FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bainey, KR Armstrong, PW Fonarow, GC Cannon, CP Hernandez, AF Peterson, ED Peacock, WF Laskey, WK Zhao, X Schwamm, LH Bhatt, DL AF Bainey, Kevin R. Armstrong, Paul W. Fonarow, Gregg C. Cannon, Christopher P. Hernandez, Adrian F. Peterson, Eric D. Peacock, W. Frank Laskey, Warren K. Zhao, Xin Schwamm, Lee H. Bhatt, Deepak L. TI Use of Renin-Angiotensin System Blockers in Acute Coronary Syndromes Findings From Get With the Guidelines-Coronary Artery Disease Program SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE angiotensin-converting enzyme inhibitors; angiotensin receptor blockers; acute coronary syndrome ID ACUTE MYOCARDIAL-INFARCTION; CONVERTING ENZYME-INHIBITORS; LEFT-VENTRICULAR DYSFUNCTION; QUALITY-IMPROVEMENT PROGRAM; BYPASS GRAFT-SURGERY; HEART-FAILURE; AMERICAN-COLLEGE; RISK PATIENTS; TASK-FORCE; MORTALITY AB Background- Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) initiated after myocardial infarction (MI) reduce mortality and are American College of Cardiology/American Heart Association guideline recommended. Yet the extent to which ACEI/ARB therapy is applied in patients with acute coronary syndrome at hospital discharge is unclear. Methods and Results- We performed an observational analysis of 80 241 patients admitted with an acute coronary syndrome and discharged home from 311 US hospitals participating in the Get With the Guidelines-Coronary Artery Disease Program from January 2005 to December 2009. Among the 60 847 patients with an American College of Cardiology/American Heart Association class I indication (left ventricular dysfunction or medical history of heart failure, hypertension, diabetes mellitus, or chronic kidney disease), 49 682 (81.7%) received ACEI/ARB with an increase in the rate of treatment over the study period (76.7%-84.6%; adjusted odds ratio, 1.17; 95% confidence interval, 1.10-1.24; P < 0.001, per calendar year). In-hospital coronary artery bypass grafting and renal insufficiency were independently associated with lower use (adjusted odds ratio, 0.55; 95% confidence interval, 0.48-0.63 and adjusted odds ratio, 0.58; 95% confidence interval, 0.52-0.64, respectively). Conclusions- Results from this large US national registry suggest that 1 in 5 eligible patients hospitalized for acute coronary syndrome failed to receive American College of Cardiology/American Heart Association class I guideline-recommended ACEI/ARB therapy, and the use varies by patient factors. In particular, the low likelihood of ACEI/ARB after coronary artery bypass grafting surgery or in patients with renal insufficiency raises concern. These findings highlight an unmet need in this population and provide an incentive for additional quality improvement efforts. C1 [Bainey, Kevin R.; Armstrong, Paul W.] Univ Alberta, Mazankowski Alberta Heart Inst, Canadian VIGOUR Ctr, Edmonton, AB, Canada. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90024 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA. [Hernandez, Adrian F.; Peterson, Eric D.; Zhao, Xin] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Sch Med, Div Cardiol, Albuquerque, NM 87131 USA. [Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA. EM DLBHATTMD@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Merck/Schering-Plough Pharmaceutical; Pfizer; AHA FX GWTG-CAD is a program of the AHA and is supported, in part, by an unrestricted educational grant from Merck/Schering-Plough Pharmaceutical and Pfizer. The analysis of registry data was performed at Duke Clinical Research Institute (Durham, NC), which receives funding from the AHA. NR 38 TC 6 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2014 VL 7 IS 2 BP 227 EP 235 DI 10.1161/CIRCOUTCOMES.113.000422 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD0ZA UT WOS:000332962100005 PM 24569634 ER PT J AU Jackevicius, CA AF Jackevicius, Cynthia A. TI How Do the 2013 Cholesterol Guidelines Compare With Previous Cholesterol Guideline Reports? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE guideline; cholesterol; lipids ID TREATMENT PANEL-III C1 [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pharm, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Univ Hlth Network, Dept Pharm, Toronto, ON, Canada. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E Second St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu NR 5 TC 1 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2014 VL 7 IS 2 BP 306 EP 310 DI 10.1161/CIRCOUTCOMES.113.000769 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD0ZA UT WOS:000332962100015 PM 24594553 ER PT J AU Deipolyi, AR Golberg, A Yarmush, ML Arellano, RS Oklu, R AF Deipolyi, Amy R. Golberg, Alexander Yarmush, Martin L. Arellano, Ronald S. Oklu, Rahmi TI Irreversible electroporation: evolution of a laboratory technique in interventional oncology SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review ID PULSED ELECTRIC-FIELDS; MUSCLE-CELLS ABLATION; PANCREATIC ADENOCARCINOMA; CLINICAL-IMPLICATIONS; ANTITUMOR TREATMENT; THERAPY; LIVER; ELECTROCHEMOTHERAPY; TUMORS; TRIAL AB Electroporation involves applying electric field pulses to cells, leading to the alteration or destruction of cell membranes. Irreversible electroporation (IRE) creates permanent defects in cell membranes and induces cell death. By directly targeting IRE to tumors, percutaneous nonthermal ablation is possible. The history of IRE, evolution of concepts, theory, biological applications, and clinical data regarding its safety and efficacy are discussed. C1 [Deipolyi, Amy R.; Arellano, Ronald S.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Intervent Radiol, Boston, MA 02163 USA. [Golberg, Alexander; Yarmush, Martin L.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Intervent Radiol, Boston, MA 02163 USA. EM roklu@mgh.harvard.edu OI Deipolyi, Amy/0000-0003-3144-386X NR 48 TC 9 Z9 10 U1 0 U2 16 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 EI 1305-3612 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD MAR-APR PY 2014 VL 20 IS 2 BP 147 EP 154 DI 10.5152/dir.2013.13304 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AE2NJ UT WOS:000333809600008 PM 24412820 ER PT J AU Parsons, GR Hidrue, MK Kempton, W Gardner, MP AF Parsons, George R. Hidrue, Michael K. Kempton, Willett Gardner, Meryl P. TI Willingness to pay for vehicle-to-grid (V2G) electric vehicles and their contract terms SO ENERGY ECONOMICS LA English DT Article DE Electric vehicles; Vehicle-to-grid; Stated preference; Latent-class model ID LATENT-CLASS MODEL; DISCRETE-CHOICE; DISCOUNT RATES; POTENTIAL DEMAND; STATED CHOICE; FUEL VEHICLES; PREFERENCES; DECISIONS AB Vehicle-to-grid (V2G) electric vehicles can return power stored in their batteries back to the power grid and be programmed to do so at times when the grid needs reserve power. Since providing this service can lead to payments to owners, it effectively reduces the life-cycle cost of owning an electric vehicle. Using data from a national stated preference survey, this paper presents a study of the potential consumer demand for V2G electric vehicles. In a choice experiment, 3029 respondents compared their preferred gasoline vehicle with two V2G electric vehicles. The V2G vehicles were described by a set of electric vehicle attributes and V2G contract requirements such as "required plug-in time" and "guaranteed minimum driving range". The contract requirements specify a contract between drivers and a power aggregator for providing reserve power to the grid. Our findings suggest that the V2G concept is most likely to help EVs on the market if power aggregators operate either on pay-as-you-go basis (more pay for more service provided) or provide consumers with advanced cash payment (upfront discounts on the price of EVs), rather than imposing fixed requirements on participants. (C) 2014 Elsevier B.V. All rights reserved. C1 [Parsons, George R.; Kempton, Willett] Univ Delaware, Sch Marine Sci & Policy, Newark, DE 19716 USA. [Hidrue, Michael K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gardner, Meryl P.] Univ Delaware, Newark, DE 19716 USA. RP Parsons, GR (reprint author), Univ Delaware, Sch Marine Sci & Policy, Newark, DE 19716 USA. EM gparsons@udel.edu RI Kempton, Willett/H-5176-2012 OI Kempton, Willett/0000-0002-7284-8954 NR 44 TC 16 Z9 16 U1 4 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0140-9883 EI 1873-6181 J9 ENERG ECON JI Energy Econ. PD MAR PY 2014 VL 42 BP 313 EP 324 DI 10.1016/j.eneco.2013.12.018 PG 12 WC Economics SC Business & Economics GA AE2BN UT WOS:000333778400032 ER PT J AU Zanobetti, A Luttmann-Gibson, H Horton, ES Cohen, A Coull, BA Hoffmann, B Schwartz, JD Mittleman, MA Li, YS Stone, PH de Souza, C Lamparello, B Koutrakis, P Gold, DR AF Zanobetti, Antonella Luttmann-Gibson, Heike Horton, Edward S. Cohen, Allison Coull, Brent A. Hoffmann, Barbara Schwartz, Joel D. Mittleman, Murray A. Li, Yongsheng Stone, Peter H. de Souza, Celine Lamparello, Brooke Koutrakis, Petros Gold, Diane R. TI Brachial Artery Responses to Ambient Pollution, Temperature, and Humidity in People with Type 2 Diabetes: A Repeated-Measures Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PARTICULATE AIR-POLLUTION; HEALTHY-HUMAN VOLUNTEERS; CASE-ONLY ANALYSIS; ENDOTHELIAL FUNCTION; BLOOD-PRESSURE; VASCULAR REACTIVITY; OXIDATIVE STRESS; VAPOR-PRESSURE; DIESEL EXHAUST; EXPOSURE AB BACKGROUND: Extreme weather and air pollution are associated with increased cardiovascular risk in people with diabetes. OBJECTIVES: In a population with diabetes, we conducted a novel assessment of vascular brachial artery responses both to ambient pollution and to weather (temperature and water vapor pressure, a measure of humidity). METHODS: Sixty-four 49- to 85-year-old Boston residents with type 2 diabetes completed up to five study visits (279 repeated measures). Brachial artery diameter (BAD) was measured by ultrasound before and after brachial artery occlusion [i.e., flow-mediated dilation (FMD)] and before and after nitroglycerin-mediated dilation (NMD). Ambient concentrations of fine particulate mass (PM2.5), black carbon (BC), organic carbon (OC), elemental carbon, particle number, and sulfate were measured at our monitoring site; ambient concentrations of carbon monoxide, nitrogen dioxide, and ozone were obtained from state monitors. Particle exposure in the home and during each trip to the clinic (home/trip exposure) was measured continuously and as a 5-day integrated sample. We used linear models with fixed effects for participants, adjusting for date, season, temperature, and water vapor pressure on the day of each visit, to estimate associations between our outcomes and interquartile range increases in exposure. RESULTS: Baseline BAD was negatively associated with particle pollution, including home/trip-integrated BC (-0.02 mm; 95% CI: -0.04, -0.003, for a 0.28 mu g/m(3) increase in BC), OC (-0.08 mm; 95% CI: -0.14, -0.03, for a 1.61 mu g/m(3) increase) as well as PM2.5, 5-day average ambient PM2.5, and BC. BAD was positively associated with ambient temperature and water vapor pressure. However, exposures were not consistently associated with FMD or NMD. CONCLUSION: Brachial artery diameter, a predictor of cardiovascular risk, decreased in association with particle pollution and increased in association with ambient temperature in our study population of adults with type 2 diabetes. C1 [Zanobetti, Antonella; Luttmann-Gibson, Heike; Schwartz, Joel D.; de Souza, Celine; Koutrakis, Petros; Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Horton, Edward S.; Cohen, Allison; Li, Yongsheng; Lamparello, Brooke] Joslin Diabet Ctr, Boston, MA 02215 USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Hoffmann, Barbara] Univ Dusseldorf, IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany. [Hoffmann, Barbara] Univ Dusseldorf, Sch Med, Dusseldorf, Germany. [Mittleman, Murray A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Stone, Peter H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Gold, Diane R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02215 USA. RP Zanobetti, A (reprint author), Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth,Landmark Ctr, 401 Pk Dr,Suite 415,POB 15698, Boston, MA 02215 USA. EM azanobet@hsph.harvard.edu FU National Institute of Environmental Health, National Institutes of Heath [PO1 ES-09825, R21ES020194-01]; U.S. Environmental Protection Agency (EPA) [RD-83241601, RD-83479801] FX This study was funded by the National Institute of Environmental Health, National Institutes of Heath (grants PO1 ES-09825 and R21ES020194-01) and by the U.S. Environmental Protection Agency (EPA; grants RD-83241601 and RD-83479801. NR 43 TC 19 Z9 20 U1 1 U2 27 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2014 VL 122 IS 3 BP 242 EP 248 DI 10.1289/ehp.1206136 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA AE0QH UT WOS:000333670500013 PM 24398072 ER PT J AU Bind, MA Lepeule, J Zanobetti, A Gasparrini, A Baccarelli, A Coull, BA Tarantini, L Vokonas, PS Koutrakis, P Schwartz, J AF Bind, Marie-Abele Lepeule, Johanna Zanobetti, Antonella Gasparrini, Antonio Baccarelli, Andrea Coull, Brent A. Tarantini, Letizia Vokonas, Pantel S. Koutrakis, Petros Schwartz, Joel TI Air pollution and gene-specific methylation in the Normative Aging Study SO EPIGENETICS LA English DT Article DE air pollution; traffic; gene-specific DNA methylation; effect modification; mediation analysis; elderly ID NITRIC-OXIDE SYNTHASE; DNA METHYLATION; PARTICULATE MATTER; CARDIOVASCULAR-DISEASE; TISSUE FACTOR; PROMOTER METHYLATION; INTERFERON-GAMMA; LEAD-EXPOSURE; INFLAMMATION; THROMBOSIS AB The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999-2009). We repeatedly measured methylation at multiple CpG sites within each gene's promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN- and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICAM-1 protein through a decrease in ICAM-1 methylation. C1 [Bind, Marie-Abele; Lepeule, Johanna; Zanobetti, Antonella; Baccarelli, Andrea; Koutrakis, Petros; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Bind, Marie-Abele; Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gasparrini, Antonio] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England. [Tarantini, Letizia] Univ Milan, Ctr Mol & Genet Epidemiol, Milan, Italy. [Vokonas, Pantel S.] VA Boston Healthcare Syst, Boston, MA 02118 USA. [Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Bind, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM ma.bind@mail.harvard.edu RI Gasparrini, Antonio/F-7627-2012; LEPEULE, Johanna/K-1085-2016 OI Gasparrini, Antonio/0000-0002-2271-3568; FU US Environmental Protection Agency [EPA RD-827353, RD-832416]; National Institute of Environmental Health Sciences (NIEHS) [RO1-ES015172, 2RO1-ES015172, ES014663, ES00002, PO1-ES008925]; Clean Air Act (CLARC) grant [RD83479701]; Medical Research Council-UK [G1002296]; Cooperative Studies Program/Epidemiology Research and Information Center of the US. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts FX This study was supported by the US Environmental Protection Agency grants EPA RD-827353 and RD-832416; National Institute of Environmental Health Sciences (NIEHS) grants RO1-ES015172, 2RO1-ES015172, ES014663, ES00002, PO1-ES008925, Clean Air Act (CLARC) grant RD83479701, and Medical Research Council-UK G1002296. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts. NR 41 TC 32 Z9 33 U1 4 U2 24 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 EI 1559-2308 J9 EPIGENETICS-US JI Epigenetics PD MAR 1 PY 2014 VL 9 IS 3 BP 448 EP 458 DI 10.4161/epi.27584 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AE0JC UT WOS:000333649600013 PM 24385016 ER PT J AU Williams, KA Labidi-Galy, SI Terry, KL Vitonis, AF Welch, WR Goodman, A Cramer, DW AF Williams, Kristina A. Labidi-Galy, S. Intidhar Terry, Kathryn L. Vitonis, Allison F. Welch, William R. Goodman, Annekathryn Cramer, Daniel W. TI Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Risk factors; CA125 ID INFLAMMATORY CYTOKINES; INCESSANT OVULATION; RISK; EXPRESSION; SURVIVAL; LIN28B; ANTIBODIES; SMOKING; HEIGHT; COUNT AB Objective. To investigate the neutrophil-to-lymphocyte ratio (NLR) from peripheral blood, a general measure of inflammation, in ovarian cancer. Methods. White cell counts and CA125 levels before treatment, tumor features, and questionnaire data on 519 women with ovarian cancer at two Boston hospitals were recorded. Counts were log-transformed and effects on these by tumor features and epidemiologic variables assessed by analysis of variance and generalized linear models. Cox proportional hazards models were used to assess effects on overall survival. Results. Greater NLR was associated with higher tumor stage and grade, presence of ascites, and bilateral disease and correlated with risk factors including Jewish ethnicity, taller height, more ovulatory cycles, and family history of cancer in premenopausal women and talc use in all women. CA125 was positively correlated with neutrophil count, monocyte count, and NLR and inversely correlated with lymphocyte count. In a multivariate adjusted analysis, high NLR predicted poorer survival and high lymphocyte count better survival. Conclusion. An elevated NLR before treatment signals more aggressive disease and correlates with risk factors for ovarian cancer. CA125 directly correlates with neutrophils which may reflect secretion of both CA125 and neutrophilic growth factors by the tumor. CA125 inversely correlates with lymphocytes which may reflect the ability of some neutrophilic factors to,induce lymphopenia and/or binding of CA125 to lymphocytes removing CA125 from the serum pool. Links between NLR, CA125, and epidemiologic factors may provide new clues about the pathogenesis and progression of ovarian cancer. (C) 2014 Elsevier Inc. All rights reserved. C1 [Williams, Kristina A.; Terry, Kathryn L.; Vitonis, Allison F.; Cramer, Daniel W.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Williams, Kristina A.; Terry, Kathryn L.; Goodman, Annekathryn; Cramer, Daniel W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Labidi-Galy, S. Intidhar] Dana Farber Canc Inst, Boston, MA 02115 USA. [Terry, Kathryn L.; Cramer, Daniel W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Welch, William R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Goodman, Annekathryn] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Cramer, DW (reprint author), Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave,RFB 365, Boston, MA 02115 USA. EM dcramer@partners.org OI labidi-galy, sana intidhar/0000-0002-0824-3475 FU Department of Defense [W81XWH-10-1-0280]; NCI [R01 CA054419] FX Supported by grants from the Department of Defense, W81XWH-10-1-0280 (Terry) and NCI, R01 CA054419 (Cramer). NR 35 TC 32 Z9 32 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2014 VL 132 IS 3 BP 542 EP 550 DI 10.1016/j.ygyno.2014.01.026 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AD8IF UT WOS:000333509000006 PM 24462730 ER PT J AU Guseh, SH Rauh-Hain, JA Tambouret, RH Davis, M Clark, RM Boruta, DM Goodman, A Growdon, WB Schorge, JO del Carmen, MG AF Guseh, Stephanie H. Rauh-Hain, J. Alejandro Tambouret, Rosemary H. Davis, Michelle Clark, Rachel M. Boruta, David M. Goodman, Annekathryn Growdon, Whitfield B. Schorge, John O. del Carmen, Marcela G. TI Transitional cell carcinoma of the ovary: A case-control study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Transitional cell carcinoma of the ovary; Chemotherapy; Survival ID CHEMOTHERAPY; PLATINUM; PATTERN AB Objectives. The aim of this study is to compare response to chemotherapy and survival between patients with transitional call carcinoma of the ovary (TCCO) and papillary serous ovarian cancer (PSOC). Methods. We identified women with both pure and mixed TCCO who were treated between 2000 and 2010. Each case was matched to two women with PSOC by age, grade, stage, and year of diagnosis. Correlation between categorical variables was assessed with chi square test. The Kaplan-Meier survival analysis was used to generate overall survival data (OS). Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. Results. Eighty-one women diagnosed with TCCO were selected as cases and compared to 162 controls. Women with TCCO had a lower rate of platinum resistance compared to controls (9% vs. 25%; p = 0.01). When multivariate logistic regression was used to control for other factors independently associated with platinum resistance, patients with TCCO had a significantly lower risk of platinum resistance compared to PSOC. Median progression-free survival was not significantly different (27 months vs. 22 months; p = 0.15) for women with TCCO and PSOC, respectively. Median OS, however, was significantly different at 83 months vs. 52 months for the TCCO and PSOC groups, respectively (p = 0.01). A Cox proportional hazards model identified optimal cytoreduction, transitional cell histology, age, stage, and platinum and paclitaxel chemotherapy as independent predictors of OS. Conclusions. Patients with TCCO are less likely to demonstrate resistance to platinum chemotherapy and have improved overall survival when compared to patients with PSOC. (C) 2014 Elsevier Inc. All rights reserved. C1 [Guseh, Stephanie H.; Rauh-Hain, J. Alejandro; Tambouret, Rosemary H.; Davis, Michelle; Clark, Rachel M.; Boruta, David M.; Goodman, Annekathryn; Growdon, Whitfield B.; 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, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mdelcarmen@partners.org NR 16 TC 3 Z9 4 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2014 VL 132 IS 3 BP 649 EP 653 DI 10.1016/j.ygyno.2014.01.020 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AD8IF UT WOS:000333509000023 PM 24462804 ER PT J AU Davis, M Rauh-Hain, JA Andrade, C Boruta, DM Schorge, JO Horowitz, NS May, T del Carmen, MG AF Davis, Michelle Rauh-Hain, J. Alejandro Andrade, Carolina Boruta, David M., II Schorge, John O. Horowitz, Neil S. May, Taymaa del Carmen, Marcela G. TI Comparison of clinical outcomes of patients with clear cell and endometrioid ovarian cancer associated with endometriosis to papillary serous carcinoma of the ovary SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Ovarian cancer; Endometriosis; Endometrioid carcinoma; Clear cell carcinoma ID POSTMENOPAUSAL WOMEN; TUMOR TYPE; ADENOCARCINOMA; THERAPY; PROGNOSIS; ARID1A; RISK; INFERTILITY; PREVALENCE; MUTATIONS AB Objective. The aim of this investigation was to compare outcomes of patients with dear cell carcinoma (CCC) and endometrioid carcinoma (EC) of the ovary associated with endometriosis to patients with ovarian papillary serous carcinoma (PSC). Methods. Patients with CCC and EC of the ovary associated with endometriosis were identified and matched by age and stage to PSC controls. Student's t test and chi square test were used to analyze continuous and categorical data. The Kaplan-Meier method was used for survival analysis. Results. 67 cases associated with endometriosis were identified, of which 45 were arising in endometriosis. Cases were matched to 134 PSC controls. 27 patients with tumors associated with endometriosis presented at stage I (40.3%), 27 at stage 11 (403%), ten at stage III (14.9%) and three at stage IV (4.5%). There was no difference in rate of optimal cytoreduction or response to chemotherapy in cases vs. PSC controls. There was a significant increase in synchronous endometrial cancer in tumors associated with endometriosis compared to PSC (25.4% vs. 3.7%; P < 0.001). 18 cases (26.9%) had recurrent disease vs. 55 (41%) controls (P = 0.03). The 5-year disease-free survival (DFS) and overall survival (OS) of patients with tumors associated with endometriosis compared to PSC controls were 75% vs. 55% (P = 0.03) and 85% vs. 77% (P = 0.2), respectively. Conclusions. Patients with tumors associated with endometriosis had a higher rate of synchronous endometrial cancer. Cases also demonstrated a lower rate of recurrence and improved 5 year DFS; however, this did not translate into a difference in OS. (C) 2014 Elsevier Inc. All rights reserved. C1 [Davis, Michelle; Rauh-Hain, J. Alejandro; Andrade, Carolina; 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. [Davis, Michelle; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. [May, Taymaa] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Div Gynecol Oncol, Toronto, ON, Canada. 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 OI Davis, Michelle/0000-0002-6925-9139 NR 37 TC 11 Z9 12 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2014 VL 132 IS 3 BP 760 EP 766 DI 10.1016/j.ygyno.2014.01.012 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AD8IF UT WOS:000333509000040 PM 24440832 ER PT J AU Wang, JM Iacovelli, J Spencer, C Saint-Geniez, M AF Wang, Jinmei Iacovelli, Jared Spencer, Carrie Saint-Geniez, Magali TI Direct Effect of Sodium Iodate on Neurosensory Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE sodium iodate; retinal degeneration; cytotoxicity; photoreceptor; oxidative stress ID PIGMENT EPITHELIUM DAMAGE; OXIDATIVE STRESS; SUBRETINAL SPACE; HEME OXYGENASE-1; REACTIVE OXYGEN; ARPE-19 CELLS; INDUCED MODEL; GROWTH-FACTOR; BONE-MARROW; STEM-CELLS AB PURPOSE. To systematically characterize the effects of NaIO3 on retinal morphology and function. METHODS. NaIO3 at 10, 20, or 30 mg/kg was administered by retro-orbital injection into adult C57BL/6J mice. Phenotypic and functional changes of the retina were assessed at 1, 3, 5, and 8 days postinjection by fundus imaging, optical coherence tomography (OCT), ERG, and histology. Direct NaIO3 cytotoxicity on ARPE-19 and 661W cells was quantified using lactate dehydrogenase (LDH) apoptosis assay. Effect of NaIO3 on RPE and photoreceptor gene expression was assessed in vitro and in vivo by quantitative PCR. RESULTS. While little to no change was observed in the 10 mg/kg NaIO3-injected group, significant retinal anomalies, such as RPE atrophy and retinal thinning, were observed in both 20 and 30 mg/kg NaIO3-injected groups. Gene expression analysis showed rapid downregulation of RPE-specific genes, increase in heme oxygenase 1 expression, and induction of the ratio of Bax to Bcl-2. Electroretinographic response loss and photoreceptor gene repression preceded gross morphological changes. High NaIO3 toxicity on 661W cells was observed in vitro along with reactive oxygen species (ROS) induction. NaIO3 treatment also disrupted oxidative stress, phototransduction, and apoptosis gene expression in 661W cells. Exposure of ARPE-19 cells to NaIO3 increased expression of neurotrophins and protected photoreceptors from direct NaIO3 cytotoxicity. CONCLUSIONS. Systematic characterization of changes associated with NaIO3 injection revealed a large variability in the severity of toxicity induced. Treatment with > 20 mg/kg NaIO3 induced visual dysfunction associated with rapid suppression of phototransduction genes and induced oxidative stress in photoreceptors. These results suggest that NaIO3 can directly alter photoreceptor function and survival. C1 [Wang, Jinmei; Iacovelli, Jared; Spencer, Carrie; Saint-Geniez, Magali] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Wang, Jinmei; Iacovelli, Jared; Saint-Geniez, Magali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Saint-Geniez, M (reprint author), Massachusetts Eye & Ear, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM magali_saintgeniez@meei.harvard.edu FU National Institutes of Health through the NIH Director's New Innovator Award Program [1-DP2-OD006649]; National Eye Institute [T32EY007145] FX Supported by the National Institutes of Health through the NIH Director's New Innovator Award Program, 1-DP2-OD006649 (MSG) and the award number T32EY007145 from the National Eye Institute (JI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health. NR 42 TC 18 Z9 20 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2014 VL 55 IS 3 BP 1941 EP 1952 DI 10.1167/iovs.13-13075 PG 12 WC Ophthalmology SC Ophthalmology GA AE0HZ UT WOS:000333645900032 PM 24481259 ER PT J AU Hamilos, DL AF Hamilos, Daniel L. TI Host-microbial interactions in patients with chronic rhinosinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Chronic rhinosinusitis; host; microbial; biofilm; innate; immunity; antimicrobial ID ENDOSCOPIC SINUS SURGERY; TOLL-LIKE RECEPTORS; EXPERIMENTAL RHINOVIRUS INFECTION; CHRONIC MAXILLARY SINUSITIS; SECRETORY LEUCOPROTEASE INHIBITOR; REFRACTORY CHRONIC RHINOSINUSITIS; SURFACTANT PROTEIN-A; NASAL EXPLANT MODEL; SERUM-AMYLOID-A; BACTERIAL BIOFILMS AB There has been considerable investigation of host-microbial interactions in patients with chronic rhinosinusitis (CRS) in hopes of elucidating mechanisms of disease and better treatment. Most attention has been paid to bacterial infection and potential underlying defects in innate immunity. Bacterial biofilm is present in most patients with CRS undergoing surgical intervention, and its presence is associated with more severe disease and worse surgical outcomes. A role for viral or fungal infection in patients with CRS is less clear. There is no evidence for a primary defect in mucociliary clearance in most patients with CRS. Decreased levels of certain antimicrobial proteins, most notably lactoferrin, have been found in sinus secretions, whereas levels of other antimicrobial proteins have been found to be normal. No primary defects in Toll-like receptors have been found in patients with CRS, although a 50% reduced expression of Toll-like receptor 9 was reported in patients with recalcitrant nasal polyps. A polymorphism in a bitter taste receptor was recently associated with refractory CRS and persistent Pseudomonas aeruginosa infection. A downregulation of innate immunity by maladaptive TH2 tissue inflammation has also been described in patients with recalcitrant nasal polyps, suggesting a link to persistent infection. To date, an effective means of restoring host-microbial balance and mitigating disease in patients with CRS remains elusive. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. EM dhamilos@partners.org FU Merck FX D. L. Hamilos has consultant arrangements with and has received grants from Merck and received royalties from UpToDate. NR 195 TC 33 Z9 34 U1 1 U2 13 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 MAR PY 2014 VL 133 IS 3 BP 640 EP + DI 10.1016/j.jaci.2013.06.049 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA AC3EK UT WOS:000332397600004 PM 24290275 ER PT J AU Harris, WH AF Harris, William H. TI Last Decade in THA: Unsettling and Disappointing SO JOURNAL OF ARTHROPLASTY LA English DT Letter C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. NR 0 TC 2 Z9 3 U1 1 U2 3 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 MAR PY 2014 VL 29 IS 3 BP 648 EP 648 DI 10.1016/j.arth.2013.10.011 PG 1 WC Orthopedics SC Orthopedics GA AD9JI UT WOS:000333580800041 PM 24295801 ER PT J AU Westra, SJ Li, XH Gulati, K Singh, S Liu, B Kalra, MK Abbara, S AF Westra, Sjirk J. Li, Xinhua Gulati, Kavita Singh, Sarabjeet Liu, Bob Kalra, Mannudeep K. Abbara, Suhny TI Entrance skin dosimetry and size-specific dose estimate from pediatric chest CTA SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Chest CT angiography; Pediatric; Radiation dose; Effective dose; Breast dose; CT image quality ID CONGENITAL HEART-DISEASE; TUBE CURRENT MODULATION; DUAL-SOURCE CT; LENGTH PRODUCT; CARDIAC-CATHETERIZATION; CARDIOVASCULAR CT; MULTIDETECTOR CT; YOUNG-CHILDREN; RADIATION RISK; BREAST-CANCER AB Background: Size-specific dose estimate (SSDE), which corrects CT dose index (CTDI) for body diameter and is a better measure of organ dose than is CTDI, has not yet been validated in vivo. Objective: The purpose was to determine the correlation between SSDE and measured breast entrance skin dose (ESD) for pediatric chest CT angiography across a variety of techniques, scanner models, and patient sizes. Methods: During 42 examinations done on 4 different scanners over 7 years, we measured mid-sternal ESD as an approximation of breast dose with skin dosimeters. We recorded age, weight, effective tube current, kilovoltage potential, console CTDI, and dose-length product, from which we calculated effective dose. We measured effective chest diameter to convert CTDI to SSDE, and we correlated SSDE with measured ESD, using linear regression. We evaluated image quality to answer the clinical question. Results: Patient mean (+/- SD) age was 8.4 +/- 6.1 years (median, 7.9 years; range, 0.02-19.5 years); mean weight was 35 +/- 27 kg (median, 26 kg range, 3.5-115 kg); effective chest diameter was 20 +/- 7 cm (median, 19 cm; range, 10-35 cm). Mean effective dose was 2.9 +/- 2.8 mSv (median, 2.2 mSv; range, 0.1-14.4 mSv). We observed a linear correlation (R-2= 0.98, P <. 005) between SSDE (mean, 11 +/- 11mGy; median, 7 mGy; range, 0.5-40 mGy) and breast ESD (mean, 12 +/- 11 mGy; median, 7 mGy; range, 0.3-44 mGy). Our doses, which compared favorably with those previously reported, decreased significantly (P < .05) during the course of our study, because of the introduction of automatic exposure control, low kilovoltage, and high pitch techniques. All studies were of diagnostic quality. Conclusion: SSDE is a valid dose measure in children undergoing chest CT angiography over a wide range of scanner platforms, techniques, and patient sizes, and it may be used to model breast dose and to document the results of dose reduction strategies. (C) 2014 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Westra, Sjirk J.; Li, Xinhua; Gulati, Kavita; Singh, Sarabjeet; Liu, Bob; Kalra, Mannudeep K.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 55 Fruit St,White 246 A, Boston, MA 02114 USA. EM swestra@partners.org FU Society for Pediatric Radiology Research and Education Foundation; General Electric Inc FX Dr Kalra has received research support from General Electric Inc that is unrelated to the topic of this article. Dr Westra is supported by a grant from the Society for Pediatric Radiology Research and Education Foundation for the performance of this work. None of the remaining authors report any potential conflicts of interest or commercial involvement. NR 44 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAR-APR PY 2014 VL 8 IS 2 BP 97 EP 107 DI 10.1016/j.jcct.2013.08.002 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AE1LA UT WOS:000333729600003 PM 24211194 ER PT J AU Azzalini, L Ghoshhajra, BB Elmariah, S Passeri, JJ Inglessis, I Palacios, IF Abbara, S AF Azzalini, Lorenzo Ghoshhajra, Brian B. Elmariah, Sammy Passeri, Jonathan J. Inglessis, Ignacio Palacios, Igor F. Abbara, Suhny TI The aortic valve calcium nodule score (AVCNS) independently predicts paravalvular regurgitation after transcatheter aortic valve replacement (TAVR) SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Aortic valve; Computed tomography; Paravalvular regurgitation; Transcatheter aortic valve replacement; Calcification; Calcium ID CORONARY-ARTERY CALCIUM; MULTIDETECTOR ROW CT; COREVALVE REVALVING SYSTEM; HIGH-RISK PATIENTS; COMPUTED-TOMOGRAPHY; IMPLANTATION IMPACT; CONSENSUS DOCUMENT; QUANTIFICATION; PROSTHESIS; STENOSIS AB Background: Paravalvular regurgitation (PVR) is an important predictor of mortality after transcatheter aortic valve replacement (TAVR). Aortic valve (AV) calcification is strongly associated with PVR. Objectives: This study proposes a new metric to quantify AV total calcium burden and its composition in large calcium nodules (CNs) and explores its relation with PVR after TAVR. Methods: In 133 patients that underwent TAVR, calcium burden of the AV was quantified with multidetector row CT as calcium mass. Each CN was characterized. The AV CN score (AVCNS) was defined as AV calcium mass x mass of the largest CN. PVR was assessed with echocardiography at 1 month. Logistic regression analysis was conducted to identify predictors of PVR. Results: Mean age was 84.1. 7.6 years (56% women). TAVR access was transapical in 56%. Procedural success was achieved in 92%. In-hospital mortality was 5%. At follow-up, the prevalence of absent/trace, mild, moderate, and severe PVR was 58%, 31%, 11%, and 0%, respectively. The only independent predictors of at least mild PVR were AVCNS (odds ratio [OR], 2.269; 95% CI, 1.433-3.593; P <.001), number of CNs on aortic annulus (OR, 1.822; 95% CI, 1.137-2.921; P =.013), and aortic annulus area (OR, 1.112; 95% CI, 1.010-1.223; P =.030). This model showed an area under the curve of 0.895 (95% CI, 0.830-0.960) for PVR prediction. Conclusions: AVCNS, a variable that comprises the total burden of AV calcification as well as calcification agglomeration in form of large nodules, is a novel and powerful independent predictor of PVR after TAVR. (c) 2014 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Azzalini, Lorenzo; Ghoshhajra, Brian B.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Azzalini, Lorenzo; Elmariah, Sammy; Passeri, Jonathan J.; Inglessis, Ignacio; Palacios, Igor F.] Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. [Azzalini, Lorenzo] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM Suhny.Abbara@utsouthwestem.edu NR 33 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAR-APR PY 2014 VL 8 IS 2 BP 131 EP 140 DI 10.1016/j.jcct.2013.12.013 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AE1LA UT WOS:000333729600007 PM 24661826 ER PT J AU Barake, M Klibanski, A Tritos, NA AF Barake, Maya Klibanski, Anne Tritos, Nicholas A. TI Effects of Recombinant Human Growth Hormone Therapy on Bone Mineral Density in Adults With Growth Hormone Deficiency: A Meta-Analysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH REPLACEMENT THERAPY; BODY-COMPOSITION; SUBSTITUTION THERAPY; ENDOCRINE-SOCIETY; MULTICENTER TRIAL; CUSHINGS-DISEASE; ONSET; METABOLISM; MASS; HYPOPITUITARISM AB Objective: GH deficiency is associated with decreased bone mineral density (BMD) and increased fracture risk. Because the effects of recombinant human GH (rhGH) therapy on BMD and bone mineral content have not been systematically investigated, we conducted a meta-analysis of pertinent studies. Design: A thorough search of the literature (MEDLINE, EMBASE, and the Cochrane Register) was performed. Relevant studies were divided and analyzed according to their design (randomized/controlled or prospective/retrospective) and duration of rhGH therapy (<12 months and >12 months). Results: Administration of rhGH led to a significant increase in lumbar spine (LS) and femoral neck (FN) BMD in randomized/controlled studies of more than 1 year [weighted mean difference (95% confidence interval)] of 0.038 g/cm(2) (0.011-0.065) and 0.021 g/cm(2) (0.006-0.037) at the LS and FN, respectively, and a nonsignificant drop at the same sites in studies of shorter duration. In prospective studies, a significant increase in the LS and FN BMD was obtained. On meta-regression, a negative association was observed between the change in LS and FN BMD and subjects' age and a positive association between the BMD change and treatment duration. In a subgroup analysis, the increase in LS and FN BMD was significant in men [0.048 g/cm(2) (0.033-0.064) and 0.051 g/cm(2) (0.003-0.098), respectively] but not in women. Conclusion: This meta-analysis suggests a beneficial effect of rhGH replacement on BMD in adults with GH deficiency. This effect is affected by gender, age, and treatment duration. Larger studies are needed to evaluate the effect of rhGH on fracture risk. C1 [Barake, Maya; Klibanski, Anne; Tritos, Nicholas A.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA USA. [Barake, Maya; Klibanski, Anne; Tritos, Nicholas A.] Harvard Univ, Sch Med, Boston, MA USA. [Barake, Maya] Bellevue Univ, Med Ctr, Beirut 00961, Lebanon. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org FU Ipsen; Novartis; Rhythm Pharmaceuticals; Pfizer, Inc; Ipsen, US FX M.B. has nothing to disclose. A. K. has received grant support from Ipsen, Novartis, and Rhythm Pharmaceuticals. N.A.T. has received research support from Pfizer, Inc and Ipsen, US and consulted for Pfizer, Inc. NR 49 TC 14 Z9 15 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2014 VL 99 IS 3 BP 852 EP 860 DI 10.1210/jc.2013-3921 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7RD UT WOS:000333461600046 PM 24423364 ER PT J AU Sidhoum, VF Chan, YM Lippincott, MF Balasubramanian, R Quinton, R Plummer, L Dwyer, A Pitteloud, N Hayes, FJ Hall, JE Martin, KA Boepple, PA Seminara, SB AF Sidhoum, Valerie F. Chan, Yee-Ming Lippincott, Margaret F. Balasubramanian, Ravikumar Quinton, Richard Plummer, Lacey Dwyer, Andrew Pitteloud, Nelly Hayes, Frances J. Hall, Janet E. Martin, Kathryn A. Boepple, Paul A. Seminara, Stephanie B. TI Reversal and Relapse of Hypogonadotropic Hypogonadism: Resilience and Fragility of the Reproductive Neuroendocrine System SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; KALLMANN-SYNDROME; PHENOTYPIC SPECTRUM; HOMOZYGOUS MUTATION; LUTEINIZING-HORMONE; TESTOSTERONE LEVELS; DELAYED PUBERTY; GNRH RECEPTOR; SECRETION; GENE AB Context: A subset of patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH) later achieves activation of their hypothalamic-pituitary-gonadal axis with normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal. Objective: The objective of this study was to determine the natural history of reversal and to identify associated phenotypes and genotypes. Design, Setting, and Subjects: This was a retrospective review of clinical, biochemical, and genetic features of patients with IHH evaluated at an academic medical center. Main Outcome Measures: History of spontaneous fertility, regular menses, testicular growth, or normalization of serum sex steroids, LH secretory profiles, brain imaging findings, and sequences of 14 genes associated with IHH were reviewed. Results: Of 308 patients with IHH, 44 underwent reversal. Time-to-event analysis estimated a lifetime incidence of reversal of 22%. There were no differences in the rates of cryptorchidism, micropenis, or partial pubertal development in patients with reversal vs IHH patients without reversal. Fifteen patients with reversal (30%) had Kallmann syndrome (IHH and anosmia); one had undetectable olfactory bulbs on a brain magnetic resonance imaging scan. Subjects with reversal were enriched for mutations affecting neurokinin B signaling compared with a cohort of IHH patients without reversal (10% vs 3%, P = .044), had comparable frequencies of mutations in FGFR1, PROKR2, and GNRHR, and had no mutations in KAL1. Five men did not sustain their reversal and again developed hypogonadotropism. Conclusions: Reversal of IHH may be more widespread than previously appreciated and occurs across a broad range of genotypes and phenotypes. Enrichment for mutations that disrupt neurokinin B signaling in patients who reversed indicates that, despite the importance of this signaling pathway for normal pubertal timing, its function is dispensable later in life. The occurrence of reversal in a patient with no olfactory bulbs demonstrates that these structures are not essential for normal reproductive function. Patients with IHH require lifelong monitoring for reversal and, if reversal occurs, subsequent relapse also may occur. C1 [Sidhoum, Valerie F.; Chan, Yee-Ming; Lippincott, Margaret F.; Balasubramanian, Ravikumar; Plummer, Lacey; Dwyer, Andrew; Pitteloud, Nelly; Hayes, Frances J.; Hall, Janet E.; Martin, Kathryn A.; Boepple, Paul A.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Ctr Reprod Endocrine Sci, Boston, MA 02114 USA. [Sidhoum, Valerie F.; Chan, Yee-Ming; Lippincott, Margaret F.; Balasubramanian, Ravikumar; Plummer, Lacey; Dwyer, Andrew; Pitteloud, Nelly; Hayes, Frances J.; Hall, Janet E.; Martin, Kathryn A.; Boepple, Paul A.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Quinton, Richard] Newcastle Univ, Inst Human Genet, Dept Endocrinol, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,55 Fruit St, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Lippincott, Margaret/0000-0002-3533-1999; Hall, Janet/0000-0003-4644-3061 FU Lung GO Sequencing Project [HL-102923]; Women's Health Initiative Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010]; National Institutes of Health [U54 HD028138, R01 HD015788]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [M01-RR-01066, UL1 RR025758, UL1TR000170]; Harvard University FX We thank members of the Massachusetts General Hospital Reproductive Endocrine Unit for discussions and reading of the manuscript, Dr Hang Lee for statistical advice, staff of the Harvard Catalyst Clinical Research Center for assistance with the frequent sampling studies, and all physicians who referred these patients. We also thank the National Heart, Lung, and Blood Institute Grand Opportunity (GO) Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the Women's Health Initiative Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010).; This work was supported by Grants U54 HD028138 and R01 HD015788 from the National Institutes of Health and by the Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Awards M01-RR-01066, UL1 RR025758, and UL1TR000170, and financial contributions from Harvard University and its affiliated academic health care centers). NR 53 TC 27 Z9 31 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2014 VL 99 IS 3 BP 861 EP 870 DI 10.1210/jc.2013-2809 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7RD UT WOS:000333461600047 PM 24423288 ER PT J AU Balasubramanian, R Cohen, DA Klerman, EB Pignatelli, D Hall, JE Dwyer, AA Czeisler, CA Pitteloud, N Crowley, WF AF Balasubramanian, Ravikumar Cohen, Daniel A. Klerman, Elizabeth B. Pignatelli, Duarte Hall, Janet E. Dwyer, Andrew A. Czeisler, Charles A. Pitteloud, Nelly Crowley, William F., Jr. TI Absence of Central Circadian Pacemaker Abnormalities in Humans With Loss of Function Mutation in Prokineticin 2 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUPRACHIASMATIC NUCLEUS; KALLMANN-SYNDROME; MICE LACKING; SLEEP; RHYTHMS; PERFORMANCE; GENETICS; REPRODUCTION; NEURONS; CLOCK AB Context: Loss of prokineticin 2 (PROK2) signaling in mice disrupts circadian rhythms, but the role of PROK2 signaling in the regulation of circadian rhythms in humans is undetermined. Objective: The aim of the study was to examine the circadian rhythms of humans with a complete loss-of-function PROK2 mutation using an inpatient constant routine (CR) protocol. Design and Setting: We conducted a case study in an academic medical center. Subjects and Methods: Two siblings (one male and one female, ages 67 and 62 y, respectively) with isolated GnRH deficiency (IGD) due to a biallelic loss-of-function PROK2 mutation were studied using an inpatient CR protocol. Historical data from inpatient CR protocols conducted in healthy controls (ages 65-81 y) were used for comparison. Main Outcome Measures: We measured circadian phase markers (melatonin, cortisol, and core body temperature) and neurobehavioral performance (psychomotor vigilance task [PVT] and subjective alertness scale). Results: Circadian waveforms of melatonin and cortisol did not differ between the IGD participants with PROK2 mutation and controls. In both IGD participants, neurobehavioral testing with PVT showed disproportionate worsening of PVT lapses and median reaction time in the second half of the CR. Conclusions: Humans with loss of PROK2 signaling lack abnormalities in circadian phase markers, indicating intact central circadian pacemaker activity in these patients. These results suggest that PROK2 signaling in humans is not required for central circadian pacemaker function. However, impaired PVT in the PROK2-null participants despite preserved endocrine rhythms suggests that PROK2 may transmit circadian timing information to some neurobehavioral neural networks. C1 [Balasubramanian, Ravikumar; Hall, Janet E.; Dwyer, Andrew A.; Pitteloud, Nelly; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Balasubramanian, Ravikumar; Hall, Janet E.; Dwyer, Andrew A.; Pitteloud, Nelly; Crowley, William F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Cohen, Daniel A.; Klerman, Elizabeth B.; Czeisler, Charles A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Cohen, Daniel A.; Klerman, Elizabeth B.; Czeisler, Charles A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Pignatelli, Duarte] Hosp Sao Joao, Dept Endocrinol, P-4200319 Oporto, Portugal. [Pignatelli, Duarte] Fac Med, Dept Expt Biol, P-4200319 Oporto, Portugal. [Pignatelli, Duarte] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, P-4200319 Oporto, Portugal. RP Balasubramanian, R (reprint author), Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, 55 Fruit St, Boston, MA 02114 USA. EM rbalasubramanian@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Pignatelli, Duarte/0000-0002-5555-7004; Hall, Janet/0000-0003-4644-3061 FU National Institutes of Health [R01 HD15788, U54 HD028138, K02-HD045459, P01-AG009975, RC2-HL101340, K24-HL105664, T32-HLO701-10, M01-RR-02635]; Vanda Pharmaceuticals; Bombardier, Inc.; Boston Red Sox; Boston Celtics; Cephalon, Inc.; Michael Jackson's mother and children; Koninklijke Philips Electronics, N.V.; Novartis; United Parcel Service (UPS); Vanda Pharmaceuticals, Inc.; Zeo Inc.; Cephalon; National Football League Charities; ResMed; Philips Respironics FX This work was supported by National Institutes of Health Grants R01 HD15788 and U54 HD028138 (to W. F. C.), K02-HD045459 (to E. B. K.), P01-AG009975, RC2-HL101340, K24-HL105664 (to E. B. K.), T32-HLO701-10 (to D. A. C.), and M01-RR-02635.; W.F.C. is a consultant for Quest and Athena Diagnostics. E. B. K. is supported for clinical work but is not the site-responsible investigator on a multi-center trial supported by Vanda Pharmaceuticals. C. A. C. has received consulting fees from or served as a paid member of scientific advisory boards for: Bombardier, Inc.; Boston Red Sox; Boston Celtics; Cephalon, Inc. (acquired by Teva Pharmaceutical Industries Ltd. October 2011); Michael Jackson's mother and children; Koninklijke Philips Electronics, N.V.; Novartis; United Parcel Service (UPS); and Vanda Pharmaceuticals, Inc.; and Zeo Inc. C. A. C. owns an equity interest in Lifetrac, Inc.; Somnus Therapeutics, Inc.; and Vanda Pharmaceuticals, Inc., and received royalties from McGraw Hill, Penguin Press/Houghton Mifflin Harcourt, and Philips Respironics, Inc. C. A. C. has also received research support from Cephalon, National Football League Charities, ResMed and Philips Respironics. C. A. C. is the incumbent of an endowed professorship provided to Harvard University by Cephalon, Inc. and holds a number of process patents in the field of sleep/circadian rhythms (e.g., photic resetting of the human circadian pacemaker). Since 1985, C. A. C. has also served as an expert witness on various legal cases related to sleep and/or circadian rhythms. The other authors have nothing to declare. NR 33 TC 1 Z9 1 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2014 VL 99 IS 3 BP E561 EP E566 DI 10.1210/jc.2013-2096 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7RD UT WOS:000333461600023 PM 24423319 ER PT J AU Ma, RS Minsky, N Morshed, SA Davies, TF AF Ma, Risheng Minsky, Noga Morshed, Syed A. Davies, Terry F. TI Stemness in Human Thyroid Cancers and Derived Cell Lines: The Role of Asymmetrically Dividing Cancer Stem Cells Resistant to Chemotherapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TO-MESENCHYMAL TRANSITION; CARCINOMA; DIVISION; MEDULLOBLASTOMA; IDENTIFICATION; EQUILIBRIUM; POPULATION; EXPRESSION; MARKER; STATE AB Context: Cancer stem cells (CSCs) have the ability to self-renew through symmetric and asymmetric cell division. CSCs may arise from mutations within an embryonic stem cell/progenitor cell population or via epithelial-mesenchymal transition (EMT), and recent advances in the study of thyroid stem cells have led to a growing recognition of the likely central importance of CSCs in thyroid tumorigenesis. Objective: The objectives of this study were to establish the presence of a stem cell population in human thyroid tumors and to identify, isolate, and characterize CSCs in thyroid cancer cell lines. Results: 1) Human thyroid cancers (n = 10) and thyroid cancer cell lines (n = 6) contained a stem cell population as evidenced by pluripotent stem cell gene expression. 2) Pulse-chase experiments with thyroid cancer cells identified a label-retaining cell population, a primary characteristic of CSCs, which at mitosis divided their DNA both symmetrically and asymmetrically and included a population of cells expressing the progenitor marker, stage-specific embryonic antigen 1 (SSEA-1). 3) Cells positive for SSEA-1 expressed additional stem cell markers including Oct4, Sox2, and Nanog were confirmed as CSCs by their tumor-initiating properties in vivo, their resistance to chemotherapy, and their multipotent capability. 4) SSEA-1-positive cells showed enhanced vimentin expression and decreased E-cadherin expression, indicating their likely derivation via EMT. Conclusions: Cellular diversity in thyroid cancer occurs through both symmetric and asymmetric cell division, and SSEA-1-positive cells are one form of CSCs that appear to have arisen via EMT and may be the source of malignant thyroid tumor formation. This would suggest that thyroid cancer CSCs were the result of thyroid cancer transformation rather than the source. C1 Icahn Sch Med Mt Sinai, Thyroid Res Unit, New York, NY 10468 USA. James J Peters VA Med Ctr, New York, NY 10468 USA. RP Ma, RS (reprint author), VA Med Ctr, Room 2F-27,130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM risheng.ma@mssm.edu FU National Institutes of Health [DK080459, DK069713, DK052464]; VA Merit Review Program; David Owen Segal Endowment Fund FX This work was supported in part by Grants DK080459, DK069713, and DK052464 from the National Institutes of Health, by the VA Merit Review Program, and by the David Owen Segal Endowment Fund. NR 39 TC 13 Z9 14 U1 2 U2 11 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2014 VL 99 IS 3 BP E400 EP E409 DI 10.1210/jc.2013-3545 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD7RD UT WOS:000333461600002 PM 24823711 ER PT J AU Utzschneider, KM Largajolli, A Bertoldo, A Marcovina, S Nelson, JE Yeh, MM Kowdley, KV Kahn, SE AF Utzschneider, Kristina M. Largajolli, Anna Bertoldo, Alessandra Marcovina, Santica Nelson, James E. Yeh, Matthew M. Kowdley, Kris V. Kahn, Steven E. TI Serum ferritin is associated with non-alcoholic fatty liver disease and decreased B-cell function in non-diabetic men and women SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Insulin sensitivity; Ferritin; Insulin secretion in vivo; Fatty liver ID TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; HEREDITARY HEMOCHROMATOSIS; MAJOR DETERMINANTS; METABOLIC SYNDROME; IRON DEPLETION; HUMAN OBESITY; SENSITIVITY AB Aims: We sought to determine whether NAFLD is associated with poorer beta-cell function and if any beta-cell dysfunction is associated with abnormal markers of iron or inflammation. Methods: This was a cross-sectional study of 15 non-diabetic adults with NAFLD and 15 non-diabetic age and BMI-matched controls. Insulin sensitivity was measured by isotope-labeled hyperinsulinemic-euglycemic clamps and beta-cell function by both oral (OGTT) and intravenous glucose tolerance tests. Liver and abdominal fat composition was evaluated by CT scan. Fasting serum levels of ferritin, transferrin-iron saturation, IL-6, TNF alpha and hsCRP were measured. Results: Compared to controls, subjects with NAFLD had lower hepatic and systemic insulin sensitivity and 12,cell function was decreased as measured by the oral disposition index. Fasting serum ferritin and transferrin-iron saturation were higher in NAFLD and were positively associated with liver fat. Serum ferritin was negatively associated with beta-cell function measured by both oral and intravenous tests, but was not associated with insulin sensitivity. IL-6, TNF alpha and hsCRP did not differ between groups and did not correlate with serum ferritin, liver fat or measures of beta-cell function. Conclusions: These findings support a potential pathophysiological link between iron metabolism, liver fat and diabetes risk. Published by Elsevier Inc. C1 [Utzschneider, Kristina M.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Endocrinol & Metab, Seattle, WA USA. [Utzschneider, Kristina M.; Kahn, Steven E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Largajolli, Anna; Bertoldo, Alessandra] Univ Padua, Padua, Italy. [Nelson, James E.; Kowdley, Kris V.] Virginia Mason Med Ctr, Inst Digest Dis, Seattle, WA 98101 USA. [Nelson, James E.; Kowdley, Kris V.] Benaroya Res Inst, Seattle, WA USA. [Yeh, Matthew M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Kowdley, Kris V.] Univ Washington, Dept Med, Div Gastroenterol Hepatol, Seattle, WA USA. [Marcovina, Santica] Univ Washington, Dept Med, Seattle, WA USA. [Marcovina, Santica] Northwest Lipid Metab & Diabet Res Lab, Seattle, WA USA. RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst 151, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU United States Department of Veterans Affairs (Office of Research and Development Medical Research Service); [UL1RR025014]; [P30DK017047]; [P30DK035816]; [T32DK007247] FX This work was supported by the United States Department of Veterans Affairs (Office of Research and Development Medical Research Service) and grant numbers UL1RR025014, P30DK017047, P30DK035816 and T32DK007247. NR 49 TC 5 Z9 6 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2014 VL 28 IS 2 BP 177 EP 184 DI 10.1016/j.jdiacomp.2013.11.007 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD8VD UT WOS:000333542900015 PM 24360972 ER PT J AU Newhouse, JP McWilliams, JM Price, M Huang, J Fireman, B Hsu, J AF Newhouse, Joseph P. McWilliams, J. Michael Price, Mary Huang, Jie Fireman, Bruce Hsu, John TI Do Medicare Advantage plans select enrollees in higher margin clinical categories? (vol 6, pg 1278, 2013) SO JOURNAL OF HEALTH ECONOMICS LA English DT Correction C1 [Newhouse, Joseph P.] Harvard Univ, Kennedy Sch, Boston, MA 02115 USA. [Newhouse, Joseph P.; McWilliams, J. Michael; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [McWilliams, J. Michael] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Hsu, John] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Newhouse, JP (reprint author), Harvard Univ, 180 Longwood Ave, Boston, MA 02115 USA. EM joseph_newhouse@harvard.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 EI 1879-1646 J9 J HEALTH ECON JI J. Health Econ. PD MAR PY 2014 VL 34 BP 144 EP 144 DI 10.1016/j.jhealeco.2014.01.003 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AE2EX UT WOS:000333787200012 ER PT J AU Battaglia, PJ Maeda, Y Welk, A Hough, B Kettner, N AF Battaglia, Patrick J. Maeda, Yumi Welk, Aaron Hough, Brad Kettner, Norman TI RELIABILITY OF THE GOUTALLIER CLASSIFICATION IN QUANTIFYING MUSCLE FATTY DEGENERATION IN THE LUMBAR MULTIFIDUS USING MAGNETIC RESONANCE IMAGING SO JOURNAL OF MANIPULATIVE AND PHYSIOLOGICAL THERAPEUTICS LA English DT Article DE Magnetic Resonance Imaging; Low-Back Pain; Skeletal Muscle ID LOW-BACK-PAIN; PARASPINAL MUSCLES; ASYMPTOMATIC VOLUNTEERS; MR SPECTROSCOPY; QUANTIFICATION; ATROPHY; CT; ASSOCIATION; AGREEMENT; SYSTEM AB Objective: The purpose of this study was to investigate the reliability of the Goutallier classification system (GCS) for grading muscle fatty degeneration in the lumbar multifidus (LM) using magnetic resonance imaging (MRI) examinations. Methods: Lumbar spine MRI scans were obtained retrospectively from the radiology department imaging system. Two examiners (a chiropractic diagnostic imaging resident and a board certified chiropractic radiologist with 30 years of experience) independently graded each LM at the L4/5 and L5/S1 intervertebral level. ImageJ pixel analysis software (version 1.47; National Institutes of Health, Bethesda, MD) was used independently by 2 observers to quantify the percent fat of the LM and allow correlation between LM percent fat and GCS grade. Twenty-five subject MRIs were randomly selected. Magnetic resonance imaging scans were included if they were obtained using a 1.5 T imaging system and were excluded if there was evidence of spinal infection, tumor, fracture, or postoperative changes. For all tests, P < .05 was defined as significant. Results: Intraobserver reliability grading LM fat ranged from a weighted. (kappa(w)) of 0.71 to 0.93. Mean interobserver reliability grading LM fat was kappa(w), 0.76 to kappa(w), 0.85. There was a significant (P < .001) correlation between LM percent fat and GCS grade. Furthermore, interobserver reliability in determining percent fat was between intraclass correlation coefficient, 0.73 to intraclass correlation coefficient, 0.90. Conclusions: In this study, the GCS was reliable in grading LM fatty degeneration and correlated positively with a quantified percent fat value. In addition, ImageJ software (National Institutes of Health) was reliable between raters when quantifying LM percent fat. C1 [Battaglia, Patrick J.; Maeda, Yumi; Welk, Aaron; Kettner, Norman] Logan Univ, Dept Radiol, Chesterfield, MO 63006 USA. [Maeda, Yumi] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Hough, Brad] Logan Univ, Dept Informat Technol Serv, Chesterfield, MO USA. RP Battaglia, PJ (reprint author), Logan Univ, Dept Radiol, 1851 Schoettler Rd, Chesterfield, MO 63006 USA. EM Patrick.battaglia@logan.edu NR 29 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-4754 J9 J MANIP PHYSIOL THER JI J. Manip. Physiol. Ther. PD MAR-APR PY 2014 VL 37 IS 3 BP 190 EP 197 DI 10.1016/j.jmpt.2013.12.010 PG 8 WC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation SC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation GA AE2KS UT WOS:000333802400006 PM 24630770 ER PT J AU Powers, CJ Hirsch, JA Hussain, MS Patsalides, AT Blackham, KA Narayanan, S Lee, SK Fraser, JF Bulsara, KR Prestigiacomo, CJ Gandhi, CD Abruzzo, T Do, HM Meyers, PM Albuquerque, FC Frei, D Kelly, ME Pride, GL Jayaraman, MV AF Powers, Ciaran J. Hirsch, Joshua A. Hussain, M. Shazam Patsalides, Athos T. Blackham, Kristine A. Narayanan, Sandra Lee, Seon-Kyu Fraser, Justin F. Bulsara, Ketan R. Prestigiacomo, Charles J. Gandhi, Chirag D. Abruzzo, Todd Do, Huy M. Meyers, Philip M. Albuquerque, Felipe C. Frei, Donald Kelly, Michael E. Pride, G. Lee Jayaraman, Mahesh V. CA Soc NeuroInterventional Surg TI Standards of practice and reporting standards for carotid artery angioplasty and stenting SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article DE Standards ID RANDOMIZED CONTROLLED-TRIAL; SYMPTOMATIC PATIENTS; NEUROINTERVENTIONAL SURGERY; STROKE ASSOCIATION; PROTECTION DEVICES; EMBOLIC PROTECTION; PLAQUE ULCERATION; HEART-ASSOCIATION; ISCHEMIC-STROKE; ENDARTERECTOMY C1 [Powers, Ciaran J.] Wexner Med Ctr, Dept Neurosurg, Columbus, OH USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA. [Hussain, M. Shazam] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44106 USA. [Patsalides, Athos T.] Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Neurol Surg, New York, NY USA. [Blackham, Kristine A.] Case Western Reserve Univ, Univ Hosp Dept Radiol, Cleveland, OH 44106 USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Lee, Seon-Kyu] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Fraser, Justin F.] Univ Kentucky, Dept Neurol Surg, Lexington, KY USA. [Bulsara, Ketan R.] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Prestigiacomo, Charles J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. [Gandhi, Chirag D.] Univ Med & Dent New Jersey, New Jersey Med Sch, Neurol Inst New Jersey, Newark, NJ 07103 USA. [Abruzzo, Todd] Univ Cincinnati, Dept Neurosurg, Cincinnati, OH USA. [Do, Huy M.] Stanford Univ, Med Ctr, Dept Radiol, Stanford, CA 94305 USA. [Do, Huy M.] Stanford Univ, Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA. [Meyers, Philip M.] Columbia Univ, Dept Radiol, New York, NY USA. [Meyers, Philip M.] Columbia Univ, Dept Neurol Surg, New York, NY USA. [Albuquerque, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. [Frei, Donald] Radiol Imaging Associates, Dept Intervent Neuroradiol, Englewood, CO USA. [Kelly, Michael E.] Univ Saskatchewan, Royal Univ Hosp, Dept Neurosurg, Saskatoon, SK, Canada. [Pride, G. Lee] UT Southwestern, Dept Neuroradiol, Dallas, TX USA. [Jayaraman, Mahesh V.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. RP Jayaraman, MV (reprint author), Brown Univ, Warren Alpert Sch Med, 593 Eddy St,Room 377, Providence, RI 02912 USA. EM MJayaraman@Lifespan.org; MJayaraman@Lifespan.org RI Powers, Ciaran/E-3890-2011; OI Fraser, Justin/0000-0002-5980-3989 NR 41 TC 4 Z9 4 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAR PY 2014 VL 6 IS 2 BP 87 EP 90 DI 10.1136/neurintsurg-2013-011013 PG 4 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AD8RP UT WOS:000333533600012 PM 24198273 ER PT J AU Hirsch, JA Becker, GJ Derdeyn, CP Jayaraman, MV Traynelis, VC Meyers, PM AF Hirsch, Joshua A. Becker, Gary J. Derdeyn, Colin P. Jayaraman, Mahesh V. Traynelis, Vincent C. Meyers, Philip M. TI Maintenance of certification: part 2-continuous certification SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article DE Standards C1 [Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NeuroEndovasc Div, Boston, MA 02114 USA. [Becker, Gary J.] Amer Board Radiol, Tucson, AZ USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA. [Jayaraman, Mahesh V.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Providence, RI 02903 USA. [Traynelis, Vincent C.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Meyers, Philip M.] Neurol Inst, Dept Neurol Surg, New York, NY 10032 USA. RP Hirsch, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NeuroEndovasc Div, Boston, MA 02114 USA. EM Hirsch@snisonline.org OI Derdeyn, Colin/0000-0002-5932-2683 NR 15 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 EI 1759-8486 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD MAR PY 2014 VL 6 IS 2 BP 156 EP 160 DI 10.1136/neurintsurg-2013-010693 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA AD8RP UT WOS:000333533600025 PM 23502705 ER PT J AU Zash, RM Ajose-Popoola, O Stordal, K Souda, S Ogwu, A Dryden-Peterson, S Powis, K Lockman, S Makhema, J Essex, M Shapiro, RL AF Zash, Rebecca M. Ajose-Popoola, Olubunmi Stordal, Ketil Souda, Sajini Ogwu, Anthony Dryden-Peterson, Scott Powis, Kathleen Lockman, Shahin Makhema, Joe Essex, Max Shapiro, Roger L. TI Risk factors for mortality among human immunodeficiency virus-exposed and unexposed infants admitted to a neonatal intensive care unit in Botswana SO JOURNAL OF PAEDIATRICS AND CHILD HEALTH LA English DT Article DE neonatal intensive care unit; feeding method; neonatal mortality; Botswana; HIV ID HIV-INFECTED MOTHERS; SUB-SAHARAN AFRICA; UNINFECTED CHILDREN; SYSTEMATIC ANALYSIS; UNDER-5 MORTALITY; BORN; PREDICTORS; COUNTRIES; SURVIVAL; PROGRESS AB Aim Newborns admitted to neonatal units (NNUs) in resource-limited settings face a high risk of mortality, but the epidemiology of these deaths is poorly understood. We describe risk factors for NNU mortality in an area with high prevalence of human immunodeficiency virus (HIV). Methods We performed a prospective cohort study of infants admitted to the NNU at a public referral hospital in Gaborone, Botswana. The primary outcome was neonatal death, defined as death within 28 days of a live delivery. Cox proportional hazard models were used to evaluate risk factors for mortality. Results From October 2008 to April 2009, 449 neonates were admitted to the NNU. Cumulative mortality was 24.5% (110/449). Factors associated with increased risk of death included lack of enteral feeding (hazard ratio (HR) 18.8, 95% confidence interval (CI) 10.3, 34.2), gestational age <28 weeks (HR 2.0, 95% CI 1.1, 3.8) and Apgar score <7 at 10 min (HR 2.5, 95% CI 1.5, 4.2). Among 348 (78%) infants who were fed, there was no difference in mortality between infants who were breastfed compared with those who were formula fed or had mixed feeding (P = 0.76). There was no significant mortality difference by HIV exposure status; 35 (28%) of 128 HIV-exposed infants died compared with 55 (21%) of 272 HIV-unexposed infants (P = 0.19). Conclusions This study identified low Apgar scores, extreme prematurity and lack of enteral feeding as the most important risk factors for mortality in this NNU setting. HIV exposure and formula feeding were not significantly associated with death in neonates who were very ill. C1 [Zash, Rebecca M.; Shapiro, Roger L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Publ Hlth, Div Infect Dis, Boston, MA 02215 USA. [Dryden-Peterson, Scott; Lockman, Shahin] Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Infect Dis Unit, Boston, MA 02115 USA. [Powis, Kathleen] Harvard Univ, Dept Internal Med, Sch Publ Hlth, Boston, MA 02115 USA. [Powis, Kathleen] Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA 02115 USA. [Powis, Kathleen; Lockman, Shahin; Essex, Max; Shapiro, Roger L.] Harvard Univ, Dept Immunol & Infect Dis, Sch Publ Hlth, Boston, MA 02115 USA. [Ajose-Popoola, Olubunmi] Univ Calif, Irvine Med Ctr, Dept Otolaryngol Head & Neck Surg, Orange, CA 92668 USA. [Zash, Rebecca M.; Souda, Sajini; Ogwu, Anthony; Dryden-Peterson, Scott; Powis, Kathleen; Lockman, Shahin; Makhema, Joe; Essex, Max; Shapiro, Roger L.] Botswana Harvard AIDS Inst Partnership HIV Res &, Gaborone, Botswana. [Stordal, Ketil] Princess Marina Hosp, Gaborone, Botswana. [Stordal, Ketil] Norwegian Inst Publ Hlth, Oslo, Norway. RP Zash, RM (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Lowry Med Off Bldg,Suite GB,110 Francis St, Boston, MA 02215 USA. EM rzash@bidmc.harvard.edu RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 FU Pasteur Clinical Research Program; Office of Enrichment Programs at Harvard Medical School; Doris Duke Clinical Research Foundation; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Center for Advancing Translational Sciences, National Institutes of Health Award) [8UL1TR000170-05]; Harvard University FX We are grateful to the staff of maternity ward and special care baby unit at PMH and to our research assistants Kelebogile Binda, Onalenna Nthase and Itereleng Kelapile. We would like to thank the Pasteur Clinical Research Program, Office of Enrichment Programs at Harvard Medical School and the Doris Duke Clinical Research Foundation for providing financial support for this study. This work was also conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Center for Advancing Translational Sciences, National Institutes of Health Award 8UL1TR000170-05, and financial contributions from Harvard University and its affiliated academic health-care centres). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health-care centres, or the National Institutes of Health. NR 33 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1034-4810 EI 1440-1754 J9 J PAEDIATR CHILD H JI J. Paediatr. Child Health PD MAR PY 2014 VL 50 IS 3 BP 189 EP 195 DI 10.1111/jpc.12454 PG 7 WC Pediatrics SC Pediatrics GA AD7SA UT WOS:000333464700005 PM 24372811 ER PT J AU Prigerson, HG Maciejewski, PK AF Prigerson, Holly G. Maciejewski, Paul K. TI Predicting Prolonged Grief Disorder: Caregiver Prodrome Turns Bereaved Survivor Syndrome. Commentary on Thomas et al. SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Editorial Material ID MENTAL-HEALTH C1 [Prigerson, Holly G.; Maciejewski, Paul K.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, McGraw Patterson Ctr Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.; Maciejewski, Paul K.] Harvard Univ, Sch Med, Boston, MA USA. [Maciejewski, Paul K.] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA. RP Prigerson, HG (reprint author), Weill Cornell Med Coll, Dept Med, 525 East 68th St,1404 Baker Bldg, New York, NY 10065 USA. EM hgp2001@med.cornell.edu NR 3 TC 1 Z9 1 U1 2 U2 5 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 MAR PY 2014 VL 47 IS 3 BP 516 EP 517 DI 10.1016/j.jpainsymman.2013.10.002 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AD4YE UT WOS:000333257000004 PM 24269032 ER PT J AU Bona, K Dussel, V Orellana, L Kang, T Geyer, R Feudtner, C Wolfe, J AF Bona, Kira Dussel, Veronica Orellana, Liliana Kang, Tammy Geyer, Russ Feudtner, Chris Wolfe, Joanne TI Economic Impact of Advanced Pediatric Cancer on Families SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Pediatric; oncology; palliative care; financial; poverty; disparities ID HEALTH-CARE NEEDS; CHILDHOOD-CANCER; PALLIATIVE CARE; CHILDREN; COSTS; PARENTS; INCOME AB Context. Despite emerging evidence of substantial financial distress in families of children with complex illness, little is known about economic hardship in families of children with advanced cancer. Objectives. To describe perceived financial hardship, work disruptions, income losses, and associated economic impact in families of children with advanced cancer stratified by federal poverty level (FPL). Methods. Cross-sectional survey of 86 parents of children with progressive, recurrent, or nonresponsive cancer at three children's hospitals. Seventy-one families with complete income data (82%) are included in this analysis. Results. Parental work disruptions were prevalent across all income levels, with 67 (94%) families reporting some disruption. At least one parent quit a job because of the child's illness in 29 (42%) families. Nineteen (27%) families described their child's illness as a great economic hardship. Income losses because of work disruptions were substantial for all families; families at or below 200% FPL, however, were disproportionately affected. Six (50%) of the poorest families lost more than 40% of their annual income as compared with two (5%) of the wealthiest families (P = 0.006). As a result of income losses, nine (15%) previously nonpoor families fell from above to below 200% FPL. Conclusion. The economic impact of pediatric advanced cancer on families is significant at all income levels, although poorer families suffer disproportionate losses. Development of ameliorative intervention strategies is warranted. J Pain Symptom Manage 2014; 47: 594-603. (C) 2014 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Bona, Kira; Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Bona, Kira; Wolfe, Joanne] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02215 USA. [Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. [Bona, Kira; Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA. [Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Orellana, Liliana] Univ Buenos Aires, Inst Calculus, Sch Sci, Buenos Aires, DF, Argentina. [Kang, Tammy; Feudtner, Chris] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Geyer, Russ] Seattle Childrens Hosp, Div Pediat Hematol Oncol, Washington, DC USA. [Geyer, Russ] Fred Hutchinson Canc Res Ctr, Washington, DC USA. [Geyer, Russ] Univ Washington, Washington, DC USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Pediat Palliat Care Serv, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA. EM Joanne_wolfe@dfci.harvard.edu RI Orellana, Liliana/S-3302-2016 OI Orellana, Liliana/0000-0003-3736-4337 FU NIH/NCI [1K07 CA096746-01]; Charles H. Hood Foundation Child Health Research Award; American Cancer Society Pilot and Exploratory Project Award in Palliative Care of Cancer Patients and Their Families FX This project was part of the PediQUEST study (Evaluation of Pediatric Quality of Life and Evaluation of Symptoms Technology in Children with Cancer) and funded by NIH/NCI 1K07 CA096746-01, a Charles H. Hood Foundation Child Health Research Award, and an American Cancer Society Pilot and Exploratory Project Award in Palliative Care of Cancer Patients and Their Families. The authors have no financial relationships or conflicts of interest relevant to this article to disclose. NR 27 TC 21 Z9 21 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 EI 1873-6513 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2014 VL 47 IS 3 BP 594 EP 603 DI 10.1016/j.jpainsymman.2013.04.003 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AD4YE UT WOS:000333257000012 PM 23870843 ER PT J AU McMahan, RD Sudore, R AF McMahan, Ryan D. Sudore, Rebecca TI Advance Directives, Advance Care Planning, and Shared Decision Making: Promoting Synergy Over Exclusivity in Contemporary Context Reply SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Letter ID LIFE CARE; TRIAL; END C1 [McMahan, Ryan D.; Sudore, Rebecca] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA. RP McMahan, RD (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA. EM rebecca.sudore@ucsf.edu NR 9 TC 0 Z9 0 U1 1 U2 5 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 MAR PY 2014 VL 47 IS 3 BP E3 EP E4 DI 10.1016/j.jpainsymman.2013.12.228 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA AD4YE UT WOS:000333257000002 PM 24508005 ER PT J AU Hilgeman, MM Mahaney-Price, AF Stanton, MP McNeal, SF Pettey, KM Tabb, KD Litaker, MS Parmelee, P Hamner, K Martin, MY Hawn, MT Kertesz, SG Davis, LL AF Hilgeman, Michelle M. Mahaney-Price, Ann F. Stanton, Marietta P. McNeal, Sandre F. Pettey, Kristin M. Tabb, Kroshona D. Litaker, Mark S. Parmelee, Patricia Hamner, Karl Martin, Michelle Y. Hawn, Mary T. Kertesz, Stefan G. Davis, Lori L. CA Alabama Vet Rural Hlth Initiative TI Alabama Veterans Rural Health Initiative: A Pilot Study of Enhanced Community Outreach in Rural Areas SO JOURNAL OF RURAL HEALTH LA English DT Article DE veterans; motivational interviewing; utilization of health services; access to care; evaluation design and research ID ILLNESS RATING-SCALE; QUALITY-OF-LIFE; OUTPATIENT CLINICS; URBAN VETERANS; VA HOSPITALS; CARE; ACCESS; SERVICES; DISTANCE; AFFAIRS AB Purpose Access, enrollment, and engagement with primary and specialty health care services present significant challenges for rural populations worldwide. The Alabama Veterans Rural Health Initiative evaluated an innovative outreach intervention combining motivational interviewing, patient navigation, and health services education to promote utilization of the United States Veterans Administration Healthcare System (VA) by veterans who live in rural locations. Methods Community outreach workers completed the intervention and assessment, enrolling veterans from 31 counties in a southern state. A total 203 participants were randomized to either an enhanced enrollment and engagement outreach condition (EEE, n = 101) or an administrative outreach (AO, n = 102) condition. Findings EEE participants enrolled and attended VA appointments at higher rates and within fewer days than those who received AO. Eighty-seven percent of EEE veterans attended an appointment within 6 months, compared to 58% of AO veterans (P < .0001). The median time to first appointment was 12 days for the EEE group and 98 days for the AO group (P < .0001). Additionally, a race by outreach group interaction emerged: black and white individuals benefited equally from the EEE intervention; however, black individuals who received AO took significantly longer to attend appointments than their white counterparts. Conclusions Results provide needed empirical support for a specific outreach intervention that speeds enrollment and engagement for rural individuals in VA services. Planned interventions to improve service utilization should ameliorate ambivalence about accessing health care in addition to addressing traditional systems or environmental-level barriers. C1 [Hilgeman, Michelle M.; Mahaney-Price, Ann F.; Davis, Lori L.] Tuscaloosa VA Med Ctr, Res & Dev Serv, Tuscaloosa, AL 35404 USA. [Hilgeman, Michelle M.; Mahaney-Price, Ann F.; Davis, Lori L.] Tuscaloosa Res & Educ Adv Corp, Tuscaloosa, AL USA. [Hilgeman, Michelle M.; Parmelee, Patricia] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. [Stanton, Marietta P.; Hamner, Karl] Univ Alabama, Coll Nursing, Tuscaloosa, AL USA. [McNeal, Sandre F.; Tabb, Kroshona D.; Hawn, Mary T.; Kertesz, Stefan G.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [McNeal, Sandre F.] Univ Alabama Birmingham, Dept Surg, Sect GI Surg, Birmingham, AL 35294 USA. [Pettey, Kristin M.] VA Southeast Vet Integrated Serv Network VISN, Off 7, Dept Vet Affairs, Tuscaloosa, AL USA. [Litaker, Mark S.] Univ Alabama Birmingham, Dept Clin & Community Sci, Div Behav & Populat Sci, Birmingham, AL USA. [Hamner, Karl] Univ Alabama, Sch Social Work, Tuscaloosa, AL USA. [Martin, Michelle Y.; Kertesz, Stefan G.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Davis, Lori L.] Univ Alabama Birmingham, Sch Med, Dept Psychiat & Behav Med, Birmingham, AL USA. RP Hilgeman, MM (reprint author), Tuscaloosa VA Med Ctr, Res & Dev Serv, 3701 Loop Rd, Tuscaloosa, AL 35404 USA. EM Michelle.Hilgeman@va.gov FU VA Office of Rural Health FX Funding: The VA Office of Rural Health funded staff salaries and provided resources for the outreach activities described in this study; however, the sponsor did not have a role in study design, collection, analysis, interpretation of data, preparation of this report, or the decision to submit the paper for publication. NR 48 TC 2 Z9 2 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0890-765X EI 1748-0361 J9 J RURAL HEALTH JI J. Rural Health PD SPR PY 2014 VL 30 IS 2 BP 153 EP 163 DI 10.1111/jrh.12054 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AE0YI UT WOS:000333691800005 PM 24330220 ER PT J AU Greenfield, TK Ye, Y Bond, J Kerr, WC Nayak, MB Kaskutas, LA Anton, RF Litten, RZ Kranzler, HR AF Greenfield, Thomas K. Ye, Yu Bond, Jason Kerr, William C. Nayak, Madhabika B. Kaskutas, Lee Ann Anton, Raymond F. Litten, Raye Z. Kranzler, Henry R. TI Risks of Alcohol Use Disorders Related to Drinking Patterns in the US General Population SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID MAXIMUM NUMBER; UNITED-STATES; CONSEQUENCES; CONSUMPTION; GUIDELINES; DEPENDENCE; TRENDS; DRUNK; DRUNKENNESS; QUANTITY AB Objective: The purpose of this study was to examine the relations between drinking (mean quantity and heavy drinking patterns) and alcohol use disorders (AUDs) in the U.S. general population. Method: Data from three telephone National Alcohol Surveys (in 2000, 2005, and 2010) were pooled, with separate analyses for men and women restricted to current drinkers (ns = 5,922 men, 6,270 women). Predictors were 12-month volume (mean drinks per day), rates of heavy drinking (5+14+ drinks in a day for men/women), and very heavy drinking (8+, 12+, and 24+ drinks in a day). Outcomes were negative alcohol-related consequences constituting abuse (1+ of 4 DSM-IV-based domains assessed by 13 items) and alcohol dependence (symptoms in 3+ of 7 DSM-IV based domains), together taken to indicate an AUD. Segmentation analyses were used to model risks of problem outcomes from drinking patterns separately by gender. Results: In the general population, men and women who consumed <= 1 drink/day on average with no heavy drinking days did not incur substantial risks of an AUD (<10%). Men who drank from 1 to 2 drinks/day on average but never 5+ incurred a 16% risk of reporting an AUD (3.5% alcohol dependence). At higher volumes, men and women who indicated higher rates of drinking larger amounts per day and/or involving 8+ and 12+ drinks/day (and even 24+ drinks/day for men) showed much higher risks of experiencing AUDs. Conclusions: The findings provide quantitative guidance for primary care practitioners who wish to make population-based recommendations to patients who might benefit by reducing both overall intake and amounts per occasion in an effort to lower their risks of developing AUDs. C1 [Greenfield, Thomas K.; Ye, Yu; Bond, Jason; Kerr, William C.; Nayak, Madhabika B.; Kaskutas, Lee Ann] Inst Publ Hlth, Alcohol Res Grp, Emeryville, CA USA. [Greenfield, Thomas K.] Univ Calif San Francisco, Dept Psychiat, Clin Serv Res Training Program, San Francisco, CA USA. [Kaskutas, Lee Ann] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Litten, Raye Z.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Greenfield, TK (reprint author), Alcohol Res Grp, 6475 Christie Ave,Suite 400, Oakland, CA 94608 USA. EM tgreenfield@arg.org OI /0000-0002-3108-4812 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [P50 AA005595, K24 AA13736]; American Society of Clinical Psychopharmacology; Eli Lilly; Alkermes; Lundbeck; AbbVie FX This research was supported by Center Grant P50 AA005595 (to the Public Health Institute, Alcohol Research Group), including a supplement from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and Grant K24 AA13736 to Dr. Kranzler. Dr. Litten's contribution was supported by NIAAA. Drs. Anton and Kranzler performed this work in conjunction with their affiliation with the Alcohol Clinical Trials Initiative (ACTIVE) sponsored by the American Society of Clinical Psychopharmacology and funded in part by the following pharmaceutical companies: Eli Lilly, Alkermes, Lundbeck, and AbbVie (formerly Abbott Laboratories). In addition, Dr. Anton in the last 12 months was a member of the Scientific Advisory Board for Lundbeck and acted as a consultant for GlaxoSmithKline. In the last 12 months, Dr. Kranzler was a consultant to Alkermes, Lilly, Lundbeck, Pfizer, and Roche. Opinions are those of the authors and not the sponsoring institutions. Pharmaceutical companies listed herein have not reviewed or commented on the research. NR 50 TC 14 Z9 14 U1 3 U2 9 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAR PY 2014 VL 75 IS 2 BP 319 EP 327 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA AE0LL UT WOS:000333657700014 PM 24650826 ER PT J AU Falk, DE Litten, RZ Anton, RF Kranzler, HR Johnson, BA AF Falk, Daniel E. Litten, Raye Z. Anton, Raymond F. Kranzler, Henry R. Johnson, Bankole A. CA Active Workgrp TI Cumulative Proportion of Responders Analysis (CPRA) as a Tool to Assess Treatment Outcome in Alcohol Clinical Trials SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PAIN TRIALS; DEPENDENCE; DRINKING; EFFICACY; INTERVENTIONS; NALTREXONE AB Objective: Several definitions of treatment response have been proposed for alcohol clinical trials (e.g., abstinence and no heavy drinking). However, each of these outcomes allows only one definition of successful response. In contrast, the cumulative proportion of responders analysis (CPRA) includes all of the possible drinking response cutoff points, providing a more complete picture of the therapeutic effects of a treatment. CPRA has been used to examine the efficacy of analgesics but not alcohol pharmacotherapy. To demonstrate its potential utility, we conducted CPRA in two large alcohol treatment trials: the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) trial (naltrexone) and a multisite topiramate trial. CPRA was used to demonstrate the efficacy of naltrexone and topiramate on continuous measures of in-treatment drinking heavy drinking days and drinks per day and their reductions from pretreatment. Method: All possible cutoff points were portrayed for each measure. We provide graphs to illustrate the effects of the active medications compared with placebo and examined them statistically over a number of salient drinking outcomes to evaluate their efficacy. Results: Treatment group responder curves were not parallel across the entire range of cutoff points; rather, they separated only at lower levels of drinking. In general, effect sizes increased by 0.10-0.15 when going from the lowest drinking level cutoff (i.e., abstinence and no heavy drinking) to the cutoff associated with the maximal treatment effect. Conclusions: CPRA may be useful in designing subsequent trials and helping to illustrate for treatment providers the likelihood of treatment success given various definitions of a positive response. C1 [Falk, Daniel E.; Litten, Raye Z.] NIAAA, Div Treatment & Recovery Res, Rockville, MD 20852 USA. [Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Vet Integrated Serv Network 4, Philadelphia, PA USA. [Johnson, Bankole A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Falk, DE (reprint author), NIAAA, NIH, 5635 Fishers Lane,Room 2040, Rockville, MD 20852 USA. EM falkde@mail.nih.gov FU NIAAA NIH HHS [K05 AA017435] NR 33 TC 4 Z9 4 U1 0 U2 3 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD MAR PY 2014 VL 75 IS 2 BP 335 EP 346 PG 12 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA AE0LL UT WOS:000333657700016 PM 24650828 ER PT J AU Zappaterra, M Jim, L Pangarkar, S AF Zappaterra, Mauro Jim, Lysander Pangarkar, Sanjog TI Chronic pain resolution after a lucid dream: A case for neural plasticity? SO MEDICAL HYPOTHESES LA English DT Article ID LOW-BACK-PAIN; SYNAPTIC PLASTICITY; REHABILITATION; KETAMINE; TRIALS AB Chronic pain is often managed using a multidisciplinary, biopsychosocial approach. Interventions targeting the biological, psychological, and social aspects of both the patient and the pain have been demonstrated to provide objective and subjective improvement in chronic pain symptoms. The mechanism by which pain attenuation occurs after these interventions remains to be elucidated. While there is a relatively large body of empirical literature suggesting that functional and structural changes in the peripheral and central nervous systems are key in the development and maintenance of chronic pain states, less is known about changes that take place in the nervous system as a whole after biopsychosocial interventions. Using as a model the unique case of Mr. S, a patient suffering with chronic pain for 22 years who experienced a complete resolution of pain after a lucid dream following 2 years of biopsychosocial treatments, we postulate that central nervous system (CNS) reorganization (i.e., neural plasticity) serves as a possible mechanism for the therapeutic benefit of multidisciplinary treatments, and may set a neural framework for healing, in this case via a lucid dream. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Zappaterra, Mauro; Jim, Lysander; Pangarkar, Sanjog] VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. RP Zappaterra, M (reprint author), Dept Vet Affairs, Room W117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM maurozappaterra@gmail.com NR 26 TC 0 Z9 0 U1 3 U2 24 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PD MAR PY 2014 VL 82 IS 3 BP 286 EP 290 DI 10.1016/j.mehy.2013.12.011 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AD8CM UT WOS:000333494100009 PM 24398162 ER PT J AU Sahai, I Bailey, J Burke, L Eaton, RB Garganta, C Hecht, L Ingham, C Levy, HL Martin, M Phornphutkul, C Smith, W Zytkovicz, TH AF Sahai, I. Bailey, J. Burke, L. Eaton, R. B. Garganta, C. Hecht, L. Ingham, C. Levy, H. L. Martin, M. Phornphutkul, C. Smith, W. Zytkovicz, T. H. TI LOW CITRULLINE AS A MARKER FOR THE PROXIMAL UREA CYCLE DEFECTS: EIGHT YEAR EXPERIENCE OF THE NEW ENGLAND NEWBORN SCREENING PROGRAM SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD) CY MAR 09-12, 2014 CL Pacific Grove, CA SP Soc Inherited Metab Disorders C1 [Sahai, I.; Bailey, J.; Eaton, R. B.; Zytkovicz, T. H.] Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, MA USA. [Sahai, I.; Eaton, R. B.; Martin, M.; Zytkovicz, T. H.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Sahai, I.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Sahai, I.; Hecht, L.; Levy, H. L.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Burke, L.] Vermont Reg Genet Ctr, Burlington, VT USA. [Garganta, C.] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [Hecht, L.; Levy, H. L.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Ingham, C.] Vermont Dept Hlth, Vermont Newborn Screening Program, Burlington, VT 05402 USA. [Martin, M.] Univ Massachusetts, Med Ctr, Dept Pediat, Worcester, MA USA. [Phornphutkul, C.] Brown Univ, Rhode Isl Hosp, Dept Pediat, Providence, RI 02903 USA. [Smith, W.] Maine Med Ctr, Div Genet, Portland, ME 04102 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 MAR PY 2014 VL 111 IS 3 BP 273 EP 273 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AC4OI UT WOS:000332500200096 ER PT J AU Rugen, KW Watts, SA Janson, SL Angelo, LA Nash, M Zapatka, SA Brienza, R Gilman, SC Bowen, JL Saxe, JM AF Rugen, Kathryn Wirtz Watts, Sharon A. Janson, Susan L. Angelo, Laura A. Nash, Melanie Zapatka, Susan A. Brienza, Rebecca Gilman, Stuart C. Bowen, Judith L. Saxe, JoAnne M. TI Veteran Affairs Centers of Excellence in Primary Care Education: Transforming nurse practitioner education SO NURSING OUTLOOK LA English DT Article DE Interprofessional education; Nurse practitioner education; Primary care ID CHRONIC DISEASE; COMMUNITY; HOME AB To integrate health care professional learners into patient-centered primary care delivery models, the Department of Veterans Affairs has funded five Centers of Excellence in Primary Care Education (CoEPCEs). The main goal of the CoEPCEs is to develop and test innovative structural and curricular models that foster transformation of health care training from profession-specific "silos" to interprofessional, team-based educational and care delivery models in patient-centered primary care settings. CoEPCE implementation emphasizes four core curricular domains: shared decision making, sustained relationships, interprofessional collaboration, and performance improvement. The structural models allow interprofessional learners to have longitudinal learning experiences and sustained and continuous relationships with patients, faculty mentors, and peer learners. This article presents an overview of the innovative curricular models developed at each site, focusing on nurse practitioner (NP) education. Insights on transforming NP education in the practice setting and its impact on traditional NP educational models are offered. Preliminary outcomes and sustainment examples are also provided. C1 [Rugen, Kathryn Wirtz; Gilman, Stuart C.; Bowen, Judith L.] VA Off Acad Affiliat, Washington, DC USA. [Watts, Sharon A.] Louis Stokes Cleveland VA Med Ctr, Cleveland, OH USA. [Janson, Susan L.; Saxe, JoAnne M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Angelo, Laura A.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Nash, Melanie] Boise VA Med Ctr, Boise, ID USA. [Zapatka, Susan A.; Brienza, Rebecca] VA Connecticut Healthcare Syst, West Haven, CT USA. [Brienza, Rebecca] Yale Univ, Sch Med, New Haven, CT USA. RP Rugen, KW (reprint author), Jesse Brown VA Med Ctr, VA Ctr Excellence Primary Care Educ, Off Acad Affiliat, 820 South Damen, Chicago, IL 60612 USA. EM kathryn.rugen@va.gov FU Office of Academic Affiliations, Veterans Health Administration, US Department of Veterans Affairs FX The Centers of Excellence in Primary Care Education are funded by the Office of Academic Affiliations, Veterans Health Administration, US Department of Veterans Affairs. The authors would like to recognize Office of Academic Affiliations leadership, Malcolm Cox, MD; and site Co-Directors: Rebecca Shunk, MD (San Francisco VA Medical Center); Mamta Singh, MD (Louis Stokes Cleveland VA Medical Center); C. Scott Smith, MD (Boise VA Medical Center) and Joyce Wipf, MD (VA Puget Sound Healthcare System). NR 14 TC 8 Z9 8 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 EI 1528-3968 J9 NURS OUTLOOK JI Nurs. Outlook PD MAR-APR PY 2014 VL 62 IS 2 BP 78 EP 88 DI 10.1016/j.outlook.2013.11.004 PG 11 WC Nursing SC Nursing GA AD9FZ UT WOS:000333571500005 PM 24630678 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Neoadjuvant Pertuzumab: the Exception That Proves the Rule? SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID EARLY BREAST-CANCER; PLUS TRASTUZUMAB; TRIAL; CHEMOTHERAPY; SAFETY C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Harvard Univ, Sch Med, Boston, MA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2014 VL 28 IS 3 BP 197 EP 199 PG 3 WC Oncology SC Oncology GA AD8YF UT WOS:000333550900006 PM 24855726 ER PT J AU Wain, JC AF Wain, John C. TI Invasive Staging and Aggressive Surgical Resection: Essential to Management of Central NSCLC SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID CELL LUNG-CANCER; CHEMORADIATION; CARCINOMA; SURVIVAL C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wain, JC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2014 VL 28 IS 3 BP 228 EP + PG 2 WC Oncology SC Oncology GA AD8YF UT WOS:000333550900011 PM 24855731 ER PT J AU Goske, MJ Frush, DP Brink, JA Kaste, SC Butler, PF Pandharipande, PV AF Goske, Marilyn J. Frush, Donald P. Brink, James A. Kaste, Sue C. Butler, Priscilla F. Pandharipande, Pari V. TI Curbing Potential Radiation-Induced Cancer Risks in Oncologic Imaging: Perspectives From the 'Image Gently' and 'Image Wisely' Campaigns SO ONCOLOGY-NEW YORK LA English DT Article ID COMPUTED-TOMOGRAPHY SCANS; IONIZING-RADIATION; PEDIATRIC-PATIENTS; TESTICULAR CANCER; MULTIDETECTOR CT; DOSE REDUCTION; EXPOSURE; SURVEILLANCE; PROTECTION; CHILDREN AB Medical imaging that uses ionizing radiation, such as CT, radiography, nuclear medicine, and fluoroscopy, is a cornerstone of the care of oncology patients and provides great benefit. Ionizing radiation at high doses is a known carcinogen. The exact degree of the risk of carcinogenesis from the lower doses of. ionizing radiation used in medical imaging is less clear. The purpose of this review is to provide the oncology community with knowledge about the doses used in medical imaging, radiation-induced cancer risks from imaging, considerations to keep in mind when balancing imaging benefits and risks in pediatric and adult oncologic settings, dose reduction strategies, and the "Image Gently" and "Image Wisely" campaigns; the latter campaigns facilitate the translation of existing evidence into best practices for providers and patients. C1 [Goske, Marilyn J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Frush, Donald P.] Duke Univ, Med Ctr, Durham, NC USA. [Brink, James A.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kaste, Sue C.] St Jude Childrens Res Hosp, Memphis, TN USA. [Kaste, Sue C.] Univ Tennessee, Ctr Hlth Sci, Coll Med, Memphis, TN 38163 USA. [Butler, Priscilla F.] Amer Coll Radiol, Reston, VA USA. RP Goske, MJ (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM marilyn.goske@cchmc.org RI Frush, Donald/M-6457-2015 OI Frush, Donald/0000-0002-6928-4465 FU Medical Imaging and Technology Alliance FX Dr. Pandharipande receives research funding from the Medical Imaging and Technology Alliance. The other authors have no financial interest or other relationship with the manufacturer of any product or provider of any service mentioned in the article. NR 52 TC 11 Z9 11 U1 0 U2 3 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2014 VL 28 IS 3 BP 232 EP + PG 8 WC Oncology SC Oncology GA AD8YF UT WOS:000333550900012 PM 24855732 ER PT J AU Menezes, AR Lavie, CJ Milani, RV Forman, DE King, M Williams, MA AF Menezes, Arthur R. Lavie, Carl J. Milani, Richard V. Forman, Daniel E. King, Marjorie Williams, Mark A. TI Cardiac Rehabilitation in the United States SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Coronary heart disease; Cardiac rehabilitation; Risk factors ID AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE PROFESSIONALS; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; PULMONARY-REHABILITATION; SECONDARY PREVENTION AB Coronary heart disease (CHD) is a significant cause of morbidity and mortality in the United States (US). In addition to this, many of the risk factors of CHD, such as obesity, sedentary lifestyle, diabetes mellitus, and poor nutrition, are disproportionately high in the US. Despite the many known benefits of cardiac rehabilitation (CR), referral and participation rates in these programs are paradoxically low. Over the course of this review, we will discuss some of the many benefits of CR, some of the risk factors for CHD in the US, and factors that affect referral and participation in these programs. (C) 2014 Elsevier Inc. All rights reserved. C1 [Menezes, Arthur R.; Lavie, Carl J.; Milani, Richard V.] Univ Queensland, Ochsner Clin Sch, John Ochsner Heart & Vasc Inst, Dept Cardiovasc Dis,Sch Med, Brisbane, Qld, Australia. [Lavie, Carl J.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Dept Prevent Cardiol, Baton Rouge, LA USA. [Forman, Daniel E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Forman, Daniel E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [King, Marjorie] Helen Hayes Hosp, W Haverstraw, NY USA. [King, Marjorie] Columbia Univ, New York, NY USA. [Williams, Mark A.] Creighton Univ, Sch Med, Div Cardiol, Omaha, NE USA. RP Lavie, CJ (reprint author), Univ Queensland, Sch Med, Ochsner Clin Sch, John Ochsner Heart & Vasc Inst, 1514 Jefferson Highway, New Orleans, LA 70121 USA. EM clavie@ochsner.org RI Lavie, Carl/A-6014-2011; Milani, Richard/A-6045-2011 NR 75 TC 30 Z9 30 U1 6 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAR-APR PY 2014 VL 56 IS 5 BP 522 EP 529 DI 10.1016/j.pcad.2013.09.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD8UV UT WOS:000333542100008 PM 24607017 ER PT J AU Jorge, RE Arciniegas, DB AF Jorge, Ricardo E. Arciniegas, David B. TI Mood Disorders After TBI SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article DE Traumatic brain injury; Mood disorders; Depressive disorders ID TRAUMATIC BRAIN-INJURY; SEROTONIN TRANSPORTER POLYMORPHISMS; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; RANDOMIZED-TRIAL; AGGRESSIVE-BEHAVIOR; BIPOLAR DISORDER; HEAD-INJURY; AXIS-I; INDIVIDUALS AB In this article, we examine the epidemiology and risk factors for the development of the most common mood disorders observed in the aftermath of TBI: depressive disorders and bipolar spectrum disorders. We describe the classification approach and diagnostic criteria proposed in the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders. We also examine the differential diagnosis of post-TBI mood disorders and describe the mainstay of the evaluation process. Finally, we place a special emphasis on the analysis of the different therapeutic options and provide guidelines for the appropriate management of these conditions. C1 [Jorge, Ricardo E.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Michael E DeBakey Vet Affairs Med Ctr, Mental Hlth Care Line, Houston, TX 77030 USA. [Jorge, Ricardo E.; Arciniegas, David B.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Beth K & Stuart C Yudofsky Div Neuropsychiat, Houston, TX 77030 USA. [Arciniegas, David B.] TIRR Mem Hermann, Brain Injury Res Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Jorge, RE (reprint author), One Baylor Plaza, Houston, TX 77030 USA. EM jorge@bcm.edu FU NIMH NIH HHS [R01 MH065134, R01 MH65134 01, R01MH53592]; NINDS NIH HHS [R01 NS055827] NR 89 TC 13 Z9 14 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X EI 1558-3147 J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2014 VL 37 IS 1 BP 13 EP + DI 10.1016/j.psc.2013.11.005 PG 18 WC Psychiatry SC Psychiatry GA AD8UM UT WOS:000333541200003 PM 24529421 ER PT J AU Eden, U Lagali, N Dellby, A Utheim, TP Riise, R Chen, XJ Fagerholm, P AF Eden, Ulla Lagali, Neil Dellby, Anette Utheim, Tor P. Riise, Ruth Chen, Xiangjun Fagerholm, Per TI Cataract development in Norwegian patients with congenital aniridia SO ACTA OPHTHALMOLOGICA LA English DT Letter ID PAX6 MUTATION C1 [Eden, Ulla; Lagali, Neil; Dellby, Anette; Fagerholm, Per] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. [Utheim, Tor P.] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway. [Utheim, Tor P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. [Riise, Ruth] Innland Hosp, Dept Ophthalmol, Elverum, Norway. [Chen, Xiangjun] Synslaser Kirurgi AS, Oslo, Norway. RP Eden, U (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. EM ulla.eden@gmail.com OI Chen, Xiangjun/0000-0003-0331-9028; Lagali, Neil/0000-0003-1079-4361 NR 9 TC 3 Z9 3 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-375X EI 1755-3768 J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD MAR PY 2014 VL 92 IS 2 BP E165 EP E167 DI 10.1111/aos.12225 PG 3 WC Ophthalmology SC Ophthalmology GA AB3WF UT WOS:000331720200030 PM 23826968 ER PT J AU Oldenburg, CE Biello, KB Colby, D Closson, EF Nguyen, T Trang, NNN Lan, HX Mayer, KH Mimiaga, MJ AF Oldenburg, Catherine E. Biello, Katie B. Colby, Donn Closson, Elizabeth F. Thi Nguyen Trang, Nguyen N. N. Lan, Hang X. Mayer, Kenneth H. Mimiaga, Matthew J. TI Engagement with Peer Health Educators Is Associated with Willingness to Use Pre-Exposure Prophylaxis Among Male Sex Workers in Ho Chi Minh City, Vietnam SO AIDS PATIENT CARE AND STDS LA English DT Letter ID YOUNG MEN; HIV; PREVALENCE; RISKS C1 [Oldenburg, Catherine E.; Biello, Katie B.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Biello, Katie B.; Closson, Elizabeth F.; Mayer, Kenneth H.; Mimiaga, Matthew J.] Fenway Community Hlth Boston, Fenway Inst, Boston, MA USA. [Colby, Donn; Thi Nguyen] Harvard Med Sch AIDS Initiat Vietnam, Ho Chi Minh City, Vietnam. [Colby, Donn] Ctr Appl Res Men & Hlth, Ho Chi Minh City, Vietnam. [Trang, Nguyen N. N.; Lan, Hang X.] Life Ctr, Ctr Promot Qual Life, Ho Chi Minh City, Vietnam. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mimiaga, MJ (reprint author), 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@hsph.harvard.edu OI colby, donn/0000-0003-3931-5926 FU NIAID NIH HHS [T32AI007535] NR 12 TC 9 Z9 9 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAR 1 PY 2014 VL 28 IS 3 BP 109 EP 112 DI 10.1089/apc.2013.0372 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AC2HF UT WOS:000332319800001 PM 24601733 ER PT J AU Zanoni, BC Mayer, KH AF Zanoni, Brian C. Mayer, Kenneth H. TI The Adolescent and Young Adult HIV Cascade of Care in the United States: Exaggerated Health Disparities SO AIDS PATIENT CARE AND STDS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; TRANSMITTED DRUG-RESISTANCE; PERINATALLY ACQUIRED HIV; SICKLE-CELL-DISEASE; MEDICAL-CARE; RISK BEHAVIORS; INFECTED ADOLESCENTS; PSYCHIATRIC-DISORDERS; POSITIVE ADOLESCENTS AB Little is known about how adolescents and young adults contribute to the declines in the cascade of care from HIV-1 diagnosis to viral suppression. We reviewed published literature from the Unites States reporting primary data for youth (13-29 years of age) at each stage of the HIV cascade of care. Approximately 41% of HIV-infected youth in the United States are aware of their diagnosis, while only 62% of those diagnosed engage medical care within 12 months of diagnosis. Of the youth who initiate antiretroviral therapy, only 54% achieve viral suppression and a further 57% are not retained in care. We estimate less than 6% of HIV-infected youth in the United States remain virally suppressed. We explore the cascade of care from HIV diagnosis through viral suppression for HIV-infected adolescents and young adults in the United States to highlight areas for improvement in the poor engagement of the infected youth population. C1 [Zanoni, Brian C.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Charlestown, MA USA. [Zanoni, Brian C.; Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Fenway Hlth, Boston, MA 02115 USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Mayer, KH (reprint author), Fenway Hlth, 1340 Boylston St, Boston, MA 02115 USA. EM kmayer@fenwayhealth.org NR 101 TC 49 Z9 49 U1 7 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAR 1 PY 2014 VL 28 IS 3 BP 128 EP 135 DI 10.1089/apc.2013.0345 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AC2HF UT WOS:000332319800004 PM 24601734 ER PT J AU Pedrelli, P Parkin, S AF Pedrelli, Paola Parkin, Susannah TI Distress tolerance, alcohol use and alcohol related problems among female and male college students SO ALCOHOL LA English DT Meeting Abstract CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-09, 2014 CL Volterra, ITALY SP Natl Inst Hlth Natl Inst Alcohol Abuse & Alcoholism, Fondazione Cassa Risparmio Volterra, Cassa Risparmio Volterra Spa, Univ Camerino, Mitsubishi Pharma, Volterra Rotary Club, Lundbeck, Soc Study Addict, European Fdn Alcohol Res, Distilled Spirits Council US, Comune Volterra, ULS 5, Auxilium Vitae Volterra Spa, Consorzio Turistico Volterra Valdicecina Valdera, Toscana Sempre C1 [Pedrelli, Paola; Parkin, Susannah] Massachusetts Gen Hosp, Depress Clin Res Program, Boston, MA 02114 USA. NR 0 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 0741-8329 EI 1873-6823 J9 ALCOHOL JI Alcohol PD MAR PY 2014 VL 48 IS 2 BP 168 EP 169 PG 2 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA AD8GR UT WOS:000333505000046 ER PT J AU Edelman, EA Lin, BK Doksum, T Drohan, B Edelson, V Dolan, SM Hughes, KS O'Leary, J Galvin, SL Degroat, N Pardanani, S Feero, WG Adams, C Jones, R Scott, J AF Edelman, Emily A. Lin, Bruce K. Doksum, Teresa Drohan, Brian Edelson, Vaughn Dolan, Siobhan M. Hughes, Kevin S. O'Leary, James Galvin, Shelley L. Degroat, Nicole Pardanani, Setul Feero, W. Gregory Adams, Claire Jones, Renee Scott, Joan TI Implementation of an electronic genomic and family health history tool in primary prenatal care SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE performance measure; prenatal care; clinical decision support; genetic screening; family health history ID DECISION-SUPPORT; CYSTIC-FIBROSIS; RISK; GUIDELINES; CHILD AB "The Pregnancy and Health Profile," (PHP) is a free genetic risk assessment software tool for primary prenatal providers that collects patient-entered family (FHH), personal, and obstetrical health history, performs risk assessment, and presents the provider with clinical decision support during the prenatal encounter. The tool is freely available for download at . We evaluated the implementation of PHP in four geographically diverse clinical sites. Retrospective chart reviews were conducted for patients seen prior to the study period and for patients who used the PHP to collect data on documentation of FHH, discussion of cystic fibrosis (CF) and hemoglobinopathy (HB) carrier screening, and CF and HB interventions (tests, referrals). Five hundred pre-implementation phase and 618 implementation phase charts were reviewed. Documentation of a 3-generation FHH or pedigree improved at three sites; patient race/ethnicity at three sites, father of the baby (FOB) race/ethnicity at all sites, and ancestry for the patient and FOB at three sites (P < 0.001-0001). CF counseling improved for implementation phase patients at one site (8% vs. 48%, P < 0.0001) and CF screening/referrals at two (2% vs. 14%, P < 0.0001; 6% vs. 14%; P = 0.05). Counseling and intervention rates did not increase for HB. This preliminary study suggests that the PHP can improve documentation of FHH, race, and ancestry, as well as the compliance with current CF counseling and intervention guidelines in some prenatal clinics. Future evaluation of the PHP should include testing in a larger number of clinical environments, assessment of additional performance measures, and evaluation of the system's overall clinical utility. (c) 2014 Wiley Periodicals, Inc. C1 [Edelman, Emily A.] Natl Coalit Hlth Profess Educ Genet, Lutherville Timonium, MD 21093 USA. [Lin, Bruce K.] March Dimes, Special Initiat, White Plains, NY USA. [Drohan, Brian; Hughes, Kevin S.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. [Dolan, Siobhan M.; Pardanani, Setul] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY USA. [Dolan, Siobhan M.] Univ Hosp Einstein, Montefiore Med Ctr, Div Reprod Genet, New York, NY USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Breast Screening Program, Boston, MA 02114 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Breast & Ovarian Canc Genet & Risk Assessment Pro, Boston, MA 02114 USA. [Galvin, Shelley L.] Mt Area Hlth Educ Ctr, Res Ctr, Asheville, NC USA. [Galvin, Shelley L.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Degroat, Nicole; Pardanani, Setul] Montefiore Med Ctr, New York, NY USA. [Pardanani, Setul] Univ Hosp Einstein, New York, NY USA. [Feero, W. Gregory; Adams, Claire] Maine Dartmouth Family Med Residency Program, Augusta, GA USA. [Jones, Renee] Community Hlth Network, Indiana, PA USA. RP Edelman, EA (reprint author), Natl Coalit Hlth Profess Educ Genet, 2360 W Joppa Rd,Suite 320, Lutherville Timonium, MD 21093 USA. EM emily.edelman@jax.org OI Hughes, Kevin/0000-0003-4084-6484 FU Health Resources and Services Administration (HRSA) [U33MC12786] FX Grant sponsor: Health Resources and Services Administration (HRSA); Grant number: #U33MC12786. NR 30 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 EI 1552-4876 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAR PY 2014 VL 166 IS 1 SI SI BP 34 EP 44 DI 10.1002/ajmg.c.31389 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA AD1AL UT WOS:000332966100005 PM 24616345 ER PT J AU Mwangi, SM Nezami, BG Obukwelu, B Anitha, M Marri, S Fu, P Epperson, MF Le, NA Shanmugam, M Sitaraman, SV Tseng, YH Anania, FA Srinivasan, S AF Mwangi, Simon Musyoka Nezami, Behtash Ghazi Obukwelu, Blessing Anitha, Mallappa Marri, Smitha Fu, Ping Epperson, Monica F. Ngoc-Anh Le Shanmugam, Malathy Sitaraman, Shanthi V. Tseng, Yu-Hua Anania, Frank A. Srinivasan, Shanthi TI Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE hepatic steatosis; energy expenditure; beta-adrenergic signaling; beta-oxidation; neurotrophic ID SUBCUTANEOUS ADIPOSE-TISSUE; NERVOUS-SYSTEM CONTROL; AGE-RELATED OBESITY; INSULIN-RESISTANCE; ENERGY-EXPENDITURE; GENE-EXPRESSION; LINKING OBESITY; FACTOR GDNF; FOOD-INTAKE; RECEPTOR AB Obesity is a growing epidemic with limited effective treatments. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to enhance beta-cell mass and improve glucose control in rodents. Its role in obesity is, however, not well characterized. In this study, we investigated the ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF transgenic (Tg) mice that overexpress GDNF under the control of the glial fibrillary acidic protein promoter and wild-type (WT) littermates were maintained on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure, and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and 3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice resisted the HFD-induced weight gain, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food intake and activity levels. They exhibited significantly ( P < 0.001) higher energy expenditure than WT mice and increased expression in skeletal muscle and brown adipose tissue of peroxisome proliferator activated receptor- alpha and beta(1) and beta(3)-adrenergic receptor genes, which are associated with increased lipolysis and enhanced lipid beta-oxidation. In vitro, GDNF enhanced beta-adrenergic-mediated cAMP release in brown adipocytes and suppressed lipid accumulation in differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies demonstrate a novel role for GDNF in the regulation of high-fat diet-induced obesity through increased energy expenditure. They show that GDNF and its receptor agonists may be potential targets for the treatment or prevention of obesity. C1 [Mwangi, Simon Musyoka; Nezami, Behtash Ghazi; Obukwelu, Blessing; Anitha, Mallappa; Marri, Smitha; Fu, Ping; Sitaraman, Shanthi V.; Anania, Frank A.; Srinivasan, Shanthi] Emory Univ, Div Digest Dis, Sch Med, Atlanta, GA 30322 USA. [Mwangi, Simon Musyoka; Obukwelu, Blessing; Epperson, Monica F.; Ngoc-Anh Le; Anania, Frank A.; Srinivasan, Shanthi] Atlanta VA Med Ctr, Decatur, GA USA. [Shanmugam, Malathy] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Srinivasan, S (reprint author), Emory Univ, Div Digest Dis, Whitehead Res Bldg,Suite 201A,615 Michael St, Atlanta, GA 30322 USA. EM ssrini2@emory.edu FU U. S. National Institutes of Health(NIH) [NIH-RO1 DK080684, NIH DK062092]; VA- MERIT Award; [VA BX001746a] FX This study was supported in part by U. S. National Institutes of Health (NIH) grants NIH-RO1 DK080684 (S. Srinivasan) and NIH DK062092 (F. Anania) and VA- MERIT Award (S. Srinivasan) and VA BX001746a (F. Anania). NR 41 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2014 VL 306 IS 6 BP G515 EP G525 DI 10.1152/ajpgi.00364.2013 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA AD3XL UT WOS:000333179700007 PM 24458024 ER PT J AU Rice, MB Thurston, GD Balmes, JR Pinkerton, KE AF Rice, Mary B. Thurston, George D. Balmes, John R. Pinkerton, Kent E. TI Climate Change A Global Threat to Cardiopulmonary Health SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE climate change; air pollution; cardiovascular health; pulmonary health ID EMERGENCY-DEPARTMENT VISITS; OBSTRUCTIVE PULMONARY-DISEASE; GREENHOUSE-GAS EMISSIONS; CASE-CROSSOVER ANALYSIS; DUST STORM EVENTS; AIR-POLLUTION; HOSPITAL ADMISSIONS; EXCESS MORTALITY; OZONE EXPOSURE; AMBIENT OZONE AB Recent changes in the global climate system have resulted in excess mortality and morbidity, particularly among susceptible individuals with preexisting cardiopulmonary disease. These weather patterns are projected to continue and intensify as a result of rising CO2 levels, according to the most recent projections by climate scientists. In this Pulmonary Perspective, motivated by the American Thoracic Society Committees on Environmental Health Policy and International Health, we review the global human health consequences of projected changes in climate for which there is a high level of confidence and scientific evidence of health effects, with a focus on cardiopulmonary health. We discuss how many of the climate-related health effects will disproportionally affect people from economically disadvantaged parts of the world, who contribute relatively little to CO2 emissions. Last, we discuss the financial implications of climate change solutions from a public health perspective and argue for a harmonized approach to clean air and climate change policies. C1 [Rice, Mary B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Rice, Mary B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Thurston, George D.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Balmes, John R.] Univ Calif San Francisco, Dept Med, Div Environm Hlth Sci, San Francisco, CA USA. [Balmes, John R.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Pinkerton, Kent E.] Univ Calif Davis, Ctr Hlth & Environm, Davis, CA 95616 USA. [Pinkerton, Kent E.] Univ Calif Davis, John Muir Inst Environm, Davis, CA 95616 USA. RP Rice, MB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM mrice2@partners.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU National Institute of Environmental Health Sciences [1F32ES023352-01]; National Heart, Lung, and Blood Institute [T32HL007374]; California Air Resources Board; New York University-National Institute of Environmental Health Sciences Center of Excellence [ES00260]; California National Primate Research Center [P51 OD0011107]; National Institute for Occupational Safety and Health [U54 OH007550] FX Supported by the National Institute of Environmental Health Sciences grant 1F32ES023352-01 (M.B.R.), the National Heart, Lung, and Blood Institute grant T32HL007374 (M.B.R.), the California Air Resources Board (J.R.B.), the New York University-National Institute of Environmental Health Sciences Center of Excellence Grant ES00260 (G.D.T.), the California National Primate Research Center grant P51 OD0011107 (K.E.P.), and the National Institute for Occupational Safety and Health grant U54 OH007550 (K.E.P.). NR 100 TC 9 Z9 9 U1 2 U2 24 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2014 VL 189 IS 5 BP 512 EP 519 DI 10.1164/rccm.201310-1924PP PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AC4TA UT WOS:000332512500005 PM 24400619 ER PT J AU Kovtun, KA Wolfsberger, L Niedermayr, T Sugar, EN Graham, PL Murciano-Goroff, Y Beard, C D'Amico, AV Martin, NE Orio, PF Nguyen, PL AF Kovtun, Konstantin A. Wolfsberger, Luciant Niedermayr, Thomas Sugar, Emily N. Graham, Powell L. Murciano-Goroff, Yonina Beard, Clair D'Amico, Anthony V. Martin, Neil E. Orio, Peter F. Nguyen, Paul L. TI Dosimetric quality and evolution of edema after low-dose-rate brachytherapy for small prostates: Implications for the use of newer isotopes SO BRACHYTHERAPY LA English DT Article DE Prostate brachytherapy; Low dose rate; Small prostate; (1251) seeds ID IMPLANTS; VOLUME; SEEDS; SIZE; MEN AB PURPOSE: To characterize prostate swelling and dosimetry in patients with small ptostate volumes (PVs) undergoing brachytherapy. METHODS AND MATERIALS: We studied 25 patients with PV < 25 cc (range, 15.1-24.8) and 65 patients with PV >= 25 cc (range, 25.0-66.2) based on three-dimensional ultrasound contours who underwent brachytherapy monotherapy with intraoperative planning. Postoperative Days 1 and 30 dosimetry was done by CT-MRI fusion. RESULTS: Small PVs had greater Day 1 swelling than large PVs (32.5% increase in volume vs. but by Day 30, swelling was minimal and not significantly different (p = 0.44). Small PVs had greater seed and needle densities at implant (p < 0.001). Rectal and urethral doses were nearly identical by Day 30 (small PV rectum receiving 100% of the prescription dose [145 Gy] [V-100] = 0.32 cc; large PV rectum V-100 = 0.33 cc, p = 0.99; small PV urethra receiving 150% of the prescription dose [145 Gy] [V-150] = 0.20, large PV urethra V-150 = 0.20, p = 0.91). Swelling at Day 1 created some cool implants (rate dose that covers 90% of the prostate volume [D-90 < 140 Gy = 12.0% and 9.4% for the small and large PV groups, respectively, p = 0.71), but Day 30 planning target volume coverage was excellent (rate D90 < 140 Gy = 0% for both groups). CONCLUSIONS: Although smaller prostates have greater Day 1 swelling, good Day 30 dosimetry can be achieved, making them excellent candidates for I-125 seeds (half-life [M] = 60 days). Smaller prostates may be suboptimal for shorter t(1/2) sources such as Cs-131 (t(1/2) = 9.7 days), in which the majority of the dose may be delivered to an edematous gland, unless the planning is adjusted to anticipate the edema. (C) 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Kovtun, Konstantin A.; Wolfsberger, Luciant; Niedermayr, Thomas; Sugar, Emily N.; Graham, Powell L.; Murciano-Goroff, Yonina; Beard, Clair; D'Amico, Anthony V.; Martin, Neil E.; Orio, Peter F.; Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Heritage Medical Research Institute/Prostate Cancer Foundation Young Investigator Award; Fitz's Cancer Warriors; David and Cynthia' Chapin FX This work was funded by a grant from an anonymous family foundation, a Heritage Medical Research Institute/Prostate Cancer Foundation Young Investigator Award, Fitz's Cancer Warriors, and David and Cynthia' Chapin. NR 12 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD MAR-APR PY 2014 VL 13 IS 2 BP 152 EP 156 DI 10.1016/j.brachy.2013.05.006 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AD7ID UT WOS:000333436400007 PM 23911279 ER PT J AU Kerr, DA Pitman, MB Sweeney, B Arpin, RN Wilbur, DC Faquin, WC AF Kerr, Darcy A. Pitman, Martha B. Sweeney, Brenda Arpin, Ronald N., III Wilbur, David C. Faquin, William C. TI Performance of the Roche cobas 4800 high-risk human papillomavirus test in cytologic preparations of squamous cell carcinoma of the head and neck SO CANCER CYTOPATHOLOGY LA English DT Article DE squamous cell carcinoma; head and neck; human papillomavirus; polymerase chain reaction; cobas; fine-needle aspiration; cytology ID FINE-NEEDLE-ASPIRATION; IN-SITU HYBRIDIZATION; OROPHARYNGEAL CANCER; HPV STATUS; P16; SURVIVAL; IMMUNOHISTOCHEMISTRY; METASTASIS; INFECTION; SPECIMEN AB BACKGROUND Determining high-risk human papillomavirus (HR-HPV) status of head and neck squamous cell carcinoma (HNSCC) defines a tumor subset with important clinical implications. Cytologic sampling often provides the sentinel or sole diagnostic specimen. The authors assessed the performance characteristics for the Roche cobas 4800 HPV real-time polymerase chain reaction (PCR)-based system (cobas) on cytologic specimens of HNSCC compared with standard methods of in situ hybridization (ISH) for HR-HPV and immunohistochemistry (IHC) for p16 on formalin-fixed, paraffin-embedded (FFPE) tissue. METHODS Samples of HNSCC were collected by fine-needle aspiration and from surgical biopsies or resections, fixed, and processed with the cobas system. Available corresponding FFPE samples were synchronously evaluated for HR-HPV using ISH and IHC. Discrepant cases underwent additional PCR studies for adjudication. RESULTS Thirty-six samples from 33 patients were analyzed. Forty-two percent (n = 15) of tumors were positive for HR-HPV according to cobas. Corresponding histology with ISH (n = 30) was concordant in 91% of samples. Compared with the adjudication PCR standard, there were 3 false-positive cases according to cobas. Ninety-two percent (n = 12) of cases were the HPV16 subtype. The overall sensitivity for the cobas system was 100%, and the specificity was 86%. CONCLUSIONS Concordance in HNSCC HR-HPV status between cobas and ISH/IHC was > 90%, and cobas demonstrated a sensitivity of 100% and a specificity of 86%, broadening options for HR-HPV testing of fine-needle aspiration samples. Advantages for this system include subtyping of HR-HPV and the ability to discern HR-HPV status earlier in a patient's treatment course. Cancer (Cancer Cytopathol) 2014;122:167-174. (c) 2013 American Cancer Society. C1 [Kerr, Darcy A.; Pitman, Martha B.; Sweeney, Brenda; Arpin, Ronald N., III; Wilbur, David C.; Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kerr, Darcy A.; Pitman, Martha B.; Sweeney, Brenda; Arpin, Ronald N., III; Wilbur, David C.; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org FU Roche Ventana Medical Systems FX Mr. Arpin has received personal consulting fees from Roche Ventana Medical Systems outside the submitted work. Dr. Wilbur serves on the Corista Scientific Advisory Board and on the Vision Gate Medical Advisory Board. NR 40 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD MAR PY 2014 VL 122 IS 3 BP 167 EP 174 DI 10.1002/cncy.21372 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA AC4OC UT WOS:000332499600004 PM 24259368 ER PT J AU Chu, SH Zhou, ZM Karri, S Li, ZQ Zhao, JM AF Chu, S-H Zhou, Z-M Karri, S. Li, Z-Q Zhao, J-M TI In vitro and in vivo radiosensitization of human glioma U251 cells induced by upregulated expression of SLC22A18 SO CANCER GENE THERAPY LA English DT Article DE glioma; SLC22A18; irradiation; radiosensitization ID CHROMOSOME 11P15.5; RADIATION; GENE; CANCER; GLIOBLASTOMA; PROGRESSION; INHIBITION; MUTATIONS; BWR1A; TSSC5 AB Our previous study showed that solute carrier family 22 (organic cation transporter) member 18 (SLC22A18) downregulation via promoter methylation was associated with the development and progression of glioma, and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea. In this study, we investigated the possible upregulated expression of SLC22A18-induced enhancement of radiosensitivity of human glioma U251 cells in order to provide evidence in support of further clinical investigations. Stably overexpressing SLC22A18 human glioma U251 cells were generated to investigate the effect of SLC22A18 on the sensitivity of cells to irradiation in vitro using clonogenic survival assay. The apoptosis of U251 cells was examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. DNA damage and repair were measured using gamma H2AX foci. The effect of SLC22A18 on the in vivo tumor radiosensitivity was investigated in the orthotopic mice model. Upregulated expression of SLC22A18 enhanced the radiosensitivity of glioma U251 cells and also enhanced irradiation-induced apoptosis of U251 cells, but irradiation-induced apoptosis did not correlate with radiosensitizing effect of upregulated expression of SLC22A18. The repair of irradiation-induced double-strand-breaks was retarded in stably overexpressing SLC22A18 U251 cells. In the orthotopic mice model, the upregulated expression of SLC22A18 in U251 cells enhanced the effect of irradiation treatment and increased the survival time of mice. These results show that upregulated expression of SLC22A18 radiosensitizes human glioma U251 cells by suppressing DNA repair capacity. C1 [Chu, S-H] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 3, Sch Med, Dept Neurosurg, Shanghai 201900, Peoples R China. [Zhou, Z-M] Dujiangyan Med Ctr, Dept Neurosurg, Chengdu, Peoples R China. [Karri, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Li, Z-Q] Wuhan Univ, Zhongnan Hosp, Dept Neurosurg, Wuhan 430072, Peoples R China. [Zhao, J-M] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 3, Sch Med, Dept Radiol, Shanghai 201900, Peoples R China. RP Chu, SH (reprint author), Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 3, Sch Med, Dept Neurosurg, Shanghai 201900, Peoples R China. EM shenghuachu@126.com FU Natural Science Foundation of China [30901535]; Shanghai Municipal Education Commission [12YZ046]; Research Fund of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine [10XJ22010]; New One Hundred Person Project of Shanghai Jiao Tong University of School of Medicine [10XBR01] FX This work was supported by grants from the Natural Science Foundation of China (30901535), Innovation Program of Shanghai Municipal Education Commission (12YZ046), Research Fund of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (10XJ22010) and the New One Hundred Person Project of Shanghai Jiao Tong University of School of Medicine (10XBR01). We would like to thank Department of Chemotherapy and Radiation Oncology, Zhongnan Hospital of Wuhan University for providing help. NR 26 TC 3 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAR PY 2014 VL 21 IS 3 BP 103 EP 109 DI 10.1038/cgt.2014.4 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA AD2MK UT WOS:000333069600003 PM 24481489 ER PT J AU Christiani, DC AF Christiani, David C. TI Radiation Risk From Lung Cancer Screening Glowing in the Dark? SO CHEST LA English DT Editorial Material ID CT C1 [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,I-1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2014 VL 145 IS 3 BP 439 EP 440 DI 10.1378/chest.13-2588 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AC8NS UT WOS:000332790700002 PM 24590012 ER PT J AU Moy, ML Teylan, M Weston, NA Gagnon, DR Danilack, VA Garshick, E AF Moy, Marilyn L. Teylan, Merilee Weston, Nicole A. Gagnon, David R. Danilack, Valery A. Garshick, Eric TI Daily Step Count Is Associated With Plasma C-Reactive Protein and IL-6 in a US Cohort With COPD SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; PHYSICAL-ACTIVITY MONITORS; DAILY-LIFE; SYSTEMIC INFLAMMATION; POPULATION; BIOMARKERS; MORTALITY; EXERCISE; RISK; REHABILITATION AB Background: Physical activity is an important clinical marker of disease status in COPD. COPD is also characterized by low-grade systemic inflammation. However, the relationship between physical activity and systemic inflammation in COPD is unclear. Methods: We monitored daily step count, a directly measured physical activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in 171 people with stable COPD. Exercise capacity was assessed with the 6-min walk test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear regression models examined the cross-sectional associations of daily step count and 6MWT distance with CRP and IL-6 levels. Results: Subjects had a mean age 72 +/- 8 years and mean FEV1 1.5 +/- 0.57 L (54 +/- 20% predicted). Median daily step count was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR, 1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in CRP (P = .020) and IL-6 (P = .044) levels, respectively, adjusting for age, FEV1 % predicted, pack-years smoked, cardiac disease, current statin use, history of acute exacerbations, and season. There was a significant linear trend of increasing daily step count by quartiles and decreasing CRP (P = .0007) and IL- 6 (P = .023) levels. Higher 6MWT distance was also significantly associated with lower CRP and IL-6 values. Conclusion: People with COPD who walked the most had the lowest plasma CRP and IL- 6 levels. These results provide the conceptual basis to study whether an intervention to promote walking will reduce systemic inflammation in people with COPD. C1 [Moy, Marilyn L.; Garshick, Eric] Rehabil Res & Dev Serv, Vet Hlth Adm, Dept Vet Affairs, Boston, MA USA. [Moy, Marilyn L.; Teylan, Merilee; Weston, Nicole A.; Danilack, Valery A.; Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Sect, West Roxbury, MA 02132 USA. [Moy, Marilyn L.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Moy, Marilyn L.; Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Gagnon, David R.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gagnon, David R.] VA Cooperat Studies, Boston, MA USA. [Danilack, Valery A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. RP Moy, ML (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Sect, 1400 VFW Pkwy,Mail Code 111PI, West Roxbury, MA 02132 USA. EM marilyn.moy@va.gov FU Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award; Center for Integration of Medicine and Innovative Technology, Boston, MA; VA Rehabilitation Research and Development Service [B6618R] FX This research was supported by the Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award to Dr Moy. It also was supported in part by the Center for Integration of Medicine and Innovative Technology, Boston, MA (Dr Moy), and in part by the VA Rehabilitation Research and Development Service [Grant B6618R to Dr Garshick]. NR 48 TC 12 Z9 12 U1 2 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2014 VL 145 IS 3 BP 542 EP 550 DI 10.1378/chest.13-1052 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AC8NS UT WOS:000332790700021 PM 24091482 ER PT J AU DeBoer, EM Swiercz, W Heltshe, SL Anthony, MM Szefler, P Klein, R Strain, J Brody, AS Sagel, SD AF DeBoer, Emily M. Swiercz, Waldemar Heltshe, Sonya L. Anthony, Margaret M. Szefler, Paul Klein, Rebecca Strain, John Brody, Alan S. Sagel, Scott D. TI Automated CT Scan Scores of Bronchiectasis and Air Trapping in Cystic Fibrosis SO CHEST LA English DT Article ID RESOLUTION COMPUTED-TOMOGRAPHY; THIN-SECTION CT; LUNG-DISEASE; PULMONARY-FUNCTION; SCORING SYSTEM; YOUNG-CHILDREN; ACUTE EXACERBATION; CLINICAL-TRIALS; UNITED-STATES; CHEST AB Background: Computer analysis of high-resolution CT (HRCT) scans may improve the assessment of structural lung injury in children with cystic fibrosis (CF). The goal of this cross-sectional pilot study was to validate automated, observer-independent image analysis software to establish objective, simple criteria for bronchiectasis and air trapping. Methods: HRCT scans of the chest were performed in 35 children with CF and compared with scans from 12 disease control subjects. Automated image analysis software was developed to count visible airways on inspiratory images and to measure a low attenuation density (LAD) index on expiratory images. Among the children with CF, relationships among automated measures, Brody HRCT scanning scores, lung function, and sputum markers of inflammation were assessed. Results: The number of total, central, and peripheral airways on inspiratory images and LAD (%) on expiratory images were significantly higher in children with CF compared with control subjects. Among subjects with CF, peripheral airway counts correlated strongly with Brody bronchiectasis scores by two raters (r = 0.86, P < .0001; r = 0.91, P < .0001), correlated negatively with lung function, and were positively associated with sputum free neutrophil elastase activity. LAD (%) correlated with Brody air trapping scores (r = 0.83, P < .0001; r = 0.69, P < .0001) but did not correlate with lung function or sputum inflammatory markers. Conclusions: Quantitative airway counts and LAD (%) on HRCT scans appear to be useful surrogates for bronchiectasis and air trapping in children with CF. Our automated methodology provides objective quantitative measures of bronchiectasis and air trapping that may serve as end points in CF clinical trials. C1 [DeBoer, Emily M.; Anthony, Margaret M.; Szefler, Paul; Klein, Rebecca; Sagel, Scott D.] Univ Colorado, Sch Med, Childrens Hosp Colorado, Dept Pediat, Aurora, CO USA. [Strain, John] Univ Colorado, Sch Med, Childrens Hosp Colorado, Dept Radiol, Aurora, CO USA. [Swiercz, Waldemar] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Heltshe, Sonya L.] Seattle Childrens, Dept Pediat, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. [Brody, Alan S.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. RP DeBoer, EM (reprint author), Childrens Hosp Colorado, 13123 E 16th Ave,B-395, Aurora, CO 80045 USA. EM emily.deboer@childrenscolorado.org FU National Institutes of Health (NIH) [K23 RR018611]; NIH/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Institute [UL1 TR000154] FX This research was supported by the National Institutes of Health (NIH) [K23 RR018611] and by the NIH/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Institute [Grant UL1 TR000154]. NR 48 TC 11 Z9 11 U1 0 U2 7 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2014 VL 145 IS 3 BP 593 EP 603 DI 10.1378/chest.13-0588 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AC8NS UT WOS:000332790700028 PM 24114359 ER PT J AU Bittencourt, MS Hulten, E Ghoshhajra, B O'Leary, D Christman, MP Montana, P Truong, QA Steigner, M Murthy, VL Rybicki, FJ Nasir, K Gowdak, LHW Hainer, J Brady, TJ Di Carli, MF Hoffmann, U Abbara, S Blankstein, R AF Bittencourt, Marcio Sommer Hulten, Edward Ghoshhajra, Brian O'Leary, Daniel Christman, Mitalee P. Montana, Philip Truong, Quynh A. Steigner, Michael Murthy, Venkatesh L. Rybicki, Frank J. Nasir, Khurram Gowdak, Luis Henrique W. Hainer, Jon Brady, Thomas J. Di Carli, Marcelo F. Hoffmann, Udo Abbara, Suhny Blankstein, Ron TI Prognostic Value of Nonobstructive and Obstructive Coronary Artery Disease Detected by Coronary Computed Tomography Angiography to Identify Cardiovascular Events SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE risk assessment; prognosis; coronary artery disease ID INTERNATIONAL MULTICENTER REGISTRY; ALL-CAUSE MORTALITY; CT ANGIOGRAPHY; CLINICAL-OUTCOMES; SYMPTOMATIC PATIENTS; VULNERABLE PLAQUE; RISK; SEVERITY; ATHEROSCLEROSIS; PREDICTION AB Background- The contribution of plaque extent to predict cardiovascular events among patients with nonobstructive and obstructive coronary artery disease (CAD) is not well defined. Our objective was to evaluate the prognostic value of plaque extent detected by coronary computed tomography angiography. Methods and Results- All consecutive patients without prior CAD referred for coronary computed tomography angiography to evaluate for CAD were included. Examination findings were classified as normal, nonobstructive (< 50% stenosis), or obstructive (>= 50%). Based on the number of segments with disease, extent of CAD was classified as nonextensive (<= 4 segments) or extensive (> 4 segments). The cohort included 3242 patients followed for the primary outcome of cardiovascular death or myocardial infarction for a median of 3.6 (2.1-5.0) years. In a multivariable analysis, the presence of extensive nonobstructive CAD (hazard ratio, 3.1; 95% confidence interval, 1.5-6.4), nonextensive obstructive (hazard ratio, 3.0; 95% confidence interval, 1.3-6.9), and extensive obstructive CAD (hazard ratio, 3.9; 95% confidence interval, 2.2-7.2) were associated with an increased rate of events, whereas nonextensive, nonobstructive CAD was not. The addition of plaque extent to a model that included clinical probability as well as the presence and severity of CAD improved risk prediction. Conclusions- Among patients with nonobstructive CAD, those with extensive plaque experienced a higher rate of cardiovascular death or myocardial infarction, comparable with those who have nonextensive disease. Even among patients with obstructive CAD, greater extent of nonobstructive plaque was associated with higher event rate. Our findings suggest that regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by coronary computed tomography angiography enhances risk assessment. C1 [Bittencourt, Marcio Sommer; Hulten, Edward; O'Leary, Daniel; Christman, Mitalee P.; Montana, Philip; Steigner, Michael; Rybicki, Frank J.; Hainer, Jon; Di Carli, Marcelo F.; Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Dept Med,Med Sch, Boston, MA 02115 USA. [Bittencourt, Marcio Sommer; Hulten, Edward; O'Leary, Daniel; Christman, Mitalee P.; Montana, Philip; Steigner, Michael; Rybicki, Frank J.; Hainer, Jon; Di Carli, Marcelo F.; Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Dept Radiol,Med Sch, Boston, MA 02115 USA. [Bittencourt, Marcio Sommer; Gowdak, Luis Henrique W.] Univ Sao Paulo, Heart Inst InCor, Sao Paulo, Brazil. [Ghoshhajra, Brian; Brady, Thomas J.; Hoffmann, Udo; Abbara, Suhny] Harvard Univ, Sch Med, Dept Radiol,Massachusetts Gen Hosp, Cardiac MR PET CT Program,Div Cardiac Imaging, Boston, MA 02115 USA. [Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Nasir, Khurram] Baptist Hlth South Florida, Ctr Prevent & Wellness Res, Miami Beach, FL USA. [Nasir, Khurram] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. [Nasir, Khurram] Baptist Hlth South Florida, Baptist Cardiovasc Inst, Miami, FL USA. [Nasir, Khurram] Florida Int Univ, Robert Stempel Coll Publ Hlth, Dept Epidemiol, Miami, FL 33199 USA. [Nasir, Khurram] Herbert Wertheim Coll Med, Dept Med, Miami, FL USA. RP Blankstein, R (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM rblankstein@partners.org RI Murthy, Venkatesh/B-3448-2013; Wolff Gowdak, Luis Henrique/C-4844-2012; Bittencourt, Marcio/C-1444-2011 OI Murthy, Venkatesh/0000-0002-7901-1321; Wolff Gowdak, Luis Henrique/0000-0002-6785-7506; Bittencourt, Marcio/0000-0002-3711-1754 FU J.P. Lemann Foundation FX Dr Bittencourt was supported by the J.P. Lemann Foundation as a Jorge Paulo Lemann Harvard Medical School Cardiovascular Fellow at Brigham and Women's Hospital. NR 34 TC 76 Z9 76 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2014 VL 7 IS 2 BP 282 EP 291 DI 10.1161/CIRCIMAGING.113.001047 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AD1LB UT WOS:000332994400010 PM 24550435 ER PT J AU Waks, JW Sabatine, MS Cannon, CP Morrow, DA Gibson, CM Wiviott, SD Giugliano, RP Sloan, S Scirica, BM AF Waks, Jonathan W. Sabatine, Marc S. Cannon, Christopher P. Morrow, David A. Gibson, C. Michael Wiviott, Stephen D. Giugliano, Robert P. Sloan, Sarah Scirica, Benjamin M. TI Clinical Implications and Correlates of Q Waves in Patients With ST-Elevation Myocardial Infarction Treated With Fibrinolysis: Observations from the CLARITY-TIMI 28 Trial SO CLINICAL CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; ABNORMAL Q-WAVES; INITIAL Q-WAVES; SEGMENT ELEVATION; PRESENTING ELECTROCARDIOGRAM; THROMBOLYTIC THERAPY; REPERFUSION; CLOPIDOGREL; STREPTOKINASE; RESOLUTION C1 [Waks, Jonathan W.; Sabatine, Marc S.; Cannon, Christopher P.; Morrow, David A.; Gibson, C. Michael; Wiviott, Stephen D.; Giugliano, Robert P.; Sloan, Sarah; Scirica, Benjamin M.] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Sch Med, Boston, MA 02115 USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02215 USA. EM bscirica@partners.org NR 23 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2014 VL 37 IS 3 BP 160 EP 166 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC7CU UT WOS:000332685600005 PM 24452727 ER PT J AU Sharmeen, F Rosenthal, MH Howard, SAH AF Sharmeen, Farhana Rosenthal, Michael H. Howard, Stephanie A. H. TI The management of retroperitoneal lymphadenopathy in spermatocytic seminoma of the testicle SO CLINICAL IMAGING LA English DT Article DE Spermatocytic seminoma; Lymphoma; Sarcomatous transformation AB Spermatocytic seminoma is an extremely rare clinically and pathologically distinct subtype of testicular cancer that infrequently metastasizes and typically yields a good prognosis. While retroperitoneal lymphadenopathy in the typical testicular cancer patient often harbors metastatic disease, in a patient with spermatocytic seminoma this finding should be viewed with suspicion, and pathologic confirmation of metastatic disease is essential. We present a 49-year-old man with spermatocytic seminoma and retroperitoneal and mesenteric lymphadenopathy who was found to have concurrent low-grade lymphoma. (c) 2014 Elsevier Inc. All rights reserved. C1 [Sharmeen, Farhana; Rosenthal, Michael H.; Howard, Stephanie A. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Rosenthal, Michael H.; Howard, Stephanie A. H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Rosenthal, Michael H.; Howard, Stephanie A. H.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Sharmeen, F (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM farshar@gmail.com RI Rosenthal, Michael/D-4080-2015 NR 14 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 0899-7071 EI 1873-4499 J9 CLIN IMAG JI Clin. Imaging PD MAR-APR PY 2014 VL 38 IS 2 BP 202 EP 204 DI 10.1016/j.clinimag.2013.11.006 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD6NW UT WOS:000333378500024 PM 24361173 ER PT J AU Conley, DM Henton, F Barnes, C Lee, S AF Conley, D. M. Henton, F. Barnes, C. Lee, S. TI National Association of Clinical Nurse Specialist News President's Message SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Conley, D. M.] Nebraska Methodist Hosp, Omaha, NE USA. [Conley, D. M.; Henton, F.; Barnes, C.] Nebraska Methodist Coll, Omaha, NE USA. [Lee, S.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 EI 1538-9782 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2014 VL 28 IS 2 BP E1 EP E2 DI 10.1097/01.NUR.0000443072.05277.7a PG 2 WC Nursing SC Nursing GA AB2VA UT WOS:000331649000003 ER PT J AU Gavaghan, S DaCunha, S Klemmer, S Cleary, M Bulette, CA Capasso, V Belcher, D AF Gavaghan, S. DaCunha, S. Klemmer, S. Cleary, M. Bulette, C. A. Capasso, V Belcher, D. TI A Multidisciplinary and Cost-Effective Approach to Improving Nutritional Status of Patients At-Risk for Pressure Ulcers to Improve Quality of Care and Clinical Outcomes SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Gavaghan, S.; DaCunha, S.; Klemmer, S.; Cleary, M.; Bulette, C. A.; Capasso, V; Belcher, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 EI 1538-9782 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2014 VL 28 IS 2 BP E36 EP E37 PG 2 WC Nursing SC Nursing GA AB2VA UT WOS:000331649000102 ER PT J AU Ryan, C Carroll, D AF Ryan, C. Carroll, D. TI The Impact of the Surgical Intensive Care Unit End of Life Guideline SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Ryan, C.; Carroll, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 EI 1538-9782 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2014 VL 28 IS 2 BP E25 EP E25 PG 1 WC Nursing SC Nursing GA AB2VA UT WOS:000331649000070 ER PT J AU Staples, M Beauchamp, K Gavaghan, S Gryglik, C LaSala, C Ryan, C Wrigley, P AF Staples, M. Beauchamp, K. Gavaghan, S. Gryglik, C. LaSala, C. Ryan, C. Wrigley, P. TI Development of a Clinical Nurse Specialist Orientation Process to Onboard New Clinical Nurse Specialists SO CLINICAL NURSE SPECIALIST LA English DT Meeting Abstract C1 [Staples, M.; Beauchamp, K.; Gavaghan, S.; Gryglik, C.; LaSala, C.; Ryan, C.; Wrigley, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 EI 1538-9782 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD MAR-APR PY 2014 VL 28 IS 2 BP E13 EP E13 PG 1 WC Nursing SC Nursing GA AB2VA UT WOS:000331649000037 ER PT J AU Toeg, HD Al-Atassi, T Garcia, JP Ruel, M AF Toeg, Hadi Daood Al-Atassi, Talal Garcia, Jose Perez Ruel, Marc TI An update on mechanical circulatory support for heart failure therapy SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE cardiac surgery; heart failure; left ventricular assist device ID VENTRICULAR ASSIST DEVICE; TOTAL ARTIFICIAL-HEART; AXILLARY ARTERY APPROACH; CONTINUOUS-FLOW; PATIENT SELECTION; DESTINATION THERAPY; CARDIOGENIC-SHOCK; TRANSPLANTATION; BRIDGE; PUMP AB Purpose of reviewThis article aims to review contemporary studies that utilized mechanical circulatory support (MCS) in the treatment of heart failure and to elaborate on prospective mechanical alternatives.Recent findingsThere is a growing need for a well-tolerated, durable and effective MCS option in patients with refractory heart failure. In previous years, the primary indication for MCS therapy supported bridge to transplantation. These early left ventricular assist devices (LVADs) suffered significant adverse events, thereby limiting their prolonged use. With the introduction of newer continuous flow LVADs, with lower morbidity, neurological events, pump failure and the expanded indication use (i.e. destination therapy), the overall number of implanted patients has grown.SummaryThere has been a dramatic advancement of durability found in the second and third-generation, continuous flow LVADs, along with improved survival rates in patients receiving these devices for destination therapy. MCS may soon become the treatment option of choice in refractory heart failure patients, especially with further evolution of less invasive approaches, smaller designs, and energy sources. C1 [Toeg, Hadi Daood; Al-Atassi, Talal; Ruel, Marc] Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7, Canada. [Garcia, Jose Perez] Harvard Univ, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02115 USA. RP Ruel, M (reprint author), Univ Ottawa, Inst Heart, Div Cardiac Surg, 3402-40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM mruel@ottawaheart.ca OI RUEL, MARC/0000-0002-0487-1319 FU Medtronic Inc. FX M.R. received research support and honoraria from Medtronic Inc. NR 44 TC 3 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 EI 1531-7080 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAR PY 2014 VL 29 IS 2 BP 167 EP 173 DI 10.1097/HCO.0000000000000037 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD7OJ UT WOS:000333453200008 PM 24395064 ER PT J AU Kamer, KJ Mootha, VK AF Kamer, Kimberli J. Mootha, Vamsi K. TI MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter SO EMBO REPORTS LA English DT Article DE mitochondria; uniporter; calcium; MICU1; MICU2 ID RAT KIDNEY MITOCHONDRIA; CA2+ UPTAKE; PROTEIN; MEMBRANE; MCU AB Abstract The mitochondrial uniporter is a selective Ca2+ channel regulated by MICU1, an EF hand-containing protein in the organelle's intermembrane space. MICU1 physically associates with and is co-expressed with a paralog, MICU2. To clarify the function of MICU1 and its relationship to MICU2, we used gene knockout (KO) technology. We report that HEK-293T cells lacking MICU1 or MICU2 lose a normal threshold for Ca2+ intake, extending the known gating function of MICU1 to MICU2. Expression of MICU1 or MICU2 mutants lacking functional Ca2+-binding sites leads to a striking loss of Ca2+ uptake, suggesting that MICU1/2 disinhibit the channel in response to a threshold rise in [Ca2+]. MICU2's activity and physical association with the pore require the presence of MICU1, though the converse is not true. We conclude that MICU1 and MICU2 are nonredundant and together set the [Ca2+] threshold for uniporter activity. Synopsis image The mitochondrial calcium uniporter is regulated by MICU1 and MICU2. Using gene knockouts, Ca2+ physiology, and biochemistry, this study shows that MICU1 and MICU2 operate together, with nonredundant roles, in inhibiting Ca2+ uptake when cytosolic [Ca2+] is below threshold, but permitting transport when [Ca2+] rises. MICU1 and MICU2 play nonredundant roles in preventing mitochondrial calcium uptake via MCU when outside calcium is low MICU1 and MICU2 permit calcium uptake in response to a stimulus above the threshold. C1 [Kamer, Kimberli J.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Kamer, Kimberli J.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu FU National Science Foundation; National Institutes of Health [DK080261] FX We thank members of the Mootha laboratory for constructive feedback, especially Z. Grabarek, T. Kitami, E. Kovacs-Bogdan, A. Li, and Y. Sancak. K.J.K. was supported by a graduate research fellowship from the National Science Foundation. This work was supported by National Institutes of Health Grant DK080261. V.K.M. is an Investigator of the Howard Hughes Medical Institute. NR 21 TC 49 Z9 51 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD MAR PY 2014 VL 15 IS 3 BP 299 EP 307 DI 10.1002/embr.201337946 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AC3BO UT WOS:000332390200019 PM 24503055 ER PT J AU Kuriti, M Pearce, EN Braverman, LE He, XM Leung, AM AF Kuriti, Manikya Pearce, Elizabeth N. Braverman, Lewis E. He, Xuemei Leung, Angela M. TI IODINE CONTENT OF US WEIGHT-LOSS FOOD SO ENDOCRINE PRACTICE LA English DT Article ID NATIONAL-HEALTH; UNITED-STATES; BOSTON-AREA; POPULATION AB Objective: The recommended iodine intake is 150 mu g/day in adults, 220 mu g/day during pregnancy, and 290 mu g/day during lactation. Individuals exclusively consuming restricted diets as part of a weight-loss program may be at risk for mild to moderate iodine deficiency. The purpose of this study was to assess the iodine content in meals and snacks from 3 U. S. commercial weight-loss programs, all of which are intended to be the sole source of dietary intake during the desired weight-loss period. Methods: The iodine contents in the products representing 1 week of all meals and snacks from 3 U.S. commercial weight-loss programs were measured by spectrophotometry. The measured total iodine content in 1 week's worth of food from each program is reported as an average level per day. Results: A total of 53 total items were analyzed (29 different items [7 breakfasts, 7 lunches, 7 dinners, 6 snacks, 2 desserts] from Jenny Craig (R), 21 different items [7 breakfasts, 7 lunches, 7 dinners] from Nutrisystem (R), and 3 different items [1 breakfast, 1 lunch, 1 dinner; each to be intended to be eaten daily for 1 week] from Medifast (R)). Daily iodine content (mean +/- SD) of meals and snacks from the weight-loss programs were 34.2 +/- 1.2 (Jenny Craig (R)), 12.2 +/- 0.7 (Nutrisystem (R)), and 70.1 +/- 1.1 (Medifast) mu g/day. Conclusion: These results indicate that the dietary content in the foods from 3 U. S. commercial weight-loss programs is far less than the recommendations for iodine intake of 150 mu g/day in nonpregnant, nonlactating adults. Individuals following each weight-loss program should be advised to take a multivitamin containing 150 mu g of iodine daily. C1 [Kuriti, Manikya] Tufts Univ, Dept Internal Med, St Elizabeth Med Ctr, Boston, MA 02111 USA. [Pearce, Elizabeth N.; Braverman, Lewis E.; He, Xuemei] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90095 USA. RP Leung, AM (reprint author), VA Greater Los Angeles Healthcare Syst, Div Endocrinol, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM amleung@mednet.ucla.edu OI Leung, Angela M./0000-0001-8935-9332 FU National Institutes of Health [NIH 7K23HD06855204] FX This work was supported by a grant from the National Institutes of Health (NIH 7K23HD06855204) to A.M.L. This work was previously presented at the Endocrine Society annual meeting (June 15-18, 2013, San Francisco, California) as a poster abstract on June 17, 2013. NR 14 TC 1 Z9 1 U1 1 U2 9 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAR PY 2014 VL 20 IS 3 BP 232 EP 235 DI 10.4158/EP13310.OR PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AD2VP UT WOS:000333094200009 PM 24246349 ER PT J AU Groarke, JD Nguyen, PL Nohria, A Ferrari, R Cheng, SS Moslehi, J AF Groarke, John D. Nguyen, Paul L. Nohria, Anju Ferrari, Roberto Cheng, Susan Moslehi, Javid TI Cardiovascular complications of radiation therapy for thoracic malignancies: the role for non-invasive imaging for detection of cardiovascular disease SO EUROPEAN HEART JOURNAL LA English DT Review DE Radiation therapy; Non-invasive imaging ID CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; BREAST-CANCER PATIENTS; TERM-FOLLOW-UP; AORTIC-VALVE IMPLANTATION; HODGKINS-DISEASE; MEDIASTINAL IRRADIATION; CONSTRICTIVE PERICARDITIS; COMPUTED-TOMOGRAPHY; CHILDHOOD-CANCER AB Radiation exposure to the thorax is associated with substantial risk for the subsequent development of cardiovascular disease. Thus, the increasing role of radiation therapy in the contemporary treatment of cancer, combined with improving survival rates of patients undergoing this therapy, contributes to a growing population at risk of cardiovascular morbidity and mortality. Associated cardiovascular injuries include pericardial disease, coronary artery disease, valvular disease, conduction disease, cardiomyopathy, and medium and large vessel vasculopathy-any of which can occur at varying intervals following irradiation. Higher radiation doses, younger age at the time of irradiation, longer intervals from the time of radiation, and coexisting cardiovascular risk factors all predispose to these injuries. The true incidence of radiation-related cardiovascular disease remains uncertain due to lack of large multicentre studies with a sufficient duration of cardiovascular follow-up. There are currently no consensus guidelines available to inform the optimal approach to cardiovascular surveillance of recipients of thoracic radiation. Therefore, we review the cardiovascular consequences of radiation therapy and focus on the potential role of non-invasive cardiovascular imaging in the assessment and management of radiation-related cardiovascular disease. In doing so, we highlight characteristics that can be used to identify individuals at risk for developing post-radiation cardiovascular disease and propose an imaging-based algorithm for their clinical surveillance. C1 [Groarke, John D.; Nohria, Anju; Cheng, Susan; Moslehi, Javid] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nohria, Anju; Moslehi, Javid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Adult Survivorship Clin, Boston, MA 02115 USA. [Ferrari, Roberto] Univ Hosp Ferrara, Dept Cardiol, Lumezzane, Italy. [Ferrari, Roberto] Univ Hosp Ferrara, LTTA Ctr, Lumezzane, Italy. [Ferrari, Roberto] Salvatore Maugeri Fdn IRCCS, Lumezzane, Italy. [Moslehi, Javid] Harvard Univ, Sch Med, Div Med Oncol, Boston, MA 02115 USA. [Moslehi, Javid] Harvard Univ, Sch Med, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Cheng, SS (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM scheng3@partners.org; jmoslehi@partners.org FU NIH [K08-HL097031]; Watkins Discovery Award Program; Cardiovascular Leadership Council Investigator Award; Brigham and Women's Hospital FX No funding was obtained for completing this work. Dr. Moslehi is a recipient of a NIH K-grant (K08-HL097031) and the Watkins Discovery Award Program and Cardiovascular Leadership Council Investigator Award, Brigham and Women's Hospital. NR 113 TC 18 Z9 19 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD MAR PY 2014 VL 35 IS 10 BP 612 EP + DI 10.1093/eurheartj/eht114 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AD2DO UT WOS:000333043700008 PM 23666251 ER PT J AU Santiago, JG Walia, S Sun, JK Cavallerano, JD Haddad, ZA Aiello, LP Silva, PS AF Santiago, J. G. Walia, S. Sun, J. K. Cavallerano, J. D. Haddad, Z. A. Aiello, L. P. Silva, P. S. TI Influence of diabetes and diabetes type on anatomic and visual outcomes following central rein vein occlusion SO EYE LA English DT Article DE central retinal vein occlusion; diabetes mellitus; retinal neovascularization; retinal ischemia; panretinal laser photocoagulation ID BEAVER DAM EYE; NATURAL-HISTORY; RISK-FACTORS; INTRAOCULAR-PRESSURE; STANDARD CARE; RETINOPATHY; DISEASES; SCORE; EPIDEMIOLOGY; POPULATION AB Purpose To determine the influence of diabetes and diabetes type on ocular outcomes following central retinal vein occlusion (CRVO). Methods Retrospective chart review of all patients evaluated over a 4-year period in a tertiary diabetes eye care center. Ophthalmic findings were recorded including visual acuity and the presence of retinal neovascularization at presentation, after 3-6 months, and at last follow-up. Results The records of 19 648 patients (13 571 diabetic; 6077 nondiabetic) were reviewed. The prevalence of CRVO in diabetic patients (N = 72) and nondiabetic patients (N = 27) were 0.5 and 0.4%, respectively. Disc neovascularization (21.3 vs 0.0%, P = 0.05) and panretinal photocoagulation (PRP) (48.7 vs 21.4%, P = 0.01) were more common in diabetic patients compared with nondiabetic patients. Compared with type 2 diabetic patients, retinal neovascularization (28.6 vs 3.7%, P = 0.004) and subsequent PRP (78.6 vs 41.9%, P = 0.01) were more likely in type 1 patients. Optic nerve head collateral vessels (CVs) were observed less than half as often (21.4 vs 56.5%, P = 0.04) in patients with type 1 diabetes. Presence of optic nerve head CVs at baseline was associated with less likelihood of PRP (14.3 vs 46.1%, P = 0.03). Conclusions In this cohort, the rates of CRVO in diabetic and nondiabetic patients were similar to previously published population-based studies. Following CRVO, diabetic patients had higher rates of disc neovascularization and were more likely to require subsequent PRP than nondiabetic patients. As compared with CRVO patients with type 2 diabetes, patients with type 1 diabetes and CRVO had worse anatomic outcomes with substantially increased risks of retinal neovascularization and PRP; however, final visual acuity outcomes were similar. C1 [Santiago, J. G.; Walia, S.; Sun, J. K.; Cavallerano, J. D.; Haddad, Z. A.; Aiello, L. P.; Silva, P. S.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Sun, J. K.; Cavallerano, J. D.; Aiello, L. P.; Silva, P. S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu NR 38 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PD MAR PY 2014 VL 28 IS 3 BP 260 EP 268 PG 9 WC Ophthalmology SC Ophthalmology GA AD0QO UT WOS:000332939400004 ER PT J AU Hamilton, AB Oishi, S Yano, EM Gammage, CE Marshall, NJ Scheuner, MT AF Hamilton, Alison B. Oishi, Sabine Yano, Elizabeth M. Gammage, Cynthia E. Marshall, Nell J. Scheuner, Maren T. TI Factors influencing organizational adoption and implementation of clinical genetic services SO GENETICS IN MEDICINE LA English DT Article DE clinical genetic services; diffusion of innovations; implementation ID GENOMIC MEDICINE; HEALTH-CARE; INNOVATIONS; CHALLENGES; DIFFUSION; BARRIERS; TESTS AB Purpose:'We sought to identify characteristics of genetic services that facilitate or hinder adoption. Methods: We conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology; pathology/laboratory medicine) within 13 Veterans; Administration facilities. Results: Genetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as ! advantageous for their facilities or their patients; compatible with organizational florins of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had-knowledgeable clinicians interested in developing services and; organizational-level; facilitators such as at cesable genetic test-ordering processes. Conclusion: Adoption and implementation of genetic services will ! require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic; medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of; genetic information for the outcomes that matter to health-care-organizations. C1 [Hamilton, Alison B.; Oishi, Sabine; Yano, Elizabeth M.; Gammage, Cynthia E.; Marshall, Nell J.; Scheuner, Maren T.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. [Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Yano, Elizabeth M.; Marshall, Nell J.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Scheuner, Maren T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Hamilton, AB (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. EM alison.hamilton@va.gov FU VA Health Services Research & Development (HSRD) Service [IBD 09-101]; HSR&D-funded Health Services Genomics Pilot Program [DNA 08-128]; National Institute of Mental Health [R25 MH080916-01A2]; VA HSRD QUERI; VA HSR&D Senior Research Career Scientist Award [RCS 05-195]; VA Greater Los Angeles HSR&D Center of Excellence [HFP 94-028]; VA HSRD Service FX This study was funded by the VA Health Services Research & Development (HSR&D) Service (IBD 09-101); pilot work conducted through the HSR&D-funded Health Services Genomics Pilot Program (DNA 08-128) also informed this paper. At the time of the study, A.B.H. was an investigator with the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University, St. Louis; supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and VA HSR&D QUERI. E.M.Y.'s effort was supported by a VA HSR&D Senior Research Career Scientist Award (RCS 05-195). This work was further supported by the VA Greater Los Angeles HSR&D Center of Excellence (HFP 94-028). A.B.H. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors are employed by the Department of Veterans Affairs. A.B.H., E.M.Y., and M.T.S. receive research funding from the VA HSR&D Service. NR 18 TC 7 Z9 7 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD MAR PY 2014 VL 16 IS 3 BP 238 EP 245 DI 10.1038/gim.2013.101 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AC3SP UT WOS:000332441800006 PM 23949572 ER PT J AU Boone, BA Zeh, HJ Mock, BK Johnson, PJ Dvorchik, I Lee, K Moser, AJ Bartlett, DL Marsh, JW AF Boone, Brian A. Zeh, Herbert J. Mock, Brady K. Johnson, Paul J. Dvorchik, Igor Lee, Ken Moser, A. James Bartlett, David L. Marsh, J. Wallis TI Resection of isolated local and metastatic recurrence in periampullary adenocarcinoma SO HPB LA English DT Article ID PANCREATIC DUCTAL ADENOCARCINOMA; LONG-TERM SURVIVAL; CURATIVE RESECTION; REMNANT PANCREAS; CANCER; FOLFIRINOX; GEMCITABINE; CARCINOMA; SURGERY; PANCREATICODUODENECTOMY AB BackgroundThe majority of patients with periampullary cancer develop local or metastatic recurrence despite successful negative margin resection. Unfortunately, there are no established therapeutic strategies for managing these patients. The literature on the surgical resection of recurrent disease is limited. MethodsThis is a retrospective study evaluating patients who underwent reoperative resection of recurrent periampullary cancer at a single institution between 1990 and 2011. Perioperative outcomes were compared with those of the original primary resections for patients with local recurrence. Kaplan-Meier curves were used to evaluate survival. ResultsTwenty-two patients underwent reoperative resection following the successful primary resection of periampullary cancers. Median survival from the time of reoperation was 28.1 months. A greater survival benefit was seen in patients undergoing reoperative resection with >15 months between the primary resection and recurrence (40.6 months versus 8.2 months; P < 0.05). Complication rates were lower after reoperative resection compared with the primary resection (20% versus 70%). Perioperative characteristics including operative time, estimated blood loss and hospital stay were similar in both the primary and reoperation procedures. ConclusionsSurgical resection of periampullary cancer recurrence is feasible, safe and may offer survival benefits in comparison with alternative treatment modalities. Reoperative resection should be considered, especially in patients in whom the time to recurrence is lengthy. C1 [Boone, Brian A.; Zeh, Herbert J.; Dvorchik, Igor; Lee, Ken; Bartlett, David L.; Marsh, J. Wallis] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Mock, Brady K.; Johnson, Paul J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Moser, A. James] BIDMC, Dept Surg, Boston, MA USA. RP Marsh, JW (reprint author), Univ Pittsburgh Med Ctr UPMC Montefiore, 7 South,3459 Fifth Ave, Pittsburgh, PA 15213 USA. EM marshw@upmc.edu RI Dvorchik, Igor/D-1749-2013 FU National Institutes of Health under the Ruth L. Kirschstein National Research Service Award [T32CA113263] FX This work was supported by the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award, grant number T32CA113263. NR 36 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD MAR PY 2014 VL 16 IS 3 BP 197 EP 203 DI 10.1111/hpb.12119 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AB0CC UT WOS:000331458400001 PM 23601033 ER PT J AU Vagefi, PA Parekh, J Ascher, NL Roberts, JP Freise, CE AF Vagefi, Parsia A. Parekh, Justin Ascher, Nancy L. Roberts, John P. Freise, Chris E. TI Ex vivo split-liver transplantation: the true right/left split SO HPB LA English DT Article ID 2 ADULT RECIPIENTS; DECEASED DONOR LIVER; LIVING DONOR; WHOLE LIVER; OUTCOMES AB BackgroundSuccessful left lateral segment (sectionectomy) and right trisegmentectomy (trisectionectomy) split-liver transplantation (SLT) have been achieved. However, there are few reports of the use of true right/left splitting in SLT. MethodsA single-centre retrospective review of true right/left ex vivo split-liver transplants performed during the period 1993-2010 was conducted. Nine cadaveric liver grafts underwent splitting and the resultant 18 allografts were used in transplants performed at the study centre. ResultsIn the nine right lobe recipients, 10-year patient and graft survival rates were both 74%. There were no vascular complications, one biliary complication and one re-exploration. In the nine left lobe recipients, 10-year patient and graft survival rates were 78% and 66%, respectively. Postoperative complications included six biliary complications, four of which required surgical revision and all of which occurred within 5 months of transplantation, and two vascular complications, including one early hepatic artery thrombosis (HAT) and one late HAT, one of which required retransplantation. Five left lobe recipients required re-exploration, and one patient developed small-for-size syndrome following SLT, which resolved with conservative measures. ConclusionsTrue right/left ex vivoSLT remains a viable option for facilitating the expansion of the adult cadaver donor pool and allows for excellent patient and graft survival. Postoperative morbidity remains high, especially in recipients of the left lobe graft, and must be balanced with the benefits to be derived from transplant. C1 [Vagefi, Parsia A.] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Vagefi, Parsia A.] Harvard Univ, Sch Med, Boston, MA USA. [Parekh, Justin; Ascher, Nancy L.; Roberts, John P.; Freise, Chris E.] Univ Calif San Francisco, Div Transplant Surg, San Francisco, CA 94143 USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 544b, Boston, MA 02114 USA. EM pvagefi@partners.org FU NIDDK NIH HHS [P30 DK026743] NR 18 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD MAR PY 2014 VL 16 IS 3 BP 267 EP 274 DI 10.1111/hpb.12113 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AB0CC UT WOS:000331458400010 PM 23601002 ER PT J AU Mani, V Woodward, M Samber, D Bucerius, J Tawakol, A Kallend, D Rudd, JHF Abt, M Fayad, ZA AF Mani, Venkatesh Woodward, Mark Samber, Daniel Bucerius, Jan Tawakol, Ahmed Kallend, David Rudd, James H. F. Abt, Markus Fayad, Zahi A. TI Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Fluorodeoxyglucose-positron emission tomography; Inflammation; Magnetic resonance imaging; Plaque burden ID POSITRON-EMISSION-TOMOGRAPHY; APOLIPOPROTEIN-A-I; CARDIOVASCULAR EVENTS; VASCULAR-DISEASE; UP-REGULATION; F-18-FDG PET; RISK-FACTORS; FDG PET/CT; DALCETRAPIB; AORTA AB Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A(2), apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints. C1 [Mani, Venkatesh; Samber, Daniel; Bucerius, Jan; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. [Mani, Venkatesh; Samber, Daniel; Bucerius, Jan; Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY USA. [Woodward, Mark] Univ Sydney, George Inst, Sydney, NSW 2006, Australia. [Bucerius, Jan] Maastricht Univ, Med Ctr, Dept Nucl Med, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands. [Tawakol, Ahmed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kallend, David; Abt, Markus] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. [Rudd, James H. F.] Univ Cambridge, Div Cardiovasc Med, Cambridge, England. [Fayad, Zahi A.] Icahn Sch Med Mt Sinai, Cardiovasc Inst, New York, NY USA. RP Mani, V (reprint author), Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, New York, NY 10029 USA. EM Venkatesh.mani@mssm.edu RI Mani, Venkatesh/B-8939-2011; Woodward, Mark/D-8492-2015; OI Rudd, James/0000-0003-2243-3117; Mani, Venkatesh/0000-0002-0432-2918 FU F. Hoffmann-La Roche Ltd. FX The authors thank Michael E. Farkouh and Valentin Fuster for their review and feedback of the manuscript. This study was funded by F. Hoffmann-La Roche Ltd. Editorial assistance was provided by Prime Healthcare during the preparation of this report, and funded by F. Hoffmann-La Roche Ltd. All opinions expressed are those of the authors. NR 33 TC 10 Z9 11 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 EI 1573-0743 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD MAR PY 2014 VL 30 IS 3 BP 571 EP 582 DI 10.1007/s10554-014-0370-7 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AD4IQ UT WOS:000333212900013 PM 24458953 ER PT J AU Badani, S Na, S AF Badani, Shelby Na, Sopheap TI Chronic Concern Over an Acute-Phase Reactant A Teachable Moment SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID C-REACTIVE PROTEIN; SURGERY C1 [Badani, Shelby] Univ Colorado, Sch Med, Aurora, CO 80045 USA. [Na, Sopheap] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Badani, S (reprint author), Univ Colorado, Sch Med, 2101 N Ursula St,Apt 402, Aurora, CO 80045 USA. EM shelby.badani@ucdenver.edu NR 7 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 MAR PY 2014 VL 174 IS 3 BP 319 EP 319 DI 10.1001/jamainternmed.2013.12762 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AD2GK UT WOS:000333052100002 PM 24322671 ER PT J AU Goroll, AH AF Goroll, Allan H. TI Moving Toward Evidence-Based Complementary Care SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID MEDICINE C1 [Goroll, Allan H.] Harvard Univ, Sch Med, Boston, MA USA. [Goroll, Allan H.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Goroll, AH (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 15 Parkman St,Ste 645, Boston, MA 02114 USA. EM ahgoroll@partners.org NR 10 TC 1 Z9 1 U1 1 U2 3 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 MAR PY 2014 VL 174 IS 3 BP 368 EP 369 DI 10.1001/jamainternmed.2013.12995 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AD2GK UT WOS:000333052100014 PM 24395188 ER PT J AU Thilen, SR Treggiari, MM Lange, JM Lowy, E Weaver, EM Wijeysundera, DN AF Thilen, Stephan R. Treggiari, Miriam M. Lange, Jane M. Lowy, Elliott Weaver, Edward M. Wijeysundera, Duminda N. TI Preoperative Consultations for Medicare Patients Undergoing Cataract Surgery SO JAMA INTERNAL MEDICINE LA English DT Article ID MAJOR NONCARDIAC SURGERY; PERIOPERATIVE MEDICINE; PRACTICE STYLES; ASCRS MEMBERS; UNITED-STATES; PHYSICIANS; HEALTH; PREFERENCES; OUTCOMES; IMPACT AB IMPORTANCE Low-risk elective surgical procedures are common, but there are no clear guidelines for when preoperative consultations are required. Such consultations may therefore represent a substantial discretionary service. OBJECTIVE To assess temporal trends, explanatory factors, and geographic variation for preoperative consultation in Medicare beneficiaries undergoing cataract surgery, a common low-risk elective procedure. DESIGN, SETTING, AND PARTICIPANTS Cohort study using a 5% national random sample of Medicare part B claims data including a cohort of 556 637 patients 66 years or older who underwent cataract surgery from 1995 to 2006. Temporal trends in consultations were evaluated within this entire cohort, whereas explanatory factors and geographic variation were evaluated within the 89 817 individuals who underwent surgery from 2005 to 2006. MAIN OUTCOMES AND MEASURES Separately billed preoperative consultations (performed by family practitioners, general internists, pulmonologists, endocrinologists, cardiologists, nurse practitioners, or anesthesiologists) within 42 days before index surgery. RESULTS The frequency of preoperative consultations increased from 11.3% in 1998 to 18.4% in 2006. Among individuals who underwent surgery in 2005 to 2006, hierarchical logistic regression modeling found several factors to be associated with preoperative consultation, including increased age (75-84 years vs 66-74 years: adjusted odds ratio [AOR], 1.09 [95% CI, 1.04-1.13]), race (African American race vs other: AOR, 0.71 [95% CI, 0.65-0.78]), urban residence (urban residence vs isolated rural town: AOR, 1.64 [95% CI, 1.49-1.81]), facility type (outpatient hospital vs ambulatory surgical facility: AOR, 1.10 [95% CI, 1.05-1.15]), anesthesia provider (anesthesiologist vs non-medically directed nurse anesthetist: AOR, 1.16 [95% CI, 1.10-1.24), and geographic region (Northeast vs South: AOR, 3.09 [95% CI, 2.33-4.10]). The burden of comorbidity was associated with consultation, but the effect size was small (< 10%). Variation in frequency of consultation across hospital referral regions was substantial (median [range], 12% [0-69%]), even after accounting for differences in patient-level, anesthesia provider-level, and facility-level characteristics. CONCLUSIONS AND RELEVANCE Between 1995 and 2006, the frequency of preoperative consultation for cataract surgery increased substantially. Referrals for consultation seem to be primarily driven by nonmedical factors, with substantial geographic variation. C1 [Thilen, Stephan R.; Treggiari, Miriam M.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA. [Treggiari, Miriam M.] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [Lange, Jane M.] Univ Washington, Dept Biostat, Seattle, WA 98104 USA. [Lowy, Elliott; Weaver, Edward M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Lowy, Elliott] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Weaver, Edward M.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Wijeysundera, Duminda N.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. [Wijeysundera, Duminda N.] Toronto Gen Hosp, Dept Anesthesia & Pain Management, Toronto, ON, Canada. [Wijeysundera, Duminda N.] Univ Toronto, Dept Anesthesia, Toronto, ON, Canada. [Wijeysundera, Duminda N.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Wijeysundera, Duminda N.] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. RP Thilen, SR (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, 325 Ninth Ave,POB 359724, Seattle, WA 98104 USA. EM sthilen@uw.edu OI Wijeysundera, Duminda/0000-0002-5897-8605 FU Department of Anesthesiology and Pain Medicine, University of Washington, Seattle; National Institutes of Health [T32GM086270]; Canadian Institutes of Health Research; Department of Anesthesia at the University of Toronto, Toronto, Ontario, Canada; Veterans Affairs Puget Sound Health Care System, Seattle, Washington FX This study was partially supported by funds from the Department of Anesthesiology and Pain Medicine, University of Washington, Seattle. Dr Thilen is supported by grant T32GM086270 from the National Institutes of Health, and by the Department of Anesthesiology and Pain Medicine, University of Washington, Seattle. Dr Wijeysundera is supported by a Clinician Scientist Award from the Canadian Institutes of Health Research and a Merit Award from the Department of Anesthesia at the University of Toronto, Toronto, Ontario, Canada. Drs Weaver and Lowy are partially supported by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 30 TC 9 Z9 10 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2014 VL 174 IS 3 BP 380 EP 388 DI 10.1001/jamainternmed.2013.13426 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AD2GK UT WOS:000333052100017 PM 24366269 ER PT J AU Chinn, GM Liu, PH Klabunde, CN Kahn, KL Keating, NL AF Chinn, Garrett M. Liu, Pang-Hsiang Klabunde, Carrie N. Kahn, Katherine L. Keating, Nancy L. TI Physicians' Preferences for Hospice if They Were Terminally Ill and the Timing of Hospice Discussions With Their Patients SO JAMA INTERNAL MEDICINE LA English DT Letter ID OF-LIFE CARE C1 [Chinn, Garrett M.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Chinn, Garrett M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, Pang-Hsiang; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Klabunde, Carrie N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu RI Liu, Michael Pang-Hsiang/B-9903-2015 OI Liu, Michael Pang-Hsiang/0000-0001-8842-2264 FU NCI NIH HHS [R01 CA164021, 1R01CA164021-01A1, U01 CA093324, U01 CA093326, U01 CA093329, U01 CA093332, U01 CA093339, U01 CA093344, U01 CA093348, U01CA093329] NR 6 TC 4 Z9 4 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2014 VL 174 IS 3 BP 466 EP 468 DI 10.1001/jamainternmed.2013.12825 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AD2GK UT WOS:000333052100037 PM 24342971 ER PT J AU Patel, MS Reed, DA Loertscher, L McDonald, FS Arora, VM AF Patel, Mitesh S. Reed, Darcy A. Loertscher, Laura McDonald, Furman S. Arora, Vineet M. TI Teaching Residents to Provide Cost-Conscious Care: A National Survey of Residency Program Directors SO JAMA INTERNAL MEDICINE LA English DT Letter ID PHYSICIANS C1 [Patel, Mitesh S.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Patel, Mitesh S.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Reed, Darcy A.] Mayo Clin, Div Primary Care Internal Med, Rochester, MN USA. [Loertscher, Laura] Providence St Vincent Med Ctr, Portland, OR USA. [McDonald, Furman S.] Mayo Clin, Gen & Hosp Internal Med, Rochester, MN USA. [Arora, Vineet M.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. RP Patel, MS (reprint author), Univ Penn, VA Robert Wood Johnson Clin Scholars Program, 423 Guardian Dr,1303B Blockley Hall, Philadelphia, PA 19104 USA. EM mpatel@upenn.edu OI Arora, Vineet/0000-0002-4745-7599 NR 6 TC 13 Z9 13 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2014 VL 174 IS 3 BP 470 EP 472 DI 10.1001/jamainternmed.2013.13222 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AD2GK UT WOS:000333052100039 PM 24343037 ER PT J AU McConnell, M Downs, JR Good, CB AF McConnell, Mark Downs, John R. Good, Chester B. TI Decrease the Incentives to Order Lipid Panels SO JAMA INTERNAL MEDICINE LA English DT Letter ID TARGETS C1 [McConnell, Mark] Tomah VA Med Ctr, Tomah, WI 54660 USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. [Good, Chester B.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP McConnell, M (reprint author), Tomah VA Med Ctr, 500 E Vet St, Tomah, WI 54660 USA. EM mark.mcconnell@va.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR PY 2014 VL 174 IS 3 BP 473 EP 473 DI 10.1001/jamainternmed.2013.12872 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AD2GK UT WOS:000333052100040 PM 24590082 ER PT J AU Liu, J Khan, A Johnson, S Grigorian, C Li, T AF Liu, Joseph Khan, Ambereen Johnson, Samuel Grigorian, Cheryl Li, Tao TI The usefulness of gestational sac and placental sonographic morphology in differentiating between second-trimester tubal and abdominal pregnancy: Case report and a review of literature SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE abdominal pregnancy; crescent-shaped placenta; GS morphology; advanced tubal pregnancy; second-trimester tubal pregnancy ID ADVANCED ECTOPIC PREGNANCY; DIAGNOSIS AB Second-trimester tubal pregnancy is rarely encountered and published cases are limited. There are no established sonographic criteria to differentiate it from abdominal pregnancy; however, differences in their medical management make this distinction important. We report a case of a 14-week 5-day tubal pregnancy that presented near rupture. Sonography demonstrated many overlapping features with abdominal pregnancy. In addition, the extrauterine gestational sac was rounded and well defined and the placenta was crescent-shaped. We propose that these sonographic features represent a second-trimester tubal pregnancy rather than an abdominal pregnancy. (c) 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:162-168, 2014 C1 [Liu, Joseph; Khan, Ambereen; Johnson, Samuel; Grigorian, Cheryl] Wayne State Univ, Dept Radiol, Detroit Med Ctr, Detroit, MI 48201 USA. [Li, Tao] Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Liu, J (reprint author), Wayne State Univ, Dept Radiol, Detroit Med Ctr, 4201 St Antoine St,DRH 3L-8, Detroit, MI 48201 USA. NR 27 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-2751 EI 1097-0096 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD MAR PY 2014 VL 42 IS 3 BP 162 EP 168 DI 10.1002/jcu.22076 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA AC2KI UT WOS:000332329300007 PM 23913766 ER PT J AU Palaganas, JC Epps, C Raemer, DB AF Palaganas, Janice C. Epps, Chad Raemer, Daniel B. TI A history of simulation-enhanced interprofessional education SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Education; healthcare; history; interprofessional; mannequin; simulation ID RESOURCE-MANAGEMENT; HEALTH-CARE; TEAMWORK; TECHNOLOGY; RESIDENTS; FIDELITY AB This article explores the evolution and history of interprofessional education (IPE) using healthcare simulation (HCS). The evolution described here demonstrates an achievement of patient safety efforts as a consequence of the historical roots of healthcare and highlights HCS as a progressive method synergistic with IPE. This paper presents a descriptive review that covers the HCS and IPE literature, indicating factors that led to the use of HCS in IPE. Understanding the history of simulation-enhanced IPE provides healthcare educators with fertile ground to support future IPE. A number of benefits in using HCS to address common challenges to IPE are outlined, including natural relevance and engagement for learners, faculty attraction to its use, and the opportunity to explore socio-historical issues in teams. Several promising directions for future research are suggested. C1 [Palaganas, Janice C.] Harvard Univ, Sch Med, Ctr Med Simulat, Boston, MA 02129 USA. [Epps, Chad] Univ Alabama Birmingham, Dept Clin & Diagnost Sci, Birmingham, AL USA. [Raemer, Daniel B.] Massachusetts Gen Hosp, Ctr Med Simulat, Boston, MA 02114 USA. RP Palaganas, JC (reprint author), Harvard Univ, Sch Med, Ctr Med Simulat, 100 First Ave,Bldg 39,Fourth Floor, Boston, MA 02129 USA. EM jpalaganas@mgh.harvard.edu NR 60 TC 14 Z9 14 U1 1 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD MAR PY 2014 VL 28 IS 2 BP 110 EP 115 DI 10.3109/13561820.2013.869198 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AC4HM UT WOS:000332481800005 PM 24372044 ER PT J AU Munro, MG Nichols, JE Levy, B Vleugels, MPH Veersema, S AF Munro, M. G. Nichols, J. E. Levy, B. Vleugels, M. P. H. Veersema, S. TI Hysteroscopic Sterilization: 10-Year Retrospective Analysis of Worldwide Pregnancy Reports SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Contraception; Essure; Female sterilization; Hysteroscopic sterilization; Permanent birth control ID ESSURE STERILIZATION; TUBAL-STERILIZATION; MICRO-INSERT; FOLLOW-UP; ULTRASOUND; PLACEMENT; CONFIRMATION; MICROINSERTS; TRIAL AB Study Objective: To identify factors that might contribute to pregnancies reported after hysteroscopic sterilization worldwide. Design: Retrospective review of commercial data compiled from the MAUDE database, medical literature, and manufacturer reports received during commercial distribution of hysteroscopic sterilization micro-inserts from 2001 through 2010 (Canadian Taskforce classification ill descriptive study). Measurements and Main Results: From 2001 through 2010, 497 305 hysteroscopic sterilization kits were distributed worldwide, and 748 pregnancies were reported, i.e., 0.15% of the estimated user population based on the number of distributed kits. The data were sufficient to enable analysis of 508 pregnancies for potential contributing factors and showed most to be associated with patient or physician noncompliance (n = 264) or misinterpreted confirmation tests (n = 212). Conceptions deemed to have occurred within 2 weeks of the procedure and therefore too early for detection were identified in 32 cases. Conclusion: Although there are limitations to the dataset and the study design is retrospective, it represents the largest body of cumulative hysterosdopic sterilization data available to date. Of the 748 pregnancies reported, it is apparent that some might have been prevented with greater patient and clinician attention to interim contraceptive use and counseling and with more rigorous evaluation and informed interpretation of the procedure confirmation tests. Although the estimated pregnancy rate based on such a dataset is likely an underestimation, it does suggest that the evaluable field performance of hysteroscopic sterilization micro-inserts is consistent with the labeled age-adjusted effectiveness of 99.74% at 5 years. (c) 2014 AAGL. All rights reserved. C1 [Munro, M. G.] Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Munro, M. G.] W Los Angeles Vet Affairs Med Ctr, Kaiser Permanente, Gynecol Serv, Los Angeles, CA 90073 USA. [Nichols, J. E.] Piedmont Reprod Endocrinol Grp, Greenville, SC 29615 USA. [Levy, B.] Amer Congress Obstetricians & Gynecologists, Advocacy Div, Washington, DC USA. [Vleugels, M. P. H.] Rivierenland Hosp, Tiel CASA Clin, Nijmegen, Netherlands. [Veersema, S.] St Antonius Hosp, Utrecht, Netherlands. RP Nichols, JE (reprint author), Piedmont Reprod Endocrinol Grp, 17 Caledon Ct, Greenville, SC 29615 USA. EM j.nichols@yahoo.com NR 17 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 EI 1553-4669 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD MAR-APR PY 2014 VL 21 IS 2 BP 245 EP 251 DI 10.1016/j.jmig.2013.09.016 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AD7IN UT WOS:000333437500016 PM 24126261 ER PT J AU Miltner, RS Johnson, KD Deierhoi, R AF Miltner, Rebecca S. Johnson, Kimberly D. Deierhoi, Rhiannon TI Exploring the Frequency of Blood Pressure Documentation in Emergency Departments SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE documentation; Emergency Severity Index (ESI); emergency department; Vital sign monitoring ID VITAL SIGNS; SEVERITY INDEX; CARE; TRIAGE; DETERIORATION; RECORDS; NURSES AB Purpose One of the most commonly performed task in the emergency department (ED) is reported as the monitoring of vital signs, yet there are no published standards of care that provide guidelines for the frequency of obtaining vital signs in the ED. The purpose of this exploratory study was to determine the frequency of documentation of vital signs recorded during ED visits across Veterans Health Administration (VHA) facilities. Methods Deidentified patient level data from the VHA electronic health record (EHR) were abstracted for emergency department visits for 12 randomly selected days in calendar year 2011. The dataset included vital signs data, associated time stamps, facility, length of stay, triage category based on the Emergency Severity Index (ESI), and patient disposition for all patients. Descriptive statistics were used to describe the frequency of the specific vital sign measures, and parametric and nonparametric tests were used to examine study variables by ESI. Findings The sample consisted of over 43,232 unique patient visits to 94 VHA EDs with a median length of stay of 173.3 min (interquartile range [IQR], 96.1-286.9). The mean number of times that blood pressure (BP) was recorded per visit was 1.23 (SD 1.175). For the entire sample, median time between blood pressure measurements was 139.7 min (IQR, 81.6-230.1). There was a significant difference in median length of stay and median time between blood pressure by ESI category. Conclusions In this dataset, median time between documentation of BP in the ED was every 2.3 hr for all patients. While the median time was statistically significant between ESI categories, these times may not be clinically relevant. More important was the inconsistent documentation of vital signs of ED patients in the designated fields in the EHR. Most facilities (84.1%) documented BP for >75% of patient visits. However, eight facilities (9.1%) had BP documented in Clinical Relevance It seems unlikely that vital signs are not monitored in the ED; nurses anecdotally report that vital signs are recorded on a paper chart and later scanned as an image into the EHR. However, lack of consistent process in documentation of vital signs may decrease the care team's ability to note early warning signs of physiological instability or deterioration. C1 [Miltner, Rebecca S.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. [Miltner, Rebecca S.; Deierhoi, Rhiannon] Birmingham VA Med Ctr, Birmingham, AL USA. [Johnson, Kimberly D.] Univ Cincinnati, Coll Nursing, Cincinnati, OH USA. [Deierhoi, Rhiannon] Univ Alabama Birmingham, Dept GI Surg, Birmingham, AL USA. RP Miltner, RS (reprint author), 1449 Haddon Pl, Hoover, AL 35226 USA. EM smiltner@uab.edu OI Miltner, Rebecca/0000-0002-4653-0328 FU Veterans Administration Nursing Academy FX This article was supported in part by the Veterans Administration Nursing Academy, a partnership between the Birmingham Veterans Administration Medical Center and the University of Alabama at Birmingham School of Nursing. The content is solely the responsibility of the authors and does not necessarily represent the views of the Veterans Health Administration. NR 28 TC 4 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 EI 1547-5069 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD MAR PY 2014 VL 46 IS 2 BP 98 EP 105 DI 10.1111/jnu.12060 PG 8 WC Nursing SC Nursing GA AC2HT UT WOS:000332321400005 PM 24355058 ER PT J AU Singh, JA Luo, RL Landon, GC Suarez-Almazor, M AF Singh, Jasvinder A. Luo, Ruili Landon, Glenn C. Suarez-Almazor, Maria TI Reliability and Clinically Important Improvement Thresholds for Osteoarthritis Pain and Function Scales: A Multicenter Study SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RELIABILITY; SENSITIVITY TO CHANGE; KNEE; HIP; ARTHRITIS; PAIN ID OUTCOME SCORE KOOS; PHYSICAL-FUNCTION; HEALTH-STATUS; KNEE INJURY; PORTUGUESE VERSION; HIP DISABILITY; HOOS-PS; RESPONSIVENESS; VALIDITY; REPLACEMENT AB Objective. To assess the reliability and clinically meaningful thresholds of intermittent and constant osteoarthritis pain (ICOAP) score, the Knee injury and Osteoarthritis Outcome Score Physical function Short-form (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score Physical function Short-form (HOOS-PS), and the Quality of life subscales of HOOS/KOOS (HOOS-QOL/KOOS-QOL) in patients with knee or hip arthritis. Methods. One hundred and ninety-five patients (141 knee, 54 hip) seen at 2 orthopedic outpatient clinics with a diagnosis of knee or hip OA completed patient-reported questionnaires (ICOAP pain scale, KOOS-PS, HOOS-PS, KOOS-QOL, HOOS-QOL) at baseline and 2-week followup. Reliability was assessed using intraclass correlation coefficients (ICC). We calculated minimum clinically important difference (MCID) and moderate improvement in the subgroup that reported change in the status of their affected joint. Results. The reliability as assessed by ICC was as follows: ICOAP pain scale, 0.63 (0.48, 0.74) in patients with knee arthritis, and 0.86 (0.73, 0.93) for hip arthritis; KOOS-PS, 0.66 (0.52, 0.77); HOOS-PS, 0.82 (0.66, 0.91); KOOS-QOL, 0.79 (0.69, 0.86); and HOOS-QOL, 0.67 (0.42, 0.83). MCID and moderate improvement estimates in patients with knee arthritis were ICOAP pain scale, 18.5 and 26.7; KOOS-PS, 2.2 and 15.0; and KOOS-QOL, 8.0 and 15.6. A smaller sample in patients with hip arthritis precluded MCID and moderate improvement estimates. Conclusion. We found that ICOAP pain and KOOS-PS/HOOS-PS scales were reasonably reliable in patients with hip OA. Reliability of these scales was much lower in patients with knee arthritis. Thresholds for clinically meaningful change in pain or function on these scales were estimated for patients with knee arthritis. C1 Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Div Epidemiol, Sch Publ Hlth, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Dept Hlth Sci Res, Sch Med, Rochester, MN USA. [Singh, Jasvinder A.] Mayo Clin, Dept Orthoped Surg, Sch Med, Rochester, MN USA. [Luo, Ruili; Suarez-Almazor, Maria] Univ Texas MD Anderson Canc Ctr, Sect Rheumatol & Clin Immunol, Houston, TX 77030 USA. [Landon, Glenn C.] St Lukes Episopal Hlth Syst, Houston, TX USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU US National Institutes of Health Clinical Translational Science Award [1 KL2 RR024151-01]; Pfizer; Expansciences; Novartis; Negma Lerads; Rottapharm; Fidia; Pierre Fabre Sante laboratories; European League Against Rheumatism; National Institute for Arthritis, Musculoskeletal, and Skin Disorders [AR053593]; Takeda; Savient; Regeneron; Allergan FX Supported by US National Institutes of Health Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research), and the resources and facilities at the Birmingham VA Medical Center, Alabama, USA. The original study was supported by unrestricted grants to scientific societies (Osteoarthritis Research Society International and Outcome Measures in Rheumatology) from pharmaceutical companies: Pfizer, Expansciences, Novartis, Negma Lerads, Rottapharm, Fidia, and Pierre Fabre Sante laboratories, and a research grant from the European League Against Rheumatism. Dr. Suarez-Almazor is the recipient of a K24 award from the National Institute for Arthritis, Musculoskeletal, and Skin Disorders (AR053593). Dr. Singh has received research and travel grants from Takeda and Savient, and consultant fees from Savient, Regeneron, Takeda, and Allergan. NR 31 TC 10 Z9 12 U1 2 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2014 VL 41 IS 3 BP 509 EP 515 DI 10.3899/jrheum.130609 PG 7 WC Rheumatology SC Rheumatology GA AD0FX UT WOS:000332911000015 PM 24429183 ER PT J AU Dalbeth, N Zhong, CS Grainger, R Khanna, D Khanna, PP Singh, JA McQueen, FM Taylor, WJ AF Dalbeth, Nicola Zhong, Cathy S. Grainger, Rebecca Khanna, Dinesh Khanna, Puja P. Singh, Jasvinder A. McQueen, Fiona M. Taylor, William J. TI Outcome Measures in Acute Gout: A Systematic Literature Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE GOUT; PAIN; MEASUREMENT; OUTCOME ID DOUBLE-BLIND; TRIAMCINOLONE ACETONIDE; CONTROLLED-TRIAL; ACUTE FLARES; ARTHRITIS PATIENTS; CLINICAL-TRIALS; PAIN INTENSITY; INDOMETHACIN; MULTICENTER; CANAKINUMAB AB Objective. Five core domains have been endorsed by Outcome Measures in Rheumatology (OMERACT) for acute gout: pain, joint swelling, joint tenderness, patient global assessment, and activity limitation. We evaluated instruments for these domains according to the OMERACT filter: truth, feasibility, and discrimination. Methods. A systematic search strategy for instruments used to measure the acute gout core domains was formulated. For each method, articles were assessed by 2 reviewers to summarize information according to the specific components of the OMERACT filter. Results. Seventy-seven articles and abstracts met the inclusion criteria. Pain was most frequently reported (76 studies, 20 instruments). The pain instruments used most often were 100 mm visual analog scale (VAS) and 5-point Likert scale. Both methods have high feasibility, face and content validity, and within- and between-group discrimination. Four-point Likert scales assessing index joint swelling and tenderness have been used in numerous acute gout studies; these instruments are feasible, with high face and content validity, and show within- and between-group discrimination. Five-point Patient Global Assessment of Response to Treatment (PGART) scales are feasible and valid, and show within- and between-group discrimination. Measures of activity limitations were infrequently reported, and insufficient data were available to make definite assessments of the instruments for this domain. Conclusion. Many different instruments have been used to assess the acute gout core domains. Pain VAS and 5-point Likert scales, 4-point Liken scales of index joint swelling and tenderness and 5-point PGART instruments meet the criteria for the OMERACT filter. C1 [Dalbeth, Nicola; Zhong, Cathy S.] Univ Auckland, Dept Med, Auckland, New Zealand. [Grainger, Rebecca; Taylor, William J.] Univ Otago, Dept Med, Wellington, New Zealand. [Khanna, Dinesh; Khanna, Puja P.] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. RP Dalbeth, N (reprint author), Univ Auckland, Dept Med, Fac Med & Hlth Sci, 85 Pk Rd, Auckland, New Zealand. EM n.dalbeth@auckland.ac.nz FU University of Auckland; Ardea Biosciences; Metabolex; Novartis; Takeda; Fonterra; Ardea; Savient; Regeneron; Allergan; URL pharmaceuticals FX Supported by a University of Auckland summer studentship (CSZ). Dr. Dalbeth has received consultant fees from Ardea Biosciences, Metabolex, Novartis, and Takeda; her institution has received funding from Fonterra; and she is inventor on a patent related to milk products and gout. Dr. D. Khanna has received consultant fees from Ardea,Takeda, Novartis, and Savient, and has served on a speakers bureau for Savient. Dr. P. Khanna serves on the speakers bureau for Takeda. J.A. Singh has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL pharmaceuticals, and Novartis. J.A. Singh is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. NR 61 TC 6 Z9 6 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2014 VL 41 IS 3 BP 558 EP 568 DI 10.3899/jrheum.131244 PG 11 WC Rheumatology SC Rheumatology GA AD0FX UT WOS:000332911000023 PM 24334652 ER PT J AU Singh, JA Taylor, WJ Dalbeth, N Simon, LS Sundy, J Grainger, R Alten, R March, L Strand, V Wells, G Khanna, D McQueen, F Schlesinger, N Boonen, A Boers, M Saag, KG Schumacher, HR Edwards, NL AF Singh, Jasvinder A. Taylor, William J. Dalbeth, Nicola Simon, Lee S. Sundy, John Grainger, Rebecca Alten, Rieke March, Lyn Strand, Vibeke Wells, George Khanna, Dinesh McQueen, Fiona Schlesinger, Naomi Boonen, Annelies Boers, Maarten Saag, Kenneth G. Schumacher, H. Ralph Edwards, N. Lawrence TI OMERACT Endorsement of Measures of Outcome for Studies of Acute Gout SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; OUTCOME MEASURES; PSYCHOMETRICS ID CLINICAL-TRIALS; INDOMETHACIN; ETORICOXIB; PROGRESS; SCALES AB Objective:To determine the extent to which participants at the Outcome Measures in Rheumatology (OMERACT) 11 meeting agree that instruments used in clinical trials to measure OMERACT core outcome domains in acute gout fulfill OMERACT filter requirements of truth, discrimination, and feasibility; and where future research efforts need to be directed. Methods. Results of a systematic literature review and analysis of individual-level data from recent clinical studies of acute gout were presented to OMERACT participants. The information was discussed in breakout groups, and opinion was defined by subsequent voting in a plenary session. Endorsement was defined as at least 70% of participants voting in agreement with the proposition (where the denominator excluded those participants who did not vote or who voted "don't know"). Results. The following measures were endorsed for use in clinical trials of acute gout: (1) 5-point Likert scale and/or visual analog scale (0 to 100 mm) to measure pain; (2) 4-point Likert scale for joint swelling; (3) 4-point Likert scale for joint tenderness; and (4) 5-point Likert scale for patient global assessment of response to treatment. Measures for the activity limitations domain were not endorsed. Conclusion. Measures of pain, joint swelling, joint tenderness, and patient global assessment in acute gout were endorsed at OMERACT 11. These measures should now be used in clinical trials of acute gout. C1 [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.; Saag, Kenneth G.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Taylor, William J.; Grainger, Rebecca] Univ Otago, Dept Med, Wellington, New Zealand. [Dalbeth, Nicola] Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [Sundy, John] Duke Univ, Sch Med, Durham, NC USA. [Sundy, John] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Alten, Rieke] Charite, Schlosspk Klin Teaching Hosp, D-13353 Berlin, Germany. [March, Lyn] Univ Sydney, Inst Bone & Joint Res, Sydney, NSW 2006, Australia. [March, Lyn] Royal N Shore Hosp, Dept Rheumatol, Sydney, NSW, Australia. [Strand, Vibeke] Stanford Univ, Div Rheumatol & Immunol, Portolo Valley, CA USA. [Wells, George] Univ Ottawa, London, ON, Canada. [Khanna, Dinesh] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Schlesinger, Naomi] Univ Auckland, Dept Mol Med & Pathol, Auckland 1, New Zealand. [Schlesinger, Naomi] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Boonen, Annelies] Maastricht Univ, Med Ctr, Div Rheumatol, Maastricht, Netherlands. [Boonen, Annelies] Univ Maastricht, Caphri Res Inst, Maastricht, Netherlands. [Boers, Maarten] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Schumacher, H. Ralph] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Edwards, N. Lawrence] Univ Florida, Dept Rheumatol, Gainesville, FL USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Takeda; Savient; Ardea; Regeneron; Allergan; URL pharmaceuticals; Novartis; Fonterra; Savient Pharmaceuticals; Ardea Biosciences; Metabolex; Nuon Therapeutics; Pharmos; Biosciences; BioCryst; Takeda Pharmaceutical; Savient Pharmaceutical; Regeneron Pharmaceuticals; Metabolex Pharmaceuticals; BioCryst Pharmaceuticals FX Supported with the resources and the use of facilities at the Birmingham VA Medical Center, Alabama, USA (J. Singh) and University of Otago, New Zealand (W. Taylor). J. Singh has received research grants from Takeda and Savient; and consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL pharmaceuticals and Novartis; and is a member of the executive of OMERACT, which receives arms-length funding from 36 companies; a member of the American College of Rheumatology Guidelines Subconmittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. N. Dalbeth has acted as a consultant for Ardea Biosciences, Metabolex, Novartis, and Takeda; her institution has received funding from Fonterra, and she is a named inventor on a patent related to milk products and gout. L. Simon has served on the Board of Directors for Savient Pharmaceuticals, and as a consultant for Takeda. J. Sundy has received research support from Savient Pharmaceuticals, Regeneron, Ardea Biosciences, Metabolex, Nuon Therapeutics, Pharmos; and consulting funds from Savient Pharmaceuticals, Regeneron, Novartis, Ardea Biosciences, Metabolex, Nuon Therapeutics, BioCryst, and Pharmos. V Strand has received consultant fees from Metabolex, Novartis, and Savient. D. Khanna has received consultant fees. from Ardea, Takeda, Novartis, and Savient; and has served on a Speaker Bureau for Savient. N. Schlesinger has received research grants from Novartis, worked on the Advisory Board for Novartis, Takeda, Savient, Enzyme Rx, URL Pharma; served on the Speaker Bureau for Novartis, Takeda, and Savient; and received consultant fees from Novartis and Takeda. K. Saag has received consultant fees from Ardea, Regeneron, and Takeda and served on the Data Safety Monitoring Board for BioCryst. R. Schumacher has received a grant from Takeda and is a consultant with Regeneron, Novartis, Ardea, Metabolex, Savient, BioCryst, Westward, and Pfizer. N. Edwards has received consultant fees from Takeda Pharmaceutical, Savient Pharmaceutical, Ardea Biosciences, Regeneron Pharmaceuticals, Metabolex Pharmaceuticals, and BioCryst Pharmaceuticals. Views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 15 TC 5 Z9 5 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2014 VL 41 IS 3 BP 569 EP 573 DI 10.3899/jrheum.131246 PG 5 WC Rheumatology SC Rheumatology GA AD0FX UT WOS:000332911000024 PM 24334651 ER PT J AU Taylor, WJ Redden, D Dalbeth, N Schumacher, HR Edwards, NL Simon, LS John, MR Essex, MN Watson, DJ Evans, R Rome, K Singh, JA AF Taylor, William J. Redden, David Dalbeth, Nicola Schumacher, H. Ralph Edwards, N. Lawrence Simon, Lee S. John, Markus R. Essex, Margaret N. Watson, Douglas J. Evans, Robert Rome, Keith Singh, Jasvinder A. TI Application of the OMERACT Filter to Measures of Core Outcome Domains in Recent Clinical Studies of Acute Gout SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE GOUT; OUTCOME MEASURES; PSYCHOMETRICS ID HEALTH-STATUS; IMPAIRMENT; ARTHRITIS AB Objective. To determine the extent to which instruments that measure core outcome domains in acute gout fulfill the Outcome Measures in Rheumatology (OMERACT) filter requirements of truth, discrimination, and feasibility. Methods. Patient-level data from 4 randomized controlled trials of agents designed to treat acute gout and 1 observational study of acute gout were analyzed. For each available measure, construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic, and repeated measures generalized estimating equations were assessed. Floor and ceiling effects were also assessed and minimal clinically important difference was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement. Results. There was evidence for construct validity and discriminative ability for 3 measures of pain [0 to 4 Likert, 0 to 10 numeric rating scale (NRS), 0 to 100 mm visual analog scale (VAS)]. Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment. Conclusion.. There is sufficient evidence to support measures of pain (using Likert, NRS, or VAS), joint tenderness, and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required. C1 [Taylor, William J.] Univ Otago, Dept Med, Wellington, New Zealand. [Redden, David] Univ Alabama Birmingham, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA. [Dalbeth, Nicola] Univ Auckland, Dept Med, Auckland, New Zealand. [Schumacher, H. Ralph] Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs VA Med Ctr, Philadelphia, PA USA. [Edwards, N. Lawrence] Univ Florida, Dept Med, Gainesville, FL USA. [Simon, Lee S.] SDG LLC, Cambridge, MA USA. [John, Markus R.] Novartis Pharma AG, Integrated Hosp Care Franchise, Immunol, Basel, Switzerland. [Essex, Margaret N.] Pfizer Inc, New York, NY USA. [Watson, Douglas J.] Merck Sharp & Dohme Corp, Epidemiol, Whitehouse Stn, NY USA. [Evans, Robert] Regeneron Pharmaceut, Clin Sci, Tarrytown, NJ USA. [Rome, Keith] Auckland Univ Technol, Hlth & Rehabil Res Inst, Auckland, New Zealand. [Rome, Keith] Auckland Univ Technol, Sch Podiatry, Auckland, New Zealand. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. RP Taylor, WJ (reprint author), Univ Otago, Dept Med, POB 7343, Wellington, New Zealand. EM will.taylor@otago.ac.nz FU Ardea Biosciences; Metabolex; Novartis; Takeda; Fonterra; Takeda Pharmaceutical; Savient Pharmaceutical; Regeneron Pharmaceuticals; Metabolex Pharmaceuticals; BioCryst Pharmaceuticals; Ardea; Allergan; URL Pharmaceuticals FX Supported with resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA (J.A.S. and D. Redden). N. Dalbeth has received consulting fees from Ardea Biosciences, Metabolex, Novartis, and Takeda. Her institution has received funding from Fonterra, and she is a named inventor on a patent related to milk products and gout. H.R. Schumacher has been a consultant for Regeneron, Novartis, Pfizer, Savient, Ardea, Metabolex, and BioCryst, and he has received a grant from Takeda. N.L. Edwards has received consultant fees from Novartis, Takeda Pharmaceutical, Savient Pharmaceutical, Ardea Biosciences, Regeneron Pharmaceuticals, Metabolex Pharmaceuticals, and BioCryst Pharmaceuticals. L.L. Simon has served on the board of directors for Savient Pharmaceuticals, and has consulted for Takeda. M.R. John is employed by Novartis and sometimes owns shares in the company. M.N. Essex is employed by Pfizer and owns shares in the company. DJ. Watson is an employee of and owns stock in Merck & Co. Inc.; the marketing authorization holder for etoricoxib and sponsor of the etorcoxib clinical trials that contributed data for this work. R. Evans is employed by Regeneron and owns shares of stock. J.A. Singh has received research grants from Takeda and Savient and consultant fees from Savient, Takeda, Ardea, Regeneron, Allergan, URL Pharmaceuticals and Novartis. He is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies; a member of the American College of Rheumatology's Guidelines Subcommittee of the Quality of Care Committee; and a member of the Veterans Affairs Rheumatology Field Advisory Committee. NR 9 TC 4 Z9 4 U1 1 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2014 VL 41 IS 3 BP 574 EP 580 DI 10.3899/jrheum.131245 PG 7 WC Rheumatology SC Rheumatology GA AD0FX UT WOS:000332911000025 PM 24429178 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Research Priorities in Gout: The Patient Perspective SO JOURNAL OF RHEUMATOLOGY LA English DT Letter ID NOMINAL GROUP TECHNIQUE; GENERAL-PRACTICE; POPULATION; MANAGEMENT C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Sch Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU NIA NIH HHS [U01 AG018947]; NIAMS NIH HHS [P50 AR060772] NR 11 TC 4 Z9 4 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X EI 1499-2752 J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2014 VL 41 IS 3 BP 615 EP 616 DI 10.3899/jrheum.131258 PG 2 WC Rheumatology SC Rheumatology GA AD0FX UT WOS:000332911000030 PM 24585526 ER PT J AU Kloek, CE Borboli-Gerogiannis, S Chang, K Kuperwaser, M Newman, LR Lane, AM Loewenstein, JI AF Kloek, Carolyn E. Borboli-Gerogiannis, Sheila Chang, Kenneth Kuperwaser, Mark Newman, Lori R. Lane, Anne Marie Loewenstein, John I. TI A Broadly Applicable Surgical Teaching Method: Evaluation of a Stepwise Introduction to Cataract Surgery SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE surgical curriculum; deliberate practice; medical education; procedural training; cataract; cataract surgery ID PERFORMANCE; SKILLS; SIMULATOR; IMPACT AB OBJECTIVE: Although cataract surgery is one of the most commonly performed surgeries in the country, it is a microsurgical procedure that is difficult to learn and to teach. This study aims to assess the effectiveness of a new method for introducing postgraduate year (PGY)-3 ophthalmology residents to cataract surgery. SETTING: Hospital-based ophthalmology residency program. DESIGN: Retrospective cohort study. PARTICIPANTS: PGY-3 and PGY-4 residents of the Harvard Medical School Ophthalmology Residency from graduating years 2010 to 2012. RESULTS: In July 2009, a new method of teaching PGY-3 ophthalmology residents cataract surgery was introduced, which was termed "the stepwise introduction to cataract surgery." This curriculum aimed to train residents to perform steps of cataract surgery by deliberately practicing each of the steps of surgery under a structured curriculum with faculty feedback. Assessment methods included surveys administered to the PGY-4 residents who graduated before the implementation of these measures (n = 7), the residents who participated in the first and second years of the new curriculum (n = 16), faculty who teach PGY-4 residents cataract surgery (n = 8), and review of resident Accreditation Council for Graduate Medical Education surgical logs. Resident survey response rate was 100%. Residents who participated in the new curriculum performed more of each step of cataract surgery in the operating room, spent more time practicing each step of cataract surgery on a cataract surgery simulator during the PGY-3 year, and performed more primary cataract surgeries during the PGY-3 year than those who did not. Faculty survey response rate was 63%. Faculty noted an increase in resident preparedness following implementation of the new curriculum. There was no statistical difference between the precurriculum and postcurriculum groups in the percentage turnover of cataracts for the first 2 cataract surgery rotations of the PGY-4 year of training. CONCLUSIONS: The introduction of cataract surgery to PGY-3 residents in an organized, stepwise manner improved resident preparedness for the PGY-4 year of residency. This surgical teaching method can be easily applied to other surgical specialties. (c) 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Kloek, Carolyn E.; Borboli-Gerogiannis, Sheila; Chang, Kenneth; Lane, Anne Marie; Loewenstein, John I.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Kuperwaser, Mark] Beth Israel Deaconess Med Ctr, Dept Ophthalmol, Boston, MA 02215 USA. [Newman, Lori R.] Harvard Univ, Sch Med, Shapiro Inst Med Educ & Res, Boston, MA USA. RP Kloek, CE (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM carolyn_kloek@meei.harvard.edu NR 27 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD MAR-APR PY 2014 VL 71 IS 2 BP 169 EP 175 DI 10.1016/j.jsurg.2013.07.007 PG 7 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA AD7HR UT WOS:000333435100007 PM 24602704 ER PT J AU Mainthia, R Ley, MJT Davidson, M Tarpley, JL AF Mainthia, Rajshri Tarpley, Margaret J. Davidson, Mario Tarpley, John L. TI Achievement in Surgical Residency: Are Objective Measures of Performance Associated With Awards Received in Final Years of Training? SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE resident evaluation; resident awards; United States Medical Licensing Examination (USMLE); general surgery; education; residency application ID SUCCESS AB OBJECTIVE: For the past 15 years at our institution's general surgery residency program, 3 of the senior residents' have been chosen to be awarded either (1) Best Resident in Research, (2) Best Resident in Teaching, or (3) Best Resident Overall. Considering that these awards serve as data representing outstanding performance as surgical residents, the objective of this study was to determine the association between receiving one of these awards and objective measures of performance. METHODS: Individual files were reviewed for the 103 residents who graduated from our institution's general surgery program from 1994 to 2010. These data were studied as a whole, and then divided into an award-winning group and a non award winning group and subsequently compared across several objective parameters, including The United States Medical Licensing Examination (USMLE) scores, American Board of Surgery In-Training Examination (ABSITE) scores, first-time American Board of Surgery Certifying and Qualifying Examination pass rates, Alpha Omega Alpha membership status, and number of research years, using a logistic regression model. RESULTS: Overall, 103 residents completed their general surgery residency training at our institution from 1994 to 2010, and of these residents, 16 (16%) received the Best Resident in Research award, 15 (16%) received the Best Resident in Teaching award, and 17 (17%) received the Best Resident Overall award in their final years of training. Compared with those who did not receive an award, a hypothesis-based one-tailed test revealed that award winners had a significantly lower median USMLE Step 1 scores (p = 0.04) and marginally lower median USMLE Step 2 scores (p = 0.05). Alpha Omega Alpha membership status, median ABSITE percent correct overall, first-time American Board of Surgery examination pass rates, and number of research years during residency were not significantly different between the 2 groups. CONCLUSION: Many factors contribute to success during general surgery residency. Our study showed that higher USMLE and ABSITE scores were not associated with receiving top awards in final years of training at one institution over 15 years. (c) 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Mainthia, Rajshri; Tarpley, Margaret J.; Tarpley, John L.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN 37232 USA. [Mainthia, Rajshri] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Davidson, Mario] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA. RP Mainthia, R (reprint author), Vanderbilt Univ, Med Ctr, Dept Surg, Med Ctr North D 4314, Nashville, TN 37232 USA. EM Rmainthia@partners.org FU Department of Surgery at Vanderbilt University FX This study was solely funded by the Department of Surgery at Vanderbilt University. NR 16 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD MAR-APR PY 2014 VL 71 IS 2 BP 176 EP 181 DI 10.1016/j.jsurg.2013.07.012 PG 6 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA AD7HR UT WOS:000333435100008 PM 24602705 ER PT J AU Aniemeke, C Jawad, M Thompson, R Lee, S Sanchez-Reilly, S AF Aniemeke, C. Jawad, M. Thompson, R. Lee, S. Sanchez-Reilly, S. TI INTEGRATING AN ADVANCE CARE PLANNING CLINICAL AND EDUCATIONAL INTERVENTION (I-ACP) TO IMPROVE PATIENT-CENTERED CARE AMONG CHRONICALLY ILL OLDER ADULTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Aniemeke, C.; Sanchez-Reilly, S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Aniemeke, C.; Thompson, R.; Lee, S.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, GRECC GEC, San Antonio, TX USA. [Jawad, M.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S110 EP S110 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500301 ER PT J AU Aspinall, S Zhao, X Schmader, K Pugh, M Semla, T Cunningham, F Hanlon, J AF Aspinall, S. Zhao, X. Schmader, K. Pugh, M. Semla, T. Cunningham, F. Hanlon, J. TI Epidemiology of Drug-Disease Interactions (DDIs) in Older Veteran Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Aspinall, S.; Semla, T.; Cunningham, F.] VA Pharm Benefits Management Serv, Hines, IL USA. [Aspinall, S.; Zhao, X.; Hanlon, J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Schmader, K.] Durham VA Med Ctr, Durham, NC USA. [Pugh, M.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S44 EP S45 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500118 ER PT J AU Belland, L Rivera, L Genes, N Thum, F Hwang, U AF Belland, L. Rivera, L. Genes, N. Thum, F. Hwang, U. TI Evaluating the effectiveness of a novel clinical decision support system (CDS) to improve acute abdominal pain for older adults in the Emergency Department (ED) SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Belland, L.; Rivera, L.; Genes, N.; Thum, F.; Hwang, U.] Icahn Sch Med Mt Sinai, New York, NY USA. [Hwang, U.] James J Peters VAMC, GRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S102 EP S102 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500279 ER PT J AU Booth, K Vaughan, C Fix, K Burgio, K Goode, P Redden, D Markland, A AF Booth, K. Vaughan, C. Fix, K. Burgio, K. Goode, P. Redden, D. Markland, A. TI Bladder, Bowel, and Skin Care (BASiC) Toolkit for Home-Based Primary Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Booth, K.; Fix, K.; Burgio, K.; Goode, P.; Redden, D.; Markland, A.] Univ Alabama Birmingham, Birmingham, AL USA. [Vaughan, C.; Burgio, K.; Goode, P.; Markland, A.] Birmingham Atlanta GRECC, Birmingham, AL USA. [Vaughan, C.] Emory Univ, Decatur, GA USA. [Booth, K.; Fix, K.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S7 EP S8 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500019 ER PT J AU Bouldin, EL Littman, AJ Rice, K Reiber, GE AF Bouldin, E. L. Littman, A. J. Rice, K. Reiber, G. E. TI Chronic wound care and outcomes among older veterans using VA and Medicare SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Bouldin, E. L.; Littman, A. J.; Reiber, G. E.] VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. [Bouldin, E. L.; Littman, A. J.; Rice, K.; Reiber, G. E.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S270 EP S270 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500743 ER PT J AU Broe, KE Hannan, MT Samelson, EJ McLean, RR Meng, CA Hogan, ME Carroll, DM Zhang, X Cupples, LA Bouxsein, ML Kiel, DP AF Broe, K. E. Hannan, M. T. Samelson, E. J. McLean, R. R. Meng, C. A. Hogan, M. E. Carroll, D. M. Zhang, X. Cupples, L. A. Bouxsein, M. L. Kiel, D. P. TI Physical Activity in Midlife Is Associated with Peripheral Bone Density and Microarchitecture in Later Life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Broe, K. E.; Hannan, M. T.; Samelson, E. J.; McLean, R. R.; Meng, C. A.; Hogan, M. E.; Carroll, D. M.; Zhang, X.; Kiel, D. P.] Heb SeniorLife, Boston, MA USA. [Hannan, M. T.; Samelson, E. J.; McLean, R. R.; Bouxsein, M. L.; Kiel, D. P.] Harv Med Sch, Boston, MA USA. [Cupples, L. A.] BU SPH, Boston, MA USA. [Bouxsein, M. L.] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S13 EP S13 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500032 ER PT J AU Chiu, C Feuz, MA McMahan, RD Miao, Y Sudore, RL AF Chiu, C. Feuz, M. A. McMahan, R. D. Miao, Y. Sudore, R. L. TI "I Don't Want to Make My Own Decisions": Decision Control Preferences in a Diverse Elderly Population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Chiu, C.; Feuz, M. A.; McMahan, R. D.; Miao, Y.; Sudore, R. L.] UCSF, Div Geriatr, San Francisco, CA USA. [Feuz, M. A.; McMahan, R. D.; Miao, Y.; Sudore, R. L.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S107 EP S107 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500292 ER PT J AU Echeverri, JH Ramadan, F AF Echeverri, J. Hincapie Ramadan, F. TI Why is my finger blue ? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Echeverri, J. Hincapie; Ramadan, F.] Massachusetts Gen Hosp, Malden, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR PY 2014 VL 62 SU 1 SI SI BP S29 EP S29 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500074 ER PT J AU Eng, JA Allison, TA Kao, H Williams, BA Barnes, DE Ritchie, CS AF Eng, J. A. Allison, T. A. Kao, H. Williams, B. A. Barnes, D. E. Ritchie, C. S. TI Roll-out of GRACE in Two Urban Health Systems: an Early Implementation Science Analysis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Eng, J. A.; Allison, T. A.; Kao, H.; Williams, B. A.; Ritchie, C. S.] UCSF, Div Geriatr, San Francisco, CA USA. [Eng, J. A.; Allison, T. A.; Williams, B. A.; Ritchie, C. S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Barnes, D. E.] UCSF, Dept Psychiat, San Francisco, CA USA. [Barnes, D. E.] UCSF, Dept Epidemiol & Biostat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S139 EP S140 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500380 ER PT J AU Franco, E Reyes, B AF Franco, E. Reyes, B. TI GIFTS - Geriatric Inpatient Fracture Trauma Service SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Franco, E.; Reyes, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Franco, E.; Reyes, B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S225 EP S225 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500616 ER PT J AU Fung, CH Igodan, U Alessi, C Martin, JL Dzierzewski, JM Josephson, K Kramer, J AF Fung, C. H. Igodan, U. Alessi, C. Martin, J. L. Dzierzewski, J. M. Josephson, K. Kramer, J. TI A qualitative study of human factors barriers to positive airway pressure therapy in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Fung, C. H.; Igodan, U.; Alessi, C.; Martin, J. L.; Dzierzewski, J. M.; Josephson, K.; Kramer, J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, C. H.; Alessi, C.; Martin, J. L.; Dzierzewski, J. M.; Kramer, J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Anglees, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S158 EP S158 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500431 ER PT J AU Fung, CH Martin, J Jouldjian, S Dzierzewski, J Rodriguez, J Mitchell, M Josephson, K Alessi, C AF Fung, C. H. Martin, J. Jouldjian, S. Dzierzewski, J. Rodriguez, J. Mitchell, M. Josephson, K. Alessi, C. TI Medical, mental health, and demographic factors associated with a strong belief in using sleeping pills to improve sleep and daytime function SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Fung, C. H.; Martin, J.; Jouldjian, S.; Dzierzewski, J.; Alessi, C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, C. H.; Martin, J.; Dzierzewski, J.; Rodriguez, J.; Mitchell, M.; Josephson, K.; Alessi, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 1 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 MAR PY 2014 VL 62 SU 1 SI SI BP S116 EP S117 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500318 ER PT J AU Garcia, LE Pastewait, S Rebecca, R Chen-pin, W MacCarthy, D Moris, M Gonzalez, E Conde, A Espinoza, SE AF Garcia, L. E. Pastewait, S. Rebecca, R. Chen-pin, W. MacCarthy, D. Moris, M. Gonzalez, E. Conde, A. Espinoza, S. E. TI A Pharmacy-based Transitional Care Program to Reduce Hospital Readmissions in High Risk Older Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Garcia, L. E.; Pastewait, S.; Rebecca, R.; Chen-pin, W.; MacCarthy, D.; Moris, M.; Gonzalez, E.; Conde, A.; Espinoza, S. E.] UTHSCSA, San Antonio, TX USA. [Garcia, L. E.; Pastewait, S.; Rebecca, R.; Chen-pin, W.; MacCarthy, D.; Moris, M.; Gonzalez, E.; Conde, A.; Espinoza, S. E.] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S230 EP S231 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500631 ER PT J AU Greene, M Covinsky, K Deeks, S Miao, Y Madamba, J Mattes, M Lampiris, H Martin, J Valcour, V AF Greene, M. Covinsky, K. Deeks, S. Miao, Y. Madamba, J. Mattes, M. Lampiris, H. Martin, J. Valcour, V. TI Geriatric Syndromes in Older HIV-Infected Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Greene, M.; Covinsky, K.; Deeks, S.; Miao, Y.; Madamba, J.; Lampiris, H.; Martin, J.; Valcour, V.] UCSF, San Francisco, CA USA. [Greene, M.; Covinsky, K.; Miao, Y.; Mattes, M.; Lampiris, H.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S11 EP S11 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500027 ER PT J AU Harris, BM Restrepo, M Bryson, CD Ross, JS Espinoza, SE Sanchez-Reilly, S Villarreal, D AF Harris, B. M. Restrepo, M. Bryson, C. D. Ross, J. S. Espinoza, S. E. Sanchez-Reilly, S. Villarreal, D. TI Changing the Practice of Intensive Care to Improve the Lives of Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Harris, B. M.; Restrepo, M.; Ross, J. S.; Espinoza, S. E.; Sanchez-Reilly, S.; Villarreal, D.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Harris, B. M.; Restrepo, M.; Bryson, C. D.; Ross, J. S.; Espinoza, S. E.; Sanchez-Reilly, S.; Villarreal, D.] South Texas Vet Hlth Care Syst, GRECC GEC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S135 EP S136 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500369 ER PT J AU Harris, BM Washington, F Ross, J Oakes, SL AF Harris, B. M. Washington, F. Ross, J. Oakes, S. L. TI Stopping the Revolving Door: Decreasing Admissions from a Community Nursing Home to Hospital using INTERACT 2 and Palliative Care Interventions SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Harris, B. M.; Ross, J.; Oakes, S. L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Harris, B. M.; Ross, J.; Oakes, S. L.] South Texas Vet Hlth Care Syst, GRECC GECC, San Antonio, TX USA. [Washington, F.] Buena Vida Nursing Home & Rehab, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S136 EP S136 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500370 ER PT J AU Healy, JM Chappell, P Lee, S Villarreal, D Ross, J Sanchez-Reilly, S AF Healy, J. M. Chappell, P. Lee, S. Villarreal, D. Ross, J. Sanchez-Reilly, S. TI The Double Parallel Curriculum in Palliative Care (DP-PC): Using a Double Parallel Education Strategy with Multimedia to Enhance Learners' Knowledge and Skills in End of Life Palliative Care (EOL-PC) SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Healy, J. M.; Chappell, P.; Ross, J.; Sanchez-Reilly, S.] UTHSCSA, Geriatr HPM, San Antonio, TX USA. [Healy, J. M.; Lee, S.; Villarreal, D.; Ross, J.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S113 EP S113 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500308 ER PT J AU Higbea, AM Thorpe, C Coley, K McGivney, M Klatt, P Schleiden, L Zaharoff, J Corbo, J Haver, A Cox-Vance, L Balestrino, V Sakely, H AF Higbea, A. M. Thorpe, C. Coley, K. McGivney, M. Klatt, P. Schleiden, L. Zaharoff, J. Corbo, J. Haver, A. Cox-Vance, L. Balestrino, V. Sakely, H. TI Patient perceptions of Pharmacist-led InterVentions on Transitions of Seniors (PIVOTS): A Patient Survey SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Higbea, A. M.; Klatt, P.; Corbo, J.; Haver, A.; Cox-Vance, L.; Balestrino, V.; Sakely, H.] UPMC St Margaret, Pittsburgh, PA USA. [Thorpe, C.; Coley, K.; McGivney, M.; Schleiden, L.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Thorpe, C.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Zaharoff, J.] Presbyterian Senior Care, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S276 EP S276 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500760 ER PT J AU Hsu, A Nakagawa, S Walter, L Van den Eeden, S Brown, J Thom, D Lee, S Huang, A AF Hsu, A. Nakagawa, S. Walter, L. Van den Eeden, S. Brown, J. Thom, D. Lee, S. Huang, A. TI Nocturia in women: a consequence of other urinary disorders or a clinical entity in its own right? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Hsu, A.; Walter, L.; Lee, S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Nakagawa, S.; Brown, J.; Thom, D.; Huang, A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Van den Eeden, S.] Kaiser Permanente Div Res, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S104 EP S105 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500286 ER PT J AU Jackson, CD Viswanathan, AN Driver, JA AF Jackson, C. D. Viswanathan, A. N. Driver, J. A. TI Frailty Measure Predicts Outcomes after Curative Treatment for Endometrial Cancer in Women >= Age 60 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Jackson, C. D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Jackson, C. D.; Viswanathan, A. N.; Driver, J. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Viswanathan, A. N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Driver, J. A.] Boston VA Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S10 EP S10 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500025 ER PT J AU Jennings, LA Reuben, D Kim, S Keeler, E Roth, C Zingmond, D Wenger, N Ganz, D AF Jennings, L. A. Reuben, D. Kim, S. Keeler, E. Roth, C. Zingmond, D. Wenger, N. Ganz, D. TI Number of positive responses to a 3-item screen predicts injurious falls among high risk community-dwelling older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Jennings, L. A.; Reuben, D.; Ganz, D.] Univ Calif Los Angeles, Div Geriatr, Los Angeles, CA USA. [Zingmond, D.; Wenger, N.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. [Kim, S.; Keeler, E.; Roth, C.] RAND Hlth, Santa Monica, CA USA. [Ganz, D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S119 EP S119 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500324 ER PT J AU Kim, M Shu, Z Shi, Y Kamat, A AF Kim, M. Shu, Z. Shi, Y. Kamat, A. TI Role of Lipin-1 in Beta-Adrenergic Receptor (beta-AR)-Mediated Hepatic Steatosis during Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Kim, M.; Shu, Z.; Shi, Y.; Kamat, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shu, Z.; Shi, Y.; Kamat, A.] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S255 EP S255 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500701 ER PT J AU Kinosian, B Edes, T Becker, P Hossain, M AF Kinosian, B. Edes, T. Becker, P. Hossain, M. TI Expanding VA's Home Based Primary Care (HBPC) while Improving Performance: 2006-2012 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Kinosian, B.] Univ Penn, Philadelphia, PA 19104 USA. [Edes, T.; Becker, P.; Hossain, M.] Dept Vet Affairs, Washington, DC USA. [Kinosian, B.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAR PY 2014 VL 62 SU 1 SI SI BP S136 EP S136 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500371 ER PT J AU Kinosian, B Phibbs, C Dally, S Intrator, O Shay, K AF Kinosian, B. Phibbs, C. Dally, S. Intrator, O. Shay, K. TI Using Cost-Projection Models to evaluate the Department of Veteran Affairs (VA's) T-21 Geriatric Pilots SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Kinosian, B.] Univ Penn, Philadelphia, PA 19104 USA. [Intrator, O.] Univ Rochester, Rochester, NY USA. [Phibbs, C.] Stanford Univ, Palo Alto, CA 94304 USA. [Kinosian, B.; Phibbs, C.; Dally, S.; Intrator, O.; Shay, K.] US Dept Vet Affairs, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S18 EP S18 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500045 ER PT J AU Kostas, TR Zimmerman, K Salow, M Simone, M Whitmire, N Rudolph, JL McMahon, GT AF Kostas, T. R. Zimmerman, K. Salow, M. Simone, M. Whitmire, N. Rudolph, J. L. McMahon, G. T. TI Improving medication management competency among geriatric trainees SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Kostas, T. R.; McMahon, G. T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kostas, T. R.; Simone, M.; Rudolph, J. L.; McMahon, G. T.] Harvard Univ, Sch Med, Boston, MA USA. [Zimmerman, K.] Massachusetts Coll Pharm & Allied Hlth Sci, Boston, MA USA. [Zimmerman, K.] Hlth Sci Univ, Boston, MA USA. [Salow, M.; Rudolph, J. L.] VA Boston Healthcare Syst, Boston, MA USA. [Simone, M.] Mt Auburn Hosp, Cambridge, MA USA. [Whitmire, N.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. RI McMahon, Graham/D-3740-2009 OI McMahon, Graham/0000-0003-4288-6535 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S51 EP S52 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500138 ER PT J AU Krain, A Olutunmbi, F St Germain, R Gainsley, B Lyons, E Capone-Swearer, D Linkin, D Schwab, E AF Krain, A. Olutunmbi, F. St Germain, R. Gainsley, B. Lyons, E. Capone-Swearer, D. Linkin, D. Schwab, E. TI "Standing Order" Influenza Vaccination Protocol at a Long Term Care Facility SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Krain, A.; Linkin, D.; Schwab, E.] Univ Penn, Philadelphia, PA 19104 USA. [Olutunmbi, F.; St Germain, R.; Gainsley, B.; Lyons, E.; Capone-Swearer, D.; Linkin, D.; Schwab, E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S152 EP S152 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500413 ER PT J AU Lai, E Wong, M Iwata, I Zhang, Y Yang, YK Hsieh, C AF Lai, E. Wong, M. Iwata, I. Zhang, Y. Yang, Y. Kao Hsieh, C. TI Comparative Risk of Pneumonia among Different Cholinesterase Inhibitors SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Lai, E.; Zhang, Y.] Duke Clin Res Inst, Durham, NC USA. [Lai, E.; Yang, Y. Kao; Hsieh, C.] Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Tainan 70101, Taiwan. [Wong, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iwata, I.] Univ N Carolina, Chapel Hill, NC USA. [Yang, Y. Kao] Natl Cheng Kung Univ, Hlth Outcome Res Ctr, Tainan 70101, Taiwan. [Hsieh, C.] Tainan Sin Lau Hosp, Tainan, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S248 EP S249 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500684 ER PT J AU Maggiore, R Dale, W Buss, M Hurria, A Chapman, A Dotan, E Klepin, H Naeim, A Mohile, S AF Maggiore, R. Dale, W. Buss, M. Hurria, A. Chapman, A. Dotan, E. Klepin, H. Naeim, A. Mohile, S. TI Geriatric Oncology Attitudes and Skills among Hematology/Oncology Fellows SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Maggiore, R.] Portland VAMC OHSU, Portland, OR USA. [Dale, W.] Univ Chicago, Chicago, IL 60637 USA. [Buss, M.] Harvard Univ, BIDMC, Boston, MA 02115 USA. [Hurria, A.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Chapman, A.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Dotan, E.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Klepin, H.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Naeim, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Mohile, S.] Univ Rochester, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S48 EP S48 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500129 ER PT J AU Marcum, ZA Driessen, J Thorpe, C Donohue, J Gellad, W AF Marcum, Z. A. Driessen, J. Thorpe, C. Donohue, J. Gellad, W. TI Geographic variation in uptake of a novel drug class: the case of incretin mimetics SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Marcum, Z. A.; Driessen, J.; Thorpe, C.; Donohue, J.; Gellad, W.] UPITT, Pittsburgh, PA USA. [Thorpe, C.; Gellad, W.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S132 EP S132 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500360 ER PT J AU Mayans, K Boockvar, K Garrido, MM AF Mayans, K. Boockvar, K. Garrido, M. M. TI Site Differences in Mental Health Care Receipt among Veterans Receiving Palliative Care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Mayans, K.; Boockvar, K.; Garrido, M. M.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY USA. [Boockvar, K.; Garrido, M. M.] James J Peters Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S272 EP S273 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500750 ER PT J AU Mishaw, S Healy, J Sanchez, C Lee, S Sanchez-Reilly, S AF Mishaw, S. Healy, J. Sanchez, C. Lee, S. Sanchez-Reilly, S. TI Cost Analysis of Palliative Care Consults in the Geriatric vs. Non-Geriatric Population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Mishaw, S.; Healy, J.; Sanchez-Reilly, S.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Sanchez, C.] Univ Hlth Syst, San Antonio, TX USA. [Lee, S.; Sanchez-Reilly, S.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S275 EP S275 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500756 ER PT J AU Mori, T Crandall, CJ Ganz, DA AF Mori, T. Crandall, C. J. Ganz, D. A. TI COST-EFFECTIVENESS OF COMBINED FALL PREVENTION EXERCISE AND ORAL BISPHOSPHONATE THERAPY FOR FRACTURE PREVENTION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Mori, T.; Ganz, D. A.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. [Mori, T.; Crandall, C. J.; Ganz, D. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S131 EP S132 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500358 ER PT J AU Nathaniel, J Garrido, MM Chai, E Goldstein, NE AF Nathaniel, J. Garrido, M. M. Chai, E. Goldstein, N. E. TI Cost Analysis of the Palliative Care Unit at Mount Sinai Hospital SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Nathaniel, J.; Garrido, M. M.; Chai, E.; Goldstein, N. E.] Icahn Sch Med, Dept Geriatr & Palliat Med, Mt Sinai, NY USA. [Garrido, M. M.; Goldstein, N. E.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S139 EP S139 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500379 ER PT J AU Patel, C Reilly, SS Karnad, A Lee, S AF Patel, C. Reilly, S. Sanchez Karnad, A. Lee, S. TI To Treat or Not to Treat: An Overview on Cancer Survivorship among Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Patel, C.; Reilly, S. Sanchez; Karnad, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patel, C.; Reilly, S. Sanchez; Karnad, A.; Lee, S.] South Texas Vet Hlth Care Syst, GEC GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S86 EP S86 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500235 ER PT J AU Platts-Mills, TF Pereira, GF Isenberg, EE Weaver, MA Rathlev, NK Hendry, PL Peak, DA Jones, JS Swor, RA Lee, DC Domeier, RM McLean, SA AF Platts-Mills, T. F. Pereira, G. F. Isenberg, E. E. Weaver, M. A. Rathlev, N. K. Hendry, P. L. Peak, D. A. Jones, J. S. Swor, R. A. Lee, D. C. Domeier, R. M. McLean, S. A. TI Older Adults with Persistent Musculosketal Pain after Motor Vehicle Collision are at Increased Risk of Functional Decline SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Platts-Mills, T. F.; McLean, S. A.] Univ N Carolina, Chapel Hill, NC USA. [Pereira, G. F.; Isenberg, E. E.; Weaver, M. A.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Rathlev, N. K.] Baystate Med Ctr, Springfield, MA USA. [Hendry, P. L.] Univ Florida, Jacksonville, FL USA. [Peak, D. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, J. S.] Spectrum Hlth, Grand Rapids, MI USA. [Swor, R. A.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Lee, D. C.] N Shore Univ Hosp, Manhasset, NY USA. [Domeier, R. M.] Joseph Mercy Hosp, Ypsilanti, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S103 EP S104 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500283 ER PT J AU Redding, SE Liu, S Hung, W Boockvar, K AF Redding, S. E. Liu, S. Hung, W. Boockvar, K. TI Opioid Interruptions, Pain, and Withdrawal Symptoms during Acute Illness in Nursing Home Residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Redding, S. E.; Liu, S.; Hung, W.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Boockvar, K.] Jewish Home Lifecare, Geriatr, New York, NY USA. [Hung, W.; Boockvar, K.] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S59 EP S59 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500160 ER PT J AU Rodriguez, JC Dzierzewski, J Jouldjian, S Fung, C Martin, J Josephson, K Mitchell, M Alessi, C AF Rodriguez, J. C. Dzierzewski, J. Jouldjian, S. Fung, C. Martin, J. Josephson, K. Mitchell, M. Alessi, C. TI The impact of pain on the efficacy of Cognitive Behavioral Therapy for Insomnia in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Rodriguez, J. C.; Fung, C.; Martin, J.; Alessi, C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Dzierzewski, J.; Jouldjian, S.; Fung, C.; Martin, J.; Josephson, K.; Mitchell, M.; Alessi, C.] VA Greater Angeles Healthcare Syst, Educ & Clin Ctr, Geriatr Res, Los Angeles, CA USA. [Rodriguez, J. C.] Pontificia Univ Catolica Chile, Santiago, Chile. NR 0 TC 0 Z9 0 U1 1 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 MAR PY 2014 VL 62 SU 1 SI SI BP S146 EP S146 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500398 ER PT J AU Romine, P Kiely, DK Holt, N Kurlinski, L Goldstein, R Percac-Lima, S Leveille, S Bean, J AF Romine, P. Kiely, D. K. Holt, N. Kurlinski, L. Goldstein, R. Percac-Lima, S. Leveille, S. Bean, J. TI Task Specific Fatigue Among Geriatric Primary Care Patients SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Romine, P.; Bean, J.] Harvard Univ, Sch Med, Boston, MA USA. [Kiely, D. K.; Holt, N.; Kurlinski, L.; Goldstein, R.; Bean, J.] Spaulding Rehabil Hosp, Cambridge, MA USA. [Percac-Lima, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Leveille, S.] Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S292 EP S292 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500805 ER PT J AU Salinas, R AF Salinas, R. TI Late Latent Syphilis: A Red-Herring in a Patient with Spastic Gait, Cognitive Decline, and Upper Motor Findings SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Salinas, R.] VA Puget Sound Hlth Care Syst, Madigan Army Med Ctr, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S175 EP S175 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500477 ER PT J AU Sheffrin, M Miao, Y Steinman, MA AF Sheffrin, M. Miao, Y. Steinman, M. A. TI Weight Loss Associated with Cholinesterase Inhibitors in a National Healthcare System SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 UCSF, Div Geriatr Med, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S12 EP S13 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500031 ER PT J AU Simone, MJ Kostas, T Bernacki, R Schaefer, K Smith, G Fabiny, A McMahon, G AF Simone, M. J. Kostas, T. Bernacki, R. Schaefer, K. Smith, G. Fabiny, A. McMahon, G. TI A Clinical Skills Workshop for Internal Medicine Residents During A Geriatrics Rotation Improves Confidence And Long-Term Use Of Geriatric Skills SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Simone, M. J.] Mt Auburn Hosp, Cambridge, MA USA. [Simone, M. J.; Kostas, T.; Bernacki, R.; Schaefer, K.; Smith, G.; Fabiny, A.; McMahon, G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kostas, T.; McMahon, G.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bernacki, R.; Schaefer, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fabiny, A.] Cambridge Hlth Alliance, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 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 MAR PY 2014 VL 62 SU 1 SI SI BP S209 EP S210 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500574 ER PT J AU Tang, V Stijacic, I Lee, S AF Tang, V. Stijacic, I. Lee, S. TI Lagtime to Benefit after Flexible Sigmoidoscopy Screening for Colorectal Cancer in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Tang, V.; Stijacic, I.; Lee, S.] San Francisco VA Med Ctr, Dept Geriatr, San Francisco, CA USA. [Tang, V.; Stijacic, I.; Lee, S.] UCSF, Dept Geriatr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S132 EP S132 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500359 ER PT J AU Thorpe, CT Obrosky, DS Zhao, X Gellad, W Hanlon, J AF Thorpe, C. T. Obrosky, D. S. Zhao, X. Gellad, W. Hanlon, J. TI Tight Glycemic Control, Use of High-Risk Hypoglycemic Medications, and Associated Factors in Older VA Nursing Home Residents with Diabetes and Comorbid Dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 15-17, 2014 CL Orlando, FL SP Amer Geriatr Soc C1 [Thorpe, C. T.; Obrosky, D. S.; Zhao, X.; Gellad, W.; Hanlon, J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, C. T.; Gellad, W.; Hanlon, J.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2014 VL 62 SU 1 SI SI BP S127 EP S127 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AD6XT UT WOS:000333405500347 ER PT J AU Jalian, HR Tam, J Garibyan, L Anderson, RR AF Jalian, H. Ray Tam, Joshua Garibyan, Lilit Anderson, R. Rox TI SELECTIVE CRYOLYSIS OF SEBACEOUS GLANDS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 [Jalian, H. Ray; Tam, Joshua; Garibyan, Lilit; Anderson, R. Rox] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 5 BP 2 EP 2 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800006 ER PT J AU Owczarek, W Wydrzyska, A Lebkowska, K Nawrocka, A Paluchowska, E Podolec, K Pirowska, M Wojas-Pelc, A Paithankar, D Anderson, RR AF Owczarek, Witold Wydrzyska, A. Lebkowska, K. Nawrocka, A. Paluchowska, E. Podolec, K. Pirowska, M. Wojas-Pelc, Anna Paithankar, Dilip Anderson, R. Rox TI TREATMENT OF ACNE WITH SELECTIVE PHOTOTHERMOLYSIS OF THE SEBACEOUS FOLLICLE WITH GOLD-COATED MICROPARTICLES, A CLINICAL STUDY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 Mil Inst Med, Warsaw, Poland. Dermatol Klin, Krakow, Poland. Sebacia Inc, Wayland, MA USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 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 MAR PY 2014 VL 46 SU 25 MA 7 BP 3 EP 3 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800008 ER PT J AU Ortiz, A Franco, W Taghados, S Gutierrez-Herrera, E Purschke, M Tam, J Farinelli, W Doukas, A Jiang, B Anderson, RR AF Ortiz, Arisa Franco, Walfre Taghados, Seyed Gutierrez-Herrera, Enoch Purschke, Martin Tam, Joshua Farinelli, William Doukas, Apostolos Jiang, Brian Anderson, R. Rox TI A NOVEL CAMERA DEVICE THAT CAPTURES TRYPTOPHAN AUTOFLUORESCENCE IN RAPID EPIDERMAL PROLIFERATIONS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 Univ Calif San Diego, San Diego, CA 92103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 62 BP 21 EP 21 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800059 ER PT J AU Taudorf, EH Lerche, CM Vissing, AC Hannibal, J D'Alvise, JT Hansen, SH Janfelt, C Paasch, U Anderson, RR Haedersdal, M AF Taudorf, Elisabeth Hjardem Lerche, Catharina Margrethe Vissing, Anne-Cathrine Hannibal, Jens D'Alvise, Janina Thunig Hansen, Steen Honore Janfelt, Christian Paasch, Uwe Anderson, Richard Rox Haedersdal, Merete TI TOPICALLY APPLIED METHOTREXATE IS RAPIDLY ABSORBED INTO SKIN PROCESSED WITH ABLATIVE FRACTIONAL LASER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 Univ Copenhagen, Bispebjerg Hosp, Copenhagen, Denmark. Univ Copenhagen, Copenhagen, Denmark. Univ Leipzig, D-04109 Leipzig, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RI D'Alvise, Janina/E-5468-2015 OI D'Alvise, Janina/0000-0002-1543-7040 NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 74 BP 24 EP 24 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800068 ER PT J AU Tremaine, AM Avram, M AF Tremaine, Anne Marie Avram, Mathew TI MAUDE DATA ON COMPLICATIONS WITH LASER AND LIGHT-BASED DEVICES SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 [Tremaine, Anne Marie; Avram, Mathew] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 76 BP 25 EP 25 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800070 ER PT J AU Evers, M Ha, L Welford, D Birngruber, R Manstein, D AF Evers, Michael Linh Ha Welford, David Birngruber, Reginald Manstein, Dieter TI WAVELENGTH-DEPENDENCE OF FRACTIONAL ABLATIONS IN BIOLOGICAL MATERIALS USING A TUNABLE CR2+:ZNSE/S INFRARED LASER SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. Med Univ Lubeck, Inst Biomed Opt, D-23538 Lubeck, Germany. Endeavour Laser Technol Inc, Hathorne, MA USA. RI Birngruber, Reginald/Q-2342-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 119 BP 38 EP 39 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800109 ER PT J AU Gutierrez-Herrera, E Wang, Y Ortiz, A Taghados, JS Doukas, AG Anderson, RR Franco, W AF Gutierrez-Herrera, Enoch Wang, Ying Ortiz, Arisa Taghados, Javid S. Doukas, Apostolos G. Anderson, R. Rox Franco, Walfre TI STUDY OF ENDOGENOUS SKIN UV-FLUORESCENCE EMISSION IN WOUND HEALING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 [Gutierrez-Herrera, Enoch; Wang, Ying; Ortiz, Arisa; Taghados, Javid S.; Doukas, Apostolos G.; Anderson, R. Rox; Franco, Walfre] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 117 BP 38 EP 38 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800108 ER PT J AU Kawakubo, M Kositratna, G Chan, H Manstein, D AF Kawakubo, Masayoshi Kositratna, Garuna Chan, Henry Manstein, Dieter TI WOUND HEALING OF MICE LIVER TISSUE AFTER ABLATIVE FRACTIONAL CO2 LASER EXPOSURE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 [Kawakubo, Masayoshi; Kositratna, Garuna; Chan, Henry; Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 123 BP 40 EP 40 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800113 ER PT J AU Ferrick, B Izikson, L Ibrahimi, O Jalian, HR Kroshinsky, D Anderson, RR Sakamoto, F AF Ferrick, Bradford Izikson, Leonid Ibrahimi, Omar Jalian, H. Ray Kroshinsky, Daniela Anderson, R. Rox Sakamoto, Fernanda TI QUANTITATIVE VOLUMETRIC CHANGES AFTER CONVENTIONAL ALA-PDT COMPARED TO A NEW INHIBITORY PDT METHOD (I-PDT) TO REDUCE INFLAMMATION IN A PRELIMINARY STUDY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 [Ferrick, Bradford; Izikson, Leonid; Ibrahimi, Omar; Jalian, H. Ray; Kroshinsky, Daniela; Anderson, R. Rox; Sakamoto, Fernanda] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR PY 2014 VL 46 SU 25 MA 137 BP 43 EP 44 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800124 ER PT J AU Hamblin, M AF Hamblin, Michael TI CAN TRANSCRANIAL LOW-LEVEL LASER LIGHT THERAPY INDUCE THE BRAIN TO REPAIR ITSELF? SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 [Hamblin, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 164 BP 52 EP 52 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800151 ER PT J AU Yildirim, M Ferhanoglu, O Kobler, J Zeitels, S Ben-Yakar, A AF Yildirim, Murat Ferhanoglu, Onur Kobler, James Zeitels, Steven Ben-Yakar, Adela TI BIOGEL INJECTION IN SCAR TISSUE ENABLED BY ULTRAFAST LASER ABLATION: MODEL FOR TREATMENT OF VOCAL FOLD SCAR SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 34th Annual Conference of the American-Society-for-Laser-Medicine-and-Surgery (ASLMS) CY APR 02-06, 2014 CL Phoenix, AZ SP Amer Soc Laser Med & Surg C1 Univ Texas Austin, Austin, TX 78712 USA. Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2014 VL 46 SU 25 MA 179 BP 56 EP 57 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2HQ UT WOS:000333055800163 ER PT J AU Ocio, EM Richardson, PG Rajkumar, SV Palumbo, A Mateos, MV Orlowski, R Kumar, S Usmani, S Roodman, D Niesvizky, R Einsele, H Anderson, KC Dimopoulos, MA Avet-Loiseau, H Mellqvist, UH Turesson, I Merlini, G Schots, R McCarthy, P Bergsagel, L Chim, CS Lahuerta, JJ Shah, J Reiman, A Mikhael, J Zweegman, S Lonial, S Comenzo, R Chng, WJ Moreau, P Sonneveld, P Ludwig, H Durie, BGM Miguel, JFS AF Ocio, E. M. Richardson, P. G. Rajkumar, S. V. Palumbo, A. Mateos, M. V. Orlowski, R. Kumar, S. Usmani, S. Roodman, D. Niesvizky, R. Einsele, H. Anderson, K. C. Dimopoulos, M. A. Avet-Loiseau, H. Mellqvist, U-H Turesson, I. Merlini, G. Schots, R. McCarthy, P. Bergsagel, L. Chim, C. S. Lahuerta, J. J. Shah, J. Reiman, A. Mikhael, J. Zweegman, S. Lonial, S. Comenzo, R. Chng, W. J. Moreau, P. Sonneveld, P. Ludwig, H. Durie, B. G. M. Miguel, J. F. S. CA Int Myeloma Working Grp TI New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG) SO LEUKEMIA LA English DT Review DE multiple myeloma; new drugs; targeted agents; phase I clinical trials ID SINGLE-AGENT CARFILZOMIB; PHASE-I TRIAL; LENALIDOMIDE PLUS DEXAMETHASONE; HISTONE DEACETYLASE INHIBITOR; LOW-DOSE DEXAMETHASONE; NATURAL-KILLER-CELL; 1/2 OPEN-LABEL; MONOCLONAL-ANTIBODY; ANTIMYELOMA ACTIVITY; REFRACTORY MYELOMA AB Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting. C1 [Ocio, E. M.; Mateos, M. V.; Miguel, J. F. S.] Univ Hosp, Dept Hematol, Salamanca 37007, Spain. [Ocio, E. M.; Mateos, M. V.; Miguel, J. F. S.] Univ Salamanca IBSAL, Canc Res Ctr, IBMCC USAL CSIC, Salamanca 37007, Spain. [Richardson, P. G.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Rajkumar, S. V.; Kumar, S.] Mayo Clin, Dept Hematol, Rochester, MN USA. [Palumbo, A.] Univ Turin, Dept Hematol, Turin, Italy. [Orlowski, R.; Shah, J.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Usmani, S.] MIRT UAMS, Little Rock, AR USA. [Roodman, D.] Indiana Univ, Indianapolis, IN 46204 USA. [Niesvizky, R.] Weill Cornell Med Coll, Dept Hematol, New York, NY USA. [Einsele, H.] Univ Wurzburg, Dept Internal Med, D-97070 Wurzburg, Germany. [Dimopoulos, M. A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Avet-Loiseau, H.] Univ Toulouse, Dept Hematol, Toulouse, France. [Mellqvist, U-H] Sahlgrens Univ Hosp, Sect Hematol, Dept Med, Gothenburg, Sweden. [Turesson, I.] Skane Univ Hosp, Dept Med, Sect Hematol, Malmo, Sweden. [Merlini, G.] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy. [Schots, R.] Univ Ziekenhuis, Dept Clin Hematol, Brussels, Belgium. [Schots, R.] Univ Ziekenhuis, Stem Cell Lab, Brussels, Belgium. [McCarthy, P.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Bergsagel, L.; Mikhael, J.] Mayo Clin, Div Hematol & Oncol, Scottsdale, AZ USA. [Chim, C. S.] Queen Mary Hosp, Dept Hematol, Hong Kong, Hong Kong, Peoples R China. [Lahuerta, J. J.] Hosp Univ 12 Octubre, Dept Hematol, Madrid, Spain. [Reiman, A.] Univ New Brunswick, St John Reg Hosp, Dept Oncol, St John, NB E2L 4L5, Canada. [Zweegman, S.] Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands. [Lonial, S.] Shanghai Chang Zheng Hosp, Dept Hematol & Med Oncol, Atlanta, GA USA. [Comenzo, R.] Tufts Med Sch, Dept Hematol, Boston, MA USA. [Chng, W. J.] Natl Univ Canc Inst, Dept Hematol Oncol, Singapore, Singapore. [Moreau, P.] Univ Hosp, Dept Hematol, Nantes, France. [Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [Ludwig, H.] Wilhelminenspital Stadt Wien, Ctr Oncol Hematol & Palliat Care, Dept Med, Vienna, Austria. [Durie, B. G. M.] Oschin Canc Ctr, Los Angeles, CA USA. [Miguel, J. F. S.] Univ Navarra, Dept Clin & Translat Med, E-31080 Pamplona, Spain. RP Ocio, EM (reprint author), Univ Hosp, Dept Hematol, Paseo San Vicente 58-182, Salamanca 37007, Spain. EM emocio@usal.es RI Merlini, Giampaolo/A-3817-2008; richard, chrystelle/K-8595-2015; Kumar, Shaji/A-9853-2008 OI Merlini, Giampaolo/0000-0001-7680-3254; SAN MIGUEL, JESUS/0000-0002-9183-4857; Rajkumar, S. Vincent/0000-0002-5862-1833; Kumar, Shaji/0000-0001-5392-9284 FU Celgene; Onyx; Pharmamar; Array Pharmaceuticals; Millenium; Johnson Johnson; Millennium; Novartis; Celphalon; Sanofi; Eli Lilly; Janssen; Janssen-Cilag; Bristol Myers Squibb; Astra Zeneca; Prothena Biotech; Roche; Mundi Pharma FX EMO-consultancy: Onyx, Bristol Myers Squibb, Array Pharmaceuticals; research funding: Celgene, Onyx, Pharmamar, Array Pharmaceuticals. PGR-consultancy: Celgene, Millennium Takeda, Johnson & Johnson, Novartis, Bristol Myer Squibb; research funding: Celgene and Millenium. SVR-no conflicts to disclose. AP-consultancy and honoraria: Amgen, Bristol Myers Squibb, Celgene, Janssen-Cilag, Millennium, ONYX. MVM-consultancy: Janssen-Cilag, Celgene, Millennium. RO-consultancy: Abbott Laboratories, Centocor Ortho Biotech, Cephalon, Millennium, Novartis, Onyx; research funding: Celgene, Johnson & Johnson, Millennium, Onyx. SK-consultancy: Millennium, Celgene, Onyx; research funding: Celgene, Millennium, Novartis, Celphalon, Sanofi, Onyx. SU-consultancy: Celgene; honoraria: Celgene, Onyx; research funding: Celgene, Onyx, Millennium. DR-honoraria: Amgen; research funding: Eli Lilly. RN-consultancy: Onyx, Millennium, Celgene; honoraria: Onyx, Millennium, Celgene; research funding: Onyx, Millennium, Celgene. HE-consultancy: Celgene, Janssen; honoraria: Celgene, Janssen; research funding: Celgene, Janssen. KCA-consultancy: Gilead, Sanofi-Aventis, Onyx, Celgene; stock ownership: Acetylon, Oncoprep. MAD-consultancy: Celgene, Ortho Biotech; honoraria: Celgene, Ortho Biotech; research funding: Celgene. HA-honoraria: Celgene, Janssen, Onyx. UHM-honoraria: Celgene, Janssen-Cilag. IT-No conflicts to disclose. GM-consultancy: Millennium Takeda, Neotype; honoraria: Millennium Takeda, Pfizer. RS-No conflicts to disclose. PM-consultancy: Celgene, Janssen; honoraria: Celgene, Janssen. PLB-honoraria: Onyx. CSC-No conflicts to disclose. JJL-honoraria: Celgene; research funding: Celgene, Janssen-Cilag. JS-research funding: Janssen-Cilag, Celgene, Onyx. AR-consultancy: Celgene; research funding: Celgene, Bristol Myers Squibb, Millennium, Astra Zeneca, Onyx. JM-research funding: Celgene, Onyx, Sanofi. SZ-research funding: Celgene, Janssen-Cilag, Millennium. SL-consultancy: Celgene, Millennium, Novartis, Bristol Myers Squibb, Onyx, Janssen-Cilag. RC-consultancy: Millennium; research funding: Millennium, Prothena Biotech. WJC-honoraria: Janssen, Celgene, Novartis; research funding: Celgene, Roche. PM-consultancy: Celgene, Janssen, Millennium; honoraria: Celgene, Janssen. PS-research funding: Janssen-Cilag, Celgene, Onyx. HL-honoraria: Celgene, Mundi Pharma, Janssen-Cilag; research funding: Celgene, Mundi Pharma, Janssen-Cilag. BD-honoraria: Celgene Corporation, Onyx Pharmaceutical, Millennium Pharmaceutical, The Takeda Company. JFSM-consultancy and honoraria: Janssen-Cilag, Millennium, Celgene, Onyx, Novartis, Bristol Myers Squibb. NR 200 TC 92 Z9 95 U1 9 U2 46 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 MAR PY 2014 VL 28 IS 3 BP 525 EP 542 DI 10.1038/leu.2013.350 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA AC9HR UT WOS:000332845700006 PM 24253022 ER PT J AU Stankov, MV El Khatib, M Thakur, BK Heitmann, K Panayotova-Dimitrova, D Schoening, J Bourquin, JP Schweitzer, N Leverkus, M Welte, K Reinhardt, D Li, Z Orkin, SH Behrens, GMN Klusmann, JH AF Stankov, M. V. El Khatib, M. Thakur, B. Kumar Heitmann, K. Panayotova-Dimitrova, D. Schoening, J. Bourquin, J. P. Schweitzer, N. Leverkus, M. Welte, K. Reinhardt, D. Li, Z. Orkin, S. H. Behrens, G. M. N. Klusmann, J. H. TI Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy SO LEUKEMIA LA English DT Article DE HDAC inhibitor; autophagy; AML; Down syndrome; ATG7 ID ACUTE MEGAKARYOBLASTIC LEUKEMIA; CELL-CYCLE ARREST; DOWN-SYNDROME; HDAC INHIBITORS; VALPROIC ACID; CANCER; CHILDREN; THERAPY; P53; ACETYLTRANSFERASE AB Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL) blasts. Investigating the antileukemic function of HDACis revealed their transcriptional and post-translational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian target of rapamycin (mTOR) activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells. C1 [Stankov, M. V.; Behrens, G. M. N.] Hannover Med Sch, Dept Clin Immunol & Rheumatol, D-30625 Hannover, Germany. [El Khatib, M.; Thakur, B. Kumar; Heitmann, K.; Schoening, J.; Reinhardt, D.; Klusmann, J. H.] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, Germany. [Panayotova-Dimitrova, D.; Leverkus, M.] Heidelberg Univ, Med Fac Mannheim, Dept Dermatol Venerol & Allergol, Mol Dermatol Sect, Mannheim, Germany. [Bourquin, J. P.] Univ Kinderklin Zurich, Div Pediat Oncol, Zurich, Switzerland. [Schweitzer, N.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany. [Welte, K.] Hannover Med Sch, Dept Mol Hematopoiesis, D-30625 Hannover, Germany. [Li, Z.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Orkin, S. H.] Harvard Univ, Sch Med, Boston, MA USA. [Orkin, S. H.] Harvard Stem Cell Inst, Boston, MA USA. [Orkin, S. H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, S. H.] Childrens Hosp, Boston, MA 02115 USA. [Orkin, S. H.] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Klusmann, JH (reprint author), Hannover Med Sch, Dept Pediat Hematol & Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM Klusmann.jan-henning@mh-hannover.de RI Klusmann, Jan-Henning/M-9655-2015; Behrens, Georg/Q-4486-2016 OI Klusmann, Jan-Henning/0000-0002-1070-0727; FU Wilhelm Sander-Foundation [2011.057.1]; German Research Foundation (DFG) [KL-2374/1-1]; NIH; DFG [BE-2089/2-1, EXC62/1, SFB/TR77, LE-953/8-1, LE-953/6-1]; Mildred-Scheel-Stiftung [109891]; NIH [R01 HL107663] FX We thank Dr Bradner for sharing the reagents, the Mizushima and Levine laboratories for valuable methodological advice, and C Reimer and L Queisser for technical assistance. This work was supported by a grant to JHK and DR from the Wilhelm Sander-Foundation (2011.057.1), the German Research Foundation (DFG; KL-2374/1-1) and to SHO from the NIH. JHK is a fellow of the Emmy Noether-Programme from the DFG (KL-2374/2-1). SHO is an Investigator of the Howard Hughes Medical Institute. GMNB and MVS were supported by the DFG (BE-2089/2-1 and EXC62/1), NS by the SFB/TR77, ML by the DFG (LE-953/8-1 and LE-953/6-1) and the Mildred-Scheel-Stiftung (#109891) and KH by the Hannover Biomedical Research School. ZL was a Fellow of the Leukemia & Lymphoma Society and is supported by NIH grant R01 HL107663. NR 56 TC 28 Z9 28 U1 0 U2 17 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 MAR PY 2014 VL 28 IS 3 BP 577 EP 588 DI 10.1038/leu.2013.264 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA AC9HR UT WOS:000332845700010 PM 24080946 ER PT J AU Bachanova, V Marks, DI Zhang, MJ Wang, H de Lima, M Aljurf, MD Arellano, M Artz, AS Bacher, U Cahn, JY Chen, YB Copelan, EA Drobyski, WR Gale, RP Greer, JP Gupta, V Hale, GA Kebriaei, P Lazarus, HM Lewis, ID Lewis, VA Liesveld, JL Litzow, MR Loren, AW Miller, AM Norkin, M Oran, B Pidala, J Rowe, JM Savani, BN Saber, W Vij, R Waller, EK Wiernik, PH Weisdorf, DJ AF Bachanova, V. Marks, D. I. Zhang, M-J Wang, H. de Lima, M. Aljurf, M. D. Arellano, M. Artz, A. S. Bacher, U. Cahn, J-Y Chen, Y-B Copelan, E. A. Drobyski, W. R. Gale, R. P. Greer, J. P. Gupta, V. Hale, G. A. Kebriaei, P. Lazarus, H. M. Lewis, I. D. Lewis, V. A. Liesveld, J. L. Litzow, M. R. Loren, A. W. Miller, A. M. Norkin, M. Oran, B. Pidala, J. Rowe, J. M. Savani, B. N. Saber, W. Vij, R. Waller, E. K. Wiernik, P. H. Weisdorf, D. J. TI Ph plus ALL patients in first complete remission have similar survival after reduced intensity and myeloablative allogeneic transplantation: impact of tyrosine kinase inhibitor and minimal residual disease SO LEUKEMIA LA English DT Article DE acute lymphoblastic leukemia; Philadelphia chromosome; reduced intensity conditioning; allograft; minimal residual disease; tyrosine kinase inhibitor ID ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; UNRELATED DONOR TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; IMATINIB-BASED THERAPY; ADULT PATIENTS; PROLONGED SURVIVAL; ELDERLY-PATIENTS; T-CELLS AB The efficacy of reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is uncertain. We analyzed 197 adults with Ph+ ALL in first complete remission; 67 patients receiving RIC were matched with 130 receiving myeloablative conditioning (MAC) for age, donor type and HCT year. Over 75% received pre-HCT tyrosine kinase inhibitors (TKIs), mostly imatinib; 39% (RIC) and 49% (MAC) were minimal residual disease (MRD)(neg) pre-HCT. At a median 4.5 years follow-up, 1-year transplant-related mortality (TRM) was lower in RIC (13%) than MAC (36%; P = 0.001) while the 3-year relapse rate was 49% in RIC and 28% in MAC (P = 0.058). Overall survival (OS) was similar (RIC 39% (95% confidence interval (CI) 27-52) vs 35% (95% CI 27-44); P = 0.62). Patients MRDpos pre-HCT had higher risk of relapse with RIC vs MAC (hazard ratio (HR) 1.97; P = 0.026). However, patients receiving pre-HCT TKI in combination with MRD negativity pre-RIC HCT had superior OS (55%) compared with a similar MRD population after MAC (33%; P = 0.0042). In multivariate analysis, RIC lowered TRM (HR 0.6; P = 0.057), but absence of pre-HCT TKI (HR 1.88; P = 0.018), RIC (HR 1.891; P = 0.054) and pre-HCT MRDpos (HR 1.6; P = 0.070) increased relapse risk. RIC is a valid alternative strategy for Ph+ ALL patients ineligible for MAC and MRDneg status is preferred pre-HCT. C1 [Bachanova, V.; Weisdorf, D. J.] Univ Minnesota, Blood & Marrow Transplant Program, Med Ctr, Minneapolis, MN 55455 USA. [Marks, D. I.] Bristol Childrens Hosp, Bristol Adult BMT Unit, Bristol, Avon, England. [Zhang, M-J; Wang, H.; Saber, W.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. [de Lima, M.; Lazarus, H. M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Aljurf, M. D.] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi Arabia. [Arellano, M.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Artz, A. S.] Univ Chicago Med, Dept Hematol & Oncol, Chicago, IL USA. [Bacher, U.] Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Stammzelltransplantat, Hamburg, Germany. [Cahn, J-Y] Univ Hosp, Dept Hematol, Grenoble, France. [Chen, Y-B] Massachusetts Gen Hosp, Dept Bone Marrow Transplantat, Boston, MA 02114 USA. [Copelan, E. A.] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA. [Drobyski, W. R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Sect Hematol, London, England. [Greer, J. P.; Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Hematol & Stem Cell Transplantat, Nashville, TN USA. [Gupta, V.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hale, G. A.] Univ S Florida, All Childrens Hosp, Dept Pediat Hematol & Oncol, St Petersburg, FL 33701 USA. [Kebriaei, P.; Oran, B.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Lewis, I. D.] Royal Adelaide Hosp SA Pathol, Dept Haematol, Adelaide, SA, Australia. [Lewis, I. D.] Royal Adelaide Hosp SA Pathol, Bone Marrow Transplant Unit, Adelaide, SA, Australia. [Lewis, V. A.] Alberta Childrens Prov Gen Hosp, Dept Hematol & Oncol, Calgary, AB T2T 5C7, Canada. [Liesveld, J. L.] Univ Rochester, Med Ctr, Strong Mem Hosp, Dept Hematol & Oncol, Rochester, NY 14642 USA. [Litzow, M. R.] Mayo Clin Rochester, Dept Hematol & Internal Med, Rochester, MN USA. [Loren, A. W.] Univ Penn, Dept Hematol & Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Miller, A. M.] Baylor Univ, Med Ctr, Dept Oncol, Dallas, TX USA. [Norkin, M.] Shands HealthCare, Dept Hematol & Oncol, Gainesville, FL USA. [Norkin, M.] Univ Florida, Gainesville, FL USA. [Pidala, J.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Blood & Marrow Transplantat, Tampa, FL 33682 USA. [Rowe, J. M.] Rambam Med Ctr, Dept Hematol, Haifa, Israel. [Vij, R.] Washington Univ, Sch Med, Barnes Jewish Hosp, Dept Bone Marrow Transplantat & Leukemia, St Louis, MO USA. [Waller, E. K.] Emory Univ Hosp, Bone Marrow & Stem Cell Transplant Ctr, Atlanta, GA 30322 USA. [Wiernik, P. H.] Our Lady Mercy Med Ctr, Bronx, NY USA. RP Bachanova, V (reprint author), Univ Minnesota, Blood & Marrow Transplant Program, Mayo Mail Code 480,420 Delaware St SE, Minneapolis, MN 55455 USA. EM bach0173@umn.edu RI Cahn, Jean-Yves/M-6493-2014; OI Bachanova, Veronika/0000-0002-9325-432X FU Novartis; National Cancer Institute (NCI) [U24 CA076518]; National Heart, Lung and Blood Institute (NHLBI) [U24 CA076518]; National Institute of Allergy and Infectious Diseases (NIAID) [U24 CA076518]; NHLBI [U10 HL069294]; NCI [U10 HL069294]; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Allos Therapeutics, Inc.; Amgen, Inc. FX This work was supported in part by Novartis providing the grant to CIBMTR for supplemental data collection. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24 CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement U10 HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from Allos Therapeutics, Inc.; Amgen, Inc. Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; the Leukemia and Lymphoma Society; the Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense or any other agency of the US Government. NR 42 TC 29 Z9 31 U1 1 U2 11 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 MAR PY 2014 VL 28 IS 3 BP 658 EP 665 DI 10.1038/leu.2013.253 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA AC9HR UT WOS:000332845700018 PM 23989431 ER PT J AU Minami, J Suzuki, R Mazitschek, R Gorgun, G Ghosh, B Cirstea, D Hu, Y Mimura, N Ohguchi, H Cottini, F Jakubikova, J Munshi, NC Haggarty, SJ Richardson, PG Hideshima, T Anderson, KC AF Minami, J. Suzuki, R. Mazitschek, R. Gorgun, G. Ghosh, B. Cirstea, D. Hu, Y. Mimura, N. Ohguchi, H. Cottini, F. Jakubikova, J. Munshi, N. C. Haggarty, S. J. Richardson, P. G. Hideshima, T. Anderson, K. C. TI Histone deacetylase 3 as a novel therapeutic target in multiple myeloma SO LEUKEMIA LA English DT Article DE multiple myeloma; histone deacetylase 3; STAT3; bortezomib ID PROTEASOME INHIBITOR BORTEZOMIB; MULTITARGETED KINASE INHIBITOR; DOWN-REGULATION; IN-VITRO; STAT3; CELLS; ACETYLATION; COMBINATION; CYTOTOXICITY; ACTIVATION AB Histone deacetylases (HDACs) represent novel molecular targets for the treatment of various types of cancers, including multiple myeloma (MM). Many HDAC inhibitors have already shown remarkable antitumor activities in the preclinical setting; however, their clinical utility is limited because of unfavorable toxicities associated with their broad range HDAC inhibitory effects. Isoform-selective HDAC inhibition may allow for MM cytotoxicity without attendant side effects. In this study, we demonstrated that HDAC3 knockdown and a small-molecule HDAC3 inhibitor BG45 trigger significant MM cell growth inhibition via apoptosis, evidenced by caspase and poly (ADP-ribose) polymerase cleavage. Importantly, HDAC3 inhibition downregulates phosphorylation (tyrosine 705 and serine 727) of signal transducers and activators of transcription 3 (STAT3). Neither interleukin-6 nor bone marrow stromal cells overcome this inhibitory effect of HDAC3 inhibition on phospho-STAT3 and MM cell growth. Moreover, HDAC3 inhibition also triggers hyperacetylation of STAT3, suggesting crosstalk signaling between phosphorylation and acetylation of STAT3. Importantly, inhibition of HDAC3, but not HDAC1 or 2, significantly enhances bortezomib-induced cytotoxicity. Finally, we confirm that BG45 alone and in combination with bortezomib trigger significant tumor growth inhibition in vivo in a murine xenograft model of human MM. Our results indicate that HDAC3 represents a promising therapeutic target, and validate a prototype novel HDAC3 inhibitor BG45 in MM. C1 [Minami, J.; Suzuki, R.; Gorgun, G.; Cirstea, D.; Hu, Y.; Mimura, N.; Ohguchi, H.; Cottini, F.; Jakubikova, J.; Munshi, N. C.; Richardson, P. G.; Hideshima, T.; Anderson, K. C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. [Mazitschek, R.; Ghosh, B.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Ghosh, B.; Haggarty, S. J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, 450 Brookline Ave,Mayer 557, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU National Institute of Health [SPORE-P50100707, P01 CA78378, R01 CA50947, R01 DA02830, P50CA086355] FX This study was supported by the National Institute of Health Grants (SPORE-P50100707, P01 CA78378, R01 CA50947 (KCA), R01 DA02830 (SJH) and P50CA086355 (RM)). KCA is an American Cancer Society Clinical Research Professor. NR 33 TC 33 Z9 33 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD MAR PY 2014 VL 28 IS 3 BP 680 EP 689 DI 10.1038/leu.2013.231 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA AC9HR UT WOS:000332845700021 PM 23913134 ER PT J AU Ng, CEL Sinha, A Krivtsov, A Dias, S Chang, J Armstrong, SA Kalaitzidis, D AF Ng, C. E. L. Sinha, A. Krivtsov, A. Dias, S. Chang, J. Armstrong, S. A. Kalaitzidis, D. TI KRas(G12D)-evoked leukemogenesis does not require beta-catenin SO LEUKEMIA LA English DT Letter ID LEUKEMIA STEM-CELLS; ONCOGENIC KRAS; HEMATOPOIESIS; MODULATION; RAS; CML; AML C1 [Ng, C. E. L.; Dias, S.; Armstrong, S. A.; Kalaitzidis, D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Ng, C. E. L.; Dias, S.; Armstrong, S. A.; Kalaitzidis, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ng, C. E. L.; Dias, S.; Armstrong, S. A.; Kalaitzidis, D.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Ng, CEL (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. EM armstros@mskcc.org; dkalaitzidis@partners.org FU NCI NIH HHS [CA140575, P30 CA008748, R01 CA140575, CA66996, P01 CA066996]; NIDDK NIH HHS [K01DK092300, K01 DK092300] NR 15 TC 1 Z9 1 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 MAR PY 2014 VL 28 IS 3 BP 698 EP 702 DI 10.1038/leu.2013.328 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA AC9HR UT WOS:000332845700025 PM 24189294 ER PT J AU Richards, JB Wilcox, SR Roberts, DH Schwartzstein, RM AF Richards, Jeremy B. Wilcox, Susan R. Roberts, David H. Schwartzstein, Richard M. TI Twelve tips for overnight teaching SO MEDICAL TEACHER LA English DT Article ID SLEEP-DEPRIVATION; NIGHT FLOAT; DUTY HOURS; MEDICAL-EDUCATION; CLINICAL SKILLS; WORK HOURS; RESIDENTS; PERFORMANCE; PHYSICIANS; SHIFT AB Background: The European Working Time Directive and the United States' duty hour restrictions have changed resident physicians' schedules, specifically increasing overnight shifts and decreasing overall time spent in the hospital. As residents' perception of night shifts is that they have little educational value, efforts to improve educational opportunities and night attending teaching are desirable. However, resources about and recommendations for best practices for overnight teaching by faculty are scarce. Aim: To provide 12 tips to highlight strategies intended to optimize attending physicians' overnight teaching skills and strategies. Method: The tips provided are based on our experiences and reflections as in-house faculty supervising residents working overnight, by our experience and group discussions as medical educators, and the available literature. Results: The 12 tips presented offer specific strategies to optimize attending physicians' overnight teaching for resident physicians, specifically highlighting the unique logistics, pedagogy and follow-up of overnight teaching. Conclusion: Preparation for teaching is important in any environment, but understanding the unique timing and circumstances associated with overnight teaching is vital to ensure that overnight teaching is effective. Acknowledging and addressing the physical and cognitive obstacles associated with overnight teaching and learning is necessary to maximize the educational value of overnight teaching. C1 [Richards, Jeremy B.; Schwartzstein, Richard M.] Harvard Univ, Sch Med, Boston, MA USA. [Roberts, David H.] Harvard Univ, Sch Med, Shapiro Inst Educ & Res, Boston, MA USA. [Richards, Jeremy B.; Wilcox, Susan R.; Roberts, David H.; Schwartzstein, Richard M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Emergency Med & Surg Intens Care Unit, Boston, MA 02114 USA. RP Richards, JB (reprint author), 330 Brookline Ave,KSB 23, Boston, MA 02215 USA. EM jbrichar@bidmc.harvard.edu OI Wilcox, Susan/0000-0001-7477-7531 NR 42 TC 1 Z9 1 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X EI 1466-187X J9 MED TEACH JI Med. Teach. PD MAR PY 2014 VL 36 IS 3 BP 196 EP 200 DI 10.3109/0142159X.2013.847911 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AD3WF UT WOS:000333176300002 PM 24164552 ER PT J AU Mastroianni, M Barone, AAL Shanmugarajah, K Leonard, DA Di Rosa, L Feingold, RS Israeli, R Cetrulo, CL AF Mastroianni, Melissa Barone, Angelo A. Leto Shanmugarajah, Kumaran Leonard, David A. Di Rosa, Luigi Feingold, Randall S. Israeli, Ron Cetrulo, Curtis L., Jr. TI LOWER EXTREMITY SOFT TISSUE DEFECT RECONSTRUCTION WITH THE SERRATUS ANTERIOR FLAP SO MICROSURGERY LA English DT Article ID ANTEROLATERAL THIGH FLAP; OPEN TIBIAL FRACTURES; FREE-MUSCLE; LATISSIMUS-DORSI; BONE; ANKLE; FOOT; EXPERIENCE; HAND AB Reconstruction of limb-threatening lower extremity defects presents unique challenges. The selected method must provide adequate coverage of exposed bone, joints, and tendons while maximizing function of the limb. The traditional workhorse flaps, the free latissimus dorsi and rectus abdominis flaps, have been associated with donor site morbidity and bulkiness that can impair rehabilitation. We report a case series (n = 18) in which the free serratus anterior muscle flap and split thickness skin graft (STSG) was used for lower limb soft tissue coverage. Injuries were due to diabetes (9/18), trauma (7/18), and chronic venous stasis (2/18). A 94% flap survival rate was observed and all but one patient was ambulatory. No donor site morbidity was reported. Our series demonstrates that serratus anterior is an advantageous, reliable free flap with minimal donor site morbidity. (c) 2013 Wiley Periodicals, Inc. Microsurgery 34:183-187, 2014. C1 [Mastroianni, Melissa; Barone, Angelo A. Leto; Shanmugarajah, Kumaran; Leonard, David A.; Cetrulo, Curtis L., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. [Feingold, Randall S.; Israeli, Ron] Univ Palermo, Sch Med, Dept Surg Oncol & Stomatol Sci, Dept Plast & Reconstruct Surg, Palermo, Italy. [Di Rosa, Luigi] N Shore Univ Hosp, Hofstra North Shore LIJ Sch Med, Div Plast & Reconstruct Surg, Manhasset, NY USA. RP Cetrulo, CL (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM ccetrulo@partners.org NR 37 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0738-1085 EI 1098-2752 J9 MICROSURG JI Microsurgery PD MAR PY 2014 VL 34 IS 3 BP 183 EP 187 DI 10.1002/micr.22191 PG 5 WC Surgery SC Surgery GA AC2IY UT WOS:000332325100003 PM 24307318 ER PT J AU Bailey, ST Miron, PL Choi, YJ Kochupurakkal, B Maulik, G Rodig, SJ Tian, RY Foley, KM Bowman, T Miron, A Brown, M Iglehart, JD Biswas, DK AF Bailey, Shannon T. Miron, Penelope L. Choi, Yoon J. Kochupurakkal, Bose Maulik, Gautam Rodig, Scott. J. Tian, Ruiyang Foley, Kathleen M. Bowman, Teresa Miron, Alexander Brown, Myles Iglehart, J. Dirk. Biswas, Debajit K. TI NF-kappa B Activation-Induced Anti-apoptosis Renders HER2-Positive Cells Drug Resistant and Accelerates Tumor Growth SO MOLECULAR CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; DAVID BIOINFORMATICS RESOURCES; GENE-EXPRESSION PROFILES; MOLECULAR SUBTYPES; TARGETED THERAPIES; KINASE INHIBITORS; DRIVEN RESISTANCE; PREDICTOR; SIGNATURE; BIOLOGY AB Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2-positive breast cancer, but resistance inevitably occurs. We previously found that NF-kappa B is hyperactivated in a subset of HER2-positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-kappa B rendered HER2-positive cancer cells resistant to anti-HER2 drugs and cells selected for lapatinib resistance upregulated NF-kappa B. In both circumstances, cells were antiapoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-kappa B inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-kappa B-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-kappa B signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-kappa B activation, and selection for resistance results in NF-kappa B activation, suggesting that this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-kappa B suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-kappa B activation. (C)2013 AACR. C1 [Bailey, Shannon T.; Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Bailey, Shannon T.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Miron, Penelope L.; Choi, Yoon J.; Kochupurakkal, Bose; Tian, Ruiyang; Foley, Kathleen M.; Miron, Alexander; Iglehart, J. Dirk.; Biswas, Debajit K.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Iglehart, J. Dirk.; Biswas, Debajit K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. [Rodig, Scott. J.; Bowman, Teresa] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 958, Boston, MA 02215 USA. EM debajit_biswas@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute; Eileen and Mark Epstein Family Fund; NCI SPORE in Breast Cancer at Dana-Farber Cancer Institute [P50CA89303] FX This study was supported by funds from Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, by the Eileen and Mark Epstein Family Fund, and by funds from the NCI SPORE in Breast Cancer at Dana-Farber Cancer Institute (P50CA89303). NR 57 TC 13 Z9 14 U1 0 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 MAR PY 2014 VL 12 IS 3 BP 408 EP 420 DI 10.1158/1541-7786.MCR-13-0206-T PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AD4XQ UT WOS:000333255500010 PM 24319068 ER PT J AU Zou, J Lippert, C Heckerman, D Aryee, M Listgarten, J AF Zou, James Lippert, Christoph Heckerman, David Aryee, Martin Listgarten, Jennifer TI Epigenome-wide association studies without the need for cell-type composition SO NATURE METHODS LA English DT Article ID LINEAR MIXED MODELS; LARGE GENE LISTS; DNA METHYLATION; BREAST-CANCER; GENOMIC CONTROL; RECEPTOR AB In epigenome-wide association studies, cell-type composition often differs between cases and controls, yielding associations that simply tag cell type rather than reveal fundamental biology. Current solutions require actual or estimated cell-type composition-information not easily obtainable for many samples of interest. We propose a method, FaST-LMM-EWASher, that automatically corrects for cell-type composition without the need for explicit knowledge of it, and then validate our method by comparison with the state-of-the-art approach. C1 [Zou, James; Lippert, Christoph; Heckerman, David; Listgarten, Jennifer] Microsoft Res, eSci Res Grp, Los Angeles, CA 90024 USA. [Zou, James] MIT, Broad Inst, Cambridge, MA 02139 USA. [Zou, James] Harvard Univ, Cambridge, MA 02138 USA. [Zou, James] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Aryee, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Aryee, Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zou, J (reprint author), Microsoft Res, eSci Res Grp, Los Angeles, CA 90024 USA. EM jzou@fas.harvard.edu RI Lippert, Christoph/M-2992-2016; OI Lippert, Christoph/0000-0001-6363-2556; Aryee, Martin/0000-0002-6848-1344 NR 21 TC 62 Z9 62 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD MAR PY 2014 VL 11 IS 3 BP 309 EP U283 DI 10.1038/NMETH.2815 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AB9CE UT WOS:000332086100026 PM 24464286 ER PT J AU Jungmann, R Avendano, MS Woehrstein, JB Dai, MJ Shih, WM Yin, P AF Jungmann, Ralf Avendano, Maier S. Woehrstein, Johannes B. Dai, Mingjie Shih, William M. Yin, Peng TI Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT SO NATURE METHODS LA English DT Article ID OPTICAL RECONSTRUCTION MICROSCOPY; ORIGAMI; BINDING; CELLS; SHAPES; SYSTEM; PROBES; STORM; LIMIT; DYES AB Super-resolution fluorescence microscopy is a powerful tool for biological research, but obtaining multiplexed images for a large number of distinct target species remains challenging. Here we use the transient binding of short fluorescently labeled oligonucleotides (DNA-PAINT, a variation of point accumulation for imaging in nanoscale topography) for simple and easy-to-implement multiplexed super-resolution imaging that achieves sub-10-nm spatial resolution in vitro on synthetic DNA structures. We also report a multiplexing approach (Exchange-PAINT) that allows sequential imaging of multiple targets using only a single dye and a single laser source. We experimentally demonstrate ten-color super-resolution imaging in vitro on synthetic DNA structures as well as four-color two-dimensional (2D) imaging and three-color 3D imaging of proteins in fixed cells. C1 [Jungmann, Ralf; Avendano, Maier S.; Woehrstein, Johannes B.; Dai, Mingjie; Shih, William M.; Yin, Peng] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. [Jungmann, Ralf; Avendano, Maier S.; Yin, Peng] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Dai, Mingjie] Harvard Univ, Program Biophys, Cambridge, MA USA. [Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Cambridge, MA USA. [Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Yin, P (reprint author), Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. EM py@hms.harvard.edu RI Jungmann, Ralf/A-6357-2015; OI Jungmann, Ralf/0000-0003-4607-3312; Dai, Mingjie/0000-0002-8665-4966 FU US National Institutes of Health (NIH) Director's New Innovator Award [1DP2OD007292]; NIH Transformative Research Award [1R01EB018659]; NIH [5R21HD072481]; Office of Naval Research (ONR) Young Investigator Program Award [N000141110914]; ONR [N000141010827, N000141310593]; US National Science Foundation (NSF) Faculty Early Career Development Award [CCF1054898]; NSF [CCF1162459]; Wyss Institute for Biologically Engineering Faculty Startup Fund; NIH Director's New Innovator Award [1DP2OD004641]; Wyss Institute for Biologically Inspired Engineering Faculty Award; Alexander von Humboldt-Foundation through a Feodor-Lynen Fellowship; Howard Hughes Medical Institute International Student Research Fellowships FX We thank J. Nicoludis and M. T. Strauss for help with DNA origami design, T. Schlichthaerle for transmission electron microscopy imaging support and M. Zhang for help with DLD1 cells. We thank C. Steinhauer for help with DNA-PAINT software development and fruitful discussions. We thank R. D. Barish for critical reading and commenting on the manuscript. This work is supported by a US National Institutes of Health (NIH) Director's New Innovator Award (1DP2OD007292), an NIH Transformative Research Award (1R01EB018659), an NIH grant (5R21HD072481), an Office of Naval Research (ONR) Young Investigator Program Award (N000141110914), ONR grants (N000141010827 and N000141310593), a US National Science Foundation (NSF) Faculty Early Career Development Award (CCF1054898), an NSF grant (CCF1162459) and a Wyss Institute for Biologically Engineering Faculty Startup Fund to P.Y., and an NIH Director's New Innovator Award (1DP2OD004641) and a Wyss Institute for Biologically Inspired Engineering Faculty Award to W.M.S. R.J. acknowledges support from the Alexander von Humboldt-Foundation through a Feodor-Lynen Fellowship. M. S. A. and M. D. acknowledge support from Howard Hughes Medical Institute International Student Research Fellowships. NR 34 TC 93 Z9 96 U1 19 U2 140 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD MAR PY 2014 VL 11 IS 3 BP 313 EP U292 DI 10.1038/NMETH.2835 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AB9CE UT WOS:000332086100027 PM 24487583 ER PT J AU Settle, PD AF Settle, Peggy Doyle TI Nurse Activism in the newborn intensive care unit: Actions in response to an ethical dilemma SO NURSING ETHICS LA English DT Article DE Ethical action; newborn intensive care unit nurses; Rest's model ID BIRTH-WEIGHT INFANTS; MORAL DISTRESS; DECISION-MAKING; THRESHOLD; VIABILITY; ENVIRONMENT; EXPERIENCE; MORTALITY; OUTCOMES; FUTILE AB Nurses working in a newborn intensive care unit report that treatment decision disagreements for infants in their care may lead to ethical dilemmas involving all health-care providers. Applying Rest's Four-Component Model of Moral Action as the theoretical framework, this study examined the responses of 224 newborn intensive care unit nurses to the Nurses Ethical Involvement Survey. The three most frequent actions selected were as follows: talking with other nurses, talking with doctors, and requesting a team meeting. The multiple regression analysis indicates that newborn intensive care unit nurses with greater concern for the ethical aspects of clinical practice (p = .001) and an increased perception of their ability to influence ethical decision making (p = .018) were more likely to display Nurse Activism. Future research is necessary to identify other factors leading to and inhibiting Nurse Activism as these findings explained just 8.5% of the variance. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Settle, PD (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM msettle@partners.org FU Yvonne L. Munn Post-Doctoral Fellowship Munn Center for Nursing Research at Massachusetts General Hospital FX No grant funding was received to conduct the research. The manuscript preparation was sponsored in part with support from the Yvonne L. Munn Post-Doctoral Fellowship Munn Center for Nursing Research at Massachusetts General Hospital. NR 57 TC 1 Z9 1 U1 4 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0969-7330 EI 1477-0989 J9 NURS ETHICS JI Nurs. Ethics PD MAR PY 2014 VL 21 IS 2 BP 198 EP 209 DI 10.1177/0969733012475254 PG 12 WC Nursing SC Nursing GA AC5YI UT WOS:000332596500008 PM 23454980 ER PT J AU Chen, YE Gerstle, T Verma, K Treiser, MD Kimball, AB Orgill, DP AF Chen, Y. Erin Gerstle, Theodore Verma, Kapil Treiser, Matthew D. Kimball, Alexandra B. Orgill, Dennis P. TI Management of Hidradenitis Suppurativa Wounds with an Internal Vacuum- Assisted Closure Device SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SUBATMOSPHERIC PRESSURE; DOUBLE-BLIND; BLOOD-FLOW; THERAPY; CLINDAMYCIN; GRANULATION; EXPERIENCE; EXCISION; BRIDGE; TRIAL AB Background: Hidradenitis suppurativa is a chronic, debilitating disease that is difficult to treat. Once medical management fails, wide local excision offers the best chance for cure. However, the resultant wound often proves too large or contaminated for immediate closure. Methods: The authors performed a retrospective chart review of hidradenitis cases managed surgically between 2005 and 2010. Data collected included patient characteristics, management method, and outcomes. Approximately half of the patients received internal vacuum-assisted closure therapy using the vacuum-assisted closure system and delayed closure and half of the patients received immediate primary closure at the time of their excision. Delayed closure consisted of closing the majority of the wound in a linear fashion following internal vacuum-assisted closure while accepting healing by means of secondary intention for small wound areas. Results: Patients managed with internal vacuum-assisted closure had wounds on average four times larger in area than patients managed without internal vacuum-assisted closure. In both groups, all wounds were eventually closed primarily. Healing times averaged 2.2 months with internal vacuum-assisted closure and 2.7 months without. At an average follow-up time of 2.3 months, all patients with internal vacuum-assisted closure had no recurrence of their local disease. Conclusions: Severe hidradenitis presents a treatment challenge, as surgical excisions are often complicated by difficult closures and unsatisfactory recurrence rates. This study demonstrates that wide local excision with reasonable outcomes can be achieved using accelerated delayed primary closure. This method uses internal vacuum-assisted closure as a bridge between excision and delayed primary closure, facilitating closure without recurrence in large, heavily contaminated wounds. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. C1 Beth Israel Deaconess Med Ctr, Dept Med, New York, NY 10003 USA. Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. Georgetown Univ Hosp, Dept Plast Surg, Washington, DC USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Orgill, DP (reprint author), 75 Francis St, Boston, MA 02115 USA. EM dorgill@partners.org FU Kinetic Concepts, Inc. FX Dr. Orgill has been an expert witness, consultant, and grant recipient of funding provided by Kinetic Concepts, Inc., the manufacturer of the V.A.C. devices mentioned in this article. The remaining authors have no financial interests to disclose. NR 36 TC 11 Z9 12 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2014 VL 133 IS 3 BP 370E EP 377E DI 10.1097/PRS.0000000000000080 PG 8 WC Surgery SC Surgery GA AD4TN UT WOS:000333243600017 PM 24572882 ER PT J AU Lee, JH McCormack, MC Austen, WG AF Lee, Jeffrey H. McCormack, Michael C. Austen, William Gerald, Jr. TI Reply: The Effect of Pressure and Shear on Autologous Fat Grafting SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Lee, Jeffrey H.; McCormack, Michael C.; Austen, William Gerald, Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2014 VL 133 IS 3 BP 420E EP 421E DI 10.1097/01.prs.0000438465.36711.98 PG 2 WC Surgery SC Surgery GA AD4TN UT WOS:000333243600024 PM 24572889 ER PT J AU Colwell, AS Tessler, O Lin, AM Liao, E Winograd, J Cetrulo, CL Tang, R Smith, BL Austen, WG AF Colwell, Amy S. Tessler, Oren Lin, Alex M. Liao, Eric Winograd, Jonathan Cetrulo, Curtis L. Tang, Rong Smith, Barbara L. Austen, William G. TI Breast Reconstruction following Nipple- Sparing Mastectomy: Predictors of Complications, Reconstruction Outcomes, and 5-Year Trends SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ONCOLOGICALLY SAFE PROCEDURE; ACELLULAR DERMAL MATRIX; IMMEDIATE RECONSTRUCTION; SUBCUTANEOUS MASTECTOMY; RADIATION-THERAPY; AREOLA COMPLEX; ENVELOPE MASTECTOMY; SKIN; CANCER; RISK AB Background: Nipple-sparing mastectomy is increasingly used for treatment and prevention of breast cancer. Few data exist on risk factors for complications and reconstruction outcomes. Methods: A single-institution retrospective review was performed between 2007 and 2012. Results: Two hundred eighty-five patients underwent 500 nipple-sparing mastectomy procedures for breast cancer (46 percent) or risk reduction (54 percent). The average body mass index was 24, and 6 percent were smokers. The mean follow-up was 2.17 years. Immediate breast reconstruction (reconstruction rate, 98.8 percent) was performed with direct-to-implant (59 percent), tissue expander/implant (38 percent), or autologous (2 percent) reconstruction. Acellular dermal matrix was used in 71 percent and mesh was used in 11 percent. Seventy-seven reconstructions had radiotherapy. Complications included infection (3.3 percent), skin necrosis (5.2 percent), nipple necrosis (4.4 percent), seroma (1.7 percent), hematoma (1.7 percent), and implant loss (1.9 percent). Positive predictors for total complications included smoking (OR, 3.3; 95 percent CI, 1.289 to 8.486) and periareolar incisions (OR, 3.63; 95 percent CI, 1.850 to 7.107). Increasing body mass index predicted skin necrosis (OR, 1.154; 95 percent CI, 1.036 to 1.286) and preoperative irradiation predicted nipple necrosis (OR, 4.86; 95 percent CI, 1.0197 to 23.169). An inframammary fold incision decreased complications (OR, 0.018; 95 percent CI, 0.0026 to 0.12089). Five-year trends showed increasing numbers of nipple-sparing mastectomy with immediate reconstruction and more single-stage versus two-stage reconstructions (p < 0.05). Conclusions: Nipple-sparing mastectomy reconstructions have a low number of complications. Smoking, body mass index, preoperative irradiation, and incision type were predictors of complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. C1 [Colwell, Amy S.; Tessler, Oren; Lin, Alex M.; Liao, Eric; Winograd, Jonathan; Cetrulo, Curtis L.; Tang, Rong; Smith, Barbara L.; Austen, William G.] Harvard Univ, Massachusetts Gen Hosp, Div Plast Surg, Sch Med, Boston, MA 02111 USA. RP Colwell, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Plast Surg, Sch Med, Boston, MA 02111 USA. EM acolwell@partners.org NR 46 TC 49 Z9 49 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2014 VL 133 IS 3 BP 496 EP 506 DI 10.1097/01.prs.0000438056.67375.75 PG 11 WC Surgery SC Surgery GA AD4TN UT WOS:000333243600048 PM 24572843 ER PT J AU Fernandes, JR Salinas, HM Broelsch, GF McCormack, MC Meppelink, AM Randolph, MA Redmond, RW Austen, WG AF Fernandes, Justin R. Salinas, Harry M. Broelsch, G. Felix McCormack, Michael C. Meppelink, Amanda M. Randolph, Mark A. Redmond, Robert W. Austen, William G., Jr. TI Prevention of Capsular Contracture with Photochemical Tissue Passivation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BREAST AUGMENTATION; PATIENT SATISFACTION; LONG-TERM; IMPLANTS; SMOOTH; RECONSTRUCTION; COMPLICATIONS; ANTIBIOTICS; MAMMAPLASTY; FIBROBLAST AB Background: Capsular contracture is the most common complication following the insertion of breast implants. Within a decade, half of patients will develop capsular contracture, leading to significant morbidity and need for reoperation. There is no preventative treatment available and the recurrence rate remains high. Photochemical tissue passivation is a novel tissue-stabilization technique that results in collagen cross-linking. It can rapidly link collagen fibers in situ, preserving normal tissue architecture. By using this therapy to passivate the collagenous tissues of the implant pocket, the authors hope to prevent the development of pathogenic collagen bundles and subsequent capsule contracture. Methods: Six-cubic centimeter tissue expanders were placed below the panniculus carnosus muscle along the dorsum of New Zealand white rabbits. Fibrin glue was instilled into each implant pocket to induce contracture. Treated pockets received photochemical tissue passivation by coating them with a photosensitizing dye and exposing the area to a 532-nm light. After 8 weeks, capsule tissue was harvested for histologic evaluation. Results: Implant capsule thickness is the number one prognostic factor for contracture development. The authors demonstrated a 52 percent decrease in capsule thickness in the passivated group compared with controls. Photochemical tissue passivation resulted in fewer fibrohistiocytic cells and macrophages and in reduced synovial metaplasia and smooth muscle actin deposition. Conclusions: Photochemical tissue passivation significantly decreased both capsule thickness and smooth muscle actin deposition. It is a promising technique for preventing capsular contracture that can be performed at the time of initial surgery without a significant increase in procedure time. C1 [Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA. EM wausten@partners.org NR 29 TC 6 Z9 6 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2014 VL 133 IS 3 BP 571 EP 577 DI 10.1097/01.prs.0000438063.31043.79 PG 7 WC Surgery SC Surgery GA AD4TN UT WOS:000333243600057 PM 24263392 ER PT J AU Aldwin, CM Jeong, YJ Igarashi, H Spiro, A AF Aldwin, Carolyn M. Jeong, Yu-Jin Igarashi, Heidi Spiro, Avron, III TI Do Hassles and Uplifts Change With Age? Longitudinal Findings From the VA Normative Aging Study SO PSYCHOLOGY AND AGING LA English DT Article DE affect; aging; emotion regulation; hedonic treadmill; stress appraisals ID ADULT LIFE-SPAN; DAILY STRESSORS; NEGATIVE AFFECT; DEVELOPMENTAL PERSPECTIVE; EMOTIONAL EXPERIENCE; HEDONIC TREADMILL; PERCEIVED STRESS; VULNERABILITY; HAPPINESS; EXPOSURE AB To examine emotion regulation in later life, we contrasted the modified hedonic treadmill theory with developmental theories, using hassles and uplifts to assess emotion regulation in context. The sample was 1,315 men from the VA Normative Aging Study aged 53 to 85 years, who completed 3,894 observations between 1989 and 2004. We computed 3 scores for both hassles and uplifts: intensity (ratings reflecting appraisal processes), exposure (count), and summary (total) scores. Growth curves over age showed marked differences in trajectory patterns for intensity and exposure scores. Although exposure to hassles and uplifts decreased in later life, intensity scores increased. Group-based modeling showed individual differences in patterns of hassles and uplifts intensity and exposure, with relative stability in uplifts intensity, normative nonlinear changes in hassles intensity, and complex patterns of individual differences in exposure for both hassles and uplifts. Analyses with the summary scores showed that emotion regulation in later life is a function of both developmental change and contextual exposure, with different patterns emerging for hassles and uplifts. Thus, support was found for both hedonic treadmill and developmental change theories, reflecting different aspects of emotion regulation in late life. C1 [Aldwin, Carolyn M.; Jeong, Yu-Jin; Igarashi, Heidi] Oregon State Univ, Sch Social & Behav Hlth Sci, Coll Publ Hlth & Human Sci, Program Human Dev & Family Sci, Corvallis, OR 97331 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Aldwin, CM (reprint author), Oregon State Univ, Sch Social & Behav Hlth Sci, 424 Waldo Hall, Corvallis, OR 97331 USA. EM Carolyn.Aldwin@oregonstate.edu FU NIA NIH HHS [AG018436, AG002287, R01 AG018436, R01 AG032037] NR 51 TC 3 Z9 3 U1 1 U2 11 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 MAR PY 2014 VL 29 IS 1 BP 57 EP 71 DI 10.1037/a0035042 PG 15 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA AD7RY UT WOS:000333464400005 PM 24660796 ER PT J AU Freer, PE Wang, JL Rafferty, EA AF Freer, Phoebe E. Wang, Jessica L. Rafferty, Elizabeth A. TI Digital Breast Tomosynthesis in the Analysis of Fat-containing Lesions SO RADIOGRAPHICS LA English DT Article ID OF-THE-LITERATURE; MAMMARY HAMARTOMA; NEEDLE-BIOPSY; RADIAL SCARS; MAMMOGRAPHY; GALACTOCELE; APPEARANCES; EXCISION; CANCER AB Digital breast tomosynthesis (DBT) is rapidly emerging as an important clinical tool for both screening and diagnosis. DBT improves upon mammography by depicting breast tissue on a dynamic sequence of cross-sectional images reconstructed in planes corresponding to their mammographic planes of acquisition. DBT results in markedly reduced summation of overlapping tissue and depicts the margins of masses in far greater detail than mammography. Fat is commonly recognized in both benign and malignant breast masses at DBT, even when no fat is appreciated at mammography. In cases of encapsulated fat-containing masses, the increased detail at DBT often allows the radiologist to definitively classify a mass as benign (eg, lipoma, hamartoma, galactocele, lipid cyst) when mammographic findings alone are equivocal, thereby avoiding unnecessary biopsy or workup. However, when learning to read DBT images, many radiologists misinterpret this rule, mistaking the presence of any fat within a mass for an indication of benignity or an artifact and falsely concluding that an otherwise suspicious mass is not worrisome. If fat seen in breast masses at DBT is not appropriately analyzed, malignant breast masses may be incorrectly classified as probably or even definitely benign. With use of radiologic-pathologic correlation, the authors illustrate cases in which the presence of fat can help correctly classify a mass as benign, and pitfalls in which the presence or absence of fat within a mass is irrelevant and should not influence analysis. (C) RSNA, 2014 . radiographics.rsna.org C1 [Freer, Phoebe E.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Avon Comprehens Care Ctr, MGH Imaging, Dept Radiol, Boston, MA 02114 USA. [Wang, Jessica L.] Massachusetts Gen Hosp, Avon Comprehens Care Ctr, Dept Pathol, Boston, MA 02114 USA. RP Freer, PE (reprint author), Massachusetts Gen Hosp, Avon Comprehens Care Ctr, MGH Imaging, Dept Radiol, 15 Parkman St,Wang ACC-240, Boston, MA 02114 USA. EM pfreer@partners.org OI Freer, Phoebe/0000-0001-6886-7100 FU Hologic FX E.A.R.: Financial activities related to the present article: grant from Hologic. NR 29 TC 3 Z9 3 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2014 VL 34 IS 2 BP 343 EP + DI 10.1148/rg.342135082 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AD0SS UT WOS:000332945000009 PM 24617683 ER PT J AU Choi, J Choi, KH Reddy, LF Fiszdon, JM AF Choi, Jimmy Choi, Kee-Hong Reddy, L. Felice Fiszdon, Joanna M. TI Measuring motivation in schizophrenia: Is a general state of motivation necessary for task-specific motivation? SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Motivation; Psychosocial rehabilitation; Intrinsic motivation; Quality of life scale; Schizophrenia ID SELF-DETERMINATION THEORY; NEGATIVE SYNDROME SCALE; INTRINSIC MOTIVATION; COMPETENCE; REHABILITATION; NEUROCOGNITION; INDIVIDUALS; INVENTORY; FACTORIAL; COMMUNITY AB Despite the important role of motivation in rehabilitation and functional outcomes in schizophrenia, to date, there has been little emphasis on how motivation is assessed. This is important, since different measures may tap potentially discrete motivational constructs, which in turn may have very different associations to important outcomes. In the current study, we used baseline data from 71 schizophrenia spectrum outpatients enrolled in a rehabilitation program to examine the relationship between task-specific motivation, as measured by the Intrinsic Motivation Inventory (IMI), and a more general state of volition/initiation, as measured by the three item Quality of Life (QLS) motivation index. We also examined the relationship of these motivation measures to demographic, clinical and functional variables relevant to rehabilitation outcomes. The two motivation measures were not correlated, and participants with low general state motivation exhibited a full range of task-specific motivation. Only the QLS motivation index correlated with variables relevant to rehabilitation outcomes. The lack of associations between QLS motivation index and IMI subscales suggests that constructs tapped by these measures may be divergent in schizophrenia, and specifically that task-specific intrinsic motivation is not contingent on a general state of motivation. That is, even in individuals with a general low motivational state (i.e. amotivation), interventions aimed at increasing task-specific motivation may still be effective. Moreover, the pattern of interrelationships between the QLS motivation index and variables relevant to psychosocial rehabilitation supports its use in treatment outcome studies. (C) 2014 Elsevier B. V. All rights reserved. C1 [Choi, Jimmy] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Choi, Kee-Hong] Korea Univ, Dept Psychol, Seoul 136701, South Korea. [Reddy, L. Felice] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC 210A, Los Angeles, CA USA. [Reddy, L. Felice] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. [Fiszdon, Joanna M.] VA Connecticut Healthcare Syst, Psychol Serv, West Haven, CT 06511 USA. [Fiszdon, Joanna M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. RP Choi, J (reprint author), Columbia Univ, Med Ctr, 1051 Riverside Dr,Mailbox 100, New York, NY 10032 USA. EM jc3110@columbia.edu; kchoi1@korea.ac.kr; lenafelice@ucla.edu; Joanna.fiszdon@yale.edu FU Department of Veterans Affairs Rehabilitation Research & Development Service [F3195V]; National Institute of Mental Health [K23MH086755] FX This work was supported by the Department of Veterans Affairs Rehabilitation Research & Development Service (J.M.F., F3195V) and the National Institute of Mental Health (J.C., K23MH086755). NR 39 TC 15 Z9 16 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR PY 2014 VL 153 IS 1-3 BP 209 EP 213 DI 10.1016/j.schres.2014.01.027 PG 5 WC Psychiatry SC Psychiatry GA AD2GQ UT WOS:000333052800031 PM 24529609 ER PT J AU Rodriguez, AE Palacios, I Rodriguez-Granillo, AM Mieres, JR Tarragona, S Fernandez-Pereira, C Solorzano, L Pauletto, R Serruys, PW Antoniucci, D AF Rodriguez, Alfredo E. Palacios, Igor Rodriguez-Granillo, Alfredo M. Mieres, Juan R. Tarragona, Sonia Fernandez-Pereira, Carlos Solorzano, Leonardo Pauletto, Ricardo Serruys, Patrick W. Antoniucci, David CA ORAR-3 Investigators TI Comparison of Cost-Effectiveness of Oral Rapamycin Plus Bare-Metal Stents Versus First Generation of Drug-Eluting Stents (from the Randomized Oral Rapamycin in Argentina [ORAR] 3 Trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CLINICAL FOLLOW-UP; PERCUTANEOUS CORONARY INTERVENTION; IMMUNOSUPPRESSIVE THERAPY; RESTENOSIS PREVENTION; III TRIAL; IMPLANTATION; SIROLIMUS; ARTERY; REVASCULARIZATION; OUTCOMES AB The aim of this study was to compare 5-year cost-effectiveness and clinical outcomes of patients with oral rapamycin (OR) plus bare-metal stent versus the drug-eluting stent (DES) strategy. During 2006 to 2007, a total of 200 patients were randomized to OR (n = 100) and DES (n = 100). Primary end point was to compare costs of initial procedure and cost-effectiveness of both revascularization strategies. Safety was evaluated by the composite of death, myocardial infarction, and cerebrovascular accident. Efficacy was assessed by target vessel and target lesion revascularizations. The 2 groups had similar baseline demographic, clinical, and angiographic characteristics. In the DES group, paclitaxel-, zotarolimus-, and sirolimus-eluting stents were used. Five-year clinical follow-up was accomplished in 99% patients. The DES group had significantly higher procedural (p <0.001), discharge to first-year (p = 0.02), and 1- to 5-year costs (p <0.001) compared with the OR group. At 5 years, the composite end point of death, myocardial infarction, and cerebrovascular accident (12% in the OR group vs 25% in the DES group, p = 0.01) was significantly less in the OR group. Target vessel revascularization (14.5% in the OR group vs 21% in the DES group, p = 0.16) and target lesion revascularization (10% in the OR group vs 17.6% in the DES group, p = 0.05) were not significantly different. In conclusion, a strategy of OR plus bare-metal stent was cost saving than a first-generation DES. (C) 2014 Elsevier Inc. All rights reserved. C1 [Rodriguez, Alfredo E.; Rodriguez-Granillo, Alfredo M.] Ctr Estudios Cardiol Intervencionista, Buenos Aires, DF, Argentina. [Rodriguez, Alfredo E.; Mieres, Juan R.; Solorzano, Leonardo; Pauletto, Ricardo] Sanatorio Otamendi & Miroli, Dept Cardiol, Buenos Aires, DF, Argentina. [Rodriguez, Alfredo E.; Mieres, Juan R.; Pauletto, Ricardo] Sanatorio Los Lomas, Dept Cardiol, Buenos Aires, DF, Argentina. [Palacios, Igor] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Tarragona, Sonia] Argentina Assoc Hlth & Econ, Buenos Aires, DF, Argentina. [Fernandez-Pereira, Carlos; Solorzano, Leonardo] Clin IMA, Dept Cardiol, Buenos Aires, DF, Argentina. [Serruys, Patrick W.] Erasmus Thoraxctr, Dept Cardiol, Rotterdam, Netherlands. [Antoniucci, David] Careggi Hosp, Dept Cardiol, Florence, Italy. RP Rodriguez, AE (reprint author), Ctr Estudios Cardiol Intervencionista, Buenos Aires, DF, Argentina. EM rodrigueza@sanatorio-otamendi.co NR 29 TC 3 Z9 4 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2014 VL 113 IS 5 BP 815 EP 821 DI 10.1016/j.amjcard.2013.11.033 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB9UW UT WOS:000332142200011 PM 24528614 ER PT J AU Stefanescu, A Macklin, EA Lin, E Dudzinski, DM Johnson, J Kennedy, KF Jacoby, D Yeh, DD Lewis, GD Yeh, RW Liberthson, R Lui, G Bhatt, AB AF Stefanescu, Ada Macklin, Eric A. Lin, Elaine Dudzinski, David M. Johnson, Jacob Kennedy, Kevin F. Jacoby, Daniel Yeh, Doreen DeFaria Lewis, Gregory D. Yeh, Robert W. Liberthson, Richard Lui, George Bhatt, Ami B. TI Usefulness of the Seattle Heart Failure Model to Identify Adults With Congenital Heart Disease at High Risk of Poor Outcome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GREAT-ARTERIES; PREDICTS SURVIVAL; CARDIAC-SURGERY; EXERCISE; TRANSPOSITION; MORTALITY; MANAGEMENT; CAPACITY AB Our objective was to determine whether the Seattle Heart Failure Model (SHFM) differentiates patients with adult congenital heart disease (ACHD) at high versus low risk for cardiovascular outcomes and poor exercise capacity. The ACHD population is growing and presents increasingly for care in the community and at tertiary centers. Few strategies exist to identify the patients with ACHD at high risk for heart failure and mortality. We studied 153 adults with transposition of the great arteries, Ebstein anomaly, tetralogy of Fa not, double outlet right ventricle, and single ventricle from 2 ACHD centers. The primary outcome was cardiovascular death, with a secondary composite outcome of death, transplant, ventricular assist device, cardiovascular admission, and treatment for arrhythmia. We defined risk groups based on SHFM 5-year predicted survival: high (predicted survival <70%), intermediate (70% to 85%), and low risk (>85%). Ten patients had the primary outcome of death, and 46 the combined end point. The hazard of death in the SHFM high versus the intermediate-risk group was 7.09 (95% confidence interval 1.5 to 33.4, p = 0.01; no deaths in the low-risk group) and the hazard of the composite outcome between the high-versus low-risk group was 6.64 (95% confidence interval 2.5 to 17.6, p = 0.0001). Kaplan-Meier survival analysis showed greater probability of all-cause mortality (p = 0.003) in the high-risk group. In conclusion, the SHFM can help identify subjects with ACHD at risk for adverse outcome and poor cardiopulmonary efficiency. This may add to the care of patients with ACHD in the community and streamline care at tertiary centers. (C) 2014 Elsevier Inc. All rights reserved. C1 [Stefanescu, Ada; Dudzinski, David M.; Yeh, Doreen DeFaria; Lewis, Gregory D.; Yeh, Robert W.; Liberthson, Richard; Bhatt, Ami B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Johnson, Jacob] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Macklin, Eric A.; Kennedy, Kevin F.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Macklin, Eric A.; Kennedy, Kevin F.] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Elaine] Montefiore Med Ctr, Div Cardiol, Bronx, NY 10467 USA. [Lin, Elaine] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Jacoby, Daniel] Yale Univ, Med Ctr, Div Cardiol, New Haven, CT USA. [Lui, George] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Bhatt, AB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM abhatt@mgh.harvard.edu OI Stefanescu Schmidt, Ada/0000-0002-5692-2616; Macklin, Eric/0000-0003-1618-3502 NR 26 TC 5 Z9 5 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2014 VL 113 IS 5 BP 865 EP 870 DI 10.1016/j.amjcard.2013.11.043 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB9UW UT WOS:000332142200019 PM 24411285 ER PT J AU Geyer, BC Xu, M Kabrhel, C AF Geyer, Brian C. Xu, Maria Kabrhel, Christopher TI Patient preferences for testing for pulmonary embolism in the ED using a shared decision-making model SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT; PRETEST PROBABILITY; RANDOMIZED-TRIAL; CT; ANGIOGRAPHY; THRESHOLD; CARE AB Introduction: Shared decision making (SDM) is a process whereby patients and clinicians work together to make informed medical decisions that incorporate patient values. Recent data suggest that, for patients with low pretest probability of pulmonary embolism (PE), doubling the standard D-dimer cutoff may reduce the need for imaging with minimal increase in missed PE diagnoses. We used an SDM approach to determine patient preferences regarding this diagnostic approach. Methods: We prospectively enrolled a consecutive sample of emergency department (ED) patients presenting with chest pain or dyspnea. We provided patients with a standardized description of the diagnostic workup for PE. We also provided image arrays describing the risks of computed tomography in low pretest probability patients and the risks of deferring imaging assuming a D-dimer was less than twice the value normally considered positive. We surveyed patients for their preference to undergo or defer imaging in this scenario. Results: We enrolled 203 ED patients. Mean age was 55 +/- 17 years, and 61% were male. Seventy-four patients (37%) elected to defer computed tomography of the pulmonary arteries testing. Patients with a previous PE diagnosis were less likely to defer computed tomography of the pulmonary arteries testing (P = .007). There was no association between the decision to defer testing and age, sex, family history of PE, or self-assessed risk-taking tendency. Conclusions: When presented with a hypothetical scenario, more than one-third of patients deferred imaging for PE based on low clinical probability and a D-dimer less than twice the normal threshold. An SDM approach is acceptable to patients and may decrease imaging for PE. (C) 2014 Elsevier Inc. All rights reserved. C1 [Geyer, Brian C.; Xu, Maria; Kabrhel, Christopher] Massachusetts Gen Hosp, Ctr Vasc Emergencies, Dept Emergency Med, Boston, MA 02114 USA. RP Geyer, BC (reprint author), BWH MGH Harvard Affiliated Emergency Med Residenc, Boston, MA 02115 USA. EM bgeyer@partners.org; mmxu@partners.org; ckabrhel@partners.org OI Kabrhel, Christopher/0000-0002-8699-7176 FU Massachusetts College of Emergency Medicine FX Massachusetts College of Emergency Medicine. NR 24 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAR PY 2014 VL 32 IS 3 BP 233 EP 236 DI 10.1016/j.ajem.2013.11.019 PG 4 WC Emergency Medicine SC Emergency Medicine GA AC4XV UT WOS:000332525500007 PM 24370071 ER PT J AU Jakobiec, FA Werdich, X AF Jakobiec, Frederick A. Werdich, Xiang TI Androgen Receptor Identification in the Diagnosis of Eyelid Sebaceous Carcinomas SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; EXPRESSION; SKIN; DIFFERENTIATION; MUTATIONS; ADENOMA; GLANDS; CANCER; TUMORS AB PURPOSE: To assess the role of androgen receptor detection in diagnosing eyelid sebaceous carcinomas and to compare it with that of adipophilin. DESIGN: Retrospective, clinicopathologic study. METHODS: Ten sebaceous carcinomas (8 invasive, 2 intraepithelial only) were stained immunohistochemically for androgen receptors and were compared with adipophilin staining. Receptor staining also was performed on benign sebaceous tumors (a sebaceoma and an adenoma) and as controls on eyelid basal cell carcinomas, eyelid squamous cell carcinomas, conjunctival squamous dysplasias, and conjunctival melanomas. RESULTS: All 8 patients with an invasive component of sebaceous carcinoma underwent a biopsy in which the tumor cells showed diffusely positive results for androgen receptors ( >20% of cells and usually >40%) and positive results for adipophilin. Eight cases displaying an intraepithelial (or pagetoid) component of spread also showed diffusely positive results for androgen receptors and adipophilin in at least 1 of multiple biopsy samples from each patient. However, in 8 of 21 separate conjunctival biopsy specimens with intraepithelial cytologic atypia, adipophilin results were negative. A sebaceoma and a sebaceous adenoma also showed positive results for both of these biomarkers. Among the controls, squamous carcinomas and melanomas showed negative results for androgen receptors and adipophilin. Basal cell carcinomas displayed focal receptor positivity in fewer than 5% of cells and showed negative results for adipophilin. CONCLUSIONS: Androgen receptors and adipophilin can separate sebaceous tumors immunohistochemically from squamous carcinomas and melanomas, which showed negative results for both, and from basal cell carcinomas, which showed positive receptor results in a distant minority of cells. Regarding intraepithelial (or pagetoid) spread, androgen receptor detection was more sensitive and reliable than adipophilin in highlighting this component of the disease. C1 [Jakobiec, Frederick A.; Werdich, Xiang] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Suite 328, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 36 TC 8 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2014 VL 157 IS 3 BP 687 EP 696 DI 10.1016/j.ajo.2013.12.009 PG 10 WC Ophthalmology SC Ophthalmology GA AC2QX UT WOS:000332350100025 PM 24333189 ER PT J AU Araki, T Sholl, LM Gerbaudo, VH Hatabu, H Nishino, M AF Araki, Tetsuro Sholl, Lynette M. Gerbaudo, Victor H. Hatabu, Hiroto Nishino, Mizuki TI Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; CT attenuation; lymphoid hyperplasia; thymic hyperplasia; thymus ID POSITRON-EMISSION-TOMOGRAPHY; COMPUTED-TOMOGRAPHY; MYASTHENIA-GRAVIS; EPITHELIAL TUMORS; ABNORMAL THYMUS; FDG UPTAKE; CT; THYMOMA; GLAND; PET AB OBJECTIVE. The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS. Thirty-one patients (nine men and 22 women; age range, 20-68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS. No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in-and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION. CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia. C1 [Araki, Tetsuro; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nishino, Mizuki] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. RP Nishino, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU National Cancer Institutes [1K23CA157631] FX M. Nishino was supported by the National Cancer Institutes (grant 1K23CA157631). NR 33 TC 14 Z9 14 U1 1 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2014 VL 202 IS 3 BP 471 EP 478 DI 10.2214/AJR.13.11210 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC4SK UT WOS:000332510900022 PM 24555583 ER PT J AU Walker, CM Abbott, GF Greene, RE Shepard, JAO Vummidi, D Digumarthy, SR AF Walker, Christopher M. Abbott, Gerald F. Greene, Reginald E. Shepard, Jo-Anne O. Vummidi, Dharshan Digumarthy, Subba R. TI Imaging Pulmonary Infection: Classic Signs and Patterns SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE abscess; fungus; infection; signs ID TREE-IN-BUD; REVERSED HALO SIGN; HIGH-RESOLUTION CT; THIN-SECTION CT; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; RADIOLOGIC-PATHOLOGICAL CORRELATION; NORTH-AMERICAN PARAGONIMIASIS; CRAZY-PAVING PATTERN; HYDATID-DISEASE; COMPUTED-TOMOGRAPHY AB OBJECTIVE. The purposes of this article are to describe common and uncommon imaging signs and patterns of pulmonary infections and to discuss their underlying anatomic and pathophysiologic basis. CONCLUSION. Imaging plays an integral role in the diagnosis and management of suspected pulmonary infections and may reveal useful signs on chest radiographs and CT scans. Detected early, these signs can often be used to predict the causative agent and pathophysiologic mechanism and possibly to optimize patient care. C1 [Walker, Christopher M.; Abbott, Gerald F.; Greene, Reginald E.; Shepard, Jo-Anne O.; Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Thorac Imaging Div, Boston, MA 02114 USA. [Vummidi, Dharshan] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. RP Walker, CM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Thorac Imaging Div, 55 Fruit St, Boston, MA 02114 USA. EM walk0060@gmail.com NR 83 TC 8 Z9 9 U1 1 U2 10 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2014 VL 202 IS 3 BP 479 EP 492 DI 10.2214/AJR.13.11463 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC4SK UT WOS:000332510900023 PM 24555584 ER PT J AU Bennett, DL Cronin, AM Palmer, WE Kattapuram, SV Huang, AJ AF Bennett, Debbie L. Cronin, Angel M. Palmer, William E. Kattapuram, Susan V. Huang, Ambrose J. TI Optimization and Standardization of Technique for Fluoroscopically Guided Suprascapular Nerve Blocks SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE fluoroscopy; intervention; pain management; suprascapular nerve ID CHRONIC SHOULDER PAIN; ROTATOR CUFF TEAR; SUPRASPINATUS; ENTRAPMENT; MANAGEMENT; NEUROPATHY; ANATOMY AB OBJECTIVE. The purpose of this study is to standardize the fluoroscopically guided suprascapular nerve block technique by optimizing patient positioning and imaging features that predict suprascapular notch visibility. MATERIALS AND METHODS. One hundred fifty-five consecutive patients underwent suprascapular nerve block from January 2010 through August 2012. The effect of arm position on suprascapular notch visibility and procedure parameters such as fluoroscopy time were evaluated using a chi-square test and a nonparametric Mann-Whitney U test, respectively. The coracoid process " in profile," a clear space between the coracoid process tip and the top of the glenoid, a visible glenohumeral joint space, and bisection of the glenoid by the projection of the scapular spine were identified as possible predictors for suprascapular notch visualization. Their ability to predict suprascapular notch visibility was assessed using positive predictive value (PPV), sensitivity, logistic regression, and receiver operating characteristic (ROC) curve analysis. RESULTS. Procedures performed with the affected arm positioned above the shoulder (" arm up") yielded increased suprascapular notch visualization (91% vs 47%; p < 0.0001) and decreased fluoroscopy time (1.3 vs 2.0 minutes; p = 0.002) compared with those performed with the affected arm positioned at the patient's side (" arm down"). The four imaging features had 91-95% PPVs for suprascapular notch visibility. Concurrent visualization of all four features yielded the highest discriminative accuracy for suprascapular notch visualization (area under the ROC curve [AUC], 0.870). Discriminative accuracy was good with visualization of only two features (AUC, 0.767-0.844) and fair with visualization of only one feature (AUC, 0.644-0.769). CONCLUSION. Positioning patients arm up and optimizing several key imaging features allows fluoroscopically guided suprascapular nerve blocks to be performed reliably and confidently. C1 [Bennett, Debbie L.; Palmer, William E.; Kattapuram, Susan V.; Huang, Ambrose J.] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA. [Cronin, Angel M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Huang, AJ (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM ajhuang@mgh.harvard.edu NR 26 TC 2 Z9 2 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2014 VL 202 IS 3 BP 576 EP 584 DI 10.2214/AJR.13.10924 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC4SK UT WOS:000332510900033 PM 24555594 ER PT J AU Giralt, S Costa, L Schriber, J DiPersio, J Maziarz, R McCarty, J Shaughnessy, P Snyder, E Bensinger, W Copelan, E Hosing, C Negrin, R Petersen, FB Rondelli, D Soiffer, R Leather, H Pazzalia, A Devine, S AF Giralt, Sergio Costa, Luciano Schriber, Jeffrey DiPersio, John Maziarz, Richard McCarty, John Shaughnessy, Paul Snyder, Edward Bensinger, William Copelan, Edward Hosing, Chitra Negrin, Robert Petersen, Finn Bo Rondelli, Damiano Soiffer, Robert Leather, Helen Pazzalia, Amy Devine, Steven TI Optimizing Autologous Stem Cell Mobilization Strategies to Improve Patient Outcomes: Consensus Guidelines and Recommendations SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Mobilization; Optimal collection; Mobilization failure; Chemomobilization; Plerixafor; Growth factors ID BLOOD PROGENITOR CELLS; COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMA; PLUS G-CSF; LARGE-VOLUME LEUKAPHERESIS; MULTIPLE-MYELOMA PATIENTS; HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER PATIENTS; BONE-MARROW TRANSPLANTATION; CXCR4 ANTAGONIST AMD3100 AB Autologous hematopoietic stem cell transplantation (aHSCT) is a well-established treatment for malignancies such as multiple myeloma (MM) and lymphomas. Various changes in the field over the past decade, including the frequent use of tandem aHSCT in MM, the advent of novel therapies for the treatment of MM and lymphoma, and the addition of new stem cell mobilization techniques, have led to the need to reassess current stem cell mobilization strategies. Mobilization failures with traditional strategies are common and result in delays in treatment and increased cost and resource utilization. Recently, plerixafor-containing strategies have been shown to significantly reduce mobilization failure rates, but the ideal method to maximize stem cell yields and minimize costs associated with collection has not yet been determined. A panel of experts convened to discuss the currently available data on autologous hematopoietic stem cell mobilization and transplantation and to devise guidelines to optimize mobilization strategies. Herein is a summary of their discussion and consensus. (c) 2014 American Society for Blood and Marrow Transplantation. C1 [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Costa, Luciano] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Schriber, Jeffrey] Virginia G Piper Canc Ctr, Canc Transplant Inst, Scottsdale, AZ USA. [DiPersio, John] Washington Univ Sch Med St Louis, St Louis, MO USA. [Maziarz, Richard] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [McCarty, John] Virginia Commonwealth Univ, Richmond, VA USA. [Shaughnessy, Paul] Texas Transplant Inst, San Antonio, TX USA. [Snyder, Edward] Yale Univ Med Sch, New Haven, CT USA. [Bensinger, William] Fred Hutchinson Canc Res Inst, Seattle, WA USA. [Copelan, Edward] Carolinas HealthCare Syst, Levine Canc Inst 1, Charlotte, NC USA. [Hosing, Chitra] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Negrin, Robert] Stanford Sch Med, Stanford, CA USA. [Petersen, Finn Bo] Intermt Healthcare, Intermt Blood & Marrow Transplant Program, Salt Lake City, UT USA. [Rondelli, Damiano] Univ Illinois Chicago Canc Ctr, Sect Hematol Oncol, Chicago, IL USA. [Soiffer, Robert] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Leather, Helen; Pazzalia, Amy] Univ Florida, Gainesville, FL USA. [Devine, Steven] Ohio State Univ Comprehens Canc Ctr, Dept Internal Med Hematol Oncol, Columbus, OH USA. RP Giralt, S (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Translantat Serv, New York, NY 10065 USA. EM GiraltS@mskcc.org OI Hosing, Chitra/0000-0003-0409-5556 FU Celgene; Millennium; Sanofi; Onyx; Genentech; Novartis; Genzyme; Therakos; Seattle Genetics; Spectrum Pharmaceuticals; Otsuka FX This project was funded by Celgene, Millennium, Sanofi, Onyx, Genentech, Novartis, Genzyme, Therakos, Seattle Genetics, Spectrum Pharmaceuticals, and Otsuka. NR 200 TC 48 Z9 50 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2014 VL 20 IS 3 BP 295 EP 308 DI 10.1016/j.bbmt.2013.10.013 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AC8WV UT WOS:000332816700003 PM 24141007 ER PT J AU Palmer, J Williams, K Inamoto, Y Chai, XY Martin, PJ Tomas, LS Cutler, C Weisdorf, D Kurland, BF Carpenter, PA Pidala, J Pavletic, SZ Wood, W Jacobsohn, D Arai, S Arora, M Jagasia, M Vogelsang, GB Lee, SJ AF Palmer, Jeanne Williams, Kirsten Inamoto, Yoshihiro Chai, Xiaoyu Martin, Paul J. Tomas, Linus Santo Cutler, Corey Weisdorf, Daniel Kurland, Brenda F. Carpenter, Paul A. Pidala, Joseph Pavletic, Steven Z. Wood, William Jacobsohn, David Arai, Sally Arora, Mukta Jagasia, Madan Vogelsang, Georgia B. Lee, Stephanie J. TI Pulmonary Symptoms Measured by the National Institutes of Health Lung Score Predict Overall Survival, Nonrelapse Mortality, and Patient-Reported Outcomes In Chronic Graft-Versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic graft-versus-host disease; Bronchiolitis obliterans syndrome ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; BRONCHIOLITIS OBLITERANS SYNDROME; AIR-FLOW OBSTRUCTION; LONG-TERM SURVIVORS; CONCORDANCE CORRELATION-COEFFICIENT; TOTAL-BODY IRRADIATION; RISK-FACTORS; CHRONIC GVHD; COMPLICATIONS AB The 2005 National Institutes of Health (NIH) Consensus Conference recommended assessment of lung function in patients with chronic graft-versus-host disease (GVHD) by both pulmonary function tests (PFTs) and assessment of pulmonary symptoms. We tested whether pulmonary measures were associated with nonrelapse mortality (NRM), overall survival (OS), and patient-reported outcomes (PRO). Clinician and patient-reported data were collected serially in a prospective, multicenter, observational study. Available PFT data were abstracted. Cox regression models were fit for outcomes using a time-varying covariate model for lung function measures and adjusting for patient and transplantation characteristics and nonlung chronic GVHD severity. A total of 1591 visits (496 patients) were used in this analysis. The NIH symptom-based lung score was associated with NRM (P = .02), OS (P = .02), patient-reported symptoms (P < .001) and functional status (P < .001). Worsening of NIH symptom-based lung score over time was associated with higher NRM and lower survival. All other measures were not associated with OS or NRM; although, some were associated with patient-reported lung symptoms. In conclusion, the NIH symptom-based lung symptom score of 0 to 3 is associated with NRM, OS, and PRO measures in patients with chronic GVHD. Worsening of the NIH symptom-based lung score was associated with increased mortality. (C) 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Palmer, Jeanne] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Williams, Kirsten; Jacobsohn, David] Ctr Canc & Blood Disorders, Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Washington, DC USA. [Inamoto, Yoshihiro; Chai, Xiaoyu; Martin, Paul J.; Carpenter, Paul A.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Tomas, Linus Santo] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weisdorf, Daniel; Arora, Mukta] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Kurland, Brenda F.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Pavletic, Steven Z.] NCI, NIH, Bethesda, MD 20892 USA. [Wood, William] Univ N Carolina, Linenberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Arai, Sally] Stanford Univ Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA USA. [Jagasia, Madan] Vanderbilt Univ Sch Med, Hematol & Stem Cell Transplant Program, Nashville, TN USA. [Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Palmer, J (reprint author), Blood & Marrow Transplant Program, 5777 East Mayo Blvd, Phoenix, AZ 85054 USA. EM palmer.jeanne@mayo.edu OI Wood, William/0000-0001-7439-2543; Kurland, Brenda/0000-0002-5669-0595 FU National Institutes of Health (NIH) [CA118953, CA163438]; NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science; National Cancer Institute; Fred Hutchinson Cancer Research Center FX This work was supported by grants CA118953 and CA163438 from the National Institutes of Health (NIH). The Chronic GVHD Consortium (U54 CA163438) is a part of the NIH Rare Diseases Clinical Research Network, supported through collaboration between the NIH Office of Rare Diseases Research at the National Center for Advancing Translational Science, the National Cancer Institute, and the Fred Hutchinson Cancer 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. NR 35 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2014 VL 20 IS 3 BP 337 EP 344 DI 10.1016/j.bbmt.2013.11.025 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AC8WV UT WOS:000332816700008 PM 24315845 ER PT J AU Sabloff, M Sobecks, RM Ahn, KW Zhu, XC de Lima, M Brown, JR Inamoto, Y Holland, HK Aljurf, MD Laughlin, MJ Kamble, RT Hsu, JW Wirk, BM Seftel, M Lewis, ID Arora, M Alyea, EP Kalaycio, ME Cortes, J Maziarz, RT Gale, RP Saber, W AF Sabloff, Mitchell Sobecks, Ronald M. Ahn, Kwang Woo Zhu, Xiaochun de Lima, Marcos Brown, Jennifer R. Inamoto, Yoshihiro Holland, H. Kent Aljurf, Mahmoud D. Laughlin, Mary J. Kamble, Rammurti T. Hsu, Jack W. Wirk, Baldeep M. Seftel, Matthew Lewis, Ian D. Arora, Mukta Alyea, Edwin P. Kalaycio, Matt E. Cortes, Jorge Maziarz, Richard T. Gale, Robert Peter Saber, Wael TI Does Total Body Irradiation Conditioning Improve Outcomes of Myeloablative Human Leukocyte Antigen-Identical Sibling Transplantations for Chronic Lymphocytic Leukemia? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Chronic lymphocytic leukemia; Total body irradiation; Conditioning; Myeloablative ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; VITAMIN-E; REQUIREMENTS; COPPER; SELENIUM; ZINC AB An allogeneic hematopoietic cell transplantation from an HLA-identical donor after high-dose (myeloablative) pretransplantation conditioning is an effective therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a highly radiosensitive cancer, we hypothesized that total body irradiation (TB!) conditioning regimens may be associated with better outcomes than those without TBI. To answer this, we analyzed data from 180 subjects with CLL receiving myeloablative doses of TBI (n = 126) or not (n = 54), who received transplants from an HLA-identical sibling donor between 1995 and 2007 and reported to the Center for International Blood & Marrow Transplant Research. At 5 years, treatment-related mortality was 48% (95% confidence interval [CI], 39% to 57%) versus 50% (95% CI, 36% to 64%); P = NS. Relapse rates were 17% (95% CI, 11% to 25%) versus 22% (95% Cl, 11% to 35%); P = NS. Five-year progression-free survival and overall survival were 34% (95% CI, 26% to 43%) versus 28% (95% CL 15% to 42%); P = NS and 42% (95% CI, 33% to 51%) versus 33% (95% CI, 19% to 48%); P = NS, respectively. The single most common cause of death in both cohorts was recurrent/progressive CLL. No variable tested in the multivariate analysis was found to significantly affect these outcomes, including having failed fludarabine. Within the limitations of this study, we found no difference in HLA-identical sibling transplantation outcomes between myeloablative TBI and chemotherapy pretransplantation conditioning in persons with CLL. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Sabloff, Mitchell] Univ Ottawa, Dept Med, Div Hematol, Ottawa, ON K1H 8L6, Canada. [Sabloff, Mitchell] Ottawa Hosp Res Inst, Ottawa, ON K1H 8L6, Canada. [Sobecks, Ronald M.; Kalaycio, Matt E.] Cleveland Clin Fdn, Div Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA. [Ahn, Kwang Woo] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Zhu, Xiaochun; Saber, Wael] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI 53226 USA. [de Lima, Marcos] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Div Hematol Malignancies & Stem Cell Transplantat, Cleveland, OH USA. [Brown, Jennifer R.; Alyea, Edwin P.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Inamoto, Yoshihiro] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Holland, H. Kent] Northside Hosp, Blood & Marrow Transplant Program, Div Hematol & Oncol, Atlanta, GA USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi Arabia. [Laughlin, Mary J.] Univ Virginia Hlth Syst, Univ Hosp Case Med Ctr, Hematopoiet Cell Transplantat Program, Charlottesville, VA USA. [Kamble, Rammurti T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Hsu, Jack W.] Shands Healthcare, Dept Med, Div Hematol & Oncol, Gainesville, FL USA. [Hsu, Jack W.] Univ Florida, Gainesville, FL USA. [Wirk, Baldeep M.] SUNY Stony Brook, Div Hematol & Oncol, Med Ctr, Stony Brook, NY 11794 USA. [Seftel, Matthew] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada. [Lewis, Ian D.] Royal Adelaide Hosp, Haematol & Bone Marrow Transplant Unit, Adelaide, SA 5000, Australia. [Arora, Mukta] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplant, Minneapolis, MN USA. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Sect Hematol, London, England. RP Sabloff, M (reprint author), Univ Ottawa, Dept Med, Div Hematol, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. EM msabloff@ottawahospital.on.ca OI Sabloff, Mitchell/0000-0002-0122-6138 FU Otsuka Pharmaceutical Co., Ltd., Japan FX Financial disclosure: Fees for measurement of vitamins and trace elements were covered by Otsuka Pharmaceutical Co., Ltd., Japan. NR 16 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2014 VL 20 IS 3 BP 421 EP 434 DI 10.1016/j.bbmt.2013.11.032 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AC8WV UT WOS:000332816700020 PM 24321745 ER PT J AU Tripathi, MM Hajjarian, Z Van Cott, EM Nadkarni, SK AF Tripathi, Markandey M. Hajjarian, Zeinab Van Cott, Elizabeth M. Nadkarni, Seemantini K. TI Assessing blood coagulation status with laser speckle rheology SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID DIFFUSING-WAVE-SPECTROSCOPY; SURFACE-PLASMON RESONANCE; WHOLE-BLOOD; COMPLEX FLUIDS; ATHEROSCLEROTIC PLAQUES; VISCOELASTIC PROPERTIES; MONITORING COAGULATION; MECHANICAL-PROPERTIES; TISSUE; THROMBOELASTOGRAPHY AB We have developed and investigated a novel optical approach, Laser Speckle Rheology (LSR), to evaluate a patient's coagulation status by measuring the viscoelastic properties of blood during coagulation. In LSR, a blood sample is illuminated with laser light and temporal speckle intensity fluctuations are measured using a high-speed CMOS camera. During blood coagulation, changes in the viscoelastic properties of the clot restrict Brownian displacements of light scattering centers within the sample, altering the rate of speckle intensity fluctuations. As a result, blood coagulation status can be measured by relating the time scale of speckle intensity fluctuations with clinically relevant coagulation metrics including clotting time and fibrinogen content. Our results report a close correlation between coagulation metrics measured using LSR and conventional coagulation results of activated partial thromboplastin time, prothrombin time and functional fibrinogen levels, creating the unique opportunity to evaluate a patient's coagulation status in real-time at the point of care. (C) 2014 Optical Society of America C1 [Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02144 USA. RP Tripathi, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM snadkarni@mgh.harvard.edu FU Air Force Office of Scientific Research [FA9550-11-1-0331]; NIH-NHLBI [5U54EB015408-02]; Partners Healthcare systems Innovation; Wellman-Bullock Fellowship FX This work has been supported by grants from the Air Force Office of Scientific Research #FA9550-11-1-0331 (SN), NIH-NHLBI #5U54EB015408-02 (S.N), Partners Healthcare systems Innovation grant (S.N) and the Wellman-Bullock Fellowship grant (M.T). The authors thank Haemonetics Inc. for providing supplies and reagents, and Mr. Blake Maddux from the MGH special coagulation laboratory for his assistance in obtaining blood specimens used in this project. NR 61 TC 14 Z9 14 U1 0 U2 18 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAR 1 PY 2014 VL 5 IS 3 BP 817 EP 831 DI 10.1364/BOE.5.000817 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AC6YF UT WOS:000332671800014 PM 24688816 ER PT J AU Nambudiri, VE Tsiaras, WG Schmidt, BA Huang, JT AF Nambudiri, V. E. Tsiaras, W. G. Schmidt, B. A. Huang, J. T. TI Total leukoderma and leukotrichia in a child after hematopoietic SCT: report of a case and review of the literature SO BONE MARROW TRANSPLANTATION LA English DT Letter ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CELL TRANSPLANTATION; VITILIGO C1 [Nambudiri, V. E.; Tsiaras, W. G.] Harvard Combined Dermatol Residency Program, Boston, MA 02114 USA. [Nambudiri, V. E.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Schmidt, B. A.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Huang, J. T.] Boston Childrens Hosp, Dermatol Program, Dept Pediat, Boston, MA USA. [Huang, J. T.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Nambudiri, VE (reprint author), Harvard Combined Dermatol Residency Program, Boston, MA 02114 USA. EM Jennifer.Huang@childrens.harvard.edu NR 10 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2014 VL 49 IS 3 BP 460 EP 462 DI 10.1038/bmt.2013.200 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA AC6MQ UT WOS:000332638100027 PM 24335999 ER PT J AU Almendro, V Kim, HJ Cheng, YK Gonen, M Itzkovitz, S Argani, P van Oudenaarden, A Sukumar, S Michor, F Polyak, K AF Almendro, Vanessa Kim, Hee Jung Cheng, Yu-Kang Goenen, Mithat Itzkovitz, Shalev Argani, Pedram van Oudenaarden, Alexander Sukumar, Saraswati Michor, Franziska Polyak, Kornelia TI Genetic and Phenotypic Diversity in Breast Tumor Metastases SO CANCER RESEARCH LA English DT Article ID CANCER CELLS; MATHEMATICAL-THEORY; IN-SITU; CARCINOMAS; HETEROGENEITY; PROGRESSION; PATTERNS; COMMUNICATION; AMPLIFICATION; RESISTANCE AB Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance, our knowledge of how cancer cell populations change during metastatic progression is limited. Here, we investigated intratumor genetic and phenotypic heterogeneity during metastatic progression of breast cancer. Weanalyzed cellular genotypes and phenotypes at the single cell level by performing immunoFISH in intact tissue sections of distant metastatic tumors from rapid autopsy cases and from primary tumors and matched lymph node metastases collected before systemic therapy. Wecalculated the Shannon index of intratumor diversity in all cancer cells and within phenotypically distinct cell populations. We found that the extent of intratumor genetic diversity was similar regardless of the chromosomal region analyzed, implying that it may reflect an inherent property of the tumors. We observed that genetic diversity was highest in distant metastases and was generally concordant across lesions within the same patient, whereas treatment-naive primary tumors and matched lymph node metastases were frequently genetically more divergent. In contrast, cellular phenotypes were more discordant between distant metastases than primary tumors and matched lymph node metastases. Diversity for 8q24 was consistently higher in HER2_ tumors compared with other subtypes and in metastases of triple-negative tumors relative to primary sites. We conclude that our integrative method that couples ecologic models with experimental data in human tissue samples could be used for the improved prognostication of patients with cancer and for the design of more effective therapies for progressive disease. (C) 2014 AACR. C1 [Almendro, Vanessa; Kim, Hee Jung; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Cheng, Yu-Kang; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Almendro, Vanessa; Kim, Hee Jung; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Almendro, Vanessa; Kim, Hee Jung; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Cheng, Yu-Kang; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Itzkovitz, Shalev; van Oudenaarden, Alexander] MIT, Dept Phys, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Itzkovitz, Shalev; van Oudenaarden, Alexander] MIT, Dept Biol, Koch Inst Integrat Canc Res, Cambridge, MA USA. [Polyak, Kornelia] Harvard Stem Cell Inst, Cambridge, MA USA. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Argani, Pedram] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Sukumar, Saraswati] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Almendro, Vanessa] Hosp Clin Barcelona, Dept Med Oncol, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain. [Kim, Hee Jung] MizMedi Hosp, Dept Pathol, Seoul, South Korea. [Itzkovitz, Shalev] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. [van Oudenaarden, Alexander] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, Netherlands. [van Oudenaarden, Alexander] Univ Med Ctr Utrecht, Utrecht, Netherlands. RP Polyak, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D740C, Boston, MA 02215 USA. EM michor@jimmy.harvard.edu; Kornelia_polyak@dfci.harvard.edu FU National Cancer Institute Physical Sciences-Oncology Centers [U54CA143874, U54CA143798]; Cellex foundation; Breast Cancer Research Foundation FX This work was supported by the National Cancer Institute Physical Sciences-Oncology Centers, U54CA143874 (A.V. Oudenaarden) and U54CA143798 (F. Michor and M. Gonen), the Cellex foundation (V. Almendro), and the Breast Cancer Research Foundation (K. Polyak). NR 35 TC 63 Z9 64 U1 2 U2 19 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 MAR 1 PY 2014 VL 74 IS 5 BP 1338 EP 1348 DI 10.1158/0008-5472.CAN-13-2357-T PG 11 WC Oncology SC Oncology GA AC4FG UT WOS:000332475900008 PM 24448237 ER PT J AU Peng, HZ Talebzadeh-Farrooji, M Osborne, MJ Prokop, JW McDonald, PC Karar, J Hou, ZY He, M Kebebew, E Orntoft, T Herlyn, M Caton, AJ Fredericks, W Malkowicz, B Paterno, CS Carolin, AS Speicher, DW Skordalakes, E Huang, QH Dedhar, S Borden, KLB Rauscher, FJ AF Peng, Hongzhuang Talebzadeh-Farrooji, Mehdi Osborne, Michael J. Prokop, Jeremy W. McDonald, Paul C. Karar, Jayashree Hou, Zhaoyuan He, Mei Kebebew, Electron Orntoft, Torben Herlyn, Meenhard Caton, Andrew J. Fredericks, William Malkowicz, Bruce Paterno, Christopher S. Carolin, Alexandra S. Speicher, David W. Skordalakes, Emmanuel Huang, Qihong Dedhar, Shoukat Borden, Katherine L. B. Rauscher, Frank J., III TI LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic Lesions That Regulates Cell Motility and Tumor Progression by Directly Binding to and Activating the Integrin-Linked Kinase SO CANCER RESEARCH LA English DT Article ID ANKYRIN REPEAT DOMAIN; TRANSCRIPTIONAL REPRESSION; STRUCTURAL BASIS; BACK AGAIN; PINCH; ILK; ADHESION; CANCER; DIFFERENTIATION; COMPLEX AB Proteins that communicate signals from the cytoskeleton to the nucleus are prime targets for effectors of metastasis as they often transduce signals regulating adhesion, motility, and invasiveness. LIM domain proteins shuttle between the cytoplasm and the nucleus, and bind to partners in both compartments, often coupling changes in gene expression to extracellular cues. In this work, we characterize LIMD2, a mechanistically undefined LIM-only protein originally found to be overexpressed in metastatic lesions but absent in the matched primary tumor. LIMD2 levels in fresh and archival tumors positively correlate with cell motility, metastatic potential, and grade, including bladder, melanoma, breast, and thyroid tumors. LIMD2 directly contributes to these cellular phenotypes as shown by overexpression, knockdown, and reconstitution experiments in cell culture models. The solution structure of LIMD2 that was determined using nuclear magnetic resonance revealed a classic LIM-domain structure that was highly related to LIM1 of PINCH1, a core component of the integrin-linked kinase-parvin-pinch complex. Structural and biochemical analyses revealed that LIMD2 bound directly to the kinase domain of integrin-linked kinase (ILK) near the active site and strongly activated ILK kinase activity. Cells that were null for ILK failed to respond to the induction of invasion by LIMD2. This strongly suggests that LIMD2 potentiates its biologic effects through direct interactions with ILK, a signal transduction pathway firmly linked to cell motility and invasion. In summary, LIMD2 is a new component of the signal transduction cascade that links integrin-mediated signaling to cell motility/metastatic behavior and may be a promising target for controlling tumor spread. (c) 2014 AACR. C1 [Peng, Hongzhuang; Karar, Jayashree; Hou, Zhaoyuan; Herlyn, Meenhard; Caton, Andrew J.; Paterno, Christopher S.; Carolin, Alexandra S.; Speicher, David W.; Skordalakes, Emmanuel; Huang, Qihong; Rauscher, Frank J., III] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Fredericks, William; Malkowicz, Bruce] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Fredericks, William; Malkowicz, Bruce] Vet Affairs Med Ctr, Philadelphia, PA USA. [He, Mei; Kebebew, Electron] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Prokop, Jeremy W.] Univ Akron, Akron, OH 44325 USA. [Orntoft, Torben] Aarhus Univ Hosp, Skejby, Denmark. [Talebzadeh-Farrooji, Mehdi; Osborne, Michael J.; Borden, Katherine L. B.] Univ Montreal, Inst Res Immunol & Canc, Dept Pathol & Cell Biol, Montreal, PQ H3C 3J7, Canada. [McDonald, Paul C.; Dedhar, Shoukat] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3, Canada. RP Borden, KLB (reprint author), Univ Montreal, Inst Res Immunol & Canc, Dept Pathol & Cell Biol, Montreal, PQ H3C 3J7, Canada. EM katherine.borden@umontreal.ca; rauscher@wistar.org OI Skordalakes, Emmanuel/0000-0002-7600-2833 FU NIH [CA129833, CA010815, CA163761]; DOD-BCRP [W81XWH-11-1-0494] FX Work in the Rauscher laboratory is supported by NIH grants CA129833, CA010815, CA163761, and DOD-BCRP W81XWH-11-1-0494, The Samuel Waxman Cancer Research Foundation, Susan G. Komen for the Cure, and The Noreen O'Neill Foundation for Melanoma Research. K. L. B. Borden holds a Canada Research Chair and is supported by NIH grants NIH RO1-80728 and NIH 98571. NR 40 TC 7 Z9 10 U1 1 U2 12 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 MAR 1 PY 2014 VL 74 IS 5 BP 1390 EP 1403 DI 10.1158/0008-5472.CAN-13-1275 PG 14 WC Oncology SC Oncology GA AC4FG UT WOS:000332475900013 PM 24590809 ER PT J AU Hines, WC Su, Y Kuhn, I Polyak, K Bissell, MJ AF Hines, William C. Su, Ying Kuhn, Irene Polyak, Kornelia Bissell, Mina J. TI Sorting Out the FACS: A Devil in the Details SO CELL REPORTS LA English DT Editorial Material C1 [Hines, William C.; Kuhn, Irene; Bissell, Mina J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. [Su, Ying; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Su, Ying; Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Su, Ying; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hines, WC (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Mailstop 977R225A,1 Cyclotron Rd, Berkeley, CA 94720 USA. EM chines@lbl.gov; ying_su@dfci.harvard.edu FU NCI NIH HHS [R01CA140663,, CA116235-04S1, P01 CA080111, P50 CA89383, R37CA064786,, U01 CA143233, U54CA112970,, U54CA143836] NR 7 TC 22 Z9 22 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD MAR PY 2014 VL 6 IS 5 BP 779 EP 781 DI 10.1016/j.celrep.2014.02.021 PG 3 WC Cell Biology SC Cell Biology GA AD2BL UT WOS:000333037800001 PM 24630040 ER PT J AU Villani, E Baudouin, C Efron, N Hamrah, P Kojima, T Patel, SV Pflugfelder, SC Zhivov, A Dogru, M AF Villani, Edoardo Baudouin, Christophe Efron, Nathan Hamrah, Pedram Kojima, Takashi Patel, Sanjay V. Pflugfelder, Stephen C. Zhivov, Andrey Dogru, Murat TI In Vivo Confocal Microscopy of the Ocular Surface: From Bench to Bedside SO CURRENT EYE RESEARCH LA English DT Review DE Confocal microscopy; dry eye; glaucoma; keratitis; keratoplasty ID CONTACT-LENS WEAR; FUCHS ENDOTHELIAL DYSTROPHY; LASER-SCANNING MICROSCOPY; SUBBASAL NERVE PLEXUS; KERATOMILEUSIS FEMTOSECOND-LASER; MEIBOMIAN GLAND DYSFUNCTION; PRIMARY SJOGRENS-SYNDROME; CORNEAL LIGHT SCATTER; LONG-TERM WEAR; DRY EYE AB In vivo confocal microscopy (IVCM) is an emerging technology that provides minimally invasive, high resolution, steady-state assessment of the ocular surface at the cellular level. Several challenges still remain but, at present, IVCM may be considered a promising technique for clinical diagnosis and management. This mini-review summarizes some key findings in IVCM of the ocular surface, focusing on recent and promising attempts to move "from bench to bedside''. IVCM allows prompt diagnosis, disease course follow-up, and management of potentially blinding atypical forms of infectious processes, such as acanthamoeba and fungal keratitis. This technology has improved our knowledge of corneal alterations and some of the processes that affect the visual outcome after lamellar keratoplasty and excimer keratorefractive surgery. In dry eye disease, IVCM has provided new information on the whole-ocular surface morphofunctional unit. It has also improved understanding of pathophysiologic mechanisms and helped in the assessment of prognosis and treatment. IVCM is particularly useful in the study of corneal nerves, enabling description of the morphology, density, and disease-or surgically induced alterations of nerves, particularly the subbasal nerve plexus. In glaucoma, IVCM constitutes an important aid to evaluate filtering blebs, to better understand the conjunctival wound healing process, and to assess corneal changes induced by topical antiglaucoma medications and their preservatives. IVCM has significantly enhanced our understanding of the ocular response to contact lens wear. It has provided new perspectives at a cellular level on a wide range of contact lens complications, revealing findings that were not previously possible to image in the living human eye. The final section of this mini-review provides a focus on advances in confocal microscopy imaging. These include 2D wide-field mapping, 3D reconstruction of the cornea and automated image analysis. C1 [Villani, Edoardo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Villani, Edoardo] San Giuseppe Hosp, Eye Clin, Milan, Italy. [Villani, Edoardo] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Eye Clin, Milan, Italy. [Baudouin, Christophe] Quinze Vingts Natl Ophthalmol Hosp, Paris, France. [Efron, Nathan] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Sch Optometry & Vis Sci, Brisbane, Qld 4001, Australia. [Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv,Med Sch, Dept Ophthalmol,Ocular Surface Imaging Ctr, Boston, MA USA. [Kojima, Takashi; Dogru, Murat] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. [Patel, Sanjay V.] Mayo Clin, Dept Ophthalmol, Rochester, MN USA. [Pflugfelder, Stephen C.] Baylor Coll Med, Cullen Eye Inst, Dept Ophthalmol, Ocular Surface Ctr, Houston, TX 77030 USA. [Zhivov, Andrey] Univ Rostock, Dept Ophthalmol, D-18055 Rostock, Germany. RP Villani, E (reprint author), Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. EM edoardo.villani@unimi.it OI Villani, Edoardo/0000-0003-3811-5893 FU Research to Prevent Blindness Grant Program, New York, NY; Mayo Foundation, Rochester, MN [National Institutes of Health [EY11915]; Oshman Foundation, Houston, TX; William Stamps Farish Fund, Houston, TX; Hamill Foundation, Houston, TX FX This work was supported in part by: Research to Prevent Blindness Grant Program, New York, NY (Unrestricted Departmental Grant; to S. V. P. as Olga Keith Wiess Scholar and to S. C. P.), the Mayo Foundation, Rochester, MN [National Institutes of Health Grant EY11915 (to S. C. P.), the Oshman Foundation, Houston, TX (to S. C. P.), the William Stamps Farish Fund, Houston, TX (to S. C. P.) and the Hamill Foundation, Houston, TX (to S.C.P.) NR 165 TC 46 Z9 48 U1 7 U2 22 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD MAR PY 2014 VL 39 IS 3 BP 213 EP 231 DI 10.3109/02713683.2013.842592 PG 19 WC Ophthalmology SC Ophthalmology GA AD1YS UT WOS:000333030200001 PM 24215436 ER PT J AU May, CJ Compton, N Falsey, RR Knezevich, S AF May, Caitlin J. Compton, Nicholas Falsey, Ryan R. Knezevich, Stevan TI The best diagnosis is: a. chondroid syringoma b. dermatofibroma c. leiomyosarcoma d. myofibroma e. schwannoma SO CUTIS LA English DT Editorial Material ID FEATURES C1 [May, Caitlin J.; Falsey, Ryan R.] Univ Washington, Div Dermatol, Seattle, WA 98195 USA. [Knezevich, Stevan] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Compton, Nicholas; Knezevich, Stevan] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP May, CJ (reprint author), 660 S Columbian Way, Seattle, WA 98108 USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU QUADRANT HEALTHCOM INC PI PARSIPPANY PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA SN 0011-4162 EI 2326-6929 J9 CUTIS JI Cutis PD MAR PY 2014 VL 93 IS 3 BP 129 EP + PG 3 WC Dermatology SC Dermatology GA AD2MW UT WOS:000333070800004 PM 24738101 ER PT J AU Conant, KD Finucane, B Cleary, N Martin, A Muss, C Delany, M Murphy, EK Rabe, O Luchsinger, K Spence, SJ Schanen, C Devinsky, O Cook, EH LaSalle, J Reiter, LT Thibert, RL AF Conant, Kerry D. Finucane, Brenda Cleary, Nicole Martin, Ashley Muss, Candace Delany, Mary Murphy, Erin K. Rabe, Olivia Luchsinger, Kadi Spence, Sarah J. Schanen, Carolyn Devinsky, Orrin Cook, Edwin H. LaSalle, Janine Reiter, Lawrence T. Thibert, Ronald L. TI A survey of seizures and current treatments in 15q duplication syndrome SO EPILEPSIA LA English DT Article DE Dup15q; Epilepsy; Isodicentric chromosome 15q; Seizures ID INV DUP 15; AUTISM-SPECTRUM DISORDERS; ANGELMAN-SYNDROME; GABA(A) RECEPTOR; PROXIMAL 15Q; INTERSTITIAL DUPLICATIONS; GENERALIZED EPILEPSY; MARKER CHROMOSOMES; MECP2 DEFICIENCY; NATURAL-HISTORY AB ObjectiveSeizures are common in individuals with duplications of chromosome 15q11.2-q13 (Dup15q). The goal of this study was to examine the phenotypes and treatments of seizures in Dup15q in a large population. MethodsA detailed electronic survey was conducted through the Dup15q Alliance containing comprehensive questions regarding seizures and their treatments in Dup15q. ResultsThere were 95 responses from Dup15q families. For the 83 with idic(15), 63% were reported to have seizures, of which 81% had multiple seizure types and 42% had infantile spasms. Other common seizure types were tonic-clonic, atonic, myoclonic, and focal. Only 3 of 12 individuals with int dup(15) had seizures. Broad spectrum antiepileptic drugs (AEDs) were the most effective medications, but carbamazepine and oxcarbazepine were also effective, although typical benzodiazepines were relatively ineffective. There was a 24% response rate (>90% seizure reduction) to the first AED tried. For those with infantile spasms, adrenocorticotropic hormone (ACTH) was more effective than vigabatrin. SignificanceThis is the largest study assessing seizures in Duplication 15q syndrome, but because this was a questionnaire-based study with a low return rate, it is susceptible to bias. Seizures are common in idic(15) and typically difficult to control, often presenting with infantile spasms and progressing to a Lennox-Gastaut-type syndrome. Seizures in those with int dup(15) are less common, with a frequency similar to the general autism population. In addition to broad spectrum AED, medications such as carbamazepine and oxcarbazepine are also relatively effective in controlling seizures in this population, suggesting a possible multifocal etiology, which may also explain the high rate of infantile spasms. Our small sample suggests a relative lack of efficacy of vigabatrin and other -aminobutyric acid (GABA)ergic medications, such as typical benzodiazepines, which may be attributable to abnormal GABAergic transmission resulting from the duplication of a cluster of GABA3 receptor genes in the 15q11.2-13 region. C1 [Conant, Kerry D.; Martin, Ashley; Murphy, Erin K.; Rabe, Olivia; Thibert, Ronald L.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Finucane, Brenda] Geisinger Hlth Syst, Lewisburg, PA USA. [Finucane, Brenda; Cleary, Nicole; Luchsinger, Kadi; Spence, Sarah J.; Schanen, Carolyn; Devinsky, Orrin; Cook, Edwin H.; Reiter, Lawrence T.; Thibert, Ronald L.] Dup15q Alliance, Alliance, NY USA. [Muss, Candace; Delany, Mary] Elwyn, Elwyn, PA USA. [Spence, Sarah J.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Schanen, Carolyn] DuPont Co Inc, Wilmington, DC USA. [Devinsky, Orrin] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA. [Cook, Edwin H.] Univ Illinois, Chicago, IL USA. [Reiter, Lawrence T.] Univ Calif Davis, Genome Ctr, MIND Inst, Davis, CA 95616 USA. [Reiter, Lawrence T.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. RP Thibert, RL (reprint author), 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM rthibert@partners.org OI Reiter, Lawrence/0000-0002-4100-2630; Devinsky, Orrin/0000-0003-0044-4632; LaSalle, Janine/0000-0002-3480-2031 FU NIEHS NIH HHS [R01 ES021707] NR 40 TC 20 Z9 23 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD MAR PY 2014 VL 55 IS 3 BP 396 EP 402 DI 10.1111/epi.12530 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AC7CQ UT WOS:000332685000008 PM 24502430 ER PT J AU Heck, CN King-Stephens, D Massey, AD Nair, DR Jobst, BC Barkley, GL Salanova, V Cole, AJ Smith, MC Gwinn, RP Skidmore, C Van Ness, PC Bergey, GK Park, YD Miller, I Geller, E Rutecki, PA Zimmerman, R Spencer, DC Goldman, A Edwards, JC Leiphart, JW Wharen, RE Fessler, J Fountain, NB Worrell, GA Gross, RE Eisenschenk, S Duckrow, RB Hirsch, LJ Bazil, C O'Donovan, CA Sun, FT Courtney, TA Seale, CG Morrell, MJ AF Heck, Christianne N. King-Stephens, David Massey, Andrew D. Nair, Dileep R. Jobst, Barbara C. Barkley, Gregory L. Salanova, Vicenta Cole, Andrew J. Smith, Michael C. Gwinn, Ryder P. Skidmore, Christopher Van Ness, Paul C. Bergey, Gregory K. Park, Yong D. Miller, Ian Geller, Eric Rutecki, Paul A. Zimmerman, Richard Spencer, David C. Goldman, Alica Edwards, Jonathan C. Leiphart, James W. Wharen, Robert E. Fessler, James Fountain, Nathan B. Worrell, Gregory A. Gross, Robert E. Eisenschenk, Stephan Duckrow, Robert B. Hirsch, Lawrence J. Bazil, Carl O'Donovan, Cormac A. Sun, Felice T. Courtney, Tracy A. Seale, Cairn G. Morrell, Martha J. TI Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial SO EPILEPSIA LA English DT Article DE Cortical stimulation; Partial seizures; Focal seizures; Responsive stimulation; Neurostimulator ID QUALITY-OF-LIFE; DEEP-BRAIN-STIMULATION; RANDOMIZED CONTROLLED-TRIAL; VAGUS NERVE-STIMULATION; TEMPORAL-LOBE EPILEPSY; REFRACTORY EPILEPSY; LONG-TERM; STANDARDS-SUBCOMMITTEE; ELECTRICAL-STIMULATION; ANTIEPILEPTIC DRUGS AB ObjectiveTo demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. MethodsRandomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2years of postimplant follow-up. ResultsAll 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p=0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1year and 53% at 2years, which represents a progressive and significant improvement with time (p<0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. SignificanceResponsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures. C1 [Heck, Christianne N.] Univ So Calif, Los Angeles, CA USA. [King-Stephens, David] Calif Pacific Med Ctr, San Francisco, CA USA. [Massey, Andrew D.] Via Christi Comprehens Epilepsy Ctr, Wichita, KS USA. [Nair, Dileep R.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Jobst, Barbara C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Barkley, Gregory L.] Henry Ford Hosp, Detroit, MI 48202 USA. [Salanova, Vicenta] IU Sch Med, Indianapolis, IN USA. [Cole, Andrew J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Smith, Michael C.] Rush Univ Med Ctr, Chicago, IL USA. [Gwinn, Ryder P.] Seattle Neurosci Inst, Seattle, WA USA. [Skidmore, Christopher] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Van Ness, Paul C.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Bergey, Gregory K.] Johns Hopkins Med, Dept Neurol, Baltimore, MD USA. [Park, Yong D.] Georgia Regents Univ, Augusta, GA USA. [Miller, Ian] Miami Childrens Hosp, Miami, FL USA. [Geller, Eric] Inst Neurol & Neurosurg St Barnabas, Livingston, NJ USA. [Rutecki, Paul A.] Univ Wisconsin, WA Middleton VA Hosp, Madison, WI USA. [Zimmerman, Richard] Mayo Clin Arizona, Phoenix, AZ USA. [Spencer, David C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Goldman, Alica] Baylor Coll Med, Peter Kellaway Sect Neurophysiol Neurol, Houston, TX 77030 USA. [Edwards, Jonathan C.] Med Univ S Carolina, Charleston, SC 29425 USA. [Leiphart, James W.] George Washington Univ, Washington, DC USA. [Wharen, Robert E.] Mayo Clin Florida, Jacksonville, FL USA. [Fessler, James] Univ Rochester, Rochester, NY USA. [Fountain, Nathan B.] Univ Virginia Sch Med, Dept Neurol, Charlottesville, VA USA. [Worrell, Gregory A.] Mayo Clin, Sect Electroencephalog, Rochester, MN USA. [Gross, Robert E.] Emory Univ, Atlanta, GA 30322 USA. [Eisenschenk, Stephan] Univ Florida, Gainesville, FL USA. [Duckrow, Robert B.; Hirsch, Lawrence J.] Yale Univ, Sch Med, New Haven, CT USA. [Bazil, Carl] Columbia Presbyterian Med Ctr, New York, NY 10032 USA. [O'Donovan, Cormac A.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Sun, Felice T.; Courtney, Tracy A.; Seale, Cairn G.; Morrell, Martha J.] NeuroPace, Mountain View, CA USA. [Morrell, Martha J.] Stanford Univ, Stanford, CA 94305 USA. RP Morrell, MJ (reprint author), 455 N Bernardo Ave, Mountain View, CA 94043 USA. EM mmorrell@neuropace.com NR 40 TC 88 Z9 90 U1 6 U2 39 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD MAR PY 2014 VL 55 IS 3 BP 432 EP 441 DI 10.1111/epi.12534 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AC7CQ UT WOS:000332685000012 PM 24621228 ER PT J AU Mitri, J Nelson, J Ruthazer, R Garganta, C Nathan, DM Hu, FB Dawson-Hughes, B Pittas, AG AF Mitri, J. Nelson, J. Ruthazer, R. Garganta, C. Nathan, D. M. Hu, F. B. Dawson-Hughes, B. Pittas, A. G. CA Diabet Prevention Program Res Grp TI Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE metabolic syndrome; vitamin D; diabetes; Diabetes Prevention Program ID SERUM VITAMIN-D; PARATHYROID-HORMONE LEVELS; LIFE-STYLE INTERVENTION; INSULIN-SECRETION; 1,25-DIHYDROXYVITAMIN D-3; GLUCOSE-TOLERANCE; NATIONAL-HEALTH; RAT PANCREAS; D DEFICIENCY; US ADULTS AB BACKGROUND/OBJECTIVES: Low blood levels of 25-hydroxyvitamin D (25OHD) have been associated with cardiometabolic disease but results are inconsistent. The objective of the study was to investigate the association of 25OHD with metabolic syndrome in a population at increased risk for diabetes. SUBJECTS/METHODS: Using baseline data from the placebo and lifestyle intervention arms of the Diabetes Prevention Program (N = 2000), multivariable logistic regression models were used to estimate the odds of prevalent metabolic syndrome and each of its individual components across 25OHD tertiles. Multivariable linear regression was used to estimate the adjusted mean difference of insulin secretion and sensitivity across the same 25OHD tertiles. In participants free of metabolic syndrome at baseline (N 546), incident metabolic syndrome in the first 2 years of follow-up was assessed using discrete-time proportional hazards regression to test its association with 25OHD concentration. RESULTS: After multivariate adjustment, participants in the highest tertile of 25OHD had lower odds of prevalent metabolic syndrome (odds ratio = 0.62; 95% confidence interval (CI) = 0.45-0.84), smaller waist circumference, higher high-density lipoprotein and lower fasting plasma glucose compared with participants in the lowest tertile of 25OHD. Higher plasma 25OHD concentration was associated with greater insulin sensitivity and lower insulin secretion. After multivariate adjustment, there was a nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD (hazard ratio = 0.79; 95% CI = 0.48-1.32) compared with the lowest tertile. CONCLUSIONS: In a population at increased risk for diabetes, higher plasma 25OHD concentration was inversely associated with prevalent metabolic syndrome and nonsignificantly with incident metabolic syndrome. C1 [Mitri, J.; Dawson-Hughes, B.; Pittas, A. G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02111 USA. [Nelson, J.; Ruthazer, R.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Garganta, C.] Tufts Med Ctr, Floating Hosp Children, Dept Clin Genet, Boston, MA 02111 USA. [Nathan, D. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Nathan, D. M.] Harvard Univ, Sch Med, Boston, MA USA. [Hu, F. B.] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. [Hu, F. B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Dawson-Hughes, B.] Tufts Univ, Bone Metab Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Mitri, J (reprint author), Tufts Med Ctr, Div Endocrinol Diabet & Metab, Box 268,800 Washington St,268, Boston, MA 02111 USA. EM joannamitri@hotmail.com FU National Institute of Diabetes and Digestive and Kidney Disease [R01DK79003, U34DK091958, U01DK098245]; Office Of The Director-National Institutes of Health; National Institutes of Health Office of Dietary Supplements; National Center for Research Resources [UL1RR025752]; National Center for Advancing Translational Sciences, National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health to the DPP clinical centers [U01DK48489]; Coordinating Center for the design and conduct of the DPP study; National Institute of Child Health and Human Development; National Institute on Aging; National Eye Institute; National Heart Lung and Blood Institute; Office of Research on Women's Health; National Center for Minority Health and Human Disease; Centers for Disease Control and Prevention; Indian Health Service; American Diabetes Association FX We thank David Kent, MD MSc, Associate Professor of Medicine, Director of the Clinical and Translational Science MS/PhD Program at the Sackler School, for his valuable input into interpretation of the results. We also acknowledge the commitment and dedication of the DPP participants. A portion of the work was presented at the 2012 Endocrine Society meeting as an oral presentation, on 23 June 2012, in Houston, TX. This study was supported by research grants R01DK79003, U34DK091958 and U01DK098245 (to AGP) from the National Institute of Diabetes and Digestive and Kidney Disease, the Office Of The Director-National Institutes of Health, and the National Institutes of Health Office of Dietary Supplements; UL1RR025752 (to Tufts University) from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health. The US Department of Agriculture Agreement 58-1950-9001 (to BDH); the Marilyn Fishman Grant for Diabetes Research (to JM) from the Endocrine Fellows Foundation; U01DK48489 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health to the DPP clinical centers and the Coordinating Center for the design and conduct of the DPP study. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the Office of Research on Women's Health, the National Center for Minority Health and Human Disease, the Centers for Disease Control and Prevention, the Indian Health Service, and the American Diabetes Association. Lipha (Merck-Sante) provided medication. LifeScan Inc., Merck-Medco Managed Care, Inc., and Merck and Co. donated materials, equipment or medicines for concomitant conditions. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the above listed institutions. NR 48 TC 5 Z9 6 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 EI 1476-5640 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD MAR PY 2014 VL 68 IS 3 BP 376 EP 383 DI 10.1038/ejcn.2013.293 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AC6LL UT WOS:000332634300015 PM 24448494 ER PT J AU Zhang, ZY Cypess, AM Miao, Q Ye, HY Liew, CW Zhang, QY Xue, RD Zhang, S Zuo, CT Xu, ZS Tang, QQ Hu, RM Guan, YH Li, YM AF Zhang, Zhaoyun Cypess, Aaron M. Miao, Qing Ye, Hongying Liew, Chong Wee Zhang, Qiongyue Xue, Ruidan Zhang, Shuo Zuo, Chuantao Xu, Zhensheng Tang, Qiqun Hu, Renming Guan, Yihui Li, Yiming TI The prevalence and predictors of active brown adipose tissue in Chinese adults SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ADAPTIVE THERMOGENESIS; F-18-FDG PET/CT; FDG UPTAKE; OBESITY; FAT; MECHANISMS; HUMANS; CANCER; LIVER AB Objective: Previous studies have shown that active brown adipose tissue (BAT) is present in adults and may play important roles in the regulation of energy homeostasis. However, nearly every study has been carried out in patients undergoing scanning for cancer surveillance (CS), whose metabolism and BAT activity may not reflect those of healthy individuals. The objective of this study was to investigate the prevalence and predictors of active BAT in Chinese adults, particularly in healthy individuals. Design: A total of 31 088 consecutive subjects aged >= 18 years who had undergone positron emission tomography/computed tomography (PET/CT) scanning of BAT were evaluated in this study. Methods: We measured BAT activity via 18 F-fluorodeoxyglucose PET/CT in subjects who had undergone scanning for either a routine medical checkup (MC) or CS in Shanghai. Then, we investigated the predictors of active BAT, particularly in healthy individuals. Results: In both groups, the prevalence of BAT was higher in women than in men. Using a multivariate logistic analysis, we found age, sex, BMI, and high thyroid glucose uptake to be significant predictors of BAT activity in the MC group. Similarly, we found age, sex, and BMI to be significant predictors of BAT activity, but not thyroid high glucose uptake, in the CS group. Conclusions: In Chinese adults, BAT activity inversely correlates with BMI and thyroid high glucose uptake, which reinforces the central role of brown fat in adult metabolism and provides clues to a potential means for treating the metabolic syndrome. C1 [Zhang, Zhaoyun; Miao, Qing; Ye, Hongying; Zhang, Qiongyue; Xue, Ruidan; Zhang, Shuo; Hu, Renming; Li, Yiming] Fudan Univ, Dept Internal Med, Div Endocrinol & Metab, Shanghai 200433, Peoples R China. [Zuo, Chuantao; Xu, Zhensheng; Guan, Yihui] Fudan Univ, Huashan Hosp, PET Ctr, Shanghai 200433, Peoples R China. [Tang, Qiqun] Fudan Univ, Dept Biochem & Mol Biol, Shanghai Med Sch, Shanghai 200433, Peoples R China. [Cypess, Aaron M.; Liew, Chong Wee] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Tang, Qiqun] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. RP Guan, YH (reprint author), Fudan Univ, Huashan Hosp, PET Ctr, Shanghai 200433, Peoples R China. EM guangyihui@hotmail.com; yimingli.fudan@gmail.com FU National Natural Science Foundation of China [30771024, 30900502, 30800344, 81070680]; Shanghai Committee of Science and Technology, China [10JC1401002, 11PJ1402000]; National Basic Research Program of China (973 Program) [2011CB91020]; 985 Project [III-YFX0302]; Shanghai Municipal Health Bureau [XYQ2011002]; Specialized Research Fund (State Education Ministry 131); NIH [DK046200, DK081604]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [P30 DK036836]; Eli Lilly Foundation FX This work was supported by the National Natural Science Foundation of China (No. 30771024, No. 30900502, No. 30800344, and No. 81070680), the Shanghai Committee of Science and Technology, China (No. 10JC1401002 and No. 11PJ1402000), the National Basic Research Program of China (973 Program) (No. 2011CB910201), the 985 Project (III-YFX0302), the Shanghai Municipal Health Bureau (No. XYQ2011002), the Specialized Research Fund for the Doctoral Program of Higher Education (State Education Ministry 131), and the NIH grants DK046200, DK081604 (A M Cypess), and P30 DK036836 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Eli Lilly Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National NIDDK or the NIH. NR 29 TC 6 Z9 6 U1 2 U2 7 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 MAR PY 2014 VL 170 IS 3 BP 359 EP 366 DI 10.1530/EJE-13-0712 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AC8KL UT WOS:000332781800005 PM 24288355 ER PT J AU Abousayed, M Kwon, JY AF Abousayed, Mostafa Kwon, John Y. TI Hallux Claw Toe SO FOOT AND ANKLE CLINICS LA English DT Article DE HaIlux claw toe; Jones technique; Modified Jones technique AB Claw hallux is a deformity of the great toe attributed to muscular imbalance. This article describes diagnosis and treatment of this condition. Particular attention is given to surgical techniques such as Jones technique and modified Jones technique. C1 [Abousayed, Mostafa; Kwon, John Y.] Massachusetts Gen Hosp, Dept Orthopaed, Orthopaed Associates, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. RP Kwon, JY (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Orthopaed Associates, Yawkey Ctr Outpatient Care, 55 Fruit St,Suite 3F, Boston, MA 02114 USA. EM jkwon@partners.org NR 11 TC 1 Z9 1 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1083-7515 EI 1558-1934 J9 FOOT ANKLE CLIN JI Foot Ankle Clin. PD MAR PY 2014 VL 19 IS 1 BP 59 EP + DI 10.1016/j.fc1.2013.11.001 PG 6 WC Orthopedics SC Orthopedics GA AC3MM UT WOS:000332425900006 PM 24548509 ER PT J AU Spain, RI Mancini, M Horak, FB Bourdette, D AF Spain, Rebecca I. Mancini, Martina Horak, Fay B. Bourdette, Dennis TI Body-worn sensors capture variability, but not decline, of gait and balance measures in multiple sclerosis over 18 months SO GAIT & POSTURE LA English DT Article DE Multiple sclerosis; Gait; Postural balance; Outcome assessment; Accelerometry ID DISABILITY STATUS SCALE; FUNCTIONAL COMPOSITE; PROGRESSION; IMPAIRMENT; PEOPLE; SCORES; EDSS; MS AB Gait and balance deficits are a frequent complaint in MS but poorly captured by stopwatch-timed tests or rating scales. Body-worn accelerometers and gyroscopes are able to detect gait and balance abnormalities in people with MS who have normal walking speeds. Few longitudinal studies exist using this technology to study the evolution of mobility deficits. The purpose of this study was to determine if body-worn sensors detected any decline in gait and balance measures in people with MS over time. Twenty-seven people with MS (13 mildly disabled, self-rated expanded disability status scale 0-3.5; 14 moderately disabled, SR-EDSS 4.0-5.5) who had normal walking speeds and 18 matched control subjects underwent gait and balance testing using body-worn sensors every 6 months for 18 months. While no parameter worsened over time, the moderately disabled MS cohort performed more poorly than the mildly disabled MS cohort who, in turn, was worse than control subjects for both objective and subjective walking and balance measures. Furthermore, the moderately disabled MS cohort demonstrated greater variation in between-visit performance than did the less disabled MS cohort or controls (Bonferroni-corrected p < 0.05). Variability may be a key indicator of worsening gait and balance disability in MS. Published by Elsevier B. V. C1 [Spain, Rebecca I.; Bourdette, Dennis] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. [Spain, Rebecca I.; Bourdette, Dennis] Portland VA Med Ctr, MS Ctr Excellence West, Portland, OR USA. [Spain, Rebecca I.; Mancini, Martina; Horak, Fay B.; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Spain, RI (reprint author), Oregon Hlth & Sci Univ, L226,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM spainr@ohsu.edu FU National MS Society [GNEUR0615A]; Oregon Clinical and Translational Research Institute (OCTRI) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research FX This work was supported by a Pilot Grant from the National MS Society [grant number GNEUR0615A]; and the Oregon Clinical and Translational Research Institute (OCTRI) [grant number UL1 RR024140] from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. NR 24 TC 11 Z9 11 U1 2 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD MAR PY 2014 VL 39 IS 3 BP 958 EP 964 DI 10.1016/j.gaitpost.2013.12.010 PG 7 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA AD0YM UT WOS:000332960600022 PM 24405749 ER PT J AU Akbay, EA Moslehi, J Christensen, CL Saha, S Tchaicha, JH Ramkissoon, SH Stewart, KM Carretero, J Kikuchi, E Zhang, HK Cohoon, TJ Murray, S Liu, W Uno, K Fisch, S Jones, K Gurumurthy, S Gliser, C Choe, S Keenan, M Son, J Stanley, I Losman, JA Padera, R Bronson, RT Asara, JM Abdel-Wahab, O Amrein, PC Fathi, AT Danial, NN Kimmelman, AC Kung, AL Ligon, KL Yen, KE Kaelin, WG Bardeesy, N Wong, KK AF Akbay, Esra A. Moslehi, Javid Christensen, Camilla L. Saha, Supriya Tchaicha, Jeremy H. Ramkissoon, Shakti H. Stewart, Kelly M. Carretero, Julian Kikuchi, Eiki Zhang, Haikuo Cohoon, Travis J. Murray, Stuart Liu, Wei Uno, Kazumasa Fisch, Sudeshna Jones, Kristen Gurumurthy, Sushma Gliser, Camelia Choe, Sung Keenan, Marie Son, Jaekyoung Stanley, Illana Losman, Julie A. Padera, Robert Bronson, Roderick T. Asara, John M. Abdel-Wahab, Omar Amrein, Philip C. Fathi, Amir T. Danial, Nika N. Kimmelman, Alec C. Kung, Andrew L. Ligon, Keith L. Yen, Katharine E. Kaelin, William G., Jr. Bardeesy, Nabeel Wong, Kwok-Kin TI D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice SO GENES & DEVELOPMENT LA English DT Article DE D-2HG; D2HGA; IDH2; cardiomyopathy; glycogen; myopathy; vacuolar leukoencephalopathy ID L-2-HYDROXYGLUTARIC ACIDURIA; CODON 132; MUTATIONS; 2-HYDROXYGLUTARATE; COLLAGEN; DISEASE; GLIOMAS; DIFFERENTIATION; TRANSFORMATION; GLIOBLASTOMAS AB Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2(R140Q) and IDH2(R172K) alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life span, recapitulating the abnormalities observed in D2HGA patients. The diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant up-regulation of genes involved in glycogen biosynthesis. Notably, mild cardiac hypertrophy was also observed in nude mice implanted with IDH2(R140Q) expressing xenografts,suggesting that 2HG may potentially act in a paracrine fashion. Finally, we show that silencing of IDH2(R140Q) in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition. C1 [Akbay, Esra A.; Christensen, Camilla L.; Tchaicha, Jeremy H.; Ramkissoon, Shakti H.; Kikuchi, Eiki; Zhang, Haikuo; Cohoon, Travis J.; Losman, Julie A.; Ligon, Keith L.; Kaelin, William G., Jr.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Akbay, Esra A.; Christensen, Camilla L.; Saha, Supriya; Tchaicha, Jeremy H.; Ramkissoon, Shakti H.; Zhang, Haikuo; Son, Jaekyoung; Losman, Julie A.; Danial, Nika N.; Ligon, Keith L.; Kaelin, William G., Jr.; Bardeesy, Nabeel; Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Akbay, Esra A.; Christensen, Camilla L.; Tchaicha, Jeremy H.; Kikuchi, Eiki; Zhang, Haikuo; Cohoon, Travis J.; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02215 USA. [Moslehi, Javid] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Moslehi, Javid; Fathi, Amir T.] Dana Farber Canc Inst, Cardiooncol Program, Boston, MA 02115 USA. [Saha, Supriya; Amrein, Philip C.; Ligon, Keith L.; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Ramkissoon, Shakti H.; Padera, Robert] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stewart, Kelly M.; Murray, Stuart; Liu, Wei; Gliser, Camelia; Choe, Sung; Keenan, Marie; Yen, Katharine E.] Agios Pharmaceut, Cambridge, MA 02139 USA. [Carretero, Julian] Univ Valencia, Dept Physiol, Valencia 46010, Spain. [Uno, Kazumasa; Fisch, Sudeshna] Harvard Univ, Sch Med, Cardiac Muscle Res Lab, Cardiovasc Div,Brigham & Womens Hosp, Boston, MA 02115 USA. [Jones, Kristen] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02215 USA. [Gurumurthy, Sushma; Wong, Kwok-Kin] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Son, Jaekyoung; Kimmelman, Alec C.] Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02215 USA. [Stanley, Illana; Danial, Nika N.] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02215 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Med, Div Signal Transduct,Beth Israel Deaconess Med Ct, Boston, MA 02215 USA. [Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Kung, Andrew L.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM kwong1@partners.org RI Kikuchi, Eiki/M-9688-2014; Carretero, Julian/N-5214-2014; OI Carretero, Julian/0000-0001-7269-8506; Abdel-Wahab, Omar/0000-0002-3907-6171; Kung, Andrew/0000-0002-9091-488X; wong, kwok kin/0000-0001-6323-235X FU National Institute of Health (NIH) [CA122794, CA140594, CA163896, CA166480, CA154303, 5T32HL007627-28, 5P30CA006516, 5P01CA120964, P50CA1270003]; TargetCancer Foundation; Gallagher Chair in GI Cancer Research FX We thank Ronglih Liao for cardiology expertise; Brigham and Women's Hospital Cardiac Physiology core for help with the physiology experiments; Dana-Farber Microarray Core for microarray gene expression profiling; Beth Israel Deaconess Medical Center Mass Spectrometry Core, Min Yuan, and Susanne Breitkopf for 2HG measurements; Brigham and Women's Hospital Transgenic Facility for blastocyst injections; Jinhee K. Oh for help with the maintenance of mouse colonies; Harvard Medical School Electron Microscopy Core for help with electron microscopy; Christine Lam for tissue processing; and Jacob B. Reibel for reading the manuscript. This work was supported by National Institute of Health (NIH) grants CA122794, CA140594, CA163896, CA166480, and CA154303 to K.K.W.; NIH grant 5T32HL007627-28 to S.H.R.; NIH 5P30CA006516 and 5P01CA120964 to J.M.A.; and NIH grant P50CA1270003, TargetCancer Foundation, and the Gallagher Chair in GI Cancer Research to N.B. NR 53 TC 15 Z9 15 U1 0 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2014 VL 28 IS 5 BP 479 EP 490 DI 10.1101/gad.231233.113 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA AC4FE UT WOS:000332475600006 PM 24589777 ER PT J AU Frazier, JA McDougle, CJ AF Frazier, Jean A. McDougle, Christopher J. TI Introduction SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material ID AUTISM SPECTRUM DISORDER; STUDENTS; COLLEGE C1 [Frazier, Jean A.] Univ Massachusetts Med Sch, Univ Massachusetts Hlth Care, Worcester, MA 01655 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Frazier, JA (reprint author), Univ Massachusetts Med Sch, Univ Massachusetts Hlth Care, Worcester, MA 01655 USA. EM Jean.Frazier@umassmed.edu; cmcdougle@partners.org NR 17 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2014 VL 22 IS 2 SI SI BP 61 EP 64 DI 10.1097/HRP.0000000000000028 PG 4 WC Psychiatry SC Psychiatry GA AD2QS UT WOS:000333080800001 PM 24614761 ER PT J AU Talkowski, ME Minikel, EV Gusella, JF AF Talkowski, Michael E. Minikel, Eric Vallabh Gusella, James F. TI Autism Spectrum Disorder Genetics: Diverse Genes with Diverse Clinical Outcomes SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE autism; chromosome rearrangement; common polymorphic variation; copy-number variation; exome sequencing; genetic architecture; genetic association; single-nucleotide variation ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; BALANCED CHROMOSOME REARRANGEMENTS; GENOME-WIDE ASSOCIATION; INTELLECTUAL DISABILITY; DEVELOPMENTAL DELAY; MICRODELETION SYNDROME; STRUCTURAL VARIATION; TUBEROUS SCLEROSIS; EXONIC DELETIONS AB The last several years have seen unprecedented advances in deciphering the genetic etiology of autism spectrum disorders (ASDs). Heritability studies have repeatedly affirmed a contribution of genetic factors to the overall disease risk. Technical breakthroughs have enabled the search for these genetic factors via genome-wide surveys of a spectrum of potential sequence variations, from common single-nucleotide polymorphisms to essentially private chromosomal abnormalities. Studies of copy-number variation have identified significant roles for both recurrent and nonrecurrent large dosage imbalances, although they have rarely revealed the individual genes responsible. More recently, discoveries of rare point mutations and characterization of balanced chromosomal abnormalities have pinpointed individual ASD genes of relatively strong effect, including both loci with strong a priori biological relevance and those that would have otherwise been unsuspected as high-priority biological targets. Evidence has also emerged for association with many common variants, each adding a small individual contribution to ASD risk. These findings collectively provide compelling empirical data that the genetic basis of ASD is highly heterogeneous, with hundreds of genes capable of conferring varying degrees of risk, depending on their nature and the predisposing genetic alteration. Moreover, many genes that have been implicated in ASD also appear to be risk factors for related neurodevelopmental disorders, as well as for a spectrum of psychiatric phenotypes. While some ASD genes have evident functional significance, like synaptic proteins such as the SHANKs, neuroligins, and neurexins, as well as fragile x mental retardation-associated proteins, ASD genes have also been discovered that do not present a clear mechanism of specific neurodevelopmental dysfunction, such as regulators of chromatin modification and global gene expression. In its sum, the progress from genetic studies to date has been remarkable and increasingly rapid, but the interactive impact of strong-effect genetic lesions coupled with weak-effect common polymorphisms has not yet led to a unified understanding of ASD pathogenesis or explained its highly variable clinical expression. With an increasingly firm genetic foundation, the coming years will hopefully see equally rapid advances in elucidating the functional consequences of ASD genes and their interactions with environmental/experiential factors, supporting the development of rational interventions. C1 [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Boston, MA USA. [Talkowski, Michael E.; Gusella, James F.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Talkowski, Michael E.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Talkowski, Michael E.; Minikel, Eric Vallabh; Gusella, James F.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu FU Simons Foundation for Autism Research; Nancy Lurie Marks Family Foundation; NARSAD; March of Dimes; Charles Hood Foundation; Autism Speaks; National Institutes of Health [MH095867, GM061354] FX Funded, in part, by the Simons Foundation for Autism Research and Nancy Lurie Marks Family Foundation (Drs. Talkowski and Gusella); NARSAD, March of Dimes, and Charles Hood Foundation (Dr. Talkowski); Autism Speaks (Dr. Gusella); and National Institutes of Health (MH095867 to Dr. Talkowski and GM061354 to Dr. Gusella). NR 113 TC 16 Z9 16 U1 6 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2014 VL 22 IS 2 SI SI BP 65 EP 75 DI 10.1097/HRP.0000000000000002 PG 11 WC Psychiatry SC Psychiatry GA AD2QS UT WOS:000333080800002 PM 24614762 ER PT J AU Politte, LC Henry, CA McDougle, CJ AF Politte, Laura C. Henry, Charles A. McDougle, Christopher J. TI Psychopharmacological Interventions in Autism Spectrum Disorder SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE anticonvulsants; antidepressants; atypical antipsychotics; autism; autismspectrumdisorders; mood stabilizers; oxytocin; pervasive developmental disorders; psychopharmacology; stimulants ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED TRIAL; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OPEN-LABEL TRIAL; OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; CONTROLLED-RELEASE MELATONIN; GUANFACINE EXTENDED-RELEASE; N-ACETYL CYSTEINE; DEFICIT HYPERACTIVITY DISORDER AB Learning Objectives: After participating in this educational activity, the physician should be better able to 1. Prescribe the appropriate psychotropic medication to treat symptoms of ASD. 2. Identify the side effects of the psychotropic medications used to treat ASD. Autism spectrum disorders (ASDs) are characterized by core deficits in social communication and language, and restrictive and repetitive behaviors that cause significant functional impairment and distress for affected individuals and their caregivers. The increasing prevalence of ASD, most recently estimated as 1 in 88 children, presents an ever-increasing burden on families, schools, medical systems, and society at large. Individuals with ASD commonly present for treatment of associated emotional and behavioral disturbances that include anxiety, symptoms of ADHD, compulsions and other repetitive behaviors, mood lability, irritability, aggression, and sleep disturbance. Psychotropic medications are widely utilized in alleviating these symptoms, though rigorous clinical trials in ASD are lacking for most areas of impairment. Strong evidence from randomized, placebo-controlled trials supports the use of atypical antipsychotics, particularly risperidone and aripiprazole, for managing severe irritability and aggression in ASD. Serotonin reuptake inhibitors are commonly used to treat anxiety and compulsions, though reports of efficacy in the literature are mixed, and behavioral side effects in children are common. Minimal evidence supports the utility of anticonvulsants and traditionalmood stabilizers in managing mood lability and aggression. Stimulant and nonstimulant ADHD medications can be effective for reducing hyperactivity, inattention, and impulsivity, though to a lesser degree than in ADHD populations without ASD and with greater risk of adverse effects. Psychopharmacological interventions in development for core symptoms of autism include those that target the glutamatergic and GABAergic neurotransmitter systems and the neuropeptide oxytocin. Further research is needed to establish evidence-based interventions in ASD populations. C1 Harvard Univ, Sch Med, Lexington, MA USA. [Politte, Laura C.] Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA. MassGen Hosp Children, Lexington, MA USA. RP Politte, LC (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, 1 Maguire Rd, Lexington, MA 02421 USA. EM lpolitte@partners.org NR 189 TC 20 Z9 20 U1 16 U2 46 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2014 VL 22 IS 2 SI SI BP 76 EP 92 DI 10.1097/HRP.0000000000000030 PG 17 WC Psychiatry SC Psychiatry GA AD2QS UT WOS:000333080800003 PM 24614763 ER PT J AU Hazen, EP Stornelli, JL O'Rourke, JA Koesterer, K McDougle, CJ AF Hazen, Eric P. Stornelli, Jennifer L. O'Rourke, Julia A. Koesterer, Karmen McDougle, Christopher J. TI Sensory Symptoms in Autism Spectrum Disorders SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE autism spectrum disorder; pervasive developmental delay; sensory integration; sensory overresponsitivity; sensory processing ID SELF-INJURIOUS-BEHAVIOR; REPETITIVE BEHAVIORS; OVER-RESPONSIVITY; YOUNG-CHILDREN; CORPUS-CALLOSUM; DEVELOPMENTAL DISORDERS; PRESCHOOL-CHILDREN; ADAPTIVE-BEHAVIOR; WILLIAMS-SYNDROME; DEEP PRESSURE AB The aim of this review is to summarize the recent literature regarding abnormalities in sensory functioning in individuals with autism spectrum disorder (ASD), including evidence regarding the neurobiological basis of these symptoms, their clinical correlates, and their treatment. Abnormalities in responses to sensory stimuli are highly prevalent in individuals with ASD. The underlying neurobiology of these symptoms is unclear, but several theories have been proposed linking possible etiologies of sensory dysfunction with known abnormalities in brain structure and function that are associated with ASD. In addition to the distress that sensory symptoms can cause patients and caregivers, these phenomena have been correlated with several other problematic symptoms and behaviors associated with ASD, including restrictive and repetitive behavior, self-injurious behavior, anxiety, inattention, and gastrointestinal complaints. It is unclear whether these correlations are causative in nature or whether they are due to shared underlying pathophysiology. The best-known treatments for sensory symptoms in ASD involve a program of occupational therapy that is specifically tailored to the needs of the individual and that may include sensory integration therapy, a sensory diet, and environmental modifications. While some empirical evidence supports these treatments, more research is needed to evaluate their efficacy, and other means of alleviating these symptoms, including possible psychopharmacological interventions, need to be explored. Additional research into the sensory symptoms associated with ASD has the potential to shed more light on the nature and pathophysiology of these disorders and to open new avenues of effective treatments. C1 [Hazen, Eric P.; O'Rourke, Julia A.; McDougle, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. [Hazen, Eric P.; McDougle, Christopher J.] Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. [Stornelli, Jennifer L.; O'Rourke, Julia A.; Koesterer, Karmen; McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA 02114 USA. [O'Rourke, Julia A.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Stornelli, Jennifer L.] Spaulding Outpatient Ctr Children, Lexington, MA USA. RP Hazen, EP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM ehazen@partners.org NR 121 TC 15 Z9 15 U1 13 U2 90 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2014 VL 22 IS 2 SI SI BP 112 EP 124 DI 10.1097/01.HRP.0000445143.08773.58 PG 13 WC Psychiatry SC Psychiatry GA AD2QS UT WOS:000333080800006 PM 24614766 ER PT J AU Jackson, GR Scott, IU Kim, IK Quillen, DA Iannaccone, A Edwards, JG AF Jackson, Gregory R. Scott, Ingrid U. Kim, Ivana K. Quillen, David A. Iannaccone, Alessandro Edwards, John G. TI Diagnostic Sensitivity and Specificity of Dark Adaptometry for Detection of Age-Related Macular Degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE age-related macular degeneration; dark adaptation; human; diagnostic ID MACULOPATHY; ADAPTATION; ROD AB PURPOSE. Difficulty with night vision is a common complaint of patients with age-related macular degeneration (AMD). Consistent with this complaint, dark adaptation (DA) is substantially impaired in these patients. Because of the severity of the deficit, measurement of DA has been suggested as a means for the diagnosis of AMD. Previous methods for measurement of DA were time intensive (>30 minutes), which made them unsuitable for clinical use. This study evaluated a rapid DA test (<= 6.5 minutes) for the detection of AMD. METHODS. Dark adaptation was measured by using the AdaptDx dark adaptometer in two groups: subjects with normal retinal health and subjects with AMD. Subjects were assigned to their group by clinical examination and grading of fundus photographs. Subjects were classified as having DA consistent with normal retinal health (rod intercept <= 6.5 minutes) or having dark adaptation consistent with AMD (rod intercept > 6.5 minutes). RESULTS. The eligible sample for analysis included 21 normal adults and 127 AMD patients. The rapid test was found to have a diagnostic sensitivity of 90.6% (P < 0.001) and specificity of 90.5% (P < 0.027). Thus, abnormal DA was detected in 115 of 127 AMD patients, and normal DA was found in 19 of 21 normal adults. CONCLUSIONS. The high diagnostic sensitivity and specificity compared favorably to long-duration research methods for the measurement of DA, and slit lamp biomicroscopy performed by a retina specialist. These results suggest that a rapid DA test is useful for the detection of AMD. C1 [Jackson, Gregory R.; Scott, Ingrid U.; Quillen, David A.] Penn State Coll Med, Penn State Hershey Eye Ctr, Hershey, PA 17033 USA. [Kim, Ivana K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Iannaccone, Alessandro] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Edwards, John G.] MacuLogix Inc, Hummelstown, PA USA. RP Jackson, GR (reprint author), Penn State Coll Med, 500 Univ Dr,HU19, Hershey, PA 17033 USA. EM gjackson@maculogix.com FU National Institute on Aging at the National Institutes of Health [R44 AG 26222-02] FX Supported by the National Institute on Aging at the National Institutes of Health (R44 AG 26222-02). The authors alone are responsible for the content and writing of the paper. NR 17 TC 20 Z9 20 U1 1 U2 13 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2014 VL 55 IS 3 BP 1427 EP 1431 DI 10.1167/iovs.13-13745 PG 5 WC Ophthalmology SC Ophthalmology GA AD2BA UT WOS:000333036500032 PM 24550363 ER PT J AU Villarreal, G Chatterjee, A Oh, SS Oh, DJ Rhee, DJ AF Villarreal, Guadalupe, Jr. Chatterjee, Ayan Oh, Sarah S. Oh, Dong-Jin Rhee, Douglas J. TI Pharmacological Regulation of SPARC by Lovastatin in Human Trabecular Meshwork Cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE statins; SPARC; KLF4; TGF-beta 2; glaucoma; trabecular meshwork ID OPEN-ANGLE GLAUCOMA; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX SYNTHESIS; AQUEOUS-HUMOR OUTFLOW; INTRAOCULAR-PRESSURE; VISUAL IMPAIRMENT; MICE EXHIBIT; HUMAN EYES; EXPRESSION; PROTEINS AB PURPOSE. Statins have been shown to increase aqueous outflow facility. The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is a critical mediator of aqueous outflow and intraocular pressure (IOP). Here, we examine the effects of lovastatin on SPARC expression in trabecular meshwork (TM) cells, exploring the molecular mechanisms involved. METHODS. Primary cultured human TM cells were incubated for 24, 48, and 72 hours with 10 mu M lovastatin. In separate cultures, media was supplemented with either farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) for the duration of the 72-hour time point experiment. Trabecular meshwork cells were also pretreated for 24 hours with lovastatin followed by 24-hour stimulation with 3 ng/mL TGF-beta 2. Cell lysates and media were harvested and relative mRNA and protein level changes were determined. Kruppel-like factor 4 (KLF4) localization in normal human anterior segments was examined by immunofluorescence. Adenovirus expressing human KLF4 was used and relative changes in SPARC mRNA and protein levels were assessed. RESULTS. Incubating TM cells with lovastatin suppressed SPARC mRNA and protein levels. This effect was reversed upon media supplementation with GGPP but not FPP. Pretreating cells with lovastatin inhibited TGF-beta 2 induction of SPARC. The KLF4 transcription factor was expressed throughout the TM and the inner and outer walls of Schlemm's canal. Lovastatin treatment upregulated KLF4 mRNA and protein levels. Overexpression of KLF4 downregulated SPARC expression. CONCLUSIONS. Collectively, our data identify lovastatin as an important pharmacological suppressor of SPARC expression in TM cells, and provide further insight into the molecular mechanisms mediating statin enhancement of aqueous outflow facility. C1 [Villarreal, Guadalupe, Jr.; Chatterjee, Ayan; Oh, Sarah S.; Oh, Dong-Jin; Rhee, Douglas J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM DougRhee@aol.com FU Howard Hughes Medical Institute Research Training Fellowship for Medical Students; National Eye Institute [EY 019654-01]; MEEI Vision-Core Grant [EY 014104] FX Supported by a Howard Hughes Medical Institute Research Training Fellowship for Medical Students (AC), National Eye Institute Grant EY 019654-01 (DJR), and MEEI Vision-Core Grant EY 014104. NR 55 TC 7 Z9 7 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2014 VL 55 IS 3 BP 1657 EP 1665 DI 10.1167/iovs.13-12712 PG 9 WC Ophthalmology SC Ophthalmology GA AD2BA UT WOS:000333036500059 PM 24474275 ER PT J AU Velez, NF Karia, PS Vartanov, AR Davids, MS Brown, JR Schmults, CD AF Velez, Nicole F. Karia, Pritesh S. Vartanov, Alexander R. Davids, Matthew S. Brown, Jennifer R. Schmults, Chrysalyne D. TI Association of Advanced Leukemic Stage and Skin Cancer Tumor Stage With Poor Skin Cancer Outcomes in Patients With Chronic Lymphocytic Leukemia SO JAMA DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ORGAN TRANSPLANT RECIPIENTS; HIGH RECURRENCE RATES; MOHS SURGERY; MELANOMA; MANAGEMENT; THERAPIES; DIAGNOSIS; FEATURES; RISK AB IMPORTANCE Although it has been well established that patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing skin cancer, few studies have investigated the effect of CLL stage on the risk of poor skin cancer outcomes. The present study of CLL staging assesses outcomes of melanoma, squamous cell carcinoma, and Merkel cell carcinoma in this high-risk population. OBJECTIVE To determine if progression of CLL measured by advanced Rai stage (III or IV) is associated with worse skin cancer outcomes. DESIGN, SETTING, AND PARTICIPANTS Twenty-year retrospective study at 2 academic centers in Boston, Massachusetts, of adults with CLL and either melanoma, squamous cell carcinoma, or Merkel cell carcinoma. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) for the development of poor skin cancer outcomes (local recurrence, nodal metastasis, distant metastasis, or death from skin cancer). RESULTS In total, 133 patients with 377 primary skin cancers and a median follow-up of 41 months were included. Squamous cell carcinoma predominated (92.0%). The risk of death from skin cancer was equivalent to the risk of death from CLL (13.5%). On multivariate analysis, advanced Rai stage (III or IV) at the time of the first skin cancer diagnosis (HR, 4.5; 95% CI, 2.3-8.9) and a high skin cancer tumor (T) stage (HR, 4.9; 95% CI, 2.2-10.8) were associated with poor skin cancer outcomes. Those with both a low skin cancer T stage and a low Rai stage (n = 265) had a low risk (5.3%; 95% CI, 3.2%-8.7%) of poor skin cancer outcomes. Those with a low T stage and a high Rai stage (n = 89) had a significantly higher risk of poor skin cancer outcomes (16.9%; 95% CI, 10.9%-26.0%). The 23 patients with a high T stage had high risks of poor outcomes regardless of CLL status (27.3% if a low Rai stage and 50.0% if a high Rai stage, with wide 95% CIs). CONCLUSIONS AND RELEVANCE In patients with CLL and non-basal cell carcinoma skin cancer, mortality is as high from skin cancer as from CLL. The Rai stage and skin cancer T stage should be considered when risk-stratifying patients with skin cancer. Regular communication between dermatologists and oncologists will help facilitate the identification of patients with CLL who are at high risk of having poor skin cancer outcomes. C1 [Velez, Nicole F.; Karia, Pritesh S.; Schmults, Chrysalyne D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02130 USA. [Vartanov, Alexander R.; Davids, Matthew S.; Brown, Jennifer R.] Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Dept Med Oncol, Boston, MA 02130 USA. RP Schmults, CD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, 1153 Ctr St, Boston, MA 02130 USA. EM cschmults@partners.org NR 27 TC 7 Z9 7 U1 1 U2 5 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 MAR PY 2014 VL 150 IS 3 BP 280 EP 287 DI 10.1001/jamadermatol.2013.6249 PG 8 WC Dermatology SC Dermatology GA AD2DQ UT WOS:000333043900010 PM 24429548 ER PT J AU Wieczorek, IT Propert, KJ Okawa, J Werth, VP AF Wieczorek, Isabela T. Propert, Kathleen J. Okawa, Joyce Werth, Victoria P. TI Systemic Symptoms in the Progression of Cutaneous to Systemic Lupus Erythematosus SO JAMA DERMATOLOGY LA English DT Article ID DISEASE-ACTIVITY; INDEX; SEVERITY; LESIONS AB IMPORTANCE Patients with cutaneous lupus erythematosus (CLE) who develop systemic lupus erythematosus (SLE) may have few and mild systemic symptoms. OBJECTIVE To characterize the types and severity of systemic symptoms in a longitudinal cohort of patients with CLE. DESIGN, SETTING, AND PARTICIPANTS Prospective, longitudinal cohort study of 77 patients with CLE who presented between January 2007 and April 2011 at a university autoimmune skin disease clinic. MAIN OUTCOMES AND MEASURES Systemic symptoms and severity were determined from data recorded at each study visit and from medical records. RESULTS Of 77 patients with CLE, 13 (17%) went on to meet criteria for SLE, with a mean (SD) time from CLE diagnosis to SLE of 8.03 (6.20) years. Of the 13 patients, 1 (8%) solely met the mucocutaneous American College of Rheumatology (ACR) criteria of malar rash, discoid rash, photosensitivity, and oral ulcers, and 3 (23%) met the mucocutaneous ACR criteria plus positive antinuclear and other antibody titers. After a mean (SD) follow-up time of 2.81 (1.34) years, only 5 of the 13 patients with CLE (38%) who progressed to meet SLE criteria developed moderate to severe additional systemic disease. CONCLUSIONS AND RELEVANCE Patients with CLE who developed SLE during our study did so mostly by meeting the mucocutaneous ACR criteria, and the majority developed none to mild additional systemic disease during the study period. Thus, our study suggests that a small percentage of patients with CLE eventually develop SLE and that even if they do, most patients will have mild systemic disease. C1 [Wieczorek, Isabela T.; Okawa, Joyce; Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA USA. [Wieczorek, Isabela T.; Okawa, Joyce; Werth, Victoria P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Propert, Kathleen J.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, 3600 Spruce St,2 Rhoads Pavil, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development); National Institutes of Health [NIH K24-AR 02207]; Lupus Foundation of America, Philadelphia Tri-State Chapter FX This study was supported in part by the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (grant NIH K24-AR 02207) (Dr Werth); and The Lupus Foundation of America, Philadelphia Tri-State Chapter (Dr Wieczorek). NR 14 TC 9 Z9 9 U1 0 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 MAR PY 2014 VL 150 IS 3 BP 291 EP 296 DI 10.1001/jamadermatol.2013.9026 PG 6 WC Dermatology SC Dermatology GA AD2DQ UT WOS:000333043900013 PM 24477339 ER PT J AU Park, JJ Hawryluk, EB Tahan, SR Flaherty, K Kim, CC AF Park, June J. Hawryluk, Elena B. Tahan, Steven R. Flaherty, Keith Kim, Caroline C. TI Cutaneous Granulomatous Eruption and Successful Response to Potent Topical Steroids in Patients Undergoing Targeted BRAF Inhibitor Treatment for Metastatic Melanoma SO JAMA DERMATOLOGY LA English DT Article ID EPITHELIOID GRANULOMAS; MUTATIONS; VEMURAFENIB; DISEASE AB IMPORTANCE Targeted BRAF inhibitor therapy (vemurafenib. dabrafenib) is an effective, novel treatment for patients with metastatic melanoma with the V600E BRAF mutation. This therapy is associated with squamous cell carcinomas and keratoacanthomas. Granulomatous eruptions have not been previously reported. OBSERVATIONS Two patients with melanoma developed cutaneous granulomatous eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption concerning for progression of disease prompted cessation of treatment. After the histopathologic diagnosis of granulomas, the patient was treated with clobetasol ointment with resolution within days and resumption of therapy. In case 2, after 5 months of vemurafenib treatment, the patient developed a granulomatous eruption, which resolved 3 weeks after cessation of therapy. CONCLUSIONS AND RELEVANCE We report 2 cases of cutaneous granulomatous eruptions on treatment with targeted BRAF inhibitors, a previously unreported association. Although additional investigations are necessary to better elucidate the pathogenic mechanisms, our report includes a treatment plan that prevents unnecessary discontinuation of therapy. Given the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should be aware of this possible cutaneous reaction and treatment option to optimize patient management. C1 [Park, June J.] Univ Illinois, Coll Med, Chicago, IL USA. [Hawryluk, Elena B.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tahan, Steven R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Flaherty, Keith] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Div Hematol Oncol, Boston, MA 02114 USA. [Kim, Caroline C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Pigmented Les Clin,Dept Dermatol, Boston, MA 02215 USA. [Kim, Caroline C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cutaneous Oncol Program,Dept Dermatol, Boston, MA 02215 USA. RP Kim, CC (reprint author), Beth Israel Deaconess Med Ctr, Dept Dermatol, 330 Brookline Ave,Shapiro 2, Boston, MA 02215 USA. EM ckim3@caregroup.harvard.edu FU Roche; GlaxoSmithKline; Kevin Reagan Memorial Fund; Eleanor and Miles Shore/Beth Israel Deaconess Medical Center Department of Dermatology Fellowship FX Roche and GlaxoSmithKline funded the underlying clinical trials in which the patients in this report participated. Dr Kim was supported by the Kevin Reagan Memorial Fund and the Eleanor and Miles Shore/Beth Israel Deaconess Medical Center Department of Dermatology Fellowship. NR 15 TC 13 Z9 13 U1 0 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 MAR PY 2014 VL 150 IS 3 BP 307 EP 311 DI 10.1001/jamadermatol.2013.7919 PG 5 WC Dermatology SC Dermatology GA AD2DQ UT WOS:000333043900018 PM 24352115 ER PT J AU Jalian, HR Avram, MM Garibyan, L Mihm, MC Anderson, RR AF Jalian, H. Ray Avram, Mathew M. Garibyan, Lilit Mihm, Martin C. Anderson, R. Rox TI Paradoxical Adipose Hyperplasia After Cryolipolysis SO JAMA DERMATOLOGY LA English DT Article ID NONINVASIVE FAT REMOVAL; DENERVATION; TISSUE AB IMPORTANCE Cryolipolysis is the noninvasive reduction of fat with localized cutaneous cooling. Since initial introduction, over 650 000 cryolipolysis treatment cycles have been performed worldwide. We present a previously unreported, rare adverse effect following cryolipolysis: paradoxical adipose hyperplasia. OBSERVATIONS A man in his 40s underwent a single cycle of cryolipolysis to his abdomen. Three months following his treatment, a gradual enlargement of the treatment area was noted. This enlargement was a large, well-demarcated subcutaneous mass, slightly tender to palpation. Imaging studies revealed accumulation of adipose tissue with normal signal intensity within the treatment area. CONCLUSIONS AND RELEVANCE Paradoxical adipose hyperplasia is a rare, previously unreported adverse effect of cryolipolysis with an incidence of 0.0051%. No single unifying risk factor has been identified. The phenomenon seems to be more common in male patients undergoing cryolipolysis. At this time, there is no evidence of spontaneous resolution. Further studies are needed to characterize the pathogenesis and histologic findings of this rare adverse event. C1 [Jalian, H. Ray] Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. [Jalian, H. Ray; Avram, Mathew M.; Garibyan, Lilit; Anderson, R. Rox] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Avram, Mathew M.; Garibyan, Lilit; Anderson, R. Rox] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Mihm, Martin C.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP Jalian, HR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St,Thier 2,Room 204, Boston, MA 02114 USA. EM hjalian@partners.org FU Zeltiq Aesthetics Inc. FX Drs Jalian and Anderson serve as investigators for a clinical trial sponsored by Zeltiq Aesthetics Inc. Drs Avram and Anderson serve on the Medical Advisory Board for Zeltiq Aesthetics Inc. Dr Anderson's employer, Massachusetts General Hospital, receives royalties for licensing intellectual property to Zeltiq Aesthetics Inc. No other disclosures are reported. NR 9 TC 24 Z9 24 U1 2 U2 3 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 MAR PY 2014 VL 150 IS 3 BP 317 EP 319 DI 10.1001/jamadermatol.2013.8071 PG 3 WC Dermatology SC Dermatology GA AD2DQ UT WOS:000333043900020 PM 24382640 ER PT J AU Ducros, A Hajj-Ali, RA Singhal, AB Wang, SJ AF Ducros, Anne Hajj-Ali, Rula A. Singhal, Aneesh Bhim Wang, Shuu-Jiun TI Reversible Cerebral Vasoconstriction Syndrome SO JAMA NEUROLOGY LA English DT Letter C1 [Ducros, Anne] Montpellier Univ Hosp, Dept Neurol, Montpellier, France. [Hajj-Ali, Rula A.] Cleveland Clin Fdn, Ctr Vasculitis Care & Res, Cleveland, OH 44195 USA. [Singhal, Aneesh Bhim] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wang, Shuu-Jiun] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, Taipei, Taiwan. RP Ducros, A (reprint author), Hop Gui de Chauliac, Dept Neurol, 80 Ave Augustin Fliche, F-34295 Montpellier 05, France. EM a-ducros@chu-montpellier.fr RI Ducros, Anne/D-1899-2010 OI Ducros, Anne/0000-0001-5560-5013 NR 5 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD MAR PY 2014 VL 71 IS 3 BP 368 EP 368 DI 10.1001/jamaneurol.2013.5875 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AC9CL UT WOS:000332831600020 PM 24614989 ER PT J AU Gupta, P Green, JW Tang, XY Gall, CM Gossett, JM Rice, TB Kacmarek, RM Wetzel, RC AF Gupta, Punkaj Green, Jerril W. Tang, Xinyu Gall, Christine M. Gossett, Jeffrey M. Rice, Tom B. Kacmarek, Robert M. Wetzel, Randall C. TI Comparison of High-Frequency Oscillatory Ventilation and Conventional Mechanical Ventilation in Pediatric Respiratory Failure SO JAMA PEDIATRICS LA English DT Article ID INDUCED LUNG INJURY; DISTRESS-SYNDROME; MODEL; PULMONARY; TRIAL AB IMPORTANCE Outcomes associated with use of high-frequency oscillatory ventilation (HFOV) in children with acute respiratory failure have not been established. OBJECTIVE To compare the outcomes of HFOV with those of conventional mechanical ventilation (CMV) in children with acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective, observational study using deidentified data obtained from all consecutive patients receiving mechanical ventilation aged 1 month to 18 years in the Virtual PICU System database from January 1, 2009, through December 31, 2011. The study population was divided into 2 groups: HFOV and CMV. The HFOV group was further divided into early and late HFOV. Propensity score matching was performed as a 1-to-1 match of HFOV and CMV patients. A similar matching process was performed for early HFOV and CMV patients. EXPOSURE High-frequency oscillatory ventilation. MAIN OUTCOMES AND MEASURES Length of mechanical ventilation, intensive care unit (ICU) length of stay, ICU mortality, and standardized mortality ratio (SMR). RESULTS A total of 9177 patients from 98 hospitals qualified for inclusion. Of these, 902 (9.8%) received HFOV, whereas 8275 (90.2%) received CMV. A total of 1764 patients were matched to compare HFOV and CMV, whereas 942 patients were matched to compare early HFOV and CMV. Length of mechanical ventilation (CMV vs HFOV: 14.6 vs 20.3 days, P < .001; CMV vs early HFOV: 14.6 vs 15.9 days, P < .001), ICU length of stay (19.1 vs 24.9 days, P < .001; 19.3 vs 19.5 days, P = .03), and mortality (8.4% vs 17.3%, P < .001; 8.3% vs 18.1%, P < .001) were significantly higher in HFOV and early HFOV patients compared with CMV patients. The SMR in the HFOV group was 2.00 (95% CI, 1.71-2.35) compared with an SMR in the CMV group of 0.85 (95% CI, 0.68-1.07). The SMR in the early HFOV group was 1.62 (95% CI, 1.31-2.01) compared with an SMR in the CMV group of 0.76 (95% CI, 0.62-1.16). CONCLUSIONS AND RELEVANCE Application of HFOV and early HFOV compared with CMV in children with acute respiratory failure is associated with worse outcomes. The results of our study are similar to recently published studies in adults comparing these 2 modalities of ventilation for acute respiratory distress syndrome. C1 [Gupta, Punkaj; Green, Jerril W.] Univ Arkansas, Med Ctr, Dept Pediat, Div Pediat Crit Care, Little Rock, AR 72204 USA. [Gupta, Punkaj] Univ Arkansas, Med Ctr, Dept Pediat, Div Pediat Cardiol, Little Rock, AR 72204 USA. [Tang, Xinyu; Gossett, Jeffrey M.] Univ Arkansas, Med Ctr, Dept Pediat, Div Biostat, Little Rock, AR 72204 USA. [Gall, Christine M.; Rice, Tom B.; Wetzel, Randall C.] Virtual PICU Syst LLC, Los Angeles, CA USA. [Rice, Tom B.] Med Coll Wisconsin, Dept Pediat, Div Pediat Crit Care, Milwaukee, WI 53226 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kacmarek, Robert M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Crit Care & Pain Med, Boston, MA USA. [Wetzel, Randall C.] Univ So Calif, Keck Sch Med, Dept Anesthesiol, Los Angeles, CA 90033 USA. [Wetzel, Randall C.] Univ So Calif, Keck Sch Med, Dept Pediat, Div Pediat Crit Care, Los Angeles, CA 90033 USA. RP Gupta, P (reprint author), Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Coll Med,Sect Pediat Cardiol, One Childrens Way,Slot 512-3, Little Rock, AR 72202 USA. EM pgupta2@uams.edu FU Hollister; Covidien FX Dr Kacmarek reported serving as a consultant for Covidien/Newport, reported receiving honorarium for lecturing from Maquet, and has reported receiving research grants from Hollister and Covidien. No other disclosures were reported. NR 24 TC 20 Z9 23 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD MAR PY 2014 VL 168 IS 3 BP 243 EP 249 DI 10.1001/jamapediatrics.2013.4463 PG 7 WC Pediatrics SC Pediatrics GA AC8GR UT WOS:000332772000011 PM 24445980 ER PT J AU Chirinos, JA Townsend, RR AF Chirinos, Julio A. Townsend, Raymond R. TI Systemic Arterial Hemodynamics and the " Renal Resistive Index:" What is in a Name? SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material ID TARGET ORGAN DAMAGE; PULSE PRESSURE; BLOOD-PRESSURE; HYPERTENSION; RESISTANCE; DISEASE; VARIABILITY; THERAPY; IMPACT C1 [Chirinos, Julio A.] Univ Penn, Cardiovasc Div, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Chirinos, Julio A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Div Nephrol Hypertens, Philadelphia, PA 19104 USA. RP Chirinos, JA (reprint author), Rm 8B111,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu NR 17 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD MAR PY 2014 VL 16 IS 3 BP 170 EP 171 DI 10.1111/jch.12276 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AC6HY UT WOS:000332623700005 PM 24548453 ER PT J AU Zeng, Q Ng, YH Singh, T Jiang, K Sheriff, KA Ippolito, R Zahalka, S Li, Q Randhawa, P Hoffman, RA Ramaswami, B Lund, FE Chalasani, G AF Zeng, Qiang Ng, Yue-Harn Singh, Tripti Jiang, Ke Sheriff, Khaleefathullah A. Ippolito, Renee Zahalka, Salwa Li, Qi Randhawa, Parmjeet Hoffman, Rosemary A. Ramaswami, Balathiripurasundari Lund, Frances E. Chalasani, Geetha TI B cells mediate chronic allograft rejection independently of antibody production SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LONG-TERM; MICE; VASCULOPATHY; DEPLETION; LYMPHOCYTES; EXPRESSION; EFFECTOR; SURVIVAL; IMMUNITY; DISEASE AB Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence that chronic rejection of vascularized heart allografts occurs in the complete absence of antibodies, but requires the presence of B cells. Mice that were deficient for antibodies but not B cells experienced the same chronic allograft vasculopathy (CAV), which is a pathognomonic feature of chronic rejection, as WT mice; however, mice that were deficient for both B cells and antibodies were protected from CAV. B cells contributed to CAV by supporting splenic lymphoid architecture, T cell cytokine production, and infiltration of T cells into graft vessels. In chimeric mice, in which B cells were present but could not present antigen, both T cell responses and CAV were markedly reduced. These findings establish that chronic rejection can occur in the complete absence of antibodies and that B cells contribute to this process by supporting T cell responses through antigen presentation and maintenance of lymphoid architecture. C1 [Zeng, Qiang; Ng, Yue-Harn; Singh, Tripti; Jiang, Ke; Sheriff, Khaleefathullah A.; Ippolito, Renee; Li, Qi; Randhawa, Parmjeet; Hoffman, Rosemary A.; Ramaswami, Balathiripurasundari; Chalasani, Geetha] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Zeng, Qiang; Jiang, Ke; Sheriff, Khaleefathullah A.; Ippolito, Renee; Li, Qi; Hoffman, Rosemary A.; Ramaswami, Balathiripurasundari] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Ng, Yue-Harn; Singh, Tripti; Zahalka, Salwa; Chalasani, Geetha] Univ Pittsburgh, Sch Med, Dept Med Renal Electrolyte, Pittsburgh, PA USA. [Ng, Yue-Harn] Natl Univ Singapore Hosp, Dept Med Nephrol, Singapore, Singapore. [Jiang, Ke] Union Hosp, Tongji Med Coll, Dept Thorac Surg, Wuhan, Peoples R China. [Randhawa, Parmjeet] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Hoffman, Rosemary A.; Chalasani, Geetha] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. [Lund, Frances E.] Univ Alabama, Dept Microbiol, Birmingham, PA USA. [Chalasani, Geetha] VA Pittsburgh Healthcare Syst, Dept Med Nephrol, Pittsburgh, PA USA. RP Chalasani, G (reprint author), BST W1554,200 Lothrop St, Pittsburgh, PA 15261 USA. EM gec12@pitt.edu FU NIH [A1079 177, AI068056]; ROTRF [978906253]; American Heart Association postdoctoral fellowship; American Society of Transplantation postdoctoral fellowship; Thomas E. Starzl postdoctoral fellowship; University of Pittsburgh Department of Medicine Junior Scholar Award FX This work was supported by grants NIH A1079 177 (to G. Chalasani) and ROTRF 978906253 (to G. Chalasani), an American Heart Association postdoctoral fellowship (to Y-.H. Ng), an American Society of Transplantation postdoctoral fellowship (to K.A. Sheriff), a Thomas E. Starzl postdoctoral fellowship (to K. Jiang), and a University of Pittsburgh Department of Medicine Junior Scholar Award (to G. Chalasani). NIH AI068056 (to F.E. Lund) funds were used to develop, characterize and maintain AIDALS KO mice. We thank Fadi Lakkis and David Rothstein for valuable input and critical comments. NR 28 TC 13 Z9 15 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2014 VL 124 IS 3 BP 1052 EP 1056 DI 10.1172/JCI70084 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AC2PZ UT WOS:000332347700025 PM 24509079 ER PT J AU Muraro, PA Robins, H Malhotra, S Howell, M Phippard, D Desmarais, C Sousa, ADA Griffith, LM Lim, N Nash, RA Turka, LA AF Muraro, Paolo A. Robins, Harlan Malhotra, Sachin Howell, Michael Phippard, Deborah Desmarais, Cindy Sousa, Alessandra de Paula Alves Griffith, Linda M. Lim, Noha Nash, Richard A. Turka, Laurence A. TI T cell repertoire following autologous stem cell transplantation for multiple sclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TOLERANCE; NETWORK; DISEASE; NUMBER AB Autologous hematopoietic stem cell transplantation (HSCT) is commonly employed for hematologic and non-hematologic malignancies. In clinical trials, HSCT has been evaluated for severe autoimmunity as a method to "reset" the immune system and produce a new, non-autoimmune repertoire. While the feasibility of eliminating the vast majority of mature T cells is well established, accurate and quantitative determination of the relationship of regenerated T cells to the baseline repertoire has been difficult to assess. Here, in a phase II study of HSCT for poor-prognosis multiple sclerosis, we used high-throughput deep TCR beta chain sequencing to assess millions of individual TCRs per patient sample. We found that HSCT has distinctive effects on CD4(+) and CD8(+) T cell repertoires. In CD4(+) T cells, dominant TCR clones present before treatment were undetectable following reconstitution, and patients largely developed a new repertoire. In contrast, dominant CD8(+) clones were not effectively removed, and the reconstituted CD8(+) T cell repertoire was created by clonal expansion of cells present before treatment. Importantly, patients who failed to respond to treatment had less diversity in their T cell repertoire early during the reconstitution process. These results demonstrate that TCR characterization during immunomodulatory treatment is both feasible and informative, and may enable monitoring of pathogenic or protective T cell clones following HSCT and cellular therapies. C1 [Muraro, Paolo A.; Sousa, Alessandra de Paula Alves] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Brain Sci, London, England. [Robins, Harlan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Malhotra, Sachin; Howell, Michael; Phippard, Deborah; Lim, Noha; Turka, Laurence A.] Immune Tolerance Network, Bethesda, MD USA. [Desmarais, Cindy] Adapt Biotechnol, Seattle, WA USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Nash, Richard A.] Colorado Blood Canc Inst PSL, Denver, CO USA. [Turka, Laurence A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA USA. RP Turka, LA (reprint author), Transplantat Biol Res Ctr MGH East, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM lturka@partners.org OI Muraro, Paolo/0000-0002-3822-1218 FU NIAID; NIDDK; Juvenile Diabetes Research Foundation (JDRF); Autoimmune Disease Clinical Trials Statistical and Clinical Coordinating Center; UK MS society [938/10]; Multiple Sclerosis Trial Collaboration [WMCN P36769] FX This work was supported by the ITN, funded by the NIAID, with support from the NIDDK and the Juvenile Diabetes Research Foundation (JDRF). Additional support was received from the Autoimmune Disease Clinical Trials Statistical and Clinical Coordinating Center funded by the NIAID. P.A. Muraro was supported by the UK MS society (ref. 938/10). A.P.A. Sousa was supported by the Multiple Sclerosis Trial Collaboration (ref. WMCN P36769). We thank Alice Long (Benaroya Research Institute) for outstanding technical assistance. We also thank the patients who participated in this study. NR 15 TC 57 Z9 58 U1 3 U2 19 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2014 VL 124 IS 3 BP 1168 EP 1172 DI 10.1172/JCI71691 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AC2PZ UT WOS:000332347700034 PM 24531550 ER PT J AU Lee, RJ Kofonow, JM Rosen, PL Siebert, AP Chen, B Doghramji, L Xiong, GX Adappa, ND Palmer, JN Kennedy, DW Kreindler, JL Margolskee, RF Cohen, NA AF Lee, Robert J. Kofonow, Jennifer M. Rosen, Philip L. Siebert, Adam P. Chen, Bei Doghramji, Laurel Xiong, Guoxiang Adappa, Nithin D. Palmer, James N. Kennedy, David W. Kreindler, James L. Margolskee, Robert F. Cohen, Noam A. TI Bitter and sweet taste receptors regulate human upper respiratory innate immunity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SOLITARY CHEMOSENSORY CELLS; BRONCHIAL EPITHELIAL-CELLS; AIRWAY SURFACE LIQUID; CHRONIC RHINOSINUSITIS; ANTIMICROBIAL PEPTIDES; GLUCOSE-HOMEOSTASIS; CHEMORECEPTOR CELLS; FLUID SECRETION; NASAL CAVITY; SINUS MUCOSA AB Bitter taste receptors (T2Rs) in the human airway detect harmful compounds, including secreted bacterial products. Here, using human primary sinonasal air-liquid interface cultures and tissue explants, we determined that activation of a subset of airway T2Rs expressed in nasal solitary chemosensory cells activates a calcium wave that propagates through gap junctions to the surrounding respiratory epithelial cells. The T2R-dependent calcium wave stimulated robust secretion of antimicrobial peptides into the mucus that was capable of killing a variety of respiratory pathogens. Furthermore, sweet taste receptor (T1R2/3) activation suppressed T2R-mediated antimicrobial peptide secretion, suggesting that T1R2/3-mediated inhibition of T2Rs prevents full antimicrobial peptide release during times of relative health. In contrast, during acute bacterial infection, T1R2/3 is likely deactivated in response to bacterial consumption of airway surface liquid glucose, alleviating T2R inhibition and resulting in antimicrobial peptide secretion. We found that patients with chronic rhinosinusitis have elevated glucose concentrations in their nasal secretions, and other reports have shown that patients with hyperglycemia likewise have elevated nasal glucose levels. These data suggest that increased glucose in respiratory secretions in pathologic states, such as chronic rhinosinusitis or hyperglycemia, promotes tonic activation of T1R2/3 and suppresses T2R-mediated innate defense. Furthermore, targeting T1R2/3-dependent suppression of T2Rs may have therapeutic potential for upper respiratory tract infections. C1 [Lee, Robert J.; Kofonow, Jennifer M.; Rosen, Philip L.; Siebert, Adam P.; Chen, Bei; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Xiong, Guoxiang] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Kreindler, James L.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Margolskee, Robert F.] Monell Chem Senses Ctr, Philadelphia, PA USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Univ Penn, Perelman Sch Med, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686 FU Flight Attendants Medical Research Institute [082478]; NIH [DC03055]; RLG Foundation Inc. FX We thank D.M. Sabatini, G.K. Beauchamp, and D.R. Reed for helpful discussions and suggestions; W. Meyerhof and D.R. Reed for absinthin; P. Jiang for T2R47-transfected HEK293 cells; and D. LaRosa for Myd88 knockout mice. This work was supported by grant 082478 from Flight Attendants Medical Research Institute (to N:A. Cohen), a philanthropic contribution from the RLG Foundation Inc. (to NA. Cohen), and NIH grant DC03055 (to R.F. Margolskee). NR 75 TC 83 Z9 83 U1 4 U2 36 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2014 VL 124 IS 3 BP 1393 EP 1405 DI 10.1172/JCI72094 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AC2PZ UT WOS:000332347700053 PM 24531552 ER PT J AU Serra, V Eichhorn, PJA Garcia-Garcia, C Ibrahim, YH Prudkin, L Sanchez, G Rodriuez, O Anton, P Parra, JL Marlow, S Scaltriti, M Perez-Garcia, J Prat, A Arribas, J Hahn, WC Kim, SY Baselga, J AF Serra, Violeta Eichhorn, Pieter J. A. Garcia-Garcia, Celina Ibrahim, Yasir H. Prudkin, Ludmila Sanchez, Gertrudis Rodriguez, Olga Anton, Pilar Parra, Josep-Lluis Marlow, Sara Scaltriti, Maurizio Perez-Garcia, Jose Prat, Aleix Arribas, Joaquin Hahn, William C. Kim, So Young Baselga, Jose TI RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Correction C1 [Serra, Violeta; Garcia-Garcia, Celina; Ibrahim, Yasir H.; Prudkin, Ludmila; Sanchez, Gertrudis; Rodriguez, Olga; Anton, Pilar; Prat, Aleix] Vall Hebron Inst Oncol, Barcelona, Spain. [Eichhorn, Pieter J. A.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Parra, Josep-Lluis] Vall Hebron Inst Oncol, Growth Factors Grp, Barcelona, Spain. [Marlow, Sara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Scaltriti, Maurizio] Human Oncol & Pathogenesis Program, New York, NY USA. [Scaltriti, Maurizio] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Perez-Garcia, Jose] Vall Hebron Inst Oncol, Breast Canc & Melanoma Grp, Barcelona, Spain. RP Serra, V (reprint author), Vall Hebron Inst Oncol, Barcelona, Spain. RI Arribas, Joaquin/M-4482-2014; Prat, Aleix/P-8561-2014 OI Arribas, Joaquin/0000-0002-0504-0664; Prat, Aleix/0000-0003-2377-540X NR 1 TC 0 Z9 0 U1 2 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2014 VL 124 IS 3 BP 1418 EP 1418 DI 10.1172/JCI75534 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AC2PZ UT WOS:000332347700056 ER PT J AU Agarwalla, PK Walcott, BP Dunn, IF Thiex, R Frerichs, K Narang, S Friedlander, RM AF Agarwalla, Pankaj K. Walcott, Brian P. Dunn, Ian F. Thiex, Ruth Frerichs, Kai Narang, Sanjeet Friedlander, Robert M. TI Fusiform aneurysms of the lenticulostriate artery SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Review DE Brain edema; Fusiform; Intracranial aneurysm; Intracranial hemorrhage; Lenticulostriate; Stroke ID SMALL CEREBRAL ANEURYSMS; HELICAL CT ANGIOGRAPHY; OF-THE-LITERATURE; SUBARACHNOID HEMORRHAGE; ENDOVASCULAR TREATMENT; SURGICAL-TREATMENT; CASE ILLUSTRATION; SURGERY; AGONISTS; CHILD AB Lenticulostriate artery aneurysms are rare, can be difficult to diagnoze, and when they rupture they are often associated with deep intraparenchymal hemorrhages. In particular, fusiform, dissecting aneurysms of a distal lenticulostriate artery are extremely rare. Typically, they are usually associated with underlying systemic conditions such as systemic lupus erythematosus, moyamoya disease, and substance abuse. Given their usual small size and location, these aneurysms may be difficult to detect with angiography and can be challenging to treat with either endovascular or microsurgical techniques. We provide background information, review the existing treatment experiences reported in the literature, and present a discussion regarding the optimal management using an illustrative clinical vignette. Parent artery obliteration can be a safe and effective treatment in these rare aneurysms. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Agarwalla, Pankaj K.; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Agarwalla, Pankaj K.; Walcott, Brian P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Dunn, Ian F.; Thiex, Ruth; Frerichs, Kai] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Thiex, Ruth] Brigham & Womens Hosp, Dept Neuroradiol, Boston, MA 02115 USA. [Narang, Sanjeet] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Friedlander, Robert M.] UPMC, Presbyterian Hosp, Dept Neurol Surg, Pittsburgh, PA USA. RP Agarwalla, PK (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM PAgarwalla@partners.org RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 49 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD MAR PY 2014 VL 21 IS 3 BP 373 EP 377 DI 10.1016/j.jocn.2013.07.009 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AD2NX UT WOS:000333073500002 PM 24156904 ER PT J AU Fazeli, PK Klibanski, A AF Fazeli, Pouneh K. Klibanski, Anne TI Determinants of GH resistance in malnutrition SO JOURNAL OF ENDOCRINOLOGY LA English DT Review DE growth hormone; IGF; neuroendocrinology; pituitary ID GROWTH-FACTOR-I; PROTEIN-ENERGY MALNUTRITION; PLASMA SOMATOMEDIN ACTIVITY; ANOREXIA-NERVOSA; HORMONE-SECRETION; BINDING-PROTEINS; PPAR-ALPHA; IGF-I; METABOLIC REGULATOR; ENDOCRINE FUNCTION AB States of undernutrition are characterized by GH resistance. Decreased total energy intake, as well as isolated protein-calorie malnutrition and isolated nutrient deficiencies, result in elevated GH levels and low levels of IGF1. We review various states of malnutrition and a disease state characterized by chronic undernutrition - anorexia nervosa - and discuss possible mechanisms contributing to the state of GH resistance, including fibroblast growth factor 21 and Sirtuin 1. We conclude by examining the hypothesis that GH resistance is an adaptive response to states of undernutrition, in order to maintain euglycemia and preserve energy. C1 [Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM pkfazeli@partners.org FU NIH [K23 DK094820, R01 DK052625] FX NIH grants K23 DK094820 (P K F) and R01 DK052625 (A K). NR 79 TC 18 Z9 18 U1 3 U2 10 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 2014 VL 220 IS 3 BP R56 EP R64 DI 10.1530/JOE-13-0477 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AC7FN UT WOS:000332693200003 PM 24363451 ER PT J AU El-Hage, N Dever, SM Rodriquez, M Masvekaar, RR Shacka, JJ Hauser, KF Gewirtz, DA AF El-Hage, N. Dever, S. M. Rodriquez, M. Masvekaar, R. R. Shacka, J. J. Hauser, K. F. Gewirtz, D. A. TI Opiate and encephalitis mediated dysregulation of autophagy in HIV infected microglia SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Meeting Abstract C1 [El-Hage, N.; Dever, S. M.; Hauser, K. F.; Gewirtz, D. A.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. [Shacka, J. J.] Univ Alabama Birmingham, Dept Pathol, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Masvekaar, R. R.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. [Rodriquez, M.] Univ Cent Caribe, Dept Microbiol & Immunol, Bayamon, PR 00970 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 EI 1557-1904 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD MAR PY 2014 VL 9 IS 1 BP 15 EP 16 PG 2 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AD3ER UT WOS:000333121600034 ER PT J AU Chan, LN Paski, SC AF Chan, Lingtak-Neander Paski, Shirley C. TI Using Plasma Vitamin D Concentration as a Surrogate Marker to Predict Drug Response A New Chapter in the Management of Inflammatory Bowel Disease and Beyond? SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Editorial Material DE nutrition; inflammatory bowel disease; research and diseases; gastroenterology; drug-nutrient interactions; vitamin D ID CROHNS-DISEASE; D-RECEPTOR; TRIAL; MAINTENANCE; ADALIMUMAB; INFLIXIMAB; COLITIS; ALPHA C1 [Chan, Lingtak-Neander] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Chan, Lingtak-Neander] Univ Washington, Grad Program Nutr Sci, Sch Publ Hlth, Seattle, WA 98195 USA. [Paski, Shirley C.] Univ Washington, Div Gastroenterol, Dept Med, Sch Med,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Chan, LN (reprint author), Univ Washington, Sch Pharm, HSC, Box 357630,1959 NE Pacific St,H-361B, Seattle, WA 98195 USA. EM neander@u.washington.edu NR 20 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 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAR PY 2014 VL 38 IS 3 BP 279 EP 280 DI 10.1177/0148607114525470 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AC7DV UT WOS:000332688300001 PM 24590306 ER PT J AU Zator, ZA Cantu, SM Konijeti, GG Nguyen, DD Sauk, J Yajnik, V Ananthakrishnan, AN AF Zator, Zachary A. Cantu, Stephanie M. Konijeti, Gauree Gupta Nguyen, Deanna D. Sauk, Jenny Yajnik, Vijay Ananthakrishnan, Ashwin N. TI Pretreatment 25-Hydroxyvitamin D Levels and Durability of Anti-Tumor Necrosis Factor-alpha Therapy in Inflammatory Bowel Diseases SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article DE Crohn's disease; biologic therapy; ulcerative colitis; vitamin D ID VITAMIN-D DEFICIENCY; ANTI-TNF THERAPY; CROHNS-DISEASE; D-RECEPTOR; REDUCED RISK; COLITIS; ASSOCIATION; SURGERY; IBD AB Introduction: Emerging evidence supports an immunologic role for 25-hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined if pretreatment vitamin D status influences durability of anti-tumor necrosis factor (TNF)-alpha therapy in patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: All IBD patients who had plasma 25(OH)D level checked <3 months prior to initiating anti-TNF-alpha therapy were included in this retrospective single-center cohort study. Our main predictor variable was insufficient plasma 25(OH)D (<30 ng/mL). Cox proportional hazards model adjusting for potential confounders was used to identify the independent effect of pretreatment vitamin D on biologic treatment cessation. Results: Our study included 101 IBD patients (74 CD; median disease duration 9 years). The median index 25(OH)D level was 27 ng/mL (interquartile range, 20-33 ng/mL). One-third of the patients had prior exposure to anti-TNF-alpha therapy. On multivariate analysis, patients with insufficient vitamin D demonstrated earlier cessation of anti-TNF-alpha therapy (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.39; P = .04). This effect was significant in patients who stopped treatment for loss of response (HR, 3.49; 95% CI, 1.34-9.09) and stronger for CD (HR, 2.38; 95% CI, 0.95-5.99) than UC (P = NS). Conclusions: Our findings suggest that vitamin D levels may influence durability of anti-TNF-alpha induction and maintenance therapy. Larger cohort studies and clinical trials of supplemental vitamin D use with disease activity as an end point may be warranted. C1 [Zator, Zachary A.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Cantu, Stephanie M.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Konijeti, Gauree Gupta; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institutes of Health [K23 DK097142, P30 DK043351] FX Dr Ananthakrishnan is supported in part by a grant from the National Institutes of Health (K23 DK097142). This work is also supported by the National Institutes of Health (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. NR 32 TC 26 Z9 26 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0148-6071 EI 1941-2444 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAR PY 2014 VL 38 IS 3 BP 385 EP 391 DI 10.1177/0148607113504002 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AC7DV UT WOS:000332688300006 PM 24088707 ER PT J AU Mori, S Dong, L Starkschall, G Mohan, R Chen, GTY AF Mori, Shinichiro Dong, Lei Starkschall, George Mohan, Radhe Chen, George T. Y. TI A serial 4DCT study to quantify range variations in charged particle radiotherapy of thoracic cancers SO JOURNAL OF RADIATION RESEARCH LA English DT Article DE charged particle radiotherapy; intrafractional range variation; interfractional range variation; dose distribution perturbation ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; CELL LUNG-CANCER; INTERFRACTIONAL REPRODUCIBILITY; RESPIRATORY MOTION; TUMOR MOTION; CT; THERAPY AB Weekly serial 4DCT scans were acquired under free breathing conditions to assess water-equivalent path length (WEL) variations due to both intrafractional and interfractional changes in tissue thickness and density and to calculate proton dose distributions resulting from anatomical variations observed in serial 4DCT. A template of region of interests (ROIs) was defined on the anterior-posterior (AP) beam's eye view, and WEL measurements were made over these ROIs to quantify chest wall thickness variations. Interfractional proton dose distributions were calculated to assess changes in the expected dose distributions caused by range variations. Mean intrafractional chest wall WEL changes during respiration varied by: -4.1 mm (<-10.2 mm), -3.6 mm (<-7.1 mm), -3.2 mm (<-5.6 mm) and -2.5 mm (<-5.1 mm) during respiration in the ITV, upper, middle and lower lung regions, respectively. The mean interfractional chest wall WEL variation at Week 6 decreased by -4.0 mm (<-8.6 mm), -9.1 mm (<-17.9 mm), -9.4 mm (<-25.3 mm) and -4.5 mm (<-15.6 mm) in the ITV, upper, middle and lower lung regions, respectively. The variations were decomposed into anterior and posterior chest wall thickness changes. Dose overshoot beyond the target was observed when the initial boli was applied throughout the treatment course. This overshoot is due to chest wall thickness variations and target positional variations. The radiological path length can vary significantly during respiration as well as over the course of several weeks of charged particle therapy. Intrafractional/interfractional chest wall thickness changes can be a significant source of range variation in treatment of lung tumors with charged particle beams, resulting in dose distribution perturbations from the initial plan. Consideration of these range variations should be made in choosing the therapeutic charged particle beam range. C1 [Mori, Shinichiro] Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Inage Ku, Chiba 260, Japan. [Dong, Lei; Starkschall, George; Mohan, Radhe] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Chen, George T. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Mori, S (reprint author), Natl Inst Radiol Sci, Res Ctr Charged Particle Therapy, Chiba 260, Japan. EM shinshin@nirs.go.jp FU NIH/NCI [CA19138] FX This work is supported in part by NIH/NCI Grant No. CA19138. NR 18 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0449-3060 EI 1349-9157 J9 J RADIAT RES JI J. Radiat. Res. PD MAR PY 2014 VL 55 IS 2 BP 309 EP 319 DI 10.1093/jrr/rrt114 PG 11 WC Biology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA AD2SK UT WOS:000333085300013 PM 24142967 ER PT J AU Boland, GW Duszak, R Dreyer, K AF Boland, Giles W. Duszak, Richard, Jr. Dreyer, Keith TI Appropriateness, Scheduling, and Patient Preparation SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID CLINICAL DECISION-SUPPORT; ORDER ENTRY; RADIOLOGY C1 [Boland, Giles W.; Dreyer, Keith] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Boland, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org RI Duszak, Richard/L-1811-2016 OI Duszak, Richard/0000-0003-0425-3008 NR 7 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2014 VL 11 IS 3 BP 225 EP 226 DI 10.1016/j.jacr.2013.12.004 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC2SR UT WOS:000332354800005 PM 24589391 ER PT J AU Trattner, S Pearson, GDN Chin, C Cody, DD Gupta, R Hess, CP Kalra, MK Kofler, JM Krishnann, MS Einstein, AJ AF Trattner, Sigal Pearson, Gregory D. N. Chin, Cynthia Cody, Dianna D. Gupta, Rajiv Hess, Christopher P. Kalra, Mannudeep K. Kofler, James M., Jr. Krishnann, Mayil S. Einstein, Andrew J. TI Standardization and Optimization of CT Protocols to Achieve Low Dose SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE CT; radiation dose; optimization; justification ID COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; IMAGE QUALITY; APPROPRIATE USE; RISK; ANGIOGRAPHY; REDUCTION; CANCER; MULTICENTER; CHILDHOOD AB The increase in radiation exposure due to CT scans has been of growing concern in recent years. CT scanners differ in their capabilities, and various indications require unique protocols, but there remains room for standardization and optimization. In this paper, the authors summarize approaches to reduce dose, as discussed in lectures constituting the first session of the 2013 UCSF Virtual Symposium on Radiation Safety and Computed Tomography. The experience of scanning at low dose in different body regions, for both diagnostic and interventional CT procedures, is addressed. An essential primary step is justifying the medical need for each scan. General guiding principles for reducing dose include tailoring a scan to a patient, minimizing scan length, use of tube current modulation and minimizing tube current, minimizing tube potential, iterative reconstruction, and periodic review of CT studies. Organized efforts for standardization have been spearheaded by professional societies such as the American Association of Physicists in Medicine. Finally, all team members should demonstrate an awareness of the importance of minimizing dose. C1 [Trattner, Sigal; Einstein, Andrew J.] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY 10032 USA. [Trattner, Sigal; Pearson, Gregory D. N.; Einstein, Andrew J.] New York Presbyterian Hosp, New York, NY USA. [Pearson, Gregory D. N.; Einstein, Andrew J.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10032 USA. [Chin, Cynthia; Hess, Christopher P.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Chin, Cynthia; Hess, Christopher P.] Univ Calif San Francisco, Dept Biomed Engn, San Francisco, CA 94143 USA. [Cody, Dianna D.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Div Diagnost Imaging, Houston, TX 77030 USA. [Gupta, Rajiv; Kalra, Mannudeep K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kofler, James M., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Krishnann, Mayil S.] Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. RP Einstein, AJ (reprint author), Columbia Univ, Med Ctr, Dept Med, Div Cardiol, 622 West 168th St,PH 10-203A, New York, NY 10032 USA. EM andrew.einstein@columbia.edu OI Hess, Christopher/0000-0002-5132-5302 FU National Heart, Lung, and Blood Institute (Bethesda, Maryland) [R01 109711]; GE Healthcare (Little Chalfont, United Kingdom) FX Dr Einstein was supported by grant R01 109711 from the National Heart, Lung, and Blood Institute (Bethesda, Maryland) and by a Victoria and Esther Aboodi Assistant Professorship, a Herbert Irving Assistant Professorship, and the Louis V. Gerstner Jr Scholars Program.; Dr Trattner has received support for other research from Philips Healthcare (Best, The Netherlands). Dr Cody has received an in-kind research grant from GE Healthcare. Dr Hess has received support for other research from GE Healthcare (Little Chalfont, United Kingdom). Dr Einstein has served as a consultant for the International Atomic Energy Agency (Vienna, Austria) and the Radiation Effects Research Foundation (Hiroshima, Japan) and has received support for other research from GE Healthcare, Philips Healthcare, and Spectrum Dynamics (Caesarea, Israel). NR 31 TC 13 Z9 14 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2014 VL 11 IS 3 BP 271 EP 278 DI 10.1016/j.jacr.2013.10.016 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC2SR UT WOS:000332354800018 PM 24589403 ER PT J AU Yarmish, GM Smith, MP Rosen, MP Baker, ME Blake, MA Cash, BD Hindman, NM Kamel, IR Kaur, H Nelson, RC Piorkowski, RJ Qayyum, A Tulchinsky, M AF Yarmish, Gail M. Smith, Martin P. Rosen, Max P. Baker, Mark E. Blake, Michael A. Cash, Brooks D. Hindman, Nicole M. Kamel, Ihab R. Kaur, Harmeet Nelson, Rendon C. Piorkowski, Robert J. Qayyum, Aliya Tulchinsky, Mark TI ACR Appropriateness Criteria Right Upper Quadrant Pain SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness Criteria; cholescintigraphy; ultrasound; cholecystitis; abdominal pain; comparative studies ID SUSPECTED ACUTE CHOLECYSTITIS; ACUTE ACALCULOUS CHOLECYSTITIS; LAPAROSCOPIC CHOLECYSTECTOMY; CT FINDINGS; PERCUTANEOUS CHOLECYSTOSTOMY; ULTRASOUND; SONOGRAPHY; EXPERIENCE; DIAGNOSIS; DISEASE AB Acute right upper quadrant pain is a common presenting symptom in patients with acute cholecystitis. When acute cholecystitis is suspected in patients with right upper quadrant pain, in most clinical scenarios, the initial imaging modality of choice is ultrasound. Although cholescintigraphy has been shown to have slightly higher sensitivity and specificity for diagnosis, ultrasound is preferred as the initial study for a variety of reasons, including greater availability, shorter examination time, lack of ionizing radiation, morphologic evaluation, confirmation of the presence or absence of gallstones, evaluation of bile ducts, and identification or exclusion of alternative diagnoses. CT or MRI may be helpful in equivocal cases and may identify complications of acute cholecystitis. When ultrasound findings are inconclusive, MRI is the preferred imaging test in pregnant patients who present with right upper quadrant pain. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Yarmish, Gail M.] Staten Isl Univ Hosp, Staten Isl, NY USA. [Smith, Martin P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rosen, Max P.] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Baker, Mark E.] Cleveland Clin, Cleveland, OH 44106 USA. [Blake, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cash, Brooks D.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Cash, Brooks D.] Amer Gastroenterol Assoc, Bethesda, MD USA. [Hindman, Nicole M.] NYU Med Ctr, New York, NY 10016 USA. [Kamel, Ihab R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kaur, Harmeet] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Nelson, Rendon C.] Duke Univ, Med Ctr, Durham, NC USA. [Piorkowski, Robert J.] Hartford Hosp, Hartford, CT 06115 USA. [Piorkowski, Robert J.] Amer Coll Surg, Chicago, IL USA. [Qayyum, Aliya] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tulchinsky, Mark] Milton S Hershey Med Ctr, Hershey, PA USA. [Tulchinsky, Mark] Soc Nucl Med & Mol Imaging, Reston, VA USA. RP Yarmish, GM (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM gyarmish@gmail.com OI Hindman, Nicole/0000-0003-4762-8041 FU NCI NIH HHS [P30 CA006973] NR 48 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2014 VL 11 IS 3 BP 316 EP 322 DI 10.1016/j.jacr.2013.11.017 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC2SR UT WOS:000332354800024 PM 24485592 ER PT J AU Cleary, JM Rodig, S Barr, PM Shinagare, AB Clark, JW Shapiro, GI Armand, P AF Cleary, James M. Rodig, Scott Barr, Paul M. Shinagare, Atul B. Clark, Jeffrey W. Shapiro, Geoffrey I. Armand, Philippe TI Crizotinib as Salvage and Maintenance With Allogeneic Stem Cell Transplantation for Refractory Anaplastic Large Cell Lymphoma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID LUNG-CANCER; ALK; PHASE-1; SAFETY AB The NPM-ALK fusion protein is found in ALK(+) anaplastic large cell lymphomas harboring the t(2; 5) chromosomal translocation. Patients harboring ALK translocations typically have an excellent prognosis with conventional chemotherapy and a reported 5-year survival rate of 70%. Although most patients with ALK(+) anaplastic large cell lymphoma have a good prognosis, some patients do not respond to standard therapies. In patients with refractory anaplastic large cell lymphoma who can achieve remission, allogeneic stem cell transplant is a potentially curative option. This article describes a patient with refractory ALK(+) anaplastic large cell lymphoma who experienced a complete response to the ALK inhibitor crizotinib and then underwent an allogeneic stem cell transplant followed by crizotinib maintenance therapy. C1 [Cleary, James M.; Shinagare, Atul B.; Shapiro, Geoffrey I.; Armand, Philippe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Rodig, Scott] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Barr, Paul M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Cleary, JM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jcleary@partners.org NR 14 TC 5 Z9 5 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2014 VL 12 IS 3 BP 323 EP 326 PG 4 WC Oncology SC Oncology GA AC8IV UT WOS:000332777600006 PM 24616538 ER PT J AU Denlinger, CS Carlson, RW Are, M Baker, KS Davis, E Edge, SB Friedman, DL Goldman, M Jones, L King, A Kvale, E Langbaum, TS Ligibel, JA McCabe, MS McVary, KT Melisko, M Montoya, JG Mooney, K Morgan, MA O'Connor, T Paskett, ED Raza, M Syrjala, KL Urba, SG Wakabayashi, MT Zee, P McMillian, N Freedman-Cass, D AF Denlinger, Crystal S. Carlson, Robert W. Are, Madhuri Baker, K. Scott Davis, Elizabeth Edge, Stephen B. Friedman, Debra L. Goldman, Mindy Jones, Lee King, Allison Kvale, Elizabeth Langbaum, Terry S. Ligibel, Jennifer A. McCabe, Mary S. McVary, Kevin T. Melisko, Michelle Montoya, Jose G. Mooney, Kathi Morgan, Mary Ann O'Connor, Tracey Paskett, Electra D. Raza, Muhammad Syrjala, Karen L. Urba, Susan G. Wakabayashi, Mark T. Zee, Phyllis McMillian, Nicole Freedman-Cass, Deborah TI Survivorship: Sexual Dysfunction (Male), Version 1.2013 SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID LOCALIZED PROSTATE-CANCER; ERECTILE DYSFUNCTION; CARDIOVASCULAR-DISEASE; RADIOTHERAPY; OUTCOMES; PREVALENCE; SILDENAFIL; MEN AB Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction. C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Carlson, Robert W.; Montoya, Jose G.] Stanford Canc Inst, Stanford, CA USA. [Are, Madhuri] Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Baker, K. Scott; Syrjala, Karen L.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Davis, Elizabeth] Tewksbury Hosp, Tewksbury, MA USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Buffalo, NY USA. [Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Goldman, Mindy; Melisko, Michelle] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Jones, Lee] Duke Canc Inst, Durham, NC USA. [King, Allison] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [King, Allison] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Kvale, Elizabeth] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Langbaum, Terry S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Ligibel, Jennifer A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [McVary, Kevin T.; Zee, Phyllis] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Mooney, Kathi] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Morgan, Mary Ann] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [O'Connor, Tracey] Roswell Pk Canc Inst, Buffalo, NY USA. [Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Paskett, Electra D.] Solove Res Inst, Columbus, OH USA. [Raza, Muhammad] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wakabayashi, Mark T.] City Hope Comprehens Canc Ctr, Duarte, CA USA. RP Denlinger, CS (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. OI King, Allison/0000-0002-1951-6176 FU NCI NIH HHS [UM1 CA173642] NR 27 TC 2 Z9 2 U1 2 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2014 VL 12 IS 3 BP 356 EP 363 PG 8 WC Oncology SC Oncology GA AC8IV UT WOS:000332777600009 PM 24616541 ER PT J AU Picard, M Matulonis, UA Castells, M AF Picard, Matthieu Matulonis, Ursula A. Castells, Mariana TI Chemotherapy Hypersensitivity Reactions in Ovarian Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CARBOPLATIN HYPERSENSITIVITY; COMPLEMENT ACTIVATION; DESENSITIZATION PROTOCOL; RAPID DESENSITIZATION; ETOPOSIDE PHOSPHATE; PACLITAXEL PREMEDICATION; RISK STRATIFICATION; CROSS-SENSITIVITY; RANDOMIZED-TRIAL; FLUID RETENTION AB Ovarian cancer is the fifth leading cause of cancer death among women in the United States. Chemotherapy using a taxane and platinum combination is key in improving survival in patients with newly diagnosed advanced ovarian cancer and is also used to treat recurrent platinum-sensitive disease. However, hypersensitivity reactions (HSRs) to chemotherapeutic agents are increasingly common and can greatly limit their use. Moreover, because of the frequent lack of equally effective alternative agents, chances of survival can be compromised. Therefore, physicians caring for these patients must be familiar with the management of HSRs to chemotherapy, and major advancements have recently been made in this field. Most HSRs implicate mast cell and basophil activation either through an IgE-mediated (ie, platinum agents) or nonspecific (ie, taxanes) mechanism. Therefore, these reactions have the potential to lead to anaphylaxis, at which time they should be treated with intramuscular epinephrine. Serum tryptase, which is released alongside histamine after mast cell activation, may be measured after an acute HSR to document mast cell involvement. After an HSR, the decision to re-treat with the same agent or a closely related one will vary depending on the causative drug, the type of HSR, and its severity. Drug desensitization has emerged as a safe and effective way of reintroducing a chemotherapeutic agent or monoclonal antibody responsible for an HSR in a patient who is expected to benefit from its continued use and for whom alternatives are considered less effective and/or more toxic. Currently, candidates for desensitization are preferably evaluated in academic settings with expertise in those procedures, because their use is still limited. Efforts are now needed to increase awareness about desensitization procedures so that more patients may benefit. This challenge will require the close collaboration of patients, nurses, oncologists, and allergists. C1 [Picard, Matthieu; Castells, Mariana] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Matulonis, Ursula A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Castells, M (reprint author), Brigham & Womens Hosp, 1 Jimmy Fund Way,Smith Bldg, Boston, MA 02115 USA. EM mcastells@partners.org NR 110 TC 2 Z9 2 U1 0 U2 7 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2014 VL 12 IS 3 BP 389 EP 402 PG 14 WC Oncology SC Oncology GA AC8IV UT WOS:000332777600012 PM 24616544 ER PT J AU Drain, PK Hyle, EP Noubary, F Freedberg, KA Wilson, D Bishai, WR Rodriguez, W Bassett, IV AF Drain, Paul K. Hyle, Emily P. Noubary, Farzad Freedberg, Kenneth A. Wilson, Douglas Bishai, William R. Rodriguez, William Bassett, Ingrid V. TI Diagnostic point-of-care tests in resource-limited settings SO LANCET INFECTIOUS DISEASES LA English DT Review ID PORTABLE CLINICAL ANALYZER; HIV-INFECTED PATIENTS; MODEL-BASED ANALYSIS; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; LIKELIHOOD RATIOS; DEVELOPING-WORLD; PULMONARY TUBERCULOSIS; PERFORMANCE EVALUATION; ASSESSING AGREEMENT AB The aim of diagnostic point-of-care testing is to minimise the time to obtain a test result, thereby allowing dinicians and patients to make a quick clinical decision. Because point-of-care tests are used in resource-limited settings, the benefits need to outweigh the costs. To optimise point-of-care testing in resource-limited settings, diagnostic tests need rigorous assessments focused on relevant clinical outcomes and operational costs, which differ from assessments of conventional diagnostic tests. We reviewed published studies on point-of-care testing in resource-limited settings, and found no dearly defined metric for the clinical usefulness of point-of-care testing. Therefore, we propose a framework for the assessment of point-of-care tests, and suggest and define the term test efficacy to describe the ability of a diagnostic test to support a clinical decision within its operational context. We also propose revised criteria for an ideal diagnostic point-of-care test in resource-limited settings. Through systematic assessments, comparisons between centralised testing and novel point-of-care technologies can be more formalised, and health officials can better establish which point-of-care technologies represent valuable additions to their clinical programmes. C1 [Drain, Paul K.; Hyle, Emily P.; Noubary, Farzad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practice Evaluat Ctr, Boston, MA USA. [Noubary, Farzad] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Noubary, Farzad] Tufts Univ, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Wilson, Douglas] Edendale Hosp, Pietermaritzburg, South Africa. [Bishai, William R.] Johns Hopkins Univ, Baltimore, MD USA. [Bishai, William R.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Rodriguez, William] Daktari Diagnost, Boston, MA USA. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. EM pdrain@partners.org OI Drain, Paul/0000-0003-3300-3817 FU Harvard Global Health Institute, Boston, MA, USA; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University, Nashville, TN, USA [R24 TW007988]; NIH Program for AIDS Clinical Research Training [T32 AI007433]; National Institutes of Health [R01 MH090326, R01 AI062476, R01 AI079590, R01 AI097138]; Howard Hughes Medical Institute, Chevy Chase, MD, USA FX This Review was supported by the Harvard Global Health Institute, Boston, MA, USA (PKD); the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University, Nashville, TN, USA (R24 TW007988; PKD); an NIH Program for AIDS Clinical Research Training (Grant T32 AI007433; PKD, EPH); National Institutes of Health grants R01 MH090326 (IVB), R01 AI062476 (KAF), R01 AI079590 (WRB), and R01 AI097138 (WRB), and a grant from Howard Hughes Medical Institute, Chevy Chase, MD, USA (WRB). The corresponding author had access to all the data in the study, and had final responsibility to submit for publication. The funding sources had no role in the conception, design, or reporting of this report. NR 147 TC 65 Z9 67 U1 3 U2 60 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD MAR PY 2014 VL 14 IS 3 BP 239 EP 249 DI 10.1016/S1473-3099(13)70250-0 PG 11 WC Infectious Diseases SC Infectious Diseases GA AC8YN UT WOS:000332821100029 PM 24332389 ER PT J AU Yin, R Lin, L Xiao, Y Hao, F Hamblin, MR AF Yin, Rui Lin, Lin Xiao, Yan Hao, Fei Hamblin, Michael R. TI Combination ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) on the treatment of severe acne SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE ablative fractional laser; photodynamic therapy; atrophic scars; erbium: yttrium-aluminum-garnet laser; acne vulgaris; 5-aminolevulinic acid ID PHOTODYNAMIC THERAPY; VULGARIS; SCARS; SKIN; EFFICACY; PHOTOTHERMOLYSIS; UPDATE; SAFETY; BASICS AB Background Scarring is a very common complication of severe acne and is difficult to treat by conventional methods. 5-Aminolevulinic acid (ALA) photodynamic therapy (PDT) is a novel treatment for improving acne lesions. Fractional laser resurfacing is a promising treatment for scar treatment because of its unique ability to stimulate the wound healing response and its depth of penetration. Objective To evaluate the efficacy of combination therapies of ALA-PDT and ablative fractional Er:YAG laser (2,940 nm) for scarring lesions in severe acne patients. Methods A prospective, single-arm, pilot study. Forty subjects with severe acne were treated with 15% ALA-PDT for four times at 10-day intervals. They then received ablative fractional Er:YAG laser treatment five times at 4-week intervals. Three independent investigators evaluated subject outcomes at 1, 3, 6, and 12 months post-treatment (primary outcome); patients also provided self-assessments of improvement (secondary outcome). Results Significant reductions in acne score (P < 0.01) were obtained at follow-up visits after 1, 3, 6, and 12 months. After 6 month, the lesions showed overall improvement in all of subjects (good to excellent in acne inflammatory lesions), 80% overall improvement in acne scars. After 12 months, most of subjects had improved hypertrophic/atrophic scars (good to excellent in 85%) and no one had recurrent acne inflammatory lesions. Patient self-evaluation also revealed good to excellent improvements (on average) in acne lesions and scarring, with significant improvements in self-esteem after 6 months post-treatment. Conclusions PDT can control the inflammation and improve the severity of acne lesions. Fractional resurfacing is a promising new treatment modality for scars by stimulating wound healing and remodeling. The combination therapy is a promising option for severe acne to prevent and improve car formation. Lasers Surg. Med. 46:165-172, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Yin, Rui; Lin, Lin; Xiao, Yan; Hao, Fei] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Yin, R (reprint author), Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. EM swyinrui@gmail.com OI Hamblin, Michael/0000-0001-6431-4605 FU National Natural Science Foundation of China [81172495]; NIH [R01AI050875]; ASLM FX Contract grant sponsor: National Natural Science Foundation of China; Contract grant number: 81172495; Contract grant sponsor: NIH Grant; Contract grant number: R01AI050875; Contract grant sponsor: ASLM. NR 29 TC 7 Z9 7 U1 1 U2 7 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 MAR PY 2014 VL 46 IS 3 BP 165 EP 172 DI 10.1002/lsm.22219 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2ON UT WOS:000333075100001 PM 24391075 ER PT J AU Frigerio, A Bhama, PK Tan, OT AF Frigerio, Alice Bhama, Prabhat K. Tan, Oon T. TI Quantitative three-dimensional assessment of port-wine stain clearance after laser treatments SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE laser photocoagulation; port-wine stain; 3dMD ID PULSED DYE-LASER; STURGE-WEBER SYNDROME; PHOTOTHERMOLYSIS AB Background and Objective Outcomes analysis of laser treatment for port-wine stains has been hampered by the lack of an objective measure of surface area and volume; moreover, treatment success is often gauged by clinician subjective assessment. Three-dimensional (3D) surface imaging has been applied in several medical disciplines to quantify surface changes, with promising results. We hypothesized that 3D surface imaging could be used to objectively measure changes in area and volume of port-wine stains following laser treatment. Study Design/Materials and Methods We performed a retrospective review of consecutive patients with port-wine stains treated over a 20-month time period. Area and volume of the lesions were measured using 3dMD photogrammetric software (3dMD, Atlanta, GA) before and after a series of sequential pulsed dye laser and/or alexandrite laser treatments. Results Fifty-five patients with 59 port-wine stains were included in the study. The initial average measured area was 44.3 cm(2); final average measured area decreased to 36.9 cm(2) (P < 0.001). The average volume change was 1.20 cc for all PWS included in the study and 1.90 cc for lesions that received at least 5 laser treatments within the study period. Conclusion Three-dimensional photography demonstrated area and volume changes in patients with port-wine stains after laser treatments. Future studies to determine if statistically significant changes correlate with clinically appreciable changes are warranted. Lasers Surg. Med. 46:180-185, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Frigerio, Alice; Tan, Oon T.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, Boston, MA 02114 USA. [Bhama, Prabhat K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Div Facial Plast & Reconstru, Boston, MA USA. RP Frigerio, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Carolyn & Peter Lynch Ctr Laser & Reconstruct Sur, 243 Charles St, Boston, MA 02114 USA. EM alice_frigerio@meei.harvard.edu OI Frigerio, Alice/0000-0001-9202-9553 FU Lynch Foundation FX Contract grant sponsor: Lynch Foundation. NR 17 TC 1 Z9 1 U1 2 U2 6 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 MAR PY 2014 VL 46 IS 3 BP 180 EP 185 DI 10.1002/lsm.22193 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA AD2ON UT WOS:000333075100003 PM 24155123 ER PT J AU Lamphier, M Zheng, WJ Latz, E Spyvee, M Hansen, H Rose, J Genest, M Yang, H Shaffer, C Zhao, Y Shen, YC Liu, C Liu, D Mempel, TR Rowbottom, C Chow, J Twine, NC Yu, M Gusovsky, F Ishizaka, ST AF Lamphier, Marc Zheng, Wanjun Latz, Eicke Spyvee, Mark Hansen, Hans Rose, Jeffrey Genest, Melinda Yang, Hua Shaffer, Christina Zhao, Yan Shen, Yongchun Liu, Carrie Liu, Diana Mempel, Thorsten R. Rowbottom, Christopher Chow, Jesse Twine, Natalie C. Yu, Melvin Gusovsky, Fabian Ishizaka, Sally T. TI Novel Small Molecule Inhibitors of TLR7 and TLR9: Mechanism of Action and Efficacy In Vivo SO MOLECULAR PHARMACOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; IMMUNOSTIMULATORY CPG-OLIGODEOXYNUCLEOTIDES; AUTOANTIBODY PRODUCTION; MURINE LUPUS; DNA; DISEASE; HYDROXYCHLOROQUINE; RECOGNITION; CHLOROQUINE; CELLS AB The discovery that circulating nucleic acid-containing complexes in the serum of autoimmune lupus patients can stimulate B cells and plasmacytoid dendritic cells via Toll-like receptors 7 and 9 suggested that agents that block these receptors might be useful therapeutics. We identified two compounds, AT791 {3-[4-(6-(3-(dimethylamino)propoxy)benzo[d]oxazol-2-yl)phenoxy]-N, N-dimethylpropan-1-amine} and E6446 {6-[3-(pyrrolidin-1-yl) propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole}, that inhibit Toll-like receptor (TLR) 7 and 9 signaling in a variety of human and mouse cell types and inhibit DNA-TLR9 interaction in vitro. When administered to mice, these compounds suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9. When given chronically in spontaneous mouse lupus models, E6446 slowed development of circulating antinuclear antibodies and had a modest effect on anti-double-stranded DNA titers but showed no observable impact on proteinuria or mortality. We discovered that the ability of AT791 and E6446 to inhibit TLR7 and 9 signaling depends on two properties: weak interaction with nucleic acids and high accumulation in the intracellular acidic compartments where TLR7 and 9 reside. Binding of the compounds to DNA prevents DNA-TLR9 interaction in vitro and modulates signaling in vivo. Our data also confirm an earlier report that this same mechanism may explain inhibition of TLR7 and 9 signaling by hydroxychloroquine (Plaquenil; Sanofi-Aventis, Bridgewater, NJ), a drug commonly prescribed to treat lupus. Thus, very different structural classes of molecules can inhibit endosomal TLRs by essentially identical mechanisms of action, suggesting a general mechanism for targeting this group of TLRs. C1 [Lamphier, Marc; Zheng, Wanjun; Spyvee, Mark; Hansen, Hans; Rose, Jeffrey; Genest, Melinda; Yang, Hua; Shaffer, Christina; Zhao, Yan; Shen, Yongchun; Liu, Carrie; Liu, Diana; Rowbottom, Christopher; Chow, Jesse; Twine, Natalie C.; Yu, Melvin; Gusovsky, Fabian; Ishizaka, Sally T.] Eisai Inc, Andover, MA 01810 USA. [Latz, Eicke] Univ Massachusetts, Dept Infect Dis & Immunol, Worcester, MA 01605 USA. [Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany. [Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Mempel, Thorsten R.] Harvard Univ, Sch Med, Ctr Syst Biol, Charlestown, MA USA. RP Ishizaka, ST (reprint author), Eisai Inc, 4 Corp Dr, Andover, MA 01810 USA. EM sally_ishizaka@eisai.com NR 33 TC 25 Z9 25 U1 0 U2 22 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2014 VL 85 IS 3 BP 429 EP 440 DI 10.1124/mol.113.089821 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC9PB UT WOS:000332865500005 PM 24342772 ER PT J AU Lin, DJ Hermann, KL Schmahmann, JD AF Lin, David J. Hermann, Katherine L. Schmahmann, Jeremy D. TI Multiple System Atrophy of the Cerebellar Type: Clinical State of the Art SO MOVEMENT DISORDERS LA English DT Review DE multiple system atrophy; cerebellum; ataxia; idiopathic late-onset cerebellar ataxia; sporadic adult-onset ataxia of unknown etiology ID NEUROGENIC ORTHOSTATIC HYPOTENSION; TRANSGENIC MOUSE MODEL; GLIAL CYTOPLASMIC INCLUSIONS; PROGRESSIVE SUPRANUCLEAR PALSY; MACHADO-JOSEPH-DISEASE; ADULT-ONSET ATAXIA; LESION RAT MODEL; CROSS BUN SIGN; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE AB Multiple system atrophy (MSA) is a late-onset, sporadic neurodegenerative disorder clinically characterized by autonomic failure and either poorly levodopa-responsive parkinsonism or cerebellar ataxia. It is neuropathologically defined by widespread and abundant central nervous system -synuclein-positive glial cytoplasmic inclusions and striatonigral and/or olivopontocerebellar neurodegeneration. There are two clinical subtypes of MSA distinguished by the predominant motor features: the parkinsonian variant (MSA-P) and the cerebellar variant (MSA-C). Despite recent progress in understanding the pathobiology of MSA, investigations into the symptomatology and natural history of the cerebellar variant of the disease have been limited. MSA-C presents a unique challenge to both clinicians and researchers alike. A key question is how to distinguish early in the disease course between MSA-C and other causes of adult-onset cerebellar ataxia. This is a particularly difficult question, because the clinical framework for conceptualizing and studying sporadic adult-onset ataxias continues to undergo flux. To date, several investigations have attempted to identify clinical features, imaging, and other biomarkers that may be predictive of MSA-C. This review presents a clinically oriented overview of our current understanding of MSA-C with a focus on evidence for distinguishing MSA-C from other sporadic, adult-onset ataxias. (c) 2014 International Parkinson and Movement Disorder Society C1 [Lin, David J.; Hermann, Katherine L.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Lab Neuroanat & Cerebellar Neurobiol, Ataxia Unit, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM jschmahmann@partners.org FU National Ataxia Foundation; National Organization for Rare Disorders; Birmingham Foundation; Mindlink Foundation FX This study was supported by the National Ataxia Foundation, the National Organization for Rare Disorders, the Birmingham Foundation, and the Mindlink Foundation. NR 139 TC 18 Z9 18 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2014 VL 29 IS 3 BP 294 EP 304 DI 10.1002/mds.25847 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AC8ZG UT WOS:000332823000003 PM 24615754 ER PT J AU Cook, JF Hill, DF Snively, BM Boggs, N Suerken, CK Haq, I Stacy, M McCall, WV Ozelius, LJ Sweadner, KJ Brashear, A AF Cook, Jared F. Hill, Deborah F. Snively, Beverly M. Boggs, Niki Suerken, Cynthia K. Haq, Ihtsham Stacy, Mark McCall, W. Vaughn Ozelius, Laurie J. Sweadner, Kathleen J. Brashear, Allison TI Cognitive Impairment in Rapid-Onset Dystonia-Parkinsonism SO MOVEMENT DISORDERS LA English DT Article DE dystonia; RDP; DYT-12; rapid-onset dystonia-parkinsonism ID ALTERNATING HEMIPLEGIA; ATP1A3 MUTATIONS; BASAL GANGLIA; MOTOR; CEREBELLUM; CHILDHOOD; DEFICITS; DISORDERS; ISOFORM; ATAXIA AB Rapid-onset dystonia-parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation-negative controls. We studied 22 familial RDP patients, 3 non-motor-manifesting mutation-positive family members, 29 mutation-negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive battery of memory and learning, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed and similarly for severity of depressive symptoms. A majority of RDP patients had onset of motor symptoms by age 25 and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean +/- SD, 52.1 +/- 29.5) and UPDRS motor subscore (29.8 +/- 12.7) confirmed dystonia-parkinsonism. The affected RDP patients performed more poorly, on average, than mutation-negative controls for all memory and learning, psychomotor speed, attention, and executive function scores (all P0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP. (c) 2014 International Parkinson and Movement Disorder Society C1 [Cook, Jared F.; Hill, Deborah F.; Haq, Ihtsham; Brashear, Allison] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA. [Snively, Beverly M.; Suerken, Cynthia K.] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Boggs, Niki; McCall, W. Vaughn] Wake Forest Baptist Hlth, Wake Forest Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC USA. [Stacy, Mark] Duke Univ, Sch Med, Dept Neurol, Duke Hlth, Durham, NC USA. [Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Sweadner, Kathleen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [McCall, W. Vaughn] Georgia Hlth Sci Univ, Dept Psychiat & Hlth Behav, Augusta, GA USA. RP Brashear, A (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Baptist Med Ctr, Dept Neurol, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. EM abrashea@wakehealth.edu RI Brashear, Allison/G-3853-2015 FU NINDS [5R01NS058949-04] FX This study was supported by NINDS 5R01NS058949-04 (to Allison Brashear). NR 35 TC 16 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2014 VL 29 IS 3 BP 344 EP 350 DI 10.1002/mds.25790 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AC8ZG UT WOS:000332823000013 PM 24436111 ER PT J AU Fu, YF Sander, JD Reyon, D Cascio, VM Joung, JK AF Fu, Yanfang Sander, Jeffry D. Reyon, Deepak Cascio, Vincent M. Joung, J. Keith TI Improving CRISPR-Cas nuclease specificity using truncated guide RNAs SO NATURE BIOTECHNOLOGY LA English DT Article ID ZINC-FINGER TARGETER; HUMAN-CELLS; TRANSCRIPTION FACTORS; HUMAN GENOME; TOOL; NICKASES; SYSTEMS; NICKING; GENES; ZIFIT AB Clustered, regularly interspaced, short palindromic repeat (CRISPR) RNA-guided nucleases (RGNs) are highly efficient genome editing tools(1-3). CRISPR-associated 9 (Cas9) RGNs are directed to genomic loci by guide RNAs (gRNAs) containing 20 nucleotides that are complementary to a target DNA sequence. However, RGNs can induce mutations at sites that differ by as many as five nucleotides from the intended target(4-6). Here we report that truncated gRNAs, with shorter regions of target complementarity <20 nucleotides in length, can decrease undesired mutagenesis at some off-target sites by 5,000-fold or more without sacrificing on-target genome editing efficiencies. In addition, use of truncated gRNAs can further reduce off-target effects induced by pairs of Cas9 variants that nick DNA (paired nickases). Our results delineate a simple, effective strategy to improve the specificities of Cas9 nucleases or paired nickases. C1 [Fu, Yanfang; Sander, Jeffry D.; Reyon, Deepak; Cascio, Vincent M.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Fu, Yanfang; Sander, Jeffry D.; Reyon, Deepak; Cascio, Vincent M.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. [Fu, Yanfang; Sander, Jeffry D.; Reyon, Deepak; Cascio, Vincent M.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Fu, Yanfang; Sander, Jeffry D.; Reyon, Deepak; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jsander@alumni.iastate.edu; jjoung@mgh.harvard.edu FU National Institutes of Health (NIH) Director's Pioneer Award [DP1 GM105378]; NIH [R01 GM088040, NIH P50 HG005550]; Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award; US Army Research Laboratory; US Army-Research Office [W911NF-11-2-0056] FX We thank M. Maeder, S. Tsai and J. Angstman for helpful discussions and comments on the manuscript and J. Foden for technical assistance. This work was funded by a National Institutes of Health (NIH) Director's Pioneer Award (DP1 GM105378), NIH R01 GM088040, NIH P50 HG005550, and the Jim and Ann Orr Massachusetts General Hospital (MGH) Research Scholar Award. This material is based upon work supported by, or in part by, the US Army Research Laboratory and the US Army-Research Office under grant number W911NF-11-2-0056. NR 28 TC 437 Z9 474 U1 45 U2 240 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2014 VL 32 IS 3 BP 279 EP 284 DI 10.1038/nbt.2808 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AC8YA UT WOS:000332819800027 PM 24463574 ER PT J AU Liu, JK Coady, S Carr, JJ Hoffmann, U Taylor, HA Fox, CS AF Liu, Jiankang Coady, Sean Carr, J. Jeffery Hoffmann, Udo Taylor, Herman A. Fox, Caroline S. TI Differential Associations of Abdominal Visceral, Subcutaneous Adipose Tissue with Cardiometabolic Risk Factors between African and European Americans SO OBESITY LA English DT Article ID ETHNIC-DIFFERENCES; HERITAGE FAMILY; INSULIN ACTION; FAT; HEART; RACE; DISEASE; OBESITY; HEALTH; ADULTS AB Objective: To examine the relative association of abdominal visceral adipose tissue (VAT) with cardiometabolic risk factors between African and European Americans. Methods: A cross-sectional study of 2,035 African Americans from the Jackson Heart Study (JHS) and 3,170 European Americans from the Framingham Heart Study (FHS) who underwent computed tomography assessment of VAT and subcutaneous adipose tissue (SAT) was conducted. The FHS participants were weighted to match the age distribution of the JHS participants, and the metabolic risk factors were examined by study groups in relation to VAT. Results: JHS participants had higher rates of obesity, hypertension, diabetes, and metabolic syndrome than FHS participants (all P = 0.001). The associations were weaker in JHS women for VAT with blood pressure, triglycerides, HDL-C, and total cholesterol (P-interaction = 0.03-0.001) than FHS women. In contrast, JHS men had stronger associations for VAT with high triglycerides, low HDL, and metabolic syndrome (all P-interaction = 0.001) compared to FHS men. Similar associations and gender patterns existed for SAT with most metabolic risk factors. Conclusions: The relative association between VAT and cardiometabolic risk factors is weaker in JHS women compared to FHS women, whereas stronger associations with triglycerides and HDL were observed in JHS men. C1 [Liu, Jiankang; Taylor, Herman A.] Jackson State Univ, Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS USA. [Coady, Sean; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Coady, Sean; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Carr, J. Jeffery] Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27109 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. EM jliu@umc.edu; foxca@nhlbi.nih.gov RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU National Heart, Lung, and Blood Institute; National Center on Minority Health and Health Disparities [N01-HC-95170, N01-HC-95171, N01-C-95172, N01-HC-25195] FX The Jackson Heart Study and the Framingham Heart Study are supported by the National Heart, Lung, and Blood Institute, and the National Center on Minority Health and Health Disparities (N01-HC-95170, N01-HC-95171, N01-C-95172 and N01-HC-25195). NR 22 TC 9 Z9 9 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD MAR PY 2014 VL 22 IS 3 BP 811 EP 818 DI 10.1002/oby.20307 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AC0ZU UT WOS:000332224800028 PM 23408700 ER PT J AU Ankuda, CK Block, SD Cooper, Z Correll, DJ Hepner, DL Lasic, M Gawande, AA Bader, AM AF Ankuda, Claire K. Block, Susan D. Cooper, Zara Correll, Darin J. Hepner, David L. Lasic, Morana Gawande, Atul A. Bader, Angela M. TI Measuring critical deficits in shared decision making before elective surgery SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Shared surgical decision making; Health care disparities ID CONSENT; CARE; RECALL AB Objective: Identifying patient factors correlated with specific needs in preoperative decision making is of clinical and ethical importance. We examined patterns and predictors of deficiencies in informed surgical consent and shared decision-making in preoperative patients. Methods: Validated measures were used to survey 1034 preoperative patients in the preoperative clinic after signed informed consent. Principal component analysis defined correlated groupings of factors. Multivariable analysis assessed patient factors associated with resultant groupings. Results: 13% of patients exhibited deficits in their informed consent process; 33% exhibited other types of deficits. Informed consent deficits included not knowing the procedure being performed or risks and benefits. Other deficits included not having addressed patient values, preferences and goals. Non-English language and lower educational level were factors correlated with higher risk for deficits. Conclusion: Deficits exist in over a third of patients undergoing preoperative decision-making. Sociodemographic factors such as language and educational level identified particularly vulnerable groups at risk for having an incomplete, and possibly ineffective, decision-making process. Practice implications: Interventions to identify vulnerable groups and address patient centered surgical decision making in the pre-operative setting are needed. Focused interventions to address the needs of at-risk patients have potential to improve the surgical decision-making process and reduce disparities. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Ankuda, Claire K.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Block, Susan D.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Block, Susan D.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA USA. [Cooper, Zara] Harvard Univ, Sch Med, Dept Surg, Brigham & Womens Hosp, Boston, MA 02115 USA. [Correll, Darin J.; Hepner, David L.; Lasic, Morana; Bader, Angela M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Gawande, Atul A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. [Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Bader, AM (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM abader@partners.org NR 15 TC 14 Z9 14 U1 0 U2 2 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 MAR PY 2014 VL 94 IS 3 BP 328 EP 333 DI 10.1016/j.pec.2013.11.013 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AC3SJ UT WOS:000332441200006 PM 24382399 ER PT J AU Rork, JF Huang, JT Gordon, LB Kleinman, M Kieran, MW Liang, MG AF Rork, Jillian F. Huang, Jennifer T. Gordon, Leslie B. Kleinman, Monica Kieran, Mark W. Liang, Marilyn G. TI Initial Cutaneous Manifestations of Hutchinson- Gilford Progeria Syndrome SO PEDIATRIC DERMATOLOGY LA English DT Article ID OF-THE-LITERATURE; SUBCUTANEOUS FAT NECROSIS; PHENOTYPE; SKIN; SCLERODERMA; FEATURES AB Hutchinson-Gilford progeria syndrome (HGPS) is a rare, uniformly fatal, premature aging disease with distinct dermatologic features. We sought to identify and describe the initial skin and hair findings as potential diagnostic signs of the disease. We performed a chart review of the structured initial intake histories of 39 individuals with HGPS enrolled in clinical trials from 2007 to 2010 at Boston Children's Hospital, limited to cutaneous history from birth to 24months. Medical photographs were provided through the clinical trials and the Progeria Research Foundation Medical and Research Database at Brown University Center for Gerontology and Healthcare Research. All 39 patients reported skin and hair abnormalities within the first 24months of life. Pathologies included sclerodermoid change, prominent superficial veins, dyspigmentation, and alopecia. The mean age of presentation for each finding was <12months. The most frequently reported skin feature was sclerodermoid change, which commonly involved the abdomen and bilateral lower extremities. Prominent superficial vasculature manifested as circumoral cyanosis and pronounced veins on the scalp and body. Hypo- and hyperpigmentation were observed over areas of sclerodermoid change. Scalp alopecia progressed in a distinct pattern, with preservation of the hair over the midscalp and vertex areas for the longest period of time. HGPS has distinct cutaneous manifestations during the first 2years of life that may be the first signs of disease. Awareness of these findings could expedite diagnosis. C1 [Rork, Jillian F.; Huang, Jennifer T.; Liang, Marilyn G.] Harvard Univ, Sch Med, Dept Dermatol, Boston Childrens Hosp, Boston, MA 02115 USA. [Gordon, Leslie B.; Kleinman, Monica] Harvard Univ, Sch Med, Dept Anesthesia, Boston Childrens Hosp, Boston, MA 02115 USA. [Gordon, Leslie B.; Kleinman, Monica] Harvard Univ, Sch Med, Div Crit Care Med, Boston Childrens Hosp, Boston, MA USA. [Gordon, Leslie B.] Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Warren Alpert Med Sch, Providence, RI 02912 USA. [Kieran, Mark W.] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. [Kieran, Mark W.] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Liang, MG (reprint author), Boston Childrens Hosp, Dermatol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM marilyn.liang@childrens.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU Progeria Research Foundation; National Institutes of Health [1RC2HL101631-01]; Boston Children's Hospital; Stop&Shop Pediatric Brain Tumor Fund at the Dana-Farber Cancer Institute FX This study was supported by the Progeria Research Foundation, National Institutes of Health grant 1RC2HL101631-01, Boston Children's Hospital, and the Stop&Shop Pediatric Brain Tumor Fund at the Dana-Farber Cancer Institute. NR 24 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 EI 1525-1470 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAR PY 2014 VL 31 IS 2 BP 196 EP 202 DI 10.1111/pde.12284 PG 7 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA AC3AW UT WOS:000332388400025 PM 24456199 ER PT J AU McKinley, SK Huang, JT Tan, J Kroshinsky, D Gellis, S AF McKinley, Sophia K. Huang, Jennifer T. Tan, Jennifer Kroshinsky, Daniela Gellis, Stephen TI A Case of Recalcitrant Epidermolysis Bullosa Acquisita Responsive to Rituximab Therapy SO PEDIATRIC DERMATOLOGY LA English DT Article ID OF-THE-LITERATURE; VII COLLAGEN; MONOCLONAL-ANTIBODY; B-CELLS; DISORDERS; DEPLETION; VULGARIS; DISEASES AB Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disorder that occurs infrequently in children. Although typically associated with a good prognosis in children, there are rare cases that are refractory to treatment with conventional immunosuppressive therapy. Rituximab, an anti-CD20 monoclonal antibody, has been reported to be effective in the adult form of EBA. We report a case of a child with severe and recalcitrant EBA exhibiting a sustained response to treatment with rituximab. C1 [McKinley, Sophia K.] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Jennifer T.; Tan, Jennifer; Gellis, Stephen] Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. [Huang, Jennifer T.; Tan, Jennifer; Gellis, Stephen] Harvard Univ, Sch Med, Dept Dermatol, Childrens Hosp Boston, Boston, MA 02115 USA. [Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Huang, JT (reprint author), Fegan 6,300 Longwood Ave, Boston, MA 02115 USA. EM jenhuang711@gmail.com NR 17 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 EI 1525-1470 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAR PY 2014 VL 31 IS 2 BP 241 EP 244 DI 10.1111/pde.12006 PG 4 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA AC3AW UT WOS:000332388400035 PM 23106762 ER PT J AU Campbell, MS Schatz, DA Chen, V Wong, JC Steck, A Tamborlane, WV Smith, J Beck, RW Cengiz, E Laffel, LM Miller, KM Haller, MJ AF Campbell, Meredith S. Schatz, Desmond A. Chen, Vincent Wong, Jenise C. Steck, Andrea Tamborlane, William V. Smith, Jennifer Beck, Roy W. Cengiz, Eda Laffel, Lori M. Miller, Kellee M. Haller, Michael J. CA T1D Exchange Clinic Network TI A contrast between children and adolescents with excellent and poor control: the T1D exchange clinic registry experience SO PEDIATRIC DIABETES LA English DT Article DE pediatric; blood glucose self-monitoring; type 1 diabetes mellitus; diabetes mellitus; insulin ID DIABETES-MELLITUS; GLYCEMIC CONTROL; COMPLICATIONS; HBA1C AB Objectives Optimizing glycemic control in pediatric type 1 diabetes (T1D) is essential to minimizing long-term risk of complications. We used the T1D Exchange database from 58 US diabetes clinics to identify differences in diabetes management characteristics among children categorized as having excellent vs. poor glycemic control. Methods Among registry participants 6-17 yr old with diabetes duration >= 2 yr, those with excellent control [(A1c <7%)(53 mmol/mol) (N = 588)] were compared with those with poor control [(A1c >= 9% )(75 mmol/mol) (N = 2684)] using logistic regression. Results The excellent and poor control groups differed substantially in diabetes management (p < 0.001 for all) with more of the excellent control group using insulin pumps, performing blood glucose monitoring >= 5x/d, missing fewer boluses, bolusing before meals rather than at the time of or after a meal, using meal-specific insulin:carbohydrate ratios, checking their blood glucose prior to giving meal time insulin, giving insulin for daytime snacks, giving more bolus insulin, and using a lower mean total daily insulin dose than those in poor control. After adjusting for demographic and socioeconomic factors, diabetes management characteristics were still strongly associated with good vs. poor control. Notably, frequency of severe hypoglycemia was similar between the groups while DKA was more common in the poorly controlled group. Conclusions Children with excellent glycemic control tend to exhibit markedly different diabetes self-management techniques than those with poor control. This knowledge may further inform diabetes care providers and patients about specific characteristics and behaviors that can be augmented to potentially improve glycemic control. C1 [Campbell, Meredith S.; Schatz, Desmond A.; Haller, Michael J.] Univ Florida, Coll Med, Gainesville, FL 32610 USA. [Chen, Vincent; Beck, Roy W.; Miller, Kellee M.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Wong, Jenise C.] Univ San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Steck, Andrea] Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. [Tamborlane, William V.; Cengiz, Eda] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Smith, Jennifer] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Laffel, Lori M.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Haller, MJ (reprint author), Univ Florida, Gainesville, FL 32605 USA. EM hallemj@peds.ufl.edu OI Blackman, Scott/0000-0002-4532-6421; Zeitler, Philip/0000-0001-5756-7858 FU Leona M. and Harry B. Helmsley Charitable Trust FX Funding was provided by the Leona M. and Harry B. Helmsley Charitable Trust. NR 11 TC 24 Z9 27 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X EI 1399-5448 J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAR PY 2014 VL 15 IS 2 BP 110 EP 117 DI 10.1111/pedi.12067 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA AD2JF UT WOS:000333060300005 PM 23957219 ER PT J AU Katz, ML Volkening, LK Butler, DA Anderson, BJ Laffel, LM AF Katz, Michelle L. Volkening, Lisa K. Butler, Deborah A. Anderson, Barbara J. Laffel, Lori M. TI Family-based psychoeducation and care ambassador intervention to improve glycemic control in youth with type 1 diabetes: a randomized trial SO PEDIATRIC DIABETES LA English DT Article DE type 1 diabetes mellitus; patient adherence ID SCHOOL-AGE-CHILDREN; METABOLIC-CONTROL; HEALTH OUTCOMES; IMPACT; ADOLESCENTS; INVOLVEMENT; MANAGEMENT; ADHERENCE; PARENT; PREDICTORS AB Objective Youth with type 1 diabetes frequently do not achieve glycemic targets. We aimed to improve glycemic control with a Care Ambassador (CA) and family-focused psychoeducational intervention. Research design and methods In a 2-yr, randomized, clinical trial, we compared three groups: (i) standard care, (ii) monthly outreach by a CA, and (iii) monthly outreach by a CA plus a quarterly clinic-based psychoeducational intervention. The psychoeducational intervention provided realistic expectations and problem-solving strategies related to family diabetes management. Data on diabetes management and A1c were collected, and participants completed surveys assessing parental involvement in management, diabetes-specific family conflict, and youth quality of life (QOL). The primary outcome was A1c at 2 yr; secondary outcomes included maintaining parent involvement and avoiding deterioration in glycemic control. Results We studied 153 youth (56% female, median age 12.9 yr) with type 1 diabetes (mean A1c 8.4 +/- 1.4%). There were no differences in A1c across treatment groups. Among youth with suboptimal baseline A1c >= 8%, more youth in the psychoeducation group maintained or improved their A1c and maintained or increased parent involvement than youth in the other two groups combined (77 vs. 52%, p = 0.03; 36 vs. 11%, p = 0.01, respectively) without negative impact on youth QOL or increased diabetes-specific family conflict. Conclusions No differences in A1c were detected among the three groups at 2 yr. The psychoeducational intervention was effective in maintaining or improving A1c and parent involvement in youth with suboptimal baseline glycemic control. C1 [Katz, Michelle L.; Volkening, Lisa K.; Butler, Deborah A.; Laffel, Lori M.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Anderson, Barbara J.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Laffel, LM (reprint author), Joslin Diabet Ctr, Genet & Epidemiol Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU Charles H. Hood Foundation; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund; Eleanor Chesterman Beatson Fund; NIH [T32 DK 7260-35]; Health Resources and Services Administration [T32 HP10018, K12 DK094721-02, P30DK036836] FX Research support from the Charles H. Hood Foundation, the Katherine Adler Astrove Youth Education Fund, the Maria Griffin Drury Pediatric Fund, the Eleanor Chesterman Beatson Fund, NIH T32 DK 7260-35 to the Joslin Diabetes Center; Health Resources and Services Administration grant T32 HP10018 to the Harvard Pediatric Health Services Research Fellowship Program, K12 DK094721-02 to the Joslin Diabetes Center/Children's Hospital Boston and grant P30DK036836 to the Diabetes and Endocrinology Research Center. NR 32 TC 25 Z9 25 U1 10 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X EI 1399-5448 J9 PEDIATR DIABETES JI Pediatr. Diabetes PD MAR PY 2014 VL 15 IS 2 BP 142 EP 150 DI 10.1111/pedi.12065 PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA AD2JF UT WOS:000333060300009 PM 23914987 ER PT J AU Smucny, J Stevens, KE Tregellas, JR AF Smucny, Jason Stevens, Karen E. Tregellas, Jason R. TI Acute administration of Delta(9) tetrahydrocannabinol does not prevent enhancement of sensory gating by clozapine in DBA/2 mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Cannabinoid; Clozapine; DBA/2; Gating; P50; Schizophrenia ID NICOTINIC ACETYLCHOLINE-RECEPTORS; SUBSTANCE USE DISORDERS; CANNABIS USE; HIPPOCAMPAL INTERNEURONS; ATYPICAL ANTIPSYCHOTICS; PYRAMIDAL CELLS; SCHIZOPHRENIA; OUTCOMES; ABUSE; RAT AB Despite high rates of marijuana abuse in schizophrenia, the physiological interactions between tetrahydrocannabinol (THC) and antipsychotic medications are poorly understood. A well-characterized feature of schizophrenia is poor gating of the P50 auditory-evoked potential. This feature has been translationally modeled by the DBA/2 mouse, which exhibits poor suppression of the P20-N40 AEP, the rodent analog of the human P50. Previous work has demonstrated that this deficit is reversed by the antipsychotic clozapine. It is unknown, however, if this effect is altered by THC administration. Using a conditioning-testing paradigm with paired auditory stimuli, the effects of clozapine and dronabinol (a pharmaceutical THC formulation) on inhibitory P20-N40 AEP processing were assessed from in vivo hippocampal CA3 recordings in anesthetized DBA/2 mice. The effects of clozapine (0.33 mg/kg) and dronabinol (10 mg/kg) were assessed alone and in combination (033,1 or 1.83 mg/kg clozapine with 10 mg/kg dronabinol). Improved P20-N40 AEP gating was observed after acute administration of 0.33 mg/kg clozapine. Co-injection of 0.33 mg/kg clozapine and 10 mg/kg THC, however, did not improve gating relative to baseline. This effect was overcome by higher doses of clozapine (1 and 1.83 mg/kg), as these doses improved gating relative to baseline in the presence of 10 mg/kg THC. 10 mg/kg THC alone did not affect gating. In conclusion, THC does not prevent improvement of P20-N40 gating by clozapine. (C) 2014 Elsevier Inc. All rights reserved. C1 [Smucny, Jason; Tregellas, Jason R.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA. [Smucny, Jason; Stevens, Karen E.; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA. [Smucny, Jason; Stevens, Karen E.; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. RP Smucny, J (reprint author), Univ Colorado, Dept Psychiat, Anschutz Med Campus, Aurora, CO 80045 USA. EM Jason.Smucny@ucdenver.edu RI Tregellas, Jason/J-3637-2015; OI Smucny, Jason/0000-0001-5656-7987 FU Clinical Science Research and Development Service; Brain and Behavior Foundation; Blowitz-Ridgeway Foundation [5P50-MH086383-04]; VA Biomedical Laboratory FX The authors thank Lijun Zheng, B.S. for technical assistance. This work was supported by the VA Biomedical Laboratory and Clinical Science Research and Development Service, the Brain and Behavior Foundation, the Blowitz-Ridgeway Foundation, and 5P50-MH086383-04. NR 48 TC 2 Z9 2 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAR PY 2014 VL 118 BP 22 EP 29 DI 10.1016/j.pbb.2014.01.001 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA AC8ZC UT WOS:000332822600004 PM 24418217 ER PT J AU Fischer, BL Gleason, CE Gangnon, RE Janczewski, J Shea, T Mahoney, JE AF Fischer, Barbara L. Gleason, Carey E. Gangnon, Ronald E. Janczewski, Jodi Shea, Terry Mahoney, Jane E. TI Declining Cognition and Falls: Role of Risky Performance of Everyday Mobility Activities SO PHYSICAL THERAPY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY FUNCTION; DWELLING OLDER-ADULTS; EXECUTIVE FUNCTION; ELDERLY PATIENTS; DOUBLE-BLIND; BALANCE; IMPAIRMENT; ATTENTION; ASSOCIATION AB Background. Declining cognition is a risk factor for falls among older adults. The extent to which impaired judgment in performance of daily activities increases fall risk is unclear. Objective. The aim of this study was to determine whether engagement in mobility activities in a risky mariner explains the association between declining cognition and rate of falls. Design. This study was a secondary analysis of baseline and prospective data from older adults enrolled in the intervention arm of a randomized clinical trial. Methods. Two hundred forty-five community-dwelling older adults (79% female; mean age=79 years, SD=8.0) who were at risk for falls received physical, cognitive, and functional evaluations. Cognition was assessed with the Short Portable Mental Status Questionnaire (SPMSQ). Using interview and in-home assessment data, physical therapists determined whether participants were at risk for falls when performing mobility-related activities of daily living (ADL) and instrumental ADL (IADL). Falls were measured prospectively for 1 year using monthly falls diaries. Results. Declining cognition was associated with increased number of mobility activities designated as risky (1.5% of mobility activities performed in a risky manner per SPMSQ point) and with increased rate of falls (rate ratio=1.16 for each unit change in SPMSQ score). Risky performance of mobility activities mediated the relationship between cognition and rate of falls. Limitations. Risk assessment was based on the clinical judgment of experienced physical therapists. Cognition was measured with a relatively insensitive instrument, and only selected mobility activities were evaluated. Conclusions. Engagement in mobility ADL and IADL tasks in a risky manner emerged as a link between declining cognition and increased number of falls, suggesting a mechanism through which the rate of falls may increase. Specifically, declining cognition is associated with performance of mobility activities in an unsafe manner, thereby increasing the risk for falls. C1 [Fischer, Barbara L.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Gleason, Carey E.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. [Gleason, Carey E.; Mahoney, Jane E.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Geriatr, Madison, WI USA. [Gangnon, Ronald E.] Univ Wisconsin Madison, Dept Biostat, Madison, WI USA. [Gangnon, Ronald E.] Univ Wisconsin Madison, Dept Med Informat & Populat Hlth Sci, Madison, WI USA. [Janczewski, Jodi; Shea, Terry] Univ Wisconsin Hosp & Clin, Dept Orthoped & Rehabil, Madison, WI 53792 USA. RP Fischer, BL (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terr, Madison, WI 53705 USA. EM barbaralfischer@gmail.com FU Centers for Disease Control and Prevention, National Center for Injury Prevention and Control [02151]; National Institutes of Health, National Institute on Aging [K23 AG024302]; Alzheimer's Disease Research Center [P50 AG033514] FX This work was supported by the Centers for Disease Control and Prevention, National Center for Injury Prevention and Control (grant PA #02151 to Dr Mahoney); the National Institutes of Health, National Institute on Aging (grant #K23 AG024302 to Dr Gleason); and the Alzheimer's Disease Research Center (grant #P50 AG033514 to Dr Gleason). NR 52 TC 7 Z9 9 U1 3 U2 12 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 EI 1538-6724 J9 PHYS THER JI Phys. Ther. PD MAR PY 2014 VL 94 IS 3 BP 355 EP 362 DI 10.2522/ptj.20130195 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA AC2RI UT WOS:000332351300009 PM 24231226 ER PT J AU Bush, NE Prins, A Laraway, S O'Brien, K Ruzek, J Ciulla, RP AF Bush, Nigel E. Prins, Annabel Laraway, Sean O'Brien, Karen Ruzek, Josef Ciulla, Robert P. TI A Pilot Evaluation of the AfterDeployment.org Online Posttraumatic Stress Workshop for Military Service Members and Veterans SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress; military; online; veterans ID MENTAL-HEALTH PROBLEMS; RANDOMIZED CONTROLLED-TRIAL; NATIONAL-GUARD SOLDIERS; CLINICAL-SIGNIFICANCE; DEPRESSION; DISORDER; CARE; INTERNET; COMBAT; IRAQ AB This pilot study employed a nonconcurrent, multiple-baseline single-case design to examine the impact of an online self-management posttraumatic stress (PTS) workshop on self-reported symptoms of PTS, depression, and functional impairment. Eleven student veterans with PTS first completed between three and five weekly baseline measures. Second, they took part in eight weekly online workshop sessions, each accompanied by symptom assessments. Third, they completed postintervention outcome measures. We found statistically significant reductions in PTS from baseline across workshop sessions for four of 11 participants, and significant overall reductions in PTS between enrollment and postintervention for five participants. One participant also demonstrated significantly reduced depressive symptoms from baseline across the intervention, and two evidenced significant overall reductions from enrollment to postintervention. Three student veterans showed significantly improved general functioning across the sessions and one reported significant overall functional increase. Finally, five of six participants who completed extended measures of educational function showed significant improvements from enrollment to postintervention. Among secondary outcomes, more than 80% of those taking part said they would recommend the online PTS workshop to a colleague or fellow student with PTS issues. These preliminary findings show that our online PTS workshop can be effective in reducing PTS symptoms in some cases, but also suggest that additional research is needed. With increasing numbers of service members and veterans using the Internet and many reluctant or unable to seek in-person care because of stigma or limited access, the time seems right to further examine the utility of networked PTS resources. C1 [Bush, Nigel E.] US Dept Def, Natl Ctr Telehlth & Technol T2, Tacoma, WA USA. [Prins, Annabel; Ruzek, Josef] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Menlo Pk, CA USA. [Prins, Annabel; Laraway, Sean] San Jose State Univ, Dept Psychol, San Jose, CA 95192 USA. [O'Brien, Karen; Ciulla, Robert P.] US Dept Def, Natl Ctr Telehlth & Technol, Tacoma, WA USA. RP Bush, NE (reprint author), Natl Ctr Telehlth & Technol T2, OMAMC, Joint Base Lewis McChord, 9933 West Hayes St, Tacoma, WA 98431 USA. EM nigel.bush@us.army.mil NR 49 TC 2 Z9 2 U1 2 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2014 VL 6 IS 2 BP 109 EP 119 DI 10.1037/a0032179 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AD2VU UT WOS:000333094800002 ER PT J AU Foynes, MM Platt, M Hall, GCN Freyd, JJ AF Foynes, Melissa Ming Platt, Melissa Hall, Gordon C. N. Freyd, Jennifer J. TI The Impact of Asian Values and Victim-Perpetrator Closeness on the Disclosure of Emotional, Physical, and Sexual Abuse SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE emotional abuse; physical abuse; sexual abuse; disclosure; Asian values ID AMERICAN COLLEGE-STUDENTS; SOCIAL SUPPORT; CULTURE; CHINESE; SAMPLE; POPULATIONS; RELIABILITY; PREVALENCE; ETHNICITY; SURVIVORS AB Prior research indicates that survivors of abuse characterized by very close victim-perpetrator relationships (VC traumas) are significantly more likely to delay disclosure for 1 or more years, or never to disclose, than survivors of abuse characterized by not very close victim-perpetrator relationships (NVC traumas) (M. M. Foynes, J. J. Freyd, & A. P. Deprince, 2009, Child abuse, betrayal and disclosure, Child Abuse & Neglect, 33, 209-217). Nondisclosure of abuse may serve a protective function in that it allows for the maintenance of a necessary, albeit abusive, relationship. This dynamic may be particularly relevant for people who adhere strongly to Asian cultural values of interdependence and may be differentially applicable to disclosure of physical, sexual, and emotional abuse. An online study was conducted with Asian Americans (AAs) and European Americans (EAs; N = 266) to test the hypothesis that Asian values, rather than ethnic group membership, would be associated with decreased disclosure of VC abuse, but not affect disclosure of NVC abuse. The impact of Asian values was expected to be the strongest for disclosure of VC sexual abuse. A series of backward stepwise logistic regressions revealed that Asian values, but not ethnicity, were significantly associated with nondisclosure of VC sexual and emotional abuse, but not VC physical abuse. Neither ethnicity nor Asian values was associated with disclosure of any type of NVC abuse. Female gender increased the odds of VC abuse disclosure only. By examining the impact of cultural values on disclosure of particular abuse types and uncovering the limitations of attending to ethnicity alone, we hope to inform efforts toward facilitating recovery from trauma and creating more supportive environments for survivors. C1 [Foynes, Melissa Ming] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Foynes, Melissa Ming] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Platt, Melissa; Hall, Gordon C. N.; Freyd, Jennifer J.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. RP Foynes, MM (reprint author), VA Boston Healthcare Syst, 116B,150 South Huntington Ave, Boston, MA 02130 USA. EM melissa.foynes2@va.gov NR 45 TC 2 Z9 2 U1 2 U2 19 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2014 VL 6 IS 2 BP 134 EP 141 DI 10.1037/a0032098 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AD2VU UT WOS:000333094800005 ER PT J AU Nillni, YI Berenz, EC Pineles, SL Coffey, SF Zvolensky, MJ AF Nillni, Yael I. Berenz, Erin C. Pineles, Suzanne L. Coffey, Scott F. Zvolensky, Michael J. TI Anxiety Sensitivity as a Moderator of the Association Between Premenstrual Symptoms and Posttraumatic Stress Disorder Symptom Severity SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE anxiety sensitivity; premenstrual symptoms; posttraumatic stress disorder ID ADMINISTERED PTSD SCALE; DYSPHORIC DISORDER; PSYCHOMETRIC PROPERTIES; MENSTRUAL DISTRESS; RISK-FACTORS; TRAUMA; PREVALENCE; EVENTS; WOMEN; QUESTIONNAIRE AB Experience of premenstrual symptoms may be an important factor involved in understanding posttraumatic stress disorder (PTSD) symptom vulnerability. Correlations between PTSD and premenstrual dysphoric disorder (PMDD) have been identified in epidemiological studies, however, the nature of this relation is not clear. The current study examined the incremental validity of premenstrual symptoms, as well as their interaction with anxiety sensitivity, in the prediction of PTSD symptom severity above and beyond other theoretically relevant covariates. A community sample of trauma-exposed women (N = 63) completed questionnaires assessing premenstrual symptoms, anxiety sensitivity, and neuroticism and were administered the Clinician-Administered PTSD Scale to assess PTSD symptom severity. A series of hierarchical linear regressions revealed that premenstrual symptoms uniquely predicted PTSD total, reexperiencing, avoidance, and hyperarousal symptoms above and beyond other theoretically relevant covariates (i.e., number of potentially traumatic events, neuroticism, panic attack history, and anxiety sensitivity). Additionally, anxiety sensitivity emerged as a moderator of the association between premenstrual symptoms and PTSD symptom severity such that greater premenstrual symptoms were associated with greater PTSD total, reexperiencing, and numbing symptom severity for individuals high, but not low, in anxiety sensitivity. Experience of premenstrual symptoms may be an important sex-specific mechanism involved in increasing vulnerability for PTSD symptoms, particularly among women high in anxiety sensitivity. C1 [Nillni, Yael I.] Univ Mississippi, VA Boston Healthcare Syst, Dept Psychiat & Human Behav, Med Ctr,Natl Ctr PTSD,Womens Hlth Sci Div, Boston, MA USA. [Nillni, Yael I.; Pineles, Suzanne L.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Berenz, Erin C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. [Nillni, Yael I.; Pineles, Suzanne L.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Coffey, Scott F.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Boston, MA USA. [Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX 77004 USA. RP Nillni, YI (reprint author), Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA. EM yael.nillni2@va.gov FU NIAAA NIH HHS [K99 AA022385]; NIMH NIH HHS [F31 MH080453] NR 41 TC 1 Z9 1 U1 3 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2014 VL 6 IS 2 BP 167 EP 175 DI 10.1037/a0032087 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AD2VU UT WOS:000333094800009 PM 26973758 ER PT J AU Huffman, JC Niazi, SK Rundell, JR Sharpe, M Katon, WJ AF Huffman, Jeff C. Niazi, Shehzad K. Rundell, James R. Sharpe, Michael Katon, Wayne J. TI Essential Articles on Collaborative Care Models for the Treatment of Psychiatric Disorders in Medical Settings: A Publication by the Academy of Psychosomatic Medicine Research and Evidence-Based Practice Committee SO PSYCHOSOMATICS LA English DT Article AB Background: Collaborative care interventions for psychiatric disorders combine several components integrated into the medical setting: (1) systematic psychiatric assessment, (2) use of a nonphysician care manager to perform longitudinal symptom monitoring, treatment interventions, and care coordination, and (3) specialist-provided stepped-care recommendations. Collaborative care interventions have now been evaluated in a wide spectrum of care settings and offer great promise as a way of increasing quality of patient care, improving health of populations, and reducing health care costs. Methods: A systematic search of PubMedl MEDLINE databases was performed for publications between January 1970 and May 2013 to identify articles describing collaborative care and related interventions. Identified articles were then evaluated independently by multiple reviewers for quality and importance: additional articles were identified by searching reference lists and through recommendations of senior content-matter experts. The articles considered to be both of high quality and most important were then placed into categories and annotated reviews performed. Results: Over 600 articles were identified of which 67 were selected for annotated review. The results reported in these articles indicate that collaborative care interventions for psychiatric disorders have been consistently successful in improving key outcomes in both research and clinical intervention studies; cost analyses also suggest that this model is cost effective. Conclusions: Collaborative care models for psychiatric disorders are likely to serve an increasingly large role in health care given their effect on patient and population outcomes and their focus on integration of care. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Mayo Clin, Dept Psychiat, Jacksonville, FL 32224 USA. Tamber Hlth, Minneapolis, MN USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. Univ Oxford, Dept Psychiat, Oxford, England. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM jhuffman@partners.org NR 0 TC 22 Z9 23 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2014 VL 55 IS 2 BP 109 EP 122 PG 14 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AD2SN UT WOS:000333085600001 PM 24370112 ER PT J AU Stevens, JR Jarrahzadeh, T Brendel, RW Stern, TA AF Stevens, Jonathan R. Jarrahzadeh, Tiana Brendel, Rebecca Weintraub Stern, Theodore A. TI Strategies for the Prescription of Psychotropic Drugs with Black Box Warnings SO PSYCHOSOMATICS LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; ADOLESCENT DEPRESSION; PEDIATRIC DEPRESSION; MALPRACTICE CLAIMS; INFORMED-CONSENT; MEDICATION USE; UNITED-STATES; CHILDREN AB Background: The Black Box Warning (BBW) is the Food and Drug Administration's highest level of drug warning. It signifies that a medication has serious (or potentially lift-threatening) side effects and is prominently displayed on a medication's package insert. It literally consists of the medication it and is surrounded by a bold black border. Objective: This article aims to review data related to BBWs on psycho tropic medications currently used in clinical practice, with special attention to clinical situations and questions relevant to consultation-liaison psychiatrists, Results: We review 3 clinical advisories or BBWs for psychotropic medications (antidepressant medication and suicidality in the pediatric population, stimulant medication and sudden death in the pediatric population, and antipsychotic medication and increased mortality in the elderly) and discuss the effect they have had on prescribing practices. We provide a table of current BBWs relevant to psycho tropic medications. Conclusions: BBWs can have unintended and far-reaching consequences, albeit with a limited ability to target specific populations and practice patterns. Although it is critical for clinicians to be aware of these serious potential side effects and to inform patients about these warnings, medications with boxed warnings remain Food and Drug Administration-approved and may have critically important therapeutic roles. C1 [Stevens, Jonathan R.] Henry Ford Hlth Syst, Dearborn, MI 48126 USA. Wayne State Univ, Detroit, MI USA. Michigan State Univ, E Lansing, MI 48824 USA. Red Sox Fdn, Boston, MA USA. Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MGH, Avery D Weisman Psychiat Consultat Serv, Boston, MA USA. RP Stevens, JR (reprint author), Henry Ford Hlth Syst, 5111 Auto Club Rd,Suite 112, Dearborn, MI 48126 USA. EM jsteven8@hfhs.org NR 63 TC 3 Z9 3 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2014 VL 55 IS 2 BP 123 EP 133 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AD2SN UT WOS:000333085600002 PM 24360525 ER PT J AU Mansoor, D Ganzini, L AF Mansoor, David Ganzini, Linda TI Musical Hallucinations Successfully Treated with Antipsychotic Medications: Three Case Reports SO PSYCHOSOMATICS LA English DT Article ID ACQUIRED DEAFNESS; PHENOMENOLOGY; HALLUCINOSIS C1 [Mansoor, David; Ganzini, Linda] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Psychiat, Portland, OR 97239 USA. RP Mansoor, D (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Psychiat, 3710 SW US Vet Hosp Rd,Mail Code R&D 66, Portland, OR 97239 USA. EM mansoord@ohsu.edu NR 16 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2014 VL 55 IS 2 BP 191 EP 193 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AD2SN UT WOS:000333085600010 PM 23756119 ER PT J AU Nash, KC Kelemen, SM Gopalan, P Azzam, PN AF Nash, Kenneth C. Kelemen, Sheena M. Gopalan, Priya Azzam, Pierre N. TI The Early Career Consultation Psychiatrist: Manager, Director, Boss-Leadership and Psychiatric Practice SO PSYCHOSOMATICS LA English DT Letter C1 [Nash, Kenneth C.; Kelemen, Sheena M.; Gopalan, Priya] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. [Azzam, Pierre N.] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Nash, KC (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. NR 7 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 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2014 VL 55 IS 2 BP 205 EP 206 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AD2SN UT WOS:000333085600014 PM 24075123 ER PT J AU Taylor, JB AF Taylor, John B. TI Psychological Adaptive Mechanisms: Ego Defense Recognition in Practice and Research SO PSYCHOSOMATICS LA English DT Book Review C1 [Taylor, John B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Taylor, JB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2014 VL 55 IS 2 BP 210 EP 211 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA AD2SN UT WOS:000333085600017 ER PT J AU Warren, SA Huszti, E Bradley, SM Chan, PS Bryson, CL Fitzpatrick, AL Nichol, G AF Warren, Sam A. Huszti, Ella Bradley, Steven M. Chan, Paul S. Bryson, Chris L. Fitzpatrick, Annette L. Nichol, Graham CA Amer Heart Assoc Get TI Adrenaline (epinephrine) dosing period and survival after in-hospital cardiac arrest: A retrospective review of prospectively collected data SO RESUSCITATION LA English DT Article DE Arrhythmia; Cardiopulmonary resuscitation; Heart arrest; Pharmacology ID AMERICAN-HEART-ASSOCIATION; CARDIOPULMONARY-RESUSCITATION; DOSE EPINEPHRINE; HYPOTHERMIA; OUTCOMES; TRIAL; CARE AB Background and aim: Expert guidelines for treatment of cardiac arrest recommend administration of adrenaline (epinephrine) every three to five minutes. However, the effects of different dosing periods of epinephrine remain unclear. We sought to evaluate the association between epinephrine average dosing period and survival to hospital discharge in adults with an in-hospital cardiac arrest (IHCA). Methods: We performed a retrospective review of prospectively collected data on 20,909 IHCA events from 505 hospitals participating in the Get With The Guidelines-Resuscitation (GWTG-R) quality improvement registry. Epinephrine average dosing period was defined as the time between the first epinephrine dose and the resuscitation endpoint, divided by the total number of epinephrine doses received subsequent to the first epinephrine dose. Associations with survival to hospital discharge were assessed by using generalized estimating equations to construct multivariable logistic regression models. Results: Compared to a referent epinephrine average dosing period of 4 to <5 min per dose, survival to hospital discharge was significantly higher in patients with the following epinephrine average dosing periods: for 6 to <7 min/dose, adjusted odds ratio [OR], 1.41 (95%CI: 1.12, 1.78); for 7 to <8 min/dose, adjusted OR, 1.30 (95%CI: 1.02, 1.65); for 8 to <9 min/dose, adjusted OR, 1.79 (95%CI: 1.38, 2.32); for 9 to <10 min/dose, adjusted OR, 2.17 (95%CI: 1.62, 2.92). This pattern was consistent for both shockable and non-shockable cardiac arrest rhythms. Conclusion: Less frequent average epinephrine dosing than recommended by consensus guidelines was associated with improved survival of in-hospital cardiac arrest. (C) 2013 Elsevier Ireland Ltd. All rights reserved. C1 [Warren, Sam A.; Huszti, Ella; Nichol, Graham] Univ Washington, Harborview Ctr Prehosp Emergency Care, Seattle, WA 98124 USA. [Warren, Sam A.; Huszti, Ella; Bradley, Steven M.; Bryson, Chris L.; Nichol, Graham] Dept Med, Seattle, WA USA. [Warren, Sam A.; Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Chan, Paul S.] St Lukes Midamer Heart & Vasc Inst, Kansas City, MO USA. [Chan, Paul S.] Univ Missouri, Kansas City, MO 64110 USA. [Bradley, Steven M.; Bryson, Chris L.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. [Fitzpatrick, Annette L.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98124 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Global Hlth, Seattle, WA 98124 USA. [Nichol, Graham] Univ Washington, Dept Biostat, Clin Trial Ctr, Seattle, WA 98195 USA. RP Warren, SA (reprint author), Univ Washington, Harborview Med Ctr, Harborview Ctr Prehosp Emergency Care, Dept Med, Box 359702,325 Ninth Ave, Seattle, WA 98124 USA. EM sawarren@u.washington.edu FU Get With The Guidelines-Resuscitation; American Heart Association; Department of Health and Human Services, Public Health Services [HP10002-21-00] FX Data acquisition was funded by Get With The Guidelines-Resuscitation which is supported by the American Heart Association and membership fees paid by participating hospitals. The remainder of the study was funded by a Fellowship training grant from Department of Health and Human Services, Public Health Services, Grant Type 6, Activity T32, ID Serial No. HP10002-21-00, Principal Investigator: Paula Lozano, MD, MPH. NR 24 TC 8 Z9 10 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD MAR PY 2014 VL 85 IS 3 BP 350 EP 358 DI 10.1016/j.resuscitation.2013.10.004 PG 9 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA AC8IR UT WOS:000332777200017 PM 24252225 ER PT J AU Federation, AJ Bradner, JE Meissner, A AF Federation, Alexander J. Bradner, James E. Meissner, Alexander TI The use of small molecules in somatic-cell reprogramming SO TRENDS IN CELL BIOLOGY LA English DT Review DE induced pluripotent stem cells; small molecules; reprogramming; chemical biology; epigenetics ID PLURIPOTENT STEM-CELLS; DNA METHYLATION; HISTONE METHYLTRANSFERASE; HUMAN FIBROBLASTS; DEFINED FACTORS; GENERATION; INDUCTION; INHIBITORS; CANCER; 5-AZACYTIDINE AB Pioneering work over the past years has highlighted the remarkable ability of manipulating cell states through exogenous, mostly transcription factor-induced reprogramming. The use of small molecules and reprogramming by transcription factors share a common history starting with the early AZA and MyoD experiments in fibroblast cells. Recent work shows that a combination of small molecules can replace all of the reprogramming factors and many previous studies have demonstrated their use in enhancing efficiencies or replacing individual factors. Here we provide a brief introduction to reprogramming followed by a detailed review of the major classes of small molecules that have been used to date and what future opportunities can be expected from these. C1 [Federation, Alexander J.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Federation, Alexander J.; Bradner, James E.; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Federation, Alexander J.] Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA. [Bradner, James E.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. [Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Meissner, A (reprint author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM alexander_meissner@harvard.edu FU National Science Foundation Graduate Research Fellowship; National Institute of General Medical Sciences [P01GM099117]; Robertson Investigator of The New York Stem Cell Foundation FX The authors thank members of the Meissner and Bradner laboratories for their discussions and critiques of the manuscript. They specifically thank Katharin Shaw for her insight regarding figure design and layout. A.J.F. is supported by a National Science Foundation Graduate Research Fellowship. A.M. is supported by the National Institute of General Medical Sciences (P01GM099117) and is a Robertson Investigator of The New York Stem Cell Foundation. NR 70 TC 22 Z9 24 U1 1 U2 29 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAR PY 2014 VL 24 IS 3 BP 179 EP 187 DI 10.1016/j.tcb.2013.09.011 PG 9 WC Cell Biology SC Cell Biology GA AD0DY UT WOS:000332905900005 PM 24183602 ER PT J AU Grelotti, DJ Closson, EF Smit, JA Mabude, Z Matthews, LT Safren, SA Bangsberg, DR Mimiaga, MJ AF Grelotti, David J. Closson, Elizabeth F. Smit, Jennifer A. Mabude, Zonke Matthews, Lynn T. Safren, Steven A. Bangsberg, David R. Mimiaga, Matthew J. TI Whoonga: Potential Recreational Use of HIV Antiretroviral Medication in South Africa SO AIDS AND BEHAVIOR LA English DT Article DE Recreational HIV antiretroviral use; Substance abuse; South Africa; Whoonga and nyaope; Antiretroviral diversion ID ALCOHOL-USE; DRUG-USERS; INFECTION; EFAVIRENZ; THERAPY AB Whoonga is a drug cocktail in South Africa rumored to contain illicit drugs and HIV antiretroviral (ARV) medication. Although its use may adversely impact adherence to HIV treatment and may have the potential to generate ARV resistance, there is a paucity of research characterizing whoonga. We learned of whoonga during semi-structured interviews about substance abuse and HIV risk at "club-events" known as inkwaris in an urban township of Durban, South Africa. Whoonga was an emerging theme spontaneously identified as a problem for the community by 17 out of 22 informants. Perceptions of whoonga suggest that it is highly addictive, contains ARVs (notably efavirenz), is used by individuals as young as 14, and poses a threat to the health and safety of those who use it, including increasing the risk of HIV infection. Our informants provide preliminary evidence of the dangers of whoonga and reinforce the need for further study. C1 [Grelotti, David J.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Grelotti, David J.; Safren, Steven A.; Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Closson, Elizabeth F.; Safren, Steven A.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Smit, Jennifer A.; Mabude, Zonke] Univ Witwatersrand, Fac Hlth Sci, Dept Obstet & Gynaecol, Maternal Adolescent & Child Hlth MatCH, Durban, South Africa. [Matthews, Lynn T.; Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] MGH MIT & Harvard, Ragon Inst, Boston, MA USA. RP Grelotti, DJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM grelotti@hsph.harvard.edu FU NIAID NIH HHS [5P30AI060354-09, P30 AI060354]; NIMH NIH HHS [5K24MH094214, K24 MH094214, K23 MH095655, T32 MH017119, K24 MH087227]; PHS HHS [10K24087227] NR 31 TC 9 Z9 10 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD MAR PY 2014 VL 18 IS 3 BP 511 EP 518 DI 10.1007/s10461-013-0575-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AC5RI UT WOS:000332577800008 PM 23955659 ER PT J AU Vijayaraghavan, M Penko, J Vittinghoff, E Bangsberg, DR Miaskowski, C Kushel, MB AF Vijayaraghavan, Maya Penko, Joanne Vittinghoff, Eric Bangsberg, David R. Miaskowski, Christine Kushel, Margot B. TI Smoking Behaviors in a Community-Based Cohort of HIV-Infected Indigent Adults SO AIDS AND BEHAVIOR LA English DT Article DE Hardcore smokers; HIV-infected persons; Nicotine dependence; Smoking cessation ID ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED-CLINICAL-TRIAL; CIGARETTE-SMOKING; POSITIVE SMOKERS; NICOTINE DEPENDENCE; HOMELESS SMOKERS; UNITED-STATES; HAART ERA; DRUG-USE; CESSATION AB We conducted a longitudinal study of a community-based cohort of HIV-infected indigent adults to examine smoking behaviors and factors associated with quitting. We assessed "hardcore" smoking behaviors associated with a low probability of quitting. Of the 296 participants, 218 were current smokers (73.6 %). The prevalence of "hardcore" smoking was high: 59.6 % smoked a parts per thousand yen15 cigarettes per day, and 67.3 % were daily smokers. During the study interval, 20.6 % made at least one quit attempt. Of these, 53.3 % were abstinent at 6 months. The successful quit rate over 2 years was 4.6 %. Illegal substance use (adjusted odds ratio, AOR 0.2, 95 % CI 0.1-0.6) and smoking within 30 min of waking (AOR 0.2, 95 % CI 0.1-0.7) were associated with lower likelihood of making a quit attempt. Interventions that reduce nicotine dependence prior to smoking cessation and those that are integrated with substance use treatment may be effective for this population. C1 [Vijayaraghavan, Maya] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Penko, Joanne; Vittinghoff, Eric; Kushel, Margot B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Vittinghoff, Eric] UCSF Dept Epidemiol & Biostat, San Francisco, CA USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard,Ctr Global Hlth, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA. [Kushel, Margot B.] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. RP Vijayaraghavan, M (reprint author), Univ Calif San Diego, Moores UCSD Canc Ctr, 3855 Hlth Sci Dr,MC 0901, La Jolla, CA 92093 USA. EM mvijayaraghavan@ucsd.edu FU NCRR NIH HHS [UL1 RR024131]; NIDA NIH HHS [R01 DA022550, R01DA022550]; NIMH NIH HHS [R01MH54907, R01 MH054907] NR 61 TC 6 Z9 6 U1 1 U2 5 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 MAR PY 2014 VL 18 IS 3 BP 535 EP 543 DI 10.1007/s10461-013-0576-z PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AC5RI UT WOS:000332577800011 PM 23918243 ER PT J AU Waldo, SW Brenner, DA Li, S Alexander, K Ganz, P AF Waldo, Stephen W. Brenner, Daniel A. Li, Shuang Alexander, Karen Ganz, Peter TI Reperfusion times and in-hospital outcomes among patients with an isolated posterior myocardial infarction: Insights from the National Cardiovascular Data Registry (NCDR) SO AMERICAN HEART JOURNAL LA English DT Article ID ST-SEGMENT ELEVATION; ACUTE CORONARY TREATMENT; MORTALITY; LEADS; GUIDELINES; MANAGEMENT; DIAGNOSIS; NETWORK AB Background A posterior myocardial infarction (PMI) is associated with significant morbidity and delays in recognition may prevent the timely revascularization of these patients. The present study sought to evaluate the reperfusion times and in-hospital outcomes among patients with an isolated PMI. Methods Clinical characteristics and reperfusion times were compared between those with an isolated PMI and those with all other ST-elevation myocardial infarctions (STEMI) in the NCDR ACTION-GWTG Registry from 2007 to 2012. Logistic generalized estimating equations were used to examine risk-adjusted mortality. Results Among 117,739 subjects with a STEMI, 824 (0.7%) had evidence of an isolated PMI. The median time between patient arrival and initial electrocardiogram was similar between those with an isolated PMI and those with a non-PMI STEMI (6 vs. 6 minutes, P = .48). However, the median time from initial electrocardiogram to percutaneous coronary intervention was significantly longer among subjects with a PMI (69 vs 61 minutes, P < .01) and fewer patients achieved a door-to-balloon time less than 90 minutes (83% vs 89%, P < .01). After multivariable adjustment, in-hospital mortality was similar for PMI patients compared to those with a non-PMI STEMI (AOR: 1.11, 95% CI: 0.83-1.50). Conclusion The door-to-balloon times are significantly longer for those with an isolated PMI resulting in fewer patients receiving reperfusion within the guideline recommended time period. Ongoing educational initiatives to increase recognition of a PMI are needed to improve the reperfusion times and outcomes associated with this condition. C1 [Waldo, Stephen W.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Brenner, Daniel A.] Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Li, Shuang; Alexander, Karen] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Ganz, Peter] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Ganz, Peter] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. RP Waldo, SW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM swaldo@partners.org FU American College of Cardiology Foundation; American Heart Association; Society of Chest Pain Centers; American College of Emergency Physicians; Society of Hospital Medicine FX ACTION Registry-GWTG is an initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from the Society of Chest Pain Centers, the American College of Emergency Physicians and the Society of Hospital Medicine. NR 18 TC 3 Z9 3 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 MAR PY 2014 VL 167 IS 3 BP 350 EP 354 DI 10.1016/j.ahj.2013.11.011 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC3DT UT WOS:000332395900012 PM 24576519 ER PT J AU Harskamp, RE Wang, TY Bhatt, DL Wiviott, SD Amsterdam, EA Li, S Thomas, L de Winter, RJ Roe, MT AF Harskamp, Ralf E. Wang, Tracy Y. Bhatt, Deepak L. Wiviott, Stephen D. Amsterdam, Ezra A. Li, Shuang Thomas, Laine de Winter, Robbert J. Roe, Matthew T. TI Hospital patterns of medical management strategy use for patients with non-ST-elevation myocardial infarction and 3-vessel or left main coronary artery disease SO AMERICAN HEART JOURNAL LA English DT Article ID INTERVENTION OUTCOMES NETWORK; ASSOCIATION TASK-FORCE; QUALITY IMPROVEMENT; HEART-ASSOCIATION; PRACTICE GUIDELINES; REVASCULARIZATION; ANGIOGRAPHY; SOCIETY; TRIAL AB Background Patients with non-ST-elevation myocardial infarction (NSTEMI) and three-vessel or left main coronary disease (3VD/LMD) have a high risk of long-term mortality when treated with a medical management strategy (MMS) compared with revascularization. Methods We evaluated patterns of use and patient features across United States hospitals designated by MMS for NSTEMI patients with 3VD/LMD included in the ACTION Registry-GWTG from 2007-2012. Results A total of 42,535 patients without prior bypass surgery were found to have 3VD (>= 50% stenosis in all major coronary vessels) or LMD (>= 50% lesion) during in-hospital angiography at 423 hospitals with percutaneous and surgical revascularization capabilities. Hospitals (n = 316) with an adequate volume (>= 25 NSTEMI patients treated) were stratified into tertiles defined by use of MMS; differences in patient characteristics and outcomes were analyzed. The proportion of NSTEMI patients treated with MMS at all hospitals varied from 16% to 19% each quarter and did not change significantly from 2007 to 2012 (P trend = .11). Among hospitals with adequate volume, the proportion of patients treated with MMS also varied widely (median 17.1%, range: 0.0-44.8%, P < .0001). Patient baseline characteristics, predicted mortality risk, actual in-hospital mortality rates, and discharge treatments were similar across hospital tertiles. Conclusions Close to 20% of patients with NSTEMI and 3VD/LMD identified during in-hospital angiography are treated with MMS without revascularization in contemporary practice. Since the use of MMS varies widely across hospitals despite a relatively similar hospital-level case mix, these findings suggest that there is no standard threshold for the use of revascularization in NSTEMI patients with 3VD/LMD. C1 [Harskamp, Ralf E.; Wang, Tracy Y.; Li, Shuang; Thomas, Laine; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC 27705 USA. [Harskamp, Ralf E.; de Winter, Robbert J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Bhatt, Deepak L.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.; Wiviott, Stephen D.] TIMI Study Grp, Boston, MA USA. [Bhatt, Deepak L.; Wiviott, Stephen D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.; Wiviott, Stephen D.] Harvard Univ, Sch Med, Boston, MA USA. [Amsterdam, Ezra A.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. RP Roe, MT (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 7035, Durham, NC 27705 USA. EM matthew.roe@duke.edu FU American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR) - Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines (ACTION-GWTG); Society of Chest Pain Centers; American College of Emergency Physicians; Society of Hospital Medicine FX This analysis was supported by the American College of Cardiology Foundation's National Cardiovascular Data Registry (NCDR) - Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines (ACTION-GWTG). The ACTION Registry(r)-GWTG(tm) is an initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from the Society of Chest Pain Centers, the American College of Emergency Physicians, and the Society of Hospital Medicine. The views expressed in this manuscript represent those of the author(s), and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. NR 15 TC 2 Z9 2 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 MAR PY 2014 VL 167 IS 3 BP 355 EP + DI 10.1016/j.ahj.2013.12.004 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC3DT UT WOS:000332395900013 PM 24576520 ER PT J AU Lichtman, JH Wang, YF Jones, SB Leifheit-Limson, EC Shaw, LJ Vaccarino, V Rumsfeld, JS Krumholz, HM Curtis, JP AF Lichtman, Judith H. Wang, Yongfei Jones, Sara B. Leifheit-Limson, Erica C. Shaw, Leslee J. Vaccarino, Viola Rumsfeld, John S. Krumholz, Harlan M. Curtis, Jeptha P. TI Age and sex differences in inhospital complication rates and mortality after percutaneous coronary intervention procedures: Evidence from the NCDR (R) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR CONSORTIUM BMC2; AMERICAN-HEART-ASSOCIATION; INSTITUTE DYNAMIC REGISTRY; IN-HOSPITAL MORTALITY; BODY-SURFACE AREA; CROSS BLUE-SHIELD; GENDER-DIFFERENCES; CLINICAL-OUTCOMES; ACUITY TRIAL AB Background Older women experience higher complication rates and mortality after percutaneous coronary intervention (PCI) than men, but there is limited evidence about sex-based differences in outcomes among younger patients. We compared rates of complications and inhospital mortality by sex for younger and older PCI patients. Methods A total of 1,079,751 hospital admissions for PCI were identified in the CathPCI Registry (R) from 2005 to 2008. Complication rates (general, bleeding, bleeding with transfusion, and vascular) and inhospital mortality after PCI were compared by sex and age (<55 and >= 55 years). Analyses were adjusted for demographic and clinical factors and stratified by PCI type (elective, urgent, or emergency). Results Overall, 6% of patients experienced complications, and 1% died inhospital. Unadjusted complication rates were higher for women compared with men in both age groups. In risk-adjusted analyses, younger women (odds ratio 1.24, 95% CI 1.16-1.33) and older women (1.27, 1.09-1.47) were more likely to experience any complication than similarly aged men. The increased risk persisted across complication categories and PCI type. Within age groups, risk-adjusted mortality was marginally higher for young women (1.19, 1.00-1.41), but not for older women (1.03, 0.97-1.10). In analyses stratified by PCI type, young women had twice the mortality risk after an elective procedure as young men (2.04, 1.15-3.61). Conclusions Women, regardless of age, experience more complications after PCI than men; young women are at increased mortality risk after an elective PCI. Identifying strategies to reduce adverse outcomes, particularly for women younger than 55 years, is important. C1 [Lichtman, Judith H.; Jones, Sara B.; Leifheit-Limson, Erica C.; Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Lichtman, Judith H.; Wang, Yongfei; Krumholz, Harlan M.; Curtis, Jeptha P.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Shaw, Leslee J.; Vaccarino, Viola] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Krumholz, Harlan M.; Curtis, Jeptha P.] Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Lichtman, JH (reprint author), Yale Univ, Sch Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM Judith.Lichtman@yale.edu NR 46 TC 20 Z9 23 U1 0 U2 2 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 MAR PY 2014 VL 167 IS 3 BP 376 EP 383 DI 10.1016/j.ahj.2013.11.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AC3DT UT WOS:000332395900016 PM 24576523 ER PT J AU Holman, LL Lu, KH Bast, RC Hernandez, MA Bodurka, DC Skates, S Sun, CC AF Holman, Laura L. Lu, Karen H. Bast, Robert C., Jr. Hernandez, Mary A. Bodurka, Diane C. Skates, Steven Sun, Charlotte C. TI Risk perception, worry, and test acceptance in average-risk women who undergo ovarian cancer screening SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE acceptability of screening; cancer worry; ovarian cancer screening; risk perception ID GYNECOLOGIC CANCER; AWARENESS; KNOWLEDGE AB OBJECTIVE: We evaluated baseline knowledge of ovarian cancer risk and perceptions toward ovarian cancer screening (OCS) by initiating the normal risk ovarian screening study. STUDY DESIGN: Average-risk, postmenopausal women were enrolled between 2001 and 2011 as they entered the normal risk ovarian screening study. Participants completed baseline surveys of risk perception, cancer worry (Cancer Worry Scale), anxiety (State-Trait Anxiety Inventory), health and well-being survey (SF-36 HEALTH SURVEY), and acceptability of OCS. RESULTS: Of the 1242 women who were enrolled, 925 women (74.5%) completed surveys. The respondents estimated a mean lifetime risk of ovarian cancer of 29.9%, which is much higher than the actual risk of 1.4% for women in the United States. Only 2.8% of participants correctly estimated their risk; 35.4% of the participants reported their lifetime risk to be >= 50%. Cancer worry was low, with a median Cancer Worry Scale score of 7 of 24. Anxiety was comparable with published norms for women in this age group, with median STAI-State and STAI-Trait scores of 30 and 29 of 80, respectively. Overall, women reported good physical and mental well-being. In terms of OCS acceptability, 97.2% of respondents agreed or strongly agreed that "the benefits of screening outweigh the difficulties." Very few women were reluctant to undergo OCS because of time constraints (1.1%), pain (2.0%), or embarrassment (1.9%). CONCLUSION: Average-risk women who underwent OCS highly overestimated their risk of ovarian cancer. Despite this, participants reported low cancer worry and anxiety. The discrepancy between knowledge of and attitudes toward ovarian cancer risk highlights the need for educational efforts in this area. C1 [Holman, Laura L.; Lu, Karen H.; Bodurka, Diane C.; Sun, Charlotte C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Bast, Robert C., Jr.; Hernandez, Mary A.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Skates, Steven] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Lu, KH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Unit 1362, 1155 Herman Pressler,CPB6-3244, Houston, TX 77030 USA. EM khlu@mdanderson.org RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU National Cancer Institute Ovarian SPORE Supplement - V-Foundation FX We thank Alexandra Perez for her technical support. Ms Perez is a Data Research Coordinator at The University of Texas M. D. Anderson Cancer Center, Office of Translational Research; her position is funded by the National Cancer Institute Ovarian SPORE Supplement - V-Foundation (Yow Fund and Golfer's Against Cancer). NR 19 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2014 VL 210 IS 3 AR 257.e1 DI 10.1016/j.ajog.2013.11.022 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AC3FV UT WOS:000332402000025 PM 24246524 ER PT J AU Oberg, AS Hernandez-Diaz, S Palmsten, K Almqvist, C Bateman, BT AF Oberg, Anna Sara Hernandez-Diaz, Sonia Palmsten, Kristin Almqvist, Catarina Bateman, Brian T. TI Patterns of recurrence of postpartum hemorrhage in a large population-based cohort SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE epidemiology; postpartum hemorrhage; recurrence; retained placenta; uterine atony ID VON-WILLEBRANDS-DISEASE; HOSPITAL DISCHARGE DATA; OBSTETRIC HEMORRHAGE; BLEEDING DISORDERS; VAGINAL BIRTH; RISK-FACTORS; PREGNANCY; EPIDEMIOLOGY; WOMEN; CARE AB OBJECTIVE: Although a history of postpartum hemorrhage (PPH) is a recognized risk factor for PPH in subsequent pregnancies, little is known about how the risk accumulates over multiple pregnancies, how recurrence varies by PPH subtype, and whether recurrence can be explained by chronic maternal conditions. STUDY DESIGN: Risks of PPH were assessed according to a history of PPH, severity, and subtype (atony, retained placenta, or lacerations) in 538,332 primiparous women whose data were included in the Swedish Medical Birth Register from 1997-2009. The role of stable maternal risk factors was evaluated in regression models that predicted probability of recurrent PPH in second and third pregnancy. RESULTS: Women with a history of PPH had a 3-fold increased risk of PPH in their second pregnancy compared with unaffected women (15.0% vs 5.0%, respectively). Adjustment for stable maternal risk factors did not attenuate this risk significantly (adjusted relative risk, 3.0; 95% confidence interval, 2.9-3.1). In a third pregnancy, the risk of PPH was 26.6% after 2 previously affected pregnancies, compared with 4.4% in women with no previous PPH. A history of a specific type of PPH predicted recurrence of PPH in the second pregnancy, not only of the same type but other causes as well. CONCLUSION: PPH risk is highest among women with >1 previously affected delivery and in those with a previous severe PPH. Chronic conditions that are known to be risk factors for PPH do not explain the recurrence risks. The recurrence patterns across PPH subtypes may point to shared pathologic mechanisms underlying the varying PPH causes. C1 [Oberg, Anna Sara; Hernandez-Diaz, Sonia; Palmsten, Kristin] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA. [Oberg, Anna Sara; Almqvist, Catarina] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Almqvist, Catarina] Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden. RP Oberg, AS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RI Oberg, Anna/M-7469-2014 OI Oberg, Anna/0000-0001-6638-1895 FU Swedish Research Council [2012-340, 2011-306]; Strategic Research Program in Epidemiology at Karolinska Institutet; National Institutes of Health [R01HS018533]; Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health [K08HD075831]; Reproductive, Perinatal and Pediatric Epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [T32HD060454] FX Supported by the Swedish Research Council grant 2012-340 (ASO) and grant 2011-3060 (C. A.), The Strategic Research Program in Epidemiology at Karolinska Institutet (C. A.), and National Institutes of Health grant R01HS018533 (S.H.-D.); the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number K08HD075831 (B. T. B.); and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (K.P.). NR 35 TC 4 Z9 4 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2014 VL 210 IS 3 AR 229.e1 DI 10.1016/j.ajog.2013.10.872 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AC3FV UT WOS:000332402000014 PM 24351791 ER PT J AU Reed, SD Guthrie, KA Newton, KM Anderson, GL Booth-LaForce, C Caan, B Carpenter, JS Cohen, LS Dunn, AL Ensrud, KE Freeman, EW Hunt, JR Joffe, H Larson, JC Learman, LA Rothenberg, R Seguin, RA Sherman, KJ Sternfeld, BS LaCroix, AZ AF Reed, Susan D. Guthrie, Katherine A. Newton, Katherine M. Anderson, Garnet L. Booth-LaForce, Cathryn Caan, Bette Carpenter, Janet S. Cohen, Lee S. Dunn, Andrea L. Ensrud, Kristine E. Freeman, Ellen W. Hunt, Julie R. Joffe, Hadine Larson, Joseph C. Learman, Lee A. Rothenberg, Robin Seguin, Rebecca A. Sherman, Karen J. Sternfeld, Barbara S. LaCroix, Andrea Z. TI Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE exercise; menopause; omega-3; quality of life; randomized controlled trial; yoga ID RANDOMIZED CONTROLLED-TRIAL; MIDDLE-AGED WOMEN; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; BREAST-CANCER; HOT FLASHES; CLINICAL-TRIAL; UNITED-STATES; HEALTH; SYMPTOMS AB OBJECTIVE: The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. STUDY DESIGN: We conducted a 12-week 3 x 2 randomized, controlled, factorial design trial. Peri-and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). RESULTS: Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). CONCLUSION: All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect. C1 [Reed, Susan D.] Univ Washington, Dept Obstet & Gynecol, Sch Med, Seattle, WA 98115 USA. [Reed, Susan D.] Univ Washington, Dept Epidemiol, Sch Med, Seattle, WA 98115 USA. [Guthrie, Katherine A.; Anderson, Garnet L.; Hunt, Julie R.; Larson, Joseph C.; Seguin, Rebecca A.; LaCroix, Andrea Z.] Univ Washington, Fred Hutchinson Canc Res Ctr, Data Coordinating Ctr, Seattle, WA 98115 USA. [Newton, Katherine M.; Sherman, Karen J.] Univ Washington, Grp Hlth Res Inst, Seattle, WA 98115 USA. [Booth-LaForce, Cathryn] Univ Washington, Sch Nursing, Seattle, WA 98115 USA. [Rothenberg, Robin] Essential Yoga Therapy, Fall City, WA USA. [Caan, Bette; Sternfeld, Barbara S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Carpenter, Janet S.] Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. [Cohen, Lee S.; Joffe, Hadine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Joffe, Hadine] Brigham & Womens Hosp, Boston, MA 02115 USA. [Joffe, Hadine] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dunn, Andrea L.] Klein Buendel Inc, Golden, CO USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, VA Med Ctr, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Freeman, Ellen W.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Learman, Lee A.] Indiana Univ Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA. [Seguin, Rebecca A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. RP Reed, SD (reprint author), Univ Washington, Dept Obstet & Gynecol, 325 9th Ave,Box 359865, Seattle, WA 98115 USA. EM reeds@u.washington.edu FU National Institutes of Health; NIA [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana University [UL1RR02571]; Astra-Zeneca Pharmaceuticals; Bristol-Myers Squibb; Cephalon, Inc; Ortho-McNeil Janssen; Sunovion Pharmaceuticals, Inc; Forest Laboratories, Inc; Bionovo; Cephalon/Teva FX Supported by the National Institutes of Health as a cooperative agreement among National Institute of Aging (NIA), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Complementary and Alternative Medicine (NCCAM), Office of Research on Women's Health (ORWH), and grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700 from NIA. There was partial support from UL1RR02571 (Indiana University). The omega-3 study supplement (omega-3, n-3, or polyunsaturated fatty acids) was manufactured as EPA and donated, with matching placebo, by Nordic Naturals, Watsonville, CA.; L.S.C. receives research support from Astra-Zeneca Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Inc, Ortho-McNeil Janssen, and Sunovion Pharmaceuticals, Inc, and is a consultant for Noven Pharmaceuticals. A. L. D. received honorarium/royalties from the Japanese Sport Psychiatry Association and Human Kinetics, Inc. K. E. E. serves as a Data and Safety Monitoring Board consultant for Merck Sharpe & Dohme. E. W. F. receives research support from Forest Laboratories, Inc, and Bionovo. H.J. receives research support from Cephalon/Teva, is on the advisory board for Noven Pharmaceuticals, and is an unpaid consultant for Sunovion. The remaining authors have no financial disclosure to report. NR 47 TC 2 Z9 2 U1 2 U2 24 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2014 VL 210 IS 3 AR 244.e1 DI 10.1016/j.ajog.2013.11.016 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AC3FV UT WOS:000332402000020 PM 24215858 ER PT J AU Vital, P Castro, P Tsang, S Ittmann, M AF Vital, Paz Castro, Patricia Tsang, Susan Ittmann, Michael TI The Senescence-Associated Secretory Phenotype Promotes Benign Prostatic Hyperplasia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EPITHELIAL GROWTH-FACTOR; URINARY-TRACT SYMPTOMS; CELLULAR SENESCENCE; CANCER PROGRESSION; REACTIVE STROMA; CATHEPSIN-D; PARACRINE INDUCER; GENE-EXPRESSION; CELLS; PROLIFERATION AB Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and considerable morbidity in a majority of older men. Senescent cells accumulate in human tissues, including the prostate, with increasing age. Expression of proinflammatory cytokines is increased in these senescent cells, a manifestation of the senescence-associated secretory phenotype. Multiplex analysis revealed that multiple cytokines are increased in BPH, including GM-CSF, IL-1 alpha, and IL-4, and that these are also increased in senescent prostatic epithelial cells in vitro. Tissue levels of these cytokines were correlated with a marker of senescence (cathepsin D), which was also strongly correlated with prostate weight. IHC analysis revealed the multifocal epithelial expression of cathepsin D and coexpression with IL-1a in BPH tissues. In tissue recombination studies in nude mice with immortalized prostatic epithelial cells expressing IL-1 alpha and prostatic stromal cells, both epithelial and stromal cells exhibited increased growth. Expression of IL-1 alpha in prostatic epithelial cells in a transgenic mouse model resulted in increased prostate size and bladder obstruction. In summary, both correlative and functional evidence support the hypothesis that the senescence-associated secretory phenotype can promote the development of BPH, which is the single most common age-related pathology in older men. C1 [Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, One Baylor Plaza, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU NIH [R01-DK083244, P20-DK097775, T32-DK007763, T32-AG000183, P30-CA125123] FX Supported by NIH grants R01-DK083244 (Md.), P20-DK097775 (M.I.), T32-DK007763 (DL.), T32-AG000183 (L.D.), and P30-CA125123 (Human Tissue Acquisition and Pathology, Genetically Engineered Mouse, and Proteomics cores) and by use of the facilities of the Michael E. DeBakey Veterans Affairs Medical Center. NR 44 TC 3 Z9 3 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2014 VL 184 IS 3 BP 721 EP 731 DI 10.1016/j.ajpath.2013.11.015 PG 11 WC Pathology SC Pathology GA AB8QQ UT WOS:000332055500014 PM 24434012 ER PT J AU Zhu, X Cho, ES Sha, Q Peng, JB Oksov, Y Kam, SY Ho, M Walker, RH Leer, S AF Zhu, Xiang Cho, Eun-Sook Sha, Quan Peng, Jianbin Oksov, Yelena Kam, Siok Yuen Ho, Mengfatt Walker, Ruth H. Leer, Soohee TI Giant Axon Formation in Mice Lacking Kell, XK, or Kell and XK Animal Models of McLeod Neuroacanthocytosis Syndrome SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; BLOOD-GROUP PROTEIN; NEUROFILAMENT ACCUMULATION; NERVOUS-SYSTEM; MOUSE KELL; GENE KEL; TRANSPORT; EXPRESSION; COMPLEX; ORGANIZATION AB McLeod neuroacanthocytosis syndrome (MLS) is a rare X-Linked muttisystem disease caused by XK gene mutations and characterized by hematological and neurological abnormalities. XK, a putative membrane transporter, is expressed ubiquitously and is covalently linked to Kell, an endothelin-3-converting enzyme (ECE-3). Absence of XK results in reduction of Kell at sites where both proteins are coexpressed. To elucidate the functional roles of XK, Kell, and the XK-Kell complex associated with pathogenesis in MIS, we studied the pathology of the spinal cord, anterior roots, sciatic nerve, and skeletal muscle from knockout mouse models, using Kel(-/-), Xk(-/-), Kel(-/-)Xk(-/-), and wild-type mice aged 6 to 18 months. A striking finding was that giant axons were frequently associated with paranodaL demyelination. The pathology suggests probable anterograde progression from the spinal cord to the sciatic nerve. The neuropathologicaL abnormalities were found in all three genotypes, but were more marked in the double-knockout Kel(-/-)Xk(-/-) mice than in either Kel(-/-) or Xk/- mice. Skeletal muscles from Xk(-/-) and Kel(-/-)Xk(-/-) mice showed mild abnormalities, but those from Kel(-/-) mice were similar to the wild type. The more marked neuropathological abnormalities in Kel(-/-)Xk(-/-) mice suggest a possible functional association between XK and Kell in nonerythroid tissues. C1 [Zhu, Xiang] Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China. [Zhu, Xiang; Sha, Quan; Peng, Jianbin; Oksov, Yelena; Leer, Soohee] New York Blood Ctr, New York, NY 10021 USA. [Cho, Eun-Sook] Rutgers State Univ, New Jersey Med Sch, Dept Pathol & Lab Med Neuropathol, Newark, NJ 07102 USA. [Sha, Quan] Immunomedics, Dept Cell Line Dev, Morris Plains, NJ USA. [Kam, Siok Yuen; Ho, Mengfatt] Natl Canc Ctr, Div Med Sci, Singapore, Singapore. [Walker, Ruth H.] James J Peters VAMC, Dept Neurol, Bronx, NY USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. RP Zhu, X (reprint author), Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China. EM zhuxiangbjmu@163.com FU NIH [R01 HL075716] FX Supported by NIH grant R01 HL075716 (S.L.). NR 43 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2014 VL 184 IS 3 BP 800 EP 807 DI 10.1016/j.ajpath.2013.11.013 PG 8 WC Pathology SC Pathology GA AB8QQ UT WOS:000332055500021 PM 24405768 ER PT J AU Merali, HS Sing, H AF Merali, Hasan S. Sing, Heng TI Mediastinal Mass Causing Spinal Cord Compression SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material AB A 4-year-old Cambodian male presented to the emergency room with 2 weeks of gradually increasing leg weakness until he could no longer stand. He was also reported to have a deformity on his back, intermittent fevers and cough. His physical exam was notable for a 2 cm x 1 cm bony protrusion at his T4 vertebrae, and 2/5 strength and positive Babinski reflexes in his lower extremities. A chest x-ray showed a 3.2 cm x 2.9 cm mass in the middle mediastinum extending to the posterior mediastinum. A purified protein derivative test was positive. A computed tomography scan showed findings consistent with pulmonary tuberculosis and a paravertebral mass with amorphous calcifications, which involved destruction of the T4-T5 vertebrae and evidence of cord compression. These findings were all consistent with tuberculous spondylitis (Pott's disease). C1 MassGen Hosp Children, Dept Pediat, Boston, MA USA. Angkor Hosp Children, Dept Pediat, Siem Reap, Cambodia. [Merali, Hasan S.] MassGen Hosp Children, Boston, MA 02114 USA. [Sing, Heng] Angkor Hosp Children, Siem Reap, Cambodia. RP Merali, HS (reprint author), MassGen Hosp Children, 175 Cambridge St,CPZS-501C, Boston, MA 02114 USA. EM Hasan_Merali@post.harvard.edu; hengsing2003@yahoo.com NR 5 TC 0 Z9 0 U1 0 U2 7 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2014 VL 90 IS 3 BP 391 EP 392 DI 10.4269/ajtmh.13-0381 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AC2RY UT WOS:000332352900002 PM 24598764 ER PT J AU Stoney, RJ Jentes, ES Sotir, MJ Kozarsky, P Rao, SR LaRocque, RC Ryan, ET AF Stoney, Rhett J. Jentes, Emily S. Sotir, Mark J. Kozarsky, Phyllis Rao, Sowmya R. LaRocque, Regina C. Ryan, Edward T. CA Global TravEpiNet Consortium TI Pre-Travel Preparation of US Travelers Going Abroad to Provide Humanitarian Service, Global TravEpiNet 2009-2011 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INTERNATIONAL TRAVELERS; GEOSENTINEL EXPERIENCE; AMERICAN MISSIONARIES; FOREIGN BACKPACKERS; HEALTH-CARE; RISK; PREEXPOSURE; PREVENTION; KNOWLEDGE; ATTITUDES AB We analyzed characteristics of humanitarian service workers (HSWs) seen pre-travel at Global TravEpiNet (GTEN) practices during 2009-2011. Of 23,264 travelers, 3,663 (16%) travelers were classified as HSWs. Among HSWs, 1,269 (35%) travelers were medical workers, 1,298 (35%) travelers were non-medical service workers, and 990 (27%) travelers were missionaries. Median age was 29 years, and 63% of travelers were female. Almost one-half (49%) traveled to 1 of 10 countries; the most frequent destinations were Haiti (14%), Honduras (8%), and Kenya (6%). Over 90% of travelers were vaccinated for or considered immune to hepatitis A, typhoid, and yellow fever. However, for hepatitis B, 292 (29%) of 990 missionaries, 228 (18%) of 1,298 non-medical service workers, and 76 (6%) of 1,269 medical workers were not vaccinated or considered immune. Of HSWs traveling to Haiti during 2010, 5% of travelers did not receive malaria chemoprophylaxis. Coordinated efforts from HSWs, HSW agencies, and clinicians could reduce vaccine coverage gaps and improve use of malaria chemoprophylaxis. C1 Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Travelers Hlth Branch, Atlanta, GA 30333 USA. [Rao, Sowmya R.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth, Worcester, MA USA. Bedford Vet Affairs Med Ctr, CHOIR, Bedford, MA USA. [LaRocque, Regina C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Stoney, Rhett J.; Jentes, Emily S.; Sotir, Mark J.; Kozarsky, Phyllis] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA 30333 USA. [Rao, Sowmya R.] Bedford Vet Adm Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Stoney, RJ (reprint author), Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, 1600 Clifton Rd,MS E-03, Atlanta, GA 30333 USA. EM uyn2@cdc.gov; ejentes@cdc.gov; mps6@cdc.gov; pbk7@cdc.gov; sowmya.rao@umassmed.edu; rclarcque@partners.org; etryan@partners.org FU US Centers for Disease Control and Prevention [U19C1000514, U01CK000175]; Centers for Disease Control and Prevention FX This work was supported by US Centers for Disease Control and Prevention Grants U19C1000514 and U01CK000175. This research was supported, in part, by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the Centers for Disease Control and Prevention. NR 34 TC 4 Z9 4 U1 0 U2 7 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2014 VL 90 IS 3 BP 553 EP 559 DI 10.4269/ajtmh.13-0479 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AC2RY UT WOS:000332352900025 PM 24445203 ER PT J AU LeMaster, CH Hoffart, N Chafe, T Benzer, T Schuur, JD AF LeMaster, Christopher H. Hoffart, Nancy Chafe, Tom Benzer, Ted Schuur, Jeremiah D. TI Implementing the Central Venous Catheter Infection Prevention Bundle in the Emergency Department: Experiences Among Early Adopters SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID BLOOD-STREAM INFECTIONS; INTENSIVE-CARE-UNIT; INTERVENTION; QUALITY; ICU; RATES AB Study objective: Central line-associated bloodstream infections (CLABSI) cause preventable morbidity and mortality. Hospitals have reduced CLABSI by using a bundle of evidence-based infection prevention practices. Systems factors in the emergency department (ED) present unique barriers to bundle adoption, and no guidelines exist for bundle implementation. We aim to identify barriers and facilitators to central line bundle adoption in EDs. Methods: We used a qualitative, grounded theory approach, enrolling 6 EDs that were early adopters of the central line bundle. We interviewed 49 administrators and staff (nurses and physicians) through 26 semistructured interviews and 3 focus groups of 6 to 8 individuals. Investigators read each transcript and then iteratively built and refined a set of themes that emerged from the data. Results: Barriers to central line bundle adoption included high acuity, time constraints, staffing, space, ED culture, high ED volume and acuity, role ambiguity, and a lack of methods to track compliance and infection surveillance. Facilitators included champions, staff engagement, workflow redesign that includes a checklist and central line kit or cart, clear staff responsibilities, observer empowerment, and compliance and infection surveillance data. Conclusion: The strategies for implementing and sustaining a central line infection prevention bundle in the ED are distinct from those of other clinical settings. Our findings describe the central line bundle workflow in the ED, staff motivations, and the critical systems factors that impede and foster its use. Knowledge of these systems factors should improve bundle adoption in the ED and thereby reduce hospital incidence of CLABSIs. C1 [LeMaster, Christopher H.; Chafe, Tom; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [LeMaster, Christopher H.; Benzer, Ted] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [LeMaster, Christopher H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Los Angeles, CA 90095 USA. [Hoffart, Nancy] Lebanese Amer Univ, Alice Ramez Chagoury Sch Nursing, Beirut, Lebanon. [Benzer, Ted; Schuur, Jeremiah D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP LeMaster, CH (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM christopher.h.lemaster@kp.org FU Emergency Medicine Foundation; Agency for Healthcare Research and Quality [R18-HS020013] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. Dr. LeMaster and Dr. Schuur received support for the project by a Resident Research Grant from the Emergency Medicine Foundation. Dr. Schuur is supported by a grant (R18-HS020013) from the Agency for Healthcare Research and Quality. NR 36 TC 4 Z9 6 U1 2 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2014 VL 63 IS 3 BP 340 EP 350 DI 10.1016/j.annemergmed.2013.09.006 PG 11 WC Emergency Medicine SC Emergency Medicine GA AC7YZ UT WOS:000332751500015 PM 24120627 ER PT J AU Lee, BC Lee, J AF Lee, Byung-Cheol Lee, Jongsoon TI Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Adipose tissue; Obesity-induced Inflammation; Adipose tissue immune cell; Insulin resistance ID DIET-INDUCED OBESITY; KILLER T-CELLS; NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; TYPE-2 DIABETES-MELLITUS; TERMINAL KINASE JNK; DENDRITIC CELLS; TNF-ALPHA; MACROPHAGE POLARIZATION; SYSTEMIC INFLAMMATION AB There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. (C) 2013 Elsevier B.V. All rights reserved. C1 [Lee, Byung-Cheol; Lee, Jongsoon] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. [Lee, Byung-Cheol; Lee, Jongsoon] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Lee, Byung-Cheol] Kyung Hee Univ, Dept Internal Med, Coll Korean Med, Seoul, South Korea. RP Lee, J (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA. EM jongsoon.lee@joslin.harvard.edu FU National Institutes of Health (NIH) [DK80380R01, DK036836, DK046200]; American Diabetes Association [RA 110BS97] FX This study was supported by National Institutes of Health (NIH) DK80380R01, DK036836 and DK046200 and the American Diabetes Association grant RA 110BS97 to J.L. NR 171 TC 96 Z9 105 U1 17 U2 94 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD MAR PY 2014 VL 1842 IS 3 SI SI BP 446 EP 462 DI 10.1016/j.bbadis.2013.05.017 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AB3EM UT WOS:000331674100013 PM 23707515 ER PT J AU Tanwar, PS Mohapatra, G Chiang, S Engler, DA Zhang, LH Kaneko-Tarui, T Ohguchi, Y Birrer, MJ Teixeira, JM AF Tanwar, Pradeep S. Mohapatra, Gayatry Chiang, Sarah Engler, David A. Zhang, LiHua Kaneko-Tarui, Tomoko Ohguchi, Yasuyo Birrer, Michael J. Teixeira, Jose M. TI Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer SO CARCINOGENESIS LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; PEUTZ-JEGHERS-SYNDROME; MOUSE MODEL; CONDITIONAL INACTIVATION; ENDOMETRIAL CANCER; CELLS; MICE; BRCA1; P53; LEIOMYOSARCOMAS AB Epithelial ovarian cancer presents mostly with serous, endometrioid or mucinous histology but is treated as a single disease. The development of histotype-specific therapy has been challenging because of the relative lack of studies attributing disrupted pathways to a distinct histotype differentiation. mTOR activation is frequently associated with poor prognosis in serous ovarian cancer, which is the most common and most deadly histotype. However, the mechanisms dysregulating mTOR in the pathogenesis of ovarian cancer are unknown. We detected copy number loss and correlated lower expression levels of LKB1, TSC1, TSC2 and PTEN tumor suppressor genes for upstream regulators of mTOR activity in up to 80% in primary ovarian serous tumor databases, with LKB1 allelic loss-predominant. Reduced LKB1 protein was usually associated with increased mTOR activity in both serous ovarian cancer cell lines and primary tumors. Conditional deletion of Lkb1 in murine ovarian surface epithelial (OSE) cells caused papillary hyperplasia and shedding but not tumors. Simultaneous deletion of Lkb1 and Pten, however, led to development of high-grade ovarian serous histotype tumors with 100% penetrance that expressed WT1, ER, PAX8, TP53 and cytokeratin 8, typical markers used in the differential diagnosis of serous ovarian cancer. Neither hysterectomy nor salpingectomy interfered with progression of ovarian tumorigenesis, suggesting that neither uterine nor Fallopian tube epithelial cells were contributing to tumorigenesis. These results implicate LKB1 loss in the OSE in the pathogenesis of serous ovarian cancer and provide a compelling rationale for investigating the therapeutic potential of targeting LKB1 signaling in patients with this deadly disease. C1 [Tanwar, Pradeep S.; Zhang, LiHua; Kaneko-Tarui, Tomoko; Ohguchi, Yasuyo] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Mohapatra, Gayatry; Birrer, Michael J.] Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. [Chiang, Sarah] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chiang, Sarah] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Engler, David A.] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA. [Teixeira, Jose M.] Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, Grand Rapids, MI 49503 USA. RP Teixeira, JM (reprint author), Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, 333 Bostwick Ave,NE 4018A, Grand Rapids, MI 49503 USA. EM jose.teixeira@hc.msu.edu FU National Institutes of Health [OD012206]; Vincent Memorial Research Funds FX National Institutes of Health (OD012206); Vincent Memorial Research Funds (to J.M.T.). NR 51 TC 13 Z9 13 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2014 VL 35 IS 3 BP 546 EP 553 DI 10.1093/carcin/bgt357 PG 8 WC Oncology SC Oncology GA AC7RZ UT WOS:000332730900005 PM 24170201 ER PT J AU Overton, LC Heinrich, MC AF Overton, Lindsay C. Heinrich, Michael C. TI Regorafenib for treatment of advanced gastrointestinal stromal tumors SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE gastrointestinal stromal tumor; kinase inhibitors; KIT; platelet-derived growth factor receptor alpha; sarcoma; vascular endothelial growth factor receptor ID METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; PHASE-I; IMATINIB RESISTANCE; ANTITUMOR-ACTIVITY; RANDOMIZED-TRIAL; BAY 73-4506; SUNITINIB; KIT AB Introduction: Gastrointestinal stromal tumors (GISTs) are abdominal sarcomas which are extremely refractory to chemotherapy treatment. The treatment of GISTs has been revolutionized by use of KIT/platelet-derived growth factor receptor-alpha (PDGFRA) kinase inhibitors. Unfortunately, most tumors develop resistance to front-line (imatinib) or second-line (sunitinib) therapy. Regorafenib, a KIT/PDGFRA/vascular endothelial growth factor receptor (VEGFR) oral kinase inhibitor, has been shown to improve progression-free survival in the third- or fourth-line setting. Areas covered: This review covers the preclinical and clinical studies of regorafenib for treatment of GIST. A literature search on regorafenib was carried out using the PubMed database up to October 2013. Expert opinion: Currently, imatinib and sunitinib represent the only proven first- and second-line therapies, respectively, for advanced GISTs. Based on the results of a Phase III study, regorafenib is now established as the only proven third-line therapy. Regorafenib activity in this setting is believed to be due to its activity against oncogenic forms of KIT/PDGFRA. Although side effects are common with this agent, they can be effectively managed with a combination of supportive care, dose interruptions/reductions. The toxicity profile is similar to other oral kinase inhibitors with anti-VEGFR activity. Regorafenib is mainly metabolized by CYP3A4, and concomitant use of strong inducers/inhibitors of this enzyme should be avoided. C1 [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. [Heinrich, Michael C.] OHSU Knight Canc Inst, Portland, OR 97239 USA. RP Heinrich, MC (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,Bldg 103 Lab E223,R&D 19, Portland, OR 97239 USA. EM Heinrich@ohsu.edu FU VA Merit Review Grant; GIST Cancer Research Fund; Life Raft Group FX M Heinrich: Consultant - Ariad, Molecular MD, Novartis, Pfizer. Speaker's honorarium - Onyx, Novartis. Equity interest Molecular MD. Intellectual property - patent on treatment of GIST with imatinib - assigned to my institution and licensed to Novartis. L Overton has no conflicts of interest. This paper has been supported by a VA Merit Review Grant, GIST Cancer Research Fund, Life Raft Group. NR 59 TC 6 Z9 6 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD MAR PY 2014 VL 15 IS 4 BP 549 EP 558 DI 10.1517/14656566.2014.877888 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AC5XQ UT WOS:000332594700010 PM 24405315 ER PT J AU Beitler, JR Shaefi, S Montesi, SB Devlin, A Loring, SH Talmor, D Malhotra, A AF Beitler, Jeremy R. Shaefi, Shahzad Montesi, Sydney B. Devlin, Amy Loring, Stephen H. Talmor, Daniel Malhotra, Atul TI Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis SO INTENSIVE CARE MEDICINE LA English DT Review DE Acute respiratory distress syndrome; Acute lung injury; Prone position; Patient positioning; Meta-analysis; Randomized controlled trial ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; LONG-TERM OUTCOMES; PROTECTIVE-VENTILATION; BERLIN DEFINITION; CLINICAL-TRIALS; SEVERE SEPSIS; SEPTIC SHOCK; FAILURE AB Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials. Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (> 8 ml/kg predicted body weight) or low (a parts per thousand currency sign8 ml/kg PBW) mean baseline tidal volume was planned a priori. Seven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95 % CI 0.68-1.02; p = 0.073; I (2) = 64 %). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95 % CI 0.50-0.86; p = 0.002; I (2) = 25 %). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis. Prone positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume. C1 [Beitler, Jeremy R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Shaefi, Shahzad; Loring, Stephen H.; Talmor, Daniel] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Montesi, Sydney B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Devlin, Amy] Beth Israel Deaconess Med Ctr, Div Rheumatol, Boston, MA 02215 USA. [Malhotra, Atul] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. RP Beitler, JR (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care Med, 221 Longwood Ave,BLI 036, Boston, MA 02115 USA. EM jbeitler@partners.org FU NIH [T32 HL007633, K24 HL093218, UM1 HL108724] FX The authors would like to thank Gregor Voggenreiter, MD, for providing additional data for the analysis [15], Paul A. Bain, PhD, for his assistance with the literature search strategy, and Michael A. Stoto, PhD, for his assistance in development of the analysis plan. This work was supported by NIH T32 HL007633, K24 HL093218, and UM1 HL108724. NR 51 TC 38 Z9 42 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD MAR PY 2014 VL 40 IS 3 BP 332 EP 341 DI 10.1007/s00134-013-3194-3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA AC3YL UT WOS:000332457400003 PM 24435203 ER PT J AU PrabhuDas, M Bowdish, D Drickamer, K Febbraio, M Herz, J Kobzik, L Krieger, M Loike, J Means, TK Moestrup, SK Post, S Sawamura, T Silverstein, S Wang, XY El Khoury, J AF PrabhuDas, Mercy Bowdish, Dawn Drickamer, Kurt Febbraio, Maria Herz, Joachim Kobzik, Lester Krieger, Monty Loike, John Means, Terry K. Moestrup, Soren K. Post, Steven Sawamura, Tatsuya Silverstein, Samuel Wang, Xiang-Yang El Khoury, Joseph TI Standardizing Scavenger Receptor Nomenclature SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PATTERN-RECOGNITION RECEPTOR; HOST-DEFENSE; SR-BI; CHOLESTEROL DEPOSITION; EXTRACELLULAR DOMAIN; INTERNATIONAL UNION; MACROPHAGE ADHESION; EXPRESSION CLONING; ENDOTHELIAL-CELLS AB Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a variety of ligands, including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the U. S. National Institute of Allergy and Infectious Diseases, National Institutes of Health to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of non-self or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. The discussion and nomenclature recommendations described in this report only refer to mammalian scavenger receptors. The purpose of this article is to describe the proposed mammalian nomenclature and classification developed at the workshop and to solicit additional feedback from the broader research community. C1 [PrabhuDas, Mercy] NIAID, NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Bowdish, Dawn] McMaster Univ, McMaster Immunol Res Ctr, MG DeGroote Inst Infect Dis Res, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada. [Drickamer, Kurt] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England. [Febbraio, Maria] Univ Alberta, Fac Med & Dent, Katz Grp Ctr Pharm & Hlth Res, Dept Dent, Edmonton, AB T6G 2E1, Canada. [Herz, Joachim] Univ Texas SW Med Ctr Dallas, Dept Mol Genet Neurosc & Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Kobzik, Lester] Harvard Univ, Sch Med, Dept Environm Hlth, Boston, MA 02115 USA. [Krieger, Monty] MIT, Dept Biol, Cambridge, MA 02139 USA. [Loike, John] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Means, Terry K.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Means, Terry K.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Means, Terry K.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Moestrup, Soren K.] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark. [Post, Steven] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72211 USA. [Sawamura, Tatsuya] Res Inst, Natl Cerebral & Cardiovasc Ctr, Dept Vasc Physiol, Suita, Osaka 5658565, Japan. [Silverstein, Samuel] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA. [Wang, Xiang-Yang] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Inst Mol Med,Dept Humen & Mol Genet, Richmond, VA 23298 USA. [El Khoury, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory,Infect Dis Div, Charlestown, MA 02129 USA. RP PrabhuDas, M (reprint author), NIAID, NIH, Div Allergy Immunol & Transplantat, 6610 Rockledge Dr, Bethesda, MD 20892 USA. EM mprabhudas@niaid.nih.gov; jelkhoury@mgh.harvard.edu RI Sawamura, Tatsuya/E-7103-2010; Moestrup, Soren Kragh/A-1403-2014; OI Moestrup, Soren Kragh/0000-0003-3862-2107; Post, Steven/0000-0002-4711-1723 FU NCI NIH HHS [R01 CA129111, R01 CA154708]; NHLBI NIH HHS [R37 HL063762]; NIAID NIH HHS [U24 AI082660]; NINDS NIH HHS [R01 NS059005] NR 77 TC 30 Z9 33 U1 3 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2014 VL 192 IS 5 BP 1997 EP 2006 DI 10.4049/jimmunol.1490003 PG 10 WC Immunology SC Immunology GA AC7IL UT WOS:000332701400001 PM 24563502 ER PT J AU Carlson, TJ Pellerin, A Djuretic, IM Trivigno, C Koralov, SB Rao, A Sundrud, MS AF Carlson, Thaddeus J. Pellerin, Alex Djuretic, Ivana M. Trivigno, Catherine Koralov, Sergei B. Rao, Anjana Sundrud, Mark S. TI Halofuginone-Induced Amino Acid Starvation Regulates Stat3-Dependent Th17 Effector Function and Reduces Established Autoimmune Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PATHOGENIC T(H)17 CELLS; HELPER T-CELLS; GENOME-WIDE ASSOCIATION; TRANSFER-RNA SYNTHETASE; SMALL-INTESTINE; CUTTING EDGE; DIFFERENTIATION; CYTOKINE; RECEPTOR; IL-23 AB The IL-23 pathway is genetically linked to autoimmune disease in humans and is required for pathogenic Th17 cell function in mice. However, because IL-23R-expressing mature Th17 cells are rare and poorly defined in mice at steady-state, little is known about IL-23 signaling. In this study, we show that the endogenous CCR6(+) memory T cell compartment present in peripheral lymphoid organs of unmanipulated mice expresses Il23r ex vivo, displays marked proinflammatory responses to IL-23 stimulation in vitro, and is capable of transferring experimental autoimmune encephalomyelitis. The prolyl-tRNA synthetase inhibitor halofuginone blocks IL-23-induced Stat3 phosphorylation and IL-23-dependent proinflammatory cytokine expression in endogenous CCR6(+) Th17 cells via activation of the amino acid starvation response (AAR) pathway. In vivo, halofuginone shows therapeutic efficacy in experimental autoimmune encephalomyelitis, reducing both established disease progression and local Th17 cell effector function within the CNS. Mechanistically, AAR activation impairs Stat3 responses downstream of multiple cytokine receptors via selective, posttranscriptional suppression of Stat3 protein levels. Thus, our study reveals latent pathogenic functions of endogenous Th17 cells that are regulated by both IL-23 and AAR pathways and identifies a novel regulatory pathway targeting Stat3 that may underlie selective immune regulation by the AAR. C1 [Carlson, Thaddeus J.; Pellerin, Alex; Djuretic, Ivana M.; Sundrud, Mark S.] Tempero Pharmaceut Inc, Cambridge, MA 02139 USA. [Trivigno, Catherine; Sundrud, Mark S.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA. [Koralov, Sergei B.; Rao, Anjana; Sundrud, Mark S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Koralov, Sergei B.; Rao, Anjana; Sundrud, Mark S.] Immune Dis Inst, Boston, MA USA. RP Sundrud, MS (reprint author), Scripps Res Inst, Dept Canc Biol, 130 Scripps Way 2C2, Jupiter, FL 33458 USA. EM msundrud@scripps.edu FU National Institutes of Health [AI40127, CA42471]; State of Florida; GlaxoSmithKline FX This work was supported in part by National Institutes of Health Grants AI40127 and CA42471 (to A. R.). Additional support (to M. S. S.) was provided to Scripps Florida from The State of Florida. Tempero Pharmaceuticals, Inc. is majority owned and funded by GlaxoSmithKline. NR 47 TC 7 Z9 8 U1 1 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2014 VL 192 IS 5 BP 2167 EP 2176 DI 10.4049/jimmunol.1302316 PG 10 WC Immunology SC Immunology GA AC7IL UT WOS:000332701400020 PM 24489094 ER PT J AU Severa, M Islam, SA Waggoner, SN Jiang, ZZ Kim, ND Ryan, G Kurt-Jones, E Charo, I Caffrey, DR Boyartchuk, VL Luster, AD Fitzgerald, KA AF Severa, Martina Islam, Sabina A. Waggoner, Stephen N. Jiang, Zhaozhao Kim, Nancy D. Ryan, Glennice Kurt-Jones, Evelyn Charo, Israel Caffrey, Daniel R. Boyartchuk, Victor L. Luster, Andrew D. Fitzgerald, Katherine A. TI The Transcriptional Repressor BLIMP1 Curbs Host Defenses by Suppressing Expression of the Chemokine CCL8 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELTA-T-CELLS; LISTERIA-MONOCYTOGENES INFECTION; CYCLIC-DI-GMP; BONE-MARROW; BACTERIAL-INFECTION; INNATE IMMUNITY; TERMINAL DIFFERENTIATION; GENE-EXPRESSION; DENDRITIC CELLS; CRITICAL ROLES AB The transcriptional repressor B lymphocyte-induced maturation protein 1 (BLIMP1) is a master regulator of B and T cell differentiation. To examine the role of BLIMP1 in innate immunity, we used a conditional knockout (CKO) of Blimp1 in myeloid cells and found that Blimp1 CKO mice were protected from lethal infection induced by Listeria monocytogenes. Transcriptome analysis of Blimp1 CKO macrophages identified the murine chemokine (C-C motif) ligand 8, CCL8, as a direct target of Blimp1-mediated transcriptional repression in these cells. BLIMP1-deficient macrophages expressed elevated levels of Ccl8, and consequently Blimp1 CKO mice had higher levels of circulating CCL8, resulting in increased neutrophils in the peripheral blood, promoting a more aggressive antibacterial response. Mice lacking the Ccl8 gene were more susceptible to L. monocytogenes infection than were wild-type mice. Although CCL8 failed to recruit neutrophils directly, it was chemotactic for gamma/delta T cells, and CCL8-responsive gamma/delta T cells were enriched for IL-17F. Finally, CCL8-mediated enhanced clearance of L. monocytogenes was dependent on gamma/delta T cells. Collectively, these data reveal an important role for BLIMP1 in modulating host defenses by suppressing expression of the chemokine CCL8. C1 [Severa, Martina; Jiang, Zhaozhao; Ryan, Glennice; Kurt-Jones, Evelyn; Caffrey, Daniel R.; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, Worcester, MA 01605 USA. [Severa, Martina] Ist Super Sanita, Dipartimento Malattie Infett Parassitarie & Immun, I-00161 Rome, Italy. [Islam, Sabina A.; Kim, Nancy D.; Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02482 USA. [Waggoner, Stephen N.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. [Waggoner, Stephen N.] Univ Massachusetts, Sch Med, Program Immunol & Virol, Worcester, MA 01655 USA. [Charo, Israel] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Boyartchuk, Victor L.; Fitzgerald, Katherine A.] Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Dept Canc Res & Mol Med, N-7489 Trondheim, Norway. RP Fitzgerald, KA (reprint author), Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, LRB Room 308,364 Plantation St, Worcester, MA 01605 USA. EM kate.fitzgerald@umassmed.edu RI SEVERA, MARTINA/J-8782-2016 OI SEVERA, MARTINA/0000-0002-0411-4545 FU National Institutes of Health [AI067497, R37AI040618, AI060991]; Italy-USA Program Grant [28C6] FX This work was supported by the National Institutes of Health (Grants AI067497 to K.A.F., R37AI040618 to A.D.L., and AI060991 to V.L.B.) and by Italy-USA Program Grant 28C6 (to M.S.). NR 78 TC 6 Z9 6 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2014 VL 192 IS 5 BP 2291 EP 2304 DI 10.4049/jimmunol.1301799 PG 14 WC Immunology SC Immunology GA AC7IL UT WOS:000332701400034 PM 24477914 ER PT J AU Lu, YF DiPierro, M Chen, LJ Chin, R Fava, M Yeung, A AF Lu, Yifan DiPierro, Moneika Chen, Lingjun Chin, Richard Fava, Maurizio Yeung, Albert TI The evaluation of a culturally appropriate, community-based lifestyle intervention program for elderly Chinese immigrants with chronic diseases: a pilot study SO JOURNAL OF PUBLIC HEALTH LA English DT Article DE elderly; chronic diseases; community-based; treatment; Chinese Americans ID OLDER-ADULTS; CARE; PERFORMANCE; SERVICES; PAIN AB The Healthy Habits Program is a 6-month community-based program, which offers exercise facilities, training and weekly health education group to underserved elderly Chinese Americans with chronic medical diseases in their native languages. This pilot study evaluates the acceptability and the health effects of the Healthy Habits Program. Ninety-nine subjects participated in the Healthy Habits Program in 2011. Before and after the program, the participants were assessed in their physical and mental health using various fitness tests as well as measures of disability and psychological functioning. Participants provided overwhelmingly positive feedback on the program, which was associated with significant improvements in physical and mental health including a significant decrease in body mass index (BMI), blood pressure and increase in stamina. The participants reported lower mean scores on the Patient Health Questionnaire-9 item Scale (PHQ-9), indicating improved psychological well-being. These promising pilot study results from this lifestyle intervention program for elderly Chinese American immigrants with chronic diseases inform the design of a more definitive trial using a randomized design and larger sample size. C1 [Lu, Yifan] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [DiPierro, Moneika; Chen, Lingjun; Fava, Maurizio; Yeung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Chen, Lingjun; Yeung, Albert] South Cove Community Hlth Ctr, Boston, MA 02111 USA. [Chin, Richard] YMCA Greater Boston, Wang Branch, Boston, MA 02111 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, One Bowdoin Sq,6-F, Boston, MA 02114 USA. EM ayeung@partners.org FU Asian Healthcare Foundation of Massachusetts, Inc. FX The study was supported by a grant from the Asian Healthcare Foundation of Massachusetts, Inc. NR 18 TC 2 Z9 2 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-3842 EI 1741-3850 J9 J PUBLIC HEALTH-UK JI J. Public Health PD MAR PY 2014 VL 36 IS 1 BP 149 EP 155 DI 10.1093/pubmed/fdt037 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AC3LT UT WOS:000332421300022 PM 23596196 ER PT J AU Peev, MP Rago, A Hwabejire, JO Duggan, MJ Beagle, J Marini, J Zugates, G Busold, R Freyman, T Velmahos, GS Demoya, MA Yeh, DD Fagenholz, PJ Sharma, U King, DR AF Peev, Miroslav P. Rago, Adam Hwabejire, John O. Duggan, Michael J. Beagle, John Marini, John Zugates, Greg Busold, Rany Freyman, Toby Velmahos, George S. Demoya, Marc A. Yeh, Daniel Dante Fagenholz, Peter J. Sharma, Upma King, David Richard TI Self- expanding foam for prehospital treatment of severe intra- abdominal hemorrhage: Dose finding study SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Bleeding; prehospital; noncompressible hemorrhage; liver; swine ID EXTREMITY VASCULAR INJURY; SEVERE SPLENIC INJURY; DECREASES BLOOD-LOSS; 2 ADVANCED DRESSINGS; FIBRIN SEALANT FOAM; BALAD AIR BASE; HEMOSTATIC EFFICACY; COMPLETE MANAGEMENT; LOCAL-POPULATION; LIVER-INJURIES AB BACKGROUND Noncompressible abdominal bleeding is a significant cause of preventable death on the battlefield and in the civilian trauma environment, with no effective therapies available at point of injury. We previously described the development of a percutaneously administered, self-expanding, poly(urea)urethane foam that improved survival in a lethal Grade V hepatic and portal vein injury model in swine. In this study, we hypothesized that survival with foam treatment is dose dependent. METHODS A high-grade hepatoportal injury was created in a closed abdominal cavity, resulting in massive noncompressible hemorrhage. After injury, the animals were divided into five groups. The control group (n = 12) was treated only with fluid resuscitation, and four polymer groups received different dose volumes (Group 1, n = 6, 64 mL; Group 2, n = 6, 85 mL; Group 3, n = 18, 100 mL; and Group 4, n = 10, 120 mL) in addition to fluids. Ten minutes after injury, the foam was percutaneously administered, and animals were monitored for 3 hours. RESULTS Survival with hepatoportal injury was highest in Group 4 (90%) and decreased in a dose-dependent fashion (Group 3, 72%; Group 2, 33%; Group 1, 17%). All polymer groups survived significantly longer than the controls (8.3%). Hemorrhage rate was reduced in all groups but lowest in Group 4 versus the control group (0.34 [0.052] vs. 3.0 [1.3] mL/kg/min, p < 0.001). Increasing foam dose volume was associated with increased peak intra-abdominal pressure (88.2 [38.9] in Group 4 vs. 9.5 [3.2] in the controls, p < 0.0001) and increased incidence of focal bowel injuries. CONCLUSION The self-expanding foam significantly improves survival in a dose-dependent fashion in an otherwise lethal injury. Higher doses are associated with better survival but resulted in the need for bowel resection. C1 [Peev, Miroslav P.; Hwabejire, John O.; Duggan, Michael J.; Beagle, John; Velmahos, George S.; Demoya, Marc A.; Yeh, Daniel Dante; Fagenholz, Peter J.; King, David Richard] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02141 USA. Harvard Univ, Sch Med, Boston, MA USA. [Rago, Adam; Marini, John; Zugates, Greg; Busold, Rany; Freyman, Toby; Sharma, Upma] Arsenal Med Inc, Watertown, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 FU DARPA; ARO [W911NF-10-C-0089, W911NF-12-C-0066] FX This study was supported by DARPA and ARO contract W911NF-10-C-0089 and W911NF-12-C-0066. NR 30 TC 13 Z9 14 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2014 VL 76 IS 3 BP 619 EP 623 DI 10.1097/TA.0000000000000126 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AB8YW UT WOS:000332077100015 PM 24553527 ER PT J AU Sheridan, RL Stoddard, FJ Kazis, LE Lee, A Li, NC Kagan, RJ Palmieri, TL Meyer, WJ Nicolai, M Stubbs, TK Chan, G Hinson, MI Herndon, DN Tompkins, RG AF Sheridan, Robert L. Stoddard, Frederick J. Kazis, Lewis E. Lee, Austin Li, Nien-Chen Kagan, Richard J. Palmieri, Tina L. Meyer, Walter J. Nicolai, Marc Stubbs, Teresa K. Chan, Grace Hinson, Michelle I. Herndon, David N. Tompkins, Ronald G. CA Multi-Ctr Benchmarking Study TI Long- term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: Effects durable at 4 years SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Burns; pediatric; outcomes; posttraumatic stress; pain control ID ACUTE PAIN; DISORDER; ADOLESCENTS; DISTRESS; PTSD; PREVALENCE; SURVIVORS; MORPHINE; SURGERY; INJURY AB BACKGROUND Children surviving serious burns are at risk for developing posttraumatic stress disorder (PTSD) as a function both of the injury and of its treatment. Short-term studies in such children have demonstrated reduced PTSD symptoms with intensive early pain control. However, the long-term impact of early pain control strategies on posttraumatic stress symptoms in children recovering from serious burn injuries has not been examined. METHODS This was a retrospective review of a multiple time point data collection involving a cohort of 147 infants, children, and teenagers with 4 years of follow-up after serious burns conducted at 4 pediatric burn centers to examine the impact of early opiate dosing on long-term posttraumatic stress symptoms. The main outcome measure was the nine-item Short Form Child Stress Disorders Checklist, which is an established and validated assessment. The impact of total opiate dosing during the first 7 days on these scores was assessed. RESULTS Subjects had an average age of 11 years and average injury size of 22% total body surface area burned (%TBS). The correlation between opiate units (OUs) and %TBS was 0.46 at baseline, OU increasing with increasing %TBS. OUs were strongly predictive of Child Stress Disorders Checklist scores up to 4 years, with higher OU (10 units vs. 6 and 2 units) remaining constantly different up to 4 years in predicting lower stress scores for both smaller and larger burns. CONCLUSION Early opiate management of pain associated with acute burn wounds and burn treatment predicts the development and resolution rate of PTSD symptoms in a large multicenter sample of children hospitalized for serious burns. The effect seems to be dose related and durable at least up to 4 years in a range of burn sizes. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level II. C1 [Sheridan, Robert L.; Stoddard, Frederick J.; Hinson, Michelle I.; Tompkins, Ronald G.] Boston Univ, Sch Publ Hlth, Shriners Hosp Children, Boston, MA USA. [Sheridan, Robert L.; Stoddard, Frederick J.; Lee, Austin; Tompkins, Ronald G.] Boston Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Boston, MA USA. [Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, CAPP, Boston, MA USA. [Meyer, Walter J.; Nicolai, Marc; Herndon, David N.] Shriners Hosp Children, Galveston, TX 77550 USA. [Kagan, Richard J.; Stubbs, Teresa K.] Shriners Hosp Children, Cincinnati, OH USA. [Palmieri, Tina L.; Chan, Grace] Shriners Hosp Children Northern Calif, Sacramento, CA USA. RP Sheridan, RL (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM rsheridan@mgh.harvard.edu FU Shriners Hospitals for Children FX This study was supported by grants from Shriners Hospitals for Children. NR 29 TC 10 Z9 10 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD MAR PY 2014 VL 76 IS 3 BP 828 EP 832 DI 10.1097/TA.0b013e3182ab111c PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA AB8YW UT WOS:000332077100052 PM 24553556 ER PT J AU Wilson, BG Helming, KC Wang, XF Kim, Y Vazquez, F Jagani, Z Hahn, WC Roberts, CWM AF Wilson, Boris G. Helming, Katherine C. Wang, Xiaofeng Kim, Youngha Vazquez, Francisca Jagani, Zainab Hahn, William C. Roberts, Charles W. M. TI Residual Complexes Containing SMARCA2 (BRM) Underlie the Oncogenic Drive of SMARCA4 (BRG1) Mutation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN REMODELING COMPLEXES; MAMMALIAN SWI/SNF COMPLEXES; CANCER-CELL-LINES; TUMOR-SUPPRESSOR; GENETIC LANDSCAPE; DIFFERENTIATION; ACTIVATION; EXPRESSION; RECEPTOR; SUBUNITS AB Collectively, genes encoding subunits of the SWI/SNF (BAF) chromatin remodeling complex are mutated in 20% of all human cancers, with the SMARCA4 (BRG1) subunit being one of the most frequently mutated. The SWI/SNF complex modulates chromatin remodeling through the activity of two mutually exclusive catalytic subunits, SMARCA4 and SMARCA2 (BRM). Here, we show that a SMARCA2-containing residual SWI/SNF complex underlies the oncogenic activity of SMARCA4 mutant cancers. We demonstrate that a residual SWI/SNF complex exists in SMARCA4 mutant cell lines and plays essential roles in cellular proliferation. Further, using data from loss-of-function screening of 165 cancer cell lines, we identify SMARCA2 as an essential gene in SMARCA4 mutant cancer cell lines. Mechanistically, we reveal that Smarca4 inactivation leads to greater incorporation of the nonessential SMARCA2 subunit into the SWI/SNF complex. Collectively, these results reveal a role for SMARCA2 in oncogenesis caused by SMARCA4 loss and identify the ATPase and bromodomain-containing SMARCA2 as a potential therapeutic target in these cancers. C1 [Wilson, Boris G.; Helming, Katherine C.; Wang, Xiaofeng; Kim, Youngha; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Roberts, Charles W. M.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Vazquez, Francisca; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vazquez, Francisca; Hahn, William C.; Roberts, Charles W. M.] Broad Inst Harvard & MIT, Canc Program, Boston, MA USA. [Hahn, William C.; Roberts, Charles W. M.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Jagani, Zainab] Novartis Inst BioMed Res, Cambridge, MA USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu FU Childhood Cancer Research Grant from the Pablove Foundation; David Abraham Foundation; Rally Foundation; U01 NCI Mouse Models of Cancer Consortium Award; Garrett B. Smith Foundation; Miles for Mary; Cure AT/RT Now foundation; [R01CA172152]; [R01CA113794] FX B.G.W. was supported by a Childhood Cancer Research Grant from the Pablove Foundation. X. W. was supported by a postdoctoral fellowshipfrom the David Abraham Foundation and Rally Foundation. This work was supported by R01CA172152 (C. W. M. R.) and R01CA113794 (C. W. M. R.), as well as by a U01 NCI Mouse Models of Cancer Consortium Award (C. W. M. R.). The Garrett B. Smith Foundation, Miles for Mary, and the Cure AT/RT Now foundation (C. W. M. R.) provided additional support. NR 49 TC 42 Z9 42 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2014 VL 34 IS 6 BP 1136 EP 1144 DI 10.1128/MCB.01372-13 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AB7UI UT WOS:000331995800018 PM 24421395 ER PT J AU Luttrell, LM AF Luttrell, Louis M. TI Minireview: More Than Just a Hammer: Ligand "Bias" and Pharmaceutical Discovery SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID PROTEIN-COUPLED RECEPTOR; BETA(2) ADRENERGIC-RECEPTOR; PARATHYROID-HORMONE PTH; RESONANCE ENERGY-TRANSFER; GROWTH-FACTOR RECEPTOR; KAPPA-OPIOID RECEPTORS; FUNCTIONAL SELECTIVITY; BETA(2)-ADRENERGIC RECEPTOR; ACTIVATED RECEPTOR-2; IN-VIVO AB Conventional orthosteric drug development programs targeting G protein-coupled receptors (GPCRs) have focused on the concepts of agonism and antagonism, in which receptor structure determines the nature of the downstream signal and ligand efficacy determines its intensity. Over the past decade, the emerging paradigms of "pluridimensional efficacy" and "functional selectivity" have revealed that GPCR signaling is not monolithic, and that ligand structure can "bias" signal output by stabilizing active receptor states in different proportions than the native ligand. Biased ligands are novel pharmacologic entities that possess the unique ability to qualitatively change GPCR signaling, in effect creating "new receptors" with distinct efficacy profiles driven by ligand structure. The promise of biased agonism lies in this ability to engender "mixed" effects not attainable using conventional agonists or antagonists, promoting therapeutically beneficial signals while antagonizing deleterious ones. Indeed, arrestin pathway-selective agonists for the type 1 parathyroid hormone and angiotensin AT(1) receptors, and G protein pathway-selective agonists for the GPR109A nicotinic acid and mu-opioid receptors, have demonstrated unique, and potentially therapeutic, efficacy in cell-based assays and preclinical animal models. Conversely, activating GPCRs in "unnatural" ways may lead to downstream biological consequences that cannot be predicted from prior knowledge of the actions of the native ligand, especially in the case of ligands that selectively activate as-yet poorly characterized G protein-independent signaling networks mediated via arrestins. Although much needs to be done to realize the clinical potential of functional selectivity, biased GPCR ligands nonetheless appear to be important new additions to the pharmacologic toolbox. C1 [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 Clin Sci Bldg, Charleston, SC 29425 USA. EM luttrell@musc.edu FU National Institutes of Health [DK055524, R01 GM095497]; Research Service of the Charleston, South Carolina Veterans Affairs Medical Center FX This work was supported by National Institutes of Health Grants DK055524 and R01 GM095497 (to L.M.L.), and the Research Service of the Charleston, South Carolina Veterans Affairs Medical Center. NR 169 TC 40 Z9 42 U1 1 U2 31 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 2014 VL 28 IS 3 BP 281 EP 294 DI 10.1210/me.2013-1314 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AC2ZJ UT WOS:000332384500002 PM 24433041 ER PT J AU Verdeguer, F Blattler, SM Cunningham, JT Hall, JA Chim, H Puigserver, P AF Verdeguer, Francisco Blaettler, Sharon M. Cunningham, John T. Hall, Jessica A. Chim, Helen Puigserver, Pere TI Decreased Genetic Dosage of Hepatic Yin Yang 1 Causes Diabetic-Like Symptoms SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID INSULIN-RESISTANCE; SKELETAL-MUSCLE; LIVER; LIPOGENESIS; DISEASE; MTOR; MICE; GLUCONEOGENESIS; METABOLISM; STEATOSIS AB Insulin sensitivity in liver is characterized by the ability of insulin to efficiently inhibit glucose production and fatty acid oxidation as well as promote de novo lipid biosynthesis. Specific dysregulation of glucose and lipid metabolism in liver is sufficient to cause insulin resistance and type 2 diabetes; this is seen by a selective inability of insulin to suppress glucose production while remaining insulin-sensitive to de novo lipid biosynthesis. We have previously shown that the transcription factor Yin Yang 1 (YY1) controls diabetic-linked glucose and lipid metabolism gene sets in skeletal muscle, but whether liver YY1-targeted metabolic genes impact a diabetic phenotype is unknown. Here we show that decreased genetic dosage of YY1 in liver causes insulin resistance, hepatic lipid accumulation, and dyslipidemia. Indeed, YY1 liver-specific heterozygous mice exhibit blunted activation of hepatic insulin signaling in response to insulin. Mechanistically, YY1, through direct recruitment to promoters, functions as a suppressor of genes encoding for metabolic enzymes of the gluconeogenic and lipogenic pathways and as an activator of genes linked to fatty acid oxidation. These counterregulatory transcriptional activities make targeting hepatic YY1 an attractive approach for treating insulin-resistant diabetes. C1 [Verdeguer, Francisco; Blaettler, Sharon M.; Cunningham, John T.; Hall, Jessica A.; Chim, Helen; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Verdeguer, Francisco; Blaettler, Sharon M.; Cunningham, John T.; Hall, Jessica A.; Chim, Helen; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,CLSB 11144, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu OI Cunningham, John/0000-0001-6490-4533 FU EMBO Long-Term Fellowship; Swiss National Science Foundation; American Heart Association predoctoral fellowship; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [RO1 DK081418] FX This work was supported in part by a postdoctoral fellowship from a EMBO Long-Term Fellowship (to F.V.), the Swiss National Science Foundation (to S.M.B.), an American Heart Association predoctoral fellowship (to J.A.H.), and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant RO1 DK081418 (to P.P.). NR 28 TC 1 Z9 2 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 2014 VL 28 IS 3 BP 308 EP 316 DI 10.1210/me.2013-1173 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AC2ZJ UT WOS:000332384500004 PM 24467246 ER PT J AU Rutkove, SB Caress, JB Cartwright, MS Burns, TM Warder, J David, WS Goyal, N Maragakis, NJ Benatar, M Sharma, KR Narayanaswami, P Raynor, EM Watson, ML Shefner, JM AF Rutkove, Seward B. Caress, James B. Cartwright, Michael S. Burns, Ted M. Warder, Judy David, William S. Goyal, Namita Maragakis, Nicholas J. Benatar, Michael Sharma, Khema R. Narayanaswami, Pushpa Raynor, Elizabeth M. Watson, Mary Lou Shefner, Jeremy M. TI ELECTRICAL IMPEDANCE MYOGRAPHY CORRELATES WITH STANDARD MEASURES OF ALS SEVERITY SO MUSCLE & NERVE LA English DT Article DE ALSFRS-R; amyotrophic lateral sclerosis; biomarkers; electrical impedance myography; handheld dynamometry AB Introduction: Electrical impedance myography (EIM) can be used to assess amyotrophic lateral sclerosis (ALS) progression. The relationship between EIM values and standard assessment measures, however, is unknown. Methods: EIM 50 kHz phase data from 60 subjects who participated in a longitudinal natural history study of ALS were correlated with handheld dynamometry (HHD), the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and motor unit number estimation (MUNE). Results: Moderate strength correlations between EIM parameters and HHD were observed for both whole-body and individual upper and lower extremity values. Similarly, moderate strength correlations were observed between EIM and ALSFRS-R upper and lower extremity subscores, but not total ALSFRS-R scores. MUNE correlated significantly with single muscle EIM data but not with whole body or upper or lower extremity values. Conclusions: These results support the concept that EIM can serve as a meaningful measure of disease severity in ALS. Muscle Nerve49:441-443, 2014 C1 [Rutkove, Seward B.; Narayanaswami, Pushpa; Raynor, Elizabeth M.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Caress, James B.; Cartwright, Michael S.] Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA. [Burns, Ted M.; Warder, Judy] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [David, William S.; Goyal, Namita] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Maragakis, Nicholas J.] Johns Hopkins Med Ctr, Dept Neurol, Baltimore, MD USA. [Benatar, Michael; Sharma, Khema R.] Univ Miami, Dept Neurol, Miami, FL USA. [Watson, Mary Lou; Shefner, Jeremy M.] SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. RP Rutkove, SB (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave,TCC 810, Boston, MA 02215 USA. EM srutkove@bidmc.harvard.edu OI Caress, James/0000-0002-5814-6083 FU ALS Association FX This study was funded by the ALS Association. NR 9 TC 19 Z9 19 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD MAR PY 2014 VL 49 IS 3 BP 441 EP 443 DI 10.1002/mus.24128 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AB7VP UT WOS:000331999300020 PM 24273034 ER PT J AU Helming, KC Wang, XF Wilson, BG Vazquez, F Haswell, JR Manchester, HE Kim, Y Kryukov, GV Ghandi, M Aguirre, AJ Jagani, Z Wang, Z Garraway, LA Hahn, WC Roberts, CWM AF Helming, Katherine C. Wang, Xiaofeng Wilson, Boris G. Vazquez, Francisca Haswell, Jeffrey R. Manchester, Haley E. Kim, Youngha Kryukov, Gregory V. Ghandi, Mahmoud Aguirre, Andrew J. Jagani, Zainab Wang, Zhong Garraway, Levi A. Hahn, William C. Roberts, Charles W. M. TI ARID1B is a specific vulnerability in ARID1A-mutant cancers SO NATURE MEDICINE LA English DT Article ID CHROMATIN REMODELING FACTOR; TUMOR-SUPPRESSOR AB Recent studies have revealed that ARID1A, encoding AT-rich interactive domain 1A (SWI-like), is frequently mutated across a variety of human cancers and also has bona fide tumor suppressor properties. Consequently, identification of vulnerabilities conferred by ARID1A mutation would have major relevance for human cancer. Here, using a broad screening approach, we identify ARID1B, an ARID1A homolog whose gene product is mutually exclusive with ARID1A in SWI/SNF complexes, as the number 1 gene preferentially required for the survival of ARID1A-mutant cancer cell lines. We show that loss of ARID1B in ARID1A-deficient backgrounds destabilizes SWI/SNF and impairs proliferation in both cancer cells and primary cells. We also find that ARID1A and ARID1B are frequently co-mutated in cancer but that ARID14-deficient cancers retain at least one functional ARID1B allele. These results suggest that loss of ARID1A and ARID1B alleles cooperatively promotes cancer formation but also results in a unique functional dependence. The results further identify ARID1B as a potential therapeutic target for ARID1A-mutant cancers. C1 [Helming, Katherine C.; Wang, Xiaofeng; Wilson, Boris G.; Haswell, Jeffrey R.; Manchester, Haley E.; Kim, Youngha; Roberts, Charles W. M.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Helming, Katherine C.; Wang, Xiaofeng; Wilson, Boris G.; Haswell, Jeffrey R.; Manchester, Haley E.; Kim, Youngha; Roberts, Charles W. M.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Helming, Katherine C.; Wang, Xiaofeng; Wilson, Boris G.; Haswell, Jeffrey R.; Manchester, Haley E.; Kim, Youngha; Roberts, Charles W. M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Helming, Katherine C.] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA USA. [Vazquez, Francisca; Kryukov, Gregory V.; Ghandi, Mahmoud; Aguirre, Andrew J.; Garraway, Levi A.; Hahn, William C.; Roberts, Charles W. M.] Broad Inst Harvard & MIT, Boston, MA USA. [Vazquez, Francisca; Garraway, Levi A.; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Aguirre, Andrew J.; Garraway, Levi A.; Hahn, William C.; Roberts, Charles W. M.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Jagani, Zainab] Novartis Inst Biomed Res, Cambridge, MA USA. [Wang, Zhong] Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. RP Roberts, CWM (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu RI Kryukov, Gregory/A-9592-2008; OI Ghandi, Mahmoud/0000-0003-1897-2265 FU David Abraham Foundation; Rally Foundation; St. Baldrick's Foundation; Pablove Foundation; US National Institutes of Health [R01HL109054, R01CA172152, R01CA113794]; U01 NCI Mouse Models of Cancer Consortium Award; Garrett B. Smith Foundation; Miles for Mary; Cure AT/RT Now foundation FX We thank Ping Lu for technical assistance with the setup of the sucrose sedimentation assay. X.W. was supported by a post-doctoral fellowship from David Abraham Foundation and Rally Foundation and a research grant from St. Baldrick's Foundation. B.G.W. was supported by a Childhood Cancer Research Grant from the Pablove Foundation. Z.W. is supported by US National Institutes of Health grant R01HL109054. This work was supported by US National Institutes of Health grants R01CA172152 (C.W.M.R.) and R01CA113794 (C.W.M.R.) and a U01 NCI Mouse Models of Cancer Consortium Award (C.W.M.R.). The Garrett B. Smith Foundation, Miles for Mary and the Cure AT/RT Now foundation (C.W.M.R.) provided additional support. NR 20 TC 62 Z9 63 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD MAR PY 2014 VL 20 IS 3 BP 251 EP 254 DI 10.1038/nm.3480 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AC5XZ UT WOS:000332595600019 PM 24562383 ER PT J AU Karabacak, NM Spuhler, PS Fachin, F Lim, EJ Pai, V Ozkumur, E Martel, JM Kojic, N Smith, K Chen, PI Yang, J Hwang, H Morgan, B Trautwein, J Barber, TA Stott, SL Maheswaran, S Kapur, R Haber, DA Toner, M AF Karabacak, Nezihi Murat Spuhler, Philipp S. Fachin, Fabio Lim, Eugene J. Pai, Vincent Ozkumur, Emre Martel, Joseph M. Kojic, Nikola Smith, Kyle Chen, Pin-i Yang, Jennifer Hwang, Henry Morgan, Bailey Trautwein, Julie Barber, Thomas A. Stott, Shannon L. Maheswaran, Shyamala Kapur, Ravi Haber, Daniel A. Toner, Mehmet TI Microfluidic, marker-free isolation of circulating tumor cells from blood samples SO NATURE PROTOCOLS LA English DT Article ID BREAST-CANCER PATIENTS; DETERMINISTIC LATERAL DISPLACEMENT; PERIPHERAL-BLOOD; MONOCLONAL-ANTIBODIES; IMMUNOMAGNETIC ENRICHMENT; PROSTATE-CANCER; SEPARATION; PROGRESSION; CARCINOMA; ANTIGEN AB The ability to isolate and analyze rare circulating tumor cells (CTCs) has the potential to further our understanding of cancer metastasis and enhance the care of cancer patients. In this protocol, we describe the procedure for isolating rare CTCs from blood samples by using tumor antigen-independent microfluidic CTC-iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial focusing and magnetophoresis to sort up to 10(7) cells/s. By using two-stage magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log depletion of white blood cells and a 97% yield of rare cells with a sample processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with standard cytopathological and RNA-based characterization methods. This protocol describes device production, assembly, blood sample preparation, system setup and the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including setup time, and chip production requires 2-5 d. C1 [Karabacak, Nezihi Murat; Spuhler, Philipp S.; Fachin, Fabio; Lim, Eugene J.; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M.; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Barber, Thomas A.; Stott, Shannon L.; Kapur, Ravi; Toner, Mehmet] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Karabacak, Nezihi Murat; Spuhler, Philipp S.; Fachin, Fabio; Lim, Eugene J.; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M.; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Barber, Thomas A.; Stott, Shannon L.; Kapur, Ravi; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Trautwein, Julie; Stott, Shannon L.; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Karabacak, Nezihi Murat; Spuhler, Philipp S.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM mtoner@hms.harvard.edu RI Karabacak, N Murat/D-7227-2013 OI Karabacak, N Murat/0000-0003-2761-5593 FU US National Institutes of Health (NIH) P41 Resource Center; NIH National Institute of Biomedical Imaging and Bioengineering Quantum Grant; Stand Up to Cancer; Howard Hughes Medical Institute; Prostate Cancer Foundation and the Charles Evans Foundation; Johnson and Johnson FX We express our gratitude to all patients and healthy volunteers who participated in this study and contributed blood samples. We thank L. Libby, O. Hurtado and A.J. Aranyosi for coordination of the research laboratories; D. M. Lewis and B. Hamza for expertise in device fabrication; and L. Nieman and J. Walsh for expertise in microscopy. This work was supported by the US National Institutes of Health (NIH) P41 Resource Center (M.T.); a NIH National Institute of Biomedical Imaging and Bioengineering Quantum Grant (M.T. and D.A.H.); Stand Up to Cancer (D.A.H., M.T. and S.M.); the Howard Hughes Medical Institute (D.A.H.); the Prostate Cancer Foundation and the Charles Evans Foundation (D.A.H. and M.T.); and Johnson and Johnson (M.T. and S.M.). NR 70 TC 150 Z9 158 U1 35 U2 258 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD MAR PY 2014 VL 9 IS 3 BP 694 EP 710 DI 10.1038/nprot.2014.044 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AC0ZM UT WOS:000332224000015 PM 24577360 ER PT J AU Ferguson, CJ Ceranoglu, TA AF Ferguson, Christopher J. Ceranoglu, T. Atilla TI Attention Problems and Pathological Gaming: Resolving the 'Chicken and Egg' in a Prospective Analysis SO PSYCHIATRIC QUARTERLY LA English DT Article DE Video games; Addiction; Pathological gaming; Attention problems; Grades ID VIDEO GAME ADDICTION; HYPERACTIVITY; PSYCHOTHERAPY; EXPERIENCE; ENGAGEMENT; CHILDREN; HEALTH AB Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon. C1 [Ferguson, Christopher J.] Stetson Univ, Dept Psychol & Commun, DeLand, FL 32708 USA. [Ceranoglu, T. Atilla] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ferguson, CJ (reprint author), Stetson Univ, Dept Psychol & Commun, 421 N Woodland Blvd, DeLand, FL 32708 USA. EM CJFerguson1111@aol.com NR 31 TC 4 Z9 4 U1 3 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-2720 EI 1573-6709 J9 PSYCHIAT QUART JI Psychiatr. Q. PD MAR PY 2014 VL 85 IS 1 BP 103 EP 110 DI 10.1007/s11126-013-9276-0 PG 8 WC Psychiatry SC Psychiatry GA AC4KS UT WOS:000332490500011 PM 24132870 ER PT J AU Duncan, DT Kawachi, I Melly, SJ Blossom, J Sorensen, G Williams, DR AF Duncan, Dustin T. Kawachi, Ichiro Melly, Steven J. Blossom, Jeffrey Sorensen, Glorian Williams, David R. TI Student Column DEMOGRAPHIC DISPARITIES IN THE TOBACCO RETAIL ENVIRONMENT IN BOSTON: A CITYWIDE SPATIAL ANALYSIS SO PUBLIC HEALTH REPORTS LA English DT Article ID SMALL-AREA ESTIMATION; OUTLET DENSITY; HEALTH DISPARITIES; NEIGHBORHOOD CHARACTERISTICS; TRACT LEVEL; FAST-FOOD; NEW-YORK; PRIORITIZING COMMUNITIES; SOCIOECONOMIC MEASURES; GEOGRAPHIC ANALYSIS C1 [Duncan, Dustin T.; Kawachi, Ichiro; Sorensen, Glorian; Williams, David R.] HSPH, Dept Social & Behav Sci, Boston, MA USA. [Duncan, Dustin T.; Kawachi, Ichiro; Sorensen, Glorian; Williams, David R.] HSPH, Lung Canc Dispar Ctr, Boston, MA USA. [Melly, Steven J.] HSPH, Dept Environm Hlth, Boston, MA USA. [Blossom, Jeffrey] Harvard Univ, Ctr Geog Anal, Cambridge, MA 02138 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Williams, David R.] Harvard Univ, Dept African & African Amer Studies, Cambridge, MA 02138 USA. [Williams, David R.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. RP Duncan, DT (reprint author), NYU, Sch Med, Dept Populat Hlth, 227 E 30th St,Room 621, New York, NY 10016 USA. EM dustin.duncan@nyumc.org FU Alonzo Smythe Yerby Postdoctoral Fellowship at Harvard School of Public Health (HSPH); National Cancer Institute [1P50CA148596] FX Dustin Duncan was supported by the Alonzo Smythe Yerby Postdoctoral Fellowship at Harvard School of Public Health (HSPH). David Williams was supported in part by a grant from the National Cancer Institute (grant #1P50CA148596) to the Lung Cancer Disparities Center at HSPH. The views and opinions expressed in this article are those of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 54 TC 2 Z9 2 U1 1 U2 11 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 2014 VL 129 IS 2 BP 209 EP 215 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AC3RW UT WOS:000332439900016 PM 24587559 ER PT J AU Chao, LL Mohlenhoff, BS Weiner, MW Neylan, TC AF Chao, Linda L. Mohlenhoff, Brian S. Weiner, Michael W. Neylan, Thomas C. TI Associations between Subjective Sleep Quality and Brain Volume in Gulf War Veterans SO SLEEP LA English DT Article DE Frontal lobe; structural imaging; Freesurfer; Pittsburgh Sleep Quality Index; Gulf War Veterans ID GRAY-MATTER CONCENTRATION; ADMINISTERED PTSD SCALE; US ARMY VETERANS; PREFRONTAL CORTEX; CYCLOSARIN EXPOSURE; NARCOLEPSY PATIENTS; HIPPOCAMPAL VOLUME; CHILDHOOD TRAUMA; PRIMARY INSOMNIA; OLDER-ADULTS AB Study Objectives: To investigate whether subjective sleep quality is associated with brain volume independent of comorbid psychiatric conditions. Design: Cross-sectional. Setting: Department of Veterans Affairs (VA) Medical Center. Participants: One hundred forty-four Gulf War Veterans (mean age 45 years; range: 31-70 years; 14% female). Interventions: None. Measurements and Results: Total cortical, lobar gray matter, and hippocampal volumes were quantified from 1.5 Tesla magnetic resonance images using Freesurfer version 4.5. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regressions were used to determine the association of sleep quality with total and regional brain volumes. The global PSQI score was positively correlated with lifetime and current posttraumatic stress disorder (PTSD) and current depressive symptoms (P < 0.001) and was higher in veterans with Gulf War Illness, trauma exposure, and those using psychotropic medication (P <= 0.03). After adjusting for these comorbid variables, age, intracranial volume, and multiple comparisons, global PSQI was inversely associated with total cortical and frontal gray matter volume (adjusted P <= 0.03). Within the frontal lobe, total PSQI was inversely associated with the superior and middle frontal, orbitofrontal, anterior cingulate, and frontal pole volumes (adjusted P <= 0.02). Examination of the 3-factor structure of the PSQI revealed that the associations were driven by perceived sleep quality. Conclusions: Poorer subjective sleep quality was associated with reduced total cortical and regional frontal lobe volumes independent of comorbid psychiatric conditions. Future work will be needed to examine if effective treatment of disturbed sleep leads to improved structural and functional integrity of the frontal lobes. C1 [Chao, Linda L.; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Chao, Linda L.; Mohlenhoff, Brian S.; Weiner, Michael W.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Chao, Linda L.; Mohlenhoff, Brian S.; Weiner, Michael W.] Dept Vet Affairs Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. [Neylan, Thomas C.] Dept Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. RP Chao, LL (reprint author), San Francisco VA Med Ctr, 4150 Clement St,114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu FU Department of Defense [DAMD17-01-1-0764]; Department of Defense Gulf War Illnesses Research Program, US Army Medical Research and Materiel Command; Mental Illness Research, Education and Clinical Center at VA VISN 21; Department of Defense and study medication from Glaxo Smith Kline [GSK561679]; Department of Veterans Affairs; Pfizer; Merck; Avid; Departments of Defense and Veterans' Affairs; NIA; Abbott; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Anonymous Foundation; AstraZeneca; Bayer Healthcare; BioClinica Inc; Bristol-Meyers Squibb; Cure Alzheimer's Fund < Eisai; Elan; Gene Network Sciences; Genetech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson Johnson; Eli Lilly Company; Medpace; Novartis; Pfizer Inc; Roche; Schering Plough; Wyeth; [R25MH060482] FX This was not an industry supported study. This study was supported by Department of Defense Grant DAMD17-01-1-0764, entitled, "Magnetic Resonance and Spectroscopy of the Human Brain in Gulf War Illness," awarded to the Northern California Institute for Research and Education from the Department of Defense Gulf War Illnesses Research Program, US Army Medical Research and Materiel Command. Further support was provided by the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration. Brian S. Mohlenhoff received funding from R25MH060482 and the Mental Illness Research, Education and Clinical Center at VA VISN 21. Resources and the use of facilities were provided by the Veterans Administration Medical Center, San Francisco, California. Dr. Neylan has received study medication (almorexant) from Actelion for a study funded by the Department of Defense and study medication (GSK561679) from Glaxo Smith Kline for a study funded by the Department of Veterans Affairs. Neither is relevant to the content of this report. Dr. Weiner has served on the scientific advisory boards of Pfizer & BOLT international in 2011. He has served as a consultant for Pfizer, Janssen, KLK Associates, Easton Associates, Harvard University, KLJ Associates, in Thought, INC, Research, Inc, University of California (Los Angeles), Alzheimer's Drug Discovery Foundation, Alzheimer's Drug Discovery Foundation, Avid Radio Pharmaceuticals, Eli Lilly, and Sanofi-Aventis. He has received funding for travel from Pfizer, AD PD meeting, Paul Sabatier University, Novartis, Tohoku University, from the MCI Group, France, Travel eDreams, Inc, Neuroscience School of Advanced Studies, Danone Trading, VB, CTAD ANT Congress, ADRC, University of California (Los Angeles), and from AD/PD, ADRC, UCLA. He serves on the editorial advisory boards of Alzheimer's & Dementia and MRI. He has received honoraria from Pfizer, Tohoku University, and from Danone Trading BV. He has received commercial entities research support from Merck and Avid. He has received government entities research support from the Departments of Defense and Veterans' Affairs. He has stock options in Elan. Organizations contributing to the Foundation for NIH and thus to the NIA funded Alzheimer's Disease Neuroimaging Initiative (ADNI) include the following: Abbott, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Anonymous Foundation, AstraZeneca, Bayer Healthcare, BioClinica Inc, Bristol-Meyers Squibb, Cure Alzheimer's Fund < Eisai, Elan, Gene Network Sciences, Genetech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly & Company, Medpace, Merck, Novartis, Pfizer Inc, Roche, Schering Plough, Wyeth. The other authors have indicated not financial conflicts of interest. This study does not include any off-label or investigational use. NR 65 TC 5 Z9 5 U1 3 U2 10 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD MAR 1 PY 2014 VL 37 IS 3 BP 445 EP 452 DI 10.5665/sleep.3472 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AC4VY UT WOS:000332520400003 PM 24587566 ER PT J AU Jakobiec, FA Werdich, XQ Chodosh, J Freitag, SK AF Jakobiec, Frederick A. Werdich, Xiang Q. Chodosh, James Freitag, Suzanne K. TI An analysis of conjunctival and periocular venous malformations: clinicopathologic and immunohistochemical features with a comparison of racemose and cirsoid lesions SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE conjunctiva; venous malformation; arteriovenous malformation; venous angioma; varix; hemorrhagic lymphangiectasia; racemose hemangioma; cirsoid hemangioma; immunohistochemistry ID WYBURN-MASON-SYNDROME; PAPILLARY ENDOTHELIAL HYPERPLASIA; KAPOSIS-SARCOMA; HEMORRHAGIC LYMPHANGIECTASIA; ARTERIOVENOUS-MALFORMATION; VASCULAR MALFORMATIONS; CAVERNOUS HEMANGIOMAS; ORBITAL VARIX; LYMPHANGIOMA; ANOMALIES AB Vascular tumors (in contrast to dilations or ectasias) of the conjunctiva and other adnexal tissues are rare, with no previous convincing example of a congenital, purely venous conjunctival malformation having been described. A 33-year-old man with a previously well-tolerated racemose conjunctival lesion present from birth developed bothersome symptoms when it underwent multifocal thrombosis with papillary endothelial cell hyperplasia as part of the process of thrombotic organization. Conservative subtotal excision with placement of an amniotic graft led to an acceptable cosmetic appearance, abatement of symptoms, and retention of full ocular function. Histopathologically, the lesion was composed of patulous vascular channels with thin walls displaying a negligible and irregular muscularis, diffuse supportive mural fibrosis, and the absence of an elastic lamina. Immunohistochemically the endothelial cells were CD31- and CD34-positive (vascular origin) but D2-40-negative (lymphatic origin). An associated neovascular capillary bed was not detected. Venous (racemose or grape-like) malformations should be distinguished from: arteriovenous (cirsoid or twisted) malformations in which the vessels possess thicker and more uniform muscular walls, some of which are endowed with an elastica; varices (hemorrhoidal dilations typically of a pre-existent vein); and venous angiomas (noncongenital lesions acquired in middle life) composed of regularly structured muscular channels devoid of an elastic lamina. Other conditions not to be confused with congenital venous malformations include hemorrhagic lymphangiectasia (of Leber), hemorrhagic lymphangiomas, and complex lymphaticovenous malformations. (C) 2014 Elsevier Inc. All rights reserved. C1 [Jakobiec, Frederick A.; Werdich, Xiang Q.; Chodosh, James; Freitag, Suzanne K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu FU Research to Prevent Blindness, New York, NY FX The authors thank Dr Karina A. Lund for providing clinical information. Dr. Chodosh is supported by a Senior Scientific Investigator Award from Research to Prevent Blindness, New York, NY. NR 56 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAR-APR PY 2014 VL 59 IS 2 BP 236 EP 244 DI 10.1016/j.survophthal.2013.06.003 PG 9 WC Ophthalmology SC Ophthalmology GA AB9UV UT WOS:000332142100008 PM 24355066 ER PT J AU Espaldon, R Kirby, KA Fung, KZ Hoffman, RM Powell, AA Freedland, SJ Walter, LC AF Espaldon, Roxanne Kirby, Katharine A. Fung, Kathy Z. Hoffman, Richard M. Powell, Adam A. Freedland, Stephen J. Walter, Louise C. TI Probability of an Abnormal Screening Prostate-specific Antigen Result Based on Age, Race, and Prostate-specific Antigen Threshold SO UROLOGY LA English DT Article ID REFERENCE RANGES; MEN; CANCER; OLDER AB OBJECTIVE To determine the distribution of screening prostate-specific antigen (PSA) values in older men, and how different PSA thresholds affect the proportion of white, black, and Latino men who would have an abnormal screening result across advancing age groups. METHODS We used linked national Veterans Affairs and Medicare data to determine the value of the first screening PSA test (ng/mL) of 327,284 men older than 65 years who underwent PSA screening in the Veterans Affairs health care system in 2003. We calculated the proportion of men with an abnormal PSA result based on age, race, and common PSA thresholds. RESULTS Among men older than 65 years, 8.4% had a PSA >4.0 ng/mL. The percentage of men with a PSA >4.0 ng/mL increased with age and was highest in black men (13.8%) vs white (8.0%) or Latino men (10.0%) (P < .001). Combining age and race, the probability of having a PSA >4.0 ng/mL ranged from 5.1% of Latino men aged 65-69 years to 27.4% of black men older than 85 years. Raising the PSA threshold from >4.0 ng/mL to >10.0 ng/mL reclassified the greatest percentage of black men older than 85 years (18.3% absolute change) and the lowest percentage of Latino men aged 65-69 years (4.8% absolute change) as being under the biopsy threshold (P < .001). CONCLUSION Age, race, and PSA threshold together affect the pretest probability of an abnormal screening PSA result. Based on screening PSA distributions, stopping screening among men whose PSA < 3 ng/mL means more than 80% of white and Latino men older than 70 years would stop further screening, and increasing the biopsy threshold to >10 ng/mL has the greatest effect on reducing the number of older black men who will face biopsy decisions after screening. (C) 2014 Elsevier Inc. C1 Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ New Mexico, Dept Med, New Mexico VA Hlth Care Syst, Albuquerque, NM 87131 USA. Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Durham VA Med Ctr, Durham, NC USA. Duke Univ, Duke Prostate Ctr, Durham, NC USA. RP Walter, LC (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr 181G,4150 Clement St, San Francisco, CA 94121 USA. EM Louise.Walter@ucsf.edu FU National Cancer Institute at the National Institutes of Health [R01 CA134425]; National Institute on Aging at the National Institutes of Health [K24AG041180]; Veterans Affairs Career Development Award Program [CDA 08-024]; New Mexico VA Health Care System FX This work was supported by the National Cancer Institute at the National Institutes of Health (grant number R01 CA134425 to L.W., S.F., A.P., and R.H.); the National Institute on Aging at the National Institutes of Health (grant number K24AG041180 to L.W.); the Veterans Affairs Career Development Award Program (grant number CDA 08-024 to A.P.); and the New Mexico VA Health Care System to R.H. NR 24 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2014 VL 83 IS 3 BP 599 EP 605 DI 10.1016/j.urology.2013.10.051 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AC3IR UT WOS:000332411200025 PM 24439009 ER PT J AU Espaldon, R Walter, LC AF Espaldon, Roxanne Walter, Louise C. TI Probability of an Abnormal Screening Prostate-specific Antigen Result Based on Age, Race, and Prostate-specific Antigen Threshold EDITORIAL COMMENT REPLY SO UROLOGY LA English DT Editorial Material C1 [Espaldon, Roxanne; Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Espaldon, R (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94143 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 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2014 VL 83 IS 3 BP 605 EP 605 DI 10.1016/j.urology.2013.10.056 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AC3IR UT WOS:000332411200027 ER PT J AU Gandaglia, G Trinh, QD AF Gandaglia, Giorgio Quoc-Dien Trinh TI Variations in the Open Market Costs for Prostate Cancer Surgery: A Survey of US Hospitals EDITORIAL COMMENT SO UROLOGY LA English DT Editorial Material C1 [Gandaglia, Giorgio] Ctr Hosp Univ Montreal, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Div Urol Surg, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Gandaglia, G (reprint author), Ctr Hosp Univ Montreal, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2014 VL 83 IS 3 BP 630 EP 631 DI 10.1016/j.urology.2013.09.067 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AC3IR UT WOS:000332411200033 PM 24439794 ER PT J AU Friedlander, DF Gu, XM Prasad, SM Lipsitz, SR Nguyen, PL Trinh, QD Sun, M Hu, JC AF Friedlander, David F. Gu, Xiangmei Prasad, Sandip M. Lipsitz, Stuart R. Nguyen, Paul L. Quoc-Dien Trinh Sun, Maxine Hu, Jim C. TI Population-based Comparative Effectiveness of Salvage Radical Prostatectomy vs Cryotherapy SO UROLOGY LA English DT Article ID RADIATION-THERAPY; PRIMARY RADIOTHERAPY; PATIENT SELECTION; CANCER; FAILURE; COMPLICATIONS; CARE AB OBJECTIVE To characterize population-based practice patterns, disease-specific and overall mortality, and cost associated with salvage cryotherapy (SCT) vs salvage radical prostatectomy (SRP). METHODS We retrospectively identified 440 men who failed primary radiation therapy and subsequently underwent SCT (n = 341, 77.5%) or SRP (n = 99, 22.5%) between 1992 and 2009 from Surveillance, Epidemiology, and End Results-Medicare linked data. Propensity score analyses were used to compare overall and prostate cancer-specific mortality and associated Medicare expenditures for SRP vs SCT. RESULTS Men undergoing SCT were more likely to be white (P <.001), less likely to be high school graduates (P = .008), and experienced shorter median time from diagnosis to salvage therapy (44.1 vs 60.1, P <.001) and from primary radiotherapy to salvage therapy (38.7 vs 55.8 months, P <.001). In adjusted analyses, overall mortality was higher (21.6 vs 6.1 deaths/100 person years, P <.001) for SRP vs SCT. There was a trend for higher prostate cancer-specific death rates with SRP vs SCT (6.5 vs 1.4 deaths/100 person years, P = .061). Medicare expenditures for SRP vs SCT were more than 2-fold higher ($19,543 vs $8,088, P <.001). CONCLUSION SRP vs SCT is associated with higher overall mortality and greater health care expenditures. However, longer follow-up is needed to assess long-term functional outcomes and cancer control. UROLOGY 83: 653-657, 2014. (C) 2014 Elsevier Inc. C1 Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. Med Univ S Carolina, Dept Urol, Charleston, SC 29425 USA. Ralph A Johnson VA Med Ctr, Urol Sect, Charleston, SC USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Div Urol Surg, Boston, MA 02115 USA. Univ Montreal, Fac Med, Dept Publ Hlth, Montreal, PQ H3C 3J7, Canada. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90024 USA. RP Hu, JC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, 924 Westwood Blvd,STE 1000, Los Angeles, CA 90024 USA. EM jchu@mednet.ucla.edu FU Department of Defense Prostate Cancer Physician Training Award [W81XWH-08-1-0283] FX Jim C. Hu receives salary support from a Department of Defense Prostate Cancer Physician Training Award (W81XWH-08-1-0283). The remaining authors declare that they have no relevant financial interests. NR 30 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD MAR PY 2014 VL 83 IS 3 BP 653 EP 657 DI 10.1016/j.urology.2013.11.019 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AC3IR UT WOS:000332411200040 PM 24581527 ER PT J AU Shea, JA Dinges, DF Small, DS Basner, M Zhu, JS Norton, L Ecker, AJ Novak, C Bellini, LM Dine, CJ Mollicone, DJ Volpp, KG AF Shea, Judy A. Dinges, David F. Small, Dylan S. Basner, Mathias Zhu, Jingsan Norton, Laurie Ecker, Adrian J. Novak, Cristina Bellini, Lisa M. Dine, C. Jessica Mollicone, Daniel J. Volpp, Kevin G. TI A Randomized Trial of a Three-Hour Protected Nap Period in a Medicine Training Program: Sleep, Alertness, and Patient Outcomes SO ACADEMIC MEDICINE LA English DT Article ID VIGILANCE TEST PVT; CONTINUOUS OPERATION; PROPHYLACTIC NAPS; DUTY HOURS; PERFORMANCE; INERTIA; SENSITIVITY; WAKEFULNESS; BENEFITS; CAFFEINE AB Purpose Protected sleep periods for internal medicine interns have previously resulted in increased amount slept and improved cognitive alertness but required supplemental personnel. The authors evaluated intern and patient outcomes associated with protected nocturnal nap periods of three hours that are personnel neutral. Method Randomized trial at Philadelphia Veterans Affairs Medical Center (PVAMC) Medical Service and Hospital of the University of Pennsylvania (HUP) Oncology Unit. During 2010-2011, four-week blocks were randomly assigned to a standard intern schedule (extended duty overnight shifts of up to 30 hours), or sequential protected sleep periods (phone sign-out midnight to 3:00 am [early shift] intern 1; 3:00 to 6:00 am [late shift] intern 2). Participants wore wrist Actiwatches, completed sleep diaries, and performed daily assessments of behavioral alertness. Between-group comparisons of means and proportions controlled for within-person correlations. Results HUP interns had significantly longer sleep durations during both early (2.40 hours) and late (2.44 hours) protected periods compared with controls (1.55 hours, P < .0001). At PVAMC sleep duration was longer only for the late shift group (2.40 versus 1.90 hours, P < .036). Interns assigned to either protected period were significantly less likely to have call nights with no sleep and had fewer attentional lapses on the Psychomotor Vigilance Test. Differences in patient outcomes between standard schedule months versus intervention months were not observed. Conclusions Protected sleep periods of three hours resulted in more sleep during call and reductions in periods of prolonged wakefulness, providing a plausible alternative to 16-hour shifts. C1 [Shea, Judy A.; Dinges, David F.; Basner, Mathias; Ecker, Adrian J.; Bellini, Lisa M.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dinges, David F.] Univ Penn, Dept Psychiat, Div Sleep & Chronobiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. [Zhu, Jingsan] Univ Penn, LDI Ctr Hlth Incent & Behav Econ, Perelman Sch Med, Philadelphia, PA 19104 USA. [Norton, Laurie; Novak, Cristina] Univ Penn, CHERP, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Norton, Laurie; Novak, Cristina] Univ Penn, Perelman Sch Med, CHIBE, Philadelphia, PA 19104 USA. [Bellini, Lisa M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dine, C. Jessica] Univ Penn, Perelman Sch Med, Div Pulm & Crit Care, Philadelphia, PA 19104 USA. [Mollicone, Daniel J.] Pulsar Informat Inc, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, CHERP, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Shea, JA (reprint author), 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM sheaja@mail.med.upenn.edu FU grant VA HSRD EDU [08-429] FX This work was funded by grant VA HSR&D EDU 08-429, to Dr. Volpp. NR 27 TC 2 Z9 2 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD MAR PY 2014 VL 89 IS 3 BP 452 EP 459 DI 10.1097/ACM.0000000000000144 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AB6CC UT WOS:000331874100025 PM 24448046 ER PT J AU Rand, K Lahav, A AF Rand, Katherine Lahav, Amir TI Impact of the NICU environment on language deprivation in preterm infants SO ACTA PAEDIATRICA LA English DT Review DE Deprivation; Design; Language; NICU; Preterm; Sounds ID LOW-BIRTH-WEIGHT; BIOLOGICAL MATERNAL SOUNDS; INTENSIVE-CARE-UNIT; RAT AUDITORY-CORTEX; SCHOOL-AGE-CHILDREN; SENSORY DEPRIVATION; SPEECH-PERCEPTION; HUMAN BRAIN; BORN; EXPERIENCE AB It is unclear whether the atypical language development commonly seen in preterm infants is a consequence of language deficiency experienced during their prolonged NICU stay. This review provides a novel viewpoint, which highlights the potential impact of the NICU design on the developmental origin of language disabilities in preterm infants. ConclusionFurther research is needed to identify evidence-based design solutions for providing preterm infants with a healthier linguistic hospital environment that aids growth and development. C1 [Rand, Katherine; Lahav, Amir] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Newborn Med, Boston, MA 02115 USA. [Lahav, Amir] MassGen Hosp Children, Dept Pediat, Boston, MA USA. RP Lahav, A (reprint author), Brigham & Womens Hosp, 75 Francis St CWN 418, Boston, MA 02115 USA. EM amir@hms.harvard.edu FU Jackson L. Graves Foundation; Little Giraffe Foundation; Gerber Foundation; Peter and Elizabeth C. Tower Foundation; Charles H. Hood Foundation FX This work was supported by the Jackson L. Graves Foundation, Little Giraffe Foundation, Gerber Foundation, Peter and Elizabeth C. Tower Foundation and Charles H. Hood Foundation. We would like to thank Fay Pal for assisting with graphic design and figure preparation. NR 61 TC 7 Z9 7 U1 4 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0803-5253 EI 1651-2227 J9 ACTA PAEDIATR JI Acta Paediatr. PD MAR PY 2014 VL 103 IS 3 BP 243 EP 248 DI 10.1111/apa.12481 PG 6 WC Pediatrics SC Pediatrics GA AA7IC UT WOS:000331270000016 PM 24164604 ER PT J AU Fava, M AF Fava, M. TI How can we make measures of psychotic depression symptoms more clinically useful? SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Editorial Material ID RATING-SCALE C1 [Fava, M.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Fava, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CTNI, Boston, MA USA. [Fava, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, DCRP, Boston, MA USA. RP Fava, M (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mfava@partners.org NR 12 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAR PY 2014 VL 129 IS 3 BP 161 EP 162 DI 10.1111/acps.12177 PG 2 WC Psychiatry SC Psychiatry GA AA1CC UT WOS:000330832900001 PM 23869739 ER PT J AU Wetherill, RR Jagannathan, K Lohoff, FW Ehrman, R O'Brien, CP Childress, AR Franklin, TR AF Wetherill, Reagan R. Jagannathan, Kanchana Lohoff, Falk W. Ehrman, Ronald O'Brien, Charles P. Childress, Anna Rose Franklin, Teresa R. TI Neural correlates of attentional bias for smoking cues: modulation by variance in the dopamine transporter gene SO ADDICTION BIOLOGY LA English DT Article DE Addiction; attentional bias; dopamine transporter; neuroimaging; smoking cues ID PREFRONTAL CORTEX; INDIVIDUAL-DIFFERENCES; ORBITOFRONTAL CORTEX; BRAIN ACTIVATION; PERFUSION FMRI; DRUG-ADDICTION; HUMAN AMYGDALA; RESPONSES; REWARD; VARENICLINE AB Cigarette-dependent smokers automatically and involuntarily orient attention toward smoking cues (SCs). This attentional bias is clinically significant, as it may contribute to relapse. Thus, identifying neural and genetic correlates of attentional bias is critical for improving interventions. Our previous studies show that the dopamine transporter (DAT) SLC6A3 genotype exerts profound effects on limbic responses to SCs. One potential mechanism underlying these effects is greater attentional bias for SCs. Here, we explored associations between attentional bias for SCs and neural responses to SCs among sated' smokers genotyped for the SLC6A3 polymorphism. Pseudo-continuous arterial spin-labeled perfusion functional magnetic resonance imaging images were acquired during SC exposure in 35 smokers genotyped for the SLC6A3 variable number of tandem repeats polymorphism (n=16, 9-repeats; n=19, 10/10-repeats). Participants completed a visual dot-probe attentional bias task, which contained pictures of smoking and non-smoking pictures, to examine whether genetic variation in DAT influences attentional bias and to investigate relationships between attentional bias and neural responses to SCs. Although attentional bias to smoking pictures was not significantly different between 9-repeats and 10/10-repeats, 9-repeats showed a positive correlation between attentional bias and increased SC-induced brain activity in the amygdala, whereas 10/10-repeats showed an inverse correlation in the medial orbitofrontal cortex (mOFC). In group comparisons, 9-repeats exhibited positive correlations between attentional bias and SCs in the mOFC and amygdala, relative to 10/10-repeats. Findings suggest that genetic variation in the DAT gene influences brain responses associated with attentional bias; thus, providing additional support for a SC-vulnerable endophenotype. C1 [Wetherill, Reagan R.; Jagannathan, Kanchana; Lohoff, Falk W.; O'Brien, Charles P.; Childress, Anna Rose; Franklin, Teresa R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Ehrman, Ronald] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Wetherill, RR (reprint author), Univ Penn, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM rwetherill@mail.med.upenn.edu RI Lohoff, Falk/M-7951-2016 FU National Institutes of Health [5-P60-DA-005186-18, 1R21DA025882-01A1, MH080729, EB015893] FX This work was supported by National Institutes of Health grants 5-P60-DA-005186-18, 1R21DA025882-01A1, MH080729 and EB015893. The authors wish to thank Drs. John Detre and Ze Wang for optimization of the perfusion fMRI technique, and Yin Li for aiding in imaging data preprocessing. We also thank the nursing staff at the Center for the Studies of Addiction for conducting physical evaluations; clinicians Anita Hole, PhD, Jesse Suh, PsyD, and Kathleen Marquez, MA, for conducting the psychological evaluations; Joshua Shin, BS, the lead technician on the study; and the MRI technicians at the Hospital of the University of Pennsylvania for conducting the scanning sessions. NR 65 TC 8 Z9 8 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD MAR PY 2014 VL 19 IS 2 BP 294 EP 304 DI 10.1111/j.1369-1600.2012.00507.x PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA AB1CO UT WOS:000331529100016 PM 23061530 ER PT J AU Ng, K Scott, JB Drake, BF Chan, AT Hollis, BW Chandler, PD Bennett, GG Giovannucci, EL Gonzalez-Suarez, E Meyerhardt, JA Emmons, KM Fuchs, CS AF Ng, Kimmie Scott, Jamil B. Drake, Bettina F. Chan, Andrew T. Hollis, Bruce W. Chandler, Paulette D. Bennett, Gary G. Giovannucci, Edward L. Gonzalez-Suarez, Elizabeth Meyerhardt, Jeffrey A. Emmons, Karen M. Fuchs, Charles S. TI Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial(1-4) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID COLORECTAL-CANCER PREVENTION; NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS; SERUM 25-HYDROXYVITAMIN D; 3RD NATIONAL-HEALTH; D-BINDING PROTEIN; D DEFICIENCY; UNITED-STATES; D INSUFFICIENCY; SKIN COLOR AB Background: Association studies have suggested that lower circulating 25-hydroxyvitamin D [25(OH)D] in African Americans may partially underlie higher rates of cardiovascular disease and cancer in this population. Nonetheless, the relation between vitamin D supplementation and 25(OH)D concentrations in African Americans remains undefined. Objective: Our primary objective was to determine the dose-response relation between vitamin D and plasma 25(OH)D. Design: A total of 328 African Americans in Boston, MA, were enrolled over 3 winters from 2007 to 2010 and randomly assigned to receive a placebo or 1000, 2000, or 4000 IU vitamin D-3/d for 3 mo. Subjects completed sociodemographic and dietary questionnaires, and plasma samples were drawn at baseline and 3 and 6 mo. Results: Median plasma 25(OH)D concentrations at baseline were 15.1, 16.2, 13.9, and 15.7 ng/mL for subjects randomly assigned to receive the placebo or 1000, 2000, or 4000 IU/d, respectively (P = 0.63). The median plasma 25(OH)D concentration at 3 mo differed significantly between supplementation arms at 13.7, 29.7, 34.8, and 45.9 ng/mL, respectively (P < 0.001). An estimated 1640 IU vitamin D-3/d was needed to raise the plasma 25(OH)D concentration to >= 20 ng/mL in >= 97.5% of participants, whereas a dose of 4000 IU/d was needed to achieve concentrations >= 33 ng/mL in >= 80% of subjects. No significant hypercalcemia was seen in a subset of participants. Conclusions: Within African Americans, an estimated 1640 IU vitamin D-3/d was required to achieve concentrations of plasma 25(OH)D recommended by the Institute of Medicine, whereas 4000 IU/d was needed to reach concentrations predicted to reduce cancer and cardiovascular disease risk in prospective observational studies. These results may be helpful for informing future trials of disease prevention. This trial was registered at clinicaltrials.gov as NCT00585637. C1 [Ng, Kimmie; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Scott, Jamil B.; Gonzalez-Suarez, Elizabeth; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA. [Drake, Bettina F.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. [Hollis, Bruce W.] Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. [Chandler, Paulette D.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Scott, Jamil B.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Ng, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1220, Boston, MA 02215 USA. EM kimmie_ng@dfci.harvard.edu OI Drake, Bettina/0000-0001-9340-5848 FU National Cancer Institute at the NIH [P50CA127003, K07CA148894, K22CA126992, 5K05CA124415, U01CA138962]; Department of Defense Prostate Cancer Research Program [PC081669]; American Society of Clinical Oncology (ASCO) Career Development Award; Pharmavite LLC FX Supported by the National Cancer Institute at the NIH [P50CA127003; K07CA148894 (to KN); K22CA126992 (to GGB); 5K05CA124415 (to KME); and U01CA138962 (to PDC)], the Department of Defense Prostate Cancer Research Program [PC081669 (to BD)], an American Society of Clinical Oncology (ASCO) Career Development Award (to KN), and Pharmavite LLC. NR 49 TC 30 Z9 31 U1 0 U2 13 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2014 VL 99 IS 3 BP 587 EP 598 DI 10.3945/ajcn.113.067777 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AB9VN UT WOS:000332143900022 PM 24368437 ER PT J AU Haun, N Hofer, A Greene, MT Borlaug, G Pritchett, J Scallon, T Safdar, N AF Haun, Nicholas Hofer, Adam Greene, M. Todd Borlaug, Gwen Pritchett, Jenny Scallon, Tina Safdar, Nasia TI Prevention of Clostridium difficile infection in rural hospitals SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Health care-associated; Survey; Evidence-based practices ID ACUTE-CARE; NATIONAL-SURVEY; DISEASE; FACILITIES; SURVEILLANCE; EPIDEMIC; DIARRHEA; AMERICA; STRAIN AB Background: Prevention of Clostridium difficile infection (CDI) remains challenging across the spectrum of health care. There are limited data on prevention practices for CDI in the rural health care setting. Methods: An electronic survey was administered to 21 rural facilities in Wisconsin, part of the Rural Wisconsin Health Cooperative. Data were collected on hospital characteristics and practices to prevent endemic CDI. Results: Fifteen facilities responded (71%). Nearly all respondent facilities reported regular use of dedicated patient care items, use of gown and gloves, private patient rooms, hand hygiene, and room cleaning. Facilities in which the infection preventionist thought the support of his/her leadership to be "Very good" or "Excellent" employed significantly more CDI practices (13.3 +/- 2.4 [ standard deviation]) compared with infection preventionists who thought there was less support from leadership (9.8 +/- 3.0, P = .033). Surveillance for CDI was highly variable. The most frequent barriers to implementation of CDI prevention practices included lack of adequate resources, lack of a physician champion, and difficulty keeping up with new recommendations. Conclusion: Although most rural facilities in our survey reported using evidence-based practices for prevention of CDI, surveillance practices were highly variable, and data regarding the impact of these practices on CDI rates were limited. Future efforts that correlate CDI prevention initiatives and CDI incidence will help develop evidence-based practices in these resource-limited settings. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Haun, Nicholas; Hofer, Adam; Safdar, Nasia] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Greene, M. Todd] Univ Michigan, Sch Med, Dept Internal Med, Div Gen Med, Ann Arbor, MI USA. [Greene, M. Todd] Ann Arbor VA Med Ctr, Ann Arbor, MI USA. [Borlaug, Gwen] Wisconsin Div Publ Hlth, Madison, WI USA. [Pritchett, Jenny] Grant Reg Hlth Ctr, Lancaster, WI USA. [Scallon, Tina] Sauk Prairie Mem Hosp, Sauk Prairie, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Safdar, N (reprint author), Univ Wisconsin Hosp & Clin, MFCB 5221, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu NR 22 TC 0 Z9 0 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR PY 2014 VL 42 IS 3 BP 311 EP 315 DI 10.1016/j.ajic.2013.09.011 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AC2EO UT WOS:000332311500020 PM 24406257 ER PT J AU Watnick, S Crowley, ST AF Watnick, Suzanne Crowley, Susan T. TI ESRD Care Within the US Department of Veterans Affairs: A Forward-Looking Program With an Illuminating Past SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE End-stage renal disease; public policy; US Department of Veterans Affairs ID STAGE RENAL-DISEASE; HOME DIALYSIS; UNITED-STATES; HEMODIALYSIS; VA; SYSTEM; FUTURE AB The first governmental agency to provide maintenance hemodialysis to patients with end-stage renal disease (ESRD) was the Veterans Administration (VA; now the US Department of Veterans Affairs). Many historical VA policies and programs set the stage for the later care of both veteran and civilian patients with ESRD. More recent VA initiatives that target restructuring of care models based on quality management, system-wide payment policies to promote cost-effective dialysis, and innovation grants aim to improve contemporary care. The VA currently supports an expanded and diversified nationwide treatment program for patients with ESRD using an integrated patient-centered care paradigm. This narrative review of ESRD care by the VA explores not only the medical advances, but also the historical, socioeconomic, ethical, and political forces related to the care of veterans with ESRD. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Watnick, Suzanne] Portland VA Med Ctr, Portland, OR 97207 USA. [Watnick, Suzanne] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Crowley, Susan T.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Crowley, Susan T.] Yale Univ, Sch Med, New Haven, CT USA. RP Watnick, S (reprint author), Portland VA Med Ctr, P3NEPH,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM suzanne.watnick@va.gov NR 54 TC 2 Z9 3 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2014 VL 63 IS 3 BP 521 EP 529 DI 10.1053/j.ajkd.2013.10.046 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AB3ZI UT WOS:000331728300025 PM 24331978 ER PT J AU Quillen, EE Chen, XD Almasy, L Yang, F He, H Li, X Wang, XY Liu, TQ Hao, W Deng, HW Kranzler, HR Gelernter, J AF Quillen, Ellen E. Chen, Xiang-Ding Almasy, Laura Yang, Fang He, Hao Li, Xi Wang, Xu-Yi Liu, Tie-Qiao Hao, Wei Deng, Hong-Wen Kranzler, Henry R. Gelernter, Joel TI ALDH2 Is Associated to Alcohol Dependence and Is the Major Genetic Determinant of "Daily Maximum Drinks" in a GWAS Study of an Isolated Rural Chinese Sample SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE alcohol dependence; maximum drinks; flushing response; genome-wide association; aldehyde dehydrogenase ID GENOME-WIDE ASSOCIATION; LINKAGE ANALYSIS; HAN CHINESE; RISK; RELIABILITY; POPULATION; DISEASES; DEHYDROGENASE; CONSUMPTION; VARIANTS AB Alcohol dependence (AD) is a moderately heritable phenotype with a small number of known risk genes mapped via linkage or candidate gene studies. We considered 313 males from among 595 members of documented, extended pedigrees in which AD segregates collected in Northern Hunan Province, China. A joint analysis of both males and females could not be performed as the difference in alcohol consumption variance was too large. Genome-wide association analyses were performed for approximately 300,000 single nucleotide polymorphisms (SNPs). Significant associations found in the ALDH2 region for AD (minimum P=4.73x10(-8)) and two AD-related phenotypes: flushing response (minimum P=4.75x10(-26)) and maximum drinks in a 24-hr period (minimum P=1.54x10(-16)). Association of previous candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%, 7.9%, and 22.9% of phenotypic variation, respectively, in this sample. When rs671 was considered as a candidate SNP in females, it explained 23.6% of the variation in flushing response, but alcohol consumption rates were too low among femalesdespite familial enrichment for ADfor an adequate test of association for either AD or maximum drinks. These results support a mediating effect of aldehyde dehydrogenase deficiency on alcohol consumption in males and a secondary, culturally mediated limitation on alcohol consumption by females that should be appropriately modeled in future studies of alcohol consumption in populations where this may be a factor. (c) 2013 Wiley Periodicals, Inc. C1 [Quillen, Ellen E.; Almasy, Laura] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Chen, Xiang-Ding; Yang, Fang; He, Hao; Li, Xi] Hunan Normal Univ, Hunan Inst Biol, Key Lab Prot Chem & Dev Biol, Minist Educ,Coll Life Sci, Changsha, Hunan, Peoples R China. [Wang, Xu-Yi; Liu, Tie-Qiao; Hao, Wei] Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha, Hunan, Peoples R China. [Deng, Hong-Wen] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, West Haven, CT 06516 USA. [Gelernter, Joel] VA CT Healthcare Ctr, Dept Psychiat, West Haven, CT USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA CT Healthcare Ctr S116A2, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Deng, Hong-Wen/0000-0002-0387-8818 FU NIAAA [R21 AA015973, P50 AA12870, K24 AA013736]; NIDA [R01 DA12849]; NIMH [MH059490]; SBC Foundation FX Grant sponsor: NIAAA; Grant numbers: R21 AA015973, P50 AA12870, K24 AA013736; Grant sponsor: NIDA; Grant number: R01 DA12849; Grant sponsor: NIMH; Grant number: MH059490; Grant sponsor: SBC Foundation. NR 44 TC 20 Z9 21 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2014 VL 165 IS 2 BP 103 EP 110 DI 10.1002/ajmg.b.32213 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AA8VX UT WOS:000331374200001 PM 24277619 ER PT J AU Power, RA Keller, MC Ripke, S Abdellaoui, A Wray, NR Sullivan, PF Breen, G AF Power, Robert A. Keller, Matthew C. Ripke, Stephan Abdellaoui, Abdel Wray, Naomi R. Sullivan, Patrick F. Breen, Gerome CA MDD PGC Working Grp TI A Recessive Genetic Model and Runs of Homozygosity in Major Depressive Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE runs of homozygosity; recessive risk model; major depression; inbreeding ID GENOME-WIDE ASSOCIATION; EPIDEMIOLOGY; SCHIZOPHRENIA; AUTOZYGOSITY; EVOLUTIONARY; METAANALYSIS; POPULATION; STRESS; TWIN AB Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here, we explore the possibility of such a recessive model in MDD. In a sample of 9,238 cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS we perform an analysis of ROH and common variants under a recessive model. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (P=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD. (c) 2014 Wiley Periodicals, Inc. C1 [Power, Robert A.; Breen, Gerome] Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Keller, Matthew C.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Keller, Matthew C.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Abdellaoui, Abdel] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Sullivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Breen, Gerome] South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London, England. [Breen, Gerome] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Power, RA (reprint author), Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. EM robert.r.power@kcl.ac.uk RI Power, Robert/B-3482-2012; Breen, Gerome/A-5540-2010; Wray, Naomi/C-8639-2015; OI Breen, Gerome/0000-0003-2053-1792; Wray, Naomi/0000-0001-7421-3357; KELLER, MATTHEW/0000-0002-6075-9882; de Geus, Eco/0000-0001-6022-2666 FU NIMH [MH085520, MH080403, MH072802, MH081802]; German Federal Ministry of Education and Research [01GS08144 01GS08147]; NIMH R01 [MH061686, MH059542, MH075131, MH059552, MH059541, MH060912]; Broad Institute Center [U54 RR020278]; National Alliance for Research on Schizophrenia and Depression; BMBF Program Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression [01ES0811]; Bavarian Ministry of Commerce; Federal Ministry of Education and Research (BMBF) in the framework of the National Genome Research Network [FKZ 01GS0481, 01GS08145]; The Netherlands Study of Depression and Anxiety (NESDA); Netherlands Twin Register (NTR); The Netherlands Organization for Scientific Research [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20, 916-76-125]; Spinozapremie [56-464-14192]; Geestkracht program [10-000-1002]; The Center for Medical Systems Biology (NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure, VU University's Institutes for Health and Care Research and Neuroscience Campus Amsterdam, BIC/BioAssist/RK [2008.024]; The European Science Foundation [EU/QLRT-2001-01254]; The European Community [FP7/2007-2013]; ENGAGE [HEALTH-F4-2007-201413]; The European Science Council [ERC 230374]; Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health; GAIN; Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613602, 613608, 613674, 619667]; The Australian Research Council [FT0991360, FT0991022]; The FP-5 GenomEUtwin Project [QLG2-CT- 2002-01254]; The US National Institutes of Health [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951]; The Center for Inherited Disease Research (Baltimore, MD, USA); UK Medical Research Council; GlaxoSmithKline [G0701420]; The National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health at the South London; Maudsley NHS Foundation Trust; The Institute of Psychiatry, King's College London; The UK Medical Research Council [G0000647]; European Commission Framework [LSHB-CT-2003-503428]; National Institute of Mental Health [N01MH90003] FX Grant sponsor: NIMH; Grant numbers: MH085520, MH080403, MH072802; Grant sponsor: German Federal Ministry of Education and Research; Grant number: 01GS08144 01GS08147; Grant sponsor: NIMH R01; Grant numbers: MH061686, MH059542, MH075131, MH059552, MH059541, MH060912; Grant sponsor: Broad Institute Center; Grant number: U54 RR020278; Grant sponsor: National Alliance for Research on Schizophrenia and Depression; Grant sponsor: BMBF Program Molecular Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major Depression; Grant number: 01ES0811; Grant sponsor: Bavarian Ministry of Commerce, and the Federal Ministry of Education and Research (BMBF) in the framework of the National Genome Research Network; Grant numbers: FKZ 01GS0481, 01GS08145; Grant sponsor: The Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Twin Register (NTR); Grant sponsor: The Netherlands Organization for Scientific Research; Grant numbers: 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20, 916-76-125; Grant sponsor: Spinozapremie; Grant number: 56-464-14192; Grant sponsor: Geestkracht program; Grant number: 10-000-1002; Grant sponsor: The Center for Medical Systems Biology (NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure, VU University's Institutes for Health and Care Research and Neuroscience Campus Amsterdam, BIC/BioAssist/RK; Grant number: 2008.024; Grant sponsor: The European Science Foundation; Grant number: EU/QLRT-2001-01254; Grant sponsor: The European Community's Seventh Framework Program; Grant number: FP7/2007-2013; Grant sponsor: ENGAGE; Grant number: HEALTH-F4-2007-201413; Grant sponsor: The European Science Council; Grant number: ERC 230374; Grant sponsor: Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health (partial support); Grant sponsor: GAIN and the NIMH; Grant number: MH081802; Grant sponsor: Australian National Health and Medical Research Council; Grant numbers: 241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613602, 613608, 613674, 619667; Grant sponsor: The Australian Research Council; Grant numbers: FT0991360, FT0991022; Grant sponsor: The FP-5 GenomEUtwin Project; Grant number: QLG2-CT- 2002-01254; Grant sponsor: The US National Institutes of Health; Grant numbers: AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854, DA019951; Grant sponsor: The Center for Inherited Disease Research (Baltimore, MD, USA); Grant sponsor: UK Medical Research Council and GlaxoSmithKline; Grant number: G0701420; Grant sponsor: The National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health at the South London; Grant sponsor: Maudsley NHS Foundation Trust; Grant sponsor: The Institute of Psychiatry, King's College London; Grant sponsor: The UK Medical Research Council; Grant number: G0000647; Grant sponsor: European Commission Framework; Grant number: LSHB-CT-2003-503428; Grant sponsor: National Institute of Mental Health; Grant number: N01MH90003. NR 34 TC 9 Z9 10 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2014 VL 165 IS 2 BP 157 EP 166 DI 10.1002/ajmg.b.32217 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AA8VX UT WOS:000331374200007 PM 24482242 ER PT J AU Keuthen, NJ Altenburger, EM Pauls, D AF Keuthen, Nancy J. Altenburger, Erin M. Pauls, David TI A Family Study of Trichotillomania and Chronic Hair Pulling SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE trichotillomania; hair pulling; obsessive-compulsive spectrum disorder; risk estimates ID OBSESSIVE-COMPULSIVE DISORDER; PATHOLOGICAL SKIN PICKING; COMORBIDITY; CHILDREN; OCD; GENETICS; ANXIETY; SAPAP3; SCALE; ONSET AB Little is known about the etiology of hair pulling (HP) and its relationship to other obsessive compulsive (OC) spectrum disorders. In a large-sample family study, we examined the familial aggregation of HP and co-transmission of obsessive compulsive disorder (OCD) and skin picking (SP). Our sample consisted of 110 proband cases with HP and 48 controls without HP, plus 128 first-degree case relatives and 50 first-degree control relatives. Case versus control relatives had higher recurrence risk estimates for both HP and OCD but not SP. The finding that HP is familial is consistent with the only existing twin study. Additional analyses suggest that there may be a familial subtype of HP with comorbid OCD. Those adult proband cases with HP+OCD had more anxiety and depression than cases without OCD. Probands with HP+OCD also had earlier onset of OCD. Identification of an HP subtype with comorbid OCD may have significant theoretical and treatment implications. The data did not provide evidence for an etiologic relationship between HP and SP. Replication of these findings in future studies with larger cohorts of case and control relatives is warranted. (c) 2014 Wiley Periodicals, Inc. C1 [Keuthen, Nancy J.; Altenburger, Erin M.; Pauls, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Keuthen, NJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM nkeuthen@partners.org FU Greater Kansas City Foundation FX Grant sponsor: Greater Kansas City Foundation. NR 46 TC 12 Z9 12 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2014 VL 165 IS 2 BP 167 EP 174 DI 10.1002/ajmg.b.32218 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AA8VX UT WOS:000331374200008 PM 24415254 ER PT J AU Jensen, KP Kranzler, HR Stein, MB Gelernter, J AF Jensen, Kevin P. Kranzler, Henry R. Stein, Murray B. Gelernter, Joel TI The Effects of a MAP2K5 MicroRNA Target Site SNP on Risk for Anxiety and Depressive Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE restless legs syndrome; depression; miR-330; MEK5; GWAS ID RESTLESS LEGS SYNDROME; GENOME-WIDE ASSOCIATION; PARTLY DIFFERENT ENVIRONMENTS; MAJOR DEPRESSION; SEMISTRUCTURED ASSESSMENT; ALCOHOLISM SSADDA; DRUG-DEPENDENCE; COMPLEX TRAITS; HUMAN-DISEASES; VARIANTS AB Functional variants that contribute to genomewide association study (GWAS) signals are difficult to identify. MicroRNAs could contribute to some of these gene-trait relationships. We compiled a set of GWAS trait gene SNPs that were predicted to affect microRNA regulation of mRNA. Trait associations were tested in a sample of 6725 European-American (EA) and African-American (AA) subjects that were interviewed using the polydiagnostic SSADDA to diagnose major psychiatric disorders. A predicted miR-330-3p target site SNP (rs41305272) in mitogen-activated protein kinase kinase 5 (MAP2K5) mRNA was in LD (d=1.0, r(2)=0.02) with a reported GWAS-identified variant for restless legs syndrome (RLS), a disorder frequently comorbid with anxiety and depression, possibly because of a shared pathophysiology. We examined the SNP's association with mood and anxiety-related disorders. Rs41305272 was associated with agoraphobia (Ag) in EAs (odds ratio [OR]=1.95, P=0.007; 195 cases) and AAs (OR=3.2, P=0.03; 148 cases) and major depressive disorder (MDD) in AAs (OR=2.64, P=0.01; 427 cases), but not EAs (465 cases). Rs41305272*T carrier frequency was correlated with the number of anxiety and depressive disorders diagnosed per subject. RLS was not evaluated in our subjects. Predicted miR-330-3p target genes were enriched in pathways relevant to psychiatric disorders. These findings suggest that microRNA target site information may be useful in the analysis of GWAS signals for complex traits. MiR-330-3p and MAP2K5 are potentially important contributors to mood and anxiety-related traits. With support from additional studies, these findings could add to the large number of risk genes identified through association to medical disorders that have primary psychiatric effects. (c) 2014 Wiley Periodicals, Inc. C1 [Jensen, Kevin P.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, West Haven, CT 06516 USA. [Jensen, Kevin P.; Gelernter, Joel] VA CT Hlth Care Ctr, West Haven, CT USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Ctr Studies Addict, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, West Haven, CT 06516 USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet Psychiat,VA CT Healthcare Ctr 116, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu FU NIH [DA12849, DA12690, DA18432, AA017535, DA028909, AA11330, MH64122, T32 MH014276]; VA MERIT Award FX Grant sponsor: NIH; Grant numbers: DA12849, DA12690, DA18432, AA017535, DA028909, AA11330, MH64122, T32 MH014276; Grant sponsor: VA MERIT Award. NR 63 TC 7 Z9 8 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR PY 2014 VL 165 IS 2 BP 175 EP 183 DI 10.1002/ajmg.b.32219 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AA8VX UT WOS:000331374200009 PM 24436253 ER PT J AU Martinez, EA Donelan, K Henneman, JP Berenholtz, SM Miralles, PD Krug, AE Iezzoni, LI Charnin, JE Pronovost, PJ AF Martinez, Elizabeth A. Donelan, Karen Henneman, Justin P. Berenholtz, Sean M. Miralles, Paola D. Krug, Allison E. Iezzoni, Lisa I. Charnin, Jonathan E. Pronovost, Peter J. TI Identifying Meaningful Outcome Measures for the Intensive Care Unit SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article ID BLOOD-STREAM INFECTIONS; REGIONAL-VARIATIONS; SAFETY; RISK; SATISFACTION; MORTALITY; INJURY; SYSTEM; RATES; ICU C1 [Martinez, Elizabeth A.; Donelan, Karen; Henneman, Justin P.; Miralles, Paola D.; Iezzoni, Lisa I.; Charnin, Jonathan E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berenholtz, Sean M.; Pronovost, Peter J.] Johns Hopkins Univ, Baltimore, MD USA. [Krug, Allison E.] Artemis Biomed Commun LLC, Bainbridge Isl, WA USA. RP Martinez, EA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 444, Boston, MA 02114 USA. EM martinez.elizabeth@mgh.harvard.edu FU Commonwealth Fund [2010334] FX The authors received the following financial support for the research, authorship, and/or publication of this article: The Commonwealth Fund Grant #2010334 (Drs Martinez, Berenholtz, Iezzoni, and Pronovost). NR 21 TC 2 Z9 2 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR PY 2014 VL 29 IS 2 BP 144 EP 152 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AB9VY UT WOS:000332145000008 PM 23892372 ER PT J AU Desilva, JM Gill, CM Swanson, Z Bonne-Annee, R Gill, SV AF Desilva, Jeremy M. Gill, Corey M. Swanson, Zane Bonne-Annee, Rachel Gill, Simone V. TI Reconstructing foot form and function in early hominins using modern human models SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 83rd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 08-12, 2014 CL Calgary, CANADA SP Amer Assoc Phys Anthropologists C1 [Desilva, Jeremy M.; Gill, Corey M.; Swanson, Zane; Bonne-Annee, Rachel] Boston Univ, Dept Anthropol, Boston, MA 02215 USA. [Gill, Corey M.] Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Gill, Corey M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gill, Simone V.] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 EI 1096-8644 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAR PY 2014 VL 153 SU 58 SI SI BP 104 EP 105 PG 2 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA AA6RH UT WOS:000331225100182 ER PT J AU Ingmanson, EJ May-Benson, T Braccini, S Porton, I Bauman, ML AF Ingmanson, Ellen J. May-Benson, Teresa Braccini, Stephanie Porton, Ingrid Bauman, Margaret L. TI The Holly Project: Continuing behavioral changes in a young adult female chimpanzee (Pan troglodytes) identified with sensory-integration difficulties SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 83rd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 08-12, 2014 CL Calgary, CANADA SP Amer Assoc Phys Anthropologists C1 [Ingmanson, Ellen J.] Bridgewater State Univ, Bridgewater, MA USA. [May-Benson, Teresa] Spiral Fdn, Newton, MA USA. [Braccini, Stephanie; Porton, Ingrid] St Louis Zoo, Great Apes, St Louis, MO USA. [Bauman, Margaret L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 EI 1096-8644 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAR PY 2014 VL 153 SU 58 SI SI BP 148 EP 148 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA AA6RH UT WOS:000331225100377 ER PT J AU Coker, J Castiglioni, A Kraemer, RR Massie, FS Morris, JL Rodriguez, M Russell, SW Shaneyfelt, T Willett, LL Estrada, CA AF Coker, Joshua Castiglioni, Analia Kraemer, Ryan R. Massie, F. Stanford Morris, Jason L. Rodriguez, Martin Russell, Stephen W. Shaneyfelt, Terrance Willett, Lisa L. Estrada, Carlos A. TI Evaluation of an Advanced Physical Diagnosis Course Using Consumer Preferences Methods: The Nominal Group Technique SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Internal medicine/education; Clinical clerkship/methods; Physical examination; Curriculum; Program evaluation ID SENIOR MEDICAL-STUDENTS; CURRICULUM; RESIDENTS AB Background: Current evaluation tools of medical school courses are limited by the scope of questions asked and may not fully engage the student to think on areas to improve. The authors sought to explore whether a technique to study consumer preferences would elicit specific and prioritized information for course evaluation from medical students. Methods: Using the nominal group technique (4 sessions), 12 senior medical students prioritized and weighed expectations and topics learned in a 100-hour advanced physical diagnosis course (4-week course; February 2012). Students weighted their top 3 responses (top = 3, middle = 2 and bottom = 1). Results: Before the course, 12 students identified 23 topics they expected to learn; the top 3 were review sensitivity/specificity and high-yield techniques (percentage of total weight, 18.5%), improving diagnosis (13.8%) and reinforce usual and less well-known techniques (13.8%). After the course, students generated 22 topics learned; the top 3 were practice and reinforce advanced maneuvers (25.4%), gaining confidence (22.5%) and learn the evidence (16.9%). The authors observed no differences in the priority of responses before and after the course (P = 0.07). Conclusions: In a physical diagnosis course, medical students elicited specific and prioritized information using the nominal group technique. The course met student expectations regarding education of the evidence-based physical examination, building skills and confidence on the proper techniques and maneuvers and experiential learning. The novel use for curriculum evaluation may be used to evaluate other courses-especially comprehensive and multicomponent courses. C1 [Coker, Joshua] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Castiglioni, Analia] Univ Cent Florida, Dept Med, Orlando, FL 32816 USA. [Kraemer, Ryan R.; Massie, F. Stanford; Morris, Jason L.; Russell, Stephen W.; Shaneyfelt, Terrance; Willett, Lisa L.; Estrada, Carlos A.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA. [Kraemer, Ryan R.; Morris, Jason L.; Willett, Lisa L.] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Birmingham, AL 35294 USA. [Rodriguez, Martin] Univ Alabama Birmingham, Div Infect Dis, Birmingham, AL 35294 USA. [Rodriguez, Martin] Univ Alabama Birmingham, Tinsley Harrison Med Serv, Birmingham, AL 35294 USA. [Russell, Stephen W.] Univ Alabama Birmingham, Moody Clin, Birmingham, AL 35294 USA. [Russell, Stephen W.] Univ Alabama Birmingham, Div Gen Pediat, Birmingham, AL 35294 USA. [Kraemer, Ryan R.; Morris, Jason L.; Shaneyfelt, Terrance; Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Univ Alabama Birmingham, Vet Affairs Natl Qual Scholars Program, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Div Gen Internal Med, 732 Fac Off Tower,510 20th St South, Birmingham, AL 35294 USA. EM cestrada@uab.edu FU Department of Veterans Affairs Office of Academic Affiliations (OAA) FX The Department of Veterans Affairs National Quality Scholars Fellowship (VAQS) and the Chief Resident in Quality and Safety Program are funded by the Department of Veterans Affairs Office of Academic Affiliations (OAA). The opinions expressed in this article are those of the authors alone and do not reflect the views of the Department of Veterans Affairs. NR 26 TC 1 Z9 1 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 2014 VL 347 IS 3 BP 199 EP 205 DI 10.1097/MAJ.0b013e3182831798 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AC0YF UT WOS:000332220700007 PM 23552288 ER PT J AU Magulick, JP Frei, CR Ali, SK Mortensen, EM Pugh, MJ Oramasionwu, CU Daniels, KR Mansi, IA AF Magulick, John P. Frei, Christopher R. Ali, Sayed K. Mortensen, Eric M. Pugh, Mary Jo Oramasionwu, Christine U. Daniels, Kelly R. Mansi, Ishak A. TI The Effect of Statin Therapy on the Incidence of Infections: A Retrospective Cohort Analysis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Fungal; Influenza; Infection; Statin ID COMMUNITY-ACQUIRED PNEUMONIA; COA REDUCTASE INHIBITORS; POPULATION-BASED COHORT; NITRIC-OXIDE; ENDOTHELIAL-CELLS; UNITED-STATES; MORTALITY; OUTCOMES; RISK; SEPSIS AB Background: Statins have been postulated to prevent infection through immunomodulatory effects. Objectives: To compare the incidence of infections in statin users to that in nonusers within the same health care system. Methods: This was a retrospective cohort study of patients enrolled as Tricare Prime or Plus in the San Antonio military multimarket. Statin users were patients who received a statin for at least 3 months between October 1, 2004 and September 30, 2005. Nonusers were patients who did not receive a statin within the study period (October 1, 2003-September 30, 2009). Inpatient and outpatient International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to determine the incidence of infections during the follow-up period (October 1, 2005-September 30, 2009) via multivariable regression analysis and time to infection via Cox regression analysis. Results: Of 45,247 patients who met the study criteria, 12,981 (29%) were statin users and 32,266 were nonusers. After adjustments for age, gender, Charlson Comorbidity Score, tobacco use, alcohol abuse/dependence, health care utilization and use of specific medication classes, statin use was associated with an increased incidence of common infections (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.06-1.19) but not influenza or fungal infections (OR: 1.06, 95% CI: 0.80-1.39; OR: 0.97; 95% CI: 0.91-1.04, respectively). Time-to-first infection was similar in statin users and nonusers in all infection categories examined. Conclusions: Statin use was associated with an increased incidence of common infections but not influenza or fungal infections. This study does not support a protective role of statins in infection prevention; however, the influence of potential confounders cannot be excluded. C1 [Magulick, John P.; Ali, Sayed K.] San Antonio Mil Med Ctr, Internal Med Serv, San Antonio, TX 78234 USA. [Frei, Christopher R.; Daniels, Kelly R.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Frei, Christopher R.; Daniels, Kelly R.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, Sch Med, San Antonio, TX 78229 USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, VA North Texas Hlth Care Syst, Dallas, TX 75390 USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Oramasionwu, Christine U.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. [Mansi, Ishak A.] Brooke Army Med Ctr, San Antonio, TX USA. [Mansi, Ishak A.] Uniformed Serv Univ Hlth Sci, San Antonio, TX USA. [Mansi, Ishak A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Mansi, IA (reprint author), San Antonio Mil Med Ctr, Internal Med Serv, 3551 Roger Brooke Dr, San Antonio, TX 78234 USA. EM ishak.mansi@us.army.mil OI Mortensen, Eric/0000-0002-3880-5563 FU U.S. National Institutes of Health (NIH) [RR025766]; AstraZeneca; Bristol Myers Squibb; Elan; Forest; Ortho-McNeil Janssen; Pfizer; VA Health Services Research and Development Service [DHI 09-237] FX C.R. Frei was supported by the U.S. National Institutes of Health (NIH) in the form of an NIH/KL2 career development award (RR025766) during the conduct of this study. C. R. Frei has received research grants and/or served as a scientific consultant/advisor for AstraZeneca, Bristol Myers Squibb, Elan, Forest, Ortho-McNeil Janssen and Pfizer. M.J.P. recieved support from VA Health Services Research and Development Service DHI 09-237. The remaining authors have no financial or other conflicts of interest to disclose. NR 64 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 2014 VL 347 IS 3 BP 211 EP 216 DI 10.1097/MAJ.0b013e31828318e2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AC0YF UT WOS:000332220700009 PM 23426088 ER PT J AU Mengel, M Chong, A Rothstein, DM Zorn, E Maltzman, JS AF Mengel, M. Chong, A. Rothstein, D. M. Zorn, E. Maltzman, J. S. TI AST Cutting Edge of Transplantation 2013 Meeting Report: A Comprehensive Look at B Cells and Antibodies in Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antibody-mediated rejection; B cells ID DONOR-SPECIFIC ANTIBODIES; MEDIATED REJECTION; HEART-TRANSPLANTATION; KIDNEY ALLOGRAFTS; HLA ANTIBODIES; COMPLEMENT; EXPRESSION; SURVIVAL; TARGETS; PATIENT AB Antibody-mediated rejection (ABMR) represents a significant clinical challenge for solid organ transplantation. Mechanistic understanding of ABMR is incomplete and diagnostic accuracy for ABMR is limited, and as a result, targeted treatment remains elusive and new treatment modalities are difficult to validate. Three hundred twenty-six participants from 15 countries met for the first Cutting Edge of Transplantation (CEOT) symposium organized by the American Society of Transplantation (AST) in Chandler, Arizona, February 14-16, 2013. During the 3-day interactive symposium, presentations, moderated poster sessions and round table discussions addressed cutting edge knowledge of B and plasma cell biology, mechanisms of antibody-mediated tissue injury, advances and limitations in ABMR diagnostics, as well as current and potential new treatment options for ABMR. The outcome of the meeting identified the following unmet needs for: (a) improved understanding of the regulation of B cell maturation and antibody response to enable targeted therapies; (b) more precise diagnostics of ABMR, including molecular pathology, risk stratification by sensitive antibody testing and monitoring of treatment effects; and (c) innovative multicenter trial designs that enhance observational power, in particular, in assessing synergistic multimodality therapies with reduced toxicities. The major unmet needs related to patients with antibody-mediated rejection include improved understanding of B cell maturation and antibody responses, more precise diagnostics for risk stratification and monitoring of treatment effects, and innovative multicenter trial designs to adjudicate the value of multimodality therapies. C1 [Mengel, M.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Chong, A.] Univ Chicago, Sect Transplant Surg, Chicago, IL 60637 USA. [Rothstein, D. M.] Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplant Inst, Pittsburgh, PA USA. [Zorn, E.] Harvard Univ, Sch Med, Dept Surg, Transplant Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maltzman, J. S.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Mengel, M (reprint author), Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. EM mmengel@ualberta.ca FU Astellas Pharma US, Inc.; Novartis Pharmaceuticals; One Lambda; Part of Thermo Fisher Scientific; Sanofi; Alexion FX The authors would like to thank CEOT 2013 program co-chairs Anthony Jevnikar, MD and Daniel Salomon, MD for organizing the first CEOT meeting and reviewing the manuscript. Educational grants and commercial support provided by Astellas Pharma US, Inc., Novartis Pharmaceuticals, One Lambda, Part of Thermo Fisher Scientific, Sanofi and additional nongrant/commercial support provided by Alexion, Astellas Pharma US, Inc., CSL Behring, Genentech, A Member of the Roche Group, Novartis Pharmaceuticals, One Lambda, Part of Thermo Fisher Scientific. NR 36 TC 0 Z9 0 U1 0 U2 4 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 MAR PY 2014 VL 14 IS 3 BP 524 EP 530 DI 10.1111/ajt.12593 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA AB4TQ UT WOS:000331783200007 PM 24674597 ER PT J AU Wright, AJ Fishman, JA Chung, RT AF Wright, A. J. Fishman, J. A. Chung, R. T. TI Lamivudine Compared With Newer Antivirals for Prophylaxis of Hepatitis B Core Antibody Positive Livers: A Cost-Effectiveness Analysis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Cost-effectiveness; health economics; hepatitis B virus; liver transplantation; prophylaxis ID ORGAN-TRANSPLANTATION; NEGATIVE RECIPIENTS; SURFACE-ANTIGEN; VIRUS INFECTION; DONORS; EXPERIENCE; GRAFTS; IMMUNOGLOBULIN; MECHANISMS; RESISTANCE AB There is concern over the development of de novo hepatitis B in patients receiving liver transplants from hepatitis B surface antigen negative, hepatitis B core antibody positive donors. Current practice is to place such patients on indefinite lamivudine prophylaxis; however, there is a small risk of breakthrough infection and newer antivirals for hepatitis B are available. The objective of this study was to determine the cost-effectiveness of lamivudine compared with the newer agents, tenofovir and entecavir, in the prophylaxis setting using a Markov model. Three strategies were examined which consisted of either lamivudine or entecavir monoprophylaxis with tenofovir add-on therapy after breakthrough or tenofovir monoprophylaxis with emtricitabine add-on therapy after breakthrough. In the base case scenario, lamivudine was the most cost-effective option at a threshold of $100000 per quality-adjusted life-year and this remained robust despite parameter uncertainty. Tenofovir had an incremental cost-effectiveness ratio of $3540194.77 while other strategies were superior to entecavir therapy. Until drug costs decrease, lamivudine remains the most cost-effective option for hepatitis B prophylaxis in the liver transplant setting. Using a Markov model, this study shows that lamivudine remains the most cost-effective option over tenofovir and entecavir for prophylaxis of recipients of hepatitis B core antibody positive liver transplants. C1 [Wright, A. J.; Fishman, J. A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chung, R. T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. EM chung.raymond@mgh.harvard.edu FU University of British Columbia-Pfizer; Sunovion Pharmaceuticals; NIH [DK078772]; Gilead; BMS FX The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. AJW has received educational support from a combined University of British Columbia-Pfizer and Sunovion Pharmaceuticals grant. RTC has received grant support from NIH DK078772, Gilead and BMS. No specific funding was provided for completion of this work. This work was part of a project done by AJW for a Master of Science, Epidemiology at the Harvard School for Public Health. NR 29 TC 4 Z9 7 U1 0 U2 1 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 MAR PY 2014 VL 14 IS 3 BP 629 EP 634 DI 10.1111/ajt.12598 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA AB4TQ UT WOS:000331783200018 PM 24460820 ER PT J AU Upshur, CC Weinreb, L Bharel, M AF Upshur, Carole C. Weinreb, Linda Bharel, Monica TI Homeless Women and Hazardous Drinking: Screening Results in a Primary Health Care Setting SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ALCOHOL-USE DISORDERS; IDENTIFICATION TEST AUDIT; SUBSTANCE USE; MENTAL-HEALTH; PREVALENCE; MISUSE; INTERVENTION; QUESTIONS; DRINKERS; MOTHERS AB Background and ObjectivesScreening for alcohol use in primary care is underutilized, especially for women. The current study implemented systematic women's alcohol use screening in a health care for the homeless primary care program. MethodsAll women (n=541) seeking care over 12 months were screened. ResultsOf the 541 screening forms returned, 80 women refused to answer the alcohol use questions. Of 461 completed screens, over 40% reported no alcohol use, while 43.8% reported hazardous drinking. Hazardous drinking was significantly associated with younger age, African American race, and living on the street or in a shelter. Discussion and ConclusionsHigh rates of drinking were identified among women in different housing situations and use of systematic screening was beneficial to providers. Scientific Significance and Future DirectionsHealth care settings are important sites to identify hazardous drinking as well as alcohol disorders among women with unstable housing histories. The growing integration of behavioral health care into primary care, and the medical home concept, both provide opportunities for brief interventions for at-risk drinkers, as well as treatment options for those with alcohol use disorders that may be particularly appealing to women. Findings support further investigation of the relationship of housing stability to drinking, and suggest African American women may need special attention. (Am J Addict 2014;23:117-122) C1 [Upshur, Carole C.; Weinreb, Linda] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA 01655 USA. [Bharel, Monica] Boston Univ, Med Ctr, Dept Med, Boston, MA USA. [Bharel, Monica] Massachusetts Gen Hosp, Boston Hlth Care Homeless Program, Boston, MA 02114 USA. RP Upshur, CC (reprint author), Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, 55 Lake Ave North, Worcester, MA 01655 USA. EM carole.upshur@umassmed.edu FU NIAAA NIH HHS [1R21AA018311] NR 34 TC 0 Z9 0 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD MAR PY 2014 VL 23 IS 2 BP 117 EP 122 DI 10.1111/j.1521-0391.2013.12072.x PG 6 WC Substance Abuse SC Substance Abuse GA AA9AP UT WOS:000331386400003 PM 25187047 ER PT J AU Chang, BH Sommers, E AF Chang, Bei-Hung Sommers, Elizabeth TI Acupuncture and Relaxation Response for Craving and Anxiety Reduction among Military Veterans in Recovery from Substance Use Disorder SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; AURICULAR ACUPUNCTURE; ALCOHOL DEPENDENCE; REDUCING ANXIETY; EFFICACY; ABUSE; DETOXIFICATION; METAANALYSIS; ASSOCIATION; THERAPY AB Background and ObjectivesSubstance use disorder (SUD) is a major health issue, especially among military veterans. We previously reported the effects of auricular acupuncture and the relaxation response (RR) on reducing craving and anxiety following 10-week interventions among veterans who were in recovery from SUDs. Our current analysis examines effects following each intervention session and RR daily practice. MethodsWe conducted a three-arm randomized controlled trial on residents of a homeless veteran rehabilitation program. Sixty-Seven enroled participants were randomly assigned to acupuncture (n=23), RR (n=23), or usual care (n=21). Participants in the two intervention groups rated their degree of craving for substance on a scale of 1-10 and anxiety levels on a scale of 1-4 (total score 20-80) before and after each intervention session. Mixed effects regression models were used for analysis. ResultsCraving and anxiety levels decreased significantly following one session of acupuncture (-1.04, p=.0001; -8.83, p<.0001) or RR intervention (-.43, p=.02; -4.64, p=.03). The level of craving continued to drop with additional intervention sessions (regression coefficient b=-.10, p=.01, and b=-.10, p=.02 for acupuncture and RR groups, respectively). Number of daily practice days of RR-eliciting techniques is also associated with reduction in craving ratings (b=-.02, p=.008). ConclusionsFindings demonstrate the value of attending regular acupuncture and RR-eliciting intervention sessions, as well as the daily practice of RR-eliciting techniques. Scientific SignificanceSubstance addiction is a complex disease and effective treatment remains a challenge. Our study findings add to the scientific evidence of these two non-pharmaceutical approaches for SUD. (Am J Addict 2014;23:129-136) C1 [Chang, Bei-Hung] VA Boston Healthcare Syst, Boston, MA USA. [Chang, Bei-Hung; Sommers, Elizabeth] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Sommers, Elizabeth] Pathways Wellness AIDS Care Project, Boston, MA USA. RP Chang, BH (reprint author), 150 S Huntington Ave 152H, Boston, MA 02130 USA. EM bhchang@bu.edu NR 42 TC 6 Z9 6 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD MAR PY 2014 VL 23 IS 2 BP 129 EP 136 DI 10.1111/j.1521-0391.2013.12079.x PG 8 WC Substance Abuse SC Substance Abuse GA AA9AP UT WOS:000331386400005 PM 25187049 ER PT J AU Berry, JD Cudkowicz, ME Shefner, JM AF Berry, James D. Cudkowicz, Merit E. Shefner, Jeremy M. TI Predicting success: Optimizing phase II ALS trials for the transition to phase III SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Review DE Clinical trials; phase II; RCT; biomarkers ID AMYOTROPHIC-LATERAL-SCLEROSIS; RANDOMIZED SEQUENTIAL TRIAL; MINOCYCLINE; TOPIRAMATE; SURVIVAL; DELAY AB Amyotrophic lateral sclerosis (ALS) research is advancing quickly, but the transition from phase II to phase III trials remains particularly challenging. In part, this is because of the paradox of phase II ALS trials -they are expected to inform researchers about safety, tolerability, dosage selection, and efficacy using a small number of patients, and relying on essentially the same outcome measures used in phase III trials. We examined pharmacokinetics in the cerebrospinal fluid and pharmacodynamic markers to demonstrate target engagement. In addition, primary outcome measures are often not specified or do not reach pre-specified goals for significance. We conclude that future trials should include pharmacokinetic (preferably in CSF) and pharmacodynamic markers of target engagement when possible. Primary endpoints should be pre-specified. Inclusion criteria should be used to reduce heterogeneity and target a relevant subpopulation of people with ALS when possible. Multiple phase II trials might be required before moving to a large phase III trial. C1 [Berry, James D.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Res Ctr, Boston, MA 02114 USA. [Shefner, Jeremy M.] SUNY Syracuse, Dept Neurol, Syracuse, NY USA. RP Berry, JD (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, Bigelow 1256, Boston, MA 02114 USA. EM jdberry@partners.org FU Cytokinetics; GlaxoSmithKlein; Biogen Idec; Sanofi Aventis; Neuraltus FX J. D. Berry has served as a consultant to Biogen Idec and Neuraltus Pharmaceuticals, and as a paid speaker for Oakstone Publishing. He receives research support from Cytokinetics and GlaxoSmithKlein.; J. M. Shefner has served as a consultant to Biogen Idec, Cytokinetics, Trophos, ISIS, Glaxo SmithKline, and receives research support from Cytokinetics, Biogen Idec, Sanofi Aventis, and Neuraltus. M. E. Cudkowicz served on DSMB for Synapse and Trophos and was a consultant for TEVA, Cytokinetics, Millenium, GlaxoSmithKline and Biogen. Dr. Cudkowicz has also served as a consultant to Neuraltus Pharmaceuticals. NR 30 TC 5 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD MAR PY 2014 VL 15 IS 1-2 BP 1 EP 8 DI 10.3109/21678421.2013.838969 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AC3KM UT WOS:000332417000001 PM 24588460 ER PT J AU Bucheli, M Andino, A Montalvo, M Cruz, J Atassi, N Berry, J Salameh, J AF Bucheli, Miriam Andino, Andres Montalvo, Mayra Cruz, Jose Atassi, Nazem Berry, James Salameh, Johnny TI Amyotrophic lateral sclerosis: Analysis of ALS cases in a predominantly admixed population of Ecuador SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE ALS; South America; EMG; Ecuador; ALS diagnosis ID MOTOR-NEURON DISEASE; NATURAL-HISTORY; COGNITIVE IMPAIRMENT; DIAGNOSTIC-CRITERIA; CLINICAL-FEATURES; ISIS SURVEY; FLAIL ARM; EPIDEMIOLOGY; PREVALENCE; SOUTH AB Recent studies suggest amyotrophic lateral sclerosis (ALS) prevalence, incidence, and age of onset are heterogeneous across populations. These include studies from South America (SA) where lower prevalence, earlier onset, and reduced survival time of ALS are reported. However, the scarcity of epidemiological and clinical data confounds effective comparison. To investigate ALS incidence in the predominantly admixed population of Ecuador, we analyzed patient data. We analyzed case data from two major hospitals. To confirm diagnosis, we evaluated clinical and EMG examinations in a cohort of patients. For 2000-2012, we found 116 patients with ALS diagnosis in the two hospitals. Crude incidence was 0.2-0.6 per 100,000. Median age of onset was 54.3 (+/- 15.06 SD). Clinical re-evaluation found misdiagnosis in three cases in the cohort. In conclusion, ALS incidence in the Ecuadorian hospital population is in accord with rates reported in recent studies for other admixed populations, and lower than that in the United States and Europe. Our study found that appropriate EMG administration and interpretation for the purposes of supporting a diagnosis of ALS with current consensus guidelines prevent adequate use of this test as an essential tool in the evaluation and diagnosis of ALS. Training for required standardization in Ecuador is recommended. C1 [Bucheli, Miriam] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Andino, Andres; Montalvo, Mayra; Cruz, Jose] San Francisco Univ Quito, Quito, Ecuador. [Atassi, Nazem; Berry, James] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Salameh, Johnny] Univ Massachusetts, Sch Med, Mem Med Ctr, Worcester, MA USA. RP Bucheli, M (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. EM Miriam.Bucheli@umassmed.edu OI Bucheli, Miriam/0000-0002-3757-8522 FU Program Prometheus, National Secretary of Higher Education, Science, Technology, and Innovation; Hospital Eugenio Espejo; Hospital Metropolitano; Hospital Carlos Andrade Marin; National Police Hospital FX Miriam Bucheli was supported by Program Prometheus, National Secretary of Higher Education, Science, Technology, and Innovation, Quito, Ecuador. We are thankful for the support of the neurologists: Fernando Alarcon (Chair) and Robert Salinas (Hospital Eugenio Espejo, site collaborators), Ramiro Montenegro (Hospital Metropolitano, site collaborator), Cristian Calero (Hospital Carlos Andrade Marin), Pilar Guerrero (National Police Hospital, site collaborator), and Hugo Zapata (Hospital de Los Valles, site collaborator). Additional thanks are expressed to Magdalena Sanchez (Director) and Daniel Galarraga -FUNDEM (Ecuadorian foundation for multiple sclerosis), Janet Montenegro for media relations, Ecuadorian Ministry of Public Health, the Ecuadorian Neurology Society, and University San Francisco of Quito. NR 62 TC 4 Z9 4 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD MAR PY 2014 VL 15 IS 1-2 BP 106 EP 113 DI 10.3109/21678421.2013.852590 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AC3KM UT WOS:000332417000015 PM 24245684 ER PT J AU Gomeni, R Fava, M AF Gomeni, Roberto Fava, Maurizio CA Pooled Resource Open-Access ALS TI Amyotrophic lateral sclerosis disease progression model SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Article DE ALS; disease progression model; placebo response; cluster analysis ID ALZHEIMERS-DISEASE; DRUG DEVELOPMENT; CLINICAL-TRIALS; ALSFRS-R; NONMEM; DISORDERS AB Our objective was to develop: 1) a longitudinal model to describe amyotrophic lateral sclerosis (ALS) disease progression using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R); and 2) a probabilistic model to estimate the presence of clusters of trajectories in ALS progression over 12 months of treatment. Three hundred and thirty-eight patients treated with placebo from the PRO-ACT database were included in the analyses. A non-linear Weibull model best described the ALS disease progression, and a stepwise logistic regression approach was used to select the variables predicting a slow or fast disease progression. Results identified two clusters of trajectories: 1) slow disease progressors (46% of patients with a change from baseline of 13%); 2) fast disease progressors (54% of patients with a change from baseline of 49%). ROC curve analysis estimated the optimal cut-off for classifying patients as slow or fast disease progressors given ALSFRS-R measurements at 2-4 weeks. Results showed that the degree of ALS disease progression quantified by the ALSFRS-R symptomatic change on placebo is highly heterogeneous. In conclusion, this finding indicates the potential interest of disease progression models for implementing a population enrichment strategy to control the level of heterogeneity in the patients included in new trials. C1 [Gomeni, Roberto] PharmacoMetrica, La Fouillade, France. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gomeni, R (reprint author), Pharmacometr France, Lieu Dit Longcol, F-12700 La Fouillade, France. EM roberto.gomeni@pharmacometrica.com NR 23 TC 12 Z9 12 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD MAR PY 2014 VL 15 IS 1-2 BP 119 EP 129 DI 10.3109/21678421.2013.838970 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA AC3KM UT WOS:000332417000017 PM 24070404 ER PT J AU Rosenberg, MA Lopez, FL Buzkova, P Adabag, S Chen, LY Sotoodehnia, N Kronmal, RA Siscovick, DS Alonso, A Buxton, A Folsom, AR Mukamal, KJ AF Rosenberg, Michael A. Lopez, Faye L. Buzkova, Petra Adabag, Selcuk Chen, Lin Y. Sotoodehnia, Nona Kronmal, Richard A. Siscovick, David S. Alonso, Alvaro Buxton, Alfred Folsom, Aaron R. Mukamal, Kenneth J. TI Height and risk of sudden cardiac death: the Atherosclerosis Risk in Communities and Cardiovascular Health Studies SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Body height; Risk factors; Death; Sudden; Cardiac ID GENOME-WIDE ASSOCIATION; LEFT-VENTRICULAR MASS; SHORT STATURE; COMMON VARIANTS; EPIDEMIOLOGY; POPULATION; DISEASE; ARREST; LOCI; METAANALYSIS AB Purpose: Sudden cardiac death (SCD) is an important cause of mortality in the adult population. Height has been associated with cardiac hypertrophy and an increased risk of arrhythmias but also with decreased risk of coronary heart disease, suggesting a complex association with SCD. Methods: We examined the association of adult height with the risk of physician-adjudicated SCD in two large population-based cohorts: the Cardiovascular Health Study and the Atherosclerosis Risk in Communities study. Results: Over an average follow-up time of 11.7 years in Cardiovascular Health Study, there were 199 (3.6%) cases of SCD among 5556 participants. In Atherosclerosis Risk in Communities study, over 12.6 years, there were 227 (1.5%) cases of SCD among 15,633 participants. In both cohorts, there was a trend toward decreased SCD with taller height. In fixed effects meta-analysis, the pooled hazard ratio per 10 cm of height was 0.84; 95% confidence interval, 0.73-0.98; P =.03. The association of increased height with lower risk of SCD was slightly attenuated after inclusion of risk factors associated with height, such as hypertension and left ventricular hypertrophy. The association appeared stronger among men than women in both cohorts. Conclusions: In two population-based prospective cohorts of different ages, greater height was associated with lower risk of SCD. Published by Elsevier Inc. C1 [Rosenberg, Michael A.] Harvard Univ, Sch Med, Vet Adm Hosp Boston, Div Cardiac Electrophysiol, West Roxbury, MA 02132 USA. [Rosenberg, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, West Roxbury, MA 02132 USA. [Lopez, Faye L.; Adabag, Selcuk; Alonso, Alvaro; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Buzkova, Petra; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Adabag, Selcuk] Vet Affairs Med Ctr, Div Cardiol, Minneapolis, MN USA. [Chen, Lin Y.] Univ Minnesota, Med Ctr, Div Cardiol, Minneapolis, MN 55455 USA. [Sotoodehnia, Nona; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Buxton, Alfred] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, West Roxbury, MA 02132 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care Res, Boston, MA 02215 USA. RP Rosenberg, MA (reprint author), Harvard Univ, Sch Med, Div Electrophysiol, 1400 VFW Pkwy,111CA, West Roxbury, MA 02132 USA. EM marosenberg@partners.org RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Adabag, Selcuk/0000-0003-2154-8596 FU National Heart, Lung, and Blood Institute [HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging [AG023629] FX This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhIbi.org/. NR 39 TC 5 Z9 5 U1 0 U2 1 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 MAR PY 2014 VL 24 IS 3 BP 174 EP 179 DI 10.1016/j.annepidem.2013.11.008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AC1NN UT WOS:000332263400003 PM 24360853 ER PT J AU Dienstmann, R Rodon, J Prat, A Perez-Garcia, J Adamo, B Felip, E Cortes, J Iafrate, AJ Nuciforo, P Tabernero, J AF Dienstmann, R. Rodon, J. Prat, A. Perez-Garcia, J. Adamo, B. Felip, E. Cortes, J. Iafrate, A. J. Nuciforo, P. Tabernero, J. TI Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors SO ANNALS OF ONCOLOGY LA English DT Review DE fibroblast growth factor receptor FGFR; amplification; cancer; hyperphosphatemia; oncogene; targeted therapy ID FIBROBLAST-GROWTH-FACTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; FACTOR RECEPTOR INHIBITORS; POTENT ANTITUMOR-ACTIVITY; EARLY CLINICAL-TRIALS; BREAST-CANCER; BLADDER-CANCER; GASTRIC-CANCER; ENDOMETRIAL CARCINOMA AB The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1-4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1-4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors. C1 [Dienstmann, R.; Iafrate, A. J.] Massachusetts Gen Hosp, Ctr Canc, Mol Pathol Lab, Boston, MA USA. [Rodon, J.; Prat, A.; Perez-Garcia, J.; Adamo, B.; Felip, E.; Cortes, J.; Tabernero, J.] Vall dHebron Inst Oncol, Med Oncol Dept, Barcelona, Spain. [Prat, A.] Vall dHebron Inst Oncol, Translat Genom Lab, Barcelona, Spain. [Nuciforo, P.] Vall dHebron Inst Oncol, Mol Oncol Lab, Barcelona, Spain. RP Tabernero, J (reprint author), Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Dept Med Oncol, P Vall dHebron 119-129, Barcelona 08035, Spain. EM jtabernero@vhebron.net RI Prat, Aleix/P-8561-2014; OI Prat, Aleix/0000-0003-2377-540X; Cortes, Javier/0000-0001-7623-1583; Nuciforo, Paolo/0000-0003-1380-0990 FU La Caixa International Program for Cancer Research Education FX The authors have declared no conflicts of interest related to this review article. R. Dienstmann is a recipient of "La Caixa International Program for Cancer Research & Education". NR 112 TC 85 Z9 87 U1 8 U2 44 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 MAR PY 2014 VL 25 IS 3 BP 552 EP 563 DI 10.1093/annonc/mdt419 PG 12 WC Oncology SC Oncology GA AC1MA UT WOS:000332258100002 PM 24265351 ER PT J AU Hong, F Habermann, TM Gordon, LI Hochster, H Gascoyne, RD Morrison, VA Fisher, RI Bartlett, NL Stiff, PJ Cheson, BD Crump, M Horning, SJ Kahl, BS AF Hong, F. Habermann, T. M. Gordon, L. I. Hochster, H. Gascoyne, R. D. Morrison, V. A. Fisher, R. I. Bartlett, N. L. Stiff, P. J. Cheson, B. D. Crump, M. Horning, S. J. Kahl, B. S. TI The role of body mass index in survival outcome for lymphoma patients: US intergroup experience SO ANNALS OF ONCOLOGY LA English DT Article DE body mass index; survival outcomes; diffuse large B-cell lymphoma; follicular lymphoma; Hodgkin's lymphoma ID B-CELL LYMPHOMA; MAINTENANCE RITUXIMAB; HODGKINS-LYMPHOMA; CHEMOTHERAPY; CANCER; OBESITY; CLEARANCE; WEIGHT; RISK; CHOP AB BMI was not significantly associated with clinical outcomes among patients with DLBCL, HD or FL, in three prospective phase III clinical trials.The role of body mass index (BMI) in survival outcomes is controversial among lymphoma patients. We evaluated the association between BMI at study entry and failure-free survival (FFS) and overall survival (OS) in three phase III clinical trials, among patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin's lymphoma (HL). A total of 537, 730 and 282 patients with DLBCL, HL and FL were included in the analysis. Baseline patient and clinical characteristics, treatment received and clinical outcomes were compared across BMI categories. Among patients with DLBCL, HL and FL, the median age was 70, 33 and 56; 29%, 29% and 37% were obese and 38%, 27% and 37% were overweight, respectively. Age was significantly different among BMI groups in all three studies. Higher BMI groups tended to have more favorable prognosis factors at study entry among DLBCL and HL patients. BMI was not associated with clinical outcome with P-values of 0.89, 0.30 and 0.40 for FFS, and 0.64, 0.67 and 0.09 for OS, for patients with DLBCL, HL and FL, respectively. The association remains non-significant after adjusting for other clinical factors in the Cox model. A subset analysis of males with DLBCL treated on R-CHOP revealed no differences in FFS (P = 0.48) or OS (P = 0.58). BMI was not significantly associated with clinical outcomes among patients with DLBCL, HD or FL, in three prospective phase III clinical trials. The findings contradict some previous reports of similar investigations. Further work is required to understand the observed discrepancies. C1 [Hong, F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Habermann, T. M.] Mayo Clin, Rochester, MN USA. [Gordon, L. I.] Northwestern Univ, Chicago, IL 60611 USA. [Hochster, H.] Yale Univ, New Haven, CT USA. [Gascoyne, R. D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Morrison, V. A.] Univ Minnesota, VA Med Ctr, Minneapolis, MN USA. [Fisher, R. I.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Bartlett, N. L.] Washington Univ, St Louis, MO USA. [Stiff, P. J.] Loyola Univ, Maywood, IL 60153 USA. [Cheson, B. D.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Crump, M.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Horning, S. J.] Genentech Inc, San Francisco, CA 94080 USA. [Kahl, B. S.] Univ Wisconsin, Madison, WI USA. RP Hong, F (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave,Mailstop CLSB 11007, Boston, MA 02115 USA. EM fxhong@jimmy.harvard.edu FU ECOG statistical office; Department of Biostatistics and Computational Biology at Dana-Farber Cancer Institute FX Funding support for FH is from ECOG statistical office and the Research Scientist Fund from the Department of Biostatistics and Computational Biology at Dana-Farber Cancer Institute. NR 22 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2014 VL 25 IS 3 BP 669 EP 674 DI 10.1093/annonc/mdt594 PG 6 WC Oncology SC Oncology GA AC1MA UT WOS:000332258100019 PM 24567515 ER PT J AU Best, SR Kobler, JB Friedman, AD Barbu, AM Zeitels, SM Burns, JA AF Best, Simon R. Kobler, James B. Friedman, Aaron D. Barbu, Anca M. Zeitels, Steven M. Burns, James A. TI Effect of Mandibular Tori on Glottic Exposure During Simulated Suspension Microlaryngoscopy SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE difficult airway; difficult intubation; direct laryngoscopy; glottis; laryngoscope; larynx; mandibular tori; suspension microlaryngoscopy; vocal fold ID DIFFICULT LARYNGEAL EXPOSURE; LARYNGOSCOPY; PREDICTION; AIRWAY AB Objectives: Mandibular tori have been identified as a contributing factor in difficult exposure during intubation. However, no investigation has measured the effect of mandibular tori on glottic exposure during suspension nnicrolaryngoscopy (SML). The objective of this study was to measure how the size and location of mandibular tori affect glottic exposure during simulated SML at different thyromental distances. Methods: Suspension nnicrolaryngoscopy was modeled on an anatomically accurate skull and larynx with thyrornental distances between 6 and 12 cm. Mandibular tori were simulated by protruding screws 5 to 15 mm from the lingual aspect of the mandible. The tori were positioned either 15 mm (anterior) or 25 mm (posterior) from the nnidline of the symphysis. The glottic exposure for the various-size tori in each location was measured by recording the displacement of the glottiscope tip relative to the most anterior exposure achievable without tori. The glottiscope angle relative to the horizontal plane was measured for each condition. Results: Mandibular tori of more than 10 mm had a significant impact on glottic exposure. Displacement of the glottiscope tip ranged from 2 to 9 mm for anteriorly placed tori and from 7 to 29 mm for posteriorly placed tori, with larger tori causing greater displacement. Increasing the thyromental distance increased the posterior glottiscope tip displacement regardless of torus size or location. The glottiscope angle increased with larger tori (12 degrees to 28 degrees), but this angle did not change with increasing thyromental distance. Conclusions: Larger size and more-posterior location of mandibular tori more significantly reduce glottic exposure during SML. The inner table of.the mandible is the most relevant anatomic constraint on glottic exposure, which varies with the presence or absence of mandibular tori independent of thyromental distance. C1 [Best, Simon R.; Kobler, James B.; Friedman, Aaron D.; Barbu, Anca M.; Zeitels, Steven M.; Burns, James A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Best, Simon R.; Kobler, James B.; Friedman, Aaron D.; Barbu, Anca M.; Zeitels, Steven M.; Burns, James A.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Burns, JA (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, One Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM burns.james@mgh.harvard.edu FU Eugene B. Casey Foundation; "V" Foundation; Voice Health Institute FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by the Eugene B. Casey Foundation, the "V" Foundation, and the Voice Health Institute. Dr Zeitels has an equity interest in Endocraft LLC. NR 14 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-4894 EI 1943-572X J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2014 VL 123 IS 3 BP 188 EP 194 DI 10.1177/0003489414522967 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA AC3QQ UT WOS:000332436700005 PM 24633945 ER PT J AU Sidell, DR Nassar, M Cotton, RT Zeitels, SM de Alarcon, A AF Sidell, Douglas R. Nassar, Michel Cotton, Robin T. Zeitels, Steven M. de Alarcon, Alessandro TI High-Dose Sublesional Bevacizumab (Avastin) for Pediatric Recurrent Respiratory Papillomatosis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 10-11, 2013 CL Orlando, FL SP Amer Broncho Esophagol Assoc DE bevacizumab; papilloma; pediatrics; recurrent respiratory papillomatosis ID CHILDREN; SYSTEM; LASER AB Objectives: We review and report the use of high-dose bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP) in pediatric patients. Methods: We included all patients with pediatric-onset RRP who underwent bevacizumab (25 mg/mL) injections by a single practitioner. A series of 5 consecutive subepithelial injections were administered at 4- to 6-week intervals with concomitant 532 nm KTP laser ablation. The lesions were staged according to the Derkay staging system. The outcomes included pretreatment and posttreatment Derkay scores, the time interval between procedures, and voice outcomes. The demographic data extracted included sex, age at diagnosis, and current age. Results: Nine patients were included in this study, with 1 patient lost to follow-up; their median age was 8 years (range, 3 to 21 years). The mean bevacizumab dose was 14.25 mg (range, 5 to 45 mg). There was a median Derkay score of 11.5 (range, 4 to 23) at the time of diagnosis and a median 58% improvement following therapy. All patients demonstrated an increased time interval between injections, for a median improvement of 2.05x (range, 1.6x to 3.25x). Conclusions: Evidence exists in support of vascular endothelial growth factor as an important factor in the development of RRP. Although some variability in response is demonstrated by this study, high-dose bevacizumab appears to yield promising results for pediatric patients with RRP. C1 [Sidell, Douglas R.; Nassar, Michel; Cotton, Robin T.; de Alarcon, Alessandro] Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA. [de Alarcon, Alessandro] Univ Cincinnati, Coll Med, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Zeitels, Steven M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP de Alarcon, A (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, 3333 Burnet Ave,MLC 2018, Cincinnati, OH 45229 USA. EM alessandro.dealarcon@cchmc.org NR 16 TC 5 Z9 5 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 EI 1943-572X J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2014 VL 123 IS 3 BP 214 EP 221 DI 10.1177/0003489414522977 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA AC3QQ UT WOS:000332436700008 PM 24633948 ER PT J AU Donnelly, JP Baddley, JW Wang, HE AF Donnelly, John P. Baddley, John W. Wang, Henry E. TI Antibiotic Utilization for Acute Respiratory Tract Infections in U.S. Emergency Departments SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLOSTRIDIUM-DIFFICILE INFECTION; TIMELY PRIMARY-CARE; UNITED-STATES; PNEUMONIA; COMMUNITY; RISK; FLUOROQUINOLONES; ACCURACY; BARRIERS; VISITS AB Inappropriate use of antibiotics for acute respiratory tract infections (ARTIs) has decreased in many outpatient settings. For patients presenting to U. S. emergency departments (EDs) with ARTIs, antibiotic utilization patterns are unclear. We conducted a retrospective cohort study of ED patients from 2001 to 2010 using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). We identified patients presenting to U. S. EDs with ARTIs and calculated rates of antibiotic utilization. Diagnoses were classified as antibiotic appropriate (otitis media, sinusitis, pharyngitis, tonsillitis, and nonviral pneumonia) or antibiotic inappropriate (nasopharyngitis, unspecified upper respiratory tract infection, bronchitis or bronchiolitis, viral pneumonia, and influenza). There were 126 million ED visits with a diagnosis of ARTI, and antibiotics were prescribed in 61%. Between 2001 and 2010, antibiotic utilization decreased for patients aged <5 presenting with antibiotic-inappropriate ARTI (rate ratio [RR], 0.94; confidence interval [CI], 0.88 to 1.00). Utilization also decreased significantly for antibiotic-inappropriate ARTI patients aged 5 to 19 years (RR, 0.89; CI, 0.85 to 0.94). Utilization remained stable for antibiotic-inappropriate ARTI among adult patients aged 20 to 64 years (RR, 0.99; CI, 0.97 to 1.01). Among adults, rates of quinolone use for ARTI increased significantly from 83 per 1,000 visits in 2001 to 2002 to 105 per 1,000 in 2009 to 2010 (RR, 1.08; CI, 1.03 to 1.14). Although significant progress has been made toward reduction of antibiotic utilization for pediatric patients with ARTI, the proportion of adult ARTI patients receiving antibiotics in U. S. EDs is inappropriately high. Institution of measures to reduce inappropriate antibiotic use in the ED setting is warranted. C1 [Donnelly, John P.; Wang, Henry E.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL 35294 USA. [Baddley, John W.] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. EM jbaddley@uab.edu OI Donnelly, John/0000-0002-0646-9470 FU Agency for Healthcare Research and Quality [T32 HS13852-11]; National Institute of Nursing Research [R01-NR012726] FX J.P.D. is currently supported by the Agency for Healthcare Research and Quality (grant T32 HS13852-11). H.E.W. received grant support from the National Institute of Nursing Research (R01-NR012726). NR 33 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2014 VL 58 IS 3 BP 1451 EP 1457 DI 10.1128/AAC.02039-13 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AC0HJ UT WOS:000332175100024 PM 24342652 ER PT J AU Hoang, PD Cameron, MH Gandevia, SC Lord, SR AF Hoang, Phu D. Cameron, Michelle H. Gandevia, Simon C. Lord, Stephen R. TI Neuropsychological, Balance, and Mobility Risk Factors for Falls in People With Multiple Sclerosis: A Prospective Cohort Study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Accidental falls; Multiple sclerosis; Neuropsychological tests; Postural balance; Rehabilitation; Risk factors ID PREDICTING ACCIDENTAL FALLS; COMMUNITY-DWELLING WOMEN; SENSORIMOTOR FUNCTION; POSTURAL SWAY; OLDER-PEOPLE; DISABILITY; PERFORMANCE; PREVENTION; COMPOSITE; STRENGTH AB Objectives: To determine whether impaired performance in a range of vision, proprioception, neuropsychological, balance, and mobility tests and pain and fatigue are associated with falls in people with multiple sclerosis (PwMS). Design: Prospective cohort study with 6-month follow-up. Setting: A multiple sclerosis (MS) physiotherapy clinic. Participants: Community-dwelling people (N=210; age range, 21-74y) with MS (Disease Steps 0-5). Interventions: Not applicable. Main Outcome Measures: Incidence of falls during 6 months' follow-up. Results: In the 6-month follow-up period, 83 participants (39.7%) experienced no falls, 57 (27.3%) fell once or twice, and 69 (33.0%) fell 3 or more times. Frequent falling (>= 3) was associated with increased postural sway (eyes open and closed), poor leaning balance (as assessed with the coordinated stability task), slow choice stepping reaction time, reduced walking speed, reduced executive functioning (as assessed with the difference between Trail Making Test Part B and Trail Making Test Part A), reduced fine motor control (performance on the 9-Hole Peg Test [9-HPT]), and reported leg pain. Increased sway with the eyes closed, poor coordinated stability, and reduced performance in the 9-HPT were identified as variables that significantly and independently discriminated between frequent fallers and nonfrequent fallers (model x(3)=30.1, P<.001). The area under the receiver operating characteristic curve for this model was.712 (95% confidence interval,.638.785). Conclusions: The study reveals important balance, coordination, and cognitive determinants of falls in PwMS. These should assist the development of effective strategies for prevention of falls in this high-risk group. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Hoang, Phu D.; Gandevia, Simon C.; Lord, Stephen R.] Univ New S Wales, Neurosci Res Australia, Randwick, NSW, Australia. [Cameron, Michelle H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Cameron, Michelle H.] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. RP Lord, SR (reprint author), Neurosci Res Australia, Barker St, Randwick, NSW 2031, Australia. EM s.lord@neura.edu.au RI Lord, Stephen/C-9612-2011 FU Multiple Sclerosis Research Australia; National Health and Medical Research Council (of Australia); MS International Federation (Du Pre Grant) FX Supported by Multiple Sclerosis Research Australia, the National Health and Medical Research Council (of Australia), and the MS International Federation (Du Pre Grant). NR 35 TC 32 Z9 32 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2014 VL 95 IS 3 BP 480 EP 486 DI 10.1016/j.apmr.2013.09.017 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AB8QR UT WOS:000332055600010 PM 24096187 ER PT J AU Costales, JL Sher, L AF Costales, Jesse L. Sher, Leo TI Do testosterone and brain-derived neurotrophic factor interactions play a role in the pathophysiology of suicidal behavior? SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Costales, Jesse L.; Sher, Leo] Mt Sinai Hosp, Dept Psychiat, New York, NY 10029 USA. [Sher, Leo] James J Peters Vet Adm, Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Sher, L (reprint author), James J Peters Vet Adm, Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM leo.sher@mssm.edu NR 3 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAR PY 2014 VL 48 IS 3 BP 290 EP 291 DI 10.1177/0004867413504832 PG 2 WC Psychiatry SC Psychiatry GA AB3KP UT WOS:000331690000015 PM 24042028 ER PT J AU Sher, L AF Sher, Leo TI Testosterone and homicidal behavior SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter ID NEUROTROPHIC FACTOR; SUICIDAL-BEHAVIOR; EXPRESSION; SEX C1 [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY USA. [Sher, Leo] James J Peters Vet Adm, Med Ctr, Bronx, NY 10468 USA. RP Sher, L (reprint author), James J Peters Vet Adm, Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 5 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD MAR PY 2014 VL 48 IS 3 BP 290 EP 290 DI 10.1177/0004867413504833 PG 1 WC Psychiatry SC Psychiatry GA AB3KP UT WOS:000331690000014 PM 24027080 ER PT J AU Nistala, H Makitie, O Juppner, H AF Nistala, Harikiran Makitie, Outi Jueppner, Harald TI Caffey disease: New perspectives on old questions SO BONE LA English DT Review DE Caffey disease; Collagen; Extracellular matrix; COX-2; PGE2; TGF beta ID INFANTILE CORTICAL HYPEROSTOSIS; CAMURATI-ENGELMANN-DISEASE; I COLLAGEN; BINDING SITES; TGF-BETA; MUTATIONS; ACTIVATION; EXPRESSION; COL1A1; GROWTH AB The autosomal dominant form of Caffey disease is a largely self-limiting infantile bone disorder characterized by acute inflammation of soft tissues and localized thickening of the underlying bone cortex. It is caused by a recurrent arginine-to-cysteine substitution (R836C) in the alpha 1 (I) chain of type I collagen. However, the functional link between this mutation and the underlying pathogenetic mechanisms still remains elusive. Importantly, it remains to be established as to how a point-mutation in type I collagen leads to a cascade of inflammatory events and spatio-temporally limited hyperostotic bone lesions, and how structural and inflammatory components contribute to the different organ-specific manifestations in Caffey disease. In this review we attempt to shed light on these questions based on the current understanding of other mutations in type I collagen, their role in perturbing collagen biogenesis, and consequent effects on cell-cell and cell-matrix interactions. (c) 2014 Elsevier Inc. All rights reserved. C1 [Nistala, Harikiran] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Makitie, Outi] Univ Helsinki, Cent Hosp, Div Pediat Endocrinol & Metab Bone Dis, Helsinki, Finland. [Makitie, Outi] Univ Helsinki, Helsinki, Finland. [Makitie, Outi] Folkhalsan Inst Genet, Helsinki, Finland. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM hjueppner@partners.org OI Makitie, Outi/0000-0002-4547-001X FU NIH [R01-DK46718, P01DK11794] FX We would like to thank Drs. Francesco Ramirez and Roland Baron for their insightful comments and suggestions. Supported by NIH grants R01-DK46718 and P01DK11794 (subproject IV) to HJ. NR 52 TC 4 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD MAR PY 2014 VL 60 BP 246 EP 251 DI 10.1016/j.bone.2013.12.030 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8RH UT WOS:000332057200027 PM 24389367 ER PT J AU Tanev, KS Pentel, KZ Kredlow, MA Charney, ME AF Tanev, Kaloyan S. Pentel, Kimberly Z. Kredlow, Maria A. Charney, Meredith E. TI PTSD and TBI co-morbidity: Scope, clinical presentation and treatment options SO BRAIN INJURY LA English DT Review DE Brain injury; cognitive behavioural therapy; cognitive rehabilitation; neuroimaging; pharmacotherapy; post-traumatic stress disorder ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; DIFFUSION-TENSOR; PROLONGED EXPOSURE; MILD TBI; PSYCHIATRIC DIAGNOSES; BEHAVIORAL THERAPY AB Primary objective: To summarize the literature on post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) and their co-morbidity, focusing on diagnosis, clinical symptoms and treatment issues relevant to the clinician. Research design: Review of the literature. Methods and procedures: Pubmed searches were performed using the terms post-traumatic stress disorder, traumatic brain injury, sleep, cognitive, depression, anxiety, treatment and combinations of these terms. Those articles relevant to the objective were included. Main outcomes and results: This study presents pathophysiological, neuroimaging and clinical data on co-morbid PTSD and TBI. It reviews associated conditions, emphasizing the impact of cognitive and sleep problems. It summarizes the emerging literature on treatment effectiveness for co-morbid PTSD and TBI, including psychotherapy, pharmacotherapy and cognitive rehabilitation. Conclusions: Both PTSD and TBI commonly occur in the general population, both share some pathophysiological characteristics and both are associated with cognitive impairment and sleep disruption. PTSD and TBI present with a number of overlapping symptoms, which can lead to over-diagnosis or misdiagnosis. Both conditions are associated with co-morbidities important in diagnosis and treatment planning. More research is needed to elucidate what treatments are effective in PTSD and TBI co-morbidity and on factors predictive of treatment success. C1 [Tanev, Kaloyan S.; Pentel, Kimberly Z.; Charney, Meredith E.] Massachusetts Gen Hosp, Home Base Program, Dept Psychiat, Boston, MA 02114 USA. [Kredlow, Maria A.] Boston Univ, Boston, MA 02215 USA. RP Tanev, KS (reprint author), Massachusetts Gen Hosp, Home Base Program, 101 Merrimack St,2nd Floor, Boston, MA 02114 USA. EM ktanev@partners.org NR 112 TC 19 Z9 19 U1 8 U2 27 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 EI 1362-301X J9 BRAIN INJURY JI Brain Inj. PD MAR PY 2014 VL 28 IS 3 BP 261 EP 270 DI 10.3109/02699052.2013.873821 PG 10 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AC0RI UT WOS:000332202100001 PM 24568300 ER PT J AU Siefert, ML Hong, FX Valcarce, B Berry, DL AF Siefert, Mary Lou Hong, Fangxin Valcarce, Bianca Berry, Donna L. TI Patient and Clinician Communication of Self-reported Insomnia During Ambulatory Cancer Care Clinic Visits SO CANCER NURSING LA English DT Article DE Self-reported symptoms; Sleep; Cancer; Insomnia; Patient/provider communication ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; RADIATION-THERAPY; ADJUVANT CHEMOTHERAPY; PROSTATE-CANCER; SYMPTOM CLUSTER; HOT FLASHES; FATIGUE; SLEEP AB Background: Insomnia, the most commonly reported sleep-wake disturbance in people with cancer, has an adverse effect on quality of life including emotional well-being, distress associated with other symptoms, daily functioning, relationships, and ability to work. Objective: The aim of this study was to describe the content of discussions between clinicians and 120 patients with self-reported insomnia and to examine the associations of sociodemographic, clinical, and environmental factors with insomnia. Methods: A secondary analysis was conducted with self-reported symptom data and sociodemographic, clinical, and environmental factors. Recordings of clinician and patient discussions during clinic visits were examined by conducting a content analysis. Results: Severe insomnia was more likely to be reported by women, minority, and lower-income individuals. Seven major topics were identified in the discussions. The clinicians did not always discuss insomnia; discussion rates differed by diagnosis and clinical service. Conclusions: Reporting of insomnia by the patient and clinician communication about insomnia may have differed by demographic and clinical characteristics. Clinicians attended to insomnia about half the time with management strategies likely to be effective. Explanations may be that insomnia had a low clinician priority for the clinic visit or lack of clear evidence to support insomnia interventions. Implications for Practice: A better understanding is needed about why insomnia is not addressed even when reported by patients; it is well known that structured assessments and early interventions can improve quality of life. Research is warranted to better understand potential disparities in cancer care. C1 [Siefert, Mary Lou; Valcarce, Bianca; Berry, Donna L.] Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA USA. [Hong, Fangxin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. RP Siefert, ML (reprint author), Dana Farber Canc Inst, 450 Brookline Ave LW515, Boston, MA 02215 USA. EM mlsiefet@aya.yale.edu FU National Institute of Nursing Research, National Institutes of Health [R01 NR008726] FX Funding was received from National Institute of Nursing Research, National Institutes of Health, through grant no. R01 NR008726, 2004-2007 (Dr Berry). NR 53 TC 6 Z9 6 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0162-220X EI 1538-9804 J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2014 VL 37 IS 2 BP E51 EP E59 DI 10.1097/NCC.0b013e318283a7bc PG 9 WC Oncology; Nursing SC Oncology; Nursing GA AC0GM UT WOS:000332172800007 PM 23448958 ER PT J AU Adamia, S Haibe-Kains, B Pilarski, PM Bar-Natan, M Pevzner, S Avet-Loiseau, H Lode, L Verselis, S Fox, EA Burke, J Galinsky, I Dagogo-Jack, I Wadleigh, M Steensma, DP Motyckova, G Deangelo, DJ Quackenbush, J Stone, R Griffin, JD AF Adamia, Sophia Haibe-Kains, Benjamin Pilarski, Patrick M. Bar-Natan, Michal Pevzner, Samuel Avet-Loiseau, Herve Lode, Laurence Verselis, Sigitas Fox, Edward A. Burke, John Galinsky, Ilene Dagogo-Jack, Ibiayi Wadleigh, Martha Steensma, David P. Motyckova, Gabriela Deangelo, Daniel J. Quackenbush, John Stone, Richard Griffin, James D. TI A Genome-Wide Aberrant RNA Splicing in Patients with Acute Myeloid Leukemia Identifies Novel Potential Disease Markers and Therapeutic Targets SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MESSENGER-RNA; EXPRESSION ARRAYS; EXON ARRAYS; MUTATIONS; CANCER; P53; SPLICEOSOME; PROGRESSION; GENERATION AB Purpose: Despite new treatments, acute myeloid leukemia (AML) remains an incurable disease. More effective drug design requires an expanded view of the molecular complexity that underlies AML. Alternative splicing of RNA is used by normal cells to generate protein diversity. Growing evidence indicates that aberrant splicing of genes plays a key role in cancer. We investigated genome-wide splicing abnormalities in AML and based on these abnormalities, we aimed to identify novel potential biomarkers and therapeutic targets. Experimental Design: We used genome-wide alternative splicing screening to investigate alternative splicing abnormalities in two independent AML patient cohorts [Dana-FarberCancer Institute (DFCI) (Boston, MA) and University Hospital de Nantes (UHN) (Nantes, France)] and normal donors. Selected splicing events were confirmed through cloning and sequencing analysis, and than validated in 193 patients with AML. Results: Our results show that approximately 29% of expressed genes genome-wide were differentially and recurrently spliced in patients with AML compared with normal donors bone marrow CD34(+) cells. Results were reproducible in two independent AML cohorts. In both cohorts, annotation analyses indicated similar proportions of differentially spliced genes encoding several oncogenes, tumor suppressor proteins, splicing factors, and heterogeneous-nuclear-ribonucleoproteins, proteins involved in apoptosis, cell proliferation, and spliceosome assembly. Our findings are consistent with reports for other malignances and indicate that AML-specific aberrations in splicing mechanisms are a hallmark of AML pathogenesis. Conclusions: Overall, our results suggest that aberrant splicing is a common characteristic for AML. Our findings also suggest that splice variant transcripts that are the result of splicing aberrations create novel disease markers and provide potential targets for small molecules or antibody therapeutics for this disease. (C) 2013 AACR. C1 [Adamia, Sophia; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Stone, Richard; Griffin, James D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Med Oncol, Boston, MA USA. [Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Bioinformat & Computat Genom Lab, Montreal, PQ H2W 1R7, Canada. [Pilarski, Patrick M.] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada. [Bar-Natan, Michal] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Pevzner, Samuel] Boston Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA. [Pevzner, Samuel] Boston Univ, Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Pevzner, Samuel] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Avet-Loiseau, Herve] CHU Rangueil, Univ Hosp, Lab UGM, Unit Genom Myelome, F-31054 Toulouse, France. [Lode, Laurence] Univ Hosp, Hematol Lab, Nantes, France. [Lode, Laurence] INSERM, U892, Nantes, France. [Verselis, Sigitas; Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA. [Galinsky, Ilene; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Stone, Richard; Griffin, James D.] Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. [Dagogo-Jack, Ibiayi] Brigham & Womens Hosp, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Adamia, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM sophia_adamia@dfci.harvard.edu; James_Griffin@dfci.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Steensma, David/0000-0001-5130-9284 FU ASH scholar award for Clinical/Translational Research; LLS Translational Research program grant; AACR-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research; IRCM; Alberta Innovates Centre for Machine Learning; National Library of Medicine of the U.S. NIH [R01 LM010129-01] FX S. Adamia was supported by the ASH scholar award for Clinical/Translational Research, LLS Translational Research program grant, and by the AACR-Amgen, Inc. Fellowship in Clinical/Translational Cancer Research; B. Haibe-Kains was supported by internal funding at IRCM; P. M. Pilarski was supported by the Alberta Innovates Centre for Machine Learning; and J. Quackenbush was supported by a grant from the National Library of Medicine of the U.S. NIH (R01 LM010129-01). NR 44 TC 23 Z9 23 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2014 VL 20 IS 5 BP 1135 EP 1145 DI 10.1158/1078-0432.CCR-13-0956 PG 11 WC Oncology SC Oncology GA AC3GE UT WOS:000332403100011 PM 24284058 ER PT J AU Chen, Z Akbay, E Mikse, O Tupper, T Cheng, K Wang, YC Tan, XH Altabef, A Woo, SA Chen, L Reibel, JB Janne, PA Sharpless, NE Engelman, JA Shapiro, GI Kung, AL Wong, KK AF Chen, Zhao Akbay, Esra Mikse, Oliver Tupper, Tanya Cheng, Katherine Wang, Yuchuan Tan, Xiaohong Altabef, Abigail Woo, Sue-Ann Chen, Liang Reibel, Jacob B. Janne, Pasi A. Sharpless, Norman E. Engelman, Jeffrey A. Shapiro, Geoffrey I. Kung, Andrew L. Wong, Kwok-Kin TI Co-Clinical Trials Demonstrate Superiority of Crizotinib to Chemotherapy in ALK-Rearranged Non-Small Cell Lung Cancer and Predict Strategies to Overcome Resistance SO CLINICAL CANCER RESEARCH LA English DT Article ID ENGINEERED MOUSE MODELS; ANAPLASTIC LYMPHOMA KINASE; ANTITUMOR-ACTIVITY; DRUG DEVELOPMENT; FUSION ONCOGENE; INHIBITION; EML4-ALK; MULTICENTER; HSP90 AB Purpose: To extend the results of a phase III trial in patients with non-small cell lung cancer with adenocarcinomas harboring EML4-ALK fusion. Experimental Design: We conducted a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib the standard-of-care cytotoxic agents docetaxel or pemetrexed. Results: Concordant with the clinical outcome in humans, crizotinib produced a substantially higher response rate compared with chemotherapy, associated with significantly longer progression-free survival. Overall survival was also prolonged in crizotinib- compared with chemotherapy-treated mice. Pemetrexed produced superior overall survival compared with docetaxel, suggesting that this agent may be the preferred chemotherapy in the ALK population. In addition, in the EML4-ALK-driven mouse lung adenocarcinoma model, HSP90 inhibition can overcome both primary and acquired crizotinib resistance. Furthermore, HSP90 inhibition, as well as the second-generation ALK inhibitor TAE684, demonstrated activity in newly developed lung adenocarcinoma models driven by crizotinib-insensitive EML4-ALK L1196M or F1 174L. Conclusions: Our findings suggest that crizotinib is superior to standard chemotherapy in ALK inhibitor-naive disease and support further clinical investigation of HSP90 inhibitors and second-generation ALK inhibitors in tumors with primary or acquired crizotinib resistance. (C) 2013 AACR. C1 [Chen, Zhao; Akbay, Esra; Mikse, Oliver; Janne, Pasi A.; Engelman, Jeffrey A.; Shapiro, Geoffrey I.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Chen, Zhao; Akbay, Esra; Mikse, Oliver; Cheng, Katherine; Tan, Xiaohong; Altabef, Abigail; Woo, Sue-Ann; Chen, Liang; Reibel, Jacob B.; Janne, Pasi A.; Shapiro, Geoffrey I.; Wong, Kwok-Kin] Columbia Univ, Med Ctr, Dept Med Oncol, New York, NY USA. [Wang, Yuchuan] Columbia Univ, Med Ctr, Dept Imaging, New York, NY USA. [Janne, Pasi A.; Shapiro, Geoffrey I.; Wong, Kwok-Kin] Columbia Univ, Med Ctr, Lowe Ctr Thorac Oncol, New York, NY USA. [Tupper, Tanya; Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. [Chen, Zhao; Akbay, Esra; Mikse, Oliver; Cheng, Katherine; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Engelman, Jeffrey A.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Wang, Yuchuan] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Sharpless, Norman E.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, 4 Blackfan Circle, Boston, MA 02115 USA. EM kwong1@partners.org OI Wang, Yuchuan/0000-0001-5111-6562; Kung, Andrew/0000-0002-9091-488X; wong, kwok kin/0000-0001-6323-235X FU NCI [R01 CA140594, NCI-CA122794, NCI-CA166480, NCI-CA163896, NCI-P01CA154303, NCI-P01CA120964, R01CA136851]; Uniting Against Lung Cancer Foundation; Bonnie J. Addario Lung Cancer Foundation; Claudia Barr Award in Basic Cancer Research FX This study is supported by NCI R01 CA140594, NCI-CA122794, NCI-CA166480, NCI-CA163896, NCI-P01CA154303, NCI-P01CA120964, R01CA136851, The Uniting Against Lung Cancer Foundation, The Bonnie J. Addario Lung Cancer Foundation, and The Claudia Barr Award in Basic Cancer Research. NR 32 TC 25 Z9 27 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2014 VL 20 IS 5 BP 1204 EP 1211 DI 10.1158/1078-0432.CCR-13-1733 PG 8 WC Oncology SC Oncology GA AC3GE UT WOS:000332403100017 PM 24327273 ER PT J AU Gong, JJ Xie, JP Bedolla, R Rivas, P Chakravarthy, D Freeman, JW Reddick, R Kopetz, S Peterson, A Wang, HM Fischer, SM Kumar, AP AF Gong, Jingjing Xie, Jianping Bedolla, Roble Rivas, Paul Chakravarthy, Divya Freeman, James W. Reddick, Robert Kopetz, Scott Peterson, Amanda Wang, Huamin Fischer, Susan M. Kumar, Addanki P. TI Combined Targeting of STAT3/NF-kappa B/COX-2/EP4 for Effective Management of Pancreatic Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; AMURENSE BARK EXTRACT; MOUSE PROSTATE MODEL; STELLATE CELLS; TRANSGENIC ADENOCARCINOMA; NATURAL-PRODUCTS; GROWTH-FACTOR; EP4 RECEPTOR; STAT3; PATHWAY AB Purpose: Near equal rates of incidence and mortality emphasize the need for novel targeted approaches for better management of patients with pancreatic cancer. Inflammatory molecules NF-kappa B and STAT3 are overexpressed in pancreatic tumors. Inhibition of one protein allows cancer cells to survive using the other. The goal of this study is to determine whether targeting STAB/NE-kappa B crosstalk with a natural product Nexrutine can inhibit inflammatory signaling in pancreatic cancer. Experimental Design: HPNE,HPNE-Ras,BxPC3, Capan-2, MIA PaCa-2, and AsPC-1 cells were tested for growth, apoptosis, cyclooxygenase-2 NF-kappa B, and STAT3 level in response to Nexrutine treatment. Transient expression, gel shift, chromatin immunoprecipitation assay was used to examine transcriptional regulation of COX-2. STAT3 knockdown was used to decipher STAT3/NF-kappa B crosstalk. Histopathologic and immunoblotting evaluation was performed on BK5-COX-2 transgenic mice treated with Nexrutine. In vivo expression of prostaglandin receptor E-prostanoid 4 (EP4) was analyzed in a retrospective cohort of pancreatic tumors using a tissue microarray. Results: Nexrutine treatment inhibited growth of pancreatic cancer cells through induction of apoptosis. Reduced levels and activity of STAT3, NT-kappa B, and their crosstalk led to transcriptional suppression of COX-2 and subsequent decreased levels of prostaglandin E2 (PGE2) and PGF2. STAB knockdown studies suggest. STAT3 as negative regulator of NF-kappa B activation. Nexrutine intervention reduced the levels of NE-kappa B, STAT3, and fibrosis in vivo. Expression of prostaglandin receptor EP4 that is known to play a role in fibrosis was significantly elevated in human pancreatic tumors. Conclusions: Dual inhibition of STAT3-NF-kappa B by Nexrutine may overcome problems associated with inhibition of either pathway. (C) 2014 AACR. C1 [Gong, Jingjing; Xie, Jianping; Bedolla, Roble; Rivas, Paul; Chakravarthy, Divya; Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Freeman, James W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Oncol, San Antonio, TX 78229 USA. [Reddick, Robert; Peterson, Amanda] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. [Kumar, Addanki P.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Kopetz, Scott; Wang, Huamin] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Fischer, Susan M.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. RP Kumar, AP (reprint author), Dept Urol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kumara3@uthscsa.edu FU National Center for Complementary and Alternative Medicine [AT005513-01A1, AT 007448-01]; Veterans Affairs-Merit Award [1 I01 BX 000766-01] FX This work was supported in part by funds from National Center for Complementary and Alternative Medicine AT005513-01A1, AT 007448-01, and Veterans Affairs-Merit Award 1 I01 BX 000766-01(A.P. Kumar). NR 47 TC 13 Z9 16 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2014 VL 20 IS 5 BP 1259 EP 1273 DI 10.1158/1078-0432.CCR-13-1664 PG 15 WC Oncology SC Oncology GA AC3GE UT WOS:000332403100022 PM 24520096 ER PT J AU Barnett, CM Heinrich, MC Lim, J Nelson, D Beadling, C Warrick, A Neff, T Higano, CS Garzotto, M Qian, D Corless, CL Thomas, GV Beer, TM AF Barnett, Christine M. Heinrich, Michael C. Lim, Jeong Nelson, Dylan Beadling, Carol Warrick, Andrea Neff, Tanaya Higano, Celestia S. Garzotto, Mark Qian, David Corless, Christopher L. Thomas, George V. Beer, Tomasz M. TI Genetic Profiling to Determine Risk of Relapse-Free Survival in High-Risk Localized Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PTEN GENOMIC DELETION; PROTEIN LOSS; EXPRESSION; PATHWAY; PROGRESSION; RECURRENCE; FUSION; PI3K AB Purpose: The characterization of actionable mutations in human tumors is a prerequisite for the development of individualized, targeted therapy. We examined the prevalence of potentially therapeutically actionable mutations in patients with high-risk clinically localized prostate cancer. Experimental Design: Forty-eight samples of formalin-fixed paraffin-embedded prostatectomy tissue from a neoadjuvant chemotherapy trial were analyzed. DNA extracted from microdissected tumor was analyzed for 643 common solid tumor mutations in 53 genes using mass spectroscopy-based sequencing. In addition, PTEN loss and erythroblast transformation-specific-related gene (ERC) translocations were examined using immunohistochemistry (IHC) in associated tissue microarrays. Association with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations. Results: Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 47 tumors evaluable for IHC, 36% had PTEN loss and 40% had ERG rearrangement. Individual mutations were not frequent enough to determine associations with relapse. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median relapse-free survival, 19 versus 106 months (P = 0.01). Conclusions: This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. Although point mutations alone did not have a statistically significant association with relapse, PTEN loss was associated with an increased relapse in high-risk prostate cancer treated with chemotherapy followed by surgery. (C) 2013 AACR. C1 [Barnett, Christine M.; Heinrich, Michael C.; Qian, David; Thomas, George V.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Lim, Jeong] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Nelson, Dylan; Beadling, Carol; Warrick, Andrea; Neff, Tanaya; Corless, Christopher L.] Oregon Hlth & Sci Univ, Knight Diagnost Labs, Portland, OR 97239 USA. [Heinrich, Michael C.; Garzotto, Mark] Portland VA Med Ctr, Portland, OR USA. [Higano, Celestia S.] Univ Washington, Puget Sound Oncol Consortium, Seattle Canc Care Alliance, Seattle, WA 98195 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3303 SW Bond Ave, Portland, OR 97239 USA. EM beert@ohsu.edu FU NIH/National Cancer Institute [R01CA119125]; PNW SPORE [P50CA097186]; Immunex; Sanofi FX This work was supported in part by the NIH/National Cancer Institute (R01CA119125) and PNW SPORE grant number P50CA097186. Although this work was not directly funded by the following, the original trial involving acquisition of the specimens used in this study was funded in part by Immunex and Sanofi. NR 36 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2014 VL 20 IS 5 BP 1306 EP 1312 DI 10.1158/1078-0432.CCR-13-1775 PG 7 WC Oncology SC Oncology GA AC3GE UT WOS:000332403100026 PM 24352642 ER PT J AU Romano-Clarke, G Tang, MH Xerras, DC Egan, HS Pasinski, RC Kamin, HS McCarthy, AE Newman, J Jellinek, MS Murphy, JM AF Romano-Clarke, Giusy Tang, Michael H. Xerras, Dean C. Egan, Harwood S. Pasinski, Roger C. Kamin, Hayley S. McCarthy, Alyssa E. Newman, Jennifer Jellinek, Michael S. Murphy, J. Michael TI Have Rates of Behavioral Health Assessment and Treatment Increased for Massachusetts Children Since the Rosie D. Decision? A Report From Two Primary Care Practices SO CLINICAL PEDIATRICS LA English DT Article DE pediatrics; primary health care; mental health; mandatory screening ID PEDIATRIC SYMPTOM CHECKLIST; DISORDERS; FEASIBILITY; PREVALENCE; SETTINGS AB Following a court decision (Rosie D. v. Romney), the Medicaid program in Massachusetts launched the statewide Children's Behavioral Health Initiative in 2008 to increase the recognition and treatment of behavioral health problems in pediatrics. We reviewed billing data (n = 64,194) and electronic medical records (n = 600) for well child visits in pediatrics in 2 practices to examine rates of behavioral health screening, problem identification, and treatment among children seen during the year before and 2 years after the program's implementation. According to electronic medical records, the percentage of well child visits that included any form of behavioral health assessment increased significantly during the first 2 years of the program, and pediatricians significantly increased their use of standardized screens. According to billing data, behavioral health treatment increased significantly. These findings suggest that behavioral health screening and treatment have increased following the Rosie D. decision. C1 [Romano-Clarke, Giusy; Xerras, Dean C.] MGH Chelsea HealthCare Ctr, Chelsea, MA USA. [Tang, Michael H.; McCarthy, Alyssa E.; Newman, Jennifer; Murphy, J. Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tang, Michael H.; Jellinek, Michael S.; Murphy, J. Michael] Harvard Univ, Sch Med, Boston, MA USA. [Egan, Harwood S.; Pasinski, Roger C.] MGH Revere HealthCare Ctr, Revere, MA USA. [Kamin, Hayley S.] Univ Florida, Gainesville, FL USA. [Jellinek, Michael S.] Partners HealthCare, Boston, MA USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Div Child & Adolescent Psychiat, 55 Fruit St,YAW 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org FU Fuss Family Fund FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The current data analysis and writing of this article were made possible in part by a grant from the Fuss Family Fund and the continuing support of the Department of Psychiatry at Massachusetts General Hospital. A portion of Dr Murphy's work was supported by a grant from the Fuss Family Fund. NR 30 TC 4 Z9 4 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 EI 1938-2707 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAR PY 2014 VL 53 IS 3 BP 243 EP 249 DI 10.1177/0009922813507993 PG 7 WC Pediatrics SC Pediatrics GA AA8TY UT WOS:000331369100007 PM 24220574 ER PT J AU Darracq, MA Toy, JM Chen, T Mo, C Cantrell, FL AF Darracq, M. A. Toy, J. M. Chen, T. Mo, C. Cantrell, F. L. TI A retrospective review of isolated gliptin-exposure cases reported to a state poison control system SO CLINICAL TOXICOLOGY LA English DT Article DE Sitagliptin; Saxagliptin; Linagliptin; DPP-4 inhibitors; Poison center; Diabetes mellitus type 2; Overdose ID DIPEPTIDYL PEPTIDASE-4 INHIBITORS; SITAGLIPTIN; TOLERABILITY; OVERDOSE; SAFETY AB Background. The dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin, saxagliptin, and linagliptin are approved by the US Food and Drug Administration in the treatment of type-2 diabetes. Given the limited published information regarding human overdoses to these medications, our goal was to characterize such exposures. Methods. A state poison system database was retrospectively reviewed for all single-agent exposures to sitagliptin, saxagliptin, and linagliptin from 2006 to 2012. Case notes were reviewed and an observational case series was constructed from the data collected including age, weight, gender, circumstances surrounding exposure, symptoms, and outcome. Patients with co-ingestants, confirmed non-exposure, unknown outcomes, or other coding errors were excluded. Results. A total of 197 cases were identified: 135 cases were excluded (123 cases were excluded due to co-ingestants and 12 cases were lost to follow-up); 62 were included for review. No patients experienced hypoglycemia. One of 19 exposed pediatric (0-9 years of age) patients experienced symptoms and was safely managed at home after one episode of emesis. No symptom was experienced following unintentional ingestion by three adolescent (10-18 years of age) patients. Forty single-agent adult exposures to gliptins were included. Thirty-seven involved non-self-harm exposures resulting from double or triple doses; all were safely managed at home without reported symptoms. The majority of these ingestions involved sitagliptin. Three self-harm-adult exposures to gliptins were included for review. All the three were evaluated in a healthcare facility. One patient experienced abdominal discomfort after ingesting 700 mg of sitagliptin and was ultimately discharged from the emergency department. The other two patients experienced no reported symptoms. Conclusion. The majority of gliptin-exposed adult and pediatric/adolescent patients were safely managed at home and when evaluated in a healthcare facility, did not require hospitalization. Intentional self-harm-adult gliptin exposures were managed in a healthcare facility but rarely resulted in hospitalization or serious morbidity at doses up to 18 times the adult therapeutic dose. Additional studies are necessary to determine precise triage guidelines for the management of gliptin overdose. C1 [Darracq, M. A.] UCSF, Fresno Med Educ Program, Dept Emergency Med, Fresno, CA 93701 USA. [Toy, J. M.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Chen, T.] Coram Specialty Infus Serv, Hayward, CA USA. [Mo, C.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. [Cantrell, F. L.] Calif Poison Control Syst, San Diego Div, San Diego, CA USA. RP Darracq, MA (reprint author), UCSF, Fresno Med Educ Program, Dept Emergency Med, 155 N Fresno St, Fresno, CA 93701 USA. EM mike.darracq@gmail.com NR 14 TC 1 Z9 1 U1 1 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 EI 1556-9519 J9 CLIN TOXICOL JI Clin. Toxicol. PD MAR PY 2014 VL 52 IS 3 BP 226 EP 230 DI 10.3109/15563650.2014.889302 PG 5 WC Toxicology SC Toxicology GA AC0ER UT WOS:000332168100013 PM 24580063 ER PT J AU Lewandrowski, KB AF Lewandrowski, Kent B. TI Preface Cardiac Markers SO CLINICS IN LABORATORY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 1 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP XI EP XII DI 10.1016/j.cll.2013.12.001 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500001 PM 24507796 ER PT J AU Patel, RB Secemsky, EA AF Patel, Ravi B. Secemsky, Eric A. TI Clinical Features of Heart Failure and Acute Coronary Syndromes SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers; Congestive heart failure; Acute coronary syndrome; Review; Clinical ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR DYSFUNCTION; 2013 ACCF/AHA GUIDELINE; NATRIURETIC PEPTIDE; CHEST-PAIN; UNIVERSAL DEFINITION; SYSTOLIC FUNCTION; PROGNOSTIC VALUE; CONTROLLED-TRIAL; CREATINE-KINASE AB This article provides a brief overview of the clinical presentation, laboratory and radiologic features, and basic management principles in patients with congestive heart failure (CHF) and acute coronary syndromes (ACS). CHF is a clinical syndrome that typically results in symptoms of congestion and hypoperfusion. A thorough physical examination complemented by cardiac biomarkers and imaging are essential in making the diagnosis. Medical and device therapies for CHF target improvement in survival as well as control of symptoms. The management of ACS involves making a prompt diagnosis through the use of a focused history and physical examination, electrocardiogram assessment, and cardiac biomarker evaluation. Timely revascularization along with optimal medical management have helped to improve patient outcomes and mortality. C1 [Patel, Ravi B.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Secemsky, Eric A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02109 USA. RP Secemsky, EA (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Yawkey 5B, Boston, MA 02109 USA. EM esecemsky@partners.org NR 61 TC 0 Z9 1 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 15 EP + DI 10.1016/j.cll.2013.11.006 PG 17 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500003 PM 24507784 ER PT J AU Lewandrowski, KB AF Lewandrowski, Kent B. TI Cardiac Markers of Myocardial Necrosis: A History and Discussion of Milestones and Emerging New Trends SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Cardiac markers; Biomarkers; Troponin; Creatine kinase; CK-MB; High-sensitivity troponin; Lactate dehydrogenase isoenzymes; Myoglobin ID TROPONIN ASSAYS; UNIVERSAL DEFINITION; INFARCTION; BIOMARKERS; MYOGLOBIN AB Laboratory testing for blood-based biomarkers of myocardial injury has steadily evolved over the past 60 years. Initial assays were cumbersome and were neither sensitive nor specific for myocardial necrosis. Major improvements have included the development of more cardiospecific markers, the introduction of random access immunoassays that facilitated near real-time reporting of results, the development of rapid whole-blood point-of-care testing, and progressive improvements in assay design leading to modern high-sensitivity troponin assays that are now being introduced to the market. These new high-sensitivity assays will dramatically change the approach to patients presenting with acute coronary syndromes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 21 TC 8 Z9 8 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 31 EP + PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500004 PM 24507785 ER PT J AU Gaggin, HK Januzzi, JL AF Gaggin, Hanna K. Januzzi, James L., Jr. TI Natriuretic Peptides in Heart Failure and Acute Coronary Syndrome SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers; BNP; NT-proBNP; Heart failure; Acute coronary syndrome; Natriuretic peptides ID ACUTE MYOCARDIAL-INFARCTION; EMERGENCY-DEPARTMENT PATIENTS; INCREASED PLASMA-LEVELS; ST-SEGMENT ELEVATION; ACUTE DYSPNEA; CHEST-PAIN; VAL-HEFT; SYSTOLIC DYSFUNCTION; RISK STRATIFICATION; VASOACTIVE PEPTIDES AB B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are the gold standard biomarkers in determining heart failure (HF) diagnosis and prognosis. These natriuretic peptides may also be useful in guiding HF management, but further studies are needed before they can be routinely recommended for that purpose. A novel natriuretic peptide biomarker, mid-regional pro atrial natriuretic peptide (MR-proANP), shows promise in determining diagnosis and prognosis in HF patients. BNP and NT-proBNP may be of use in excluding myocardial infarction and to assist in determining prognosis in acute coronary syndrome (ACS). Therapeutic implication of natriuretic peptides in ACS is unclear. C1 [Gaggin, Hanna K.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Ruth and James Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment FX Dr H.K. Gaggin is supported in part by the Ruth and James Clark Fund for Cardiac Research Innovation, and Dr J.L. Januzzi is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment. NR 59 TC 7 Z9 10 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 43 EP + DI 10.1016/j.cll.2013.11.007 PG 17 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500005 PM 24507786 ER PT J AU Shah, RV Januzzi, JL AF Shah, Ravi V. Januzzi, James L., Jr. TI Soluble ST2 and Galectin-3 in Heart Failure SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers ID FAMILY-MEMBER ST2; LONG-TERM MORTALITY; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; NATRIURETIC PEPTIDE; CARDIAC STRUCTURE; PLASMA-CONCENTRATIONS; 1-YEAR MORTALITY; PROGNOSTIC VALUE; ACUTE DYSPNEA AB Circulating biomarkers that directly reflect disease progression, hemodynamics, and ventricular remodeling at a molecular level are critical to risk stratification in heart failure (HF), affording unique insights into pathophysiology not fully captured by traditional risk markers. Despite the wealth of data confirming the importance of natriuretic peptides in HF diagnosis and prognosis, residual clinical risk in HF suggests that additional biomarkers complementary to natriuretic peptides may be useful. In this article, the current literature addressing the role of these biomarkers in the clinical diagnosis and risk stratification in HF is summarized. C1 [Shah, Ravi V.; Januzzi, James L., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Roche Diagnostics; Siemens; Critical Diagnostics; BG Medicine; Thermo Fisher; Singulex; Amgen; Zensun; Novartis FX Disclosures: Dr J.L. Januzzi reports having received grant support and/or consulting income from Roche Diagnostics, Siemens, Critical Diagnostics, BG Medicine, Thermo Fisher, Singulex, Amgen, Zensun, and Novartis. NR 49 TC 12 Z9 13 U1 0 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 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 87 EP + DI 10.1016/j.cll.2013.11.009 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500008 PM 24507789 ER PT J AU Grobben, RB Nathoe, HM Januzzi, JL van Kimmenade, RRJ AF Grobben, Remco B. Nathoe, Hendrik M. Januzzi, James L., Jr. van Kimmenade, Roland R. J. TI Cardiac Markers Following Cardiac Surgery and Percutaneous Coronary Intervention SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers; Troponin; CK-MB; Cardiac surgery; PCI; CABG ID CREATINE-KINASE-MB; PERIOPERATIVE MYOCARDIAL-INFARCTION; BYPASS GRAFT-SURGERY; AORTIC-VALVE IMPLANTATION; TROPONIN-I; UNIVERSAL DEFINITION; PROGNOSTIC VALUE; VASCULAR ENDOTHELIUM; NITRIC-OXIDE; ELEVATION AB Differentiation between procedure-related necrosis and postprocedural myocardial infarction (Ml) is challenging because of the inherent association of these procedures to varying levels of myocardial injury. To improve risk stratification of patients at risk of an acute MI, the universal definition of MI implemented cardiac biomarker thresholds. The cutoff points for these thresholds, however, are largely arbitrary and lack therapeutic implications. Measurement of cardiac marker concentrations after percutaneous coronary intervention and cardiac surgery should, therefore, be used as a marker of baseline risk, atherosclerosis burden, and procedural complexity rather than a conclusive marker to diagnose acute MI. C1 [Grobben, Remco B.; Nathoe, Hendrik M.; van Kimmenade, Roland R. J.] Univ Med Ctr Utrecht, Dept Cardiol, NL-3508 GA Utrecht, Netherlands. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Grobben, RB (reprint author), Univ Med Ctr Utrecht, Dept Cardiol, Postbus 85500, NL-3508 GA Utrecht, Netherlands. EM r.b.grobben@umcutrecht.nl RI Kimmenade, R.R.J./L-4432-2015 NR 53 TC 1 Z9 1 U1 0 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 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 99 EP + PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500009 PM 24507790 ER PT J AU Rudolf, J Lewandrowski, KB AF Rudolf, Joseph Lewandrowski, Kent B. TI Cholesterol, Lipoproteins, High-sensitivity C-reactive Protein, and Other Risk Factors for Atherosclerosis SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers; Atherosclerosis; Lipoprotein; Cholesterol biomarker; High-sensitivity CRP; Apo lipoprotein E ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; PHOSPHOLIPASE A(2); HDL CHOLESTEROL; LDL CHOLESTEROL; STATIN THERAPY; GENOMEWIDE ASSOCIATION; PRIMARY PREVENTION; CLINICAL UTILITY AB Coronary heart disease is a common and costly epidemic in the Western world. Intensive study has led to a deeper understanding of the pathogenesis of coronary disease and risk stratification. Traditional risk factor assessment has focused on parameters derived from the Framingham Heart Study (age, hypertension, cholesterol, family history, and cigarette smoking). New emerging risk factors, both biological and genetic, are reshaping the understanding of heart disease and the approach to risk stratification. As these emerging assays become more standardized, automated, and inexpensive to perform, they are becoming increasingly important tools in the assessment and treatment of coronary heart disease. C1 [Rudolf, Joseph; Lewandrowski, Kent B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, 55 Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 50 TC 5 Z9 7 U1 0 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 113 EP + DI 10.1016/j.cll.2013.11.003 PG 16 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500010 PM 24507791 ER PT J AU Lewandrowski, KB AF Lewandrowski, Kent B. TI Special Topics: Cardiac Markers in Myocarditis: Cardiac Transplant Rejection and Conditions Other than Acute Coronary Syndrome SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers; Troponin; Myocarditis; Cardiac transplant rejection ID TROPONIN-T; HEART-TRANSPLANTATION; DIAGNOSIS; CHILDREN AB The utility of blood biomarkers of cardiac myocyte damage such as troponin T and I in the evaluation of acute coronary syndromes and heart failure is well established. However, some of these markers may also be elevated in other conditions, such as myocarditis, cardiac transplant rejection, and several other conditions. Recognizing this phenomenon is essential to avoid misdiagnosis of acute coronary syndromes. Furthermore, identifying an elevated troponin level in patients without acute coronary syndrome or heart failure may often have diagnostic or prognostic significance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 14 TC 0 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 129 EP + DI 10.1016/j.cll.2013.11.004 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500011 PM 24507792 ER PT J AU Siuss, PM AF Siuss, Patrick M. TI Methodologies for Measurement of Cardiac Markers SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Laboratory medicine; Cardiac markers; Biomarkers; Immunoassay; Assay principles; Assay design; CKMB; Troponins ID 99TH PERCENTILE VALUES; SURROGATE END-POINTS; TROPONIN-I; NATRIURETIC PEPTIDE; EPITOPE SPECIFICITY; ASSAYS; POPULATION; VALIDATION; BIOMARKERS AB Antibody-based tests are the primary technology used for clinical measurement of cardiac biomarkers in peripheral circulation. This article focuses on the principles of immunometric methods that have been applied to cardiac biomarkers of widespread clinical utility (CKMB, Troponins, and B-type natriuretic proteins) and of more recent clinical testing (ST2, Galectin-2, and myosin binding protein C). How these principles are applied in the design of immunometric assays and how they influence assay performance in quantifying cardiac biomarkers in biologic fluids (serum or plasma) is discussed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Pathol Core Labs Special Chem,Pathol Serv, Boston, MA 02114 USA. RP Siuss, PM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin Pathol Core Labs Special Chem,Pathol Serv, GRB554,55 Fruit St, Boston, MA 02114 USA. EM sluss.patrick@mgh.harvard.edu NR 28 TC 0 Z9 0 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2014 VL 34 IS 1 BP 167 EP + DI 10.1016/j.cll.2013.11.012 PG 20 WC Medical Laboratory Technology SC Medical Laboratory Technology GA AB8QG UT WOS:000332054500014 ER PT J AU Liao, S Mei, J Song, W Liu, Y Tan, YD Chi, S Li, P Chen, X Deng, S AF Liao, S. Mei, J. Song, W. Liu, Y. Tan, Y. -D. Chi, S. Li, P. Chen, X. Deng, S. TI The impact of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) fasting glucose diagnostic criterion on the prevalence and outcomes of gestational diabetes mellitus in Han Chinese women SO DIABETIC MEDICINE LA English DT Article ID PLASMA-GLUCOSE; CLASSIFICATION; HYPERGLYCEMIA; POPULATION; TOLERANCE; REPRODUCIBILITY AB AimsThe International Association of Diabetes and Pregnancy Study Groups (IADPSG) proposed that a one-time value of fasting plasma glucose of 5.1mmol/l or over at any time of the pregnancy is sufficient to diagnose gestational diabetes. We evaluated the repercussions of the application of this threshold in pregnant Han Chinese women. MethodsThis is a retrospective study of 5360 (72.3% of total) consecutively recruited pregnant Han Chinese women in one centre from 2008 to 2011. These women underwent a two-step gestational diabetes diagnostic protocol according to the previous American Diabetes Association criteria. The IADPSG fasting plasma glucose criterion was used to reclassify these 5360 women. The prevalence, clinical characteristics and obstetric outcomes were compared among the women classified as having gestational diabetes by the previous American Diabetes Association criteria (approximately 90% were treated), those reclassified as having gestational diabetes by the single IADPSG fasting plasma glucose criterion (untreated), but not as having gestational diabetes by the previous American Diabetes Association criteria, and those with normal glucose tolerance. ResultsThere were 626 cases of gestational diabetes defined by the previous American Diabetes Association criteria (11.7%) and these cases were associated with increased risks of maternal and neonatal outcomes when compared with the women with normal glucose tolerance. With the IADPSG fasting plasma glucose criterion, another 1314 (24.5%) women were reclassified as having gestational diabetes. Gestational diabetes classified by the IADPSG fasting plasma glucose criterion was associated with gestational hypertension (P=0.0094) and neonatal admission to nursery (P=0.035) prior to adjustment for maternal age and BMI, but was no longer a predictor for adverse pregnancy outcomes after adjustment. ConclusionThe simple IADPSG fasting plasma glucose criterion increased the Chinese population with gestational diabetes by 200%. The increased population with gestational diabetes was not significantly associated with excess obstetric and neonatal morbidity. C1 [Liao, S.; Li, P.; Deng, S.] Sichuan Prov Peoples Hosp, Sichuan Acad Med Sci, Ctr Diabet, Chengdu, Peoples R China. [Mei, J.] Sichuan Prov Peoples Hosp, Sichuan Acad Med Sci, Dept Obstet & Gynecol, Chengdu, Peoples R China. [Song, W.; Chi, S.] Sichuan Prov Peoples Hosp, Sichuan Acad Med Sci, Clin Isotop Lab, Chengdu, Peoples R China. [Liu, Y.] Sichuan Univ, West China Hosp, Dept Med Genet, Chengdu 610064, Peoples R China. [Liu, Y.] Sichuan Univ, West China Hosp, Div Morbid Genom, Chengdu 610064, Peoples R China. [Tan, Y. -D.] Hunan Normal Univ, Coll Life Sci, Changsha, Hunan, Peoples R China. [Li, P.] Sichuan Prov Peoples Hosp, Sichuan Acad Med Sci, Dept Endocrinol & Metab, Chengdu, Peoples R China. [Chen, X.] Columbia Univ Coll Phys & Surg, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Deng, S.] Harvard Univ, Sch Med, Dept Surg, Human Islet Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Deng, S (reprint author), Sichuan Prov Peoples Hosp, Sichuan Acad Med Sci, Ctr Diabet, Chengdu, Peoples R China. EM sdeng10@yahoo.com FU Sichuan Provincial Department of Science and Technology [2011sz0029, 2009sz0223]; Sichuan Provincial Health Department [100450, 120074]; Department of Science and Technology in Chengdu [11PPYB050SF-289] FX This study was supported by the research grants (to SL, SD and JM) from the Key Project of Sichuan Provincial Department of Science and Technology (2011sz0029, 2009sz0223), Sichuan Provincial Health Department (100450,120074) and Department of Science and Technology in Chengdu (11PPYB050SF-289). NR 27 TC 9 Z9 11 U1 0 U2 3 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 MAR PY 2014 VL 31 IS 3 BP 341 EP 351 DI 10.1111/dme.12349 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AA8IC UT WOS:000331338200013 PM 24152069 ER PT J AU Shinagare, AB Jagannathan, JP Kurra, V Urban, T Manola, J Choy, E Demetri, GD George, S Ramaiya, NH AF Shinagare, Atul B. Jagannathan, Jyothi P. Kurra, Vikram Urban, Trinity Manola, Judith Choy, Edwin Demetri, George D. George, Suzanne Ramaiya, Nikhil H. TI Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Gastrointestinal stromal tumour; Regorafenib; Tumour response criteria; RECIST; Choi ID PHASE-II TRIAL; SOLID TUMORS; MESYLATE; EFFICACY; SAFETY; MULTICENTER; SURVIVAL; THERAPY; RECIST; KIT AB Purpose: To compare performance of various tumour response criteria (TRCs) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour (GIST) with prior failure of imatinib and sunitinib. Methods: Twenty participants in a phase II trial received oral regorafenib (median duration 47 weeks; interquartile range (IQR) 24-88) with computed tomography (CT) imaging at baseline and every two months thereafter. Tumour response was prospectively determined on using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and retrospectively reassessed for comparison per RECIST 1.0, World Health Organization (WHO) and Choi criteria, using the same target lesions. Clinical benefit rate [CBR; complete or partial response (CR or PR) or stable disease (SD) >= 16 weeks] and progression-free survival (PFS) were compared between various TRCs using kappa statistics. Performance of TRCs in predicting overall survival (OS) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics. Results: PR was more frequent by Choi (90%) than RECIST 1.1, RECIST 1.0 and WHO (20% each), however, CBR was similar between various TRCs (overall CBR 85-90%, 95-100% agreement between all TRC pairs). PFS per RECIST 1.0 was similar to RECIST 1.1 (median 44 weeks versus 58 weeks), and shorter for WHO (median 34 weeks) and Choi (median 24 weeks). With RECIST 1.1, RECIST 1.0 and WHO, there was moderate concordance between PFS and OS (c-statistics 0.596-0.679). Choi criteria had less favourable concordance (c-statistic 0.506). Conclusions: RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Shinagare, Atul B.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org FU NCI NIH HHS [P50 CA127003] NR 17 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2014 VL 50 IS 5 BP 981 EP 986 DI 10.1016/j.ejca.2013.11.037 PG 6 WC Oncology SC Oncology GA AC3FI UT WOS:000332400400014 PM 24388774 ER PT J AU Toma, M Ezekowitz, JA Bakal, JA O'Connor, CM Hernandez, AF Sardar, MR Zolty, R Massie, BM Swedberg, K Armstrong, PW Starling, RC AF Toma, Mustafa Ezekowitz, Justin A. Bakal, Jeffrey A. O'Connor, Christopher M. Hernandez, Adrian F. Sardar, Muhammad Rizwan Zolty, Ronald Massie, Barry M. Swedberg, Karl Armstrong, Paul W. Starling, Randall C. TI The relationship between left ventricular ejection fraction and mortality in patients with acute heart failure: insights from the ASCEND-HF Trial SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; Ejection fraction; Clinical trial; Outcomes ID PRESERVED SYSTOLIC FUNCTION; BRAIN NATRIURETIC PEPTIDE; NATIONAL REGISTRY ADHERE; LONG-TERM OUTCOMES; EMERGENCY-DEPARTMENT; ATRIAL-FIBRILLATION; PEP-CHF; DYSFUNCTION; DIAGNOSIS; MANAGEMENT AB Aim Acute decompensated heart failure (ADHF) is associated with significant morbidity and mortality but the relationship between LVEF and outcomes is unclear. We explored the association between LVEF and 30 and 180day mortality in 7007 ADHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. Methods and results We explored the association between LVEF and 30 and 180 day mortality in 7007 ADHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. LVEF was analysed both as a continuous variable and according to three categories: < 40% (LowEF), 40-50% [intermediate EF (IntEF)], and > 50% [preserved ejection fraction (PresEF)]. Of the patients in the trial, 4474 (78.7%) had LowEF, 674 (11.9%) had IntEF, and 539 (9.5%) had PresEF. The unadjusted 30 and 180 day mortality was similar for LowEF (3.7%, 12.3%), IntEF (3.4%, 13.1%), and PresEF (4.3%, 14.1%), respectively (P > 0.05). After multivariable adjustment, the hazard ratio (HR) for 180 day mortality remained similar for the LowEF [HR 0.96, 95% confidence interval (CI) 0.75-1.24; P = 0.77] and IntEF (0.91, 95% CI 0.66-1.3; P = 0.58) compared to PresEF patients. By contrast, when LVEF was evaluated as a continuous measure, it exhibited a U-shaped pattern with mortality. After matching for age and sex, the mortality risk attributed to LVEF was attenuated, as the LVEF increased as a continuous variable over 35%. However, in patients with EF < 35%, the mortality risk continue to increase as the LVEF declined. Conclusions Among patients with ADHF, the unadjusted mortality rates are similar across LVEF strata. However, after accounting for key patient variables, the mortality risk increases as EF falls below 35%. These data will be useful in planning future studies of ADHF. Clinical Trial Registration identifier: NCT00475852 C1 [Toma, Mustafa] Univ British Columbia, St Pauls Hosp, Div Cardiol, Vancouver, BC V5Z 1M9, Canada. [Ezekowitz, Justin A.] Univ Alberta, Mazankowski Alberta Heart Inst, Div Cardiol, Dept Med, Edmonton, AB T6G 2B7, Canada. [Bakal, Jeffrey A.; Armstrong, Paul W.] Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB T6G 2B7, Canada. [O'Connor, Christopher M.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Sardar, Muhammad Rizwan; Zolty, Ronald] Montefiore Med Ctr, Div Cardiol, Bronx, NY 10467 USA. [Massie, Barry M.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. [Swedberg, Karl] Ostra Goteborg Univ, Sahlgrenska Univ Hosp, Gothenburg, Sweden. [Starling, Randall C.] Cleveland Clin, Inst Heart & Vasc, Kaufman Ctr Heart Failure, Dept Cardiovasc Med, Cleveland, OH 44106 USA. RP Ezekowitz, JA (reprint author), Univ Alberta, Mazankowski Alberta Heart Inst, Div Cardiol, Dept Med, 2C2 WMC-8440-112 St, Edmonton, AB T6G 2B7, Canada. EM jae2@ualberta.ca RI Ezekowitz, Justin/C-4579-2013; Hernandez, Adrian F./A-7818-2016 OI Ezekowitz, Justin/0000-0002-2724-4086; Hernandez, Adrian F./0000-0003-3387-9616 FU Johnson Johnson Inc. FX The ASCEND-HF trial was funded through its sponsor, Johnson & Johnson Inc. The sponsor had no role in this study. NR 32 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD MAR PY 2014 VL 16 IS 3 BP 334 EP 341 DI 10.1002/ejhf.19 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB9FF UT WOS:000332095300012 PM 24464687 ER PT J AU Steffens, JP Herrera, BS Coimbra, LS Stephens, DN Rossa, C Spolidorio, LC Kantarci, A Van Dyke, TE AF Steffens, J. P. Herrera, B. S. Coimbra, L. S. Stephens, D. N. Rossa, C., Jr. Spolidorio, L. C. Kantarci, A. Van Dyke, T. E. TI Testosterone Regulates Bone Response to Infl ammation SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE testosterone; osteoblasts; docosahexaenoic acids; RANK ligand; osteocalcin; osteoprotegerin ID ANDROGENIC STEROID ABUSE; HORMONE-BINDING GLOBULIN; MIDDLE-AGED MEN; RESOLVIN E1; OLDER MEN; DARK SIDE; METABOLIC SYNDROME; ELDERLY-MEN; INFLAMMATION; OSTEOPROTEGERIN AB This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1 expression was increased in the L group (p<0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function. C1 [Steffens, J. P.; Coimbra, L. S.; Rossa, C., Jr.; Spolidorio, L. C.] Sao Paulo State Univ, Dept Physiol & Pathol, Sch Dent Araraquara, UNESP, BR-14801903 Araraquara, SP, Brazil. [Steffens, J. P.; Herrera, B. S.; Stephens, D. N.; Kantarci, A.; Van Dyke, T. E.] Forsyth Inst, Dept Appl Oral Sci, Ctr Periodontol, Cambridge, MA USA. RP Steffens, JP (reprint author), Sao Paulo State Univ, Rua Humaita 1680, BR-14801903 Araraquara, SP, Brazil. EM joaopaulosteffens@hotmail.com RI Rossa Jr, Carlos/D-8328-2012; Steffens, Joao Paulo/B-4953-2009; Spolidorio, Luis Carlos/G-1857-2012 OI Rossa Jr, Carlos/0000-0003-1705-5481; Steffens, Joao Paulo/0000-0002-6071-553X; FU Sao Paulo State Research Foundation (FAPESP), Sao Paulo, SP, Brazil [2010/09658-0]; Coordination for the Improvement of Higher Education Personnel (CAPES), Brasilia, DF, Brazil [5258-11-1]; FAPESP [2010/12021-4]; National Council for Scientific and Technological Development (CNPq), Brasilia, DF, Brazil [470870/2011-7]; CNPq; NIH/NIDCR [DE015566, DE020906] FX JPS was a recipient of a scholarship from the Sao Paulo State Research Foundation (FAPESP), Sao Paulo, SP, Brazil (#2010/09658-0) and from the Coordination for the Improvement of Higher Education Personnel (CAPES), Brasilia, DF, Brazil (#5258-11-1). JPS and LCS held research support grants from FAPESP (#2010/12021-4) and from the National Council for Scientific and Technological Development (CNPq), Brasilia, DF, Brazil (#470870/2011-7). LCS holds a Productivity Scholarship from CNPq. This work was supported by NIH/NIDCR grants DE015566 and DE020906 to AK and TVD. NR 54 TC 9 Z9 9 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD MAR PY 2014 VL 46 IS 3 BP 193 EP 200 DI 10.1055/s-0034-1367031 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB8SH UT WOS:000332059800005 PM 24526374 ER PT J AU Schlosser, RJ Soler, ZM Schmedes, GW Storck, K Mulligan, JK AF Schlosser, Rodney J. Soler, Zachary M. Schmedes, Gregg W. Storck, Kristina Mulligan, Jennifer K. TI Impact of vitamin D deficiency upon clinical presentation in nasal polyposis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE polyps; sinusitis; chronic rhinosinusitis; nasal polyposis; vitamin D deficiency; cholecalciferol; vitamin D ID CHRONIC RHINOSINUSITIS AB Background The objective of this work was to determine if specific chronic rhinosinusitis with nasal polyps (CRSwNP) populations are at risk for vitamin D-3 (VD3) deficiency and if VD3 levels correlate with radiographic measures of disease severity or eosinophilia. Methods This study was a retrospective review of an academic rhinology practice. CRSwNP patients who had VD3 levels and CT scan within 6 months of each other were included. CT scans were graded using Lund-Mackay scoring (LMS) and peripheral eosinophil counts were measured. Demographic data including race, gender, age, body mass index, atopic status, and presence of asthma were collected. CRSwNP was subdivided into allergic fungal rhinosinusitis (AFRS), aspirin-exacerbated respiratory disease (AERD), and other CRSwNP. Multivariate analysis was performed to examine correlations and control for confounding factors. Results Insufficient VD3 levels were found in 55% of all CRSwNP patients. VD3 correlated with African American race because nearly 80% of all African Americans had insufficient VD3 levels. Lower VD3 levels also correlated with more severe mucosal disease on CT scans as measured by LMS. There was no correlation between VD3 levels and age, gender, body mass index, atopy, asthma, or CRSwNP subtype. Conclusion VD3 insufficiency/deficiency is common in CRSwNP patients, especially those of African American race. Lower levels of VD3 are associated with worse LMS on CT. The role of VD3 in CRSwNP warrants further investigation. C1 [Schlosser, Rodney J.; Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. [Schlosser, Rodney J.; Soler, Zachary M.; Schmedes, Gregg W.; Storck, Kristina; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol, Div Rhinol & Sinus Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Div Neonatol, Charleston, SC 29425 USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, Dept Otolaryngol, Div Rhinol & Sinus Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM schlossr@musc.edu FU Flight Attendant Medical Research Institute; VA Merit grants FX Flight Attendant Medical Research Institute and VA Merit grants (both to R.J.S.). NR 11 TC 14 Z9 14 U1 2 U2 5 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 MAR PY 2014 VL 4 IS 3 BP 196 EP 199 DI 10.1002/alr.21274 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA AB9TW UT WOS:000332139600005 PM 24415576 ER PT J AU Chhabra, N Wu, AW Fay, A Metson, R AF Chhabra, Nipun Wu, Arthur W. Fay, Aaron Metson, Ralph TI Endoscopic resection of orbital hemangiomas SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE cavernous hemangioma; orbit; orbital tumor; proptosis; endoscopic orbital surgery ID CAVERNOUS HEMANGIOMAS; SURGERY; TUMORS; MANAGEMENT AB Background Cavernous hemangiomas are the most common orbital tumors in adults. Traditional orbitotomy approaches to resect these intraconal lesions are associated with patient morbidity due to difficulties with visualization and access in the region of the orbital apex. Methods In this retrospective chart review and case series, the records of 5 patients who underwent endoscopic resection of orbital hemangiomas by the senior authors (A.F. and R.M.) between 2007 and 2011 were reviewed. Patient demographics, preoperative, and postoperative variables were assessed. Results All tumors were located in the medial orbital apex. Mean tumor size was 1.7 cm in maximum dimension (range, 1.0-2.7 cm). Proptosis and/or optic neuropathy were present in all cases. Surgeries were performed through an entirely endoscopic transnasal approach. One patient underwent subtotal tumor resection. Proptosis improved by a mean +/- standard deviation of 1.75 +/- 0.87 mm. The average improvement in visual acuity was 1.8 lines on a Snellen chart (range, 1-4 lines). There were no long-term adverse sequelae. Conclusion Endoscopic techniques for the treatment of patients with hemangiomas in the posterior medial orbit appear to offer the advantage of enhanced surgical access with reduced patient morbidity compared to conventional orbitotomy approaches. C1 [Chhabra, Nipun; Wu, Arthur W.; Fay, Aaron; Metson, Ralph] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. EM ralph_metson@meei.harvard.edu NR 13 TC 13 Z9 14 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 MAR PY 2014 VL 4 IS 3 BP 251 EP 255 DI 10.1002/alr.21267 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA AB9TW UT WOS:000332139600013 PM 24415525 ER PT J AU Krezanoski, PJ Comfort, AB Tsaid, AC Bangsberg, DR AF Krezanoski, Paul J. Comfort, Alison B. Tsaid, Alexander C. Bangsberg, David R. TI Households with young children and use of freely distributed bednets in rural Madagascar SO INTERNATIONAL HEALTH LA English DT Article DE Adherence; Insecticide-treated bednets; Madagascar; Malaria ID INSECTICIDE TREATED NETS; DETERMINANTS; COVERAGE; AFRICA; WEALTH AB Malaria infections are the leading cause of death for children in Madagascar. Insecticide-treated bednets offer effective prevention, but it is unclear how well free bednet distribution programs reach young children. We conducted a secondary analysis of a free bednet distribution program in Madagascar from 20072008. Interviews were performed at baseline and 6 months. Principal components analysis was used to construct a wealth and malaria knowledge index. Coverage efficiency was calculated as coverage of children per bednet owned. Univariable and multivariable regressions were used to determine predictors of bednet use. Bednet use, among the 560 households in the study, increased from 6 to 91 after 6 months. Coverage efficiency increased from 1.29 to 1.56 children covered per bednet owned. In multivariable analysis, having a child under 5 years of age was the only variable associated with bednet use (OR 9.10; p0.001), yielding a 99 likelihood of using a bednet (95 CI 96.4 to 99.9) versus 82 (95 CI 72.2 to 88.4) in households without young children. This free bednet distribution program achieved high levels of adherence after 6 months. Household presence of children was associated with bednet use, but not household income or education, suggesting that distribution to priority groups may help overcome traditional barriers to adoption in some settings. C1 [Krezanoski, Paul J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Krezanoski, Paul J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Comfort, Alison B.] Int Hlth Div, Abt Associates, Cambridge, MA USA. [Tsaid, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsaid, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsaid, Alexander C.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, David R.] Ragon Inst MGH Massachusetts Inst Technol & Harva, Charlestown, MA USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. RP Krezanoski, PJ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM pkrezanoski@partners.org OI Tsai, Alexander/0000-0001-6397-7917 NR 19 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1876-3413 EI 1876-3405 J9 INT HEALTH JI Int. Health PD MAR PY 2014 VL 6 IS 1 BP 29 EP 34 DI 10.1093/inthealth/iht033 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AC2OW UT WOS:000332342400006 PM 24366350 ER PT J AU Baggish, AL Park, J Min, PK Isaacs, S Parker, BA Thompson, PD Troyanos, C D'Hemecourt, P Dyer, S Thiel, M Hale, A Chan, SY AF Baggish, Aaron L. Park, Joseph Min, Pil-Ki Isaacs, Stephanie Parker, Beth A. Thompson, Paul D. Troyanos, Chris D'Hemecourt, Pierre Dyer, Sophia Thiel, Marissa Hale, Andrew Chan, Stephen Y. TI Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE circulating microRNA; exercise physiology; cardiovascular biomarker; cardiorespiratory fitness biomarker; prolonged aerobic exercise ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; SKELETAL-MUSCLE; ENDURANCE EXERCISE; EXPRESSION; BIOMARKERS; CELLS; RATS; INFLAMMATION; DISEASE AB Short nonprotein coding RNA molecules, known as microRNAs (miRNAs), are intracellular mediators of adaptive processes, including muscle hypertrophy, contractile force generation, and inflammation. During basal conditions and tissue injury, miRNAs are released into the bloodstream as "circulating" miRNAs (c-miRNAs). To date, the impact of extended-duration, submaximal aerobic exercise on plasma concentrations of c-miRNAs remains incompletely characterized. We hypothesized that specific c-miRNAs are differentially upregulated following prolonged aerobic exercise. To test this hypothesis, we measured concentrations of c-miRNAs enriched in muscle (miR-1, miR-133a, miR-499-5p), cardiac tissue (miR-208a), and the vascular endothelium (miR-126), as well as those important in inflammation (miR-146a) in healthy male marathon runners (N = 21) at rest, immediately after a marathon (42-km foot race), and 24 h after the race. In addition, we compared c-miRNA profiles to those of conventional protein biomarkers reflective of skeletal muscle damage, cardiac stress and necrosis, and systemic inflammation. Candidate c-miRNAs increased immediately after the marathon and declined to prerace levels or lower after 24 h of race completion. However, the magnitude of change for each c-miRNA differed, even when originating from the same tissue type. In contrast, traditional biomarkers increased after exercise but remained elevated 24 h postexercise. Thus c-miRNAs respond differentially to prolonged exercise, suggesting the existence of specific mechanisms of c-miRNA release and clearance not fully explained by generalized cellular injury. Furthermore, c-miRNA expression patterns differ in a temporal fashion from corollary conventional tissue-specific biomarkers, emphasizing the potential of c-miRNAs as unique, real-time markers of exercise-induced tissue adaptation. C1 [Baggish, Aaron L.; Isaacs, Stephanie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Performance Program, Boston, MA USA. [Park, Joseph; Min, Pil-Ki; Thiel, Marissa; Hale, Andrew; Chan, Stephen Y.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Parker, Beth A.; Thompson, Paul D.] Hartford Hosp, Henry Low Heart Ctr, Div Cardiol, Hartford, CT 06115 USA. [Baggish, Aaron L.; Troyanos, Chris; D'Hemecourt, Pierre; Dyer, Sophia] Boston Athlet Assoc, Boston, MA USA. [Min, Pil-Ki] Yonsei Univ, Coll Med, Dept Internal Med, Cardiol Div,Gangnam Severance Hosp, Seoul, South Korea. RP Baggish, AL (reprint author), Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org FU American Heart Association; National Heart, Lung, and Blood Institute [HL-096834]; McArthur-Radovsky, Lerner, Harris, and Watkins Funds; Pulmonary Hypertension Association; Gilead Research Scholars Fund FX This work was supported by the American Heart Association (A. L. Baggish), the National Heart, Lung, and Blood Institute (HL-096834), the McArthur-Radovsky, Lerner, Harris, and Watkins Funds, and the Pulmonary Hypertension Association (S. Y. Chan). The Gilead Research Scholars Fund also supported this work. NR 69 TC 42 Z9 43 U1 2 U2 18 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2014 VL 116 IS 5 BP 522 EP 531 DI 10.1152/japplphysiol.01141.2013 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA AC3JR UT WOS:000332414300007 PM 24436293 ER PT J AU Kelly, NA Ford, MP Standaert, DG Watts, RL Bickel, CS Moellering, DR Tuggle, SC Williams, JY Lieb, L Windham, ST Bamman, MM AF Kelly, Neil A. Ford, Matthew P. Standaert, David G. Watts, Ray L. Bickel, C. Scott Moellering, Douglas R. Tuggle, S. Craig Williams, Jeri Y. Lieb, Laura Windham, Samuel T. Bamman, Marcas M. TI Novel, high-intensity exercise prescription improves muscle mass, mitochondrial function, and physical capacity in individuals with Parkinson's disease SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE Parkinson's disease; high-intensity exercise; resistance training; muscle hypertrophy; mitochondria ID PROGRESSIVE RESISTANCE EXERCISE; HUMAN SKELETAL-MUSCLE; QUALITY-OF-LIFE; OLDER-ADULTS; MYOFIBER HYPERTROPHY; PROTEIN EXPRESSION; RESPIRATORY-CHAIN; CITRATE SYNTHASE; CLUSTER-ANALYSIS; WALKING SPEED AB We conducted, in persons with Parkinson's disease (PD), a thorough assessment of neuromotor function and performance in conjunction with phenotypic analyses of skeletal muscle tissue, and further tested the adaptability of PD muscle to high-intensity exercise training. Fifteen participants with PD (Hoehn and Yahr stage 2-3) completed 16 wk of high-intensity exercise training designed to simultaneously challenge strength, power, endurance, balance, and mobility function. Skeletal muscle adaptations (P < 0.05) to exercise training in PD included myofiber hypertrophy (type I: +14%, type II: +36%), shift to less fatigable myofiber type profile, and increased mitochondrial complex activity in both subsarcolemmal and intermyofibrillar fractions (I: +45-56%, IV: +39-54%). These adaptations were accompanied by a host of functional and clinical improvements (P < 0.05): total body strength (+30-56%); leg power (+42%); single leg balance (+34%); sit-to-stand motor unit activation requirement (-30%); 6-min walk (+43 m), Parkinson's Disease Quality of Life Scale (PDQ-39, -7.8pts); Unified Parkinson's Disease Rating Scale (UPDRS) total (-5.7 pts) and motor (-2.7 pts); and fatigue severity (-17%). Additionally, PD subjects in the pretraining state were compared with a group of matched, non-PD controls (CON; did not exercise). A combined assessment of muscle tissue phenotype and neuromuscular function revealed a higher distribution and larger cross-sectional area of type I myofibers and greater type II myofiber size heterogeneity in PD vs. CON (P < 0.05). In conclusion, persons with moderately advanced PD adapt to high-intensity exercise training with favorable changes in skeletal muscle at the cellular and subcellular levels that are associated with improvements in motor function, physical capacity, and fatigue perception. C1 [Kelly, Neil A.; Ford, Matthew P.; Standaert, David G.; Watts, Ray L.; Bickel, C. Scott; Moellering, Douglas R.; Tuggle, S. Craig; Windham, Samuel T.; Bamman, Marcas M.] Univ Alabama Birmingham, UAB Ctr Exercise Med, Birmingham, AL USA. [Kelly, Neil A.; Tuggle, S. Craig; Bamman, Marcas M.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. [Ford, Matthew P.; Bickel, C. Scott] Univ Alabama Birmingham, Dept Phys Therapy, Birmingham, AL USA. [Standaert, David G.; Watts, Ray L.; Williams, Jeri Y.; Lieb, Laura] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Moellering, Douglas R.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Windham, Samuel T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Tuggle, S. Craig; Bamman, Marcas M.] Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Bamman, MM (reprint author), UAB Ctr Exercise Med, 966 McCallum Bldg,1720 2nd Ave South, Birmingham, AL 35294 USA. EM mbamman@uab.edu OI Standaert, David/0000-0003-2921-8348 FU UAB Department of Neurology; UAB School of Medicine; UAB Center for Exercise Medicine; DRTC Bio-Analytical Redox Biology Core [P30 DK079626]; UAB Center for Clinical and Translational Science [UL1 TR000165]; [1T32 HD071866] FX This work was supported by the UAB Department of Neurology, UAB School of Medicine, UAB Center for Exercise Medicine, 1T32 HD071866 (NAK), P30 DK079626 (DRTC Bio-Analytical Redox Biology Core), and the UAB Center for Clinical and Translational Science (UL1 TR000165). NR 79 TC 9 Z9 9 U1 7 U2 37 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2014 VL 116 IS 5 BP 582 EP 592 DI 10.1152/japplphysiol.01277.2013 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA AC3JR UT WOS:000332414300014 PM 24408997 ER PT J AU Yu, EW Bouxsein, ML Roy, AE Baldwin, C Cange, A Neer, RM Kaplan, LM Finkelstein, JS AF Yu, Elaine W. Bouxsein, Mary L. Roy, Adam E. Baldwin, Chantel Cange, Abby Neer, Robert M. Kaplan, Lee M. Finkelstein, Joel S. TI Bone Loss After Bariatric Surgery: Discordant Results Between DXA and QCT Bone Density SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE GASTRIC; BYPASS; DUAL-ENERGY X-RAY; ABSORPTIOMETRY; QUANTITATIVE; COMPUTED; TOMOGRAPHY; SOFT; TISSUE; ARTIFACT; BONE; METABOLISM; OSTEOPOROSIS ID X-RAY ABSORPTIOMETRY; GASTRIC BYPASS-SURGERY; MINERAL DENSITY; MORBID-OBESITY; WEIGHT-LOSS; BODY-COMPOSITION; MEDICAL THERAPY; ACCURACY; TURNOVER; FRACTURE AB Several studies, using dual-energy X-ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts. We assessed changes in BMD of the lumbar spine and proximal femur prospectively for 1 year using DXA and QCT in 30 morbidly obese adults undergoing Roux-en-Y gastric bypass surgery and 20 obese nonsurgical controls. At 1 year, subjects who underwent gastric bypass surgery lost 37 +/- 2kg compared with 3 +/- 2kg lost in the nonsurgical controls (p<0.0001). Spine BMD declined more in the surgical group than in the nonsurgical group whether assessed by DXA (-3.3 versus -1.1%, p=0.034) or by QCT (-3.4 versus 0.2%, p=0.010). Total hip and femoral neck aBMD declined significantly in the surgical group when assessed by DXA (-8.9 versus -1.1%, p<0.0001 for the total hip and -6.1 versus -2.0%, p=0.002 for the femoral neck), but no changes in hip vBMD were noted using QCT. Within the surgical group, serum P1NP and CTX levels increased by 82%+/- 10% and by 220%+/- 22%, respectively, by 6 months and remained elevated over 12 months (p<0.0001 for all). Serum calcium, vitamin D, and PTH levels remained stable in both groups. We conclude that moderate vertebral bone loss occurs in the first year after gastric bypass surgery. However, striking declines in DXA aBMD at the proximal femur were not confirmed with QCT vBMD measurements. These discordant results suggest that artifacts induced by large changes in body weight after bariatric surgery affect DXA and/or QCT measurements of bone, particularly at the hip. (c) 2014 American Society for Bone and Mineral Research. C1 [Yu, Elaine W.; Bouxsein, Mary L.; Roy, Adam E.; Baldwin, Chantel; Neer, Robert M.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Cange, Abby; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA. RP Yu, EW (reprint author), MGH Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA. EM ewyu@partners.org FU National Institutes of Health [K12 HD51959-7, K23 DK093713-01, P30 DK046200, S10 RR023405] FX We thank Ms Robbin Cleary, Ms Sarah Zhang, and Dr Bijoy Thomas for bone density measurements; the Clinical Laboratory Research Core in the Pathology Department at the Massachusetts General Hospital for batch laboratory testing; the nursing and dietary staff of the Mallinckrodt General Clinical Research Center for their dedicated care of the study participants; and Dr Keenan Brown for his helpful discussions and critical reading of the manuscript. This work was supported by National Institutes of Health grants K12 HD51959-7, K23 DK093713-01, P30 DK046200, and S10 RR023405. The Clinical Trial Registration number is NCT01098942. NR 39 TC 34 Z9 35 U1 1 U2 8 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 MAR PY 2014 VL 29 IS 3 BP 542 EP 550 DI 10.1002/jbmr.2063 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB0CF UT WOS:000331458700005 PM 23929784 ER PT J AU Turan, S Fernandez-Rebollo, E Aydin, C Zoto, T Reyes, M Bounoutas, G Chen, M Weinstein, LS Erben, RG Marshansky, V Bastepe, M AF Turan, Serap Fernandez-Rebollo, Eduardo Aydin, Cumhur Zoto, Teuta Reyes, Monica Bounoutas, George Chen, Min Weinstein, Lee S. Erben, Reinhold G. Marshansky, Vladimir Bastepe, Murat TI Postnatal Establishment of Allelic Gas Silencing as a Plausible Explanation for Delayed Onset of Parathyroid Hormone Resistance Owing to Heterozygous Gas Disruption SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE PSEUDOHYPOPARATHYROIDISM; PARATHYROID; HORMONE; STIMULATORY G PROTEIN; GNAS; IMPRINTING; RENAL; PROXIMAL; TUBULE; CYCLIC; AMP ID PROTEIN ALPHA-SUBUNIT; STIMULATORY G-PROTEIN; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PSEUDOHYPOPARATHYROIDISM TYPE-IA; G(S)ALPHA GENE GNAS1; GS-ALPHA; MOUSE MODEL; TRANSIENT PSEUDOHYPOPARATHYROIDISM; PREMATURE-INFANTS; ADENYLYL-CYCLASE AB Pseudohypoparathyroidism type-Ia (PHP-Ia), characterized by renal proximal tubular resistance to parathyroid hormone (PTH), results from maternal mutations of GNAS that lead to loss of -subunit of the stimulatory G protein (Gs) activity. Gs expression is paternally silenced in the renal proximal tubule, and this genomic event is critical for the development of PTH resistance, as patients display impaired hormone action only if the mutation is inherited maternally. The primary clinical finding of PHP-Ia is hypocalcemia, which can lead to various neuromuscular defects including seizures. PHP-Ia patients frequently do not present with hypocalcemia until after infancy, but it has remained uncertain whether PTH resistance occurs in a delayed fashion. Analyzing reported cases of PHP-Ia with documented GNAS mutations and mice heterozygous for disruption of Gnas, we herein determined that the manifestation of PTH resistance caused by the maternal loss of Gs, ie, hypocalcemia and elevated serum PTH, occurs after early postnatal life. To investigate whether this delay could reflect gradual development of paternal Gs silencing, we then analyzed renal proximal tubules isolated by laser capture microdissection from mice with either maternal or paternal disruption of Gnas. Our results revealed that, whereas expression of Gs mRNA in this tissue is predominantly from the maternal Gnas allele at weaning (3 weeks postnatal) and in adulthood, the contributions of the maternal and paternal Gnas alleles to Gs mRNA expression are equal at postnatal day 3. In contrast, we found that paternal Gs expression is already markedly repressed in brown adipose tissue at birth. Thus, the mechanisms silencing the paternal Gs allele in renal proximal tubules are not operational during early postnatal development, and this finding correlates well with the latency of PTH resistance in patients with PHP-Ia. (c) 2014 American Society for Bone and Mineral Research. C1 [Turan, Serap; Fernandez-Rebollo, Eduardo; Aydin, Cumhur; Zoto, Teuta; Reyes, Monica; Bounoutas, George; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Turan, Serap; Fernandez-Rebollo, Eduardo; Aydin, Cumhur; Zoto, Teuta; Reyes, Monica; Bounoutas, George; Marshansky, Vladimir; Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA USA. [Turan, Serap] Marmara Univ Sch Med Hosp, Istanbul, Turkey. [Fernandez-Rebollo, Eduardo] Hosp Clin Barcelona, Endocrinol & Nutr Unit, Diabet & Obes Lab, IDIBAPS, Barcelona, Spain. [Aydin, Cumhur] Gulhane Mil Med Acad, Dept Endodont, Ctr Dent Sci, Ankara, Turkey. [Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD USA. [Erben, Reinhold G.] Univ Vet Med, Dept Biomed Sci, Vienna, Austria. [Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU NIH/NIDDK [RO1DK073911]; NIDDK Division of Intramural Research; European Society for Paediatric Endocrinology through Lilly USA, LLC; Turkish Society of Pediatric Endocrinology and Diabetes FX We thank Drs Harald Juppner and Henry Kronenberg for insightful discussions and critically reviewing the manuscript. This study was funded in part by NIH/NIDDK grant RO1DK073911 to MB and by the NIDDK Division of Intramural Research. ST was supported by a Sabbatical Leave Programme grant from the European Society for Paediatric Endocrinology through an educational grant from Lilly USA, LLC, and Turkish Society of Pediatric Endocrinology and Diabetes. NR 76 TC 18 Z9 18 U1 0 U2 1 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 MAR PY 2014 VL 29 IS 3 BP 749 EP 760 DI 10.1002/jbmr.2070 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB0CF UT WOS:000331458700026 PM 23956044 ER PT J AU Matura, LA McDonough, A Carroll, DL AF Matura, Lea Ann McDonough, Annette Carroll, Diane L. TI Health-Related Quality of Life and Psychological States in Patients With Pulmonary Arterial Hypertension SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE affect; health-related quality of life; pulmonary arterial hypertension ID CONGESTIVE-HEART-FAILURE; REPORTED OUTCOMES; REVEAL REGISTRY; VALIDATION; QUESTIONNAIRE; DISABILITY; EXPERIENCE; SCLEROSIS; SYMPTOMS; CAMPHOR AB Background: Pulmonary arterial hypertension (PAH) is a chronic illness that impairs physical function and leads to right-sided heart failure and premature death. There is limited knowledge on health-related quality of life (HRQOL) and psychological states in patients with PAH. Objective: The aim of this study was to determine the HRQOL and the psychological states of patients with PAH along with predictors of HRQOL. Methods: In a cross-sectional design, participants with PAH completed the Medical Outcomes Study Short Form-36 v2 to measure generic HRQOL, the US Cambridge Pulmonary Hypertension Outcome Review to measure disease-specific HRQOL, and the Profile of Mood States to measure the psychological states. Descriptive statistics were used to calculate all sociodemographic and clinical data and were expressed as means and standard deviations for continuous variables and as frequencies and proportions for dichotomous and nominal variables. The statistical significance level was set at P < 0.05. A multiple linear regression analysis was performed to examine the sociodemographic and clinical variables as predictors of HRQOL. A bivariate analysis of the sociodemographic and clinical variables was performed to determine correlates with HRQOL. The variables that correlated with HRQOL at the 0.20 level of significance were included. Results: There were 149 participants, 127 women and 22 men, with a mean age of 53.5 years. The participants demonstrated diminished general health, physical functioning, role physical, and vitality on the Short Form-36 v2. Functional class, education level, oxygen use, years since diagnosis, and calcium channel blocker therapy were predictive of poorer HRQOL. Conclusions: Patients with PAH are experiencing diminished physical health and HRQOL. Future studies are needed to design and test interventions to improve HRQOL. C1 [Matura, Lea Ann] Univ Penn, Sch Nursing, Dept Biobehav Hlth Sci, Philadelphia, PA 19104 USA. [McDonough, Annette] Univ Massachusetts, Dept Nursing, Lowell, MA USA. [Carroll, Diane L.] Massachusetts Gen Hosp, Inst Patient Care, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Matura, LA (reprint author), Univ Penn, Sch Nursing, Claire M Fagin Hall,418 Curie Blvd,Room 322, Philadelphia, PA 19104 USA. EM matura@nursing.upenn.edu FU Bouve College of Health Sciences, Northeastern University; Sigma Theta Tau International Gamma Epsilon grant FX This study was partially funded by a Bouve College of Health Sciences, Northeastern University, intramural grant and a Sigma Theta Tau International Gamma Epsilon grant. NR 43 TC 11 Z9 11 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 EI 1550-5049 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD MAR-APR PY 2014 VL 29 IS 2 BP 178 EP 184 DI 10.1097/JCN.0b013e318275330d PG 7 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA AB2UX UT WOS:000331648700012 PM 23151837 ER PT J AU Peixoto, D Gagne, LS Hammond, SP Gilmore, ET Joyce, AC Soiffer, RJ Marty, FM AF Peixoto, Driele Gagne, Lisa S. Hammond, Sarah P. Gilmore, Erin T. Joyce, Amy C. Soiffer, Robert J. Marty, Francisco M. TI Isavuconazole Treatment of a Patient with Disseminated Mucormycosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IDENTIFICATION; ASPERGILLOSIS; POSACONAZOLE AB We report a patient with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated mucormycosis due to Rhizomucor pusillus/R. miehei involving lung, brain, and skin. After failing posaconazole and being intolerant to amphotericin, he was treated effectively with isavuconazole for over 6 months despite ongoing treatment for relapsed leukemia. C1 [Peixoto, Driele; Gagne, Lisa S.; Hammond, Sarah P.; Gilmore, Erin T.; Marty, Francisco M.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Hammond, Sarah P.; Joyce, Amy C.; Soiffer, Robert J.; Marty, Francisco M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hammond, Sarah P.; Soiffer, Robert J.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Dept Med, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. EM fmarty@partners.org FU Astellas; Merck FX F.M.M. has received research grant support from Astellas and consulting honoraria from Astellas and Merck. S.P.H. has received research grant support from Merck. All of the other authors declare that they have no conflicts of interest. NR 14 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2014 VL 52 IS 3 BP 1016 EP 1019 DI 10.1128/JCM.03176-13 PG 4 WC Microbiology SC Microbiology GA AC0DE UT WOS:000332164200052 PM 24403304 ER PT J AU Runchey, SS Boyko, EJ Ioannou, GN Utzschneider, KM AF Runchey, Shauna S. Boyko, Edward J. Ioannou, George N. Utzschneider, Kristina M. TI Relationship between serum circulating insulin-like growth factor-1 and liver fat in the United States SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE fatty liver; insulin-like growth factor binding protein-3; insulin-like growth factor I; national health and nutrition examination survey ID NUTRITION EXAMINATION SURVEY; PROTEIN-3 IGFBP-3 LEVELS; FACTOR BINDING PROTEIN-3; GH-DEFICIENT ADULTS; 3RD NATIONAL-HEALTH; NONALCOHOLIC STEATOHEPATITIS; IGF-I; HORMONE DEFICIENCY; HEPATIC STEATOSIS; QUALITY-CONTROL AB Background and AimNonalcoholic fatty liver disease (NAFLD), circulating insulin-like growth factor-1 (IGF-1), and IGF-1/IGF-binding protein-3 (IGFBP-3) concentrations are associated with adiposity and insulin resistance. We aimed to determine whether serum IGF-1, IGFBP-3, and IGF-1/IGFBP-3 are associated with presence or severity of NAFLD independent of potential confounding. MethodsWe performed a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey, 1988-1994, a representative sample of the United States adult population. Among participants who had a fasting blood draw and ultrasound examination, we excluded those with missing data, viral hepatitis, iron overload, excessive alcohol intake, pregnancy, or taking glucose-lowering therapy, yielding 4172 adults for this analysis. ResultsIn logistic regression analyses adjusted for age, gender, and race/ethnicity, higher IGF-1 and IGF-1/IGFBP-3 quartiles were associated with lower likelihood of NAFLD and lower grade steatosis. These associations became non-significant when further adjusted for adiposity (body mass index, waist circumference) with the exception of the association between IGF-1/IGFBP-3 and severity of NAFLD which remained significant after adjustment for homeostasis model assessment for insulin resistance (HOMA-IR) (odds ratio [95% CI]: Q3: 0.71 [0.53-0.96], Q4: 0.62 [0.43-0.89]) and adiposity (Q4: 0.67 [0.47-0.96]). Full adjustment (age, gender, race/ethnicity, adiposity, HOMA-IR, A1C%) further attenuated associations between IGF-1 or IGF-1/IGFBP-3 and liver fat such that they were no longer significant. ConclusionsAdiposity explains much of the observed association between IGF-1 or IGF-1/IGFBP-3 and liver fat. These findings do not support a direct role for the growth hormone-IGF-1/IGFBP-3 axis in the pathophysiology of NAFLD. C1 [Runchey, Shauna S.] Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. [Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Ioannou, George N.] VA Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA 98108 USA. [Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. [Utzschneider, Kristina M.] Univ Washington, Seattle, WA 98108 USA. RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Endocrinol, 1660 S Columbian Way 151, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu FU NIDDK DRC [P30DK017047]; [T32HL007028] FX Grants and fellowships supporting the writing of this paper: T32HL007028, NIDDK DRC grant number P30DK017047. NR 38 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0815-9319 EI 1440-1746 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2014 VL 29 IS 3 BP 589 EP 596 DI 10.1111/jgh.12437 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AB0GH UT WOS:000331469400029 PM 24716226 ER PT J AU Gilpin, SE Guyette, JP Gonzalez, G Ren, X Asara, JM Mathisen, DJ Vacanti, JP Ott, HC AF Gilpin, Sarah Elizabeth Guyette, Jacques P. Gonzalez, Gabriel Ren, Xi Asara, John M. Mathisen, Douglas J. Vacanti, Joseph P. Ott, Harald C. TI Perfusion decellularization of human and porcine lungs: Bringing the matrix to clinical scale SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE organ engineering; organ scaffolds; acellular matrix; recellularization; decellularization ID EMBRYONIC STEM-CELLS; IN-VITRO; EXTRACELLULAR-MATRIX; DE-CELLULARIZATION; RE-CELLULARIZATION; SCAFFOLDS; DIFFERENTIATION; TRANSPLANTATION; PROGENITORS; SYSTEM AB BACKGROUND: Organ engineering is a theoretical alternative to allotransplantation for end-stage organ failure. Whole-organ scaffolds can be created by detergent perfusion via the native vasculature, generating an acellular matrix suitable for recellularization with selected cell types. We aimed to up-scale this process, generating biocompatible scaffolds of a clinically relevant scale. METHODS: Rat, porcine, and human lungs were decellularized by detergent perfusion at constant pressures. Collagen, elastin, and glycosaminoglycan content of scaffolds were quantified by colorimetric assays. Proteomic analysis was performed by microcapillary liquid chromatography tandem mass spectrometry. Extracellular matrix (ECM) slices were cultured with human umbilical vein endothelial cells (HUVEC), small airway epithelial cells (SAEC), or pulmonary alveolar epithelial cells (PAECs) and evaluated by time-lapse live cell microscopy and MTT (3[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Whole-organ culture was maintained under constant-pressure media perfusion after seeding with PAECs. RESULTS: Rat lungs were decellularized using: (1) sodium dodecyl sulfate (SDS), (2) sodium deoxycholate (SDC), or (3) 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Resulting scaffolds showed comparable loss of DNA but greatest preservation of ECM components in SDS-decellularized lungs. Porcine (n = 10) and human (n = 7) lungs required increased SDS concentration, perfusion pressures, and time to achieve decellularization as determined by loss of DNA, with preservation of intact matrix composition and lung architecture. Proteomic analysis of human decellularized lungs further confirmed ECM preservation. Recellularization experiments confirmed scaffold biocompatibility when cultured with mature cell phenotypes and scaffold integrity for the duration of biomimetic culture. CONCLUSIONS: SDS-based perfusion decellularization can be applied to whole porcine and human lungs to generate biocompatible organ scaffolds with preserved ECM composition and architecture. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Gilpin, Sarah Elizabeth; Guyette, Jacques P.; Gonzalez, Gabriel; Ren, Xi; Asara, John M.; Mathisen, Douglas J.; Vacanti, Joseph P.; Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Gilpin, Sarah Elizabeth; Guyette, Jacques P.; Gonzalez, Gabriel; Ren, Xi; Asara, John M.; Mathisen, Douglas J.; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA. [Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Div Pediat Surg, Boston, MA 02114 USA. [Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Ott, Harald C.] Harvard Stem Cell Inst, Boston, MA USA. RP Ott, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 185 Cambridge St,CPZN 4812, Boston, MA 02114 USA. EM hott@partners.org OI Gonzalez, Gabriel /0000-0003-1842-3119 FU United Therapeutics Corporation; National Institutes of Health (NIH) [DP2-OD008749-01] FX This study was supported by the United Therapeutics Corporation and the National Institutes of Health (NIH) Director's New Innovator Award (DP2-OD008749-01). NR 41 TC 41 Z9 42 U1 8 U2 45 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAR PY 2014 VL 33 IS 3 BP 298 EP 308 DI 10.1016/j.healun.2013.10.030 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AC3TL UT WOS:000332444000012 PM 24365767 ER PT J AU Bates, KE Bird, GL Shea, JA Apkon, M Shaddy, RE Metlay, JP AF Bates, Katherine E. Bird, Geoffrey L. Shea, Judy A. Apkon, Michael Shaddy, Robert E. Metlay, Joshua P. TI A tool to measure shared clinical understanding following handoffs to help evaluate handoff quality SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID RESIDENT SIGN-OUT; CARE AB BACKGROUND Information exchanged during handoffs contributes importantly to a team's shared mental model. There is no established instrument to measure shared clinical understanding as a marker of handoff quality. OBJECTIVE To study the reliability, validity, and feasibility of the pediatric cardiology Patient Knowledge Assessment Tool (PKAT), a novel instrument designed to measure shared clinical understanding for pediatric cardiac intensive care unit patients. DESIGN To estimate reliability, 10 providers watched 9 videotaped simulated handoffs and then completed a PKAT for each scenario. To estimate construct validity, we studied 90 handoffs in situ by having 4 providers caring for an individual patient each complete a PKAT following handoff. Construct validity was assessed by testing the effects of provider preparation and patient complexity on agreement levels. SETTING A 24-bed pediatric cardiac intensive care unit in a freestanding children's hospital. RESULTS Video simulation results demonstrated score reliability. Average inter-rater agreement by item ranged from 0.71 to 1.00. During in situ testing, agreement by item ranged from 0.41 to 0.87 (median 0.77). Construct validity for some items was supported by lower agreement rates for patients with increased length of stay and increased complexity. DISCUSSION Results suggest that the PKAT has high inter-rater reliability and can detect differences in understanding between handoff senders and receivers for routine and complex patients. Additionally, the PKAT is feasible for use in a real-time clinical environment. The PKAT or similar instruments could be used to study effects of handoff improvement efforts in inpatient settings. Journal of Hospital Medicine 2014;9:142-147. (c) 2014 Society of Hospital Medicine C1 [Bates, Katherine E.; Shaddy, Robert E.] Childrens Hosp Philadelphia, Div Cardiol, Cardiac Ctr, Philadelphia, PA 19104 USA. [Bates, Katherine E.; Shea, Judy A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Bird, Geoffrey L.] Childrens Hosp Philadelphia, Dept Anesthesia & Crit Care Med, Cardiac Ctr, Philadelphia, PA 19104 USA. [Shea, Judy A.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Apkon, Michael] Childrens Hosp Philadelphia, Dept Anesthesia & Crit Care Med, Philadelphia, PA 19104 USA. [Metlay, Joshua P.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP Bates, KE (reprint author), Childrens Hosp Philadelphia, Div Cardiol, Cardiac Ctr, 3401 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM bateske1@email.chop.edu FU Mid-Career Investigator Award in Patient Oriented Research [K24-AI073957]; [NICHD/T32 HD060550]; [NHLBI/T32 HL07915] FX Dr. Bates was supported in part by NICHD/T32 HD060550 and NHLBI/T32 HL07915 grant funding. Dr. Metlay was supported by a Mid-Career Investigator Award in Patient Oriented Research (K24-AI073957). The authors report no conflicts of interest. NR 21 TC 4 Z9 4 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD MAR PY 2014 VL 9 IS 3 BP 142 EP 147 DI 10.1002/jhm.2147 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA AB9YW UT WOS:000332152600002 PM 24482325 ER PT J AU Pallin, DJ Espinola, JA Camargo, CA AF Pallin, Daniel J. Espinola, Janice A. Camargo, Carlos A., Jr. TI US population aging and demand for inpatient services SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID CARE; LONGEVITY AB US inpatient capacity increased until the 1970s, then declined. The US Census Bureau expects the population aged >= 65 years to more than double by 2050. The implications for national inpatient capacity requirements have not been quantified. Our objective was to calculate the number of hospital admissions that will be necessitated by population aging, ceteris paribus. We estimated 2011 nationwide age-specific hospitalization rates using data from the Nationwide Inpatient Sample and Census data. We applied these rates to the population expected by the Census Bureau to exist through 2050. By 2050, the US population is expected to increase by 41%. Our analysis suggests that based on expected changes in the population age structure by then, the annual number of hospitalizations will increase by 67%. Thus, inpatient capacity would have to expand 18% more than population growth to meet demand. Total aggregate inpatient days is projected to increase 22% more than population growth. The total projected growth in required inpatient capacity is 72%, accounting for both number of admissions and length of stay. This analysis accounts only for changes in the population's age structure. Other factors could increase or decrease demand, as discussed in the article. Journal of Hospital Medicine 2014;9:193-196. (c) 2014 Society of Hospital Medicine C1 [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 16 TC 4 Z9 4 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD MAR PY 2014 VL 9 IS 3 BP 193 EP 196 DI 10.1002/jhm.2145 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AB9YW UT WOS:000332152600011 PM 24464735 ER PT J AU De Rienzo, A Yeap, BY Cibas, ES Richards, WG Dong, LS Gill, RR Sugarbaker, DJ Bueno, R AF De Rienzo, Assunta Yeap, Beow Y. Cibas, Edmund S. Richards, William G. Dong, Lingsheng Gill, Ritu R. Sugarbaker, David J. Bueno, Raphael TI Gene Expression Ratio Test Distinguishes Normal Lung from Lung Tumors in Solid Tissue and FNA Biopsies SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID FINE-NEEDLE-ASPIRATION; PROFILING DATA; CANCER; CLASSIFICATION; MESOTHELIOMA; ADENOCARCINOMA; MANAGEMENT; CT; CARCINOMAS; DIAGNOSIS AB Lung cancer is the Leading cause of cancer-related deaths worldwide. Prognosis and survival are dependent on cell type, early detection, and surgical treatment. Hence, optimal screening strategies and new therapies are urgently required. Although surveillance with Low-dose computed tomography can reduce lung cancer mortality by 20%, the number of false-positive detections is significant. Tissue diagnosis aids in the identification of benign nodules, reducing the number of false positive detections. To determine whether molecular testing of fine-needle aspirations (FNAs) can reduce false-positive detections, we developed a gene expression-based test that distinguishes normal from cancerous Lung tissues. The test first was applied to published microarray data, showing overall sensitivity and specificity values of 95% (95% CI, 90%-98%) and 100% (95% CI, 40%-100%), respectively. Subsequently, it was validated on 30 solid and ex vivo FNA Lung cancer tumor samples and matched normal Lung specimens using real-time PCR. The validation test was 93% (95% CI, 78%-99%) sensitive and 100% (95% CI, 88%-100%) specific for the detection of tumor versus normal lung on solid samples, whereas FNA specimens yielded a sensitivity of 91% (95% CI, 72%-99%) and a specificity of 94% (95% CI, 70%-100%). This study supports the hypothesis that the gene-ratio approach reliably distinguishes normal Lung from cancerous tissues in FNA samples and can be optimized to diagnose benign nodules. C1 [De Rienzo, Assunta; Richards, William G.; Dong, Lingsheng; Sugarbaker, David J.; Bueno, Raphael] Brigham & Womens Hosp, Div Thorac Surg, Thorac Surg Oncol Lab, Boston, MA 02115 USA. [De Rienzo, Assunta; Richards, William G.; Dong, Lingsheng; Sugarbaker, David J.; Bueno, Raphael] Brigham & Womens Hosp, Div Thorac Surg, Int Mesothelioma Program, Boston, MA 02115 USA. [Gill, Ritu R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gill, Ritu R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [De Rienzo, Assunta; Richards, William G.; Sugarbaker, David J.; Bueno, Raphael] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Cibas, Edmund S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Dong, Lingsheng] Harvard Univ, Sch Med, IT Res Comp, Boston, MA 02115 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Bueno, R (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM rbueno@partners.org FU National Cancer Institute [R21CA098501, RO1CA120528]; International Mesothelioma Program at Brigham and Women's Hospital; Maurice Favell Fund at the Vancouver Foundation FX Supported by grants from the National Cancer Institute (R21CA098501 and RO1CA120528), the International Mesothelioma Program at Brigham and Women's Hospital, and the Maurice Favell Fund at the Vancouver Foundation (R.B.). NR 34 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAR PY 2014 VL 16 IS 2 BP 267 EP 272 DI 10.1016/j.jmoldx.2013.11.008 PG 6 WC Pathology SC Pathology GA AC0NZ UT WOS:000332193300014 PM 24412526 ER PT J AU Bodaghabadi, M Riazi, H Aran, S Bitaraf, MA Alikhani, M Alahverdi, M Mohamadi, M Shalileh, K Azar, M AF Bodaghabadi, Mohammad Riazi, Hooman Aran, Shima Bitaraf, Mohammad Ali Alikhani, Mazdak Alahverdi, Mahmud Mohamadi, Masoumeh Shalileh, Keivan Azar, Maziar TI Repeated Transsphenoidal Surgery or Gamma Knife Radiosurgery in Recurrent Cushing Disease After Transsphenoidal Surgery SO JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY LA English DT Article DE transsphenoidal surgery; gamma knife radiosurgery; Cushing disease ID PITUITARY-ADENOMAS; STEREOTACTIC RADIOSURGERY; MANAGEMENT AB BackgroundThis study compared Gamma knife radiosurgery (GKRS) and repeated transsphenoidal adenomectomy (TSA) to find the best approach for recurrence of Cushing disease (CD) after unsuccessful first TSA. Material and MethodsFifty-two patients with relapse of CD after TSA were enrolled and randomly underwent a second surgery or GKRS as the next therapeutic approach. They were followed for a mean period of 3.050.8 years by physical examination and hormone measurement as well as magnetic resonance imaging. ResultsNo significant difference was observed in sex ratio, mean age, adenoma type, follow-up duration, and initial hormone level between the two groups. No significant relationship was found between preoperative 24-hour free urine cortisol and disease-free months or tumor volume among both groups. Our statistical analysis showed higher recurrence-free interval in the GKRS group compared with TSA group. ConclusionWith longer recurrence-free interval, GKRS could be considered a good treatment alternative to repeated TSA in recurrent CD. C1 [Bodaghabadi, Mohammad; Bitaraf, Mohammad Ali] Univ Tehran Med Sci, Dept Neuroradiosurg, Tehran 1417753851, Iran. [Riazi, Hooman] Univ Tehran Med Sci, Imam Khomeini Hosp, Dept Neurosurg, Tehran 1417753851, Iran. [Aran, Shima] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Bitaraf, Mohammad Ali; Alikhani, Mazdak; Azar, Maziar] Iran Gamma Knife Ctr, Dept Neuroradiosurg, Tehran, Iran. [Alahverdi, Mahmud] Univ Tehran Med Sci, Dept Med Phys & Biomed Engn, Tehran 1417753851, Iran. [Mohamadi, Masoumeh] Univ Tehran Med Sci, Imam Khomeini Hosp, Dept Neuroradiosurg, Tehran 1417753851, Iran. [Shalileh, Keivan] Univ Tehran Med Sci, Dept Radiol, Tehran 1417753851, Iran. RP Bitaraf, MA (reprint author), Univ Tehran Med Sci, Imam Khomeini Hosp, Dept Neurosurg, Tehran 1417753851, Iran. EM tums.research.center@gmail.com NR 28 TC 2 Z9 2 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6315 EI 2193-6323 J9 J NEUROL SURG PART A JI J. Neurol. Surg. Part A PD MAR PY 2014 VL 75 IS 2 BP 91 EP 97 DI 10.1055/s-0033-1345688 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AB3QB UT WOS:000331704200003 PM 23965751 ER PT J AU Rannikmae, K Kalaria, RN Greenberg, SM Chui, HC Schmitt, FA Samarasekera, N Salman, RA Sudlow, CLM AF Rannikmaee, Kristiina Kalaria, Rajesh N. Greenberg, Steven M. Chui, Helena C. Schmitt, Frederick A. Samarasekera, Neshika Salman, Rustam Al-Shahi Sudlow, Cathie L. M. TI APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE Amyloid; Cerebrovascular Disease; Apolipoproteins; Meta-Analysis; Systematic Reviews ID CEREBRAL AMYLOID ANGIOPATHY; LOBAR INTRACEREBRAL HEMORRHAGE; APOLIPOPROTEIN-E EPSILON-2; GENETIC ASSOCIATION; VASCULAR PATHOLOGY; ALZHEIMERS-DISEASE; E GENOTYPE AB Objectives Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the epsilon 4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both APOE-epsilon 4 and epsilon 2 are associated with lobar ICH. The generally accepted explanation is that APOE-epsilon 4 promotes vascular amyloid deposition, while APOE-epsilon 2 promotes progression to severe CAA with associated vasculopathic changes that cause vessel rupture and ICH. We assessed the evidence for these allele-specific effects. Methods We systematically identified published studies with data on APOE genotype and histopathological assessment of postmortem brains for CAA severity. We obtained unpublished data from these for meta-analyses of the effects of epsilon 4-containing (epsilon 4+) and epsilon 2-containing (epsilon 2+) genotypes on progression to severe CAA. Results Of six eligible studies (543 eligible participants), data were available from 5 (497 participants, 353 with CAA). Meta-analyses showed a possible association of epsilon 4+ genotypes with severe CAA (epsilon 4+ vs epsilon 4-: severe vs mild/moderate CAA, OR 2.5, 95% CI 1.4 to 4.5, p=0.002; severe vs moderate CAA, OR 1.7, 95% CI 0.9 to 3.1, p=0.11). For epsilon 2+ versus epsilon 2- genotypes, there was no significant association, but the very small number of participants with epsilon 2+ genotypes (22) precluded reliable estimates. Conclusions We found a possible association of severe CAA with APOE-epsilon 4 but not APOE-epsilon 2. However, our findings do not exclude a biologically meaningful association between APOE-epsilon 2 and severe CAA. Further work is needed to elucidate fully the allele-specific associations of APOE with CAA and their mechanisms. C1 [Rannikmaee, Kristiina; Samarasekera, Neshika; Salman, Rustam Al-Shahi; Sudlow, Cathie L. M.] Univ Edinburgh, Div Clin Neurosci, Ctr Clin Brain Sci, Edinburgh EH4 2XU, Midlothian, Scotland. [Kalaria, Rajesh N.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Ctr Stroke Res, Boston, MA 02114 USA. [Chui, Helena C.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Schmitt, Frederick A.] Univ Kentucky, Dept Neurol, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. [Sudlow, Cathie L. M.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. RP Sudlow, CLM (reprint author), Univ Edinburgh, Div Clin Neurosci, Ctr Clin Brain Sci, Western Gen Hosp, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland. EM cathie.sudlow@ed.ac.uk OI Al-Shahi Salman, Rustam/0000-0002-2108-9222 FU European Neurological Society Scientific Fellowship; UK Medical Research Council research training fellowship [G0900428]; UK Medical Research Council senior clinical fellowship [G1002605]; Scottish Funding Council; National Institutes of Health [2R01 AG26484] FX This work was supported by: European Neurological Society Scientific Fellowship (KR); UK Medical Research Council research training fellowship (G0900428, NS); UK Medical Research Council senior clinical fellowship (G1002605, RA-SS); Scottish Funding Council (CLMS); and National Institutes of Health (2R01 AG26484, SMG). National Institute on Aging (P3OAGO28383; RO1AGO19241; RO1AGO38651; FAS). NR 24 TC 19 Z9 20 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAR PY 2014 VL 85 IS 3 BP 300 EP 305 DI 10.1136/jnnp-2013-306485 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA AA7HP UT WOS:000331268600015 PM 24163429 ER PT J AU Zeliadt, SB Loggers, ET Slatore, CG Au, DH Hebert, PL Klein, GJ Kessler, LG Backhus, LM AF Zeliadt, Steven B. Loggers, Elizabeth T. Slatore, Christopher G. Au, David H. Hebert, Paul L. Klein, Gregory J. Kessler, Larry G. Backhus, Leah M. TI Preoperative PET and the Reduction of Unnecessary Surgery Among Newly Diagnosed Lung Cancer Patients in a Community Setting SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE positron emission tomography; thoracotomy; community practice; non-small cell lung cancer; cancer staging ID POSITRON-EMISSION-TOMOGRAPHY; COMMON OUTCOMES; VETERANS; MANAGEMENT; TRIAL; RISK; PLUS; CT AB The goals of this study were to examine the real-world effectiveness of PET in avoiding unnecessary surgery for newly diagnosed patients with non-small cell lung cancer. Methods: A cohort of 2,977 veterans with non-small cell lung cancer between 1997 and 2009 were assessed for use of PET during staging and treatment planning. The subgroup of 976 patients who underwent resection was assessed for several outcomes, including pathologic evidence of mediastinal lymph node involvement, distant metastasis, and 12-mo mortality. We anticipated that PET may have been performed selectively on the basis of unobserved characteristics (e.g., providers ordered PET when they suspected disseminated disease). Therefore, we conducted an instrumental variable analysis, in addition to conventional multivariate logistic regression, to reduce the influence of this potential bias. This type of analysis attempts to identify an additional variable that is related to receipt of treatment but not causally associated with the outcome of interest, similar to randomized assignment. The instrument here was calendar time. This analysis can be informative when patients do not receive the treatment that the instrument suggests they "should" have received. Results: Overall, 30.3% of patients who went to surgery were found to have evidence of metastasis uncovered during the procedure or within 12 mo, indicating that nearly one third of patients underwent surgery unnecessarily. The use of preoperative PET increased substantially over the study period, from 9% to 91%. In conventional multivariate analyses, PET use was not associated with a decrease in unnecessary surgery (odds ratio, 0.87; 95% confidence interval, 0.66-1.16; P = 0.351). However, a reduction in unnecessary surgery (odds ratio, 0.53; 95% confidence interval, 0.34-0.82; P = 0.004) was identified in the instrumental variable analyses, which attempted to account for potentially unobserved confounding. Conclusion: PET has now become routine in preoperative staging and treatment planning in the community and appears to be beneficial in avoiding unnecessary surgery. Evaluating the effectiveness of PET appears to be influenced by potentially unmeasured adverse selection of patients, especially when PET first began to be disseminated in the community. C1 [Zeliadt, Steven B.; Au, David H.; Hebert, Paul L.] Dept Vet Affairs Med Ctr, Seattle, WA 98108 USA. [Zeliadt, Steven B.; Hebert, Paul L.; Klein, Gregory J.; Kessler, Larry G.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Loggers, Elizabeth T.] Grp Hlth Res Inst, Seattle, WA USA. [Loggers, Elizabeth T.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Pulm & Crit Care Sect, Portland, OR USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Pulm & Crit Care Serv, Seattle, WA USA. [Au, David H.] Univ Washington, Div Pulm Med, Seattle, WA 98195 USA. [Backhus, Leah M.] VA Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. [Backhus, Leah M.] Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA. RP Zeliadt, SB (reprint author), Dept Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM steven.zeliadt@va.gov OI Slatore, Christopher/0000-0003-0958-8122 FU National Cancer Institute for the "ADVancing Innovative Comparative Effectiveness research in cancer diagnostics (ADVICE)" [1RC2CA148433-01]; VA Puget Sound Health Care System, Seattle, Washington; Health Services Research and Development Career Development Award from the Department of Veterans Affairs and resources from the Portland VA Medical Center, Portland, Oregon FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This material is the result of work supported by a grant from the National Cancer Institute for the "ADVancing Innovative Comparative Effectiveness research in cancer diagnostics (ADVICE)" study, 1RC2CA148433-01; by resources from the VA Puget Sound Health Care System, Seattle, Washington; and in part by a Health Services Research and Development Career Development Award from the Department of Veterans Affairs and resources from the Portland VA Medical Center, Portland, Oregon. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. Government. No other potential conflict of interest relevant to this article was reported. NR 23 TC 4 Z9 4 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 2014 VL 55 IS 3 BP 379 EP 385 DI 10.2967/jnumed.113.124230 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AC2RQ UT WOS:000332352100017 PM 24449594 ER PT J AU Erickson, JI AF Erickson, Jeanette Ives TI Leading Unplanned Change SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material AB The article presents reflections on how Magnet (R) principles help nurse leaders through unplanned change using the 1-year anniversary of the Boston Marathon bombings and the response at Massachusetts General Hospital as an exemplar. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,BUL 230, Boston, MA 02114 USA. EM jiveserickson@partners.org NR 1 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAR PY 2014 VL 44 IS 3 BP 125 EP 126 DI 10.1097/NNA.0000000000000037 PG 2 WC Nursing SC Nursing GA AC0GS UT WOS:000332173400002 PM 24531281 ER PT J AU Johnson, AL Jung, L Song, Y Brown, KC Weaver, MT Richards, KC AF Johnson, Arlene L. Jung, Lorena Song, Yeonsu Brown, Kathleen C. Weaver, Michael T. Richards, Kathy C. TI Sleep Deprivation and Error in Nurses Who Work the Night Shift: Erratum SO JOURNAL OF NURSING ADMINISTRATION LA English DT Correction C1 [Song, Yeonsu] VA Greater Los Angeles, Los Angeles, CA USA. NR 1 TC 0 Z9 0 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 EI 1539-0721 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAR PY 2014 VL 44 IS 3 BP 186 EP 186 DI 10.1097/NNA.0000000000000048 PG 1 WC Nursing SC Nursing GA AC0GS UT WOS:000332173400013 ER PT J AU Ross, SG Northman, L Morris, M Green, AL Ullrich, NJ AF Ross, Sarah G. Northman, Lisa Morris, Marybeth Green, Adam L. Ullrich, Nicole J. TI Cerebellar Mutism After Posterior Fossa Tumor Resection Case Discussion and Recommendations for Psychoeducational Intervention SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING LA English DT Article DE posterior fossa syndrome; neurocognitive function; cerebellar mutism syndrome; psychoeducation; speech disorder; posterior fossa tumor ID BRAIN-TUMORS; CHILDREN; CHILDHOOD; MEDULLOBLASTOMA; THERAPY AB Cerebellar mutism (also known as posterior fossa syndrome) is a relatively common complication of posterior fossa surgery for primary brain tumors in children. Many children with cerebellar mutism experience long-term adverse neurological, cognitive, and psychological sequelae and require extensive interdisciplinary support. This study illustrates a typical case of cerebellar mutism in a child after resection of medulloblastoma, followed by a review of associated symptoms, clinical course, and modulating factors. Additionally, recommendations for providing educational support to children with cerebellar mutism are explored. C1 [Ross, Sarah G.; Northman, Lisa; Morris, Marybeth; Green, Adam L.; Ullrich, Nicole J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Green, Adam L.; Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Ullrich, NJ (reprint author), Boston Childrens Hosp, Dept Neurol, 333 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu NR 21 TC 2 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-4542 EI 1532-8457 J9 J PEDIATR ONCOL NURS JI J. Pediatr. Oncol. Nurs. PD MAR PY 2014 VL 31 IS 2 BP 78 EP 83 DI 10.1177/1043454213518975 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA AC3AY UT WOS:000332388600002 PM 24608700 ER PT J AU Galanakos, SP Bot, AGJ Zoubos, AB Soucacos, PN AF Galanakos, Spyridon P. Bot, Arjan G. J. Zoubos, Aristides B. Soucacos, Panayotis N. TI Psychological and Social Consequences after Reconstruction of Upper Extremity Trauma: Methods of Detection and Management SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE psychological and social consequences; disability; upper extremity complex trauma; detection and prevention ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; PERIPHERAL-NERVE INJURY; SATISFACTION 12 MONTHS; HAND INJURY; HEALTH-STATUS; EMOTIONAL INTELLIGENCE; PATIENT SATISFACTION AB Upper extremity trauma and resulting disability is a stressful event and can affect a patient's personality. Several studies have shown that this injury type has serious psychological and/or social consequences. We systematically reviewed the evidence on the consequences of disability after a complex trauma (combination of soft tissue, osseous, vascular, and nerve involvement) of the upper extremity. We tried to find out the potential crucial factors that could determine the final hand function. In addition, we considered the challenges that need to be addressed to eliminate the adverse or negative effects that arise from upper limb trauma. In the literature, there is a growing interest to study changes in patients' quality of life and return to work. Psychological morbidity is an important part of patients' perceived general health. These issues could play an important role in the final functional outcome of the therapy. An early identification and treatment of trauma-related distress in patients may prevent progression of psychological pathology and mitigate negative effects on general health status. It may be important to evaluate the amount of psychological distress when caring for patients with hand injuries. C1 [Galanakos, Spyridon P.; Zoubos, Aristides B.; Soucacos, Panayotis N.] Univ Athens, ATTIKON Univ Hosp, Dept Orthopaed Surg 1, Athens, Greece. [Bot, Arjan G. J.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Galanakos, SP (reprint author), Rimini 1 St, Athens 12462, Greece. EM spgalanakos@gmail.com NR 142 TC 2 Z9 2 U1 0 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X EI 1098-8947 J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD MAR PY 2014 VL 30 IS 3 BP 193 EP 205 DI 10.1055/s-0033-1361838 PG 13 WC Surgery SC Surgery GA AB8DC UT WOS:000332019300007 PM 24347334 ER PT J AU Mattei, PL Corey, KC Kimball, AB AF Mattei, P. L. Corey, K. C. Kimball, A. B. TI Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Article ID SEVERE PLAQUE PSORIASIS; RANDOMIZED CONTROLLED-TRIAL; TO-SEVERE PSORIASIS; PLACEBO-CONTROLLED TRIAL; PHASE-III TRIAL; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; OPEN-LABEL EXTENSION; OF-LIFE; DOUBLE-BLIND; REPORTED OUTCOMES AB BackgroundMultiple metrics evaluate the efficacy of psoriasis treatment, but interestingly, the correlation between the mostly widely used clinical trial efficacy end point, the physician-rendered Psoriasis Area Severity Index PASI score and, the most widely used quality of life metric, the Dermatology Life Quality Index DLQI, is not always high. ObjectiveTo perform a systematic review to determine PASI to DLQI correlation. MethodsRCTs of biological agents for the treatment of moderate-to-severe psoriasis were reviewed in accordance with PRISMA guidelines. The mean percentage PASI improvement and change in mean DLQI values were recorded and compared for treatment groups from baseline to 10-16weeks of therapy. ResultsA search of the literature yielded 155 sources, of which 13 RCTs met inclusion and exclusion criteria. Percentage of PASI improvement from baseline correlates with DLQI changes with an r(2) value of 0.80 from baseline through weeks 10-16. When grouped by mean percentage reduction in PASI, agents demonstrating >75% mean reduction in PASI demonstrated a mean DLQI improvement over agents that achieved <75%-50% mean reduction in PASI or <50% mean reduction in PASI [minimal clinically important difference (MCID) 3.2]. In addition, a reduction in mean PASI of at least 75%, predicted a mean movement from DLQI band 3 to DLQI band 1, in all nine treatment arms demonstrating such efficacy. ConclusionsMean PASI and DLQI correlate predictably in patients with chronic moderate-to-severe plaque psoriasis undergoing treatment with biological agents. A reduction in PASI of at least 75% can translate to significant quality-of-life improvement in patients treated with these therapies. C1 [Mattei, P. L.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Corey, K. C.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Kimball, A. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM harvardskinstudies@partners.org FU National Psoriasis Foundation FX National Psoriasis Foundation Grant. NR 50 TC 29 Z9 33 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0926-9959 EI 1468-3083 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD MAR PY 2014 VL 28 IS 3 BP 333 EP 337 DI 10.1111/jdv.12106 PG 5 WC Dermatology SC Dermatology GA AA8ZP UT WOS:000331383800012 PM 23425140 ER PT J AU Flaherty, KT Hennig, M Lee, SJ Ascierto, PA Dummer, R Eggermont, AMM Hauschild, A Kefford, R Kirkwood, JM Long, GV Lorigan, P Mackensen, A McArthur, G O'Day, S Patel, PM Robert, C Schadendorf, D AF Flaherty, Keith T. Hennig, Michael Lee, Sandra J. Ascierto, Paolo A. Dummer, Reinhard Eggermont, Alexander M. M. Hauschild, Axel Kefford, Richard Kirkwood, John M. Long, Georgina V. Lorigan, Paul Mackensen, Andreas McArthur, Grant O'Day, Steven Patel, Poulam M. Robert, Caroline Schadendorf, Dirk TI Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials SO LANCET ONCOLOGY LA English DT Article ID STAGE IV MELANOMA; PROGRESSION-FREE SURVIVAL; PHASE-III; DOUBLE-BLIND; PLUS DACARBAZINE; CANCER; CHEMOTHERAPY; MULTICENTER; COMBINATION; INTERFERON-ALPHA-2B AB Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29-0.90) with a random-effects assumption, 0.85 (0.59-0.95) with a fixed-effects assumption, and 0.89 (0.68-0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81-0.99), which decreased to 0.93 (0.74-0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03-0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51-0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials. C1 [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA 02114 USA. [Hennig, Michael] GlaxoSmithKline, Biostat & Epidemiol, Munich, Germany. [Lee, Sandra J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lee, Sandra J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Ascierto, Paolo A.] Ist Nazl Tumori Fdn G Pascale, Unit Melanoma Canc Immunotherapy & Innovat Therap, Naples, Italy. [Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Eggermont, Alexander M. M.; Robert, Caroline] Paris Sud Univ Grand Paris, Villejuif, France. [Hauschild, Axel] Univ Hosp Kiel, Dept Dermatol, Univ Hosp Schleswig Holstein UKSH, Kiel, Germany. [Kefford, Richard] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. [Kefford, Richard] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Skin Canc Program, Pittsburgh, PA USA. [Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Long, Georgina V.] Univ Sydney, Sydney, NSW 2006, Australia. [Lorigan, Paul] Univ Manchester, Inst Canc Sci, Fac Med & Human Sci, Manchester, Lancs, England. [Mackensen, Andreas] Univ Erlangen Nurnberg, Dept Internal Med Hematol Oncol 5, Erlangen, Germany. [McArthur, Grant] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia. [O'Day, Steven] Beverly Hills Canc Ctr, Beverly Hills, CA USA. [Patel, Poulam M.] Univ Nottingham, Acad Unit Oncol, Nottingham NG7 2RD, England. [Robert, Caroline] INSERM Unit 981, Villejuif, France. [Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, D-45122 Essen, Germany. RP Schadendorf, D (reprint author), Univ Hosp Essen, Dept Dermatol, Hufelandstr 55, D-45122 Essen, Germany. EM dirk.schadendorf@uk-essen.de RI Lorigan, Paul/J-6898-2015 OI Lorigan, Paul/0000-0002-8875-2164 FU Merck; Bristol Myers-Squibb; Roche; BMS; Novartis FX DS has received research funding from Merck, and has had consultancies or participated in advisory boards with GlaxoSmithKline, Roche, Bristol Myers-Squibb, Merck, Amgen, Delcath, and Novartis. KTF has had consultancies with Roche, GlaxoSmithKline, Celgene, and Novartis. GVL is consultant advisor to GlaxoSmithKline, Roche, Novartis, Bristol Myers-Squibb, and Amgen, and has received honoraria from GlaxoSmithKline and Roche. AM has participated in advisory boards with GlaxoSmithKline, Roche, and Bristol Myers-Squibb. PAA has received research funding from Bristol Myers-Squibb, and has had consultancies or participated in advisory boards for Bristol Myers-Squibb, Roche-Genentech, GlaxoSmithKline, and Novartis. PMP has had consultancies or participated in advisory boards with GlaxoSmithKline, Roche, Bristol Myers-Squibb, and Schering Plough Merck. CR is consultant for GlaxoSmithKline, Roche, Novartis, Bristol Myers-Squibb, Merck, Amgen, and Bayer. AH is consultant advisor and received honoraria from Roche, Genentech, Amgen, GlaxoSmithKline, Bristol Myers Squibb, Merck/MSD, Pfizer, and Novartis. RK has received institutional reimbursement for advisory board participation from GlaxoSmithKline, Novartis, Roche, BMS, and Sanofi-Aventis and institutional reimbursement-honoraria for educational symposia from Merck. SO'D has received research support from Merck, Roche, BMS, and Novartis and served on the speakers bureau of Merck and BMS. MH is an employee at GlaxoSmithKline in Germany. PL has had consultancies or participated in advisory boards of BMS, Roche, GlaxoSmithKline, Novartis, and Celgene. GM has had consultancies or participated in advisory boards with GlaxoSmithKline, Roche, Bristol Myers-Squibb, and Schering Plough/Merck. AMME received honorary fees for advisory board participation for Amgen, BMS, GlaxoSmithKline, MedImmune, and Merck. JMK has received honorary fees for advisory board participation for BMS, GlaxoSmithKline, Celgene, Vical, and Merck. All other authors declare that they have no conflicts of interest. NR 30 TC 21 Z9 21 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2014 VL 15 IS 3 BP 297 EP 304 DI 10.1016/S1470-2045(14)70007-5 PG 8 WC Oncology SC Oncology GA AC3FF UT WOS:000332399900040 PM 24485879 ER PT J AU McArthur, GA Chapman, PB Robert, C Larkin, J Haanen, JB Dummer, R Ribas, A Hogg, D Hamid, O Ascierto, PA Garbe, C Testori, A Maio, M Lorigan, P Lebbe, C Jouary, T Schadendorf, D O'Day, SJ Kirkwood, JM Eggermont, AM Dreno, B Sosman, JA Flaherty, KT Yin, M Caro, I Cheng, S Trunzer, K Hauschild, A AF McArthur, Grant A. Chapman, Paul B. Robert, Caroline Larkin, James Haanen, John B. Dummer, Reinhard Ribas, Antoni Hogg, David Hamid, Omid Ascierto, Paolo A. Garbe, Claus Testori, Alessandro Maio, Michele Lorigan, Paul Lebbe, Celeste Jouary, Thomas Schadendorf, Dirk O'Day, Stephen J. Kirkwood, John M. Eggermont, Alexander M. Dreno, Brigitte Sosman, Jefferey A. Flaherty, Keith T. Yin, Ming Caro, Ivor Cheng, Suzanne Trunzer, Kerstin Hauschild, Axel TI Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study SO LANCET ONCOLOGY LA English DT Article ID METASTATIC MELANOMA; MALIGNANT-MELANOMA; ONCOGENIC MUTATIONS; BRAF; DACARBAZINE; INHIBITION; PATHWAY; V600E; MULTICENTER; STATISTICS AB Background In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600) mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF(V600E) and BRAF(V600K) mutation subgroups. Methods Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF(V600) mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m(2) of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980. Findings 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12.5 months (IQR 7.7-16.0) on vemurafenib and 9.5 months (3.1-14.7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13.6 months [95% CI 12.0-15.2] vs 9.7 months [7.9-12.8]; hazard ratio [HR] 0.70 [95% CI 0.57-0.87]; p=0.0008), as was median progression-free survival (6.9 months [95% CI 6.1-7.0] vs 1.6 months [1.6-2.1]; HR 0.38 [95% CI 0.32-0.46]; p<0.0001). For the 598 (91%) patients with BRAF(V600E) disease, median overall survival in the vemurafenib group was 13.3 months (95% CI 11.9-14.9) compared with 10.0 months (8.0-14.0) in the dacarbazine group (HR 0.75 [95% CI 0.60-0.93]; p= 0.0085); median progression-free survival was 6.9 months (95% CI 6.2-7.0) and 1.6 months (1.6-2.1), respectively (HR 0.39 [95% CI 0.33-0.47]; p<0.0001). For the 57 (9%) patients with BRAF(V600K) disease, median overall survival in the vemurafenib group was 14.5 months (95% CI 11.2-not estimable) compared with 7.6 months (6.1-16.6) in the dacarbazine group (HR 0.43 [95% CI 0.21-0.90]; p=0.024); median progression-free survival was 5.9 months (95% CI 4.4-9.0) and 1.7 months (1.4-2.9), respectively (HR 0.30 [95% CI 0.16-0.56]; p<0.0001). The most frequent grade 3-4 events were cutaneous squamous-cell carcinoma (65 [19%] of 337 patients) and keratoacanthomas (34 [10%]), rash (30 [9%]), and abnormal liver function tests (38 [11%]) in the vemurafenib group and neutropenia (26 [9%] of 287 patients) in the dacarbazine group. Eight (2%) patients in the vemurafenib group and seven (2%) in the dacarbazine group had grade 5 events. Interpretation Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF(V600E) mutation and in patients with the less common BRAF(V600K) mutation. C1 [McArthur, Grant A.] Peter MacCallum Canc Ctr, East Melbourne, Vic 8006, Australia. [Chapman, Paul B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robert, Caroline] Inst Gustave Roussy, Paris, France. [Larkin, James] Royal Marsden Hosp, London SW3 6JJ, England. [Haanen, John B.] Netherlands Canc Inst, Amsterdam, Netherlands. [Dummer, Reinhard] Univ Zurich, Zurich, Switzerland. [Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Hogg, David] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hogg, David] Univ Hlth Network, Toronto, ON M4X 1K9, Canada. [Hamid, Omid] Angeles Clin & Res Inst, Los Angeles, CA USA. [Ascierto, Paolo A.] Ist Nazl Tumori Fdn Pascale, Naples, Italy. [Garbe, Claus] Univ Tubingen, Tubingen, Germany. [Testori, Alessandro] Ist Europeo Oncol, Milan, Italy. [Maio, Michele] Univ Hosp Siena, Ist Toscano Tumori, Siena, Italy. [Lorigan, Paul] Univ Manchester, Manchester, Lancs, England. [Lebbe, Celeste] Hop St Louis Univ, APHP Oncodermatol, Paris, France. [Jouary, Thomas] St Andre Hosp, Bordeaux, France. [Schadendorf, Dirk] Univ Hosp Essen, Essen, Germany. [O'Day, Stephen J.] Beverly Hills Canc Ctr, Beverly Hills, CA USA. [Kirkwood, John M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Eggermont, Alexander M.] Gustave Roussy Canc Ctr, Villejuif, France. [Eggermont, Alexander M.] Univ Paris 11, Villejuif, France. [Dreno, Brigitte] Nantes Univ Hosp, Nantes, France. [Sosman, Jefferey A.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yin, Ming; Caro, Ivor] Genentech Inc, San Francisco, CA 94080 USA. [Cheng, Suzanne] Roche Mol Syst Inc, Pleasanton, CA USA. [Trunzer, Kerstin] F Hoffmann La Roche, Basel, Switzerland. [Hauschild, Axel] Univ Kiel, Kiel, Germany. RP McArthur, GA (reprint author), Peter MacCallum Canc Ctr, Div Canc Med & Res, East Melbourne, Vic 8006, Australia. EM grant.mcarthur@petermac.org RI Lorigan, Paul/J-6898-2015 OI Lorigan, Paul/0000-0002-8875-2164 FU F Hoffmann-La Roche; National Institute for Health Research Biomedical Research Centre for cancer at Royal Marsden Hospital/Institute of Cancer Research FX We thank the patients who participated in this study. We also thank the clinical trial team for their support in the execution of the trial, and F Hoffmann-La Roche-Genentech for supporting the trial. Medical writing assistance was provided by David Gibson, PhD, of ApotheCom, San Francisco, CA, USA, and funded by F Hoffmann-La Roche. JL is funded by the National Institute for Health Research Biomedical Research Centre for cancer at Royal Marsden Hospital/Institute of Cancer Research. GAM is a practitioner fellow of National Health and Medical Research Council. NR 26 TC 258 Z9 264 U1 6 U2 40 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2014 VL 15 IS 3 BP 323 EP 332 DI 10.1016/S1470-2045(14)70012-9 PG 10 WC Oncology SC Oncology GA AC3FF UT WOS:000332399900043 PM 24508103 ER PT J AU Palumbo, A Bringhen, S Kumar, SK Lupparelli, G Usmani, S Waage, A Larocca, A van der Holt, B Musto, P Offidani, M Petrucci, MT Evangelista, A Zweegman, S Nooka, AK Spencer, A Dimopoulos, MA Hajek, R Cavo, M Richardson, P Lonial, S Ciccone, G Boccadoro, M Anderson, K Barlogie, B Sonneveld, P McCarthy, PL AF Palumbo, Antonio Bringhen, Sara Kumar, Shaji K. Lupparelli, Giulia Usmani, Saad Waage, Anders Larocca, Alessandra van der Holt, Bronno Musto, Pellegrino Offidani, Massimo Petrucci, Maria T. Evangelista, Andrea Zweegman, Sonja Nooka, Ajay K. Spencer, Andrew Dimopoulos, Meletios A. Hajek, Roman Cavo, Michele Richardson, Paul Lonial, Sagar Ciccone, Giovannino Boccadoro, Mario Anderson, Kenneth Barlogie, Bart Sonneveld, Pieter McCarthy, Philip L. TI Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data SO LANCET ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; MYELODYSPLASTIC SYNDROME; COMPETING RISKS; CYCLOPHOSPHAMIDE; MELPHALAN; MAINTENANCE; SECONDARY; LYMPHOMA; SURVIVAL AB Background Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure. Methods We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma between Jan 1, 2000, and Dec 15, 2012, and in which at least one group received lenalidomide were eligible for inclusion. We obtained individual patient data (age, sex, date of diagnosis, allocated treatment and received treatment, duration of treatment and cause of discontinuation, maintenance treatment, date of first relapse, date of second primary malignancy diagnosis, type of second primary malignancy, date of death or last contact, and cause of death) by direct collaboration with the principal investigators of eligible trials. Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis. Findings We found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment (2620 had received lenalidomide and 598 had not), and were included in our analyses. Cumulative incidences of all second primary malignancies at 5 years were 6.9% (95% CI 5.3-8.5) in patients who received lenalidomide and 4.8% (2.0-7.6) in those who did not (hazard ratio [HR] 1.55 [95% CI 1.03-2.34]; p=0.037). Cumulative 5-year incidences of solid second primary malignancies were 3.8% (95% CI 2.7-4.9) in patients who received lenalidomide and 3.4% (1.6-5.2) in those that did not (HR 1.1 [95% CI 0.62-2.00]; p=0.72), and of haematological second primary malignancies were 3.1% (95% CI 1.9-4.3) and 1.4% (0.0-3.6), respectively (HR 3.8 [95% CI 1.15-12.62]; p=0.029). Exposure to lenalidomide plus oral melphalan significantly increased haematological second primary malignancy risk versus melphalan alone (HR 4.86 [95% CI 2.79-8.46]; p<0.0001). Exposure to lenalidomide plus cyclophosphamide (HR 1.26 [95% CI 0.30-5.38]; p=0.75) or lenalidomide plus dexamethasone (HR 0.86 [95% CI 0.33-2.24]; p=0.76) did not increase haematological second primary malignancy risk versus melphalan alone. Interpretation Patients with newly diagnosed myeloma who received lenalidomide had an increased risk of developing haematological second primary malignancies, driven mainly by treatment strategies that included a combination of lenalidomide and oral melphalan. These results suggest that alternatives, such as cyclophosphamide or alkylating-free combinations, should be considered instead of oral melphalan in combination with lenalidomide for myeloma. C1 [Palumbo, Antonio; Bringhen, Sara; Lupparelli, Giulia; Larocca, Alessandra; Boccadoro, Mario] Azienda Osped Citta Salute & Sci Torino, Myeloma Unit, Div Hematol, I-10126 Turin, Italy. [Evangelista, Andrea; Ciccone, Giovannino] Univ Turin, Clin Epidemiol Unit, Turin, Italy. [Offidani, Massimo] Azienda Osped Univ Osped Riuniti Ancona, Clin Ematol, Ancona, Italy. [Kumar, Shaji K.] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA. [Usmani, Saad; Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Waage, Anders] Norwegian Univ Sci & Technol NTNU, Dept Hematol, St Olavs Hosp, N-7034 Trondheim, Norway. [Waage, Anders] KG Jebsen Myeloma Res Ctr, Trondheim, Norway. [van der Holt, Bronno; Sonneveld, Pieter] Erasmus MC Clin Trial Ctr, HOVON Data Ctr, Rotterdam, Netherlands. [Musto, Pellegrino] Ctr Riferimento Oncol Basilicata, Rionero In Vulture, Italy. [Petrucci, Maria T.] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy. [Zweegman, Sonja] Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands. [Nooka, Ajay K.] Winship Canc Inst, Div Bone Marrow Transplant, Atlanta, GA USA. [Lonial, Sagar] Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Spencer, Andrew] Monash Univ, Alfred Hlth, Dept Clin Hematol & Bone Marrow Transplant, Melbourne, Vic 3004, Australia. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Alexandra Hosp, GR-11527 Athens, Greece. [Hajek, Roman] Univ Ostrava, Fac Med, Univ Hosp Ostrava, CZ-70103 Ostrava, Czech Republic. [Hajek, Roman] Univ Ostrava, Dept Haematooncol, Univ Hosp Ostrava, CZ-70103 Ostrava, Czech Republic. [Cavo, Michele] Univ Bologna, Sch Med, Seragnoli Inst Hematol, Bologna, Italy. [Richardson, Paul; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sonneveld, Pieter] Erasmus MC, Dept Hematol, Rotterdam, Netherlands. [McCarthy, Philip L.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. RP Palumbo, A (reprint author), Azienda Osped Citta Salute & Sci Torino, Dipartimento Oncol Ematol, I-10126 Turin, Italy. EM appalumbo@yahoo.com RI Kumar, Shaji/A-9853-2008; Ciccone, Giovannino/K-3136-2016; evangelista, andrea/A-7802-2013; OI Kumar, Shaji/0000-0001-5392-9284; Ciccone, Giovannino/0000-0001-7644-9574; CAVO, MICHELE/0000-0003-4514-3227; Musto, Pellegrino/0000-0003-3277-6594 FU Celgene Corporation FX Celgene Corporation (Summit, NJ, USA), the manufacturers of lenalidomide, provided the drug for the source studies. We thank Rick Flemming and Frances Weir of the Investigator-Initiated Research Writing Group (part of the KnowledgePoint 360 Group) for medical writing support, which was funded by the Celgene Corporation. NR 33 TC 83 Z9 83 U1 3 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2014 VL 15 IS 3 BP 333 EP 342 DI 10.1016/S1470-2045(13)70609-0 PG 10 WC Oncology SC Oncology GA AC3FF UT WOS:000332399900044 PM 24525202 ER PT J AU Dedmon, MM Rogers, DJ Hartnick, CJ AF Dedmon, Matthew M. Rogers, Derek J. Hartnick, Christopher J. TI Management of the Difficult Pediatric Airway With Endotracheal Intubation via Telescopic Guidance SO LARYNGOSCOPE LA English DT Article C1 [Dedmon, Matthew M.; Rogers, Derek J.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Dedmon, MM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM matthew_dedmon@meei.harvard.edu NR 7 TC 0 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2014 VL 124 IS 3 BP 785 EP 788 DI 10.1002/lary.24227 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AA8VY UT WOS:000331374300045 PM 23712455 ER PT J AU Yoo, B Sheth, VR Howison, CM Douglas, MJK Pineda, CT Maine, EA Baker, AF Pagel, MD AF Yoo, Byunghee Sheth, Vipul R. Howison, Christine M. Douglas, Matthew J. K. Pineda, Carlos T. Maine, Erin A. Baker, Amanda F. Pagel, Mark D. TI Detection of In Vivo Enzyme Activity with CatalyCEST MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CEST MRI; contrast agents; enzyme activity; molecular imaging ID IMAGING CONTRAST AGENT; PARACEST MRI; 7 T; LANTHANIDE(III) COMPLEXES; CEST-FISP; PH; CANCER; MICE; PROTEASES; CELLS AB PurposeCatalyCEST MRI compares the detection of an enzyme-responsive chemical exchange saturation transfer (CEST) agent with the detection of an unresponsive control CEST agent that accounts for other conditions that influence CEST. The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI. MethodsCEST agents that were responsive and unresponsive to the activity of urokinase plasminogen activator were shown to have negligible interaction with each other. A CEST-fast imaging with steady state precession (FISP) MRI protocol was used to acquire MR CEST spectroscopic images with a Capan-2 pancreatic tumor model after intravenous injection of the CEST agents. A function of (super)-Lorentzian line shapes was fit to CEST spectra of a region-of-interest that represented the tumor. ResultsThe CEST effects from each agent showed the same initial uptake into tumor tissues, indicating that both agents had the same pharmacokinetic transport rates. Starting 5 min after injection, CEST from the enzyme-responsive agent disappeared more quickly than CEST from the unresponsive agent, indicating that the enzyme responsive agent was being catalyzed by urokinase plasminogen activator, while both agents also experienced net pharmacokinetic washout from the tumor. ConclusionCatalyCEST MRI demonstrates that dynamic tracking of enzyme-responsive and unresponsive CEST agents during the same in vivo MRI study is feasible. Magn Reson Med 71:1221-1230, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Yoo, Byunghee] Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02114 USA. [Yoo, Byunghee] Harvard Univ, Sch Med, Boston, MA USA. [Sheth, Vipul R.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Howison, Christine M.] Univ Arizona, Arizona Res Labs, Tucson, AZ 85724 USA. [Douglas, Matthew J. K.; Pineda, Carlos T.; Maine, Erin A.; Baker, Amanda F.; Pagel, Mark D.] Univ Arizona, Ctr Canc, Tucson, AZ 85724 USA. [Baker, Amanda F.] Univ Arizona, Coll Med, Hematol Oncol Sect, Tucson, AZ 85724 USA. [Pagel, Mark D.] Univ Arizona, Dept Biomed Engn, Tucson, AZ 85724 USA. [Pagel, Mark D.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85724 USA. RP Pagel, MD (reprint author), Univ Arizona, Ctr Canc, 1515 N Campbell Ave, Tucson, AZ 85724 USA. EM mpagel@u.arizona.edu RI Baker, Amanda/I-4119-2014 OI Baker, Amanda/0000-0002-0663-8369 FU NIH [R21CA133455-01, R01CA169774]; US Army Medical Research and Materiel Command [W81XWH-09-1-0053]; CWRU MSTP, NIH [T32 GM007250] FX Grant sponsor: NIH; Grant number: R21CA133455-01 and R01CA169774. Grant sponsor: US Army Medical Research and Materiel Command; Grant number: W81XWH-09-1-0053. Grant sponsor: CWRU MSTP, NIH; Grant number: T32 GM007250. NR 44 TC 16 Z9 16 U1 4 U2 22 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 MAR PY 2014 VL 71 IS 3 BP 1221 EP 1230 DI 10.1002/mrm.24763 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AB2HU UT WOS:000331614600037 PM 23640714 ER PT J AU Virk, R Shinagare, S Lauwers, GY Yajnik, V Stone, JH Deshpande, V AF Virk, Renu Shinagare, Shweta Lauwers, Gregory Y. Yajnik, Vijay Stone, John H. Deshpande, Vikram TI Tissue IgG4-positive plasma cells in inflammatory bowel disease: a study of 88 treatment-naive biopsies of inflammatory bowel disease SO MODERN PATHOLOGY LA English DT Article DE Crohn's disease; IgG4; ulcerative colitis ID ULCERATIVE-COLITIS; CROHNS-DISEASE; CHILDREN; INTERLEUKIN-4; EXPRESSION; ADULTS AB The distinction of Crohn's disease from ulcerative colitis is based on clinical, endoscopic, radiological, and histological findings, a paradigm that remains unchanged despite the advent of new understanding of the immunological and genetic basis of inflammatory bowel disease. There is a strong correlation between inflammatory bowel disease, predominantly ulcerative colitis, and autoimmune pancreatitis. We hypothesized that colonic biopsies from patients with inflammatory bowel disease would demonstrate increased numbers of IgG4-positive plasma cells and that this elevation might be restricted to ulcerative colitis. We examined a cohort of 78 cases of inflammatory bowel disease: 50 ulcerative colitis and 38 Crohn's disease. We identified treatment-naive biopsies. Additionally, four cases of inflammatory bowel disease associated with autoimmune pancreatitis and 15 cases of lymphocytic/collagenous colitis were also identified. Immunohistochemical stains for IgG4 were performed. Biopsies from patients with ulcerative colitis showed significantly higher numbers of IgG4-bearing plasma cells than those with Crohn's disease (mean IgG4 counts per high-power field (hpf) 9.8 vs 2.8, P=0.001). Samples from 19(38%) ulcerative colitis patients had IgG4 counts >10/hpf, compared with only two (5%) patients with Crohn's disease; the sensitivity and specificity of a cutoff at 10 IgG4-positive plasma cells per hpf was 38 and 95%, respectively. Among individuals <18 years, there were no statistically differences in the IgG4 counts between the two subforms of inflammatory bowel disease. Among adult patients, a cutoff of 5 IgG4 + plasma cells distinguished ulcerative colitis from Crohn's disease with a sensitivity of 53% and specificity of 83%. In comparison to inflammatory bowel disease, patients with lymphocytic/collagenous colitis showed significantly lower numbers of IgG4-positive plasma cells (P=0.0001). Ulcerative colitis with pancolitis showed higher numbers of IgG4-bearing plasma cells (mean IgG4 12.8 vs 5.8 per hpf; P=0.09). An immunohistochemical stain for IgG4 may aid in making the distinction between ulcerative colitis and Crohn's disease (with exclusion of the pediatric cases), albeit with a relatively low sensitivity. This study also provides additional support to the hypothesis that a subset of ulcerative colitis cases is associated with a Th2 response. C1 [Virk, Renu] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Shinagare, Shweta] Tufts Med Ctr, Dept Pathol, Boston, MA USA. [Lauwers, Gregory Y.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lauwers, Gregory Y.; Yajnik, Vijay; Stone, John H.; Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA USA. [Yajnik, Vijay] Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, Boston, MA 02114 USA. [Stone, John H.] Massachusetts Gen Hosp, Div Rheumatol, Dept Med, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2-55 Fruit St, Boston, MA 02114 USA. EM vikramdirdeshpande@gmail.org NR 19 TC 9 Z9 9 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2014 VL 27 IS 3 BP 454 EP 459 DI 10.1038/modpathol.2013.121 PG 6 WC Pathology SC Pathology GA AC3MP UT WOS:000332426200014 PM 23929268 ER PT J AU Zhou, L Wang, L Kang, JX Xie, WH Li, XY Wu, CQ Xu, B Wu, J AF Zhou, Li Wang, Lei Kang, Jing X. Xie, Wenhai Li, Xiaoyong Wu, Changqing Xu, Bo Wu, Ji TI Production of fat-1 transgenic rats using a post-natal female germline stem cell line SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE cell culture; cell proliferation; germ cells; animal model ID N-3 FATTY-ACIDS; ALZHEIMERS-DISEASE; CONDITIONED MEDIUM; MOUSE OVARY; IN-VITRO; MICE; OMEGA-3-FATTY-ACIDS; DIFFERENTIATION; EXPRESSION; GROWTH AB Germline stem cell lines possess the abilities of self-renewal and differentiation, and have been established from both mouse and human ovaries. Here, we established a new female germline stem cell (FGSC) line from post-natal rats by immunomagnetic sorting for Fragilis, which showed a normal karyotype, high telomerase activity, and a consistent gene expression pattern of primordial germ cells after 1 year of culture. Using an in vitro differentiation system, the FGSC line could differentiate into oocytes. After liposome-based transfection with green fluorescent protein (GFP) or fat-1 vectors, the FGSCs were transplanted into the ovaries of infertile rats. The transplanted FGSCs underwent oogenesis, and the rats produced offspring carrying the GFP or fat-1 transgene after mating with wild-type male rats. The efficiency of gene transfer was 27.8628.00, and 2 months was needed to produce transgenic rats. These findings have implications in biomedical research and potential applications in biotechnology. C1 [Zhou, Li; Wang, Lei; Xie, Wenhai; Li, Xiaoyong; Wu, Changqing; Xu, Bo; Wu, Ji] Shanghai Jiao Tong Univ, Bio X Inst, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai 200240, Peoples R China. [Kang, Jing X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Lipid Med & Technol, Charlestown, MA 02129 USA. [Wu, Ji] Ningxia Med Univ, Minist Educ, Key Lab Fertil Preservat & Maintenance, Yinchuan, Peoples R China. RP Wu, J (reprint author), Shanghai Jiao Tong Univ, Bio X Inst, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, 800 Dongchuan Rd, Shanghai 200240, Peoples R China. EM jiwu@sjtu.edu.cn FU National Basic Research Program of China [2013CB967401, 2010CB945001]; National Nature Science Foundation of China [81370675, 81200472, 81121001] FX This work was supported by National Basic Research Program of China (2013CB967401 and 2010CB945001), and the National Nature Science Foundation of China (81370675, 81200472, 81121001). NR 63 TC 23 Z9 25 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 EI 1460-2407 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAR PY 2014 VL 20 IS 3 BP 271 EP 281 DI 10.1093/molehr/gat081 PG 11 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA AB8KM UT WOS:000332039000008 PM 24258451 ER PT J AU Sakamaki, JI Fu, A Reeks, C Baird, S Depatie, C Al Azzabi, M Bardeesy, N Gingras, AC Yee, SP Screaton, RA AF Sakamaki, Jun-Ichi Fu, Accalia Reeks, Courtney Baird, Stephen Depatie, Chantal Al Azzabi, Mufida Bardeesy, Nabeel Gingras, Anne-Claude Yee, Siu-Pok Screaton, Robert A. TI Role of the SIK2-p35-PJA2 complex in pancreatic beta-cell functional compensation SO NATURE CELL BIOLOGY LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; SALT-INDUCIBLE KINASE; INSULIN-SECRETION; SIGNAL-TRANSDUCTION; DIABETES-MELLITUS; COACTIVATOR TORC2; GLUCOSE-TOLERANCE; RESISTANCE; SIK2; PHOSPHORYLATION AB Energy sensing by the AMP-activated protein kinase (AMPK) is of fundamental importance in cell biology. In the pancreatic beta-cell, AMPK is a central regulator of insulin secretion. The capacity of the beta-cell to increase insulin output is a critical compensatory mechanism in prediabetes, yet its molecular underpinnings are unclear. Here we delineate a complex consisting of the AMPK-related kinase SIK2, the CDK5 activator CDK5R1 (also known as p35) and the E3 ligase PJA2 essential for beta-cell functional compensation. Following glucose stimulation, SIK2 phosphorylates p35 at Ser 91, to trigger its ubiquitylation by PJA2 and promote insulin secretion. Furthermore, SIK2 accumulates in beta-cells in models of metabolic syndrome to permit compensatory secretion; in contrast, beta-cell knockout of SIK2 leads to accumulation of p35 and impaired secretion. This work demonstrates that the SIK2-p35-PJA2 complex is essential for glucose homeostasis and provides a link between p35-CDK5 and the AMPK family in excitable cells. C1 [Sakamaki, Jun-Ichi; Fu, Accalia; Reeks, Courtney; Baird, Stephen; Depatie, Chantal; Al Azzabi, Mufida; Screaton, Robert A.] Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON K1H 8L1, Canada. [Fu, Accalia; Screaton, Robert A.] Univ Ottawa, Dept Cellular & Mol Med, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8L1, Canada. [Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Gingras, Anne-Claude] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada. [Gingras, Anne-Claude] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada. [Yee, Siu-Pok] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. [Screaton, Robert A.] Univ Ottawa, Dept Pediat, Ottawa, ON K1H 8L1, Canada. RP Screaton, RA (reprint author), Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON K1H 8L1, Canada. EM rob@arc.cheo.ca RI Gingras, Anne-Claude/E-9982-2010 OI Gingras, Anne-Claude/0000-0002-6090-4437 FU Canadian Diabetes Association [OG-3-11-3328-RS]; Canadian Institutes of Health Research (CIHR) [MOP-97772]; Canadian Foundation for Innovation (CFI); CIHR [MOP-84314]; Japan Society for the Promotion of Science [10J00366]; Canadian Diabetes Studentship FX We would like to thank members of the R.A.S. laboratory and M. Wheeler for helpful comments and Z-Y. Lin for proteomic analysis. We acknowledge the Department of Laboratory Medicine and Pathology Core Facility at the University of Ottawa and K. Yates at the University of Ottawa Animal Care for technical assistance. This work was supported by grants from the Canadian Diabetes Association (number OG-3-11-3328-RS), the Canadian Institutes of Health Research (CIHR) MOP-97772 and the Canadian Foundation for Innovation (CFI) to R.A.S., operating grant from CIHR (MOP-84314) to A-C.G., by a Japan Society for the Promotion of Science Fellows to J.S. (10J00366), and a Canadian Diabetes Studentship to A.F. A-C.G. holds the Canada Research Chair in Functional Proteomics and the Lea Reichmann Chair in Cancer Proteomics. R.A.S. holds the Canada Research Chair in Apoptotic Signalling. NR 54 TC 24 Z9 24 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2014 VL 16 IS 3 BP 234 EP + DI 10.1038/ncb2919 PG 27 WC Cell Biology SC Cell Biology GA AB9OK UT WOS:000332124000009 PM 24561619 ER PT J AU Drain, PK Robine, M Holmes, KK Bassett, IV AF Drain, Paul K. Robine, Marion Holmes, King K. Bassett, Ingrid V. TI Global migration of clinical trials SO NATURE REVIEWS DRUG DISCOVERY LA English DT News Item C1 [Drain, Paul K.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Drain, Paul K.; Robine, Marion; Bassett, Ingrid V.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Holmes, King K.] Univ Washington, Sch Publ Hlth & Community Med, Dept Global Hlth, Seattle, WA 98104 USA. [Holmes, King K.] Univ Washington, Sch Publ Hlth & Community Med, Dept Med, Seattle, WA 98104 USA. [Bassett, Ingrid V.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA 02114 USA. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. EM pdrain@partners.org FU FIC NIH HHS [R24 TW007988]; NIAID NIH HHS [T32 AI007433]; NIMH NIH HHS [R01 MH090326] NR 0 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAR PY 2014 VL 13 IS 3 BP 166 EP 167 DI 10.1038/nrd4260 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA AB9NN UT WOS:000332121300006 PM 24577390 ER PT J AU Wen, PY AF Wen, Patrick Y. TI Controversies in neuro-oncology: does valganciclovir have a role in the treatment of high-grade gliomas? SO NEURO-ONCOLOGY LA English DT Editorial Material ID CYTOMEGALOVIRUS; GLIOBLASTOMA; INFECTION C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, 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 5 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 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD MAR PY 2014 VL 16 IS 3 BP 329 EP 329 DI 10.1093/neuonc/nou011 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AB6BK UT WOS:000331872200002 PM 24523452 ER PT J AU Kaufmann, JK Chiocca, EA AF Kaufmann, Johanna K. Chiocca, E. Antonio TI Glioma virus therapies between bench and bedside SO NEURO-ONCOLOGY LA English DT Review DE gene therapy; glioblastoma; oncolysis ID HERPES-SIMPLEX-VIRUS; THYMIDINE-KINASE GENE; PHASE-I TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; ONCOLYTIC MEASLES-VIRUS; HUMAN-MALIGNANT GLIOMA; REPLICATION-DEFICIENT RETROVIRUSES; PROSTATE-CANCER PATIENTS; SODIUM-IODIDE SYMPORTER; BRAIN-TUMORS AB Despite extensive research, current glioma therapies are still unsatisfactory, and novel approaches are pressingly needed. In recent years, both nonreplicative viral vectors and replicating oncolytic viruses have been developed for brain cancer treatment, and the mechanistic background of their cytotoxicity has been unveiled. A growing number of clinical trials have convincingly established viral therapies to be safe in glioma patients, and maximum tolerated doses have generally not been reached. However, evidence for therapeutic benefit has been limited: new generations of therapeutic vectors need to be developed in order to target not only tumor cells but also the complex surrounding microenvironment. Such therapies could also direct long-lasting immune responses toward the tumor while reducing early antiviral reactions. Furthermore, viral delivery methods are to be improved and viral spread within the tumor will have to be enhanced. Here, we will review the outcome of completed glioma virus therapy trials as well as highlight the ongoing clinical activities. On this basis, we will give an overview of the numerous strategies to enhance therapeutic efficacy of new-generation viruses and novel treatment regimens. Finally, we will conclude with approaches that may be crucial to the development of successful glioma therapies in the future. C1 Brigham & Womens Hosp, Dept Neurosurg, Harvey Cushing Neurooncol Labs, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chiocca, EA (reprint author), Childrens Hosp, Dept Neurosurg, PBB301,75 Francis St, Boston, MA 02115 USA. EM eachiocca@partners.org FU National Institutes of Health [1P01CA16320501A1]; [7U01NS061811]; [CA163205]; [CA069246] FX This work was supported by the National Institutes of Health (grant 1P01CA16320501A1, as well as grants 7U01NS061811, CA163205, and CA069246 to E.A.C.). NR 158 TC 18 Z9 18 U1 2 U2 18 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 MAR PY 2014 VL 16 IS 3 BP 334 EP 351 DI 10.1093/neuonc/not310 PG 18 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AB6BK UT WOS:000331872200005 PM 24470549 ER PT J AU Bogner, W Hess, AT Gagoski, B Tisdall, MD van der Kouwe, AJW Trattnig, S Rosen, B Andronesi, OC AF Bogner, Wolfgang Hess, Aaron T. Gagoski, Borjan Tisdall, M. Dylan van der Kouwe, Andre J. W. Trattnig, Siegfried Rosen, Bruce Andronesi, Ovidiu C. TI Real-time motion- and Bo-correction for LASER-localized spiral-accelerated 3D-MRSI of the brain at 3 T SO NEUROIMAGE LA English DT Article DE Magnetic resonance spectroscopy; USER localization; Prospective motion correction; Real-time correction; Spiral acceleration; Frequency drift correction ID MAGNETIC-RESONANCE-SPECTROSCOPY; VIVO H-1-NMR SPECTROSCOPY; IMAGE-BASED TRACKING; ADIABATIC PULSES; VOLUMETRIC NAVIGATORS; HEAD MOTION; MR SPECTRA; 7 TESLA; FREQUENCY; PHASE AB The full potential of magnetic resonance spectroscopic imaging (MRSI) is often limited by localization artifacts, motion-related artifacts, scanner instabilities, and long measurement times. Localized adiabatic selective refocusing (LASER) provides accurate B1-insensitive spatial excitation even at high magnetic fields. Spiral encoding accelerates MRSI acquisition, and thus, enables 3D-coverage without compromising spatial resolution. Real-time position- and shim/frequency-tracking using MR navigators correct motion- and scanner instability-related artifacts. Each of these three advanced MRI techniques provides superior MRSI data compared to commonly used methods. In this work, we integrated in a single pulse sequence these three promising approaches. Real-time correction of motion, shim, and frequency-drifts using volumetric dual-contrast echo planar imaging-based navigators were implemented in an MRSI sequence that uses low-power gradient modulated short-echo time LASER localization and time efficient spiral readouts, in order to provide fast and robust 3D-MRSI in the human brain at 3 T. The proposed sequence was demonstrated to be insensitive to motion- and scanner drift-related degradations of MRSI data in both phantoms and volunteers. Motion and scanner drift artifacts were eliminated and excellent spectral quality was recovered in the presence of strong movement. Our results confirm the expected benefits of combining a spiral 3D-LASER-MRSI sequence with real-time correction. The new sequence provides accurate, fast, and robust 3D metabolic imaging of the human brain at 3 T. This will further facilitate the use of 3D-MRSI for neuroscience and clinical applications. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bogner, Wolfgang; Tisdall, M. Dylan; van der Kouwe, Andre J. W.; Rosen, Bruce; Andronesi, Ovidiu C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02114 USA. [Bogner, Wolfgang; Trattnig, Siegfried] Med Univ Vienna, MR Ctr Excellence, Dept Radiol, Vienna, Austria. [Hess, Aaron T.] Univ Oxford, John Radcliffe Hosp, Ctr Clin Magnet Resonance Res, Dept Cardiovasc Med, Oxford OX3 9DU, England. [Gagoski, Borjan] Harvard Univ, Boston Childrens Hosp, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA USA. RP Bogner, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02114 USA. EM bow@nmr.mgh.harvard.edu OI Bogner, Wolfgang/0000-0002-0130-3463 FU Austrian Science Fund [KU-61, J3302-B24]; KL2 MeRIT award; Harvard Clinical and Translational Science Center [8K12TR000168-05]; NIH, National Cancer Institute [K22CA178269-01] FX This study was supported by the Austrian Science Fund (FWF): KU-61 and J3302-B24 to W.B., the KL2 MeRIT award to O.C.A. from the Harvard Clinical and Translational Science Center (8K12TR000168-05) and I K22CA178269-01 from NIH, National Cancer Institute. NR 43 TC 10 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2014 VL 88 BP 22 EP 31 DI 10.1016/j.neuroimage.2013.09.034 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AB8PH UT WOS:000332052000003 PM 24201013 ER PT J AU Yendiki, A Koldewyn, K Kakunoori, S Kanwisher, N Fischl, B AF Yendiki, Anastasia Koldewyn, Kami Kakunoori, Sita Kanwisher, Nancy Fischl, Bruce TI Spurious group differences due to head motion in a diffusion MRI study SO NEUROIMAGE LA English DT Article DE Diffusion MRI; Tractography; Motion; Autism ID AUTISM SPECTRUM DISORDER; WHITE-MATTER COMPROMISE; VOLUMETRIC NAVIGATORS; ALZHEIMERS-DISEASE; HUMAN BRAIN; CHILDREN; IMAGES; ABNORMALITIES; SEGMENTATION; REGISTRATION AB Diffusion-weighted MRI (DW-MRI) has become a popular imaging modality for probing the microstructural properties of white matter and comparing them between populations in vivo. However, the contrast in DW-MRI arises from the microscopic random motion of water molecules in brain tissues, which malces it particularly sensitive to macroscopic head motion. Although this has been known since the introduction of DW-MRI, most studies that use this modality for group comparisons do not report measures of head motion for each group and rely on registration-based correction methods that cannot eliminate the full effects of head motion on the DW-MR! contrast. In this work we use data from children with autism and typically developing children to investigate the effects of head motion on differences in anisotropy and diffusivity measures between groups. We show that group differences in head motion can induce group differences in DW-MRI measures, and that this is the case even when comparing groups that include control subjects only, where no anisotropy or diffusivity differences are expected. We also show that such effects can be more prominent in some white-matter pathways than others, and that they can be ameliorated by including motion as a nuisance regressor in the analyses. Our results demonstrate the importance of taking head motion into account in any population study where one group might exhibit more head motion than the other. (C) 2013 Elsevier Inc. All rights reserved. C1 [Yendiki, Anastasia; Kakunoori, Sita; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02114 USA. [Koldewyn, Kami; Kanwisher, Nancy] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Yendiki, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02114 USA. EM ayendiki@nmr.mgh.harvard.edu OI Koldewyn, Kami/0000-0003-3588-6449 FU Autism & Dyslexia Project; Ellison Medical Foundation; National Institute for Biomedical Imaging and Bioengineering [K99/R00-EB008129, R01-EB006758]; National Center for Research Resources [P41-RR14, Q75, U24-RR021382]; National Institute on Aging [AG022381, 5R01-AG008122-22]; National Center for Alternative Medicine [RC1-AT005728-01]; National Institute for Neurological Disorders and Stroke [R01NS052585-01, 1R21-NS072652-01, 1R01-NS070963]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; National Institutes of Health Blueprint for Neuroscience Research [5U01-MH093765] FX Support for this research was proyided in part by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, the National Institute for Biomedical Imaging and Bioengineering (Pathway to Independence award K99/R00-EB008129, R01-EB006758), the National Center for Research Resources (P41-RR14,Q75, U24-RR021382), the National Institute on Aging (AG022381, 5R01-AG008122-22), the National Center for Alternative Medicine (RC1-AT005728-01), and the National Institute for Neurological Disorders and Stroke (R01NS052585-01, 1R21-NS072652-01, 1R01-NS070963), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by the National Institutes of Health Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. NR 52 TC 60 Z9 60 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2014 VL 88 BP 79 EP 90 DI 10.1016/j.neuroimage.2013.11.027 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AB8PH UT WOS:000332052000010 PM 24269273 ER PT J AU Yeo, BTT Krienen, FM Chee, MWL Buckner, RL AF Yeo, B. T. Thomas Krienen, Fenna M. Chee, Michael W. L. Buckner, Randy L. TI Estimates of segregation and overlap of functional connectivity networks in the human cerebral cortex SO NEUROIMAGE LA English DT Article DE Intrinsic connectivity; MRI; Human Connectome Project; Default network; Dorsal attention; Resting-state fMRI ID INDEPENDENT COMPONENT ANALYSIS; RESTING-STATE NETWORKS; SPONTANEOUS BRAIN ACTIVITY; STIMULUS-DRIVEN ATTENTION; SUPERIOR PARIETAL CORTEX; HUMAN CONNECTOME PROJECT; SURFACE-BASED ANALYSIS; VISUAL AREA MT; DEFAULT MODE; CORTICAL CONNECTIONS AB The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (WA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. (C) 2013 Elsevier Inc. All rights reserved. C1 [Yeo, B. T. Thomas; Chee, Michael W. L.] Duke NUS Grad Med Sch, Ctr Cognit Neurosci, Singapore 169857, Singapore. [Krienen, Fenna M.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Dept Psychol, Cambridge, MA 02138 USA. [Krienen, Fenna M.; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Yeo, B. T. Thomas] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 117548, Singapore. RP Yeo, BTT (reprint author), Duke NUS Grad Med Sch, 8 Coll Rd,Level 6, Singapore 169857, Singapore. OI Yeo, B.T. Thomas/0000-0002-0119-3276; Chee, Michael/0000-0002-6087-0548 FU National Medical Research Council, Singapore [STaR/0004/2008]; Massachusetts General Hospital-University of California; Los Angeles Human Connectome Project [U54MH091665]; Simons Foundation; Howard Hughes Medical Institute; NIH Institutes and Centers; NIH Blueprint for Neuroscience Research; McDonnell Center for Systems Neuroscience at Washington University; [S10RR021110]; [S10RR023401]; [S10RR019307] FX This work was supported by the National Medical Research Council, Singapore (STaR/0004/2008), Massachusetts General Hospital-University of California, Los Angeles Human Connectome Project (U54MH091665), the Simons Foundation and the Howard Hughes Medical Institute. Data were provided by the Brain Genomics Superstruct Project (Principal Investigators: Randy Buckner, Jordan Smoller, and Joshua Roffman) and by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. This research also utilized resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896 and instruments supported by S10RR021110, S10RR023401 and S10RR019307 from the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital. The authors would like to thank Jesisca Tandi for help with some of the figures in this paper. NR 128 TC 24 Z9 24 U1 2 U2 37 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2014 VL 88 BP 212 EP 227 DI 10.1016/j.neuroimage.2013.10.046 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AB8PH UT WOS:000332052000023 PM 24185018 ER PT J AU Artornsombudh, P Pistilli, M Foster, CS Pujari, SS Gangaputra, SS Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Kempen, JH AF Artornsombudh, Pichaporn Pistilli, Maxwell Foster, C. Stephen Pujari, Siddharth S. Gangaputra, Sapna S. Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Kempen, John H. TI Factors Predictive of Remission of New-Onset Anterior Uveitis SO OPHTHALMOLOGY LA English DT Article ID JUVENILE IDIOPATHIC ARTHRITIS; INTRAOCULAR INFLAMMATORY DISEASE; INTERMEDIATE UVEITIS; CLINICAL-COURSE; PREVALENCE; EPIDEMIOLOGY; CHILDHOOD; BLINDNESS; FRAGMENT AB Purpose: To identify factors predictive of remission of inflammation in new-onset anterior uveitis cases treated at tertiary uveitis care facilities. Design: Retrospective cohort study. Participants: Patients seeking treatment at participating academic uveitis clinics within 90 days of initial diagnosis of anterior uveitis. Methods: Retrospective cohort study based on standardized chart review. Main Outcome Measures: Factors predictive of remission (no disease activity without corticosteroid or immunosuppressive treatments at all visits during a 90-day period). Results: Nine hundred ninety eyes (687 patients) had a first-ever diagnosis of anterior uveitis within 90 days before initial presentation and had follow-up visits thereafter. The median follow-up time was 160 days. Systemic diagnoses with juvenile idiopathic arthritis (JIA; adjusted hazard ratio [aHR], 0.38; 95% confidence interval [CI], 0.19-0.74) and Behcet's disease (aHR, 0.10; 95% CI, 0.01-0.85) were associated with a lower incidence of uveitis remission. Cases of bilateral uveitis (aHR, 0.68; 95% CI, 0.54-0.87) and those with a history of cataract surgery before presentation (aHR, 0.51; 95% CI, 0.29-0.87) also had a lower incidence of remission. Regarding clinical findings at the initial visit, a high degree of vitreous cells at initial presentation was associated with a lower incidence of remission (for 1+ or more vs. none: aHR, 0.72; 95% CI, 0.55-0.95). An initial visual acuity of 20/200 or worse, with respect to 20/40 or better, also was predictive of a lower incidence of remission (aHR, 0.52; 95% CI, 0.32-0.86). Conclusions: Factors associated with a lower incidence of remission among new-onset anterior uveitis cases included diagnosis with JIA, Behcet's disease, bilateral uveitis, history of cataract surgery, findings of 1+ or more vitreous cells at presentation, and an initial visual acuity of 20/200 or worse. Patients with these risk factors seem to be at higher risk of persistent inflammation; reciprocally, patients lacking these factors would be more likely to experience remission. Patients with risk factors for nonremission of uveitis should be managed taking into account the higher probability of a chronic inflammatory course. (C) 2014 by the American Academy of Ophthalmology. C1 [Artornsombudh, Pichaporn; Foster, C. Stephen; Pujari, Siddharth S.] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Artornsombudh, Pichaporn; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Dept Ophthalmol, Scheie Eye Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Pujari, Siddharth S.] Om Eye Care Hosp, Belgaum, Karnataka, India. [Gangaputra, Sapna S.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA. [Gangaputra, Sapna S.] Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Fundus Photograph Reading Ctr, Madison, WI USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Pistilli, Maxwell/0000-0002-4266-4150 FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [EY014943]; Research to Prevent Blindness, Inc., New York, New York; Paul and Evanina Mackall Foundation, New York, New York; Ocular Immunology and Uveitis Foundation, Cambridge, Massachusetts; Research to Prevent Blindness; National Eye Institute; United States Department of Veterans' Affairs FX Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: EY014943 [J.H.K.]); Research to Prevent Blindness, Inc., New York, New York; the Paul and Evanina Mackall Foundation, New York, New York; and the Ocular Immunology and Uveitis Foundation, Cambridge, Massachusetts. During the time of data collection, J.H.K. was an Research to Prevent Blindness James S. Adams Special Scholar Award recipient, J.E.T. was a Research to Prevent Blindness Harrington Special Scholar Award recipient, and D.A.J. and J.T.R. were Research to Prevent Blindness Senior Scientific Investigator Award recipients. G.A.L-C. is an employee of Johnson & Johnson and was previously supported by the National Eye Institute, and R.B.N. continues to be supported by intramural funds of the National Eye Institute. E.B.S. receives support from the United States Department of Veterans' Affairs. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of this manuscript. NR 31 TC 4 Z9 4 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2014 VL 121 IS 3 BP 778 EP 784 DI 10.1016/j.ophtha.2013.09.041 PG 7 WC Ophthalmology SC Ophthalmology GA AC3FT UT WOS:000332401800030 PM 24342020 ER PT J AU Slattery, WH Cassis, AM Wilkinson, EP Santos, F Berliner, K AF Slattery, William H., III Cassis, Adam M. Wilkinson, Eric P. Santos, Felipe Berliner, Karen TI Side-to-End Hypoglossal to Facial Anastomosis With Transposition of the Intratemporal Facial Nerve SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Facial paralysis; Hypoglossal facial anastomosis ID PARALYZED FACE; REGENERATION; INNERVATION; REANIMATION; MUSCLE AB Objective To describe results in a large series of patients using a recent variation of hypoglossal-facial nerve anastomosis (HFA) in which the intratemporal facial nerve segment is used, obviating the need for a sensory nerve jump graft. Study Design Retrospective chart review. Setting Tertiary neurotologic referral center. Patients Nineteen patients (12 female/7 male subjects) with facial paralysis because of posterior fossa surgery for tumor (n = 15), Bell's palsy (n = 1), facial neuroma (n = 1), hemangioma (n = 1), and trauma (n = 1) who underwent HFA from 1997 to 2011, with at least 1-year follow-up. Mean age at surgery is 47.4 years (range, 11.2-83 yr). Mean follow-up is 4.0 years. Intervention Side-to-end hypoglossal to facial anastomosis with transposition of the intratemporal facial nerve (swingdown HFA). Main Outcome Measure House-Brackmann (H-B) facial nerve grade. Results Seven patients (36.8%) achieved an H-B Grade III, 9 patients (47.4%) a grade IV, and 3 patients (15.8%) a grade V at last follow-up. No patients complained of dysphagia, dysarthria, or had evidence of oral incompetence. One patient complained of mild tongue weakness. Age at time of HFA (p 0.049, III younger than V) and time from facial nerve injury to HFA (p 0.02, III70% FXIII. We conclude that quantitative activity assays perform better for detecting FXIII deficiency than clot solubility assays, although some quantitative activity assays overestimate low FXIII levels. C1 [Hsu, Peihong; Brody, Judith; Zhang, Xinmin] Hofstra North Shore LIJ Sch Med, Dept Pathol, Lab Med, New York, NY USA. [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. [Hayward, Catherine P. M.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Smock, Kristi J.] Univ Utah, ARUP Labs, Dept Pathol, Salt Lake City, UT USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ235, Boston, MA 02114 USA. EM evancott@partners.org OI Hayward, Catherine/0000-0002-2843-0817 NR 26 TC 12 Z9 12 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 EI 1098-9064 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD MAR PY 2014 VL 40 IS 2 BP 232 EP 238 DI 10.1055/s-0034-1365841 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AB7MX UT WOS:000331975600014 PM 24497117 ER PT J AU Smock, KJ Ledford-Kraemer, MR Meijer, P Hsu, PH Van Cott, EM AF Smock, Kristi J. Ledford-Kraemer, Marlies R. Meijer, Piet Hsu, Peihong Van Cott, Elizabeth M. TI Proficiency Testing Results for Heparin-Induced Thrombocytopenia in North America SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE NASCOLA; heparin-induced thrombocytopenia; proficiency testing; ELISA; ECAT ID OPTICAL-DENSITY; ANTIBODIES; THROMBOSIS; DIAGNOSIS; ASSAY; OPINION; HIT; IGM AB Between 2010 and 2012, North American Specialized Coagulation Laboratory Association (NASCOLA) distributed five proficiency testing challenges to evaluate laboratory testing for heparin-induced thrombocytopenia (HIT). Results (n = 355) were submitted from 43 unique laboratories for 10 samples (3 positive, 2 weak positive, and 5 negative). The vast majority of results were from commercial enzyme-linked immunosorbent assay (ELISA) methods, predominantly polyvalent assays. Laboratories performed well in the classification of clear negative and positive samples. All results (100%) submitted for the five negative samples (n = 173) and 97% of immunological results submitted for the three positive samples (n = 105) were correctly classified (the incorrect responses were two borderline classifications and, from a gel-agglutination method, one negative classification). There was more difficulty in the classification of the two weak positive samples (n = 70). In one survey, 61% of results from the weak positive sample were classified as positive, while 21% were called negative, 16% were called borderline, and 2% were called inconclusive. In a second survey, 16% of results from the weak positive sample were called positive, while 56% were called negative, and 28% were called borderline. Significant interlaboratory variation was observed for ELISA results, with coefficients of variation of about 20 to 30%. We conclude that there is variability in HIT laboratory testing and that identification of weak positive samples can be challenging. C1 [Smock, Kristi J.; Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Smock, Kristi J.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Smock, Kristi J.] Univ Utah, ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Ledford-Kraemer, Marlies R.] CLOT ED Inc, Islamorada, FL USA. [Meijer, Piet] ECAT Fdn, Leiden, Netherlands. [Hsu, Peihong] Hofstra North Shore LIJ Sch Med, Dept Pathol Lab Med, Lake Success, NY USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ235, Boston, MA 02114 USA. EM evancott@partners.org NR 25 TC 7 Z9 8 U1 0 U2 6 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 EI 1098-9064 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD MAR PY 2014 VL 40 IS 2 BP 254 EP 260 DI 10.1055/s-0034-1365842 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AB7MX UT WOS:000331975600016 PM 24497121 ER PT J AU Yoo, AJ Zaidat, OO Chaudhry, ZA Berkhemer, OA Gonzalez, RG Goyal, M Demchuk, AM Menon, BK Mualem, E Ueda, D Buell, H Sit, SP Bose, A AF Yoo, Albert J. Zaidat, Osama O. Chaudhry, Zeshan A. Berkhemer, Olvert A. Gonzalez, R. Gilberto Goyal, Mayank Demchuk, Andrew M. Menon, Bijoy K. Mualem, Elan Ueda, Dawn Buell, Hope Sit, Siu Po Bose, Arani CA Penumbra Pivotal Penumbra Imaging TI Impact of Pretreatment Noncontrast CT Alberta Stroke Program Early CT Score on Clinical Outcome After Intra Arterial Stroke Therapy SO STROKE LA English DT Article DE endovascular procedures; radiography; interventional; tomography; spiral computed; stroke ID ACUTE ISCHEMIC-STROKE; DIFFUSION-WEIGHTED MRI; ENDOVASCULAR TREATMENT; HYPERACUTE STROKE; INTRAARTERIAL; TRIAL; SELECTION; PROUROKINASE; OCCLUSION AB Background and Purpose The efficacy of intra-arterial treatment remains uncertain. Because most centers performing IAT use noncontrast CT (NCCT) imaging, it is critical to understand the impact of NCCT findings on treatment outcomes. This study aimed to compare functional independence and safety among patients undergoing intra-arterial treatment stratified by the extent of ischemic change on pretreatment NCCT. Methods The study cohort was derived from multicenter trials of the Penumbra System. Inclusion criteria were anterior circulation proximal occlusion, evaluable pretreatment NCCT, and known time to reperfusion. Ischemic change was quantified using the Alberta Stroke Program Early CT Score (ASPECTS) and stratified into 3 prespecified groups for comparison: 0 to 4 (most ischemic change) versus 5 to 7 versus 8 to 10 (least ischemic change). Results A total of 249 patients were analyzed: 40 with ASPECTS 0 to 4, 83 with ASPECTS 5 to 7, and 126 with ASPECTS 8 to 10. For ASPECTS 0 to 4, 5 to 7, and 8 to 10, respectively, good outcome (modified Rankin Scale score, 0-2) rates were 5%, 38.6%, and 46% (P<0.0001), and mortality rates were 55%, 28.9%, and 19% (P=0.0001). The only significant pairwise differences were between ASPECTS 0 to 4 and other groups. Symptomatic hemorrhage was more common with lower ASPECTS (P=0.02). Shorter time to reperfusion was significantly associated with better outcomes among patients with ASPECTS 8 to 10 (P=0.01). A similar relationship was seen for ASPECTS 5 to 7 but was not statistically significant. No such relationship was seen for ASPECTS 0 to 4. Conclusions NCCT seems useful for excluding patients with the greatest burden of ischemic damage from futile intra-arterial treatment, which is unlikely to result in patient functional independence and increases the risk of hemorrhage. C1 [Yoo, Albert J.; Chaudhry, Zeshan A.; Berkhemer, Olvert A.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zaidat, Osama O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Goyal, Mayank; Demchuk, Andrew M.; Menon, Bijoy K.] Univ Calgary, Calgary, AB, Canada. [Mualem, Elan; Ueda, Dawn; Buell, Hope; Sit, Siu Po; Bose, Arani] Penumbra Inc, Alameda, CA USA. RP Yoo, AJ (reprint author), 55 Fruit St,Gray 241, Boston, MA 02114 USA. EM ajyoo@partners.org RI Demchuk, Andrew/E-1103-2012 OI Demchuk, Andrew/0000-0002-4930-7789 FU Penumbra Inc. FX The study was sponsored and funded by Penumbra Inc. The sponsor worked with stroke experts to design the trial, control the allocation schedule, and monitor, analyze, interpret, and present the data. The sponsor could not suppress publication of the report even if the results were negative or detrimental to its products. NR 26 TC 32 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2014 VL 45 IS 3 BP 746 EP 751 DI 10.1161/STROKEAHA.113.004260 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AB6DC UT WOS:000331876800033 PM 24503670 ER PT J AU Li, PY Mao, LL Liu, XR Gan, Y Zheng, J Thomson, AW Gao, YQ Chen, J Hu, XM AF Li, Peiying Mao, Leilei Liu, Xiangrong Gan, Yu Zheng, Jing Thomson, Angus W. Gao, Yanqin Chen, Jun Hu, Xiaoming TI Essential Role of Program Death 1-Ligand 1 in Regulatory T-Cell-Afforded Protection Against Blood-Brain Barrier Damage After Stroke SO STROKE LA English DT Article DE matrix metalloproteinase 9; neutrophils; programmed cell death 1 ligand 1; regulatory T-cells; stroke ID FOCAL CEREBRAL-ISCHEMIA; NEUTROPHIL INFILTRATION; EXPRESSION; MATRIX-METALLOPROTEINASE-9; PD-1; AUTOIMMUNITY; INFLAMMATION; MACROPHAGES; BREAKDOWN; ANTIGEN AB Background and Purpose Our recent research revealed that adoptively transferred regulatory T cells (Tregs) reduced acute ischemic brain injury by inhibiting neutrophil-derived matrix metalloproteinase-9 (MMP-9) and protecting against blood-brain barrier damage. The mechanisms underlying Treg interactions with neutrophils remain elusive. This study evaluates the contribution of program death 1-ligand 1 (PD-L1) to Treg-mediated neutrophil inhibition and neuroprotection after cerebral ischemia. Methods In vitro experiments were performed using a transwell system or a coculture system allowing cell-to-cell contact. Focal cerebral ischemia was induced in mice for 60 minutes. Tregs (2x10(6)) isolated from donor animals (wild-type or PD-L1(-/-)) were intravenously injected into ischemic recipients 2 hours after middle cerebral artery occlusion (MCAO). MMP-9 production, blood-brain barrier permeability, and brain infarct were assessed at 1 or 3 days after MCAO. Results In vitro experiments reveal that Treg-mediated inhibition of neutrophil MMP-9 required direct cell-to-cell contact. The suppression of MMP-9 was abolished when Tregs were pretreated with PD-L1 neutralizing antibodies or when neutrophils were pretreated with PD-1 antibodies. In vivo studies confirmed that intravenous administration of Tregs pretreated with PD-L1 antibodies or Tregs isolated from PD-L1-deficient mice failed to inhibit MMP-9 production by blood neutrophils 1 day after 60 minutes MCAO. Furthermore, the blood-brain barrier damage after MCAO was greatly ameliorated in PD-L1-competent Treg-treated mice but not in PD-L1-compromised Treg-treated mice. Consequently, PD-L1 dysfunction abolished Treg-mediated brain protection and neurological improvements 3 days after MCAO. Conclusions PD-L1 plays an essential role in the neuroprotection afforded by Tregs against cerebral ischemia by mediating the suppressive effect of Tregs on neutrophil-derived MMP-9. C1 [Li, Peiying; Mao, Leilei; Liu, Xiangrong; Gao, Yanqin; Chen, Jun; Hu, Xiaoming] Fudan Univ, Huashan Hosp, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Li, Peiying; Mao, Leilei; Liu, Xiangrong; Gao, Yanqin; Chen, Jun; Hu, Xiaoming] Fudan Univ, Huashan Hosp, Inst Brain Sci, Dept Anesthesiol, Shanghai 200433, Peoples R China. [Li, Peiying; Mao, Leilei; Gan, Yu; Zheng, Jing; Chen, Jun; Hu, Xiaoming] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Thomson, Angus W.] Univ Pittsburgh, Sch Med, Dept Surg, Starzl Transplantat Inst, Pittsburgh, PA 15213 USA. [Thomson, Angus W.] Univ Pittsburgh, Sch Med, Dept Immunol, Starzl Transplantat Inst, Pittsburgh, PA 15213 USA. [Li, Peiying; Hu, Xiaoming] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Liu, Xiangrong] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Dis Res Inst, Beijing, Peoples R China. RP Hu, XM (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu; hux2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819 FU Veterans Health Administration (GRECC); National Institutes of Health [NS36736, NS43802, NS45048]; American Heart Association [13SDG14570025]; Shanghai Natural Science Foundation [13ZR1452200] FX This work was supported by the Veterans Health Administration (GRECC pilot grant to Dr Chen), the National Institutes of Health Grants (NS36736, NS43802, and NS45048 to Dr Chen), a grant from the American Heart Association (13SDG14570025 to Dr Hu), and Shanghai Natural Science Foundation (13ZR1452200 to Dr Li). NR 32 TC 21 Z9 21 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAR PY 2014 VL 45 IS 3 BP 857 EP 864 DI 10.1161/STROKEAHA.113.004100 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AB6DC UT WOS:000331876800050 PM 24496394 ER PT J AU LeBrun, DG Chackungal, S Chao, TE Knowlton, LM Linden, AF Notrica, MR Solis, CV McQueen, KAK AF LeBrun, Drake G. Chackungal, Smita Chao, Tiffany E. Knowlton, Lisa M. Linden, Allison F. Notrica, Michelle R. Solis, Carolina V. McQueen, K. A. Kelly TI Prioritizing essential surgery and safe anesthesia for the Post-2015 Development Agenda: Operative capacities of 78 district hospitals in 7 low- and middle-income countries SO SURGERY LA English DT Article ID SURGICAL-CARE; SIERRA-LEONE; COST-EFFECTIVENESS; PUBLIC HOSPITALS; INFRASTRUCTURE; HEALTH; EMERGENCY; SERVICES; DISEASES; BANGLADESH AB Background. Surgery has been neglected in low- and middle-income countries for decades. It is vital that the Post-2015 Development Agenda reflect that surgery is an important part of a comprehensive global health care delivery model. We compare the operative capacities of multiple low- and middle-income countries and identify critical gaps in surgical infrastructure. Methods. The Harvard Humanitarian Initiative survey tool was used to assess the operative capacities of 78 government district hospitals in Bangladesh (n = 7), Bolivia (n = 11), Ethiopia (n = 6), Liberia (n = 11), Nicaragua (n = 10), Rwanda (n = 21), and Uganda (n = 12) from 2011 to 2012. Key outcome measures included infrastructure, equipment availability, physician and nonphysician surgical providers, operative volume, and pharmaceutical capacity. Results. Seventy of 78 district hospitals performed operations. There was fewer than one surgeon or anesthesiologist per 100,000 catchment population in all countries except Bolivia. There were no physician anesthesiologists in any surveyed hospitals in Rwanda, Liberia, Uganda, or in the majority of hospitals in Ethiopia. Mean annual operations per hospital ranged from 374 in Nicaragua to 3,215 in Bangladesh. Emergency operations and obstetric, operations constituted 57.5% and 40% of all operations performed, respectively. Availability of pulse oximetry, essential medicines, and key infrastructure (water, electricity, oxygen) varied widely between and within countries. Conclusion. The need for operative procedures is not being met by the limited operative capacity in numerous low- and middle-income countries. It is of paramount importance that this gap be addressed by prioritizing essential surgery and safe anesthesia in the Post-2015 Development Agenda. C1 [LeBrun, Drake G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19146 USA. [Chackungal, Smita] Univ Western Ontario, Dept Surg, London, ON N6A 3K7, Canada. [Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chao, Tiffany E.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. [Knowlton, Lisa M.] Univ British Columbia, Div Gen Surg, Vancouver, BC V5Z 1M9, Canada. [Linden, Allison F.] Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. [Notrica, Michelle R.] Global Surg Consortium, Phoenix, AZ USA. [Solis, Carolina V.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Solis, Carolina V.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [McQueen, K. A. Kelly] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. RP LeBrun, DG (reprint author), Univ Penn, Perelman Sch Med, 2520 Kimball St, Philadelphia, PA 19146 USA. EM Drake.LeBrun@gmail.com FU Harvard Humanitarian Initiative; Harvard Program in Global Surgery and Social Change; Massachusetts General Hospital (MGH) Global Health Center of Expertise; MGH International Trauma and Disaster Institute; Brigham and Women's Hospital Department of Emergency Medicine; Thomas J. Watson Foundation; Global Surgical Consortium; Duke Global Health Residency/Fellowship Pathway; US Fulbright Program; Harvard School of Public Health FX Funded by the Harvard Humanitarian Initiative, Harvard Program in Global Surgery and Social Change, Massachusetts General Hospital (MGH) Global Health Center of Expertise, MGH International Trauma and Disaster Institute, Brigham and Women's Hospital Department of Emergency Medicine, Thomas J. Watson Foundation, Global Surgical Consortium, Duke Global Health Residency/Fellowship Pathway, US Fulbright Program, and the Harvard School of Public Health. NR 57 TC 29 Z9 29 U1 1 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2014 VL 155 IS 3 BP 365 EP 373 DI 10.1016/j.eurg.2013.10.008 PG 9 WC Surgery SC Surgery GA AB7SO UT WOS:000331991200001 PM 24439745 ER PT J AU Isaac, C Byars-Winston, A McSorley, R Schultz, A Kaatz, A Carnes, ML AF Isaac, Carol Byars-Winston, Angela McSorley, Rebecca Schultz, Alexandra Kaatz, Anna Carnes, Mary L. TI A qualitative study of work-life choices in academic internal medicine SO ADVANCES IN HEALTH SCIENCES EDUCATION LA English DT Article DE Social role theory; Career development; Physicians; Women's issues; Work stress; Retention ID CAREER CHOICE; GENDER; PHYSICIANS; FACULTY; FAMILY; HEALTH; GENERATION AB The high attrition rate of female physicians pursuing an academic medicine research career has not been examined in the context of career development theory. We explored how internal medicine residents and faculty experience their work within the context of their broader life domain in order to identify strategies for facilitating career advancement. Semi-structured interviews were conducted with a purposeful sample of 18 residents and 34 faculty members representing male and female physicians at different career stages. Using thematic analysis, three themes emerged: (1) the love of being a physician ("Raison d'tre"), (2) family obligations ("2nd Shift"), and (3) balancing work demands with non-work life ("Negotiating Academic Medicine"). Female researchers and educators reported more strategies for multiple role planning and management than female practitioners. Interventions aimed at enhancing academic internists' planning and self-efficacy for multiple role management should be investigated as a potential means for increasing participation and facilitate advancement. C1 [Isaac, Carol; Byars-Winston, Angela; McSorley, Rebecca; Schultz, Alexandra; Kaatz, Anna; Carnes, Mary L.] Univ Wisconsin, SMPH, Ctr Womens Hlth Res, Dept Med, Madison, WI 53715 USA. [McSorley, Rebecca; Schultz, Alexandra] Univ Wisconsin, SMPH, Madison, WI 53715 USA. [Kaatz, Anna] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Carnes, Mary L.] Univ Wisconsin, SMPH, Dept Med, Madison, WI 53715 USA. [Carnes, Mary L.] Univ Wisconsin, SMPH, Dept Psychiat, Madison, WI 53715 USA. [Carnes, Mary L.] Univ Wisconsin, Coll Engn, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Mary L.] Univ Wisconsin, Coll Engn, Women Sci & Engn Leadership Inst WISELI, Madison, WI 53715 USA. [Carnes, Mary L.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Byars-Winston, A (reprint author), Univ Wisconsin, SMPH, Ctr Womens Hlth Res, Dept Med, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM ambwinst@medicine.wisc.edu FU NIH [T32 AG00265, R25 GM083252, R01 GM094573, R01 GM088477]; Meriter Hospital; Shapiro Research Fellowship for medical students; Jean Manchester Biddick-Bascom Professorship FX NIH T32 AG00265 (Isaac), R25 GM083252 (Kaatz), R01 GM094573 (Byars-Winston), R01 GM088477 (Carnes), Meriter Hospital, the Shapiro Research Fellowship for medical students (McSorley and Schultz), and the Jean Manchester Biddick-Bascom Professorship (Carnes). Dr. Carnes is a part time staff physician at the William S. Middleton Veterans Hospital (GRECC Publication Number XXXX). NR 37 TC 6 Z9 6 U1 1 U2 18 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4996 EI 1573-1677 J9 ADV HEALTH SCI EDUC JI Adv. Health Sci. Educ. PD MAR PY 2014 VL 19 IS 1 BP 29 EP 41 DI 10.1007/s10459-013-9457-5 PG 13 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AB2NU UT WOS:000331630200004 PM 23605099 ER PT J AU Zambrana, RE Lopez, L Dinwiddie, GY Ray, RM Phillips, LS Trevisan, M Wassertheil-Smoller, S AF Zambrana, Ruth E. Lopez, Lenny Dinwiddie, Gniesha Y. Ray, Roberta M. Phillips, Lawrence S. Trevisan, Maurizio Wassertheil-Smoller, Sylvia TI Prevalence and Incident Prehypertension and Hypertension in Postmenopausal Hispanic Women: Results from the Womens Health Initiative SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; cardiovascular risk; Hispanic; hypertension; postmenopausal; women; Womens Health Initiative ID UNITED-STATES; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; MEXICAN-AMERICANS; METABOLIC SYNDROME; NATIONAL-HEALTH; ADULTS; RISK; DISPARITIES; WHITES AB There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women. The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year 3 in postmenopausal Hispanic women. For the analyses in this paper, we included a total of 4,680 Hispanic women who participated in the Womens Health Initiative (WHI), a randomized clinical trial and observational study, at baseline (19941998) and at third-year follow-up and for whom blood pressure was measured at year 3 (n 3,848). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of hypertension status, defined as systolic blood pressure 140mm Hg and/or diastolic blood pressure 90mm Hg, to assess the odds of incident hypertension at year 3 of follow-up in association with the factors included in the baseline models. At year 3 of follow-up, 27.3% of Hispanic women who were normotensive at baseline had progressed to prehypertension, and 9.0% had become hypertensive. Among the prehypertensive participants at baseline, 30.4% had progressed to hypertension. Compared with normotensive Hispanic women, hypertensive participants had a higher number of cardiovascular risk factors: body mass index 30kg/m(2) (OR 3.76; 95% CI 3.014.71), a family history of diabetes, stroke, and/or myocardial infarction (OR 1.12; 95% CI 1.031.23), treated hypercholesterolemia (OR 1.57; 95% CI 1.231.99), treated diabetes (OR 2.04; 95% CI 1.402.97), and a history of cardiovascular disease (OR 2.04; 95% CI 1.582.64). Hispanic women seem to experience an increased risk of incident hypertension in later adulthood. On a practical level, recommendations for preventive care and population-wide adoption of health behaviors, such as community-focused campaigns to engage in physical activity, may contribute to reductions in hypertension risk factors. Trial Number NCT00000611. C1 [Zambrana, Ruth E.] Univ Maryland, Dept Womens Studies, College Pk, MD 20742 USA. [Zambrana, Ruth E.] Univ Maryland, Consortium Race Gender & Ethn, College Pk, MD 20742 USA. [Zambrana, Ruth E.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Lopez, Lenny] Harvard Univ, Sch Med, Boston, MA USA. [Dinwiddie, Gniesha Y.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dinwiddie, Gniesha Y.] Univ Maryland, African Amer Studies Dept, College Pk, MD 20742 USA. [Dinwiddie, Gniesha Y.] Univ Maryland, Maryland Populat Res Ctr, College Pk, MD 20742 USA. [Ray, Roberta M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Phillips, Lawrence S.] Atlanta VA Med Ctr, Decatur, GA USA. [Phillips, Lawrence S.] Emory Univ, Sch Med, Div Endocrinol & Metab, Atlanta, GA USA. [Trevisan, Maurizio] CUNY City Coll, Sch Biomed Educ, New York, NY 10031 USA. [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Div Epidemiol, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Zambrana, RE (reprint author), Univ Maryland, Dept Womens Studies, College Pk, MD 20742 USA. EM rzambran@umd.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268 201100004C, HHSN271201100004C] FX The WHI program is 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. We gratefully acknowledge the initial contributions of Drs Guangyu Zhang and Darrell Gaskin and those of Laura A. Logie, PhD, who assisted with review of the literature. We also would like to thank the anonymous reviewers for their thoughtful comments and feedback on our manuscript. We acknowledge all WHI Centers and their principal investigators for their participation in this research and the dedicated and committed participants of the WHI who made this work possible. Program Office (National Heart, Lung, and Blood Institute, Bethesda, Maryland): 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. For a list of all the investigators who have contributed to WHI science, please visit: https://cleo.whi.org/researchers/SitePages/Write%20a%20Paper.aspx. NR 40 TC 4 Z9 5 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2014 VL 27 IS 3 BP 372 EP 381 DI 10.1093/ajh/hpt279 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AB5QB UT WOS:000331842300013 PM 24480867 ER PT J AU Weinberg, I Gona, P O'Donnell, CJ Jaff, MR Murabito, JM AF Weinberg, Ido Gona, Philimon O'Donnell, Christopher J. Jaff, Michael R. Murabito, Joanne M. TI The Systolic Blood Pressure Difference Between Arms and Cardiovascular Disease in the Framingham Heart Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Cardiovascular disease; Cardiovascular risk; Interarm blood pressure difference ID SUBCLAVIAN ARTERY-STENOSIS; PRIMARY-CARE; BILATERAL INDIRECT; VASCULAR-DISEASE; RISK-FACTOR; PREVALENCE; METAANALYSIS; ASSOCIATION; MANAGEMENT; COHORT AB BACKGROUND: An increased interarm systolic blood pressure difference is an easily determined physical examination finding. The relationship between interarm systolic blood pressure difference and risk of future cardiovascular disease is uncertain. We described the prevalence and risk factor correlates of interarm systolic blood pressure difference in the Framingham Heart Study (FHS) original and offspring cohorts and examined the association between interarm systolic blood pressure difference and incident cardiovascular disease and all-cause mortality. METHODS: An increased interarm systolic blood pressure difference was defined as >= 10 mm Hg using the average of initial and repeat blood pressure measurements obtained in both arms. Participants were followed through 2010 for incident cardiovascular disease events. Multivariable Cox proportional hazards regression analyses were performed to investigate the effect of interarm systolic blood pressure difference on incident cardiovascular disease. RESULTS: We examined 3390 (56.3% female) participants aged 40 years and older, free of cardiovascular disease at baseline, mean age of 61.1 years, who attended a FHS examination between 1991 and 1994 (original cohort) and from 1995 to 1998 (offspring cohort). The mean absolute interarm systolic blood pressure difference was 4.6 mm Hg (range 0-78). Increased interarm systolic blood pressure difference was present in 317 (9.4%) participants. The median follow-up time was 13.3 years, during which time 598 participants (17.6%) experienced a first cardiovascular event, including 83 (26.2%) participants with interarm systolic blood pressure difference >= 10 mm Hg. Compared with those with normal interarm systolic blood pressure difference, participants with an elevated interarm systolic blood pressure difference were older (63.0 years vs 60.9 years), had a greater prevalence of diabetes mellitus (13.3% vs 7.5%,), higher systolic blood pressure (136.3 mm Hg vs 129.3 mm Hg), and a higher total cholesterol level (212.1 mg/dL vs 206.5 mg/dL). Interarm systolic blood pressure difference was associated with a significantly increased hazard of incident cardiovascular events in the multivariable adjusted model (hazard ratio 1.38; 95% CI, 1.09-1.75). For each 1-SD-unit increase in absolute interarm systolic blood pressure difference, the hazard ratio for incident cardiovascular events was 1.07 (95% CI, 1.00-1.14) in the fully adjusted model. There was no such association with mortality (hazard ratio 1.02; 95% CI 0.76-1.38). CONCLUSIONS: In this community-based cohort, an interarm systolic blood pressure difference is common and associated with a significant increased risk for future cardiovascular events, even when the absolute difference in arm systolic blood pressure is modest. These findings support research to expand clinical use of this simple measurement. (C) 2014 Elsevier Inc. All rights reserved. C1 [Weinberg, Ido; O'Donnell, Christopher J.; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA. [Gona, Philimon; O'Donnell, Christopher J.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Biostat & Hlth Serv Res, Worcester, MA USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, 55 Fruit St,Warren 905, Boston, MA 02114 USA. EM mjaff@partners.org FU NHLBI Framingham Heart Study [N01-HC-25195]; NHLBI Division of Intramural Research FX The Framingham Heart Study is supported by the NHLBI Framingham Heart Study (contract N01-HC-25195). Analysis for this project was supported by the NHLBI Division of Intramural Research. NR 39 TC 22 Z9 23 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD MAR PY 2014 VL 127 IS 3 BP 209 EP 215 DI 10.1016/j.amjmed.2013.10.027 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AB3YD UT WOS:000331725200024 PM 24287007 ER PT J AU Stepanczuk, BC Dicianno, BE Webb, TS AF Stepanczuk, Beth C. Dicianno, Brad E. Webb, Thomas S. TI Young Adults with Spina Bifida May Have Higher Occurrence of Prehypertension and Hypertension SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Prehypertension; Meningomyelocele; Cardiovascular Diseases; Hypertension ID CARDIOVASCULAR-DISEASE RISK; JOINT NATIONAL COMMITTEE; MEDICAL-MANAGEMENT; BLOOD-PRESSURE; CORD-INJURY; PREVALENCE; ADOLESCENTS; ANOMALIES; CARE AB Objective The aims of this study were to determine the occurrence of prehypertension and high blood pressure in adults with spina bifida (SB) and to examine relationships among blood pressure, cardiovascular disease risk factors, and SB-specific factors. Design This is a cross-sectional, retrospective analysis of adults with SB. SB-specific factors and cardiovascular disease risk factors were compared among subjects with high blood pressure, subjects with blood pressure in the prehypertensive range, and normotensive subjects using the chi(2), Kruskal-Wallis, or Fisher's exact tests. Results Of 225 subjects, the occurrence of prehypertension and high blood pressure was 27% (n = 22) and 27% (n = 22) for ages 18-29 yrs, 35% (n = 26) and 41% (n = 30) for ages 30-39 yrs, 18% (n = 8) and 66% (n = 29) for ages 40-49 yrs, and 21% (n = 5) and 67% (n = 16) for 50 yrs or older, respectively. Of the subjects with high blood pressure, 56% were men, 14% had obstructive sleep apnea, 14% had diabetes, 19% had renal dysfunction, 38% used tobacco, 16% had hydronephrosis, and 71% had a shunt. The groups differed significantly with respect to diabetes (P = 0.004), bladder procedures (P = 0.001), and renal dysfunction (P < 0.001), with higher proportions of subjects with high blood pressure having these comorbidities. Conclusions Fewer than half of the subjects were considered normotensive. A greater proportion of young adults with SB appear to have high blood pressure compared with the general United States population. Because elevated blood pressure is an independent, modifiable risk factor of cardiovascular disease, these findings support early screening and intervention for elevated blood pressure in individuals with SB. C1 [Stepanczuk, Beth C.; Dicianno, Brad E.] Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. [Dicianno, Brad E.] Univ Pittsburgh, Med Ctr, Adult Outpatient Spina Bifida Clin, Pittsburgh, PA 15213 USA. [Dicianno, Brad E.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Dicianno, Brad E.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15213 USA. [Webb, Thomas S.] Huntersville Pediat & Internal Med, Huntersville, NC USA. RP Dicianno, BE (reprint author), Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, 3471 5th Ave,Suite 202, Pittsburgh, PA 15213 USA. FU Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center FX Supported by funds from the Department of Physical Medicine and Rehabilitation, University of Pittsburgh Medical Center. NR 23 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAR PY 2014 VL 93 IS 3 BP 200 EP 206 DI 10.1097/PHM.0b013e3182a92b03 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AB3RH UT WOS:000331707400002 PM 24088776 ER PT J AU Nelson, CC Wagner, GR Caban-Martinez, AJ Buxton, OM Kenwood, CT Sabbath, EL Hashimoto, DM Hopcia, K Allen, J Sorensen, G AF Nelson, Candace C. Wagner, Gregory R. Caban-Martinez, Alberto J. Buxton, Orfeu M. Kenwood, Christopher T. Sabbath, Erika L. Hashimoto, Dean M. Hopcia, Karen Allen, Jennifer Sorensen, Glorian TI Physical Activity and Body Mass Index The Contribution of Age and Workplace Characteristics SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID LIFE-STYLE INTERVENTION; PATIENT-CARE WORKERS; SHORT-SLEEP DURATION; RACIAL-DISCRIMINATION; SEXUAL-HARASSMENT; AGING WORKFORCE; BLOOD-PRESSURE; OBESITY; CANCER; RISK AB Background: The workplace is an important domain for adults, and many effective interventions targeting physical activity and weight reduction have been implemented in the workplace. However, the U.S. workforce is aging, and few studies have examined the relationship of BMI, physical activity, and age as they relate to workplace characteristics. Purpose: This paper reports on the distribution of physical activity and BMI by age in a population of hospital-based healthcare workers and investigates the relationships among workplace characteristics, physical activity, and BMI. Methods: Data from a survey of patient care workers in two large academic hospitals in the Boston area were collected in late 2009 and analyzed in early 2013. Results: In multivariate models, workers reporting greater decision latitude (OR=1.02, 95% CI=1.01, 1.03) and job flexibility (OR=-1.05, 95% CI=1.01, 1.10) reported greater physical activity. Overweight and obesity increased with age (p <0.01), even after adjusting for workplace characteristics. Sleep deficiency (OR=1.56, 95% CI=1.15, 2.12) and workplace harassment (OR=1.62, 95% CI=1.20, 2.18) were also associated with obesity. Conclusions: These findings underscore the persistent impact of the work environment for workers of all ages. Based on these results, programs or policies aimed at improving the work environment, especially decision latitude, job flexibility, and workplace harassment should be included in the design of worksite-based health promotion interventions targeting physical activity or obesity. (C) 2014 American Journal of Preventive Medicine C1 [Nelson, Candace C.; Wagner, Gregory R.; Caban-Martinez, Alberto J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. [Buxton, Orfeu M.] Harvard Univ, Sch Med, Div Sleep Med, Cambridge, MA 02138 USA. [Sabbath, Erika L.] Harvard Univ, Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. [Buxton, Orfeu M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hashimoto, Dean M.] Partners Healthcare Syst, Boston, MA USA. [Allen, Jennifer] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Kenwood, Christopher T.] New England Res Inst Inc, Watertown, MA USA. [Hopcia, Karen; Sorensen, Glorian] Univ Illinois, Coll Nursing, Chicago, IL USA. [Wagner, Gregory R.] NIOSH, Washington, DC USA. RP Nelson, CC (reprint author), 677 Huntington Ave, Boston, MA 02115 USA. EM cnelson@hsph.harvard.edu RI Allen, Jennifer/M-2113-2015; OI Caban-Martinez, Alberto/0000-0002-5960-1308 FU Harvard School of Public Health (Harvard-Liberty Postdoctoral Fellowship); CDC/National Institute for Occupational Safety and Health (NIOSH); NIOSH [U19 OH008861, 6U190H008861]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [T32 AR055885]; Clinical Orthopedic and Musculoskeletal Education and Training (COMET) Program at Brigham and Women's Hospital, Harvard Medical School and Harvard School of Public Health; Sunovion [ESRC-0004, ESRC-0977]; Takeda Pharmaceuticals North America; American Academy of Craniofacial Pain; National Heart, Lung, Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Postdoctoral Association; Oklahoma State University; New York University; Oregon Health Sciences University; SUNY Downstate Medical Center; American Diabetes Association; John D. and Catherine T. MacArthur Foundation Network on an Aging Society; NIA [5R01AG040248-02] FX There are no conflicts of interest to report, but in the interest of full disclosure, Dr. Nelson receives her funding from Harvard School of Public Health (Harvard-Liberty Postdoctoral Fellowship), Dr. Wagner receives his funding from CDC/National Institute for Occupational Safety and Health (NIOSH), Dr. Caban-Martinez from the NIOSH, Grant U19 OH008861; the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Grant T32 AR055885; and the Clinical Orthopedic and Musculoskeletal Education and Training (COMET) Program at Brigham and Women's Hospital, Harvard Medical School and Harvard School of Public Health. Dr. Buxton has received two investigator-initiated grants from Sepracor Inc (now Sunovion; ESRC-0004 and ESRC-0977, ClinicalTrials.gov Identifiers NCT00555750, NCT00900159), and two investigator-initiated grants from Cephalon Inc (now Teva; ClinicalTrials.gov Identifier: NCT00895570). OMB received Speaker's Bureau, CME and non-CME lecture honoraria, and an unrestricted educational grant from Takeda Pharmaceuticals North America. OMB serves as a consultant and expert witness for Dinsmore LLC, consulting fees for serving on the Scientific Advisory Board of Matsutani America, and consulting fees from the Wake Forest University Medical Center (North Carolina). OMB received speaking fees and/or travel support for speaking from American Academy of Craniofacial Pain, National Heart, Lung, Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Postdoctoral Association, Oklahoma State University, Oregon Health Sciences University, SUNY Downstate Medical Center, American Diabetes Association, and New York University. Mr. Kenwood from NIOSH, Grant: 6U190H008861, Dr. Sabbath from the John D. and Catherine T. MacArthur Foundation Network on an Aging Society and NIA (Grant 5R01AG040248-02), Dr. Hashimoto is an employee of Partners Healthcare System, Dr. Hopcia is funded by the University of Illinois at Chicago, NR 37 TC 4 Z9 5 U1 0 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAR PY 2014 VL 46 IS 3 SU 1 BP S42 EP S51 DI 10.1016/j.amepre.2013.10.035 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AB2AU UT WOS:000331596200006 PM 24512930 ER PT J AU Oliva, E Egger, JF Young, RH AF Oliva, Esther Egger, Jean-Francois Young, Robert H. TI Primary Endometrioid Stromal Sarcoma of the Ovary A Clinicopathologic Study of 27 Cases With Morphologic and Behavioral Features Similar to Those of Uterine Low-grade Endometrial Stromal Sarcoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; endometrioid stromal sarcoma; endometriosis ID SMOOTH-MUSCLE TUMORS; GRANULOSA-CELL TUMORS; OF-THE-LITERATURE; SEX-CORD TUMORS; CLINICOPATHOLOGICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS; MESENCHYMAL TUMORS; UTERINE SARCOMAS; UTERUS; NEOPLASMS AB Twenty-seven endometrioid stromal sarcomas of the ovary from patients 38 to 76 (mean 56) years of age are reported. The tumors were unilateral in 20 cases and bilateral in 7. They were solid (9), solid and cystic (9), or predominantly cystic (6) when this information was known and ranged from 1 to 20 (mean 9.5) cm. The solid areas typically had a tan-yellow cut surface, with areas of hemorrhage and/or necrosis noted in 6; however, in addition, blood was often present in the cyst lumens. On microscopic examination, the predominant and frequently exclusive pattern was a diffuse growth of small cells with interspersed arterioles, the latter appearing round to elongated. A fibromatous pattern was present in 14 of the tumors but was extensive in only 3. A vague nodular growth was observed in 10 tumors but was never striking; a storiform growth was seen in 2 tumors, being conspicuous in 1. Hyaline plaques were present in 10 tumors but were striking in only 2. Sex cord-like or smooth muscle differentiation was seen in 7 and 6 tumors, respectively, being striking in 2 and 3 of them. Foam cells were present in 6 tumors. The tumors showed minimal cytologic atypia. The mitotic index ranged from < 1 to 17/10 high-power fields (HPF), being < 1/10 HPF in 12, 1 to 5/10 HPF in 9, 6 to 10/10 HPF in 2, and > 10/10 HPF in 4 tumors. Infarct-type necrosis was noted in 12 tumors. Hemorrhage, typically recent, was seen in 20 cases, being conspicuous in 5. Ovarian endometriosis was intimately associated with the tumor in 16 cases. Seven patients had stage I tumors, 5 stage II, 13 stage III, and 2 stage IV. Follow-up information was available for 21 patients; 10 were alive and free of disease from 4 to 21 years postoperatively (follow-up being >= 11 y in 5); 6 were alive with disease from 1 to 22 years postoperatively; 5 patients are known to have died of disease, with the interval being unknown in 1, and 2, 4, 13, and 17 years in the others. Follow-up information was unavailable in the remaining 6 patients. These findings indicate that these tumors, as in the uterus, often have an indolent course with a better prognosis than other ovarian sarcomas, indicating the importance of correct diagnosis. The differential diagnosis of these neoplasms is in the first instance with a metastasis from the uterus; knowledge of the status of the uterus is paramount in this distinction. Associated ovarian endometriosis suggests a primary tumor. When a primary ovarian origin is determined, the differential diagnosis is most often with a sex cord-stromal tumor, particularly a granulosa cell tumor because of a diffuse growth of cells with scant cytoplasm. C1 [Oliva, Esther; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,James Homer Wright Pathol, Boston, MA 02115 USA. [Egger, Jean-Francois] Univ Geneva, Dept Pathol, Viollier Weintraub Lab, CH-1211 Geneva, Switzerland. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM eoliva@partners.org NR 53 TC 6 Z9 7 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2014 VL 38 IS 3 BP 305 EP 315 DI 10.1097/PAS.0000000000000145 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA AB2XQ UT WOS:000331655900003 PM 24525500 ER PT J AU Huppmann, AR Nicolae, A Slack, GW Pittaluga, S Davies-Hill, T Ferry, JA Harris, NL Jaffe, ES Hasserjian, RP AF Huppmann, Alison R. Nicolae, Alina Slack, Graham W. Pittaluga, Stefania Davies-Hill, Theresa Ferry, Judith A. Harris, Nancy Lee Jaffe, Elaine S. Hasserjian, Robert P. TI EBV May Be Expressed in the LP Cells of Nodular Lymphocyte-predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE nodular lymphocyte-predominant Hodgkin lymphoma; immunohistochemistry; epidemiology; Epstein-Barr virus; Hodgkin lymphoma ID EPSTEIN-BARR-VIRUS; LATENT MEMBRANE-PROTEIN; POLYMERASE-CHAIN-REACTION; EUROPEAN TASK-FORCE; TUMOR-CELLS; UNITED-STATES; H-CELLS; DISEASE; ASSOCIATION; CHILDHOOD AB Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and classical Hodgkin lymphoma (CHL) are classified separately because of their distinct clinical and pathologic features. Whereas Epstein-Barr virus (EBV) is detected in the neoplastic cells of 25% to 70% of CHL, NLPHL is generally considered to be EBV-. We assessed EBV status in 302 pediatric and adult cases of NLPHL. A total of 145 pediatric (age 18 y or younger) and 157 adult cases of NLPHL were retrieved from 3 North American centers and tested for EBV by in situ hybridization (EBV-encoded small RNA). Clinical and pathologic features were analyzed. Five (3.4%) pediatric and 7 (4.5%) adult NLPHL cases contained EBV+ lymphocyte-predominant (LP) cells. Although all 12 cases met the criteria for diagnosis of NLPHL, atypical features were present, including capsular fibrosis, atrophic germinal centers, and pleomorphic or atypical LP cells. CD20 and OCT-2 were strongly and diffusely positive in all except 1 case. However, PAX5 and CD79a were weak and/or variable in 7/8 and 6/6 cases tested, respectively. EBV+ cases were more likely to be CD30(+) (75%) compared with EBV- cases (25%) (P=0.0007); CD15 was negative in all cases. Our results show that EBV+ LP cells may occur in NLPHL. Distinguishing EBV+ NLPHL from CHL can be challenging, as EBV+ NLPHL can have partial expression of CD30 and weak PAX5 staining as well as pleomorphic-appearing LP cells. However, the overall appearance and maintenance of B-cell phenotype, with strong and diffuse CD20 and OCT-2 expression, support the diagnosis of NLPHL in these cases. C1 [Huppmann, Alison R.; Nicolae, Alina; Pittaluga, Stefania; Davies-Hill, Theresa; Jaffe, Elaine S.] NCI, Bethesda, MD 20892 USA. [Ferry, Judith A.; Harris, Nancy Lee; Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Slack, Graham W.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Jaffe, ES (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Jaffe, Elaine/0000-0003-4632-0301 FU Intramural NIH HHS [ZIA SC000550-33] NR 36 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2014 VL 38 IS 3 BP 316 EP 324 DI 10.1097/PAS.0000000000000107 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA AB2XQ UT WOS:000331655900004 PM 24525501 ER PT J AU Vaszar, LT Orzechowski, NM Specks, U Ytterberg, SR Loftus, EV Mark, EJ Tazelaar, HD AF Vaszar, Laszlo T. Orzechowski, Nicole M. Specks, Ulrich Ytterberg, Steven R. Loftus, Edward V., Jr. Mark, Eugene J. Tazelaar, Henry D. TI Coexistent Pulmonary Granulomatosis With Polyangiitis (Wegener Granulomatosis) and Crohn Disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Crohn disease; granuloma; pulmonary granulomatosis with polyangiitis (Wegener); inflammatory bowel disease; review ID INFLAMMATORY-BOWEL-DISEASE; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; OF-THE-LITERATURE; ULCERATIVE-COLITIS; OLMSTED COUNTY; SARCOIDOSIS; VASCULITIS; PATIENT; LUNG; MANIFESTATIONS AB Crohn disease (CD) may be associated with various extraintestinal manifestations, including, rarely, respiratory tract involvement. When necrobiotic pulmonary nodules are present, the differential diagnosis includes granulomatosis with polyangiitis (Wegener granulomatosis) (GPA). The respiratory tract manifestations of CD and GPA may mimic each other, complicating the diagnosis and suggesting the possible coexistence of these 2 conditions. The aim of this study was to describe the clinical, radiographic, and pathologic features of patients in whom CD and GPA coexist. We reviewed the teaching files of the authors and searched the Mayo Clinic medical records for coexistent inflammatory bowel diseases and antineutrophilic cytoplasmic antibodies (ANCA)-associated vasculitides. We reviewed in detail 97 patient charts and excluded cases of ulcerative colitis and those in whom only one of the diagnoses was present. Pulmonary and gastrointestinal biopsies were reviewed when available. We also searched the medical literature for previously published cases. We found 6 cases of coexistent CD and pulmonary GPA and 4 cases with extrapulmonary GPA; 3 cases (all with extrapulmonary GPA) have been published previously. The diagnosis of CD preceded that of GPA in 11 cases. Proteinase 3-ANCA was positive in 6 cases, negative in 2, and not reported in 5 cases. Myeloperoxidase-ANCA was negative in 6 cases and unavailable in the remainder of patients. Pathology revealed features diagnostic of GPA in all cases with necrotizing granulomatous inflammation and segmental vasculitis. Pulmonary findings in patients with CD or the presence of granulomatous colitis in patients with GPA should prompt the inclusion in the differential diagnosis of a possible coexistence of CD and GPA. C1 [Vaszar, Laszlo T.] Mayo Clin, Div Thorac Med, Scottsdale, AZ 85259 USA. [Tazelaar, Henry D.] Mayo Clin, Dept Lab Med & Pathol, Scottsdale, AZ 85259 USA. [Orzechowski, Nicole M.] Dartmouth Hitchcock Med Ctr, Rheumatol Sect, Lebanon, NH 03766 USA. [Specks, Ulrich] Mayo Clin, Div Thorac Med, Rochester, MN USA. [Ytterberg, Steven R.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Loftus, Edward V., Jr.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Vaszar, LT (reprint author), Mayo Clin, Div Thorac Med, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM vaszar.laszlo@mayo.edu RI Loftus, Edward/E-8304-2011 NR 42 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2014 VL 38 IS 3 BP 354 EP 359 DI 10.1097/PAS.0000000000000135 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA AB2XQ UT WOS:000331655900009 PM 24525506 ER PT J AU Hilsabeck, RC Hietpas, TL Mccoy, KJM AF Hilsabeck, Robin C. Hietpas, Tammy L. Mccoy, Karin J. M. TI Satisfaction of Referring Providers with Neuropsychological Services within a Veterans Administration Medical Center SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Assessment; Professional issues ID UNITED-STATES AB With the implementation of healthcare reform, it is essential for neuropsychologists to establish themselves as important members of healthcare teams and to work efficiently and effectively. The purpose of this study was to survey the satisfaction of referring providers with neuropsychological services, including turn-around time of reports and their essential elements, within a hospital system that uses electronic medical records. Findings revealed that referral sources are generally satisfied with neuropsychological services and find them valuable. They especially appreciate the neuropsychological report and detailed testing of cognitive and functional abilities and prefer the report within 2 weeks of the patient's appointment. Most find all sections of the report completely essential with the exception of test scores, and most are comfortable with recommendations made by neuropsychologists. With few exceptions, there were no differences among types of referring providers (i.e., physicians, psychologists, and social workers). Future surveys may wish to examine how neuropsychological services affect patient outcomes. C1 [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.; Hietpas, Tammy L.; Mccoy, Karin J. M.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Hietpas, Tammy L.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. RP Hilsabeck, RC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM hilsabeck@uthscsa.edu NR 8 TC 1 Z9 1 U1 0 U2 2 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 MAR PY 2014 VL 29 IS 2 BP 131 EP 140 DI 10.1093/arclin/act084 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA AB8FY UT WOS:000332026800002 PM 24200634 ER PT J AU Hulten, E Bittencourt, MS Ghoshhajra, B O'Leary, D Christman, MP Blaha, MJ Truong, Q Nelson, K Montana, P Steigner, M Rybicki, F Hainer, J Brady, TJ Hoffmann, U Di Carli, MF Nasir, K Abbara, S Blankstein, R AF Hulten, Edward Bittencourt, Marcio Sommer Ghoshhajra, Brian O'Leary, Daniel Christman, Mitalee P. Blaha, Michael J. Quynh Truong Nelson, Kyle Montana, Philip Steigner, Michael Rybicki, Frank Hainer, Jon Brady, Thomas J. Hoffmann, Udo Di Carli, Marcelo F. Nasir, Khurram Abbara, Suhny Blankstein, Ron TI Incremental prognostic value of coronary artery calcium score versus CT angiography among symptomatic patients without known coronary artery disease SO ATHEROSCLEROSIS LA English DT Article DE Coronary computed tomography angiography; Coronary artery calcium score; Atherosclerosis; Epidemiology ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; CARDIOVASCULAR RISK-ASSESSMENT; EXPERT CONSENSUS DOCUMENT; AMERICAN-COLLEGE; CHEST-PAIN; TASK-FORCE; DIAGNOSIS; CALCIFICATION; PROBABILITY; PREVALENCE AB Objective: To evaluate the prognostic value and test characteristics of coronary artery calcium (CAC) score for the identification of obstructive coronary artery disease (CAD) in comparison with coronary computed tomography angiography (CCTA) among symptomatic patients. Methods: Retrospective cohort study at two large hospitals, including all symptomatic patients without prior CAD who underwent both CCTA and CAC. Accuracy of CAC for the identification of >= 50% and >= 70% stenosis by CCTA was evaluated. Prognostic value of CAC and CCTA were compared for prediction of major adverse cardiovascular events (MACE, defined as non-fatal myocardial infarction, cardiovascular death, late coronary revascularization (>90 days), and unstable angina requiring hospitalization). Results: Among 1145 included patients, the mean age was 55 +/- 12 years and median follow up 2.4 (IQR: 1.5-3.5) years. Overall, 406 (35%) CCTA were normal, 454 (40%) had <50% stenosis, and 285 (25%) had >= 50% stenosis. The prevalence of >= 70% stenosis was 16%. Among 483 (42%) patients with CAC zero, 395 (82%) had normal CCTA, 81 (17%) <50% stenosis, and 7 (1.5%) >= 50% stenosis. 2 (0.4%) patients had >= 70% stenosis. For diagnosis of >= 50% stenosis, CAC had a sensitivity of 98% and specificity of 55%. The negative predictive value (NPV) for CAC was 99% for >= 50% stenosis and 99.6% for >= 70% stenosis by CCTA. There were no adverse events among the 7 patients with zero calcium and >50% CAD. For prediction of MACE, the c-statistic for clinical risk factors of 0.62 increased to 0.73 (p < 0.001) with CAC versus 0.77 (p = 0.02) with CCTA. Conclusion: Among symptomatic patients with CAC zero, a 1-2% prevalence of potentially obstructive CAD occurs, although this finding was not associated with future coronary revascularization or adverse prognosis within 2 years. Published by Elsevier Ireland Ltd. C1 [Hulten, Edward; Bittencourt, Marcio Sommer; O'Leary, Daniel; Christman, Mitalee P.; Nelson, Kyle; Montana, Philip; Steigner, Michael; Rybicki, Frank; Hainer, Jon; Di Carli, Marcelo F.; Blankstein, Ron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program,Dept Med, Boston, MA 02115 USA. [Hulten, Edward; Bittencourt, Marcio Sommer; O'Leary, Daniel; Christman, Mitalee P.; Nelson, Kyle; Montana, Philip; Steigner, Michael; Rybicki, Frank; Hainer, Jon; Di Carli, Marcelo F.; Blankstein, Ron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Hulten, Edward] Walter Reed Natl Mil Med Ctr, Dept Med, Serv Cardiol, Bethesda, MD USA. [Bittencourt, Marcio Sommer] Univ Sao Paulo, Heart Inst InCor, Sao Paulo, Brazil. [Ghoshhajra, Brian; Brady, Thomas J.; Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol,Div Cardiac Imaging,Med Sch, Boston, MA 02115 USA. [Blaha, Michael J.] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD USA. [Quynh Truong] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA USA. [Nasir, Khurram] Baptist Hlth South Florida, Miami, FL USA. RP Blankstein, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program,Dept Med, 75 Francis St, Boston, MA 02115 USA. EM rblankstein@partners.org RI Bittencourt, Marcio/C-1444-2011 OI Bittencourt, Marcio/0000-0002-3711-1754 FU Siemens Medical Systems; Toshiba Medical Systems Corporation FX Dr. Hoffmann reports research support from Siemens Medical Systems. Dr. Rybicki reports research support from Toshiba Medical Systems Corporation. The opinions and assertions contained herein are the authors' alone and do not represent the views of the Walter Reed National Military Medical Center, the US Army, or the Department of Defense. NR 31 TC 14 Z9 14 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 EI 1879-1484 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAR PY 2014 VL 233 IS 1 BP 190 EP 195 DI 10.1016/j.atherosclerosis.2013.12.029 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AB1OZ UT WOS:000331563400032 PM 24529143 ER PT J AU Reese, HE Scahill, L Peterson, AL Crowe, K Woods, DW Piacentini, J Walkup, JT Wilhelm, S AF Reese, Hannah E. Scahill, Lawrence Peterson, Alan L. Crowe, Katherine Woods, Douglas W. Piacentini, John Walkup, John T. Wilhelm, Sabine TI The Premonitory Urge to Tic: Measurement, Characteristics, and Correlates in Older Adolescents and Adults SO BEHAVIOR THERAPY LA English DT Article DE Tourette syndrome; chronic tic disorder; premonitory urge; older adolescents; adults ID DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE COMPULSIVE SCALE; TOURETTES-SYNDROME; DOUBLE-BLIND; BEHAVIOR; RELIABILITY; VALIDITY; THERAPY; PLACEBO; TRIAL AB In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD. C1 [Reese, Hannah E.; Crowe, Katherine; Wilhelm, Sabine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Scahill, Lawrence] Emory Univ, Yale Child Study Ctr, Atlanta, GA 30322 USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Crowe, Katherine] Fordham Univ, Bronx, NY 10458 USA. [Woods, Douglas W.] Univ Wisconsin, Texas A&M Univ, Madison, WI 53706 USA. [Piacentini, John] Univ Calif Los Angeles, Los Angeles, CA USA. [Walkup, John T.] Weill Cornell Med Coll, Johns Hopkins Med Inst, New York, NY USA. RP Reese, HE (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM hreese@partners.org OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [R01MH069875, R01MH069874, R01 MH069877, R01 MH069875, R01 MH069874, 5R01MH069877] NR 30 TC 22 Z9 23 U1 1 U2 9 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2014 VL 45 IS 2 BP 177 EP 186 PG 10 WC Psychology, Clinical SC Psychology GA AB7RY UT WOS:000331989600003 PM 24491193 ER PT J AU Baker, AS Litwack, SD Clapp, JD Beck, JG Sloan, DM AF Baker, Aaron S. Litwack, Scott D. Clapp, Joshua D. Beck, J. Gayle Sloan, Denise M. TI The Driving Behavior Survey as a Measure of Behavioral Stress Responses to MVA-Related PTSD SO BEHAVIOR THERAPY LA English DT Article DE PTSD; stress response; exposure; treatment; driving; assessment ID VEHICLE ACCIDENT SURVIVORS; POSTTRAUMATIC-STRESS; ANXIETY DISORDERS; TRAFFIC ACCIDENTS; DRIVER STRESS; THERAPY; VETERANS; TRAUMA; EPIDEMIOLOGY; PERFORMANCE AB Numerous treatments are available that address the core symptoms of posttraumatic stress disorder (PTSD). However, there are a number of related behavioral stress responses that are not assessed with PTSD measures, yet these behavioral stress responses affect quality of life. The goal of the current study was to investigate whether a recently developed measure of behavioral stress response, the Driving Behavior Survey (DBS), was sensitive to change associated with treatment among a group of participants diagnosed with PTSD. The DBS indexes anxious driving behavior, which is frequently observed among individuals with motor vehicle accident-related PTSD. Participants (n = 40) were racially diverse adults (M age = 40.78, 63% women) who met diagnostic criteria for motor vehicle accident-related PTSD. Hierarchical linear modeling analyses indicated that participants who were assigned to a brief, exposure-based intervention displayed significant reductions on the DBS subscales relative to participants assigned to the wait-list control condition (r = .41-.43). Moreover, mediational analyses indicated that the observed reductions on the DBS subscales were not better accounted for by reductions in PTSD. Taken together, these findings suggest that the DBS subscales are sensitive to changes associated with PTSD treatment and can be used to augment outcome assessment in PTSD treatment trials. C1 [Baker, Aaron S.; Litwack, Scott D.; Sloan, Denise M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Baker, Aaron S.; Litwack, Scott D.; Sloan, Denise M.] Boston Univ, Boston, MA 02215 USA. [Baker, Aaron S.] Univ LaVerne, La Verne, CA USA. [Clapp, Joshua D.] Univ Wyoming, Laramie, WY 82071 USA. [Beck, J. Gayle] Univ Memphis, Memphis, TN 38152 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 South Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov FU NIMH NIH HHS [T32MH019836, R34 MH077658, T32 MH019836, R34MH077658-02] NR 50 TC 1 Z9 1 U1 2 U2 11 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD MAR PY 2014 VL 45 IS 2 BP 263 EP 272 PG 10 WC Psychology, Clinical SC Psychology GA AB7RY UT WOS:000331989600011 PM 24491201 ER PT J AU Chiorean, EG Sweeney, C Youssoufian, H Qin, A Dontabhaktuni, A Loizos, N Nippgen, J Amato, R AF Chiorean, E. Gabriela Sweeney, Christopher Youssoufian, Hagop Qin, Amy Dontabhaktuni, Aruna Loizos, Nick Nippgen, Johannes Amato, Robert TI A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFR alpha) monoclonal antibody, in patients with advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Olaratumab; IMC-3G3; Platelet-derived growth factor receptor; Solid tumors; Phase I ID GASTROINTESTINAL STROMAL TUMORS; POTENTIAL THERAPEUTIC TARGET; TYROSINE KINASE INHIBITOR; PROSTATE-CANCER CELLS; EXPRESSION; PROGRESSION; SAFETY; BETA; OVEREXPRESSION; XENOGRAFTS AB The platelet-derived growth factor receptor (PDGFR) has an important role in tumorigenesis and tumor progression. Olaratumab (IMC-3G3) is a fully human monoclonal antibody that selectively binds human PDGFR alpha and blocks ligand binding. This phase I study assessed the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), pharmacokinetics, and preliminary antitumor activity of olaratumab in patients with advanced solid tumors. Patients were enrolled into five dose-escalating cohorts of 3-6 patients each. Olaratumab was administered intravenously weekly at 4, 8, or 16 mg/kg (cohorts 1-3) or once every other week at 15 or 20 mg/kg (cohorts 4-5), with 4 weeks/cycle. Nineteen patients were treated in five cohorts. There were no dose-limiting toxicities; the MTD was not identified with the doses studied. The most common olaratumab-related adverse events (AE) were fatigue and infusion reactions (10.5 % each). With the exception of 1 patient (20 mg/kg) experiencing two grade 3 drug-related AEs after the dose-limiting toxicity assessment period, all drug-related AEs were grade 1 or 2. The trough concentrations (C (min)) for 16 mg/kg weekly and 20 mg/kg biweekly were higher than 155 mu g/mL, and the concentration found to be efficacious in preclinical xenograft models. Twelve patients (63.2 %) had a best response of stable disease [median duration of 3.9 months (95 % CI 2.3-8.7)]. Olaratumab was well tolerated and showed preliminary antitumor activity. RP2Ds are 16 mg/kg weekly and 20 mg/kg biweekly. Phase II studies of olaratumab as monotherapy and in combination are ongoing in several tumor types. C1 [Chiorean, E. Gabriela] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Chiorean, E. Gabriela] Indiana Univ, Indianapolis, IN 46204 USA. [Sweeney, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Youssoufian, Hagop; Qin, Amy; Dontabhaktuni, Aruna; Loizos, Nick] ImClone Syst LLC, Bridgewater, NJ USA. [Nippgen, Johannes] ImClone Syst LLC, Heidelberg, Germany. [Amato, Robert] Univ Texas Hlth Sci Ctr Houston, Mem Hermann Canc Ctr, Texas Med Ctr, Houston, TX 77030 USA. RP Chiorean, EG (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, 825 Eastlake Ave East,G4830, Seattle, WA 98109 USA. EM gchiorea@uw.edu FU ImClone Systems, LLC, a wholly owned subsidiary of Eli Lilly and Company FX The authors wish to acknowledge the patients, their families, and the study personnel who participated in this clinical trial. We thank Chirag Jani for assistance with figure preparation. The authors thank Lori Kornberg (InVentiv Health Clinical) and Susan Johnson (ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company) for medical writing assistance. This trial was supported by ImClone Systems, LLC, a wholly owned subsidiary of Eli Lilly and Company. NR 42 TC 13 Z9 15 U1 0 U2 5 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 MAR PY 2014 VL 73 IS 3 BP 595 EP 604 DI 10.1007/s00280-014-2389-9 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AB7FC UT WOS:000331953700018 PM 24452395 ER PT J AU Miyamoto, N Pham, LDD Seo, JH Kim, KW Lo, EH Arai, K AF Miyamoto, Nobukazu Pham, Loc-Duyen D. Seo, Ji Hae Kim, Kyu-Won Lo, Eng H. Arai, Ken TI Crosstalk between cerebral endothelium and oligodendrocyte SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Oligodendrocytes; Oligodendrocyte precursor cells; Cerebral endothelial cells; Oligovascular niche; Neurovascular unit ID CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; ACUTE ISCHEMIC-STROKE; SPINAL-CORD-INJURY; NEURAL STEM-CELLS; GROWTH-FACTOR; SUBVENTRICULAR ZONE; NEUROTROPHIC FACTOR; PROGENITOR CELLS; WHITE-MATTER AB It is now relatively well accepted that the cerebrovascular system does not merely provide inert pipes for blood delivery to the brain. Cerebral endothelial cells may compose an embedded bunker of trophic factors that contribute to brain homeostasis and function. Recent findings suggest that soluble factors from cerebral endothelial cells nourish neighboring cells, such as neurons and astrocytes. Although data are strongest in supporting mechanisms of endothelial-neuron and/or endothelial-astrocyte trophic coupling, it is likely that similar interactions also exist between cerebral endothelial cells and oligodendrocyte lineage cells. In this mini-review, we summarize current advances in the field of endothelial-oligodendrocyte trophic coupling. These endothelial-oligodendrocyte interactions may comprise the oligovascular niche to maintain their cellular functions and sustain ongoing angiogenesis/oligodendrogenesis. Importantly, it should be noted that the cell-cell interactions are not static-the trophic coupling is disturbed under acute phase after brain injury, but would be recovered in the chronic phase to promote brain remodeling and repair. Oligodendrocyte lineage cells play critical roles in white matter function, and under pathological conditions, oligodendrocyte dysfunction lead to white matter damage. Therefore, a deeper understanding of the mechanisms of endothelial-oligodendrocyte trophic coupling may lead to new therapeutic approaches for white matter-related diseases, such as stroke or vascular dementia. C1 [Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. [Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. [Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea. RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH East 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU National Institutes of Health; Uehara Memorial Foundation; National Research Foundation of Korea through the World Class University Program [R31-2008-000-10103-0]; Global Research Laboratory Program [2011-0021874] FX This work was supported in part by the National Institutes of Health, Research Abroad from the Uehara Memorial Foundation, National Research Foundation of Korea through the World Class University Program (R31-2008-000-10103-0), and the Global Research Laboratory Program (2011-0021874). NR 135 TC 18 Z9 18 U1 0 U2 18 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2014 VL 71 IS 6 BP 1055 EP 1066 DI 10.1007/s00018-013-1488-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AB2WX UT WOS:000331653900008 PM 24132511 ER PT J AU Xu, G Takahashi, E Folkerth, RD Haynes, RL Volpe, JJ Grant, PE Kinney, HC AF Xu, Gang Takahashi, Emi Folkerth, Rebecca D. Haynes, Robin L. Volpe, Joseph J. Grant, P. Ellen Kinney, Hannah C. TI Radial Coherence of Diffusion Tractography in the Cerebral White Matter of the Human Fetus: Neuroanatomic Insights SO CEREBRAL CORTEX LA English DT Article DE axons; blood vessels; encephalopathy of prematurity; periventricular leukomalacia; radial glial fibers; vimentin ID STATE FREE PRECESSION; HUMAN FETAL-BRAIN; PERIVENTRICULAR LEUKOMALACIA; GLIAL-CELLS; NEURONS; SYSTEM; CORTEX; ENCEPHALOPATHY; TELENCEPHALON; CONNECTIVITY AB High angular resolution diffusion imaging (HARDI) demonstrates transient radial coherence of telencephalic white matter in the human fetus. Our objective was to define the neuroanatomic basis of this radial coherence through correlative HARDI- and postmortem tissue analyses. Applying immunomarkers to radial glial fibers (RGFs), axons, and blood vessels in 18 cases (19 gestational weeks to 3 postnatal years), we compared their developmental profiles to HARDI tractography in brains of comparable ages (n 11). At midgestation, radial coherence corresponded with the presence of RGFs. At 3031 weeks, the transition from HARDI-defined radial coherence to corticocortical coherence began simultaneously with the transformation of RGFs to astrocytes. By term, both radial coherence and RGFs had disappeared. White matter axons were radial, tangential, and oblique over the second half of gestation, whereas penetrating blood vessels were consistently radial. Thus, radial coherence in the fetal white matter likely reflects a composite of RGFs, penetrating blood vessels, and radial axons of which its transient expression most closely matches that of RGFs. This study provides baseline information for interpreting radial coherence in tractography studies of the preterm brain in the assessment of the encephalopathy of prematurity. C1 [Xu, Gang; Folkerth, Rebecca D.; Haynes, Robin L.; Kinney, Hannah C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Takahashi, Emi; Grant, P. Ellen] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Takahashi, Emi; Grant, P. Ellen] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Newborn Med, Boston, MA 02115 USA. [Takahashi, Emi; Grant, P. Ellen] Harvard Univ, Sch Med, Childrens Hosp Boston, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA. [Folkerth, Rebecca D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Neuropathol, Boston, MA 02115 USA. [Volpe, Joseph J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. [Grant, P. Ellen] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA. RP Takahashi, E (reprint author), Childrens Hosp, Div Newborn Med, 1 Autumn St 654, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu RI Haynes, Robin/M-4401-2016 OI Haynes, Robin/0000-0003-4909-9585 FU National Institute of Neurological Diseases and Stroke [PO1-NS38475]; Cerebral Palsy International Research Foundation; Eunice Shriver Kennedy National Institute of Child Health and Development [R21HD069001, P30-HD018655]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health; NCRR Shared Instrumentation Grant Program [1S10RR023401, 1S10RR019307, 1S10RR023043]; High-End Instrumentation Grant Program [S10RR016811] FX The authors thank the Eunice Kennedy Shriver NICHD Brain and Tissue Bank for Developmental Disorders (NO1-HD-9-0011) for the provision of developmental cerebral cortical tissue for HARDI (brain slice at 3 postnatal months) and tissue analysis. This work was supported by the National Institute of Neurological Diseases and Stroke (PO1-NS38475) (HCK, JJV), Cerebral Palsy International Research Foundation (RLH), and Eunice Shriver Kennedy National Institute of Child Health and Development (R21HD069001) (ET), (P30-HD018655) (Children's Hospital Developmental Disabilities Research Center). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program (1S10RR023401, 1S10RR019307, and 1S10RR023043) and High-End Instrumentation Grant Program (S10RR016811). The content of the manuscript is the view of the authors and not that the official view of the Eunice Shriver Kennedy National Institute of Child Health and Development. Conflict of Interest: None declared. NR 51 TC 11 Z9 11 U1 0 U2 6 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 MAR PY 2014 VL 24 IS 3 BP 579 EP 592 DI 10.1093/cercor/bhs330 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AB5RI UT WOS:000331845700002 PM 23131806 ER PT J AU Kong, LQ Michalka, SW Rosen, ML Sheremata, SL Swisher, JD Shinn-Cunningham, BG Somers, DC AF Kong, Lingqiang Michalka, Samantha W. Rosen, Maya L. Sheremata, Summer L. Swisher, Jascha D. Shinn-Cunningham, Barbara G. Somers, David C. TI Auditory Spatial Attention Representations in the Human Cerebral Cortex SO CEREBRAL CORTEX LA English DT Article DE audition; intraparietal sulcus; multivoxel pattern analysis; spatial maps; visuotopy ID POSTERIOR PARIETAL CORTEX; HUMAN VISUAL-CORTEX; INTERAURAL TIME DIFFERENCES; SURFACE-BASED ANALYSIS; HUMAN FRONTAL-CORTEX; WORKING-MEMORY; CORTICAL SURFACE; FMRI DATA; INTRAPARIETAL SULCUS; PREFRONTAL CORTEX AB Auditory spatial attention serves important functions in auditory source separation and selection. Although auditory spatial attention mechanisms have been generally investigated, the neural substrates encoding spatial information acted on by attention have not been identified in the human neocortex. We performed functional magnetic resonance imaging experiments to identify cortical regions that support auditory spatial attention and to test 2 hypotheses regarding the coding of auditory spatial attention: 1) auditory spatial attention might recruit the visuospatial maps of the intraparietal sulcus (IPS) to create multimodal spatial attention maps; 2) auditory spatial information might be encoded without explicit cortical maps. We mapped visuotopic IPS regions in individual subjects and measured auditory spatial attention effects within these regions of interest. Contrary to the multimodal map hypothesis, we observed that auditory spatial attentional modulations spared the visuotopic maps of IPS; the parietal regions activated by auditory attention lacked map structure. However, multivoxel pattern analysis revealed that the superior temporal gyrus and the supramarginal gyrus contained significant information about the direction of spatial attention. These findings support the hypothesis that auditory spatial information is coded without a cortical map representation. Our findings suggest that audiospatial and visuospatial attention utilize distinctly different spatial coding schemes. C1 [Kong, Lingqiang; Shinn-Cunningham, Barbara G.] Boston Univ, Boston, MA 02215 USA. [Michalka, Samantha W.; Shinn-Cunningham, Barbara G.; Somers, David C.] Boston Univ, Neurosci Program, Boston, MA 02215 USA. [Rosen, Maya L.; Somers, David C.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Kong, Lingqiang; Michalka, Samantha W.; Rosen, Maya L.; Shinn-Cunningham, Barbara G.; Somers, David C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Sheremata, Summer L.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA USA. [Swisher, Jascha D.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Shinn-Cunningham, Barbara G.; Somers, David C.] Ctr Computat Neurosci & Neural Technol, Boston, MA USA. RP Somers, DC (reprint author), Boston Univ, Dept Psychol, 2 Cummington Mall, Boston, MA 02215 USA. EM somers@bu.edu RI Somers, David/G-5802-2010; OI Somers, David/0000-0002-4169-5895 FU National Science Foundation [SBE-0354378, BCS-0726061]; National Institutes of Health [R01EY022229, R01DC009477, F32EY019448]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute FX This work was supported by the National Science Foundation (grant numbers SBE-0354378, BCS-0726061); the National Institutes of Health (grant numbers R01EY022229, R01DC009477, F32EY019448); the National Center for Research Resources (grant P41RR14075); and the Mental Illness and Neuroscience Discovery Institute. Conflict of Interest: None declared. NR 101 TC 24 Z9 25 U1 3 U2 15 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 MAR PY 2014 VL 24 IS 3 BP 773 EP 784 DI 10.1093/cercor/bhs359 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AB5RI UT WOS:000331845700019 PM 23180753 ER PT J AU Mian, MK Sheth, SA Patel, SR Spiliopoulos, K Eskandar, EN Williams, ZM AF Mian, Matthew K. Sheth, Sameer A. Patel, Shaun R. Spiliopoulos, Konstantinos Eskandar, Emad N. Williams, Ziv M. TI Encoding of Rules by Neurons in the Human Dorsolateral Prefrontal Cortex SO CEREBRAL CORTEX LA English DT Article DE abstract rules; deep brain stimulation; human neurophysiology; prefrontal cortex ID ANTERIOR CINGULATE CORTEX; SHORT-TERM-MEMORY; BEHAVIORAL-CONTROL; TEMPORAL CORTEX; SINGLE NEURONS; WORKING-MEMORY; FRONTAL-CORTEX; ABSTRACT RULES; BRAIN IMAGES; TASK AB We use rules to extend learned behavior beyond specific instances to general scenarios. The prefrontal cortex (PFC) is thought to play an important role in representing rules, as evidenced by subjects who have difficulty in following rules after PFC damage and by animal studies demonstrating rule sensitivity of individual PFC neurons. How rules are instantiated at the single-neuronal level in the human brain, however, remains unclear. Here, we recorded from individual neurons in the human dorsolateral prefrontal cortex (DLPFC) as subjects performed a task in which they evaluated pairs of images using either of 2 abstract rules. We find that DLPFC neurons selectively encoded these rules while carrying little information about the subjects responses or the sensory cues used to guide their decisions. C1 [Mian, Matthew K.; Sheth, Sameer A.; Patel, Shaun R.; Spiliopoulos, Konstantinos; Eskandar, Emad N.; Williams, Ziv M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nayef al Rodhan Labs,Dept Neurosurg, Boston, MA 02114 USA. [Patel, Shaun R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Williams, ZM (reprint author), Harvard Univ, Sch Med, Ctr Nervous Syst Repair, Massachusetts Gen Hosp, 55 Fruit St,WAC 745K, Boston, MA 02114 USA. EM zwilliams1@partners.org FU National Institutes of Health [5R01-HD059852, R25-NS065743]; PECASE; Whitehall Foundation; Esther A. & Joseph Klingenstein Fund; Sackler Scholar Programme in Psychobiology; [1R01-EY017658]; [1R01-NS63249]; [5P5MH086400] FX This work was supported by National Institutes of Health (grant number 5R01-HD059852), PECASE, and the Whitehall Foundation (to Z.M.W.); by National Institutes of Health (grant number R25-NS065743 (to S. A. S.); grant numbers 1R01-EY017658, 1R01-NS63249, 5P5MH086400), the Esther A. & Joseph Klingenstein Fund (to E.N.E.), and the Sackler Scholar Programme in Psychobiology (to S.R.P.). NR 56 TC 9 Z9 9 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 MAR PY 2014 VL 24 IS 3 BP 807 EP 816 DI 10.1093/cercor/bhs361 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AB5RI UT WOS:000331845700021 PM 23172774 ER PT J AU Charles, RC Liang, L Khanam, F Abu Sayeed, M Hung, C Leung, DT Baker, S Ludwig, A Harris, JB LaRocque, RC Calderwood, SB Qadri, F Felgner, PL Ryan, ET AF Charles, Richelle C. Liang, Li Khanam, Farhana Abu Sayeed, M. Hung, Chris Leung, Daniel T. Baker, Stephen Ludwig, Albrecht Harris, Jason B. LaRocque, Regina C. Calderwood, Stephen B. Qadri, Firdausi Felgner, Philip L. Ryan, Edward T. TI Immunoproteomic Analysis of Antibody in Lymphocyte Supernatant in Patients with Typhoid Fever in Bangladesh SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID ENTERICA SEROVAR TYPHI; PERIPHERAL-BLOOD LYMPHOCYTES; SALMONELLA-ENTERICA; IMMUNE-RESPONSES; GENE-EXPRESSION; PARATYPHI-A; TYPHIMURIUM; CELLS; MICE; INFECTION AB We have previously shown that an assay based on detection of anti-Salmonella enterica serotype Typhi antibodies in supernatant of lymphocytes harvested from patients presenting with typhoid fever (antibody in lymphocyte supernatant [ALS] assay) can identify 100% of patients with blood culture-confirmed typhoid fever in Bangladesh. In order to define immunodominant proteins within the S. Typhi membrane preparation used as antigen in these prior studies and to identify potential biomarkers unique to S. Typhi bacteremic patients, we probed microarrays containing 2,724 S. Typhi proteins with ALS collected at the time of clinical presentation from 10 Bangladeshis with acute typhoid fever. We identified 62 immunoreactive antigens when evaluating both the IgG and IgA responses. Immune responses to 10 of these antigens discriminated between individuals with acute typhoid infection and healthy control individuals from areas where typhoid infection is endemic, as well as Bangladeshi patients presenting with fever who were subsequently confirmed to have a nontyphoid illness. Using an ALS enzyme-linked immunosorbent assay (ELISA) format and purified antigen, we then confirmed that immune responses against the antigen with the highest immunoreactivity (hemolysin E [HlyE]) correctly identified individuals with acute typhoid or paratyphoid fever in Dhaka, Bangladesh. These observations suggest that purified antigens could be used with ALS and corresponding acute-phase activated B lymphocytes in diagnostic platforms to identify acutely infected patients, even in areas where enteric fever is endemic. C1 [Charles, Richelle C.; Leung, Daniel T.; Harris, Jason B.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Leung, Daniel T.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Liang, Li; Hung, Chris; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Khanam, Farhana; Abu Sayeed, M.; Leung, Daniel T.; Qadri, Firdausi] Bangladesh Icddr B, Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Baker, Stephen] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam. [Ludwig, Albrecht] Klinikum Johann Wolfgang Goethe Univ, Inst Med Mikrobiol, Frankfurt, Germany. [Ludwig, Albrecht] Klinikum Johann Wolfgang Goethe Univ, Krankenhaushygiene, Frankfurt, Germany. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM rccharles@partners.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI100023, AI077883, AI058935, AI073672, AI078213]; Training Grant in Vaccine Development and Public Health [D43 TW005572]; Career Development Awards [K08 AI089721, K08 AI100923]; Massachusetts General Hospital Physician Scientist Development Award; Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases; Deutsche Forschungsgemeinschaft [LU 842/1-1] FX This work was supported by the icddr,b and grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI100023 and AI077883 [E.T.R. and F.Q.], AI058935 [S.B.C., E.T.R., and F.Q.], AI073672 [L.L. and P.L.F.], AI078213 [L.L. and P.L.F.], Sida [F.Q. and F.K.], Training Grant in Vaccine Development and Public Health (D43 TW005572 [F.K., E.T.R., and F.Q.]), Career Development Awards (K08 AI089721 [R.C.C.], K08 AI100923 [D.T.L.]), a Massachusetts General Hospital Physician Scientist Development Award (R.C.C.), a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases (D.T.L.), and grants from the Deutsche Forschungsgemeinschaft (LU 842/1-1 [A.L.]). NR 42 TC 5 Z9 5 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 EI 1556-679X J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAR PY 2014 VL 21 IS 3 BP 280 EP 285 DI 10.1128/CVI.00661-13 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AB8JT UT WOS:000332036900003 PM 24371257 ER PT J AU Anderson, JP Tchetgen, EJT Lo Re, V Tate, JP Williams, PL Seage, GR Horsburgh, CR Lim, JK Goetz, MB Rimland, D Rodriguez-Barradas, MC Butt, AA Klein, MB Justice, AC AF Anderson, Jeffrey P. Tchetgen, Eric J. Tchetgen Lo Re, Vincent, III Tate, Janet P. Williams, Paige L. Seage, George R., III Horsburgh, C. Robert Lim, Joseph K. Goetz, Matthew Bidwell Rimland, David Rodriguez-Barradas, Maria C. Butt, Adeel A. Klein, Marina B. Justice, Amy C. TI Antiretroviral Therapy Reduces the Rate of Hepatic Decompensation Among HIV- and Hepatitis C Virus-Coinfected Veterans SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; hepatitis C; coinfection; hepatic decompensation; marginal structural model ID HUMAN-IMMUNODEFICIENCY-VIRUS; MARGINAL STRUCTURAL MODELS; LIVER FIBROSIS PROGRESSION; INFECTED PATIENTS; PROTECTIVE FACTOR; DISEASE; COHORT; NEVIRAPINE; IMPACT; DEATH AB Background. Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure. Methods. We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of >= 3 drugs from >= 2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation. Results. We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI], .54-.94). When we removed individuals with HIV RNA <= 400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI, .43-.82). Conclusions. Initiation of ART significantly reduced the rate of hepatic decompensation by 28%-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease. C1 [Anderson, Jeffrey P.; Tchetgen, Eric J. Tchetgen; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tchetgen, Eric J. Tchetgen; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lo Re, Vincent, III] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Tate, Janet P.; Lim, Joseph K.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Tate, Janet P.; Lim, Joseph K.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Horsburgh, C. Robert] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Horsburgh, C. Robert] Boston Univ, Sch Med, Boston Med Ctr, Infect Dis Sect, Boston, MA 02215 USA. [Goetz, Matthew Bidwell] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rimland, David] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates. [Klein, Marina B.] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. RP Tate, JP (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave, West Haven, CT 06516 USA. EM janet.tate2@va.gov RI Lo Re, Vincent/N-7817-2015; OI Butt, Adeel/0000-0002-1118-1826; Goetz, Matthew/0000-0003-4542-992X FU National Institutes of Health [T32 AI007358, T32 AI007535]; National Institute on Alcohol Abuse and Alcoholism [U01 AA13566, U24 AA020794, U01 AA020790]; National Heart, Lung and Blood Institute [R01 HL095136, R01 HL090342, RCI HL100347]; National Institute of Allergy and Infectious Diseases [U01 A1069918]; Veterans Health Administration Office of Research and Development [VA REA 08266]; National Institute on Aging; National Institute of Mental Health; Veterans Health Administration FX This work was supported by the National Institutes of Health (grant numbers T32 AI007358 and T32 AI007535 to J. P. A.). The Veterans Aging Cohort Study has been funded by the National Institute on Alcohol Abuse and Alcoholism (grant numbers U01 AA13566, U24 AA020794, U01 AA020790); the National Heart, Lung and Blood Institute (grant numbers R01 HL095136, R01 HL090342, RCI HL100347); the National Institute of Allergy and Infectious Diseases (grant number U01 A1069918); the Veterans Health Administration Office of Research and Development (grant number VA REA 08266); and an interagency agreement between the National Institute on Aging, the National Institute of Mental Health, and the Veterans Health Administration. NR 40 TC 26 Z9 26 U1 2 U2 8 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 MAR 1 PY 2014 VL 58 IS 5 BP 719 EP 727 DI 10.1093/cid/cit779 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AB5RR UT WOS:000331846700023 PM 24285848 ER PT J AU Nadal, R Bellmunt, J AF Nadal, Rosa Bellmunt, Joaquim TI New Treatments for Bladder Cancer: When Will We Make Progress? SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article DE Bladder cancer; Targeted therapies; Molecular markers; Urothelial tumors ID TRANSITIONAL-CELL CARCINOMA; EPIDERMAL-GROWTH-FACTOR; PHASE-II TRIAL; METASTATIC UROTHELIAL CANCER; TYROSINE KINASE INHIBITOR; FACTOR RECEPTOR; ONCOLOGY-GROUP; ADENOCARCINOMA CELLS; 1ST-LINE TREATMENT; RANDOMIZED-TRIAL AB The prognosis and long-term survival for patients with metastatic urothelial carcinoma patients is poor. Traditionally, the mainstay of treatment has been combination chemotherapy with gemcitabine and cisplatin or with the classical M-VAC. Vinflunine has become an EMA-approved second-line option in Europe. Urothelial carcinomas contain genetic alteration in multiple genes that are potentially treated by targeted therapies. Recently, a number of these new therapies have been developed in this disease. But not one has been approved for clinical use in urothelial cancers. While clinical evaluation of these agents is still in its early days, some promising findings have begun to emerge. For example, everolimus demonstrated activity in those metastatic urothelial cancer patients who harbors TSC1 mutation. With the identification of the most relevant drug targets for tumors initiation and maintenance and the best way to assess drug candidates that may only account for a small fraction of patients, it is anticipated that the therapeutic arsenal for urothelial cancers will be expanded in the future. C1 [Nadal, Rosa] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Bellmunt, Joaquim] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Bellmunt, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM joaquim_bellmunt@dfci.harvard.edu FU Astellas FX Joaquim Bellmunt has received consultancy and lecture fees from Astellas. NR 71 TC 7 Z9 7 U1 0 U2 2 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 MAR PY 2014 VL 15 IS 1 BP 99 EP 114 DI 10.1007/s11864-013-0271-3 PG 16 WC Oncology SC Oncology GA AB7GB UT WOS:000331956400009 PM 24415439 ER PT J AU Franks, PW Christophi, CA Jablonski, KA Billings, LK Delahanty, LM Horton, ES Knowler, WC Florez, JC AF Franks, Paul W. Christophi, Costas A. Jablonski, Kathleen A. Billings, Liana K. Delahanty, Linda M. Horton, Edward S. Knowler, William C. Florez, Jose C. CA Diabet Prevention Program Res Grp TI Common variation at PPARGC1A/B and change in body composition and metabolic traits following preventive interventions: the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Article DE Cholesterol; Dyslipidaemia; Gene x environment interaction; Gene x lifestyle interaction; Genetics; Lifestyle intervention; Metformin; Pharmacogenetics; PPARGC1A; PPARGC1B; Randomised controlled trial; Triacylglycerol ID LIFE-STYLE INTERVENTION; GAMMA COACTIVATOR-1-ALPHA PGC-1-ALPHA; ENVIRONMENT INTERACTIONS; INSULIN SENSITIVITY; CANDIDATE GENES; GLY482SER; ASSOCIATION; VARIANTS; RISK; POLYMORPHISMS AB PPARGC1A and PPARGCB encode transcriptional coactivators that regulate numerous metabolic processes. We tested associations and treatment (i.e. metformin or lifestyle modification) interactions with metabolic traits in the Diabetes Prevention Program, a randomised controlled trial in persons at high risk of type 2 diabetes. We used Tagger software to select 75 PPARGCA1 and 94 PPARGC1B tag single-nucleotide polymorphisms (SNPs) for analysis. These SNPs were tested for associations with relevant cardiometabolic quantitative traits using generalised linear models. Aggregate genetic effects were tested using the sequence kernel association test. In aggregate, PPARGC1A variation was strongly associated with baseline triacylglycerol concentrations (p = 2.9 x 10(-30)), BMI (p = 2.0 x 10(-5)) and visceral adiposity (p = 1.9 x 10(-4)), as well as with changes in triacylglycerol concentrations (p = 1.7 x 10(-5)) and BMI (p = 9.9 x 10(-5)) from baseline to 1 year. PPARGC1B variation was only associated with baseline subcutaneous adiposity (p = 0.01). In individual SNP analyses, Gly482Ser (rs8192678, PPARGC1A) was associated with accumulation of subcutaneous adiposity and worsening insulin resistance at 1 year (both p < 0.05), while rs2970852 (PPARGC1A) modified the effects of metformin on triacylglycerol levels (p (interaction) = 0.04). These findings provide several novel and other confirmatory insights into the role of PPARGC1A variation with respect to diabetes-related metabolic traits. Trial registration ClinicalTrials.gov NCT00004992. C1 [Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden. [Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Franks, Paul W.; Christophi, Costas A.; Jablonski, Kathleen A.] George Washington Univ, Diabet Prevent Program, Ctr Biostat, Coordinating Ctr, Rockville, MD 20852 USA. [Billings, Liana K.; Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Billings, Liana K.; Delahanty, Linda M.; Horton, Edward S.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Horton, Edward S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Franks, PW (reprint author), George Washington Univ, Diabet Prevent Program, Ctr Biostat, Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM paul.franks@med.lu.se RI Uwaifo, Gabriel/M-2361-2016; OI Uwaifo, Gabriel/0000-0002-6962-9304; Franks, Paul/0000-0002-0520-7604 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Centers for Disease Control and Prevention; Office of Research on Women's Health; American Diabetes Association; Swedish Research Council; Swedish Diabetes Association; Swedish Heart-Lung Foundation; Pahlssons Foundation; Novo Nordisk Foundation; [R01 DK072041] FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centres and the coordinating centre for the design and conduct of the study, and for collection, management, analysis and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centres. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women's Health and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. The DPP was also supported, in part, by the intramural research programme of the NIDDK. LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck, Nike Sports Marketing, Slim Fast Foods and Quaker Oats donated materials, equipment or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating centre. The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. The work described in this paper was supported in part by R01 DK072041 to D. Altshuler (Broad Institute of Harvard and MIT, Cambridge, MA, USA), JCF and KAJ (WCK and PWF were unpaid co-investigators). PWF was supported by the Swedish Research Council, Swedish Diabetes Association, Swedish Heart-Lung Foundation, Pahlssons Foundation and Novo Nordisk Foundation. NR 30 TC 8 Z9 8 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2014 VL 57 IS 3 BP 485 EP 490 DI 10.1007/s00125-013-3133-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB1NG UT WOS:000331558400008 PM 24317794 ER PT J AU Hussey, SE Lum, H Alvarez, A Cipriani, Y Garduno-Garcia, J Anaya, L Dube, J Musi, N AF Hussey, Sophie E. Lum, Helen Alvarez, Andrea Cipriani, Yolanda Garduno-Garcia, Jesus Anaya, Luis Dube, John Musi, Nicolas TI A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle SO DIABETOLOGIA LA English DT Article DE Acylcarnitine; Ceramide; Diacylglycerol; Inflammation; Insulin resistance ID INDUCED INSULIN-RESISTANCE; FREE FATTY-ACIDS; TYPE-2 DIABETIC SUBJECTS; HUMAN SKELETAL-MUSCLE; PROTEIN-KINASE-C; KAPPA-B; 3-KINASE ACTIVITY; ACTIVATION; EXPRESSION; GLUCOSE AB Insulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor kappa B [NF kappa B] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals. Twelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp. Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of kappa B kinase-NF kappa B (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended to reduce the content of inhibitor of kappa B alpha (p = 0.09). The muscle content of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. A sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression and TLR-driven signalling (NF kappa B and MAPK) in lean individuals. The activation of this pathway by NEFA may be involved in the pathogenesis of insulin resistance in humans. Trial registration ClinicalTrials.gov NCT01740817. C1 [Hussey, Sophie E.; Lum, Helen; Alvarez, Andrea; Cipriani, Yolanda; Garduno-Garcia, Jesus; Anaya, Luis; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA. [Dube, John] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Ctr Hlth Aging, San Antonio, TX 78229 USA. [Musi, Nicolas] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Musi, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA. EM musi@uthscsa.edu FU National Institutes of Health (NIH) [RO1-DK80157, RO1-DK089229]; American Diabetes Association; University of Texas Health Science Center at San Antonio Clinical and Translational Science Award [TR000149]; NIH National Service Research Award [F32 (1F32DK095565-01A1)]; Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (MUSC) [P30 CA138313]; Lipidomics Core in the South Carolina Lipidomics and Pathobiology COBRE, Department Biochemistry, MUSC [P20 RR017677]; National Center for Research Resources; Office of the Director of the NIH [C06 RR018823] FX This work was supported by grants from the National Institutes of Health (NIH) (RO1-DK80157 and RO1-DK089229) and the American Diabetes Association to NM. This grant was supported by a University of Texas Health Science Center at San Antonio Clinical and Translational Science Award (TR000149) and an NIH National Service Research Award, Parent F32 (1F32DK095565-01A1) to SH. The research was supported in part by the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (MUSC) (P30 CA138313) and the Lipidomics Core in the South Carolina Lipidomics and Pathobiology COBRE, Department Biochemistry, MUSC (P20 RR017677). This project also was supported by the National Center for Research Resources and the Office of the Director of the NIH (C06 RR018823) to MUSC. NR 50 TC 12 Z9 12 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2014 VL 57 IS 3 BP 582 EP 591 DI 10.1007/s00125-013-3111-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB1NG UT WOS:000331558400018 PM 24337154 ER PT J AU Blay, JY Sleijfer, S Schoffski, P Kawai, A Brodowicz, T Demetri, GD Maki, RG AF Blay, Jean-Yves Sleijfer, Stefan Schoeffski, Patrick Kawai, Akira Brodowicz, Thomas Demetri, George D. Maki, Robert G. TI International expert opinion on patient-tailored management of soft tissue sarcomas SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE Soft tissue sarcoma; Management; Treatment ID GASTROINTESTINAL STROMAL TUMORS; PROGNOSTIC-FACTORS; PHASE-II; EUROPEAN ORGANIZATION; RETROSPECTIVE ANALYSIS; IMATINIB MESYLATE; CLINICAL-TRIALS; PART SARCOMA; CHEMOTHERAPY; CANCER AB Background: Soft tissue sarcomas (STS) are a heterogeneous group of cancers comprising over 50 histological subtypes. Current treatment strategies for sarcomas are increasingly adapted to histological and molecular subtype, and several patient- and tumour-related factors influence treatment decision. Methods: Seven oncologists specialising in the management of STS, from Europe, the United States of America and Japan, met to develop a practical model to identify parameters guiding treatment decision-making in advanced STS. Literature searches were carried out to identify key published evidence, in particular phase II and III randomised trials, to validate the model, and extensive clinical experience was used as expert evidence. A document was developed to provide a logical approach to advanced STS management and was analysed critically by a second group of STS specialists. Results: Broad consensus was reached during this exercise and the following parameters were identified as key factors influencing treatment decision: chemosensitivity of histological subtype, natural history of the diagnosis, tumour burden, tumour site, locally advanced primary and/or metastases, patient's general condition, relevant comorbidities, previous chemotherapy, treatment goal and patient acceptance. These parameters, judged useful for treatment selection, were based on published literature, the selection process within clinical trials and expert opinion (some factors have not been formerly defined in published literature). C1 [Blay, Jean-Yves] Univ Lyon 1, F-69008 Lyon, France. [Sleijfer, Stefan] Erasmus MC Canc Inst, Rotterdam, Netherlands. [Schoeffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium. [Kawai, Akira] Natl Canc Ctr, Tokyo, Japan. [Brodowicz, Thomas] Med Univ Vienna, Gen Hosp, Comprehens Canc Ctr MusculoSkeletal Tumors, Div Clin Oncol, Vienna, Austria. [Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Maki, Robert G.] Mt Sinai Med Ctr, New York, NY USA. RP Blay, JY (reprint author), Univ Lyon 1, Ctr Leon Berard, 28 Rue Laennec, F-69008 Lyon, France. EM jean-yves.blay@lyon.unicancer.fr RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU FWG Scientific Communications; Bridge Medical Consulting FX The authors thank the following advisors who reviewed the manuscript and provided editorial input: Peter Reichardt, Alexander Fedenko and Carlos Barrios. Writing and editing assistance was provided by Joanne Parker of FWG Scientific Communications, with financial support from GlaxoSmithKline. Dr. Paul Gandhi of Bridge Medical Consulting, with financial support from GlaxoSmithKline, facilitated the expert meetings. NR 47 TC 15 Z9 16 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2014 VL 50 IS 4 BP 679 EP 689 DI 10.1016/j.ejca.2013.11.011 PG 11 WC Oncology SC Oncology GA AB3UI UT WOS:000331715300001 PM 24295638 ER PT J AU Manji, R Bythrow, M Branda, JA Burnham, CAD Ferraro, MJ Garner, OB Jennemann, R Lewinski, MA Mochon, AB Procop, GW Richter, SS Rychert, JA Sercia, L Westblade, LF Ginocchio, CC AF Manji, R. Bythrow, M. Branda, J. A. Burnham, C. -A. D. Ferraro, M. J. Garner, O. B. Jennemann, R. Lewinski, M. A. Mochon, A. B. Procop, G. W. Richter, S. S. Rychert, J. A. Sercia, L. Westblade, L. F. Ginocchio, C. C. TI Multi-center evaluation of the VITEKA (R) MS system for mass spectrometric identification of non-Enterobacteriaceae Gram-negative bacilli SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID DESORPTION IONIZATION-TIME; CYSTIC-FIBROSIS PATIENTS; BURKHOLDERIA-CEPACIA COMPLEX; BACTERIAL IDENTIFICATION; CLINICAL MICROBIOLOGY; RAPID IDENTIFICATION; ROUTINE IDENTIFICATION; DIAGNOSTIC MICROBIOLOGY; ACINETOBACTER-BAUMANNII; COST-EFFECTIVENESS AB Studies have demonstrated that matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid, accurate method for the identification of clinically relevant bacteria. The purpose of this study was to evaluate the performance of the VITEK MS v2.0 system (bioM,rieux) for the identification of the non-Enterobacteriaceae Gram-negative bacilli (NEGNB). This multi-center study tested 558 unique NEGNB clinical isolates, representing 18 genera and 33 species. Results obtained with the VITEK MS v2.0 were compared with reference 16S rRNA gene sequencing and when indicated recA sequencing and phenotypic analysis. VITEK MS v2.0 provided an identification for 92.5 % of the NEGNB isolates (516 out of 558). VITEK MS v2.0 correctly identified 90.9 % of NEGNB (507 out of 558), 77.8 % to species level and 13.1 % to genus level with multiple species. There were four isolates (0.7 %) incorrectly identified to genus level and five isolates (0.9 %), with one incorrect identification to species level. The remaining 42 isolates (7.5 %) were either reported as no identification (5.0 %) or called "mixed genera" (2.5 %) since two or more different genera were identified as possible identifications for the test organism. These findings demonstrate that the VITEK MS v2.0 system provides accurate results for the identification of a challenging and diverse group of Gram-negative bacteria. C1 [Manji, R.; Bythrow, M.; Ginocchio, C. C.] North Shore LIJ Hlth Syst Labs, Dept Pathol & Lab Med, Lake Success, NY 11042 USA. [Branda, J. A.; Ferraro, M. J.; Rychert, J. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Branda, J. A.; Ferraro, M. J.; Rychert, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Burnham, C. -A. D.; Westblade, L. F.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Garner, O. B.; Lewinski, M. A.; Mochon, A. B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Jennemann, R.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Procop, G. W.; Richter, S. S.; Sercia, L.] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. [Westblade, L. F.; Ginocchio, C. C.] Hofstra North Shore LIJ Sch Med, Dept Pathol & Lab Med, Hempstead, NY USA. RP Ginocchio, CC (reprint author), North Shore LIJ Hlth Syst Labs, Dept Pathol & Lab Med, 10 Nevada Dr, Lake Success, NY 11042 USA. EM cginocch@nshs.edu FU bioMerieux, Durham. NC, USA FX This study was sponsored by bioMerieux, Durham. NC, USA. We sincerely thank the technical staff at each clinical trial site for their support. We thank David Pincus, Constance Bradford, and Karen MacDonald for providing technical support and statistical analysis. NR 64 TC 19 Z9 19 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0934-9723 EI 1435-4373 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAR PY 2014 VL 33 IS 3 BP 337 EP 346 DI 10.1007/s10096-013-1961-2 PG 10 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA AB3SE UT WOS:000331709700007 PM 24019163 ER PT J AU Friedman, LS AF Friedman, Lawrence S. TI Becoming a Clinician-Educator: Lessons Learned SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Friedman, Lawrence S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Friedman, Lawrence S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Friedman, LS (reprint author), Newton Wellesley Hosp, Dept Med, 2014 Washington St, Newton, MA 02462 USA. EM lfriedman@partners.org NR 14 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2014 VL 146 IS 3 BP 599 EP 601 DI 10.1053/j.gastro.2014.01.037 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AB3ZY UT WOS:000331729900009 PM 24462529 ER PT J AU Patti, ME Goldfine, AB AF Patti, Mary-Elizabeth Goldfine, Allison B. TI Hypoglycemia After Gastric Bypass: The Dark Side of GLP-1 SO GASTROENTEROLOGY LA English DT Editorial Material ID HYPERINSULINEMIC HYPOGLYCEMIA; BARIATRIC SURGERY; INSULIN-SECRETION; ISLET HYPERPLASIA; DUMPING SYNDROME; MEDICAL THERAPY; MIXED-MEAL; INCRETIN; ACARBOSE; GLUCOSE C1 [Patti, Mary-Elizabeth] Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Room 620,One Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [R56 DK095451, DK036836, P30 DK036836] NR 28 TC 17 Z9 17 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2014 VL 146 IS 3 BP 605 EP 608 DI 10.1053/j.gastro.2014.01.038 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AB3ZY UT WOS:000331729900011 PM 24468184 ER PT J AU Gheorghiade, M Vaduganathan, M Greene, SJ Mentz, RJ Adams, KF Anker, SD Arnold, M Baschiera, F Cleland, JGF Cotter, G Fonarow, GC Giordano, C Metra, M Misselwitz, F Muhlhofer, E Nodari, S Peacock, WF Pieske, BM Sabbah, HN Sato, N Shah, MR Stockbridge, NL Teerlink, JR van Veldhuisen, DJ Zalewski, A Zannad, F Butler, J AF Gheorghiade, Mihai Vaduganathan, Muthiah Greene, Stephen J. Mentz, Robert J. Adams, Kirkwood F., Jr. Anker, Stefan D. Arnold, Malcolm Baschiera, Fabio Cleland, John G. F. Cotter, Gadi Fonarow, Gregg C. Giordano, Christopher Metra, Marco Misselwitz, Frank Muehlhofer, Eva Nodari, Savina Peacock, W. Frank Pieske, Burkert M. Sabbah, Hani N. Sato, Naoki Shah, Monica R. Stockbridge, Norman L. Teerlink, John R. van Veldhuisen, Dirk J. Zalewski, Andrew Zannad, Faiez Butler, Javed TI Site selection in global clinical trials in patients hospitalized for heart failure: perceived problems and potential solutions SO HEART FAILURE REVIEWS LA English DT Article DE Heart failure; Site selection; Clinical trials; FDA ID QUALITY-OF-CARE; UNITED-STATES; OPTIMIZE-HF; END-POINTS; OUTCOMES; ASSOCIATION; RATIONALE; REGISTRY; PROGRAM; DESIGN AB There are over 1 million hospitalizations for heart failure (HF) annually in the United States alone, and a similar number has been reported in Europe. Recent clinical trials investigating novel therapies in patients with hospitalized HF (HHF) have been negative, and the post-discharge event rate remains unacceptably high. The lack of success with HHF trials stem from problems with understanding the study drug, matching the drug to the appropriate HF subgroup, and study execution. Related to the concept of study execution is the importance of including appropriate study sites in HHF trials. Often overlooked issues include consideration of the geographic region and the number of patients enrolled at each study center. Marked differences in baseline patient co-morbidities, serum biomarkers, treatment utilization and outcomes have been demonstrated across geographic regions. Furthermore, patients from sites with low recruitment may have worse outcomes compared to sites with higher enrollment patterns. Consequently, sites with poor trial enrollment may influence key patient end points and likely do not justify the costs of site training and maintenance. Accordingly, there is an unmet need to develop strategies to identify the right study sites that have acceptable patient quantity and quality. Potential approaches include, but are not limited to, establishing a pre-trial registry, developing site performance metrics, identifying a local regionally involved leader and bolstering recruitment incentives. This manuscript summarizes the roundtable discussion hosted by the Food and Drug Administration between members of academia, the National Institutes of Health, industry partners, contract research organizations and academic research organizations on the importance of selecting optimal sites for successful trials in HHF. C1 [Gheorghiade, Mihai; Greene, Stephen J.] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Mentz, Robert J.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC USA. [Adams, Kirkwood F., Jr.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Anker, Stefan D.] Ctr Clin & Basic Res, IRCCS San Raffaele, Rome, Italy. [Arnold, Malcolm] Univ Western Ontario, Div Cardiol, London, ON, Canada. [Baschiera, Fabio] Novartis Pharma AG, Basel, Switzerland. [Cleland, John G. F.] Castle Hill Hosp, Kingston Upon Hull, Yorks, England. [Cotter, Gadi] Momentum Res Inc, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Giordano, Christopher] Quintiles, Cardiovasc & Metab Therapeut Delivery Unit, Durham, NC USA. [Metra, Marco; Nodari, Savina] Univ Brescia, Div Cardiol, Brescia, Italy. [Misselwitz, Frank] Bayer Healthcare Pharmaceut, Berlin, Germany. [Muehlhofer, Eva] Bayer Vital GmbH, Leverkusen, Germany. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. [Pieske, Burkert M.] Med Univ Graz, Div Cardiol, Graz, Austria. [Sabbah, Hani N.] Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. [Sato, Naoki] Musahi Kosugi Hosp, Nippon Med Sch, Dept Internal Med & Cardiol, Kanagawa, Japan. [Shah, Monica R.] NHLBI, Bethesda, MD 20892 USA. [Stockbridge, Norman L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Zalewski, Andrew] Novartis Pharmaceut, E Hanover, NJ USA. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, INSERM, CIC 9501, Nancy, France. [Zannad, Faiez] Univ Lorraine, CHU Cardiol, U961, Nancy, France. [Butler, Javed] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI van Veldhuisen, Dirk Jan/E-8967-2014; OI Metra, Marco/0000-0001-6691-8568; Cleland, John/0000-0002-1471-7016 FU Vifor International; PsiOxus Therapeutics; Bayer Healthcare; Corthera; Novartis; Cytokinetics; Amgen; NIH; Roche Diagnostics; BG Medicine; Pfizer; Sorbent; Vifor; GE Healthcare; Medtronic FX Mihai Gheorghiade: Consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare AG, CorThera, Cytokinetics, DebioPharm S. A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical and Trevena Therapeutics. Stefan D Anker: Consultant for Vifor International, Amgen, Bayer, Bosch GmbH, PsiOxus Therapeutics, Professional Dietetics, Novartis. Research support from Vifor International, PsiOxus Therapeutics. John G F Cleland: Received an honorarium from Bayer for an advisory board. Gregg C Fonarow: Consultant to Medtronic, Novartis, Gambro and Ortho-McNeill. Marco Metra: Received honoraria from Bayer, Corthera, Novartis, and Servier for speeches or participation in advisory boards/steering committees. Frank Misselwitz and Eva Muhlhofer: Employed by Bayer Healthcare. Hani N Sabbah: Research Grants and Consultant to Bayer Healthcare. Naoki Sato: Consultant to Chugai Pharmaceutical Company and honoraria from Daiichi-Sankyo, Otsuka, Philips Respironics, Astellas, Ono, Eisai, Chugai, Mitsubishi-Tanabe, Sanofi-Aventis, and Novartis pharmaceuticals. John R Teerlink: Research Grants from Corthera, Novartis, Cytokinetics, Amgen, NIH. Consultant to Amgen, Anexon, Cardio3 Bioscience, CardioMEMS, Cytokinetics, Gambro, Johnson and Johnson, Merck, NovaCardia, Novartis, Scios, Sorbent Therapeutics, St. Jude Medical, Teva, Theravance, Trevena. Faiez Zannad: Reports receiving consultant honoraria from Servier, Pfizer, Novartis, ResMed, Takeda, and Boston Scientific, and that his institution receives research grants from Roche Diagnostics and BG Medicine. Dirk J van Veldhuisen: Board Membership fees from Amgen, BG Medicine, Pfizer, Sorbent and Vifor. Javed Butler: Consultant to Cardiomems, Trevena, Bayer Healthcare, Takeda, Gambro, Ono Pharma, and Amgen; Events Committee for WorldHeart, Corthera, Abbott Vascular, Celladon, Research Support, NIH, GE Healthcare and Medtronic. All other authors have no conflicts of interest to declare. NR 30 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 EI 1573-7322 J9 HEART FAIL REV JI Heart Fail. Rev. PD MAR PY 2014 VL 19 IS 2 BP 135 EP 152 DI 10.1007/s10741-012-9361-8 PG 18 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB5JY UT WOS:000331825900001 PM 23099992 ER PT J AU Lin, HH Sinner, MF Brody, JA Arking, DE Lunetta, KL Rienstra, M Lubitz, SA Magnani, JW Sotoodehnia, N McKnight, B McManus, DD Boerwinkle, E Psaty, BM Rotter, JI Bis, JC Gibbs, RA Muzny, D Kovar, CL Morrison, AC Gupta, M Folsom, AR Kaab, S Heckbert, SR Alonso, A Ellinor, PT Benjamin, EJ AF Lin, Honghuang Sinner, Moritz F. Brody, Jennifer A. Arking, Dan E. Lunetta, Kathryn L. Rienstra, Michiel Lubitz, Steven A. Magnani, Jared W. Sotoodehnia, Nona McKnight, Barbara McManus, David D. Boerwinkle, Eric Psaty, Bruce M. Rotter, Jerome I. Bis, Joshua C. Gibbs, Richard A. Muzny, Donna Kovar, Christie L. Morrison, Alanna C. Gupta, Mayetri Folsom, Aaron R. Kaeaeb, Stefan Heckbert, Susan R. Alonso, Alvaro Ellinor, Patrick T. Benjamin, Emelia J. CA CHARGE Atrial Fibrillation Working TI Targeted sequencing in candidate genes for atrial fibrillation: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study SO HEART RHYTHM LA English DT Article DE Arrhythmia; Genetics; Atrial fibrillation; Epidemiology ID WIDE ASSOCIATION; RARE VARIANTS; RISK-FACTOR; INFLAMMATION; COMMON; SUSCEPTIBILITY; RECEPTOR; MARKERS; DESIGN; LOCI AB BACKGROUND Genome-wide association studies (GWAS) have identified common genetic variants that predispose to atrial fibrillation (AF). It is unclear whether rare and low-frequency variants in genes implicated by such GWAS confer additional risk of AF. OBJECTIVE To study the association of genetic variants with AF at GWAS top loci. METHODS In the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study, we selected and sequenced 77 target gene regions from GWAS loci of complex diseases or traits, including 4 genes hypothesized to be related to AF (PRRX1, CAV1, CAV2, and ZFHX3). Sequencing was performed in participants with (n = 948) and without (n = 3330) AF from the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Massachusetts General Hospital. RESULTS One common variant (rs11265611; P = 1.70 x 10-6) intronic to IL6R (interleukin-6 receptor gene) was significantly associated with AF after Bonferroni correction (odds ratio 0.70; 95% confidence interval 0.58-0.85). The variant was not genotyped or imputed by prior GWAS, but it is in linkage disequilibrium (r2 =.69) with the single-nucleotide polymorphism, with the strongest association with AF so far at this locus (rs4845625). In the rare variant joint analysis, damaging variants within the PRRX1 region showed significant association with AF after Bonferroni correction (P =.01). CONCLUSIONS We identified 1 common single-nucleotide polymorphism and 1 gene region that were significantly associated with AF. Future sequencing efforts with larger sample sizes and more comprehensive genome coverage are anticipated to identify additional AF-related variants. (C) 2014 Heart Rhythm Society. All rights reserved. C1 [Lin, Honghuang; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Lin, Honghuang; Sinner, Moritz F.; Lunetta, Kathryn L.; Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Sinner, Moritz F.; Rienstra, Michiel; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany. [Brody, Jennifer A.; Sotoodehnia, Nona; Psaty, Bruce M.; Bis, Joshua C.; Heckbert, Susan R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Lunetta, Kathryn L.; Gupta, Mayetri] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Folsom, Aaron R.; Alonso, Alvaro] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Boerwinkle, Eric; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Gibbs, Richard A.; Muzny, Donna; Kovar, Christie L.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA. RP Lin, HH (reprint author), Boston Univ, Sch Med, Dept Med, 72 E Concord St,B-616, Boston, MA 02118 USA. EM hhlin@bu.edu RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health (NIB) through the American Recovery and Reinvestment Act [5RC211L102419]; National Heart, Lung, and Blood Institute (NHLBI) [HH5N268201100005C, HHSN268201100006C, HSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820110000.E0C, HHSN2682011000011 C, HH5N2682011000012C]; NHLBI in collaboration with the Boston University [N0I-HC-25195]; Linux Cluster for Genetic Analysis; NIILBI [N01-11C-85239, N01-11C-85079, NO 1-HC-85080, N01-HC-85081, NO1-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, NOI-HC-75150, NO1-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756]; National Institute on Aging of the Nzitional Institutes of Public Health [AC 021629 AG-15928, AG-20098, AG-027058]; NIH [NOI-HC 25195, 6R01-NS 17950, 1ROHIL092577, 5R21DA027021, 1R0111L104156, 1K24111-105780, IRO1 HL102214, 1RC1111-101056]; American Heart Association [09SDG2280087, 016.136.055]; Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University FX Dr Lin, Dr Sinner, Dr Ellinor, and Dr Benjamin contributed equally to this work. Funding support for "Building on GWAS for NHLB1-diseases: the U.S. CHARGE Consortium" was provided by the National Institutes of Health (NIB) through the American Recovery and Reinvestment Act of 2009 (5RC211L102419). Data for "Building on GWAS for MILBI-diseases: the U.S. CHARGE Consortium" were provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities Study; L Adrienne Cupples, principal investigator for the Framingham Heart Study; and Bruce Psaty, principal investigator for the Cardiovascular Health Study. Sequencing was carried out at the Baylor Genome Center (U54 HG003273). The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HH5N268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820110000.E0C, HHSN2682011000011 C, and HH5N2682011000012C). The Framingham Heart Study is conducted and supported by the NHLBI in collaboration with the Boston University (contract no. N0I-HC-25195) and its contract with Affymetrix, Inc, for genome-wide genotyping services (contract no. NO2-11L-6-4278) and for quality control by Framingham Heart Study investigators using genotypes in the SNP Health Association Resource project. A portion of this research was conducted by using the Linux Cluster for Genetic Analysis computing resources at Boston University Medical Campus. This CHS research was supported by NIILBI contracts N01-11C-85239, N01-11C-85079, NO 1-HC-85080, N01-HC-85081, NO1-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, NOI-HC-75150, NO1-HC-45133, and HHSN268201200036C as well as by NHLBI grants HL080295, HL087652, HL105756, with additional contribution from NINT)S. Additionzil support was provided through National Institute on Aging of the Nzitional Institutes of Public Health giants AC 021629 AG-15928. AG-20098, and AG-027058. See also h This project was also supported by NIH grants NOI-HC 25195 and 6R01-NS 17950 (to Dr Beamin); 1ROHIL092577, 5R21DA027021, 1R0111L104156, 1K24111-105780, IRO1 HL102214, and 1RC1111-101056 (to Dr Ellinory 1RC111L099452 and American Heart Association grant 09SDG2280087 (to Dr Mons), and the Netherlands Organisation for Scientific Research grant (Veni grant 016.136.055; to Dr Rienstral. This work was partially supported by thc Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University ainp://www.bitmc.1%.ediiievanseenteribrO. Dr Psaty serves on the Data and Safety Monitoring Board of a clinical trial of a device funded by Zoll LifeCor and on the Steering Committee of die Yale Open Data Access Project funded by Medtronic. NR 34 TC 9 Z9 11 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2014 VL 11 IS 3 BP 452 EP 457 DI 10.1016/j.hrthm.2014.11.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB4AJ UT WOS:000331731000022 PM 24239840 ER PT J AU Lemaitre, RN Johnson, CO Hesselson, S Sotoodhenia, N McKnight, B Sitlani, CM Rea, TD King, IB Kwok, PY Mak, A Li, G Brody, J Larson, E Mozaffarian, D Psaty, BM Huertas-Vazquez, A Tardif, JC Albert, CM Lyytikainen, LP Arking, DE Kaab, S Huikuri, HV Krijthe, BP Eijgelsheim, M Wang, YA Reinier, K Lehtimaki, T Pulit, SL Brugada, R Muller-Nurasyid, M Newton-Cheh, CH Karhunen, PJ Stricker, BH Goyette, P Rotter, JI Chugh, SS Chakravarti, A Jouven, X Siscovick, DS AF Lemaitre, Rozenn N. Johnson, Catherine O. Hesselson, Stephanie Sotoodhenia, Nona McKnight, Barbara Sitlani, Colleen M. Rea, Thomas D. King, Irena B. Kwok, Pui-Yan Mak, Angel Li, Guo Brody, Jennifer Larson, Eric Mozaffarian, Dariush Psaty, Bruce M. Huertas-Vazquez, Adriana Tardif, Jean-Claude Albert, Christine M. Lyytikaeinen, Leo-Pekka Arking, Dan E. Kaeaeb, Stefan Huikuri, Heikki V. Krijthe, Bouwe P. Eijgelsheim, Mark Wang, Ying A. Reinier, Kyndaron Lehtimaeki, Terho Pulit, Sara L. Brugada, Ramon Mueller-Nurasyid, Martina Newton-Cheh, Chris H. Karhunen, Pekka J. Stricker, Bruno H. Goyette, Philippe Rotter, Jerome I. Chugh, Sumeet S. Chakravarti, Aravinda Jouven, Xavier Siscovick, David S. TI Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest SO HEART RHYTHM LA English DT Article DE Death; Sudden; Genetic epidemiology ID LIPID DROPLETS; MYOCARDIAL-INFARCTION; DEATH; HEART; ATHEROSCLEROSIS; ASSOCIATION; ARRHYTHMIAS; ISCHEMIA; PHOSPHATIDYLCHOLINE; EPIDEMIOLOGY AB BACKGROUND There is limited information on genetic factors OBJECTIVE To assess the association of common variation in associated with sudden cardiac arrest (SCA). genes in fatty acid pathways with SCA risk. METHODS We selected 85 candidate genes and 1155 single nucleotide poLymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used Linear Logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases. RESULTS Eight SN Ps in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the CPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% Lower SCA risk (95% confidence interval 21% to 5%) in the discovery phase and 9 /a lower SCA risk ( 9 5 % confidence interval 16% to 1%) in the replication phase. CONCLUSIONS While none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation. (C) 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. C1 [Lemaitre, Rozenn N.; Johnson, Catherine O.; Sotoodhenia, Nona; Sitlani, Colleen M.; Rea, Thomas D.; Li, Guo; Brody, Jennifer; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98101 USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Hesselson, Stephanie; Kwok, Pui-Yan; Mak, Angel] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Hesselson, Stephanie; Kwok, Pui-Yan; Mak, Angel] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [King, Irena B.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. [Larson, Eric; Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA. [Mozaffarian, Dariush] Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA. [Mozaffarian, Dariush; Albert, Christine M.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Albert, Christine M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Pulit, Sara L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Huertas-Vazquez, Adriana; Reinier, Kyndaron; Chugh, Sumeet S.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. [Tardif, Jean-Claude; Goyette, Philippe] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Tardif, Jean-Claude; Goyette, Philippe] Univ Montreal, Montreal, PQ, Canada. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Karhunen, Pekka J.] Fimlab Labs, Dept Forens Med, Tampere, Finland. [Karhunen, Pekka J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kaeaeb, Stefan; Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [Huikuri, Heikki V.] Univ Oulu, Med Res Ctr Oulu, Inst Clin Med, Oulu, Finland. [Krijthe, Bouwe P.; Eijgelsheim, Mark; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Wang, Ying A.] Novartis Inst BioMed Res, Cambridge, MA USA. [Pulit, Sara L.] Broad Inst Massachusetts Inst Technol & Harvard U, Program Med & Populat Genet, Cambridge, MA USA. [Brugada, Ramon] IDIBGI Univ Girona, Inst Invest Biomed Girona, Cardiovasc Genet Ctr, Girona, Spain. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Newton-Cheh, Chris H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Chris H.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Chris H.] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. [Stricker, Bruno H.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands. [Rotter, Jerome I.] Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Jouven, Xavier] Univ Paris 05, Dept Cardiol, Paris, France. [Jouven, Xavier] Univ Paris 05, Dept Epidemiol, Paris, France. RP Lemaitre, RN (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave, Suite 1360, Seattle, WA 98101 USA. EM rozenl@uw.edu RI Kwok, Pui-Yan/F-7725-2014; Lyytikainen, Leo-Pekka/C-8544-2016 OI Kwok, Pui-Yan/0000-0002-5087-3059; Lyytikainen, Leo-Pekka/0000-0002-7200-5455 FU National Lune; Heart, and Blood Institute [R0111E092144, R01-11L092111, R01-11L088456] FX Dr Mozaffarian has received research grants from (3laxoSmithKlinc, Sigma Tau; Pronova; and the National Institutes of Health for an investigatorinitiated, not-for-protit clinical trial of fish oil and postsurgical complications as well as small annual royalties from UpToDate for an online scientific chapter on fish oil. The Sudden Cardiac Blood Repository Study was financed by the National Lune; Heart, and Blood Institute (grants R0111E092144, R01-11L092111, and R01-11L088456). Funding sources for the other contributing studies are listed in the Online Supplement. NR 35 TC 5 Z9 5 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD MAR PY 2014 VL 11 IS 3 BP 471 EP 477 DI 10.1016/j.hrthm.2014.01.008 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB4AJ UT WOS:000331731000026 PM 24418166 ER PT J AU Sanchez-Mas, J Lax, A Asensio-Lopez, MC Fernandez-Del Palacio, MJ Caballero, L Garrido, IP Pastor, F Januzzi, JL Pascual-Figal, DA AF Sanchez-Mas, J. Lax, A. Asensio-Lopez, M. C. Fernandez-Del Palacio, M. J. Caballero, L. Garrido, I. P. Pastor, F. Januzzi, J. L. Pascual-Figal, D. A. TI Galectin-3 expression in cardiac remodeling after myocardial infarction SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Galectin-3; Heart failure; Myocardial infarction; Cardiac remodeling; Fibrosis ID HEART-FAILURE C1 [Sanchez-Mas, J.; Lax, A.; Asensio-Lopez, M. C.; Caballero, L.; Garrido, I. P.; Pastor, F.; Pascual-Figal, D. A.] Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Fernandez-Del Palacio, M. J.] Univ Murcia, Dept Vet Med & Surg, Vet Teaching Hosp, Murcia, Spain. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Sanchez-Mas, J.; Lax, A.; Asensio-Lopez, M. C.; Caballero, L.; Garrido, I. P.; Pastor, F.; Pascual-Figal, D. A.] Univ Murcia, Sch Med, Dept Internal Med, Murcia, Spain. RP Sanchez-Mas, J (reprint author), Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM jsanmas@um.es OI Pascual Figal, Domingo A./0000-0002-4993-9540 NR 8 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 EI 1874-1754 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 1 PY 2014 VL 172 IS 1 BP E98 EP E101 DI 10.1016/j.ijcard.2013.12.129 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB3WT UT WOS:000331721600038 PM 24433619 ER PT J AU Papadaki, ME Kaban, LB Troulis, MJ AF Papadaki, M. E. Kaban, L. B. Troulis, M. J. TI Endoscopic vertical ramus osteotomy: a long-term prospective study SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE endoscopic vertical ramus osteotomy; mandibular prognathism; rigid fixation ID INVASIVE ORTHOGNATHIC SURGERY; MANDIBULAR PROGNATHISM; RECONSTRUCTION; CONDYLECTOMY; FRACTURES; FIXATION AB The purpose of this prospective study was to evaluate the outcomes of endoscopic vertical ramus osteotomy (EVRO) with rigid fixation for the treatment of mandibular prognathism or asymmetry. Inclusion criteria were age >15 years, adequate clinical and radiographic documentation, and minimum postoperative follow-up of 3 years. Exclusion criteria were refusal to consent, rheumatoid arthritis, steroid use, and smoking. Demographic data, pre-operative (TO), immediate postoperative (T1), and latest follow-up (T2) clinical examinations and cephalometric analysis, procedure data, complications, and length of hospital stay (LOS) were documented. Ten fulfilled the inclusion criteria. Diagnoses included mandibular hyperplasia (n = 5), stable condylar hyperplasia (n = 4), and mandibular asymmetry secondary to condylar resorption (n = 1). In total, 17 EVROs were performed. The mean operative time was 33 min per side. Mean mandibular setback was 4.7 mm. Mean LOS was 1.9 days. Latest follow-up ranged from 3 to 5 years. Skeletal stability was confirmed in nine patients. One patient exhibited recurrence of mandibular prognathism at 5 years due to late growth. No VII nerve deficits were encountered. Inferior alveolar nerve (IAN) paresthesia was noted in four patients, which resolved postoperatively. EVRO was fast and resulted in minimal blood loss, quick recovery, and skeletal stability. C1 [Papadaki, M. E.; Kaban, L. B.; Troulis, M. J.] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Papadaki, ME (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. EM mpapadaki@partners.org FU Hanson Foundation (Boston, MA, USA); AO Foundation/Synthes (Paoli, PA, USA); MGH Department of OMFS Education Research Fund; NIH [5K23DE14070-5] FX This study was funded in part by the Hanson Foundation (Boston, MA, USA); AO Foundation/Synthes (Paoli, PA, USA); MGH Department of OMFS Education & Research Fund; NIH (Grant Number 5K23DE14070-5, PI: Maria Troulis). NR 27 TC 2 Z9 2 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 EI 1399-0020 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD MAR PY 2014 VL 43 IS 3 BP 305 EP 310 DI 10.1016/j.ijom.2013.09.012 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA AB5UK UT WOS:000331854000007 PM 24246948 ER PT J AU Warren, LEG Miller, CL Horick, N Skolny, MN Jammallo, LS Sadek, BT Shenouda, MN O'Toole, JA MacDonald, SM Specht, MC Taghian, AG AF Warren, Laura E. G. Miller, Cynthia L. Horick, Nora Skolny, Melissa N. Jammallo, Lauren S. Sadek, Betro T. Shenouda, Mina N. O'Toole, Jean A. MacDonald, Shannon M. Specht, Michelle C. Taghian, Alphonse G. TI The Impact of Radiation Therapy on the Risk of Lymphedema After Treatment for Breast Cancer: A Prospective Cohort Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID AXILLARY DISSECTION; NODE DISSECTION; POSTOPERATIVE RADIOTHERAPY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; ARM LYMPHEDEMA; IRRADIATION; WOMEN; MORBIDITY; BIOPSY AB Purpose/Objective: Lymphedema after breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiation therapy-related risk factors for lymphedema. Methods and Materials: From 2005 to 2012, we prospectively performed arm volume measurements on 1476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099 of 1501 patients (73%) received radiation therapy. Arm measurements were performed preoperatively and postoperatively. Lymphedema was defined as >= 10% arm volume increase occurring > 3 months postoperatively. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. Results: At a median follow-up time of 25.4 months (range, 3.4-82.6 months), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiation therapy type was as follows: 3.0% no radiation therapy, 3.1% breast or chest wall alone, 21.9% supraclavicular (SC), and 21.1% SC and posterior axillary boost (PAB). On multivariate analysis, the hazard ratio for regional lymph node radiation (RLNR) (SC +/- PAB) was 1.7 (P = .025) compared with breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC + PAB (P = .96). Other independent risk factors included early postoperative swelling (P<. 0001), higher body mass index (P<. 0001), greater number of lymph nodes dissected (P = .018), and axillary lymph node dissection (P = .0001). Conclusions: In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased the risk of lymphedema compared with breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease against the increased risk of lymphedema. (C) 2014 Elsevier Inc. C1 [Warren, Laura E. G.; Miller, Cynthia L.; Skolny, Melissa N.; Jammallo, Lauren S.; Sadek, Betro T.; Shenouda, Mina N.; MacDonald, Shannon M.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, 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. [Specht, Michelle C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), 100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 FU National Cancer Institute [RO1CA139118, P50CA0893932] FX Supported by Award # RO1CA139118 (A. Taghian) and Award # P50CA0893932 (A. Taghian) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institutes of Health. NR 35 TC 42 Z9 43 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2014 VL 88 IS 3 BP 565 EP 571 DI 10.1016/j.ijrobp.2013.11.232 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AB3YO UT WOS:000331726300008 PM 24411624 ER PT J AU Paly, JJ Hallemeier, CL Biggs, PJ Niemierko, A Roeder, F Martinez-Monge, R Whitson, J Calvo, FA Fastner, G Sedlmayer, F Wong, WW Ellis, RJ Haddock, MG Choo, R Shipley, WU Zietman, AL Efstathiou, JA AF Paly, Jonathan J. Hallemeier, Christopher L. Biggs, Peter J. Niemierko, Andrzej Roeder, Falk Martinez-Monge, Rafael Whitson, Jared Calvo, Felipe A. Fastner, Gerd Sedlmayer, Felix Wong, William W. Ellis, Rodney J. Haddock, Michael G. Choo, Richard Shipley, William U. Zietman, Anthony L. Efstathiou, Jason A. TI Outcomes in a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADICAL NEPHRECTOMY; SURGICAL-TREATMENT; RADIOTHERAPY; STRATEGIES; SURVIVAL AB Purpose/Objective(s): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). Methods and Materials: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. Results: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P < .01), presence of sarcomatoid features (HR 3.7-6.9, P < .05), and higher IORT dose (HR 1.3, P < .001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P = .03). For locally recurrent tumors, positive margin status (HR 2.6, P = .01) was associated with decreased OS. Conclusions: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to similar cohorts treated by local resection alone suggesting the potential for improved DFS with IORT. (C) 2014 Elsevier Inc. C1 [Paly, Jonathan J.; Biggs, Peter J.; Niemierko, Andrzej; Shipley, William U.; Zietman, Anthony L.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hallemeier, Christopher L.; Haddock, Michael G.; Choo, Richard] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Roeder, Falk] Heidelberg Univ, Dept Radiat Oncol, Heidelberg, Germany. [Martinez-Monge, Rafael] Univ Navarra, Div Radiat Oncol, E-31080 Pamplona, Spain. [Whitson, Jared] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Calvo, Felipe A.] Hosp Gen Univ Gregorio Maranon, Dept Oncol, Madrid, Spain. [Fastner, Gerd; Sedlmayer, Felix] Paracelsus Med Univ Clin, Dept Radiotherapy & Radiooncol, Salzburg, Austria. [Wong, William W.] Mayo Clin, Dept Radiat Oncol, Scottsdale, AZ USA. [Ellis, Rodney J.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Dept Radiat Oncol, Cleveland, OH USA. RP Efstathiou, JA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM jefstathiou@partners.org OI Sedlmayer, Felix/0000-0002-1181-0178 NR 19 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2014 VL 88 IS 3 BP 618 EP 623 DI 10.1016/j.ijrobp.2013.11.207 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AB3YO UT WOS:000331726300015 PM 24411190 ER PT J AU Michaelson, EM Chen, YH Silver, B Tishler, RB Marcus, KJ Stevenson, MA Ng, AK AF Michaelson, Evan M. Chen, Yu-Hui Silver, Barbara Tishler, Roy B. Marcus, Karen J. Stevenson, Mary Ann Ng, Andrea. K. TI Thyroid Malignancies in Survivors of Hodgkin Lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID CHILDHOOD-CANCER SURVIVOR; THERAPEUTIC RADIATION; EXTERNAL RADIATION; CLINICAL BEHAVIOR; NATURAL-HISTORY; POOLED ANALYSIS; FOLLOW-UP; RISK; DISEASE; CARCINOMAS AB Purpose: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes. Methods and Materials: Thyroid cancer cases were retrospectively identified from a multiinstitutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model. Results: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, >= 10 years, >= 15 years, and >= 20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively. Conclusions: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and >= 10 years from HL treatment owing to their higher risk, which increases over time. (C) 2014 Elsevier Inc. C1 [Michaelson, Evan M.; Silver, Barbara; Tishler, Roy B.; Marcus, Karen J.; Ng, Andrea. K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Michaelson, Evan M.; Silver, Barbara; Tishler, Roy B.; Marcus, Karen J.; Ng, Andrea. K.] Childrens Hosp, Boston, MA 02115 USA. [Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Stevenson, Mary Ann] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM ang@lroc.harvard.edu NR 33 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2014 VL 88 IS 3 BP 636 EP 641 DI 10.1016/j.ijrobp.2013.11.237 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AB3YO UT WOS:000331726300018 PM 24521679 ER PT J AU Sethi, RV Giantsoudi, D Raiford, M Malhi, I Niemierko, A Rapalino, O Caruso, P Yock, TI Tarbell, NJ Paganetti, H MacDonald, SM AF Sethi, Roshan V. Giantsoudi, Drosoula Raiford, Michael Malhi, Imran Niemierko, Andrzej Rapalino, Otto Caruso, Paul Yock, Torunn I. Tarbell, Nancy J. Paganetti, Harald MacDonald, Shannon M. TI Patterns of Failure After Proton Therapy in Medulloblastoma: Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID CRANIOSPINAL RADIATION-THERAPY; AVERAGE-RISK MEDULLOBLASTOMA; CRANIAL-SPINAL IRRADIATION; 3D CONFORMAL RADIOTHERAPY; TUMOR BED BOOST; PEDIATRIC-ONCOLOGY; ADJUVANT CHEMOTHERAPY; FRENCH-SOCIETY; CHILDREN; RECURRENCE AB Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n = 8), spinal compartment (n = 11), and posterior fossa (n = 5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons formedulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence inmedulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy. (C) 2014 Elsevier Inc. C1 [Sethi, Roshan V.] Harvard Univ, Sch Med, Boston, MA USA. [Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Rapalino, Otto; Caruso, Paul] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Yawkey 112,55 Fruit St, Boston, MA 02114 USA. EM smacdonald@partners.org OI Paganetti, Harald/0000-0002-6257-2413 FU Doris Duke Charitable Foundation; National Cancer Institute of the National Institutes of Health [P01CA021239]; Federal Share of program income earned by Massachusetts General Hospital [C06 CA059267]; Proton Therapy Research and Treatment Center FX Supported by the Doris Duke Charitable Foundation (R.V.S.). Research was supported by the National Cancer Institute of the National Institutes of Health under Award Number P01CA021239 and the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 34 TC 22 Z9 22 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2014 VL 88 IS 3 BP 655 EP 663 DI 10.1016/j.ijrobp.2013.11.239 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AB3YO UT WOS:000331726300021 PM 24521681 ER PT J AU Kroshus, E Baugh, CM Daneshvar, DH Viswanath, K AF Kroshus, Emily Baugh, Christine M. Daneshvar, Daniel H. Viswanath, Kasisomayajula TI Understanding Concussion Reporting Using a Model Based on the Theory of Planned Behavior SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescent; Brain concussion; Sports; Education ID INJURY PREVENTION; FOOTBALL PLAYERS; HEAD-INJURY; ICE HOCKEY; EDUCATION; SPORT; KNOWLEDGE; YOUTH; COLLEGE; RETURN AB Purpose: Athlete's report of concussion symptoms to coaching or medical personnel is an important component of concussion risk reduction. This study applies a model based on the Theory of Planned Behavior (TPB) to the prediction of concussive symptom underreporting among late adolescent and young adult male ice hockey players. Methods: Participants were members of an American Tier III Junior A ice hockey league (ages 18-21 years; male; n - 256). Twelve of 14 league teams and 97% of players within these teams agreed to participate. Written survey items assessed symptom reporting behavior, intention, perceived norms, self-efficacy, perceived outcomes of reporting, and concussion knowledge. Structural equation modeling was used to assess the significance of relationships hypothesized by the TPB-based model and the overall model fit. Data were collected in January 2013. Results: Results supported the fit of the TPB-based model in explaining reporting behavior; all model pathways were significant in the hypothesized direction. Of the perceived reporting outcomes assessed, those related to athletic performance were identified as most strongly associated with reporting intention. Conclusions: Results of this study suggest the importance of considering factors such as perceived outcomes of reporting, perceived norms, and self-efficacy, in addition to knowledge, when analyzing concussion underreporting among adolescent athletes. As concussion education for athletes becomes increasingly mandated, testing and applying psychosocial theories such as TPB may help increase program efficacy. (C) 2014 Society for Adolescent Health and Medicine. All rights reserved. C1 [Kroshus, Emily; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Baugh, Christine M.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Baugh, Christine M.; Daneshvar, Daniel H.] Boston Univ, Sch Med, Ctr Study Traumat Encephalopathy, Boston, MA 02118 USA. [Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kroshus, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,Kresge Bldg 172, Boston, MA 02115 USA. EM emk329@mail.harvard.edu OI Daneshvar, Daniel/0000-0003-3691-9513 NR 40 TC 22 Z9 22 U1 2 U2 26 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 MAR PY 2014 VL 54 IS 3 BP 269 EP + DI 10.1016/j.jadohealth.2013.11.011 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA AB3XF UT WOS:000331722800006 PM 24560034 ER PT J AU Koudstaal, S Bastings, MMC Feyen, DAM Waring, CD van Slochteren, FJJ Dankers, PYW Torella, D Sluijter, JPG Nadal-Ginard, B Doevendans, PA Ellison, GM Chamuleau, SAJ AF Koudstaal, Stefan Bastings, Maartje M. C. Feyen, Dries A. M. Waring, Cheryl D. van Slochteren, Frebus J. Dankers, Patricia Y. W. Torella, Daniele Sluijter, Joost P. G. Nadal-Ginard, Bernardo Doevendans, Pieter A. Ellison, Georgina M. Chamuleau, Steven A. J. TI Sustained Delivery of Insulin-Like Growth Factor-1/Hepatocyte Growth Factor Stimulates Endogenous Cardiac Repair in the Chronic Infarcted Pig Heart SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Cardiac stem/progenitor cells; IGF-1; HGF; Chronicmyocardial infarction; Regeneration ID CARDIOSPHERE-DERIVED CELLS; STEM-CELLS; MYOCARDIAL-INFARCTION; REGENERATION; CARDIOMYOCYTES; MULTIPOTENT; COMMITMENT; ACTIVATION; SURVIVAL; EFFICACY AB Activation of endogenous cardiac stem/progenitor cells (eCSCs) can improve cardiac repair after acute myocardial infarction. We studied whether the in situ activation of eCSCs by insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) could be increased using a newly developed hydrogel in chronic myocardial infarction (MI). One-month post-MI pigs underwent NOGA-guided intramyocardial injections of IGF-1/HGF (GF: both 0.5 mu g/mL, n = 5) or IGF-1/HGF incorporated in UPy hydrogel (UPy-GF; both 0.5 mu g/mL, n = 5). UPy hydrogel without added growth factors was administered to four control (CTRL) pigs. Left ventricular ejection fraction was increased in the UPy-GF and GF animals compared to CTRLs. UPy-GF delivery reduced pathological hypertrophy, led to the formation of new, small cardiomyocytes, and increased capillarization. The eCSC population was increased almost fourfold in the border zone of the UPy-GF-treated hearts compared to CTRL hearts. These results show that IGF-1/HGF therapy led to an improved cardiac function in chronic MI and that effect size could be further increased by using UPy hydrogel. C1 [Koudstaal, Stefan; Feyen, Dries A. M.; van Slochteren, Frebus J.; Sluijter, Joost P. G.; Doevendans, Pieter A.; Chamuleau, Steven A. J.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, NL-3508 GA Utrecht, Netherlands. [Koudstaal, Stefan; Sluijter, Joost P. G.; Doevendans, Pieter A.] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. [Bastings, Maartje M. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dankers, Patricia Y. W.] Eindhoven Univ Technol, Inst Complex Mol Syst, NL-5600 MB Eindhoven, Netherlands. [Dankers, Patricia Y. W.] Eindhoven Univ Technol, Biol Chem Lab, NL-5600 MB Eindhoven, Netherlands. [Waring, Cheryl D.; Torella, Daniele; Ellison, Georgina M.] Liverpool JM Univ, Stem Cell & Regenerat Biol Unit BioStem, Liverpool, Merseyside, England. [Torella, Daniele] Magna Graecia Univ Catanzaro, Dept Med, Catanzaro, Italy. [Koudstaal, Stefan; Nadal-Ginard, Bernardo; Ellison, Georgina M.] Kings Coll London, Sch Biomed Sci, Ctr Human & Aerosp Physiol Sci, London SE1 1UL, England. [Koudstaal, Stefan; Nadal-Ginard, Bernardo; Ellison, Georgina M.] Kings Coll London, Sch Biomed Sci, Ctr Stem Cells & Regenerat Med, London SE1 1UL, England. RP Chamuleau, SAJ (reprint author), Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Room E03-511,POB 85500, NL-3508 GA Utrecht, Netherlands. EM s.a.j.chamuleau@umcutrecht.nl RI Ellison, Georgina/B-4597-2016; OI Ellison, Georgina/0000-0002-2733-3361; TORELLA, Daniele/0000-0002-4915-5084; Sluijter, Joost/0000-0003-2088-9102 FU HGG Group BV; Wijnand M. Pon Stichting; Novartis Foundation for Cardiovascular Excellence; Dutch Ministry of Economic Affairs, Agriculture and Innovation; CARE-MI FP7-HEALTH [242038]; Endostem FP7-HEALTH [241440] FX We thank the following persons for their technical assistance: Patricia Kracht, Beverley Henning, Esther van Eeuwijk, Corina Metz, and Arjan Schoneveld. Cees Verlaan, Marlijn Jansen, Joyce Visser, Merel Schurink, and Maringa Emons are acknowledged for their excellent technical assistance with the animal experiments. This work was supported by the HGG Group BV (SK), the "Wijnand M. Pon Stichting" (SC, SK), and the Novartis Foundation for Cardiovascular Excellence (JS). This research forms part of the Project P1.04 SMARTCARE of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation (DF, FvS). This work was supported by grants from CARE-MI FP7-HEALTH-2009 (242038) and Endostem FP7-HEALTH-2009 (241440) (GME, BNG and DT). NR 30 TC 26 Z9 26 U1 3 U2 18 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 MAR PY 2014 VL 7 IS 2 SI SI BP 232 EP 241 DI 10.1007/s12265-013-9518-4 PG 10 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA AB7HZ UT WOS:000331961700010 PM 24395494 ER PT J AU Motiwala, SR Szymonifka, J Belcher, A Weiner, RB Baggish, AL Gaggin, HK Bhardwaj, A Januzzi, JLJ AF Motiwala, Shweta R. Szymonifka, Jackie Belcher, Arianna Weiner, Rory B. Baggish, Aaron L. Gaggin, Hanna K. Bhardwaj, Anju Januzzi, James L., Jr. TI Measurement of Novel Biomarkers to Predict Chronic Heart Failure Outcomes and Left Ventricular Remodeling SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Heart failure; Biomarkers; Outcomes; Prognosis; Remodeling ID FIBROBLAST-GROWTH-FACTOR; NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT; MUSCULAR-DYSTROPHY; THERAPY PROTECT; SERUM-LEVELS; BIGLYCAN; PROTEOGLYCANS; ENDOSTATIN; DECORIN AB Myocardial remodeling is pivotal in the progression and complication of chronic heart failure (HF). We assessed serial measurement of five biomarkers with biologic links to remodeling (biglycan, secreted frizzled-related protein 3, endostatin, insulin-like growth factor binding protein 7 [IGFBP7], mimecan) in 142 patients with HF followed through 882 office visits. IGFBP7 and mimecan were most associated with events; in fully adjusted models, lower IGFBP7 concentrations across visits independently predicted fewer events (odds ratio [OR] = 0.83; 95 % confidence interval [CI] = 0.73-0.95, p = 0.01). Subjects with rising mimecan had greater decrease in left ventricular end diastolic (p = 0.07) and systolic (p = 0.01) volumes, greater increase in ejection fraction (p = 0.02), and had lowest event rates. Statistical models suggested several HF medications might lead to changes in both IGFBP7 and mimecan values. The results suggest serial measurement of IGFBP7 provides prognostic information, while changes in mimecan provide unique information regarding myocardial remodeling. C1 [Motiwala, Shweta R.; Szymonifka, Jackie; Belcher, Arianna; Weiner, Rory B.; Baggish, Aaron L.; Gaggin, Hanna K.; Bhardwaj, Anju] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Januzzi, JLJ (reprint author), Massachusetts Gen Hosp, Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Roche Diagnostics; Dennis and Marilyn Barry Fellowship in Cardiology; Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment FX This study is supported in part by Roche Diagnostics, which had no role in data analysis or manuscript preparation. Dr. Motiwala is supported by the Dennis and Marilyn Barry Fellowship in Cardiology, Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation, and Dr. Januzzi is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment. NR 30 TC 14 Z9 14 U1 1 U2 4 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 MAR PY 2014 VL 7 IS 2 SI SI BP 250 EP 261 DI 10.1007/s12265-013-9522-8 PG 12 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA AB7HZ UT WOS:000331961700012 PM 24309956 ER PT J AU Scherrer, JF Svrakic, DM Freedland, KE Chrusciel, T Balasubramanian, S Bucholz, KK Lawler, EV Lustman, PJ AF Scherrer, Jeffrey F. Svrakic, Dragan M. Freedland, Kenneth E. Chrusciel, Timothy Balasubramanian, Sumitra Bucholz, Kathleen K. Lawler, Elizabeth V. Lustman, Patrick J. TI Prescription Opioid Analgesics Increase the Risk of Depression SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE prescription opioid analgesics; depression; propensity score; epidemiology; administrative medical records; veteran ID MENTAL-HEALTH DISORDERS; INVERSE PROBABILITY; PROPENSITY SCORE; NONCANCER PAIN; DRUG-ABUSE; CONFOUNDERS; ASSOCIATION; COMORBIDITY; THERAPY; ILLNESS AB BACKGROUND: Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring substance use and major depression. Little is known about depressogenic effects of opioid use in other populations. The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression. Retrospective cohort study, new user design. Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000. Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007. Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90-180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05-1.46 for 90-180 days, and HR = 1.51; 95 % CI:1.31-1.74 for > 180 days). In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression. C1 [Scherrer, Jeffrey F.; Chrusciel, Timothy; Balasubramanian, Sumitra] St Louis VA Med Ctr, Res Serv, Clin Res & Epidemiol Workgroup, St Louis, MO USA. [Scherrer, Jeffrey F.; Bucholz, Kathleen K.] St Louis Univ, Sch Med, Dept Family & Community Med, St Louis, MO 63103 USA. [Scherrer, Jeffrey F.; Svrakic, Dragan M.; Freedland, Kenneth E.; Balasubramanian, Sumitra; Lustman, Patrick J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Svrakic, Dragan M.; Lustman, Patrick J.] John Cochran Hosp, St Louis VA Med Ctr, Bell St Clin, St Louis, MO USA. [Lawler, Elizabeth V.] Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, VA Boston Healthcare Syst, Jamaica Plain, MA USA. [Lawler, Elizabeth V.] Harvard Univ, Sch Med, Boston, MA USA. [Lawler, Elizabeth V.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Scherrer, JF (reprint author), St Louis Univ, Sch Med, Dept Family & Community Med, St Louis, MO 63103 USA. EM scherrjf@slu.edu FU Veteran's Administration Career Development Award FX Veteran's Administration Career Development Award to Dr. Scherrer NR 39 TC 34 Z9 34 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2014 VL 29 IS 3 BP 491 EP 499 DI 10.1007/s11606-013-2648-1 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB7II UT WOS:000331962600015 PM 24165926 ER PT J AU Zulman, DM Asch, SM Martins, SB Kerr, EA Hoffman, BB Goldstein, MK AF Zulman, Donna M. Asch, Steven M. Martins, Susana B. Kerr, Eve A. Hoffman, Brian B. Goldstein, Mary K. TI Quality of Care for Patients with Multiple Chronic Conditions: The Role of Comorbidity Interrelatedness SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review ID HEALTH-CARE; DIABETES CARE; PRACTICE GUIDELINES; MEDICAL CONDITIONS; INTERNAL-MEDICINE; DECISION-MAKING; MENTAL-ILLNESS; CO-MORBIDITY; MULTIMORBIDITY; PERFORMANCE AB Multimorbidity-the presence of multiple chronic conditions in a patient-has a profound impact on health, health care utilization, and associated costs. Definitions of multimorbidity in clinical care and research have evolved over time, initially focusing on a patient's number of comorbidities and the associated magnitude of required care processes, and later recognizing the potential influence of comorbidity characteristics on patient care and outcomes. In this article, we review the relationship between multimorbidity and quality of care, and discuss how this relationship may be mediated by the degree to which conditions interact with one another to generate clinical complexity (comorbidity interrelatedness). Drawing on established theoretical frameworks from cognitive engineering and biomedical informatics, we describe how interactions among conditions result in clinical complexity and may affect quality of care. We discuss how this comorbidity interrelatedness influences the value of existing quality guidelines and performance metrics, and describe opportunities to quantify this construct using data widely available through electronic health records. Incorporating comorbidity interrelatedness into conceptualizations of multimorbidity has the potential to enhance clinical and research efforts that aim to improve care for patients with multiple chronic conditions. C1 [Zulman, Donna M.; Asch, Steven M.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Zulman, Donna M.; Asch, Steven M.] Stanford Univ, Dept Internal Med, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Martins, Susana B.; Goldstein, Mary K.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA USA. [Kerr, Eve A.] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA. [Kerr, Eve A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Hoffman, Brian B.] VA Boston Hlth Care Syst, West Roxbury Div, Boston, MA USA. [Hoffman, Brian B.] Harvard Univ, Sch Med, Boston, MA USA. [Goldstein, Mary K.] Stanford Univ, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. RP Zulman, DM (reprint author), Stanford Univ, VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Div Gen Med Disciplines, 795 Willow Rd 152-MPD, Menlo Pk, CA 94025 USA. EM dzulman@stanford.edu FU Department of Veterans Affairs Health Services Research and Development (HSRD) [IMV 04-062]; HSR&D Career Development Award [CDA 12-173] FX This study was supported in part by Department of Veterans Affairs Health Services Research and Development (HSR&D) grant IMV 04-062 (PI: Goldstein). Dr. Zulman is supported by a HSR&D Career Development Award (CDA 12-173). NR 68 TC 17 Z9 17 U1 1 U2 14 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 MAR PY 2014 VL 29 IS 3 BP 529 EP 537 DI 10.1007/s11606-013-2616-9 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB7II UT WOS:000331962600025 PM 24081443 ER PT J AU Robertson, J Landham, JB Estrada, CA AF Robertson, Jeffrey Landham, Jonathan B. Estrada, Carlos A. TI Splenic Infarcts Associated with Immune Reconstitution Inflammatory Syndrome SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE splenic infarction; immune reconstitution inflammatory syndrome; HIV infections/drug therapy; HIV infections/complications; inflammation; mycobacterium infections/etiology C1 [Robertson, Jeffrey] Tinsley Harrison Internal Med Residency Training, Birmingham, AL USA. [Robertson, Jeffrey; Landham, Jonathan B.; Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, 732 FOT,510 20th St South, Birmingham, AL 35294 USA. EM cestrada@uab.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2014 VL 29 IS 3 BP 541 EP 542 DI 10.1007/s11606-013-2599-6 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AB7II UT WOS:000331962600028 PM 24002634 ER PT J AU Palaia, JM McConnell, M Achenbach, JE Gustafson, CE Stoermer, KA Nolan, M Guay, LA Leitner, TK Matovu, F Taylor, AW Fowler, MG Janoff, EN AF Palaia, Jana M. McConnell, Michelle Achenbach, Jenna E. Gustafson, Claire E. Stoermer, Kristina A. Nolan, Monica Guay, Laura A. Leitner, Thomas K. Matovu, Flavia Taylor, Allan W. Fowler, Mary Glenn Janoff, Edward N. TI Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda SO JOURNAL OF INFECTION LA English DT Article DE Breast milk; HIV; Neutralization; IgG,IgA; Uganda; Subtype A; Subtype D; Mucosal immunity ID IMMUNODEFICIENCY-VIRUS TYPE-1; LACTATING RHESUS-MONKEYS; CELL-FREE HIV; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; SECRETORY IGA; TRANSMISSION; RESPONSES; INFANT; TRANSCYTOSIS AB Objectives: Among HIV-exposed infants in resource-limited countries, 8e12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIVinhibitory activity of breast milk. Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. Results: Milk inhibited p24 production by >= 50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n Z 5), not IgA, diminished neutralization (mean 78 +/- 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers. (C) 2013 Published by Elsevier Ltd on behalf of The British Infection Association. C1 [Palaia, Jana M.; Achenbach, Jenna E.; Gustafson, Claire E.; Stoermer, Kristina A.; Janoff, Edward N.] Univ Colorado, MAVRC, Aurora, CO 80045 USA. [Palaia, Jana M.; Gustafson, Claire E.; Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. [McConnell, Michelle; Nolan, Monica; Taylor, Allan W.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Guay, Laura A.; Matovu, Flavia; Fowler, Mary Glenn] Johns Hopkins Univ, Makerere Univ, Kampala, Uganda. [Leitner, Thomas K.] Los Alamos Natl Lab, Los Alamos, NM 87544 USA. RP Janoff, EN (reprint author), Univ Colorado Denver, MAVRC, Box B-168,12700 E 19th Ave, Aurora, CO 80045 USA. EM Edward.Janoff@ucdenver.edu FU NIH [R01-HD059527, R01-AI41361, R01 AI097265]; United States Centers for Disease Control; Elisabeth Glaser Pediatric AIDS Foundation (EGPAF) [MV00- 9-900-01432-0-00]; University of Colorado Denver's Office of Interdisciplinary Women's Health Research Grant; Mucosal and Vaccine Research Colorado Program (MAVRC); University of Colorado Cancer Center DNA Sequencing and Analysis Core [P30 CA046934] FX This work supported by NIH R01-HD059527, R01-AI41361, R01 AI097265, the United States Centers for Disease Control (CDC; " Pathobiology of Breast Milk among HIV-1 infected Ugandan women receiving intrapartum nevirapine" study), the Elisabeth Glaser Pediatric AIDS Foundation (EGPAF) MV00- 9-900-01432-0-00, University of Colorado Denver's Office of Interdisciplinary Women's Health Research Grant, the Mucosal and Vaccine Research Colorado Program (MAVRC) and the University of Colorado Cancer Center DNA Sequencing and Analysis Core (Grant # P30 CA046934). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the United States Centers for Disease Control and Prevention. We thank Jacinta Cooper for technical support and advice and the women in Kampala, Uganda for their participation. NR 52 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD MAR PY 2014 VL 68 IS 3 BP 264 EP 272 DI 10.1016/j.jinf.2013.11.002 PG 9 WC Infectious Diseases SC Infectious Diseases GA AB3TC UT WOS:000331712100008 PM 24239588 ER PT J AU Sulkowski, MS Kang, M Matining, R Wyles, D Johnson, VA Morse, GD Amorosa, V Bhattacharya, D Coughlin, K Wong-Staal, F Glesby, MJ AF Sulkowski, Mark S. Kang, Minhee Matining, Roy Wyles, David Johnson, Victoria A. Morse, Gene D. Amorosa, Valerianna Bhattacharya, Debika Coughlin, Kristine Wong-Staal, Flossie Glesby, Marshall J. CA AIDS Clinical Trials Grp A5277 TI Safety and Antiviral Activity of the HCV Entry Inhibitor ITX5061 in Treatment-Naive HCV-Infected Adults: A Randomized, Double-Blind, Phase 1b Study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 20th Conference on Retroviruses and Opportunistic Infections (CROI) CY MAR 03-06, 2013 CL Atlanta, GA DE HCV; SRB1; entry inhibitors ID C VIRUS-INFECTION; SCAVENGER RECEPTOR BI; HDL RECEPTOR; ITX 5061; SR-BI; HEPATITIS; IDENTIFICATION; ASSOCIATION AB Background. Hepatitis C virus (HCV) entry involves scavenger receptor B1 (SRB1). In vitro, SRB1 inhibition by ITX5061 impedes HCV replication. Methods. Multicenter study to assess safety/activity of ITX5061 in previously untreated, noncirrhotic, HCV genotype 1 infected adults. Design included sequential cohorts of 10 subjects with ITX5061 (n = 8) or placebo (n = 2) to escalate duration (3 to 14 to 28 days) or deescalate dose (150 to 75 to 25 mg) based on predefined criteria for safety and activity (>= 4 of 8 subjects with HCV RNA decline >= 1 log(10) IU/mL). Results. Thirty subjects enrolled in 3 cohorts: ITX5061 150 mg/day by mouth for 3 (A150), 14 (B150), and 28 (C150) days. Six subjects had grade >= 3 adverse events (one in placebo); none were treatment related. One of the 7 C150 subjects (14.3%, 95% confidence interval [CI], .7%-55.4%) had >= 1 log(10) IU/mL decline in HCV RNA (1.49 log(10) IU/mL), whereas none of the 6 placebo, 8 A150 or 8 B150 subjects showed such decline. Conclusions. Oral ITX5061 150 mg/day for up to 28 days was safe and well tolerated. In the 28-day cohort, 1 of 7 subjects showed antiviral activity; however, predefined criteria for antiviral activity were not met at the doses and durations studied. C1 [Sulkowski, Mark S.] Johns Hopkins Univ, Baltimore, MD USA. [Kang, Minhee; Matining, Roy] Harvard Univ, Boston, MA 02115 USA. [Wyles, David] Univ Calif San Diego, San Diego, CA 92103 USA. [Johnson, Victoria A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Johnson, Victoria A.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Morse, Gene D.] SUNY Buffalo, Buffalo, NY 14260 USA. [Amorosa, Valerianna] Univ Penn, Philadelphia, PA 19104 USA. [Bhattacharya, Debika] Univ Calif Los Angeles, Los Angeles, CA USA. [Coughlin, Kristine] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Wong-Staal, Flossie] iTherxPharma, San Diego, CA USA. [Glesby, Marshall J.] Weill Cornell Med Coll, New York, NY USA. RP Sulkowski, MS (reprint author), 1830 Bldg,Rm 445,600 North Wolfe St, Baltimore, MD 21287 USA. EM msulkowski@jhmi.edu FU NCATS NIH HHS [UL1 TR001079, UL1 TR000042, UL1 TR000124, UL1 TR000165, UL1TR000124, UL1TR00165]; NCRR NIH HHS [NIH UL1RR025005, UL1 RR 025005, UL1 RR024160, UL1 RR025005]; NIAID NIH HHS [5-P30-AI-045008-15, 5UM1-AI069484-07, 5UM1AI069415-07, 5UO1 AI069502, AI-069467-07, AI-069513, AI69432, AI69465, K24 AI078884, P30 AI027767, P30 AI045008, U01 AI068636, U01 AI069432, U01 AI069452, U01 AI069465, U01 AI069467, U01 AI069502, U01 AI069513, U01AI068636, U01AI069452, UAB CFAR P30AI27767-24, UM1 AI068634, UM1 AI068636, UM1 AI069415, UM1 AI069419, UM1 AI069424, UM1 AI069432, UM1 AI069465, UM1 AI069467, UM1 AI069484, UM1 AI069511, UM1 AI069513, UM1 AI106701, UMI AI069511]; NIDA NIH HHS [K24 DA000432, K24 DA034621, K24DA00432, R01 DA016065]; PHS HHS [NIH/NIAID 7UM1AI068636] NR 23 TC 23 Z9 27 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 MAR 1 PY 2014 VL 209 IS 5 BP 658 EP 667 DI 10.1093/infdis/jit503 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AB6BY UT WOS:000331873700006 PM 24041792 ER PT J AU Yuen, GJ Ausubel, FM AF Yuen, Grace J. Ausubel, Frederick M. TI Enterococcus Infection Biology: Lessons from Invertebrate Host Models SO JOURNAL OF MICROBIOLOGY LA English DT Review DE Enterococcus; innate immunity; Caenorhabditis elegans; Galleria mellonella ID BIOSYNTHESIS-ACTIVATING PHEROMONE; GRAM-POSITIVE BACTERIA; GROUP-D STREPTOCOCCI; CYCLIC-DI-GMP; CAENORHABDITIS-ELEGANS; VIRULENCE FACTORS; BIOFILM FORMATION; DROSOPHILA-MELANOGASTER; GALLERIA-MELLONELLA; TRANSLATIONAL INHIBITION AB The enterococci are commensals of the gastrointestinal tract of many metazoans, from insects to humans. While they normally do not cause disease in the intestine, they can become pathogenic when they infect sites outside of the gut. Recently, the enterococci have become important nosocomial pathogens, with the majority of human enterococcal infections caused by two species, Enterococcus faecalis and Enterococcus faecium. Studies using invertebrate infection models have revealed insights into the biology of enterococcal infections, as well as general principles underlying host innate immune defense. This review highlights recent findings on Enterococcus infection biology from two invertebrate infection models, the greater wax moth Galleria mellonella and the free-living bacteriovorous nematode Caenorhabditis elegans. C1 [Yuen, Grace J.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Yuen, Grace J.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NIAID NIH HHS [P01 AI083214] NR 115 TC 4 Z9 4 U1 5 U2 31 PU MICROBIOLOGICAL SOCIETY KOREA PI SEOUL PA KOREA SCIENCE & TECHNOLOGY CENTER 803, 635-4 YEOGSAM-DONG, KANGNAM-KU, SEOUL 135-703, SOUTH KOREA SN 1225-8873 EI 1976-3794 J9 J MICROBIOL JI J. Microbiol. PD MAR PY 2014 VL 52 IS 3 BP 200 EP 210 DI 10.1007/s12275-014-4011-6 PG 11 WC Microbiology SC Microbiology GA AB8OK UT WOS:000332049700003 PM 24585051 ER PT J AU Narayanan, KL Subramaniam, S Bengston, CP Irmady, K Unsicker, K von Bohlen, O Halbach AF Narayanan, K. Lakshmi Subramaniam, Srinivasa Bengston, C. Peter Irmady, Krithi Unsicker, Klaus von Bohlen, Oliver Halbach TI Role of Transient Receptor Potential Channel 1 (TRPC1) in Glutamate-Induced Cell Death in the Hippocampal Cell Line HT22 SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE TRPC1; HT22 cells; Glutamate; Cell death ID MGLUR5 ANTAGONISTS MPEP; OXIDATIVE STRESS; NEURONAL DEATH; GLUTATHIONE DEPLETION; IN-VITRO; ACTIVATION; APOPTOSIS; TOXICITY; CALCIUM; EXCITOTOXICITY AB Transient receptor potential channel 1 (TRPC1; a cation channel activated by store depletion and/or through an intracellular messenger) is expressed in a variety of tissues, including the brain. To study the physiological function of TRPC1, we investigated the role of endogenously expressed TRPC1 in glutamate-induced cell death, using the murine hippocampal cell line HT22. Knocking down TRPC1 mRNA using TRPC1-shRNA or blocking of TRPC channels using 2-APB (a parts per thousand yen200 mu M) robustly attenuated glutamate-induced cell death after 24 h of incubation with 5 mM glutamate. Glutamate toxicity in HT22 cells seems to involve metabotropic glutamate receptor mGluR5 since MPEP (2-methyl-6-(phenylethynyl)-pyridine), an mGluR5 antagonist (a parts per thousand yen100 mu M), abrogated glutamate toxicity. Furthermore, a direct activation of mGluR5 by CHPG [(RS)-chloro-5-hydroxyphenylglycine; 100 mu M or 300 mu M] promoted HT22 cell death. TRPC1 knock-down markedly reduced CHPG-induced cell death. These observations suggest that glutamate-induced cell death in HT22 cells activates mGluR5 receptors, which significantly increases Ca2+ influx through TRPC1 channels. TRPC1 knock-down prevented glutamate- and CHPG-induced cell death, suggesting that glutamate-induced toxicity in HT22 cells is mediated through TRPC1 channels and an mGluR5-dependent pathway. Together, this work provides evidence for a novel receptor activation pathway of TRPC1 in glutamate-induced toxicity. C1 [Narayanan, K. Lakshmi] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Charlestown, MA 02129 USA. [Unsicker, Klaus] Univ Freiburg, Dept Mol Embryol, Inst Anat & Cell Biol, D-79104 Freiburg, Germany. [Subramaniam, Srinivasa] Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA. [Bengston, C. Peter] Heidelberg Univ, Dept Neurobiol, Interdisciplinary Ctr Neurosci IZN, D-69120 Heidelberg, Germany. [Irmady, Krithi] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10065 USA. [von Bohlen, Oliver; Halbach] Univ Med Greifswald, Inst Anat & Cell Biol, D-17487 Greifswald, Germany. RP Halbach (reprint author), Univ Med Greifswald, Inst Anat & Cell Biol, D-17487 Greifswald, Germany. EM oliver.vonbohlen@uni-greifswald.de RI von Bohlen und Halbach, Oliver/A-1060-2008; OI Oliver, von Bohlen und Halbach/0000-0002-2613-2517 FU German Research Foundation [SFB636/A5] FX We wish to thank H. Bading for his indispensable help for this project. We also want to thank Alexei Egorov for providing reagents and Jutta Fey for technical assistance in cell culture. This study was supported by a grant from the German Research Foundation (SFB636/A5). NR 38 TC 2 Z9 2 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD MAR PY 2014 VL 52 IS 3 BP 425 EP 433 DI 10.1007/s12031-013-0171-9 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AB3OI UT WOS:000331699700013 PM 24242951 ER PT J AU Cahill, JE Gilbert, MR Armstrong, TS AF Cahill, Jennifer E. Gilbert, Mark R. Armstrong, Terri S. TI Personal health records as portal to the electronic medical record SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE Electronic medical records; Patient access; Personal health records; Brain tumors ID CANCER-PATIENTS; PATIENT ACCESS; COMMUNICATION; INFORMATION; EXPERIENCES; PREFERENCES; CONCOMITANT; PROGNOSIS; ADULTS; CARE AB This topic review discusses the evolving clinical challenges associated with the implementation of electronic personal health records (PHR) that are fully integrated with electronic medical records (EMR). The benefits of facilitating patient access to the EMR through web-based, PHR-portals may be substantial; foremost is the potential to enhance the flow of information between patient and healthcare practitioner. The benefits of improved communication and transparency of care are presumed to be a reduction in clinical errors, increased quality of care, better patient-management of disease, and better disease and symptom comprehension. Yet PHR databases allow patients open access to newly-acquired clinical data without the benefit of concurrent expert clinical interpretation, and therefore may create the potential for greater patient distress and uncertainty. With specific attention to neuro-oncology patients, this review focuses on the developing conflicts and consequences associated with the use of a PHR that parallels data acquisition of the EMR in real-time. We conclude with a discussion of recommendations for implementing fully-integrated PHR for neuro-oncology patients. C1 [Cahill, Jennifer E.; Armstrong, Terri S.] Univ Texas Houston, Sch Nursing, Dept Family Hlth, Houston, TX 77030 USA. [Cahill, Jennifer E.] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. [Gilbert, Mark R.; Armstrong, Terri S.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Cahill, JE (reprint author), Univ Texas Houston, Sch Nursing, Dept Family Hlth, 6901 Bertner Ave, Houston, TX 77030 USA. EM jecahill@partners.org RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 23 TC 9 Z9 9 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAR PY 2014 VL 117 IS 1 BP 1 EP 6 DI 10.1007/s11060-013-1333-x PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AB7JB UT WOS:000331964600001 PM 24477621 ER PT J AU Gupta, A Ly, S Castroneves, LA Frates, MC Benson, CB Feldman, HA Wassner, AJ Smith, JR Marqusee, E Alexander, EK Barletta, J Muyide, F Doubilet, PM Peters, HE Webb, S Modi, BP Paltiel, HJ Martins, Y Burmeister, K Kozakewich, H Hollowell, M Cibas, ES Moore, FD Shamberger, RC Larsen, PR Huang, SA AF Gupta, Anjuli Ly, Samantha Castroneves, Luciana A. Frates, Mary C. Benson, Carol B. Feldman, Henry A. Wassner, Ari J. Smith, Jessica R. Marqusee, Ellen Alexander, Erik K. Barletta, Justine Muyide, Funmilayo Doubilet, Peter M. Peters, Hope E. Webb, Susan Modi, Biren P. Paltiel, Harriet J. Martins, Yolanda Burmeister, Kelly Kozakewich, Harry Hollowell, Monica Cibas, Edmund S. Moore, Francis D., Jr. Shamberger, Robert C. Larsen, P. Reed Huang, Stephen A. TI How Are Childhood Thyroid Nodules Discovered: Opportunities for Improving Early Detection SO JOURNAL OF PEDIATRICS LA English DT Article ID CHILDREN; CANCER; MANAGEMENT AB In a retrospective analysis of childhood thyroid nodules, 18% were radiographic incidentalomas and 41% were discovered by a clinician's palpation; 40% were discovered by patients' families. The latter group had the largest nodules and highest rates of thyroid cancer metastasis, suggesting opportunities for earlier detection through annual well-child visits. C1 [Gupta, Anjuli; Ly, Samantha; Castroneves, Luciana A.; Feldman, Henry A.; Wassner, Ari J.; Smith, Jessica R.; Muyide, Funmilayo; Webb, Susan; Huang, Stephen A.] Childrens Hosp Boston, Thyroid Program, Div Endocrinol, Boston, MA 02115 USA. [Paltiel, Harriet J.] Childrens Hosp Boston, Dept Radiol, Boston, MA 02115 USA. [Kozakewich, Harry; Hollowell, Monica] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Martins, Yolanda; Burmeister, Kelly] Childrens Hosp Boston, Clin Res Program, Boston, MA 02115 USA. [Modi, Biren P.; Shamberger, Robert C.] Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. [Wassner, Ari J.; Smith, Jessica R.; Marqusee, Ellen; Alexander, Erik K.; Larsen, P. Reed; Huang, Stephen A.] Brigham & Womens Hosp, Thyroid Sect, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Frates, Mary C.; Benson, Carol B.; Doubilet, Peter M.; Peters, Hope E.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Barletta, Justine; Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Moore, Francis D., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Marqusee, Ellen; Alexander, Erik K.; Martins, Yolanda; Larsen, P. Reed; Huang, Stephen A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Huang, SA (reprint author), Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM stephen.huang@childrens.harvard.edu OI Martins, Yolanda/0000-0002-3983-3531; Wassner, Ari/0000-0003-0894-9301 FU Harvard Catalyst, The Harvard Clinical and Translational Science Center [National Center for Research Resources]; National Center for Advancing Translational Sciences, National Institutes of Health [8UL1TR000170-05]; Harvard University and its affiliated academic health care centers FX We are indebted to the patients and families evaluated in this series and to Christian Botte, MD (supported by the Harvard Catalyst, The Harvard Clinical and Translational Science Center [National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health 8UL1TR000170-05], and financial contributions from Harvard University and its affiliated academic health care centers) for his expertise and assistance in REDCap database design. NR 7 TC 4 Z9 4 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2014 VL 164 IS 3 BP 658 EP 660 DI 10.1016/j.jpeds.2013.10.090 PG 3 WC Pediatrics SC Pediatrics GA AB1GI UT WOS:000331539100045 PM 24345455 ER PT J AU Clark-Cutaia, MN Ren, DX Hoffman, LA Burke, LE Sevick, MA AF Clark-Cutaia, Maya N. Ren, Dianxu Hoffman, Leslie A. Burke, Lora E. Sevick, Mary Ann TI Adherence to Hemodialysis Dietary Sodium Recommendations: Influence of Patient Characteristics, Self-Efficacy, and Perceived Barriers SO JOURNAL OF RENAL NUTRITION LA English DT Article ID STAGE RENAL-DISEASE; PATIENTS RECEIVING HEMODIALYSIS; MEDICATION ADHERENCE; SOCIOECONOMIC-STATUS; PRACTICE PATTERNS; HEALTH BELIEFS; BLOOD-PRESSURE; OLDER-ADULTS; NONADHERENCE; RESTRICTIONS AB Objective: To identify characteristics of hemodialysis patients most likely to experience difficulty adhering to sodium restrictions associated with their dietary regimen. Design: Secondary analysis using baseline data from an ongoing randomized clinical trial examining the effects of a technology-supported behavioral intervention on dietary sodium intake in hemodialysis patients. Setting: Thirteen dialysis centers in southwestern Pennsylvania. Subjects: We included 122 participants (61% women; 48% African American) aged 61 +/- 14 years undergoing maintenance, intermittent hemodialysis for end-stage renal disease. Main Outcome Measures: Normalized dietary sodium intake, adjusted interdialytic weight gain, perceived problems, and self-efficacy for restricting dietary sodium. Results: Younger participants were more likely to report problems managing their hemodialysis diet and low self-efficacy for restricting sodium intake. Consistent with these findings, younger participants had a higher median sodium intake and higher average adjusted interdialytic weight gain. Females reported more problems managing their diet. Race, time on dialysis, and perceived income adequacy did not seem to influence outcome measures. Conclusion: Our findings suggest that patients who are younger and female encounter more difficulty adhering to the hemodialysis regimen. Hence, there may be a need to individualize counseling and interventions for these individuals. Further investigation is needed to understand the independent effects of age and gender on adherence to hemodialysis dietary recommendations and perceived self-fficacy. (C) 2014 by the National Kidney Foundation, Inc. All rights reserved. C1 [Clark-Cutaia, Maya N.] Univ Penn, Ctr Hlth Equity Res, Philadelphia, PA 19104 USA. [Clark-Cutaia, Maya N.] Univ Penn, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Ren, Dianxu; Burke, Lora E.] Univ Pittsburgh, Dept Hlth & Community Syst, Pittsburgh, PA USA. [Hoffman, Leslie A.] Univ Pittsburgh, Pittsburgh, PA USA. [Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sevick, Mary Ann] Univ Pittsburgh, Nursing Ctr Res Hlth Care, Pittsburgh, PA USA. RP Clark-Cutaia, MN (reprint author), Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA. EM mayan@nursing.upenn.edu FU [NIH-R01-NR010135]; [NIH-K24-NR012226]; [NIH 1F31NR013410] FX Study was supported by grants NIH-R01-NR010135, NIH-K24-NR012226 for MAS, and NIH 1F31NR013410 for MNC. The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. NR 42 TC 10 Z9 11 U1 8 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD MAR PY 2014 VL 24 IS 2 BP 92 EP 99 DI 10.1053/j.jrn.2013.11.007 PG 8 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA AB5FS UT WOS:000331814900007 PM 24462498 ER PT J AU Fallon, EM Nehra, D Carlson, SJ Brown, DW Nedder, AP Rueda, BR Puder, M AF Fallon, Erica M. Nehra, Deepika Carlson, Sarah J. Brown, David W. Nedder, Arthur P. Rueda, Bo R. Puder, Mark TI Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Sunitinib; Sutent; Adhesions; Anastomosis; Bursting strength; Cardiotoxicity; Echocardiogram; Hepatotoxicity; Rabbit; Safety ID TYROSINE KINASE INHIBITOR; EXPERIMENTAL INTESTINAL ANASTOMOSES; HEART-FAILURE; CELL-CARCINOMA; LARGE-BOWEL; MODEL; CARDIOTOXICITY; ADHESIONS; RESECTION; THERAPY AB Background: Sunitinib (Sutent) is a Food and Drug Administration-approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits. Materials and methods: Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated. Results: All animals survived until designated euthanasia. There was no evidence of intraabdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal. Conclusions: These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal. (C) 2014 Elsevier Inc. All rights reserved. C1 [Fallon, Erica M.; Nehra, Deepika; Carlson, Sarah J.; Puder, Mark] Boston Childrens Hosp, Dept Surg, Boston, MA 02115 USA. [Fallon, Erica M.; Nehra, Deepika; Carlson, Sarah J.; Puder, Mark] Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Fallon, Erica M.; Nehra, Deepika; Carlson, Sarah J.; Brown, David W.; Rueda, Bo R.; Puder, Mark] Harvard Univ, Sch Med, Boston, MA USA. [Brown, David W.] Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Nedder, Arthur P.] Anim Resources Childrens Hosp, Boston, MA USA. [Rueda, Bo R.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Puder, M (reprint author), Boston Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 3, Boston, MA 02115 USA. EM mark.puder@tch.harvard.edu FU Department of Defense [W81XWH-05-1-0115]; Children's Hospital Surgical Foundation; Vascular Biology Program, Boston, MA; Joshua Ryan Rappaport Fellowship, Boston, MA; National Institutes of Health [T32DK007754-12] FX This work was funded by a Congressionally Funded Project entitled "Angiogenesis and Tissue Engineering Research," Department of Defense, grant #W81XWH-05-1-0115; the Children's Hospital Surgical Foundation and The Vascular Biology Program, Boston, MA (E.M.F, D.N., S.J.C., M. P.); the Joshua Ryan Rappaport Fellowship, Boston, MA (E.M.F.); and the National Institutes of Health grant #T32DK007754-12 (D.N.). The authors would like to thank the veterinary staff at the large animal facility with special thanks to Kathryn Mullen in addition to the chemotherapy pharmacy at Boston Children's Hospital for their dedication and invaluable assistance with the study. NR 25 TC 2 Z9 2 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2014 VL 187 IS 1 BP 101 EP 106 DI 10.1016/j.jss.2013.10.016 PG 6 WC Surgery SC Surgery GA AB2FB UT WOS:000331607500016 PM 24189178 ER PT J AU Okon, L Rosenbach, M Krathen, M Rose, M Propert, K Okawa, J Werth, V AF Okon, Lauren Rosenbach, Misha Krathen, Michael Rose, Mathew Propert, Kathleen Okawa, Joyce Werth, Victoria TI Lenalidomide in treatment-refractory cutaneous lupus erythematosus: Efficacy and safety in a 52-week trial SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID THERAPY; LESIONS; RISK C1 [Okon, Lauren; Rosenbach, Misha; Krathen, Michael; Rose, Mathew; Okawa, Joyce; Werth, Victoria] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Okon, Lauren; Rosenbach, Misha; Krathen, Michael; Rose, Mathew; Okawa, Joyce; Werth, Victoria] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Propert, Kathleen] Univ Penn, Perelman Sch Med, Dept Biostat, HUP, Philadelphia, PA 19104 USA. RP Werth, V (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207, K24 AR002207] NR 5 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2014 VL 70 IS 3 BP 583 EP 584 DI 10.1016/j.jaad.2013.11.007 PG 2 WC Dermatology SC Dermatology GA AB2FA UT WOS:000331607400035 PM 24528907 ER PT J AU Jacobs, LM Wade, D McSwain, NE Butler, FK Fabbri, W Eastman, A Conn, A Burns, KJ AF Jacobs, Lenworth M. Wade, David McSwain, Norman E. Butler, Frank K. Fabbri, William Eastman, Alexander Conn, Alasdair Burns, Karyl J. TI Hartford Consensus: A Call to Action for THREAT, a Medical Disaster Preparedness Concept SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID COMBAT CASUALTY CARE; MAJOR LIMB TRAUMA; BATTLEFIELD; DEATH; INJURY; SWINE; MODEL C1 [Jacobs, Lenworth M.; Burns, Karyl J.] Univ Connecticut, Hartford Hosp, Hartford, CT 06112 USA. [Wade, David; Fabbri, William] Fed Bur Invest, Washington, DC USA. [Butler, Frank K.] Joint Trauma Syst, Comm Tact Combat Casualty Care, Dept Def, Washington, DC USA. [McSwain, Norman E.] Tulane Univ, Dept Surg, New Orleans, LA 70118 USA. [Eastman, Alexander] UT Southwestern Med Ctr, Dallas Police Dept, Dallas, TX USA. [Conn, Alasdair] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacobs, LM (reprint author), Hartford Hosp, 80 Seymour St, Ishikari, Hokkaido 06102, Japan. EM lenworth.jacobs@hhchealth.org NR 47 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2014 VL 218 IS 3 BP 467 EP 475 DI 10.1016/j.jamcollsurg.2013.12.009 PG 9 WC Surgery SC Surgery GA AB3VN UT WOS:000331718400023 PM 24559957 ER PT J AU Swanson, SJ Miller, DL McKenna, RJ Howington, J Marshall, MB Yoo, AC Moore, M Gunnarsson, CL Meyers, BF AF Swanson, Scott J. Miller, Daniel L. McKenna, Robert Joseph, Jr. Howington, John Marshall, M. Blair Yoo, Andrew C. Moore, Matthew Gunnarsson, Candace L. Meyers, Bryan F. TI Comparing robot-assisted thoracic surgical lobectomy with conventional video-assisted thoracic surgical lobectomy and wedge resection: Results from a multihospital database (Premier) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CELL LUNG-CANCER; SURGERY LOBECTOMY; OPEN THORACOTOMY; EXPERIENCE; OUTCOMES; TRIALS AB Background: Video-assisted thoracic surgical (VATS) lobectomies and wedge resections result in less morbidity and shorter length of stay than resections via thoracotomy. The impact of robot-assisted thoracic surgical (RATS) lobectomy on clinical and economic outcomes has not been examined. This study compared hospital costs and clinical outcomes for VATS lobectomies and wedge resections versus RATS. Methods: Using the Premier hospital database, patients aged >= 18 years with a record of thoracoscopic lobectomy, segmental resection, or excision of a lesion or tissue from the lung between 2009 and 2011 were identified. Procedures using robotic technology were identified if 1 of 2 conditions were met: (1) a robotic International Classification of Diseases, Ninth Revision procedure code or (2) the text fields in the hospital record indicated that the robot was used. Using a propensity score and based on severity and comorbidities, certain demographics and hospital characteristics were matched. The association between VATS or RATS and adverse events, hospital costs, surgery time, and length of stay was examined. Results: Of 15,502 patient records analyzed, 96% (n = 14,837) were performed without robotic assistance. Using robotic assistance was associated with higher average hospital costs per patient. The average cost of inpatient procedures with RATS was $ 25,040.70 versus $ 20,476.60 for VATS (P =.0001) for lobectomies and $ 19,592.40 versus $ 16,600.10 (P -.0001) for wedge resections, respectively. Inpatient operating times were longer for RATS lobectomy than VATS lobectomy (4.49 hours vs 4.23 hours; P =.0959) and wedge resection (3.26 vs 2.86 hours; P =.0003). Length of stay was similar with no differences in adverse events. Conclusions: RATS lobectomy and wedge resection seem to have higher hospital costs and longer operating times, without any differences in adverse events. C1 [Swanson, Scott J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Minimally Invas Thorac, Boston, MA 02115 USA. [Miller, Daniel L.] Emory Univ Healthcare, Div Thorac Surg, Atlanta, GA USA. [McKenna, Robert Joseph, Jr.] Cedars Sinai Med Ctr, Div Thorac Surg, Los Angeles, CA 90048 USA. [Howington, John] NorthShore Univ Hlth Syst, Div Thorac Surg & Surg Qual, Evanston, IL USA. [Marshall, M. Blair] Georgetown Univ, Med Ctr, Div Thorac Surg, Washington, DC 20007 USA. [Yoo, Andrew C.] Ethicon Endosurg Inc, Cincinnati, OH USA. [Moore, Matthew] Ethicon Endosurg, Healthcare Policy & Econ, Cincinnati, OH USA. [Gunnarsson, Candace L.] S2 Stat Solut Inc, Cincinnati, OH USA. [Meyers, Bryan F.] Washington Univ, Div Cardiothorac Surg, St Louis, MO USA. RP Gunnarsson, CL (reprint author), 11176 Main St, Cincinnati, OH 45241 USA. EM candaceg@s2stats.com FU Ethicon Endo-Surgery; Varian FX John Howington reports consulting fees from Ethicon Endo-Surgery. M. Blair Marshall reports consulting fees from Thoracic Surgery Clinics, Clinical Key, and Ethicon. Andrew C. Yoo is a full-time employee of Ethicon Endo-Surgery and reports equity ownership in Johnson and Johnson. Matthew Moore was a full-time employee of Ethicon Endo-Surgery at the time this research was completed. Candace L. Gunnarsson reports consulting fees from Ethicon Endo- Surgery. Bryan F. Meyers reports consulting fees from Ethicon Endo-Surgery and lecture fees from Varian. All other authors have nothing to disclose with regard to commercial support. NR 16 TC 35 Z9 38 U1 0 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2014 VL 147 IS 3 BP 929 EP 937 DI 10.1016/j.jtcvs.2013.09.046 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AB1MF UT WOS:000331555300030 PM 24210834 ER PT J AU Stock, C Gukasyan, N Muniappan, A Wright, C Mathisen, D AF Stock, Cameron Gukasyan, Natalie Muniappan, Ashok Wright, Cameron Mathisen, Douglas TI Hyperbaric oxygen therapy for the treatment of anastomotic complications after tracheal resection and reconstruction SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID DIABETIC FOOT ULCERS; LARYNGOTRACHEAL RESECTION; STENOSIS; RATS AB Objective: Failure of anastomotic healing is a rare but serious complication of laryngotracheal resection. Treatment options include reoperation, tracheostomy, or T-tube placement. Hyperbaric oxygen therapy (HBOT) is the delivery of 100% O-2 at pressures greater than 1 atm, and has been shown to enhance wound healing after tracheal resection in animal models. To date, there have been no reports describing its usefulness in humans after tracheal resection. Methods: Five consecutive patients with varying degrees of failed anastomotic healing, from necrotic cartilage to partial separation identified by bronchoscopy were treated with HBOT. HBOT was administered for 90 minutes via a hyperbaric chamber pressurized to 2 atm with 100% oxygen. Patients were treated with daily or twice daily HBOT. Four of 5 patients had buttressing of the anastomosis by strap muscle at the initial surgery. Results: All patients had evidence of anastomotic healing on bronchoscopy. None of the patients in this series required tracheostomy, T-tube, or reoperation after initiation of HBOT. On average it took 9.6 days for healing to occur (5-14 days). The size of the anastomotic defect ranged between 3 and 13 mm. One patient required bilateral tympanostomy tubes for inner ear discomfort and experienced blurry vision as complications of HBOT. One patient developed tracheal stenosis from granulation tissue that required bronchoscopic debridement. Conclusions: In select patients with anastomotic complications after tracheal resection, HBOT may aid in healing and avoid tracheostomy. Future investigations are necessary to further define the benefits of HBOT in the management of airway anastomotic complications. C1 [Stock, Cameron; Gukasyan, Natalie; Muniappan, Ashok; Wright, Cameron; Mathisen, Douglas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA USA. RP Mathisen, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA 02115 USA. EM dmathisen@partners.org NR 16 TC 10 Z9 10 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2014 VL 147 IS 3 BP 1030 EP 1035 DI 10.1016/j.jtcvs.2013.11.014 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AB1MF UT WOS:000331555300049 PM 24342903 ER PT J AU Fathi, AT Chen, YB AF Fathi, Amir T. Chen, Yi-Bin TI CD30: a new target for ALL? SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID BRENTUXIMAB VEDOTIN SGN-35; PHASE-II; EXPRESSION; RECEPTOR; LYMPHOMA C1 [Fathi, Amir T.; Chen, Yi-Bin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Fathi, AT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org NR 11 TC 1 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2014 VL 55 IS 3 BP 478 EP 479 DI 10.3109/10428194.2013.823496 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA AB5ZB UT WOS:000331866100004 PM 23837494 ER PT J AU Raiser, DM Narla, A Ebert, BL AF Raiser, David M. Narla, Anupama Ebert, Benjamin L. TI The emerging importance of ribosomal dysfunction in the pathogenesis of hematologic disorders SO LEUKEMIA & LYMPHOMA LA English DT Review DE Ribosomies; p53 pathway; Diamond-Blackfan anemia; myelodysplastic syndrome; hematologic malignancies ID DIAMOND-BLACKFAN ANEMIA; CARTILAGE-HAIR HYPOPLASIA; MESSENGER-RNA TRANSLATION; PROTEIN S19 DEFICIENCY; TREACHER-COLLINS-SYNDROME; ACUTE MYELOID-LEUKEMIA; BONE-MARROW FAILURE; L-LEUCINE IMPROVES; DYSKERATOSIS-CONGENITA; MYELODYSPLASTIC SYNDROME AB More than a decade has passed since the initial identification of ribosomal protein gene mutations in patients with Diamond-Blackfan anemia (DBA), a hematologic disorder that became the founding member of a class of diseases known as ribosomopathies. In these diseases, genetic abnormalities that result in defective ribosome biogenesis cause strikingly tissue-specific phenotypes in patients, specifically bone marrow failure, craniofacial abnormalities and skeletal defects. Several animal models and numerous in vitro studies have demonstrated that the p53 pathway is central to the ribosomopathy phenotype. Additionally, there is mounting evidence of a link between the dysregulation of components of the translational machinery and the pathology of various malignancies. The importance of the role of ribosomal dysfunction in the pathogenesis of hematologic disorders is becoming clearer, and elucidation of the underlying mechanisms could have broad implications for both basic cellular biology and clinical intervention strategies. C1 [Raiser, David M.; Narla, Anupama; Ebert, Benjamin L.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Narla, Anupama; Ebert, Benjamin L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Narla, Anupama] Childrens Hosp, Boston, MA 02115 USA. RP Ebert, BL (reprint author), Karp Family Res Labs, 5-211,1 Blackfan Circle, Boston, MA 02115 USA. EM Benjamin_Ebert@dfci.harvard.edu FU NIH [R01 HL082945, P01 CA108631]; Leukemia and Lymphoma Society; Burroughs-Wellcome Fund FX This work was funded by the NIH (grants R01 HL082945 and P01 CA108631), the Leukemia and Lymphoma Society and the Burroughs-Wellcome Fund. NR 141 TC 17 Z9 17 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2014 VL 55 IS 3 BP 491 EP 500 DI 10.3109/10428194.2013.812786 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA AB5ZB UT WOS:000331866100007 PM 23863123 ER PT J AU Soumerai, JD Hellmann, MD Feng, Y Sohani, AR Toomey, CE Barnes, JA Takvorian, RW Neuberg, D Hochberg, EP Abramson, JS AF Soumerai, Jacob D. Hellmann, Matthew D. Feng, Yang Sohani, Aliyah R. Toomey, Christiana E. Barnes, Jeffrey A. Takvorian, Ronald W. Neuberg, Donna Hochberg, Ephraim P. Abramson, Jeremy S. TI Treatment of primary mediastinal B-cell lymphoma with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone is associated with a high rate of primary refractory disease SO LEUKEMIA & LYMPHOMA LA English DT Article DE Diffuse large B-cell lymphoma; DLBCL; non-Hodgkin lymphoma; PMBCL; primary mediastinal B-cell lymphoma; R-CHOP ID CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; CHOP-LIKE CHEMOTHERAPY; HODGKIN LYMPHOMA; ELDERLY-PATIENTS; MULTICENTER; EXPERIENCE; FEATURES; THERAPY AB The optimal therapy for primary mediastinal B-cell lymphoma is a subject of ongoing debate, with no accepted standard of care. We performed a retrospective analysis of 63 patients in the modern era treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), with or without radiation. Median age was 37 years (range 20 -82). Eighty percent had limited stage disease and 71% were bulky. By age-adjusted International Prognostic Index (IPI), 15% were low-risk, 52% low-intermediate, 27% high-intermediate and 6% high-risk. Some 77% of responding patients received consolidative radiotherapy. Overall and complete response rates were 79% and 71%. Primary induction failure occurred in 13 (21%) patients. Five-year PFS and OS were 68% and 79%, respectively. Adverse prognostic features included increased IPI, advanced stage, advanced age and multiple extranodal sites. These data demonstrate an unacceptably high rate of primary refractory disease on R-CHOP, particularly among patients with high-risk features. Novel treatment approaches are needed that reduce primary refractory disease and reliance on mediastinal radiation in young people. C1 [Soumerai, Jacob D.; Hellmann, Matthew D.; Toomey, Christiana E.; Barnes, Jeffrey A.; Takvorian, Ronald W.; Hochberg, Ephraim P.; Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA 02114 USA. [Soumerai, Jacob D.; Hellmann, Matthew D.; Sohani, Aliyah R.; Barnes, Jeffrey A.; Takvorian, Ronald W.; Hochberg, Ephraim P.; Abramson, Jeremy S.] Harvard Univ, Sch Med, Boston, MA USA. [Feng, Yang; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, 55 Fruit St,Yawkey 9A, Boston, MA 02114 USA. EM jabramson@partners.org NR 23 TC 21 Z9 21 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2014 VL 55 IS 3 BP 538 EP 543 DI 10.3109/10428194.2013.810738 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA AB5ZB UT WOS:000331866100014 PM 23734654 ER PT J AU Verstovsek, S Tam, CS Wadleigh, M Sokol, L Smith, CC Bui, LA Song, CY Clary, DO Olszynski, P Cortes, J Kantarjian, H Shah, NP AF Verstovsek, Srdan Tam, Constantine S. Wadleigh, Martha Sokol, Lubomir Smith, Catherine C. Bui, Lynne A. Song, Chunyan Clary, Douglas O. Olszynski, Patrycja Cortes, Jorge Kantarjian, Hagop Shah, Neil P. TI Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor SO LEUKEMIA RESEARCH LA English DT Article DE Myelofibrosis; JAK2; XL019; Mutation; Inhibitor ID AGNOGENIC MYELOID METAPLASIA; MYELOPROLIFERATIVE NEOPLASMS; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; BLAST PHASE; MYELOFIBROSIS; RUXOLITINIB; MANAGEMENT; EFFICACY; MUTATION AB This phase I study evaluated selective JAK2 inhibitor XL019 in 30 patients with myelofibrosis. The initial dose cohorts were 100, 200, and 300 mg orally on days 1-21 of a 28-day cycle. Central and/or peripheral neurotoxicity developed in all patients. Subsequently, patients were treated on lower doses; neurotoxicity was again observed, leading to study termination. Peripheral neuropathy resolved in 50%, and central neurotoxicity in all patients within months after therapy cessation. Myelosuppression was minimal. The terminal half-life of XL019 was approximately 21 h, with steady state reached by Day 8. International Working Group defined responses were seen in three (10%) patients. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Verstovsek, Srdan; Tam, Constantine S.; Cortes, Jorge; Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sokol, Lubomir] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Smith, Catherine C.; Olszynski, Patrycja; Shah, Neil P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Bui, Lynne A.; Song, Chunyan; Clary, Douglas O.] Exelixis Inc, San Francisco, CA USA. RP Verstovsek, S (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA. EM sverstov@mdanderson.org FU Leukemia & Lymphoma Society; UCSF T-32 Molecular Mechanisms of Cancer grant; MD Anderson Cancer Center Support Grant [CA016672]; Art and Alison Kern FX This work was supported by funding from the Leukemia & Lymphoma Society (to CCS and NPS), the UCSF T-32 Molecular Mechanisms of Cancer grant (to CCS), the MD Anderson Cancer Center Support Grant CA016672, and Art and Alison Kern. NR 29 TC 18 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAR PY 2014 VL 38 IS 3 BP 316 EP 322 DI 10.1016/j.leukres.2013.12.006 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA AB3WV UT WOS:000331721800013 PM 24374145 ER PT J AU Benedek, G Zhu, WB Libal, N Casper, A Yu, XL Meza-Romero, R Vandenbark, A Alkayed, N Offner, H AF Benedek, Gil Zhu, Wenbin Libal, Nicole Casper, Amanda Yu, Xiaolin Meza-Romero, Roberto Vandenbark, Arthur A. Alkayed, Nabil J. Offner, Halina TI A novel HLA-DR alpha 1-MOG-35-55 construct treats experimental stroke SO METABOLIC BRAIN DISEASE LA English DT Article DE Stroke; Inflammation; Immunotherapy; Recombinant T-cell receptor Ligand; MHC class II invariant chain ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MIGRATION INHIBITORY FACTOR; CELL-RECEPTOR LIGANDS; ACUTE ISCHEMIC-STROKE; CLASS-II CONSTRUCTS; CYTOKINE SWITCH; INFARCT VOLUME; T-CELLS; MICE; INFLAMMATION AB Chemoattraction of leukocytes into the brain after induction of middle cerebral artery occlusion (MCAO) increases the lesion size and worsens disease outcome. Our previous studies demonstrated that partial MHC class II constructs can reverse this process. However, the potential application of pMHC to human stroke is limited by the need to rapidly match recipient MHC class II with the beta 1 domain of the pMHC construct. We designed a novel recombinant protein comprised of the HLA-DR alpha 1 domain linked to MOG-35-55 peptide but lacking the beta 1 domain found in pMHC and treated MCAO after 4 h reperfusion in humanized DR2 mice. Infarct volumes were quantified after 96 h reperfusion and immune cells from the periphery and CNS were evaluated for expression of CD74 and other cell surface, cytokine and pathway markers. This study demonstrates that four daily treatments with DR alpha 1-MOG-35-55 reduced infarct size by 40 % in the cortex, striatum and hemisphere, inhibited the migration of activated CD11b(+)CD45(high) cells from the periphery to the brain and reversed splenic atrophy. Furthermore, DR alpha 1-MOG-35-55 bound to CD74 on monocytes and blocked both binding and downstream signaling of macrophage migration inhibition factor (MIF) that may play a key role in infarct development. The novel DR alpha 1-MOG-35-55 construct is highly therapeutic in experimental stroke and could be given to all patients at least 4 h after stroke onset without the need for tissue typing due to universal expression of DR alpha 1 in humans. C1 [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Zhu, Wenbin; Libal, Nicole; Casper, Amanda; Alkayed, Nabil J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH [NS076013, NS047661]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors wish to thank Melissa S. Barber for assistance with manuscript submission. This work was supported by NIH Grants #NS076013 (STTR), and NS047661 and by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 29 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD MAR PY 2014 VL 29 IS 1 BP 37 EP 45 DI 10.1007/s11011-013-9440-0 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AB7JM UT WOS:000331965900004 PM 24122483 ER PT J AU Bodhankar, S Chen, YX Vandenbark, AA Murphy, SJ Offner, H AF Bodhankar, Sheetal Chen, Yingxin Vandenbark, Arthur A. Murphy, Stephanie J. Offner, Halina TI Treatment of experimental stroke with IL-10-producing B-cells reduces infarct size and peripheral and CNS inflammation in wild-type B-cell-sufficient mice SO METABOLIC BRAIN DISEASE LA English DT Article DE MCAO; Inflammatorycells; RegulatoryB-cells; IL-10 ID REGULATORY T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FOCAL CEREBRAL-ISCHEMIA; DEFICIENT MICE; IMMUNE-SYSTEM; BRAIN; MECHANISMS; IL-10; ROLES; IMMUNOSUPPRESSION AB Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that absence of B-cells led to larger infarct volumes and CNS damage after middle cerebral artery occlusion (MCAO) that could be prevented by transfer of IL-10(+) B-cells. The purpose of this study was to determine if the beneficial immunoregulatory effects on MCAO of the IL-10(+) B-cell subpopulation also extends to B-cell-sufficient mice that would better represent stroke subjects. CNS inflammation and infarct volumes were evaluated in male C57BL/6J (WT) mice that received either RPMI or IL-10(+) B-cells and underwent 60 min of middle cerebral artery occlusion (MCAO) followed by 96 h of reperfusion. Transfer of IL-10(+) B-cells markedly reduced infarct volume in WT recipient mice when given 24 h prior to or 4 h after MCAO. B-cell protected (24 h pre-MCAO) mice had increased regulatory subpopulations in the periphery, reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres of the IL-10(+) B-cell-treated group. Moreover, transfer of IL-10(+) B-cells 24 h before MCAO led to a significant preservation of regulatory immune subsets in the IL-10(+) B-cell protected group presumably indicating their role in immunomodulatory mechanisms, post-stroke. Our studies are the first to demonstrate a major immunoregulatory role for IL-10(+) regulatory B-cells in preventing and treating MCAO in WT mice and also implicating their potential role in attenuating complications due to post-stroke immunosuppression. C1 [Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] VA Med Ctr, Portland, OR USA. [Bodhankar, Sheetal; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Chen, Yingxin; Murphy, Stephanie J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Murphy, Stephanie J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Offner, Halina] Portland VA Med Ctr, R&D 31, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH/NINDS [1RO1 NS075887]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors wish to thank Andrew Lapato for technical assistance and Melissa S. Barber for assistance with manuscript submission. This work was supported by NIH/NINDS 1RO1 NS075887. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 47 TC 19 Z9 19 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD MAR PY 2014 VL 29 IS 1 BP 59 EP 73 DI 10.1007/s11011-013-9474-3 PG 15 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AB7JM UT WOS:000331965900006 PM 24374817 ER PT J AU Hodge, JC Mitchell, E Pillalamarri, V Toler, TL Bartel, F Kearney, HM Zou, YS Tan, WH Hanscom, C Kirmani, S Hanson, RR Skinner, SA Rogers, RC Everman, DB Boyd, E Tapp, C Mullegama, SV Keelean-Fuller, D Powell, CM Elsea, SH Morton, CC Gusella, JF DuPont, B Chaubey, A Lin, AE Talkowski, ME AF Hodge, J. C. Mitchell, E. Pillalamarri, V. Toler, T. L. Bartel, F. Kearney, H. M. Zou, Y. S. Tan, W. H. Hanscom, C. Kirmani, S. Hanson, R. R. Skinner, S. A. Rogers, R. C. Everman, D. B. Boyd, E. Tapp, C. Mullegama, S. V. Keelean-Fuller, D. Powell, C. M. Elsea, S. H. Morton, C. C. Gusella, J. F. DuPont, B. Chaubey, A. Lin, A. E. Talkowski, M. E. TI Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities SO MOLECULAR PSYCHIATRY LA English DT Article DE chromosomal microarray; MBD5; 2q23.1 microdeletion syndrome; next-generation sequencing; regression ID SMITH-MAGENIS-SYNDROME; PRADER-WILLI-SYNDROME; COMPARATIVE GENOMIC HYBRIDIZATION; CLINICAL DIAGNOSTIC-CRITERIA; DE-LANGE-SYNDROME; 2Q23.1 MICRODELETION; MENTAL-RETARDATION; CHROMOSOMAL-ABNORMALITIES; DEVELOPMENTAL DELAY; 22Q11.2 DELETIONS AB Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions and the associated human psychopathology, 22 individuals with genomic disruption of MBD5 (translocation, point mutation and deletion) were identified through whole-genome sequencing or cytogenomic microarray at 11 molecular diagnostic centers. The genomic impact ranged from a single base pair to 5.4 Mb. Parents were available for 11 cases, all of which confirmed that the rearrangement arose de novo. Phenotypes were largely indistinguishable between patients with full-segment 2q23.1 deletions and those with intragenic MBD5 rearrangements, including alterations confined entirely to the 5'-untranslated region, confirming the critical impact of non-coding sequence at this locus. We identified heterogeneous, multisystem pathogenic effects of MBD5 disruption and characterized the associated spectrum of psychopathology, including the novel finding of anxiety and bipolar disorder in multiple patients. Importantly, one of the unique features of the oldest known patient was behavioral regression. Analyses also revealed phenotypes that distinguish MBD5 disruptions from seven well-established syndromes with significant diagnostic overlap. This study demonstrates that haploinsufficiency of MBD5 causes diverse phenotypes, yields insight into the spectrum of resulting neurodevelopmental and behavioral psychopathology and provides clinical context for interpretation of MBD5 structural variations. Empirical evidence also indicates that disruption of non-coding MBD5 regulatory regions is sufficient for clinical manifestation, highlighting the limitations of exon-focused assessments. These results suggest an ongoing perturbation of neurological function throughout the lifespan, including risks for neurobehavioral regression. C1 [Hodge, J. C.; Mitchell, E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Hodge, J. C.; Kirmani, S.] Mayo Clin, Dept Med Genet, Rochester, MN 55905 USA. [Pillalamarri, V.; Hanscom, C.; Gusella, J. F.; Lin, A. E.; Talkowski, M. E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Toler, T. L.; Lin, A. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bartel, F.; Skinner, S. A.; Rogers, R. C.; DuPont, B.; Chaubey, A.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Kearney, H. M.; Boyd, E.] Mission Hlth, Fullerton Genet Ctr, Asheville, NC USA. [Zou, Y. S.] Pathol Associates Med Labs, Clin Cytogenet Lab, Spokane, WA USA. [Tan, W. H.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Tan, W. H.; Morton, C. C.] Harvard Univ, Sch Med, Boston, MA USA. [Hanson, R. R.] Mayo Clin, Dept Neurosci, Eau Claire, WI USA. [Tapp, C.] Agnesian Hlth Care, Outpatient Behav Hlth, Fond Du Lac, WI USA. [Mullegama, S. V.; Elsea, S. H.] Virginia Commonwealth Univ, Sch Med, Dept Human & Mol Genet, Richmond, VA USA. [Keelean-Fuller, D.; Powell, C. M.] Univ N Carolina, Dept Pediat & Genet, Chapel Hill, NC USA. [Elsea, S. H.] Virginia Commonwealth Univ, Sch Med, Dept Pediat, Richmond, VA USA. [Morton, C. C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Morton, C. C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Morton, C. C.; Gusella, J. F.; Talkowski, M. E.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Morton, C. C.; Gusella, J. F.; Talkowski, M. E.] MIT, Cambridge, MA 02139 USA. [Gusella, J. F.; Talkowski, M. E.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Gusella, J. F.; Talkowski, M. E.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. RP Hodge, JC (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 First St South West,Hilton Bldg Room 970, Rochester, MN 55905 USA. EM hodge.jennelle@mayo.edu; talkowski@chgr.mgh.harvard.edu RI Powell, Cynthia/L-5903-2015; OI Toler, Tomi/0000-0002-1637-8310 FU NIH [GM061354, MH09586]; Fondation Jerome Lejeune; Simons Foundation for Autism Research; Nancy Lurie Marks Family Foundation; NARSAD FX This work was funded by grants from the NIH GM061354 (CCM, JFG) and MH09586 (MET), and from the Fondation Jerome Lejeune (SHE). MET is also supported by the Simons Foundation for Autism Research, the Nancy Lurie Marks Family Foundation and NARSAD. We thank the patients and their families and physicians for participating in this study. NR 60 TC 18 Z9 18 U1 1 U2 7 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 MAR PY 2014 VL 19 IS 3 BP 368 EP 379 DI 10.1038/mp.2013.42 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AB7EH UT WOS:000331951600016 PM 23587880 ER PT J AU Jensen, KB Petrovic, P Kerr, CE Kirsch, I Raicek, J Cheetham, A Spaeth, R Cook, A Gollub, RL Kong, J Kaptchuk, TJ AF Jensen, K. B. Petrovic, P. Kerr, C. E. Kirsch, I. Raicek, J. Cheetham, A. Spaeth, R. Cook, A. Gollub, R. L. Kong, J. Kaptchuk, T. J. TI Sharing pain and relief: neural correlates of physicians during treatment of patients SO MOLECULAR PSYCHIATRY LA English DT Article DE patient-provider; doctor-patient; placebo; pain; analgesia ID IRRITABLE-BOWEL-SYNDROME; PLACEBO ANALGESIA; INDIVIDUAL-DIFFERENCES; INDUCED EXPECTATIONS; PERSPECTIVE-TAKING; OPIOID ACTIVITY; BRAIN ACTIVITY; EMPATHY; RESPONSES; NETWORK AB Patient-physician interactions significantly contribute to placebo effects and clinical outcomes. While the neural correlates of placebo responses have been studied in patients, the neurobiology of the clinician during treatment is unknown. This study investigated physicians' brain activations during patient-physician interaction while the patient was experiencing pain, including a 'treatment`, 'no-treatment' and 'control' condition. Here, we demonstrate that physicians activated brain regions previously implicated in expectancy for pain-relief and increased attention during treatment of patients, including the right ventrolateral and dorsolateral prefrontal cortices. The physician's ability to take the patients' perspective correlated with increased brain activations in the rostral anterior cingulate cortex, a region that has been associated with processing of reward and subjective value. We suggest that physician treatment involves neural representations of treatment expectation, reward processing and empathy, paired with increased activation in attention-related structures. Our findings further the understanding of the neural representations associated with reciprocal interactions between clinicians and patients; a hallmark for successful treatment outcomes. C1 [Jensen, K. B.; Raicek, J.; Cheetham, A.; Spaeth, R.; Cook, A.; Gollub, R. L.; Kong, J.] Harvard Univ, Sch Med, Dept Psychiat, Mass Gen Hosp, Boston, MA 02115 USA. [Jensen, K. B.; Gollub, R. L.; Kong, J.; Kaptchuk, T. J.] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Jensen, K. B.; Kirsch, I.; Gollub, R. L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies & Therapeut Encounter, Boston, MA 02215 USA. [Petrovic, P.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Kerr, C. E.] Brown Univ, Dept Family Med, Providence, RI 02912 USA. [Kirsch, I.] Univ Plymouth, Sch Psychol, Plymouth PL4 8AA, Devon, England. RP Jensen, KB (reprint author), MGH Psychiat Neuroimaging, Bldg 120,2nd Ave, Charlestown, MA 02129 USA. EM karinj@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044; Jensen, Karin/0000-0003-2521-3160 FU Swedish Society for Medical Research (SSMF, Osher Center for Integrative Medicine); Swedish Council for Working Life and Social Research; Swedish Research Council; NCCAM [K24 AT004095, R01 AT004662, P01 AT006663, KO1AT003883, R21AT004497, R01AT006364, R01AT005280]; NIDA [R03AT218317]; National Center for Research Resources (NCRR) [M01-RR-01066, UL1 RR025758-01]; NCRR [P41RR14075] FX We thank Dr Jonathan Berrebi and Dr Chantal Berna who provided technical and clinical expertise for this study. We also thank Professor Martin Ingvar for the valuable theoretical contributions to the study design and Magnus Gyllensward for help with graphic illustrations. The work was supported by the Swedish Society for Medical Research (SSMF, Osher Center for Integrative Medicine) and the Swedish Council for Working Life and Social Research to K. Jensen, Swedish Research Council to P Petrovic, K24 AT004095 (NCCAM) and R01 AT004662 (NCCAM) to T Kaptchuk, P01 AT006663 (NCCAM) to Bruce Rosen, KO1AT003883 (NCCAM), R21AT004497 (NCCAM), R03AT218317 (NIDA), R01AT006364 (NCCAM) to J Kong, R01AT005280 (NCCAM) to R Gollub, M01-RR-01066 and UL1 RR025758-01 for Clinical Research Center Biomedical Imaging Core from National Center for Research Resources (NCRR), and P41RR14075 for Center for Functional Neuroimaging Technologies from NCRR. NR 51 TC 16 Z9 16 U1 2 U2 22 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 MAR PY 2014 VL 19 IS 3 BP 392 EP 398 DI 10.1038/mp.2012.195 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AB7EH UT WOS:000331951600019 PM 23358155 ER PT J AU Janoff, EN Rubins, JB Fasching, C Charboneau, D Rahkola, JT Plaut, AG Weiser, JN AF Janoff, E. N. Rubins, J. B. Fasching, C. Charboneau, D. Rahkola, J. T. Plaut, A. G. Weiser, J. N. TI Pneumococcal IgA1 protease subverts specific protection by human IgA1 SO MUCOSAL IMMUNOLOGY LA English DT Article ID FC-ALPHA-RECEPTOR; STREPTOCOCCUS-PNEUMONIAE; IMMUNOGLOBULIN-A1 PROTEASE; CAPSULAR POLYSACCHARIDES; HAEMOPHILUS-INFLUENZAE; NEISSERIA-GONORRHOEAE; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; SECRETORY IGA AB Bacterial immunoglobulin A1 (IgA1) proteases may sabotage the protective effects of IgA. In vitro, both exogenous and endogenously produced IgA1 protease inhibited phagocytic killing of Streptococcus pneumoniae by capsule-specific IgA1 human monoclonal antibodies (hMAbs) but not IgA2. These IgA1 proteases cleaved and reduced binding of the the effector Fc alpha 1 heavy chain but not the antigen-binding F(ab)/light chain to pneumococcal surfaces. In vivo, IgA1 protease-resistant IgA2, but not IgA1 protease-sensitive IgA1, supported 60% survival in mice infected with wild-type S. pneumoniae. IgA1 hMAbs protected mice against IgA1 protease-deficient but not -producing pneumococci. Parallel mouse sera with human IgA2 showed more efficient complement-mediated reductions in pneumococci with neutrophils than did IgA1, particularly with protease-producing organisms. After natural human pneumococcal bacteremia, purified serum IgG inhibited IgA1 protease activity in 7 of 11 patients (64%). These observations provide the first evidence in vivo that IgA1 protease can circumvent killing of S. pneumoniae by human IgA. Acquisition of IgA1 protease-neutralizing IgG after infection directs attention to IgA1 protease both as a determinant of successful colonization and infection and as a potential vaccine candidate. C1 [Janoff, E. N.; Rahkola, J. T.] Univ Colorado Denver, Div Infect Dis, Mucosal & Vaccine Res Colorado MAVRC, Aurora, CO 80045 USA. [Rubins, J. B.; Charboneau, D.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Fasching, C.] Denver Vet Affairs Med Ctr, Vet Affairs Med Ctr, Denver, CO USA. [Plaut, A. G.] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. [Plaut, A. G.] Tufts Univ New England Med Ctr, Div Gastroenterol, Boston, MA USA. [Weiser, J. N.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Weiser, J. N.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. RP Janoff, EN (reprint author), Univ Colorado Denver, Div Infect Dis, Mucosal & Vaccine Res Colorado MAVRC, Aurora, CO 80045 USA. EM Edward.Janoff@ucdenver.edu FU National Institutes of Health [AI-092468, AI-48796, AI-42240, HD-41361, AI092468, AI-38446, DE15844]; Tufts Digestive Disease Research Center [P30 DK34928]; Mucosal and Vaccine Research Center at the University of Colorado School of Medicine; Department of Veterans Affairs Research Service FX All human and mouse studies were approved by the Human and Animal Subjects Subcommittees, and written informed consent was obtained from patients. We thank Ann Emery for secretarial support. This work was supported by the National Institutes of Health Grants AI-092468, AI-48796, AI-42240, HD-41361, AI092468 (ENJ), AI-38446 (JNW), DE15844, the Tufts Digestive Disease Research Center P30 DK34928 (AGP), the Mucosal and Vaccine Research Center at the University of Colorado School of Medicine, and the Department of Veterans Affairs Research Service. NR 53 TC 10 Z9 10 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD MAR PY 2014 VL 7 IS 2 BP 249 EP 256 DI 10.1038/mi.2013.41 PG 8 WC Immunology SC Immunology GA AB7DA UT WOS:000331948300006 PM 23820749 ER PT J AU Mahajan, A Go, MJ Zhang, WH Below, JE Gaulton, KJ Ferreira, T Horikoshi, M Johnson, AD Ng, MCY Prokopenko, I Saleheen, D Wang, X Zeggini, E Abecasis, GR Adair, LS Almgren, P Atalay, M Aung, T Baldassarre, D Balkau, B Bao, YQ Barnett, AH Barroso, I Basit, A Been, LF Beilby, J Bell, GI Benediktsson, R Bergman, RN Boehm, BO Boerwinkle, E Bonnycastle, LL Burtt, N Cai, QY Campbell, H Carey, J Cauchi, S Caulfield, M Chan, JCN Chang, LC Chang, TJ Chang, YC Charpentier, G Chen, CH Chen, H Chen, YT Chia, KS Chidambaram, M Chines, PS Cho, NH Cho, YM Chuang, LM Collins, FS Cornelis, MC Couper, DJ Crenshaw, AT van Dam, RM Danesh, J Das, D de Faire, U Dedoussis, G Deloukas, P Dimas, AS Dina, C Doney, ASF Donnelly, PJ Dorkhan, M van Duijn, C Dupuis, J Edkins, S Elliott, P Emilsson, V Erbel, R Eriksson, JG Escobedo, J Esko, T Eury, E Florez, JC Fontanillas, P Forouhi, NG Forsen, T Fox, C Fraser, RM Frayling, TM Froguel, P Frossard, P Gao, YT Gertow, K Gieger, C Gigante, B Grallert, H Grant, GB Groop, LC Groves, CJ Grundberg, E Guiducci, C Hamsten, A Han, BG Hara, K Hassanali, N Hattersley, AT Hayward, C Hedman, AK Herder, C Hofman, A Holmen, OL Hovingh, K Hreidarsson, AB Hu, C Hu, FB Hui, J Humphries, SE Hunt, SE Hunter, DJ Hveem, K Hydrie, ZI Ikegami, H Illig, T Ingelsson, E Islam, M Isomaa, B Jackson, AU Jafar, T James, A Jia, WP Jockel, KH Jonsson, A Jowett, JBM Kadowaki, T Kang, HM Kanoni, S Kao, WHL Kathiresan, S Kato, N Katulanda, P Keinanen-Kiukaanniemi, SM Kelly, AM Khan, H Khaw, KT Khor, CC Kim, HL Kim, S Kim, YJ Kinnunen, L Klopp, N Kong, A Korpi-Hyovalti, E Kowlessur, S Kraft, P Kravic, J Kristensen, MM Krithika, S Kumar, A Kumate, J Kuusisto, J Kwak, SH Laakso, M Lagou, V Lakka, TA Langenberg, C Langford, C Lawrence, R Leander, K Lee, JM Lee, NR Li, M Li, XZ Li, Y Liang, JB Liju, S Lim, WY Lind, L Lindgren, CM Lindholm, E Liu, CT Liu, JJ Lobbens, S Long, JR Loos, RJF Lu, W Luan, JA Lyssenko, V Ma, RCW Maeda, S Magi, R Mannisto, S Matthews, DR Meigs, JB Melander, O Metspalu, A Meyer, J Mirza, G Mihailov, E Moebus, S Mohan, V Mohlke, KL Morris, AD Muhleisen, TW Muller-Nurasyid, M Musk, B Nakamura, J Nakashima, E Navarro, P Ng, PK Nica, AC Nilsson, PM Njolstad, I Nothen, MM Ohnaka, K Ong, TH Owen, KR Palmer, CNA Pankow, JS Park, KS Parkin, M Pechlivanis, S Pedersen, NL Peltonen, L Perry, JRB Peters, A Pinidiyapathirage, JM Platou, CGP Potter, S Price, JF Qi, L Radha, V Rallidis, L Rasheed, A Rathmann, W Rauramaa, R Raychaudhuri, S Rayner, NW Rees, SD Rehnberg, E Ripatti, S Robertson, N Roden, M Rossin, EJ Rudan, I Rybin, D Saaristo, TE Salomaa, V Saltevo, J Samuel, M Sanghera, DK Saramies, J Scott, J Scott, LJ Scott, RA Segre, AV Sehmi, J Sennblad, B Shah, N Shah, S Shera, AS Shu, XO Shuldiner, AR Sigurdsson, G Sijbrands, E Silveira, A Sim, X Sivapalaratnam, S Small, KS So, WY Stancakova, A Stefansson, K Steinbach, G Steinthorsdottir, V Stirrups, K Strawbridge, RJ Stringham, HM Sun, Q Suo, C Syvanen, AC Takayanagi, R Takeuchi, F Tay, WT Teslovich, TM Thorand, B Thorleifsson, G Thorsteinsdottir, U Tikkanen, E Trakalo, J Tremoli, E Trip, MD Tsai, FJ Tuomi, T Tuomilehto, J Uitterlinden, AG Valladares-Salgado, A Vedantam, S Veglia, F Voight, BF Wang, CR Wareham, NJ Wennauer, R Wickremasinghe, AR Wilsgaard, T Wilson, JF Wiltshire, S Winckler, W Wong, TY Wood, AR Wu, JY Wu, Y Yamamoto, K Yamauchi, T Yang, MY Yengo, L Yokota, M Young, R Zabaneh, D Zhang, F Zhang, R Zheng, W Zimmet, PZ Altshuler, D Bowden, DW Cho, YS Cox, NJ Cruz, M Hanis, CL Kooner, J Lee, JY Seielstad, M Teo, YY Boehnke, M Parra, EJ Chambers, JC Tai, ES McCarthy, MI Morris, AP AF Mahajan, Anubha Go, Min Jin Zhang, Weihua Below, Jennifer E. Gaulton, Kyle J. Ferreira, Teresa Horikoshi, Momoko Johnson, Andrew D. Ng, Maggie C. Y. Prokopenko, Inga Saleheen, Danish Wang, Xu Zeggini, Eleftheria Abecasis, Goncalo R. Adair, Linda S. Almgren, Peter Atalay, Mustafa Aung, Tin Baldassarre, Damiano Balkau, Beverley Bao, Yuqian Barnett, Anthony H. Barroso, Ines Basit, Abdul Been, Latonya F. Beilby, John Bell, Graeme I. Benediktsson, Rafn Bergman, Richard N. Boehm, Bernhard O. Boerwinkle, Eric Bonnycastle, Lori L. Burtt, Noel Cai, Qiuyin Campbell, Harry Carey, Jason Cauchi, Stephane Caulfield, Mark Chan, Juliana C. N. Chang, Li-Ching Chang, Tien-Jyun Chang, Yi-Cheng Charpentier, Guillaume Chen, Chien-Hsiun Chen, Han Chen, Yuan-Tsong Chia, Kee-Seng Chidambaram, Manickam Chines, Peter S. Cho, Nam H. Cho, Young Min Chuang, Lee-Ming Collins, Francis S. Cornelis, Marilyn C. Couper, David J. Crenshaw, Andrew T. van Dam, Rob M. Danesh, John Das, Debashish de Faire, Ulf Dedoussis, George Deloukas, Panos Dimas, Antigone S. Dina, Christian Doney, Alex S. F. Donnelly, Peter J. Dorkhan, Mozhgan van Duijn, Cornelia Dupuis, Josee Edkins, Sarah Elliott, Paul Emilsson, Valur Erbel, Raimund Eriksson, Johan G. Escobedo, Jorge Esko, Tonu Eury, Elodie Florez, Jose C. Fontanillas, Pierre Forouhi, Nita G. Forsen, Tom Fox, Caroline Fraser, Ross M. Frayling, Timothy M. Froguel, Philippe Frossard, Philippe Gao, Yutang Gertow, Karl Gieger, Christian Gigante, Bruna Grallert, Harald Grant, George B. Groop, Leif C. Groves, Christopher J. Grundberg, Elin Guiducci, Candace Hamsten, Anders Han, Bok-Ghee Hara, Kazuo Hassanali, Neelam Hattersley, Andrew T. Hayward, Caroline Hedman, Asa K. Herder, Christian Hofman, Albert Holmen, Oddgeir L. Hovingh, Kees Hreidarsson, Astradur B. Hu, Cheng Hu, Frank B. Hui, Jennie Humphries, Steve E. Hunt, Sarah E. Hunter, David J. Hveem, Kristian Hydrie, Zafar I. Ikegami, Hiroshi Illig, Thomas Ingelsson, Erik Islam, Muhammed Isomaa, Bo Jackson, Anne U. Jafar, Tazeen James, Alan Jia, Weiping Joeckel, Karl-Heinz Jonsson, Anna Jowett, Jeremy B. M. Kadowaki, Takashi Kang, Hyun Min Kanoni, Stavroula Kao, Wen Hong L. Kathiresan, Sekar Kato, Norihiro Katulanda, Prasad Keinanen-Kiukaanniemi, Sirkka M. Kelly, Ann M. Khan, Hassan Khaw, Kay-Tee Khor, Chiea-Chuen Kim, Hyung-Lae Kim, Sangsoo Kim, Young Jin Kinnunen, Leena Klopp, Norman Kong, Augustine Korpi-Hyovalti, Eeva Kowlessur, Sudhir Kraft, Peter Kravic, Jasmina Kristensen, Malene M. Krithika, S. Kumar, Ashish Kumate, Jesus Kuusisto, Johanna Kwak, Soo Heon Laakso, Markku Lagou, Vasiliki Lakka, Timo A. Langenberg, Claudia Langford, Cordelia Lawrence, Robert Leander, Karin Lee, Jen-Mai Lee, Nanette R. Li, Man Li, Xinzhong Li, Yun Liang, Junbin Liju, Samuel Lim, Wei-Yen Lind, Lars Lindgren, Cecilia M. Lindholm, Eero Liu, Ching-Ti Liu, Jian Jun Lobbens, Stephane Long, Jirong Loos, Ruth J. F. Lu, Wei Luan, Jian'an Lyssenko, Valeriya Ma, Ronald C. W. Maeda, Shiro Maegi, Reedik Mannisto, Satu Matthews, David R. Meigs, James B. Melander, Olle Metspalu, Andres Meyer, Julia Mirza, Ghazala Mihailov, Evelin Moebus, Susanne Mohan, Viswanathan Mohlke, Karen L. Morris, Andrew D. Muehleisen, Thomas W. Mueller-Nurasyid, Martina Musk, Bill Nakamura, Jiro Nakashima, Eitaro Navarro, Pau Peng-Keat Ng Nica, Alexandra C. Nilsson, Peter M. Njolstad, Inger Noethen, Markus M. Ohnaka, Keizo Ong, Twee Hee Owen, Katharine R. Palmer, Colin N. A. Pankow, James S. Park, Kyong Soo Parkin, Melissa Pechlivanis, Sonali Pedersen, Nancy L. Peltonen, Leena Perry, John R. B. Peters, Annette Pinidiyapathirage, Janani M. Platou, Carl G. P. Potter, Simon Price, Jackie F. Qi, Lu Radha, Venkatesan Rallidis, Loukianos Rasheed, Asif Rathmann, Wolfgang Rauramaa, Rainer Raychaudhuri, Soumya Rayner, N. William Rees, Simon D. Rehnberg, Emil Ripatti, Samuli Robertson, Neil Roden, Michael Rossin, Elizabeth J. Rudan, Igor Rybin, Denis Saaristo, Timo E. Salomaa, Veikko Saltevo, Juha Samuel, Maria Sanghera, Dharambir K. Saramies, Jouko Scott, James Scott, Laura J. Scott, Robert A. Segre, Ayellet V. Sehmi, Joban Sennblad, Bengt Shah, Nabi Shah, Sonia Shera, A. Samad Shu, Xiao Ou Shuldiner, Alan R. Sigurdsson, Gunnar Sijbrands, Eric Silveira, Angela Sim, Xueling Sivapalaratnam, Suthesh Small, Kerrin S. So, Wing Yee Stancakova, Alena Stefansson, Kari Steinbach, Gerald Steinthorsdottir, Valgerdur Stirrups, Kathleen Strawbridge, Rona J. Stringham, Heather M. Sun, Qi Suo, Chen Syvanen, Ann-Christine Takayanagi, Ryoichi Takeuchi, Fumihiko Tay, Wan Ting Teslovich, Tanya M. Thorand, Barbara Thorleifsson, Gudmar Thorsteinsdottir, Unnur Tikkanen, Emmi Trakalo, Joseph Tremoli, Elena Trip, Mieke D. Tsai, Fuu Jen Tuomi, Tiinamaija Tuomilehto, Jaakko Uitterlinden, Andre G. Valladares-Salgado, Adan Vedantam, Sailaja Veglia, Fabrizio Voight, Benjamin F. Wang, Congrong Wareham, Nicholas J. Wennauer, Roman Wickremasinghe, Ananda R. Wilsgaard, Tom Wilson, James F. Wiltshire, Steven Winckler, Wendy Wong, Tien Yin Wood, Andrew R. Wu, Jer-Yuarn Wu, Ying Yamamoto, Ken Yamauchi, Toshimasa Yang, Mingyu Yengo, Loic Yokota, Mitsuhiro Young, Robin Zabaneh, Delilah Zhang, Fan Zhang, Rong Zheng, Wei Zimmet, Paul Z. Altshuler, David Bowden, Donald W. Cho, Yoon Shin Cox, Nancy J. Cruz, Miguel Hanis, Craig L. Kooner, Jaspal Lee, Jong-Young Seielstad, Mark Teo, Yik Ying Boehnke, Michael Parra, Esteban J. Chambers, John C. Tai, E. Shyong McCarthy, Mark I. Morris, Andrew P. CA DIAbet Genetics Replication & Meta Asian Genetic Epidemiology Network South Asian Type Diabet SAT2D Cons Mexican Amer Type 2 Diabet MAT2D C Type 2 Diabet Genetic Exploration TI Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility SO NATURE GENETICS LA English DT Article ID SCALE ASSOCIATION ANALYSIS; TRANSETHNIC METAANALYSIS; GLUCOSE-HOMEOSTASIS; LOCI; VARIANTS; POPULATIONS; MAP; INDIVIDUALS; IMPUTATION; CHROMATIN AB To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. C1 [Mahajan, Anubha; Gaulton, Kyle J.; Ferreira, Teresa; Horikoshi, Momoko; Prokopenko, Inga; Dimas, Antigone S.; Donnelly, Peter J.; Hedman, Asa K.; Ingelsson, Erik; Kumar, Ashish; Lagou, Vasiliki; Lindgren, Cecilia M.; Mirza, Ghazala; Perry, John R. B.; Rayner, N. William; Robertson, Neil; Trakalo, Joseph; Wiltshire, Steven; McCarthy, Mark I.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Go, Min Jin; Han, Bok-Ghee; Kim, Young Jin; Lee, Jong-Young] Natl Inst Hlth, Ctr Genome Sci, Gangoe Myeon, Yeonje Ri, South Korea. [Zhang, Weihua; Boehm, Bernhard O.; Elliott, Paul; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, London, England. [Below, Jennifer E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Horikoshi, Momoko; Prokopenko, Inga; Groves, Christopher J.; Hassanali, Neelam; Katulanda, Prasad; Matthews, David R.; Owen, Katharine R.; Rayner, N. William; Robertson, Neil; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England. [Johnson, Andrew D.; Dupuis, Josee; Fox, Caroline] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ng, Maggie C. Y.; Bowden, Donald W.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Ng, Maggie C. Y.; Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA. [Prokopenko, Inga; Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. [Saleheen, Danish; Danesh, John; Khan, Hassan; Khaw, Kay-Tee; Young, Robin] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Saleheen, Danish; Frossard, Philippe; Rasheed, Asif; Samuel, Maria; Shah, Nabi] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan. [Wang, Xu; Chia, Kee-Seng; Lee, Jen-Mai; Peng-Keat Ng; Ong, Twee Hee; Teo, Yik Ying; Tai, E. Shyong] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore. [Zeggini, Eleftheria; Barroso, Ines; Deloukas, Panos; Edkins, Sarah; Hunt, Sarah E.; Kanoni, Stavroula; Langford, Cordelia; Peltonen, Leena; Potter, Simon; Ripatti, Samuli; Small, Kerrin S.; Stirrups, Kathleen] Wellcome Trust Sanger Inst, Cambridge, England. [Abecasis, Goncalo R.; Jackson, Anne U.; Kang, Hyun Min; Scott, Laura J.; Sim, Xueling; Stringham, Heather M.; Teslovich, Tanya M.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Almgren, Peter; Dorkhan, Mozhgan; Groop, Leif C.; Jonsson, Anna; Kravic, Jasmina; Lindholm, Eero; Lyssenko, Valeriya; Melander, Olle; Nilsson, Peter M.] Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden. [Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland. [Aung, Tin; Khor, Chiea-Chuen; Tay, Wan Ting; Wong, Tien Yin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore. [Aung, Tin; Wong, Tien Yin] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore. [Baldassarre, Damiano; Tremoli, Elena; Veglia, Fabrizio] IRCCS, Ctr Cardiol Monzino, Milan, Italy. [Baldassarre, Damiano; Tremoli, Elena] Univ Milan, Dept Pharmacol Sci, Milan, Italy. [Balkau, Beverley] INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France. [Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France. [Bao, Yuqian; Hu, Cheng; Jia, Weiping; Wang, Congrong; Zhang, Rong] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Key Lab Diabet Mellitus,Shanghai Diabet, Shanghai 200030, Peoples R China. [Barnett, Anthony H.; Kelly, Ann M.; Rees, Simon D.] Univ Birmingham, Coll Med & Dent Sci, Birmingham, W Midlands, England. [Barnett, Anthony H.; Kelly, Ann M.; Rees, Simon D.] Heart England Natl Hlth Serv NHS Fdn Trust, Ctr Biomed Res, Birmingham, W Midlands, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England. [Basit, Abdul; Hydrie, Zafar I.] Baqai Inst Diabetol & Endocrinol, Karachi, Pakistan. [Been, Latonya F.; Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat,Sect Genet, Oklahoma City, OK 73190 USA. [Beilby, John; Hui, Jennie; James, Alan; Musk, Bill] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia. [Beilby, John] Queen Elizabeth II Med Ctr, PathWest Lab Med Western Australia, Nedlands, WA, Australia. [Beilby, John] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Bell, Graeme I.; Cox, Nancy J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bell, Graeme I.; Cox, Nancy J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Benediktsson, Rafn; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Benediktsson, Rafn; Hreidarsson, Astradur B.; Sigurdsson, Gunnar] Landspitali Univ Hosp, Reykjavik, Iceland. [Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA. [Boehm, Bernhard O.] Univ Med Ctr Ulm, Div Endocrinol & Diabet, Dept Internal Med, Ulm, Germany. [Boehm, Bernhard O.] Nanyang Technol Univ, Lee Kong Chian LKC Sch Med, Singapore 639798, Singapore. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Bonnycastle, Lori L.; Chines, Peter S.; Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Burtt, Noel; Carey, Jason; Crenshaw, Andrew T.; Fontanillas, Pierre; Grant, George B.; Guiducci, Candace; Kathiresan, Sekar; Lindgren, Cecilia M.; Parkin, Melissa; Peltonen, Leena; Raychaudhuri, Soumya; Rossin, Elizabeth J.; Segre, Ayellet V.; Voight, Benjamin F.; Winckler, Wendy; Altshuler, David] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA. [Cai, Qiuyin; Long, Jirong; Shu, Xiao Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37212 USA. [Campbell, Harry; Fraser, Ross M.; Price, Jackie F.; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Campbell, Harry; Hayward, Caroline; Navarro, Pau; Wilson, James F.] Univ Edinburgh, Western Gen Hosp, MRC, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Cauchi, Stephane; Eury, Elodie; Froguel, Philippe; Lobbens, Stephane; Yengo, Loic] CNRS, Unite Mixte Rech UMR 8199, Inst Biol, Lille, France. [Cauchi, Stephane; Eury, Elodie; Froguel, Philippe; Lobbens, Stephane; Yengo, Loic] Univ Lille 2, Inst Pasteur, Lille, France. [Caulfield, Mark] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England. [Caulfield, Mark] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Barts & London Genome Ctr, London, England. [Chan, Juliana C. N.; Ma, Ronald C. W.; So, Wing Yee] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Chang, Li-Ching; Chen, Chien-Hsiun; Chen, Yuan-Tsong; Wu, Jer-Yuarn] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Chang, Tien-Jyun; Chang, Yi-Cheng; Chuang, Lee-Ming] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Charpentier, Guillaume] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France. [Chen, Chien-Hsiun; Tsai, Fuu Jen; Wu, Jer-Yuarn] China Med Univ, Sch Chinese Med, Taichung, Taiwan. [Chen, Han; Dupuis, Josee; Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Chia, Kee-Seng; Khor, Chiea-Chuen; Lim, Wei-Yen; Sim, Xueling; Suo, Chen; Teo, Yik Ying] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. [Chidambaram, Manickam; Liju, Samuel; Mohan, Viswanathan; Radha, Venkatesan] Indian Council Med Res, Adv Ctr Genom Diabet, Madras Diabet Res Fdn, Dept Mol Genet, Madras, Tamil Nadu, India. [Cho, Nam H.] Ajou Univ, Sch Med, Dept Prevent Med, Suwon 441749, South Korea. [Cho, Young Min; Kwak, Soo Heon; Park, Kyong Soo] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Chuang, Lee-Ming; Maeda, Shiro] Natl Taiwan Univ, Sch Med, Grad Inst Clin Med, Taipei 10764, Taiwan. [Cornelis, Marilyn C.; van Dam, Rob M.; Hu, Frank B.; Hunter, David J.; Kraft, Peter; Qi, Lu; Sun, Qi] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Das, Debashish; Sehmi, Joban; Kooner, Jaspal; Chambers, John C.] Ealing Hosp NHS Trust, Southall, Middx, England. [de Faire, Ulf; Gigante, Bruna; Leander, Karin] Karolinska Inst, Inst Environm Med, Divis Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [Dimas, Antigone S.; Nica, Alexandra C.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Dimas, Antigone S.] Biomed Sci Res Ctr Alexander Fleming, Vari, Greece. [Dina, Christian] INSERM, UMR 1087, Nantes, France. [Dina, Christian] CNRS, UMR 6291, Nantes, France. [Dina, Christian] Univ Nantes, Nantes, France. [Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Diabet Res Ctr, Dundee, Scotland. [Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland. [Donnelly, Peter J.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [van Duijn, Cornelia; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [van Duijn, Cornelia; Uitterlinden, Andre G.] Netherlands Consortium Healthy Ageing, Netherland Genom Initiat, Rotterdam, Netherlands. [van Duijn, Cornelia; Uitterlinden, Andre G.] Ctr Med Syst Biol, Rotterdam, Netherlands. [Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC, Hlth Protect Agcy, Ctr Environm & Hlth, London, England. [Emilsson, Valur; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland. [Erbel, Raimund] Univ Duisburg Essen, Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, Essen, Germany. [Eriksson, Johan G.; Mannisto, Satu; Peltonen, Leena; Ripatti, Samuli; Salomaa, Veikko; Tikkanen, Emmi] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Eriksson, Johan G.; Forsen, Tom] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Gen Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.; Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Escobedo, Jorge] Inst Mexicano Seguro Social, Hosp Gen Reg 1, Unidad Invest Epidemiol Clin, Mexico City, DF, Mexico. [Esko, Tonu; Maegi, Reedik; Metspalu, Andres; Mihailov, Evelin] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Esko, Tonu; Florez, Jose C.; Rossin, Elizabeth J.; Vedantam, Sailaja] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Esko, Tonu; Florez, Jose C.; Vedantam, Sailaja] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. [Florez, Jose C.; Meigs, James B.; Segre, Ayellet V.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Florez, Jose C.; Kathiresan, Sekar; Segre, Ayellet V.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Forouhi, Nita G.; Langenberg, Claudia; Loos, Ruth J. F.; Luan, Jian'an; Scott, Robert A.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Forsen, Tom] Vaasa Hlth Care Ctr, Vaasa, Finland. [Fox, Caroline] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. [Fox, Caroline; Hu, Frank B.; Hunter, David J.; Qi, Lu; Sun, Qi] Harvard Univ, Sch Med, Boston, MA USA. [Frayling, Timothy M.; Perry, John R. B.; Wood, Andrew R.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Gao, Yutang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Gertow, Karl; Hamsten, Anders; Sennblad, Bengt; Silveira, Angela; Strawbridge, Rona J.] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden. [Gertow, Karl; Hamsten, Anders; Sennblad, Bengt; Silveira, Angela; Strawbridge, Rona J.] Karolinska Univ, Hosp Solna, Ctr Mol Med, Stockholm, Sweden. [Gieger, Christian; Meyer, Julia; Mueller-Nurasyid, Martina] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany. [Grallert, Harald; Illig, Thomas; Klopp, Norman] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany. [Grallert, Harald] Univ Munich, Clin Cooperat Grp Diabet, Munich, Germany. [Grallert, Harald] Helmholtz Zentrum Muenchen, Munich, Germany. [Grallert, Harald] Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Munich, Germany. [Grallert, Harald] German Ctr Diabet Res DZD, Neuherberg, Germany. [Grundberg, Elin; Small, Kerrin S.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Hara, Kazuo; Kadowaki, Takashi; Yamauchi, Toshimasa] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan. [Hattersley, Andrew T.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany. [Holmen, Oddgeir L.; Hveem, Kristian; Platou, Carl G. P.] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway. [Hovingh, Kees; Sivapalaratnam, Suthesh; Trip, Mieke D.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Hu, Frank B.; Hunter, David J.; Qi, Lu; Sun, Qi] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hui, Jennie; Musk, Bill] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Humphries, Steve E.] UCL, Inst Cardiovasc Sci, London, England. [Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Ikegami, Hiroshi] Kinki Univ, Sch Med, Dept Diabet Endocrinol & Metab, Osaka 589, Japan. [Illig, Thomas; Klopp, Norman] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany. [Ingelsson, Erik] Univ Uppsala Hosp, Dept Mol Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Islam, Muhammed; Jafar, Tazeen] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Jafar, Tazeen] Aga Khan Univ, Dept Med, Karachi, Pakistan. [James, Alan] Queen Elizabeth II Med Ctr, West Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia. [James, Alan; Musk, Bill] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Joeckel, Karl-Heinz; Moebus, Susanne; Pechlivanis, Sonali] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Jowett, Jeremy B. M.; Kristensen, Malene M.; Zimmet, Paul Z.] Heart & Diabet Inst, Baker Int Diabet Inst IDI, Melbourne, Australia. [Kao, Wen Hong L.; Li, Man] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kato, Norihiro; Takeuchi, Fumihiko] Natl Ctr Global Hlth & Med, Res Inst, Shinjuku Ku, Tokyo, Japan. [Katulanda, Prasad] Univ Colombo, Dept Clin Med, Diabet Res Unit, Colombo, Sri Lanka. [Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland. [Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland. [Khor, Chiea-Chuen; Liu, Jian Jun; Seielstad, Mark; Teo, Yik Ying] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore. [Kim, Hyung-Lae] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul, South Korea. [Kim, Sangsoo] Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea. [Kinnunen, Leena; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Kong, Augustine; Stefansson, Kari; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Korpi-Hyovalti, Eeva] South Ostrobothnia Cent Hosp, Seinajoki, Finland. [Kowlessur, Sudhir] Minist Hlth, Port Louis, Mauritius. [Krithika, S.; Parra, Esteban J.] Univ Toronto, Dept Anthropol, Mississauga, ON L5L 1C6, Canada. [Kumate, Jesus] Fdn IMSS, Mexico City, DF, Mexico. [Kuusisto, Johanna; Laakso, Markku; Stancakova, Alena] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku; Stancakova, Alena] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland. [Lawrence, Robert] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia. [Lee, Nanette R.] Univ San Carlos, Off Populat Studies Fdn Inc, Cebu, Philippines. [Li, Xinzhong; Scott, James; Sehmi, Joban; Kooner, Jaspal] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England. [Li, Yun; Mohlke, Karen L.; Wu, Ying] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Li, Yun] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Liang, Junbin; Yang, Mingyu; Zhang, Fan] Beijing Genom Inst, Shenzhen, Peoples R China. [Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden. [Loos, Ruth J. F.] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA. [Loos, Ruth J. F.] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY USA. [Loos, Ruth J. F.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA. [Lu, Wei] Shanghai Inst Prevent Med, Shanghai, Peoples R China. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Mohan, Viswanathan] Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. [Musk, Bill] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Nakamura, Jiro; Nakashima, Eitaro] Nagoya Univ, Grad Sch Med, Div Endocrinol & Diabet, Dept Internal Med, Nagoya, Aichi 4648601, Japan. [Nakashima, Eitaro] Chubu Rosai Hosp, Dept Endocrinol & Diabet, Nagoya, Aichi, Japan. [Njolstad, Inger; Wilsgaard, Tom] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway. [Ohnaka, Keizo] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Higashi Ku, Fukuoka 812, Japan. [Owen, Katharine R.; McCarthy, Mark I.] Churchill Hosp, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford OX3 7LJ, England. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Park, Kyong Soo] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, World Class Univ Program, Seoul, South Korea. [Park, Kyong Soo] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Pedersen, Nancy L.; Rehnberg, Emil] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Peltonen, Leena; Ripatti, Samuli; Tikkanen, Emmi] Inst Mol Med Finland FIMM, Helsinki, Finland. [Peters, Annette; Thorand, Barbara] Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany. [Pinidiyapathirage, Janani M.; Wickremasinghe, Ananda R.] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka. [Platou, Carl G. P.] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway. [Rallidis, Loukianos] Univ Gen Hosp Attikon, Athens, Greece. [Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany. [Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland. [Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Partners Ctr Personalized Genom Med, Boston, MA USA. [Roden, Michael] Univ Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany. [Roden, Michael] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany. [Rossin, Elizabeth J.] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA. [Rossin, Elizabeth J.] MIT, Boston, MA USA. [Rossin, Elizabeth J.] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Saaristo, Timo E.] Finnish Diabet Assoc, Tampere, Finland. [Saaristo, Timo E.] Pirkanmaa Hosp Dist, Tampere, Finland. [Saltevo, Juha] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland. [Saramies, Jouko] South Karelia Cent Hosp, Lappeenranta, Finland. [Shah, Sonia; Zabaneh, Delilah] UCL, Dept Genet Evolut & Environm, Genet Inst, London, England. [Shera, A. Samad] Diabet Assoc Pakistan, Karachi, Pakistan. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalised & Genom Med, Baltimore, MD 21201 USA. [Sijbrands, Eric; Uitterlinden, Andre G.; Wennauer, Roman] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Steinbach, Gerald] Univ Ulm, Dept Clin Chem, D-89069 Ulm, Germany. [Steinbach, Gerald] Univ Ulm, Cent Lab, D-89069 Ulm, Germany. [Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Takayanagi, Ryoichi] Kyushu Univ, Grad Sch Med Sci, Dept Internal Med & Bioregulatory Sci, Higashi Ku, Fukuoka 812, Japan. [Tuomi, Tiinamaija] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland. [Tuomilehto, Jaakko] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia. [Valladares-Salgado, Adan; Cruz, Miguel] IMSS, Ctr Med Nacl Siglo 21, Hosp Especialidades, Unidad Invest Med Bioquim, Mexico City, DF, Mexico. [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Wong, Tien Yin] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia. [Yamamoto, Ken] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 812, Japan. [Yengo, Loic] Univ Lille 1, Math Lab, CNRS UMR 8524, MODAL Team,INRIA Lille Nord Europe, F-59655 Villeneuve Dascq, France. [Yokota, Mitsuhiro] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Bowden, Donald W.] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA. [Bowden, Donald W.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea. [Hanis, Craig L.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Kooner, Jaspal; Chambers, John C.] Imperial Coll Healthcare NHS Trust, London, England. [Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Seielstad, Mark] Blood Syst Res Inst, San Francisco, CA USA. [Teo, Yik Ying] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore. [Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Tai, E. Shyong] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore. [Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England. RP Boehnke, M (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. EM boehnke@umich.edu; esteban.parra@utoronto.ca; john.chambers@imperial.ac.uk; e_shyong_tai@nuhs.edu.sg; mark.mccarthy@drl.ox.ac.uk; a.p.morris@liverpool.ac.uk RI Kinnunen, Leena/B-7059-2012; Prokopenko, Inga/H-3241-2014; Thorand, Barbara/B-5349-2014; Chan, Juliana /B-7918-2016; Peters, Annette/A-6117-2011; Rudan, Igor/I-1467-2012; Veglia, Fabrizio/K-1958-2016; Study, GoDARTS/K-9448-2016; Hayward, Caroline/M-8818-2016; Johnson, Andrew/G-6520-2013; Leander, Karin/C-7261-2017; Ma, Ronald/C-2788-2009; Yengo, Loic/D-2692-2017; Baldassarre, Damiano/J-3295-2016; Palmer, Colin/C-7053-2008; Shah, Sonia/N-7547-2013; Deloukas, Panos/B-2922-2013; Strawbridge, Rona/H-5422-2012; Jia, Weiping/B-7483-2012; Dina, Christian/D-3535-2015; Hu, Cheng/C-3346-2008; Boehm, Bernhard/F-8750-2015; Kwak, Soo Heon/H-1463-2011; Grallert, Harald/B-3424-2013; Tsai, Fuu-Jen/J-4140-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; OI Kumar, Ashish/0000-0002-7075-5930; Fraser, Ross/0000-0003-0488-2592; Kinnunen, Leena/0000-0001-8739-4812; van Dam, Rob/0000-0002-7354-8734; Lakka, Timo/0000-0002-9199-2871; Gigante, Bruna/0000-0003-4508-7990; Humphries, Stephen E/0000-0002-8221-6547; Gieger, Christian/0000-0001-6986-9554; Hydrie, Muhammad/0000-0002-1317-6975; Magi, Reedik/0000-0002-2964-6011; Sijbrands, Eric/0000-0001-8857-7389; Rybin, Denis/0000-0002-3657-4829; Chang, Yi-Cheng/0000-0002-8077-5011; Pinidiyapathirage, Mohitha/0000-0003-2947-3015; Seielstad, Mark/0000-0001-5783-1401; CHANG, TIEN-JYUN/0000-0001-9437-5847; TREMOLI, ELENA/0000-0002-0929-6106; Prokopenko, Inga/0000-0003-1624-7457; Thorand, Barbara/0000-0002-8416-6440; Chan, Juliana /0000-0003-1325-1194; Rudan, Igor/0000-0001-6993-6884; Veglia, Fabrizio/0000-0002-9378-8874; Hayward, Caroline/0000-0002-9405-9550; Leander, Karin/0000-0002-1404-9222; Ma, Ronald/0000-0002-1227-803X; Yengo, Loic/0000-0002-4272-9305; Baldassarre, Damiano/0000-0002-2766-8882; Palmer, Colin/0000-0002-6415-6560; Shah, Sonia/0000-0001-5860-4526; Deloukas, Panos/0000-0001-9251-070X; Strawbridge, Rona/0000-0001-8506-3585; Dina, Christian/0000-0002-7722-7348; Kwak, Soo Heon/0000-0003-1230-0919; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Small, Kerrin/0000-0003-4566-0005; Khor, Chiea Chuen/0000-0002-1128-4729; Eriksson, Johan/0000-0002-2516-2060; Tai, E Shyong/0000-0003-2929-8966; Pankow, James/0000-0001-7076-483X; Hattersley, Andrew/0000-0001-5620-473X; Zeggini, Eleftheria/0000-0003-4238-659X; CHUANG, LEE-MING/0000-0003-0978-2662; Manickam, Chidambaram/0000-0001-8750-8576; Hedman, Asa/0000-0001-5413-204X; Forouhi, Nita/0000-0002-5041-248X; Nothen, Markus/0000-0002-8770-2464; Chen, Han/0000-0002-9510-4923; Tuomi, Tiinamaija/0000-0002-8306-6202; Navarro, Pau/0000-0001-5576-8584; parra, esteban J/0000-0002-2057-8577 FU Canadian Institutes of Health Research; European Commission (ENGAGE FP7) [HEALTH-F4-2007-201413]; Medical Research Council UK [G0601261]; Mexico Convocatoria [SSA/IMMS/ISSSTE-CONACYT 2012-2, clave 150352, IMSS R-2011-785-018, CONACYT Salud-2007-C01-71068]; US National Institutes of Health [DK062370, HG000376, DK085584, DK085545, DK073541, DK085501]; Wellcome Trust [WT098017, WT090532, WT090367, WT098381, WT081682, WT085475] FX Funding for the research undertaken in this study has been received from the following: the Canadian Institutes of Health Research; the European Commission (ENGAGE FP7 HEALTH-F4-2007-201413); the Medical Research Council UK (G0601261); the Mexico Convocatoria (SSA/IMMS/ISSSTE-CONACYT 2012-2, clave 150352, IMSS R-2011-785-018 and CONACYT Salud-2007-C01-71068); the US National Institutes of Health (DK062370, HG000376, DK085584, DK085545, DK073541 and DK085501); and the Wellcome Trust (WT098017, WT090532, WT090367, WT098381, WT081682 and WT085475). We acknowledge the many colleagues who contributed to collection and phenotypic characterization of the clinical samples and the genotyping and analysis of the GWAS data, full details of which are provided in the contributing consortia papers5,11,13,15. We also thank those individuals who agreed to participate in this study. NR 51 TC 207 Z9 208 U1 18 U2 119 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAR PY 2014 VL 46 IS 3 BP 234 EP + DI 10.1038/ng.2897 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AB8JR UT WOS:000332036700007 ER PT J AU Joshi, I Yoshida, T Jena, N Qi, XQ Zhang, JW Van Etten, RA Georgopoulos, K AF Joshi, Ila Yoshida, Toshimi Jena, Nilamani Qi, Xiaoqing Zhang, Jiangwen Van Etten, Richard A. Georgopoulos, Katia TI Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia SO NATURE IMMUNOLOGY LA English DT Article ID FOCAL ADHESION KINASE; TYROSINE KINASE; IG-BETA; TRANSCRIPTION FACTOR; GENE RECOMBINATION; TUMOR-SUPPRESSOR; BONE-MARROW; DIFFERENTIATION; RECEPTOR; EXPRESSION AB Deletion of the DNA-binding domain of the transcription factor Ikaros generates dominant-negative isoforms that interfere with its activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic leukemia (B-ALL). Here we found that conditional inactivation of the Ikaros DNA-binding domain in early pre-B cells arrested their differentiation at a stage at which integrin-dependent adhesion to niches augmented signaling via mitogen-activated protein kinases, proliferation and self-renewal and attenuated signaling via the pre-B cell signaling complex (pre-BCR) and the differentiation of pre-B cells. Transplantation of polyclonal Ikaros-mutant pre-B cells resulted in long-latency oligoclonal pre-B-ALL, which demonstrates that loss of Ikaros contributes to multistep B cell leukemogenesis. Our results explain how normal pre-B cells transit from a highly proliferative and stroma-dependent phase to a stroma-independent phase during which differentiation is enabled, and suggest potential therapeutic strategies for Ikaros-mutant B-ALL. C1 [Joshi, Ila; Yoshida, Toshimi; Qi, Xiaoqing; Georgopoulos, Katia] Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02138 USA. [Jena, Nilamani; Van Etten, Richard A.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA. [Zhang, Jiangwen] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02138 USA. EM vanetten@uci.edu; katia.georgopoulos@cbrc2.mgh.harvard.edu FU US National Institutes of Allergy and Infectious Diseases [5R01AI 42254-14]; National Cancer Institute [5R01CA162092-20, CA090576] FX We thank B. Czyzewski for mouse husbandry; K. White, J.M. Park, B. Morgan, R. Bakshi, E. Alonzo and J. Seavitt for critical review of the manuscript; R. Bakshi for assistance with statistical analysis; and R. Arya for assistance with confocal microscopy. High-throughput DNA sequencing was done at the Bauer Center for Genomic Research (Harvard University). Supported by the US National Institutes of Allergy and Infectious Diseases (American Recovery and Reinvestment Act supplement to 5R01AI 42254-14) and the National Cancer Institute (5R01CA162092-20 to K.G. and CA090576 to R.A.V.E.). NR 50 TC 42 Z9 45 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2014 VL 15 IS 3 BP 294 EP 304 DI 10.1038/ni.2821 PG 11 WC Immunology SC Immunology GA AB3HY UT WOS:000331683100015 PM 24509510 ER PT J AU O'Donoghue, ML AF O'Donoghue, Michelle L. TI Targeting inflammation-what has the VISTA-16 trial taught us? SO NATURE REVIEWS CARDIOLOGY LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; A(2) AB The VISTA-16 trial of varespladib, a secretory phospholipase A(2) (sPLA(2)) inhibitor, in patients with an acute coronary syndrome was terminated prematurely owing to futility and a signal towards harm. Despite these discouraging results, therapies that target inflammation to modify pathways in atherogenesis remain an area of active investigation. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org NR 10 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 EI 1759-5010 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD MAR PY 2014 VL 11 IS 3 BP 130 EP 131 DI 10.1038/nrcardio.2013.220 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AB7AA UT WOS:000331940500001 PM 24419257 ER PT J AU Leung, AM Braverman, LE AF Leung, Angela M. Braverman, Lewis E. TI Consequences of excess iodine SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Review ID AMIODARONE-INDUCED THYROTOXICOSIS; THYROID-FUNCTION; URINARY IODINE; CONTRAST-MEDIA; SUBCLINICAL HYPOTHYROIDISM; DIETARY IODINE; POLYVINYLPYRROLIDONE-IODINE; CONGENITAL HYPOTHYROIDISM; EUTHYROID PATIENTS; SUFFICIENT AREA AB Iodine is a micronutrient that is essential for the production of thyroid hormones. The primary source of iodine is the diet via consumption of foods that have been fortified with iodine, including salt, dairy products and bread, or that are naturally abundant in the micronutrient, such as seafood. Recommended daily iodine intake is 150 mu g in adults who are not pregnant or lactating. Ingestion of iodine or exposure above this threshold is generally well-tolerated. However, in certain susceptible individuals, including those with pre-existing thyroid disease, the elderly, fetuses and neonates, or patients with other risk factors, the risk of developing iodine-induced thyroid dysfunction might be increased. Hypothyroidism or hyperthyroidism as a result of supraphysiologic iodine exposure might be either subclinical or overt, and the source of the excess iodine might not be readily apparent. C1 [Leung, Angela M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol,VA Greater Los Angeles Healthcare, Los Angeles, CA 90073 USA. [Braverman, Lewis E.] Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. RP Braverman, LE (reprint author), Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, 88 East Newton St, Boston, MA 02118 USA. EM lewis.braverman@bmc.org OI Leung, Angela M./0000-0001-8935-9332 FU NIH [7K23HD06855204] FX A. M. Leung would like to acknowledge the support of NIH grant 7K23HD06855204. NR 80 TC 45 Z9 48 U1 6 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD MAR PY 2014 VL 10 IS 3 BP 136 EP 142 DI 10.1038/nrendo.2013.251 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AB6HS UT WOS:000331888800005 PM 24342882 ER PT J AU Hou, SS Rice, WL Bacskai, BJ Kumar, ATN AF Hou, Steven S. Rice, William L. Bacskai, Brian J. Kumar, Anand T. N. TI Tomographic lifetime imaging using combined early- and late-arriving photons SO OPTICS LETTERS LA English DT Article ID FLUORESCENCE TOMOGRAPHY; TURBID MEDIA; ALLOWS AB We present a novel, hybrid approach for time domain fluorescence tomography that efficiently combines lifetime multiplexing using late-arriving or asymptotic photons, with the high spatial resolution capability of early photon tomography. We also show that a decay amplitude-based asymptotic approach is superior to direct inversion of late-arriving photons for tomographic lifetime imaging within turbid media. The hybrid reconstruction approach is experimentally shown to recover fluorescent inclusions separated as close as 1.4 mm, with improved resolution and reduced cross talk compared to just using early photons or the asymptotic approach alone. (C) 2014 Optical Society of America C1 [Hou, Steven S.; Bacskai, Brian J.] Harvard Univ, Sch Med, Alzheimers Dis Res Unit, Massachusetts Gen Hosp,Dept Neurol, Charlestown, MA 02129 USA. [Rice, William L.; Kumar, Anand T. N.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Charlestown, MA 02129 USA. RP Kumar, ATN (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Charlestown, MA 02129 USA. EM ankumar@nmr.mgh.harvard.edu FU National Institutes of Health [R01 EB015325, R01 EB000768] FX This work was supported by the National Institutes of Health Grants R01 EB015325 and R01 EB000768. NR 15 TC 13 Z9 13 U1 1 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD MAR 1 PY 2014 VL 39 IS 5 BP 1165 EP 1168 DI 10.1364/OL.39.001165 PG 4 WC Optics SC Optics GA AC1DB UT WOS:000332233300016 PM 24690697 ER PT J AU Platt, M Dilwali, S Elackattu, A Parikh, JR Stankovic, KM AF Platt, Michael Dilwali, Sonam Elackattu, Alphi Parikh, Jignesh R. Stankovic, Konstantina M. TI Mining Immune Epitopes in the Inner Ear SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE computational; Meniere's disease; epitopes; hearing loss; bioinformatics; cross-reactivity; autoimmune inner ear disease; inner ear disease ID HEARING-LOSS AB Etiologies for many inner ear disorders, including autoimmune inner ear disease, sudden sensorineural hearing loss, and Meniere's disease, remain unknown. Indirect evidence suggests an immune-mediated process involving an allergic or autoimmune mechanism. We examined whether known immunogenic proteins share sequence similarity with inner ear proteins, which may lead to cross-reactivity and detrimental immune activation. Comprehensive bioinformatic analyses of primary sequences of intact and mutated proteins associated with human hearing loss and all proteins known to be expressed in the human inner ear were compared with all immune epitopes in the Immune Epitope Database. The exact match and basic local alignment search tool computational algorithms identified 3036 and 106 unique epitope matches, respectively, the majority of which were infectious epitopes. If validated in future clinical trials, these candidate immune epitopes in the inner ear would be potential novel targets for diagnosis and treatment of some inner ear disorders and the resulting hearing loss. C1 [Platt, Michael; Elackattu, Alphi] Boston Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. [Dilwali, Sonam; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Dilwali, Sonam; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Dilwali, Sonam; Stankovic, Konstantina M.] Harvard Massachusetts Inst Technol Joint Div Hlth, Program Speech & Hearing Biosci & Technol, Cambridge, MA USA. [Parikh, Jignesh R.] Boston Univ, Dept Engn, Boston, MA 02215 USA. [Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Konstantina_stankovic@meei.harvard.edu FU National Institutes of Health NIDCD [K08 DC010419, T32 DC00038]; Bertarelli Foundation FX We are grateful for support from the National Institutes of Health NIDCD grants K08 DC010419 (K. M. S.) and T32 DC00038 (S. D.), and the Bertarelli Foundation (K.M.S.). NR 5 TC 2 Z9 3 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2014 VL 150 IS 3 BP 460 EP 463 DI 10.1177/0194599813514725 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AB3QR UT WOS:000331705800022 PM 24367049 ER PT J AU Majnoon, MT Mamishi, S Moazzami, K Shahbaznejad, L Izadyar, M Sabouni, F Koochakzadeh, L Ramyar, A Aghamohammadi, A Rezaei, N AF Majnoon, Mohammad Taghi Mamishi, Setareh Moazzami, Kasra Shahbaznejad, Leila Izadyar, Mina Sabouni, Farah Koochakzadeh, Leila Ramyar, Asghar Aghamohammadi, Asghar Rezaei, Nima TI Spectrum of Bone Marrow Failures of Myeloid Series: New Report of Neutropenic Patients from a Referral Pediatric Center in Iran SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE infections; neutropenia; severe congenital neutropenia ID SEVERE CONGENITAL NEUTROPENIA; PRIMARY IMMUNODEFICIENCY DISORDERS; X-LINKED AGAMMAGLOBULINEMIA; HAX1 DEFICIENCY; MUTATIONS; DIAGNOSIS; DISEASES; REGISTRY; CHILDREN AB Neutropenia is a reduction of the absolute neutrophil count (ANC), which could be seen in different conditions, while its association with a number of primary immunodeficiency diseases has been reported. This study was performed in all neutropenic patients who were admitted in a referral pediatric hospital during a 6-year period (2006-2011). One hundred and forty patients with ANC of below 1500/mm(3) were investigated in this study. The most common causes of neutropenia were severe congenital neutropenia (41%), aplastic anemia (19%), cyclic neutropenia (11%), hyperimmunoglobulin M syndrome (9%), and fanconi anemia (7%). The patients experienced their first manifestation at a median age of 1 year, while the median diagnostic age was 21 months. Parental consanguinity was present in about half of the cases. The most common clinical manifestations of the patients were sinusitis (62 cases), periodontitis (51 cases), acute diarrhea (39 cases), pneumonia (38 cases), abscess (36 cases), skin rashes (35 cases), and otitis media (31 cases). Twenty two patients (16%) died during the study period. Considering the differential diagnosis of neutropenia, making the diagnosis and appropriate treatments are the keys in management of patients with neutropenia to avoid further complications. C1 [Majnoon, Mohammad Taghi; Mamishi, Setareh; Shahbaznejad, Leila; Izadyar, Mina; Sabouni, Farah; Koochakzadeh, Leila; Ramyar, Asghar; Aghamohammadi, Asghar; Rezaei, Nima] Univ Tehran Med Sci, Childrens Med Ctr, Pediat Ctr Excellence, Tehran, Iran. [Mamishi, Setareh; Sabouni, Farah] Univ Tehran Med Sci, Pediat Infect Dis Res Ctr, Tehran, Iran. [Moazzami, Kasra] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Aghamohammadi, Asghar; Rezaei, Nima] Univ Tehran Med Sci, Childrens Med Ctr, Res Ctr Immunodeficiencies, Tehran, Iran. [Rezaei, Nima] Univ Tehran Med Sci, Sch Med, Tehran, Iran. [Rezaei, Nima] Univ Tehran Med Sci, Sch Med, Dept Immunol, Tehran, Iran. RP Rezaei, N (reprint author), Childrens Med Ctr Hosp, Dr Qarib St,Keshavarz Blvd, Tehran 14194, Iran. EM rezaei_nima@tums.ac.ir RI Rezaei, Nima/B-4245-2008 OI Rezaei, Nima/0000-0002-3836-1827 FU Tehran University of Medical Sciences [90-03-30-14657] FX This work was supported by a grant (90-03-30-14657) from Tehran University of Medical Sciences. NR 28 TC 0 Z9 0 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0888-0018 EI 1521-0669 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD MAR PY 2014 VL 31 IS 2 BP 109 EP 116 DI 10.3109/08880018.2012.762594 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AB6OM UT WOS:000331909200001 PM 23363289 ER PT J AU LaMotte, AD Taft, CT Weatherill, RP Scott, JP Eckhardt, CI AF LaMotte, Adam D. Taft, Casey T. Weatherill, Robin P. Scott, Jillian Panuzio Eckhardt, Christopher I. TI Examining Intimate Partner Aggression Assessment Among Returning Veterans and Their Partners SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE intimate partner aggression; concordance; veterans; OIF/OEF ID POSTTRAUMATIC-STRESS-DISORDER; CONFLICT-TACTICS-SCALES; REPORTING CONCORDANCE; VIETNAM VETERANS; VIOLENCE; AGREEMENT; MILITARY; MARRIAGE; RATES; MEN AB There is a growing research base focusing on intimate partner aggression (IPA) in combat veterans, although little work has focused on IPA assessment. In the current study, the authors investigated IPA assessment among 65 male Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) combat veterans and their female partners. Specifically, we compared overall levels of veteran- and partner-perpetrated IPA, conducted concordance analyses to examine the degree of interpartner agreement on IPA occurrence and frequency, and investigated both veterans' and partners' relationship satisfaction and posttraumatic stress disorder (PTSD) symptoms as correlates of concordance. Results indicated that female partners perpetrated higher levels of physical IPA than did the male veterans, according to both veteran and combined reports. Concordance analyses revealed low to moderate levels of agreement between veterans and their partners on the perpetration of physical and psychological IPA, with particularly low agreement on the veterans' physical IPA. Female partners' relationship satisfaction was associated with reporting less of the veterans' and their own IPA relative to the veterans' reports, and their PTSD symptoms were associated with reporting more of the veterans' and their own IPA. In contrast, the veterans' PTSD symptoms were associated with reporting less of their own IPA relative to their partners' reports. The findings emphasize the need for those researching and treating IPA among military couples to assess IPA perpetrated by both members of the relationship and to consider possible factors that might impact the accuracy of IPA reporting. C1 [LaMotte, Adam D.; Taft, Casey T.; Weatherill, Robin P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Taft, Casey T.; Weatherill, Robin P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Scott, Jillian Panuzio] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. [Eckhardt, Christopher I.] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B-4, Boston, MA 02130 USA. EM casey.taft@va.gov NR 38 TC 10 Z9 10 U1 0 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 2014 VL 26 IS 1 BP 8 EP 15 DI 10.1037/a0034579 PG 8 WC Psychology, Clinical SC Psychology GA AB5ZJ UT WOS:000331866900002 PM 24079959 ER PT J AU Eshleman, AJ Forster, MJ Wolfrum, KM Johnson, RA Janowsky, A Gatch, MB AF Eshleman, Amy J. Forster, Michael J. Wolfrum, Katherine M. Johnson, Robert A. Janowsky, Aaron Gatch, Michael B. TI Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function SO PSYCHOPHARMACOLOGY LA English DT Article DE Substituted phenethylamines; Drug discrimination; Serotonin receptor; Locomotor activity; Lysergic acid diethylamide (LSD); (-)-2,5-dimethoxy-4-methylamphetamine; Drug abuse ID LYSERGIC-ACID DIETHYLAMIDE; 5-HT2C RECEPTORS; PHOSPHOLIPASE-C; HALLUCINOGENIC PHENETHYLAMINE; PHOSPHOINOSITIDE HYDROLYSIS; SEROTONIN 5-HT2A; STIMULUS; AGONIST; MDMA; LSD AB Psychoactive-substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2); and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. This study compares the behavioral effects and the mechanisms of action of these substituted phenethylamines with those of hallucinogens and a stimulant. The effects of these compounds on mouse locomotor activity and in rats trained to discriminate dimethyltryptamine, (-)-DOM, (+)-LSD, (+/-)-MDMA, and S(+)-methamphetamine were assessed. Binding and functional activity of the phenethylamines at 5-HT1A, 5-HT2A, 5-HT2C receptors and monoamine transporters were assessed using cells heterologously expressing these proteins. The phenethylamines depressed mouse locomotor activity, although 2C-D and 2C-E stimulated activity at low doses. The phenethylamines except 2C-T-2 fully substituted for at least one hallucinogenic training compound, but none fully substituted for (+)-methamphetamine. At 5-HT1A receptors, only 2C-T-2 and 2C-I were partial-to-full very low potency agonists. In 5-HT2A arachidonic acid release assays, the phenethylamines were partial to full agonists except 2C-I which was an antagonist. All compounds were full agonists at 5-HT2A and 5-HT2C receptor inositol phosphate assays. Only 2C-I had moderate affinity for, and very low potency at, the serotonin transporter. The discriminative stimulus effects of 2C-C, 2C-D, 2C-E, 2C-I, and DOC were similar to those of several hallucinogens, but not methamphetamine. Additionally, the substituted phenethylamines were full agonists at 5-HT2A and 5-HT2C receptors, but for 2C-T-2, this was not sufficient to produce hallucinogen-like discriminative stimulus effects. Additionally, the 5-HT2A inositol phosphate pathway may be important in 2C-I's psychoactive properties. C1 [Eshleman, Amy J.; Wolfrum, Katherine M.; Johnson, Robert A.; Janowsky, Aaron] Portland VA Med Ctr, Res Serv, Portland, OR USA. [Eshleman, Amy J.; Janowsky, Aaron] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Eshleman, Amy J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Forster, Michael J.; Gatch, Michael B.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Janowsky, Aaron] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland, OR 97239 USA. RP Eshleman, AJ (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. EM eshleman@ohsu.edu FU National Institutes of Health National Institute on Drug Abuse/Veterans Affairs Interagency agreements [Y1 DA 5007-05, Y1-DA-0101-01]; Methamphetamine Abuse Research Center [P50 DA018165]; Veterans Affairs Research Career program; Veterans Affairs Merit Review program; National Institute on Drug Abuse [N01DA2-8822, N01DA-7-8872] FX Funding for this study was provided by National Institutes of Health National Institute on Drug Abuse/Veterans Affairs Interagency agreements (Y1 DA 5007-05, Y1-DA-0101-01), The Methamphetamine Abuse Research Center (P50 DA018165), the Veterans Affairs Research Career and Merit Review programs, and by the National Institute on Drug Abuse contracts (N01DA2-8822 and N01DA-7-8872). The NIDA project officers contributed to study design and had no further role in the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the paper for publication. NR 50 TC 8 Z9 8 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2014 VL 231 IS 5 BP 875 EP 888 DI 10.1007/s00213-013-3303-6 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AB3VU UT WOS:000331719100007 PM 24142203 ER PT J AU Politte, LC McDougle, CJ AF Politte, Laura C. McDougle, Christopher J. TI Atypical antipsychotics in the treatment of children and adolescents with pervasive developmental disorders SO PSYCHOPHARMACOLOGY LA English DT Review DE Atypical antipsychotics; Autism; Autistic disorder; Irritability; Neuroleptics; Pervasive developmental disorders ID AUTISM SPECTRUM DISORDERS; LONG-TERM SAFETY; OPEN-LABEL TRIAL; BEHAVIORAL SYMPTOMS; DOUBLE-BLIND; RISPERIDONE TREATMENT; ARIPIPRAZOLE; IRRITABILITY; HALOPERIDOL; ZIPRASIDONE AB Autism and related pervasive developmental disorders (PDD) are characterized by impairments in social interaction and communication, restricted interests, and repetitive and stereotyped patterns of behavior. Individuals with PDD frequently display irritability and disruptive behaviors including tantrums, self-injurious behavior, and aggression. Atypical antipsychotics are currently the most efficacious pharmacological interventions available for treatment of irritability associated with PDD. This article aims to review the body of literature pertaining to the use of atypical antipsychotics in the treatment of patients with PDD. A PubMed literature search was conducted using the following key words: autism, pervasive developmental disorders, atypical antipsychotics, risperidone, aripiprazole, quetiapine, ziprasidone, olanzapine, clozapine, paliperidone, iloperidone, asenapine, and lurasidone. Search terms were limited to English language, human subjects, and publication from 1999 to present. Relevant references from identified articles were also reviewed. The efficacy and tolerability of risperidone and aripiprazole for the treatment of irritability in autism have been established with multi-site, randomized, controlled trials. Studies supporting the use of other atypical antipsychotics are either limited in scope or less robust in their findings, though newer agents such as ziprasidone and paliperidone show promise. Atypical antipsychotics are currently first-line pharmacological agents for the treatment of irritability and associated behaviors in children with PDD. Further placebo-controlled studies are warranted to characterize the efficacy and tolerability of the majority of these medications. There is also a need for the development of novel, targeted drugs with more favorable long-term side effect profiles. C1 [Politte, Laura C.; McDougle, Christopher J.] Harvard Univ, Sch Med, Dept Psychiat & Pediat, Lurie Ctr Autism,Massachusetts Gen Hosp,MassGen H, Lexington, MA 02421 USA. [Politte, Laura C.; McDougle, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA. RP Politte, LC (reprint author), Harvard Univ, Sch Med, Dept Psychiat & Pediat, Lurie Ctr Autism,Massachusetts Gen Hosp,MassGen H, Lexington, MA 02421 USA. EM lpolitte@partners.org NR 57 TC 29 Z9 29 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2014 VL 231 IS 6 BP 1023 EP 1036 DI 10.1007/s00213-013-3068-y PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AB8FL UT WOS:000332025500005 PM 23552907 ER PT J AU Delahaye, J Kovacs, E Sikora, D Hall, TA Orlich, F Clemons, TE van der Weerd, E Glick, L Kuhlthau, K AF Delahaye, Jennifer Kovacs, Erica Sikora, Darryn Hall, Trevor A. Orlich, Felice Clemons, Traci E. van der Weerd, Emma Glick, Laura Kuhlthau, Karen TI The relationship between Health-Related Quality of Life and sleep problems in children with Autism Spectrum Disorders SO RESEARCH IN AUTISM SPECTRUM DISORDERS LA English DT Article DE Autism Spectrum Disorders; Health-Related Quality of Life; Sleep problems; Pediatrics; PedsQL; Children's Sleep Habits Questionnaire ID INTELLECTUAL DISABILITY; PSYCHOMETRIC PROPERTIES; HABITS QUESTIONNAIRE; ADOLESCENTS; POPULATION; SYMPTOMS; PEDSQL(TM)-4.0; DISTURBANCES; ASSOCIATIONS; RECOGNITION AB Although children with Autism Spectrum Disorders (ASD) are thought to experience sleep problems at a much higher rate than typically developing peers, the relationship between sleep disturbance and Health-Related Quality of Life (HRQoL) has not been explored within this pediatric population. Further, little is understood about the HRQoL of children with ASD in general. This study assessed the HRQoL and sleep health of a sample of children with ASD and investigated the relationship between HRQoL and overall sleep problems within the context of key clinical characteristics. Study participants included 86 parents of children with ASD between the ages of 4 and 12 years. Subjects were recruited from 3 autism specialty clinics at large academic medical centers and asked to proxy-report on their children's HRQoL and sleep habits. Adjusted regression models showed a consistent negative relationship between sleep disturbance and HRQoL, with greater overall sleep problems being associated with poorer total, physical, and psychosocial HRQoL. Sleep duration and sleep anxiety were also found to be negatively associated with HRQoL. These findings suggest that treatments that are effective in treating sleep disturbances may improve children's HRQoL. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Delahaye, Jennifer; van der Weerd, Emma; Kuhlthau, Karen] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Kovacs, Erica] Columbia Med Ctr, New York, NY 10019 USA. [Sikora, Darryn; Hall, Trevor A.] Oregon Hlth & Sci Univ, Child Dev & Rehabil Ctr, Portland, OR 97207 USA. [Orlich, Felice] Univ Washington, Seattle Childrens Hosp, CAC Autism Ctr 4909, Seattle, WA 98105 USA. [Clemons, Traci E.] EMMES Corp, Rockville, MD 20850 USA. [Glick, Laura] Tufts Univ, Somerville, MA 02144 USA. RP Delahaye, J (reprint author), MGH CAHRP, 15th Floor C100,100 Cambridge St, Boston, MA 02114 USA. EM jdelahaye@partners.org NR 74 TC 7 Z9 7 U1 8 U2 28 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1750-9467 EI 1878-0237 J9 RES AUTISM SPECT DIS JI Res. Autism Spectr. Disord. PD MAR PY 2014 VL 8 IS 3 BP 292 EP 303 DI 10.1016/j.rasd.2013.12.015 PG 12 WC Education, Special; Psychology, Developmental; Psychiatry; Rehabilitation SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation GA AB0TR UT WOS:000331505500017 ER PT J AU Lombardero, A Campbell, DG Harris, KJ Chaney, EF Lanto, AB Rubenstein, LV AF Lombardero, Anayansi Campbell, Duncan G. Harris, Kari J. Chaney, Edmund F. Lanto, Andrew B. Rubenstein, Lisa V. TI Prevalence and correlates of smoking status among Veterans Affairs primary care patients with probable Major Depressive Disorder SO ADDICTIVE BEHAVIORS LA English DT Article DE Smoking; Depression; PTSD; Veterans; Primary care; Alcohol misuse ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; SOCIAL SUPPORT SURVEY; CIGARETTE-SMOKING; SUICIDAL IDEATION; MENTAL-HEALTH; PSYCHIATRIC-DISORDERS; ALCOHOL-CONSUMPTION; SUBSEQUENT RISK; FOLLOW-UP AB In an attempt to guide planning and optimize outcomes for population-specific smoking cessation efforts, the present study examined smoking prevalence and the demographic, clinical and psychosocial characteristics associated with smoking among a sample of Veterans Affairs primary care patients with probable major depression. Survey data were collected between 2003 and 2004 from 761 patients with probable major depression who attended one of 10 geographically dispersed VA primary care clinics. Current smoking prevalence was 39.8%. Relative to nonsmokers with probable major depression, bivariate comparisons revealed that current smokers had higher depression severity, drank more heavily, and were more likely to have comorbid PTSD. Smokers with probable major depression were also more likely than nonsmokers with probable major depression to have missed a health care appointment and to have missed medication doses in the previous 5 months. Smokers were more amenable than non-smokers to depression treatment and diagnosis, and they reported more frequent visits to a mental health specialist and less social support Alcohol abuse and low levels of social support were significant concurrent predictors of smoking status in controlled multivariable logistic regression. In conclusion, smoking prevalence was high among primary care patients with probable major depression, and these smokers reported a range of psychiatric and psychosocial characteristics with potential to complicate systems-level smoking cessation interventions. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Lombardero, Anayansi; Campbell, Duncan G.] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. [Harris, Kari J.] Univ Montana, Sch Publ & Community Hlth Sci, Missoula, MT 59812 USA. [Chaney, Edmund F.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Chaney, Edmund F.] Univ Washington, Sch Med, Warren G Magnuson Hlth Sci Ctr, Seattle, WA 98195 USA. [Lanto, Andrew B.; Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Rubenstein, Lisa V.] RAND Hlth Program, Santa Monica, CA 90407 USA. RP Lombardero, A (reprint author), Univ Montana, Dept Psychol, 32 Campus Dr, Missoula, MT 59812 USA. EM anayansilombardero@gmail.com FU VA Health Services Research & Development service; VA Mental Health Quality Enhancement Research Initiative [MHI-99-375, MNT 01-027, MHQ 10-06] FX This work was funded by the VA Health Services Research & Development service and the VA Mental Health Quality Enhancement Research Initiative (MHI-99-375, MNT 01-027, and MHQ 10-06). NR 87 TC 5 Z9 5 U1 6 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD MAR PY 2014 VL 39 IS 3 BP 538 EP 545 DI 10.1016/j.addbeh.2013.10.030 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AA5SU UT WOS:000331160700007 PM 24290879 ER PT J AU Gilmore, AK Koo, KH Nguyen, HV Granato, HF Hughes, TL Kaysen, D AF Gilmore, Amanda K. Koo, Kelly H. Nguyen, Hong V. Granato, Holline F. Hughes, Tonda L. Kaysen, Debra TI Sexual assault, drinking norms, and drinking behavior among a national sample of lesbian and bisexual women SO ADDICTIVE BEHAVIORS LA English DT Article DE Alcohol use; Sexual assault; Lesbian and bisexual women; Drinking norms ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE-USE; ALCOHOL-CONSUMPTION; COLLEGE-STUDENTS; SOCIAL NORMS; NORMATIVE MISPERCEPTIONS; RISK BEHAVIORS; BINGE DRINKING; MENTAL-HEALTH; VICTIMIZATION AB Childhood sexual abuse (CSA) and adolescent/adult sexual assault (ASA) are strongly associated with women's alcohol use and the rates of both alcohol use and sexual assault history are higher among lesbian and bisexual women than heterosexual women. Although descriptive drinking norms are one of the highest predictors of alcohol use in emerging adults, this is the first study to examine the relationship between sexual assault history, drinking norms, and alcohol use in lesbian and bisexual women. We found that CSA severity was associated with a higher likelihood of experiencing more severe alcohol-involved ASA, more severe physically forced ASA, and was indirectly associated with more drinking behavior and higher drinking norms. Additionally, more severe alcohol-involved ASA was associated with higher drinking norms and more drinking behavior, but physically forced ASA was not. These findings help explain previous contradictory findings and provide information for interventions. Published by Elsevier Ltd. C1 [Gilmore, Amanda K.; Nguyen, Hong V.; Granato, Holline F.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Koo, Kelly H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Koo, Kelly H.] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA 94121 USA. [Hughes, Tonda L.] Univ Illinois, Coll Nursing, Chicago, IL 60612 USA. [Kaysen, Debra] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98105 USA. RP Gilmore, AK (reprint author), Univ Washington, Dept Psychol, Box 351525, Seattle, WA 98195 USA. EM amandakg@uw.edu FU NIAAA [R01-AA018292]; NIAAA Grants [R01-AA018292, F31-AA020134, T32-AA007455, F31-AA018237]; Substance Abuse and Mental Health Services Administration (SAMHSA) Grant [1T06SM60563-38] FX Funding for data collection of this study was provided by NIAAA Grant R01-AA018292. Funding for analysis and interpretation of the data and writing the manuscript was provided by NIAAA Grants R01-AA018292, F31-AA020134, T32-AA007455, and F31-AA018237 and Substance Abuse and Mental Health Services Administration (SAMHSA) Grant 1T06SM60563-38. NIAAA and SAMHSA had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 72 TC 5 Z9 5 U1 9 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD MAR PY 2014 VL 39 IS 3 BP 630 EP 636 DI 10.1016/j.addbeh.2013.11.015 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AA5SU UT WOS:000331160700020 PM 24360780 ER PT J AU Knutson, KH Wei, MH Straus, JH Sarvet, B Masek, BJ Stein, BD AF Knutson, Katherine Hobbs Wei, Marlynn H. Straus, John H. Sarvet, Barry Masek, Bruce J. Stein, Bradley D. TI Medico-Legal Risk Associated with Pediatric Mental Health Telephone Consultation Programs SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Referral and consultation; Child and adolescent psychiatry; Primary care; Community mental health services ID PRIMARY-CARE; CURBSIDE CONSULTATION; DEPRESSION; MANAGEMENT; IDENTIFICATION; CHILDREN; ADOLESCENTS; MORBIDITY; DECLINE AB Clinicians providing consultation through mental health telephone consultation programs express concern about the potential legal risk of the practice. In this survey of six state mental health telephone consultation program directors, we report the annual number of children referred for consultation and the number of lawsuits against consultant clinicians. Between 2004 and 2010, 3,652 children per year were referred nationally, and there were no medical malpractice lawsuits against clinicians related to telephone consultation program activity. Although medico-legal risk is always present, the findings of this national study suggest the risk for clinicians providing mental health telephone consultation may be lower than perceived. C1 [Knutson, Katherine Hobbs; Masek, Bruce J.] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. [Wei, Marlynn H.] NYU, Sch Med, Bellevue Hosp, New York, NY USA. [Straus, John H.] Massachusetts Behav Hlth Partnership, Boston, MA USA. [Sarvet, Barry] Baystate Hlth, Div Child Psychiat, Springfield, MA USA. [Stein, Bradley D.] Univ Pittsburgh, Sch Med, RAND Corp, Pittsburgh, PA USA. RP Knutson, KH (reprint author), Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM kknutson@partners.org RI chen, jing/D-8438-2014 NR 18 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAR PY 2014 VL 41 IS 2 BP 215 EP 219 DI 10.1007/s10488-012-0448-2 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AA6HV UT WOS:000331200300007 ER PT J AU Berger, J Forss-Petter, S Eichler, FS AF Berger, J. Forss-Petter, S. Eichler, F. S. TI Pathophysiology of X-linked adrenoleukodystrophy SO BIOCHIMIE LA English DT Review DE ABC transporter; Axonopathy; Demyelination; Inflammation; Leukodystrophy; Peroxisome ID CHAIN FATTY-ACIDS; HEMATOPOIETIC-CELL TRANSPLANTATION; PEROXISOMAL ABC-TRANSPORTER; CENTRAL-NERVOUS-SYSTEM; ADRENO-LEUKODYSTROPHY; OXIDATIVE STRESS; GENE-THERAPY; MOUSE MODEL; ALD GENE; AXONAL DEGENERATION AB Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype-phenotype correlation in X-ALD. The default manifestation of mutations in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in childhood (35-40%) or in adulthood (20%), an initial, clinically silent, myelin destabilization results in conversion to a devastating, rapidly progressive form of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility gene, necessary but not sufficient for inflammatory demyelination to occur. Although the accumulation of very long-chain fatty acids appears to be essential for the pathomechanism of all phenotypes, the molecular mechanisms underlying these phenotypes are fundamentally different. Cell autonomous processes such as oxidative stress and energy shortage in axons as well as non-cell autonomous processes involving axon-glial interactions seem pertinent to the dying-back axonopathy. Various dynamic mechanisms may underlie the initiation of inflammation, the altered immune reactivity, the propagation of inflammation, as well as the mechanisms leading to the arrest of inflammation after hematopoietic stem cell transplantation. An improved understanding of the molecular mechanisms involved in these events is required for the development of urgently needed therapeutics. (C) 2013 The Authors. Published by Elsevier Masson SAS. All rights reserved. C1 [Berger, J.; Forss-Petter, S.] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria. [Eichler, F. S.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berger, J (reprint author), Med Univ Vienna, Ctr Brain Res, Spitalgasse 4, A-1090 Vienna, Austria. EM johannes.berger@meduniwien.ac.at RI Berger, Johannes/A-9122-2014 OI Berger, Johannes/0000-0003-0182-2658 FU Austrian Science Fund (FWF) [P26112-B19] FX This work was supported by the Austrian Science Fund (FWF): P26112-B19. The authors thank Dr. Ali Fatemi for providing the image for Fig. 1B and Dr. Wolfgang Kohler for his discussion and contribution to Fig. 1A. NR 94 TC 23 Z9 23 U1 1 U2 24 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 EI 1638-6183 J9 BIOCHIMIE JI Biochimie PD MAR PY 2014 VL 98 BP 135 EP 142 DI 10.1016/j.biochi.2013.11.023 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AB0TE UT WOS:000331504200015 PM 24316281 ER PT J AU Leow, JJ Feldman, AS Wagner, AA Chung, BI Chang, SL AF Leow, J. J. Feldman, A. S. Wagner, A. A. Chung, B. I. Chang, S. L. TI Propensity matched comparison of morbidity and costs associated with open, laparoscopic, and robot-assisted partial nephrectomies: a contemporary population-based analysis in the United States SO BJU INTERNATIONAL LA English DT Meeting Abstract CT Conference on Changing Paradigms in Urology (UROFAIR) CY MAR 06-08, 2014 CL SINGAPORE C1 [Leow, J. J.; Chang, S. L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Leow, J. J.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Feldman, A. S.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wagner, A. A.] Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02215 USA. [Chung, B. I.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. [Chang, S. L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD MAR PY 2014 VL 113 SU 3 SI SI BP 12 EP 12 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AA8OC UT WOS:000331353800030 ER PT J AU Chang, SL Leow, JJ Borza, T Chung, BI AF Chang, S. L. Leow, J. J. Borza, T. Chung, B. I. TI Postoperative complications of radical nephrectomy with atrial thrombectomy: a contemporary population-based analysis SO BJU INTERNATIONAL LA English DT Meeting Abstract CT Conference on Changing Paradigms in Urology (UROFAIR) CY MAR 06-08, 2014 CL SINGAPORE C1 [Chang, S. L.; Leow, J. J.; Borza, T.] Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Chang, S. L.; Leow, J. J.; Borza, T.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Chang, S. L.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Hosp, Ctr Canc, Boston, MA USA. [Chung, B. I.] Stanford Univ, Med Ctr, Dept Urol, Stanford, CA 94305 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD MAR PY 2014 VL 113 SU 3 SI SI BP 29 EP 29 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AA8OC UT WOS:000331353800078 ER PT J AU Chen, JZ Elfiky, A Han, M Chen, C Saif, MW AF Chen, Jiezhong Elfiky, Aymen Han, Mei Chen, Chen Saif, M. Wasif TI The Role of Src in Colon Cancer and Its Therapeutic Implications SO CLINICAL COLORECTAL CANCER LA English DT Review DE Immune response; MAPK; Metastasis; PI3K/Akt; STAT3; Targeted therapy ID ENDOTHELIAL GROWTH-FACTOR; FOCAL ADHESION KINASE; FAMILY TYROSINE KINASES; ADVANCED COLORECTAL CANCERS; PP60C-SRC PROTEIN-KINASE; NATURAL-KILLER-CELLS; C-SRC; CARCINOMA-CELLS; IN-VITRO; FACTOR RECEPTOR AB Src is a member of a superfamily of membrane-associated nonreceptor protein tyrosine kinases. It is stimulated by receptors of growth hormone, cytokines, and adipokines, and it regulates multiple signaling pathways, including phosphatidylinositide 3 kinase-Akt, mitogen-activated protein kinase, signal transducer and activator of transcription 3, interleukin 8, and vascular endothelial growth factor pathways, and cytoskeletal pathways to cause a cascade of cellular responses. Eighty percent of patients with colon cancer overexpress Src in tumor tissue. Evidence has shown that the overexpression of Src in colon cancer accelerates metastasis and causes chemotherapeutic drug resistance via multiple downstream signaling pathways. Therefore, the inhibition of Src may be useful for the treatment of colon cancer. However, the inhibition of Src may also weaken immune responses that are essential for the eradication of cancer cells. Overcoming the problem of inhibiting Src in cancer cells while retaining immune system efficacy is the key to the successful application of Src-inhibition therapy. Different Src family members are used by the immune system and colon cancer. This differential use may provide a good opportunity to develop Src family member-specific inhibitors to avoid immune inhibition. (C) 2014 Elsevier Inc. All rights reserved. C1 [Chen, Jiezhong; Chen, Chen] Univ Queensland, Sch Biomed Sci, St Lucia, Qld, Australia. [Elfiky, Aymen] Dana Farber Canc Ctr, Boston, MA USA. [Han, Mei] Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW, Australia. [Saif, M. Wasif] Tufts Univ, Sch Med, Gastrointestinal Colorectal Oncol Program, Boston, MA 02111 USA. [Saif, M. Wasif] Tufts Univ, Sch Med, Expt Therapeut Program, Boston, MA 02111 USA. RP Saif, MW (reprint author), Tufts Univ, Sch Med, GI Oncol Program, 800 Washington St, Boston, MA 02111 USA. EM wsaif@tuftsmedicalcenter.org RI Chen, Chen/B-4284-2010 OI Chen, Chen/0000-0003-2104-534X NR 135 TC 20 Z9 21 U1 0 U2 14 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD MAR PY 2014 VL 13 IS 1 BP 5 EP 13 DI 10.1016/j.clcc.2013.10.003 PG 9 WC Oncology SC Oncology GA AA9BD UT WOS:000331387800004 PM 24361441 ER PT J AU Couto, C de Souza, ICC Torres, ILS Fregni, F Caumo, W AF Couto, Claudio de Souza, Izabel Cristina C. Torres, Iraci L. S. Fregni, Felipe Caumo, Wolnei TI Paraspinal Stimulation Combined With Trigger Point Needling and Needle Rotation for the Treatment of Myofascial Pain: A Randomized Sham-controlled Clinical Trial SO CLINICAL JOURNAL OF PAIN LA English DT Article DE myofascial pain syndrome; acupuncture; intramuscular stimulation; sleep quality; pain threshold ID CHRONIC NECK; ACUPUNCTURE; METAANALYSIS; VALIDATION; DEPRESSION; MANAGEMENT; LIDOCAINE; CRITERIA; ANXIETY AB Background: There are different types and parameters of dry needling (DN) that can affect its efficacy in the treatment of pain that have not been assessed properly. Objective: To test the hypothesis that either multiple deep intramuscular stimulation therapy multiple deep intramuscular stimulation therapy (MDIMST) or TrP lidocaine injection (LTrP-I) is more effective than a placebo-sham for the treatment of myofascial pain syndrome (MPS) and that MDIMST is more effective than LTrP-I for improving pain relief, sleep quality, and the physical and mental state of the patient. Methods: Seventy-eight females aged 20 to 40 who were limited in their ability to perform active and routine activities due to MPS in the previous 3 months were recruited. The participants were randomized into 1 of the 3 groups as follows: placebo-sham, LTrP-I, or MDIMST. The treatments were provided twice weekly over 4 weeks using standardized MDIMST and LTrP-I protocols. Results: There was a significant interaction (time vs. group) for the main outcomes. Compared with the sham-treated group, MDIMST and LTrP-I administration improved pain scores based on a visual analog scale, the pain pressure threshold (P < 0.001 for all analyses), and analgesic use (P < 0.01 for all analyses). In addition, when comparing the active groups for these outcomes, MDIMST resulted in better improvement than LTrP-I (P < 0.01 for all analyses). In addition, both active treatments had a clinical effect, as assessed by a sleep diary and by the SF-12 physical and mental health scores. Conclusions: This study highlighted the greater efficacy of MDIMST over the placebo-sham and LTrP-I and indicated that both active treatments are more effective than placebo-sham for MPS associated with limitations in active and routine activities. C1 [Caumo, Wolnei] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Pain & Palliat Care Serv, BR-90046900 Porto Alegre, RS, Brazil. [Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Pharmacol Dept, Inst Ciencias Basicas Saude, BR-90046900 Porto Alegre, RS, Brazil. [Couto, Claudio; de Souza, Izabel Cristina C.; Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Sch Med, Post Grad Program Med Sci, BR-90046900 Porto Alegre, RS, Brazil. [de Souza, Izabel Cristina C.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Lab Pain & Neuromodulat, Hosp Clin Porto Alegre, BR-90046900 Porto Alegre, RS, Brazil. [Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Sandwich, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fregni, Felipe; Caumo, Wolnei] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Caumo, W (reprint author), Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. EM caumo@cpovo.net RI Torres, iraci/G-6693-2012 OI Torres, iraci/0000-0002-3081-115X FU Committee for the Development of Higher Education Personnel-CAPES-PNPD/CAPES; National Council for Scientific and Technological Development-CNPq; Foundation of Support of Research at Rio Grande do Sul (FAPERGS); NIH [5R21DK081773-03] FX Supported by grants from the following Brazilian agencies: The Committee for the Development of Higher Education Personnel-CAPES-PNPD/CAPES (for W. C. and I. C. C. S), the National Council for Scientific and Technological Development-CNPq (I. L. S. T. and W. C.); and the Foundation of Support of Research at Rio Grande do Sul (FAPERGS). F. F. is supported by an NIH grant (5R21DK081773-03). The authors declare no conflict of interest. NR 55 TC 14 Z9 14 U1 1 U2 14 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 MAR PY 2014 VL 30 IS 3 BP 214 EP 223 DI 10.1097/AJP.0b013e3182934b8d PG 10 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AB0CM UT WOS:000331459400005 PM 23629597 ER PT J AU Levi, A Kornowski, R Vaduganathan, M Eisen, A Vaknin-Assa, H Abu-Foul, S Lev, EI Brosh, D Bental, T Assali, AR AF Levi, Amos Kornowski, Ran Vaduganathan, Muthiah Eisen, Alon Vaknin-Assa, Hana Abu-Foul, Salma Lev, Eli I. Brosh, David Bental, Tamir Assali, Abid R. TI Incidence, predictors, and outcomes of failed primary percutaneous coronary intervention: a 10-year contemporary experience SO CORONARY ARTERY DISEASE LA English DT Article DE acute myocardial infarction; angioplasty; primary percutaneous coronary intervention ID ACUTE MYOCARDIAL-INFARCTION; IN-HOSPITAL MORTALITY; PRIMARY ANGIOPLASTY; BYPASS-SURGERY; PROGNOSIS; TERM; WOMEN; SEX; REPERFUSION; FAILURE AB BackgroundLimited contemporary data exist regarding the incidence, predictors, and outcomes of failure of primary percutaneous coronary intervention (PCI) in the treatment of ST-segment elevation myocardial infarction (STEMI).Materials and methodsIn this registry-based retrospective cohort study, all consecutive unselected patients (n=1725) who were hospitalized for STEMI and underwent primary PCI from January 2001 to December 2010 were included. PCI failure was defined as a final diameter stenosis greater than 30% or postdilatation Thrombolysis in Myocardial Infarction (TIMI) flow grade of 2 or less. We examined the predictors and survival among patients who failed primary PCI.ResultsThe overall PCI failure rate was 5.4% (94 of 1725 procedures). After adjusting for prespecified baseline characteristics, independent predictors of PCI failure included age greater than 65 years (P=0.02), procedure date between 2001 and 2005 (P=0.05), night-time PCI (P=0.008), calcific lesion (P=0.008), and lower preprocedural TIMI flow grade (P=0.006). Failed PCI was associated with a 1-year mortality rate of 22% as compared with 4.2% in the successful PCI group (P<0.001). Conservative medical management was preferred in the majority of patients with failed PCI (n=78, 83%). Patients who underwent emergent surgery (n=11), conservative management (n=78), and redo PCI (n=5) experienced 30-day mortality rates of 27, 16, and 0%, respectively.ConclusionPrimary PCI failure in the setting of STEMI is not rare. It is associated with high-risk patient-related and angiographic-related characteristics. Primary PCI failure is associated with early and late mortality. C1 [Levi, Amos; Kornowski, Ran; Eisen, Alon; Vaknin-Assa, Hana; Abu-Foul, Salma; Lev, Eli I.; Brosh, David; Bental, Tamir; Assali, Abid R.] Rabin Med Ctr, Dept Cardiol, IL-49100 Petah Tiqwa, Israel. [Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Assali, AR (reprint author), Rabin Med Ctr, Dept Cardiol, 39 Jabotinski St, IL-49100 Petah Tiqwa, Israel. EM aassali@netvision.net.il NR 28 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAR PY 2014 VL 25 IS 2 BP 145 EP 151 DI 10.1097/MCA.0000000000000065 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA6OE UT WOS:000331216900011 PM 24281252 ER PT J AU Di Vito, L Yoon, JH Kato, K Yonetsu, T Vergallo, R Costa, M Bezerra, HG Arbustini, E Narula, J Crea, F Prati, F Jang, IK AF Di Vito, Luca Yoon, Joo Heung Kato, Koji Yonetsu, Taishi Vergallo, Rocco Costa, Marco Bezerra, Hiram G. Arbustini, Eloisa Narula, Jagat Crea, Filippo Prati, Francesco Jang, Ik-Kyung CA COICO Grp Consortium Investigators TI Comprehensive overview of definitions for optical coherence tomography-based plaque and stent analyses SO CORONARY ARTERY DISEASE LA English DT Review DE optical coherence tomography; plaque rupture; stent; thin-cap fibroatheroma ID DRUG-ELUTING STENTS; ACUTE CORONARY SYNDROME; ACUTE MYOCARDIAL-INFARCTION; 6-MONTH FOLLOW-UP; FIBROUS CAP THICKNESS; GUIDE DECISION-MAKING; BARE-METAL STENTS; INTRAVASCULAR ULTRASOUND; NEOINTIMAL COVERAGE; ATHEROSCLEROTIC PLAQUES AB Optical coherence tomography (OCT) is the current state-of-the-art intracoronary imaging modality that allows visualization of detailed morphological characteristics of both atherosclerotic plaque and stent. So far, three expert review documents have been released for standardization of OCT image analysis. In the real world, a variety of definitions are being used by different groups and by different core laboratories to analyze OCT findings because of different clinical/procedural contexts in which OCT research has been carried out. This comprehensive overview is aimed to summarize different applicable definitions used by different research groups in plaque and stent analysis using OCT. In addition, it presents readers with a panoramic view to select the best definition of OCT measurement for one's own study purpose. We divided this review article into two parts: Part I - Plaque analysis, and Part II - Stent analysis. The plaque analysis section summarizes the definitions of plaque composition, rupture, erosion, protruding calcific nodules, macrophages, microvessels, and cholesterol crystal. The stent analysis section includes the classification of stent struts, features of neointimal hyperplasia, and other stent-related findings such as tissue protrusion, thrombus, intrastent, and stent edge dissections. In each case of controversy, an explanation for the specific context is provided. C1 [Di Vito, Luca; Crea, Filippo] Univ Cattolica Sacro Cuore, Dept Cardiovasc Med, Policlin A Gemelli, I-00168 Rome, Italy. [Di Vito, Luca; Prati, Francesco] San Giovanni Addolorata Hosp, Intervent Cardiol Unit, I-00184 Rome, Italy. [Di Vito, Luca; Prati, Francesco] CLI Fdn, I-00184 Rome, Italy. [Arbustini, Eloisa] Fdn IRCCS Policlin San Matteo, Transplant Res Area, Ctr Inherited Cardiovasc Dis, Pavia, Italy. [Yoon, Joo Heung] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Kato, Koji; Yonetsu, Taishi; Vergallo, Rocco; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Costa, Marco; Bezerra, Hiram G.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Narula, Jagat] Icahn Sch Med Mt Sinai, Zena & Michael A Weiner Cardiovasc Inst, New York, NY USA. RP Di Vito, L (reprint author), San Giovanni Addolorata Hosp, Intervent Cardiol Unit, Via Amba Aradam 8, I-00184 Rome, Italy. EM divitoluca.rm@gmail.com OI Arbustini, Eloisa/0000-0003-2948-7994 NR 89 TC 29 Z9 29 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAR PY 2014 VL 25 IS 2 BP 172 EP 185 DI 10.1097/MCA.0000000000000072 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AA6OE UT WOS:000331216900015 PM 24356250 ER PT J AU Muralidharan, R Mateen, FJ Rabinstein, AA AF Muralidharan, R. Mateen, F. J. Rabinstein, A. A. TI Outcome of fulminant bacterial meningitis in adult patients SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE bacteria; coma; immunosuppression; meningitis; treatment ID STAPHYLOCOCCUS-AUREUS MENINGITIS; INTENSIVE-CARE-UNIT; PNEUMOCOCCAL MENINGITIS; PROGNOSTIC-FACTORS; CLINICAL-FEATURES; CASE-SERIES; COMA SCALE; 4 SCORE; COMPLICATIONS; DEXAMETHASONE AB Background and purposeThe objective of our study was to identify neurological factors associated with poor outcome in adult patients with fulminant bacterial meningitis. MethodsThis was a retrospective review of consecutive adult patients with fulminant bacterial meningitis, defined as meningitis causing coma within 24-48h of hospitalization, at Mayo Clinic Rochester between January 2000 and November 2010. Functional status was assessed at discharge and upon last follow-up using the modified Rankin scale (mRS). The primary end-point was death or new major disability (increase of >2 on the mRS) at last follow-up. ResultsThirty-nine patients were identified. Encephalopathy (44%), coma (28%), focal seizures (3%) or a combination of these (26%) were present on admission. The most common pathogen was Streptococcus pneumoniae (57%). All patients were treated with broad spectrum antibiotics and 51% received steroids. Serious systemic complications were seen in 23 patients. Sixteen patients (41%) died during hospitalization. Median mRS at hospital discharge for surviving patients was 3; four patients had new major disability with a mean follow-up of 11months. Predictors of death or new major disability included lower Glasgow Coma Scale score at nadir [P=0.002; age- and sex-adjusted odds ratio (OR) 0.46, 95% confidence interval (CI) 0.28-0.48], longer duration of symptoms before hospitalization (P=0.045; adjusted OR 2.34, 95% CI 1.02-5.37), abnormal head imaging at presentation (P=0.008; adjusted OR 9.40, 95% CI 1.78-49.6) and use of intracranial pressure monitoring (P=0.010, adjusted OR 51.0, 95% CI 2.51-1036). ConclusionMany adult patients who survive hospitalization are able to regain their pre-morbid level of function. Aggressive management of bacterial meningitis is justified even in comatose adult patients. C1 [Muralidharan, R.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Mateen, F. J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Rabinstein, A. A.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. RP Rabinstein, AA (reprint author), Mayo Clin, Dept Neurol, W8B,200 First St SW, Rochester, MN 55905 USA. EM rabinstein.alejandro@mayo.edu NR 20 TC 4 Z9 5 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAR PY 2014 VL 21 IS 3 BP 447 EP 453 DI 10.1111/ene.12328 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3ER UT WOS:000330976200014 PM 24351087 ER PT J AU Shahim, P Rejdak, R Ksiazek, P Blennow, K Zetterberg, H Mattsson, N Rejdak, K AF Shahim, P. Rejdak, R. Ksiazek, P. Blennow, K. Zetterberg, H. Mattsson, N. Rejdak, K. TI Cerebrospinal fluid biomarkers of beta-amyloid metabolism and neuronal damage in epileptic seizures SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE amyloid; heart-type fatty acid binding protein; neuronal injury; seizures; amyloid precursor protein; tau ID ACID-BINDING PROTEIN; ALZHEIMERS-DISEASE; IN-VIVO; TAU; MODELS; BRAIN; HYPEREXCITABILITY; PATHOLOGY; RELEASE; NETWORK AB Background and purposeThe main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of -amyloid (A), as reflected by cerebrospinal fluid (CSF) levels of different isoforms of A peptides and soluble amyloid precursor protein (APP), and neuronal degeneration, as reflected by CSF biomarker signs of acute neuronal injury. MethodsForty-five patients were included, 21 of whom had single generalized tonic-clonic seizures sGTCS), 11 had repetitive GTCS, 7 had repetitive partial seizures (rPS), 6 had single partial seizure (sPS) and 4 fulfilled the criterion for non-convulsive status epilepticus (nSE). CSF was analyzed for Ax-38, Ax-40, Ax-42, A1-42, soluble APP fragments (sAPP-/), total-tau (T-tau) and phosphorylated tau (P-tau), as well as heart-type fatty acid binding protein (H-FABP). ResultsPatients with seizures had decreased levels of T-tau (P=0.0016) and P-tau (P=0.0028) compared with controls, but no differences in H-FABP (P=0.67). There were no overall differences in A or sAPP peptides between seizure patients and controls. In patients with rPS, the levels of Ax-38 and Ax-40 were elevated compared with nSE (P<0.01), sPS (P<0.05) and controls (P<0.05), and Ax-42 was elevated in rPS relative to nSE (P<0.05). ConclusionsThe findings of this study argue against acute neuronal injury following medically treated seizures but suggest that seizures may reduce CSF levels of tau. Although seizures generally did not affect CSF levels of A or sAPP peptides, our findings suggest that different types of seizures may have different effects on APP metabolism. C1 [Shahim, P.; Blennow, K.; Zetterberg, H.; Mattsson, N.] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Clin Neurochem Lab, Molndal, Sweden. [Rejdak, R.] Med Univ Lublin, Dept Gen Ophthalmol, Lublin, Poland. [Rejdak, R.; Rejdak, K.] Polish Acad Sci, Med Res Ctr, Warsaw, Poland. [Ksiazek, P.] Med Univ Lublin, Dept Publ Hlth, Lublin, Poland. [Zetterberg, H.] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Zetterberg, H.] UCL Inst Neurol, Reta Lilla Weston Labs, London, England. [Mattsson, N.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA. [Rejdak, K.] Med Univ Lublin, Dept Neurol, Lublin, Poland. RP Shahim, P (reprint author), Sahlgrenska Univ Hosp Molndal, Clin Neurochem Lab, S-43180 Molndal, Sweden. EM pashtun.shahim@neuro.gu.se NR 27 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAR PY 2014 VL 21 IS 3 BP 486 EP 491 DI 10.1111/ene.12336 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AA3ER UT WOS:000330976200020 PM 24372994 ER PT J AU Konijeti, GG Shrime, MG Ananthakrishnan, AN Chan, AT AF Konijeti, Gauree Gupta Shrime, Mark G. Ananthakrishnan, Ashwin N. Chan, Andrew T. TI Cost-effectiveness analysis of chromoendoscopy for colorectal cancer surveillance in patients with ulcerative colitis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; COLONOSCOPIC SURVEILLANCE; OLMSTED COUNTY; DYSPLASIA; POPULATION; RECOMMENDATIONS; METAANALYSIS; MORTALITY; COLECTOMY; NEOPLASIA AB Background: Recent studies report that the risk of colorectal cancer (CRC) among patients with ulcerative colitis (UC) may be lower than previously estimated. Although white-light endoscopy (WLE) with random biopsies is recommended for dysplasia detection in patients with UC, several studies reported increased detection of dysplasia by chromoendoscopy. Objective: To analyze the cost effectiveness of chromoendoscopy relative to WLE or no endoscopy for CRC surveillance in patients with UC. Design: Decision-analytic state-transition (Markov) model with Monte Carlo simulation. Setting: To simulate the clinical course of chronic UC, we estimated dysplasia and CRC incidence and progression, endoscopic test characteristics, stage-specific mortality rates, and costs from published literature and Medicare reimbursement data. Patients: Patients from a population-based age distribution with ulcerative colitis for >= 8 years. Intervention: We compared 3 different strategies at various surveillance intervals: chromoendoscopy with targeted biopsies, WLE with random biopsies, and no surveillance. The robustness of the model was assessed by using probabilistic sensitivity analysis. One-way sensitivity analyses were performed to evaluate individual variables, and 3-dimensional analysis was used to examine the effects of varying screening intervals. Main Outcome Measurements: Incremental cost-effectiveness ratio (ICER). Results: Chromoendoscopy was found to be more effective and less costly than WLE at all surveillance intervals. However, compared with no surveillance, chromoendoscopy was cost effective only at surveillance intervals of at least 7 years, with an ICER of $ 77,176. Chromoendoscopy was the most cost effective strategy at sensitivity levels > 0.23 for dysplasia detection and cost < $2200, regardless of the level of sensitivity of WLE for dysplasia detection. The estimated population lifetime risk of developing CRC ranged from 2.5% (annual chromoendoscopy) to 5.9% (chromoendoscopy every 10 years). Limitations: Estimates used for the model are based on best available data in the literature. Conclusion: Chromoendoscopy is both more effective and less costly than WLE and becomes cost effective relative to no surveillance when performed at intervals of >= 7 years. C1 [Konijeti, Gauree Gupta; Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Konijeti, Gauree Gupta; Shrime, Mark G.; Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Interfaculty Initiat Hlth Policy, Cambridge, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, 55 Fruit St,GRJ 825C, Boston, MA 02114 USA. EM achan@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [T32DK007191, K23 DK091742, K24 DK098311, P30 DK043351] FX Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Awards T32DK007191, K23 DK091742, K24 DK098311, and P30 DK043351. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A. Ananthakrishnan served on scientific advisory boards for Prometheus, Inc, Janssen pharmaceuticals, and Cubist pharmaceuticals. A. Chan served as a consultant for Bayer HealthCare, Pfizer Inc, and Millennium Pharmaceuticals. All other authors disclosed no financial relationships relevant to this publication. NR 47 TC 16 Z9 16 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2014 VL 79 IS 3 BP 455 EP 465 DI 10.1016/j.gie.2013.10.026 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AA6UI UT WOS:000331233200014 PM 24262637 ER PT J AU Baldwin, ML Marcus, SC AF Baldwin, Marjorie L. Marcus, Steven C. TI THE IMPACT OF MENTAL AND SUBSTANCE-USE DISORDERS ON EMPLOYMENT TRANSITIONS SO HEALTH ECONOMICS LA English DT Article ID LABOR-MARKET OUTCOMES; PROBLEM DRINKING; JOB LOSS; ATTITUDES; DISABILITIES; ILLNESS; HEALTH; WORK C1 [Baldwin, Marjorie L.] Arizona State Univ, WP Carey Sch Business, Dept Econ, Tempe, AZ 85287 USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Baldwin, ML (reprint author), Arizona State Univ, WP Carey Sch Business, Dept Econ, POB 879801, Tempe, AZ 85287 USA. EM marjorie.baldwin@asu.edu FU National Institute on Drug and Alcohol Abuse [R03 DA019860-01A2] FX This research was supported by the National Institute on Drug and Alcohol Abuse (grant no. R03 DA019860-01A2). NR 24 TC 5 Z9 5 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9230 EI 1099-1050 J9 HEALTH ECON JI Health Econ. PD MAR PY 2014 VL 23 IS 3 BP 332 EP 344 PG 13 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA AA8OH UT WOS:000331354300006 PM 23784938 ER PT J AU MacCarthy, S Bangsberg, DR Fink, G Reich, M Gruskin, S AF MacCarthy, S. Bangsberg, D. R. Fink, G. Reich, M. Gruskin, S. TI Late presentation to HIV/AIDS testing, treatment or continued care: clarifying the use of CD4 evaluation in the consensus SO HIV MEDICINE LA English DT Article DE CD4 evaluations; HIV; AIDS; late presentation; testing; treatment ID LATE HIV DIAGNOSIS; ANTIRETROVIRAL THERAPY; RISK-FACTORS; INFECTED PATIENTS; CELL COUNTS; PREVENTION; INDIVIDUALS; MORTALITY; DISEASE; AIDS AB ObjectivesLate presentation to HIV/AIDS services compromises treatment outcomes and misses opportunities for biomedical and behavioural prevention. There has been significant heterogeneity in how the term late presentation' (LP) has been used in the literature. In 2011, a consensus definition was reached using CD4 counts to define and measure late presenters and, while it is useful for clinical care, the consensus definition has several important limitations that we discuss in this article. MethodsUsing the spectrum of engagement in HIV care presented by Gardner and colleagues, this article highlights issues and opportunities associated with use of the consensus definition. ResultsThe consensus definition is limited by three principal factors: (1) the CD4 count threshold of 350cells/L is being increasingly questioned as the biomedical justification grows for earlier initiation of treatment; (2) CD4 evaluations are conducted at multiple services providing HIV care; thus it remains unclear to which service the patient is presenting late; and (3) the limited availability of CD4 evaluation restricts its use in determining the prevalence of LP in many settings. ConclusionsThe consensus definition is useful because it describes the level of disease progression and allows for consistent evaluation of the prevalence and determinants of LP. Suggestions are provided for improving the application of the consensus definition in future research. C1 [MacCarthy, S.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [MacCarthy, S.] Miriam Hosp, Providence, RI 02906 USA. [Bangsberg, D. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA. [Bangsberg, D. R.] Mbarara Univ Sci & Technol, Mbarara, Mbarara Distric, Uganda. [Fink, G.; Reich, M.; Gruskin, S.] Dept Global Hlth & Populat, Boston, MA USA. [Gruskin, S.] Univ So Calif, Inst Global Hlth, Program Global Hlth & Human Rights, Los Angeles, CA USA. RP MacCarthy, S (reprint author), 164 Summit Ave, Providence, RI 02906 USA. EM sarah_maccarthy@brown.edu FU [T32DA13911-12] FX This publication resulted from research supported by the training grant titled 'HIV and Other Infectious Consequences of Substance Abuse' (T32DA13911-12). In addition, this publication was made possible with help from the Lifespan/Tufts/Brown Center for AIDS Research (P30AI042853) from the National Institute of Allergy and Infectious Diseases. NR 39 TC 11 Z9 11 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-2662 EI 1468-1293 J9 HIV MED JI HIV Med. PD MAR PY 2014 VL 15 IS 3 BP 130 EP 134 DI 10.1111/hiv.12088 PG 5 WC Infectious Diseases SC Infectious Diseases GA AA7IP UT WOS:000331271300002 PM 24024559 ER PT J AU Huynh, A Zhang, R Turka, LA AF Huynh, Alexandria Zhang, Ruan Turka, Laurence A. TI Signals and pathways controlling regulatory T cells SO IMMUNOLOGICAL REVIEWS LA English DT Review DE T cells; transplantation; tolerance; suppression; anergy ID TRANSCRIPTION FACTOR FOXP3; INDUCIBLE FACTOR-I; CUTTING EDGE; NEGATIVE SELECTION; REG CELLS; CD28 COSTIMULATION; AUTOIMMUNE-DISEASE; CYCLOSPORINE-A; RECEPTOR-ALPHA; KAPPA-B AB Induction of specific immune tolerance to grafts remains the sought-after standard following transplantation. Defined by expression of the Foxp3 (forkhead box protein 3) transcription factor, the regulatory T-cell (Treg) lineage has been noted to exert potent immunoregulatory functions that contribute to specific graft tolerance. In this review, we discuss the known signals and pathways which govern Treg development, both in the thymus and in peripheral sites, as well as lineage maintenance and homeostasis. In particular, we highlight the roles of T-cell receptor signaling, CD28 costimulation, and signals through phosphatidyl inositol 3-kinase (PI3K) and related metabolic pathways in multiple aspects of Treg biology. C1 [Huynh, Alexandria] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. [Huynh, Alexandria; Zhang, Ruan; Turka, Laurence A.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Huynh, Alexandria; Zhang, Ruan; Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA USA. RP Turka, LA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St,Room 5101, Boston, MA 02129 USA. EM lturka@partners.org NR 189 TC 19 Z9 21 U1 2 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD MAR PY 2014 VL 258 IS 1 SI SI BP 117 EP 131 DI 10.1111/imr.12148 PG 15 WC Immunology SC Immunology GA AA7AD UT WOS:000331248500008 PM 24517429 ER PT J AU Griesemer, A Yamada, K Sykes, M AF Griesemer, Adam Yamada, Kazuhiko Sykes, Megan TI Xenotransplantation: immunological hurdles and progress toward tolerance SO IMMUNOLOGICAL REVIEWS LA English DT Review DE xenotransplantation; tolerance; thymus transplant; mixed chimerism; genetically modified swine; NK cells ID NATURAL-KILLER-CELLS; PORCINE ENDOTHELIAL-CELLS; ISLET XENOGRAFT REJECTION; MIXED HEMATOPOIETIC CHIMERISM; THYMIC LOBE TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; N-GLYCOLYLNEURAMINIC ACID; DECAY-ACCELERATING FACTOR; GENE-KNOCKOUT PIGS; LARGE-ANIMAL-MODEL AB The discrepancy between organ need and organ availability represents one of the major limitations in the field of transplantation. One possible solution to this problem is xenotransplantation. Research in this field has identified several obstacles that have so far prevented the successful development of clinical xenotransplantation protocols. The main immunologic barriers include strong T-cell and B-cell responses to solid organ and cellular xenografts. In addition, components of the innate immune system can mediate xenograft rejection. Here, we review these immunologic and physiologic barriers and describe some of the strategies that we and others have developed to overcome them. We also describe the development of two strategies to induce tolerance across the xenogeneic barrier, namely thymus transplantation and mixed chimerism, from their inception in rodent models through their current progress in preclinical large animal models. We believe that the addition of further beneficial transgenes to Gal knockout swine, combined with new therapies such as Treg administration, will allow for successful clinical application of xenotransplantation. C1 [Griesemer, Adam; Sykes, Megan] Columbia Univ Coll Phys & Surg, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Sykes, M (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 650 West 168th St,BB1502, New York, NY 10032 USA. EM megan.sykes@columbia.edu FU Louis V. Gerstner Jr. Scholars Program; NIH [NIAID P01 AI45897, NIAID R01 AI084903, NIAID P01 AI045897, NHLBI P01 HL18646] FX AG receives support from the Louis V. Gerstner Jr. Scholars Program. KY receives support from the NIH (NIAID P01 AI45897). MS receives support from the NIH (NIAID R01 AI084903; NIAID P01 AI045897; NHLBI P01 HL18646). We thank Jennifer Colozzi and Shavree Washington for assistance in preparing the manuscript. The authors declare no competing financial interests. NR 230 TC 29 Z9 30 U1 2 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD MAR PY 2014 VL 258 IS 1 SI SI BP 241 EP 258 DI 10.1111/imr.12152 PG 18 WC Immunology SC Immunology GA AA7AD UT WOS:000331248500016 PM 24517437 ER PT J AU Pallin, DJ Camargo, CA Yokoe, DS Espinola, JA Schuur, JD AF Pallin, Daniel J. Camargo, Carlos A., Jr. Yokoe, Deborah S. Espinola, Janice A. Schuur, Jeremiah D. TI Variability of Contact Precaution Policies in US Emergency Departments SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; HEALTH-CARE SETTINGS; INFECTIONS; TRANSMISSION; STRATEGIES; ORGANISMS; HOSPITALS AB Contact precautions policies in US emergency departments have not been studied. We surveyed a structured random sample and found wide variation; for example, 45% required contact precautions for stool incontinence or diarrhea, 84% for suspected Clostridium difficile, and 79% for suspected methicillin-resistant Staphylococcus aureus infection. Emergency medicine departments and organizations should enact policies. C1 [Pallin, Daniel J.; Yokoe, Deborah S.; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.; Espinola, Janice A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Pallin, DJ (reprint author), 75 Francis St,Neville House 304-D, Boston, MA 02115 USA. EM dpallin@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 FU Agency for Healthcare Research and Quality (AHRQ) [R18HS020013]; AHRQ [R13HS021616] FX Financial support. D.J.P., C. A. C., and J.D.S. are supported by a grant (R18HS020013) from the Agency for Healthcare Research and Quality (AHRQ). J.D.S. is supported by a grant (R13HS021616) from the AHRQ. The study was designed independently by the authors; the sponsor had no role in manuscript development or writing. NR 10 TC 2 Z9 2 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR 1 PY 2014 VL 35 IS 3 BP 310 EP 312 DI 10.1086/675285 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AA6MH UT WOS:000331211900017 PM 24521599 ER PT J AU Drain, PK Mosam, A Gounder, L Gosnell, B Manzini, T Moosa, MYS AF Drain, Paul K. Mosam, Anisa Gounder, Lilishia Gosnell, Bernadett Manzini, Thandekile Moosa, Mahomed-Yunus S. TI Recurrent giant molluscum contagiosum immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy in an HIV-infected man SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article ID TOPICAL CIDOFOVIR; PATIENT; RESOLUTION C1 [Drain, Paul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis,Dept Med, Boston, MA USA. [Mosam, Anisa] Univ KwaZulu Natal, Dept Dermatol, Nelson Mandela Sch Med, Durban, South Africa. [Gounder, Lilishia; Gosnell, Bernadett; Manzini, Thandekile; Moosa, Mahomed-Yunus S.] Univ KwaZulu Natal, Dept Infect Dis, Nelson Mandela Sch Med, Durban, South Africa. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,943, Boston, MA 02114 USA. EM pdrain@partners.org OI Drain, Paul/0000-0003-3300-3817 FU Harvard Global Health Institute; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; Program for AIDS Clinical Research Training Grant [T32 AI007433] FX Dr Drain was supported by the Harvard Global Health Institute, the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988), and a Program for AIDS Clinical Research Training Grant (T32 AI007433). NR 20 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 EI 1758-1052 J9 INT J STD AIDS JI Int. J. STD AIDS PD MAR PY 2014 VL 25 IS 3 BP 235 EP 238 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AA9CZ UT WOS:000331392600011 PM 23970647 ER PT J AU Allen, JD Perez, JE Tom, L Leyva, B Diaz, D Torres, MI AF Allen, Jennifer D. Perez, John E. Tom, Laura Leyva, Bryan Diaz, Daisy Torres, Maria Idali TI A Pilot Test of a Church-Based Intervention to Promote Multiple Cancer-Screening Behaviors among Latinas SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Latinas; Hispanic; Health; Disparities; Church; Cancer screening; Religion; Spirituality ID PREVENTION; BREAST; WOMEN; ADULTS; TRIAL AB We assessed the feasibility, acceptability, and initial impact of a church-based educational program to promote breast, cervical, and colorectal cancer screening among Latinas ages 18 years and over. We used a one-group pre-/post-evaluation within a low-income, Latino Baptist church in Boston, MA. Participants completed interviewer-administered assessments at baseline and at the end of the 6-month intervention. Under the guidance of a patient navigator (PN), women from the church (peer health advisors, or PHAs) were trained to deliver evidence-based screening interventions, including one-to-one outreach, small group education, client reminders, and reduction of structural barriers to screening. The PN and PHAs also implemented a health fair, and the pastor integrated health information into regular sermons. At pre-intervention, nearly half of the sample did not meet screening guidelines. The majority (97 %, n = 35) of those who completed the post-intervention assessment participated in intervention activities. Two thirds (67 %) reported talking with the PN or PHAs about health issues. Participation in small group education sessions was highest (72 %), with health fairs (61 %) and goal setting (50 %) also being popular activities. Fourteen percent also reported receiving help from the PN in finding a primary care provider. This study supports the feasibility and acceptability of churches as a setting to promote cancer screening among Latinas. C1 [Allen, Jennifer D.; Tom, Laura; Diaz, Daisy] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA. [Perez, John E.] Univ San Francisco, San Francisco, CA 94117 USA. [Leyva, Bryan] NCI, Bethesda, MD 20892 USA. [Torres, Maria Idali] Univ Massachusetts, Boston, MA 02125 USA. [Allen, Jennifer D.] Dana Farber Canc Inst, Phyllis Cantor Ctr Nursing Res & Patient Care Ser, Ctr Community Based Res, Boston, MA 02215 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Phyllis Cantor Ctr Nursing Res & Patient Care Ser, Ctr Community Based Res, 450 Brookline Ave, Boston, MA 02215 USA. EM jennifer_allen@dfci.harvard.edu RI Allen, Jennifer/M-2113-2015 FU National Cancer Institute [U56 CA118641, U54CA156732]; American Recovery and Reinvestment Act [3U56CA118635-05S2]; Centers for Disease Control and Prevention [U48DP001946] FX This study was supported by grants from the National Cancer Institute (U56 CA118641 and U54CA156732) with supplemental funding support from the American Recovery and Reinvestment Act of 2009 (3U56CA118635-05S2). It was also supported by Cooperative Agreement Number U48DP001946 from the Centers for Disease Control and Prevention. The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention. We gratefully acknowledge the leadership and support of Drs. Karen Emmons and Adan Colon-Carmona. We also thank the following for their participation and support: Milagros Abreu, Erick Alcantata, Esteban Barreto, Lois Biener, Karen Burns White, Katia Canenguez, Magnolia Contreras, Ana Galeas, Maria De Jesus, Ericka Gonzalez, Elizabeth Gonzalez Suarez, David Hurtado, Thelma Juarez, Yolanda Martins, Yudy Muneton, Maria Nieves Sesma, Leyla Perez-Gualdron, Max Stewart, and Jamielle Walker. NR 25 TC 12 Z9 12 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 EI 1543-0154 J9 J CANCER EDUC JI J. Cancer Educ. PD MAR PY 2014 VL 29 IS 1 BP 136 EP 143 DI 10.1007/s13187-013-0560-3 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA AA3DK UT WOS:000330972900025 PM 24132541 ER PT J AU Motraghi, TE Seim, RW Meyer, EC Morissette, SB AF Motraghi, Terri E. Seim, Richard W. Meyer, Eric C. Morissette, Sandra B. TI Virtual Reality Exposure Therapy for the Treatment of Posttraumatic Stress Disorder: A Methodological Review Using CONSORT Guidelines SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED-TRIALS; PTSD; ANXIETY; STATEMENT; VETERANS; QUALITY; FEAR C1 [Seim, Richard W.] Cincinnati VA Med Ctr, Cincinnati, OH USA. [Morissette, Sandra B.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Morissette, SB (reprint author), 4800 Mem Dr 51C, Waco, TX 76711 USA. EM sandra.morissette@va.gov NR 36 TC 16 Z9 17 U1 3 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9762 EI 1097-4679 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAR PY 2014 VL 70 IS 3 BP 197 EP 208 PG 12 WC Psychology, Clinical SC Psychology GA AA5HD UT WOS:000331125800001 PM 24108479 ER PT J AU Skaf, A Taneja, AK AF Skaf, Abdalla Taneja, Atul K. TI Osteochondrosis of the inferior pole of the scapula (Roca disease) SO JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B LA English DT Article DE ossification center; osteochondrosis; scapula; shoulder pain AB We report a rare case of osteochondrosis of the inferior pole of the scapula in a 14-year-old boy, an amateur swimmer, that was diagnosed by a combination of clinical and imaging findings. Also known as Roca disease, this is the first article to report this entity in the English literature and demonstrates its computerized tomography and MRI features. C1 [Skaf, Abdalla; Taneja, Atul K.] Heart Hosp HCor, Dept Musculoskeletal Radiol, Sao Paulo, Brazil. [Skaf, Abdalla; Taneja, Atul K.] Teleimagem, BR-04004030 Sao Paulo, Brazil. [Skaf, Abdalla] Alta Diagnost, Dept Musculoskeletal Radiol, Sao Paulo, Brazil. [Taneja, Atul K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Taneja, Atul K.] Harvard Univ, Sch Med, Musculoskeletal Imaging & Intervent Div, Boston, MA USA. RP Taneja, AK (reprint author), Teleimagem, R Des Eliseu Guilherme 53,7 Andar, BR-04004030 Sao Paulo, Brazil. EM atultaneja@gmail.com RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1060-152X EI 1473-5865 J9 J PEDIATR ORTHOP B JI J. Pediatr. Orthop.-Part B PD MAR PY 2014 VL 23 IS 2 BP 155 EP 157 DI 10.1097/BPB.0b013e3283642229 PG 3 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA AA7QH UT WOS:000331291500012 PM 23838852 ER PT J AU Shi, LL Boykin, RE Lin, A Warner, JJP AF Shi, Lewis L. Boykin, Robert E. Lin, Albert Warner, Jon J. P. TI Association of suprascapular neuropathy with rotator cuff tendon tears and fatty degeneration SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Suprascapular nerve; rotator cuff tear; fatty degeneration; electromyography; nerve conduction velocity ID MUSCLE; NERVE; SUPRASPINATUS; INFILTRATION; ATROPHY; REPAIR AB Background: The mutual influence of suprascapular neuropathy (SSN) and rotator cuff tendon tears on muscle pathology is unclear. Debate continues as to how retracted cuff tears can lead to SSN and whether SSN or tendon retraction causes muscle fatty degeneration. Methods: A cohort of 87 patients suspected of having SSN was identified from a prospectively collected registry. All underwent electromyography/nerve conduction velocity study (EMG/NCV) and magnetic resonance imaging (MRI) of their shoulders. EMG/NCVs were performed and interpreted by electrodiagnosticians, and MRI cuff tendon quality and muscle fatty degeneration were interpreted by two surgeons. Results: Out of 87 patients, 32 patients had SSN on EMG/NCV, and 55 patients had normal suprascapular nerve. MRI showed that 59 of 87 supraspinatus had no fatty degeneration or mild fatty streaks (Goutallier grades 0 and 1), and 28 patients had significant fatty degeneration (grades 2-4); infraspinatus fatty degeneration was similar. Review of supraspinatus tendon showed 41 patients with intact tendons or partial tears, and 46 with full tears. Infraspinatus tendons pathology was similar. Tendon pathology and fatty degeneration were related (P-value < .001), with more severe tendon pathology leading to higher degree of fatty degeneration. Infraspinatus tendon tears were associated with SSN (P = .01), but SSN was not related to fatty degeneration of either supraspinatus or infraspinatus (P-values.65,.54). Conclusion: The exact association and etiology of SSN in patients with rotator cuff pathology remain unclear. SSN is correlated to tendon tear size, but it does not have significant influence on fatty degeneration of either supraspinatus or infraspinatus. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Shi, Lewis L.] Univ Chicago, Med Ctr, Dept Orthopaed Surg & Rehabil Med, Chicago, IL 60637 USA. [Boykin, Robert E.] Blue Ridge Bone & Joint Clin, Asheville, NC USA. [Lin, Albert] Univ Pittsburgh UPMC, Ctr Sports Med, Div Shoulder Surg & Sports Med, Pittsburgh, PA USA. [Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), 55 Fruit St,Yawkey 3G, Boston, MA 02114 USA. EM jwarner@partners.org NR 22 TC 12 Z9 12 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR PY 2014 VL 23 IS 3 BP 339 EP 346 DI 10.1016/j.jse.2013.06.011 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AA5KD UT WOS:000331135300012 PM 24054975 ER PT J AU deCamp, A Hraber, P Bailer, RT Seaman, MS Ochsenbauer, C Kappes, J Gottardo, R Edlefsen, P Self, S Tang, HL Greene, K Gao, HM Daniell, X Sarzotti-Kelsoe, M Gorny, MK Zolla-Pazner, S LaBranche, CC Mascola, JR Korber, BT Montefiori, DC AF deCamp, Allan Hraber, Peter Bailer, Robert T. Seaman, Michael S. Ochsenbauer, Christina Kappes, John Gottardo, Raphael Edlefsen, Paul Self, Steve Tang, Haili Greene, Kelli Gao, Hongmei Daniell, Xiaoju Sarzotti-Kelsoe, Marcella Gorny, Miroslaw K. Zolla-Pazner, Susan LaBranche, Celia C. Mascola, John R. Korber, Bette T. Montefiori, David C. TI Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; HIV-1-INFECTED INDIVIDUALS; POTENT NEUTRALIZATION; BROAD NEUTRALIZATION; CROSS-REACTIVITY; CD4-BINDING SITE; STRUCTURAL BASIS; RATIONAL DESIGN; V3 DOMAIN AB Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env. IMC. LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. IMPORTANCE An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies. Efforts to elicit broadly cross-reactive neutralizing antibodies that will protect against infection by most circulating strains of the virus are guided in part by in vitro assays that determine the ability of vaccine-elicited antibodies to neutralize genetically diverse HIV-1 variants. Until now, little information was available on how many and which strains of the virus are best suited for this purpose. We applied robust statistical methods to evaluate a large neutralization data set and identified a small panel of viruses that are a good representation of the global epidemic. The neutralization properties of this new panel of reference strains should facilitate the development of an effective HIV-1 vaccine. C1 [deCamp, Allan; Gottardo, Raphael; Edlefsen, Paul; Self, Steve] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hraber, Peter; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM USA. [Bailer, Robert T.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Seaman, Michael S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA. [Ochsenbauer, Christina; Kappes, John] Univ Alabama Birmingham, Birmingham, AL USA. [Kappes, John] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. [Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; LaBranche, Celia C.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Sarzotti-Kelsoe, Marcella] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Gorny, Miroslaw K.; Zolla-Pazner, Susan] NYU, Dept Pathol, Langone Sch Med, New York, NY 10016 USA. [Zolla-Pazner, Susan] Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, New York, NY USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. EM monte@duke.edu OI Gorny, Miroslaw/0000-0002-2714-8780; Korber, Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897 FU Bill & Melinda Gates Foundation [38619, 1032144]; Intramural Research Program of the Vaccine Research Center, NIAID, NIH; Virology Core of the Birmingham Center for AIDS Research (CFAR) [AI27767] FX This work was funded by grants from the Bill & Melinda Gates Foundation (Collaboration for AIDS Vaccine Discovery no. 38619 and 1032144) and by the Intramural Research Program of the Vaccine Research Center, NIAID, NIH. This work was further supported by the Virology Core of the Birmingham Center for AIDS Research (CFAR, AI27767). NR 85 TC 37 Z9 37 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2014 VL 88 IS 5 BP 2489 EP 2507 DI 10.1128/JVI.02853-13 PG 19 WC Virology SC Virology GA AA5JK UT WOS:000331131700012 PM 24352443 ER PT J AU Porichis, F Hart, MG Zupkosky, J Barblu, L Kwon, DS McMullen, A Brennan, T Ahmed, R Freeman, GJ Kavanagh, DG Kaufmann, DE AF Porichis, Filippos Hart, Meghan G. Zupkosky, Jennifer Barblu, Lucie Kwon, Douglas S. McMullen, Ashley Brennan, Thomas Ahmed, Rafi Freeman, Gordon J. Kavanagh, Daniel G. Kaufmann, Daniel E. TI Differential Impact of PD-1 and/or Interleukin-10 Blockade on HIV-1-Specific CD4 T Cell and Antigen-Presenting Cell Functions SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTION; DISEASE PROGRESSION; VIRAL-INFECTION; CD154 EXPRESSION; IL-10; EXHAUSTION; DYSFUNCTION; ACTIVATION; RECEPTOR AB Antigen persistence in chronic infections and cancer upregulates inhibitory networks, such as the PD-1 and interleukin-10 (IL-10) pathways, that impair immunity and lead to disease progression. These pathways are attractive targets for immunotherapy, as demonstrated by recent clinical trials of PD-1/PD-L1 blockade in cancer patients. However, in HIV-1 infection not all subjects respond to inhibition of either pathway and the mechanistic interactions between these two networks remain to be better defined. Here we demonstrate that in vitro blockade of PD-L1 and/or IL-10R alpha results in markedly different profiles of HIV-1-specific CD4 T cell restoration. Whereas PD-L1 blockade leads to balanced increase in gamma interferon (IFN-gamma), IL-2, and IL-13 secretion, IL-10R alpha blockade preferentially restores IFN-gamma production. In viremic subjects, combined PD-L1/IL-10R alpha blockade results in a striking 10-fold increase in IFN-gamma secretion by HIV-1-specific CD4 T cells that is not observed in subjects with spontaneous (elite controllers) or therapy-induced control of viral replication. In contrast to the dramatic increase in IFN-gamma production, concurrent blockade has a marginal additive effect on IL-2 production, IL-13 secretion, and HIV-1-specific CD4 T cell proliferation. IFN-gamma produced by Thelper cells upregulates PD-L1, HLA I/II, and IL-12 expression by monocytes. The effect of combined blockade on IFN-gamma was dependent on reciprocal reinforcement through IL-12. These studies provide crucial information on the different immunoregulatory qualities of PD-1 and IL-10 in progressive disease and link exhausted virus-specific CD4 T cells and monocytes in the regulation of IFN-gamma and IL-12 secretion. IMPORTANCE Infection with HIV results in most people in uncontrolled viral replication and progressive weakening of the body defenses. In the absence of antiviral therapy, this process results in clinical disease, or AIDS. An important reason why HIV continues to multiply is that a population of white blood cells called CD4 T cells that targets the virus fails to work properly. At least part of this impairment is under the control of inhibitory mechanisms that can be blocked to improve the function of these CD4 T cells. In this report, we show that blocking one or two of the molecules involved, called PD-1 and IL-10, has different effects on the individual functions of these cells and that one is strongly improved. We investigate how these effects are caused by interactions between CD4 T cells and antigen-presenting cells. These observations can have implications for new therapeutic approaches in HIV infection. C1 [Porichis, Filippos; Hart, Meghan G.; Zupkosky, Jennifer; Barblu, Lucie; Kwon, Douglas S.; McMullen, Ashley; Brennan, Thomas; Kavanagh, Daniel G.; Kaufmann, Daniel E.] MIT, Ragon Inst MGH, Boston, MA USA. [Porichis, Filippos; Hart, Meghan G.; Zupkosky, Jennifer; Barblu, Lucie; Kwon, Douglas S.; McMullen, Ashley; Brennan, Thomas; Kavanagh, Daniel G.; Kaufmann, Daniel E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Barblu, Lucie; Kaufmann, Daniel E.] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ, Canada. [Kwon, Douglas S.; Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Ahmed, Rafi; Kaufmann, Daniel E.] Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. RP Kaufmann, DE (reprint author), MIT, Ragon Inst MGH, Boston, MA USA. EM daniel.kaufmann@umontreal.ca FU NIH [RO1 HL-092565, P01 AI-080192]; NIAID [UM1AI100663]; Harvard Global Health Institute; FRQS; [P01 AI056299]; [P01 AI078897]; [AI56299] FX The study was supported by the NIH (RO1 HL-092565 [D. E. K.]; P01 AI-080192 [R.A., D.E.K., D.G.K., and G.J.F.]; NIAID UM1AI100663 [CHAVI-ID] [D.E.K. and R.A.]; and P01 AI056299, P01 AI078897, and AI56299 [G.J.F.]). F.P. is supported by a fellowship grant of MGH and the Harvard Global Health Institute. D.E.K. is supported by a Career Award of the FRQS. NR 42 TC 17 Z9 20 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2014 VL 88 IS 5 BP 2508 EP 2518 DI 10.1128/JVI.02034-13 PG 11 WC Virology SC Virology GA AA5JK UT WOS:000331131700013 PM 24352453 ER PT J AU Veillette, M Desormeaux, A Medjahed, H Gharsallah, NE Coutu, M Baalwa, J Guan, YJ Lewis, G Ferrari, G Hahn, BH Haynes, BF Robinson, JE Kaufmann, DE Bonsignori, M Sodroski, J Finzi, A AF Veillette, Maxime Desormeaux, Anik Medjahed, Halima Gharsallah, Nour-Elhouda Coutu, Mathieu Baalwa, Joshua Guan, Yongjun Lewis, George Ferrari, Guido Hahn, Beatrice H. Haynes, Barton F. Robinson, James E. Kaufmann, Daniel E. Bonsignori, Mattia Sodroski, Joseph Finzi, Andres TI Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 INNER DOMAIN; VACCINE EFFICACY TRIAL; VPU PROTEIN; CONFORMATIONAL TRANSITIONS; TRANSMEMBRANE GLYCOPROTEIN; DISEASE PROGRESSION; EFFECTOR FUNCTION; AIDS PATIENTS; HTLV-III AB Anti-HIV-1 envelope glycoprotein (Env) antibodies without broadly neutralizing activity correlated with protection in the RV144 clinical trial, stimulating interest in other protective mechanisms involving antibodies, such as antibody-dependent cell-mediated cytotoxicity (ADCC). Env epitopes targeted by many antibodies effective at mediating ADCC are poorly exposed on the unliganded Env trimer. Here we investigated the mechanism of exposure of ADCC epitopes on Env and showed that binding of Env and CD4 within the same HIV-1-infected cell effectively exposes these epitopes. Env capacity to transit to the CD4-bound conformation is required for ADCC epitope exposure. Importantly, cell surface CD4 downregulation by Nef and Vpu accessory proteins and Vpu-mediated BST-2 antagonism modulate exposure of ADCC-mediating epitopes and reduce the susceptibility of infected cells to this effector function in vitro. Significantly, Env conformational changes induced by cell surface CD4 are conserved among Env from HIV-1 and HIV-2/SIVmac lineages. Altogether, our observations describe a highly conserved mechanism required to expose ADCC epitopes that might help explain the evolutionary advantage of downregulation of cell surface CD4 by the HIV-1 Vpu and Nef proteins. IMPORTANCE HIV-1 envelope epitopes targeted by many antibodies effective at mediating antibody-dependent cell-mediated cytotoxicity (ADCC) are poorly exposed on the unliganded envelope trimer. Here we investigated the mechanism of exposure of these epitopes and found that envelope interaction with the HIV-1 CD4 receptor is required to expose some of these epitopes. Moreover, our results suggest that HIV-1 CD4 downregulation might help avoid the killing of HIV-1-infected cells by this immune mechanism. C1 [Veillette, Maxime; Desormeaux, Anik; Medjahed, Halima; Gharsallah, Nour-Elhouda; Coutu, Mathieu; Kaufmann, Daniel E.; Finzi, Andres] Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada. [Veillette, Maxime; Medjahed, Halima; Coutu, Mathieu; Kaufmann, Daniel E.; Finzi, Andres] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada. [Baalwa, Joshua] Univ Alabama Birmingham, Dept Pathol & Med, Birmingham, AL USA. [Guan, Yongjun; Lewis, George] Univ Maryland, Sch Med, Div Basic Sci & Vaccine Res, Inst Human Virol, Baltimore, MD 21201 USA. [Ferrari, Guido; Haynes, Barton F.; Bonsignori, Mattia] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Hahn, Beatrice H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. [Robinson, James E.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div AIDS, Boston, MA USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Kaufmann, Daniel E.; Sodroski, Joseph] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. [Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. RP Finzi, A (reprint author), Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada. EM andres.finzi@umontreal.ca RI Ferrari, Guido/A-6088-2015 FU Canada Foundation for Innovation Program Leader grant [29866]; CIHR [257792, 291485]; FRQS Establishment of Young Scientist [24639]; Grand Challenges Explorations grant from the Bill and Melinda Gates Foundation [OPP1042670]; Center for HIV/AIDS Vaccine Immunology and Immunogen Design [U19 AI100645]; National Institutes of Health [AI67854]; International AIDS Vaccine Initiative; FRSQ Chercheur Boursier Junior 1 fellowship [24639] FX This work was supported by Canada Foundation for Innovation Program Leader grant 29866, by CIHR operating grant 257792, by FRQS Establishment of Young Scientist grant 24639, by a Grand Challenges Explorations grant from the Bill and Melinda Gates Foundation (OPP1042670) to A.F., by the Center for HIV/AIDS Vaccine Immunology and Immunogen Design (U19 AI100645), by the National Institutes of Health (AI67854), by the International AIDS Vaccine Initiative, and by the late William F. McCarty-Cooper. A.F. is the recipient of FRSQ Chercheur Boursier Junior 1 fellowship 24639. M.V. was supported by CIHR Doctoral Research Award 291485. NR 69 TC 79 Z9 79 U1 1 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2014 VL 88 IS 5 BP 2633 EP 2644 DI 10.1128/JVI.03230-13 PG 12 WC Virology SC Virology GA AA5JK UT WOS:000331131700024 PM 24352444 ER PT J AU Lai, JI Licht, AF Dugast, AS Suscovich, T Choi, I Bailey-Kellogg, C Alter, G Ackerman, ME AF Lai, Jennifer I. Licht, Anna F. Dugast, Anne-Sophie Suscovich, Todd Choi, Ickwon Bailey-Kellogg, Chris Alter, Galit Ackerman, Margaret E. TI Divergent Antibody Subclass and Specificity Profiles but Not Protective HLA-B Alleles Are Associated with Variable Antibody Effector Function among HIV-1 Controllers SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; VACCINE EFFICACY TRIAL; IMMUNOGLOBULIN-G; PHAGOCYTIC-ACTIVITY; IGG2 ANTIBODIES; HIGH-THROUGHPUT; INFECTION; RESPONSES; DETERMINANTS; PROGRESSION AB Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector function and biophysical features of HIV-specific antibodies in a cohort of controllers with and without protective HLA-B alleles in order to investigate whether there was evidence for multiple paths to HIV-1 control, or whether cellular and humoral arms of immunity might exhibit coordinated profiles. However, with the exception of IgG2 antibodies to gp41, HLA status was not associated with divergent humoral responses. This finding did not result from uniform antibody responses across subjects, as controllers could be regrouped according to strong differences in their HIV-specific antibody subclass specificity profiles. These divergent antibody profiles were further associated with significant differences in nonneutralizing antibody effector function, with levels of HIV-specific IgG1 acting as the major distinguishing factor. Thus, while HLA background among controllers was associated with minimal differences in humoral function, antibody subclass and specificity profiles were associated with divergent effector function, suggesting that these features could be used to make functional predictions. Because these nonneutralizing antibody activities have been associated with spontaneous viral control, reduced viral load, and nonprogression in infected subjects and protection in vaccinated subjects, understanding the specific features of IgGs with potentiated effector function may be critical to vaccine and therapeutic antibody development. IMPORTANCE In this study, we investigated whether the humoral and cellular arms of adaptive immunity exhibit coordinated or compensatory activity by studying the antibody response among HIV-1 controllers with different genetic backgrounds. C1 [Lai, Jennifer I.; Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Licht, Anna F.; Dugast, Anne-Sophie; Suscovich, Todd; Alter, Galit] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02139 USA. [Licht, Anna F.; Dugast, Anne-Sophie; Suscovich, Todd; Alter, Galit] Harvard Univ, Cambridge, MA 02138 USA. [Choi, Ickwon; Bailey-Kellogg, Chris] Dartmouth Coll, Dept Comp Sci, Hanover, NH 03755 USA. [Ackerman, Margaret E.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH USA. RP Ackerman, ME (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. EM margaret.e.ackerman@dartmouth.edu RI Dugast, AnneSophie/L-9541-2015 FU Collaboration for AIDS Vaccine Discovery [OPP1032817]; Harvard University Center for AIDS Research Postdoctoral Fellowship (HU CFAR NIH/NIAID fund) [2P30AI060354-07]; NSF [IIS-0905206]; NIH [NIH1R01AI102691, NIH 3R01Al080289-02S1, 5R01Al080289-03] FX These studies were supported by the Collaboration for AIDS Vaccine Discovery (OPP1032817: Leveraging Antibody Effector Function to M. E. A., G. A., and C.B.-K.), NIH1R01AI102691 to M. E. A., and NIH 3R01Al080289-02S1 and 5R01Al080289-03 to G. A. M. E. A. was supported by a Harvard University Center for AIDS Research Postdoctoral Fellowship (HU CFAR NIH/NIAID fund 2P30AI060354-07). I. C. was supported by NSF grant IIS-0905206. HIV immunoglobulin was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH, from NABI and NHLBI. NR 37 TC 14 Z9 14 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2014 VL 88 IS 5 BP 2799 EP 2809 DI 10.1128/JVI.03130-13 PG 11 WC Virology SC Virology GA AA5JK UT WOS:000331131700038 PM 24352471 ER PT J AU Lee, BJ August, DA AF Lee, Brian J. August, David A. TI COLDS: A heuristic preanesthetic risk score for children with upper respiratory tract infection SO PEDIATRIC ANESTHESIA LA English DT Letter ID ANESTHESIA; COMPLICATIONS; EVENTS C1 [Lee, Brian J.; August, David A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Lee, BJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM daugust@partners.org NR 5 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 EI 1460-9592 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD MAR PY 2014 VL 24 IS 3 BP 349 EP 350 DI 10.1111/pan.12337 PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA AA6MX UT WOS:000331213500025 PM 24372849 ER PT J AU Saoncella, S Tassone, B Deklic, E Avolio, F Jon, C Tornillo, G De Luca, E Di Iorio, E Piva, R Cabodi, S Turco, E Pandolfi, PP Calautti, E AF Saoncella, Stefania Tassone, Beatrice Deklic, Erika Avolio, Fabio Jon, Cristina Tornillo, Giusy De Luca, Elisa Di Iorio, Enzo Piva, Roberto Cabodi, Sara Turco, Emilia Pandolfi, Pier Paolo Calautti, Enzo TI Nuclear Akt2 Opposes Limbal Keratinocyte Stem Cell Self-Renewal by Repressing a FOXO-mTORC1 Signaling Pathway SO STEM CELLS LA English DT Article DE Akt2-FOXO-mTORC1 signaling in keratinocyte; Akt isoforms in stratified epithelial stem cells; Akt2 knockout mice/human limbal keratinocyte stem cells ID EPITHELIAL-MESENCHYMAL TRANSITION; FORKHEAD TRANSCRIPTION FACTOR; KINASE-B-GAMMA; CORNEAL REGENERATION; OCULAR SURFACE; MICE LACKING; STEM/PROGENITOR CELLS; GLUCOSE-HOMEOSTASIS; INSULIN-RESISTANCE; CANCER-CELLS AB Signals downstream of Akt can either favor or oppose stem cell (SC) maintenance, but how this dual role can be achieved is still undefined. Using human limbal keratinocyte stem cells (LKSCs), a SC type used in transplantation therapies for corneal regeneration, we show that Akt signaling is prominent in SC populations both in vivo and in vitro, and that Akt1 promotes while Akt2 opposes SC self-renewal. Noteworthy, loss of Akt2 signaling enhances LKSC maintenance ex vivo, whereas Akt1 depletion anticipates SC exhaustion. Mechanistically, the antagonistic functions of Akt1 and Akt2 in SC control are mainly dictated by their differential subcellular distribution, being nuclear Akt2 selectively implicated in FOXO inhibition. Akt2 downregulation favors LKSC maintenance as a result of a gain of FOXO functions, which attenuates the mechanistic target of rapamycin complex one signaling via tuberous sclerosis one gene induction, and promotes growth factor signaling through Akt1. Consistently, Akt2 deficiency also enhances limbal SCs in vivo. Thus, our findings reveal distinct roles for nuclear versus cytosolic Akt signaling in normal epithelial SC control and suggest that the selective Akt2 inhibition may provide novel pharmacological strategies for human LKSC expansion in therapeutic settings and mechanistic research. Stem Cells 2014;32:754-769 C1 [Saoncella, Stefania; Tassone, Beatrice; Deklic, Erika; Avolio, Fabio; Jon, Cristina; Tornillo, Giusy; De Luca, Elisa; Cabodi, Sara; Turco, Emilia; Calautti, Enzo] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy. [Di Iorio, Enzo] Veneto Eye Bank Fdn, Venice, Italy. [Di Iorio, Enzo] Univ Padua, Dept Mol Med, Padua, Italy. [Piva, Roberto] Univ Turin, Dept Mol Biotechnol & Hlth Sci, CERMS, Turin, Italy. [Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Genet Program,Dept Med & Pathol, Boston, MA 02215 USA. RP Calautti, E (reprint author), Via Nizza 52, I-10126 Turin, Italy. EM vincenzo.calautti@unito.it OI Piva, Roberto/0000-0002-2273-3470; CALAUTTI, Vincenzo/0000-0002-4439-9709; Tassone, Beatrice/0000-0002-3746-4605 FU Telethon, Italy [TCP 06001]; Piemonte Region (PISTEM); Piemonte Region (Converging Technologies); Italian Association for Cancer Research (AIRC) [IG-11346, IG-8675] FX We thank Michele De Luca and Graziella Pellegrini for their helpful advice and support on the human limbal epithelial model system; Diego Ponzin and the Veneto Eye Bank Foundation for providing this study with the human specimens for the in vivo studies, and Federico Genzano for providing additional corneal specimens; Paolo Dotto, Stefano Gustincich, Francesca Persichetti, Sandro Goruppi and Caterina Missero for critical reading of the manuscript; Annalisa Camporeale for help with FACS analysis; Paolo Provero for advice in statistical analysis. This manuscript is dedicated to the loving memory of Maria Luisa Vinay Calautti. The financial support of Telethon, Italy (TCP 06001) (E.C.), the Piemonte Region (PISTEM and Converging Technologies Grants) (E.C.), the Italian Association for Cancer Research (AIRC), IG-11346 (S.C.) and IG-8675 (R.P.). are gratefully acknowledged. F.A. is currently affiliated with Inserm U1091, IBV, Diabetes Genetics Team, Universite de Nice-Sophia Antipolis, Nice, France; G.T. is currently affiliated with Cardiff School of Biosciences, Cardiff, Wales, U.K.; E.D.L. is currently affiliated with Center for Bio-Molecular Nanotechnology, Italian Institute of Technology, Arnesano (LE), Italy. NR 82 TC 5 Z9 6 U1 0 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 MAR PY 2014 VL 32 IS 3 BP 754 EP 769 DI 10.1002/stem.1565 PG 16 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AA9BR UT WOS:000331389200014 PM 24123662 ER PT J AU Li, XG Romain, RD Park, D Scadden, DT Merchant, JL Arnaout, MA AF Li, Xiangen Romain, Rachael D. Park, Dongsu Scadden, David T. Merchant, Juanita L. Arnaout, M. Amin TI Stress Hematopoiesis Is Regulated by the Kruppel-Like Transcription Factor ZBP-89 SO STEM CELLS LA English DT Article DE Stress hematopoiesis; Hematopoietic stem cells; Transcription factors; Erythroid progenitors; Transplantation ID CELL LEUKEMIA GENE; STEM-CELLS; MACROPHAGE DIFFERENTIATION; CHROMATIN OCCUPANCY; LINEAGE COMMITMENT; PROGENITOR CELLS; POST-HYPOXIA; PU.1; ERYTHROPOIESIS; PROMOTER AB Previous studies have shown that ZBP-89 (Zfp148) plays a critical role in erythroid lineage development, with its loss at the embryonic stage causing lethal anemia and thrombocytopenia. Its role in adult hematopoiesis has not been described. We now show that conditional deletion of ZBP-89 in adult mouse hematopoietic stem/progenitor cells (HSPC) causes anemia and thrombocytopenia that are transient in the steady state, but readily uncovered following chemically induced erythro/megakaryopoietic stress. Unexpectedly, stress induced by bone marrow transplantation of ZBP89(-/-) HSPC also resulted in a myeloid-to-B lymphoid lineage switch in bone marrow recipients. The erythroid and myeloid/B lymphoid lineage anomalies in ZBP89(-/-) HSPC are reproduced in vitro in the ZBP-89-silenced multipotent hematopoietic cell line FDCP-Mix A4, and are associated with the upregulation of PU.1 and downregulation of SCL/Tal1 and GATA-1 in ZBP89-deficient cells. Chromatin immunoprecipitation and luciferase reporter assays show that ZBP-89 is a direct repressor of PU.1 and activator of SCL/Tal1 and GATA-1. These data identify an important role for ZBP-89 in regulating stress hematopoiesis in adult mouse bone marrow. Stem Cells 2014;32:791-801 C1 [Li, Xiangen; Arnaout, M. Amin] Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. [Romain, Rachael D.; Merchant, Juanita L.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Park, Dongsu; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Park, Dongsu; Scadden, David T.; Arnaout, M. Amin] Harvard Stem Cell Inst, Cambridge, MA USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. EM aarnaout1@partners.org FU NIH [DK081920, DK55732]; National Institutes of Health (NIDDK); Roche Foundation for Anaemia Research FX We thank Dr. Hanno Hock (MGH Cancer Center) for providing MX1-Cre transgenic mice, Dr. Daniel Tenen (BIDMC, Boston, MA), and Dr. Kinuko Ohneda (Takasaki University of Health and Welfare, Takasaki, Japan) for plasmids and Dr. Ursula Just (University of Kiel, Germany) for FDCP-Mix A4 cells. This work was supported by NIH grants DK081920 (to M.A.A.) and DK55732 (to J.L.M.) from the National Institutes of Health (NIDDK), and a grant from The Roche Foundation for Anaemia Research (to M.A.A.). NR 42 TC 2 Z9 2 U1 0 U2 3 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 MAR PY 2014 VL 32 IS 3 BP 791 EP 801 DI 10.1002/stem.1598 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AA9BR UT WOS:000331389200017 PM 24549639 ER PT J AU Dwivedi, N Radic, M AF Dwivedi, Nishant Radic, Marko TI Citrullination of autoantigens implicates NETosis in the induction of autoimmunity SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review DE Rheumatoid Arthritis; Systemic Lupus Erythematosus; Autoimmunity; Ant-CCP ID NEUTROPHIL EXTRACELLULAR TRAPS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; EARLY RHEUMATOID-ARTHRITIS; MYELIN BASIC-PROTEIN; ANTI-DNA ANTIBODIES; TOLL-LIKE RECEPTORS; PEPTIDYLARGININE DEIMINASE; FELTYS-SYNDROME; MULTIPLE-SCLEROSIS; APOPTOTIC CELLS AB Tolerance blocks the expression of autoantibodies, whereas autoimmunity promotes it. How tolerance breaks and autoantibody production begins thus are crucial questions for understanding and treatment of autoimmune diseases. Evidence implicates cell death and autoantigen modifications in the initiation of autoimmune reactions. One form of neutrophil cell death called NETosis deserves attention because it requires the post-translational modification of histones and results in the extracellular release of chromatin. NETosis received its name from NET, the acronym given to Neutrophil Extracellular Trap. The extracellular chromatin incorporates histones in which arginines have been converted to citrullines by peptidylarginine deiminase IV (PAD4). The deiminated chromatin may function to capture or trap' bacterial pathogens, thus generating an extracellular complex of deiminated histones and bacterial cell adjuvants. The complex of bacterial antigens and deiminated chromatin may be internalised by host phagocytes during acute inflammatory conditions, as arise during bacterial infections or chronic autoinflammatory disorders. The uptake and processing of deiminated chromatin together with bacterial adjuvants by phagocytes may induce the presentation of modified histone epitopes and co-stimulation, thus yielding a powerful stimulus to break tolerance. Autoantibodies to deiminated histones are prevalent in Felty's syndrome patients and are present in systemic lupus erythematosus (SLE) and patients with rheumatoid arthritis (RA). These observations clearly implicate histone deimination as an epigenetic mark that can act as an autoantibody stimulant. C1 [Dwivedi, Nishant] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Dwivedi, Nishant] Harvard Univ, Sch Med, Boston, MA USA. [Radic, Marko] Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA. RP Radic, M (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, 858 Madison Ave,Rm 211, Memphis, TN 38163 USA. EM mradic@uthsc.edu NR 128 TC 37 Z9 39 U1 5 U2 24 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2014 VL 73 IS 3 BP 483 EP 491 DI 10.1136/annrheumdis-2013-203844 PG 9 WC Rheumatology SC Rheumatology GA AA0VK UT WOS:000330815300009 PM 24291655 ER PT J AU Krajewski, KM Nishino, M Franchetti, Y Ramaiya, NH Van den Abbeele, AD Choueiri, TK AF Krajewski, Katherine M. Nishino, Mizuki Franchetti, Yoko Ramaiya, Nikhil H. Van den Abbeele, Annick D. Choueiri, Toni K. TI Intraobserver and Interobserver Variability in Computed Tomography Size and Attenuation Measurements in Patients With Renal Cell Carcinoma Receiving Antiangiogenic Therapy SO CANCER LA English DT Article ID RESPONSE EVALUATION CRITERIA; TARGETED THERAPY; SOLID TUMORS; LUNG-CANCER; SUNITINIB; RECIST; CT; LESIONS; TRIAL; COEFFICIENT C1 [Krajewski, Katherine M.; Nishino, Mizuki; Ramaiya, Nikhil H.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Krajewski, Katherine M.; Nishino, Mizuki; Franchetti, Yoko; Ramaiya, Nikhil H.; Van den Abbeele, Annick D.] Harvard Univ, Sch Med, Boston, MA USA. [Franchetti, Yoko] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Choueiri, Toni K.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Krajewski, KM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM kmkrajewski@partners.org FU Association of University Radiologists-General Electric Radiology Research Academic Fellowship; National Cancer Institute [1K23CA157631] FX Supported by the Association of University Radiologists-General Electric Radiology Research Academic Fellowship (to Dr. Krajewski) and grant 1K23CA157631 from the National Cancer Institute to Dr. Nishino. NR 34 TC 14 Z9 14 U1 0 U2 6 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 MAR 1 PY 2014 VL 120 IS 5 BP 711 EP 721 PG 11 WC Oncology SC Oncology GA AB0AM UT WOS:000331454200012 PM 24264883 ER PT J AU George, S Feng, Y Manola, J Nucci, MR Butrynski, JE Morgan, JA Ramaiya, N Quek, R Penson, RT Wagner, AJ Harmon, D Demetri, GD Krasner, C AF George, Suzanne Feng, Yang Manola, Judith Nucci, Marisa R. Butrynski, James E. Morgan, Jeffrey A. Ramaiya, Nikhil Quek, Richard Penson, Richard T. Wagner, Andrew J. Harmon, David Demetri, George D. Krasner, Carolyn TI Phase 2 Trial of Aromatase Inhibition With Letrozole in Patients With Uterine Leiomyosarcomas Expressing Estrogen and/or Progesterone Receptors SO CANCER LA English DT Article ID SOFT-TISSUE SARCOMAS; IMMUNOHISTOCHEMICAL EXPRESSION; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; BREAST-CANCER; THERAPY; CHEMOTHERAPY; TRABECTEDIN; DOXORUBICIN; TAMOXIFEN C1 [George, Suzanne; Butrynski, James E.; Morgan, Jeffrey A.; Quek, Richard; Wagner, Andrew J.; Demetri, George D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Feng, Yang; Manola, Judith] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Nucci, Marisa R.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Ramaiya, Nikhil] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Penson, Richard T.; Harmon, David; Krasner, Carolyn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA USA. RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM suzanne_george@dfci.harvard.edu FU Novartis; Pfizer; GlaxoSmithKline; Janssen; Johnson Johnson; Merck; Ariad Pharmaceuticals; Bayer; ZioPharm Oncology Inc. FX Dr. George received consulting fees from Novartis and Pfizer for content related to gastrointestinal stromal tumors as well as drug support for a separate investigator-initiated trial and financial support to the Dana-Farber Cancer Institute for Novartis- and Pfizer-sponsored clinical trials. She also received consulting fees for content related to gastrointestinal stromal tumors as well as financial support to the Dana-Farber Cancer Institute from Ariad Pharmaceuticals for an Ariad-sponsored clinical trial; consulting fees including travel support for content related to gastrointestinal stromal tumors and financial support and drug support to the Dana-Farber Cancer Institute for an investigator-initiated clinical trial from Bayer as well as support for a Bayer-sponsored clinical trial; and consulting fees including travel support from GlaxoSmithKline. Dr. Quek has received grants from Novartis and Janssen. Dr. Wagner has received a grant and personal fees from Novartis. Dr. Demetri has received grants and consulting fees from Novartis, GlaxoSmithKline, Johnson & Johnson, and Merck as well as research support to the Dana-Farber Cancer Institute for specific clinical trial agreements in the sarcoma unit. He has also provided unpaid expert regulatory testimony for GlaxoSmithKline, Johnson & Johnson, and Merck and has acted as a paid member of the Scientific Advisory Board for ZioPharm Oncology Inc. NR 20 TC 14 Z9 16 U1 0 U2 3 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 MAR 1 PY 2014 VL 120 IS 5 BP 738 EP 743 PG 6 WC Oncology SC Oncology GA AB0AM UT WOS:000331454200015 PM 24222211 ER PT J AU Sun, PZ Wang, Y Lu, J AF Sun, Phillip Zhe Wang, Yu Lu, Jie TI Sensitivity-enhanced chemical exchange saturation transfer (CEST) MRI with least squares optimization of Carr Purcell Meiboom Gill multi-echo echo planar imaging SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE amide proton transfer (APT); Carr-Purcell-Meiboom-Gill (CPMG); chemical exchange saturation transfer (CEST); echo planar imaging (EPI); pH ID ACUTE ISCHEMIC-STROKE; PH-WEIGHTED MRI; RF IRRADIATION; IN-VIVO; MAGNETIZATION-TRANSFER; PROTON-EXCHANGE; 7 T; CONTRAST; AGENTS; RELAXATION AB Chemical exchange saturation transfer (CEST) imaging is a novel MRI technique that is sensitive to biomolecules, local pH and temperature, and offers considerable advantages for in vivo applications. However, the magnitude of CEST effect for dilute CEST agents undergoing slow or intermediate chemical exchange is typically small, requiring the use of signal averaging to enhance its sensitivity. Given that T-2-induced signal loss can be normalized by asymmetry analysis, the magnitude of CEST effect is independent of echo time. Therefore, CEST MRI with multi-echo echo planar imaging (EPI) readout should yield the same CEST effect as conventional single echo acquisition. Importantly, CEST multi-echo (CESTme) EPI images can be averaged to enhance CEST MRI sensitivity. The goal of this study was to validate CESTme EPI using a creatine-agarose gel CEST phantom with similar T-2 as biological tissue. Using least-squares optimization, we found that the sensitivity of CESTme sequence was significantly higher than that obtained by conventional single echo CEST-EPI acquisition. Specifically, signal-to-noise ratio and contrast-to-noise ratio from the proposed CESTme EPI were approximately equivalent to that obtained by doubling the number of signal averages of the standard single echo CEST MRI sequence. In summary, our results demonstrated CESTme EPI for sensitivity-enhanced CEST imaging. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Sun, Phillip Zhe; Wang, Yu] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sun, Phillip Zhe; Wang, Yu] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wang, Yu; Lu, Jie] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing, Peoples R China. RP Sun, PZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu; lujie@xwh.ccmu.edu.cn FU AHA/SDG [0835384N]; [NIBIB-1K01EB009771]; [NINDS-1R01NS083654]; [NCRR-P41RR14075]; [NSFC-30900365] FX This study was supported in part by grants from the AHA/SDG 0835384N, NIBIB-1K01EB009771, NINDS-1R01NS083654, NCRR-P41RR14075 and NSFC-30900365. The authors would like to thank Drs Bruce Rosen, Douglas Greve and Bruce Fischl for stimulating discussions and Ms Nichole Eusemann for editorial assistance. NR 50 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1555-4309 EI 1555-4317 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD MAR PY 2014 VL 9 IS 2 BP 177 EP 181 DI 10.1002/cmmi.1546 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AA6KE UT WOS:000331206400008 PM 24523063 ER PT J AU Guerrero-Berroa, E Ravona-Springer, R Schmeidler, J Silverman, JM Sano, M Koifmann, K Preiss, R Hoffman, H Heymann, A Beeri, MS AF Guerrero-Berroa, Elizabeth Ravona-Springer, Ramit Schmeidler, James Silverman, Jeremy M. Sano, Mary Koifmann, Keren Preiss, Rachel Hoffman, Hadas Heymann, Anthony Beeri, Michal Schnaider TI Age, gender, and education are associated with cognitive performance in an older Israeli sample with type 2 diabetes SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE neuropsychology; CERAD; cognitive functioning; diabetes; demographics; older adults ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; ALZHEIMERS-DISEASE CERAD; MINI-MENTAL-STATE; NORMATIVE DATA; SPANISH-SPEAKING; AFRICAN-AMERICAN; LACUNAR INFARCTIONS; SEMANTIC FLUENCY; ENGLISH-SPEAKING; WAIS-R AB ObjectiveTo evaluate the relationships of age, education, and gender with performance on neuropsychological tests in a cognitively intact, older Israeli sample with type 2 diabetes (T2D). MethodsWe examined 862 participants, 65-84years old, enrolled in the Israel Diabetes and Cognitive Decline study. Multiple regression assessed associations of performance on 17 neuropsychological tests, including the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery, with age, education, and gender. ResultsHigher education and younger age were consistently associated with better performance. Women outperformed men on all memory tasks; men outperformed women on two non-verbal measures. These patterns of demographic associations with cognitive performance were very similar to those of US cohorts. ConclusionsIn a cognitively intact, older Israeli sample with T2D, better test performance is associated primarily with higher education, followed by younger age and gender differences. Although T2D is associated with cognitive deficits, it recapitulates the patterns of relationships between cognitive performance and demographic characteristics seen in non-T2D diabetic samples. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Guerrero-Berroa, Elizabeth; Schmeidler, James; Silverman, Jeremy M.; Sano, Mary; Beeri, Michal Schnaider] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ravona-Springer, Ramit; Koifmann, Keren; Beeri, Michal Schnaider] Joseph Sagol Neurosci Ctr, Sheba Med Ctr, Ramat Gan, Israel. [Guerrero-Berroa, Elizabeth; Silverman, Jeremy M.; Sano, Mary] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Preiss, Rachel; Hoffman, Hadas; Heymann, Anthony] Maccabi Healthcare Serv, Tel Aviv, Israel. RP Guerrero-Berroa, E (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. EM elizabeth.guerrero-berroa@mssm.edu FU NIA [R01 AG034087, P50 AG05138]; Helen Bader Foundation; Irma T. Hirschl Scholar award; American Federation for Aging Research (AFAR) Young Investigator award; Alzheimer's Association [NIRG-11-205083] FX This study was supported by NIA grants R01 AG034087 to Dr. Beeri and P50 AG05138 to Dr. Sano, the Helen Bader Foundation and the Irma T. Hirschl Scholar award to Dr. Beeri, the American Federation for Aging Research (AFAR) Young Investigator award, and the Alzheimer's Association grant NIRG-11-205083 to Dr. Ravona-Springer. NR 46 TC 8 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAR PY 2014 VL 29 IS 3 BP 299 EP 309 DI 10.1002/gps.4008 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AA2EJ UT WOS:000330907600010 PM 23925856 ER PT J AU Schneider, CE White, T Hass, J Geisler, D Wallace, SR Roessner, V Holt, DJ Calhoun, VD Gollub, RL Ehrlich, S AF Schneider, Claudia E. White, Tonya Hass, Johanna Geisler, Daniel Wallace, Stuart R. Roessner, Veit Holt, Daphne J. Calhoun, Vince D. Gollub, Randy L. Ehrlich, Stefan TI Smoking status as a potential confounder in the study of brain structure in schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Smoking; MRI; Brain volume; Hippocampus; DLPFC ID GRAY-MATTER VOLUMES; 1ST EPISODE SCHIZOPHRENIA; CHRONIC CIGARETTE-SMOKING; VOXEL-BASED MORPHOMETRY; HUMAN CEREBRAL-CORTEX; COORDINATE SYSTEM; LOBE DYSFUNCTION; WORKING-MEMORY; BOLD RESPONSE; METAANALYSIS AB Several but not all MRI studies have reported volume reductions in the hippocampus and dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. Given the high prevalence of smoking among schizophrenia patients and the fact that smoking has also been associated with alterations in brain morphology, this study evaluated whether a proportion of the known gray matter reductions in key brain regions may be attributed to smoking rather than to schizophrenia alone. We examined structural MRI data of 112 schizophrenia patients (53 smokers and 59 non-smokers) and 77 healthy non-smoker controls collected by the MCIC study of schizophrenia. An automated atlas based probabilistic method was used to generate volumetric measures of the hippocampus and DLPFC. The two patient groups were matched with respect to demographic and clinical variables. Smoker schizophrenia patients showed significantly lower hippocampal and DLPFC volumes than nonsmoker schizophrenia patients. Gray matter volume reductions associated with smoking status ranged between 2.2% and 2.8%. Furthermore, we found significant volume differences between smoker patients and healthy controls in the hippocampus and DLPFC, but not between non-smoker patients and healthy controls. Our data suggest that a proportion of the volume reduction seen in the hippocampus and DLPFC in schizophrenia is associated with smoking rather than with the diagnosis of schizophrenia. These results may have important implications for brain imaging studies comparing schizophrenia patients and other groups with a lower smoking prevalence. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Schneider, Claudia E.; Hass, Johanna; Geisler, Daniel; Roessner, Veit; Ehrlich, Stefan] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, D-01307 Dresden, Germany. [White, Tonya] Erasmus MC, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [White, Tonya] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [White, Tonya] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN USA. [Wallace, Stuart R.; Holt, Daphne J.; Gollub, Randy L.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wallace, Stuart R.; Holt, Daphne J.; Gollub, Randy L.; Ehrlich, Stefan] Harvard Univ, Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging,Med Sch, Charlestown, MA USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Image Anal & MR Res, Mind Res Network, Albuquerque, NM USA. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, Fetscherstr 74, D-01307 Dresden, Germany. EM transden.lab@gmail.com OI Ehrlich, Stefan/0000-0003-2132-4445; Gollub, Randy L./0000-0002-9434-4044 FU National Institutes of Health [NIH/NCRR P41RR14075]; Department of Energy [DE-FG02-99ER62764]; Mind Research Network; Morphometry BIRN [1U24, RR021382A]; Function BIRN [U24RR021992-01]; Deutsche Forschungsgemeinschaft; NARSAD; NIH.NCRR [MO1 RR025758-01]; NIMH [1RC1MH089257] FX This work was supported by the National Institutes of Health (NIH/NCRR P41RR14075), Department of Energy (DE-FG02-99ER62764), Mind Research Network, Morphometry BIRN (1U24, RR021382A), Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257 to VDC), the Deutsche Forschungsgemeinschaft (research fellowship to SE) and the NARSAD Young Investigator Grant (SE). NR 80 TC 11 Z9 12 U1 2 U2 7 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 MAR PY 2014 VL 50 BP 84 EP 91 DI 10.1016/j.jpsychires.2013.12.004 PG 8 WC Psychiatry SC Psychiatry GA AA5SV UT WOS:000331160800012 PM 24373929 ER PT J AU Park, E Kim, Y Ryu, H Kowall, NW Lee, J Ryu, H AF Park, Elizabeth Kim, Yunha Ryu, Hyun Kowall, Neil W. Lee, Junghee Ryu, Hoon TI Epigenetic Mechanisms of Rubinstein-Taybi Syndrome SO NEUROMOLECULAR MEDICINE LA English DT Review DE RTS; Histone acetylation; Histone methylation; CBP; HDAC ID LONG-TERM-MEMORY; HISTONE DEACETYLASE INHIBITORS; SYNAPTIC PLASTICITY; HUNTINGTONS-DISEASE; CREBBP GENE; MOUSE MODEL; DNA-DAMAGE; ACETYLTRANSFERASE ACTIVITY; CHROMOSOME 16P13.3; MOLECULAR ANALYSIS AB Rubinstein-Taybi syndrome (RTS) is an incurable genetic disorder with combination of mental retardation and physical features including broad thumbs and toes, craniofacial abnormalities, and growth deficiency. While the autosomal dominant mode of transmission is limitedly known, the majority of cases are attributable to de novo mutations in RTS. The first identified gene associated with RTS is CREB-binding protein (CREBBP/CBP). Alterations of the epigenetic 'histone code' due to dysfunction of the CBP histone acetyltransferase activity deregulate gene transcriptions that are prominently linked to RTS pathogenesis. In this review, we discuss how CBP mutation contributes to modifications of histone and how histone deacetylase inhibitors are therapeutically applicable to epigenetic conditioning in RTS. Since most genetic mutations are irreversible and therapeutic approaches are limited, therapeutic targeting of reversible epigenetic components altered in RTS may be an ideal strategy. Expeditious further study on the role of the epigenetic mechanisms in RTS is encouraged to identify novel epigenetic markers and therapeutic targets to treat RTS. C1 [Park, Elizabeth; Ryu, Hyun; Kowall, Neil W.; Lee, Junghee; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Park, Elizabeth; Ryu, Hyun; Kowall, Neil W.; Lee, Junghee; Ryu, Hoon] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Kim, Yunha] Korea Inst Sci & Technol, Brain Sci Inst, Lab Neuronal Gene Regulat & Epigenet, Ctr Neuromed, Seoul 110799, South Korea. [Kowall, Neil W.; Lee, Junghee] VA Boston Healthcare Syst, Dept Neurol, Boston, MA 02130 USA. RP Ryu, H (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM hoonryu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIH [NS 067283]; Korea Institute of Science and Technology (KIST) [2E24380] FX This study was supported by NIH NS 067283 (H. R.) and Brain Science Flagship Grant (2E24380) (H. R.) from Korea Institute of Science and Technology (KIST). NR 77 TC 14 Z9 14 U1 2 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2014 VL 16 IS 1 BP 16 EP 24 DI 10.1007/s12017-013-8285-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA AA4YF UT WOS:000331101900003 PM 24381114 ER PT J AU Armstrong, A Mattsson, N Appelqvist, H Janefjord, C Sandin, L Agholme, L Olsson, B Svensson, S Blennow, K Zetterberg, H Kagedal, K AF Armstrong, Andrea Mattsson, Niklas Appelqvist, Hanna Janefjord, Camilla Sandin, Linnea Agholme, Lotta Olsson, Bob Svensson, Samuel Blennow, Kaj Zetterberg, Henrik Kagedal, Katarina TI Lysosomal Network Proteins as Potential Novel CSF Biomarkers for Alzheimer's Disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE PICALM; DRAM; TFEB; Cathepsins; Proteasome; hsc70 ID UBIQUITIN PROTEASOME SYSTEM; MILD COGNITIVE IMPAIRMENT; HUMAN CEREBROSPINAL-FLUID; NEURODEGENERATIVE DISEASES; EARLY ENDOSOMES; DOWN-SYNDROME; AUTOPHAGY; DEMENTIA; PLASMA; STANDARDIZATION AB The success of future intervention strategies for Alzheimer's disease (AD) will likely rely on the development of treatments starting early in the disease course, before irreversible brain damage occurs. The pre-symptomatic stage of AD occurs at least one decade before the clinical onset, highlighting the need for validated biomarkers that reflect this early period. Reliable biomarkers for AD are also needed in research and clinics for diagnosis, patient stratification, clinical trials, monitoring of disease progression and the development of new treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and autophagy systems, are among the first alterations observed in an AD brain. In this study, we performed a targeted search for lysosomal network proteins in human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins 1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3), Rab3 and Rab7, were significantly increased in the CSF from AD patients compared with neurological controls. These results were confirmed in a validation cohort of CSF samples, and patients with no neurochemical evidence of AD, apart from increased total-tau, were found to have EEA1 levels corresponding to the increased total-tau levels. These findings indicate that increased levels of LAMP-1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased EEA1 levels may be a sign of general neurodegeneration. These six lysosomal network proteins are potential AD biomarkers and may be used to investigate lysosomal involvement in AD pathogenesis. C1 [Armstrong, Andrea; Appelqvist, Hanna; Janefjord, Camilla; Sandin, Linnea; Agholme, Lotta; Kagedal, Katarina] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. [Armstrong, Andrea; Svensson, Samuel] AlzeCure Fdn, Stockholm, Sweden. [Mattsson, Niklas; Olsson, Bob; Blennow, Kaj; Zetterberg, Henrik] Sahlgrens Univ Hosp, Dept Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Mattsson, Niklas] Univ Calif San Francisco, Ctr Imaging Neurodegenerat Dis, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Svensson, Samuel] Linkoping Univ, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. [Zetterberg, Henrik] UCL Inst Neurol, London WC1N 3BG, England. RP Armstrong, A (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. EM andrea.armstrong@liu.se OI Olsson, Bob/0000-0002-6368-6172 NR 43 TC 21 Z9 22 U1 1 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2014 VL 16 IS 1 BP 150 EP 160 DI 10.1007/s12017-013-8269-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA AA4YF UT WOS:000331101900015 PM 24101586 ER PT J AU McBride, SM Busse, PM Clark, JR Wirth, LJ Ancukiewicz, M Chan, AW AF McBride, Sean M. Busse, Paul M. Clark, John R. Wirth, Lori J. Ancukiewicz, Marek Chan, Annie W. TI Long-term survival after distant metastasis in patients with oropharyngeal cancer SO ORAL ONCOLOGY LA English DT Article DE Oropharyngeal carcinoma; Distant metastasis; Human papilloma virus; Prognostic factors ID SQUAMOUS-CELL CARCINOMA; NECK-CANCER; HUMAN-PAPILLOMAVIRUS; PULMONARY METASTASES; HEAD; RADIOTHERAPY; RESECTION AB Objectives: For patients with oropharyngeal squamous cell carcinoma (OPSCC), especially for those with HPV-positive tumors, locoregional control is excellent. Distant metastasis, however, remains a substantial problem. The purpose of our study was to evaluate outcomes and predictors of survival after distant metastasis in OPSCC. Materials and methods: Between June 2002 and January 2011, 25 OPSCC patients treated with curative intent subsequently developed distant metastasis. The primary end-points evaluated were time-to-distant metastasis and overall survival after development of distant metastasis. Predictors of outcome were evaluated with median regression analysis or Cox regression. Best subset models were chosen to minimize the Bayesian Information Criterion (BIC). A prognostic index for survival after distant failure was created based on the selected model. Results: Median time-to-distant metastasis after completion of radiation was 7.9 months (range, 1.6-25.4). Median overall survival from distant metastasis was 18.3 months (95% CI, 14.3-39.8). The overall survival rates at 1-and 2-year after development of distant metastasis were 72.0% (95% confidence interval [CI], 53.4-89.6) and 40.8% (95% CI, 20.6-61.0), respectively. In multivariate analysis, Karnofsky Performance Status score (KPS) >= 80 (p = 0.01, hazard ratio [HR] 0.15, 95% CI, 0.04-0.52) and limited, single-organ disease (p = 0.003, HR 0.13, 95% CI 0.03-0.61) predicted for increased survival from distant metastasis. Patients with both limited disease and good KPS formed the most favorable risk group with a 2-year survival of 100%. Two patients with human papilloma virus (HPV)-positive tumors were alive without any evidence of disease at 64.6 and 60.4 months, respectively, after aggressive local treatment of solitary metastasis. Conclusion: For OPSCC patients with limited, single-organ disease and good KPS, long-term survival can be achieved. (C) 2013 Published by Elsevier Ltd. C1 [McBride, Sean M.; Busse, Paul M.; Ancukiewicz, Marek; Chan, Annie W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [McBride, Sean M.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Clark, John R.; Wirth, Lori J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med Oncol,Dept Med, Boston, MA USA. RP Chan, AW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 337,55 Fruit St, Boston, MA 02114 USA. EM awchan@partners.org NR 22 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD MAR PY 2014 VL 50 IS 3 BP 208 EP 212 DI 10.1016/j.oraloncology.2013.10.020 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA AA3BV UT WOS:000330968800009 PM 24387975 ER PT J AU Hernandez-Diaz, S Boeke, CE Romans, AT Young, B Margulis, AV McElrath, TF Ecker, JL Bateman, BT AF Hernandez-Diaz, Sonia Boeke, Caroline E. Romans, Anna Thornton Young, Brett Margulis, Andrea V. McElrath, Thomas F. Ecker, Jeffrey L. Bateman, Brian T. TI Triggers of Spontaneous Preterm Delivery - Why Today? SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE preterm labour; spontaneous rupture of membranes; risk factors; case-crossover design ID CASE-CROSSOVER DESIGN; CIRCADIAN INCIDENCE; PREMATURE RUPTURE; RISK-FACTORS; PREGNANCY; BIRTH; MEMBRANES; LABOR; EPIDEMIOLOGY; GESTATION AB BackgroundOur goal is to study the triggers of spontaneous preterm delivery using a case-crossover design. MethodsIn a pilot study, we enrolled 50 women with spontaneous preterm labour (PTL) and 50 with preterm premature rupture of membranes (PPROM) between 2011 and 2012. To assess non-transient risk factors, we also enrolled a control group of 158 pregnant women at their regular prenatal care visits matched to cases by gestational age and calendar time. The index time was defined as the onset of PTL/PPROM (for cases) or interview (for controls). Detailed data were collected through structured interviews regarding factors of interest during the 72h that preceded the index time. Within case subjects, we compared the frequency of transient factors from 0 to 24h before index time with that from 48 to 72h before index time, and estimated matched odds ratios (OR) and 95% confidence intervals (CI). ResultsPreviously hypothesised chronic risk factors for spontaneous preterm delivery, including mood disorders and stressful events, were more common among cases than among controls. Within cases, skipped meals [OR 4.3, 95% CI 1.2, 15.2], disturbed sleep [OR 4.5, 95% CI 1.5, 13.3], sexual activity [OR 6.0, 95% CI 0.7, 69.8], and intake of spicy foods [OR 7.0, 95% CI 1.6, 30.8] were associated with an increased risk for PTL/PPROM within the subsequent 24h. For physical exertion and other potential risk factors evaluated, the OR was close to the null. ConclusionSkipping meals and disturbed sleep may be associated with imminent PTL/PPROM; sexual activity and spicy food may trigger PTL/PPROM in susceptible women. Larger case-crossover studies will be able to evaluate the impact of modifiable risk factors and acute predictors of PTL/PPROM, and might help guide obstetrical management. C1 [Hernandez-Diaz, Sonia; Boeke, Caroline E.; Margulis, Andrea V.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Boeke, Caroline E.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Romans, Anna Thornton; Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Young, Brett; Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Vincent Obstet & Gynecol, Boston, MA 02114 USA. [McElrath, Thomas F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02215 USA. [Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02215 USA. RP Hernandez-Diaz, S (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02215 USA. EM shernan@hsph.harvard.edu FU Harvard School of Public Health Initiative; [T32 CA 09001]; [T32 GM007592] FX This study was supported by the Harvard School of Public Health Initiative. Caroline Boeke was funded by the T32 CA 09001, and Brian Bateman was funded by T32 GM007592. NR 36 TC 4 Z9 4 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAR PY 2014 VL 28 IS 2 BP 79 EP 87 DI 10.1111/ppe.12105 PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AA7JN UT WOS:000331273800002 PM 24384058 ER PT J AU James-Todd, T Janevic, T Brown, FM Savitz, DA AF James-Todd, Tamarra Janevic, Teresa Brown, Florence M. Savitz, David A. TI Race/Ethnicity, Educational Attainment, and Pregnancy Complications in New York City Women with Pre-existing Diabetes SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE pre-existing diabetes; preterm birth; small-for-gestational age; large-for-gestational age; pre-eclampsia; race; non-Hispanic blacks; Hispanics; South Asians; education ID ADVERSE BIRTH OUTCOMES; MATERNAL OBESITY; PRETERM BIRTH; PERINATAL OUTCOMES; UNITED-STATES; HIGH-RATES; MELLITUS; TYPE-1; HEALTH; DISPARITIES AB BackgroundMore women are entering pregnancy with pre-existing diabetes. Disease severity, glycaemic control, and predictors of pregnancy complications may differ by race/ethnicity or educational attainment, leading to differences in adverse pregnancy outcomes. MethodsWe used linked New York City hospital record and birth certificate data for 6291 singleton births among women with pre-existing diabetes between 1995 and 2003. We defined maternal race/ethnicity as non-Hispanic white, non-Hispanic black, Hispanic, South Asian, and East Asian, and education level as <12, 12, and >12 years. Our outcomes were pre-eclampsia, preterm birth (PTB) (<37 weeks gestation and categorised as spontaneous or medically indicated), as well as small-for-gestational age (SGA) and large-for-gestational age (LGA). Using multivariable binomial regression, we estimated the risk ratios for pre-eclampsia, SGA, and LGA. We used multivariable multinomial regression to estimate odds ratios (OR) for PTB. ResultsCompared with non-Hispanic white women with pre-existing diabetes, non-Hispanic black and Hispanic women with pre-existing diabetes had a 1.50-fold increased risk of pre-eclampsia compared with non-Hispanic whites with pre-existing diabetes, after full adjustment. Non-Hispanic black and Hispanic women with pre-existing diabetes had adjusted ORs of 1.72 [adj. 95% confidence interval (CI) 1.38, 2.15] and 1.65 [adj.95% CI 1.32, 2.05], respectively, for medically indicated PTB. South Asian women with pre-existing diabetes had the highest risk for having an SGA infant [adj. OR: 2.29; adj. 95% CI 1.73, 3.03]. East Asian ethnicity was not associated with these pregnancy complications. ConclusionsNon-Hispanic black, Hispanic, and South Asian women with pre-existing diabetes may benefit from targeted interventions to improve pregnancy outcomes. C1 [James-Todd, Tamarra] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA. [James-Todd, Tamarra; Brown, Florence M.] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Janevic, Teresa] Rutgers Sch Publ Hlth, Dept Epidemiol, Piscataway, NJ USA. [Brown, Florence M.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Savitz, David A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Savitz, David A.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. RP James-Todd, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Womens Hlth, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM tjames-todd@bics.bwh.harvard.edu FU National Institute of Child Health and Human Development [R21-HD050739, K12-HD051959] FX This work was supported by Grant #R21-HD050739 and Grant K12-HD051959 from the National Institute of Child Health and Human Development. The authors declare that no conflicts of interests exist. NR 41 TC 2 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-5022 EI 1365-3016 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAR PY 2014 VL 28 IS 2 BP 157 EP 165 DI 10.1111/ppe.12100 PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA AA7JN UT WOS:000331273800010 PM 24354778 ER PT J AU Van Allen, EM Foye, A Wagle, N Kim, W Carter, SL McKenna, A Simko, JP Garraway, LA Febbo, PG AF Van Allen, E. M. Foye, A. Wagle, N. Kim, W. Carter, S. L. McKenna, A. Simko, J. P. Garraway, L. A. Febbo, P. G. TI Successful whole-exome sequencing from a prostate cancer bone metastasis biopsy SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE bone biopsy; whole-exome sequencing; genomics; precision medicine ID POLY(ADP-RIBOSE) POLYMERASE; INCREASED SURVIVAL; MUTATIONS; SAMPLES; CHEMOTHERAPY; INHIBITION AB BACKGROUND: Comprehensive molecular characterization of cancer that has metastasized to bone has proved challenging, which may limit the diagnostic and potential therapeutic opportunities for patients with bone-only metastatic disease. METHODS: We describe successful tissue acquisition, DNA extraction, and whole-exome sequencing from a bone metastasis of a patient with metastatic, castration-resistant prostate cancer (PCa). RESULTS: The resulting high-quality tumor sequencing identified plausibly actionable somatic genomic alterations that dysregulate the phosphoinostide 3-kinase pathway, as well as a theoretically actionable germline variant in the BRCA2 gene. CONCLUSIONS: We demonstrate the feasibility of diagnostic bone metastases profiling and analysis that will be required for the widespread application of prospective 'precision medicine' to men with advanced PCa. C1 [Van Allen, E. M.; Wagle, N.; Garraway, L. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Van Allen, E. M.; Wagle, N.; Carter, S. L.; McKenna, A.; Garraway, L. A.] MIT, Broad Inst, Canc Program, Cambridge, MA USA. [Foye, A.; Kim, W.; Febbo, P. G.] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [McKenna, A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Simko, J. P.; Febbo, P. G.] Univ Calif San Francisco, Dept Urol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Simko, J. P.] Univ Calif San Francisco, Dept Pathol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94140 USA. [Simko, J. P.] Univ Calif San Francisco, Dept Radiat Oncol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94140 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard; pfebbo@genomichealth.com FU Stand Up To Cancer; Prostate Cancer Foundation; Prostate Dream Team Translational Cancer Research Grants; Movember Foundation; Starr Cancer Consortium [I4-A424]; NIH [5 U01 CA157703]; Department of Defense [W81XWH-10-PCRP-SIDA] FX This work was supported by Stand Up To Cancer, Prostate Cancer Foundation, Prostate Dream Team Translational Cancer Research Grants, made possible by the generous support of the Movember Foundation (EMV, AF, LAG, PGF), the Prostate Cancer Foundation (EMV, PGF), the Starr Cancer Consortium (I4-A424; LAG), the NIH (5 U01 CA157703; PGF), and the Department of Defense (W81XWH-10-PCRP-SIDA; LAG). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. The authors acknowledge Deborah Farlow for her project management contribution to this effort. NR 26 TC 10 Z9 10 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 EI 1476-5608 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD MAR PY 2014 VL 17 IS 1 BP 23 EP 27 DI 10.1038/pcan.2013.37 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA AA8FP UT WOS:000331331300005 PM 24366412 ER PT J AU Schapira, L AF Schapira, Lidia TI Handling uncertainty SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Uncertainty; Communication; Coping ID ADVANCED CANCER; BREAST-CANCER; LIFE; END; PATIENT; NONABANDONMENT; COMMUNICATION; DISCUSSIONS; INFORMATION; CAREGIVER AB Uncertainty is triggered by many events during the experience of illness - from hearing bad news to meeting a new doctor. Oncology professionals need to recognize the intense feelings associated with uncertainty and respond empathically to patients. This article describes opportunities to strengthen the therapeutic connection and minimize uncertainty. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Schapira, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM LSCHAPIRA@PARTNERS.ORG NR 16 TC 2 Z9 2 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAR PY 2014 VL 22 IS 3 BP 859 EP 861 DI 10.1007/s00520-013-2086-y PG 3 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA AA3FR UT WOS:000330978800031 PM 24337763 ER PT J AU Trifonova, RT Lieberman, J van Baarle, D AF Trifonova, Radiana T. Lieberman, Judy van Baarle, Debbie TI Distribution of Immune Cells in the Human Cervix and Implications for HIV Transmission SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE dendritic cells; ectocervix; endocervix; menopause; T cells ID FEMALE REPRODUCTIVE-TRACT; IMMUNODEFICIENCY-VIRUS-INFECTION; CD4(+) T-CELLS; DENDRITIC CELLS; MUCOSAL TRANSMISSION; VAGINAL TRANSMISSION; SEXUAL TRANSMISSION; ADAPTIVE IMMUNITY; GENITAL-TRACT; BLT MICE AB Problem Knowledge of the mucosal immune cell composition of the human female genital tract is important for understanding susceptibility to HIV-1. Method of studyWe developed an optimized procedure for multicolor flow cytometry analysis of immune cells from human cervix to characterize all major immune cell subsets in the endocervix and ectocervix. ResultsHalf of tissue hematopoietic cells were CD14(+), many of which were macrophages and about a third were CD11c(+), most of which were CD103(-)CD11b(+)CX3CR1(+)DC-SIGN(+) dendritic cells (DCs). The other dominant population were T cells, with more CD8 than CD4 cells. T cells (both CD8 and CD4) and B cells were more abundant in the ectocervix than endocervix of pre-menopausal women; however, CD8(+) T cell and B cell numbers declined in the ectocervix after menopause, while CD4 T cell counts remained higher. B, NK and conventional myeloid and plasmocytoid DCs each were a few percent of tissue hematopoietic cells. Although the ectocervix had more HIV-susceptible CD4(+) T cells, polarized endocervical explants supported HIV replication significantly better. ConclusionDue to their abundance in the genital tract, CX3CR1(+)DC-SIGN(+) DCs might be important in HIV transmission. Our data also suggest that the columnar epithelium of the upper genital tract might be a preferential site for HIV transmission. C1 [Trifonova, Radiana T.; Lieberman, Judy; van Baarle, Debbie] Harvard Univ, Boston Childrens Hosp, Program Cellular & Mol Med, Sch Med, Boston, MA 02115 USA. [van Baarle, Debbie] Univ Med Ctr Utrecht, Dept Internal Med & Infect Dis, NL-3584 EA Utrecht, Netherlands. [van Baarle, Debbie] Univ Med Ctr Utrecht, Dept Immunol, NL-3584 EA Utrecht, Netherlands. RP Lieberman, J (reprint author), Harvard Univ, Boston Childrens Hosp, Program Cellular & Mol Med, Sch Med, 200 Longwood Ave, Boston, MA 02115 USA. EM Judy.Lieberman@childrens.harvard.edu; D.vanBaarle@umcutrecht.nl RI Lieberman, Judy/A-2717-2015 FU NIH [AI102816]; Harvard University CFAR [P30 AI060354]; University Medical Center Utrech FX This study was funded by NIH Grant AI102816 (JL), the Harvard University CFAR (P30 AI060354) (RT) and an Internationalizing grant from the University Medical Center Utrecht (DvB). We thank the staff at MGH Pathology Research Services (Mohammad Miri, Alexandra Bodo and Alexander Brunelle) for their assistance in collecting cervical tissue samples for our study. NR 43 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 2014 VL 71 IS 3 BP 252 EP 264 DI 10.1111/aji.12198 PG 13 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 304LJ UT WOS:000330748100006 PM 24410939 ER PT J AU Mulle, JG Pulver, AE McGrath, JA Wolyniec, PS Dodd, AF Cutler, DJ Sebat, J Malhotra, D Nestadt, G Conrad, DF Hurles, M Barnes, CP Ikeda, M Iwata, N Levinson, DF Gejman, PV Sanders, AR Duan, J Mitchell, AA Peter, I Sklar, P O'Dushlaine, CT Grozeva, D O'Donovan, MC Owen, MJ Hultman, CM Kahler, AK Sullivan, PF Kirov, G Warren, ST AF Mulle, Jennifer Gladys Pulver, Ann E. McGrath, John A. Wolyniec, Paula S. Dodd, Anne F. Cutler, David J. Sebat, Jonathan Malhotra, Dheeraj Nestadt, Gerald Conrad, Donald F. Hurles, Matthew Barnes, Chris P. Ikeda, Masashi Iwata, Nakao Levinson, Douglas F. Gejman, Pablo V. Sanders, Alan R. Duan, Jubao Mitchell, Adele A. Peter, Inga Sklar, Pamela O'Dushlaine, Colm T. Grozeva, Detelina O'Donovan, Michael C. Owen, Michael J. Hultman, Christina M. Kahler, Anna K. Sullivan, Patrick F. Kirov, George Warren, Stephen T. CA Mol Genetics Schizophrenia Consort TI Reciprocal Duplication of the Williams-Beuren Syndrome Deletion on Chromosome 7q11.23 Is Associated with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Autism; 7q11.23 duplication syndrome; psychiatric genetics; schizophrenia; schizophrenia genetics; Williams-Beuren syndrome ID COPY-NUMBER VARIANTS; SUPRAVALVULAR AORTIC STENOSIS; CARDIO-FACIAL SYNDROME; CANDIDATE GENES; HIGH-RISK; POPULATION; EPILEPSY; AUTISM; MICRODELETIONS; REARRANGEMENTS AB Background: Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.23 were associated with autism spectrum disorders. The reciprocal deletion of this region causes Williams-Beuren syndrome. Methods: We assayed an Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for genome-wide CNV. An excess of large rare and de novo CNVs were observed, including a 1.4 Mb duplication on chromosome 7q11.23 identified in two unrelated patients. To test whether this 7q11.23 duplication is also associated with SZ, we obtained data for 14,387 SZ cases and 28,139 controls from seven additional studies with high-resolution genome-wide CNV detection. We performed a meta-analysis, correcting for study population of origin, to assess whether the duplication is associated with SZ. Results: We found duplications at 7q11.23 in 11 of 14,387 SZ cases with only 1 in 28,139 control subjects (unadjusted odds ratio 21.52, 95% confidence interval: 3.13-922.6, p value 5.5 x 10(-5); adjusted odds ratio 10.8, 95% confidence interval: 1.46-79.62, p value.007). Of three SZ duplication carriers with detailed retrospective data, all showed social anxiety and language delay premorbid to SZ onset, consistent with both human studies and animal models of the 7q11.23 duplication. Conclusions: We have identified a new CNV associated with SZ. Reciprocal duplication of the Williams-Beuren syndrome deletion at chromosome 7q11.23 confers an approximately tenfold increase in risk for SZ. C1 [Mulle, Jennifer Gladys; Dodd, Anne F.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30222 USA. [Pulver, Ann E.; McGrath, John A.; Wolyniec, Paula S.; Nestadt, Gerald] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30222 USA. [Mulle, Jennifer Gladys; McGrath, John A.; Wolyniec, Paula S.; Nestadt, Gerald] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Pulver, Ann E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Sebat, Jonathan; Malhotra, Dheeraj] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA. [Sebat, Jonathan; Malhotra, Dheeraj] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Sebat, Jonathan] Univ Calif San Diego, Dept Cellular Mol & Mol Med, La Jolla, CA 92093 USA. [Sebat, Jonathan] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Conrad, Donald F.; Hurles, Matthew] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England. [Barnes, Chris P.] UCL, Dept Cell & Dev Biol, London, England. [Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Toyoake, Aichi, Japan. [Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Gejman, Pablo V.; Sanders, Alan R.; Duan, Jubao] NorthShore Univ HealthSystem, Dept Psychiat & Behav Sci, Evanston, IL USA. [Gejman, Pablo V.; Sanders, Alan R.; Duan, Jubao] Univ Chicago, Dept Psychiat & Behav Sci, Chicago, IL 60637 USA. [Mitchell, Adele A.] Off Chief Med Examiner, Dept Forens Biol, New York, NY USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Sklar, Pamela] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Sklar, Pamela; O'Dushlaine, Colm T.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY USA. [Grozeva, Detelina; O'Donovan, Michael C.; Owen, Michael J.; Kirov, George] Cardiff Univ, Dept Psychol Med, Cardiff CF10 3AX, S Glam, Wales. [Hultman, Christina M.; Kahler, Anna K.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Kahler, Anna K.; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Kahler, Anna K.; Sullivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Kahler, Anna K.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Warren, Stephen T.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. [Warren, Stephen T.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. RP Mulle, JG (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, CNR 4053,1518 Clifton Rd, Atlanta, GA 30222 USA. EM jmulle@emory.edu RI Kahler, Anna/J-2874-2012; OI Sebat, Jonathan/0000-0002-9087-526X; O'Donovan, Michael/0000-0001-7073-2379; Barnes, Chris/0000-0002-9459-1395 FU National Institutes of Health [MH080129, MH083722]; National Alliance for Research on Schizophrenia and Depression Young Investigator Award; Stanley Center for Psychiatric Research at the Broad Institute from a Grant from Stanley Medical Research Institute; Karolinska Institutet, Karolinska University Hospital; Swedish Research Council; Swedish County Council; Sderstrm Knigska Foundation; National Institute of Mental Health Schizophrenia Genetics Initiative [U01s: MH46276, MH46289, MH46318, 2 R01s: MH67257, MH59588, MH59571, MH59565, MH59587, MH60870, MH59566, MH59586, MH61675, MH60879]; [MH077139] FX Funding for this study was provided by National Institutes of Health Grants MH080129 and MH083722 to STW and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award to JGM. Support was provided by MH077139 (PFS), the Stanley Center for Psychiatric Research at the Broad Institute from a Grant from Stanley Medical Research Institute, the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, ALF grant from Swedish County Council, and Sderstrm Knigska Foundation. Funding support for the companion studies, Genome-Wide Association Study of Schizophrenia (Genetic Association Information Network [GAIN]) and Molecular Genetics of Schizophrenia-nonGAIN Sample (MGS_ nonGAIN), was provided by Genomics Research Branch at the National Institute of Mental Health and the genotyping and analysis of samples was provided through GAIN and under the Molecular Genetics of Schizophrenia (MGS) U01s: MH79469 and MH79470. Assistance with data cleaning was provided by the National Center for Biotechnology Information. The MGS datasets used for the analyses described in this manuscript were obtained from the database of Genotype and Phenotype (dbGaP) found at http://www.ncbi.nlm. nih. gov/gap through dbGaP accession numbers phs000021. v2. p1 (GAIN) and phs000167. v1. p1 (nonGAIN). Samples and associated phenotype data for the MGS genome-wide association study were collected under the following grants: National Institute of Mental Health Schizophrenia Genetics Initiative U01s: MH46276 (C. R. Cloninger), MH46289 (C. Kaufmann), and MH46318 (M. T. Tsuang); and MGS Part 1 and MGS Part 2 R01s: MH67257 (N. G. Buccola), MH59588 (B. J. Mowry), MH59571 (P. V. Gejman), MH59565 (R. Freedman), MH59587 (F. Amin), MH60870 (W. F. Byerley), MH59566 (D. W. Black), MH59586 (J. M. Silverman), MH61675 (D. F. Levinson), and MH60879 (C. R. Cloninger). Further details of collection sites, individuals, and institutions may be found in data supplement Table 1 of Sanders et al. (40) and at the study dbGaP pages. NR 44 TC 24 Z9 24 U1 1 U2 27 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2014 VL 75 IS 5 BP 371 EP 377 DI 10.1016/j.biopsych.2013.05.040 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304CQ UT WOS:000330724100008 PM 23871472 ER PT J AU Bramon, E Pirinen, M Strange, A Lin, K Freeman, C Bellenguez, C Su, Z Band, G Pearson, R Vukcevic, D Langford, C Deloukas, P Hunt, S Gray, E Dronov, S Potter, SC Tashakkori-Ghanbaria, A Edkins, S Bumpstead, SJ Arranz, MJ Bakker, S Bender, S Bruggeman, R Cahn, W Chandler, D Collier, DA Crespo-Facorro, B Dazzan, P de Haan, L di Forti, M Dragovic, M Giegling, I Hall, J Iyegbe, C Jablensky, A Kahn, RS Kalaydjieva, L Kravariti, E Lawrie, S Lins-Zen, DH Mata, I McDonald, C McIntosh, A Myin-Germeys, I Ophoff, RA Pariante, CM Paunio, T Picchioni, M Ripke, S Rujescu, D Sauer, H Shaikh, M Sussmann, J Suvisaari, J Tosato, S Toulopoulou, T Van Os, J Walshe, M Weisbrod, M Whalley, H Wiersma, D Blackwell, JM Brown, MA Casas, JP Corvin, A Duncanson, A Jankowski, JAZ Markus, HS Mathew, CG Palmer, CNA Plomin, R Rautanen, A Sawcer, SJ Trembath, RC Wood, NW Barroso, I Peltonen, L Lewis, CM Murray, RM Donnelly, P Powell, J Spencer, CCA AF Bramon, Elvira Pirinen, Matti Strange, Amy Lin, Kuang Freeman, Colin Bellenguez, Celine Su, Zhan Band, Gavin Pearson, Richard Vukcevic, Damjan Langford, Cordelia Deloukas, Panos Hunt, Sarah Gray, Emma Dronov, Serge Potter, Simon C. Tashakkori-Ghanbaria, Avazeh Edkins, Sarah Bumpstead, Suzannah J. Arranz, Maria J. Bakker, Steven Bender, Stephan Bruggeman, Richard Cahn, Wiepke Chandler, David Collier, David A. Crespo-Facorro, Benedicto Dazzan, Paola de Haan, Lieuwe di Forti, Marta Dragovic, Milan Giegling, Ina Hall, Jeremy Iyegbe, Conrad Jablensky, Assen Kahn, Rene S. Kalaydjieva, Luba Kravariti, Eugenia Lawrie, Stephen Lins-Zen, Don H. Mata, Ignacio McDonald, Colm McIntosh, Andrew Myin-Germeys, Inez Ophoff, Roel A. Pariante, Carmine M. Paunio, Tiina Picchioni, Marco Ripke, Stephan Rujescu, Dan Sauer, Heinrich Shaikh, Madiha Sussmann, Jessika Suvisaari, Jaana Tosato, Sarah Toulopoulou, Timothea Van Os, Jim Walshe, Muriel Weisbrod, Matthias Whalley, Heather Wiersma, Durk Blackwell, Jenefer M. Brown, Matthew A. Casas, Juan P. Corvin, Aiden Duncanson, Audrey Jankowski, Janusz A. Z. Markus, Hugh S. Mathew, Christopher G. Palmer, Colin N. A. Plomin, Robert Rautanen, Anna Sawcer, Stephen J. Trembath, Richard C. Wood, Nicholas W. Barroso, Ines Peltonen, Leena Lewis, Cathryn M. Murray, Robin M. Donnelly, Peter Powell, John Spencer, Chris C. A. CA Psychiat Genomics Consortium Psychosis Endophenotypes Int Conso Wellcome Trust Case-Control Consor TI A Genome-wide Association Analysis of a Broad Psychosis Phenotype Identifies Three Loci for Further Investigation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Bipolar disorder; genome-wide association; meta-analysis; polygenic score analysis; psychosis; schizophrenia ID BIPOLAR-DISORDER; PSYCHIATRIC-DISORDERS; COMMON VARIANTS; GENETIC RISK; SUSCEPTIBILITY LOCUS; GENERAL-POPULATION; CONFERRING RISK; WINNERS CURSE; HAN CHINESE; FOLLOW-UP AB Background: Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. Methods: 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). Results: No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p.003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 x 10(-14)) and explained approximately 2% of the phenotypic variance. Conclusions: Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through metaanalysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data. C1 [Bramon, Elvira] UCL, Mental Hlth Sci Unit, London WC1E 6BT, England. [Bramon, Elvira] UCL, Inst Cognit Neurosci, London WC1E 6BT, England. [Bramon, Elvira; Lin, Kuang; Bumpstead, Suzannah J.; Collier, David A.; Dazzan, Paola; di Forti, Marta; Iyegbe, Conrad; Kravariti, Eugenia; Pariante, Carmine M.; Picchioni, Marco; Shaikh, Madiha; Toulopoulou, Timothea; Van Os, Jim; Walshe, Muriel; Lewis, Cathryn M.; Murray, Robin M.; Powell, John] Kings Coll London, Inst Psychiat, London, England. [Pirinen, Matti; Strange, Amy; Freeman, Colin; Bellenguez, Celine; Su, Zhan; Band, Gavin; Pearson, Richard; Vukcevic, Damjan; Rautanen, Anna; Donnelly, Peter; Spencer, Chris C. A.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England. [Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C.; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Barroso, Ines; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Bumpstead, Suzannah J.; Arranz, Maria J.] Univ Barcelona, Fundacio Docencia & Recerca Mutua Terrassa, Catalonia, Spain. [Bakker, Steven; Cahn, Wiepke; Kahn, Rene S.; Ophoff, Roel A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands. [Bender, Stephan] Tech Univ Dresden, Dresden, Germany. [Bender, Stephan; Weisbrod, Matthias] Sect Expt Psychopathol & Neurophysiol, Heidelberg, Germany. [Bruggeman, Richard; Wiersma, Durk] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 AB Groningen, Netherlands. [Chandler, David; Kalaydjieva, Luba] Univ Western Australia, Western Australian Inst Med Res, Perth, WA 6009, Australia. [Chandler, David; Kalaydjieva, Luba] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia. [Crespo-Facorro, Benedicto; Mata, Ignacio] Univ Cantabria, Sch Med, Univ Hosp Marques Valdecilla, Dept Psychiat,IFIMAV, E-39005 Santander, Spain. [Crespo-Facorro, Benedicto; Mata, Ignacio] CIBERSAM, Madrid, Spain. [de Haan, Lieuwe; Lins-Zen, Don H.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands. [Dragovic, Milan; Jablensky, Assen] Univ Western Australia, Ctr Clin Res Neuropsychiat, Perth, WA 6009, Australia. [Giegling, Ina; Myin-Germeys, Inez; Rujescu, Dan] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Hall, Jeremy; Lawrie, Stephen; McIntosh, Andrew; Sussmann, Jessika; Whalley, Heather] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland. [McDonald, Colm] Natl Univ Ireland, Inst Clin Sci, Dept Psychiat, Galway, Ireland. [Lins-Zen, Don H.; Van Os, Jim] Maastricht Univ, Med Ctr, EURON, South Limburg Mental Hlth Res & Teaching Network, Maastricht, Netherlands. [Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Paunio, Tiina] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Paunio, Tiina] Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. [Picchioni, Marco; Toulopoulou, Timothea] St Andrews Acad Ctr, Inst Psychiat, Northampton, England. [Ripke, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA USA. [Ripke, Stephan] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany. [Sauer, Heinrich] Univ Hosp Jena, Dept Psychiat & Psychotherapy, Jena, Germany. [Shaikh, Madiha] Royal Holloway Univ London, Dept Psychol, Egham, Surrey, England. [Suvisaari, Jaana] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Helsinki, Finland. [Tosato, Sarah] Univ Verona, Sect Psychiat, I-37100 Verona, Italy. [Toulopoulou, Timothea] Univ Hong Kong, Dept Psychol, Hong Kong, Hong Kong, Peoples R China. [Toulopoulou, Timothea] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Blackwell, Jenefer M.] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Subiaco, WA, Australia. [Blackwell, Jenefer M.] Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge, England. [Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantia Inst, Brisbane, Qld, Australia. [Casas, Juan P.] Hlth London Sch Hyg & Trop Med, Dept Epidemiol & Populat, London, England. [Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England. [Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland. [Jankowski, Janusz A. Z.] Queen Mary Univ London, Blizard Inst, Ctr Digest Dis, London, England. [Jankowski, Janusz A. Z.] Univ Oxford, Churchill Hosp, Dept Med Oncol, Oxford OX1 2JD, England. [Jankowski, Janusz A. Z.] Leicester Royal Infirm, Digest Dis Acad Ctr, Leicester, Leics, England. [Markus, Hugh S.; Trembath, Richard C.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Mathew, Christopher G.] Kings Coll London, Kings Hlth Partners Guys Hosp, Dept Med & Mol Genet, London, England. [Palmer, Colin N. A.; Lewis, Cathryn M.] Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee, Scotland. [Plomin, Robert] Kings Coll London, Ctr Inst Psychiat, London, England. [Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. [Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. RP Bramon, E (reprint author), UCL, Mental Hlth Sci Unit, London WC1E 6BT, England. EM e.bramon@ucl.ac.uk RI Lewis, Cathryn/A-5225-2010; Palmer, Colin/C-7053-2008; Deloukas, Panos/B-2922-2013; McDonald, Colm/C-1430-2009; Jablensky, Assen/H-5116-2014; Blackwell, Jenefer/H-3015-2015; Jankowski, Janusz/H-2706-2012; Wood, Nicholas/C-2505-2009; OI Lewis, Cathryn/0000-0002-8249-8476; Palmer, Colin/0000-0002-6415-6560; Deloukas, Panos/0000-0001-9251-070X; Plomin, Robert/0000-0002-0756-3629; Suvisaari, Jaana/0000-0001-7167-0990; Jankowski, Janusz/0000-0003-2130-9181; Wood, Nicholas/0000-0002-9500-3348; Hunt, Sarah/0000-0002-8350-1235; Myin-Germeys, Inez/0000-0002-3731-4930; Gillman, Matthew/0000-0002-2340-6930; Bruggeman, Richard/0000-0002-3238-8471; Trembath, Richard/0000-0003-0550-3400; Walshe, Muriel/0000-0001-6829-1105 FU Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project [085475/B/08/Z, 085475/Z/08/Z]; MRC New Investigator Award; MRC Centenary Award; National Institute of Health Research UK; Psychiatry Research Trust; Schizophrenia Research Fund; Brain and Behavior Research foundation's (NARSAD's) Young Investigator Award; Wellcome Trust Research Training Fellowship; NIHR Biomedical Research Centre for Mental Health at the South London; Maudsley NHS Foundation Trust; Institute of Psychiatry Kings College London; Royal Society Wolfson Merit Award; Wellcome Trust Fellowship [097364/Z/11/Z]; Academy of Finland [257654]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02]; UK National Blood Service controls; Wellcome Trust; People of the British Isles collection; Wellcome Trust Centre for Human Genetics core grants [072894/Z/03/Z, 090532/Z/09/Z, 075491/Z/04/B]; Wellcome Trust Research Training Fellowship [064971]; NARSAD independent investigator award; Health Foundation Clinician Scientist Award; Wellcome Trust Clinical Research Training Fellowship; Royal Society Dorothy Hodgkin Fellowship; Geestkracht programme of the Dutch Health Research Council [10-000-1002]; EU Seventh Framework Programme [HEALTH-F2-2009-241909]; German Research Community (Deutsche Forschungsgemeinschaft, DFG) [WE-1996/ 1-3]; NIMH grant [1R01MH078075]; National Health and Medical Research Council, Australia [513874]; North Metropolitan Health Service, Perth, Australia; Instituto de Salud Carlos III [PI020499, PI050427, PI060507]; SENY Fundacic [CI 20050308007]; Fundacion Ramon Areces; Fundacion Marques de Valdecilla [API07/011, API10/13] FX The principal funding for this study was provided by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (Grant Nos. 085475/B/08/Z and 085475/Z/08/Z). E. Bramon currently holds a MRC New Investigator Award and a MRC Centenary Award. E. Bramon was further supported by the National Institute of Health Research UK (post-doctoral fellowship), the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behavior Research foundation's (NARSAD's) Young Investigator Award, a Wellcome Trust Research Training Fellowship and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry Kings College London.; P. Donnelly was supported in part by a Royal Society Wolfson Merit Award. C. Spencer was supported by a Wellcome Trust Fellowship (097364/Z/11/Z). M. Pirinen is supported by the Academy of Finland (257654). We acknowledge use of the British 1958 Birth Cohort DNA collection funded by the Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02), the UK National Blood Service controls funded by the Wellcome Trust and the People of the British Isles collection, funded by the Wellcome Trust. Work was supported in part by Wellcome Trust Centre for Human Genetics core grants 072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B.; M. Picchioni acknowledges a Wellcome Trust Research Training Fellowship (064971). T. Toulopoulou acknowledges the European Community's Sixth Framework Programme through a Marie Curie Training Network (MRTN-CT-2006-035987; Local Co-PIs Murray and Toulopoulou) called the European Twin Study Network on Schizophrenia (EUTwinsS), NARSAD (through a Young Investigator Award), the Economic and Social Research Council/Medical Research Council, the Psychiatry Research Trust (PTA-037-27-0002) and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry Kings College London. All co-authors based at the Institute of PsychiatryKing's College London acknowledge the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry Kings College London.; The Edinburgh cohort was supported by: a NARSAD independent investigator award and a Health Foundation Clinician Scientist Award (to A. McIntosh), a Wellcome Trust Clinical Research Training Fellowship (to Jessika Sussman) and a Royal Society Dorothy Hodgkin Fellowship (to Heather Whalley).; The GROUP study was supported by: (i) The Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1002). (ii) The EU Seventh Framework Programme (consortium name: EU-GEI; No. HEALTH-F2-2009-241909) and matching funds from participating universities and mental health care organizations (Site Amsterdam: Academic Psychiatric Centre AMC, Ingeest, Arkin, Dijk en Duin, Rivierduinen, Erasmus MC, GGZ Noord Holland Noord; Site Utrecht: University Medical Centre Utrecht, Altrecht, Symfora, Meerkanten, Riagg Amersfoort, Delta; Site Groningen: University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Adhesie, Mediant, GGZ De Grote Rivieren and Parnassia psycho-medical centre; Site Maastricht: Maastricht University Medical Center, GGZ Eindhoven, GGZ Midden-Brabant, GGZ Oost-Brabant, GGZ Noord-Midden Limburg, Mondriaan Zorggroep, Prins Clauscentrum Sittard, RIAGG Roermond, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem). (iii) NIMH grant to R. A. Ophoff (1R01MH078075).; The Heidelberg cohort work was supported by a grant (WE-1996/ 1-3) from the German Research Community (Deutsche Forschungsgemeinschaft, DFG) to M. Weisbrod. We would like to thank Dr. Anuradha Sharma for her help with the management of the Heidelberg dataset.; The Perth cohort was supported by grant 513874 of the National Health and Medical Research Council, Australia and by the North Metropolitan Health Service, Perth, Australia. The Santander cohort was supported by Instituto de Salud Carlos III (PI020499, PI050427, PI060507), SENY Fundacic (CI 20050308007), Fundacion Ramon Areces and Fundacion Marques de Valdecilla (API07/011, API10/13). NR 115 TC 11 Z9 11 U1 4 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2014 VL 75 IS 5 BP 386 EP 397 DI 10.1016/j.biopsych.2013.03.033 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304CQ UT WOS:000330724100010 ER PT J AU van Erp, TGM Guella, I Vawter, MP Turner, J Brown, GG McCarthy, G Greve, DN Glover, GH Calhoun, VD Lim, KO Bustillo, JR Belger, A Ford, JM Mathalon, DH Diaz, M Preda, A Nguyen, D Macciardi, F Potkin, SG AF van Erp, Theo G. M. Guella, Ilaria Vawter, Marquis P. Turner, Jessica Brown, Gregory G. McCarthy, Gregory Greve, Douglas N. Glover, Gary H. Calhoun, Vince D. Lim, Kelvin O. Bustillo, Juan R. Belger, Aysenil Ford, Judith M. Mathalon, Daniel H. Diaz, Michele Preda, Adrian Nguyen, Dana Macciardi, Fabio Potkin, Steven G. TI Schizophrenia miR-137 Locus Risk Genotype Is Associated with Dorsolateral Prefrontal Cortex Hyperactivation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Genes; imaging; mir137; rs1625579; schizophrenia; working memory ID MELANOMA-CELL LINES; WORKING-MEMORY; BRAIN ACTIVATION; RATING-SCALE; STEM-CELLS; MICRORNA; FMRI; PERFORMANCE; VARIANT; MIR137 AB Background: miR-137 dysregulation has been implicated in the etiology of schizophrenia, but its functional role remains to be determined. Methods: Functional magnetic resonance imaging scans were acquired on 48 schizophrenia patients and 63 healthy volunteers (total sample size N 111 subjects), with similar mean age and sex distribution, while subjects performed a Sternberg Item Response Paradigm with memory loads of one, three, and five numbers. Dorsolateral prefrontal cortex (DLPFC) retrieval activation for the working memory load of three numbers, for which hyperactivation had been shown in schizophrenia patients compared with control subjects, was extracted. The genome-wide association study confirmed schizophrenia risk single nucleotide polymorphism rs1625579 (miR-137 locus) was genotyped (schizophrenia: GG n 0, GT n 9, TT n 39; healthy volunteers: GG 2, GT n 15, and TT n 46). Fisher's exact test examined the effect of diagnosis on rs1625579 allele frequency distribution (p nonsignificant). Mixed model regression analyses examined the effects of diagnosis and genotype on working memory performance measures and DLPFC activation. Results: Patients showed significantly higher left DLPFC retrieval activation on working memory load 3, lower working memory performance, and longer response times compared with controls. There was no effect of genotype on working memory performance or response times in either group. However, individuals with the rs1625579 TT genotype had significantly higher left DLPFC activation than those with the GG/GT genotypes. Conclusions: Our study suggests that the rs1625579 TT (miR-137 locus) schizophrenia risk genotype is associated with the schizophrenia risk phenotype DLPFC hyperactivation commonly considered a measure of brain inefficiency. C1 [van Erp, Theo G. M.; Guella, Ilaria; Preda, Adrian; Nguyen, Dana; Macciardi, Fabio; Potkin, Steven G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Guella, Ilaria; Vawter, Marquis P.] Univ Calif Irvine, Dept Psychiat & Human Behav, Funct Genom Lab, Irvine, CA 92717 USA. [Turner, Jessica; Calhoun, Vince D.] Univ New Mexico, Mind Res Network, Albuquerque, NM 87131 USA. [Turner, Jessica; Bustillo, Juan R.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Turner, Jessica; Bustillo, Juan R.] Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA. [Brown, Gregory G.] Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA. [Brown, Gregory G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [McCarthy, Gregory] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Glover, Gary H.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Lim, Kelvin O.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Belger, Aysenil] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Diaz, Michele] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC USA. RP Potkin, SG (reprint author), Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, 5251 Calif Ave,Suite 240, Irvine, CA 92617 USA. EM sgpotkin@uci.edu RI Turner, Jessica/H-7282-2015; Macciardi, Fabio/N-3768-2014; Preda, Adrian /K-8889-2013; OI Potkin, Steven/0000-0003-1028-1013; Turner, Jessica/0000-0003-0076-8434; Macciardi, Fabio/0000-0003-0537-4266; Preda, Adrian /0000-0003-3373-2438; Belger, Aysenil/0000-0003-2687-1966; Mathalon, Daniel/0000-0001-6090-4974 FU National Center for Research Resources at the National Institutes of Health (NIH) [NIH 1 U24 RR021992]; Function Biomedical Informatics Research Network [NIH 1 U24 RR025736-01]; Biomedical Informatics Research Network Coordinating Center; William Lion Penzner Foundation (University of California, Irvine, Department of Psychiatry and Human Behavior); National Institutes of Mental Health [R01MH085801]; Amgen; Baxter; Bristol-Myers Squibb; Cephalon, Inc.; Eli Lilly; Forest Laboratories; Genentech; Janssen Pharmaceutical; Merck; Otsuka; Pfizer; Roche; Sunovion; Takeda Pharmaceutical; Vanda Pharmaceutical; National Institute on Alcohol Abuse and Alcoholism; National Institute of Biomedical Imaging and Bioengineering; NIH/National Center for Research Resources; University of Southern California; University of California at San Francisco; University of California at San Diego; Baylor College of Medicine; Pritzker Neuropsychiatric Disorders Research Consortium and National Institute of Mental Health [MH099440, MH085801] FX This work was supported by the National Center for Research Resources at the National Institutes of Health (NIH; Grant Nos.: NIH 1 U24 RR021992, Function Biomedical Informatics Research Network; NIH 1 U24 RR025736-01, Biomedical Informatics Research Network Coordinating Center; http:// www. birncommunity. org), the William Lion Penzner Foundation (University of California, Irvine, Department of Psychiatry and Human Behavior), and the National Institutes of Mental Health (Grant No. R01MH085801 to MVP).; Dr. van Erp is funded by NIH. Dr. Potkin is funded by the NIH. Dr. Potkin has financial interests in Bristol-Myers Squibb, Eisai, Inc., Eli Lilly, Forest Laboratories, Genentech, Janssen Pharmaceutical, Lundbeck, Merck, Novartis, Organon, Pfizer, Roche, Sunovion, Takeda Pharmaceutical, Vanda Pharmaceutical, and has received grant funding from Amgen, Baxter, Bristol-Myers Squibb, Cephalon, Inc., Eli Lilly, Forest Laboratories, Genentech, Janssen Pharmaceutical, Merck, Otsuka, Pfizer, Roche, Sunovion, Takeda Pharmaceutical, Vanda Pharmaceutical, National Institute on Alcohol Abuse and Alcoholism, National Institute of Biomedical Imaging and Bioengineering, NIH/National Center for Research Resources, University of Southern California, University of California at San Francisco, University of California at San Diego, and Baylor College of Medicine. Dr. Vawter is funded by Pritzker Neuropsychiatric Disorders Research Consortium and National Institute of Mental Health Grant Nos. MH099440 and MH085801. Dr. Bustillo has consulted with Novartis and Otsuke Pharmaceuticals. Dr. Mathalon consults for Bristol-Myers Squibb. The remaining authors report no biomedical financial interests or potential conflicts of interest. NR 64 TC 27 Z9 27 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2014 VL 75 IS 5 BP 398 EP 405 DI 10.1016/j.biopsych.2013.06.016 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304CQ UT WOS:000330724100011 PM 23910899 ER PT J AU Mckay, RR Kroeger, N Xie, W Lee, JL Knox, JJ Bjarnason, GA MacKenzie, MJ Wood, L Srinivas, S Vaishampayan, UN Rha, SY Pal, SK Donskov, F Tantravahi, SK Rini, BI Heng, DYC Choueiri, TK AF Mckay, Rana R. Kroeger, Nils Xie, Wanling Lee, Jae-Lyun Knox, Jennifer J. Bjarnason, Georg A. MacKenzie, Mary J. Wood, Lori Srinivas, Sandy Vaishampayan, Ulka N. Rha, Sun-Young Pal, Sumanta K. Donskov, Frede Tantravahi, Srinivas K. Rini, Brian I. Heng, Daniel Y. C. Choueiri, Toni K. TI Impact of Bone and Liver Metastases on Patients with Renal Cell Carcinoma Treated with Targeted Therapy SO EUROPEAN UROLOGY LA English DT Article DE Bone metastases; Liver metastases; mTOR inhibitors; Outcome; Renal cell carcinoma; VEGF therapy ID PROGNOSTIC-FACTORS; PROGRESSION-FREE; SURVIVAL; SUNITINIB; CANCER; BISPHOSPHONATES; EVEROLIMUS; MODEL AB Background: The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC). Objective: To analyze outcomes based on the presence of bone metastases (BMs) and/or liver metastases (LMs) in patients with RCC treated with targeted therapy. Design, setting, and participants: We conducted a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC. Outcome measurements and statistical analysis: We analyzed the impact of the site of metastasis on overall survival (OS) and time-to-treatment failure. Statistical analyses were performed using multivariable Cox regression. Results and limitations: The presence of BMs was 34% overall, and when stratified by IMDC risk groups was 27%, 33%, and 43% in the favorable-, intermediate-, and poor-risk groups, respectively (p < 0.001). The presence of LMs was 19% overall and higher in the poor-risk patients (23%) compared with the favorable- or intermediate-risk groups (17%) (p = 0.003). When patients were classified into four groups based on the presence of BMs and/or LMs, the hazard ratio, adjusted for IMDC risk factors, was 1.4 (95% confidence interval [CI], 1.22-1.62) for BMs, 1.42 (95% CI, 1.17-1.73) for LMs, and 1.82 (95% CI, 1.47-2.26) for both BMs and LMs compared with other metastatic sites (p < 0.0001). The prediction model performance for OS was significantly improved when BMs and LMs were added to the IMDC prognostic model (likelihood ratio test p < 0.0001). Data in this analysis were collected retrospectively. Conclusions: The presence of BMs and LMs in patients treated with targeted agents has a negative impact on survival. Patients with BMs and/or LMs may benefit from earlier inclusion on clinical trials of novel agents or combination-based therapies. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Mckay, Rana R.; Choueiri, Toni K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kroeger, Nils; Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Dept Oncol, Calgary, AB, Canada. [Kroeger, Nils] Univ Med Greifswald, Dept Urol, Greifswald, Germany. [Xie, Wanling] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Lee, Jae-Lyun] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Knox, Jennifer J.] Princess Margaret Hosp, Dept Hematol, Toronto, ON M4X 1K9, Canada. [Knox, Jennifer J.] Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. [Bjarnason, Georg A.] Univ Toronto, Sunnybrook Odette Canc Ctr, Div Med Oncol Hematol, Toronto, ON, Canada. [MacKenzie, Mary J.] London Reg Canc Program, Dept Med Oncol, London, ON, Canada. [Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Div Med Oncol, Halifax, NS, Canada. [Srinivas, Sandy] Stanford Med Ctr, Div Oncol, Stanford, CA USA. [Vaishampayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI USA. [Rha, Sun-Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Div Med Oncol, Seoul 120749, South Korea. [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA USA. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Tantravahi, Srinivas K.] Univ Utah, Huntsman Canc Inst, Div Med Oncol Hematol, Salt Lake City, UT USA. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM toni_choueiri@DFCI.harvard.edu OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Bayer; Pfizer; Novartis; GlaxoSmithKline; Bayer Korea FX Toni K. Choueiri certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Jae-Lyun Lee has received honoraria from Novartis, Bayer, and Pfizer and research funding from Bayer. Jennifer J. Knox has been a consultant and played an advisory role at Aveo and has received research funding from Pfizer. Georg A. Bjarnason has been a consultant and played an advisory role at Pfizer and received honoraria and research funding from Pfizer. Mary J. MacKenzie has an advisory role at Novartis and Pfizer and has received research funding from both. Lori Wood has an advisory role at Pfizer and Novartis and has received research funding from Pfizer, Novartis, and GlaxoSmithKline. Ulka N. Vaishamayan has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. Sun-Young Rha has an advisory role at Novartis, Pfizer, and GlaxoSmithKline and has received research funding from Novartis and Bayer Korea. Frede Donskov has received research funding from Novartis. Brian I. Rini has an advisory role at Pfizer, GlaxoSmithKline, Aveo, Bayer, and Onyx and has received research funding from GlaxoSmithKline and Pfizer. Daniel Y.C. Heng has an advisory role at Aveo, Pfizer, Novartis, and Bayer. Toni K. Choueiri has received research funding from Pfizer and has an advisory role at Aveo, Pfizer, Novartis, GlaxoSmithKline, Genentech, Bayer, and Onyx. All remaining authors have nothing to disclose. NR 21 TC 47 Z9 48 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD MAR PY 2014 VL 65 IS 3 BP 577 EP 584 DI 10.1016/j.eururo.2013.08.012 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 302AC UT WOS:000330572600018 PM 23962746 ER PT J AU Saylor, PJ Smith, MR O'Malley, AJ Keating, NL AF Saylor, Philip J. Smith, Matthew R. O'Malley, A. James Keating, Nancy L. TI Androgen-deprivation Therapy and Risk for Biliary Disease in Men with Prostate Cancer SO EUROPEAN UROLOGY LA English DT Article DE Androgen deprivation therapy; Biliary disease; GnRH agonist; Prostate cancer; Orchiectomy ID GALLBLADDER-DISEASE; GALLSTONE DISEASE; PERFORM CHOLECYSTECTOMY; CARDIOVASCULAR-DISEASE; ACUTE CHOLECYSTITIS; INCREASED MORBIDITY; INSULIN-RESISTANCE; ELDERLY-PATIENTS; POPULATION; OBESITY AB Background: Androgen-deprivation therapy (ADT) by either a gonadotropin-releasing hormone (GnRH) agonist or bilateral orchiectomy improves disease-related outcomes of men with prostate cancer but has a variety of adverse metabolic effects including obesity, increased abdominal girth, increased triglycerides, and insulin resistance. Each is a risk factor for gallstone disease. Additionally, GnRH agonist treatment was recently shown in metabolomic analyses to increase plasma levels of some bile acids. Objective: To assess the relationship between ADT and the incidence of biliary disease in men with prostate cancer. Design, setting, and participants: We studied 183 842 men >65 yr of age living in Surveillance, Epidemiology, and End Results regions who were diagnosed with prostate cancer from 1992 to 2007 and followed through 2009. Outcome measurements and statistical analysis: We calculated incidence rates for biliary disease during treatment with GnRH agonists, orchiectomy, or no therapy. We used Cox proportional hazardmodels to assess the association of ADT with biliary disease. Results and limitations: Among 183 842 men with locoregional prostate cancer, 48.4% received GnRH agonist treatment and 2.2% underwent bilateral orchiectomy during follow-up. GnRH agonist treatment was associated with a significantly higher incidence of biliary disease compared with no treatment (15.7 vs 13.4 cases per 1000 personyears; p < 0.001). In adjusted analyses, GnRH agonist use was associated with the risk of biliary disease (adjusted hazard ratio: 1.10; 95% confidence interval, 1.05-1.15; p < 0.001). Orchiectomy was not significantly associated with biliary disease. Conclusions: GnRH agonist treatment may be associated with a greater risk of incident biliary disease. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Saylor, Philip J.; Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [O'Malley, A. James; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7E,55 Fruit St, Boston, MA 02114 USA. EM psaylor@partners.org FU Prostate Cancer Foundation; National Institutes of Health [5K24CA121990-02] FX The Prostate Cancer Foundation provided financial support for the conduct of this research. Dr. Smith is supported by a career grant from the National Institutes of Health (5K24CA121990-02). NR 30 TC 0 Z9 0 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD MAR PY 2014 VL 65 IS 3 BP 642 EP 649 DI 10.1016/j.eururo.2013.02.003 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 302AC UT WOS:000330572600028 PM 23428068 ER PT J AU Nepple, KG Kibel, AS AF Nepple, Kenneth G. Kibel, Adam S. TI Reply to Michael Froehner's Letter to the Editor re: Kenneth G. Nepple, Andrew J. Stephenson, Dorina Kallogjeri, et al. Mortality After Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy, or Brachytherapy in Men Without Comorbidity. Eur Urol 2013;64:372-8 SO EUROPEAN UROLOGY LA English DT Letter C1 [Nepple, Kenneth G.; Kibel, Adam S.] Washington Univ, Sch Med, St Louis, MO USA. [Nepple, Kenneth G.] Univ Iowa, Iowa City, IA 52242 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nepple, KG (reprint author), Univ Iowa, Dept Urol, 3228 RCP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM kenneth-nepple@uiowa.edu NR 2 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD MAR PY 2014 VL 65 IS 3 BP E42 EP E42 DI 10.1016/j.eururo.2013.11.036 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 302AC UT WOS:000330572600004 PM 24315707 ER PT J AU Rodriguez, EK Boulton, C Weaver, MJ Herder, LM Morgan, JH Chacko, AT Appleton, PT Zurakowski, D Vrahas, MS AF Rodriguez, Edward K. Boulton, Christina Weaver, Michael J. Herder, Lindsay M. Morgan, Jordan H. Chacko, Aron T. Appleton, Paul T. Zurakowski, David Vrahas, Mark S. TI Predictive factors of distal femoral fracture nonunion after lateral locked plating: A retrospective multicenter case-control study of 283 fractures SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Supracondylar; Distal femur fracture; Locked plating; Nonunion; LISS; Periprosthetic ID INVASIVE STABILIZATION SYSTEM; TOTAL KNEE ARTHROPLASTY; FEMUR FRACTURES; INTERNAL-FIXATION; LOCKING PLATE; LISS; REDUCTION AB Introduction: Reported initial success rates after lateral locked plating (LLP) of distal femur fractures have led to more concerning outcomes with reported nonunion rates now ranging from 0 to 21%. Reported factors associated with nonunion include comorbidities such as obesity, age and diabetes. In this study, our goal was to identify patient comorbidities, injury and construct characteristics that are independent predictors of nonunion risk in LLP of distal femur fractures; and to develop a predictive algorithm of nonunion risk, irrespective of institutional criteria for clinical intervention variability. Patients and methods: A retrospective review of 283 distal femoral fractures in 278 consecutive patients treated with LLP at three Level1 academic trauma centers. Nonunion was liberally defined as need for secondary procedure to manage poor healing based on unrestricted surgeon criteria. Patient demographics (age, gender), comorbidities (obesity, smoking, diabetes, chronic steroid use, dialysis), injury characteristics (AO type, periprosthetic fracture, open fracture, infection), and management factors (institution, reason for intervention, time to intervention, plate length, screw density, and plate material) were obtained for all participants. Multivariable analysis was performed using logistic regression to control for confounding in order to identify independent risk factors for nonunion. Results: 28 of the 283 fractures were treated for nonunion, 13 were referred to us from other institutions. Obesity (BMI > 30), open fracture, occurrence of infection, and use of stainless steel plate were significant independent risk factors (P < 0.01). A predictive algorithm demonstrates that when none of these variables are present (titanium instead of stainless steel) the risk of nonunion requiring intervention is 4%, but increases to 96% with all factors present. When a stainless plate is used, obesity alone carries a risk of 44% while infection alone a risk of 66%. While Chi-square testing suggested no institutional differences in nonunion rates, the time to intervention for nonunion varied inversely with nonunion rates between institutions, indicating varying trends in management approach. Discussion: Obesity, open fracture, occurrence of infection, and the use of stainless steel are prognostic risk factors of nonunion in distal femoral fractures treated with LLP independent of differing trends in how surgeons intervene in the management of nonunion. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Rodriguez, Edward K.; Herder, Lindsay M.; Chacko, Aron T.; Appleton, Paul T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Boston, MA 02215 USA. [Boulton, Christina] Univ Maryland, Dept Orthopaed, Baltimore, MD 21201 USA. [Weaver, Michael J.; Morgan, Jordan H.; Vrahas, Mark S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Anesthesia, Boston Childrens Hosp, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Surg, Boston Childrens Hosp, Boston, MA 02115 USA. [Morgan, Jordan H.; Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Rodriguez, EK (reprint author), Beth Israel Deaconess Med Ctr, Orthopaed Trauma Dept Orthopaed Surg, 330 Brookline Ave,Stoneman 10, Boston, MA 02215 USA. EM ekrodrig@bidmc.harvard.edu NR 34 TC 18 Z9 20 U1 0 U2 15 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 MAR PY 2014 VL 45 IS 3 BP 554 EP 559 DI 10.1016/j.injury.2013.10.042 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 302BH UT WOS:000330575800017 PM 24275357 ER PT J AU Chipman, JJ Sanda, MG Dunn, RL Wei, JT Litwin, MS Crociani, CM Regan, MM Chang, P AF Chipman, Jonathan J. Sanda, Martin G. Dunn, Rodney L. Wei, John T. Litwin, Mark S. Crociani, Catrina M. Regan, Meredith M. Chang, Peter CA PROST-QA Consortium TI Measuring and Predicting Prostate Cancer Related Quality of Life Changes Using EPIC for Clinical Practice SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; quality of life; questionnaires; outcome assessment (health care) ID INDEX COMPOSITE; VALIDATION; INSTRUMENT; SURVIVORS; VERSION AB Purpose: We expanded the clinical usefulness of EPIC-CP (Expanded Prostate Cancer Index Composite for Clinical Practice) by evaluating its responsiveness to health related quality of life changes, defining the minimally important differences for an individual patient change in each domain and applying it to a sexual outcome prediction model. Materials and Methods: In 1,201 subjects from a previously described multicenter longitudinal cohort we modeled the EPIC-CP domain scores of each treatment group before treatment, and at short-term and long-term followup. We considered a posttreatment domain score change from pretreatment of 0.5 SD or greater clinically significant and p <= 0.01 statistically significant. We determined the domain minimally important differences using the pooled 0.5 SD of the 2, 6, 12 and 24-month posttreatment changes from pretreatment values. We then recalibrated an EPIC-CP based nomogram model predicting 2-year post-prostatectomy functional erection from that developed using EPIC-26. Results: For each health related quality of life domain EPIC-CP was sensitive to similar posttreatment health related quality of life changes with time, as was observed using EPIC-26. The EPIC-CP minimally important differences in changes in the urinary incontinence, urinary irritation/obstruction, bowel, sexual and vitality/hormonal domains were 1.0, 1.3, 1.2, 1.6 and 1.0, respectively. The EPIC-CP based sexual prediction model performed well (AUC 0.76). It showed robust agreement with its EPIC-26 based counterpart with 10% or less predicted probability differences between models in 95% of individuals and a mean +/- SD difference of 0.0 +/- 0.05 across all individuals. Conclusions: EPIC-CP is responsive to health related quality of life changes during convalescence and it can be used to predict 2-year post-prostatectomy sexual outcomes. It can facilitate shared medical decision making and patient centered care. C1 [Chipman, Jonathan J.; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Crociani, Catrina M.; Chang, Peter] Beth Israel Deaconess Med Ctr, Dept Surg, Div Urol, Boston, MA 02215 USA. [Regan, Meredith M.; Chang, Peter] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Sanda, Martin G.] Emory Univ, Dept Urol, Atlanta, GA 30322 USA. [Dunn, Rodney L.; Wei, John T.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA. [Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Chang, P (reprint author), Harvard Univ, Div Urol, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave,Rabb 440, Boston, MA 02215 USA. EM pchang@bidmc.harvard.edu RI Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012 FU Beth Israel Deaconess Medical Center FX PROST-QA Data Coordinating Center project management was provided by Jill Hardy, Michigan State University, East Lansing, Michigan; and Erin Najuch and Jonathan Chipman, Dana Farber Cancer Institute, and Catrina Crociani, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Beth Doiron, Beth Israel Deaconess Medical Center, provided grant administration. NR 22 TC 15 Z9 15 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD MAR PY 2014 VL 191 IS 3 BP 638 EP 645 DI 10.1016/j.juro.2013.09.040 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AA5GF UT WOS:000331123400019 PM 24076307 ER PT J AU Sammon, JD Zhu, G Sood, A Sukumar, S Kim, SP Sun, M Karakiewicz, PI Menon, M Trinh, QD Elder, JS AF Sammon, Jesse D. Zhu, Grace Sood, Akshay Sukumar, Shyam Kim, Simon P. Sun, Maxine Karakiewicz, Pierre I. Menon, Mani Quoc-Dien Trinh Elder, Jack S. TI Pediatric Nephrectomy: Incidence, Indications and Use of Minimally Invasive Techniques SO JOURNAL OF UROLOGY LA English DT Article DE nephrectomy; pediatrics; surgical procedures, minimally invasive ID LAPAROSCOPIC NEPHRECTOMY; RADICAL NEPHRECTOMY; UNITED-STATES; TRENDS; TRANSPERITONEAL; SURGERY AB Purpose: There is a paucity of knowledge regarding nephrectomy in contemporary United States pediatric populations. Usage patterns, indications and demographics of children undergoing nephrectomy are unknown. Given the significant increases in the use of minimally invasive nephrectomy in adults, we hypothesized similar trends may be seen in the pediatric population. Materials and Methods: An estimated total of 27,615 children undergoing nephrectomy between 1998 and 2010 was extracted from the Nationwide Inpatient Sample. Trends in use were analyzed with the estimated annual percent change methodology using linear regression and proportions by chi-square. Determinants of minimally invasive nephrectomy were evaluated using generalized linear models adjusted for clustering with generalized estimating equations. Results: The annual incidence of pediatric nephrectomy was 2.90 per 100,000 patient-years and remained stable. Nephrectomy was most common in children 0 to 1 year old (36%) and least common in children 6 to 9 years old (14%). However, nephrectomy for malignancy was most common in children 3 to 4 years old. Minimally invasive nephrectomy usage increased from 1.1% to 11.6% during the study period (estimated annual percent change 72.82%, p = 0.007). On multivariable analysis patients with malignancy (OR 0.07, p <0.001) had a lower rate of minimally invasive nephrectomy. Increased use was associated with increasing age (OR 1.07, p <0.001), treatment at a teaching institution (OR 1.95, p = 0.008) and increasing hospital volume (OR 1.01, p = 0.001). Conclusions: While the annual incidence of nephrectomy is stable, the use of minimally invasive nephrectomy is expanding in the pediatric population. Benign pathology and increasing age as well as nephrectomy at high volume teaching institutions are independently associated with minimally invasive nephrectomy use. C1 [Sammon, Jesse D.; Zhu, Grace; Sood, Akshay; Sukumar, Shyam; Menon, Mani; Quoc-Dien Trinh; Elder, Jack S.] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI 48202 USA. [Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA. [Sun, Maxine; Karakiewicz, Pierre I.] Univ Montreal, Canc Prognost & Hlth Outcomes Unit, Ctr Hlth, Montreal, PQ, Canada. [Sun, Maxine] Univ Montreal, Fac Med, Dept Publ Hlth, Montreal, PQ H3C 3J7, Canada. RP Sammon, JD (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM jsammon79@gmail.com FU University of Montreal Health Center Urology Specialists; Fonds de la Recherche en Sante du Quebec; University of Montreal Department of Surgery; University of Montreal Health Center (CHUM) Foundation FX Supported by University of Montreal Health Center Urology Specialists, Fonds de la Recherche en Sante du Quebec, University of Montreal Department of Surgery and University of Montreal Health Center (CHUM) Foundation. Funding sources had no impact in design, collection, data analysis and interpretation of data. All researchers are independent from funding sources. NR 23 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD MAR PY 2014 VL 191 IS 3 BP 764 EP 770 DI 10.1016/j.juro.2013.09.063 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AA5GF UT WOS:000331123400079 PM 24095907 ER PT J AU Chen, HX Craft, DL Gierga, DP AF Chen, Huixiao Craft, David L. Gierga, David P. TI Multicriteria optimization informed VMAT planning SO MEDICAL DOSIMETRY LA English DT Article DE MCO-IMRT; VMAT; Prostate; Head/neck ID VOLUMETRIC-MODULATED ARC; RADIATION-THERAPY; SINGLE-ARC; IMRT; RADIOTHERAPY; CANCER; DELIVERY; QUALITY; NUMBER; HEAD AB We developed a patient-specific volumetric-modulated arc therapy (VMAT) optimization procedure using dose-volume histogram (DVH) information from multicriteria optimization (MCO) of intensity-modulated radiotherapy (IMRT) plans. The study included 10 patients with prostate cancer undergoing standard fractionation treatment, 10 patients with prostate cancer undergoing hypofractionation treatment, and 5 patients with head/neck cancer. MCO-IMRT plans using 20 and 7 treatment fields were generated for each patient on the RayStation treatment planning system (clinical version 2.5, RaySearch Laboratories, Stockholm, Sweden). The resulting DVH of the 20-field MCO-IMRT plan for each patient was used as the reference DVH, and the extracted point values of the resulting DVH of the MCO-IMRT plan were used as objectives and constraints for VMAT optimization. Weights of objectives or constraints of VMAT optimization or both were further tuned to generate the best match with the reference DVH of the MCO-IMRT plan. The final optimal VMAT plan quality was evaluated by comparison with MCO-IMRT plans based on homogeneity index, conformity number of planning target volume, and organ at risk sparing. The influence of gantry spacing, arc number, and delivery time on VMAT plan quality for different tumor sites was also evaluated. The resulting VMAT plan quality essentially matched the 20-field MCO-IMRT plan but with a shorter delivery time and less monitor units. VMAT plan quality of head/neck cancer cases improved using dual arcs whereas prostate cases did not VMAT plan quality was improved by fine gantry spacing of 2 for the head/neck cancer cases and the hypofractionation-treated prostate cancer cases but not for the standard fractionation-treated prostate cancer cases. MCO-informed VMAT optimization is a useful and valuable way to generate patient-specific optimal VMAT plans, though modification of the weights of objectives or constraints extracted from resulting DVH of MCO-IMRT or both is necessary. (C) 2014 American Association of Medical Dosimetrists. C1 [Chen, Huixiao; Craft, David L.; Gierga, David P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gierga, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM dgierga@partners.org FU NCI; RaySearch Laboratories FX The authors thank RaySearch Laboratories for their continuous technical support during the project. Funding support provided by NCI federal share proton beam income grant and RaySearch Laboratories. NR 25 TC 6 Z9 9 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 EI 1873-4022 J9 MED DOSIM JI Med. Dosim. PD SPR PY 2014 VL 39 IS 1 BP 64 EP 73 DI 10.1016/j.meddos.2013.10.001 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AA2MD UT WOS:000330927800013 PM 24360919 ER PT J AU Torriani, M Taneja, AK Hosseini, A Gill, TJ Bredella, MA Li, GA AF Torriani, Martin Taneja, Atul K. Hosseini, Ali Gill, Thomas J. Bredella, Miriam A. Li, Guoan TI T2 relaxometry of the infrapatellar fat pad after arthroscopic surgery SO SKELETAL RADIOLOGY LA English DT Article DE T2 relaxometry; Infrapatellar fat pad; Fibrosis; Arthroscopy; MRI ID PATELLAR TENDON; FIBROSIS; RESECTION; KNEE AB Objective To investigate the T2 relaxation values of the infrapatellar fat pad (IFP) after arthroscopic surgery. This study was approved by the institutional review board; all individuals signed informed consent. We performed MRI in 16 knees from 8 subjects. Prior to imaging, each subject had unilateral arthroscopic knee surgery and an asymptomatic non-operated contralateral knee. We used a 10-echo multiple-TE fast-spin echo pulse sequence for creation of T2 relaxation time maps. Two musculoskeletal radiologists independently placed regions of interest in the IFP, suprapatellar subcutaneous and deep intermuscular adipose tissue. Qualitative assessments were performed to assess fibrotic changes affecting patellar retinaculum and IFP. Statistical analyses of T2 values determined differences between groups, correlation with time after surgery, and cut-off values to differentiate groups. The average time between arthroscopy and imaging was 3.5 +/- 0.4 years. IFP of knees with prior surgery had significantly shorter mean T2 values (133 +/- 14 ms) compared with control knees (147 +/- 8 ms, P = 0.03). There was no significant difference between operated and control knees regarding T2 values of suprapatellar subcutaneous (P = 0.3) or deep intermuscular adipose tissue (P = 0.2). There was no correlation between IFP T2 values and time after surgery (P > 0.2). IFP T2 values a parts per thousand currency signaEuro parts per thousand 139 ms had 75 % sensitivity and 88 % specificity in identifying prior arthroscopy. Shortening of T2 relaxation values is present in IFP chronically after arthroscopic surgery and may be an indicator of adipose tissue fibrosis. C1 [Torriani, Martin; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Torriani, Martin; Hosseini, Ali; Gill, Thomas J.; Bredella, Miriam A.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Taneja, Atul K.] Hosp Coracao HCor, Dept Radiol, Div Musculoskeletal Imaging, Teleimagem, Sao Paulo, Brazil. [Taneja, Atul K.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil. [Hosseini, Ali; Li, Guoan] Massachusetts Gen Hosp, Dept Orthoped, Bioengn Lab, Boston, MA 02114 USA. [Gill, Thomas J.] Massachusetts Gen Hosp, Dept Orthoped, Ctr Sports Med, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA. EM mtorriani@mgh.harvard.edu RI Taneja, Atul/N-3133-2014 OI Taneja, Atul/0000-0002-4655-2033 FU National Institutes of Health [R01 AR055612]; MGH Department of Radiology FX This study was supported by the National Institutes of Health (R01 AR055612) and MGH Department of Radiology. NR 21 TC 1 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2014 VL 43 IS 3 BP 315 EP 321 DI 10.1007/s00256-013-1791-4 PG 7 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 302RJ UT WOS:000330622300007 PM 24343788 ER PT J AU Lee, JJ Bredella, MA Springfield, DS Nielsen, GP AF Lee, Jonathan J. Bredella, Miriam A. Springfield, Dempsey S. Nielsen, Gunnlauger P. TI Soft tissue angiofibroma: a case report SO SKELETAL RADIOLOGY LA English DT Article DE Soft tissue angiofibroma; Angiofibroma ID GIANT-CELL TUMOR; LARGE REFERRAL POPULATION; TENDON SHEATH; EPITHELIOID SARCOMA; VILLONODULAR SYNOVITIS; PLANTAR FIBROMATOSIS; TRANSLOCATION; DIAGNOSES; LOCATION; NEOPLASM AB Soft tissue angiofibroma is a recently described neoplasm that typically presents as a slowly growing, painless mass in the soft tissues of the lower extremities. Cytogenetic and molecular studies have identified a recurrent t(5;8) translocation. Treatment is simple excision. Existing data suggest that this tumor is benign and has a low rate of local recurrence. The radiologic and pathologic differential diagnoses for this lesion include both benign and malignant lesions, including plantar fibromatosis, tenosynovial giant cell tumor, fibroma of tendon sheath, epithelioid sarcoma, and low-grade myxofibrosarcoma. Proper identification of this benign lesion through radiologic and pathologic correlation is important to prevent misdiagnosis of a low-grade sarcoma. C1 [Lee, Jonathan J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Springfield, Dempsey S.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Nielsen, Gunnlauger P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lee, JJ (reprint author), Harvard Univ, Sch Med, 250 Longwood Ave, Boston, MA 02115 USA. EM jonathan_lee@hms.harvard.edu NR 30 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 2014 VL 43 IS 3 BP 403 EP 407 DI 10.1007/s00256-013-1742-0 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 302RJ UT WOS:000330622300020 PM 24113908 ER EF