greater number of nodes dissected (P=0.0324) were associated with increased lymphedema risk.Conclusions:This prospective study suggests that in patients for whom implant-based reconstruction is available, immediate implant reconstruction does not increase the risk of lymphedema compared to mastectomy alone. C1 [Miller, Cynthia L.; Skolny, Melissa N.; Jammallo, Lauren S.; Shenouda, Mina N.; Sadek, Betro T.; Swaroop, Meyha N.; Ferguson, Chantal M.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. [Colwell, Amy S.] Massachusetts Gen Hosp, Dept Plast & Reconstruct Surg, Boston, MA 02114 USA. [Horick, Nora] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [O'Toole, Jean A.] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Smith, Barbara L.; Specht, Michelle C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org FU National Cancer Institute [R01CA139118, P50CA089393]; Adele McKinnon Research Fund; AirXpanders FX The study described was supported by Award No. R01CA139118 (A.G.T.) and Award No. P50CA089393 (A.G.T.) from the National Cancer Institute and the Adele McKinnon Research Fund for breast cancer-related lymphedema. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. A.S.C. is a compensated consultant for Lifecell and Allergan and has received research funding from AirXpanders. For the remaining authors, none were declared. NR 70 TC 5 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD FEB PY 2016 VL 263 IS 2 BP 399 EP 405 DI 10.1097/SLA.0000000000001128 PG 7 WC Surgery SC Surgery GA DD8TP UT WOS:000370200100031 PM 25607768 ER PT J AU Vick, CW AF Vick, C. Whitley TI Say what? SO APPLIED RADIOLOGY LA English DT Editorial Material C1 [Vick, C. Whitley] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vick, C. Whitley] Virginia Commonwealth Univ Med Coll Virginia, Richmond, CA USA. RP Vick, CW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ANDERSON PUBLISHING, INC PI SCOTCH PLAINS PA 180 GLENSIDE AVE, SCOTCH PLAINS, NJ 07076 USA SN 0160-9963 EI 1879-2898 J9 APPL RADIOL JI Appl. Radiol. PD FEB PY 2016 VL 45 IS 2 BP 6 EP + PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE4RL UT WOS:000370617500001 ER PT J AU Soble, JR Osborn, KE Mattingly, ML Vale, FL Benbadis, SR Rodgers-Neame, NT Schoenberg, MR AF Soble, Jason R. Osborn, Katie E. Mattingly, Michelle L. Vale, Fernando L. Benbadis, Selim R. Rodgers-Neame, Nancy T. Schoenberg, Mike R. TI Utility of Green's Word Memory Test Free Recall Subtest as a Measure of Verbal Memory: Initial Evidence from a Temporal Lobe Epilepsy Clinical Sample SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Epilepsy; Assessment; Learning and memory; Lateralization ID SYMPTOM VALIDITY TEST; SURGERY CANDIDATES; NEUROPSYCHOLOGICAL ASSESSMENT; EXTERNAL INCENTIVES; AMERICAN-ACADEMY; TEST-PERFORMANCE; BRAIN-INJURY; RELIABILITY; SENSITIVITY; IMPAIRMENT AB This study investigated the Word Memory Test (WMT) Free Recall (FR) subtest as a conventional memory measure. Nineteen participants with pharmacoresistant left temporal lobe epilepsy (LTLE) and 16 with right temporal lobe epilepsy (RTLE) completed the WMT, Rey Auditory Verbal Learning Test (RAVLT), and Wechsler Memory Scale-Fourth Edition Logical Memory (LM) subtest during presurgical evaluation. LTLE participants performed significantly worse on FR subtest (p < .05, eta(2)(p) = 0.17) and RAVLT Trial 7 (p < .01, eta(2)(p) = 0.25), but not on LM subtest. Age was a significant covariate for FR (p < .01, eta(2)(p) = 0.22). Logistic regression revealed FR plus age and RAVLT age-adjusted T-scores both yielded 77.1% classification accuracy and respective diagnostic odds ratios of 11.36 and 11.84. Receiver operating characteristic curves to classify seizure laterality found that RAVLT and FR were significant (area under the curve [AUC] = 0.82 and 0.74), whereas LM was nonsignificant (AUC = 0.67). Cut scores and positive/negative predictive values were established for improved clinical classification. C1 [Soble, Jason R.] South Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA. [Osborn, Katie E.; Mattingly, Michelle L.; Schoenberg, Mike R.] Univ S Florida, Dept Psychiat & Behav Neurosci, Morsani Coll Med, Tampa, FL USA. [Vale, Fernando L.; Schoenberg, Mike R.] Univ S Florida, Morsani Coll Med, Dept Neurosurg & Brain Repair, Tampa, FL USA. [Benbadis, Selim R.; Schoenberg, Mike R.] Univ S Florida, Dept Neurol, Morsani Coll Med, Tampa, FL 33620 USA. [Rodgers-Neame, Nancy T.] Florida Comprehens Epilepsy & Seizure Disorders C, Tampa, FL USA. RP Schoenberg, MR (reprint author), 3515 E Fletcher Ave,MDC Box 14, Tampa, FL 33613 USA. EM mschoenb@health.usf.edu NR 54 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD FEB PY 2016 VL 31 IS 1 BP 79 EP 87 DI 10.1093/arclin/acv084 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA DD8QQ UT WOS:000370192400011 PM 26663824 ER PT J AU Torrence, ND John, SE Gavett, BE O'Bryant, SE AF Torrence, Nicole D. John, Samantha E. Gavett, Brandon E. O'Bryant, Sid E. TI An Empirical Comparison of Competing Factor Structures for the Repeatable Battery for the Assessment of Neuropsychological Status: A Project FRONTIER Study SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Validity; Factor analysis; Statistical model; Cognition; Neuropsychology ID ITEM BIFACTOR ANALYSIS; CLOCK DRAWING TASK; FIT INDEXES; DEMENTIA; VALIDITY; MODELS; CRITERIA; SAMPLE; RBANS AB The original factor structure of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has received little empirical support, but at least eight alternative factor structures have been identified in the literature. The current study used confirmatory factor analysis to compare the original RBANS model with eight alternatives, which were adjusted to include a general factor. Participant data were obtained from Project FRONTIER, an epidemiological study of rural health, and comprised 341 adults (229 women, 112 men) with mean age of 61.2 years (SD = 12.1) and mean education of 12.4 years (SD = 3.3). A bifactor version of the model proposed by Duff and colleagues provided the best fit to the data (CFI = 0.98; root-mean-squared error of approximation = 0.07), but required further modification to produce appropriate factor loadings. The results support the inclusion of a general factor and provide partial replication of the Duff and colleagues RBANS model. C1 [Torrence, Nicole D.; John, Samantha E.; Gavett, Brandon E.] Univ Colorado, Dept Psychol, 1420 Austin Bluffs Pkwy, Colorado Springs, CO 80907 USA. [O'Bryant, Sid E.] Univ N Texas, Hlth Sci Ctr, Dept Internal Med, Ft Worth, TX USA. [O'Bryant, Sid E.] Univ N Texas, Hlth Sci Ctr, Inst Aging & Alzheimers Dis Res, Ft Worth, TX USA. [Torrence, Nicole D.] VA Puget Sound Hlth Care Syst, Amer Lake, VA USA. RP Gavett, BE (reprint author), Univ Colorado, Dept Psychol, 1420 Austin Bluffs Pkwy, Colorado Springs, CO 80907 USA. EM bgavett@uccs.edu OI O'Bryant, Sid/0000-0003-0582-5266; John, Samantha/0000-0003-1347-4865; Gavett, Brandon/0000-0003-1938-1854 FU National Institute on Aging (NIA); National Institute on Minority Health and Health Disparities(NIMHD) of the National Institutes of Health [R01AG039389, P30AG12300, L60MD001849]; Hogg Foundation for Mental Health [JRG-040, JRG-149]; Environmental Protection Agency [RD834794]; National Academy of Neuropsychology; Texas Tech University Health Sciences Center F. Marie Hall Institute for Rural & Community Health; Garrison Institute on Aging FX Research reported in this publication was supported by the National Institute on Aging (NIA) and National Institute on Minority Health and Health Disparities(NIMHD) of the National Institutes of Health under Award Numbers R01AG039389, P30AG12300, and L60MD001849. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research was also funded in part by grants from the Hogg Foundation for Mental Health (JRG-040 & JRG-149), the Environmental Protection Agency (RD834794), and the National Academy of Neuropsychology. Project FRONTIER is supported by Texas Tech University Health Sciences Center F. Marie Hall Institute for Rural & Community Health and the Garrison Institute on Aging. The researchers would also like to thank the Project FRONTIER participants and research staff. NR 35 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD FEB PY 2016 VL 31 IS 1 BP 88 EP 96 DI 10.1093/arclin/acv057 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA DD8QQ UT WOS:000370192400012 PM 26429558 ER PT J AU O'Brien, CM Flanagan, ME Bergman, AA Ebright, PR Frankel, RM AF O'Brien, Colleen M. Flanagan, Mindy E. Bergman, Alicia A. Ebright, Patricia R. Frankel, Richard M. TI "Anybody on this list that you're more worried about?" Qualitative analysis exploring the functions of questions during end of shift handoffs SO BMJ QUALITY & SAFETY LA English DT Article ID EMERGENCY-DEPARTMENT; HANDOVER; CARE; COMMUNICATION; DISCOURSE; DOCTORS AB Background Shift change handoffs are known to be a point of vulnerability in the quality, safety and outcomes of healthcare. Despite numerous efforts to improve handoff reliability, few interventions have produced lasting change. Although the opportunity to ask questions during patient handoff has been required by some regulatory bodies, the function of questions during handoff has been less well explored and understood. Objective To investigate questions and the functions they serve in nursing and medicine handoffs. Research design Qualitative thematic analysis based on audio recordings of nurse-to-nurse, medical resident-to-resident and surgical intern-to-intern handoffs. Subjects Twenty-seven nurse handoff dyads and 18 medical resident and surgical intern handoff dyads at one VA Medical Center. Results Our analysis revealed that the vast majority of questions were asked by the Incoming Providers. Although topics varied widely, the bulk of Incoming Provider questions requested information that would best help them understand individual patient conditions and plan accordingly. Other question types sought consensus on clinical reasoning or framing and alignment between the two professionals. Conclusions Handoffs are a type of socially constructed work. Questions emerge with some frequency in virtually all handoffs but not in a linear or predictable way. Instead, they arise in the moment, as necessary, and without preplanning. A checklist cannot model this process element because it is a static memory aid and questions occur in a relational context that is emergent. Studying the different functions of questions during end of shift handoffs provides insights into the interface between the technical context in which information is transferred and the social context in which meaning is created. C1 [O'Brien, Colleen M.; Frankel, Richard M.] Indiana Univ Sch Med, 340 W 10th St 6200, Indianapolis, IN 46202 USA. [O'Brien, Colleen M.] Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN USA. [O'Brien, Colleen M.; Flanagan, Mindy E.; Bergman, Alicia A.; Frankel, Richard M.] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Bergman, Alicia A.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Ebright, Patricia R.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Frankel, Richard M.] Mary Margaret Walther Ctr Res & Educ Palliat Care, Indianapolis, IN USA. RP O'Brien, CM (reprint author), Indiana Univ Sch Med, 340 W 10th St 6200, Indianapolis, IN 46202 USA. EM colmobri@iupui.edu FU VA Health Services Research and Development (HSR&D) Center of Excellence in Implementing Evidence-Based Practice, Indianapolis, Indiana; VA Health Services Research Grant [IIR 7-241] FX The project reported here was supported by the VA Health Services Research and Development (HSR&D) Center of Excellence in Implementing Evidence-Based Practice, Indianapolis, Indiana, and VA Health Services Research Grant No. IIR 7-241. NR 36 TC 2 Z9 2 U1 2 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD FEB PY 2016 VL 25 IS 2 BP 76 EP 83 DI 10.1136/bmjqs-2014-003853 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DD6GH UT WOS:000370022200004 PM 26217038 ER PT J AU Bergman, AA Flanagan, ME Ebright, PR O'Brien, CM Frankel, RM AF Bergman, Alicia A. Flanagan, Mindy E. Ebright, Patricia R. O'Brien, Colleen M. Frankel, Richard M. TI "Mr Smith's been our problem child today...": anticipatory management communication (AMC) in VA end of shift medicine and nursing handoffs SO BMJ QUALITY & SAFETY LA English DT Article ID SIGN-OUT; CARE; DISCONTINUITY; STRATEGIES AB Background Tools and procedures designed to improve end-of-shift handoffs through standardisation of processes and reliance on technology may miss contextually sensitive information about anticipated events that emerges during face-to-face handoff interactions. Such information, what we refer to as anticipatory management communication (AMC), is necessary to ensure timely and safe patient care, but has been little studied and understood. Objective To investigate AMC and the role it plays in nursing and medicine handoffs. Research design Qualitative thematic analysis based on audio recordings of nurse-to-nurse, medical resident-to-resident and surgical intern to-intern handoffs. Subjects 27 nurse handoff dyads and 18 medical resident and surgical intern handoff dyads at one VA Medical Center. Results Heads-up information was the most frequent type of AMC across all handoff dyads (N=257; 108 resident and 149 nursing). Indirect instructions AMC was used in a little over half the resident handoff dyads, but occurred in all nursing dyads (292 instances). Direct instructions AMC occurred in roughly equal proportion across all dyads but at a modest frequency (N=45; 28 resident and 17 nursing). Direct (if/then) contingency AMC occurred in resident handoffs more frequently than in nursing handoffs (N=32; 30 resident and 2 nursing). Conclusions The different frequencies for types of AMC likely reflect differences in how residents and nurses work and disparate professional cultures. But, verbal communication in both groups included important information unlikely to be captured in written handoff tools or the electronic medical record, underscoring the importance of direct communication to ensure safe handoffs. C1 [Bergman, Alicia A.] VA Greater Los Angeles, Ctr Study Healthcare Innovat Implementat & Policy, 16111 Plummer St,Bldg 25, North Hills, CA 91343 USA. [Flanagan, Mindy E.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA. [Bergman, Alicia A.; Flanagan, Mindy E.; Frankel, Richard M.] Richard L Roudebush VA Med Ctr, HSR&D Ctr Hlth Informat & Commun, Indianapolis, IN USA. [Ebright, Patricia R.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [O'Brien, Colleen M.] Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN USA. [Frankel, Richard M.] Indiana Univ, Dept Med, Indianapolis, IN 46204 USA. RP Bergman, AA (reprint author), VA Greater Los Angeles, Ctr Study Healthcare Innovat Implementat & Policy, 16111 Plummer St,Bldg 25, North Hills, CA 91343 USA. EM alicia.bergman@va.gov FU VA Health Services Research and Development (HSR&D) Center of Excellence in Implementing Evidence-Based Practice, Indianapolis, Indiana [IIR 07-241-2] FX VA Health Services Research and Development (HSR&D) Center of Excellence in Implementing Evidence-Based Practice, Indianapolis, Indiana, IIR 07-241-2. NR 26 TC 1 Z9 1 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD FEB PY 2016 VL 25 IS 2 BP 84 EP 91 DI 10.1136/bmjqs-2014-003694 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA DD6GH UT WOS:000370022200005 PM 26221029 ER PT J AU Eikermann, M Houle, TT AF Eikermann, M. Houle, T. T. TI Antagonism of neuromuscular block: all things are poison; only the dose makes a thing not a poison SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Editorial Material ID SUGAMMADEX; AGENTS; REVERSAL C1 [Eikermann, M.; Houle, T. T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. [Eikermann, M.] Univ Duisburg Essen, Klin Anesthesiol & Intens Med, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.; Eikermann, M (reprint author), Univ Duisburg Essen, Klin Anesthesiol & Intens Med, Essen, Germany. EM meikermann@partners.org NR 15 TC 2 Z9 2 U1 0 U2 1 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 FEB PY 2016 VL 116 IS 2 BP 157 EP 159 DI 10.1093/bja/aev448 PG 4 WC Anesthesiology SC Anesthesiology GA DD8VA UT WOS:000370203800004 PM 26787785 ER PT J AU Hung, GCL Pietras, SA Carliner, H Martin, L Seidman, LJ Buka, SL Gilman, SE AF Hung, Galen Chin-Lun Pietras, Stefanie A. Carliner, Hannah Martin, Laurie Seidman, Larry J. Buka, Stephen L. Gilman, Stephen E. TI Cognitive ability in childhood and the chronicity and suicidality of depression SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Review ID MENTAL-DISORDERS; FOLLOW-UP; MAJOR DEPRESSION; EARLY ADULTHOOD; BIRTH COHORT; LIFE-COURSE; PSYCHIATRIC MORBIDITY; SOCIOECONOMIC-STATUS; IQ SCORE; RISK AB Background There is inconsistent evidence regarding the influence of general cognitive abilities on the long-term course of depression. Aims To investigate the association between general childhood cognitive abilities and adult depression outcomes. Method We conducted a cohort study using data from 633 participants in the New England Family Study with lifetime depression. Cognitive abilities at age 7 were measured using the Wechsler Intelligence Scale for Children. Depression outcomes were assessed using structured diagnostic interviews administered up to four times in adulthood between ages 17 and 49. Results In analyses adjusting for demographic factors and parental psychiatric illness, low general cognitive ability (i.e. IQ<85 v. IQ>115) was associated with recurrent depressive episodes (odds ratio (OR)=2.19, 95% CI 1.20-4.00), longer episode duration (rate ratio 4.21, 95% CI 2.24-7.94), admission to hospital for depression (OR=3.65, 95% CI 1.34-9.93) and suicide ideation (OR=3.79, 95% CI 1.79-8.02) and attempt (OR=4.94, 95% CI 1.67-14.55). Conclusions Variation in cognitive abilities, predominantly within the normal range and established early in childhood, may confer long-term vulnerability for prolonged and severe depression. The mechanisms underlying this vulnerability need to be established to improve the prognosis of depression among individuals with lower cognitive abilities. C1 [Hung, Galen Chin-Lun] Taipei City Hosp, Taipei City Psychiat Ctr, Dept Psychiat, Taipei, Taiwan. [Hung, Galen Chin-Lun] Natl Yang Ming Univ, Sch Med, Dept Publ Hlth, Taipei 112, Taiwan. [Pietras, Stefanie A.] Math Policy Res, Cambridge, MA USA. [Carliner, Hannah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Martin, Laurie] RAND Corp, Santa Monica, CA USA. [Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Buka, Stephen L.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth Boston, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth Boston, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu OI Gilman, Stephen/0000-0002-8331-6419 FU National Institutes of Health [MH087544] FX This work was supported in part by a grant from the National Institutes of Health (MH087544). NR 43 TC 1 Z9 1 U1 3 U2 7 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 EI 1472-1465 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD FEB PY 2016 VL 208 IS 2 BP 120 EP 127 DI 10.1192/bjp.bp.114.158782 PG 8 WC Psychiatry SC Psychiatry GA DD7OO UT WOS:000370114200007 PM 26585100 ER PT J AU Ye, SN Shen, J Choy, E Yang, C Mankin, H Hornicek, F Duan, ZF AF Ye, Shunan Shen, Jacson Choy, Edwin Yang, Cao Mankin, Henry Hornicek, Francis Duan, Zhenfeng TI p53 overexpression increases chemosensitivity in multidrug-resistant osteosarcoma cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Osteosarcoma; p53; MDR; Apoptosis ID CYCLIN-DEPENDENT KINASES; LI-FRAUMENI-SYNDROME; CISPLATIN-RESISTANCE; MOLECULAR-MECHANISMS; DRUG-RESISTANCE; DNA-REPLICATION; P-GLYCOPROTEIN; BREAST-CANCER; UP-REGULATION; TUMOR-CELLS AB Multidrug resistance (MDR) is a major obstacle to the successful treatment of osteosarcoma with chemotherapy. Effectiveness of cancer therapy correlates with the ability to induce a p53-dependent apoptotic response. p53 is a tumor suppressor gene that is mutated in 22 % of osteosarcomas. While impaired p53 has been implicated in the oncogenesis of osteosarcoma, it is unclear whether overexpression of wild-type p53 can increase chemosensitivity in MDR osteosarcoma cells. We transfected a plasmid encoding the wild-type p53 gene to MDR osteosarcoma cell lines, which have different p53 statuses, U-2OSR2 with wild-type p53 (Wt-p53) and KHOSR2 with mutant p53 (Mt-p53), and determined the effect of p53 overexpression on chemosensitivities. Both of the U-2OSR2 and KHOSR2 cell lines displayed similar trends in p53-induced drug sensitivities. However, it seems that the impact of p53 overexpression is different based on the differential intrinsic p53 status in these cell lines. In the KHOSR2 cell line (Mt-p53), overexpression of p53 up-regulates the expression of pro-apoptotic protein p21 and Bax, while in the U-2OSR2 cell line (Wt-p53), overexpression of p53 down-regulates IGF-1r expression significantly. These results demonstrated that transfection of wild-type p53 increases chemosensitivity either through inhibiting IGF-1r or through increasing the expression of pro-apoptotic proteins p21 and Bax in human MDR osteosarcoma cell lines. C1 [Ye, Shunan; Shen, Jacson; Choy, Edwin; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. [Ye, Shunan; Yang, Cao] Huazhong Univ Sci & Technol, Dept Orthoped Surg, Union Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, 100 Blossom St,Jackson 1115, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu FU Gattegno fund, Stanton Foundation; Wechsler fund, Stanton Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopedic Surgery FX This work was supported in part by grants from the Gattegno and Wechsler funds, the Stanton Foundation. Dr. Duan is supported, in part, through a grant from Sarcoma Foundation of America (SFA), a grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA151452-01, a pilot grant from Sarcoma SPORE/NIH, and a grant from an Academic Enrichment Fund of MGH Orthopedic Surgery. The authors thank Yan Gao for assistance with densitometric analysis of Western blot results by Image J. NR 55 TC 4 Z9 5 U1 3 U2 6 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 FEB PY 2016 VL 77 IS 2 BP 349 EP 356 DI 10.1007/s00280-015-2944-z PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA DD8DO UT WOS:000370155300014 PM 26698867 ER PT J AU Bendell, JC Rosen, LS Mayer, RJ Goldman, JW Infante, JR Benedetti, F Lin, D 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 (vol 76, pg 925, 2015) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Correction C1 [Bendell, Johanna C.; Infante, Jeffrey R.] PLLC, Sarah Cannon Res Inst, Tennessee Oncol, 250 25th Ave North,Suite 200, Nashville, TN 37203 USA. [Rosen, Lee S.; Goldman, Jonathan W.] Univ Calif, 2020 Santa Monica Blvd,Suite 600, Santa Monica, CA 90404 USA. [Mayer, Robert J.] Dana Farber Canc Inst, 450 Brookline Ave,Dana 1602, Boston, MA 02215 USA. [Benedetti, Fabio; Mizuguchi, Hirokazu; Zergebel, Christopher] Taiho Oncol Inc, 202 Carnegie Ctr,Suite 100, Princeton, NJ 08540 USA. [Lin, Donghu] Taiho Pharmaceut Beijing Co Ltd, 9F-9A3,Hanwei Plaza,7th,Guanghua Rd, Beijing 100004, Peoples R China. [Patel, Manish R.] Sarah Cannon Res Inst, Florida Canc Specialists, 600 N Cattlemen Rd,Suite 200, Sarasota, FL 34232 USA. RP Bendell, JC (reprint author), PLLC, Sarah Cannon Res Inst, Tennessee Oncol, 250 25th Ave North,Suite 200, Nashville, TN 37203 USA. EM jbendell@tnonc.com 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 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD FEB PY 2016 VL 77 IS 2 BP 439 EP 439 DI 10.1007/s00280-015-2890-9 PG 1 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA DD8DO UT WOS:000370155300023 PM 26589791 ER PT J AU Chen, H Shen, J Choy, E Hornicek, FJ Duan, ZF AF Chen, Hua Shen, Jacson Choy, Edwin Hornicek, Francis J. Duan, Zhenfeng TI Targeting protein kinases to reverse multidrug resistance in sarcoma SO CANCER TREATMENT REVIEWS LA English DT Review DE Multidrug resistance (MDR); Protein kinase; Sarcoma ID SOFT-TISSUE SARCOMA; HUMAN OSTEOSARCOMA CELLS; GROWTH IN-VITRO; SIROLIMUS PLUS GEMCITABINE; CYCLIN-DEPENDENT KINASES; FOCAL ADHESION KINASE; INHIBITS TUMOR-GROWTH; ADVANCED SOLID TUMORS; SYNOVIAL SARCOMA; PHASE-I AB Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Chen, Hua; Shen, Jacson; Choy, Edwin; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St, Boston, MA 02114 USA. [Chen, Hua; Shen, Jacson; Choy, Edwin; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Chen, Hua] Jinan Univ, Dept Emergency Surg, ShenZhen Peoples Hosp, Clin Med Coll 2, 1017 Dongmenbei Rd, Shenzhen 518020, Guangdong, Peoples R China. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St, Boston, MA 02114 USA.; Duan, ZF (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM zduan@mgh.harvard.edu RI chen, hua/L-9462-2015 OI chen, hua/0000-0001-5703-9203 FU Kenneth Stanton Fund; Jennifer Hunter Yates Foundation; Sarcoma Foundation of America (SFA); National Cancer Institute (NCI)/National Institutes of Health (NIH) [UO1, CA 151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH Orthopaedics; Gattegno fund; Wechsler fund FX This work was supported, in part, by the Gattegno and Wechsler funds, the Kenneth Stanton Fund, and the Jennifer Hunter Yates Foundation. Dr. Duan is supported, in part, through a Grant from Sarcoma Foundation of America (SFA), a Grant from National Cancer Institute (NCI)/National Institutes of Health (NIH), UO1, CA 151452-01, a pilot Grant from Sarcoma SPORE/NIH, and a Grant from an Academic Enrichment Fund of MGH Orthopaedics. NR 116 TC 1 Z9 1 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 EI 1532-1967 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD FEB PY 2016 VL 43 BP 8 EP 18 DI 10.1016/j.ctrv.2015.11.011 PG 11 WC Oncology SC Oncology GA DE2JT UT WOS:000370454300002 PM 26827688 ER PT J AU Aronow, HD Collins, TJ Gray, WA Jaff, MR Kluck, BW Patel, RAG Rosenfield, KA Safian, RD Sobieszczyk, PS Wayangankar, SA White, CJ AF Aronow, Herbert D. Collins, Tyrone J. Gray, William A. Jaff, Michael R. Kluck, Bryan W. Patel, Rajan A. G. Rosenfield, Kenneth A. Safian, Robert D. Sobieszczyk, Piotr S. Wayangankar, Siddharth A. White, Christopher J. TI SCAI/SVM expert consensus statement on Carotid Stenting: Training and credentialing for Carotid Stenting SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE carotid stenosis; carotid stent; expert consensus document; stroke ID SURGICAL-RISK PATIENTS; CLINICAL COMPETENCE STATEMENT; TASK-FORCE; TRANSRADIAL APPROACH; VASCULAR-SURGERY; ARTERY-DISEASE; CARE REGISTRY; ENDARTERECTOMY; OUTCOMES; GUIDELINES AB Carotid artery stenting (CAS) has become an integral part of the therapeutic armamentarium offered by cardiovascular medicine programs for the prevention of stroke. The purpose of this expert consensus statement is to provide physician training and credentialing guidance to facilitate the safe and effective incorporation of CAS into clinical practice within these programs. Since publication of the 2005 Clinical Competence Statement on Carotid Stenting, there has been substantial device innovation, publication of numerous clinical trials and observational studies, accumulation of extensive real-world clinical experience and widespread participation in robust national quality improvement initiatives [5]. Collectively, these advances have led to substantial evolution in the selection of appropriate patients, as well as in the cognitive, technical and clinical skills required to perform safe and effective CAS. Herein, we summarize published guidelines, describe training pathways, outline elements of competency, offer strategies for tracking outcomes, specify facility, equipment and personnel requirements, and propose criteria for maintenance of CAS competency. (c) 2015 Wiley Periodicals, Inc. C1 [Aronow, Herbert D.] Brown Univ, Cardiovasc Inst RI, Alpert Med Sch, Providence, RI 02912 USA. [Collins, Tyrone J.; Patel, Rajan A. G.; White, Christopher J.] Ochsner Med Ctr, New Orleans, LA USA. [Gray, William A.] Columbia Univ, Med Ctr, New York, NY USA. [Jaff, Michael R.; Rosenfield, Kenneth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kluck, Bryan W.] Lehigh Valley Hosp, Allentown, PA USA. [Safian, Robert D.] Beaumont Hlth, Royal Oak, MI USA. [Sobieszczyk, Piotr S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Wayangankar, Siddharth A.] Cleveland Clin, Cleveland, OH 44106 USA. RP Aronow, HD (reprint author), 593 Eddy St,RIH APC814, Providence, RI 02903 USA. EM herbert.aronow@lifespan.org NR 48 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 EI 1522-726X J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB 1 PY 2016 VL 87 IS 2 BP 188 EP 199 DI 10.1002/ccd.26304 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE2IT UT WOS:000370451700007 PM 26602705 ER PT J AU Bui, AH Cannon, CP Steg, PG Storey, RF Husted, S Guo, JP Im, K James, SK Michelson, EL Himmelmann, A Held, C Varenhorst, C Wallentin, L Scirica, BM AF Bui, An H. Cannon, Christopher P. Steg, Philippe Gabriel Storey, Robert F. Husted, Steen Guo, Jianping Im, KyungAh James, Stefan K. Michelson, Eric L. Himmelmann, Anders Held, Claes Varenhorst, Christoph Wallentin, Lars Scirica, Benjamin M. TI Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE cardiovascular death; acute coronary syndrome; electrocardiography; tachycardia, ventricular; sudden cardiac death ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; ST-SEGMENT-ELEVATION; ARRHYTHMIAS; CLOPIDOGREL; TICAGRELOR; MORTALITY; ERA; PREVALENCE; DEFIBRILLATOR AB Background- Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. Methods and Results- In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by approximate to 5 months after ACS. Conclusions- NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event. Clinical Trial Registration- [GRAPHICS] . Unique identifier: NCT00391872. C1 [Bui, An H.; Cannon, Christopher P.; Guo, Jianping; Im, KyungAh; Scirica, Benjamin M.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Steg, Philippe Gabriel] INSERM Unite 1148, Paris, France. [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. [Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Dept Cardiol, Paris, France. [Steg, Philippe Gabriel] NHLI Imperial Coll, ICMS, Dept Cardiol, Royal Brompton Hosp, London, England. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Husted, Steen] Hosp Unit West, Dept Med, Herning Holstebro, Denmark. [James, Stefan K.; Held, Claes; Varenhorst, Christoph; Wallentin, Lars] Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden. [James, Stefan K.; Held, Claes; Varenhorst, Christoph; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Michelson, Eric L.] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. [Himmelmann, Anders] AstraZeneca Res & Dev, Gothenburg, Sweden. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA.; Scirica, BM (reprint author), Harvard Univ, Sch Med, 350 Longwood Ave, Boston, MA 02115 USA.; Scirica, BM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. EM bscirica@partners.org FU AstraZeneca FX The Platelet Inhibition and Patient Outcomes (PLATO) study was funded by AstraZeneca. Support for the analysis and interpretation of results and preparation of the article was provided through funds to the Uppsala Clinical Research Center and Duke Clinical Research Institute as part of the clinical study agreement. NR 23 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 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD FEB PY 2016 VL 9 IS 2 DI 10.1161/CIRCEP.115.002951 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE0VD UT WOS:000370342300001 ER PT J AU Hoffmann, U AF Hoffmann, Udo TI The Promise of a Warranty SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE diabetes mellitus; Editorials; risk; cardiovascular diseases; cardiac imaging techniques ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; PROGNOSTIC VALUE; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; ANGIOGRAPHY; PREDICTION; WOMEN; RISK C1 [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza Suite 400, Boston, MA 02114 USA.; Hoffmann, U (reprint author), Harvard Univ, Sch Med, 100 Charles River Plaza Suite 400, Boston, MA 02114 USA. EM uhoffmann@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD FEB PY 2016 VL 9 IS 2 DI 10.1161/CIRCIMAGING.116.004389 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DE1HS UT WOS:000370378400001 ER PT J AU Kinlay, S AF Kinlay, Scott TI Management of Critical Limb Ischemia SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE endovascular techniques; endarterectomy; angioplasty, balloon; drug-eluting stent; peripheral arterial disease ID PERIPHERAL ARTERY-DISEASE; SUPERFICIAL FEMORAL-ARTERY; BARE-METAL STENTS; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; LOWER-EXTREMITY REVASCULARIZATION; INTERVENTION APPROPRIATE USE; RANDOMIZED CONTROLLED-TRIAL; EXPERT CONSENSUS STATEMENT; PACLITAXEL-COATED BALLOON; DRUG-ELUTING BALLOON AB Critical limb ischemia (CLI) is a clinical syndrome of ischemic pain at rest or tissue loss, such as nonhealing ulcers or gangrene, related to peripheral artery disease. CLI has a high short-term risk of limb loss and cardiovascular events. Noninvasive or invasive angiography help determine the feasibility and approach to arterial revascularization. An endovascular-first approach is often advocated based on a lower procedural risk; however, specific patterns of disease may be best treated by open surgical revascularization. Balloon angioplasty and stenting form the backbone of endovascular techniques, with drug-eluting stents and drug-coated balloons offering low rates of repeat revascularization. Combined antegrade and retrograde approaches can increase success in long total occlusions. Below the knee, angiosome-directed angioplasty may lead to greater wound healing, but failing this, any straight-line flow into the foot is pursued. Hybrid surgical techniques such as iliac stenting and common femoral endarterectomy are commonly used to reduce operative risk. Lower extremity bypass grafting is most successful with a good quality, long, single-segment autogenous vein of at least 3.5-mm diameter. Minor amputations are often required for tissue loss as a part of the treatment strategy. Major amputations (at or above the ankle) limit functional independence, and their prevention is a key goal of CLI therapy. Medical therapy after revascularization targets risk factors for atherosclerosis and assesses wound healing and new or recurrent flow-limiting disease. The ongoing National Institutes of Health-sponsored Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia (BEST-CLI) study is a randomized trial of the contemporary endovascular versus open surgical techniques in patients with CLI. C1 [Kinlay, Scott] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cardiovasc Div,Dept Med,Med Sch, Boston, MA 02115 USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Dept Med, Cardiovasc Div, 1400 VFW Pkwy, Boston, MA 02132 USA. EM scott.kinlay@va.gov FU VA Clinical Science Research and Development Awards [1/01CX000440, 1/21CX000793]; Defense for Health Affairs through Gulf War Illness Research Program [W81XWH-15-1-0216] FX VA Clinical Science Research and Development Awards 1/01CX000440 and 1/21CX000793, and by the Assistant Secretary of Defense for Health Affairs, through the Gulf War Illness Research Program under Award No. W81XWH-15-1-0216. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. NR 83 TC 2 Z9 2 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7640 EI 1941-7632 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD FEB PY 2016 VL 9 IS 2 DI 10.1161/CIRCINTERVENTIONS.115.001946 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE1IL UT WOS:000370380400001 ER PT J AU Li, WQ Cho, E Khalili, H Wu, SW Chan, AT Qureshi, AA AF Li, Wen-Qing Cho, Eunyoung Khalili, Hamed Wu, Shaowei Chan, Andrew T. Qureshi, Abrar A. TI Rosacea, Use of Tetracycline, and Risk of Incident Inflammatory Bowel Disease in Women SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Dermatologic; Side Effect; NHS; Population; Antibiotic ID CROHNS-DISEASE; ULCERATIVE-COLITIS; OLMSTED COUNTY; ACNE; ISOTRETINOIN; PATIENT; COHORT; ASSOCIATION; PREVALENCE; MINNESOTA AB BACKGROUND & AIMS: Rosacea is an inflammatory skin disease. Case reports have shown rosacea as a comorbidity of inflammatory bowel disease (IBD), but no epidemiologic studies have examined rosacea and risk of subsequent IBD. The association between tetracycline use and risk of IBD was assessed, but this study produced limited findings. We examined the association between rosacea, use of tetracycline, and risk of incident Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We analyzed data from 96,314 participants in the Nurses' Health Study II (1991-2011). Information on IBD was confirmed by medical review. Participants were asked in 2005 about their lifetime histories of clinician-diagnosed rosacea and year of diagnosis. Information on ever use of tetracycline was collected in 1993. RESULTS: During 1,856,587 person-years (1991-2011), we identified 149 cases of CD and 215 cases of UC. Rosacea was not associated with risk of UC. In contrast, rosacea was significantly associated with increased risk of subsequent CD (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.15-4.18), which appeared particularly stronger for a longer duration after a diagnosis of rosacea (P-trend = .01). Tetracycline use was associated with increased risk of CD (HR, 1.56; 95% CI, 1.09-2.24) and UC (HR, 1.34; 95% CI, 1.00-1.80); there was a trend toward increased risk with increased duration of use (both P-trend <.05) (1993-2011). CONCLUSIONS: On the basis of an analysis of data from the Nurses' Health Study II, ever use of tetracycline at baseline is associated with an increased risk of CD and UC. Personal history of rosacea is associated with an increased risk of only CD. C1 [Li, Wen-Qing; Cho, Eunyoung; Wu, Shaowei; Qureshi, Abrar A.] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, 339 Eddy St, Providence, RI 02903 USA. [Li, Wen-Qing; Cho, Eunyoung; Qureshi, Abrar A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Cho, Eunyoung; Chan, Andrew T.; Qureshi, Abrar A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Khalili, Hamed; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. RP Li, WQ (reprint author), Brown Univ, Warren Alpert Med Sch, Dept Dermatol, 339 Eddy St, Providence, RI 02903 USA. EM wen-qing_li@brown.edu FU Department of Dermatology, Warren Alpert Medical School, Brown University; Nurses' Health Study II grant [UM1 CA176726] FX Supported by Department of Dermatology, Warren Alpert Medical School, Brown University and Nurses' Health Study II grant (UM1 CA176726). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 4 Z9 4 U1 5 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 FEB PY 2016 VL 14 IS 2 BP 220 EP + DI 10.1016/j.cgh.2015.09.013 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DE1GY UT WOS:000370376300014 PM 26404866 ER PT J AU Liang, PS Dominitz, JA AF Liang, Peter S. Dominitz, Jason A. TI Striving for Efficient, Patient-centered Endoscopy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID COLORECTAL-CANCER; OUTPATIENT ENDOSCOPY; NON-ATTENDANCE; COLONOSCOPY; RATES; NONATTENDANCE; CAPACITY; DEMAND C1 [Liang, Peter S.; Dominitz, Jason A.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA USA. RP Liang, PS (reprint author), Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. OI Liang, Peter/0000-0002-4160-421X FU NIDDK NIH HHS [NIH T32 DK007742] NR 19 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 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2016 VL 14 IS 2 BP 268 EP 270 DI 10.1016/j.cgh.2015.10.004 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DE1GY UT WOS:000370376300020 PM 26484705 ER PT J AU Cadoni, S Falt, P Leung, FW AF Cadoni, Sergio Falt, Premysl Leung, Felix W. TI Some Clarifications About Water-Aided Colonoscopy SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID UNSEDATED COLONOSCOPY; CECAL INTUBATION; CONTROLLED-TRIAL; INSUFFLATION; INFUSION; EXCHANGE C1 [Cadoni, Sergio] St Barbara Hosp, Digest Endoscopy Unit, Iglesias, Carbonia Iglesi, Italy. [Falt, Premysl] Vitkovice Hosp, Ctr Digest Dis, Ostrava, Czech Republic. [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, Iglesias, Carbonia Iglesi, Italy. NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD FEB PY 2016 VL 14 IS 2 BP 323 EP 323 DI 10.1016/j.cgh.2015.09.003 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DE1GY UT WOS:000370376300030 PM 26375611 ER PT J AU Olans, RN Olans, RD DeMaria, A AF Olans, Richard N. Olans, Rita D. DeMaria, Alfred, Jr. TI Antimicrobial Stewardship and the Allergist: Reclaiming our Antibiotic Armamentarium Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Olans, Richard N.] Hallmark Hlth Syst Inc, Melrose Wakefield Hosp, Div Infect Dis, Melrose, MA USA. [Olans, Rita D.] Massachusetts Gen Hosp, Inst Hlth Profess, Sch Nursing, Boston, MA 02114 USA. [DeMaria, Alfred, Jr.] William A Hinton State Lab Inst, Bur Infect Dis, Massachusetts Dept Hlth, Jamaica Plain, MA USA. RP Olans, RN (reprint author), Hallmark Hlth Syst, Melelrose Wakefield Hosp, Div Infect Dis, 585 Lebanon St, Melrose, MA 02176 USA. EM richardolans@gmail.com NR 6 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 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2016 VL 62 IS 3 BP 401 EP 402 DI 10.1093/cid/civ888 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DD8VS UT WOS:000370205600026 PM 26486700 ER PT J AU Wilcke, A Muller, B Schaadt, G Kirsten, H Boltze, J AF Wilcke, Arndt Mueller, Bent Schaadt, Gesa Kirsten, Holger Boltze, Johannes CA LEGASCREEN Consortium TI High acceptance of an early dyslexia screening test involving genetic analyses in Germany SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CANCER SUSCEPTIBILITY; ATTITUDES; CHILDREN; RISK AB Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50-70%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3-7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics. C1 [Wilcke, Arndt; Mueller, Bent; Kirsten, Holger; Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol IZI, Dept Cell Therapy, Perlickstr 1, D-04103 Leipzig, Germany. [Wilcke, Arndt; Kirsten, Holger; Boltze, Johannes] Univ Leipzig, Translat Ctr Regenerat Med TRM, D-04109 Leipzig, Germany. [Schaadt, Gesa] Max Planck Inst Human Cognit & Brain Sci, Dept Neurophysiol, Leipzig, Germany. [Schaadt, Gesa] Humboldt Univ, Dept Psychol, D-10099 Berlin, Germany. [Kirsten, Holger] Univ Leipzig, Fac Med, IMISE, D-04109 Leipzig, Germany. [Kirsten, Holger] Univ Leipzig, Fac Med, LIFE Leipzig Interdisciplinary Res Cluster Genet, D-04109 Leipzig, Germany. [Boltze, Johannes] Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. [Boltze, Johannes] Harvard Univ, Sch Med, Charlestown, MA USA. RP Wilcke, A (reprint author), Fraunhofer Inst Cell Therapy & Immunol IZI, Dept Cell Therapy, Perlickstr 1, D-04103 Leipzig, Germany. EM arndt.wilcke@izi.fraunhofer.de OI Muller, Bent/0000-0001-8308-6193 FU Fraunhofer Society; Max Planck Society within the framework of the 'Pakt fur Forschung und Innovation' FX We thank all the members of the LEGASCREEN consortium for their support during this study. LEGASCREEN is funded by the Fraunhofer Society and the Max Planck Society as a project within the framework of the 'Pakt fur Forschung und Innovation'. NR 25 TC 0 Z9 0 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2016 VL 24 IS 2 BP 178 EP 182 DI 10.1038/ejhg.2015.103 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DE2PO UT WOS:000370469400005 PM 26036858 ER PT J AU Fedorenko, E Morgan, A Murray, E Cardinaux, A Mei, C Tager-Flusberg, H Fisher, SE Kanwisher, N AF Fedorenko, Evelina Morgan, Angela Murray, Elizabeth Cardinaux, Annie Mei, Cristina Tager-Flusberg, Helen Fisher, Simon E. Kanwisher, Nancy TI A highly penetrant form of childhood apraxia of speech due to deletion of 16p11.2 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CHROMOSOME 16P11.2; INTELLIGENCE SCALE; CHILDREN; AUTISM; LOCUS; INTELLIGIBILITY; DISORDERS; PATHWAY; OBESITY; GENE AB Individuals with heterozygous 16p11.2 deletions reportedly suffer from a variety of difficulties with speech and language. Indeed, recent copy-number variant screens of children with childhood apraxia of speech (CAS), a specific and rare motor speech disorder, have identified three unrelated individuals with 16p11.2 deletions. However, the nature and prevalence of speech and language disorders in general, and CAS in particular, is unknown for individuals with 16p11.2 deletions. Here we took a genotype-first approach, conducting detailed and systematic characterization of speech abilities in a group of 11 unrelated children ascertained on the basis of 16p11.2 deletions. To obtain the most precise and replicable phenotyping, we included tasks that are highly diagnostic for CAS, and we tested children under the age of 18 years, an age group where CAS has been best characterized. Two individuals were largely nonverbal, preventing detailed speech analysis, whereas the remaining nine met the standard accepted diagnostic criteria for CAS. These results link 16p11.2 deletions to a highly penetrant form of CAS. Our findings underline the need for further precise characterization of speech and language profiles in larger groups of affected individuals, which will also enhance our understanding of how genetic pathways contribute to human communication disorders. C1 [Fedorenko, Evelina] Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,East 13th St,Room 2624, Boston, MA 02129 USA. [Morgan, Angela; Murray, Elizabeth; Mei, Cristina] Murdoch Childrens Res Inst, Language & Literacy Grp, Melbourne, Vic, Australia. [Morgan, Angela] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Cardinaux, Annie; Kanwisher, Nancy] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. [Tager-Flusberg, Helen] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Fisher, Simon E.] Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands. [Fisher, Simon E.] Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. [Kanwisher, Nancy] McGovern Inst Brain Res, Cambridge, MA USA. RP Fedorenko, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,East 13th St,Room 2624, Boston, MA 02129 USA. EM evelina9@mit.edu RI Fisher, Simon/E-9130-2012 OI Fisher, Simon/0000-0002-3132-1996 FU Simons Foundation; R00 award from NICHD [HD-057522]; Max Planck Society; NIDCD [P50 DC 13027]; NHMRC [607315]; Victorian's Government's Operational Infrastructure Support Program, Australia FX We thank the participants and their families for taking part in our study. We are also grateful to the Simons Foundation team (especially Alexandra Bowe, Debra Olchick, Nicole Takahashi, and Jennifer Tjernagel) for help with recruiting and scheduling participants. We thank Heather Mabie and Larry Shriberg for sharing the audio materials for the SRT. We thank Zuzanna Balewski, Cara Borelli, Jenelle Feather, Jeanne Gallee, Kyle Mahowald, Caitlin Malloy, and Terri Scott for help in preparing everything for testing and analyzing the data. We thank Kim Leeds for administrative support. This work was supported by a grant to NK from the Simons Foundation. EF is supported by the R00 award HD-057522 from NICHD. SEF is supported by the Max Planck Society. HTF's contribution to this research is supported by NIDCD (P50 DC 13027). AM is supported by the NHMRC (#607315). Preparation of this paper was also supported by the Victorian's Government's Operational Infrastructure Support Program, Australia. NR 47 TC 5 Z9 5 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 EI 1476-5438 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2016 VL 24 IS 2 BP 302 EP 306 DI 10.1038/ejhg.2015.149 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DE2PO UT WOS:000370469400023 PM 26173965 ER PT J AU Antoszczyk, S Rabkin, SD AF Antoszczyk, Slawomir Rabkin, Samuel D. TI Prospects and progress of oncolytic viruses for treating peripheral nerve sheath tumors SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE Virotherapy; MPNST; HSV; soft-tissue sarcoma ID HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; NEUROFIBROMATOSIS TYPE-1; MEASLES-VIRUS; SUBCUTANEOUS NEUROFIBROMAS; CANCER-IMMUNOTHERAPY; RECEPTOR EXPRESSION; PERINEURAL INVASION; NEURAL INVASION; PHASE-I AB Introduction: Peripheral nerve sheath tumors (PNSTs) are an assorted group of neoplasms originating from the neuroectoderm and growing in peripheral nerves. Malignant transformation leads to a poor prognosis and is often lethal. The current treatment of PNSTs is predominantly surgical, which is often incomplete or accompanied by significant loss of function, in conjunction with radiotherapy and/or chemotherapy, for which the benefits are inconclusive. Oncolytic viruses (OVs) efficiently kill tumor cells while remaining safe for normal tissues, and are a novel antitumor therapy for patients with PNSTs.Areas covered: Because of the low efficacy of current treatments, new therapies for PNSTs are needed. Preclinically, OVs have demonstrated efficacy in treating PNSTs and perineural tumor invasion, as well as safety. We will discuss the various PNSTs and their preclinical models, and the OVs being tested for their treatment, including oncolytic herpes simplex virus (HSV), adenovirus (Ad), and measles virus (MV). OVs can be armed' to express therapeutic transgenes or combined with other therapeutics to enhance their activity.Expert opinion: Preclinical testing of OVs in PNST models has demonstrated their therapeutic potential and provided support for clinical translation. Clinical studies with other solid tumors have provided evidence that OVs are safe in patients and efficacious. The recent successful completion of a phase III clinical trial of oncolytic HSV paves the way for oncolytic virotherapy to enter clinical practice. C1 [Antoszczyk, Slawomir; Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Boston, MA 02114 USA. [Antoszczyk, Slawomir; Rabkin, Samuel D.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. RP Rabkin, SD (reprint author), MGH Simches, Dept Neurosurg, Mol Neurosurg Lab, 185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. EM rabkin@mgh.harvard.edu FU US Department of Defense [W81XWH-070359, W81xWH-10-1-0091]; National Institute of Health [RO1 CA160762] FX The US Department of Defense has funded S Rabkin (W81XWH-070359) and S Antoszczyk (W81xWH-10-1-0091), with funding also received from the National Institute of Health (RO1 CA160762). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. NR 81 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD FEB 1 PY 2016 VL 4 IS 2 BP 129 EP 138 DI 10.1517/21678707.2016.1128322 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DD8EB UT WOS:000370156800001 PM 27867771 ER PT J AU Tsilimbaris, MK Vavvas, DG Bechrakis, NE AF Tsilimbaris, M. K. Vavvas, D. G. Bechrakis, N. E. TI Myopic foveoschisis: an ectatic retinopathy, not a schisis SO EYE LA English DT Letter C1 [Tsilimbaris, M. K.] Univ Crete, Sch Med, Dept Ophthalmol, Iraklion, Greece. [Vavvas, D. G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Bechrakis, N. E.] Med Univ Innsbruck, Dept Ophthalmol, A-6020 Innsbruck, Austria. RP Tsilimbaris, MK (reprint author), Univ Crete, Sch Med, Dept Ophthalmol, Iraklion, Greece. EM tsilimb@med.uoc.gr NR 4 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD FEB PY 2016 VL 30 IS 2 BP 328 EP 329 DI 10.1038/eye.2015.233 PG 3 WC Ophthalmology SC Ophthalmology GA DE2HX UT WOS:000370449500027 PM 26584797 ER PT J AU Rieckmann, A Hedden, T Younger, AP Sperling, RA Johnson, KA Buckner, RL AF Rieckmann, Anna Hedden, Trey Younger, Alayna P. Sperling, Reisa A. Johnson, Keith A. Buckner, Randy L. TI Dopamine Transporter Availability in Clinically Normal Aging Is Associated With Individual Differences in White Matter Integrity SO HUMAN BRAIN MAPPING LA English DT Article DE dopamine; white matter; amyloid; aging; magnetic resonance imaging; positron emission tomography ID BRAIN IRON DEPOSITION; PITTSBURGH COMPOUND-B; NORMAL OLDER-ADULTS; PARKINSONS-DISEASE; AMYLOID BURDEN; ALZHEIMERS-DISEASE; HEALTHY-ADULTS; IN-VIVO; HYPERINTENSITIES; PET AB Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imagingbased measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. (C) 2015 Wiley Periodicals, Inc. C1 [Rieckmann, Anna; Hedden, Trey; Younger, Alayna P.; Sperling, Reisa A.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Rieckmann, Anna] Umea Univ, Dept Radiat Sci Diagnost Radiol, Umea, Sweden. [Hedden, Trey; Johnson, Keith A.; Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA USA. [Buckner, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Rieckmann, A (reprint author), Dept Psychol, 52 Oxford St, Cambridge, MA 02138 USA.; Rieckmann, A (reprint author), Ctr Brain Sci, 52 Oxford St, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu FU National Institute on Aging, National Institutes of Health [P01AG036694, R01AG034556, R01AG046396, R01AG037497, K01AG040197, P50AG005134]; Alzheimer's Association [ZEN-10-174210]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health [P41EB015896]; National Institutes of Health [S10RR023401, S10RR023043, P41RR014075]; Seventh Framework Programme [FP7-PEOPLE-2011-IOF, 300217] FX Contract grant sponsor: National Institute on Aging, National Institutes of Health; Contract grant numbers: P01AG036694, R01AG034556, R01AG046396, R01AG037497, K01AG040197, P50AG005134; Contract grant sponsor: Alzheimer's Association; Contract grant number: ZEN-10-174210; Contract grant sponsor: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health; Contract grant number: P41EB015896; Contract grant sponsor: National Institutes of Health Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; Contract grant numbers: S10RR023401, S10RR023043, P41RR014075; Contract grant sponsor: Seventh Framework Programme; Contract grant number: FP7-PEOPLE-2011-IOF (to A.R.) 300217 NR 63 TC 0 Z9 0 U1 2 U2 7 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 FEB PY 2016 VL 37 IS 2 BP 621 EP 631 DI 10.1002/hbm.23054 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DD9KB UT WOS:000370243000014 PM 26542307 ER PT J AU Horst, TA Jupiter, JB AF Horst, Taylor A. Jupiter, Jesse B. TI Stabilisation of distal radius fractures: Lessons learned and future directions SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Review DE Distal radius fractures; Fracture management; Surgical fixation ID DISPLACED INTRAARTICULAR FRACTURES; PROSPECTIVE RANDOMIZED-TRIAL; EXTERNAL FIXATION; INTERNAL-FIXATION; OPEN REDUCTION; PERCUTANEOUS FIXATION; CLOSED REDUCTION; VOLAR PLATE; ARTHROSCOPIC REDUCTION; INTRAMEDULLARY NAIL AB Our understanding of the diagnosis and management of distal radius fractures has been a long developed over centuries. There has been a shift in treatment of these very common injuries from closed reduction and casting to internal fixation. The answer to the best method of treatment has yet to be found. Today, we have a multitude of treatment options available with varying degrees of evidence to support their use. This review helps to illustrate the lessons we have learned and future directions for treatment. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Horst, Taylor A.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Div Hand Surg, 55 Fruit St,Yawkey 2C-2100, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Div Hand Surg, 55 Fruit St,Yawkey 2C-2100, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 53 TC 1 Z9 1 U1 1 U2 5 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 FEB PY 2016 VL 47 IS 2 BP 313 EP 319 DI 10.1016/j.injury.2015.09.030 PG 7 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA DD9ZC UT WOS:000370283300005 PM 26553426 ER PT J AU Bleier, BS Castelnuovo, P Battaglia, P Turri-Zanoni, M Dallan, I Metson, R Sedaghat, AR Stefko, ST Gardner, PA Snyderman, CH Nogueira, JF Ramakrishnan, VR Muscatello, L Lenzi, R Freitag, S AF Bleier, Benjamin S. Castelnuovo, Paolo Battaglia, Paolo Turri-Zanoni, Mario Dallan, Iacopo Metson, Ralph Sedaghat, Ahmad R. Stefko, S. Tonya Gardner, Paul A. Snyderman, Carl H. Nogueira, Joao Flavio Ramakrishnan, Vijay R. Muscatello, Luca Lenzi, Riccardo Freitag, Suzanne TI Endoscopic endonasal orbital cavernous hemangioma resection: global experience in techniques and outcomes SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE endoscopic; orbital; intraconal; orbital cavernous hemangioma; outcomes ID DECOMPRESSION; SURGERY AB BackgroundEndoscopic orbital surgery represents the next frontier in endonasal surgery. The current literature is largely composed of small, heterogeneous, case series with little consensus regarding optimal techniques. The purpose of this study was to combine the experience of multiple international centers to create a composite of the global experience on the endoscopic management of a single type of tumor, the orbital cavernous hemangioma (OCH). MethodsThis was a retrospective study of techniques for endoscopic OCH resection from 6 centers on 3 continents. Only primary data from strictly endoscopic resection of OCHs were included. Responses were analyzed to qualitatively identify points of both consensus and variability among the different groups. ResultsData for a total of 23 patients, 10 (43.5%) male and 13 (56.5%) female were collected. The majority of lesions were intraconal (60.9%). The mean standard deviation (SD) surgical time was 150.7 +/- 75.0 minutes with a mean blood loss of 82.7 +/- 49.6 mL. Binarial approaches (26.1%) were used exclusively in the setting of intraconal lesions, which were associated with a higher rate of incomplete resection (31.3%), postoperative diplopia (25.0%), and the need for reconstruction (37.5%) than extraconal lesions. Orthotropia and symmetric orbital appearance were achieved in 60.9% and 78.3% of cases, respectively. ConclusionExtraconal lesions were managed similarly; however, greater variability was evident for intraconal lesions. These included the laterality and number of hands in the approach, methods of medial rectus retraction, and the need for reconstruction. The increased technical complexity and disparity of techniques in addressing intraconal OCHs suggests that continued research into the optimal management of this subclass of lesions is of significant priority. C1 [Bleier, Benjamin S.; Metson, Ralph; Sedaghat, Ahmad R.; Freitag, Suzanne] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. [Castelnuovo, Paolo; Battaglia, Paolo; Turri-Zanoni, Mario; Dallan, Iacopo] Univ Insubria, Div Otorhinolaryngol, Dept Biotechnol & Life Sci, Varese, Italy. [Stefko, S. Tonya; Snyderman, Carl H.] Univ Pittsburgh, Dept Ophthalmol, Med Ctr, Pittsburgh, PA 15260 USA. [Gardner, Paul A.] Univ Pittsburgh, Dept Neurol Surg, Med Ctr, Pittsburgh, PA 15260 USA. [Nogueira, Joao Flavio] Hosp Geral Fortaleza, Div Otolaryngol, Forta Leza, Brazil. [Ramakrishnan, Vijay R.] Univ Colorado, Div Otolaryngol, Denver, CO 80202 USA. [Muscatello, Luca; Lenzi, Riccardo] Gen Hosp Massa, Div Otorhinolaryngol, Massa, Italy. RP Bleier, BS (reprint author), 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu OI Ramakrishnan, Vijay/0000-0003-2748-0705; Battaglia, Paolo/0000-0001-6189-5889 NR 20 TC 2 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD FEB PY 2016 VL 6 IS 2 BP 156 EP 161 DI 10.1002/alr.21645 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA DD8SR UT WOS:000370197700009 PM 26623968 ER PT J AU Carroll, WW O'Connell, BP Schlosser, RJ Gudis, DA Karnezis, TT Lawrence, LA Soler, ZM Mulligan, JK AF Carroll, William W. O'Connell, Brendan P. Schlosser, Rodney J. Gudis, David A. Karnezis, Tom T. Lawrence, Lauren A. Soler, Zachary M. Mulligan, Jennifer K. TI Fibroblast levels are increased in chronic rhinosinusitis with nasal polyps and are associated with worse subjective disease severity SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE chronic rhinosinusitis; endoscopic sinus surgery; SNOT-22; quality of life; sinusitis ID ALLERGIC FUNGAL RHINOSINUSITIS; SINONASAL OUTCOME TEST; QUALITY-OF-LIFE; MESENCHYMAL TRANSITION; INFLAMMATORY MEDIATORS; AIRWAY RESPONSIVENESS; COLLAGEN DEPOSITION; LUNG-DISEASE; SINUSITIS; ASTHMA AB BackgroundFibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. MethodsPatients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non-hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. ResultsA total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control (p < 0.001) and CRSsNP (p < 0.01). Patients with AFRS had the most fibroblasts when compared to control (p < 0.0001), CRSsNP (p < 0.0001), and CRSwNP (p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP (p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP (p = 0.003) and AFRS (p = 0.048). ConclusionSinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS. C1 [Carroll, William W.; O'Connell, Brendan P.; Schlosser, Rodney J.; Gudis, David A.; Karnezis, Tom T.; Lawrence, Lauren A.; Soler, Zachary M.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Schlosser, Rodney J.; Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU American Academy of Otolaryngic Allery; Flight Attendant Medical Research Institute; Department of Veterans Affairs FX American Academy of Otolaryngic Allery (to B.P.O.); Flight Attendant Medical Research Institute (to J.K.M.); Department of Veterans Affairs (to R.J.S.). NR 61 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD FEB PY 2016 VL 6 IS 2 BP 162 EP 168 DI 10.1002/alr.21636 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA DD8SR UT WOS:000370197700010 PM 26370180 ER PT J AU Bleier, BS Singleton, A Nocera, AL Kocharyan, A Petkova, V Han, X AF Bleier, Benjamin S. Singleton, Amy Nocera, Angela L. Kocharyan, Armine Petkova, Victoria Han, Xue TI P-glycoprotein regulates Staphylococcus aureus enterotoxin B-stimulated interleukin-5 and thymic stromal lymphopoietin secretion in organotypic mucosal explants SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE P-glycoprotein; chronic sinusitis with nasal polyps; Th2 inflammation; sinonasal mucosa; organotypic explant; cytokine secretion; immunomodulator; zosuquidar trihydrochloride ID CHRONIC RHINOSINUSITIS; NASAL POLYPS; EPITHELIAL-CELLS; CHRONIC SINUSITIS; EXPRESSION; INFLAMMATION; MECHANISMS; MACROLIDES; MODEL; GENE AB BackgroundT-helper 2 (Th2) inflammation is a hallmark of chronic rhinosinusitis with nasal polyps (CRSwNP) although the pathogenesis is poorly understood. P-glycoprotein (permeability glycoprotein, P-gp) is an efflux pump that is capable of regulating cytokine transport and is expressed within sinonasal mucosa. The purpose of this study was to examine if the oversecretion of interleukin 5 (IL-5) and thymic stromal lymphopoietin (TSLP) in CRSwNP could be explained through P-gp-mediated secretory pathways. MethodsFifteen ethmoid mucosal explants were harvested from patients with CRS (n = 10) and CRSwNP (n = 10) and stimulated with Staphylococcus aureus enterotoxin B (SEB). P-gp was inhibited using zosuquidar trihydrochloride (herein Zosuquidar). P-gp expression was measured using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-5, IL-8, and TSLP secretion were quantified using ELISA. ResultsP-gp protein was overexpressed in CRSwNP (28.32 25.94 ng/mL per mg explant) as compared to CRS (10.74 +/- 8.61; p = 0.01, 2-tailed Mann-Whitney U test). There was no difference in messenger RNA (mRNA) expression. SEB induced a significant increase in IL-5 and TSLP but not IL-8 secretion relative to control in the CRSwNP explants only. Subsequent P-gp inhibition significantly reduced IL-5 and TSLP secretion (p = 0.04 for both, 2-tailed Student t test) to control levels. The concentration of IL-5 and TSLP secretion were strongly and significantly correlated to the concentration of P-gp within the same explant (IL-5: r = 0.791, p = 0.001; TSLP: r = 0.687, p = 0.003; 2-tailed Spearman's rank-order correlation). ConclusionP-gp protein is expressed at higher concentrations in CRSwNP as compared to CRS. This overexpression directly contributes to the relative hypersecretion of IL-5 and TSLP. These findings suggest a novel mechanism for Th2 skewing in CRSwNP. C1 [Bleier, Benjamin S.; Nocera, Angela L.; Kocharyan, Armine] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. [Singleton, Amy; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Petkova, Victoria] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM benjamin_bleier@meei.harvard.edu NR 38 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD FEB PY 2016 VL 6 IS 2 BP 169 EP 177 DI 10.1002/alr.21566 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA DD8SR UT WOS:000370197700011 PM 26625351 ER PT J AU Lawrence, LA Baker, AB Nguyen, SA Karnezis, TT Soler, ZM Schlosser, RJ AF Lawrence, Lauren A. Baker, Andrew B. Nguyen, Shaun A. Karnezis, Tom T. Soler, Zachary M. Schlosser, Rodney J. TI Predictors of 30-day morbidity and mortality in transnasal microscopic pituitary tumor excision SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE anterior skull base; postoperative; endonasal approach to the pituitary; NSQIP; outcomes; adverse events ID ENDONASAL TRANSSPHENOIDAL SURGERY; ADENOMAS; COMPLICATIONS; READMISSION; EXPERIENCE; SERIES; STAY AB BackgroundThere is a lack of population-based, multi-institutional analyses of factors associated with morbidity and mortality following pituitary tumor excision. MethodsThe American College of Surgeons National Surgical Quality Improvement Project files were used to compile information on patients that had undergone transnasal microscopic pituitary tumor resection from 2006 to 2012. Patient demographics, comorbidities, operative characteristics, and morbidity and mortality in the 30 days following surgery were included. Multivariate logistic regression was used for categorical variables and multivariate linear regression was used for continuous variables to evaluate factors leading to adverse events. ResultsA total of 658 patients were included, of which 58 (8.81%) experienced a complication, reoperation or death in the 30 days following surgery. The most common complications were reoperation (3.37%), followed by unplanned reintubation (1.99%), urinary tract infection (1.68%), and transfusion (1.68%). Predictors of any complication, reoperation, or death include preoperative sepsis (odds ratio [OR] = 7.596) and lower preoperative serum albumin (OR = 6.667). Younger age predicted surgical complications (OR = 1.105). Predictors of medical complications include higher body mass index (OR = 1.112), chronic steroid use (OR = 6.568), preoperative sepsis (OR = 15.297), and lower preoperative serum hematocrit (OR = 1.225). Predictors of increased total length of hospital stay were older age ( = 0.146), higher body mass index ( = 0.188), chronic steroid use ( = 0.142), preoperative sepsis ( = 0.489), and lower preoperative serum albumin ( = -0.213). ConclusionAlthough adverse events following pituitary tumor excision are low, awareness of factors associated with morbidity and mortality in the early postoperative period may allow for improved patient monitoring and outcomes. C1 [Lawrence, Lauren A.; Baker, Andrew B.; Nguyen, Shaun A.; Karnezis, Tom T.; Soler, Zachary M.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge,MSC 550, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Lawrence, LA (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge,MSC 550, Charleston, SC 29425 USA. EM lawre194@gmail.com OI Baker, Andrew/0000-0002-2041-5225 FU Optinose (Yardley, PA); Intersect ENT FX R.J.S. is a consultant for Olympus (Center Valley, PA) and has been provided grant support from Optinose (Yardley, PA) and Intersect ENT; none of these provided support for this investigation. Z.M.S. is also consultant for Olympus, but no support was provided for this investigation. NR 29 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 EI 2042-6984 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD FEB PY 2016 VL 6 IS 2 BP 206 EP 213 DI 10.1002/alr.21641 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA DD8SR UT WOS:000370197700016 PM 26370600 ER PT J AU Meara, JG Leather, AJM Hagander, L Alkire, BC Alonso, N Ameh, EA Bickler, SW Conteh, L Dare, AJ Davies, J Merisier, ED El-Halabi, S Farmer, PE Gawande, A Gillies, R Greenbergac, SLM Grimes, CE Gruen, RL Ismail, EA KamaraY, TB Lavy, C Lundeg, G Mkandawire, NC Raykar, NP Riesel, JN Rodasagah, E Rose, J Roy, N Shrime, MG Sullivan, R Verguet, S Wafters, D Weiser, TG Wilson, LH Yamey, G Yipaq, W AF Meara, John G. Leather, Andrew J. M. Hagander, Lars Alkire, Blake C. Alonso, Nivaldo Ameh, Emmanuel A. Bickler, Stephen W. Conteh, Lesong Dare, Anna J. Davies, Justine Merisier, Eunice Derivois El-Halabi, Shenaaz Farmer, Paul E. Gawande, Atul Gillies, Rowan Greenbergac, Sarah L. M. Grimes, Canis E. Gruen, Russell L. Ismail, Edna Adan KamaraY, Thaim Buya Lavy, Chris Lundeg, Ganbold Mkandawire, Nyengo C. Raykar, Nakul P. Riesel, Johanna N. Rodasagah, Edgar Rose, John Roy, Nobhojit Shrime, Mark G. Sullivan, Richard Verguet, Stephan Wafters, David Weiser, ThOmas G. Wilson, Lain H. Yamey, Gavin Yipaq, Winnie TI Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development SO INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA LA English DT Article C1 [Meara, John G.; Greenbergac, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Meara, John G.; Greenbergac, Sarah L. M.; Raykar, Nakul P.; Riesel, Johanna N.] Boston Childrens Hosp, Boston, MA 02115 USA. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Canis E.] Kings Hlth Partners, Kings Ctr Global Hlth, London, England. [Leather, Andrew J. M.; Dare, Anna J.; Grimes, Canis E.] Kings Coll London, London, England. [Hagander, Lars] Lund Univ, Clin Sci Lund, Dept Pediat, Pediat Surg & Global Pediat, Lund, Sweden. [Alkire, Blake C.; Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Alonso, Nivaldo] Univ Sao Paulo, Dept Plast Surg, Sao Paulo, Brazil. [Ameh, Emmanuel A.] Natl Hosp, Div Peadiat Surg, Dept Surg, Abuja, Nigeria. [Bickler, Stephen W.] Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA 92103 USA. [Rose, John] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. [Conteh, Lesong] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. [Davies, Justine] Lancet, London, England. [Merisier, Eunice Derivois] Dept Minist Hlth, Ouest, Haiti. [El-Halabi, Shenaaz] Minist Hlth, Gaborone, Botswana. [Farmer, Paul E.] Harvard Univ, Sch Med, Div Global Hlth Equity, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Farmer, Paul E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Farmer, Paul E.] Partners Hlth, Boston, MA USA. [Gawande, Atul] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. [Gawande, Atul] Ariadne Labs Boston, Boston, MA USA. [Gillies, Rowan] Royal N Shore Hosp, St Leonards, NSW 2065, Australia. [Greenbergac, Sarah L. M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gruen, Russell L.] Alfred Hosp, Melbourne, Vic, Australia. [Gruen, Russell L.] Monash Univ, Melbourne, Vic 3004, Australia. [Gruen, Russell L.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore. [Ismail, Edna Adan] Edna Adan Univ Hosp, Hargeisa, Somaliland, Somalia. [KamaraY, Thaim Buya] Connaught Hosp, Freetown, Sierra Leone. [KamaraY, Thaim Buya] Univ Sierra Leone, Dept Surg, Freetown, Sierra Leone. [Lavy, Chris] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England. [Lundeg, Ganbold] Mongolian Natl Univ Med Sci, Ulaanbaatar, Mongol Peo Rep. [Mkandawire, Nyengo C.] Univ Malawi, Coll Med, Dept Surg, Blantyre, Malawi. [Mkandawire, Nyengo C.] Flinders Univ S Australia, Sch Med, Adelaide, SA, Australia. [Raykar, Nakul P.] Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. [Riesel, Johanna N.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rodasagah, Edgar] Univ Cuenca, Cinterandes Fdn, Cuenca, Ecuador. [Rodasagah, Edgar] Univ Azuay, Cuenca, Ecuador. [Roy, Nobhojit] BARC Hosp, Mumbai, Maharashtra, India. [Shrime, Mark G.] Harvard Interfac Initiat Hlth Policy, Cambridge, MA USA. [Sullivan, Richard] Kings Coll London, Kings Ctr Global Hlth, Kings Hlth Partners Integrated Canc Ctr, Inst Canc Policy, London, England. [Verguet, Stephan] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Wafters, David] Royal Australasian Coll Surg, East Melbourne, Vic, Australia. [Wafters, David] Deakin Univ, Melbourne, Vic, Australia. [Weiser, ThOmas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Wilson, Lain H.] Royal Devon & Exeter NHS Fdn Trust, Dept Anaesthesia, Exeter, Devon, England. [Yamey, Gavin] Univ Calif San Francisco, Global Hlth Grp, Evidence Policy Initiat, San Francisco, CA 94143 USA. [Yipaq, Winnie] Univ Oxford, Blavatnik Sch Govt, Oxford, England. RP Meara, JG (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA.; Meara, JG (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA. EM john.meara@childrens.harvard.edu OI Sullivan, Richard/0000-0002-6435-1825 FU Medical Research Council [MR/K010174/1] NR 1 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-289X EI 1532-3374 J9 INT J OBSTET ANESTH JI Int. J. Obstet. Anesth. PD FEB PY 2016 VL 25 BP 75 EP 78 DI 10.1016/j.ijoa.2015.09.006 PG 4 WC Anesthesiology; Obstetrics & Gynecology SC Anesthesiology; Obstetrics & Gynecology GA DD7MY UT WOS:000370109900012 PM 26597405 ER PT J AU Riemer, C Doctor, M Dellavalle, RP AF Riemer, Christie Doctor, Monica Dellavalle, Robert P. TI Analysis of Online Ratings of Dermatologists SO JAMA DERMATOLOGY LA English DT Letter C1 [Riemer, Christie] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [Doctor, Monica] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. [Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Anschutz Med Campus, Aurora, CO USA. [Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Dermatol Serv, 1055 Clermont St,POB 165, Denver, CO 80220 USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA. RP Dellavalle, RP (reprint author), Eastern Colorado Hlth Care Syst, US Dept Vet Affairs, Dermatol Serv, 1055 Clermont St,POB 165, Denver, CO 80220 USA. NR 3 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 152 IS 2 BP 218 EP 220 DI 10.1001/jamadermatol.2015.4991 PG 4 WC Dermatology SC Dermatology GA DE4AT UT WOS:000370572300021 PM 26677133 ER PT J AU Cohen, AS Mitchell, KR Docherty, NM Horan, WP AF Cohen, Alex S. Mitchell, Kyle R. Docherty, Nancy M. Horan, William P. TI Vocal Expression in Schizophrenia: Less Than Meets the Ear SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE schizophrenia; negative; alogia; blunted affect; computer ID PSYCHIATRIC RATING-SCALE; NEGATIVE SYMPTOMS; ACOUSTIC ANALYSIS; MENTAL-ILLNESS; SPEECH FLUENCY; METAANALYSIS; DEPRESSION; DISORDERS; PROSODY; DEFICIT AB Abnormalities in nonverbal communication are a hallmark of schizophrenia. Results from studies using symptom rating scales suggest that these abnormalities are profound (i.e., 3-5 SDs) and occur across virtually every channel of vocal expression. Computerized acoustic analytic technologies, used to overcome practical and psychometric limitations with symptom rating scales, have found much more benign and isolated abnormalities. To better understand vocal deficits in schizophrenia and to advance acoustic analytic technologies for clinical and research applications, we examined archived speech samples from 5 separate studies, each using different speaking tasks (patient N = 309; control N = 117). We sought to: (a) use Principal Component Analysis (PCA) to identify independent vocal expression measures from a large set of variables, (b) quantify how patients with schizophrenia are abnormal with respect to these variables, (c) evaluate the impact of demographic and contextual factors (e.g., study site, speaking task), and (d) examine the relationship between clinically-rated psychiatric symptoms and vocal variables. PCA identified 7 independent markers of vocal expression. Most of these vocal variables varied considerably as a function of context and many were associated with demographic factors. After controlling for context and demographics, there were no meaningful differences in vocal expression between patients and controls. Within patients, vocal variables were associated with a range of psychiatric symptoms-though only pause length was significantly associated with clinically rated negative symptoms. The discussion centers on explaining the apparent discordance between clinical and computerized speech measures. C1 [Cohen, Alex S.; Mitchell, Kyle R.] Louisiana State Univ, Dept Psychol, 236 Audubon Hall, Baton Rouge, LA 70803 USA. [Docherty, Nancy M.] Kent State Univ, Dept Psychol, Kent, OH USA. [Horan, William P.] Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Cohen, AS (reprint author), Louisiana State Univ, Dept Psychol, 236 Audubon Hall, Baton Rouge, LA 70803 USA. EM acohen@lsu.edu FU National Institute of Mental Health [R03MH092622] FX This project was funded by Grant R03MH092622 from the National Institute of Mental Health to AC. We thank the patients and subjects who volunteered their time to participate in the study. We are also grateful to Matt Calamia for his statistical advice and consultation. NR 55 TC 1 Z9 1 U1 3 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X EI 1939-1846 J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 2016 VL 125 IS 2 BP 299 EP 309 DI 10.1037/abn0000136 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA DD8GJ UT WOS:000370163500014 PM 26854511 ER PT J AU Bachmann, KN Bruno, AG Bredella, MA Schorr, M Lawson, EA Gill, CM Singhal, V Meenaghan, E Gerweck, AV Eddy, KT Ebrahimi, S Koman, SL Greenblatt, JM Keane, RJ Weigel, T Dechant, E Misra, M Klibanski, A Bouxsein, ML Miller, KK AF Bachmann, Katherine N. Bruno, Alexander G. Bredella, Miriam A. Schorr, Melanie Lawson, Elizabeth A. Gill, Corey M. Singhal, Vibha Meenaghan, Erinne Gerweck, Anu V. Eddy, Kamryn T. Ebrahimi, Seda Koman, Stuart L. Greenblatt, James M. Keane, Robert J. Weigel, Thomas Dechant, Esther Misra, Madhusmita Klibanski, Anne Bouxsein, Mary L. Miller, Karen K. TI Vertebral Strength and Estimated Fracture Risk Across the BMI Spectrum in Women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOPOROSIS; BIOMECHANICS; BONE QCT ID BONE-MINERAL DENSITY; QUANTITATIVE COMPUTED-TOMOGRAPHY; OBESE PREMENOPAUSAL WOMEN; BODY-MASS INDEX; ANOREXIA-NERVOSA; POSTMENOPAUSAL WOMEN; MECHANICAL-PROPERTIES; CONTROLLED-TRIAL; ADIPOSE-TISSUE; ABDOMINAL FAT AB Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (phi), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher phi reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and phi at L-4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90 degrees, holding 5kg in each hand (holding); 3) 45 degrees trunk flexion, 5kg in each hand (lifting); 4) 20 degrees trunk right lateral bend, 10kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest phi for standing and lifting, whereas women with anorexia nervosa had highest phi for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher phi for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R=0.28 to 0.45, p 0.0001) in all groups combined and negatively with VAT (R=-[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (phi) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women. (c) 2015 American Society for Bone and Mineral Research. C1 [Bachmann, Katherine N.; Schorr, Melanie; Lawson, Elizabeth A.; Singhal, Vibha; Misra, Madhusmita; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. [Bachmann, Katherine N.; Bruno, Alexander G.; Bredella, Miriam A.; Schorr, Melanie; Lawson, Elizabeth A.; Singhal, Vibha; Eddy, Kamryn T.; Weigel, Thomas; Dechant, Esther; Misra, Madhusmita; Klibanski, Anne; Bouxsein, Mary L.; Miller, Karen K.] Harvard Univ, Sch Med, Boston, MA USA. [Bruno, Alexander G.; Bouxsein, Mary L.] MIT, Harvard MIT Hlth Sci & Technol Program, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Bruno, Alexander G.; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Bredella, Miriam A.; Gill, Corey M.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. [Singhal, Vibha; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. [Meenaghan, Erinne; Gerweck, Anu V.] Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. [Eddy, Kamryn T.] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. [Ebrahimi, Seda] Cambridge Eating Disorders Ctr, Cambridge, MA USA. [Koman, Stuart L.; Greenblatt, James M.; Keane, Robert J.] Walden Behav Care, Waltham, MA USA. [Weigel, Thomas; Dechant, Esther] McLean Hosp, Klarman Ctr, 115 Mill St, Belmont, MA 02178 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA.; Miller, KK (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Miller, KK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@mgh.harvard.edu FU NIH [T32 DK 007028, K24 HL092902, RO1 HL 077674, R01 MH083657, R01 DK052625, RO3-DK59297, M01-RR01066-27S1, M01-RR01066, UL1 RR025758, 8UL1 TR000170, 1UL1TR001102, K23 RR-23090, R01 AR053986, F31AG041629] FX This work was supported by NIH grants T32 DK 007028, K24 HL092902, RO1 HL 077674, R01 MH083657, R01 DK052625, RO3-DK59297, M01-RR01066-27S1, M01-RR01066, UL1 RR025758, 8UL1 TR000170, 1UL1TR001102, K23 RR-23090, R01 AR053986, and F31AG041629. NR 46 TC 3 Z9 3 U1 1 U2 4 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 FEB PY 2016 VL 31 IS 2 BP 281 EP 288 DI 10.1002/jbmr.2697 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD8NE UT WOS:000370182900005 PM 26332401 ER PT J AU Osazuwa-Peters, N Massa, ST Christopher, KM Walker, RJ Varvares, MA AF Osazuwa-Peters, Nosayaba Massa, Sean T. Christopher, Kara M. Walker, Ronald J. Varvares, Mark A. TI Race and sex disparities in long-term survival of oral and oropharyngeal cancer in the United States SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE Racial and sex disparities; Oral cavity cancer; Oropharyngeal cancer; Long-term survival; Outcomes ID SQUAMOUS-CELL CARCINOMA; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; CAVITY CANCER; RISK-FACTORS; HEAD; AMERICANS; HPV; EPIDEMIOLOGY; SURVIVORSHIP AB Purpose To investigate the effect of race and sex on long-term survival of oral and oropharyngeal cancer. Methods The Surveillance, Epidemiology and End Results database was queried for adult oral and oropharyngeal cancer patients with at least 25-year follow-up. Kaplan-Meier survival curves and cox proportional hazards model were used to identify differences. Results Of the 22,162 patients identified, 70.3 % were males. Only 8.9 % were alive at 25 years post-diagnosis. Black males show the poorest overall and disease-specific survival rates (p < 0.001). After controlling for covariates, Blacks had a 40 % higher hazard of mortality compared with Whites (HR 1.40, 95 % CI 1.35-1.46), while females had a 9 % reduction in mortality risk (HR 0.91, 95 % CI 0.88-0.94). Conclusions Overall and disease-specific survival is poor for oral and oropharyngeal cancer patients, and Black men fare worst. This illustrates the need for long-term cancer survival plans incorporating disparity effects in overall cancer outcomes. C1 [Osazuwa-Peters, Nosayaba; Christopher, Kara M.] St Louis Univ, Ctr Canc, 3655 Vista Ave, St Louis, MO 63110 USA. [Osazuwa-Peters, Nosayaba; Massa, Sean T.; Walker, Ronald J.; Varvares, Mark A.] St Louis Univ, Dept Otolaryngol Head & Neck Surg, Sch Med, 3655 Vista Ave,6th Floor Desloge Towers, St Louis, MO 63110 USA. [Varvares, Mark A.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Osazuwa-Peters, N (reprint author), St Louis Univ, Ctr Canc, 3655 Vista Ave, St Louis, MO 63110 USA.; Osazuwa-Peters, N (reprint author), St Louis Univ, Dept Otolaryngol Head & Neck Surg, Sch Med, 3655 Vista Ave,6th Floor Desloge Towers, St Louis, MO 63110 USA. EM nosazuwa@slu.edu NR 52 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-5216 EI 1432-1335 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD FEB PY 2016 VL 142 IS 2 BP 521 EP 528 DI 10.1007/s00432-015-2061-8 PG 8 WC Oncology SC Oncology GA DD8JR UT WOS:000370173300019 PM 26507889 ER PT J AU Sorensen, G Nagler, EM Hashimoto, D Dennerlein, JT Theron, JV Stoddard, AM Buxton, O Wallace, LM Kenwood, C Nelson, CC Tamers, SL Grant, MP Wagner, G AF Sorensen, Glorian Nagler, Eve M. Hashimoto, Dean Dennerlein, Jack T. Theron, Julie V. Stoddard, Anne M. Buxton, Orfeu Wallace, Lorraine M. Kenwood, Christopher Nelson, Candace C. Tamers, Sara L. Grant, Michael P. Wagner, Gregory TI Implementing an Integrated Health Protection/Health Promotion Intervention in the Hospital Setting Lessons Learned From the Be Well, Work Well Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PATIENT-CARE WORKERS; LOW-BACK-PAIN; PROOF-OF-CONCEPT; MUSCULOSKELETAL PAIN; REGISTERED NURSES; SLEEP DEFICIENCY; PSYCHOLOGICAL DISTRESS; OCCUPATIONAL INJURIES; FAMILY CONFLICT; RISK-FACTOR AB Objective:This study reports findings from a proof-of-concept trial designed to examine the feasibility and estimates the efficacy of the Be Well, Work Well workplace intervention.Methods:The intervention included consultation for nurse managers to implement changes on patient-care units and educational programming for patient-care staff to facilitate improvements in safety and health behaviors. We used a mixed-methods approach to evaluate feasibility and efficacy.Results:Using findings from process tracking and qualitative research, we observed challenges to implementing the intervention due to the physical demands, time constraints, and psychological strains of patient care. Using survey data, we found no significant intervention effects.Conclusions:Beyond educating individual workers, systemwide initiatives that respond to conditions of work might be needed to transform the workplace culture and broader milieu in support of worker health and safety. C1 [Sorensen, Glorian; Nagler, Eve M.; Theron, Julie V.; Wallace, Lorraine M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Dennerlein, Jack T.; Wagner, Gregory] Harvard Univ, Dept Environm Hlth, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Sorensen, Glorian; Nagler, Eve M.; Nelson, Candace C.; Grant, Michael P.] Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Hashimoto, Dean] Partners HealthCare, Boston, MA USA. [Hashimoto, Dean] Boston Coll, Sch Law, Newton, MA USA. [Hashimoto, Dean; Buxton, Orfeu] Harvard Univ, Sch Med, Boston, MA USA. [Dennerlein, Jack T.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Buxton, Orfeu] Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. [Buxton, Orfeu] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Kenwood, Christopher] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. [Tamers, Sara L.] Ctr Dis Control & Prevent, Off Total Worker Hlth Coordinat & Res Support, NIOSH, Washington, DC USA. [Wagner, Gregory] Ctr Dis Control & Prevent, Off Director, NIOSH, Washington, DC USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM glorian_sorensen@dfci.harvard.edu FU National Institute for Occupational Safety and Health for Harvard T.H. Chan School of Public Health Center for Work, Health and Well-being [U19 OH008861] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard T.H. Chan School of Public Health Center for Work, Health and Well-being. NR 64 TC 1 Z9 1 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 2016 VL 58 IS 2 BP 185 EP 194 DI 10.1097/JOM.0000000000000592 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DD8VH UT WOS:000370204500011 PM 26849263 ER PT J AU Magruder, KM Goldberg, J Forsberg, CW Friedman, MJ Litz, BT Vaccarino, V Heagerty, PJ Gleason, TC Huang, GD Smith, NL AF Magruder, Kathryn M. Goldberg, Jack Forsberg, Christopher W. Friedman, Matthew J. Litz, Brett T. Vaccarino, Viola Heagerty, Patrick J. Gleason, Theresa C. Huang, Grant D. Smith, Nicholas L. TI Long-Term Trajectories of PTSD in Vietnam-Era Veterans: The Course and Consequences of PTSD in Twins SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; DIAGNOSTIC INTERVIEW CIDI; MENTAL-HEALTH; ACCIDENT VICTIMS; DELAYED-ONSET; RISK-FACTORS; SCALE; PREVALENCE; MORTALITY AB We estimated the temporal course of posttraumatic stress disorder (PTSD) in Vietnam-era veterans using a national sample of male twins with a 20-year follow-up. The complete sample included those twins with a PTSD diagnostic assessment in 1992 and who completed a DSM-IV PTSD diagnostic assessment and a self-report PTSD checklist in 2012 (n = 4,138). Using PTSD diagnostic data, we classified veterans into 5 mutually exclusive groups, including those who never had PTSD, and 4 PTSD trajectory groups: (a) early recovery, (b) late recovery, (c) late onset, and (d) chronic. The majority of veterans remained unaffected by PTSD throughout their lives (79.05% of those with theater service, 90.85% of those with nontheater service); however, an important minority (10.50% of theater veterans, 4.45% of nontheater veterans) in 2012 had current PTSD that was either late onset (6.55% theater, 3.29% nontheater) or chronic (3.95% theater, 1.16% nontheater). The distribution of trajectories was significantly different by theater service (p < .001). PTSD remains a prominent issue for many Vietnam-era veterans, especially for those who served in Vietnam. C1 [Magruder, Kathryn M.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Goldberg, Jack; Forsberg, Christopher W.; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Goldberg, Jack; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Friedman, Matthew J.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs, White River Jct, VT USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA. [Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Epidemiol Res & Informat Ctr, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Vaccarino, Viola] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Vaccarino, Viola] Emory Univ, Dept Med, Atlanta, GA 30322 USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Gleason, Theresa C.; Huang, Grant D.] VA Off Res & Dev, Clin Sci Res & Dev, Cooperat Studies Program, Washington, DC USA. RP Magruder, KM (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. EM magrudkm@musc.edu FU Cooperative Studies Program (CSP) of Office of Research and Development, Clinical Science Research and Development of United States Department of Veterans Affairs (VA) [569]; National Institutes of Health award [K24 HL077506] FX The Cooperative Studies Program (CSP) of the Office of Research and Development, Clinical Science Research and Development of the United States Department of Veterans Affairs (VA), has provided financial support for Cooperative Study #569 and the development and maintenance of the Vietnam Era Twin (VET) Registry. Dr. Viola Vaccarino was supported in part by a National Institutes of Health award (K24 HL077506). NR 42 TC 2 Z9 2 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 EI 1573-6598 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2016 VL 29 IS 1 BP 5 EP 16 DI 10.1002/jts.22075 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DE9NW UT WOS:000370965700001 PM 26764215 ER PT J AU Ohki, T Angle, JF Yokoi, H Jaff, MR Popma, J Piegari, G Kanaoka, Y AF Ohki, Takao Angle, John F. Yokoi, Hiroyoshi Jaff, Michael R. Popma, Jeffrey Piegari, Guy Kanaoka, Yuji CA OSPREY Investigators TI One-year outcomes of the US and Japanese regulatory trial of the Misago stent for treatment of superficial femoral artery disease (OSPREY study) SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID EXPANDING NITINOL STENT; ATHEROSCLEROTIC LESIONS; CLINICAL-TRIALS; IMPLANTATION; ANGIOPLASTY; FRACTURES; PROLIFERATION; IMPACT AB Objective: The purpose of this study was to assess the safety and efficacy of the Misago stent (Terumo Corp, Tokyo, Japan) in occlusive and stenotic superficial femoral artery (SFA) disease. Methods: The safety and efficacy of the Misago SFA stent were evaluated prospectively in this initial collaboration trial between Japan and the United States. Because this trial enrolled patients mainly from Japan and the United States and because there is a question as to whether a race difference exists in SFA stent performance, the race difference on outcome was also analyzed. In addition, results were compared with a prior SFA stent trial. Results: The Misago stent was implanted in 261 subjects with TransAtlantic Inter-Society Consensus (TASC) type A and type B SFA lesions (201 subjects in the United States, 50 in Japan, 9 in Taiwan, 1 in South Korea). The mean age of the patients was 69.3 +/- 10.0 years, and the mean lesion length was 83.8 +/- 41.3 mm. The overall 12-month primary patency rate and clinically driven target lesion revascularization were 82.9% and 13.0%, respectively. Regional differences within the Occlusive/Stenotic Peripheral Artery Revascularization Study (OSPREY) an pd outcomes between U.S. and Asian patients were similar, including primaryatency (82.9% vs 83.0%; P = .889), clinically driven target lesion revascularization (13.4% vs 11.7%; P = .829), stent fracture rate (1.3% vs 0.0%; P = 1.000), and stent thrombosis rate (0.5% vs 0.0%; P = 1.000). Conclusions: OSPREY 12-month data showed satisfactory outcome of the Misago stent for the treatment of TASC type A and type B SFA lesions and appears to be comparable to recent stent trials. In addition, the lack of difference in outcome among races supports the value of international trials. C1 [Ohki, Takao; Kanaoka, Yuji] Jikei Univ, Sch Med, Div Vasc Surg, Dept Surg, Tokyo, Japan. [Angle, John F.] Univ Virginia, Hosp Med Ctr, Div Intervent Radiol Angiog & Special Procedures, Dept Radiol & Med Imaging, Charlottesville, VA USA. [Yokoi, Hiroyoshi] Fukuoka Sanno Hosp, Cardiovasc Ctr, Fukuoka, Japan. [Jaff, Michael R.] Massachusetts Gen Hosp, Paul & Phyllis Fireman Vasc Ctr, Boston, MA 02114 USA. [Popma, Jeffrey] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Piegari, Guy] Berks Cardiologists Ltd, Wyomissing, PA USA. RP Ohki, T (reprint author), Jikei Univ Hosp, Dept Surg, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 1058461, Japan. EM takohki@msn.com NR 20 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2016 VL 63 IS 2 BP 370 EP + DI 10.1016/j.jvs.2015.08.093 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DE6XV UT WOS:000370779100013 PM 26483003 ER PT J AU Davies, JC Cunningham, S Harris, WT Lapey, A Regelmann, WE Sawicki, GS Southern, KW Robertson, S Green, Y Cooke, J Rosenfeld, M AF Davies, Jane C. Cunningham, Steve Harris, William T. Lapey, Allen Regelmann, Warren E. Sawicki, Gregory S. Southern, Kevin W. Robertson, Sarah Green, Yulia Cooke, Jon Rosenfeld, Margaret CA KIWI Study Grp TI Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study SO LANCET RESPIRATORY MEDICINE LA English DT Article ID PRESCHOOL-CHILDREN; G551D MUTATION; LUNG-FUNCTION; INFANTS; POTENTIATOR; EFFICACY; WASHOUT; DISEASE AB Background Ivacaftor has been shown to be a safe, effective treatment for cystic fibrosis in patients aged 6 years or older with a CFTR gating mutation. We aimed to assess the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in children aged 2-5 years. Methods In the two-part KIWI study, we enrolled children aged 2-5 years weighing 8 kg or more with a confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele from 15 hospitals in the USA, UK, and Canada. Participants received oral ivacaftor 50 mg (if bodyweight <14 kg) or 75 mg (if bodyweight >= 1.4 kg) every 12 h for 4 days in part A (to establish the short-term safety of doses for subsequent assessment in part B), and then for 24 weeks in part B (to assess safety and longer-term pharmacodynamics). Children could participate in both or just one part of the study. Primary outcomes were pharmacokinetics and safety, analysed in all patients who received at least one dose of ivacaftor. Secondary outcomes were absolute change from baseline in sweat chloride concentrations and bodyweight, body-mass index (BMI), and height Z scores, and pharmacokinetic parameter estimation of ivacaftor. This study is registered with ClinicalTrials.gov, number NCT01705145. Findings Between Jan 8, 2013, and March 1, 2013, nine patients were enrolled onto part A of the study, all of whom completed the 4 day treatment period, and eight of whom took part in part B. Between June 28, 2013, and Sept 26, 2013, 34 patients were enrolled in part B, 33 of whom completed the 24 week treatment period. All patients received at least one dose of ivacaftor. Results of ivacaftor pharmacokinetics suggested that exposure was similar to that reported in adults (median C-min, were 536 ng/mL for the 50 mg dose; 580 ng/mL for the 75 mg dose; median ivacaftor AUC values were 9840 ng x h/mL and 10 200 ng x h/mL, respectively). Common adverse events in part B included cough (in 19 [56%] of 34 patients) and vomiting (in ten [29%]). Five (15%) patients had liver function test (LFT) results that were more than eight times higher than the upper limit of normal, four of whom had study drug interrupted, and one of whom had study drug discontinued. Six (18%) of 34 patients had seven serious adverse events; a raised concentration of transaminases was the only serious adverse event regarded as related to ivacaftor and the only adverse event that resulted in study treatment discontinuation. At week 24, in patients for whom we had data, sweat chloride had changed from baseline by a mean of -46.9 mmol/L (SD 26.2, p<0.0001), weight Z score by 0.2 (0.3; p<0.0001), BMI Z score by 0.4 (0.4, p<0.0001), and height Z score by -0.01 (0.3; p=0.84). Interpretation Ivacaftor at doses of 50 mg and 75 mg seems to be safe in children aged 2-5 years with cystic fibrosis with a gating mutation followed up for 24 weeks, although the frequency of elevated LFTs suggests that monitoring should be frequent in young children, particularly those with a history of elevated LFTs. Results of an ongoing extension study assessing durability of these effects and longer-term safety are warranted. C1 [Davies, Jane C.] Univ London Imperial Coll Sci Technol & Med, London, England. [Davies, Jane C.] Royal Brompton & Harefield NHS Fdn Trust, London, England. [Cunningham, Steve] Royal Hosp Sick Children, NHS Lothian, Edinburgh EH9 1LF, Midlothian, Scotland. [Harris, William T.] Univ Alabama Birmingham, Birmingham, AL USA. [Lapey, Allen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Regelmann, Warren E.] Univ Minnesota, Minneapolis, MN USA. [Sawicki, Gregory S.] Harvard Univ, Sch Med, Boston, MA USA. [Southern, Kevin W.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Robertson, Sarah] Vertex Pharmaceut Inc, Boston, MA USA. [Green, Yulia; Cooke, Jon] Vertex Pharmaceut Inc, Milton Pk, England. [Rosenfeld, Margaret] Seattle Childrens Hosp, Seattle, WA USA. RP Davies, JC (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Emmanuel Kaye Bldg,Manresa Rd, London SW3 6LR, England. EM j.c.davies@imperial.ac.uk OI Cunningham, Steve/0000-0001-7342-251X FU Vertex Pharmaceuticals Incorporated; UK National Institute for Health Research (NIHR) Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust; Imperial College London FX We thank Clare Saunders, for independent analysis of spirometry results. Medical writing and editorial support were provided by Dhrupad Patel and Bina J Patel. Dhrupad Patel is an employee of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company. Bina J Patel is an employee of Peloton Advantage, Parsippany, NJ, USA, which received funding from Vertex Pharmaceuticals Incorporated. This project was supported by the UK National Institute for Health Research (NIHR) Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, NIHR, or the Department of Health. NR 27 TC 21 Z9 21 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-2600 J9 LANCET RESP MED JI Lancet Resp. Med. PD FEB PY 2016 VL 4 IS 2 BP 107 EP 115 DI 10.1016/S2213-2600(15)00545-7 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DD7OG UT WOS:000370113400018 PM 26803277 ER PT J AU Rodriguez-Diaz, E Baffy, G Singh, SK AF Rodriguez-Diaz, Eladio Baffy, Gyoergy Singh, Satish K. TI Probe-based confocal laser endomicroscopy quantitative morphometric markers associated with portal hypertension in duodenal mucosa SO LIVER INTERNATIONAL LA English DT Article DE confocal laser endomicroscopy; endoscopy; portal hypertension ID INFLAMMATORY-BOWEL-DISEASE; IN-VIVO; BARRETTS-ESOPHAGUS; CONTROLLED-TRIAL; LIVER-CIRRHOSIS; EPITHELIAL-GAPS; GASTROPATHY; MULTICENTER; DIAGNOSIS; VARICES AB Background & Aims: Early detection of portal hypertension (PH) may help to prevent the morbidity of late-stage cirrhosis by stratifying disease severity and enabling disease-modifying interventions in potentially reversible conditions like non-alcoholic fatty liver disease and alcoholic hepatitis. This study seeks to correlate morphometric features by confocal endomicroscopy with established surrogate clinical markers of PH. Methods: Patients with and without PH scheduled for upper endoscopy at VA Boston participated in this IRB-approved study. Real-time probe-based confocal endomicroscopy (pCLE) was performed in the duodenum. Vascular and epithelial morphometry was performed off-line, in a blinded manner, using image-processing software. Results: Morphometric analysis of pCLE images from 16 patients with PH and 15 control patients was performed. Statistically significant differences were observed among control and PH patients for average vessel diameter (AVD: 11.7 mu m vs. 17.1 mu m), average vessel branching (AVB: 0.11 vs. 0.31 bifurcations per image frame), and average columnar cell height (ACCH: 40.0 mu m vs. 52.0 mu m). Spearman correlations comparing AVD, AVB and ACCH to portal gastropathy scores (0.86, 0.44 and 0.70) and to grade of oesophageal varices (0.88, 0.41 and 0.66) were statistically significant. Similarly, Pearson correlations of AVD and ACCH to spleen size (0.72 and 0.57), platelet count (-0.69 and -0.40) and the platelet count/spleen size ratio (-0.69 and -0.41) were also found to be statistically significant. Conclusions: Duodenal pCLE reveals microvascular dilatation and altered epithelial cell volume/morphology in PH. These morphometric pCLE markers correlate with surrogate markers of PH. Additional studies will define the correlation between microscopic vascular patterns, epithelial cell volume and the hepatic venous pressure gradient. C1 [Rodriguez-Diaz, Eladio; Singh, Satish K.] Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Suite 504,650 Albany St, Boston, MA 02118 USA. [Rodriguez-Diaz, Eladio; Baffy, Gyoergy; Singh, Satish K.] VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA USA. [Baffy, Gyoergy; Singh, Satish K.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Singh, Satish K.] Boston Univ, Dept Biomed Engn, Coll Engn, Boston, MA 02215 USA. RP Singh, SK (reprint author), Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Suite 504,650 Albany St, Boston, MA 02118 USA. EM singhsk@bu.edu FU VA CSRD MERIT Awards [1I01CX000347, 1I0ICX001146]; Wallace H. Coulter Foundation; Center for the Integration of Medicine & Innovative Technology FX The study was funded in part by VA CSR&D MERIT Awards: 1I01CX000347 and 1I0ICX001146; Wallace H. Coulter Foundation; Center for the Integration of Medicine & Innovative Technology. NR 42 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1478-3223 EI 1478-3231 J9 LIVER INT JI Liver Int. PD FEB PY 2016 VL 36 IS 2 BP 223 EP 231 DI 10.1111/liv.12906 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DE2HY UT WOS:000370449600010 PM 26133980 ER PT J AU Polimeni, JR Bhat, H Witzel, T Benner, T Feiweier, T Inati, SJ Renvall, V Heberlein, K Wald, LL AF Polimeni, Jonathan R. Bhat, Himanshu Witzel, Thomas Benner, Thomas Feiweier, Thorsten Inati, Souheil J. Renvall, Ville Heberlein, Keith Wald, Lawrence L. TI Reducing Sensitivity Losses Due to Respiration and Motion in Accelerated Echo Planar Imaging by Reordering the Autocalibration Data Acquisition SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE GRAPPA; high-resolution fMRI; high-field fMRI; parallel imaging; image reconstruction ID GEOMETRIC DISTORTION; HUMAN BRAIN; 3 T; RESONANCE; NMR; MRI; ROBUST; GRAPPA; COIL AB Purpose: To reduce the sensitivity of echo-planar imaging (EPI) auto-calibration signal (ACS) data to patient respiration and motion to improve the image quality and temporal signal-to-noise ratio (tSNR) of accelerated EPI time-series data. Methods: ACS data for accelerated EPI are generally acquired using segmented, multishot EPI to distortion-match the ACS and time-series data. The ACS data are, therefore, typically collected over multiple TR periods, leading to increased vulnerability to motion and dynamic B-0 changes. The fast low-angle excitation echo-planar technique (FLEET) is adopted to reorder the ACS segments so that segments within any given slice are acquired consecutively in time, thereby acquiring ACS data for each slice as rapidly as possible. Results: Subject breathhold and motion phantom experiments demonstrate that artifacts in the ACS data reduce tSNR and produce tSNR discontinuities across slices in the accelerated EPI time-series data. Accelerated EPI data reconstructed using FLEET-ACS exhibit improved tSNR and increased tSNR continuity across slices. Additionally, image quality is improved dramatically when bulk motion occurs during the ACS acquisition. Conclusion: FLEET-ACS provides reduced respiration and motion sensitivity in accelerated EPI, which yields higher tSNR and image quality. Benefits are demonstrated in both conventional-resolution 3T and high-resolution 7T EPI timeseries data. (C) 2015 Wiley Periodicals, Inc. C1 [Polimeni, Jonathan R.; Witzel, Thomas; Renvall, Ville; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bhat, Himanshu; Heberlein, Keith] Siemens Med Solut USA Inc, Charlestown, MA USA. [Benner, Thomas; Feiweier, Thorsten] Siemens AG, Healthcare Sect, Erlangen, Bavaria, Germany. [Inati, Souheil J.] NIMH, Bethesda, MD 20892 USA. [Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Polimeni, JR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM jonp@nmr.mgh.harvard.edu RI Renvall, Ville/M-4165-2013; Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Renvall, Ville/0000-0002-4070-7030; Polimeni, Jonathan/0000-0002-1348-1179; FU NIH National Institute for Biomedical Imaging and Bioengineering [P41-EB015896, K01-EB011498]; NIH National Center for Research Resources [P41-RR14075, S10-RR023401, S10-RR019307, S10-RR023043, S10-RR019371, S10-RR020948]; NIH Blueprint for Neuroscience Research [U01-MH093765] FX Grant sponsor: NIH National Institute for Biomedical Imaging and Bioengineering; Grant numbers: P41-EB015896, K01-EB011498; Grant sponsor: NIH National Center for Research Resources; Grant number: P41-RR14075, S10-RR023401, S10-RR019307, S10-RR023043, S10-RR019371, S10-RR020948; Grant sponsor: the NIH Blueprint for Neuroscience Research; Grant number: U01-MH093765. NR 40 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD FEB PY 2016 VL 75 IS 2 BP 665 EP 679 DI 10.1002/mrm.25628 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE4KG UT WOS:000370597000020 PM 25809559 ER PT J AU Chebib, I Chang, CY Ken, DA Deshpande, V Nielsen, GP AF Chebib, Ivan Chang, Connie Y. Ken, Darcy A. Deshpande, Vikram Nielsen, G. Peter TI Histopathology of So-Called Synovial Cysts of the Lumbar Spine SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Miami, Miller Sch Med, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 45 BP 15A EP 15A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500046 ER PT J AU Aplin, AC Kohler, T Nicosia, R AF Aplin, Alfred C. Kohler, Ted Nicosia, Roberto TI Human Plaque-Aortic Ring Co-Culture: A Novel Assay for the Study of Atherosclerosis-Induced Angiogenesis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 316 BP 81A EP 81A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500317 ER PT J AU Fishbein, GA Onozato, ML Luk, A Givertz, MM Padera, RF Lafrate, AJ Mitchell, RN AF Fishbein, Gregor A. Onozato, Maristela L. Luk, Adriana Givertz, Michael M. Padera, Robert F., Jr. Lafrate, Anthony J. Mitchell, Richard N. TI Endothelial Cell Chimerism in Human Cardiac Allografts SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 320 BP 82A EP 82A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500321 ER PT J AU Mirkovic, J Zhao, LN Faquin, WC Jo, VY Krane, JF AF Mirkovic, Jelena Zhao, Liena Faquin, William C. Jo, Vickie Y. Krane, Jeffrey F. TI Risk-Stratified Triage of Salivary Gland Fine-Needle Aspiration Specimens SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 428 BP 109A EP 110A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500429 ER PT J AU Nagymanyoki, Z Karlon, W Faquin, WC Krane, JF Lindeman, N Hall, D Sweeney, BJ Ljung, BM Balassanian, R van Zante, A AF Nagymanyoki, Zoltan Karlon, William Faquin, William C. Krane, Jeffrey F. Lindeman, Neal Hall, Dimity Sweeney, Brenda J. Ljung, Britt-Marie Balassanian, Ronald van Zante, Annemieke TI Comparison of Molecular Platforms for Detection of HPV in FNA Biopsies of the Head and Neck SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. West Pacific Med Lab, Santa Fe Springs, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 431 BP 110A EP 110A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500432 ER PT J AU Pusztaszeri, M Sadow, PM Krane, JF Daniels, G Faquin, WC AF Pusztaszeri, Marc Sadow, Peter M. Krane, Jeffrey F. Daniels, Gilbert Faquin, William C. TI Fine-Needle Aspiration of Thyroid Malignancies Arising in Graves' Disease: A Diagnostic Challenge? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Hosp Geneva, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 441 BP 113A EP 113A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500442 ER PT J AU Rosenbaum, MW Jones, M Dudley, J Le, L Iafrate, AJ Pitman, M AF Rosenbaum, Matthew W. Jones, Martin Dudley, Jonathan Le, Long Iafrate, A. John Pitman, Martha TI Next Generation Sequencing Adds Value to the Pre-Operative Diagnosis of Pancreatic Cysts SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 442 BP 113A EP 113A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500443 ER PT J AU Strickland, KC Vivero, M Jo, VY Lowe, A Hollowell, M Qian, XH Wieczorek, T French, CA Teot, LA Eszlinger, M Paschke, R Sadow, PM Cibas, E Barletta, JA Krane, JF AF Strickland, Kyle C. Vivero, Marina Jo, Vickie Y. Lowe, Alarice Hollowell, Monica Qian, Xiaohua Wieczorek, Tad French, Christopher A. Teot, Lisa A. Eszlinger, Markus Paschke, Ralf Sadow, Peter M. Cibas, Edmund Barletta, Justine A. Krane, Jeffrey F. TI The Cytologic Diagnosis of Non-Invasive Follicular Variant of Papillary Thyroid Carcinoma: A Prospective Analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Leipzig, D-04109 Leipzig, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 458 BP 117A EP 118A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500459 ER PT J AU Wang, H Hoda, RS Faquin, WC Rossi, E Hotchandani, N Sun, TL Pusztaszeri, M Bizzarro, T Bongiovanni, M Patel, V Jhala, N Gong, Y AF Wang, He Hoda, Roza S. Faquin, William C. Rossi, Esther Hotchandani, Nihar Sun, Tianlin Pusztaszeri, Marc Bizzarro, Tommaso Bongiovanni, Massimo Patel, Viren Jhala, Nirag Gong, Yun TI Secondary Malignancies in Salivary Glands: A Multi-Institutional FNA Cohort from Trans-Atlantic Academic Institutions SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cattolica Sacro Cuore, Rome, Italy. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Hosp Geneva, Geneva, Switzerland. Univ Lausanne, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 468 BP 120A EP 120A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302500469 ER PT J AU Moy, A Murali, M Kroshinsky, D Horn, T Nazarian, R AF Moy, Andrea Murali, Mandakolathur Kroshinsky, Daniela Horn, Thomas Nazarian, Rosalynn TI Keratin 17 Expression and Immune Phenotype of Anti-TNF-alpha Refractory Psoriasis and Anti-TNF-alpha Related Psoriasiform Dermatitis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Moy, Andrea; Murali, Mandakolathur; Kroshinsky, Daniela; Horn, Thomas; Nazarian, Rosalynn] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 519 BP 133A EP 133A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501003 ER PT J AU Glomski, K Sadow, PM AF Glomski, Krzysztof Sadow, Peter M. TI Metastatic Follicular Thyroid Carcinoma: Retrospective Institutional Experience and Insight into Primary Follicular Thyroid Neoplasia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 579 BP 148A EP 148A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501063 ER PT J AU Paulson, V Shivdasani, P Howitt, BE Ducar, M Angell, T Alexander, EK Cibas, E Krane, JF Lindeman, N Barletta, JA AF Paulson, Vera Shivdasani, Priyanka Howitt, Brooke E. Ducar, Matthew Angell, Trevor Alexander, Erik K. Cibas, Edmund Krane, Jeffrey F. Lindeman, Neal Barletta, Justine A. TI Non-Invasive Follicular Variant of Papillary Thyroid Carcinoma Accounts for over Half of Carcinomas Harboring RAS Mutations SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 599 BP 153A EP 153A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501083 ER PT J AU Agoston, A Deshpande, V Odze, R AF Agoston, Agoston Deshpande, Vikram Odze, Robert TI HPV is Not Involved in the Pathogenesis of Esophageal Squamous Cell and Adenocarcinomas; Analysis Based on a Highly Sensitive and Highly Specific RNA In-Situ Hybridization Technique SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 626 BP 160A EP 160A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501110 ER PT J AU Ahn, S Lee, SJ Kim, YG Hwang, CS Kim, A Shin, N Choi, KU Lee, CH Huh, GY Lauwers, G Park, DY AF Ahn, Sangjeong Lee, So Jeong Kim, Young Geum Hwang, Chung Su Kim, Ahrong Shin, Nari Choi, Kyung Un Lee, Chang Hun Huh, Gi Young Lauwers, Gregory Park, Do Youn TI Molecular Classification in Gastric Cancer Using Immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Pusan Natl Univ, Pusan Natl Univ Hosp, Sch Med, Busan, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 2 U2 2 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 FEB PY 2016 VL 29 SU 2 MA 627 BP 160A EP 160A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501111 ER PT J AU Alpert, L Setia, N Khalili, H Lauwers, GY AF Alpert, Lindsay Setia, Namrata Khalili, Hamed Lauwers, Gregory Y. TI Lymphocytic Colitis: AreThere Pathologic Predictors of Response to Therapy? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 633 BP 161A EP 161A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501117 ER PT J AU Deshpande, V Mahadevan, KK Lauwers, GY Mattia, A Zukerberg, L Odze, R AF Deshpande, Vikram Mahadevan, Krishnan K. Lauwers, Gregory Y. Mattia, Antony Zukerberg, Lawrence Odze, Robert TI LGR5 Expression in Barrett's Esophagus and Associated Neoplasia: Support for Its Role as a Cancer Stem Cell and Diagnostic Marker SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Deshpande, Vikram; Mahadevan, Krishnan K.; Lauwers, Gregory Y.; Mattia, Antony; Zukerberg, Lawrence; Odze, Robert] Brigham & Womens Hosp, Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 667 BP 169A EP 169A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501151 ER PT J AU England, J Swager, AF Schlachter, S Sundell, B Bergman, JJGHM Lauwers, GY Odze, R AF England, Jonathan Swager, Anne-Fre Schlachter, Simon Sundell, Brian Bergman, Jacques J. G. H. M. Lauwers, Gregory Y. Odze, Robert TI Role of Mucosal Glands in the Progression of Neoplasia in Barrett's Esophagus SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NinePoint Med, Boston, MA USA. Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 0 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 FEB PY 2016 VL 29 SU 2 MA 672 BP 170A EP 170A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501156 ER PT J AU Samore, W Mahadevan, KK Deshpande, V AF Samore, Wesley Mahadevan, Krishnan K. Deshpande, Vikram TI Line-1 Methylation Status Predicts Aggressive Behavior in Pancreatic Endocrine Neoplasms SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Samore, Wesley; Mahadevan, Krishnan K.; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 782 BP 197A EP 197A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501266 ER PT J AU Setia, N Alpert, L Lauwers, GY AF Setia, Namrata Alpert, Lindsay Lauwers, Gregory Y. TI WHO Morphologic Classification of Gastric Cancer Correlates with Protein Expression Based Classification SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 792 BP 199A EP 200A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501276 ER PT J AU Shih, AR Bal, M Zukerberg, L Brown, I Lauwers, GY Liu, XL Kelly, P Oliva, E Ahn, S Kim, K Deshpande, V AF Shih, Angela R. Bal, Munita Zukerberg, Lawrence Brown, Ian Lauwers, Gregory Y. Liu, Xiuli Kelly, Paul Oliva, Esther Ahn, Soomin Kim, Kyoung Deshpande, Vikram TI Hepatoid Carcinomas of the Gastrointestinal Tract: A Reappraisal of Morphological and Immunohistochemical Features SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tata Mem Hosp, Bombay 400012, Maharashtra, India. Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. Cleveland Clin, Cleveland, OH 44106 USA. Queens Univ Belfast, Royal Victoria Hosp, Belfast, Antrim, North Ireland. Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 796 BP 200A EP 201A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501280 ER PT J AU Shih, AR Deshpande, V Fern, JA Zukerberg, L AF Shih, Angela R. Deshpande, Vikram Fern, Judith A. Zukerberg, Lawrence TI Clinicopathologic Characteristics of Systemic Mastocytosis in the Intestine SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Shih, Angela R.; Deshpande, Vikram; Fern, Judith A.; Zukerberg, Lawrence] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 797 BP 201A EP 201A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501281 ER PT J AU Williams, E Zukerberg, L Arora, K Ting, DT Deshpande, V AF Williams, Erik Zukerberg, Lawrence Arora, Kshitij Ting, David T. Deshpande, Vikram TI Epithelial to Mesenchymal Transition Predicts Distant Metastasis in MMR-Intact Colonic Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Williams, Erik; Zukerberg, Lawrence; Arora, Kshitij; Ting, David T.; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 821 BP 207A EP 207A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501305 ER PT J AU Yilmaz, O Agrawal, T Kantekure, K Suarez, Y Yilmaz, O Deshpande, V AF Yilmaz, Osman Agrawal, Tanupriya Kantekure, Kanchan Suarez, Yvelisse Yilmaz, Omer Deshpande, Vikrain TI WNT Signaling Markers, LGR5 and AXIN2, Show Unique Patterns of Expression in Colonic Polyps SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Med Ctr, Boston, MA USA. MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 831 BP 209A EP 210A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501315 ER PT J AU Cyrta, J Beltran, H Prandi, D Mosquera, JM Benelli, M Tomlin, SA Elemento, O Sboner, A Garraway, L Rubin, M Demichelis, F AF Cyrta, Joanna Beltran, Himisha Prandi, Davide Mosquera, Juan Miguel Benelli, Matteo Tomlin, Scott A. Elemento, Olivier Sboner, Andrea Garraway, Levi Rubin, Mark Demichelis, Francesca TI Integrated Molecular Classifier Determines Transdifferentiation to Neuroendocrine Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Cornell Univ, Weill Cornell Med, New York, NY 10021 USA. Univ Trento, Trento, Italy. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 889 BP 224A EP 224A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501373 ER PT J AU David, SN Arnold, S Goyal, R Goldstein, J Gellert, LL Clark, PE Hameed, O Giannico, GA AF David, Stephanie N. Arnold, Shanna Goyal, Rajen Goldstein, Jeffery Gellert, Lan L. Clark, Peter E. Hameed, Omar Giannico, Giovanna A. TI MAGI-2 is Associated with Biochemical Recurrence in Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. US Dept Vet Affairs, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 892 BP 224A EP 225A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302501376 ER PT J AU Udager, A Chinnaiyan, AM Petimar, J Cao, XH Feng, FY Loda, M Ahearn, T Kantoff, PW Mucci, LA Mehra, R AF Udager, Aaron Chinnaiyan, Arul M. Petimar, Joshua Cao, Xuhong Feng, Felix Y. Loda, Massimo Ahearn, Thomas Kantoff, Philip W. Mucci, Lorelei A. Mehra, Rohit TI Overexpression of the Long Non-Coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Michigan Hlth Syst, Ann Arbor, MI USA. Michigan Ctr Translat Pathol, Ann Arbor, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 29 SU 2 MA 1065 BP 268A EP 268A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502075 ER PT J AU Ye, HH Sowalsky, AG Schaefer, R Yuan, X Chen, SY Gerrin, SJ Montaser, L Ma, F Voznesensky, O Cai, CM Lis, R Zhang, ZW Loda, M Taplin, ME Balk, S AF Ye, Huihui Sowalsky, Adam G. Schaefer, Rachel Yuan, Xin Chen, Shao-yong Gerrin, Sean J. Montaser, Laleh Ma, Fen Voznesensky, Olga Cai, Changmeng Lis, Rosina Zhang, Zhenwei Loda, Massimo Taplin, Maly-Ellen Balk, Steven TI Diversity of Resistance Mechanisms in Prostate Cancer after Neoadjuvant Intense Androgen Deprivation Therapy SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1078 BP 271A EP 271A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502088 ER PT J AU Basnet, KM Bentley-Lewis, R Wexler, D Kilic, F Roberts, D AF Basnet, Kristen M. Bentley-Lewis, Rhonda Wexler, Deborah Kilic, Fusun Roberts, Drucilla TI Intervillous Thrombi Are Increased in Placentas from Pregnancies Complicated by Diabetes SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1096 BP 276A EP 276A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502105 ER PT J AU Goh, R Dal Cin, P Chiang, S Young, RH Oliva, E AF Goh, Ronald Dal Cin, Paola Chiang, Sarah Young, Robert H. Oliva, Esther TI Myxoid Smooth Muscle Tumors of the Uterus: Clinicopathologic Study of 40 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Singapore Gen Hosp, Singapore, Singapore. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1133 BP 285A EP 285A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502142 ER PT J AU Harrison, B Chen, A Toledo, G Arora, K Deshpande, V Oliva, E AF Harrison, Beth Chen, Athena Toledo, Gemma Arora, Kshitij Deshpande, Vikram Oliva, Esther TI The MELF Pattern of Myometrial Invasion in Endometrial Endometrioid Carcinoma Displays a Mesenchymal Gene Expression Signature: A Case Series SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Harrison, Beth; Chen, Athena; Toledo, Gemma; Arora, Kshitij; Deshpande, Vikram; Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1135 BP 285A EP 285A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502144 ER PT J AU Howitt, BE Sun, H Roemer, MGM Kelly, A Chapuy, B Aviki, EM Pak, C Gjini, E Yang, YL Lee, L Viswanathan, A Horowitz, N Neuberg, D Crum, CP Lindeman, N Kuo, F Ligon, AH Freeman, GJ Hodi, FS Shipp, MA Rodig, S AF Howitt, Brooke E. Sun, Heather Roemer, Margaretha G. M. Kelly, Alyssa Chapuy, Bjoern Aviki, Emeline M. Pak, Christine Gjini, Evisa Yang, Youling Lee, Larissa Viswanathan, Akila Horowitz, Neil Neuberg, Donna Crum, Christopher P. Lindeman, Neal Kuo, Frank Ligon, Azra H. Freeman, Gordon J. Hodi, F. Stephen Shipp, Margaret A. Rodig, Scott TI Recurrent Gains of CD274 and PDCD1LG2 in Squamous Cell Carcinomas of Cervix and Vulva SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1144 BP 287A EP 288A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502153 ER PT J AU Ordulu, Z McDonald, AG De Nictolis, M Garcia-Fernandez, E Hardisson, D Prat, J Oliva, E AF Ordulu, Zehra McDonald, Anna G. De Nictolis, Michele Garcia-Fernandez, Eugenia Hardisson, David Prat, Jaime Oliva, Esther TI Intravenous Leiomyomatosis (IVL), from Molecular Genetics to Clinical Biomarkers: A Study of 26 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. San Salvatore Hosp, Pesaro, Italy. Hosp Univ La Paz, Madrid, Spain. Wake Forest Baptist Med Ctr, Winston Salem, NC USA. Hosp Sta Creu & St Pau, Barcelona, Spain. RI Hardisson, David/E-2832-2010 OI Hardisson, David/0000-0002-2183-3699 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1195 BP 300A EP 301A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502204 ER PT J AU Parkash, V Malpica, A Matias-Guiu, X Oliva, E McCluggage, WG AF Parkash, Vinita Malpica, Anais Matias-Guiu, Xavier Oliva, Esther McCluggage, W. Glenn TI Current Practices in the Processing, Diagnosis and Reporting of Endometrial Carcinoma. Results of a Web Based Survey by the International Society of Gynecological Pathologists (ISGyP) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Yale Univ, Sch Med, Bridgeport Hosp, New Haven, CT USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Lleida, Hosp Univ Arnau de Vilanova, IRBLleida, Lleida, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Belfast Hlth & Social Care Trust, Belfast, Antrim, Ireland. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1199 BP 301A EP 302A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502208 ER PT J AU Pesci, A Shih, AR Oliva, E AF Pesci, Anna Shih, Angela R. Oliva, Esther TI Endocervical Adenocarcinoma (EEC): A Retrospective Study of 75 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Osped Sacro Cuore Don Calabria, Verona, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1201 BP 302A EP 302A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502210 ER PT J AU Pires-Luis, AS Bartosch, C Meireles, C Pinto, C Lopes, JM Shannon, KM Teixeira, MR Oliva, E AF Pires-Luis, Ana S. Bartosch, Carla Meireles, Catarina Pinto, Carla Lopes, Jose M. Shannon, Kristen M. Teixeira, Manuel R. Oliva, Esther TI Hysterectomy Specimens of Patients with Lynch Syndrome: Clinicopathologic Study of 70 Cases SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 IPO Porto, Oporto, Portugal. CHSJ, Oporto, Portugal. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Teixeira, Manuel/E-4885-2011 OI Teixeira, Manuel/0000-0002-4896-5982 NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1203 BP 302A EP 303A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502212 ER PT J AU Shih, AR Liu, XL Silva, A Pesci, A Soslow, R Deshpande, V Oliva, E AF Shih, Angela R. Liu, Xiuli Silva, Annacarolina Pesci, Anna Soslow, Robert Deshpande, Vikram Oliva, Esther TI Refined Characterization of Hepatoid Differentiation in Gynecologic Tract Neoplasms SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1227 BP 309A EP 309A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502236 ER PT J AU Silva, A Bennett, JA Ali-Fehmi, R Bandyopadhyay, S Oliva, E AF Silva, Annacarolina Bennett, Jennifer A. Ali-Fehmi, Rouba Bandyopadhyay, Sudeshna Oliva, Esther TI Ovarian Endometrioid Adenocarcinomas: Morphology, Associations and Outcomes in 79 Patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Lahey Hosp & Med Ctr, Burlington, MA USA. Wayne State Univ, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1228 BP 309A EP 309A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502237 ER PT J AU Pusztaszeri, M Bordignon, P Mckee, T Faquin, WC AF Pusztaszeri, Marc Bordignon, Patrizia McKee, Thomas Faquin, William C. TI MYC and MYB Are Coexpressed in Adenoid Cystic Carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Hosp Geneva, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1302 BP 327A EP 328A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502310 ER PT J AU Sajed, D Wu, CL Nose, V Deshpande, V AF Sajed, Dipti Wu, Chin-Lee Nose, Vania Deshpande, Vikram TI Expression of an Androgen Receptor Splice Variant in Salivary Duct Carcinoma: An Instrument of Resistance? SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Sajed, Dipti; Wu, Chin-Lee; Nose, Vania; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1306 BP 328A EP 329A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502314 ER PT J AU Ahn, J Rosado, FG Sohani, AR Vos, J AF Ahn, Janice Rosado, Flavia G. Sohani, Aliyah R. Vos, Jeffrey TI Plasmablastic Lymphoma: Characterization of Tumor Microenvironment by CD163 and PD1 Immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 W Virginia Univ, Morgantown, WV 26506 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1325 BP 333A EP 333A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502333 ER PT J AU Bledsoe, J Wallace, ZS Stone, JH Deshpande, V Ferry, JA AF Bledsoe, Jacob Wallace, Zachary S. Stone, John H. Deshpande, Vikram Ferry, Judith A. TI Lymphoma in IgG4-Related Disease SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Bledsoe, Jacob; Wallace, Zachary S.; Stone, John H.; Deshpande, Vikram; Ferry, Judith A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1336 BP 336A EP 336A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502344 ER PT J AU Bledsoe, J Redd, R Zukerberg, L Abramson, J Sohani, AR AF Bledsoe, Jacob Redd, Robert Zukerberg, Lawrence Abramson, Jeremy Sohani, Aliyah R. TI PDL1 and MUM1 Expression Are Associated with Outcome in Primary Mediastinal Large B-cell Lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1337 BP 336A EP 337A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502345 ER PT J AU Griffin, GK Lovitch, SB Kelley, A Roemer, MGM Chapuy, B Pak, C Gjini, E Freeman, GJ Hodi, FS Ligon, AH Shipp, MA Rodig, S AF Griffin, Gabriel K. Lovitch, Scott B. Kelley, Alyssa Roemer, Margaretha G. M. Chapuy, Bjoern Pak, Christine Gjini, Evisa Freeman, Gordon J. Hodi, F. Stephen Ligon, Azra H. Shipp, Margaret A. Rodig, Scott TI Copy Number Gain of PD-L1 and PD-L2 in T-Cell/Histiocyte Rich Large B-Cell Lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1379 BP 348A EP 348A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502387 ER PT J AU Hillen, L Zukerberg, L Deshpande, V Cleven, AHG Fathi, AT Hausen, AZ Hasserjian, RP AF Hillen, Lisa Zukerberg, Lawrence Deshpande, Vikram Cleven, Arjen H. G. Fathi, Amir T. Hausen, Axel zur Hasserjian, Robert P. TI Bone Marrow Morphology Predicts Response to Hypomethylating Agents SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 MUMC, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1387 BP 350A EP 350A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502395 ER PT J AU Margolskee, E Oak, J Arber, DA Hasseijian, RP Orazi, A AF Margolskee, Elizabeth Oak, Jean Arber, Daniel A. Hasseijian, Robert P. Orazi, Attilio TI Myelodysplastic Syndrome, Unclassifiable (MDS-U) with 1% Blasts Is a Distinct Subgroup of MDS-U with a Poor Prognosis SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Weill Cornell Med Coll, New York, NY USA. Stanford Univ, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1427 BP 361A EP 361A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502434 ER PT J AU Minkovsky, A Morgan, EA Charest, K Schmidt, R Briggs, D Li, B Pozdnyakova, O AF Minkovsky, Alissa Morgan, Elizabeth A. Charest, Karry Schmidt, Ryan Briggs, Debra Li, Betty Pozdnyakova, Olga TI Peripheral Blood Minimal Residual Disease Analysis by Flow Cytometry Has High Concordance with Bone Marrow Analysis for Adult Patients with Acute Lymphoblastic Leukemia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1433 BP 362A EP 363A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502440 ER PT J AU Pozdnyakova, O Aster, JC Kuo, F Brown, R Baltay, M Hasserjian, RP AF Pozdnyakova, Olga Aster, Jon C. Kuo, Frank Brown, Ronald Baltay, Michele Hasserjian, Robert P. TI Primary Myelofibrosis Displays an Inflammation-Associated Gene Profile Distinct from Polycythemia Vera and Essential Thrombocythemia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1462 BP 370A EP 371A PG 2 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502469 ER PT J AU Rogers, HJ Hsi, ED Tang, GL Wang, S Bueso-Ramos, CE Lubin, D Morrissette, JJD Bagg, A Cherukuri, DP George, TI Peterson, L Liu, YC Mathew, S Orazi, A Hasserjian, RP AF Rogers, Heesun J. Hsi, Eric D. Tang, Guilin Wang, Sa Bueso-Ramos, Carlos E. Lubin, Daniel Morrissette, Jennifer J. D. Bagg, Adam Cherukuri, Durga P. George, Tracy I. Peterson, LoAnn Liu, Yen-Chun Mathew, Susan Orazi, Attilio Hasserjian, Robert P. TI Most Myeloid Neoplasms with Deletion of Chromosome 16q Are Distinct from Acute Myeloid Leukemia with inv(16)(p13.1q22) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Northwestern Univ, Chicago, IL 60611 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1473 BP 373A EP 373A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502480 ER PT J AU Weinberg, OK Hassedian, RP Li, B Pozdnyakova, O AF Weinberg, Olga K. Hassedian, Robert P. Li, Betty Pozdnyakova, Olga TI Assessment of Myeloid And Monocytic Dysplasia by Flow Cytometry in De Novo AML Helps Define an AML with Myelodysplasia-Related Changes Category SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Boston Childrens Hosp, Boston, MA USA. Massachussets Gen Hosp, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1512 BP 383A EP 383A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502518 ER PT J AU Wertheim, G Luskin, M Gimotty, PA Smith, C Loren, AW Figueroa, M Harrison, J Sun, ZX Tallman, MS Paietta, EM Litzow, MR Levine, R Melnick, AM Fernandez, HF Luger, SM Carroll, M Master, SR AF Wertheim, Gerald Luskin, Mortise Gimotty, Phyllis A. Smith, Catherine Loren, Alison W. Figueroa, Maria Harrison, Jenna Sun, Zhuoxin Tallman, Martin S. Paietta, Elisabeth M. Litzow, Mark R. Levine, Ross Melnick, Ari M. Fernandez, Hugo F. Luger, Selina M. Carroll, Martin Master, Stephen R. TI Integration of Multi-Locus DNA Methylation and Genetic Alterations Outperforms Genetic Assessment Alone for Outcome Prediction in Adult Patients with Acute Myeloid Leukemia SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA. Mayo Clin, Rochester, MN USA. Moffit Canc Ctr, Tampa, FL USA. Weill Comell Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1514 BP 384A EP 384A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502520 ER PT J AU Wong, W Hasserjian, RP Pozdnyakova, O AF Wong, Waihay Hasserjian, Robert P. Pozdnyakova, Olga TI Mutational Status Correlates with Distinct Histologic Features in Philadelphia Chromosome (Ph)-Negative Myeloproliferative Neoplasms (MPN) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1516 BP 384A EP 384A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302502522 ER PT J AU Tse, JY Deshpande, V Ferry, JA Zukerberg, L AF Tse, Julie Y. Deshpande, Vikram Ferry, Judith A. Zukerberg, Lawrence TI Histopathologic Features of T. Pallidum Infection Differ between the Rectum and Anus SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Tse, Julie Y.; Deshpande, Vikram; Ferry, Judith A.; Zukerberg, Lawrence] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1546 BP 391A EP 391A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503020 ER PT J AU Adam, B Smith, RN Kawai, T Cosimi, AB Colvin, RB Mengel, M AF Adam, Benjamin Smith, R. Neal Kawai, Tatsuo Cosimi, A. Benedict Colvin, Robert B. Mengel, Michael TI mRNA Diagnosis of Antibody-Mediated Rejection from Routine Paraffin Sections of Renal Transplant Biopsies in a Nonhuman Primate Model SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Alberta, Edmonton, AB, Canada. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1585 BP 402A EP 402A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503059 ER PT J AU Zhou, DL Pozdnyakova, O Dewar, R Hasserjian, RP Etman, A Hoffman, R Salama, ME AF Zhou, Delu Pozdnyakova, Olga Dewar, Rajan Hasserjian, Robert P. Etman, Ali Hoffman, Ronald Salama, Mohamed E. TI Central Histopathology Review of Essential Thrombocythemia and Polycythemia Vera Bone Marrow Biopsies via Digital Tools in a Clinical Trial on Pegylated Interferon Alfa-2a SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Utah, Salt Lake City, UT USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1584 BP 402A EP 402A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503058 ER PT J AU Faulkner-Jones, BE Rosen, D Rosen, S Harrington, K Law, C AF Faulkner-Jones, Beverly E. Rosen, Devin Rosen, Seymour Harrington, Kyle Law, Charles TI Maximizing Information from the Renal Biopsy: Computer-Generated Three-Dimensional Constructs SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 BIDMC, Boston, MA USA. Kitware Inc, Clifton Pk, NY USA. NR 0 TC 0 Z9 0 U1 8 U2 8 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 FEB PY 2016 VL 29 SU 2 MA 1599 BP 405A EP 405A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503072 ER PT J AU Agrawal, T Yilmaz, O Masia, R Goyal, L Zhu, A Deshpande, V AF Agrawal, Tanupriya Yilmaz, Osman Masia, Ricard Goyal, Lipika Zhu, Andrew Deshpande, Vikram TI Distinctive Morphologic Pattern and In Situ Hybridization for Albumin Distinguishes Intrahepatic Cholangiocarcinoma from Metastatic Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Tufts Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 8 U2 8 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 FEB PY 2016 VL 29 SU 2 MA 1630 BP 413A EP 413A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503103 ER PT J AU Miller, MB Mir, S Guleria, I Chi, JH Berkowitz, AL Ligon, KL AF Miller, Michael B. Mir, Saad Guleria, Indira Chi, John H. Berkowitz, Aaron L. Ligon, Keith L. TI Tumor-like Mass Arising as a Side Effect of Intrathecal Therapeutic Stem Cell Injections SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1720 BP 434A EP 434A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503193 ER PT J AU Lennerz, JK Wang, CI Doyle, L Huynh, TG Lindeman, N Srivastava, A Del-Castillo, CF Mino-Kenudson, M AF Lennerz, Jochen K. Wang, Charlotte I. Doyle, Leona Huynh, Tiffany G. Lindeman, Neal Srivastava, Amitabh del-Castillo, Carlos Fernandez Mino-Kenudson, Mari TI Mutational Profiling of Oncocytic Intraductal Papillary Mucinous Neoplasms (IPMN-o) SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1757 BP 443A EP 443A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503230 ER PT J AU Taylor, M Sajed, D Williams, E Ting, DT Deshpande, V AF Taylor, Martin Sajed, Dipti Williams, Erik Ting, David T. Deshpande, Vikram TI LINE-1 RNA and ORF1p Protein Are Broadly Co-Expressed in Colon Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1821 BP 460A EP 460A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503294 ER PT J AU Huynh, TG Gainor, JF Nardi, V Mino-Kenudson, M AF Huynh, Tiffany G. Gainor, Justin F. Nardi, Valentina Mino-Kenudson, Mari TI Lung Adenocarcinomas with KRAS Mutations Are Biologically Heterogeneous SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 [Huynh, Tiffany G.; Gainor, Justin F.; Nardi, Valentina; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1871 BP 472A EP 472A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503344 ER PT J AU Matsubara, O Jin, Y Yamauchi, S Yamanaka, K Ishikawa, Y Mark, EJ AF Matsubara, Osamu Jin, Yasuto Yamauchi, Shuta Yamanaka, Kazuteru Ishikawa, Yuichi Mark, Eugene J. TI Programmed Death 1 (PD-1) and PD-L1 Expression in Lung Adenocarcinoma, with Lower Expression in In Situ and Minimally Invasive Tumors and Higher Expression in Larger and Invasive Tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Japanese Fdn Canc Res, Inst Canc, Tokyo 170, Japan. Hiratsuka Kyosai Hosp, Hiratsuka, Kanagawa, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2016 VL 29 SU 2 MA 1888 BP 476A EP 476A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503361 ER PT J AU Pal, P Hammerman, P Kwiatkowski, DJ Johnson, BE Sholl, LM AF Pal, Prodipto Hammerman, Peter Kwiatkowski, David J. Johnson, Bruce E. Sholl, Lynette M. TI ROS1 Immunohistochemistry as a Screen for ROS1 Rearrangements in Lung Adenocarcinoma: Application in Clinical Practice SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1900 BP 478A EP 478A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503373 ER PT J AU Redig, AJ Lydon, C Janne, PA Sholl, LM AF Redig, Amanda J. Lydon, Christine Janne, Pasi A. Sholl, Lynette M. TI Evaluation of Genomic Complexity in Next-Generation Sequencing of T1 vs Stage IV Non-Small Cell Lung Cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1909 BP 480A EP 480A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503382 ER PT J AU Shih, AR Muzikansky, A Bozkurtlar, E Chung, JH Minami, Y Hariri, LP Moreira, A Uruga, H Wang, H Yoshizawa, A Mino-Kenudson, M AF Shih, Angela R. Muzikansky, Alona Bozkurtlar, Emine Chung, Jin-Haeng Minami, Yuko Hariri, Lida P. Moreira, Andre Uruga, Hironori Wang, He Yoshizawa, Akihiko Mino-Kenudson, Mari TI Reproducibility in Classification of Small Lung Adenocarcinomas: An International Interobserver Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Marmara Univ, Istanbul, Turkey. Seoul Natl Univ, Bundang Hosp, Songnam, South Korea. Ibarakihigashi Natl Hosp, Natl Hosp Org, Naka, Ibaraki, Japan. Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. Kyoto Univ Hosp, Kyoto 606, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1920 BP 483A EP 483A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503393 ER PT J AU Sholl, LM Pal, P Alden, RS Feeney, N Paweletz, C Sacher, A Oxnard, GR AF Sholl, Lynette M. Pal, Prodipto Alden, Ryan S. Feeney, Nora Paweletz, Cloud Sacher, Adrian Oxnard, Geoffrey R. TI Predictors of High Levels of Mutant cfDNA in Plasma from Patients with Advanced Lung Adenocarcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Belfer Ctr Appl Canc Sci, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 1922 BP 483A EP 483A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503395 ER PT J AU Huck, A Hong, C DeLelys, ME Preffer, FI Sohani, AR AF Huck, Amelia Hong, Christine DeLelys, Michelle E. Preffer, Frederic I. Sohani, Aliyah R. TI A Triaging Strategy Using Absolute White Blood Cell Differential Counts and Smear Morphology Improves Diagnostic Yield of Peripheral Blood Flow Cytometry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 St Barnabas Hosp, Livingston, NJ USA. Harvard Univ, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2016 VL 29 SU 2 MA 1974 BP 496A EP 496A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503447 ER PT J AU Guilmette, J Faquin, WC Nielsen, GP Selig, M Nose, V Sadow, PM AF Guilmette, Julie Faquin, William C. Nielsen, G. Petur Selig, Martin Nose, Vama Sadow, Peter M. TI Is Mammary Analogue Secretory Carcinoma of the Salivary Glands a Distinct Entity from Acinic Cell Carcinoma: An Ultrastructural Study SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 105th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 12-18, 2016 CL Seattle, WA SP US & Canadian Acad Pathol C1 Univ Montreal, Med Ctr, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2016 VL 29 SU 2 MA 2041 BP 514A EP 514A PG 1 WC Pathology SC Pathology GA DE0GI UT WOS:000370302503514 ER PT J AU Fernandez-Carbonell, C Vargas-Lowy, D Musallam, A Healy, B McLaughlin, K Wucherpfennig, KW Chitnis, T AF Fernandez-Carbonell, Cristina Vargas-Lowy, David Musallam, Alexander Healy, Brian McLaughlin, Katherine Wucherpfennig, Kai W. Chitnis, Tanuja TI Clinical and MRI phenotype of children with MOG antibodies SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Acute disseminated encephalomyelitis; demyelinating syndromes; encephalopathy; glycoprotein; magnetic resonance imaging; multiple sclerosis; myelin; myelin oligodendrocyte glycoprotein; neuromyelitis optica; optic neuritis; pediatric multiple sclerosis; serology ID MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; PEDIATRIC MULTIPLE-SCLEROSIS; ACUTE DISSEMINATED ENCEPHALOMYELITIS; DEMYELINATING DISEASES; NEUROMYELITIS-OPTICA; SPECTRUM DISORDERS; T-CELL; CNS; AUTOIMMUNITY; DEFINITIONS AB Objective: To investigate the clinical and magnetic resonance imaging (MRI) features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-seropositive pediatric demyelinating syndromes. Methods: Serum samples collected from 74 children with suspected demyelinating disorders whom were being followed at Massachusetts General Hospital were incubated with control green fluorescent protein (GFP)- and MOG-GFP-transfected Jurkat cell clones. The binding ratios were calculated using flow cytometry. Using statistical analyses, we compared the demographic, clinical and radiological features in our seropositive and seronegative patients. Results: We found that 13 out of 74 (17.5%) patients were seropositive for MOG. The MOG-seropositive patients were younger than the seronegative patients (p = 0.049). No single disease category predominated among the seropositive patients, nor was one group more likely to have a polyphasic course. There were two out of four neuromyelitis optica (NMO) patients who had MOG antibodies; both were seronegative for aquaporin -4 (AQP4) antibodies. One had monophasic disease and the other had frequent relapses. There was a bimodal distribution of the MOG-seropositive patients by age at onset, with a distinct younger group (4-8 years) having a high prevalence of encephalopathy and an older group (13-18 years), whom presented almost exclusively with optic neuritis. MRI analysis demonstrated the absence of corpus callosum lesions in the seropositive patients (p = 0.012). The annualized relapse rate (ARR) and the Expanded Disability Status Scale (EDSS) results at 2 years did not differ between the seropositive and seronegative patients. Conclusion: MOG antibodies are found across a variety of pediatric demyelinating syndromes having some distinct clinical and MRI features. C1 [Chitnis, Tanuja] Massachusetts Gen Hosp, Partners Pediat MS Ctr, 55 Fruit St, Boston, MA USA. [Fernandez-Carbonell, Cristina; Vargas-Lowy, David; Chitnis, Tanuja] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Musallam, Alexander; Healy, Brian; Chitnis, Tanuja] Brigham & Womens Hosp, Partners MS Ctr, 75 Francis St, Boston, MA 02115 USA. [Healy, Brian] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [McLaughlin, Katherine; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Chitnis, T (reprint author), Massachusetts Gen Hosp, Partners Pediat MS Ctr, 55 Fruit St, Boston, MA USA. EM tchitnis@partners.org FU National Multiple Sclerosis Society (Pediatric Regional Centers of Excellence); Peabody Foundation; Caja Madrid; US National Institute of Health (NIH) [AI045757] FX This research was supported by the National Multiple Sclerosis Society (Pediatric Regional Centers of Excellence award to T Chitnis), the Peabody Foundation (to T Chitnis), the Caja Madrid (Fellowship Grant to C Fernandez-Carbonell), and the US National Institute of Health (NIH) (PO1 grant no. AI045757 to K Wucherpfennig). NR 36 TC 5 Z9 5 U1 3 U2 5 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 FEB PY 2016 VL 22 IS 2 BP 174 EP 184 DI 10.1177/1352458515587751 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD5RI UT WOS:000369981500008 PM 26041801 ER PT J AU Wen, PY Reardon, DA AF Wen, Patrick Y. Reardon, David A. TI Progress in glioma diagnosis, classification and treatment SO NATURE REVIEWS NEUROLOGY LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; RADIATION-THERAPY RT; RANDOMIZED PHASE-III; VINCRISTINE PCV; TUMORS; GLIOBLASTOMA; TEMOZOLOMIDE; PROCARBAZINE; TRIAL; CCNU C1 [Wen, Patrick Y.; Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org NR 10 TC 5 Z9 5 U1 8 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD FEB PY 2016 VL 12 IS 2 BP 69 EP 70 DI 10.1038/nrneurol.2015.242 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DE0KL UT WOS:000370313700003 PM 26782337 ER PT J AU Jack, CR Knopman, DS Chetelat, G Dickson, D Fagan, AM Frisoni, GB Jagust, W Mormino, EC Petersen, RC Sperling, RA van der Flier, WM Villemagne, VL Visser, PJ Vos, SJB AF Jack, Clifford R., Jr. Knopman, David S. Chetelat, Gael Dickson, Dennis Fagan, Anne M. Frisoni, Giovanni B. Jagust, William Mormino, Elizabeth C. Petersen, Ronald C. Sperling, Reisa A. van der Flier, Wiesje M. Villemagne, Victor L. Visser, Pieter J. Vos, Stephanie J. B. TI Suspected non-Alzheimer disease pathophysiology - concept and controversy SO NATURE REVIEWS NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID BIOMARKERS; POSITRON-EMISSION-TOMOGRAPHY; AMYLOID-BETA DEPOSITION; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; HIPPOCAMPAL ATROPHY; OLDER PERSONS; NEUROPATHOLOGIC ASSESSMENT AB Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-beta biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal. The term SNAP has been applied to clinically normal individuals (who do not meet criteria for either mild cognitive impairment or dementia) and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be reliably inferred from the clinical presentation. SNAP is present in similar to 23% of clinically normal individuals aged >65 years and in similar to 25% of mildly cognitively impaired individuals. APOE*epsilon 4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-beta biomarkers. In this Perspectives article, we describe the available data on SNAP and address topical controversies in the field. C1 [Jack, Clifford R., Jr.] Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. [Knopman, David S.; Petersen, Ronald C.] Mayo Clin & Mayo Fdn, Dept Neurol, 200 First St SW, Rochester, MN 55905 USA. [Chetelat, Gael] Univ Caen, CHU Caen, EPHE, INSERM,U1077, F-14032 Caen, France. [Dickson, Dennis] Mayo Clin & Mayo Fdn, Dept Pathol, 4500 San Pablo Rd South, Jacksonville, FL 32224 USA. [Fagan, Anne M.] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, Dept Neurol, 4488 Forest Pk Ave,Suite 101, St Louis, MO 63108 USA. [Frisoni, Giovanni B.] Univ Hosp, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland. [Frisoni, Giovanni B.] Univ Geneva, Rue Gabrielle Perret Gentil 4, CH-1205 Geneva, Switzerland. [Jagust, William] Univ Calif Berkeley, Helen Wills Neurosci Inst, Li Ka Shing Ctr 175, Berkeley, CA 94720 USA. [Mormino, Elizabeth C.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. [van der Flier, Wiesje M.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Neurol, Neurosci Campus Amsterdam,POB 7057, NL-1007 MB Amsterdam, Netherlands. [Villemagne, Victor L.] Austin Hlth, Ctr PET, Dept Mol Imaging & Therapy, 145 Studley Rd,POB 5555 Melbourne, Melbourne, Vic 3084, Australia. [Visser, Pieter J.; Vos, Stephanie J. B.] Maastricht Univ, Inst Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, POB 616 MD Maastricht, NL-6200 MD Maastricht, Netherlands. RP Jack, CR (reprint author), Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. EM jack.clifford@mayo.edu RI Jack, Clifford/F-2508-2010; Frisoni, Giovanni B/K-1360-2016; Visser, Pieter/C-8541-2015; Chetelat, Gael/G-2316-2015 OI Jack, Clifford/0000-0001-7916-622X; Frisoni, Giovanni B/0000-0002-6419-1753; Visser, Pieter/0000-0001-8008-9727; FU NIH [P50-AG016574, P50-NS072187, P01-AG003949]; Alexander Family Alzheimer disease Disease Research Professorship of the Mayo Foundation; CurePSP: Foundation; DIAN Pharma Consortium; Alzheimer disease Association; BrightFocus Foundation; Netherlands Organization for Scientific Research (NWO); ZonMw; Cardiovasculair Onderzoek Nederland; European Union (EU) 7" Framework Programme; EU Joint Programme-Neurodegenerative Disease Research (JPND); EU FP7; Innovative Medicines Initiative joint resources; Innovative Medicines Initiative Joint Undertaking under EMIF grant [115372] FX C.R.J.Jr receives research funding from the NIH and the Alexander Family Alzheimer disease Disease Research Professorship of the Mayo Foundation. D.D. receives research support from the NIH (P50-AG016574; P50-NS072187; P01-AG003949) and CurePSP: Foundation for PSP/CBD and Related Disorders. A.M.F. receives research funding from the the DIAN Pharma Consortium and the Alzheimer disease Association. R.A.S. received research support from the BrightFocus Foundation. W.M.v.d.E receives research funding from the Netherlands Organization for Scientific Research (NWO), ZonMw, Cardiovasculair Onderzoek Nederland, and European Union (EU) 7" Framework Programme (FP7); all funds are paid to her institution. P.J.V. receives research funding from EU Joint Programme-Neurodegenerative Disease Research (JPND) and ZonMw, and from EU FP7 and Innovative Medicines Initiative joint resources, which are composed of financial contributions from EU FP7 (FP7/2007-2013) and in-kind contributions from the European Federation of Pharmaceutical Industries and Associations (EFPIA). S.J.B.V. receives research support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no 115372, resources that are composed of financial contributions from EU FP7 (FP7/2007-2013) and in-kind contributions from EFPIA. NR 98 TC 20 Z9 20 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD FEB PY 2016 VL 12 IS 2 BP 117 EP 124 DI 10.1038/nrneurol.2015.251 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DE0KL UT WOS:000370313700011 PM 26782335 ER PT J AU Flickinger, TE Saha, S Roter, D Korthuis, PT Sharp, V Cohn, J Eggly, S Moore, RD Beach, MC AF Flickinger, Tabor E. Saha, Somnath Roter, Debra Korthuis, P. Todd Sharp, Victoria Cohn, Jonathan Eggly, Susan Moore, Richard D. Beach, Mary Catherine TI Clinician empathy is associated with differences in patient-clinician communication behaviors and higher medication self-efficacy in HIV care SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE HIV/AIDS; Patient-clinician communication; Empathy; Self-efficacy; Medication adherence ID PHYSICIAN EMPATHY; PROVIDER COMMUNICATION; HEALTH OUTCOMES; SATISFACTION; QUALITY; ADHERENCE; DISEASE; PARTNERSHIP; MULTICENTER; ASSESSMENTS AB Objective: We examined associations of clinicians' empathy with patient-clinician communication behaviors, patients' rating of care, and medication self-efficacy. Methods: We analyzed 435 adult patients and 45 clinicians at four outpatient HIV care sites in the United States. Negative binomial regressions investigated associations between clinician empathy and patient-clinician communication, assessed using the Roter Interaction Analysis System (RIAS). Logistic regressions investigated associations between clinician empathy and patient ratings of clinician communication, overall satisfaction, and medication self-efficacy. Results: Clinicians in the highest vs. lowest empathy tertile engaged in less explicitly emotional talk (IRR 0.79, p < 0.05), while clinicians in the middle vs. lowest engaged in more positive talk (IRR 1.31, p < 0.05), more questions (IRR 1.42, p < 0.05), and more patient activating talk (IRR 1.43, p < 0.05). Patients of higher empathy clinicians disclosed more psychosocial and biomedical information. Patients of clinicians in both the middle and highest (vs. lowest) empathy tertiles had greater odds of reporting highest medication self-efficacy (OR 1.80, 95% CI 1.16-2.80; OR 2.13, 95% CI 1.37-3.32). Conclusions: Clinician empathy may be expressed through addressing patient engagement in care, by fostering cognitive, rather than primarily emotional, processing. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Flickinger, Tabor E.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Saha, Somnath] Portland VA Med Ctr, Portland, OR USA. [Saha, Somnath; Korthuis, P. Todd] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Roter, Debra; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Baltimore, MD USA. [Sharp, Victoria] St Lukes Roosevelt, New York, NY USA. [Cohn, Jonathan; Eggly, Susan] Wayne State Univ, Detroit, MI USA. RP Flickinger, TE (reprint author), Univ Virginia, Sch Med, Div Gen Geriatr Palliat & Hosp Med, POB 800901, Charlottesville, VA 22908 USA. EM TES3J@hscmail.mcc.virginia.edu OI Eggly, Susan/0000-0002-8137-6098; Flickinger, Tabor/0000-0001-8820-2536 FU Health Resources Service Administration; National Institute of Drug Abuse [K23 DA019808]; Agency for Healthcare Research and Quality [K08HS013903-05, AHRQ 290-01-0012]; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019808). Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. The funding sources had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. NR 51 TC 2 Z9 2 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD FEB PY 2016 VL 99 IS 2 BP 220 EP 226 DI 10.1016/j.pec.2015.09.001 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA DE7GU UT WOS:000370804700006 PM 26395313 ER PT J AU Flickinger, TE Saha, S Roter, D Korthuis, PT Sharp, V Cohn, J Moore, RD Ingersoll, KS Beach, MC AF Flickinger, Tabor E. Saha, Somnath Roter, Debra Korthuis, P. Todd Sharp, Victoria Cohn, Jonathan Moore, Richard D. Ingersoll, Karen S. Beach, Mary Catherine TI Respecting patients is associated with more patient-centered communication behaviors in clinical encounters SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE HIV/AIDS; Patient-clinician communication; Respect ID HIV CARE; PHYSICIAN COMMUNICATION; PROVIDER COMMUNICATION; RACIAL DISPARITIES; HEALTH-CARE; SEXUAL-BEHAVIOR; WHITE PATIENTS; SUBSTANCE USE; ADHERENCE; SATISFACTION AB Objective: Attitudes towards patients may influence how clinicians interact. We investigated whether respect for patients was associated with communication behaviors during HIV care encounters. Methods: We analyzed audio-recordings of visits between 413 adult HIV-infected patients and 45 primary HIV care providers. The independent variable was clinician-reported respect for the patient and outcomes were clinician and patient communication behaviors assessed by the Roter Interaction Analysis System (RIAS). We performed negative binomial regressions for counts outcomes and linear regressions for global outcomes. Results: When clinicians had higher respect for a patient, they engaged in more rapport-building, social chitchat, and positive talk. Patients of clinicians with higher respect for them engaged in more rapport-building, social chitchat, positive talk, and gave more psychosocial information. Encounters between patients and clinicians with higher respect for them had more positive clinician emotional tone [regression coefficient 2.97 (1.92-4.59)], more positive patient emotional tone [2.71 (1.75-4.21)], less clinician verbal dominance [0.81 (0.68-0.96)] and more patient-centeredness [1.28 (1.09-1.51)]. Conclusions: Respect is associated with positive and patient-centered communication behaviors during encounters. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Flickinger, Tabor E.; Ingersoll, Karen S.] Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA. [Saha, Somnath] Portland VA Med Ctr, Dept Med, Portland, OR USA. [Saha, Somnath; Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Roter, Debra; Moore, Richard D.; Beach, Mary Catherine] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Sharp, Victoria] St Lukes Roosevelt, Dept Med, New York, NY USA. [Cohn, Jonathan] Wayne State Univ, Dept Med, Detroit, MI 48202 USA. RP Flickinger, TE (reprint author), Univ Virginia, Sch Med, Div Gen Geriatr Palliat & Hosp Med, POB 800901, Charlottesville, VA 22908 USA. EM TES3J@hscmail.mcc.virginia.edu OI Flickinger, Tabor/0000-0001-8820-2536 FU Health Resources Service Administration; Agency for Healthcare Research and Quality [AHRQ 290-01-0012, K08HS013903-05]; National Institute of Drug Abuse [K23 DA019808]; Robert Wood Johnson Generalist Physician Faculty Scholars Awards FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). In addition, Dr. Korthuis was supported by the National Institute of Drug Abuse (K23 DA019808). Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. Preliminary findings of this manuscript were presented at the National Meeting of the Society of General Internal Medicine, San Diego, California, April 2014, and the International Conference on Communication in Healthcare, Amsterdam, The Netherlands, October 2014. NR 42 TC 3 Z9 3 U1 3 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD FEB PY 2016 VL 99 IS 2 BP 250 EP 255 DI 10.1016/j.pec.2015.08.020 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA DE7GU UT WOS:000370804700010 PM 26320821 ER PT J AU Lee, LO Gatz, M Pedersen, NL Prescott, CA AF Lee, Lewina O. Gatz, Margaret Pedersen, Nancy L. Prescott, Carol A. TI Anxiety Trajectories in the Second Half of Life: Genetic and Environmental Contributions Over Age SO PSYCHOLOGY AND AGING LA English DT Article DE anxiety; aging; trajectory; twin study; longitudinal study ID OLD-AGE; LONGITUDINAL EVIDENCE; DEPRESSION SCALE; NEGATIVE AFFECT; PERSONALITY; SYMPTOMS; METAANALYSIS; INVENTORY; DECLINE; MODEL AB Clinically significant anxiety symptoms are prevalent among the elderly, yet knowledge about the longitudinal course of anxiety symptoms in later life remains scarce. The goals of this study were to (a) characterize age trajectories of state anxiety symptoms in the second half of life, and (b) estimate genetic and environmental contributions to individual differences in the age trajectory of state anxiety. This study was based on data from 1,482 participants in the Swedish Adoption/Twin Study of Aging who were aged 50 and older at their first occasion (512 complete twin pairs, 458 singletons) and had up to 6 measurement occasions spanning 11 years. Consistent with life span developmental theories of age-related emotional change, anxiety symptom levels declined during the transition from midlife to the mid-60s, followed by a mild increase that gradually plateaued in the 80s. There were substantial individual differences in the age trajectory of anxiety. After accounting for effects of sex, cohort, mode of testing, and proximity to death, this longitudinal variation was partitioned into biometric sources. Nonshared environmental variance was highest in the late 60s and declined thereafter, whereas genetic variance increased at an accelerated pace from approximately age 60 onward. There was no evidence for effects of rearing or other shared environment on anxiety symptoms in later life. These findings highlight how the etiology of anxiety symptoms changes from midlife to old age. C1 [Lee, Lewina O.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. [Lee, Lewina O.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02215 USA. [Lee, Lewina O.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Gatz, Margaret; Pedersen, Nancy L.; Prescott, Carol A.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Gatz, Margaret; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Prescott, Carol A.] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA 90089 USA. RP Lee, LO (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave 151-C, Boston, MA 02446 USA. EM lewina@bu.edu FU National Institute on Aging (NIA) [F31 AG031691]; NIA [R01 AG04563, AG10175]; MacArthur Foundation Research Network on Successful Aging; Swedish Research Council [97:0147:1B] FX This study was supported by National Institute on Aging (NIA) Grant F31 AG031691. The Swedish Adoption/Twin Study of Aging (SATSA) is supported by NIA Grants R01 AG04563 and AG10175, the MacArthur Foundation Research Network on Successful Aging, and the Swedish Research Council (Grant 97:0147:1B). The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs or other support institutions. NR 66 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 EI 1939-1498 J9 PSYCHOL AGING JI Psychol. Aging PD FEB PY 2016 VL 31 IS 1 BP 101 EP 113 DI 10.1037/pag0000063 PG 13 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA DE4AR UT WOS:000370572100012 PM 26751006 ER PT J AU Shinde, A Berhane, H Rhieu, BH Kalash, R Xu, KR Goff, J Epperly, MW Franicola, D Zhang, XC Dixon, T Shields, D Wang, H Wipf, P Parmar, K Guinan, E Kagan, V Tyurin, V Ferris, RL Zhang, XL Li, S Greenberger, JS AF Shinde, Ashwin Berhane, Hebist Rhieu, Byung Han Kalash, Ronny Xu, Karen Goff, Julie Epperly, Michael W. Franicola, Darcy Zhang, Xichen Dixon, Tracy Shields, Donna Wang, Hong Wipf, Peter Parmar, Kalindi Guinan, Eva Kagan, Valerian Tyurin, Vladimir Ferris, Robert L. Zhang, Xiaolan Li, Song Greenberger, Joel S. TI Intraoral Mitochondrial-Targeted GS-Nitroxide, JP4-039, Radioprotects Normal Tissue in Tumor-Bearing Radiosensitive Fancd2(-/-) (C57BL/6) Mice SO RADIATION RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; FANCONI-ANEMIA PROTEINS; ORAL-CAVITY MUCOSITIS; SUPEROXIDE-DISMUTASE; NECK-CANCER; RADIATION SENSITIVITY; HEAD; DAMAGE; PATHWAY; AMELIORATION AB We evaluated normal tissue specific radioprotection of the oral cavity in radiosensitive Fanconi Anemia (FA) Fancd2(-/-) mice with orally established tumors using mitochondrial-targeted GS-nitroxide (JP4-039). Adult (10-12 weeks old) Fancd2(+/+), Fancd2(+/-) and Fancd2(-/-) mice (C57BL/6 background) and subgroups with orally established TC-1 epithelial cell tumors received a single fraction of 28 Gy or four daily fractions of 8 Gy to the head and neck. Subgroups received JP4-039 in F15 emulsion (F15/JP4-039; 0.4 mg/mouse), 4-amino-Tempo in F15 emulsion (F15/4-amino-Tempo; 0.2 mg/mouse) or F15 emulsion alone prior to each irradiation. Oral mucosa of Fancd2(-/-) mice showed baseline elevated RNA transcripts for Sod2, p53, p21 and Rad51 (all P < 0.0012) and suppressed levels of Nfkb and Tgfb, (all P < 0.0020) compared with Fancd2(+/+) mice. The oral mucosa in tumor-bearing mice of all genotypes showed decreased levels of p53 and elevated Tgfb and Gadd45a (P <= 0.0001 for all three genotypes). Intraoral F15/JP4-039, but not F15/4-amino-Tempo, modulated radiation-induced normal tissue transcript elevation, ameliorated mucosal ulceration and reduced the depletion of antioxidant stores in oral cavity tissue of all genotypes, but did not radioprotect tumors. Mitochondrial targeting makes F15/JP4039 an effective normal tissue radioprotector for Fancd2(-/-) mice, as well as wild-type mice. (C) 2016 by Radiation Research Society C1 [Shinde, Ashwin; Berhane, Hebist; Rhieu, Byung Han; Kalash, Ronny; Xu, Karen; Goff, Julie; Epperly, Michael W.; Franicola, Darcy; Zhang, Xichen; Dixon, Tracy; Shields, Donna; Wang, Hong; Greenberger, Joel S.] Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. [Parmar, Kalindi; Guinan, Eva] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. [Wipf, Peter] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. [Kagan, Valerian; Tyurin, Vladimir] Univ Pittsburgh, Dept Environm Occupat Hlth, Pittsburgh, PA 15260 USA. [Ferris, Robert L.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Zhang, Xiaolan; Li, Song] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA. RP Greenberger, JS (reprint author), Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA 15213 USA.; Greenberger, JS (reprint author), Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, UPMC Canc Pavil,Room 533,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM greenbergerjs@upmc.edu RI zhang, xiaolan/K-5035-2015; OI Wang, Hong/0000-0003-0477-2908; Tyurin, Vladimir/0000-0002-3474-1697 FU National Institute of Allergy and Infectious Diseases/National Institutes of Health [U19-A1068021]; Fanconi Anemia Research Foundation; NIH [P30CA047904] FX This work was supported by the National Institute of Allergy and Infectious Diseases/National Institutes of Health (no. U19-A1068021) and the Fanconi Anemia Research Foundation. The UPCI Animal Facility used for these studies is supported in part by the NIH (grant no. P30CA047904). Conflict of interest: Drs. Greenberger, Wipf, Kagan and Epperly are inventors on patents issued for the use of JP4-039 and MMS350 as radiation protectors or mitigators. NR 34 TC 5 Z9 5 U1 1 U2 9 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2016 VL 185 IS 2 BP 134 EP 150 DI 10.1667/RR14035.1 PG 17 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA DE6HI UT WOS:000370734200004 PM 26789701 ER PT J AU Park, KR Monsky, WL Lee, CG Song, CH Kim, DH Jain, RK Fukumura, D AF Park, Kyung Ran Monsky, Wayne L. Lee, Chang Geol Song, Chang Ho Kim, Dong Heui Jain, Rakesh K. Fukumura, Dai TI Mast Cells Contribute to Radiation-Induced Vascular Hyperpermeability SO RADIATION RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HUMAN ADENOCARCINOMA LS174T; NITRIC-OXIDE SYNTHASE; X-IRRADIATION; SPINAL-CORD; MICROVASCULAR PERMEABILITY; UP-REGULATION; SCID MICE; RATS; SKIN AB Induction of vascular hyperpermeability is one of the early vascular responses to radiation exposure and is considered to contribute to subsequent fibrosis and tissue injuries. However, the mechanism underlying radiation-induced hyperpermeability has not yet been clearly elucidated. Here, we provide experimental evidence indicating that mast cells contribute to the increase in vascular permeability for albumin in normal mouse skin after irradiation. Vascular permeability in the skin of C3H mice increased after 2, 15 and 50 Gy irradiation, peaked at 24 h after irradiation and gradually decreased thereafter to the baseline level within 3-10 days. Both the extent and duration of hyperpermeability were dose dependent. We found significant degranulation of mast cells in the skin after 15 Gy irradiation. To further investigate the role of mast cells in the radiation-induced increase in vascular permeability, we measured vascular permeability in the skin of mast cell-deficient mice (WWv) and their wild-type littermates at 24 h after irradiation. Vascular permeability in WWv mice did not change, whereas that in wild-type mice significantly increased after irradiation. There were no appreciable changes in the total tissue levels of vascular endothelial growth factor or endothelial nitric oxide synthase after 15 Gy irradiation and there was no detectable expression of inducible nitric oxide synthase. Collectively, these results show that exposure to radiation induces vascular hyperpermeability in a dose-dependent manner and that mast cells contribute to this process. (C) 2016 by Radiation Research Society C1 [Park, Kyung Ran; Monsky, Wayne L.; Lee, Chang Geol; Jain, Rakesh K.; Fukumura, Dai] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA USA. [Song, Chang Ho] Chonbuk Natl Univ, Sch Med, Dept Anat, Chonju, South Korea. [Kim, Dong Heui] Yonsei Univ Wonju, Coll Med, Inst Basic Med Sci, Dept Basic Sci, Wonju, South Korea. [Park, Kyung Ran] Ewha Womans Univ, Med Ctr, Dept Radiat Oncol, Seoul, South Korea. [Monsky, Wayne L.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Lee, Chang Geol] Yonsei Univ, Coll Med, Dept Radiat Oncol, Seoul 120749, South Korea. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX-7, Boston, MA 02114 USA. EM dai@steele.mgh.harvard.edu FU National Institutes of Health [R35-CA056591, P01-CA080124, R01-CA096915] FX We thank Dr. Stephen J. Galli for his helpful advice, Dr. Kathy Held for her help with the irradiation of mice, Ms. Julia Kahn for her help with small animal surgery and Dr. Young Kun Deung for his help with the electron microscopy experiments. This research was supported in part by the National Institutes of Health [grant nos. R35-CA056591 (RKJ), P01-CA080124 (RKJ and DF) and R01-CA096915 (DF)]. No competing interests exist. NR 46 TC 3 Z9 3 U1 1 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD FEB PY 2016 VL 185 IS 2 BP 182 EP 189 DI 10.1667/RR14190.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA DE6HI UT WOS:000370734200008 PM 26771172 ER PT J AU Wintner, A Kim, MM Bechis, SK Kreydin, EI AF Wintner, Anton Kim, Michelle M. Bechis, Seth K. Kreydin, Evgeniy I. TI Voiding Dysfunction in Multiple Sclerosis SO SEMINARS IN NEUROLOGY LA English DT Article DE neurogenic bladder; voiding dysfunction; multiple sclerosis ID DETRUSOR-SPHINCTER DYSSYNERGIA; URINARY-TRACT DYSFUNCTION; SPINAL-CORD-INJURY; QUALITY-OF-LIFE; BLADDER DYSFUNCTION; SUPRASPINAL CONTROL; URODYNAMIC FINDINGS; OVERACTIVE BLADDER; ECONOMIC-IMPACT; MANAGEMENT AB Voiding dysfunction is a common and debilitating consequence of multiple sclerosis (MS). The prevalence and severity of voiding dysfunction increases with the increasing severity of MS, but even the mildest forms of the disease are associated with urinary symptoms in 30% of patients. Every component of the central nervous system is involved in regulating voiding; as a result, MS can lead to a wide variety of urinary symptoms and urologic complications. The effect of MS on voiding can be classified according to the resulting function of the bladder and the urethral sphincter during storage and emptying of urine. Therapy is targeted to the specific bladder and sphincter abnormalities that occur. The primary goals of therapy are prevention of injury to the upper urinary tract (kidneys), reduction in urinary tract infections, and maintenance of urinary continence. These goals can be achieved by interventions ranging from behavioral modification to major reconstructive surgery. C1 [Wintner, Anton; Kim, Michelle M.; Bechis, Seth K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Kreydin, Evgeniy I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 300 Stein Plaza,3rd Floor, Los Angeles, CA 90095 USA. RP Kreydin, EI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 300 Stein Plaza,3rd Floor, Los Angeles, CA 90095 USA. EM ekreydin@mednet.ucla.edu NR 45 TC 0 Z9 0 U1 1 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 EI 1098-9021 J9 SEMIN NEUROL JI Semin. Neurol. PD FEB PY 2016 VL 36 IS 1 BP 34 EP 40 DI 10.1055/s-0035-1571212 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA DE1NX UT WOS:000370394800007 PM 26866494 ER PT J AU Cheng, A Morse, KJ Rudolph, J Arab, AA Runnacles, J Eppich, W AF Cheng, Adam Morse, Kate J. Rudolph, Jenny Arab, Abeer A. Runnacles, Jane Eppich, Walter TI Learner-Centered Debriefing for Health Care Simulation Education Lessons for Faculty Development SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Debriefing; Learner-centered teaching; Instructor-centered teaching; Simulation; Education ID MEDICAL-EDUCATION; METAANALYSIS; SKILLS; TRIAL; TOOL AB Statement Better debriefing practices may enhance the impact of simulation-based education. Emerging literature suggests that learner-centered debriefing may be effective in helping instructors identify and address learner needs while building learner's engagement and sense of responsibility for learning. This contrasts with instructor-centered approaches to debriefing, where instructors maintain unilateral control over both the process and content of the debriefing, thus limiting input and direction from learners. Although different approaches to debriefing for simulation-based education exist, the simulation literature is largely mute on the topic of learner-centered debriefing. In this article we will (1) compare and contrast learner- versus instructor-centered approaches to teaching; (2) provide a rationale for applying more learner-centered approaches to debriefing; (3) introduce a conceptual framework that highlights the key dimensions of learner- versus instructor-centered debriefing; (4) describe key variables to consider when managing the balance between learner- and instructor-centered debriefing; and (5) describe practical learner-centered strategies for various phases of debriefing. C1 [Cheng, Adam] Univ Calgary, Alberta Childrens Hosp, Dept Pediat, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. [Morse, Kate J.] Drexel Univ, Nurse Practitioner Programs, Philadelphia, PA 19104 USA. [Rudolph, Jenny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA. [Eppich, Walter] Ann & Robert H Lurie Childrens Hosp Chicago, Northwestern Feinberg Sch Med, Dept Pediat & Med Educ, Chicago, IL 60611 USA. [Arab, Abeer A.] King Abdulaziz Univ, Coll Med, Dept Anesthesia & Crit Care, Jeddah 21413, Saudi Arabia. [Runnacles, Jane] Royal Free Hosp NHS Fdn Trust, Dept Pediat, London, England. RP Cheng, A (reprint author), Univ Calgary, Alberta Childrens Hosp, Dept Pediat, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada. EM chenger@me.com FU Royal College of Physicians and Surgeons of Canada; Center for Medical Simulation, Boston, MA FX A.C. receives salary support from the Royal College of Physicians and Surgeons of Canada for his role in simulation educator training. W.E. teaches on multiple simulation educator courses. He receives salary support from the Center for Medical Simulation, Boston, MA. All salary support is paid to his institution to offset clinical duties. He receives intermittent per diem honoraria from PAEDSIM, a pediatric simulation collaborative in German-speaking countries, to teach simulation educator courses. NR 54 TC 2 Z9 2 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD FEB PY 2016 VL 11 IS 1 BP 32 EP 40 DI 10.1097/SIH.0000000000000136 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DD5QB UT WOS:000369978000005 PM 26836466 ER PT J AU Antonelli, J Trippa, L Haneuse, S AF Antonelli, Joseph Trippa, Lorenzo Haneuse, Sebastien TI Mitigating Bias in Generalized Linear Mixed Models: The Case for Bayesian Nonparametrics SO STATISTICAL SCIENCE LA English DT Article DE Dirichlet process prior; generalized linear mixed models; model misspecification; random effects ID DIRICHLET PROCESS MIXTURE; RANDOM-EFFECTS MISSPECIFICATION; MAXIMUM-LIKELIHOOD-ESTIMATION; LONGITUDINAL DATA; MIXING DISTRIBUTION; ORDINAL DATA; II ERROR; INFERENCE; DISTRIBUTIONS; REGRESSION AB Generalized linear mixed models are a common statistical tool for the analysis of clustered or longitudinal data where correlation is accounted for through cluster-specific random effects. In practice, the distribution of the random effects is typically taken to be a Normal distribution, although if this does not hold then the model is misspecified and standard estimation/inference may be invalid. An alternative is to perform a so-called nonparametric Bayesian analyses in which one assigns a Dirichlet process (DP) prior to the unknown distribution of the random effects. In this paper we examine operating characteristics for estimation of fixed effects and random effects based on such an analysis under a range of "true" random effects distributions. As part of this we investigate various approaches for selection of the precision parameter of the DP prior. In addition, we illustrate the use of the methods with an analysis of post-operative complications among n = 18,643 female Medicare beneficiaries who underwent a hysterectomy procedure at N = 503 hospitals in the US. Overall, we conclude that using the DP prior in modeling the random effect distribution results in large reductions of bias with little loss of efficiency. While no single choice for the precision parameter will be optimal in all settings, certain strategies such as importance sampling or empirical Bayes can be used to obtain reasonable results in a broad range of data scenarios. C1 [Antonelli, Joseph] Harvard Univ, Chan Sch Publ Hlth, Deparment Biostat, 655 Huntington Ave, Boston, MA 02115 USA. [Trippa, Lorenzo] Dana Farber Canc Inst, Ctr Life Sci, Dept Biostat, 3 Blackfan Circle, Boston, MA 02115 USA. [Haneuse, Sebastien] Harvard Univ, Chan Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. RP Antonelli, J (reprint author), Harvard Univ, Chan Sch Publ Hlth, Deparment Biostat, 655 Huntington Ave, Boston, MA 02115 USA.; Trippa, L (reprint author), Dana Farber Canc Inst, Ctr Life Sci, Dept Biostat, 3 Blackfan Circle, Boston, MA 02115 USA.; Haneuse, S (reprint author), Harvard Univ, Chan Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM jantonelli@fas.harvard.edu; ltrippa@jimmy.harvard.edu; shaneuse@hsph.harvard.edu FU NIH [ES007142, R-01 CA181360-01]; Claudia Adams Barr Program in Innovative Basic Cancer Research FX Joseph Antonelli was supported by NIH Grant ES007142. Lorenzo Trippa was supported by the Claudia Adams Barr Program in Innovative Basic Cancer Research. Sebastien Haneuse was supported by NIH Grant R-01 CA181360-01. NR 52 TC 0 Z9 0 U1 2 U2 7 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD FEB PY 2016 VL 31 IS 1 BP 80 EP 95 DI 10.1214/15-STS533 PG 16 WC Statistics & Probability SC Mathematics GA DD9ZF UT WOS:000370283600010 ER PT J AU Sakayori, N Kikkawa, T Tokuda, H Kiryu, E Yoshizaki, K Kawashima, H Yamada, T Arai, H Kang, JX Katagiri, H Shibata, H Innis, SM Arita, M Osumi, N AF Sakayori, Nobuyuki Kikkawa, Takako Tokuda, Hisanori Kiryu, Emiko Yoshizaki, Kaichi Kawashima, Hiroshi Yamada, Tetsuya Arai, Hiroyuki Kang, Jing X. Katagiri, Hideki Shibata, Hiroshi Innis, Sheila M. Arita, Makoto Osumi, Noriko TI Maternal Dietary Imbalance between Omega-6 and Omega-3 Polyunsaturated Fatty Acids Impairs Neocortical Development via Epoxy Metabolites SO STEM CELLS LA English DT Article DE Neural stem cells; Arachidonic acid; Docosahexaenoic acid; Epoxides; Anxiety; Metabolomics ID NEURAL STEM/PROGENITOR CELLS; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; ACUTE-INFLAMMATION; LIPID MEDIATORS; STEM-CELLS; FAT-1 MICE; NEUROGENESIS; NUTRITION; RAT AB Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients. Although several studies have suggested that a balanced dietary n-6:n-3 ratio is essential for brain development, the underlying cellular and molecular mechanism is poorly understood. Here, we found that feeding pregnant mice an n-6 excess/n-3 deficient diet, which reflects modern human diets, impairsed neocortical neurogenesis in the offspring. This impaired neurodevelopment occurs through a precocious fate transition of neural stem cells from the neurogenic to gliogenic lineage. A comprehensive mediator lipidomics screen revealed key mediators, epoxy metabolites, which were confirmed functionally using a neurosphere assay. Importantly, although the offspring were raised on a well-balanced n-6: n-3 diet, they exhibited increased anxiety-related behavior in adulthood. These findings provide compelling evidence that excess maternal consumption of n-6 PUFAs combined with insufficient intake of n-3 PUFAs causes abnormal brain development that can have long-lasting effects on the offspring's mental state. C1 [Sakayori, Nobuyuki; Kikkawa, Takako; Kiryu, Emiko; Yoshizaki, Kaichi; Osumi, Noriko] Tohoku Univ, Sch Med, Dept Dev Neurosci, Ctr Neurosci,United Ctr Adv Res & Translat Med, Sendai, Miyagi 9808575, Japan. [Yamada, Tetsuya; Katagiri, Hideki] Tohoku Univ, Sch Med, Dept Metab & Diabet, Sendai, Miyagi 9808575, Japan. [Sakayori, Nobuyuki] Japan Soc Promot Sci, Tokyo, Japan. [Tokuda, Hisanori; Kawashima, Hiroshi; Shibata, Hiroshi] Suntory Wellness Ltd, Inst Hlth Care Sci, Osaka, Japan. [Arai, Hiroyuki; Arita, Makoto] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Hlth Chem, Tokyo, Japan. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Innis, Sheila M.] Univ British Columbia, Dept Paediat, Child & Family Res Inst, Vancouver, BC, Canada. [Arita, Makoto] RIKEN, Ctr Integrat Med Sci, Lab Metabol, Yokohama, Kanagawa, Japan. RP Osumi, N (reprint author), Tohoku Univ, Sch Med, United Ctr Adv Res & Translat Med, Dept Dev Neurosci,Ctr Neurosci,Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan. EM osumi@med.tohoku.ac.jp FU Japan Society for the Promotion of Science for Young Scientists from the Japan Science and Technology Agency; Mishima Kaiun Memorial Foundation; MEXT [21300115]; Asahi Glass Foundation FX We thank Drs. C. Yokoyama and F. Jacka for critically reading the manuscript; Drs. T. Sugiyama, R. A. Dyer, and R. Kimura, and Ms. S. Makino, Y. Chiba, and T. Takasugi for technical assistance; Ms. K. Ueda, J. Yoon, E. Otsuki, and A. Ogasawara and Mr. K. Koike for animal care; and all members of our laboratory for helpful discussions. This work was supported by a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists from the Japan Science and Technology Agency (to N. S.), by a Scientific Research Promotion Grant from the Mishima Kaiun Memorial Foundation (to N. S.), by a Grant-in-Aid for Scientific Research (B) from MEXT (Grant 21300115; to N.O.), and by a Research Grant from the Asahi Glass Foundation (to N.O.). NR 50 TC 2 Z9 2 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD FEB PY 2016 VL 34 IS 2 BP 470 EP 482 DI 10.1002/stem.2246 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA DE0ZA UT WOS:000370353200019 PM 26580686 ER PT J AU Scirica, BM AF Scirica, Benjamin M. TI Treating patients with diabetes and cardiovascular disease-Does the glucose matter? SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Editorial Material ID OUTCOMES C1 [Scirica, Benjamin M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. RP Scirica, BM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. EM bscirica@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD FEB PY 2016 VL 26 IS 2 BP 180 EP 181 DI 10.1016/j.tcm.2015.10.001 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DE4FJ UT WOS:000370584300012 PM 26830123 ER PT J AU Adar, T Rieder, F Michael, M AF Adar, Tomer Rieder, Florian Michael, Manns TI Young GI Angle: Young physicians and researchers within UEG - Perspectives and a toolbox for future development SO UNITED EUROPEAN GASTROENTEROLOGY JOURNAL LA English DT News Item C1 [Adar, Tomer] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Adar, Tomer] Hebrew Univ Jerusalem, Shaare Zedek Med Ctr, Jerusalem, Israel. [Rieder, Florian] Cleveland Clin Fdn, Dept Pathobiol, Lerner Res Inst, Dept Gastroenterol Hepatol & Nutr,Digest Dis Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Michael, Manns] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany. RP Adar, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2050-6406 EI 2050-6414 J9 UNITED EUR GASTROENT JI United European Gastroenterol. J. PD FEB PY 2016 VL 4 IS 1 BP 156 EP 157 DI 10.1177/2050640616629604 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DE6OF UT WOS:000370752800022 PM 26966538 ER PT J AU Wen, JC Yeh, CK Sun, YY AF Wen, Jianchuan Yeh, Chih-Ko Sun, Yuyu TI Functionalized Denture Resins as Drug Delivery Biomaterials to Control Fungal Biofilms SO ACS BIOMATERIALS SCIENCE & ENGINEERING LA English DT Article DE denture; poly(2-hydroxyethyl methacrylate); drug delivery; fungal; biofilm-controlling ID IN-VITRO; POLY(2-HYDROXYETHYL METHACRYLATE); ANTIFUNGAL ACTIVITY; SILVER NANOPARTICLES; CANDIDA-ALBICANS; STOMATITIS; PLASMA; ETIOLOGY; SURFACE; DEVICE AB Colonization and biofilm-formation of Candida species on denture surfaces cause Candida-associated denture stomatitis (CADS), a recurring fungal infection that affects up to 67% of denture wearers. We grafted poly(2-hydroxyethyl methacrylate) (PHEMA) onto poly(methyl methacrylate) (PMMA)-based denture resins through plasma-initiated grafting polymerization. The effects of reaction conditions on grafting and the physical properties of the resulting resins were evaluated. The grafted resins showed significantly increased drug binding capability toward clotrimazole, one of the most widely used antifungal drugs. The mechanisms for the enhancement in drug binding were discussed. The new clotrimazole-containing resins provided sustained drug release for longer than 28 days, and the released drugs demonstrated potent, long-term biofilm-controlling effects against Candida, pointing to an attractive strategy in controlling CADS and related fungal infections. C1 [Wen, Jianchuan; Sun, Yuyu] Univ Massachusetts, Dept Chem, 1 Univ Ave, Lowell, MA 01854 USA. [Yeh, Chih-Ko] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. RP Sun, YY (reprint author), Univ Massachusetts, Dept Chem, 1 Univ Ave, Lowell, MA 01854 USA. EM yuyu_sun@uml.edu FU NIDCR, NIH [R01 DE021084]; VA Merit Review [1I01BX001103] FX This study was partly supported by NIDCR, NIH (R01 DE021084), and VA Merit Review (1I01BX001103). NR 43 TC 1 Z9 1 U1 3 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2373-9878 J9 ACS BIOMATER SCI ENG JI ACS Biomater. Sci. Eng. PD FEB PY 2016 VL 2 IS 2 BP 224 EP 230 DI 10.1021/acsbiomaterials.5b00416 PG 7 WC Materials Science, Biomaterials SC Materials Science GA DD4FA UT WOS:000369876700010 ER PT J AU Akkina, R Allam, A Balazs, AB Blankson, JN Burnett, JC Casares, S Garcia, JV Hasenkrug, KJ Kashanchi, F Kitchen, SG Klein, F Kumar, P Luster, AD Poluektova, LY Rao, M Sanders-Beer, BE Shultz, LD Zack, JA AF Akkina, Ramesh Allam, Atef Balazs, Alejandro B. Blankson, Joel N. Burnett, John C. Casares, Sofia Garcia, J. Victor Hasenkrug, Kim J. Kashanchi, Fatah Kitchen, Scott G. Klein, Florian Kumar, Priti Luster, Andrew D. Poluektova, Larisa Y. Rao, Mangala Sanders-Beer, Brigitte E. Shultz, Leonard D. Zack, Jerome A. TI Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS ENCEPHALITIS; BROADLY NEUTRALIZING ANTIBODIES; HEMATOPOIETIC STEM-CELLS; SCID-HU MOUSE; T-CELLS; BLT MICE; IN-VIVO; VAGINAL TRANSMISSION; INFECTIOUS-DISEASES; IMMUNE-RESPONSES AB The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting. C1 [Akkina, Ramesh] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Allam, Atef] Henry M Jackson Fdn Adv Mil Med, Silver Spring, MD USA. [Allam, Atef; Rao, Mangala] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Balazs, Alejandro B.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Blankson, Joel N.] Johns Hopkins Univ, Sch Med, Dept Med, Ctr AIDS Res, Baltimore, MD 21205 USA. [Burnett, John C.] Beckman Res Inst City Hope, Dept Mol & Cellular Biol, Duarte, CA USA. [Casares, Sofia] Naval Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD USA. [Garcia, J. Victor] Univ N Carolina, Dept Med, Div Infect Dis, UNC Ctr AIDS Res, Chapel Hill, NC USA. [Hasenkrug, Kim J.] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Kashanchi, Fatah] George Mason Univ, Sch Syst Biol, Natl Ctr Biodef & Infect Dis, Manassas, VA USA. [Kitchen, Scott G.; Zack, Jerome A.] Univ Calif Los Angeles, AIDS Inst, Dept Med & Microbiol, Los Angeles, CA USA. [Kitchen, Scott G.; Zack, Jerome A.] Univ Calif Los Angeles, AIDS Inst, Dept Immunol & Mol Genet, Los Angeles, CA USA. [Klein, Florian] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany. [Klein, Florian] Univ Cologne, CMMC, D-50931 Cologne, Germany. [Kumar, Priti] Yale Univ, Sch Med, Infect Dis Internal Med, New Haven, CT USA. [Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02115 USA. [Poluektova, Larisa Y.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA. [Sanders-Beer, Brigitte E.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Shultz, Leonard D.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. RP Sanders-Beer, BE (reprint author), NIAID, BSP, DAIDS, NIH,DHHS, 5601 Fishers Lane,Room 9G58, Rockville, MD 20852 USA. EM sandersbe@niaid.nih.gov OI Burnett, John/0000-0002-8817-6064 FU National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272201100001G] FX The workshop was funded in whole with Federal funds from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272201100001G. NR 76 TC 3 Z9 3 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB 1 PY 2016 VL 32 IS 2 BP 109 EP 119 DI 10.1089/aid.2015.0258 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DD2NY UT WOS:000369760500001 PM 26670361 ER PT J AU Markmann, JF AF Markmann, J. F. TI Isolated Pancreatic Islet Transplantation: A Coming of Age SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE editorial; personal viewpoint; islet transplantation; islets of Langerhans; clinical trial C1 [Markmann, J. F.] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. EM jmarkmann@partners.org NR 7 TC 2 Z9 2 U1 0 U2 5 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 FEB PY 2016 VL 16 IS 2 BP 381 EP 382 DI 10.1111/ajt.13538 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA DD3WL UT WOS:000369853900002 PM 26595885 ER PT J AU Brennan, DC Kopetskie, HA Sayre, PH Alejandro, R Cagliero, E Shapiro, AMJ Goldstein, JS DesMarais, MR Booher, S Bianchine, PJ AF Brennan, D. C. Kopetskie, H. A. Sayre, P. H. Alejandro, R. Cagliero, E. Shapiro, A. M. J. Goldstein, J. S. DesMarais, M. R. Booher, S. Bianchine, P. J. TI Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Scope: clinical research; practice; Discipline: islet transplantation; Focus: clinical trial; immunosuppressive regimens ID IMPROVEMENT; OUTCOMES; DISEASE; TRIAL; BP AB We report the long-term follow-up of the efficacy and safety of islet transplantation in seven type 1 diabetic subjects from the United States enrolled in the multicenter international Edmonton Protocol who had persistent islet function after completion of the Edmonton Protocol. Subjects were followed up to 12 years with serial testing for sustained islet allograft function as measured by C-peptide. All seven subjects demonstrated continued islet function longer than a decade from the time of first islet transplantation. One subject remained insulin independent without the need for diabetic medications or supplemental transplants. One subject who was insulin-independent for over 8 years experienced graft failure 10.9 years after the first islet transplant. The remaining six subjects demonstrated continued islet function upon trial completion, although three had received a supplemental islet transplant each. At trial completion, five subjects were receiving insulin and two remained insulin independent, although one was treated with liraglutide. The median hemoglobin A(1c) was 6.3% (45mmol/mol). All subjects experienced progressive decline in the C-peptide/glucose ratio. No patients experienced severe hypoglycemia, opportunistic infection, or lymphoma. Thus, although the rate and duration of insulin independence was low, the Edmonton Protocol was safe in the long term. Alternative approaches to islet transplantation are under investigation. C1 [Brennan, D. C.] Washington Univ, Sch Med, St Louis, MO USA. [Kopetskie, H. A.] Rho Fed Syst Div, Chapel Hill, NC USA. [Sayre, P. H.; DesMarais, M. R.] Immune Tolerance Network, San Francisco, CA USA. [Alejandro, R.] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA. [Cagliero, E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Shapiro, A. M. J.] Univ Alberta, Edmonton, AB, Canada. [Goldstein, J. S.; Booher, S.; Bianchine, P. J.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Brennan, DC (reprint author), Washington Univ, Sch Med, St Louis, MO USA. EM dbrennan@dom.wustl.edu FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [NO1-AI-15416, HSN272200800029C]; Juvenile Diabetes Research Foundation FX Dr. Brennan is the guarantor of the work. The authors would like to thank the ITN040CT Trial Study Group and the investigators involved in the NIS01 trial. This research was performed as a project of the Immune Tolerance Network, an international clinical research consortium headquartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (award numbers NO1-AI-15416 and HSN272200800029C) and the Juvenile Diabetes Research Foundation. NR 16 TC 17 Z9 17 U1 3 U2 5 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 FEB PY 2016 VL 16 IS 2 BP 509 EP 517 DI 10.1111/ajt.13458 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA DD3WL UT WOS:000369853900016 PM 26433206 ER PT J AU Marino, J Paster, JT Trowell, A Maxwell, L Briggs, KH Bertorini, PC Benichou, G AF Marino, J. Paster, J. T. Trowell, A. Maxwell, L. Briggs, K. H. Bertorini, P. Crosby Benichou, G. TI B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE basic (laboratory) research; science; immunobiology; T cell biology; alloantigen; major histocompatibility complex (MHC); lymphocyte biology: activation ID DEFICIENT MICE; CHLAMYDIA-TRACHOMATIS; IMMUNOLOGICAL MEMORY; ALLOGRAFT-REJECTION; NONHUMAN-PRIMATES; GENERATION; TOLERANCE; INFECTION; THERAPY; CD4(+) AB Alloreactive memory T cells mediate accelerated allograft rejection and transplant tolerance resistance. Recent studies have shown that B cell deficient-MT mice fail to mount donor-specific memory T cell responses after transplantation. At the same time, other studies showed that pretransplant B cell depletion using rituximab (IgG1 anti-CD20 mAb) combined with cyclosporine A promoted the survival of islet allografts in monkeys. In this study, we investigated the effect of anti-CD20 antibody-mediated B cell depletion on the memory T cell alloresponse in mice. Wild-type and anti-OVA TCR transgenic mice were treated with an IgG2a anti-CD20 monoclonal antibody, which depleted nearly all B cells in the peripheral blood and secondary lymphoid organs but spared some B cells in the bone marrow. B cell depletion did not affect the direct alloresponse but resulted in a marked increase of indirect alloresponse after skin transplantation of naive mice. Furthermore, in allosensitized mice, anti-CD20 mAb treatment enhanced the reactivation of allospecific memory T cells and accelerated second set rejection of skin allografts. This suggests that the effect of anti-CD20 antibodies on alloimmunity and allograft rejection might vary upon the nature of the antibodies as well as the circumstances under which they are delivered. C1 [Benichou, G.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplant Sci, Boston, MA USA. [Benichou, G.] Harvard Univ, Sch Med, Boston, MA USA. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Transplant Sci, Boston, MA USA.; Benichou, G (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM gbenichou@partners.org FU NIH [R21AI100278, R03AI094235] FX This work was supported by grants from the NIH to Gilles Benichou, NIH R21AI100278 and R03AI094235. The anti-CD20 monoclonal antibody, 5D2, was a generous gift from Genentech Inc., South San Francisco, CA. NR 30 TC 4 Z9 4 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 FEB PY 2016 VL 16 IS 2 BP 672 EP 678 DI 10.1111/ajt.13483 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA DD3WL UT WOS:000369853900033 PM 26552037 ER PT J AU Koster, J AF Koester, Johannes TI Rust-Bio: a fast and safe bioinformatics library SO BIOINFORMATICS LA English DT Article ID SEQUENCE; STRINGS AB We present Rust-Bio, the first general purpose bioinformatics library for the innovative Rust programming language. Rust-Bio leverages the unique combination of speed, memory safety and high-level syntax offered by Rust to provide a fast and safe set of bioinformatics algorithms and data structures with a focus on sequence analysis. C1 [Koester, Johannes] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Funct Canc Epigenet,Dept Biostat & Computat B, Boston, MA 02215 USA. [Koester, Johannes] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Koster, J (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Funct Canc Epigenet,Dept Biostat & Computat B, Boston, MA 02215 USA.; Koster, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM koester@jimmy.harvard.edu NR 21 TC 0 Z9 0 U1 2 U2 2 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 FEB 1 PY 2016 VL 32 IS 3 BP 444 EP 446 DI 10.1093/bioinformatics/btv573 PG 3 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 DD8US UT WOS:000370203000017 PM 26446134 ER PT J AU Berber, R Skinner, J Board, T Kendoff, D Eskelinen, A Kwon, YM Padgett, DE Hart, A AF Berber, R. Skinner, J. Board, T. Kendoff, D. Eskelinen, A. Kwon, Y-M. Padgett, D. E. Hart, A. CA ISCCoMH TI International metal-on-metal multidisciplinary teams SO BONE & JOINT JOURNAL LA English DT Article ID TOTAL HIP-ARTHROPLASTY; ION LEVELS; BLOOD COBALT; PSEUDOTUMORS; REVISION; REPLACEMENT; PROSTHESES; IMPLANTS; FAILURE; COHORT AB Aims There are many guidelines that help direct the management of patients with metal-onmetal (MOM) hip arthroplasties. We have undertaken a study to compare the management of patients with MOM hip arthroplasties in different countries. Methods Six international tertiary referral orthopaedic centres were invited to participate by organising a multi-disciplinary team (MDT) meeting, consisting of two or more revision hip arthroplasty surgeons and a musculoskeletal radiologist. A full clinical dataset including history, blood tests and imaging for ten patients was sent to each unit, for discussion and treatment planning. Differences in the interpretation of findings, management decisions and rationale for decisions were compared using quantitative and qualitative methods. Results Overall agreement between the orthopaedic centres and the recommended treatment plans for the ten patients with MOM hip implants was moderate (kappa = 0.6). Full agreement was seen in a third of cases, however split decisions were also seen in a third of cases. Units differed in their interpretation of the significance of the investigation findings and put varying emphasis on serial changes, in the presence of symptoms. Discussion In conclusion, the management of raised or rising blood metal ions, cystic pseudotumours and peri-acetabular osteolysis led to inconsistency in the agreement between centres. Coordinated international guidance and MDT panel discussions are recommended to improve consensus in decision making. C1 [Skinner, J.; Board, T.; Kendoff, D.; Eskelinen, A.; Kwon, Y-M.; Padgett, D. E.; Hart, A.; ISCCoMH] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England. [Berber, R.] Royal Natl Orthopaed Hosp, Trauma & Orthopaed Surg, Brockley Hill, Stanmore HA7 4LP, Middx, England. [Hart, A.] Royal Natl Orthopaed Hosp, Orthopaed, Brockley Hill, Stanmore HA7 4LP, Middx, England. [Board, T.] Wrightington Hosp, Hall Lane, Wrightington WN6 9EP, Lancs, England. [Kendoff, D.] HELIOS Klinikum Berlin Buch, ENDOKLIN, Schwanebecker Chaussee 50, D-13125 Berlin, Germany. [Eskelinen, A.] COXA Hosp Joint Replacement, PL 652, Tampere 33101, Finland. [Kwon, Y-M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Padgett, D. E.] Hosp Special Surg, Adult Reconstruct & Joint Replacement Div, 535 E 70th St, New York, NY 10021 USA. RP Berber, R (reprint author), Royal Natl Orthopaed Hosp, Trauma & Orthopaed Surg, Brockley Hill, Stanmore HA7 4LP, Middx, England. EM reshidb@gmail.com RI Skytta, Eerik/L-2587-2016 OI Skytta, Eerik/0000-0002-5595-1001 NR 31 TC 1 Z9 1 U1 0 U2 2 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2049-4394 J9 BONE JOINT J JI Bone Joint J. PD FEB PY 2016 VL 98B IS 2 BP 179 EP 186 DI 10.1302/0301-620X.98B2.36201 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DD0TS UT WOS:000369633400007 PM 26850422 ER PT J AU Ahn, RS Moslehi, H Martin, MP Abad-Santos, M Bowcock, AM Carrington, M Liao, W AF Ahn, R. S. Moslehi, H. Martin, M. P. Abad-Santos, M. Bowcock, A. M. Carrington, M. Liao, W. TI Inhibitory KIR3DL1 alleles are associated with psoriasis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID HLA-B; SUBTYPES; DISTINCT; DISEASE C1 [Ahn, R. S.; Moslehi, H.; Abad-Santos, M.; Liao, W.] Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Box 0808, San Francisco, CA 94143 USA. [Martin, M. P.; Carrington, M.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. [Martin, M. P.; Carrington, M.] Massachusetts Gen Hosp, MIT, Ragon Inst, Cambridge, MA USA. [Martin, M. P.; Carrington, M.] Harvard Univ, Cambridge, MA 02138 USA. [Bowcock, A. M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. RP Ahn, RS (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St,Box 0808, San Francisco, CA 94143 USA. EM richard.ahn@ucsf.edu OI Ahn, Richard/0000-0002-9698-2752; Bowcock, Anne/0000-0001-8691-9090 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; NIAMS NIH HHS [R01 AR050266, 2R01AR050266, K08 AR057763, K08AR057763, R01 AR065174, R01AR065174, T32 AR007175]; PHS HHS [HHSN261200800001E] NR 15 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD FEB PY 2016 VL 174 IS 2 BP 449 EP 451 DI 10.1111/bjd.14081 PG 3 WC Dermatology SC Dermatology GA DD6DO UT WOS:000370014600044 PM 26286807 ER PT J AU Trief, D Gray, ST Jakobiec, FA Durand, ML Fay, A Freitag, SK Lee, NG Lefebvre, DR Holbrook, E Bleier, B Sadow, P Rashid, A Chhabra, N Yoon, MK AF Trief, Danielle Gray, Stacey T. Jakobiec, Frederick A. Durand, Marlene L. Fay, Aaron Freitag, Suzanne K. Lee, N. Grace Lefebvre, Daniel R. Holbrook, Eric Bleier, Benjamin Sadow, Peter Rashid, Alia Chhabra, Nipun Yoon, Michael K. TI Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Infection; Orbit ID CEREBRAL MUCORMYCOSIS; IMMUNOCOMPETENT PATIENTS; RHINOSINUSITIS; ZYGOMYCOSIS; SURVIVAL; PATIENT; EXPERIENCE; OUTCOMES AB Background/aims Invasive fungal infections of the head and neck are rare life-threatening infections where prompt diagnosis and intervention is critical for survival. The aim of this study is to determine the clinical characteristics and outcomes of invasive fungal disease of the sinus and orbit, and to compare mucormycosis and Aspergillus infection. Methods A retrospective review was conducted from a single tertiary care eye and ear hospital over 20years (1994-2014). Twenty-four patients with a confirmed pathological diagnosis of invasive fungal disease of the sinus and/or orbit were identified and their medical records were reviewed. The main outcome measures were type of fungus, location of disease, mortality and visual outcome. Results Patients with orbital involvement had a higher mortality and higher likelihood of mucormycosis infection compared with those with sinus-only disease (78.6% vs 20%, p=0.01; 86% vs 30%, p=0.01, respectively). Patients with mucormycosis had a higher mortality (71%) than patients with Aspergillus (29%); however, this was not statistically significant (p=0.16). All patients with orbital involvement and/or mucormycosis infections were immunosuppressed or had inadequately controlled diabetes, and had a cranial neuropathy or ocular motility dysfunction. All five post-transplant patients with orbital infections died, while the two transplant patients with sinus infections survived. Conclusions Patients with orbital fungal infections are more likely to be infected with mucormycosis compared with Aspergillus and have a higher mortality compared with infections sparing the orbit. History of transplant portends a dismal prognosis in orbital infections. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality. C1 [Trief, Danielle; Gray, Stacey T.; Jakobiec, Frederick A.; Durand, Marlene L.; Fay, Aaron; Freitag, Suzanne K.; Lee, N. Grace; Lefebvre, Daniel R.; Holbrook, Eric; Bleier, Benjamin; Sadow, Peter; Rashid, Alia; Chhabra, Nipun; Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Trief, Danielle; Jakobiec, Frederick A.; Fay, Aaron; Freitag, Suzanne K.; Lee, N. Grace; Lefebvre, Daniel R.; Rashid, Alia; Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Gray, Stacey T.; Holbrook, Eric; Bleier, Benjamin; Sadow, Peter; Chhabra, Nipun] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. RP Yoon, MK (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, 10th Floor,243 Charles St, Boston, MA 02114 USA. EM Michael_Yoon@meei.harvard.edu NR 25 TC 5 Z9 5 U1 1 U2 3 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 FEB PY 2016 VL 100 IS 2 BP 184 EP 188 DI 10.1136/bjophthalmol-2015-306945 PG 5 WC Ophthalmology SC Ophthalmology GA DD5VP UT WOS:000369993100008 PM 26112869 ER PT J AU Gloy, VL Briel, M Bhatt, DL Kashyap, SR Schauer, PR Mingrone, G Bucher, HC Nordmann, AJ AF Gloy, Viktoria L. Briel, Matthias Bhatt, Deepak L. Kashyap, Sangeeta R. Schauer, Philip R. Mingrone, Geltrude Bucher, Heiner C. Nordmann, Alain J. TI Bariatric surgery versus non-surgical treatment for obesity SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Editorial Material C1 [Gloy, Viktoria L.; Briel, Matthias; Bucher, Heiner C.; Nordmann, Alain J.] Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, Hebelstr 10, CH-4031 Basel, Switzerland. [Briel, Matthias] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, 75 Francis St, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Kashyap, Sangeeta R.] Cleveland Clin, Inst Endocrinol, Cleveland, OH 44106 USA. [Schauer, Philip R.] Cleveland Clin, Bariatr & Metab Inst, Cleveland, OH 44106 USA. [Mingrone, Geltrude] Univ Cattolica S Cuore, Dept Internal Med, Rome, Italy. RP Gloy, VL (reprint author), Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, Hebelstr 10, CH-4031 Basel, Switzerland. EM Viktoria.Gloy@usb.ch NR 0 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 2016 VL 50 IS 4 BP 246 EP 246 DI 10.1136/bjsports-2014-f5934rep PG 1 WC Sport Sciences SC Sport Sciences GA DD5ZR UT WOS:000370004000015 PM 26834208 ER PT J AU Hakimi, AA Ostrovnaya, I Jacobsen, A Susztak, K Coleman, JA Russo, P Winer, AG Mano, R Sankin, AI Motzer, RJ Voss, MH Offit, K Purdue, M Pomerantz, M Freedman, M Choueiri, TK Hsieh, JJ Klein, RJ AF Hakimi, A. Ari Ostrovnaya, Irina Jacobsen, Anders Susztak, Katalin Coleman, Jonathan A. Russo, Paul Winer, Andrew G. Mano, Roy Sankin, Alexander I. Motzer, Robert J. Voss, Martin H. Offit, Kenneth Purdue, Mark Pomerantz, Mark Freedman, Matthew Choueiri, Toni K. Hsieh, James J. Klein, Robert J. TI Validation and genomic interrogation of the MET variant rs11762213 as a predictor of adverse outcomes in clear cell renal cell carcinoma SO CANCER LA English DT Article DE biomarker; MET oncogene; renal cell carcinoma; The Cancer Genome Atlas (TCGA); variant ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CANCER-RISK; GROWTH; ASSOCIATION; METHYLATION; RECURRENCE; ACCURACY; SURVIVAL; PATHWAY; GENES AB BACKGROUNDThe exonic single-nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). This finding was validated with The Cancer Genome Atlas (TCGA) cohort, and the biologic implications were explored. METHODSThe genotype status for rs11762213 was available for 272 patients. Paired tumor-normal data, genomic data, and clinical information were acquired from ccRCC TCGA data sets. Cancer-specific survival (CSS) was analyzed with the competing risk method, and Cox proportional hazards regression was used for the analysis of the time to recurrence (TTR). Multivariate competing risk models were fitted to adjust for the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score. RESULTSThe variant allele of rs11762213 was detected in 10.3% of the cohort. After adjustments for the SSIGN score, the risk allele remained a significant predictor for adverse CSS (hazard ratio [HR], 3.88; 95% confidence interval [CI], 1.99-7.56; P<.0001) and for TTR (OR, 2.97; 95% CI, 1.43-6.2; P=.003). The mapping of rs11762213 to regulatory regions within the genome suggested that it might affect a DNA enhancer region. RNA and protein sequencing data for MET did not reveal differences in steady-state expression with stratification by risk allele. CONCLUSIONSThe exonic MET variant rs11762213 is an independent predictor of adverse CSS and TTR in ccRCC and should be integrated into clinical practice for prognostic stratification. Genomic analysis suggests that the single-nucleotide polymorphism may affect an enhancer region located in the coding region of MET. Further biological mechanistic interrogation is currently underway. Cancer 2016;122:402-410. (c) 2015 American Cancer Society. C1 [Hakimi, A. Ari; Ostrovnaya, Irina; Jacobsen, Anders; Coleman, Jonathan A.; Russo, Paul; Winer, Andrew G.; Mano, Roy; Sankin, Alexander I.; Motzer, Robert J.; Voss, Martin H.; Offit, Kenneth; Hsieh, James J.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Susztak, Katalin] Univ Penn, Philadelphia, PA 19104 USA. [Purdue, Mark] NCI, Bethesda, MD 20892 USA. [Pomerantz, Mark; Freedman, Matthew; Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Klein, Robert J.] Mt Sinai Sch Med, New York, NY USA. RP Hakimi, AA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, 353 East 68th St, New York, NY 10065 USA. EM hakimia@mskcc.org OI Mano, Roy/0000-0003-3855-0211; Jacobsen, Anders/0000-0001-6847-4980; Coleman, Jonathan/0000-0002-6428-7835 FU Paula Moss Trust for Research Into the Cure and Treatment of Kidney Cancer; Sidney Kimmel Center for Prostate and Urologic Cancers; Prostate Cancer Foundation; National Cancer Institute [T32 CA082088-12]; Stephen P. Hanson Family Fund Fellowship in Kidney Cancer; National Institutes of Health [U01 HG007033, R03 CA165082]; Trust Family Fund for Kidney Cancer Research; Dana-Farber Cancer Institute; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Carmel Family Cancer Research Fund; Michael Brigham Fund for Kidney Cancer Research FX This work was supported by the Paula Moss Trust for Research Into the Cure and Treatment of Kidney Cancer (to James J. Hsieh), the Sidney Kimmel Center for Prostate and Urologic Cancers, David H. Koch through the Prostate Cancer Foundation, the National Cancer Institute (training grant T32 CA082088-12 to A. Ari Hakimi, Andrew G. Winer, and Alexander I. Sankin), the Stephen P. Hanson Family Fund Fellowship in Kidney Cancer (to A. Ari Hakimi, Andrew G. Winer, and Alexander I. Sankin), the National Institutes of Health (U01 HG007033 and R03 CA165082 to Robert J. Klein), the Trust Family and Michael Brigham Funds for Kidney Cancer Research (to Toni K. Choueiri), the Dana-Farber Cancer Institute (to Toni K. Choueiri), the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, and the Carmel Family Cancer Research Fund (to Kenneth Offit). NR 30 TC 5 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD FEB 1 PY 2016 VL 122 IS 3 BP 402 EP 410 DI 10.1002/cncr.29765 PG 9 WC Oncology SC Oncology GA DC9HN UT WOS:000369532100013 PM 26505625 ER PT J AU Kaymakcalan, MD Xie, WL Albiges, L North, SA Kollmannsberger, CK Smoragiewicz, M Kroeger, N Wells, JC Rha, SY Lee, JL McKay, RR Fay, AP De Velasco, G Heng, DYC Choueiri, TK AF Kaymakcalan, Marina D. Xie, Wanling Albiges, Laurence North, Scott A. Kollmannsberger, Christian K. Smoragiewicz, Martin Kroeger, Nils Wells, J. Connor Rha, Sun-Young Lee, Jae Lyun McKay, Rana R. Fay, Andre P. De Velasco, Guillermo Heng, Daniel Y. C. Choueiri, Toni K. TI Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium SO CANCER LA English DT Article DE International Metastatic Renal Cell Carcinoma Database Consortium (IMDC); model; renal cell carcinoma; risk factors; toxicity; treatment discontinuation; VEGF-targeted therapies ID ANGIOGENESIS INHIBITOR THERAPIES; TREATMENT PATTERNS; PHASE-III; CLINICAL-PRACTICE; INTERFERON-ALPHA; COMPETING RISKS; OLDER-ADULTS; SUNITINIB; CANCER; SAFETY AB BACKGROUNDVascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies. METHODSThe baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium. A competing risk regression model was used to identify risk factors for TrTD, and it accounted for other causes as competing risks. RESULTSOverall, 198 (23.8%) experienced TrTD. Sunitinib was the most common VEGF-targeted therapy (77%), and it was followed by sorafenib (18.4%). The median time on therapy was 7.1 months for all patients and 4.4 months for patients with TrTD. The most common toxicities leading to TrTD included fatigue, diarrhea, and mucositis. In a multivariate analysis, significant predictors for TrTD were a baseline age 60 years, a glomerular filtration rate (GFR) <30 mL/min/1.73 m(2), a single metastatic site, and a sodium level <135 mmol/L. A risk group model was developed that used the number of patient risk factors to predict the risk of TrTD. CONCLUSIONSIn the largest series to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors for TrTD in mRCC patients receiving VEGF-targeted therapy. Based on the number of risk factors present, a model for predicting TrTD was built to be used as a tool for toxicity monitoring in clinical practice. Cancer 2016;122:411-419. (c) 2015 American Cancer Society. C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Kaymakcalan, Marina D.; Xie, Wanling; Albiges, Laurence; McKay, Rana R.; Fay, Andre P.; De Velasco, Guillermo; Choueiri, Toni K.] Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. [Kaymakcalan, Marina D.; Xie, Wanling; Albiges, Laurence; McKay, Rana R.; Fay, Andre P.; De Velasco, Guillermo; Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [North, Scott A.; Heng, Daniel Y. C.] Cross Canc Inst, Dept Med, Edmonton, AB T6G 1Z2, Canada. [Kollmannsberger, Christian K.; Smoragiewicz, Martin] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Kroeger, Nils; Wells, J. Connor] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Rha, Sun-Young] Yonsei Univ, Coll Med, Seoul, South Korea. [Lee, Jae Lyun] Asan Med Ctr, Seoul, South Korea. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02215 USA.; Choueiri, TK (reprint author), Harvard Univ, Sch Med, 450 Brookline Ave, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu FU Trust Family; Loker Pinard; Michael Brigham Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute; Dana-Farber/Harvard Cancer Center Kidney Cancer Program; Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence [P50 CA101942-01] FX This study was funded by the Trust Family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research at the Dana-Farber Cancer Institute (to Toni K. Choueiri), the Dana-Farber/Harvard Cancer Center Kidney Cancer Program, and the Dana-Farber/Harvard Cancer Center Kidney Cancer Specialized Program of Research Excellence (P50 CA101942-01). The funding sources had no role in the study design, analysis, interpretation, or writing of the article. NR 47 TC 2 Z9 2 U1 0 U2 1 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 FEB 1 PY 2016 VL 122 IS 3 BP 411 EP 419 DI 10.1002/cncr.29773 PG 9 WC Oncology SC Oncology GA DC9HN UT WOS:000369532100014 PM 26540173 ER PT J AU Hassett, MJ Schymura, MJ Chen, K Boscoe, FP Gesten, FC Schrag, D AF Hassett, Michael J. Schymura, Maria J. Chen, Kun Boscoe, Francis P. Gesten, Foster C. Schrag, Deborah TI Variation in breast cancer care quality in New York and California based on race/ethnicity and Medicaid enrollment SO CANCER LA English DT Article DE breast cancer; disparities; Medicaid; quality ID ADJUVANT THERAPY; AFRICAN-AMERICAN; REGISTRY DATA; WOMEN; DISPARITIES; SURVIVAL; OPPORTUNITIES; POPULATION; PHYSICIANS; ETHNICITY AB BACKGROUNDRacial/ethnic and socioeconomic disparities persist in part because our current understanding of the care provided to minority and disadvantaged populations is limited. The authors evaluated the quality of breast cancer care in 2 large states to understand the disparities experienced by African Americans, Hispanics, Asian/Pacific Islanders (APIs), and Medicaid enrollees and to prioritize remediation strategies. METHODSStatewide cancer registry data for 80,436 women in New York and 121,233 women in California who were diagnosed during 2004 to 2009 with stage 0 through III breast cancer were used to assess underuse and overuse of surgery, radiation, chemotherapy, and hormone therapy based on 34 quality measures. Concordance values were compared across racial/ethnic and Medicaid-enrollment groups. Multivariable models were used to quantify disparities across groups for each treatment in each state. RESULTSOverall concordance was 76% for underuse measures and 87% for overuse measures. The proportions of patients who received care concordant with all relevant measures were 35% in New York and 33% in California. Compared with whites, African Americans were less likely to receive recommended surgery, radiation, and hormone therapy; Hispanics and APIs were usually more likely to receive recommended chemotherapy. Across states, the same racial/ethnic groups did not always experience the same disparities. Medicaid enrollment was associated with decreased likelihood of receiving all recommended treatments, except chemotherapy, in both states. Overuse was evident for hormone therapy and axillary surgery but was not associated with race/ethnicity or Medicaid enrollment. CONCLUSIONSPatient-level measures of quality identify substantial problems with care quality and meaningful disparities. Remediating these problems will require prioritizing low-performing measures and targeting high-risk populations, possibly in different ways for different regions. Cancer 2016;122:420-431. (c) 2015 American Cancer Society. C1 [Hassett, Michael J.; Chen, Kun; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02215 USA. [Hassett, Michael J.; Schrag, Deborah] Harvard Univ, Sch Med, Boston, MA USA. [Schymura, Maria J.; Boscoe, Francis P.] New York State Dept Hlth, Canc Registry, Albany, NY USA. [Gesten, Foster C.] New York State Dept Hlth, Off Qual & Patient Safety, Albany, NY USA. RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM michael_hassett@dfci.harvard.edu FU Susan G. Komen for the Cure Career Catalyst Award; National Cancer Institute [R01CA131847] FX This work was supported by a Susan G. Komen for the Cure Career Catalyst Award to Dr. Hassett and by the National Cancer Institute (grant R01CA131847 to Dr. Schrag). NR 38 TC 2 Z9 2 U1 1 U2 1 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 FEB 1 PY 2016 VL 122 IS 3 BP 420 EP 431 DI 10.1002/cncr.29777 PG 12 WC Oncology SC Oncology GA DC9HN UT WOS:000369532100015 PM 26536043 ER PT J AU Tevaarwerk, AJ Lee, JW Terhaar, A Sesto, ME Smith, ML Cleeland, CS Fisch, MJ AF Tevaarwerk, Amye J. Lee, Ju-Whei Terhaar, Abigail Sesto, Mary E. Smith, Mary Lou Cleeland, Charles S. Fisch, Michael J. TI Working after a metastatic cancer diagnosis: Factors affecting employment in the metastatic setting from ECOG-ACRIN's Symptom Outcomes and Practice Patterns study SO CANCER LA English DT Article DE advanced cancer; employment; metastatic cancer; symptom burden; treatment toxicity ID BREAST-CANCER; SURVIVORS; IMPACT; COHORT; RETURN; STATISTICS; EXPERIENCE; MANAGEMENT; PATIENT; ABILITY AB BACKGROUNDImproved survival for individuals with metastatic cancer accentuates the importance of employment for cancer survivors. A better understanding of how metastatic cancer affects employment is a necessary step toward the development of tools for assisting survivors in this important realm. METHODSThe ECOG-ACRIN Symptom Outcomes and Practice Patterns study was analyzed to investigate what factors were associated with the employment of 680 metastatic cancer patients. Univariate and multivariate logistic regression analyses were conducted to compare patients stably working with patients no longer working. RESULTSThere were 668 metastatic working-age participants in the analysis: 236 (35%) worked full- or part-time, whereas 302 (45%) had stopped working because of illness. Overall, 58% reported some change in employment due to illness. A better performance status and non-Hispanic white ethnicity/race were significantly associated with continuing to work despite a metastatic cancer diagnosis in the multivariate analysis. The disease type, time since metastatic diagnosis, number of metastatic sites, location of metastatic disease, and treatment status had no significant impact. Among the potentially modifiable factors, receiving hormonal treatment (if a viable option) and decreasing symptom interference were associated with continuing to work. CONCLUSIONSA significant percentage of the metastatic patients remained employed; increased symptom burden was associated with a change to no longer working. Modifiable factors resulting in work interference should be minimized so that patients with metastatic disease may continue working if this is desired. Improvements in symptom control and strategies developed to help address workplace difficulties have promise for improving this aspect of survivorship. Cancer 2016;122:438-446. (c) 2015 American Cancer Society. C1 [Tevaarwerk, Amye J.; Terhaar, Abigail; Sesto, Mary E.] Univ Wisconsin, 1111 Highland Ave,WIMR 6037, Madison, WI 53705 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Mary Lou] Res Advocacy Network, Houston, TX USA. [Cleeland, Charles S.; Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Tevaarwerk, AJ (reprint author), Univ Wisconsin, 1111 Highland Ave,WIMR 6037, Madison, WI 53705 USA. EM at4@medicine.wisc.edu FU Clinical and Translational Science Award program through the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000427, KL2TR000428]; University of Wisconsin-Madison Graduate School; Public Health Service [CA189828, CA180799, CA180858]; National Cancer Institute, National Institutes of Health and the Department of Health and Human Services FX Amye J. Tevaarwerk was supported by the Clinical and Translational Science Award program through the National Center for Advancing Translational Sciences of the National Institutes of Health (grants UL1TR000427 and KL2TR000428). Abigail Terhaar received support from the University of Wisconsin-Madison Graduate School. 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 Grants CA189828, CA180799, CA180858, 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. NR 40 TC 1 Z9 1 U1 3 U2 5 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 FEB 1 PY 2016 VL 122 IS 3 BP 438 EP 446 DI 10.1002/cncr.29656 PG 9 WC Oncology SC Oncology GA DC9HN UT WOS:000369532100017 PM 26687819 ER PT J AU Li, PX Wong, YN Armstrong, K Haas, N Subedi, P Davis-Cerone, M Doshi, JA AF Li, Pengxiang Wong, Yu-Ning Armstrong, Katrina Haas, Naomi Subedi, Prasun Davis-Cerone, Margaret Doshi, Jalpa A. TI Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras SO CANCER MEDICINE LA English DT Article DE Advanced renal cell carcinoma; metastatic kidney cancer; population-based study; survival; targeted therapies ID RESISTANT PROSTATE-CANCER; CYTOREDUCTIVE NEPHRECTOMY; MITOXANTRONE; PREDNISONE; MANAGEMENT; DOCETAXEL AB Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N=6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N=7231, hazard ratio (HR) for all-cause death: 0.86, P<0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P=0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z=4.31; P<0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies. C1 [Li, Pengxiang; Doshi, Jalpa A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Li, Pengxiang; Doshi, Jalpa A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Wong, Yu-Ning] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Armstrong, Katrina] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Haas, Naomi] Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA. [Subedi, Prasun; Davis-Cerone, Margaret] Pfizer Inc, New York, NY USA. RP Doshi, JA (reprint author), 423 Guardian Dr,1223 Blockley Hall, Philadelphia, PA 19104 USA. EM jdoshi@mail.med.upenn.edu FU Pfizer Inc. FX This research was funded by a grant from Pfizer Inc. NR 26 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2045-7634 J9 CANCER MED-US JI Cancer Med. PD FEB PY 2016 VL 5 IS 2 BP 169 EP 181 DI 10.1002/cam4.574 PG 13 WC Oncology SC Oncology GA DD2HV UT WOS:000369744200004 PM 26645975 ER PT J AU Jones, SMW Guthrie, KA LaCroix, AZ Sternfeld, B Landis, CA Reed, SD Dunn, A Caan, B Cohen, LS Hunt, J Newton, KM AF Jones, Salene M. W. Guthrie, Katherine A. LaCroix, Andrea Z. Sternfeld, Barbara Landis, Carol A. Reed, Susan D. Dunn, Andrea Caan, Bette Cohen, Lee S. Hunt, Julie Newton, Katherine M. TI Is heart rate variability associated with frequency and intensity of vasomotor symptoms among healthy perimenopausal and postmenopausal women? SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Heart rate variability; Vagal tone; Hot flashes; Parasympathetic nervous system; Vasomotor symptoms ID RANDOMIZED CONTROLLED-TRIAL; CARDIAC VAGAL CONTROL; HOT FLASHES; MENOPAUSAL SYMPTOMS; EFFICACY; STRESS; DESIGN; SLEEP AB Research has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function. Women (n = 282) were recruited from three American states for a clinical trial of yoga, exercise, and omega-3 fatty acid supplements for VMS. To be eligible, women had to report at least 14 VMS per week, with some being moderate to severe. Sitting electrocardiograms were recorded for 15 min using Holter monitors at both baseline and 12-week follow-up. Time and frequency domain HRV measures were calculated. Women completed daily diary measures of VMS frequency and intensity for 2 weeks at baseline and for 1 week at the follow-up assessment 12 weeks later. Multivariable linear regression was used to assess the relationship between VMS and baseline HRV measures and to compare change in HRV with change in VMS over the 12 weeks. Baseline HRV was not associated with either VMS frequency or intensity at baseline. Change in HRV was not associated with change in VMS frequency or intensity across the follow-up. Heart rate variability (HRV) was not associated with basal VMS frequency or intensity in perimenopausal and postmenopausal women experiencing high levels of VMS. Autonomic function may be associated with the onset or presence of VMS, but not with the number or intensity of these symptoms. C1 [Jones, Salene M. W.; Newton, Katherine M.] Grp Hlth Res Inst, 1730 Minor Ave, Seattle, WA 98101 USA. [Guthrie, Katherine A.; Hunt, Julie] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, San Diego, CA 92103 USA. [Sternfeld, Barbara; Dunn, Andrea; Caan, Bette] Kaiser Permanente Div Res, Oakland, CA USA. [Landis, Carol A.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Reed, Susan D.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Jones, SMW (reprint author), Grp Hlth Res Inst, 1730 Minor Ave, Seattle, WA 98101 USA. EM wu.582@osu.edu OI Jones, Salene/0000-0003-2140-5798 FU NIA; Eunice Kennedy Shriver National Institute of Child Health and Development; National Center for Complementary and Alternative Medicine; Office of Research and Women's Health; NIA [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; National Institute on Aging [AG032682-02S1, T32 AG027677]; Indiana Clinical and Translational Sciences Institute - National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award [UL1 RR025761] FX This study was supported by a cooperative agreement issued by the NIA, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, and the Office of Research and Women's Health, and by NIA Grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700. The study was also funded in part by an administrative supplement to the Group Health Research Institute site AG032682-02S1 from the National Institute on Aging. At the Indiana University site, the project was funded in part with support from the Indiana Clinical and Translational Sciences Institute, funded in part by Grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award. The omega-3 study supplement (omega-3, n-3, or polyunsaturated fatty acids) was manufactured as eicosapentaenoic acid and donated, with matching placebo, by Nordic Naturals (Watsonville, CA). Clinical trial registration: NCT01178892 (ClinicalTrials.gov). Dr. Jones was funded by the National Institute on Aging (T32 AG027677). NR 23 TC 0 Z9 1 U1 2 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 EI 1619-1560 J9 CLIN AUTON RES JI Clin. Auton. Res. PD FEB PY 2016 VL 26 IS 1 BP 7 EP 13 DI 10.1007/s10286-015-0322-x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD5WL UT WOS:000369995300002 PM 26691637 ER PT J AU Wecht, JM Weir, JP Martinez, S Eraifej, M Bauman, WA AF Wecht, Jill M. Weir, Joseph P. Martinez, Stephanie Eraifej, Mastanna Bauman, William A. TI Orthostatic hypotension and orthostatic hypertension in American veterans SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Orthostatic hypotension; Orthostatic hypertension; American veterans; Prevalence; Prescription medications; Age ID CARDIOVASCULAR RISK-FACTOR; MALMO PREVENTIVE PROJECT; BLOOD-PRESSURE RESPONSE; ELDERLY HYPERTENSIVES; ATHEROSCLEROSIS RISK; EXTREME DIPPERS; MORTALITY; DISEASE; PREVALENCE; ADULTS AB Abnormal blood pressure (BP) response to orthostatic maneuvers may predict adverse health outcomes. Orthostatic hypotension (OH) is defined as a fall in BP of a parts per thousand yen20/10 mmHg, and orthostatic hypertension (OHTN) is defined as an increase in systolic BP (SBP) of a parts per thousand yen20 mmHg, with standing. Herein, we document the prevalence of OH and OHTN in American veterans. The influence of demographic characteristics, life habits, co-incident medical conditions, and prescription medication use on these prevalence rates and associations between abnormal orthostatic BP responses and severity of self-reported symptoms of fatigue, dizziness, trouble concentrating, and head and neck discomfort were determined. 286 veterans participated; 14 % were classified with OH, 22 % with OHTN, and 64 % with normal BP responses to standing (reference group). An increased prevalence of the diagnosis of diabetes mellitus (27 %) and hypertension (63 %) was noted, which did not differ by orthostatic BP classification. Veterans with OH were older than the reference group and were prescribed more antihypertensive medications than the reference and OHTN groups. While the prevalence of OH increased with age, the prevalence of OHTN was comparable in young (20-30 years) and old (70+ years) veterans (17 vs. 19 %, respectively). The severity of fatigue and dizziness was increased in veterans with OH and OHTN compared to the reference group. These data suggest a relatively high prevalence of OH and OHTN, which is associated with increased self-reported severity of fatigue and dizziness in American veterans, findings which may adversely impact long-term health outcomes. C1 [Wecht, Jill M.; Martinez, Stephanie; Eraifej, Mastanna; Bauman, William A.] James J Peters VA Med Ctr, Med Consequences Spinal Cord Injury, Ctr Excellence, Rm 7A-13,130 West Kingsbridge Rd, Bronx, NY 10468 USA. [Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Wecht, Jill M.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Wecht, Jill M.; Bauman, William A.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. [Weir, Joseph P.] Univ Kansas, Dept Hlth Sport & Exercise Sci, Lawrence, KS 66045 USA. RP Wecht, JM (reprint author), James J Peters VA Med Ctr, Med Consequences Spinal Cord Injury, Ctr Excellence, Rm 7A-13,130 West Kingsbridge Rd, Bronx, NY 10468 USA.; Wecht, JM (reprint author), Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.; Wecht, JM (reprint author), Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA. EM JM.Wecht@va.gov FU Veterans Affairs Rehabilitation Research and Development Service: Center of Excellence for the Medical Consequences of Spinal Cord Injury [B9212C] FX This research was supported by the Veterans Affairs Rehabilitation Research and Development Service: Center of Excellence for the Medical Consequences of Spinal Cord Injury (Grant # B9212C). NR 51 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 EI 1619-1560 J9 CLIN AUTON RES JI Clin. Auton. Res. PD FEB PY 2016 VL 26 IS 1 BP 49 EP 58 DI 10.1007/s10286-015-0328-4 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DD5WL UT WOS:000369995300007 PM 26695397 ER PT J AU Wolpert, H Kavanagh, M Atakov-Castillo, A Steil, GM AF Wolpert, H. Kavanagh, M. Atakov-Castillo, A. Steil, G. M. TI The artificial pancreas: evaluating risk of hypoglycaemia following errors that can be expected with prolonged at-home use SO DIABETIC MEDICINE LA English DT Article ID LOOP INSULIN DELIVERY; TIGHT GLYCEMIC CONTROL; GLUCOSE CONTROL; RANDOMIZED CROSSOVER; TYPE-1; MANAGEMENT; SUSPENSION; SAFETY; CARE AB Aims Artificial pancreas systems show benefit in closely monitored at-home studies, but may not have sufficient power to assess safety during infrequent, but expected, system or user errors. The aim of this study was to assess the safety of an artificial pancreas system emulating the beta-cell when the glucose value used for control is improperly calibrated and participants forget to administer pre-meal insulin boluses. Methods Artificial pancreas control was performed in a clinic research centre on three separate occasions each lasting from 10 p.m. to 2 p.m. Sensor glucose values normally used for artificial pancreas control were replaced with scaled blood glucose values calculated to be 20% lower than, equal to or 33% higher than the true blood glucose. Safe control was defined as blood glucose between 3.9 and 8.3 mmol/l. Results Artificial pancreas control resulted in fasting scaled blood glucose values not different from target (6.67 mmol/l) at any scaling factor. Meal control with scaled blood glucose 33% higher than blood glucose resulted in supplemental carbohydrate to prevent hypoglycaemia in four of six participants during breakfast, and one participant during the night. In all instances, scaled blood glucose reported blood glucose as safe. Conclusions Outpatient trials evaluating artificial pancreas performance based on sensor glucose may not detect hypoglycaemia when sensor glucose reads higher than blood glucose. Because these errors are expected to occur, in-hospital artificial pancreas studies using supplemental carbohydrate in anticipation of hypoglycaemia, which allow safety to be assessed in a controlled non-significant risk environment should be considered as an alternative. Inpatient studies provide a definitive alternative to model-based computer simulations and can be conducted in parallel with closely monitored outpatient artificial pancreas studies used to assess benefit. C1 [Wolpert, H.; Kavanagh, M.; Atakov-Castillo, A.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Steil, G. M.] Boston Childrens Hosp, Div Med Crit Care, Boston, MA USA. RP Steil, GM (reprint author), Boston Childrens Hosp, Div Med Crit Care, Boston, MA USA. EM garry.steil@childrens.harvard.edu FU Juvenile Diabetes Research Foundation FX Funding was received from the Juvenile Diabetes Research Foundation. NR 28 TC 1 Z9 1 U1 2 U2 2 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 FEB PY 2016 VL 33 IS 2 BP 235 EP 242 DI 10.1111/dme.12823 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD8FU UT WOS:000370161800014 PM 26036309 ER PT J AU Greffier, J Macri, F Larbi, A Fernandez, A Pereira, F Mekkaoui, C Beregi, JP AF Greffier, J. Macri, F. Larbi, A. Fernandez, A. Pereira, F. Mekkaoui, C. Beregi, J. -P. TI Dose reduction with iterative reconstruction in multi-detector CT: What is the impact on deformation of circular structures in phantom study? SO DIAGNOSTIC AND INTERVENTIONAL IMAGING LA English DT Article DE Computed tomography; Iterative reconstruction; Image quality; Deformation of circular structures; Noise power spectrum ID FILTERED BACK-PROJECTION; IMAGE QUALITY; COMPUTED-TOMOGRAPHY; DIFFERENT MANUFACTURERS; TO-NOISE; OPTIMIZATION; MDCT; ANGIOGRAPHY; PERFORMANCE; ALGORITHMS AB Objectives: To evaluate the distortion of circular structures induced by the increased image noise related to dose reduction and to assess the effect of iterative reconstruction (IR). Methods: MDCT acquisitions were performed with 120 kVp for 200/100/60/40/20 mAs with 100%/50%/30%/20%/10% of dose. Raw data were reconstructed by filtered back projection (FBP) and with two IR strengths. Image quality indices referred to water and acrylic were measured on a quality image phantom. Areas, perimeters, circularity were measured on the circular inserts of 4.8, 7.9 and 11.1 mm on a morphological phantom. Results: Dose reduction resulted in increased image noise and in decreased signal to noise ratio and contrast to noise ratio. IR improved these indices for the same dose without affecting the signal (number CT) and spatial resolution (modulation transfer function). The values of area, perimeter and circularity were altered compared to the actual value and the inserts were visually deformed with the dose reduction. IR improved these three parameters. Image quality indices, areas, perimeters and circularity of inserts were similar between the acquisition at 100% of the dose in FBP, 50% in strength-3 and 30% in strength-5 with different curves of noise power spectrum. Conclusion: IR associated to 70% of dose reduction modifies the images smooth (NPS) but maintains adequate image quality indices without causing distortions of circular structures. (C) 2015 Editions francaises de radiologie. Published by Elsevier Masson SAS. All rights reserved. C1 [Greffier, J.; Macri, F.; Larbi, A.; Fernandez, A.; Pereira, F.; Mekkaoui, C.; Beregi, J. -P.] Univ Nimes Hosp, Dept Radiol, EA 2415, Blvd Prof Robert Debre, F-30029 Nimes, France. [Mekkaoui, C.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA USA. [Mekkaoui, C.] Harvard Univ, Sch Med, Boston, MA USA. RP Greffier, J (reprint author), Univ Nimes Hosp, Dept Radiol, EA 2415, Blvd Prof Robert Debre, F-30029 Nimes, France. EM joel.greffier@chu-nimes.fr OI Pereira, Fabricio Ramos Silvestre/0000-0003-3317-8756; Greffier, Joel/0000-0002-1735-5129 NR 32 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 2211-5684 J9 DIAGN INTERV IMAG JI Diagn. Interv. Imaging PD FEB PY 2016 VL 97 IS 2 BP 187 EP 196 DI 10.1016/j.diii.2015.06.019 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD2OE UT WOS:000369761100007 PM 26298669 ER PT J AU Irani, Z Oklu, R AF Irani, Z. Oklu, R. TI The use of embotic protection device in tower extremity catheter-directed thrombolysis SO DIAGNOSTIC AND INTERVENTIONAL IMAGING LA English DT Editorial Material DE Thrombolysis; Embolic protection device; Stent; Thrombosis ID ARTERIAL C1 [Irani, Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc & Intervent Radiol, Boston, MA USA. [Oklu, R.] Mayo Clin, Div Intervent Radiol, Scottsdale, AZ USA. [Oklu, R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Biomat Innovat Res Ctr,Dept Med, Cambridge, MA 02138 USA. RP Irani, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM zirani@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 2211-5684 J9 DIAGN INTERV IMAG JI Diagn. Interv. Imaging PD FEB PY 2016 VL 97 IS 2 BP 273 EP 275 DI 10.1016/j.diii.2015.11.011 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DD2OE UT WOS:000369761100022 PM 26725526 ER PT J AU Cox, KH AF Cox, Kimberly H. TI A Bisphenol by Any Other Name. . . SO ENDOCRINOLOGY LA English DT Editorial Material ID ENDOCRINE-DISRUPTING CHEMICALS; THYROID-HORMONE RECEPTOR; BPA RESEARCH-PROGRAM; EARLY-LIFE EXPOSURE; SCIENTIFIC STATEMENT; SAFE ALTERNATIVES; ZEBRAFISH; REPRODUCTION; SYSTEM; HYPOTHALAMUS C1 [Cox, Kimberly H.] Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St,Bartlett Hall Extens,5th Floor, Boston, MA 02113 USA. RP Cox, KH (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St,Bartlett Hall Extens,5th Floor, Boston, MA 02113 USA. EM khcox@mgh.harvard.edu RI Cox, Kimberly/P-1931-2016 OI Cox, Kimberly/0000-0002-7097-9563 FU NICHD NIH HHS [T32 HD007396, P50 HD028138, T32 HD00739, U54 HD028138] NR 46 TC 0 Z9 0 U1 10 U2 21 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2016 VL 157 IS 2 BP 449 EP 451 DI 10.1210/en.2015-2060 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD5LT UT WOS:000369965900004 PM 26828808 ER PT J AU Zhu, Y He, Q Aydin, C Rubera, I Tauc, M Chen, M Weinstein, LS Marshansky, V Juppner, H Bastepe, M AF Zhu, Yan He, Qing Aydin, Cumhur Rubera, Isabelle Tauc, Michel Chen, Min Weinstein, Lee S. Marshansky, Vladimir Jueppner, Harald Bastepe, Murat TI Ablation of the Stimulatory G Protein alpha-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D SO ENDOCRINOLOGY LA English DT Article ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; VITAMIN-D METABOLISM; PSEUDO-PSEUDOHYPOPARATHYROIDISM; MOUSE MODEL; MOLECULAR CHARACTERISTICS; PHOSPHATE HOMEOSTASIS; DOWN-REGULATION; GNAS GENE; KINASE-C; IN-VIVO AB PTH regulates serum calcium, phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) levels by acting on bone and kidney. In renal proximal tubules (PTs), PTH inhibits reabsorption of phosphate and stimulates the synthesis of 1,25(OH)(2)D. The PTH receptor couples to multiple G proteins. We here ablated the alpha-subunit of the stimulatory G protein (Gs alpha) in mouse PTs by using Cre recombinase driven by the promoter of type-2 sodium-glucose cotransporter (Gs alpha(Sglt2KO) mice). Gs alpha(Sglt2KO) mice were normophosphatemic but displayed, relative to controls, hypocalcemia (1.19 +/- 0.01 vs 1.23 +/- 0.01 mmol/L; P < .05), reduced serum 1,25(OH)(2)D (59.3 +/- 7.0 vs 102.5 +/- 12.2 pmol/L; P < .05), and elevated serum PTH (834 +/- 133 vs 438 +/- 59 pg/mL; P < .05). PTH-induced elevation in urinary cAMP excretion was blunted in Gs alpha(Sglt2KO) mice (2-vs 4-fold over baseline in controls; P < .05). Relative to baseline in controls, PTH-induced reduction in serum phosphate tended to be blunted in Gs alpha(Sglt2KO) mice (-0.39 +/- 0.33 vs -1.34 +/- 0.36 mg/dL; P = .07). Gs alpha(Sglt2KO) mice showed elevated renal vitamin D 24-hydroxylase and bone fibroblast growth factor-23 (FGF23) mRNA abundance (similar to 3.4- and similar to 11-fold over controls, respectively; P < .05) and tended to have elevated serum FGF23 (829 +/- 76 vs 632 +/- 60 pg/mL in controls; P = .07). Heterozygous mice having constitutive ablation of the maternal Gs alpha allele (E1(m-/+)) (model of pseudohypoparathyroidism type-Ia), in which Gs alpha levels in PT are reduced, also exhibited elevated serum FGF23 (474 +/- 20 vs 374 +/- 27 pg/mL in controls; P < .05). Our findings indicate that Gs alpha is required in PTs for suppressing renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)(2)D. C1 [Zhu, Yan; He, Qing; Aydin, Cumhur; Jueppner, Harald; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St,Thier 10, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Aydin, Cumhur] Gulhane Mil Med Acad, Dept Endodont, TR-06018 Ankara, Turkey. [Rubera, Isabelle; Tauc, Michel] Univ Nice Sophia Antipolis, Fac Med, F-06107 Nice, France. [Chen, Min; Weinstein, Lee S.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Marshansky, Vladimir] Kadmon Corp, Alexandria Ctr Life Sci, Mol Signaling, New York, NY 10016 USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St,Thier 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu RI Tauc, Michel/F-1530-2013 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01DK073911, R01DK46718]; Intramural Research of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This work was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants R01DK073911 (to M.B.) and R01DK46718 (to H.J.) and the Intramural Research of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 61 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2016 VL 157 IS 2 BP 497 EP 507 DI 10.1210/en.2015-1639 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD5LT UT WOS:000369965900010 PM 26671181 ER PT J AU Allen, DB Backeljauw, P Bidlingmaier, M Biller, BMK Boguszewski, M Burman, P Butler, G Chihara, K Christiansen, J Cianfarani, S Clayton, P Clemmons, D Cohen, P Darendeliler, F Deal, C Dunger, D Erfurth, EM Fuqua, JS Grimberg, A Haymond, M Higham, C Ho, K Hoffman, AR Hokken-Koelega, A Johannsson, G Juul, A Kopchick, J Lee, P Pollak, M Radovick, S Robison, L Rosenfeld, R Ross, RJ Savendahl, L Saenger, P Sorensen, HT Stochholm, K Strasburger, C Swerdlow, A Thorner, M AF Allen, D. B. Backeljauw, P. Bidlingmaier, M. Biller, B. M. K. Boguszewski, M. Burman, P. Butler, G. Chihara, K. Christiansen, J. Cianfarani, S. Clayton, P. Clemmons, D. Cohen, P. Darendeliler, F. Deal, C. Dunger, D. Erfurth, E. M. Fuqua, J. S. Grimberg, A. Haymond, M. Higham, C. Ho, K. Hoffman, A. R. Hokken-Koelega, A. Johannsson, G. Juul, A. Kopchick, J. Lee, P. Pollak, M. Radovick, S. Robison, L. Rosenfeld, R. Ross, R. J. Savendahl, L. Saenger, P. Sorensen, H. Toft Stochholm, K. Strasburger, C. Swerdlow, A. Thorner, M. TI GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CHILDHOOD-CANCER SURVIVOR; GROWTH-HORMONE TREATMENT; RESEARCH-SOCIETY; PEDIATRIC-ENDOCRINOLOGY; CONSENSUS GUIDELINES; 2ND NEOPLASMS; RISK; STATEMENT; ASSOCIATION; MANAGEMENT AB Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement. C1 [Allen, D. B.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Backeljauw, P.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Bidlingmaier, M.] Klinikum Univ Munchen, Med Klin & Poliklin 4, Munich, Germany. [Biller, B. M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boguszewski, M.] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Burman, P.; Erfurth, E. M.] Skane Univ Hosp, Dept Endocrinol, Malmo, Sweden. [Butler, G.] Univ Coll London Hosp, London, England. [Butler, G.] UCL Inst Child Hlth, London, England. [Chihara, K.] Hyogo Prefectural Kakogawa Med Ctr, Himeji, Hyogo, Japan. [Christiansen, J.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Cianfarani, S.] Univ Roma Tor Vergata, Bambino Gesu Childrens Hosp, Mol Endocrinol Unit, Rome, Italy. [Clayton, P.] Univ Manchester, Manchester, Lancs, England. [Clayton, P.] Manchester Acad, Hlth Sci Ctr, Manchester, Lancs, England. [Clemmons, D.] UNC Sch Med, Chapel Hill, NC USA. [Cohen, P.] Univ So Calif, USC Leonard Davis Sch Gerontol, Los Angeles, CA USA. [Darendeliler, F.] Istanbul Fac Med, Istanbul, Turkey. [Deal, C.] Ctr Hosp Univ Ste Justine, Montreal, PQ, Canada. [Dunger, D.] Univ Cambridge, Cambridge, England. [Fuqua, J. S.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Grimberg, A.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA. [Haymond, M.] Baylor Coll Med, Houston, TX 77030 USA. [Higham, C.] Christie Hosp NHS Fdn Trust, Manchester, Lancs, England. [Ho, K.] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Hoffman, A. R.] Stanford Univ, Sch Med, Stanford, CA 94305, Australia. [Hokken-Koelega, A.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Johannsson, G.] Sahlgrens Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden. [Johannsson, G.] Univ Gothenburg, Inst Med, Gothenburg, Sweden. [Juul, A.] Rigshosp, Dept Growth & Reprod & EDMaRC, Copenhagen, Denmark. [Kopchick, J.] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. [Lee, P.] Hershey Med Ctr, Penn State Coll Med, Hershey, PA USA. [Pollak, M.] McGill Univ, London, England. [Radovick, S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Robison, L.] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Rosenfeld, R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Ross, R. J.] Univ Sheffield, Sheffield, S Yorkshire, England. [Savendahl, L.] Karolinska Inst, Solna, Sweden. [Saenger, P.] SUNY Stony Brook, Winthrop Univ Hosp, Stony Brook, NY USA. [Sorensen, H. Toft; Stochholm, K.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Strasburger, C.] Charite, D-13353 Berlin, Germany. [Swerdlow, A.] Univ London, Inst Canc Res, London, ON, Canada. [Thorner, M.] Univ Virginia, Charlottesville, VA USA. RP Clayton, P (reprint author), Univ Manchester, Manchester, Lancs, England.; Clayton, P (reprint author), Manchester Acad, Hlth Sci Ctr, Manchester, Lancs, England.; Ross, RJ (reprint author), Univ Sheffield, Sheffield, S Yorkshire, England. EM peter.clayton@manchester.ac.uk; r.j.ross@sheffield.ac.uk RI cianfarani, stefano/K-2079-2016; OI cianfarani, stefano/0000-0002-2580-8781; Johannsson, Gudmundur/0000-0003-3484-8440; Juul, Anders/0000-0002-0534-4350; Clayton, Peter/0000-0003-1225-4537 FU European Society of Paediatric Endocrinology (ESPE); Growth Hormone Research Society (GRS); Pediatric Endocrine Society (PES) FX The meeting was organized and funded by the European Society of Paediatric Endocrinology (ESPE), the Growth Hormone Research Society (GRS), and the Pediatric Endocrine Society (PES). Jean-Claude Carel, Universite Paris Diderot, Sorbonne Paris Cite, attended but did not approve manuscript, and S Malozowski National Institute of Diabetes, Digestive and Kidney Diseases attended but chose not to be an author. NR 18 TC 7 Z9 7 U1 1 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 2016 VL 174 IS 2 BP P1 EP P9 DI 10.1530/EJE-15-0873 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD9KM UT WOS:000370244100001 PM 26563978 ER PT J AU Sottile, R Pangigadde, PN Tan, T Anichini, A Sabbatino, F Trecroci, F Favoino, E Orgiano, L Roberts, J Ferrone, S Karre, K Colucci, F Carbone, E AF Sottile, Rosa Pangigadde, Pradeepa N. Tan, Thomas Anichini, Andrea Sabbatino, Francesco Trecroci, Francesca Favoino, Elvira Orgiano, Laura Roberts, James Ferrone, Soldano Kaerre, Klas Colucci, Francesco Carbone, Ennio TI HLA class I downregulation is associated with enhanced NK-cell killing of melanoma cells with acquired drug resistance to BRAF inhibitors SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE acquired drug resistance; cytotoxicity; combination therapy; melanoma HLA; NK cell ID NATURAL-KILLER-CELL; MONOCLONAL-ANTIBODIES; METASTATIC MELANOMA; MALIGNANT-MELANOMA; SURFACE ANTIGENS; GAMMA PRODUCTION; CANCER; RECOGNITION; VEMURAFENIB; EXPRESSION AB The frequent development of drug resistance to targeted therapies in cancer patients has stimulated interest in strategies counteracting resistance. Combining immunotherapies with targeted therapies is one such strategy. In this context, we asked whether human NK cells can target melanoma cells that have acquired resistance to selective inhibitors targeting activating mutants of the B-Raf kinase (BRAF inhibitors, BRAFi). We generated drug-resistant cell variants in vitro from human BRAF-mutant melanoma cell lines MEL-HO, COLO-38, SK-MEL-37, 1520 and from primary melanoma cells freshly isolated from two patients. All drug-resistant cell variants remained susceptible to lysis by IL-2-activated NK cells; and two BRAFi-resistant lines (BRAFi-R) became significantly more susceptible to NK-cell lysis than their parental lines. This was associated with significant HLA class I antigen downregulation and PD-L1 upregulation on the drug-resistant lines. Although blocking HLA class I enhanced the extent of lysis of both BRAFi-R and parental cells to NK-cell-mediated lysis, antibody-mediated inhibition of PD1-PD-L1 interactions had no detectable effect. HLA class I antigen expression on BRAFi-R melanoma variants thus appears to play a major role in their susceptibility to NK-cell cytotoxicity. These findings suggest that NK-cell-based immunotherapy may be a viable approach to treat melanoma patients with acquired resistance to BRAF inhibitors. C1 [Sottile, Rosa; Pangigadde, Pradeepa N.; Kaerre, Klas; Carbone, Ennio] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden. [Sottile, Rosa; Pangigadde, Pradeepa N.; Trecroci, Francesca; Carbone, Ennio] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Tan, Thomas; Orgiano, Laura; Roberts, James; Colucci, Francesco] Univ Cambridge, Sch Clin Med, NIHR Cambridge Biomed Res Ctr, Dept Obstet & Gynaecol, Cambridge, England. [Anichini, Andrea] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy. [Sabbatino, Francesco; Favoino, Elvira; Ferrone, Soldano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Carbone, E (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.; Carbone, E (reprint author), Magna Graecia Univ Catanzaro, Catanzaro, Italy. EM ennio.carbone@ki.se RI Sabbatino, Francesco/F-4992-2014; Anichini, Andrea/K-1434-2016; OI Sabbatino, Francesco/0000-0001-6431-8278; Anichini, Andrea/0000-0001-5096-5538; PANGIGADDE, PRADEEPA/0000-0003-3374-7672 FU National Institute for Health Research Cambridge Biomedical Research Center Cell Phenotyping Hub; Association for International Cancer Research [10-0238]; Medical Research Council [G0900101/1]; Associazione Italiana Ricerca Cancro [AIRC-IG 15521]; UICC International Cancer Technology Transfer Fellowship; Italian Ministry of Health [CO-2011-02348049]; National Cancer Institute [P50CA121973]; Swedish Cancer Society; Fondazione Umberto Veronesi FX We would like to thank the members of the Colucci, Carbone, Ferrone and Karre labs. This work was supported by the National Institute for Health Research Cambridge Biomedical Research Center Cell Phenotyping Hub and by project grants from the Association for International Cancer Research 10-0238 and the Medical Research Council G0900101/1 to Francesco Colucci's lab and by Associazione Italiana Ricerca Cancro AIRC-IG 15521, UICC International Cancer Technology Transfer Fellowship and Italian Ministry of Health grant CO-2011-02348049 to Ennio Carbone. Soldano Ferrone was supported P50CA121973 awarded by the National Cancer Institute and Klas Karre was supported by The Swedish Cancer Society. Francesco Sabbatino was supported by a Post-Doctoral Fellowship from the Fondazione Umberto Veronesi. NR 50 TC 4 Z9 4 U1 4 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 2016 VL 46 IS 2 BP 409 EP 419 DI 10.1002/eji.201445289 PG 11 WC Immunology SC Immunology GA DD5OA UT WOS:000369972300018 PM 26564811 ER PT J AU Ren, JQ Chen, YCI Mackey, AM Liu, PK AF Ren, Jiaqian Chen, Yinching I. Mackey, Ashley M. Liu, Philip K. TI Imaging rhodopsin degeneration in vivo in a new model of ocular ischemia in living mice SO FASEB JOURNAL LA English DT Article DE chimeric MR CA; nanotechnology; retinopathy; target-guided delivery strategies ID MANGANESE-ENHANCED MRI; DIABETIC-RETINOPATHY; CEREBRAL-ISCHEMIA; MOUSE RETINA; BRAINS; PROBES; AMPHETAMINE; HYPOTHERMIA; EXPOSURE; STROKE AB Delivery of antibodies to monitor key biomarkers of retinopathy in vivo represents a significant challenge because living cells do not take up immunoglobulins to cellular antigens. We met this challenge by developing novel contrast agents for retinopathy, which we used with magnetic resonance imaging (MRI). Biotinylated rabbit polyclonal to chick IgY (rIgPxcIgY) and phosphorylthioate-modified oligoDNA (sODN) with random sequence (bio-sODN-Ran) were conjugated with NeutrAvidin-activated superparamagnetic iron oxide nanoparticles (SPION). The resulting Ran-SPION-rIgPxcIgY carries chick polyclonal to microtubule-associated protein 2 (MAP2) as Ran-SPION-rIgP/cIgY-MAP2, or torhodopsin (Rho) as anti-Rho-SPION-Ran. We examined the uptake of Ran-SPION-rIgP/cIgY-MAP2 or SPION-rIgP/cIgY-MAP2 in normal C57black6 mice (n = 3 each, 40 mu g/kg, i. c. v.); we found retention of Ran-SPION-rIgP/cIgY-MAP2 using molecular contrastenhanced MRI in vivo and validated neuronal uptake using Cy5-goat IgPxcIgY ex vivo. Applying this novel method to monitor retinopathy in a bilateral carotid artery occlusion-induced ocular ischemia, we observed pericytes (at d 2, using Gd-nestin, by eyedrop solution), significant photoreceptor degeneration (at d 20, using anti-Rho-SPION-Ran, eyedrops, P = 0.03, Student's t test), and gliosis in M " uller cells (at 6 mo, using SPION-glial fibrillary acidic protein administered by intraperitoneal injection) in surviving mice (n >= 5). Molecular contrastenhanced MRI results were confirmed by optical and electron microscopy. We conclude that chimera and molecular contrast-enhanced MRI provide sufficient sensitivity for monitoring retinopathy and for theranostic applications.- C1 [Ren, Jiaqian; Chen, Yinching I.; Liu, Philip K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mackey, Ashley M.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Cambridge, MA 02138 USA. RP Liu, PK (reprint author), CNY149-13th St, Charlestown, MA 02129 USA. EM philipl@mgh.harvard.edu FU U.S. National Institutes of Health [R01EB013768, P30DK057521-14]; Boston Area, Diabetes Endocrinology Research Center; [S10RR023009] FX The authors thank Drs. A. Kazlauskas (Schepens Eye Research Institute at the Massachusetts Eye and Ear Infirmary, Harvard Medical School), J. Blanks, and H. Prentice (Florida Atlantic University) for discussion of retinopathy; Dr. C.-M. Liu for sODN synthesis; and Drs. C. H. Liu, J. S. Yang, and S. Wu for MRI of the brain. This project was supported by U.S. National Institutes of Health Grants R01EB013768 (P. K. Liu), P30DK057521-14, the Boston Area, Diabetes Endocrinology Research Center (J. Avruch), and S10RR023009 (J. Ackerman). NR 35 TC 1 Z9 1 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2016 VL 30 IS 2 BP 612 EP 623 DI 10.1096/fj.15-280677 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DC7IA UT WOS:000369391900014 PM 26443823 ER PT J AU Song, MY Nishihara, R Wang, ML Chan, AT Qian, ZR Inamura, K Zhang, XH Ng, K Kim, SA Mima, K Sukawa, Y Nosho, K Fuchs, CS Giovannucci, EL Wu, K Ogino, S AF Song, Mingyang Nishihara, Reiko Wang, Molin Chan, Andrew T. Qian, Zhi Rong Inamura, Kentaro Zhang, Xuehong Ng, Kimmie Kim, Sun A. Mima, Kosuke Sukawa, Yasutaka Nosho, Katsuhiko Fuchs, Charles S. Giovannucci, Edward L. Wu, Kana Ogino, Shuji TI Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status SO GUT LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; VITAMIN-D; MICROSATELLITE INSTABILITY; COLON-CANCER; ADAPTIVE IMMUNITY; DNA METHYLATION; ASPIRIN USE; T-CELLS; PREVENTION AB Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1 alpha, 25-dihydroxyvitamin D-3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case-control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25 (OH) D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend<0.001), but not risk of tumour with lower-level reaction (p for trend>0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity= 0.03; adjusted statistical significance level of alpha=0.006). Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour-host interaction. C1 [Song, Mingyang; Nishihara, Reiko; Giovannucci, Edward L.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Song, Mingyang; Wang, Molin; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nishihara, Reiko; Qian, Zhi Rong; Inamura, Kentaro; Ng, Kimmie; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishihara, Reiko; Chan, Andrew T.; Qian, Zhi Rong; Inamura, Kentaro; Zhang, Xuehong; Ng, Kimmie; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Zhang, Xuehong; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Inamura, Kentaro] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Nosho, Katsuhiko] Sapporo Med Univ, Sch Med, Dept Gastroenterol Rheumatol & Clin Immunol, Sapporo, Hokkaido, Japan. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU US National Institutes of Health (NIH) [P01 CA87969, R01 CA49449, UM1 CA186107, P01 CA55075, UM1 CA167552, R03 CA176717, R01 CA137178, K24 DK098311, P50 CA127003]; US National Institutes of Health (NIH) (DF/HCC GI SPORE Developmental Project) [R01 CA151993, K07 CA190673, K07 CA148894]; Paula and Russell Agrusa Fund for Colorectal Cancer Research; Friends of the Dana-Farber Cancer Institute; Bennett Family Fund; Entertainment Industry Foundation; Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad; Takashi Tsuruo Memorial Fund; Asian medical centre FX This work was supported by US National Institutes of Health (NIH) grants [P01 CA87969 to SE Hankinson; R01 CA49449 to SE Hankinson; UM1 CA186107 to MJ Stampfer; P01 CA55075 to WC Willett; UM1 CA167552 to WC Willett; R03 CA176717 to XZ; R01 CA137178 to ATC; K24 DK098311 to ATC; P50 CA127003 to CSF; DF/HCC GI SPORE Developmental Project to SO; R01 CA151993 to SO; K07 CA190673 to RN; and K07 CA148894 to KN], and grants from The Paula and Russell Agrusa Fund for Colorectal Cancer Research (to CSF), the Friends of the Dana-Farber Cancer Institute (SO), the Bennett Family Fund, and the Entertainment Industry Foundation. ATC is a Damon Runyon Clinical Investigator. MS is a trainee of the Harvard Transdisciplinary Research Center on Energetics and Cancer (TREC). KI is supported by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad and by Takashi Tsuruo Memorial Fund. SAK is supported by an early exchange postdoctoral fellowship grant from Asian medical centre. NR 52 TC 12 Z9 13 U1 1 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD FEB PY 2016 VL 65 IS 2 BP 296 EP 304 DI 10.1136/gutjnl-2014-308852 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DD6CC UT WOS:000370010400016 PM 25591978 ER PT J AU Jais, B Rebours, V Malleo, G Salvia, R Fontana, M Maggino, L Bassi, C Manfredi, R Moran, R Lennon, AM Zaheer, A Wolfgang, C Hruban, R Marchegiani, G Del Castillo, CF Brugge, W Ha, Y Kim, MH Oh, D Hirai, I Kimura, W Jang, JY Kim, SW Jung, W Kang, H Song, SY Kang, CM Lee, WJ Crippa, S Falconi, M Gomatos, I Neoptolemos, J Milanetto, AC Sperti, C Ricci, C Casadei, R Bissolati, M Balzano, G Frigerio, I Girelli, R Delhaye, M Bernier, B Wang, H Jang, KT Song, DH Huggett, MT Oppong, KW Pererva, L Kopchak, KV Del Chiaro, M Segersvard, R Lee, LS Conwell, D Osvaldt, A Campos, V Garcete, GA Napoleon, B Matsumoto, I Shinzeki, M Bolado, F Fernandez, JMU Keane, MG Pereira, SP Acuna, IA Vaquero, EC Angiolini, MR Zerbi, A Tang, J Leong, RW Faccinetto, A Morana, G Petrone, MC Arcidiacono, PG Moon, JH Choi, HJ Gill, RS Pavey, D Ouaissi, M Sastre, B Spandre, M De Angelis, CG Rios-Vives, MA Concepcion-Martin, M Ikeura, T Okazaki, K Frulloni, L Messina, O Levy, P AF Jais, B. Rebours, V. Malleo, G. Salvia, R. Fontana, M. Maggino, L. Bassi, C. Manfredi, R. Moran, R. Lennon, A. M. Zaheer, A. Wolfgang, C. Hruban, R. Marchegiani, G. Del Castillo, C. Fernandez Brugge, W. Ha, Y. Kim, M. H. Oh, D. Hirai, I. Kimura, W. Jang, J. Y. Kim, S. W. Jung, W. Kang, H. Song, S. Y. Kang, C. M. Lee, W. J. Crippa, S. Falconi, M. Gomatos, I. Neoptolemos, J. Milanetto, A. C. Sperti, C. Ricci, C. Casadei, R. Bissolati, M. Balzano, G. Frigerio, I. Girelli, R. Delhaye, M. Bernier, B. Wang, H. Jang, K. T. Song, D. H. Huggett, M. T. Oppong, K. W. Pererva, L. Kopchak, K. V. Del Chiaro, M. Segersvard, R. Lee, L. S. Conwell, D. Osvaldt, A. Campos, V. Garcete, G. Aguero Napoleon, B. Matsumoto, I. Shinzeki, M. Bolado, F. Fernandez, J. M. Urman Keane, M. G. Pereira, S. P. Acuna, I. Araujo Vaquero, E. C. Angiolini, M. R. Zerbi, A. Tang, J. Leong, R. W. Faccinetto, A. Morana, G. Petrone, M. C. Arcidiacono, P. G. Moon, J. H. Choi, H. J. Gill, R. S. Pavey, D. Ouaissi, M. Sastre, B. Spandre, M. De Angelis, C. G. Rios-Vives, M. A. Concepcion-Martin, M. Ikeura, T. Okazaki, K. Frulloni, L. Messina, O. Levy, P. TI Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas) SO GUT LA English DT Article ID FINE-NEEDLE-ASPIRATION; ENDOSCOPIC ULTRASOUND; FLUID ANALYSIS; DIFFERENTIAL-DIAGNOSIS; LESIONS; CYSTADENOMA; GROWTH; CT; MANAGEMENT; RECOMMENDATIONS AB Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. C1 [Jais, B.; Rebours, V.; Levy, P.] Beaujon Hosp, AP HP, Dept Gastroenterol & Pancreatol, 100 Blvd Gen Leclerc, F-92118 Clichy, France. [Malleo, G.; Salvia, R.; Fontana, M.; Maggino, L.; Bassi, C.; Manfredi, R.] Univ Verona Hosp Trust, GB Rossi Hosp, Pancreas Inst, Verona, Italy. [Moran, R.; Lennon, A. M.; Zaheer, A.; Wolfgang, C.; Hruban, R.] Johns Hopkins Univ, Sch Med, Div Gastroenterol & Hepatol, Baltimore, MD USA. [Moran, R.; Lennon, A. M.; Zaheer, A.; Wolfgang, C.; Hruban, R.] Johns Hopkins Univ, Sch Med, Div Surg, Baltimore, MD USA. [Moran, R.; Lennon, A. M.; Zaheer, A.; Wolfgang, C.; Hruban, R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA. [Marchegiani, G.; Del Castillo, C. Fernandez; Brugge, W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Marchegiani, G.; Del Castillo, C. Fernandez; Brugge, W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Ha, Y.; Kim, M. H.; Oh, D.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Gastroenterol, Seoul, South Korea. [Hirai, I.; Kimura, W.] Yamagata Univ, Fac Med, Dept Surg 1, Yamagata 990, Japan. [Jang, J. Y.; Kim, S. W.; Jung, W.] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Kang, H.; Song, S. Y.] Yonsei Univ, Coll Med, Dept Internal Med, Div Gastroenterol, Seoul 120749, South Korea. [Kang, C. M.; Lee, W. J.] Yonsei Univ, Coll Med, Dept Surg,Severance Hosp, Pancreaticobiliary Canc Clin,Yonsei Canc Ctr, Seoul 120749, South Korea. [Crippa, S.; Falconi, M.] Polytech Univ Marche Reg, Dept Surg, Pancreat Surg Unit, Ancona, Italy. [Gomatos, I.; Neoptolemos, J.] Univ Liverpool, NIHR Pancreas Biomed Res Unit, Dept Mol & Clin Canc Med, Royal Liverpool Univ Hosp,Inst Translat Med, Liverpool L69 3BX, Merseyside, England. [Milanetto, A. C.; Sperti, C.] Univ Padua, Dept Surg Oncol & Gastroenterol, Surg Clin 3, Padua, Italy. [Ricci, C.; Casadei, R.] Alma Mater Studiorum Univ Bologna, Dept Med & Surg Sci DIMEC, S Orsola Malpighi Hosp, Bologna, Italy. [Bissolati, M.; Balzano, G.] IRCCS San Raffaele Sci Inst, Pancreat Surg Unit, Milan, Italy. [Frigerio, I.; Girelli, R.] Pederzoli Hosp, Hepatopancreatobiliary Unit, Peschiera Del Garda, Italy. [Delhaye, M.; Bernier, B.] Univ Libre Bruxelles, Erasme Univ Hosp, Dept Gastroenterol Hepatopancreatol & GI Oncol, Brussels, Belgium. [Wang, H.] Third Mil Med Univ, Southwest Hosp, Inst Hepatopancreatobiliary Surg, Chongqing, Peoples R China. [Jang, K. T.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea. [Song, D. H.] Gyeongsang Natl Univ, Sch Med, Dept Pathol, Jinju, South Korea. [Huggett, M. T.; Oppong, K. W.] Freeman Rd Hosp, Hepatopancreatobiliary Unit, Newcastle Upon Tyne, Tyne & Wear, England. [Pererva, L.; Kopchak, K. V.] Nat Inst Surg & Transplantol, Kiev, Ukraine. [Del Chiaro, M.; Segersvard, R.] Karolinska Univ Hosp, Karolinska Inst, Div Surg,Ctr Digest Dis, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden. [Lee, L. S.; Conwell, D.] Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. [Osvaldt, A.; Campos, V.] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Garcete, G. Aguero; Napoleon, B.] Hop Prive Mermoz, Gastroenterol, Lyon, France. [Matsumoto, I.; Shinzeki, M.] Kobe Univ, Grad Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg, Kobe, Hyogo 657, Japan. [Bolado, F.; Fernandez, J. M. Urman] Hosp Navarra, Dept Gastroenterol, Pamplona, Spain. [Keane, M. G.; Pereira, S. P.] Univ Coll London Hosp, Dept Gastroenterol & Hepatol, London, England. [Acuna, I. Araujo; Vaquero, E. C.] Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBEREHD,IDIBAPS, Barcelona, Spain. [Angiolini, M. R.; Zerbi, A.] Humanitas Res Hosp, Dept Pancreat Surg, Milan, Italy. [Tang, J.; Leong, R. W.] Concord Hosp, Gastroenterol & Liver Serv, Sydney, NSW, Australia. [Faccinetto, A.; Morana, G.] Gen Hosp Ca Foncello, Dept Radiol, Treviso, Italy. [Petrone, M. C.; Arcidiacono, P. G.] Ist Sci San Raffaele, Div Gastroenterol & Gastrointestinal Endoscopy, I-20132 Milan, Italy. [Moon, J. H.; Choi, H. J.] Soonchunhyang Univ, Sch Med, Digest Dis Ctr, Dept Internal Med, Bucheon, South Korea. [Moon, J. H.; Choi, H. J.] Soonchunhyang Univ, Sch Med, Res Inst, Bucheon, South Korea. [Gill, R. S.; Pavey, D.] Bankstown Lidcombe Hosp, Dept Gastroenterol, Bankstown, NSW, Australia. [Ouaissi, M.; Sastre, B.] Timone Hosp, Dept Digest Surg, Marseille, France. [Spandre, M.; De Angelis, C. G.] Univ Turin, San Giovanni Battista Molinette Hosp, Dept Gastroenterol, Turin, Italy. [Rios-Vives, M. A.; Concepcion-Martin, M.] Univ Autonoma Barcelona, Inst Recerca IIB St Pau, Hosp Santa Creu & St Pau, Dept Gastroenterol, E-08193 Barcelona, Spain. [Ikeura, T.; Okazaki, K.] Kansai Med Univ, Div Gastroenterol & Hepatol, Dept Internal Med 3, Osaka, Japan. [Frulloni, L.; Messina, O.] Univ Verona, Pancreas Ctr, Dept Med, I-37100 Verona, Italy. RP Levy, P (reprint author), Beaujon Hosp, AP HP, Dept Gastroenterol & Pancreatol, 100 Blvd Gen Leclerc, F-92118 Clichy, France. EM philippe.levy@bjn.aphp.fr RI Osvaldt, Alessandro/O-2594-2013; OI Osvaldt, Alessandro/0000-0002-5863-6656; ARAUJO, ISIS K./0000-0001-7827-8019; Falconi, Massimo/0000-0001-9654-7243; Napoleon, Bertrand/0000-0001-5866-8132; Leong, Rupert/0000-0001-5944-3488; Bissolati, Massimiliano/0000-0002-2032-0138 FU Department of Health [PB-PG-0712-28114] NR 40 TC 16 Z9 16 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD FEB PY 2016 VL 65 IS 2 BP 305 EP U314 DI 10.1136/gutjnl-2015-309638 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DD6CC UT WOS:000370010400017 PM 26045140 ER PT J AU Kolesov, I Lee, J Sharp, G Vela, P Tannenbaum, A AF Kolesov, Ivan Lee, Jehoon Sharp, Gregory Vela, Patricio Tannenbaum, Allen TI A Stochastic Approach to Diffeomorphic Point Set Registration with Landmark Constraints SO IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE LA English DT Article DE Point set; deformable registration; particle filter; simulated annealing; constrained optimization ID THIN-PLATE SPLINES; NONRIGID REGISTRATION; ELASTIC REGISTRATION; OPTIMIZATION; ALGORITHM AB This work presents a deformable point set registration algorithm that seeks an optimal set of radial basis functions to describe the registration. A novel, global optimization approach is introduced composed of simulated annealing with a particle filter based generator function to perform the registration. It is shown how constraints can be incorporated into this framework. A constraint on the deformation is enforced whose role is to ensure physically meaningful fields (i.e., invertible). Further, examples in which landmark constraints serve to guide the registration are shown. Results on 2D and 3D data demonstrate the algorithm's robustness to noise and missing information. C1 [Kolesov, Ivan] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11790 USA. [Lee, Jehoon] Samsung Elect Co Ltd, Suwon, South Korea. [Sharp, Gregory] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Vela, Patricio] Georgia Inst Technol, Dept Elect & Comp Engn, Atlanta, GA 30332 USA. [Tannenbaum, Allen] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11790 USA. [Tannenbaum, Allen] SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11790 USA. RP Kolesov, I (reprint author), SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11790 USA.; Lee, J (reprint author), Samsung Elect Co Ltd, Suwon, South Korea.; Sharp, G (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Vela, P (reprint author), Georgia Inst Technol, Dept Elect & Comp Engn, Atlanta, GA 30332 USA.; Tannenbaum, A (reprint author), SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11790 USA.; Tannenbaum, A (reprint author), SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11790 USA. EM ivan.kolesov@stonybrook.edu; jehoon.lee25@gmail.com; gcsharp@partners.org; pvela@gatech.edu; arobertan@cs.stonybrook.edu FU National Center for Research Resources [P41-RR-013218]; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [P41-EB-015902]; NIH [R01 MH82918, 1U24CA18092401A1]; AFOSR [FA9550-12-1-0319, FA9550-15-1-0045] FX This project was supported by in part by grants from the National Center for Research Resources (P41-RR-013218) and the National Institute of Biomedical Imaging and Bioengineering (P41-EB-015902) of the National Institutes of Health. This work was also supported by NIH grants R01 MH82918 and 1U24CA18092401A1 as well as AFOSR grants FA9550-12-1-0319 and FA9550-15-1-0045. NR 45 TC 1 Z9 1 U1 2 U2 13 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0162-8828 EI 1939-3539 J9 IEEE T PATTERN ANAL JI IEEE Trans. Pattern Anal. Mach. Intell. PD FEB PY 2016 VL 38 IS 2 BP 238 EP 251 DI 10.1109/TPAMI.2015.2448102 PG 14 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA DD5UI UT WOS:000369989600004 PM 26761731 ER PT J AU Feris, EJ Encinales, L Awad, C Stern, JNH Tabansky, I Jimenez-Alvarez, L Ramirez-Martinez, G Cruz-Lagunas, A Bobadilla, K Marquez, E Granados-Montiel, J Rodriguez-Reyna, TS Fernandez-Vina, M Granados, J Zuniga, J Yunis, EJ AF Feris, Edmond J. Encinales, Liliana Awad, Carlos Stern, Joel N. H. Tabansky, Inna Jimenez-Alvarez, Luis Ramirez-Martinez, Gustavo Cruz-Lagunas, Alfredo Bobadilla, Karen Marquez, Eduardo Granados-Montiel, Julio Rodriguez-Reyna, Tatiana S. Fernandez-Vina, Marcelo Granados, Julio Zuniga, Joaquin Yunis, Edmond J. TI High levels of anti-tuberculin (IgG) antibodies correlate with the blocking of T-cell proliferation in individuals with high exposure to Mycobacterium tuberculosis SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Tuberculosis; Mycobacterium tuberculosis; Latent tuberculosis; Humoral immunity; Anti-tuberculin antibodies; T-cell proliferation ID LATENT TUBERCULOSIS; INFECTION AB Objectives: To determine the effect of anti-tuberculin antibodies in the T-cell proliferation in response to tuberculin and Candida antigens in individuals with different levels of tuberculosis (TB) risk. Methods: Sixteen high-risk TB individuals, 30 with an intermediate TB risk (group A), and 45 with a low TB risk (group B), as well as 49 control individuals, were studied. Tuberculin skin test (TST) results were analyzed and serum levels of antibodies (IgG and IgM) against purified protein derivative (PPD) were measured by ELISA. Tuberculin and Candida antigens were used to stimulate T-cell proliferation in the presence of human AB serum or autologous serum. Results: High levels of anti-tuberculin IgG antibodies were found to be significantly associated with the blocking of T-cell proliferation responses in cultures stimulated with tuberculin but not with Candida antigens in the presence of autologous serum. This phenomenon was particularly frequent in high-risk individuals with high levels of anti-tuberculin IgG antibodies in the autologous serum when compared to the other risk groups, which exhibited lower levels of anti-tuberculin antibodies. Conclusions: Although cellular immunity plays a central role in the protection against TB, humoral immunity is critical in the control of Mycobacterium tuberculosis infection in high-risk individuals with latent TB infection. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. C1 [Feris, Edmond J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Lebanon, NH USA. [Encinales, Liliana; Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Awad, Carlos] Hosp Santa Clara, Bogota, Colombia. [Stern, Joel N. H.] Hofstra Northwell Sch Med, Dept Neurol, Hempstead, NY USA. [Stern, Joel N. H.] Hofstra Northwell Sch Med, Dept Sci Educ, Hempstead, NY USA. [Stern, Joel N. H.] Feinstein Inst Med Res, Dept Autoimmun, Manhasset, NY USA. [Stern, Joel N. H.; Tabansky, Inna] Rockefeller Univ, New York, NY 10021 USA. [Jimenez-Alvarez, Luis; Ramirez-Martinez, Gustavo; Cruz-Lagunas, Alfredo; Bobadilla, Karen; Marquez, Eduardo; Zuniga, Joaquin] Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Immunol, Mexico City, DF, Mexico. [Granados-Montiel, Julio; Yunis, Edmond J.] Inst Nacl Rehabil, Tissue Engn Cell Therapy & Regenerat Med Res Unit, Mexico City, DF, Mexico. [Rodriguez-Reyna, Tatiana S.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico. [Fernandez-Vina, Marcelo] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Granados, Julio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Transplantat, Mexico City, DF, Mexico. RP Yunis, EJ (reprint author), Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Immunol, Mexico City, DF, Mexico. EM joazu@yahoo.com; edmond_yunis@dfci.harvard.edu FU NIH [AI49213, HL29583, HL59838, NIH F32 HD081835]; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; National Council of Science and Technology of Mexico [Conacyt SALUD 115497]; Bristol Myers Squibb Postdoctoral Fellowship; HT Langbert Charitable Trust Research Fund; Cheryl Manne Fund for the Cure of MS FX This work was supported by NIH grants AI49213, HL29583, and HL59838, funds from the Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and a grant from the National Council of Science and Technology of Mexico (Conacyt SALUD 115497).; I.T. was funded by the Bristol Myers Squibb Postdoctoral Fellowship and by NIH F32 HD081835. J.N.H.S was funded by a grant from the HT Langbert Charitable Trust Research Fund and the Cheryl Manne Fund for the Cure of MS. NR 10 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 2016 VL 43 BP 21 EP 24 DI 10.1016/j.ijid.2015.12.004 PG 4 WC Infectious Diseases SC Infectious Diseases GA DD2ZE UT WOS:000369789900005 PM 26686942 ER PT J AU Diercks, GR Hartnick, CJ AF Diercks, Gillian R. Hartnick, Christopher J. TI Response to "Moral considerations in non-EXIT airway management" SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Letter C1 [Diercks, Gillian R.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Diercks, Gillian R.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Diercks, GR (reprint author), Massachusetts Eye & Ear Infirm, Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM gillian_diercks@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD FEB PY 2016 VL 81 IS 2 BP 102 EP 102 DI 10.1016/j.ijporl.2015.11.033 PG 1 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA DD7HF UT WOS:000370093600022 PM 26774125 ER EF